Shaari CM, Farber D, Brandwein MS, et al (Mount Sinai School of Medicine, New York; City Univ of New York)
Characterizing the Antigenic Profile of the Human Trachea: Implications for Tracheal Transplantation
Head Neck 20: 522-527, 1998.
This study of 10 human tracheal wall detects Class I (Human leukocyte Antigens A,B and C) and Class II (human leukocyte antigen DR) histocompatibility antigens.
Different areas of the trachea have greatly different antigenicity. Minor salivary glands in the wall are highly antigenic. Antigenicity of the perichondrium varies. Mucopolysaccharide matrix is nonantigenic but the chondrocytes have antigenic properties. These differences in antigenicity indicate that some tracheal grafts would be more immunogenic than others and therefore more prone to rejection.
This article forms an important foundation upon which tracheal transplantation is an exciting possibility, if all the hurdles are overcome. R.A. Otto.
EI Hachem M, Bernardi S, Pianosi G, et al [ Bambino Gesu Children’s Hosp and Health Research Inst, Rome
Mucocutaneous Manifestations in Children With HIV Infection and AIDS
Pediatr Dermatol 15: 429-434, 1998
In a 5 year period with a follow-up of 31 months [average], 166 HIV positive children in an average age group of 14.8 months, were taken for study. Of these, 81 children became HIV negative spontaneously indicating lack of infection. Of the remaining 85 HIV-positive children, 76 revealed a minimum of 1 skin effect. These comprised infestations, infections, and inflammatory diseases. They increased as the immune depletion progressed. Despite tumour rarity in children Kaposi sarcoma was diagnosed in one child.
This article highlights the importance of seroreversal in infants, rare occurrence of tumours in childhood HIV infection and reports a single possible Kaposi sarcoma. Candidosis topped all other infections.
Boden D, Hurley A, Zhang L, et al [ Rockefeller Univ, New York; AIDS Healthcare Found,
Los Angeles; ViroLogic Inc, South San Francisco]
HIV-1 Drug Resistance in Newly Infected Individuals
JAMA 282: 1135-1141, 1999
Long term use of antiretroviral drugs as expected would induce resistance in the virus. 80 newly infected subjects were studied. Drug resistance was observed in 13, 10 to a nucleoside reverse transcriptase inhibitor [NRTI] 2 to a protease inhibitor and 6 to a non-NRTI. Three were multidrug resistant.
Despite good effects in reducing morbidity of the disease, a serious problem as has occurred in the management of other bacterial diseases, should be anticipated.
Little SJ, Daar ES, D’Acquila RT, et al [ Univ of California, San Diego; Univ of California, Los Angeles; Massachusetts Gen Hosp, Boston; et al]
Reduced Antiretroviral Drug Susceptibility Among Patients with Primary HIV Infection
JAMA 282: 1142-1149, 1999
It is not known how often HIV resistant to one or more antiretroviral [ARV] drugs causes new infections.
Acute and early infections in subjects were studied between the years 1989 and 1998. Plasma samples were taken from 141 such cases in 5 different centres. Drug effect on the virus were studied. A 2.5 times reduction of effect was the standard used. Five samples showed reduction in more than this level to at least 1 nucleoside reverse transcriptase inhibitor [NRTI], 2 revealed 10 times reduction and 24 samples to a non-NRTI . Only 1 showed a 10 > times reduction. A single mutation in the resistant group T215Y was discovered in 36 samples.
In HIV infections resistance 2.5 and 10 times range are common. Testing for resistant virus strains is advised in areas of high prevalence of uncontrollable AIDS.
Eckert DM, Malashkevich VN, Hong LH, et al [ Howard Hughes Med Inst, Cambridge, Mass]
Inhibiting HIV-1 Entry: Discovery of D-Peptide Inhibitors That Target the gp41 Coiled-Coil Pocket
Cell 99 : 103-115, 1999
Prevention of HIV-1 virus from entering a cell seems logical. Short chains of D-amino acids resistant to proteolysis and designated 1QN17 act by attaching to the gp41 region of the virus. These newly discovered chains thus prevent the virus from using such proteins on the cell membrane of the host. It is of interest that the agent can be given by mouth as a tablet.
Hazuda DJ, Felock P, Witmer M, et al [Merck Research Labs, West Point, Pa]
Inhibitors of Strand Transfer That Prevent Integration and Inhibit HIV-1 Replication in Cells
Science 287: 646-650, 2000
In the management of HIV-1 infection drugs acting on reverse transcriptase and protease enzymes of the virus have been relied upon. The development of resistance constitutes an important reason for search of alternatives.
HIV integrase is used by the virus to allow its DNA to be introduced into the cell genome, a step necessary for it to replicate. This article introduces diketo acids L-731,988 and L-708,906 to prevent such strand integration.
At the moment it is in the experimental stage.
Martinez E, Gatell J, Moran Y, et al [ Hosp Clinic, Barcelona]
High Incidence of Herpes Zoster in Patients with AIDS Soon After Therapy with Protease Inhibitors
Clin Infect Dis 27: 1510-1513, 1998
193 HIV-1 patients of Aids being treated with a nucleoside analogue reverse-transcriptase inhibitor [NRT1] were followed up. Those with CD4+ at base line levels were given a protease inhibitor in addition.
During a median of 64 weeks, 14 patients [7%] developed a first or recurrent episode of herpes zoster most often in the first 4 and 16 weeks, after starting the protease inhibitor. The high CD8+ counts noticed at the end of the first month may be a mechanism of this precipitation of herpes zoster.
The risk of this complication is calculated to be twice that expected in the non protease inhibitor group
Breton G, Fillet A-M, Katlama C, et al [ Hopital Pitie Salpetriere, Paris]
Acyclovir-Resistant Herpes Zoster in Human Immunodeficiency Virus Infected Patients: Results of Foscarnet Therapy
Clin Infect Dis 27: 1525-1527, 1998
Eighteen patients of isolation confirmed varicella-zoster virus [ VZV] infection manifesting as herpes zoster in HIV-1 positive subjects are reported. They were resistant to acyclovir-therapy. Thirteen subjects received IV foscarnet in a dose of 100 mgm/kg twice a day. In one patient the dose had to be reduced to 120 mgm because of hypocalcemia lesion clearance was achieved in ten patients five relapsed with recurrence in the same dermatomes in a little over three months after treatment. Three of these cleared with acyclovir or foscarnet. Of the total of 16 followed for a median of 8 months 4 died of visceral effects of VZV infections. Normally the drug is used in a dose of 40 mgm/Kg thrice a day or 60 mgm/kg twice a day. It is important to note that patients tolerated the larger dose. Message of the paper is “acyclovir resistant herpes zoster is a serious in patients of Aids.”
Cheung TW, for the TLC D-99 Study Group [Mount Sinai School of Medicine, New York; et al]
AIDS-Related Kaposi’s Sarcoma: A Phase II Study of Liposomal Doxorubicin
Clin Cancer Res 5: 3432-3437, 1999
Doxorubicin in a liposomal combination, [ the latter derived from egg phosphatidyl choline – cholesterol liposomes ] has been useful as TLC D-99 in the treatment of Aids associated Kaposi’s sarcoma. It was diagnosed histologically in 40 men [median age 35 years] suffering from Aids, and comprising the II phase of this study. They were divided into a stable of group of 21 patients and another of 19 not categorized as stable. The former received a dose of 20mg/m2 and the latter 10 mgm/m2 intravenously as a drip over a period of 1 hour every 2 weeks.
A stable state was maintained by 13 patients in each group. The group on 20 mgm/m2 showed a better response. The commonest side effect was neutropenia. Total clearance was not achieved.
Rezza G, for the Italian Seroconversion Study [Istituto Superiore di Sanita, Rome, Italy; et al]
Human Herpesvirus 8 Seropositivity and Risk of Kaposi’s Sarcoma and Other Acquired Immunodeficiency Syndrome -Related Diseases
J Natl Cancer Inst 91: 1468-2474, 1999
336 patients of AIDS were studied to determine if a prognostication for development of Kaposi Sarcoma [KS] could be made. HHV-8 and HIV have been held responsible for KS evolution. The present study between 1983 and 1996 reports on HHV-8 antibody levels and KS expression. Epstein-Barr virus antibodies were looked for.
21 cases of KS were detected in a median period of 5-8 years. A titer of 1 in 125 or higher suggests that the subject is at a greater risk of developing KS especially beyond 7 years of infection. Of the 21 patients, 19 were homosexuals, 1 was heterosexual and 1 who had KS but not HHV-8 infection was a homosexual.
Thus longer the duration of HHV-8 infection in the milieu of Aids and background of homosexuality the greater the incidence of KS.
ML Lara-Marquez, A Deykin, S Krinzman, et al (Brigham and Women’s Hosp, Boston; Harvard Med School, Boston; Harvard School of Public Health, Boston)
Analysis of T-Cell Activation After Bronchial Allergen Challenge in Patients with Atopic Asthma.
J Allergy Clin Immunol 101:699-708, 1998.
There is increasing evidence of T cell involvement in the airway inflammation in asthma patients and an important functional role may also be played by CD4+ T helper (TH) cells in regulating the immunoglobulin E synthesis.
In this article, a number of immunologic markers have been measured from the peripheral blood in 9 adult individuals undergoing either cold air challenge or entire bronchoprovocation challenge with allergen. What is found is that peripheral blood at 2 and 24 hours after allergen challenge has a significant increase in CD45RO+, IL-2 receptor positive CD4+ TH cells compared with baseline, increasing from about 12% to about 18% at both 2 and 24 hours. The major histocompatibility complex class II expression and IL-2 receptor expression were also increased but not as significantly, and coexpression of the IL-2 receptor and major histocompatibility complex class II was only found on a small population of CD45RO+ TH cells suggesting that a significant percentage of cells stimulated by bronchoprovocation and cold air co-express the same receptor leading to an up-regulation of the other immune markers on these cells may represent the effects of immune cells passing through the lung. The significance of these findings is that we need to work toward the potential identification of markers that can be viewed as somewhat reliable in identifying noninvasive markers of airway inflammation in asthma. This would get us closer towards better assessments of therapy and disease severity.
OM Kon, BS Sihra, CH Compton, et al (London Chest Hosp; Natl Heart and Lung Inst, Londong; Smithkline Beecham Pharmaceuticals, Harlow, Essex, England; et al)
Randomized, Dose-ranging, Placebo-controlled Study of Chimeric antibody to CD4 (Keliximab) in Chronic Severe Asthma.
Lancet 352: 1109-1113, 1998
CD4 lymphocytes play a significant role in the pathogenesis of chronic asthma. In the study quoted the efficacy and safety of a single IV infusion of a chimeric monoclonal antibody to CD4, were studied in patients with severe corticosteroid-dependent asthma.
The successful treatemnt of asthma with immunosuppressive agents, such as cyclosporin A, and use of monoclonal antibody in the other chronic inflammatory conditions has suggested the use of a monoclonal antibody to CD4 in patients with severe steroid-dependent asthma. This was a preliminary study with a single dose of antibody. However, along with other studies using monoclonal technology, this approach seems to be the sunrise in a new era in the treatment of allergic disorders.
S Elwany, M Bassiouny, (Alexandria Univ, Egypt)
Topical Levocabastine for the Treatment of Perennial Allergic Rhinitis
J Laryngol Otol 111: 935-940, 1997.
Oral H1-receptor antagonists which have found the primary treatment for chronic allergic rhinitis are associated with severe systemic side effects. Topical therapy should theoretically avoid these events, while producing a higher concentration at the site. A study reported shows the use of a nasal spray containing levocabastine which is a potent and highly selective H1-receptor antagonist, on the nasal mucosa in patients with chronic allergic rhinitis.
The study has some remarkable findings in that there has been a reappearance of normal cilia and microvilli and more acinar cells in the post-treatment specimens collected in the biopsy. The number and activity of goblet cells and serous glands decreased as was the evidence of vascular congestion. These changes reduced the formation of edema fluid, and the reduction in the number of pinocytotic vesicles reduced the transmission of fluid across epithelial cells. Degranulated mast cells and eosinophils however, were still present at the end of the short study.
Although perhaps not as impressive as topical corticosteroids induced changes, the reported findings certainly suggest moderate anti-inflammatory properties of this topical antihistamine. Hence one should look beyond just the antihistaminic actions of these agents by probably combining with leukotriene and lipoxygenase inhibition studies.
DE Schellhase, DD Fawcett, GE Schutze, et al (Univ of Arkansas, Little Rock)
Clinical Utility of Flexible Bronchoscopy and Bronchoalveolar Lavage in Young Children with Recurrent Wheezing.
J Pediatr 132: 312-318, 1998.
The need to evaluate recurrent wheezing in a young child is a common occurrence in primary care and consultant practice. There have been various studies which have reported the use of flexible bronchoscope for this purpose. However they have not addressed the clinical value of bronchoaveolar lavage. The study included thirty otherwise healthy children who were subjected to flexible bronchoscopy for recurrent wheezing.
The evaluation of young children with recurrent wheezing can be extremely challenging as the differential diagnosis is so extensive. In majority of cases the reason is the small airways and reactive airways disease which account for wheezing. However there are multiple other causes which can lead to wheezing in a child.
The study was performed on children with chronic wheezing who have responded poorly to b-agonist therapy. The study had a positive diagnostic finding as a result of bronchoscopy and bronchoalveolar lavage (BAL) in 28 of the 30 children. Airway abnormalities were found in 57% of the patients, with segmental trachomalacia the most common anomaly. Bronchoalveolar fluid analysis revealed abnormal differential cell counts in 41% of the patients.
This study suggest that bronchoscopy with lavage is a safe procedure which can provide valuable diagnostic information in young children with recurrent wheezing poorly responsive to b-agonist therapy.