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Biomedical subjects

H A Smith

Publications and source records attributed to H A Smith.

At least 55 records · Page 3Linked to original sources
PubMed1984

Suppression of frequently recurring genital herpes. A placebo-controlled double-blind trial of oral acyclovir.

We studied 35 otherwise healthy adults with frequently recurring genital herpes (greater than or equal to 1 episode per month), in a double-blind trial comparing oral acyclovir with placebo capsules for suppression of recurrent infection. The patients were treated for 125 days unless herpes recurred. Among 32 evaluable patients, there were significantly fewer recurrences during acyclovir treatment (4 of 16) than during placebo treatment (16 of 16, P less than 0.001). The mean duration of therapy was significantly longer for patients receiving acyclovir than for those receiving placebo (114.9 vs. 24.8 days, P less than 0.001). Of 19 patients who had recurrences in the blind trial, only 2 had recurrences when given acyclovir in a second, open-study phase. All patients had recurrences after completing acyclovir treatment. The therapy was well tolerated, with minimal gastrointestinal upset and one hypersensitivity reaction. Studies of the viral isolates demonstrated that lesions developing in patients receiving acyclovir contained drug-resistant virus. Later recurrences in these patients were associated with drug-sensitive virus. We conclude that oral acyclovir suppresses genital herpes in patients with frequent recurrences, but the potential for problems with drug resistance and the long-term safety need to be more fully explored.

Acyclovir↗
PubMed1984

Detection of varicella-zoster virus by dot-blot hybridization using a molecularly cloned viral DNA probe.

Varicella-zoster virus (VZV) infection can be definitively diagnosed by isolation of virus in cell culture, a process that usually takes 7-14 days. In order to facilitate the more rapid detection of this virus, we developed a technique for hybridization of DNA from clinical specimens using an in vitro-labeled mixture of cloned fragments of VZV DNA as a probe. The assay can be completed in 36-48 hr and can be successfully carried out in the range of 10 pg to 10 ng of viral DNA. In analyses of 38 specimens from patients with a clinical diagnosis of VZV infection, the results of viral isolation and this assay were highly concordant. The sensitivity of standard cell culture for detection of VZV was 58%, whereas the sensitivity of the assay was 76%, not significantly different (P = 0.14). The specificity of cell culture was 100%, whereas that of the assay was 94% (P = 0.49). The technique appears to be sensitive, specific, and useful for analyses of tissues and body fluids.

Autoradiography↗
PubMed1984

Oral acyclovir to suppress recurring herpes simplex virus infections in immunodeficient patients.

Thirty-two episodes of herpes simplex virus infection in four immunodeficient patients with frequent recurrences were successfully treated with oral acyclovir, one capsule five times a day for 5 days. In 23 of these episodes, the treatments were extended for 1 to 6 months using two to five capsules a day with the aim of suppressing expected recurrences. In these patients, who routinely had more than one recurrence per month before treatment, there were only six outbreaks during more than 60 patient-months of suppressive therapy. Infection always recurred after treatments were completed, but the time to recurrence was shorter after treatments with two acyclovir capsules per day than after treatments with five capsules per day (p less than 0.001).

Acyclovir↗
PubMed1983

Design of anticandidal agents: synthesis and biological properties of analogues of polyoxin L.

Six analogues of polyoxin L were synthesized from uridine. All of these analogues inhibited chitin synthetase from Candida albicans. Derivatization of the amine terminus of the polyoxin analogues resulted in loss of activity, and analogues containing aromatic amino acid residues were the most efficient inhibitors of chitin synthetase. The concentration of tryptophanyl uracil polyoxin C, 8, which caused 50% inhibition of chitin synthetase activity, was 1.6 X 10(-6) M. This was virtually identical with the activity found for polyoxin D. None of the inhibitors effectively competed with the entry of (Met)3 into C. albicans. All of the analogues caused severe morphological distortions of the yeast in culture, and a number of analogues killed C. albicans at millimolar concentrations. The results suggest that chitin synthetase inhibitors may have potential as anticandidal drugs.

Antifungal Agents↗
PubMed1983

Synthesis and biological activity of tripeptidyl polyoxins as antifungal agents.

Three tripeptidyl polyoxins were synthesized and found to inhibit Candida albicans. Compared with the naturally occurring polyoxin D, the three synthetic polyoxins had little effect on chitin synthetase when assayed with a C. albicans membrane preparation. However, all the compounds inhibited growth, affected cell morphology in a manner similar to that of polyoxin D, and were hydrolyzed by cell extracts of C. albicans. Hydrolysis did not occur extracellularly, and at least one of the synthetic polyoxins, leucyl-norleucyl-uracil polyoxin C, inhibited peptide uptake, suggesting entrance into the cell via the peptide transport system. Thus, the intact tripeptidyl polyoxins are inactive prodrugs that are converted to active moieties by cellular enzymes.

Antifungal Agents↗
PubMed1982

Acyclovir for chronic mucocutaneous herpes simplex virus infection in immunosuppressed patients.

Over 25 episodes of severe chronic and recurrent mucocutaneous herpes simplex virus infections in five immunodeficient patients were successfully treated with intravenous or oral acyclovir treatment. Acyclovir was shown to inhibit viral shedding rapidly, to be well tolerated, and to permit the complete healing of lesions. As expected, a course of acyclovir did not prevent later recurrences of the herpes virus infections. However, symptomatic recurrences were successfully suppressed during long (up to 65-day) courses of oral acyclovir.

Acyclovir↗
PubMed1981

INfluence of biotin supplementation on sow reproductive efficiency.

A herd of 116 sows was divided into two groups. Animals in one group had their food supplemented with 1160 micrograms/day of biotin in pregnancy and 2320 micrograms/day in lactation, over a 12-month period. The other group served as a control. Those receiving biotin farrowed significantly more live pigs in parities 2 and 4 than in the control animals; the increase in parity 3 only just failed to reach significance. There was no consistent effect on the weaning to service internal although a significant difference (P = 0.05) was seen with the third litters.

Animals↗
PubMed1981

Structure of varicella-zoster virus DNA.

Varicella-zoster virus (VZV) DNA was prepared from nucleocapsids and from enveloped virions of a laboratory strain (Ellen) and directly from the vesicle fluids of patients with zoster infections. VZV Ellen nucleocapsid DNA was cleaved with 11 different restriction endonucleases and electrophoresed in agarose gels. The restriction profiles of the nucleocapsid DNA were identical to those of the DNA recovered from purified virions, but differed from those of another VZV strain (KM). In vitro-labeled VZV K.M. DNA purified directly from vesicle fluid yielded a distinct restriction pattern which appeared to be unchanged after several tissue culture passages of the isolate from that fluid. Restriction endonuclease analysis (EcoRI or BglII) of VZV DNA revealed the presence of four cleavage fragments with a molar ratio of approximately 0.5. No individual fragments with molar ratios of 0.25 were noted. This observation suggests that the VZV genome may contain one invertible segment. Comparison of the electrophoretic migrations of VZV DNA fragments relative to those of DNAs of known size permitted calculation of the VZV genome size to be 72 X 10(6) to 80 X 10(6) daltons. These results were confirmed by electron microscopy which demonstrated a genome size of about 76 X 10(6) daltons for passaged and unpassaged VZV DNA. Electron microscopy also revealed that some of the DNA molecules recovered from nucleocapsids or directly from vesicle fluids were superhelical circles.

Base Composition↗
PubMed1980

Foot rot of pigs: the influence of biotin supplementation on foot lesions in sows.

A herd of 116 sows with a high frequency of foot lesions and lameness was divided into two groups, A and B. Group B was supplemented with 1160 microgram per day of biotin in pregnancy and 2320 microgram per day in lactation, over a 12-month period. No improvement occurred in the condition of the feet or skin. Gilts introduced as replacements to the herd were allocated alternately to the groups. Those receiving biotin (group B) showed significantly fewer lesions of heel erosion, white-line, heel bruising and "corn", and the severity and number of lesions of the lateral hind claws were also significantly improved.

Animals↗
PubMed1979

Cadmium, an effector in the synthesis of thionein.

Cadmium can elicit the synthesis of thionein in liver cells independent of tissue-organ interactions. The metal diffuses across the plasma membrane and is partitioned between subcellular components in a time dependent manner such that thionein synthesis responds to levels of nonspecifically and specifically bound cytoplasmic metal. Cadmium appears to function at the transcriptional level, and the metal may act to increase the pool of specific m-RNA's.

Animals↗