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Biomedical subjects

A T White

Publications and source records attributed to A T White.

30 records · Page 2Linked to original sources
PubMed1988

Histological examination of onchocercomata after therapy with ivermectin.

During chemotherapy trials in hyperendemic onchocerciasis areas in West Africa 15 adult nodule carriers in Liberia and 24 patients in Mali received single doses of ivermectin (150 or 200 micrograms/kg). Nodules were extirpated two, six and ten months after therapy and examined histologically. No macrofilaricidal effect of ivermectin was observed. Two months after therapy, in 93% of all female worms with intrauterine stretched microfilariae nearly all microfilariae were degenerated. The percentage was lower after ten months but still significantly higher than in untreated control groups. Ivermectin did not cause degeneration of the intrauterine coiled microfilariae. But the percentage of the female worms with coiled microfilariae was significantly lower two and ten months after therapy than that in the placebo or untreated control groups. Correspondingly, the percentage of nodules with intact microfilariae in the nodule tissue was also significantly lower throughout the examination period than that of the untreated control groups. There was not observed any effect on the spermatogenesis and spermatozoa were found frequently in the uteri of female worms. Using the method of histology, the long lasting inhibitory effect of a single dose of ivermectin on the intrauterine production of microfilariae could clearly be demonstrated. This proves the value of histology for the assessment of drug effects on adult O. volvulus.

Animals↗
PubMed1988

Chemotherapy of onchocerciasis with high doses of diethylcarbamazine or a single dose of ivermectin: microfilaria levels and side effects.

Fifty adult male subjects with moderate to heavy onchocerciasis from the Liberian rain forest were selected for a double-blind placebo-controlled chemotherapy study. The effects of high doses of diethylcarbamazine (DEC) - 30 mg/kg/d - over one week preceded by a one week initial treatment with normal oral doses of DEC or DEC lotion were compared with a single dose of ivermectin (150 micrograms/kg) and placebo. During the initial treatment DEC tablets or lotion caused distinctly more frequent and severe reactions than did invermectin. The reactions to ivermectin did not differ from those of the placebo patients. High doses of DEC caused, in about half of the patients, headache, dizziness, nausea or vomiting. DEC markedly increased the number of corneal microfilariae and of corneal opacities compared to ivermectin. All changes resolved with a return to pretreatment findings two months after treatment. The three treatment groups showed no differences at the ten months follow-up. In all treated patients skin microfilaria counts fell almost to zero by the end of the two week therapy. In the ivermectin group microfilaria counts remained significantly lower than in the DEC patients at the two and ten months examinations. In summary, ivermectin was much better tolerated than DEC and had a longer lasting effect on the microfilariae in the skin. Since high doses of DEC were less effective and caused more frequent and severe side effects, this approach cannot be recommended for treatment of onchocerciasis.

Adult↗
PubMed1987

An investigation of age-related factors in the age-job-satisfaction relationship.

Most researchers have found a positive linear relation between age and job satisfaction. We attempted to account for this relationship by measuring variables that had been proposed to be causal factors. Subjects were 496 city and county managers working in Florida. Potential explanatory variables were (a) job congruence (the difference between what managers prefer and what they perceive they have in a job), (b) internal-external locus of control, and (c) related demographics-age, salary, organizational tenure, position tenure, and organizational level. Multiple regression analyses found that job congruence and work locus of control accounted for almost all of the variance in the age-satisfaction relationship. This study supports the job change hypothesis, which proposes tha older workers get more of what they want out of work.

Adult↗
PubMed1987

Controlled trial and dose-finding study of ivermectin for treatment of onchocerciasis.

Ivermectin, given as a single oral dose, has shown considerable promise as a new treatment for onchocerciasis. We assessed the safety and efficacy of ivermectin and tried to determine the optimal dose. Two hundred Liberians received 100, 150, or 200 micrograms of ivermectin/kg or placebo and were followed up for 12 months. Therapy was associated with only minimal systemic and ocular side effects. A 200-micrograms/kg dose was associated with greater systemic reaction than was a 100-micrograms/kg dose. Each treatment group had significant reduction in skin microfilaria counts by day 3 and a decrease of approximately 95% at three months. At three months the proportion of persons with no microfilariae in a specimen of skin was significantly less in the 100-micrograms/kg group than in the 150-micrograms/kg or 200-micrograms/kg groups. At 12 months, the level of microfilariae in skin was still reduced approximately 80%. Significant reduction in ocular involvement was seen in all groups. These results confirm that single-dose ivermectin is effective and well-tolerated and suggest that 150 micrograms of ivermectin/kg may be the optimal dose for initial therapy.

Clinical Trials as Topic↗
PubMed1987

Ivermectin effect on microfilariae of Onchocerca volvulus after a single oral dose in humans.

Ivermectin is a broad spectrum anti-helminthic agent which is currently being tested for use in human onchocerciasis. Its activity is believed to result from its effect on GABA-mediated neurotransmission. We examined the effects of ivermectin on motility of microfilariae of O. volvulus following administration to humans. When ivermectin was given in dosages of 100, 150 and 200 mcg/kg on day 1 there was a clear reduction in motility of microfilariae obtained on day 3 when compared to microfilariae from the placebo group. The mean motility scores in microfilariae from ivermectin recipients were 3.1, 2.3, and 2.2 at 0, 12, and 24 hours of incubation compared to 3.3, 2.9, and 2.5, respectively, in microfilariae from placebo recipients (p less than 0.003, p less than 0.005, and p less than 0.012, respectively). Examination of the effect according to dose suggested a dose-response relationship. Microfilariae in the anterior chamber of the eye 2 days after a single oral dose of ivermectin showed abnormal and reduced winding and coiling. Microfilariae in 50% of ivermectin recipients showed abnormal motility compared to no such effects in subjects examined concurrently who received oral DEC, DEC lotion or placebo. These observations indicate that ivermectin has an effect on motility of microfilariae of O. volvulus following administration to humans.

Animals↗
PubMed1987

Sensitivity of skin snips in the diagnosis of onchocerciasis.

To find the optimum number and combination of skin snips for the diagnosis of onchocerciasis, data of six skin snips (two shoulder, two hip, two calf) taken from 776 Liberians aged 12 to 60 years were examined. From these data, proportions of positive skin snips from the hip, or hip and calf areas, for different levels of skin microfilaria density were calculated. These proportions were used in a mathematical model that examined 20 hypothetical populations with different levels of endemicity and skin microfilaria densities. The sensitivity of using two or four snips was then estimated. If only two snips were taken, two hip snips had the highest sensitivity (ranging from 80.7% to 100% according to the population). When the microfilaria density was high, the addition of two extra snips from the calf did not significantly improve the sensitivity. However, when the microfilaria density was low, the combination of two hip and two calf snips substantially improved the sensitivity (ranging from 80.7% to 94%). If fewer than six skin snips are desired for a particular field study, the choice of how many skin snips to be taken should be based on the expected precision required for that study. This in turn can be determined by skin microfilaria density. If such information is lacking, an estimate can be made from the findings of six snips from a small sample.

Adolescent↗
PubMed1986

Treatment of onchocerciasis. The ocular effects of ivermectin and diethylcarbamazine.

The ocular changes that occur with diethylcarbamazine treatment of onchocerciasis seriously restrict its usefulness. Ivermectin, a newly developed antifilarial drug, was compared with diethylcarbamazine for treatment of onchocerciasis in a double-masked, placebo-controlled trial. Thirty men with moderate to severe infection and ocular involvement were randomly assigned to receive ivermectin as a single oral dose (200 micrograms/kg), diethylcarbamazine (administered for eight days), or placebo. Detailed ocular examinations were performed serially over a 12-month period. Diethylcarbamazine treatment caused a marked increase in living and dead microfilariae in the cornea, punctate opacities, and limbitis during the first week of therapy. Ivermectin had no such effect. However, ivermectin therapy resulted in a long-term reduction in intraocular microfilariae comparable to that seen with diethylcarbamazine. Ivermectin appears to have few ocular complications and be a better-tolerated and more effective microfilaricidal agent than diethylcarbamazine for the treatment of onchocerciasis.

Adult↗
PubMed1985

Comparison of ivermectin and diethylcarbamazine in the treatment of onchocerciasis.

We compared ivermectin with diethylcarbamazine for the treatment of onchocerciasis in a double-blind, placebo-controlled trial. Thirty men with moderate to heavy infection and ocular involvement were randomly assigned to receive ivermectin in a single oral dose (200 micrograms per kilogram of body weight), diethylcarbamazine daily for eight days, or placebo. Diethylcarbamazine caused a significantly more severe systemic reaction than ivermectin (P less than 0.001), whereas the reaction to ivermectin did not differ from the reaction to placebo. Diethylcarbamazine markedly increased the number of punctate opacities in the eye (P less than 0.001), as well as the number of dead and living microfilariae in the cornea over the first week of therapy. Ivermectin had no such effect. Both ivermectin and diethylcarbamazine promptly reduced skin microfilaria counts, but only in the ivermectin group did counts remain significantly lower (P less than 0.005) than in the placebo group at the end of six months of observation. Analysis of adult worms isolated from nodules obtained two months after the start of therapy showed no effect of either drug on viability. Ivermectin appears to be a better tolerated, safer, and more effective microfilaricidal agent than diethylcarbamazine for the treatment of onchocerciasis.

Adult↗
PubMed1981

Study on the dehydrating effect of the red cell Na+/K+-pump in nystatin-treated cells with varying Na+ and water contents.

Using the antibiotic Nystatin, we have developed a systematic method for the preparation of red blood cells with independently selected levels of intracellular Na+ concentrations and water content. Such cells provided an experimental model to study the effect of Na+/K+ pump stimulation on red cell water content. Even in initially dehydrated cells, stimulation of the Na+/K+ pump by elevated intracellular Na+ caused subsequent further loss of cell water. Cell water loss was reflected in decreased monovalent cation content per unit mass of hemoglobin and by a shift in the density distribution of the cell populations to higher densities on discontinuous Stractan gradients. We conclude that the 3 Na+out : 2 K+in stoichiometry of the Na+/K+ pump results in a net desalting effect with increased pump activity. Under the conditions of these experiments, the cell appears to have no effective mechanism to compensate for a net loss of ions and water.

Adenosine Triphosphate↗
PubMed1980

Sequence organization of cloned intracisternal A particle genes.

Seven recombinant DNA clones containing mouse intracisternal A particle genes were isolated and analyzed by restriction enzyme digestion, Southern blot analysis and heteroduplex mapping. The sequence organization of the individual genes was found to differ, with one end of the gene region being most variable, while a central segment of 1.8 kb was missing from two of the clones. A third region, common to all the clones and containing the 3' end of the gene, is present in about 1800 copies per haploid genome, but the central portion is found in only 650 copies. The same reiteration frequency is found in both myeloma tumor and mouse liver DNA. The most abundant intracisternal A particle RNA in two different myeloma lines was found to be 3.5 kb, and RNA/DNA hybrids show that the RNA is homologous to all but a small internal segment of one of the clones.

Animals↗
PubMed1979

Morphine-induced behavioral disruption in rats chronically depleted of brain dopamine.

The ability of rats, chronically depleted of brain dopamine (DA), to develop tolerance to morphine (120 mg/kg, s.c.) given twice daily was studied using a food-reinforced operant procedure (FR-10). DA was depleted via the administration of 6-OHDA (150 ug, ict.) and desmethylimipramine (DMI; 25 mg/kg, ip.) to rats 14 days of age. This procedure resulted in a 61% depletion of brain DA when these rats were 120 days of age, while norepinephrine levels were not significantly affected. The response rates of DA-depleted and vehicle (ict.) + DMI treated controls were equally suppressed by various acute doses of morphine, but the DA-depleted group appeared to develop tolerance to the higher morphine dosage regimen (120 mg/kg, b.i.d) faster than the control group. In addition, DA-depleted rats exhibited a greater suppression of response rates 24 hr after the cessation of morphine treatment.

Animals↗