Speciality
Spotlight

       




 


Medicine


   

 




  • Tait AR, Pandit UA, Voepel-Lewis T, et al


    Use of Laryngeal Mask Airway in Children with Upper Respiratory Tract Infections: A Comparison with Endotracheal Intubation 



    Anesth Analg 86: 706-711, 1998


        


    There is debate over whether to proceed with anesthesia in children with upper respiratory infections [URI] who are sent for elective surgery. Endotracheal tube placement [ETT] may increase the risk of complications in children with URI. The laryngeal mask airway [ LMA ] provides a new approach to airway management. This study compares the LMA with ETT in children with URI. 

          


    The randomized trial included 82 children, aged 3 months to 16 years, undergoing elective surgery with URI. Those with lower respiratory tract infection were excluded. Half of the patients were managed with LMA and half with ETT, both placed under standard techniques. Both groups underwent induction of anesthesia with nitrous oxide, oxygen, and halothane. Patients were monitored from induction through postanesthesia for complications such as cough, laryngospasm, bronchospasm, breath-holding, and arrhythmias. Arterial oxygen desaturation [pulse oxymetry of less than 90%] was considered a major desaturation event.

           


    The LMA and ETT groups were comparable in terms of age, anesthesia and surgery times, number of tube placement attempts, and URI symptoms. The two methods produced similar incidence of cough, breath-holding, excessive secretions and arrythmias. There was also no difference in the incidence of laryngospasm, although one patient with an ETT required muscle relaxant for this complication. Mild bronchospasm occurred in 12% in the ETT group and none in the LMA group. Major desaturation events were also more common with ETT, 12.5% vs 0%. Respiratory complications were also more in the ETT group, 35 vs 19 in the LMA group. Still, the respiratory complications were easily managed in all with no adverse sequelae. Thus overall LMA offers a better choice than ETT in the anesthetic management of children with URI.

          

  • Harti
    DM, P Aidan, O Brugiere, et al (Universite Paris
    VII)


    Wegener’s
    Granulomatosis Presenting as a Recurrence of Chronic
    Otitis Media.

    Am J Otolaryngol  19: 54-60,
    1998.

          

    This
    is a case report of Wegener’s Granulomatosis
    manifesting otitis media with facial palsy. 
    Plasma antineutrophil cytoplasm antibodies
    were detected by means of immunofluorescence. 
    After three weeks of immunosuppressive
    therapy, facial palsy disappeared, the ESR had
    normalized and the size of pulmonary nodules had
    decreased.

          

    This
    case report highlights the need to bear in mind
    non-infectious causes of chronic otitis media with
    otorrhea.

           


  • AE-M
    Moussa, KA Abou-Elhmd (South Valley Univ, Sohag,
    Egypt)


    Wegener’s
    Granulomatosis Presenting as Mastoiditis

    Ann Otol Rhinol Laryngol  107:560-563,
    1998.

          

    Wegener’s
    granulomatosis is an uncommon auto-immune disorder,
    which has a peak incidence in the fifth decade of
    life with a slight male predominance. Typically,
    nasal problems are the initial manifestation.
    Otologic symptoms are rare.

           

    The
    authors report 2 cases of Wegener’s granulomatosis
    manifesting as mastoiditis (a fourteen-year-old girl
    and a 20-year-old woman).

          

  • LR
    Sammaritano, S Ng, R Sobel et al (Cornell Med Ctr,
    New York; North Shore Univ, Manhasset, NY; State
    Univ of New York, Stony Brook):


    Anticardiolipin IgG Subclasses:
    Association of IgG2 with Arterial and/or Venous
    Thrombosis
    .

    Arthritis
    Rheum 40:1998-2006, 1997
    .

          

    The
    presence of anticardiolipin antibodies (ACL) is
    associated with an increased risk of arterial and
    venous thrombosis, recurrent fetal loss and
    thrombocytopenia.

          

    The
    study of immunoglobulin (IgG) showed that patients
    who developed clinical thrombosis are associated
    with high ACL and related to high IgG2.
    The presence of IgG2 may be a useful
    predictor of thrombotic risk status.

          

  • WJ
    Catalona, AW Partin, KM Slawin, et al (Washington
    Univ, St. Louis, Mo; Johns Hopkins Hosp, Baltimore
    Md; Baylor College of Medicine, Houston; et al)


    Use
    of the Percentage of Free Prostate-specific Antigen
    to Enhance Differentiation of Prostate Cancer from
    Benign Prostatic Disease: A Prospective Multicenter
    Clinical Trial
    .

    JAMA
    279: 1542-1547, 1998
    .

         

    Free PSA percentage is a significant predictor of
    prostate cancer, with a sensitivity of 95% below a
    cutoff of 25%. Patients
    with prostate cancer and free PSA levels about the
    cutoff had less aggressive disease.
    Percentage of free PSA is an independent
    predictor of prostate cancer.

          

  • BA
    Julian, Jr RR Brantley, CV Barker, et al (Univ of 
    Alabama, Birmingham)


    Losartan, an Angiotensin II
    type 1 Receptor Antagonist, Lowers Hematocrit in
    Posttransplant Erythrocytes
    .

    J
    Am Soc Nephrol 9:1104-1108, 1998
    .

          

    Losartan,
    significantly lowers hematocrit in patients with
    post-transplant Anaemia (PTE).
    This suggests that angiotensin II has a
    pathogenic role in post-transplant Anaemia.

          

  • Minerva
    BMJ, 321; 8
    July 2000,.

    Gastrointestinal
    infection in children with Escherichia coli 0157:H7
    which are entero-haemolytic cause both renal
    hemorrhage and systemic hemolysis which lead to
    kidney failure.


          


    This
    complication is seen more often in children treated
    with antibiotics. It
    is likely that the toxins (called Shiga toxin) which
    is produced by this strain of e-coli 0157:H7 are
    produced in higher quantities by genetic change in
    e-coli caused by antibiotics.

          

  • JS
    Smolen and the European Leflunomide Study Group (Univ
    of Vienna; et al)


    Efficacy
    and Safety of Leflunomide Compared with Placebo and
    Sulphasalazine in Active Rheumatoid Arthritis: A
    Double-blind, Randomised, Multicentre Trial.

    Lancet
    353:259-266, 1999.

          

    In the treatment of rheumatoid arthritis,
    leflunomide is well tolerated and is more effective
    than placebo with its efficacy being similar to that
    of sulphasalazine.

          

  • L
    Guillevin, B Durand-Gasselin, et al (Hopital
    Avicenne, Bobigny, France; Hopital Tenon, Paris)


    Microscopic
    Polyangiitis: Clinical and Laboratory Findings in
    Eightyfive Patients.

    Arthritis
    Rheum 42: 421-430, 1999.

       

    Microscopic
    polyangiiits (MPA) is a disease of arterioles,
    venules and capillaries.
    Its major clinical characteristic is rapidly
    progressive glomerulonephritis.

         

    Polyarteritis
    Nodosa (PAN) involves large arteries, while MPA
    involves small arteries and arterioles.
    Proteinuria is a indicator of renal failure
    and death.

         

  • R
    Locher, PM Suter, W Vetter (Univ Hosp, Zurich,
    Switzerland)


    Ethanol Suppresses Smooth
    Muscle Cell Proliferation in the Postprandial State: 
    A

    New
    Antiatherosclerotic Mechanism of Ethanol?

    Am
    J Clin Nutr 67 : 338-341, 1998

         

    It
    is known that smooth muscle cell proliferation in
    the postprandial state (after food) may lead to
    narrowing of arteries. 
    It is well known that ethanol (alcohol)
    raises HDL cholesterol and thereby gives protection
    against atherosclerosis and heart attack. 
    It now appears that ethanol (alcohol) also
    suppresses the proliferation of smooth muscle cells
    and thereby gives additional protection in patients
    against atherosclerosis.

          

  • NJ
    Talley, for the Optimal Regimen Cures Helicobacter
    Induced Dyspepsia (ORCHID) Study Group (Univ of
    Syndey, Australia; et al)


    Eradication
    of Helicobacter pylori in functional Dyspepsia:
    Randomized Double Blind Placebo Controlled Trial
    with 12 Months’ Follow Up.

    BMJ
    318: 833-837, 1999.

          

    About
    half the patients with functional dyspepsia have
    H.pylori gastritis. Specific
    treatment of H.pylori infection cured 85% patients
    of their H.pylori infection.

         

    However,
    there was no improvement in their functional
    dyspepsia.

          

  • Positive
    opinion for Metalyse


    Scrip
    No.2592, November 15,2000, p.24


          

    Thrombolytic
    therapy after myocardial infarction requires
    administration of urokinase, streptokinase or tPA (Alteplase)
    given by infusion over many hours.

           

    A
    new compound has been developed by Genentech called
    Tenecteplase (Metalyse) which needs to be given as a
    single i.v. bolus over 5-10 secs.
    Tenecteplase has been approved in the US.
    In addition to the convenience of a single
    i.v. bolus, tenecteplase is associated with a lower
    incidence of bleeding.

           

  • R
    Gupta, Shalini Singhal. et al (Department of
    Medicine, Monilek Hospital and Research Centre,
    Jaipur)


    Antioxidant and Hypocholesterolaemic Effects
    of Terminalia
    arjuna
    Tree-Bark Powder: A Randomised
    Placebo-Controlled Trials.

    JAPI,
    Vol.49, February 2001, pg.231 – 235.

          

    One
    hundred and five successive patients with coronary
    heart disease were divided into 3 groups and treated
    with either placebo, vitamin E capsules 400
    units/day or Terminalia
    arjuna
    500mg/day in capsules.

          

    Conclusion
    by the authors was that terminalia
    arjuna
    has significant antioxidant action and
    also has a significant cholesterol lowering effect.

       

  • Maria G, Cassetta E, Gui D et al [Universita Cattolica del Sarco Cuore, Rome; Centro S Giovanni di Dio, Fatebenefratelli, Brescia, Italy]


    A Comparison of Botulinum Toxin and Saline for the Treatment of Chronic Anal Fissure



    N Engl J Med 338: 217-220, 1998


          

    Patients with chronic anal fissure have tearing of the lower half of the anal canal, possibly related to severe constipation or straining at stool. Internal anal sphincter contraction serves to maintain the fissure. Surgical sphincterotomy, the most common treatment, is done to relieve symptoms and promote healing. However, it also weakens the the internal sphincter, possibly leading to complications, such as anal deformity and incontinence. Patients received two injections of botulinum toxin A, for a total of 20 units in a volume of 0.4ml. Patients from the original treatment who had persistent fissures were retreated with botulinum toxin, 25 units. No relapses occurred through 16 months of follow-up.

           


    As an alternative to sphincterotomy, patients with chronic anal fissure may be effectively treated with local infiltration of botulinum toxin. This treatment is simple, inexpensive, and does not require anesthesia.

           


    The main alternative to this treatment is application of nitroglycerine ointment. Application of an ointment may be more acceptable to patients. 

           

  • Zeman
    C, Hunter RE, Freeman JR, et al [Orthopaedic
    Associates of Asper, Colo; Aspen Found for Sports
    Medicine, Education and Research, Colo]

    Acute Skier’s Thumb Repaired with a Proximal
    Phalanx Suture Anchor


    Am
    J Sports Med 26: 644-650, 1998


          

    58
    patients with grade III sprains of the UCL [Ulnar
    Collateral Ligament] were repaired using a suture
    anchor for fixation of thumb to the proximal
    phalanx.  After
    a year a 14 point questionnaire was administered to
    determine functional outcomes.

          

    98% of the interviewed patients were satisfied with
    the result and had a stable repair with good range
    of movements and no hindrance in their activities.
    17% reported mild discomfort and 7% experienced pain
    in the activities.

          

    This is a good method of repair.

           

  • Snyderman
    CH, Kachman K, Molseed L, et al [ Univ of
    Pittsburgh, Pa; Duquesne Univ, Pittsburgh, Pa; Univ
    of Louisville, Ky]


    Reduced Postoperative Infections with an
    Immune-Enhancing Nutritional Supplement


    Laryngoscope
    109: 915-921, 1999

           

    This
    is a randomized double blind trial on 136 patients
    who were undergoing radical excisional 
    surgery for squamous cell carcinoma of the 
    aerodigestive 
    tract and who required postoperative
    nutritional supplement.

          

    The patients were divided into four groups. [1] with
    pre and post operative supplementation with Impact
    [2] only post operative supplementation [3] pre and
    post operative standard formula [4] only
    postoperative standard formula.

          

    Group
    1 and Group 2 had significantly reduced rates of
    postoperative sepsis. Group 3 and Group 4 showed no
    effect on rate of wound sepsis healing or hospital
    stay. Postoperative albumin levels were higher in
    Group 1 and Group 2. Impact can reduce postoperative
    sepsis, hospital stay and costs.

           

  • Heyland
    DK, for the Canadian Critical Care Trials Group
    [Queen’s Univ, Kingston, Ont, Canada; et al]


    The Clinical Utility of Invasive Diagnostic
    Techniques in the Setting of Ventilator – Associated
    Pneumonia


    Chest
    115: 1076-1084, 1999

          

    Ventricular-associated
    pneumonia [VAP] is often diagnosed on clinical
    grounds alone and contributes to the morbidity,
    mortality and costs of caring for critically ill
    patients. Overdiagnosis may be disastrous with the
    use of needless antibiotics and the delay in
    recognition of the ‘true’ diagnosis.

          

    The utility of invasive investigations like
    bronchoscopy, with protected brush catheter [PBC]
    bronchoalveolar lavage [BAL] was evaluated in 92
    patients receiving ventilatory support 
    with a clinical suspicion of VAP.

          

    The results showed that VAP was often overdiagnosed
    after BAL or PBC after these procedures. Patients
    received fewer antibiotics. Both groups had similar
    duration of mechanical ventilation and ICU stay.
    Those who underwent PBC/BAL had a lower mortality.

          

    Invasive
    diagnostic testing may boost physicians confidence
    in the diagnosis and management of VAP.

           

  • Alter
    MJ, Kruszon-Moran D, Nainan OV, et al [ Ctrs for
    Disease Control and Prevention, Atlanta, Ga and
    Hyattsville, Md; Natl Inst of Allergy and Infectious
    Diseases, Bethasda, Md]


    The Prevalence of Hepatitis C Virus Infection in the
    United States, 1988 Through 1994


    N
    Engl J Med 341: 556-562, 1999

          

    Chronic
    infection with Hepatitis C virus [HCV] is a major
    cause of chronic liver disease, but is often
    asymptomatic. Sera was collected from a nationwide
    population survey to assess its prevalence.

          

    21,
    241 sera samples were tested. An enzyme immunoassay
    and a supplemental test were used to test for
    antibody to HCV [anti-HCV]. Reverse
    transcriptase-polymerase chain reaction for HCV RNA
    and gene sequencing studies were also performed.

          

    The
    result show 1.8% incidence of anti-HCV i.e. 3.9
    million persons in the US had HCV infection [95% 
    confidence level]. Nearly two thirds were
    between 30-49 years of age.

         

    Of
    those with anti-HCV, 74% tested positive for HCV
    i.e. 2.7 million Americans had chronic HCV
    infection. 74% of those had genotype 1 [ 57% – 1a 
    and 17% -1b]. Illegal drug use and high risk
    sexual behavior, poverty, poor education, divorced
    couples were significant risk factors and
    independently.

           

  • Pittet
    D, Wyssa B, Herter-Clavel C, et al [Univ Hosp of
    Geneva, Switzerland]


    Outcome of Diabetic
    Foot Infections Treated Conservatively : A
    Retrospective Cohort Study with Long-term Follow-up

    Arch
    Intern Med 159: 851-856, 1999


           

    Diabetic
    foot lesions are the cause of more hospitalizations
    than any other complications of diabetes. Effective
    guidance needs to be enunciated to minimize human
    and financial cost of diabetic foot lesions. A
    5-year retrospective cohort study with prospective
    long-term follow up was undertaken to identify
    criteria predictive of failure of conservative
    treatment of such lesions.

          

    The
    Wagner classification system was used for this
    study. Variables examined included patient
    demographics, infection and diabetes.

          

    Of
    120 patients, 74% had contiguous osteomyelitis, deep
    tissue involvement or gangrene. 13% underwent
    immediate amputation. 
    Of the remaining, conservative treatment was
    successful in 63% of cases. 21 of 26 [81%] with skin
    ulcers. 35 of 50 [70%] with deep tissue infection or
    suspected osteomyelitis and 1 of 15 [7%] with
    gangrene.

           

    Independent
    factors predictive of failure were fever, elevated
    creatinine, prior hospitalization for diabetic foot
    lesion, duration of diabetes.

           

    Conservative
    measures including prolonged culture guided
    parenteral or oral antibiotics was successful
    without amputation in 63% of diabetic foot lesion.

            

  • Furnary
    AP, Zerr KJ. Grunkemeier GL, et al [ Providence St.
    Vincent Med Ctr., Portland, Ore]

    Continuous Intravenous Insulin Infusion Reduced
    Incidence of Deep Sternal Wound Infection in
    Diabetic Patients After Cardiac Surgical Procedures



    Ann
    Thorac Surg 67: 352-362, 1999

          

    Deep
    Sternal Wound Infection [DSWI] is a very serious
    complication of cardiac surgery, and diabetes is an
    important risk factor. A new protocol to prevent
    DSWI in patients with diabetes, focusing on
    aggressive control of postoperative blood glucose
    levels by continuous insulin infusion [CII] was
    evaluated.

           

    A
    policy of aggressive glucose control with CII
    significantly reduced the incidence of DSWI, to
    equal that in non-diabetics, thus reducing
    considerably the high costs of readmission and
    mortality associated with DSWI in diabetic patients.

           

  • Jouveshomme
    S, Dautzenberg B, Bakdach H, et al [Hopital
    Pitie-Salpetriere, Paris: Centre Medico Chirurgical
    du Val d’Or, St Cloud, France]


    Preliminary
    Results of Collapse Therapy with Plombage for
    Pulmonary Disease Caused by Multidrug-resistant
    Mycobacteria

    Am
    J Respir Crit Care Med 157: 1609-1615, 1998


          

    Although
    excisional surgery is recommended for patients with
    pulmonary diseases resulting from multidrug-resistant
    mycobacteria, two thirds of patients are high risk
    and therefore not eligible.

         

    Patients
    who had multidrug-resistant strains of mycobacteria
    and extensive bilateral cavitary disease were
    treated with collapse therapy.

           

    The
    cavitary portion of the lungs was collapsed and the
    intercostal extra periostal space was filled with 5
    to 18 polystyrene spheres that were 4 cm in
    diameter.

           


    Collapse
    therapy is an effective treatment for high –risk
    patients with pulmonary disease caused by
    multidrug-resistant mycobacteria.

           

  • Veling
    MC, Windmill I, Bumpous JM [Univ of Louisville, Ky]


    Sudden
    Hearing Loss as a Presenting

    Manifestation
    of Leukemia

    Otolaryngol
    Head Neck Surg 120: 954-956, 1999, Pg. 37

          

    Sudden
    hearing loss is a rare initial manifestation of
    hematologic disorders. This report described a case
    in which sudden hearing loss was one of the
    presenting manifestations of leukemia.

          

    This
    case was unusual in that deafness was one of the
    presenting symptoms of leukemia.

           

    Typically, leukemia will cause deafness during its
    terminal stages. Leukemia can be seen as a
    presenting symptom of sudden deafness. The pathology
    of such patients, as seen from studies in temporal
    bones, suggests an immediate infiltration of
    pathologic leukemic cells throughout the
    labyrinthine spaces, followed by secondary
    degeneration of the sensory end organs and their
    cellular components.

           

  • Dange
    LA, Rogers RS III [Mayo Clinic Rochester, Minn]


    Clinical
    Assessment and Outcome in 70 Patients with
    Complaints of Burning or Sore Mouth Symptoms

    Mayo
    Clin Proc 74: 223-228, 1999


           

    Diagnoses
    of burning mouth syndrome are frequently applied to
    patients with mouth pain who have normal findings on
    oral examination. Mouth pain may also have
    associations with organic and psychiatric disorders.

           


    The most common underlying process was psychiatric
    disease [30%], followed by xerostomia [24%]
    geographic tongue [24%], nutritional deficiencies
    [21%] and allergic contract stomatitis [13%]. Liver
    and kidney function was normal in all patients.

           


    The burning mouth syndrome is quite troublesome to
    complaining patients and is equally frustrating to
    most physicians and dentists who attempt to diagnose
    and treat it.

          

    The
    No.1 etiology has been that of medication side
    effect. A comprehensive review of all medications
    currently taken by the patient as well as possible
    drug interactions is very important.

             

  • Arons
    MM, for the Ibuprofen in Sepsis Study group
    [Vanderbilt Univ., Nashville, Tenn]

    Effects of Ibuprofen on the Physiology and
    Survival of Hypothermic
    Sepsis


    Crit
    Care Med  27:699-707,
    1999


           

    Patients
    whose response to sepsis is hypothermic rather than
    febrile have a poor prognosis. It has been suggested
    that patients with hypothermic
    sepsis represent a clinically and
    biochemically distinct subgroup. This hypothesis was
    studied, along with the response to ibuprofen
    treatment in patients with hypothermic sepsis.

           

    The
    multicenter trial included 455 patients admitted to
    the ICU with severe sepsis and a known or suspected
    serious infection. 
    Patients with hypothermic sepsis were
    identified, and their clinical and physiologic
    findings were compared with those of patients with
    febrile sepsis. Plasma
    cytokines measured included tumor necrosis factor [TNF
    – alpha] and interleukin [IL]-6, along with the
    lipid mediators thromboxane B2[TxB], and
    prostacyclin. Hypothermic patients were randomized
    to receive ibuprofen [10 mg/kg IV over 30 to 60
    minutes every 6 hours for 8 doses, to a maximum of
    800 gm] or to receive a placebo.

            

    Ten
    percent of all patients with sepsis were
    hypothermic, with a temperature below 35.5 degrees
    celsius. The
    mortality rate was double in these patients compared
    to the rest [70% vs 35%], and they had significant
    baseline elevations of urinary TxB, metabolites,
    prostacyclin, and serum TNF-alpha and IL-6, compared
    with the febrile group.

           

    Twenty-four
    patients with hypothermic sepsis were assigned to
    ibuprofen and twenty two placebo. The 30-day
    morality was 54% in those receiving ibuprofen vs 90%
    in those on placebo.
    Ibuprofen treatment was also associated with
    a trend toward increased number of days free from
    major organ system failures.

            

    About
    ten percent of the patients with sepsis have
    hypothermia instead of a febrile response. Such
    patients have an increased mortality.
    Treatment with ibuprofen may reduce
    mortality, but prospective confirmation of these
    findings is needed.

            

  • Penning,
    H.A.J. Gielkens, M. Hemelaar, J.B.V.M. Delemarre,
    W.A. Bemelman, C.B.H.W. Lamers and A.A.M. Masclee [
    Departments of Gastroenterology- Hepatology and
    Surgery, Leiden University Medical Centre, Leiden,
    The Netherlands]

    Prolonged
    Ambulatory Recording of Antroduodenal Motility in
    Slow-Transit Constipation


    Br.
    J. of  Sur., 
    Volume 87, Number 2, February, 2000, Pg.
    211-217

            

    Slow
    transit constipation may be a part of a pan-enteric
    motor disorder. To test this hypothesis 24 hour
    ambulatory antroduodenal manometry was performed and
    orocaecal transit time determined in patients with
    slow transit constipation and in healthy controls.

            

    The antroduodenal motility was recorded with a
    5-channel solid-state catheter. Postprandial
    motility was recorded after consumption of 2
    standardized test meals and interdigestive motility
    was recorded nocturnally. Quantitative and
    qualitative analysis were done. The orocaecal
    transit time was determined by means of lactulose
    hydrogen breath test.

           

    There
    was no difference in the motility between patients
    and controls. However, some minor changes of
    interdigestive motility were observed.
    The proportion of phase II activity of the
    nocturnal cycles of the interdigestive migrating
    motor complex was increased in the patients while
    phase I activity was decreased. The total number of
    phase III fronts with antral onset was decreased.
    Specific motor abnormalities such as retrograde
    propagation of phase III fronts wee more frequent in
    patients.

           

    They
    conclude that in patients with slow transit
    constipation, orocaecal transit time is delayed but
    antroduodenal motility is generally well preserved
    with only minor alterations.

           

  • Zazgormik
    J, Biesenbach G, Janko O, et al [Gen Hosp Linz.  Ausria; Univ Gdansk, Poland]

    Bilateral Nephrectomy – The Best, but often
    overlooked Treatment 
    for Refractory Hypertension in Hemodialysis
    patients


    AM
    J. Hypertens 11 : 1364-1370, 1998

            

    Mean systolic and diastolic blood pressures decreased significantly 1
    month after surgery. At 12 months after surgery 9
    out of 10 patients had normal blood pressure.

            

    Bilateral
    nephrectomy is a safe and effective treatment for
    refractory hypertension in patients on hemodialysis
    and quality of life improved too.

          

  • D.S.
    Walsh, P. Siritongtaworn, K. Pattanapanyasat. P.
    Thavichaigarn, P. Kongcharoen, N. Jiarakul, P.
    Tongtawe, K. Yongvanitchit, C. Komoltri, C.
    Dheeradhada, F.C. Pearce, W.P. Wiesmann and H.K
    Webster [**]

    [** Department of Immunology and Medicine, US Army
    Medical Component, Armed Forces Research Institute
    of Medical Sciences, Departments of Surgery,
    Hematology and Clinical epidemiology, Siriraj
    Hospital, Department of Surgery, Pharmongkutklao
    [Royal Thai Army] Hospital, and Department of
    Surgery, Police Hospital, Bangkok, Thailand and
    Division of Surgery, Walter Reed Army Institute of
    Research, Washington, DC, USA ]

    Lymphocyte
    Activation After Non-Thermal Trauma


    Br.
    J. of  Sur.,  Volume 87, Number 2, February, 2000, Pg. 223-230

              

    Service
    injury causes immunologial changes that may
    contribute to a poor outcome. Longitudinal
    characterization of lymphocyte response patterns may
    provide further insight into the basis of these
    immunological alterations.

           

    Venous blood obtained seven times over 2 weeks from
    61 patients with injury severity scores over 20 was
    assessed for lymphocyte and activation markers
    together with
    serum levels
    of interleukin [IL]2, IL-4, soluble IL-2 receptor
    [sIL-2R], soluble CD4 [sCD4], soluble CD8 [sCD8] and
    interferon
    g.

           

    Severe
    injury was associated with profound changes in the
    phenotypic and activation profile in the phenotypic
    and activation profile of circulating lymphocytes.
    Activation was indicated by increased number of T
    cells expressing CD25, sIL-2R and sCD4 and sCD8 were
    found in-patients with sepsis syndrome.

           

    Polytrauma
    is associated with dramatic alterations in the
    phenotypic and activation profile of circulating
    lymphocytes which are generally independent of
    clinical course. In contrast several lymphocyte
    soluble factors including sCD4 and SIL-2R,
    paralleled the clinical course. These data provide
    new insight into lymphocyte responses after injury
    and suggest the further assessment of soluble
    factors as clinical correlates.

              

  • J.E.
    Creighton, R. Lyall, D.I. Wilson, A. Curtis and R.M.
    Charnley [Hepatopancreaticobiliary 
    Surgery Unit, Freeman Hospital, Department of
    Human Genetics, Northern Region Genetics Service,
    Royal Victoria Infirmary, and Department of Human
    Genetics and Medicine, University of
    Newcastle-upon-Tyne, Newcastle-upon-Tyne, UK]

    Mutations of the Cationic Trypsinogen Gene in
    Patients with Hereditary Pancreatitis


    Br.J.
    of  Sur.  Volume 87, Number 2, `February 2000, Pg. 170

          

    Hereditary
    pancreatitis has been known to be caused by one of
    two mutations [ R117H and N211]
    of the cationic trypsinogen gene [ PRSS1].
    Families with hereditary pancreatitis were
    investigated for these mutations.

           

    The
    R117H mutation
    was identified in three families and the N21I in
    further five The R117H mutation was associated with
    a more severe phenotype than N211 in terms of mean [s.d.] 
    age of onset of symptoms [8.4[7.2] versus
    16.5[7.1] years; p=0.007] and requirement for
    surgical intervention [8 of 12 versus 4 of 17
    respectively p= 0.029]. Haplotype analysis suggested
    that each mutation had arisen more than once.

           

  • Gu
    K, Cowie CC, Harris MI (Natl Inst of Diabetes and
    Digestive and Kidney Diseases, Bethesda, Md)

    Diabetes and Decline in Heart Disease
    Mortality in US Adults.



    J.a.m.a.


    281: 1291-1297, 1999


            

    Methods:
    Patients with and without diabetes, age 35 to 74
    years, were followed up prospectively for
    age-specific mortality rates/1000 person-years, age
    adjusted and stratified by cohort, diabetes status,
    and sex.

           

    Conclusion:
    the decline in mortality rates for all causes, heart
    disease, and ischemic heart disease is lower for
    patients with diabetes than for those without
    diabetes, particularly if they are female.

          

    Editorial
    comments
    :
    Despite the decrease in the mortality rate from
    coronary heart disease in the United States over the
    past 30 years, it is unclear whether patients with
    diabetes have followed these trends.
    The findings show that mortality from all
    causes, heart disease, and ischemic disease has
    decreased slightly in men with diabetes, and it has
    actually increased in women.
    One possible explanation for these findings
    is that patients with diabetes may have benefited
    less from improved medical treatment of heart
    disease. Moreover,
    the fact that mortality rates actually increased in
    women may suggest that women are being treated less
    aggressively for their diabetes than men.
    It should be noted, however, that this study
    could not differentiate between the types of
    diabetes and could not identify individuals with
    undiagnosed diabetes.
    Given the increasing prevalence of diabetes
    in the US population, it is possible that diabetes
    may constitute an even more important factor
    associated with heart disease mortality.

          

  • Carl
    Erik Mogensen, Steen Neldam, et al 
    (Department of Medicine, University Hospital,
    Denmark)

    Randomised
    controlled trial of dual blockade of
    renin-angiotensin system in patients with
    hypertension, microalbuminuria, and non-insulin
    dependent diabetes: the candesartan and lisinopril
    microalbuminuria (CALM) study.

    BMJ,
    9 December 2000, 321: pg.1440 – 1444

           

    The objective of the study was to assess
    and compare the effects of candesartan or
    lisinopril, or both, on blood pressure and urinary
    albumin excretion in patients with microalbuminuria,
    hypertension and type 2 diabetes.

           

    This was a prospective randomized, parallel group
    double-blind study in 199 patients with 4 week
    placebo period and 12 weeks monotherapy with
    candesartan or lisinopril followed by 12 weeks
    monotherapy or combination treatment.
    Candesartan dose was 16mg once daily and
    lisinopril dose was 20mg once daily BP and urinary
    albumin: creatinine ratio was measured.

            

    Conclusion
    of the study was that candesartan 16mg once daily is
    as effective as lisinopril 20mg once daily in
    reducing blood pressure and microalbuminuria in
    hypertensive patients with type 2 diabetes.
    Combination treatment is well tolerated and
    more effective in reducing BP.

           

  • Marco
    Pahor, Bruce M Psaty, et al (Department of Internal
    Medicine and Department of Public Health Sciences,
    USA

    Health
    Outcomes Associated with Calcium Antagonists
    compared with other First-line Antihypertensive
    Therapies: a Meta-Analysis of Randomised Controlled
    Trials.

    Lancet,
    vol.356, 9 December 2000, pg.1949-1954.

           

    Several
    randomised trials in hypertension have suggested
    that compared with other drugs, calcium antagonists
    may be associated with a higher risk of coronary
    events, despite similar blood pressure controls.
    This meta-analysis was carried out to compare
    the effects of calcium antagonists and other
    antihypertensive drugs on major cardiovascular
    events.

             

    Authors
    carried out a meta-analysis of trial in hypertension
    that assessed cardiovascular events and included at
    least 100 patients, who were randomly assigned to
    intermediate-acting or long-acting calcium
    antagonists or other antihypertensive drugs and who
    were followed up for at least 2 years.

            

    The
    conclusion of this meta-analysis was that in
    randomised controlled trials, calcium antagonists
    are inferior to other types of antihypertensive
    drugs as first-line agents in reducing the risks of
    several major complications of hypertension.
    On the basis of these data, the long-acting
    calcium antagonists cannot be recommended as
    first-line therapy for hypertension.

          

  • Blood
    pressure lowering treatment-Trialists Collaboration

    Effects
    of ACE inhibitors, calcium antagonists, and other
    blood pressure-lowering drugs: results of
    prospectively desgined overviews of randomised
    trials.

    Lancet
    : vol.356, December 9, 2000, p.1955-64

            

    This programme of overviews of randomised
    trials was established to investigate the effects of
    ACE inhibitors, calcium antagonists and other BP
    lowering drugs on mortality and major cardiovascular
    morbidity. Separate
    overviews of trials comparing active treatment
    regimens with placebo, trials comparing more
    intensive and less intensive BP lowering strategies,
    and trials comparing treatment regimens based on
    different drug classes were done.

           

    The interpretation is that there was strong evidence
    of benefits of ACE inhibitors and calcium
    antagonists as compared to placebo.
    There is weaker evidence of differences
    between treatment regimens of differing intensities
    and of differences between treatment regimens based
    on different drug classes.

            

    Commentary:
    Selection of initial anti-hypertensive drug therapy.

            

    The study done by Blood Pressure Lowering
    Treatment (BPLT) Trialist’s Collaboration (BPLT)
    has several methodological strengths. 
    The effect of ACE inhibitors on
    cardiovascular disease was impressive and was
    achieved in the context of small difference in BP
    (3/1 mm Hg) between ACE inhibitor and placebo
    groups. This
    finding raises the possibility that the beneficial
    effects of ACE inhibitors on cardiovascular disease
    in the trials were mediated not just through the
    lowering of BP.

           

    There has been intensive debate over the balance
    between the potentially beneficial and detrimental
    effects of calcium antagonists in cardiovascular
    disease.
    Overall, the data of BPLT provide evidence
    that calcium antagonists reduce the incidence and
    mortality from cardiovascular disease.

           

    The meta-analysis of Marco Pahor and colleagues
    focussed specially on comparison of calcium
    antagonists, with diuretics, beta-blockers, ACE
    inhibitors or clonidine.

           

    (1)   Diuretics or beta-blockers may be used
    initially for uncomplicated hypertension.

       

    (2)   
    ACE inhibitors – initial choice especially in
    patients at high risk of heart failure.

       

    (3)   Caution- for use of calcium antagonists as
    initial therapy in populations at high risk of CHD
    and heart failure

           (i.e. Western populations).

       

    (4)   Calcium antagonists – may be used as initial
    therapy in patients at high-risk of stroke and low
    risk of CDH

           (i.e. Asian population).

       

    (5)   If
    more than one drug needs to be used – combination of
    diuretics, beta-blockers, ACE inhibitors or calcium

           antagonists, based on patient’s absolute level of
    risk for cause-specific cardiovascular disease.

                    

  • Gill
    Spyer, Andrew T Hattersley, et al (Department of
    Vascular Medicine and Diabetes Research, London)

    Hypoglycaemic
    counter-regulation at normal blood glucose
    concentrations in patients with well controlled
    type-2 diabetes.

    Lancet
    356, December 9, 2000, pg. 1970-74.

          

    Intensive
    treatment to achieve good glycaemic control in
    diabetic patients is limited by a high frequency of
    hypoglycaemia. The
    glucose concentrations at which symptoms and release
    of counter-regulatory hormones takes place have not
    been studied in patients with well controlled type-2
    diabetes.

          

    The
    findings were that symptom response took place at
    higher whole blood glucose concentrations in
    diabetic patients than in controls.

           

    Glucose
    thresholds for counter-regulatory hormone secretion
    are altered in well controlled type-2 diabetic
    patients, so that both symptoms and
    counter-regulatory hormone release can take place at
    normal glucose values.
    This effect might protect type-2 diabetic
    patients against episodes of profound hypoglycaemia
    and make the achievement of normoglycaemia more
    challenging in clinical practice.

           

  • Abi
    Berger,

    Gut
    cells engineered to produce insulin

    BMJ,
    16 December 2000, pg.1488

           

    Engineering
    non-pancreatic cells to produce insulin in response
    to a glucose load may one day be a successful
    approach in the treatment of diabetes.
    Canadian scientists have now shown that cells
    other than pancreatic cells can be induced to
    secrete appropriate levels of insulin in response to
    eating.

            

    Previous
    attempts at gene therapy have concentrated on
    manipulation of liver cells, but hepatocytes do not
    have the ability to store hormones.

           

    Dr.
    Cheung (Dept. of Medicine, Univ. of Alberta, Canada)
    and his team have shown that mice can be genetically
    engineered to produce human insulin from K cells
    located in the duodenum. K cells usually produce glucose dependent insulinotropic
    polypeptide (GIP), so they have an advantage over
    hepatocytes in that they are already glucose
    responsive endocrine cells and have the correct
    equipment to be able to store hormones.

           

    Dr.
    Cheung showed that when K cells are genetically
    engineered to produce insulin, normal glucose
    tolerance could be achieved in animals that have had
    their own pancreatic beta cells ablated.

            

  • Vera
    Peuckmann, Michael Fisch and Eduardo Bruera (Dept.
    of Pharmacology, Univ. of Alberta, Edmonton,
    Alberta, Canada)

    Potential
    Novel Uses of Thalidomide –
    Focus on Palliative
    Care

    Drugs,
    Aug. 2000, 60(2), 273-292

           

    Thalidomide was banned in the early 1960s
    because of teratogenesis. It is being rediscovered
    because of its multiple therapeutic effects in
    serious diseases. It has anxiolytic, mild hypnotic,
    anti-emetic and adjuvant analgesic properties.
    It is highly effective in erythema nodosum
    leprosum (cutaneous manifestations of leprosy) and
    superior to aspirin in controlling leprosy
    associated fever. Promising results are seen in
    cancer cachexia and weight-loss in HIV infection.
    Its use is being explored in a variety of
    diseases such as tuberculosis, aphthous ulcers in
    HIV syndrome and Behcet’s disease, rheumatoid
    arthritis, multiple myeloma, inflammatory bowel
    disease, lupus erythematosus, Sjogren’s syndrome
    and a variety of solid tumours.
    In advanced cancer, it is effective in
    treating chronic nausea, insomnia, profuse sweating
    and pain. Hence, it is attractive for use in
    palliative care.

            

    The
    mechanism of action is probably based on suppression
    of tumour necrosis factor 
    µ
    (TNF-
    µ)
    and modulation of interleukins.

            

  • James
    Y.W.Lau, Joseph J.Y. Sung et al (Dept. of 
    Surgery, China)

    Effect
    of Intravenous Omeprazole on Recurrent Bleeding
    After Endoscopic Treatment of Bleeding Peptic
    Ulcers.

    New
    Eng J Med. August 3, 2000, Vol.343(5), pg.310-316.


            

    After
    endoscopic treatment of bleeding peptic ulcers,
    bleeding recurs in 15-20% of patients. 
    Authors assessed whether the use of a
    high-dose of a proton pump inhibitor would reduce
    the frequency of recurrent bleeding after endoscopic
    treatment of bleeding peptic ulcers.
    Patients with actively bleeding ulcers or
    ulcers with nonbleeding visible vessels were treated
    with an epinephrine injection followed by
    thermocoagulation. After
    haemostasis was achieved, the 240 patients, were
    randomly assigned in a double-blind fashion to
    receive omeprazole (given as a bolus IV injection of
    80mg followed by an infusion of 8mg/hr for 72 hrs)
    or placebo. After infusion, all patients were given 20mg of omeprazole orally
    daily for 8 weeks. The
    primary end-point
    was recurrent bleeding within 30 days after
    endoscopy.

           

    The
    conclusion of the study was, after endoscopic
    treatment of bleeding peptic ulcers, a high-dose
    infusion of omeprazole substantially reduces the
    risk of recurrent bleeding.

           

    Editorial
    – Eric D. Libby

           

    Why
    does omeprazole prevent recurrent bleeding when H2
    receptor antagonists do not ? Perhaps its beneficial
    effect results from protecting the clot rather than
    healing the ulcer.

           

  • Harvey
    D White, R John Simes, et al (Dept of 
    Medicine, Univ of Auckland, New Zealand)

    Pravastatin
    Therapy and the Risk of Stroke

    New
    Eng J Med. August 3, 2000, pg. 317-326.

           

    Several epidemiological studies have
    concluded that there is no relation between total
    cholesterol levels and the risk of stroke. 
    In some studies that classified strokes,
    according to cause, there was an association between
    increasing cholesterol levels and the risk of
    ischaemic stroke and a possible association between
    low cholesterol levels and the risk of haemorrhagic
    stroke.  Recent
    reviews of trials of HMG-CoA reductase inhibitors
    have suggested that these agents may reduce the risk
    of stroke.

           

    In
    this double-blind trial of pravastatin, it had a
    moderate effect in reducing the risk of stroke from
    any cause and the risk of nonhaemorrhagic stroke in
    patients with previous MI or unstable angina.

          

  • The
    ESPRIT investigators

    Novel
    dosing regimen of eptifibatide in planned coronary
    stent implantation (ESPRIT): a 
    randomised placebo-controlled trial.

    Lancet,
    vol.356, Dec.16, 2000, pg. 2037-2044

            

    The platelet glycoprotein Iib/IIIa inhibitors, although effective in reducing ischaemic
    complications of percutaneous coronary intervention,
    are used in few coronary stent implantation
    procedures. ESPRIT
    is a randomized placebo-controlled trial to assess
    whether a novel, double-bolus dose of eptifibatide
    could improve outcomes of patients undergoing
    coronary stenting.

           

    Authors recruited 2064 patients undergoing stent
    implantation – they were randomly allocated to
    receive eptifibatide, given as two 180 mg/kg
    boluses 10min. apart and a continuous infusion of 2 mg/kg/min
    for 18-24 hrs. or placebo, in addition to aspirin,
    heparin and a thienopyridine.

           

    It
    was observed that routine glycoprotein IIb/IIIa
    inhibitor pretreatment with eptifibatide
    substantially reduces ischaemic complications in
    coronary stent intervention
    and is better than a strategy of reserving treatment
    to the bailout situation.

            

  • Ian
    B Wilman, David J Webb, Chritison et al (Dept of
    Cardiology, Univ Wales College of Medicine, UK)

    Isolated
    systolic hypertension: a radical rethink.

    BMJ
    No.7251, June 24, 2000,pg.1685.

           

    The association between hypertension and
    a ‘hardening’ of the pulse and apoplexy has been
    recognised for hundreds of years. 
    Isolated systolic hypertension affects around
    half of people aged over 60 years.
    It confers a substantial cardiovascular risk.  Despite this, it remains underdiagnosed, and largely
    untreated, but the benefits of treatment are
    established.

           

    The relative risk reduction of cardiovascular events
    in elderly people with isolated systolic
    hypertension is similar to that in younger people.
    However, as elderly people are at much higher
    absolute risk of such events, they stand to benefit
    more from treatment than younger people.
    Elderly people tolerate antihypertensive
    drugs with few side effects.

          

    The
    latest WHO and International Society for
    hypertension guidelines for management of
    hypertension emphasise the importance of arterial
    stiffness and pulse pressure as predictors of
    cardiovascular risk and call for further indices of
    arterial stiffness.

            

  • Christopher
    D Byrne and Sarah H Wild (Univ of Southampton,
    School of Medicine, UK)

    Diabetes
    care needs evidence based interventions to reduce
    risk of vascular disease.

    BMJ,
    Vol.320, 10 June 2000, 1554-5

            

    The absolute risk of a first myocardial
    infarction is influenced by factors that include
    age, sex, blood pressure, total concentration of
    high-density lipoproteins, the cholesterol ratio and
    diabetes.

           

    The results of UK prospective diabetes study provide
    evidence that tight control of blood glucose reduces
    the risk of myocardial infarction but not of stroke.
    Tight control of blood pressure reduced the
    risk of ischaemic stroke but had little impact on
    risk of myocardial infarction. 
    When combined with the evidence from the
    hypertension optimal treatment trial, a target blood
    pressure of 130/80 and an HbAtc value
    of £7%
    seem to be desirable among diabetes patients in whom
    the absolute risk of myocardial infarction is >3%
    per year.

           

    Evidence from large randomised trials shows that
    treating people with statins reduces relative risk
    of myocardial infarction by about 30%.
    Decisions to treat patients with statins
    should not be based solely on concentrations of
    total cholesteroal or LDL cholesterol but on a
    person’s absolute risk of a vascular event.
    This is relevant with people with type-2
    diabetes, because primary lipid abnormality involves
    metabolism of triglycerides and high density
    lipoproteins, and plasma concentration of
    cholesterol may be normal.

           

    As regards fibrates, a secondary prevention trial,
    showed a 25% reduction in the risk of vascular
    events in men with diabetes who were treated with
    gemfibrozil.

           

    A further, potentially important intervention to
    reduce cardiovascular risk among people with
    diabetes, was the use of an angiotensin converting
    enzyme (ACE) inhibitors.
    Ramipril 10mg as compared to placebo reduced
    the risk of stroke by 33% and myocardial infarction
    by 22%. It is
    highly unlikely that this benefit was due to
    reduction in blood pressure because mean reductions
    systolic/diastolic were 2/3mm Hg in the ramipril
    group and 1/2mm Hg in the placebo group.

          

    People
    with type 2 diabetes have a markedly increased risk
    of myocardial infarction and stroke.
    Emphasis should be on treating people with
    therapies of proven benefit.

          

  • Stuart
    J Connolly.

    Anticoagulation
    for patients with atrial fibrillation and risk
    factors for stroke.

    BMJ,
    Vol.320, 6 May 2000, p.1219-20.

          

    The most clinically relevant advance in
    the management of cardiac arrhythmia in the pas two
    decades has been that anticoagulant treatment
    substantially reduces risk of stroke in patients
    with atrial fibrillation.
    A meta-analysis of trials shows that the risk
    is reduced by two-thirds.

           

    Major
    risk factors for stroke are age over 75, previous
    stroke or transient ischaemic attack, hypertension,
    mitral stenosis, and left ventricular dysfunction.
    Patients with atrial fibrillation and any of
    these factors face a higher than average risk (5-15%
    per year) of a stroke.

             

    Randomized
    trials evaluating aspirin, low fixed-dose warfarin
    and their combination clearly show the superiority
    of warfarin. On
    the basis of this strong evidence expert panels
    recommend that all patients with atrial fibrillation
    should be considered for treatment with
    anticoagulants and if any major risk factors are
    present their treatment should aim to keep the
    international normalised ratio between 2.0 and 3.0.

          

  • Peter
    D Inskip, Robert E Tarone, et al.

    Cellular
    Telephone Use and Brain Tumors.

    NEJM,
    Vol.344(2), Jan.11, 2001,p.79-86

          

    There is concern that the use of
    hand-held cellular telephones might cause brain
    tumours. If
    such a risk does exist, the matter would be of
    considerable public health importance, given the
    rapid increase worldwide in the use of these
    devices.

          

    Authors
    examined use of cellular telephones in a
    case-control study of intracranial tumours conducted
    between 1994 and 1998. 
    The data do not support the hypothesis that
    the recent use of hand-held cellular telephones
    causes brain tumours, but they are not sufficient to
    evaluate the risks among long-term heavy users and
    for potentially long induction periods.

          

  • Editorials

    Cristina
    Elisabetta Mapp.

    Inhaled
    Glucocorticoids in Chronic Obstructive Pulmonary
    Disease.

    NEJM,
    Vol.343 (26), December 28, 2000, pg.1960.

            

    Chronic obstructive pulmonary disease (COPD)
    is caused by at least 3 distinct pathologic
    processes that may occur separately or concurrently
    (chronic bronchitis, destruction of alveolar cells
    which causes emphysema and chronic asthma).

           

    In
    this issue, the Lung Health Study Group reports the
    result of inhaled traimcinolone (600 mg
    twice daily) during a mean follow-up period of 40
    months. The
    lack of effect on pulmonary function is consistent
    with previous findings.
    In Three other recently published trials also had
    similar results. In
    fact, the cessation of smoking is the only
    intervention that effectively slows the decline in
    pulmonary function in such patients.

           

    Thus,
    the potential benefits of inhaled glucocorticoids in
    patients with moderate to severe COPD are
    improvemnets in clinical outcomes that could be
    important to patients.
    On the basis of the results of the four
    long-term clinical trials reported to date, inhaled
    glucocorticoids can be recommended for the treatment
    of symptomatic patients with moderate to severe COPD
    and for patients with frequent exacerbations but not
    for patients with mild COPD.
    Efficacy of side-effects of budesonide,
    fluticasone and triamcinolone, were similar, except
    that only triamcinolone had deleterious effects on
    the skeleton.

                 

  • Andrew J Krentz, Clifford J Bailey et al

    Thiazolidinediones for type 2 diabetes

    New agents reduce insulin resistance but need long term clinical trials

    BMJ, Vol.321, July 29, 2000, pg. 252-253

            

    Insulin resistance (reduced action of insulin) is a prominent defect in type 2 diabetes. Before the introduction of troglitazone in 1997 metformin was the only drug able to sensitize target tissues to insulin. Troglitazone is superseded by more potent agents, rosiglitazone and pioglitazone. 

           


    Patients with insulin resistance have elevated serum TG and low HDL. This dyslipidemia contributes to risk of atherosclerotic cardiovascular disease. Thiazolidonediones increase HDL and rosiglitazone protects against endothelial dysfunction, lowers BP in insulin resistant and hypertensive rats.

           


    Clinical trials show that combination therapy using a thiazolidinedione with metformin (main action of which is to reduce glucose production by liver) or a sulphonylurea is particularly effective in lowering glucose concentrations.

           


    Extensive use of rosiglitazone and pioglitazone has produced little evidence that it has caused hepatic impairment. They are contraindicated in patients with liver damage. Cardiac failure is a contraindication and patients with reduced cardiac reserve need close monitoring. Pioglitazone induces cytochrome P450 (isoform CYP3A4) and the possibility of drug interactions e.g. with oral contraceptives.

            

  • Irene M Stratton, Amanda I Adler, et al 

    Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes
    (UKPDS 35): prospective observational study.


    BMJ, Vol.321, Aug.12, 2000, pg.405-412.

           

    The objective of the study was to determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complication in patients with type 2 diabetes. It was carried out in 4585 Asian Indian, white and Afro-Caribbean UKPDS (UK prospective diabetes study) patients. Incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbAtc was associated with reductions of risk of 21% for any end-point related to diabetes. The lowest risk being in those with HbAtc values in the normal range (<60%).

           

  • Amanda I Adler, Irene M Stratton, et al 

    Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study.

    BMJ, Vol.321, Aug.12, 2000, pg.412-419.

           

    The objective of the study was to determine the relation between systolic BP over time and the risk of macrovascular and microvascular complications in patients with type 2 diabetes.

           


    The incidence of clinical complications was significantly associated with systolic BP except for cataract extraction. Each 10 mm Hg decrease in updated mean systolic BP was associated with reductions in risk of 12% for any complication related to diabetes. No threshold of risk was observed for any endpoint.

           


    The conclusion was that in patients with type 2 diabetes the risk of diabetic complications was strongly associated with raised BP. Any reduction in BP is likely to reduce the risk of complications with the lowest risk being in those with systolic BP less than 120mm Hg.

             

  • Editorial – Jaakko Tuomilehto

    Controlling glucose and blood pressure in type 2 diabetes. 

    Starting treatment earlier may reduce complications.

    BMJ. Vol.321, Aug.12, 2000, pg.394-395.

           

    The main questions have been when should we start treatment, what is the target level during treatment and what is the best method of treatment, since there are no obvious cut-off points for B.P. or glucose or cholesterol concentrations that would guide clinical decisions.

           


    Comparisons with observational data have shown that antihypertensive drugs reduce the risk of stroke as predicted, but the reduction in the risk of myocardial infarction is less than expected. Treatment of hypercholesterolaemia with statins reduces the risk of myocardial infarction as predicted, whereas the effect on the risk of stroke seems larger than expected.

          


    The results of UKPDS studies reveal that patients with type 2 diabetes whose hypertension is tightly controlled reduce their risk of macrovascular complications to a greater extent than estimated. The data clearly show that there are no natural thresholds under which the risk of microvascular and macrovascular complications in diabetes are fully prevented but the risk increases steadily with rising levels of risk factors. The lower the level of blood glucose, HbAtcc, or BP, the lower the risk of complications.

           


    It is difficult to maintain reductions in glucose concentrations and BP even when using multiple drugs that in short term trials have produced excellent results. This was also confirmed in the UKPDS. Thus, the alternative possibility would be to start treatment at lower levels than those currently used as thresholds.

          


    A large European epidemiological study showed that postprandial glucose concentration is a better predictor of mortality than is fasting glucose. Perhaps impaired glucose tolerance should be an indication for treatment. There is a need to carry out controlled clinical trials to find out whether lowering glucose concentrations at the levels of impaired glucose tolerance will reduce microvascular and macrovascular complications.

         

  • Editorial – E Ernst

    Herbal medicines: where is the evidence ? 

    Growing evidence of effectiveness is counter balanced by inadequate regulation.

    BMJ, Vol.321, Aug.12, 2000, pg.395-396.

           

    Sales of herbal medicines are booming. Fastest growth is for St. John’s wort, a herbal antidepressant. In a meta-analysis of 23 randomized trials with mild to moderate depression, the authors concluded that extracts of hypericum were significantly more effective than placebo and as effective as conventional antidepressants.

          


    Controlled trials of ginkgo biloba for dementia showed that ginkgo was more effective than placebo. A meta-analysis showed palmetto as a symptomatic treatment for benign prostatic hyperplasia. It improved urological symptoms and flow measures significantly more than placebo. Saw palmetto was as effective as finasteride and had fewer adverse effects. A systematic review of horse chestnut seed extracts for chronic venous insufficiency indicated equivalence with other active therapies.

           


    Even though herbal remedies may be effective, do their benefits outweigh the risks ? Most herbal remedies in UK and USA are sold as food supplements. Thus, they evade regulation of their quality and safety. Two British cases of severe nephropathy caused by Chinese herbal tea administered to treat eczema illustrate this. Huge variations exist in the quality of herbal medicinal preparations.

           


    A recent study of herbal creams in UK showed that 8 of 11 preparations contained undeclared dexamethasone.

           


    The possibility of herb-drug interactions is a further important issue. Ginseng, on its own, has few serious adverse effects. When combined with warfarin, its antiplatelet activity might cause over anticoagulation.

            


    There is need for reliable information on herbal medicines, and should be met by undergraduate and postgraduate education. Detailed questions about use of herbal drugs should form a part of taking medical history.

          

  • Deborah Josefson

    Statins may reduce risk of Alzheimer’s disease

    BMJ, Vol.321, October 28, 2000, pg. 1040.

            

    Patients taking the statin class of cholesterol lowering drugs may also reduce their risk of developing Alzheimer’s disease according to a study reported in the Archives of Neurology 2000. The researchers focused on 3 statins- lovastatin, pravastatin and simvastatin. They reported that patients receiving lovastatin or pravastatin (but not simvastation) had a 70% lower prevalence of Alzheimer’s disease than a control group, comprising the entire patient population aged 60 and older

          

  • Mark B Pepys (Dept. of Medicine, London)

    The renaissance of C reactive protein


    BMJ 7277, 6TH Jan.2001, pg.4


         


    Creactive protein (CRP) has been traditionally used as an acute phase marker in tissue injury, infection and inflammation. However, now estimation of C reactive protein has become very accurate. Although C reactive protein response has no diagnostic specificity, serial measurements can be helpful in clinical management. In this respect it resembles ESR.

         


    Increased C reactive protein can predict coronary events in both stable and unstable angina. The level of C reactive protein in atherosclerotic plaques is very high.

          

  • Kelly Moriss

    Macrodoctor, come meet the manodoctors

    Lancet, vol. 357, march 10, 2000, p.778

          

    In the 1996 film Fantastic Voyage, a mini-submarine of medics travels from vein to brain to laser a clot. The scenario remains science fiction, but emerging field of nanomedicine may make it a science fact.

         

    Billions of minute, self-assembling, computerised bioelectromechanical systems ‘nanobots’ swarming to the injury site, sensing, diagnosing and activating therapeutic systems and cellular repair is envisaged. Nanobots may be one day made with molecular nanotechnology.

          

    The team at Cornell University used tiny nickel nanopropellors to link with ATPase and is investigating ways to turn light energy into ATP, generating recyclable fuel that would render such devices autonomous.

          

    Tree-like polymers called dendrimers could deliver gene therapy or intracranial implants without eliciting immune response.

          

    Tejal Desai (Univ. of Chicago) has developed silicone based microcapsules with nanopores to deliver cells, drugs, proteins, peptides and nucleic acids. Similar type capsules may travel through bloodstream and release their contents at desired locations based on binding to cell-specific receptors.

           

    PEBBLES are probes encapsulated by biological, localised embedding-nanospheres 20-200 nm wide, delivered into cells with 99% viability, via liposomes, a gene gun, or even macrophage ingestion. An individual PEBBLE can measure pH, oxygen, electrolytes, nitric oxide or early changes of apoptosis.

            

    Lethal ‘nanobots’ do not sound comfortable, but safety requirements will be built into systems.

           

    The problem is whether we want to make nanorobotics a reality. An injection of nanorobots could completely clear a stroke clot in a time that is in the order of one
    blood circulations time. Such treatment needs to
    prove itself superior to thrombolysis.

          


    Eric Drexler (Chairman of ‘Foresight’) predicts that nanomedicine will dominate medocal technology research for at least half this century.

           

  • Geoffrey Pasvol

    Targetting voracious appetite of malaria-infected red-blood cell.

    Lancet, vol.357, Feb.10,2001, pg. 408-409

           

    The malarial parasite needs nutrients and ions to satisfy its voracious appetite and rid itself of metabolites – these have to cross 3 membranes (parasite plasma membrane, parasitophorous vacuolar membrane and red-cell membrane). Channels exist in these
    membrances.

           

    Sanjay desai and colleagues have used patch-clamp technique on single RBC and describe a versatile channel. Infected RBCs had voltage-dependent currents that were 150 times bigger than uninfected
    RBCs. These currents were anionic and sensitive to chloride over the cation sodium. There is as yet no convincing electronmicrographic evidence for such a duct. Such identification of specific inhibitors of the channel might lead to new antimalarial drugs.

          

    The concentrations of drugs used in Desai’s studies are not necessarily in the therapeutic range and could be toxic, but the possibility of adjunctive therapy exists.
    Bioavailability, pharmacokinetic/pharmacodynamic issues also need to be considered because inhibition of the channel is reversible and long exposure to a channel-blocker might be required for parasite killing.

           

    Furthermore, because severe malaria may be accompanied by dehydration and
    hypoglycaemia, administration of a diuretic and/or a hypoglycaemic drug could be risky but this is a novel approach to the treatment of this deadly disease.

            

  • Kujala UM, Kaprio J, Sarna S, et al [ Inst of Biomedicine, Helsinki; Univ of Helsinki; Univ of
    Turku, Finland]

    Relationship of Leisure-Time Physical Activity and Mortality : The Finish Twin Cohort

    JAMA 279: 440-444, 1998

           


    Premature mortality may be reduced by high physical activity or fitness. High levels of physical activity or fitness may be achieved by genetic
    selection or early childhood experiences and favor the individual with longevity. Further clarification is needed regarding the relative importance of factors over which the individual has little or no control, such as sex, intrauterine and childhood environment, and family history, compared with factors that can be modified, such as diet, smoking, and physical activity. Distinguishing between physical activity and genetic and other familial factors can be clarified by studies of twins, who share some or all of the same genes and nearly always the same childhood environment. Leisure physical activity as a predisposing or preventive factor for premature mortality was investigated in a cohort of twins. A Questionnaire on physical activity and known predictors of premature mortality was filled out by 7925 healthy males and 7977 healthy females aged 25 to 64 years. Among the entire cohort, 1253 died, representing a hazard ratio for death, adjusted for age and sex, of 0.71 in occasional exercisers and 0.57 in conditioning exercisers, compared with those who were sedentary. The odds ratio for death was 0.66 in occasional exercisers and 0.44 in conditioning exercisers, compared with those who were sedentary, among the twin pairs who were healthy at baseline and discordant for death. After controlling for other predictors of mortality, the beneficial effects of physical activity remained.

           


    Even after genetic and other familial factors are taken into account, leisure-time physical activity is associated with reduced mortality.

          

  • Gerard Bodeker

    Lessons on integration from the developing world’s experience.

    BMJ, Jan.20, 2001, pg.164

           

    About half the population in industrialised countries regularly use complementary medicine.

          


    This article deals with considerations by the Common-wealth working group on Traditional and Complementary Health systems. Models adopted in China, India, Malaysia and Africa are dealt with.

          


    In India, a model was adopted through the Indian Medicine Central Council Medicine Act of 1970. The council was established to oversee the development of Indian systems of medicine and to ensure good standards of training and practice.

           

    Thirty-years on the Dept. of Indian systems of Medicine has expressed concern over the substandard quality of education in many colleges, which in the name of integration have produced hybrid curriculums and graduates unacceptable to either modern or traditional standards. The department has made it a priority to upgrade training in Indian systems of medicine.

           


    The government is adding 10 traditional medicines into its family welfare
    programme, funded by the World Bank and the Indian government. Medicines are for
    anaemia, oedema during pregnancy, postpartum problems, such as pain, uterine and abdominal complications, difficulties with lactation, nutritional deficiencies and childhood
    diarrhoea.

            


    New regulations were introduced in July 2000 to improve Indian herbal medicines by establishing standard manufacturing practices and quality control. 

           


    Randomised controlled clinical trials of selected prescriptions for Indian systems of medicine have been initiated. These will document the safety and efficacy of the prescriptions and provide the basis for their international licensure as medicines rather than simply as food supplement.

            

  • Ranjit Roy Chaudhury

    Commentary – Challenges in using traditional systems of medicien.

    BMJ. Jan.20, 2001, pg.167

          

    Integration of modern and traditional systems of medicine may result in loss of some of the basic concepts of the traditional systems of medicine. Purists in the traditional systems of medicine such as Ayurveda and Unani in India oppose this trend to ‘modernise’ their systems, particularly when such integration is carried out by experts in allopathy. They have no objection to the use of modern concepts of the methodology of clinical trials in evaluating the efficacy and side-effects of herbal preparations. Such clinical evaluation is essential to use these remedies in allopathic hospitals.

           


    However, carrying out randomised, double-blind, multicentred trials with standardised extracts is a slow and laborious process. Not all herbal medicines need to undergo vigorous trial because these preparations are already in use. The situation is complicated further because randomised trial may not be very appropriate for evaluation of medicines from traditional systems. Where Prakriti (Ayurveda) or Mijaj (Unani) of individual, determines specific therapy to be used.

          


    In the past 12 years, the Indian Council of Medical Research (ICMR) has set up a network for carrying out clinical trials of herbal medicines. Using this network, the council has shown the efficacy of several traditional medicines, including Picrorhiza kurroa in hepatitis and Pterocarpus marsupium in diabetes. As a result of these trials, these traditional medicines can be used in allopathic hospitals.

          


    The regulation of traditional systems of medicine, the products used in these systems, and the practitioners of these systems are weak in most countries. This leads to misuse of the medicines by unqualified practitioners and loss in the credibility of the system. WHO has initiated an effort in this direction and may be the appropriate body to help countries to develop a regulatory system and take steps to meet the obligations under Trade Related Intellectual Property Rights Agreement when these become applicable in the developing countries around 2005.

          

  • Martin Riedel (Germany)

    Editorial – Emergency diagnosis of pulmonary embolism

    Heart June 2001, vol.85: 607-609

          


    Emergency diagnosis of pulmonary embolism is the first prerequisite of saving the life of the patient. CT has emerged as a very valuable tool. It is both widely available and results are almost as good as angiography.

           


    Transthoracic echocardiography (TTE) is also widely available. It is non-invasive and very accurate in diagnosis of floating emboli. Transesophageal echocardiography (TOE) is perhaps even superior to TTE. It visualizes the proximal pulmonary arteries. When pulmonary embolism is suspected, TTA followed by TOE and CT gives very specific and precise diagnosis to enable surgery if indicated.

          

  • Tim Coleman and Robert West

    Editorial – Newly available treatments for nicotine addiction.

    BMJ, Vol.322, 5 May 2001, pg.1076-1077

           


    Nicotine addiction is recognised as a life-threatening but treatable disorder. Britain now has a treatment strategy for nicotine addiction, which includes provision of bupropion on prescription and the introduction of specialist smoking cessation services to provide behavioural support to people who want to stop smoking.

          


    Nicotine replacement therapy used alone can be effective, but better results are achieved when it is combined with behavioural support and counselling from a trained health professional. More intensive support seems to be more effective. Bupropion has not yet been tested without intensive behavioural support, so it is difficult to know whether it can be effective without this. The sustained one year abstinence rates achieved in the published trials of bupropion average about 20%. Nicotine replacement therapy is generally well tolerated and most side-effects arise from irritant effect of nicotine (such as rashes with nicotine patches). 

         


    Bupropion can cause seizures in about 1 in 1000 users (experience from US users) and UK initial figures are consistent with this. Most common side-effects are insomnia and dry mouth. Nicotine replacement therapy and bupropion are suitable only for heavier smokers (10-15 a day or more) who clearly want to stop and are ready to try.

          

  • A
    Fagot-Campagna, K.M.Venkat Narayan et al

    Type 2 diabetes in children

    BMJ, Vol.322, Feb.17,2001, pg.37-378

          

    Type 2 diabetes in children is being reported from USA, Canada, Japan, Hong-Kong, Australia, New Zealand, Libya and Bangladesh. Prevalence ranges from 4.1 per 1000 in US to 50.9 per 1000 in Pima Indians of Arizona.

           

    At diagnosis, the affected child may present with weight loss, ketosis and acidosis. Insulin and C-peptide levels are often raised and antibodies absent, which may help differentiate type I from type 2 diabetes, but insulin secretion may be blunted at diagnosis. Patients may have hypertension, hypertriglyceridemia, albuminuria, sleep apnoea and depression. Treatment varies considerably and several drugs used for glycaemia, blood pressure and lipid control are not approved for use in children.

           

    To respond to this emerging problem, we need to develop case definitions in children. Safety and efficacy of therapies used in adults is known but same information is not available for children. Also needed are well co-ordinated, multi-centre trials testing the feasibility of multiple risk factor reduction in children and its benefits for practical health outcomes, such as the early stages of vascular disease.

           

  • Thorkild IA Sorensen

    Obesity genes

    BMJ, Vol.322, 17 March 2001, p.630-631

           

    Obesity is influenced by environmental factors and by genetics. That obesity runs in families is an old observation. The pattern of inheritance suggests that the effect is polygenic, with each variant of many different genes making a small difference in effect. As a phenotype obesity is also heterogeneous and there are 2 distinct but frequently overlapping subtypes: general obesity and abdominal obesity. These subtypes have different physiological, clinical and prognostic implications. The phenotypes seem to have some of the same genetic and environmental influences in common.

          

    Since the identification of the leptin gene, many other single genes have also been investigated as candidates for causing obesity, and the entire genome has been scanned for loci associated with obesity. A few genes have been found to cause monogenic forms of obesity in humans.

          

    One way forward may be to conduct controlled human experiments by manipulating environmental factors that are assumed to be pertinent, such as fat intake. Its effect on both gene expression and the function of gene products in people with different genetic variants may elucidate which genes contribute to common obesity.

           

  • Roland
    Rosmond, Claude Bouchard, et al 

    Tsp5091 polymorphism in exon 2 of the glucocorticoid receptor gene in relation to obesity and cortisol secretion: cohort study.

    BMJ, Vol.322, 17 March 2001, p.652-653

          

    Chronically elevated cortisol levels can increase body fat, as seen in Cushing’s syndrome. Subjects with abdominal obesity share many of the hormonal, metabolic and circulatory characteristics of people with Cushing’s syndrome. A dysfunctional glucocorticoid receptor may add to the adverse health effects of excessive cortisol concentrations.

            

    An Asn363Ser polymorphism in exon 2 of the glucocorticoid receptor gene (GRL) might be associated with overweight and an increased sensitivity to exogenous glucocorticoids. Authors examined whether this variant was associated with altered sensitivity to glucocorticoids as well as obesity with its related metabolic and haemodynamic abnormalities in a cohort of Swedish men.

          

    It was concluded that GRL has several different polymorphisms and mutations, but that few of these are consistently associated with obesity and subtle physiological alterations in the hypothalamic-pituitary adrenal axis regulating cortisol secretion. The Asn363Ser polymorphism does not seem to be one of the variants associated with such changes.

           

  • Ann Ekberg – Jansson, Sven Larsson et al

    Editorial – Preventing exacerbations of chronic bronchitis and COPD.

    BMJ, 26 May, 2001; pg.1259-1260.

           


    Exacerbations of COPD affect quality of life and cost of managing the disease. Recent data show good correlation between hypersecretion and long-term deterioration of ventilatory function in these patients. This is why mucolytics may influence disease progression in COPD.

           


    Cochrane review reports a meta-analysis of 22 studies of 10 drugs. Treated patients showed a significant reduction over controls in the number of exacerbations and number of days each exacerbation lasted. No difference in lung function or in adverse effects was seen.

          


    Drug contributing most to the beneficial effects seems to be acetylcysteine -possibly by antioxidative effect. Ambroxol also reduces exacerbations – due to mucolytic effect and antioxidative effects. It is also a secretagogue for surfactant (this has antibacterial properties).

           


    Orally administered bacterial lysates that stimulate immune system have been used for several years. OM 85 BV, a lysate of 8 pulmonary pathogens has been evaluated in a meta-analysis.

          


    The present Cochrane report, together with that on oral vaccination with whole killed H.influenzae and the meta-analysis treatment with OM85 BV indicates that different therapeutic regimes might prevent exacerbations of chronic bronchitis and COPD.

            


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Speciality Spotlight

       

 
Medicine
   

 

  • Tait AR, Pandit UA, Voepel-Lewis T, et al
    Use of Laryngeal Mask Airway in Children with Upper Respiratory Tract Infections: A Comparison with Endotracheal Intubation 
    Anesth Analg 86: 706-711, 1998
        
    There is debate over whether to proceed with anesthesia in children with upper respiratory infections [URI] who are sent for elective surgery. Endotracheal tube placement [ETT] may increase the risk of complications in children with URI. The laryngeal mask airway [ LMA ] provides a new approach to airway management. This study compares the LMA with ETT in children with URI. 
          
    The randomized trial included 82 children, aged 3 months to 16 years, undergoing elective surgery with URI. Those with lower respiratory tract infection were excluded. Half of the patients were managed with LMA and half with ETT, both placed under standard techniques. Both groups underwent induction of anesthesia with nitrous oxide, oxygen, and halothane. Patients were monitored from induction through postanesthesia for complications such as cough, laryngospasm, bronchospasm, breath-holding, and arrhythmias. Arterial oxygen desaturation [pulse oxymetry of less than 90%] was considered a major desaturation event.
           
    The LMA and ETT groups were comparable in terms of age, anesthesia and surgery times, number of tube placement attempts, and URI symptoms. The two methods produced similar incidence of cough, breath-holding, excessive secretions and arrythmias. There was also no difference in the incidence of laryngospasm, although one patient with an ETT required muscle relaxant for this complication. Mild bronchospasm occurred in 12% in the ETT group and none in the LMA group. Major desaturation events were also more common with ETT, 12.5% vs 0%. Respiratory complications were also more in the ETT group, 35 vs 19 in the LMA group. Still, the respiratory complications were easily managed in all with no adverse sequelae. Thus overall LMA offers a better choice than ETT in the anesthetic management of children with URI.
          

  • Harti DM, P Aidan, O Brugiere, et al (Universite Paris VII)
    Wegener’s Granulomatosis Presenting as a Recurrence of Chronic Otitis Media.
    Am J Otolaryngol  19: 54-60, 1998.
          
    This is a case report of Wegener’s Granulomatosis manifesting otitis media with facial palsy.  Plasma antineutrophil cytoplasm antibodies were detected by means of immunofluorescence.  After three weeks of immunosuppressive therapy, facial palsy disappeared, the ESR had normalized and the size of pulmonary nodules had decreased.
          
    This case report highlights the need to bear in mind non-infectious causes of chronic otitis media with otorrhea.
           

  • AE-M Moussa, KA Abou-Elhmd (South Valley Univ, Sohag, Egypt)
    Wegener’s Granulomatosis Presenting as Mastoiditis
    Ann Otol Rhinol Laryngol  107:560-563, 1998.
          
    Wegener’s granulomatosis is an uncommon auto-immune disorder, which has a peak incidence in the fifth decade of life with a slight male predominance. Typically, nasal problems are the initial manifestation. Otologic symptoms are rare.
           
    The authors report 2 cases of Wegener’s granulomatosis manifesting as mastoiditis (a fourteen-year-old girl and a 20-year-old woman).
          

  • LR Sammaritano, S Ng, R Sobel et al (Cornell Med Ctr, New York; North Shore Univ, Manhasset, NY; State Univ of New York, Stony Brook):
    Anticardiolipin IgG Subclasses: Association of IgG2 with Arterial and/or Venous Thrombosis.
    Arthritis Rheum 40:1998-2006, 1997.
          
    The presence of anticardiolipin antibodies (ACL) is associated with an increased risk of arterial and venous thrombosis, recurrent fetal loss and thrombocytopenia.
          
    The study of immunoglobulin (IgG) showed that patients who developed clinical thrombosis are associated with high ACL and related to high IgG2. The presence of IgG2 may be a useful predictor of thrombotic risk status.
          

  • WJ Catalona, AW Partin, KM Slawin, et al (Washington Univ, St. Louis, Mo; Johns Hopkins Hosp, Baltimore Md; Baylor College of Medicine, Houston; et al)
    Use of the Percentage of Free Prostate-specific Antigen to Enhance Differentiation of Prostate Cancer from Benign Prostatic Disease: A Prospective Multicenter Clinical Trial.
    JAMA 279: 1542-1547, 1998.
         
    Free PSA percentage is a significant predictor of prostate cancer, with a sensitivity of 95% below a cutoff of 25%. Patients with prostate cancer and free PSA levels about the cutoff had less aggressive disease. Percentage of free PSA is an independent predictor of prostate cancer.
          

  • BA Julian, Jr RR Brantley, CV Barker, et al (Univ of  Alabama, Birmingham)
    Losartan, an Angiotensin II type 1 Receptor Antagonist, Lowers Hematocrit in Posttransplant Erythrocytes.
    J Am Soc Nephrol 9:1104-1108, 1998.
          
    Losartan, significantly lowers hematocrit in patients with post-transplant Anaemia (PTE). This suggests that angiotensin II has a pathogenic role in post-transplant Anaemia.
          

  • Minerva BMJ, 321; 8 July 2000,.
    Gastrointestinal infection in children with Escherichia coli 0157:H7 which are entero-haemolytic cause both renal hemorrhage and systemic hemolysis which lead to kidney failure.
          
    This complication is seen more often in children treated with antibiotics. It is likely that the toxins (called Shiga toxin) which is produced by this strain of e-coli 0157:H7 are produced in higher quantities by genetic change in e-coli caused by antibiotics.
          

  • JS Smolen and the European Leflunomide Study Group (Univ of Vienna; et al)
    Efficacy and Safety of Leflunomide Compared with Placebo and Sulphasalazine in Active Rheumatoid Arthritis: A Double-blind, Randomised, Multicentre Trial.
    Lancet 353:259-266, 1999.
          
    In the treatment of rheumatoid arthritis, leflunomide is well tolerated and is more effective than placebo with its efficacy being similar to that of sulphasalazine.
          

  • L Guillevin, B Durand-Gasselin, et al (Hopital Avicenne, Bobigny, France; Hopital Tenon, Paris)
    Microscopic Polyangiitis: Clinical and Laboratory Findings in Eightyfive Patients.
    Arthritis Rheum 42: 421-430, 1999.
       
    Microscopic polyangiiits (MPA) is a disease of arterioles, venules and capillaries. Its major clinical characteristic is rapidly progressive glomerulonephritis.
         
    Polyarteritis Nodosa (PAN) involves large arteries, while MPA involves small arteries and arterioles. Proteinuria is a indicator of renal failure and death.
         

  • R Locher, PM Suter, W Vetter (Univ Hosp, Zurich, Switzerland)
    Ethanol Suppresses Smooth Muscle Cell Proliferation in the Postprandial State:  A New Antiatherosclerotic Mechanism of Ethanol?
    Am J Clin Nutr 67 : 338-341, 1998
         
    It is known that smooth muscle cell proliferation in the postprandial state (after food) may lead to narrowing of arteries.  It is well known that ethanol (alcohol) raises HDL cholesterol and thereby gives protection against atherosclerosis and heart attack.  It now appears that ethanol (alcohol) also suppresses the proliferation of smooth muscle cells and thereby gives additional protection in patients against atherosclerosis.
          

  • NJ Talley, for the Optimal Regimen Cures Helicobacter Induced Dyspepsia (ORCHID) Study Group (Univ of Syndey, Australia; et al)
    Eradication of Helicobacter pylori in functional Dyspepsia: Randomized Double Blind Placebo Controlled Trial with 12 Months’ Follow Up.
    BMJ 318: 833-837, 1999.
          
    About half the patients with functional dyspepsia have H.pylori gastritis. Specific treatment of H.pylori infection cured 85% patients of their H.pylori infection.
         
    However, there was no improvement in their functional dyspepsia.
          

  • Positive opinion for Metalyse
    Scrip No.2592, November 15,2000, p.24
          
    Thrombolytic therapy after myocardial infarction requires administration of urokinase, streptokinase or tPA (Alteplase) given by infusion over many hours.
           
    A new compound has been developed by Genentech called Tenecteplase (Metalyse) which needs to be given as a single i.v. bolus over 5-10 secs. Tenecteplase has been approved in the US. In addition to the convenience of a single i.v. bolus, tenecteplase is associated with a lower incidence of bleeding.
           

  • R Gupta, Shalini Singhal. et al (Department of Medicine, Monilek Hospital and Research Centre, Jaipur)
    Antioxidant and Hypocholesterolaemic Effects of Terminalia arjuna Tree-Bark Powder: A Randomised Placebo-Controlled Trials.
    JAPI, Vol.49, February 2001, pg.231 – 235.
          
    One hundred and five successive patients with coronary heart disease were divided into 3 groups and treated with either placebo, vitamin E capsules 400 units/day or Terminalia arjuna 500mg/day in capsules.
          
    Conclusion by the authors was that terminalia arjuna has significant antioxidant action and also has a significant cholesterol lowering effect.
       

  • Maria G, Cassetta E, Gui D et al [Universita Cattolica del Sarco Cuore, Rome; Centro S Giovanni di Dio, Fatebenefratelli, Brescia, Italy]
    A Comparison of Botulinum Toxin and Saline for the Treatment of Chronic Anal Fissure
    N Engl J Med 338: 217-220, 1998
          
    Patients with chronic anal fissure have tearing of the lower half of the anal canal, possibly related to severe constipation or straining at stool. Internal anal sphincter contraction serves to maintain the fissure. Surgical sphincterotomy, the most common treatment, is done to relieve symptoms and promote healing. However, it also weakens the the internal sphincter, possibly leading to complications, such as anal deformity and incontinence. Patients received two injections of botulinum toxin A, for a total of 20 units in a volume of 0.4ml. Patients from the original treatment who had persistent fissures were retreated with botulinum toxin, 25 units. No relapses occurred through 16 months of follow-up.
           
    As an alternative to sphincterotomy, patients with chronic anal fissure may be effectively treated with local infiltration of botulinum toxin. This treatment is simple, inexpensive, and does not require anesthesia.
           
    The main alternative to this treatment is application of nitroglycerine ointment. Application of an ointment may be more acceptable to patients. 
           

  • Zeman C, Hunter RE, Freeman JR, et al [Orthopaedic Associates of Asper, Colo; Aspen Found for Sports Medicine, Education and Research, Colo]
    Acute Skier’s Thumb Repaired with a Proximal Phalanx Suture Anchor
    Am J Sports Med 26: 644-650, 1998
          
    58 patients with grade III sprains of the UCL [Ulnar Collateral Ligament] were repaired using a suture anchor for fixation of thumb to the proximal phalanx.  After a year a 14 point questionnaire was administered to determine functional outcomes.
          
    98% of the interviewed patients were satisfied with the result and had a stable repair with good range of movements and no hindrance in their activities. 17% reported mild discomfort and 7% experienced pain in the activities.
          
    This is a good method of repair.
           

  • Snyderman CH, Kachman K, Molseed L, et al [ Univ of Pittsburgh, Pa; Duquesne Univ, Pittsburgh, Pa; Univ of Louisville, Ky]
    Reduced Postoperative Infections with an Immune-Enhancing Nutritional Supplement
    Laryngoscope 109: 915-921, 1999
           
    This is a randomized double blind trial on 136 patients who were undergoing radical excisional  surgery for squamous cell carcinoma of the  aerodigestive  tract and who required postoperative nutritional supplement.
          
    The patients were divided into four groups. [1] with pre and post operative supplementation with Impact [2] only post operative supplementation [3] pre and post operative standard formula [4] only postoperative standard formula.
          
    Group 1 and Group 2 had significantly reduced rates of postoperative sepsis. Group 3 and Group 4 showed no effect on rate of wound sepsis healing or hospital stay. Postoperative albumin levels were higher in Group 1 and Group 2. Impact can reduce postoperative sepsis, hospital stay and costs.
           

  • Heyland DK, for the Canadian Critical Care Trials Group [Queen’s Univ, Kingston, Ont, Canada; et al]
    The Clinical Utility of Invasive Diagnostic Techniques in the Setting of Ventilator – Associated Pneumonia
    Chest 115: 1076-1084, 1999
          
    Ventricular-associated pneumonia [VAP] is often diagnosed on clinical grounds alone and contributes to the morbidity, mortality and costs of caring for critically ill patients. Overdiagnosis may be disastrous with the use of needless antibiotics and the delay in recognition of the ‘true’ diagnosis.
          
    The utility of invasive investigations like bronchoscopy, with protected brush catheter [PBC] bronchoalveolar lavage [BAL] was evaluated in 92 patients receiving ventilatory support  with a clinical suspicion of VAP.
          
    The results showed that VAP was often overdiagnosed after BAL or PBC after these procedures. Patients received fewer antibiotics. Both groups had similar duration of mechanical ventilation and ICU stay. Those who underwent PBC/BAL had a lower mortality.
          
    Invasive diagnostic testing may boost physicians confidence in the diagnosis and management of VAP.
           

  • Alter MJ, Kruszon-Moran D, Nainan OV, et al [ Ctrs for Disease Control and Prevention, Atlanta, Ga and Hyattsville, Md; Natl Inst of Allergy and Infectious Diseases, Bethasda, Md]
    The Prevalence of Hepatitis C Virus Infection in the United States, 1988 Through 1994
    N Engl J Med 341: 556-562, 1999
          
    Chronic infection with Hepatitis C virus [HCV] is a major cause of chronic liver disease, but is often asymptomatic. Sera was collected from a nationwide population survey to assess its prevalence.
          
    21, 241 sera samples were tested. An enzyme immunoassay and a supplemental test were used to test for antibody to HCV [anti-HCV]. Reverse transcriptase-polymerase chain reaction for HCV RNA and gene sequencing studies were also performed.
          
    The result show 1.8% incidence of anti-HCV i.e. 3.9 million persons in the US had HCV infection [95%  confidence level]. Nearly two thirds were between 30-49 years of age.
         
    Of those with anti-HCV, 74% tested positive for HCV i.e. 2.7 million Americans had chronic HCV infection. 74% of those had genotype 1 [ 57% – 1a  and 17% -1b]. Illegal drug use and high risk sexual behavior, poverty, poor education, divorced couples were significant risk factors and independently.
           

  • Pittet D, Wyssa B, Herter-Clavel C, et al [Univ Hosp of Geneva, Switzerland]
    Outcome of Diabetic Foot Infections Treated Conservatively : A Retrospective Cohort Study with Long-term Follow-up
    Arch Intern Med 159: 851-856, 1999
           
    Diabetic foot lesions are the cause of more hospitalizations than any other complications of diabetes. Effective guidance needs to be enunciated to minimize human and financial cost of diabetic foot lesions. A 5-year retrospective cohort study with prospective long-term follow up was undertaken to identify criteria predictive of failure of conservative treatment of such lesions.
          
    The Wagner classification system was used for this study. Variables examined included patient demographics, infection and diabetes.
          
    Of 120 patients, 74% had contiguous osteomyelitis, deep tissue involvement or gangrene. 13% underwent immediate amputation.  Of the remaining, conservative treatment was successful in 63% of cases. 21 of 26 [81%] with skin ulcers. 35 of 50 [70%] with deep tissue infection or suspected osteomyelitis and 1 of 15 [7%] with gangrene.
           
    Independent factors predictive of failure were fever, elevated creatinine, prior hospitalization for diabetic foot lesion, duration of diabetes.
           
    Conservative measures including prolonged culture guided parenteral or oral antibiotics was successful without amputation in 63% of diabetic foot lesion.
            

  • Furnary AP, Zerr KJ. Grunkemeier GL, et al [ Providence St. Vincent Med Ctr., Portland, Ore]
    Continuous Intravenous Insulin Infusion Reduced Incidence of Deep Sternal Wound Infection in Diabetic Patients After Cardiac Surgical Procedures
    Ann Thorac Surg 67: 352-362, 1999
          
    Deep Sternal Wound Infection [DSWI] is a very serious complication of cardiac surgery, and diabetes is an important risk factor. A new protocol to prevent DSWI in patients with diabetes, focusing on aggressive control of postoperative blood glucose levels by continuous insulin infusion [CII] was evaluated.
           
    A policy of aggressive glucose control with CII significantly reduced the incidence of DSWI, to equal that in non-diabetics, thus reducing considerably the high costs of readmission and mortality associated with DSWI in diabetic patients.
           

  • Jouveshomme S, Dautzenberg B, Bakdach H, et al [Hopital Pitie-Salpetriere, Paris: Centre Medico Chirurgical du Val d’Or, St Cloud, France]
    Preliminary Results of Collapse Therapy with Plombage for Pulmonary Disease Caused by Multidrug-resistant Mycobacteria
    Am J Respir Crit Care Med 157: 1609-1615, 1998

          
    Although excisional surgery is recommended for patients with pulmonary diseases resulting from multidrug-resistant mycobacteria, two thirds of patients are high risk and therefore not eligible.
         
    Patients who had multidrug-resistant strains of mycobacteria and extensive bilateral cavitary disease were treated with collapse therapy.
           
    The cavitary portion of the lungs was collapsed and the intercostal extra periostal space was filled with 5 to 18 polystyrene spheres that were 4 cm in diameter.
           
    Collapse therapy is an effective treatment for high –risk patients with pulmonary disease caused by multidrug-resistant mycobacteria.
           

  • Veling MC, Windmill I, Bumpous JM [Univ of Louisville, Ky]
    Sudden Hearing Loss as a Presenting Manifestation of Leukemia
    Otolaryngol Head Neck Surg 120: 954-956, 1999, Pg. 37
          
    Sudden hearing loss is a rare initial manifestation of hematologic disorders. This report described a case in which sudden hearing loss was one of the presenting manifestations of leukemia.
          
    This case was unusual in that deafness was one of the presenting symptoms of leukemia.
           
    Typically, leukemia will cause deafness during its terminal stages. Leukemia can be seen as a presenting symptom of sudden deafness. The pathology of such patients, as seen from studies in temporal bones, suggests an immediate infiltration of pathologic leukemic cells throughout the labyrinthine spaces, followed by secondary degeneration of the sensory end organs and their cellular components.
           

  • Dange LA, Rogers RS III [Mayo Clinic Rochester, Minn]
    Clinical Assessment and Outcome in 70 Patients with Complaints of Burning or Sore Mouth Symptoms
    Mayo Clin Proc 74: 223-228, 1999
           
    Diagnoses of burning mouth syndrome are frequently applied to patients with mouth pain who have normal findings on oral examination. Mouth pain may also have associations with organic and psychiatric disorders.
           
    The most common underlying process was psychiatric disease [30%], followed by xerostomia [24%] geographic tongue [24%], nutritional deficiencies [21%] and allergic contract stomatitis [13%]. Liver and kidney function was normal in all patients.
           
    The burning mouth syndrome is quite troublesome to complaining patients and is equally frustrating to most physicians and dentists who attempt to diagnose and treat it.
          
    The No.1 etiology has been that of medication side effect. A comprehensive review of all medications currently taken by the patient as well as possible drug interactions is very important.
             

  • Arons MM, for the Ibuprofen in Sepsis Study group [Vanderbilt Univ., Nashville, Tenn]
    Effects of Ibuprofen on the Physiology and Survival of Hypothermic Sepsis
    Crit Care Med  27:699-707, 1999
           
    Patients whose response to sepsis is hypothermic rather than febrile have a poor prognosis. It has been suggested that patients with hypothermic sepsis represent a clinically and biochemically distinct subgroup. This hypothesis was studied, along with the response to ibuprofen treatment in patients with hypothermic sepsis.
           
    The multicenter trial included 455 patients admitted to the ICU with severe sepsis and a known or suspected serious infection.  Patients with hypothermic sepsis were identified, and their clinical and physiologic findings were compared with those of patients with febrile sepsis. Plasma cytokines measured included tumor necrosis factor [TNF – alpha] and interleukin [IL]-6, along with the lipid mediators thromboxane B2[TxB], and prostacyclin. Hypothermic patients were randomized to receive ibuprofen [10 mg/kg IV over 30 to 60 minutes every 6 hours for 8 doses, to a maximum of 800 gm] or to receive a placebo.
            
    Ten percent of all patients with sepsis were hypothermic, with a temperature below 35.5 degrees celsius. The mortality rate was double in these patients compared to the rest [70% vs 35%], and they had significant baseline elevations of urinary TxB, metabolites, prostacyclin, and serum TNF-alpha and IL-6, compared with the febrile group.
           
    Twenty-four patients with hypothermic sepsis were assigned to ibuprofen and twenty two placebo. The 30-day morality was 54% in those receiving ibuprofen vs 90% in those on placebo. Ibuprofen treatment was also associated with a trend toward increased number of days free from major organ system failures.
            
    About ten percent of the patients with sepsis have hypothermia instead of a febrile response. Such patients have an increased mortality. Treatment with ibuprofen may reduce mortality, but prospective confirmation of these findings is needed.
            

  • Penning, H.A.J. Gielkens, M. Hemelaar, J.B.V.M. Delemarre, W.A. Bemelman, C.B.H.W. Lamers and A.A.M. Masclee [ Departments of Gastroenterology- Hepatology and Surgery, Leiden University Medical Centre, Leiden, The Netherlands]
    Prolonged Ambulatory Recording of Antroduodenal Motility in Slow-Transit Constipation

    Br. J. of  Sur.,  Volume 87, Number 2, February, 2000, Pg. 211-217
            
    Slow transit constipation may be a part of a pan-enteric motor disorder. To test this hypothesis 24 hour ambulatory antroduodenal manometry was performed and orocaecal transit time determined in patients with slow transit constipation and in healthy controls.
            
    The antroduodenal motility was recorded with a 5-channel solid-state catheter. Postprandial motility was recorded after consumption of 2 standardized test meals and interdigestive motility was recorded nocturnally. Quantitative and qualitative analysis were done. The orocaecal transit time was determined by means of lactulose hydrogen breath test.
           
    There was no difference in the motility between patients and controls. However, some minor changes of interdigestive motility were observed. The proportion of phase II activity of the nocturnal cycles of the interdigestive migrating motor complex was increased in the patients while phase I activity was decreased. The total number of phase III fronts with antral onset was decreased. Specific motor abnormalities such as retrograde propagation of phase III fronts wee more frequent in patients.
           
    They conclude that in patients with slow transit constipation, orocaecal transit time is delayed but antroduodenal motility is generally well preserved with only minor alterations.
           

  • Zazgormik J, Biesenbach G, Janko O, et al [Gen Hosp Linz.  Ausria; Univ Gdansk, Poland]
    Bilateral Nephrectomy – The Best, but often overlooked Treatment  for Refractory Hypertension in Hemodialysis patients
    AM J. Hypertens 11 : 1364-1370, 1998
            
    Mean systolic and diastolic blood pressures decreased significantly 1 month after surgery. At 12 months after surgery 9 out of 10 patients had normal blood pressure.
            
    Bilateral nephrectomy is a safe and effective treatment for refractory hypertension in patients on hemodialysis and quality of life improved too.
          

  • D.S. Walsh, P. Siritongtaworn, K. Pattanapanyasat. P. Thavichaigarn, P. Kongcharoen, N. Jiarakul, P. Tongtawe, K. Yongvanitchit, C. Komoltri, C. Dheeradhada, F.C. Pearce, W.P. Wiesmann and H.K Webster [**]
    [** Department of Immunology and Medicine, US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Departments of Surgery, Hematology and Clinical epidemiology, Siriraj Hospital, Department of Surgery, Pharmongkutklao [Royal Thai Army] Hospital, and Department of Surgery, Police Hospital, Bangkok, Thailand and Division of Surgery, Walter Reed Army Institute of Research, Washington, DC, USA ]
    Lymphocyte Activation After Non-Thermal Trauma
    Br. J. of  Sur.,  Volume 87, Number 2, February, 2000, Pg. 223-230
              
    Service injury causes immunologial changes that may contribute to a poor outcome. Longitudinal characterization of lymphocyte response patterns may provide further insight into the basis of these immunological alterations.
           
    Venous blood obtained seven times over 2 weeks from 61 patients with injury severity scores over 20 was assessed for lymphocyte and activation markers together with serum levels of interleukin [IL]2, IL-4, soluble IL-2 receptor [sIL-2R], soluble CD4 [sCD4], soluble CD8 [sCD8] and interferon
    g.
           
    Severe injury was associated with profound changes in the phenotypic and activation profile in the phenotypic and activation profile of circulating lymphocytes. Activation was indicated by increased number of T cells expressing CD25, sIL-2R and sCD4 and sCD8 were found in-patients with sepsis syndrome.
           
    Polytrauma is associated with dramatic alterations in the phenotypic and activation profile of circulating lymphocytes which are generally independent of clinical course. In contrast several lymphocyte soluble factors including sCD4 and SIL-2R, paralleled the clinical course. These data provide new insight into lymphocyte responses after injury and suggest the further assessment of soluble factors as clinical correlates.
              

  • J.E. Creighton, R. Lyall, D.I. Wilson, A. Curtis and R.M. Charnley [Hepatopancreaticobiliary  Surgery Unit, Freeman Hospital, Department of Human Genetics, Northern Region Genetics Service, Royal Victoria Infirmary, and Department of Human Genetics and Medicine, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, UK]
    Mutations of the Cationic Trypsinogen Gene in Patients with Hereditary Pancreatitis
    Br.J. of  Sur.  Volume 87, Number 2, `February 2000, Pg. 170
          
    Hereditary pancreatitis has been known to be caused by one of two mutations [ R117H and N211] of the cationic trypsinogen gene [ PRSS1]. Families with hereditary pancreatitis were investigated for these mutations.
           
    The R117H mutation was identified in three families and the N21I in further five The R117H mutation was associated with a more severe phenotype than N211 in terms of mean [s.d.]  age of onset of symptoms [8.4[7.2] versus 16.5[7.1] years; p=0.007] and requirement for surgical intervention [8 of 12 versus 4 of 17 respectively p= 0.029]. Haplotype analysis suggested that each mutation had arisen more than once.
           

  • Gu K, Cowie CC, Harris MI (Natl Inst of Diabetes and Digestive and Kidney Diseases, Bethesda, Md)
    Diabetes and Decline in Heart Disease Mortality in US Adults.
    J.a.m.a. 281: 1291-1297, 1999
            
    Methods: Patients with and without diabetes, age 35 to 74 years, were followed up prospectively for age-specific mortality rates/1000 person-years, age adjusted and stratified by cohort, diabetes status, and sex.
           
    Conclusion: the decline in mortality rates for all causes, heart disease, and ischemic heart disease is lower for patients with diabetes than for those without diabetes, particularly if they are female.
          
    Editorial comments: Despite the decrease in the mortality rate from coronary heart disease in the United States over the past 30 years, it is unclear whether patients with diabetes have followed these trends. The findings show that mortality from all causes, heart disease, and ischemic disease has decreased slightly in men with diabetes, and it has actually increased in women. One possible explanation for these findings is that patients with diabetes may have benefited less from improved medical treatment of heart disease. Moreover, the fact that mortality rates actually increased in women may suggest that women are being treated less aggressively for their diabetes than men. It should be noted, however, that this study could not differentiate between the types of diabetes and could not identify individuals with undiagnosed diabetes. Given the increasing prevalence of diabetes in the US population, it is possible that diabetes may constitute an even more important factor associated with heart disease mortality.
          

  • Carl Erik Mogensen, Steen Neldam, et al  (Department of Medicine, University Hospital, Denmark)
    Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study.
    BMJ, 9 December 2000, 321: pg.1440 – 1444
           
    The objective of the study was to assess and compare the effects of candesartan or lisinopril, or both, on blood pressure and urinary albumin excretion in patients with microalbuminuria, hypertension and type 2 diabetes.
           
    This was a prospective randomized, parallel group double-blind study in 199 patients with 4 week placebo period and 12 weeks monotherapy with candesartan or lisinopril followed by 12 weeks monotherapy or combination treatment. Candesartan dose was 16mg once daily and lisinopril dose was 20mg once daily BP and urinary albumin: creatinine ratio was measured.
            
    Conclusion of the study was that candesartan 16mg once daily is as effective as lisinopril 20mg once daily in reducing blood pressure and microalbuminuria in hypertensive patients with type 2 diabetes. Combination treatment is well tolerated and more effective in reducing BP.
           

  • Marco Pahor, Bruce M Psaty, et al (Department of Internal Medicine and Department of Public Health Sciences, USA
    Health Outcomes Associated with Calcium Antagonists compared with other First-line Antihypertensive Therapies: a Meta-Analysis of Randomised Controlled Trials.
    Lancet, vol.356, 9 December 2000, pg.1949-1954.
           
    Several randomised trials in hypertension have suggested that compared with other drugs, calcium antagonists may be associated with a higher risk of coronary events, despite similar blood pressure controls. This meta-analysis was carried out to compare the effects of calcium antagonists and other antihypertensive drugs on major cardiovascular events.
             
    Authors carried out a meta-analysis of trial in hypertension that assessed cardiovascular events and included at least 100 patients, who were randomly assigned to intermediate-acting or long-acting calcium antagonists or other antihypertensive drugs and who were followed up for at least 2 years.
            
    The conclusion of this meta-analysis was that in randomised controlled trials, calcium antagonists are inferior to other types of antihypertensive drugs as first-line agents in reducing the risks of several major complications of hypertension. On the basis of these data, the long-acting calcium antagonists cannot be recommended as first-line therapy for hypertension.
          

  • Blood pressure lowering treatment-Trialists Collaboration
    Effects of ACE inhibitors, calcium antagonists, and other blood pressure-lowering drugs: results of prospectively desgined overviews of randomised trials.
    Lancet : vol.356, December 9, 2000, p.1955-64
            
    This programme of overviews of randomised trials was established to investigate the effects of ACE inhibitors, calcium antagonists and other BP lowering drugs on mortality and major cardiovascular morbidity. Separate overviews of trials comparing active treatment regimens with placebo, trials comparing more intensive and less intensive BP lowering strategies, and trials comparing treatment regimens based on different drug classes were done.
           
    The interpretation is that there was strong evidence of benefits of ACE inhibitors and calcium antagonists as compared to placebo. There is weaker evidence of differences between treatment regimens of differing intensities and of differences between treatment regimens based on different drug classes.
            
    Commentary: Selection of initial anti-hypertensive drug therapy.
            
    The study done by Blood Pressure Lowering Treatment (BPLT) Trialist’s Collaboration (BPLT) has several methodological strengths.  The effect of ACE inhibitors on cardiovascular disease was impressive and was achieved in the context of small difference in BP (3/1 mm Hg) between ACE inhibitor and placebo groups. This finding raises the possibility that the beneficial effects of ACE inhibitors on cardiovascular disease in the trials were mediated not just through the lowering of BP.
           
    There has been intensive debate over the balance between the potentially beneficial and detrimental effects of calcium antagonists in cardiovascular disease. Overall, the data of BPLT provide evidence that calcium antagonists reduce the incidence and mortality from cardiovascular disease.
           
    The meta-analysis of Marco Pahor and colleagues focussed specially on comparison of calcium antagonists, with diuretics, beta-blockers, ACE inhibitors or clonidine.
           
    (1)   Diuretics or beta-blockers may be used initially for uncomplicated hypertension.
       
    (2)    ACE inhibitors – initial choice especially in patients at high risk of heart failure.
       
    (3)   Caution- for use of calcium antagonists as initial therapy in populations at high risk of CHD and heart failure
           (i.e. Western populations).
       
    (4)   Calcium antagonists – may be used as initial therapy in patients at high-risk of stroke and low risk of CDH
           (i.e. Asian population).
       
    (5)   If more than one drug needs to be used – combination of diuretics, beta-blockers, ACE inhibitors or calcium
           antagonists, based on patient’s absolute level of risk for cause-specific cardiovascular disease.
                    

  • Gill Spyer, Andrew T Hattersley, et al (Department of Vascular Medicine and Diabetes Research, London)
    Hypoglycaemic counter-regulation at normal blood glucose concentrations in patients with well controlled type-2 diabetes.
    Lancet 356, December 9, 2000, pg. 1970-74.
          
    Intensive treatment to achieve good glycaemic control in diabetic patients is limited by a high frequency of hypoglycaemia. The glucose concentrations at which symptoms and release of counter-regulatory hormones takes place have not been studied in patients with well controlled type-2 diabetes.
          
    The findings were that symptom response took place at higher whole blood glucose concentrations in diabetic patients than in controls.
           
    Glucose thresholds for counter-regulatory hormone secretion are altered in well controlled type-2 diabetic patients, so that both symptoms and counter-regulatory hormone release can take place at normal glucose values. This effect might protect type-2 diabetic patients against episodes of profound hypoglycaemia and make the achievement of normoglycaemia more challenging in clinical practice.
           

  • Abi Berger,
    Gut cells engineered to produce insulin
    BMJ, 16 December 2000, pg.1488
           
    Engineering non-pancreatic cells to produce insulin in response to a glucose load may one day be a successful approach in the treatment of diabetes. Canadian scientists have now shown that cells other than pancreatic cells can be induced to secrete appropriate levels of insulin in response to eating.
            
    Previous attempts at gene therapy have concentrated on manipulation of liver cells, but hepatocytes do not have the ability to store hormones.
           
    Dr. Cheung (Dept. of Medicine, Univ. of Alberta, Canada) and his team have shown that mice can be genetically engineered to produce human insulin from K cells located in the duodenum. K cells usually produce glucose dependent insulinotropic polypeptide (GIP), so they have an advantage over hepatocytes in that they are already glucose responsive endocrine cells and have the correct equipment to be able to store hormones.
           
    Dr. Cheung showed that when K cells are genetically engineered to produce insulin, normal glucose tolerance could be achieved in animals that have had their own pancreatic beta cells ablated.
            

  • Vera Peuckmann, Michael Fisch and Eduardo Bruera (Dept. of Pharmacology, Univ. of Alberta, Edmonton, Alberta, Canada)
    Potential Novel Uses of Thalidomide – Focus on Palliative Care
    Drugs, Aug. 2000, 60(2), 273-292
           
    Thalidomide was banned in the early 1960s because of teratogenesis. It is being rediscovered because of its multiple therapeutic effects in serious diseases. It has anxiolytic, mild hypnotic, anti-emetic and adjuvant analgesic properties. It is highly effective in erythema nodosum leprosum (cutaneous manifestations of leprosy) and superior to aspirin in controlling leprosy associated fever. Promising results are seen in cancer cachexia and weight-loss in HIV infection. Its use is being explored in a variety of diseases such as tuberculosis, aphthous ulcers in HIV syndrome and Behcet’s disease, rheumatoid arthritis, multiple myeloma, inflammatory bowel disease, lupus erythematosus, Sjogren’s syndrome and a variety of solid tumours. In advanced cancer, it is effective in treating chronic nausea, insomnia, profuse sweating and pain. Hence, it is attractive for use in palliative care.
            
    The mechanism of action is probably based on suppression of tumour necrosis factor  µ (TNF-µ) and modulation of interleukins.
            

  • James Y.W.Lau, Joseph J.Y. Sung et al (Dept. of  Surgery, China)
    Effect of Intravenous Omeprazole on Recurrent Bleeding After Endoscopic Treatment of Bleeding Peptic Ulcers.
    New Eng J Med. August 3, 2000, Vol.343(5), pg.310-316.
            
    After endoscopic treatment of bleeding peptic ulcers, bleeding recurs in 15-20% of patients.  Authors assessed whether the use of a high-dose of a proton pump inhibitor would reduce the frequency of recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. Patients with actively bleeding ulcers or ulcers with nonbleeding visible vessels were treated with an epinephrine injection followed by thermocoagulation. After haemostasis was achieved, the 240 patients, were randomly assigned in a double-blind fashion to receive omeprazole (given as a bolus IV injection of 80mg followed by an infusion of 8mg/hr for 72 hrs) or placebo. After infusion, all patients were given 20mg of omeprazole orally daily for 8 weeks. The primary end-point was recurrent bleeding within 30 days after endoscopy.
           
    The conclusion of the study was, after endoscopic treatment of bleeding peptic ulcers, a high-dose infusion of omeprazole substantially reduces the risk of recurrent bleeding.
           
    Editorial – Eric D. Libby
           
    Why does omeprazole prevent recurrent bleeding when H2 receptor antagonists do not ? Perhaps its beneficial effect results from protecting the clot rather than healing the ulcer.
           

  • Harvey D White, R John Simes, et al (Dept of  Medicine, Univ of Auckland, New Zealand)
    Pravastatin Therapy and the Risk of Stroke
    New Eng J Med. August 3, 2000, pg. 317-326.
           
    Several epidemiological studies have concluded that there is no relation between total cholesterol levels and the risk of stroke.  In some studies that classified strokes, according to cause, there was an association between increasing cholesterol levels and the risk of ischaemic stroke and a possible association between low cholesterol levels and the risk of haemorrhagic stroke.  Recent reviews of trials of HMG-CoA reductase inhibitors have suggested that these agents may reduce the risk of stroke.
           
    In this double-blind trial of pravastatin, it had a moderate effect in reducing the risk of stroke from any cause and the risk of nonhaemorrhagic stroke in patients with previous MI or unstable angina.
          

  • The ESPRIT investigators
    Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a  randomised placebo-controlled trial.
    Lancet, vol.356, Dec.16, 2000, pg. 2037-2044
            
    The platelet glycoprotein Iib/IIIa inhibitors, although effective in reducing ischaemic complications of percutaneous coronary intervention, are used in few coronary stent implantation procedures. ESPRIT is a randomized placebo-controlled trial to assess whether a novel, double-bolus dose of eptifibatide could improve outcomes of patients undergoing coronary stenting.
           
    Authors recruited 2064 patients undergoing stent implantation – they were randomly allocated to receive eptifibatide, given as two 180 mg/kg boluses 10min. apart and a continuous infusion of 2 mg/kg/min for 18-24 hrs. or placebo, in addition to aspirin, heparin and a thienopyridine.
           
    It was observed that routine glycoprotein IIb/IIIa inhibitor pretreatment with eptifibatide substantially reduces ischaemic complications in coronary stent intervention and is better than a strategy of reserving treatment to the bailout situation.
            

  • Ian B Wilman, David J Webb, Chritison et al (Dept of Cardiology, Univ Wales College of Medicine, UK)
    Isolated systolic hypertension: a radical rethink.
    BMJ No.7251, June 24, 2000,pg.1685.
           
    The association between hypertension and a ‘hardening’ of the pulse and apoplexy has been recognised for hundreds of years.  Isolated systolic hypertension affects around half of people aged over 60 years. It confers a substantial cardiovascular risk.  Despite this, it remains underdiagnosed, and largely untreated, but the benefits of treatment are established.
           
    The relative risk reduction of cardiovascular events in elderly people with isolated systolic hypertension is similar to that in younger people. However, as elderly people are at much higher absolute risk of such events, they stand to benefit more from treatment than younger people. Elderly people tolerate antihypertensive drugs with few side effects.
          
    The latest WHO and International Society for hypertension guidelines for management of hypertension emphasise the importance of arterial stiffness and pulse pressure as predictors of cardiovascular risk and call for further indices of arterial stiffness.
            

  • Christopher D Byrne and Sarah H Wild (Univ of Southampton, School of Medicine, UK)
    Diabetes care needs evidence based interventions to reduce risk of vascular disease.
    BMJ, Vol.320, 10 June 2000, 1554-5
            
    The absolute risk of a first myocardial infarction is influenced by factors that include age, sex, blood pressure, total concentration of high-density lipoproteins, the cholesterol ratio and diabetes.
           
    The results of UK prospective diabetes study provide evidence that tight control of blood glucose reduces the risk of myocardial infarction but not of stroke. Tight control of blood pressure reduced the risk of ischaemic stroke but had little impact on risk of myocardial infarction.  When combined with the evidence from the hypertension optimal treatment trial, a target blood pressure of 130/80 and an HbAtc value of £7% seem to be desirable among diabetes patients in whom the absolute risk of myocardial infarction is >3% per year.
           
    Evidence from large randomised trials shows that treating people with statins reduces relative risk of myocardial infarction by about 30%. Decisions to treat patients with statins should not be based solely on concentrations of total cholesteroal or LDL cholesterol but on a person’s absolute risk of a vascular event. This is relevant with people with type-2 diabetes, because primary lipid abnormality involves metabolism of triglycerides and high density lipoproteins, and plasma concentration of cholesterol may be normal.
           
    As regards fibrates, a secondary prevention trial, showed a 25% reduction in the risk of vascular events in men with diabetes who were treated with gemfibrozil.
           
    A further, potentially important intervention to reduce cardiovascular risk among people with diabetes, was the use of an angiotensin converting enzyme (ACE) inhibitors. Ramipril 10mg as compared to placebo reduced the risk of stroke by 33% and myocardial infarction by 22%. It is highly unlikely that this benefit was due to reduction in blood pressure because mean reductions systolic/diastolic were 2/3mm Hg in the ramipril group and 1/2mm Hg in the placebo group.
          
    People with type 2 diabetes have a markedly increased risk of myocardial infarction and stroke. Emphasis should be on treating people with therapies of proven benefit.
          

  • Stuart J Connolly.
    Anticoagulation for patients with atrial fibrillation and risk factors for stroke.
    BMJ, Vol.320, 6 May 2000, p.1219-20.
          
    The most clinically relevant advance in the management of cardiac arrhythmia in the pas two decades has been that anticoagulant treatment substantially reduces risk of stroke in patients with atrial fibrillation. A meta-analysis of trials shows that the risk is reduced by two-thirds.
           
    Major risk factors for stroke are age over 75, previous stroke or transient ischaemic attack, hypertension, mitral stenosis, and left ventricular dysfunction. Patients with atrial fibrillation and any of these factors face a higher than average risk (5-15% per year) of a stroke.
             
    Randomized trials evaluating aspirin, low fixed-dose warfarin and their combination clearly show the superiority of warfarin. On the basis of this strong evidence expert panels recommend that all patients with atrial fibrillation should be considered for treatment with anticoagulants and if any major risk factors are present their treatment should aim to keep the international normalised ratio between 2.0 and 3.0.
          

  • Peter D Inskip, Robert E Tarone, et al.
    Cellular Telephone Use and Brain Tumors.
    NEJM, Vol.344(2), Jan.11, 2001,p.79-86
          
    There is concern that the use of hand-held cellular telephones might cause brain tumours. If such a risk does exist, the matter would be of considerable public health importance, given the rapid increase worldwide in the use of these devices.
          
    Authors examined use of cellular telephones in a case-control study of intracranial tumours conducted between 1994 and 1998.  The data do not support the hypothesis that the recent use of hand-held cellular telephones causes brain tumours, but they are not sufficient to evaluate the risks among long-term heavy users and for potentially long induction periods.
          

  • Editorials
    Cristina Elisabetta Mapp.
    Inhaled Glucocorticoids in Chronic Obstructive Pulmonary Disease.
    NEJM, Vol.343 (26), December 28, 2000, pg.1960.
            
    Chronic obstructive pulmonary disease (COPD) is caused by at least 3 distinct pathologic processes that may occur separately or concurrently (chronic bronchitis, destruction of alveolar cells which causes emphysema and chronic asthma).
           
    In this issue, the Lung Health Study Group reports the result of inhaled traimcinolone (600 mg twice daily) during a mean follow-up period of 40 months. The lack of effect on pulmonary function is consistent with previous findings. In Three other recently published trials also had similar results. In fact, the cessation of smoking is the only intervention that effectively slows the decline in pulmonary function in such patients.
           
    Thus, the potential benefits of inhaled glucocorticoids in patients with moderate to severe COPD are improvemnets in clinical outcomes that could be important to patients. On the basis of the results of the four long-term clinical trials reported to date, inhaled glucocorticoids can be recommended for the treatment of symptomatic patients with moderate to severe COPD and for patients with frequent exacerbations but not for patients with mild COPD. Efficacy of side-effects of budesonide, fluticasone and triamcinolone, were similar, except that only triamcinolone had deleterious effects on the skeleton.
                 

  • Andrew J Krentz, Clifford J Bailey et al
    Thiazolidinediones for type 2 diabetes
    New agents reduce insulin resistance but need long term clinical trials
    BMJ, Vol.321, July 29, 2000, pg. 252-253
            
    Insulin resistance (reduced action of insulin) is a prominent defect in type 2 diabetes. Before the introduction of troglitazone in 1997 metformin was the only drug able to sensitize target tissues to insulin. Troglitazone is superseded by more potent agents, rosiglitazone and pioglitazone. 
           
    Patients with insulin resistance have elevated serum TG and low HDL. This dyslipidemia contributes to risk of atherosclerotic cardiovascular disease. Thiazolidonediones increase HDL and rosiglitazone protects against endothelial dysfunction, lowers BP in insulin resistant and hypertensive rats.
           
    Clinical trials show that combination therapy using a thiazolidinedione with metformin (main action of which is to reduce glucose production by liver) or a sulphonylurea is particularly effective in lowering glucose concentrations.
           
    Extensive use of rosiglitazone and pioglitazone has produced little evidence that it has caused hepatic impairment. They are contraindicated in patients with liver damage. Cardiac failure is a contraindication and patients with reduced cardiac reserve need close monitoring. Pioglitazone induces cytochrome P450 (isoform CYP3A4) and the possibility of drug interactions e.g. with oral contraceptives.
            

  • Irene M Stratton, Amanda I Adler, et al 
    Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.
    BMJ, Vol.321, Aug.12, 2000, pg.405-412.
           
    The objective of the study was to determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complication in patients with type 2 diabetes. It was carried out in 4585 Asian Indian, white and Afro-Caribbean UKPDS (UK prospective diabetes study) patients. Incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbAtc was associated with reductions of risk of 21% for any end-point related to diabetes. The lowest risk being in those with HbAtc values in the normal range (<60%).
           

  • Amanda I Adler, Irene M Stratton, et al 
    Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study.
    BMJ, Vol.321, Aug.12, 2000, pg.412-419.
           
    The objective of the study was to determine the relation between systolic BP over time and the risk of macrovascular and microvascular complications in patients with type 2 diabetes.
           
    The incidence of clinical complications was significantly associated with systolic BP except for cataract extraction. Each 10 mm Hg decrease in updated mean systolic BP was associated with reductions in risk of 12% for any complication related to diabetes. No threshold of risk was observed for any endpoint.
           
    The conclusion was that in patients with type 2 diabetes the risk of diabetic complications was strongly associated with raised BP. Any reduction in BP is likely to reduce the risk of complications with the lowest risk being in those with systolic BP less than 120mm Hg.
             

  • Editorial – Jaakko Tuomilehto
    Controlling glucose and blood pressure in type 2 diabetes. 
    Starting treatment earlier may reduce complications.
    BMJ. Vol.321, Aug.12, 2000, pg.394-395.
           
    The main questions have been when should we start treatment, what is the target level during treatment and what is the best method of treatment, since there are no obvious cut-off points for B.P. or glucose or cholesterol concentrations that would guide clinical decisions.
           
    Comparisons with observational data have shown that antihypertensive drugs reduce the risk of stroke as predicted, but the reduction in the risk of myocardial infarction is less than expected. Treatment of hypercholesterolaemia with statins reduces the risk of myocardial infarction as predicted, whereas the effect on the risk of stroke seems larger than expected.
          
    The results of UKPDS studies reveal that patients with type 2 diabetes whose hypertension is tightly controlled reduce their risk of macrovascular complications to a greater extent than estimated. The data clearly show that there are no natural thresholds under which the risk of microvascular and macrovascular complications in diabetes are fully prevented but the risk increases steadily with rising levels of risk factors. The lower the level of blood glucose, HbAtcc, or BP, the lower the risk of complications.
           
    It is difficult to maintain reductions in glucose concentrations and BP even when using multiple drugs that in short term trials have produced excellent results. This was also confirmed in the UKPDS. Thus, the alternative possibility would be to start treatment at lower levels than those currently used as thresholds.
          
    A large European epidemiological study showed that postprandial glucose concentration is a better predictor of mortality than is fasting glucose. Perhaps impaired glucose tolerance should be an indication for treatment. There is a need to carry out controlled clinical trials to find out whether lowering glucose concentrations at the levels of impaired glucose tolerance will reduce microvascular and macrovascular complications.
         

  • Editorial – E Ernst
    Herbal medicines: where is the evidence ? 
    Growing evidence of effectiveness is counter balanced by inadequate regulation.
    BMJ, Vol.321, Aug.12, 2000, pg.395-396.
           
    Sales of herbal medicines are booming. Fastest growth is for St. John’s wort, a herbal antidepressant. In a meta-analysis of 23 randomized trials with mild to moderate depression, the authors concluded that extracts of hypericum were significantly more effective than placebo and as effective as conventional antidepressants.
          
    Controlled trials of ginkgo biloba for dementia showed that ginkgo was more effective than placebo. A meta-analysis showed palmetto as a symptomatic treatment for benign prostatic hyperplasia. It improved urological symptoms and flow measures significantly more than placebo. Saw palmetto was as effective as finasteride and had fewer adverse effects. A systematic review of horse chestnut seed extracts for chronic venous insufficiency indicated equivalence with other active therapies.
           
    Even though herbal remedies may be effective, do their benefits outweigh the risks ? Most herbal remedies in UK and USA are sold as food supplements. Thus, they evade regulation of their quality and safety. Two British cases of severe nephropathy caused by Chinese herbal tea administered to treat eczema illustrate this. Huge variations exist in the quality of herbal medicinal preparations.
           
    A recent study of herbal creams in UK showed that 8 of 11 preparations contained undeclared dexamethasone.
           
    The possibility of herb-drug interactions is a further important issue. Ginseng, on its own, has few serious adverse effects. When combined with warfarin, its antiplatelet activity might cause over anticoagulation.
            
    There is need for reliable information on herbal medicines, and should be met by undergraduate and postgraduate education. Detailed questions about use of herbal drugs should form a part of taking medical history.
          

  • Deborah Josefson
    Statins may reduce risk of Alzheimer’s disease
    BMJ, Vol.321, October 28, 2000, pg. 1040.
            
    Patients taking the statin class of cholesterol lowering drugs may also reduce their risk of developing Alzheimer’s disease according to a study reported in the Archives of Neurology 2000. The researchers focused on 3 statins- lovastatin, pravastatin and simvastatin. They reported that patients receiving lovastatin or pravastatin (but not simvastation) had a 70% lower prevalence of Alzheimer’s disease than a control group, comprising the entire patient population aged 60 and older
          

  • Mark B Pepys (Dept. of Medicine, London)
    The renaissance of C reactive protein
    BMJ 7277, 6TH Jan.2001, pg.4
         
    Creactive protein (CRP) has been traditionally used as an acute phase marker in tissue injury, infection and inflammation. However, now estimation of C reactive protein has become very accurate. Although C reactive protein response has no diagnostic specificity, serial measurements can be helpful in clinical management. In this respect it resembles ESR.
         
    Increased C reactive protein can predict coronary events in both stable and unstable angina. The level of C reactive protein in atherosclerotic plaques is very high.
          

  • Kelly Moriss
    Macrodoctor, come meet the manodoctors
    Lancet, vol. 357, march 10, 2000, p.778
          
    In the 1996 film Fantastic Voyage, a mini-submarine of medics travels from vein to brain to laser a clot. The scenario remains science fiction, but emerging field of nanomedicine may make it a science fact.
         
    Billions of minute, self-assembling, computerised bioelectromechanical systems ‘nanobots’ swarming to the injury site, sensing, diagnosing and activating therapeutic systems and cellular repair is envisaged. Nanobots may be one day made with molecular nanotechnology.
          
    The team at Cornell University used tiny nickel nanopropellors to link with ATPase and is investigating ways to turn light energy into ATP, generating recyclable fuel that would render such devices autonomous.
          
    Tree-like polymers called dendrimers could deliver gene therapy or intracranial implants without eliciting immune response.
          
    Tejal Desai (Univ. of Chicago) has developed silicone based microcapsules with nanopores to deliver cells, drugs, proteins, peptides and nucleic acids. Similar type capsules may travel through bloodstream and release their contents at desired locations based on binding to cell-specific receptors.
           
    PEBBLES are probes encapsulated by biological, localised embedding-nanospheres 20-200 nm wide, delivered into cells with 99% viability, via liposomes, a gene gun, or even macrophage ingestion. An individual PEBBLE can measure pH, oxygen, electrolytes, nitric oxide or early changes of apoptosis.
            
    Lethal ‘nanobots’ do not sound comfortable, but safety requirements will be built into systems.
           
    The problem is whether we want to make nanorobotics a reality. An injection of nanorobots could completely clear a stroke clot in a time that is in the order of one blood circulations time. Such treatment needs to prove itself superior to thrombolysis.
          
    Eric Drexler (Chairman of ‘Foresight’) predicts that nanomedicine will dominate medocal technology research for at least half this century.
           

  • Geoffrey Pasvol
    Targetting voracious appetite of malaria-infected red-blood cell.
    Lancet, vol.357, Feb.10,2001, pg. 408-409
           
    The malarial parasite needs nutrients and ions to satisfy its voracious appetite and rid itself of metabolites – these have to cross 3 membranes (parasite plasma membrane, parasitophorous vacuolar membrane and red-cell membrane). Channels exist in these membrances.
           
    Sanjay desai and colleagues have used patch-clamp technique on single RBC and describe a versatile channel. Infected RBCs had voltage-dependent currents that were 150 times bigger than uninfected RBCs. These currents were anionic and sensitive to chloride over the cation sodium. There is as yet no convincing electronmicrographic evidence for such a duct. Such identification of specific inhibitors of the channel might lead to new antimalarial drugs.
          
    The concentrations of drugs used in Desai’s studies are not necessarily in the therapeutic range and could be toxic, but the possibility of adjunctive therapy exists. Bioavailability, pharmacokinetic/pharmacodynamic issues also need to be considered because inhibition of the channel is reversible and long exposure to a channel-blocker might be required for parasite killing.
           
    Furthermore, because severe malaria may be accompanied by dehydration and hypoglycaemia, administration of a diuretic and/or a hypoglycaemic drug could be risky but this is a novel approach to the treatment of this deadly disease.
            

  • Kujala UM, Kaprio J, Sarna S, et al [ Inst of Biomedicine, Helsinki; Univ of Helsinki; Univ of Turku, Finland]
    Relationship of Leisure-Time Physical Activity and Mortality : The Finish Twin Cohort
    JAMA 279: 440-444, 1998
           
    Premature mortality may be reduced by high physical activity or fitness. High levels of physical activity or fitness may be achieved by genetic selection or early childhood experiences and favor the individual with longevity. Further clarification is needed regarding the relative importance of factors over which the individual has little or no control, such as sex, intrauterine and childhood environment, and family history, compared with factors that can be modified, such as diet, smoking, and physical activity. Distinguishing between physical activity and genetic and other familial factors can be clarified by studies of twins, who share some or all of the same genes and nearly always the same childhood environment. Leisure physical activity as a predisposing or preventive factor for premature mortality was investigated in a cohort of twins. A Questionnaire on physical activity and known predictors of premature mortality was filled out by 7925 healthy males and 7977 healthy females aged 25 to 64 years. Among the entire cohort, 1253 died, representing a hazard ratio for death, adjusted for age and sex, of 0.71 in occasional exercisers and 0.57 in conditioning exercisers, compared with those who were sedentary. The odds ratio for death was 0.66 in occasional exercisers and 0.44 in conditioning exercisers, compared with those who were sedentary, among the twin pairs who were healthy at baseline and discordant for death. After controlling for other predictors of mortality, the beneficial effects of physical activity remained.
           
    Even after genetic and other familial factors are taken into account, leisure-time physical activity is associated with reduced mortality.
          

  • Gerard Bodeker
    Lessons on integration from the developing world’s experience.
    BMJ, Jan.20, 2001, pg.164
           
    About half the population in industrialised countries regularly use complementary medicine.
          
    This article deals with considerations by the Common-wealth working group on Traditional and Complementary Health systems. Models adopted in China, India, Malaysia and Africa are dealt with.
          
    In India, a model was adopted through the Indian Medicine Central Council Medicine Act of 1970. The council was established to oversee the development of Indian systems of medicine and to ensure good standards of training and practice.
           
    Thirty-years on the Dept. of Indian systems of Medicine has expressed concern over the substandard quality of education in many colleges, which in the name of integration have produced hybrid curriculums and graduates unacceptable to either modern or traditional standards. The department has made it a priority to upgrade training in Indian systems of medicine.
           
    The government is adding 10 traditional medicines into its family welfare programme, funded by the World Bank and the Indian government. Medicines are for anaemia, oedema during pregnancy, postpartum problems, such as pain, uterine and abdominal complications, difficulties with lactation, nutritional deficiencies and childhood diarrhoea.
            
    New regulations were introduced in July 2000 to improve Indian herbal medicines by establishing standard manufacturing practices and quality control. 
           
    Randomised controlled clinical trials of selected prescriptions for Indian systems of medicine have been initiated. These will document the safety and efficacy of the prescriptions and provide the basis for their international licensure as medicines rather than simply as food supplement.
            

  • Ranjit Roy Chaudhury
    Commentary – Challenges in using traditional systems of medicien.
    BMJ. Jan.20, 2001, pg.167
          
    Integration of modern and traditional systems of medicine may result in loss of some of the basic concepts of the traditional systems of medicine. Purists in the traditional systems of medicine such as Ayurveda and Unani in India oppose this trend to ‘modernise’ their systems, particularly when such integration is carried out by experts in allopathy. They have no objection to the use of modern concepts of the methodology of clinical trials in evaluating the efficacy and side-effects of herbal preparations. Such clinical evaluation is essential to use these remedies in allopathic hospitals.
           
    However, carrying out randomised, double-blind, multicentred trials with standardised extracts is a slow and laborious process. Not all herbal medicines need to undergo vigorous trial because these preparations are already in use. The situation is complicated further because randomised trial may not be very appropriate for evaluation of medicines from traditional systems. Where Prakriti (Ayurveda) or Mijaj (Unani) of individual, determines specific therapy to be used.
          
    In the past 12 years, the Indian Council of Medical Research (ICMR) has set up a network for carrying out clinical trials of herbal medicines. Using this network, the council has shown the efficacy of several traditional medicines, including Picrorhiza kurroa in hepatitis and Pterocarpus marsupium in diabetes. As a result of these trials, these traditional medicines can be used in allopathic hospitals.
          
    The regulation of traditional systems of medicine, the products used in these systems, and the practitioners of these systems are weak in most countries. This leads to misuse of the medicines by unqualified practitioners and loss in the credibility of the system. WHO has initiated an effort in this direction and may be the appropriate body to help countries to develop a regulatory system and take steps to meet the obligations under Trade Related Intellectual Property Rights Agreement when these become applicable in the developing countries around 2005.
          

  • Martin Riedel (Germany)
    Editorial – Emergency diagnosis of pulmonary embolism
    Heart June 2001, vol.85: 607-609
          
    Emergency diagnosis of pulmonary embolism is the first prerequisite of saving the life of the patient. CT has emerged as a very valuable tool. It is both widely available and results are almost as good as angiography.
           
    Transthoracic echocardiography (TTE) is also widely available. It is non-invasive and very accurate in diagnosis of floating emboli. Transesophageal echocardiography (TOE) is perhaps even superior to TTE. It visualizes the proximal pulmonary arteries. When pulmonary embolism is suspected, TTA followed by TOE and CT gives very specific and precise diagnosis to enable surgery if indicated.
          

  • Tim Coleman and Robert West
    Editorial – Newly available treatments for nicotine addiction.
    BMJ, Vol.322, 5 May 2001, pg.1076-1077
           
    Nicotine addiction is recognised as a life-threatening but treatable disorder. Britain now has a treatment strategy for nicotine addiction, which includes provision of bupropion on prescription and the introduction of specialist smoking cessation services to provide behavioural support to people who want to stop smoking.
          
    Nicotine replacement therapy used alone can be effective, but better results are achieved when it is combined with behavioural support and counselling from a trained health professional. More intensive support seems to be more effective. Bupropion has not yet been tested without intensive behavioural support, so it is difficult to know whether it can be effective without this. The sustained one year abstinence rates achieved in the published trials of bupropion average about 20%. Nicotine replacement therapy is generally well tolerated and most side-effects arise from irritant effect of nicotine (such as rashes with nicotine patches). 
         
    Bupropion can cause seizures in about 1 in 1000 users (experience from US users) and UK initial figures are consistent with this. Most common side-effects are insomnia and dry mouth. Nicotine replacement therapy and bupropion are suitable only for heavier smokers (10-15 a day or more) who clearly want to stop and are ready to try.
          

  • A Fagot-Campagna, K.M.Venkat Narayan et al
    Type 2 diabetes in children
    BMJ, Vol.322, Feb.17,2001, pg.37-378
          
    Type 2 diabetes in children is being reported from USA, Canada, Japan, Hong-Kong, Australia, New Zealand, Libya and Bangladesh. Prevalence ranges from 4.1 per 1000 in US to 50.9 per 1000 in Pima Indians of Arizona.
           
    At diagnosis, the affected child may present with weight loss, ketosis and acidosis. Insulin and C-peptide levels are often raised and antibodies absent, which may help differentiate type I from type 2 diabetes, but insulin secretion may be blunted at diagnosis. Patients may have hypertension, hypertriglyceridemia, albuminuria, sleep apnoea and depression. Treatment varies considerably and several drugs used for glycaemia, blood pressure and lipid control are not approved for use in children.
           
    To respond to this emerging problem, we need to develop case definitions in children. Safety and efficacy of therapies used in adults is known but same information is not available for children. Also needed are well co-ordinated, multi-centre trials testing the feasibility of multiple risk factor reduction in children and its benefits for practical health outcomes, such as the early stages of vascular disease.
           

  • Thorkild IA Sorensen
    Obesity genes
    BMJ, Vol.322, 17 March 2001, p.630-631
           
    Obesity is influenced by environmental factors and by genetics. That obesity runs in families is an old observation. The pattern of inheritance suggests that the effect is polygenic, with each variant of many different genes making a small difference in effect. As a phenotype obesity is also heterogeneous and there are 2 distinct but frequently overlapping subtypes: general obesity and abdominal obesity. These subtypes have different physiological, clinical and prognostic implications. The phenotypes seem to have some of the same genetic and environmental influences in common.
          
    Since the identification of the leptin gene, many other single genes have also been investigated as candidates for causing obesity, and the entire genome has been scanned for loci associated with obesity. A few genes have been found to cause monogenic forms of obesity in humans.
          
    One way forward may be to conduct controlled human experiments by manipulating environmental factors that are assumed to be pertinent, such as fat intake. Its effect on both gene expression and the function of gene products in people with different genetic variants may elucidate which genes contribute to common obesity.
           

  • Roland Rosmond, Claude Bouchard, et al 
    Tsp5091 polymorphism in exon 2 of the glucocorticoid receptor gene in relation to obesity and cortisol secretion: cohort study.
    BMJ, Vol.322, 17 March 2001, p.652-653
          
    Chronically elevated cortisol levels can increase body fat, as seen in Cushing’s syndrome. Subjects with abdominal obesity share many of the hormonal, metabolic and circulatory characteristics of people with Cushing’s syndrome. A dysfunctional glucocorticoid receptor may add to the adverse health effects of excessive cortisol concentrations.
            
    An Asn363Ser polymorphism in exon 2 of the glucocorticoid receptor gene (GRL) might be associated with overweight and an increased sensitivity to exogenous glucocorticoids. Authors examined whether this variant was associated with altered sensitivity to glucocorticoids as well as obesity with its related metabolic and haemodynamic abnormalities in a cohort of Swedish men.
          
    It was concluded that GRL has several different polymorphisms and mutations, but that few of these are consistently associated with obesity and subtle physiological alterations in the hypothalamic-pituitary adrenal axis regulating cortisol secretion. The Asn363Ser polymorphism does not seem to be one of the variants associated with such changes.
           

  • Ann Ekberg – Jansson, Sven Larsson et al
    Editorial – Preventing exacerbations of chronic bronchitis and COPD.
    BMJ, 26 May, 2001; pg.1259-1260.
           
    Exacerbations of COPD affect quality of life and cost of managing the disease. Recent data show good correlation between hypersecretion and long-term deterioration of ventilatory function in these patients. This is why mucolytics may influence disease progression in COPD.
           
    Cochrane review reports a meta-analysis of 22 studies of 10 drugs. Treated patients showed a significant reduction over controls in the number of exacerbations and number of days each exacerbation lasted. No difference in lung function or in adverse effects was seen.
          
    Drug contributing most to the beneficial effects seems to be acetylcysteine -possibly by antioxidative effect. Ambroxol also reduces exacerbations – due to mucolytic effect and antioxidative effects. It is also a secretagogue for surfactant (this has antibacterial properties).
           
    Orally administered bacterial lysates that stimulate immune system have been used for several years. OM 85 BV, a lysate of 8 pulmonary pathogens has been evaluated in a meta-analysis.
          
    The present Cochrane report, together with that on oral vaccination with whole killed H.influenzae and the meta-analysis treatment with OM85 BV indicates that different therapeutic regimes might prevent exacerbations of chronic bronchitis and COPD.
            

 

 

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