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Biomedical subjects

W O Thomas

Publications and source records attributed to W O Thomas.

At least 37 records · Page 2Linked to original sources

Irrigation of the abdominal cavity in the treatment of experimentally induced microbial peritonitis: efficacy of ozonated saline.

Ozone is an oxidizing agent possessing potent in vitro microbicidal capacity. This study was designed to address the extent to which irrigation of the contaminated abdominal cavity using a saline solution primed with ozone is effective in reducing morbidity and mortality. Gelatin capsules containing different quantities of a premixed slurry of filtered human fecal material were implanted in the peritoneal cavities of a preliminary series of rats. Three inocula concentrations were selected for later experiments, based upon their ability to produce morbid consequences: (1) high (100% 1-day mortality), (2) medium (70% 3-day mortality, 100% abscess rate in survivors), and (3) low (100% 10-day survival, 100% abscess rate). Fecal and abscess bacteriology were similar in all rats. The peritoneal cavities of 240 rats then underwent fecal-capsule implantation (three groups of 80 rats/inoculum concentration). At celiotomy 4 hours later, equal numbers of rats from each group were randomly assigned to one of four protocols: (1) no irrigation, (2) normal saline irrigation, (3) saline-cephalothin irrigation, and (4) ozonated saline irrigation. Each treatment lasted 5 minutes, using 100 ml of irrigation fluid. Mortality was significantly reduced when, in lieu of no irrigation, any of the irrigation solutions were used. Additionally, ozonated saline statistically proved the most effective irrigating solution for reducing abscess formation in survivors.

Abscess↗

Use of the biceps femoris following failed inferior gluteal flap transfer. Case report.

Considering the high recurrence rate of pressure ulceration in paraplegic patients, flap procedures to reconstruct a defect should not be at the expense of another possible future flap. The posterior thigh fasciocutaneous flap is useful for the coverage of ischial and trochanteric pressure sores; the biceps femoris musculocutaneous flap is a useful choice for deep ischial defects. However, the cutaneous portions of these two flaps is nearly identical. The previous transfer of the biceps flap excludes the further use of the posterior thigh flap. In contrast, use of the posterior thigh flap still permits the employment of a biceps V-Y advancement flap. Even if the donor site of the previous posterior thigh flap must be skin-grafted, the graft will remain viable on its muscular bed and function as the cutaneous portion of the flap; thus stable coverage is provided, despite previous use of 'first line' flaps. We demonstrate how careful planning of the stages of flap procedures can allow the most economic use of donor areas in this difficult patient group.

Adult↗

Ivermectin: a long-acting microfilaricidal agent.

Ivermectin is a macrocyclic lactone (fermentation) product and actinomycete (Streptomyces avermitilis) that possesses an unusually broad spectrum of potent activity against several species of nematodes, arachnids, and insects that parasitize domestic animals. From clinical trials in humans it has been found to be microfilaricidal, killing microfilariae of Onchocerca volvulus (the parasite causing onchocerciasis), and interrupting its transmission by the black fly vector. Dermal microfilariae density in patients are reduced to near zero levels for 6-12 months after a single oral dose of ivermectin 0.15-0.2 mg/kg. Its precise mechanism of action is unknown. It has a time to maximum concentration of 2.7-4.3 h, and an elimination half-life of 28 +/- 10 h. When compared with an oral solution the tablet dosage form has a relative bioavailability of approximately 60 percent. Not much is known about its metabolism in humans, and the unchanged drug is not detected in the urine. Controlled clinical trials have shown ivermectin to be associated with milder side effects than diethylcarbamazine, the current drug of choice for onchocerciasis therapy. It does not cause the severe Mazzoti-type (anaphylactoid) reactions that are associated with diethylcarbamazine use. Ivermectin is effective, safer, and more tolerable than diethylcarbamazine. It should, therefore, replace diethylcarbamazine as the drug of choice for onchocerciasis therapy.

Animals↗

Indications for placement of drains in the splenic fossa.

Drainage of the splenic fossa has for years remained a controversial issue. A large potential space exists in the left hypochondrium following splenectomy. Proponents of the use of drainage maintain that drainage is safe, efficacious in removal of blood, serum, and pancreatic enzymes, and carries little, if any, risk of subsequent infectious morbidity. Critics of the use of drainage cite the heretofore reported high incidence of subphrenic abscess formation in those patients in whom drains are placed as the reason for abandoning routine or therapeutic drainage of the splenic fossa.

Drainage↗

Determination of saliva: total plasma chloroquine levels relationship by high performance liquid chromatography.

The use of saliva chloroquine concentrations measurement as a noninvasive technique in the evaluation of the pharmacokinetics of the drug was investigated. Chloroquine concentrations in saliva and plasma were measured in eight healthy volunteers after a single oral dose of two tablets of chloroquine sulfate. The saliva: total plasma concentrations (S/P) ratio was found to be approximately constant in the absorption (0.4 +/- 0.07), distribution (0.47 +/- 0.08), and elimination (0.46 +/- 0.05) phases. Thus, saliva sampling for chloroquine concentrations was found to be a useful noninvasive technique for the estimation of all the pharmacokinetic parameters of the drug and hence, for chloroquine pharmacokinetic studies.

Adult↗

Pharmacokinetics of chloroquine and some of its metabolites in healthy volunteers: a single dose study.

Eight healthy volunteers who had not taken chloroquine 2 to 12 months previously participated in a single dose study designed to evaluate the pharmacokinetics of chloroquine and some of its metabolites. Each subject received two tablets of chloroquine sulfate (300 mg base) only. Blood and urine samples were collected just before and periodically after chloroquine administration. These samples were assayed for chloroquine and its N-dealkylated metabolites (monodesethylchloroquine, didesethylchloroquine, 7-chloro-4-aminoquinoline), chloroquine side chain N-oxide and chloroquine di-N-oxide using a high performance liquid chromatographic method. Residual levels of chloroquine and its N-oxidation metabolites were found in all subjects. 7-chloro-4-aminoquinoline was eliminated more slowly (t1/2z = 126.48 +/- 20.13 h) than the other metabolites and the unchanged drug (t1/2z = 106.43 +/- 10.13 h). Also, 7-chloro-4-aminoquinoline had a significantly faster (Student's t-test, P less than 0.05) formation clearance when compared with the other metabolites. The plasma concentration of 7-chloro-4-aminoquinoline was about twice that of the unchanged drug while the plasma concentration of monodesethylchloroquine was about 46% that of the unchanged drug. In order to investigate whether the metabolites were produced from the same binding sites or closely related sites on the cytochrome P-450 system, their formation clearances were correlated. The best correlation (r2 = 0.83) was observed for didesethylchloroquine and monodesethylchloroquine, and a fair correlation (r2 = 0.59) was observed for monodesethylchloroquine and 7-chloro-4-aminoquinoline. Formation clearances of the other metabolites were poorly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Peri-operative management of severe thyrotoxicosis with esmolol.

A case of severe thyrotoxicosis with cardiac decompensation is reported. Use of propranolol was followed by cardiovascular collapse. Esmolol, the beta-1 adrenoceptor blocking agent was successfully used to control the thyrotoxic state. A discussion of possible advantages of esmolol is provided.

Adrenergic beta-Antagonists↗

Detection and determination of salicylic acid impurity in aspirin tablet formulations' by high performance liquid chromatography.

Salicylic acid is a major hydrolytic degradation product of aspirin, responsible especially for gastric irritation during oral aspirin administration. This impurity was investigated in 12 different brands of aspirin formulation readily available in our locality. A simple, rapid and sensitive high performance liquid chromatographic method was adopted for this investigation. The mobile phase was methanol/water (20/80, v/v) adjusted to pH 2.5 with phosphoric acid and was run on a 50 mm reversed-phase column monitored at 240 nm. The limit of detection for salicylic acid was 5 ng. Only three of these formulations showed the presence of salicylic acid impurity and all these contained salicylic acid in excess of the USP 1980 limit of 0.3% salicylic acid per tablet.

Aspirin↗

Chloroquine-induced acute dystonic reactions in the presence of metronidazole.

A 30-year-old woman underwent laparotomy and was placed on a seven-day course of metronidazole and ampicillin postoperatively. Chloroquine therapy for malaria was instituted on the sixth day and the patient developed acute dystonic reactions after a single dose. Diphenhydramine therapy before chloroquine administration did not prevent the development of the dystonic reactions. The extrapyramidal symptoms subsided upon diazepam administration and chloroquine withdrawal even though metronidazole therapy was continued. The mechanism of this adverse drug reaction based on the pharmacodynamic interaction between chloroquine and metronidazole is discussed. It is suggested that the combination of pyrimethamine and sulfadoxine be used in place of chloroquine for malaria chemotherapy in patients on metronidazole therapy.

Adult↗

A retrospective analysis of inferior vena caval filtration for prevention of pulmonary embolization.

Inferior vena caval (IVC) filtration employing transvenous devices represents a substantive technologic advance in the management of patients with deep venous phlebothrombosis and pulmonary embolization. The retrospective analysis reported herein of the use of the Kim-Ray Greenfield IVC filter in 22 patients revealed a 95 per cent efficacy in its prevention of pulmonary embolization. The minor acute morbidity (9%) and chronic morbidity (27%) associated with use of the device was well tolerated by this patient population. No mortality attributable to the device was observed. The data suggest that the use of this device represented the best therapeutic option among those patients who were not candidates (18/22) or who had failed alternative therapeutic modalities (1/22) for the treatment of deep venous phlebothrombosis or pulmonary embolization. The data also suggest that use of the device in a prophylactic context (3/22) among those patients deemed at "high risk" for the development of deep venous phlebothrombosis and pulmonary embolization may be beneficial.

Adult↗

The energetics of the interaction of piroxicam with plasma albumin.

The thermodynamics of the binding of piroxicam to human and bovine plasma albumins revealed the reactions to be spontaneous and exothermic with bond strengths indicating the involvement of hydrogen and hydrophobic bonds. The association constants (K) decreased as temperature increased for both human serum albumin (HSA) and bovine serum albumin (BSA); and at all the temperatures in this study, K values obtained for BSA were higher (except at 36 degrees C) but not the bound fraction of piroxicam (beta) and the quantity of binding (V). Scatchard plots of the data indicated at least two classes of binding sites.

Animals↗

Chloroquine disposition in hypersensitive and non-hypersensitive subjects and its significance in chloroquine-induced pruritus.

Twenty-one healthy Nigerian volunteers distributed into four groups participated in a study to determine the significance of chloroquine disposition in chloroquine-induced pruritus. It involved the administration of chloroquine with or without promethazine pre-administration to the subjects. Group I consisted of 8 chloroquine non-hypersensitive subjects receiving 2 tablets of chloroquine sulphate (300 mg base); Group II consisted of 5 chloroquine non-hypersensitive subjects receiving 2 tablets of chloroquine sulphate 30 minutes after 25 mg promethazine tablet pre-administration; Group III consisted of 5 chloroquine hypersensitive subjects treated as in Group II; Group IV consisted of 3 hypersensitive subjects treated as in Group I. Blood (5 ml) and urine samples were collected periodically for up to 6 days post-dose. The samples were analysed for chloroquine and some of its oxidation metabolites by a specific HPLC method. Probit plots of cumulative drug/metabolite ratios were done to determine if there is polymorphism in chloroquine metabolism. There was bimodality only in the distribution of chloroquine/monodesethylchloroquine ratios, suggesting polymorphism in the metabolic oxidation of chloroquine in these subjects. Higher levels of monodesethylchloroquine were obtained in Group IV subjects when compared with any of the other groups. The oral clearance rate, elimination half-life, and volume distribution at steady state of chloroquine in the study groups were not significantly different (P greater than 0.05). In the absence of promethazine there appears to be an extensive metabolism of chloroquine in hypersensitive individuals to produce monodesethylchloroquine which probably determines the degree of pruritus experienced by an individual.

Adult↗