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Biomedical subjects

S Shaunak

Publications and source records attributed to S Shaunak.

At least 55 records · Page 3Linked to original sources

Geographic diversity of human immunodeficiency virus type 1: serologic reactivity to env epitopes and relationship to neutralization.

The antibody recognition of the major neutralization epitopes of human immunodeficiency virus type 1 (HIV-1) in 829 HIV-1-seropositive subjects from North America (106), Europe (241), Africa (342), and Asia (100) was investigated. Peptides derived from diverse published V3 loop sequences were used as antigen, and serum reactivity was detected by sensitive ELISAs. Antibody binding to peptides derived from the V3 loop sequence of HIV-1 isolates varies considerably depending on the geographic origin of the antibody and is associated with neutralization titer against homologous isolates. Serotype reactivity to peptides may be a simple and rapid approach to investigation of HIV-1 env diversity worldwide and may assist the choice of immunogen for development of future AIDS vaccines.

Africa↗

Clinical management of fungal infection in patients with AIDS.

The frequency of disseminated fungal infection in patients with the Acquired Immune Deficiency Syndrome (AIDS) has provided a major impetus for the reevaluation of standard antifungal protocols as well as accelerating the development and clinical testing of new agents. As a result, useful clinical guidelines regarding the use of amphotericin B and flucytosine in cryptococcosis are beginning to emerge that relate specifically to patients with AIDS. Oral agents, most notably fluconazole have shown promise and are now being evaluated in controlled clinical trials. Histoplasmosis and coccidioidomycosis have emerged as significant infections and pose new problems in both diagnosis and management. Although amphotericin B and flucytosine must still be used for induction therapy in patients with these infections, preliminary studies of itraconazole suggest that it could be useful for maintenance therapy. Despite there being considerably less clinical experience with histoplasmosis and coccidioidomycosis than with cryptococcosis, it is hoped that the lessons learnt with cryptococcosis will accelerate the development of new diagnostic assays and improved therapeutic approaches.

Acquired Immunodeficiency Syndrome↗

Genetic screening of newborns for sickle cell disease: correlation of DNA analysis with hemoglobin electrophoresis.

Although DNA analysis based on the polymerase chain reaction (PCR) offers potential advantages for screening newborns for sickle cell disease, few data are available concerning the reliability of PCR-based tests for such screening. We describe a protocol for detecting the A, S, and C alleles of the beta-globin gene in dried blood from phenylketonuria screening cards. This method is based on PCR and detection with allele-specific oligonucleotide probes. Results of a blind comparison of PCR analysis of the dried blood with hemoglobin electrophoresis of whole-blood samples agreed for 80 of 81 samples. The single discrepancy is probably not attributable to a failure of the PCR method, but rather to limitations of the electrophoresis method. The PCR method should be a highly accurate means of detecting beta-globin alleles in routine genetic screening with dried blood already collected for (e.g.) phenylketonuria screening.

Alleles↗

Amplification of HIV-1 provirus from cerebrospinal fluid and its correlation with neurologic disease.

The polymerase chain reaction (PCR) was used to detect human immunodeficiency virus type 1 (HIV-1) proviral sequences (gag and env) in nucleated cells from the cerebrospinal fluid (CSF) of 31 HIV-1-positive patients, and the results were compared with clinical and radiologic evidence of neurologic disease. Provirus was detected in 21 patients, of whom 20 had neurologic abnormalities. Provirus was not detected in another 6, all of whom were neurologically normal. No neurologic disease has developed in 4 of these 6 patients for whom 12.8 months of follow-up is available. PCR of CSF nucleated cells from HIV-positive patients provides early, rapid, direct evidence of neurologic involvement.

AIDS Dementia Complex↗

HIV-1-associated thrombocytopenia. The role of splenectomy.

Thrombocytopenic purpura is a common hematologic abnormality occurring in individuals infected with the human immunodeficiency virus, HIV-1. Of the nearly two million people infected with HIV-1, approximately 11% have platelet counts of less than 100,000/mm3. If no etiology other than HIV-1 infection can be found for the thrombocytopenia, the syndrome is referred to as HIV-1-associated thrombocytopenia (HAT). Steroids lead to an improvement in the platelet count in 60% to 80% of effected individuals but the majority of those who respond cannot maintain a normal platelet count when steroids are withdrawn. Furthermore concern over chronic steroid therapy in HIV-1-infected individuals has led to the investigation of other forms of treatment for this syndrome. This report describes the experience at Duke University Medical Center with eight patients who developed HAT and subsequently underwent splenectomy. In this group there was 1 complete response, 5 partial responses, and 2 patients who did not respond. There were no perioperative deaths and minimal perioperative morbidity. No evidence for the progression of HIV-1 infection in asymptomatic patients after splenectomy to AIDS related complex (ARC) or to the acquired immune deficiency syndrome (AIDS) was seen. In addition no increase in the susceptibility to infections by encapsulated organisms as a result of splenectomy was observed after a mean follow-up of 13.25 months. A review of 79 other cases reported in the literature suggests a higher response rate than that observed in our patients. Reasons for this discrepancy are discussed and an algorithm defining the role of splenectomy in the management of HAT is presented.

AIDS-Related Complex↗

Zidovudine-induced neutropenia: are we too cautious?

30 patients with recurrent zidovudine-induced neutropenia were followed up for a total of 493 months of treatment to evaluate their risk of bacterial infection. Zidovudine was temporarily discontinued only when the polymorphonuclear (PMN) cell count fell to less than 500/microliters. The incidence of bacterial infection during periods of severe neutropenia (PMN less than 500/microliters) was 230% higher than when the PMN count was 500-1000/microliters, and 600% higher than when the count was greater than 1000/microliters. The difference between periods when the PMU count was 500-1000/microliters and non-neutropenic periods was not significant. The findings suggest that zidovudine therapy can be continued despite neutropenia without a major increase in the incidence of bacterial infection provided the PMN count does not fall to less than 500/microliters.

Acquired Immunodeficiency Syndrome↗

Severe pulmonary hemorrhage and systemic vasculitis in association with circulating anti-neutrophil cytoplasm antibodies of IgM class only.

We report an association of severe pulmonary hemorrhage with circulating autoantibodies to neutrophil cytoplasmic antigens (ANCA) restricted to IgM class in three patients with systemic vasculitis. ANCA were detected by indirect immunofluorescence and isotype specific solid phase radioimmunoassay (SPRIA). Institution of immunosuppressive therapy was accompanied by an isotype switch to IgG ANCA and recovery in all three patients. In an associated study, ANCA activity was found in eluates from the washed glomeruli of two postmortem cases, with the same isotype distribution as was present in the sera.

Adolescent↗

Cyclophosphamide-induced liver necrosis: a possible interaction with azathioprine.

Cyclophosphamide is a valuable drug for the treatment of vasculitis and hepatic toxicity resulting from its use has been reported rarely. We describe four patients in whom cyclophosphamide was associated with liver injury when its administration had been preceded by azathioprine. Microscopy of hepatic biopsy material in three of these cases showed liver cell necrosis. In two of the patients, cyclophosphamide had been given previously without earlier azathioprine and hepatic damage had not been noted. An apparent interaction of cyclophosphamide with azathioprine to cause liver cell necrosis has important implications for the treatment of patients with vasculitis and related disorders.

Adult↗

Septic scarlet fever due to Streptococcus pyogenes cellulitis.

We report three cases of septic scarlet fever due to Streptococcus pyogenes Group A (serotype M1/T1/OF-) cellulitis in healthy young adults. Despite prompt treatment two of the patients died. Such cases of cellulitis associated with scarlet fever, severe toxaemia and septicaemia have not been reported in the post-antibiotic era.

Adult↗

Muscle strength in healthy white and Asian subjects: the relationship of quadriceps maximum voluntary contraction to age, sex, body build and vitamin D.

1. The maximum voluntary isometric contraction (MVC) of the dominant quadriceps muscle was measured in 136 healthy White and 172 healthy Hindu Asian subjects resident in London, using a specially designed chair equipped with a force measuring load cell. 2. Males were stronger than females, and for both sexes MVC declined with age. From age 20 to 60 the annual decline in MVC ranged from 0.56% in White males to 1.5% in female Asians. 3. White subjects were stronger than Asian subjects even after correcting for the effect of age, height, weight and sex in a multi-factorial analysis. 4. Only in males did MVC correlate with height and weight. Asian women were more obese than any other group, and showed an increase in body mass index with age. 5. Twenty-two per cent of Asian subjects had marked vitamin D deficiency (plasma 25-hydroxycholecalciferol less than 10 nmol/1). There was no correlation between MVC, and plasma 25-hydroxycholecalciferol.

Adult↗