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Biomedical subjects

D Pillay

Publications and source records attributed to D Pillay.

At least 91 records · Page 5Linked to original sources
PubMed1998

Urinary levels of tissue kallikrein in black and Indian hypertensives and their implications for therapy.

It is accepted that blacks differ from white and Indian hypertensives in their response to hypotensive agents. Black hypertensives in the USA have lower urinary tissue kallikrein (TK) excretion levels than white hypertensives. It has been suggested that blacks respond better to thiazide diuretics than to beta-blockers because thiazides increase TK excretion whereas beta-blockers decrease it. This study compares the excretion of urinary TK in black and Indian hypertensive and normotensive subjects. Urinary TK levels were measured with the selective, synthetic peptic substrate with the sequence of H-D-Val-Leu-Arg-pNA. Ten hypertensive patients on placebo therapy and 10 normotensive black and Indian subjects provided 3 samples at weeks 0, 2 and 4 for the determination of urinary TK. The results were analysed and analysis of variance was used to compare the two racial groups. There were no significant differences in urinary TK values of the three biweekly individual samples. Urinary TK values (ng TK/microgram protein) in Indian hypertensives were generally lower than in black hypertensives.

Adult↗
PubMed1998

Emergence and control of resistance to antiviral drugs in resistance in herpes viruses, hepatitis B virus, and HIV.

This article describes the biology of antiviral drug resistance with regard to herpes viruses, hepatitis B virus, and HIV. The emergence of antiviral drug resistance is testimony to the potency of current antiviral drugs. Natural selection of such viral variants occurs, such that the strains that are 'fittest' in the presence of the drug persist. Phenotypic and genotypic assays are now available to test clinical viral isolates for resistance. At present, the clearest indication for such testing is in aciclovir-resistant herpes simplex infection. It is important that other resistance assays are subject to studies of clinical utility before their widespread use.

Antiviral Agents↗
PubMed1997

High prevalence of hepatitis G virus in bone marrow transplant recipients and patients treated for acute leukemia.

Hepatitis G virus (HGV) is a newly described virus that has been implicated in transfusion-associated hepatitis. The prevalence of HGV in a group of multitransfused patients with hematological malignancy was studied using a reverse transcription polymerase chain reaction technique. Transfusion histories and serum aspartate aminotransferase (AST) levels were recorded. HGV was detected in 29 of 60 (48%) patients. There was no difference in HGV positivity rates between those with normal AST levels and those with raised AST levels. Analysis of patients by treatment type showed that 20 of 33 (61%) patients who received a bone marrow transplantation procedure were HGV positive compared with 9 of 27 (33%) treated with conventional combination chemotherapy (P = .036) despite similar transfusion histories. There was no significant difference in HGV positivity between patients treated before the introduction of United Kingdom blood donor screening for hepatitis C virus antibody:18 of 39 (46%) and those treated after the introduction of screening 11 of 21 (52%). HGV infection appears to be extremely common in these patients; however, the clinical significance of these findings with respect to liver dysfunction is not yet clear.

Acute Disease↗
PubMed1997

Hepatitis G virus infection in patients with bleeding disorders.

Eighty-two patients with bleeding, disorders registered with our centre were screened for infection with hepatitis G virus (HGV). 80 patients were positive for hepatitis C (HCV) antibodies, 66 of whom (83%) were HCV PCR positive. 11 patients (13%) were HGV RNA-positive, a similar prevalence rate to that of other studies of patients with bleeding disorders who received factor concentrates prior to the introduction of viral inactivation procedures. There was no significant difference in histological activity index (HAI) between the 10 HGV RNA-positive and the 31 HGV RNA-negative patients who underwent liver biopsy for assessment of HCV infection (median HAI scores 5.5, range 2-10 and four, range 0-10 respectively, P = 0.07). One patient in each group had established cirrhosis. In patients who underwent HCV quantitation there was no significant difference in HCV viral titre between HGV RNA-positive and negative patients (median HCV titre in HGV RNA-positive patients 2.10 x 10(5) DNA copies/ml (n = 8) range 4.17 x 10(2) to 4.17 x 10(6), median HCV titre in HGV RNA-negative patients 3.33 x 10(5) (n = 31) range 1.00 x 10(3) to 6.67 x 10(6), P = 0.68). In this study there was no evidence that individuals co-infected with HGV and HCV have more severe liver disease than those infected with HCV alone.

Adult↗
PubMed1997

Antibiotic susceptibility patterns and plasmid profiles of penicillinase-producing Neisseria gonorrhoeae strains in Durban, South Africa, 1990-1993.

BACKGROUND AND OBJECTIVES: The appearance of strains of Neisseria gonorrhoeae resistant, both chromosomally and plasmid-mediated, to penicillin and other antibiotics makes this versatile pathogen difficult to treat. There is, therefore, a need for surveillance of N. gonorrhoeae strains to determine the efficacy of current therapeutic measures. GOALS: To survey the antibiotic susceptibilities and plasmid profiles of penicillinase-producing N. gonorrhoeae strains isolated over a 4-year period. STUDY DESIGN: Penicillinase-producing N. gonorrhoeae strains were detected by the chromogenic cephalosporin test. Minimum inhibitory concentrations to penicillin G, tetracycline, ceftriaxone, and ciprofloxacin were determined using the E-test. Plasmid DNA was obtained by the alkaline lysis method and profiles generated. RESULTS: Penicillinase-producing N. gonorrhoeae strains increased from 16.4% to 19.0% in the period from 1990 through 1993. Although all strains were resistant to penicillin, strains were susceptible to varying levels of ciprofloxacin, ceftriaxone, and even tetracycline. All penicillinase-producing N. gonorrhoeae strains possessed the 2.6-megadalton cryptic plasmid, and in addition 87.7% contained the 24.5-megadalton conjugative plasmid. Of the six known gonococcal beta-lactamase plasmids, the 4.4-megadalton Asian and 3.2-megadalton African plasmids were predominant. The most prevalent plasmid profile contained the 2.6-megadalton cryptic, 24.5-megadalton conjugative, and 4.4-megadalton Asian plasmids. CONCLUSIONS: To ensure effective treatment of gonorrhea, continued surveillance of the antimicrobial susceptibilities and plasmid profiles of penicillinase-producing N. gonorrhoeae strains is necessary.

Drug Resistance, Microbial↗
PubMed1997

A mutation in human immunodeficiency virus type 1 protease at position 88, located outside the active site, confers resistance to the hydroxyethylurea inhibitor SC-55389A.

The hydroxyethylurea human immunodeficiency virus type 1 (HIV-1) protease inhibitors SC-55389A and SC-52151 were used to select drug-resistant variants in vitro. One clinical HIV-1 strain (89-959) and one laboratory HIV-1 strain (LAI) were passaged in peripheral blood mononuclear cells or CEMT4 cells in the presence of SC-55389A. Resistant isolates from both strains consistently had a mutation to serine for asparagine at amino acid 88 (N88S) in the protease gene either alone or in combination with a change to phenylalanine at position 10. The N88S mutation, recreated by oligonucleotide-mediated site-directed mutagenesis in HXB2, was sufficient to confer resistance to SC-55389A. In contrast, SC-52151-resistant variants selected from the monocytotropic strain SF162 had multiple substitutions in the protease gene (I11V, M461, F53L, A71V, and N88D), and the N88D mutation, re-created by oligonucleotide-mediated site-directed mutagenesis in HXB2, did not confer resistance to SC-52151. The potencies of L735,524 and Ro31-8959 were not reduced when these compounds were assayed against variants with either the N88S or N88D substitution. Position 88 is in a helix that lies behind the substrate binding pocket and may indirectly influence inhibitor binding through interactions with the amino acid at position 31. The selected mutations were persistent in the viral populations after more than 20 passages in the absence of drugs. Passaging of virus first in SC-55389A alone and then in combination with SC-52151 resulted in the accumulation of more mutations in the protease gene (L10F, D35E, D37M, I47V, 154L, A71V, V82I, and S88D) and in the selection of a variant that was cross-resistant to multiple protease inhibitors. These results indicate that a mutation in the HIV-1 protease at a position that is located outside of the substrate binding pocket confers resistance to a protease inhibitor and that mutations in the protease gene accumulate with increasing selection pressure and can persist in the absence of selection pressure.

Amino Acid Sequence↗
PubMed1997

Diagnosis of primary human herpesvirus 6 and 7 infections in febrile infants by polymerase chain reaction.

Primary human herpesvirus 6 (HHV-6) and 7 (HHV-7) infections were identified in febrile children by qualitative and quantitative polymerase chain reaction (PCR) assays. Diagnosis was based on the differential detection of viral DNA in peripheral blood mononuclear cells (PBMC), but not in saliva. Six of 41 febrile infants, but none of seven non-febrile controls, were identified with primary infections (three HHV-6, three HHV-7). These children had significantly higher viral loads in PBMC (HHV-6, median 24213 genomes/10(6) PBMC; HHV-7, median 6,040,000 genomes/10(6) PBMC) than DNA-aemic, saliva PCR positive children (HHV-6, median 1606 genomes/10(6) PBMC, p < 0.01; HHV-7, median 7089 genomes/ 10(6) PBMC, p < 0.05). Viral DNA was detected in serum by PCR in only 50% of primary infections. All three children with primary HHV-7 infection had febrile convulsions. Thus PCR, including quantitative assays, may identify primary HHV-6 and HHV-7 infections when an appropriate combination of clinical specimens is used.

DNA, Viral↗
PubMed1997

Semen characteristics in HIV-1 positive men and the effect of semen washing.

We have undertaken an analysis of semen from HIV infected men with regard to sperm counts and motility, non-spermatozoal cells, and viral nucleic acid. Regression analysis showed that sperm concentration and motility were positively associated with blood CD4 cell count. By contrast, non-spermatozoal cell concentration (round cells) was inversely related to CD4 count. Extracellular HIV RNA was detected in the majority of semen samples and proviral DNA in a minority. Percoll gradient washing of 12 semen samples yielded six samples containing adequate sperm concentration for analysis. This washing procedure reduced prewash extracellular RNA to below detectable limits in all cases; proviral DNA present in two of the six prewash samples was also reduced to below detectable limits after washing. We conclude that semen washing before artificial insemination may reduce the risk of HIV transmission from an infected man to an uninfected woman. However, further evidence from prospective analyses of such an approach is required.

CD4 Lymphocyte Count↗
PubMed1997

Zinc status in vitamin B6 deficiency.

Three groups of young male Wistar rats were maintained on diets consisting of 7 mg pyridoxine hydrochloride/kg diet (control and pair-fed groups) and 0 mg pyridoxine hydrochloride/ kg diet (deficient group) for six weeks. The zinc status of all rats was assessed by measuring their erythrocyte zinc-metallothionein-1 (Zn-Mt-1) and plasma zinc levels. A significant difference (p < 0.001) in plasma zinc levels was observed between the deficient group and the control and pair-fed groups (1.35 micrograms/ml +/- 0.08, 1.99 micrograms/ml +/- 0.06 and 2.03 micrograms/ml +/- 0.07 respectively). Erythrocyte Zn-Mt-1 levels were significantly lower in vitamin B6 deficient rats when compared to control animals. No significant difference in Zn-Mt-1 levels existed between vitamin B6 deficient and pair-fed groups suggesting that the reduced Zn-Mt-1 levels in vitamin B6 deficient rats may be due entirely to their decreased food intake (8.9 g/day compared to 15 g/day of control rats).

Animals↗
PubMed1996

Electrophoretic differentiation of soluble egg antigens from Schistosoma mansoni isolates using SDS-PAGE.

In order to detect intraspecies differences among isolates of Schistosoma mansoni from different geographical regions, soluble egg antigens (SEAs) of three isolates were characterized using SDS-PAGE. SEAs were prepared from eggs of a South African (SA), Eastern Caprivian (EC) and Puerto Rican (PR) isolate, separated by SDS-PAGE, stained and the molecular masses of constituent polypeptides determined. Protein profiles differed for all three isolates with the number of polypeptides varying from 25 for the PR isolate to 27 for the EC and SA isolates. Molecular masses of the polypeptides fall within the range of 12.0 kDa to 97.9 kDa. The EC and SA isolates shared ten common polypeptides, the PR and SA isolates five and the PR and EC isolates two. Only a 30.8 kDa and a 12.0 kDa polypeptide were common to all three isolates. These differences may, to some extent, account for regional variations in the morbidity of intestinal schistosomiasis reported for different geographical isolates of S. mansoni.

Animals↗
PubMed1996

Random-amplified polymorphic DNA (RAPD) analysis shows intraspecies differences among Xanthomonas albilineans strains.

Five strains of Xanthomonas albilineans, causal agent of leaf scald disease in sugarcane from various geographical regions, were compared using random amplification of polymorphic DNA (RAPD) to determine whether they could be differentiated at the DNA level. CsCl-purified genomic DNA from these strains were amplified by the polymerase chain reaction (PCR) using arbitrary 10-mer primers according to standard RAPD conditions and the amplification product profiles analysed by conventional agarose gel electrophoresis. Although most RAPD markers were common to all five strains, unique profiles for each strain were discernible using four 10-mer arbitrary primers individually. Reproducible DNA fingerprints indicate that RAPD analysis can be used to identify and differentiate the X. albilineans strains. This technique has the potential for use in monitoring the appearance of foreign strains of X. albilineans in various geographical regions and could be used for the construction of phylogenetic trees.

DNA Fingerprinting↗
PubMed1994

A long-term follow-up of hepatitis B vaccination in patients with congenital clotting disorders.

All patients with congenital clotting disorders attending our centre routinely receive hepatitis B vaccination. We have assessed retrospectively the vaccine responses in 167 such individuals, with a follow-up period of up to 7.5 years. The initial postvaccine anti-HBs response was lower in older patients (p = 0.001), those infected with human immunodeficiency virus (HIV) (p = 0.05), and those who received intradermal rather than subcutaneous administration of vaccine (p = 0.08). It was estimated that the median time for anti-HBs levels to fall to 100 IU l-1 was between 36 and 42 months, with a shorter period for older or HIV-infected patients. Although the persistence of protective antibody levels can be predicted to some extent from the absolute levels of initial postvaccine anti-HBs, the wide variation in antibody decline between individuals precludes recommendation of the timing of vaccine booster doses solely based on this value.

Adolescent↗
PubMed1993

Prospective cytomegalovirus surveillance in paediatric renal transplant patients.

Fifty-eight consecutive paediatric recipients of 65 renal transplants were prospectively studied for up to 72 months for evidence of cytomegalovirus (CMV) infection. Blood, urine and saliva were screened for CMV pre transplant and then weekly for the first 6 weeks, and monthly thereafter, by conventional cell culture and by detection of early antigen fluorescent foci. Donor CMV serostatus was available in 51 cases. All patients received triple therapy as immunosuppression and none had CMV prophylaxis. Twenty-six episodes of CMV infection (40% of transplants) and 10 of CMV disease (15%) were identified. Donor CMV seropositivity, regardless of recipient CMV serostatus, was significantly associated with CMV infection (P = 0.04). First CMV excretion was significantly earlier in patients who subsequently became symptomatic than in those who did not (P = 0.04), and a positive blood culture was significantly associated with CMV disease (P = 0.04). We found no association between extra anti-rejection treatment or recipient's age and CMV infection or disease. CMV disease had no influence on renal function as assessed by glomerular filtration rate at 6, 12 and 24 months post transplant, nor on graft loss. CMV disease was fatal in 1 patient. We conclude that trials of CMV prophylactic agents are indicated, particularly in recipients of CMV seropositive grafts. A positive blood culture should lead to consideration of anti-CMV therapy.

Adolescent↗