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Biomedical subjects

R A Buchanan

Publications and source records attributed to R A Buchanan.

At least 37 records · Page 2Linked to original sources
PubMed1983

Methsuximide for complex partial seizures: efficacy, toxicity, clinical pharmacology, and drug interactions.

Methsuximide (MSM; Celontin) was administered for 8 weeks to 26 patients with complex partial seizures (CPS) refractory to phenytoin and carbamazepine and phenobarbital or primidone. A 50% or greater reduction in CPS frequency was obtained in eight patients. MSM therapy was continued chronically in these eight patients, and five continued to have a 50% or greater reduction in CPS frequency after 3 to 34 months of follow-up. Drowsiness, gastrointestinal disturbance, hiccups, irritability, and headache were the common side effects of MSM. No serious toxicity occurred. N-desmethylmethsuximide was the principal substance detected in plasma and had the following pharmacokinetic values: accumulation half-life, 49.7 hours; time to steady state, 10.4 days; elimination half-life, 72.2 hours; therapeutic range of plasma concentration, 10 to 30 mg per liter. Plasma concentrations of phenytoin and phenobarbital derived from primidone rose significantly (p less than 0.05) after addition of MSM.

Adult↗
PubMed1982

Light and electron microscopy of liver in hyperlipoproteinemic patients under long-term gemfibrozil treatment.

The effects of long-term gemfibrozil (Lopid) therapy on human liver structure are not known. Studies of this nature are becoming essential in determining the risk/benefit ratio since gemfibrozil is an effective agent for the control of hyperlipoproteinemia types IIa, IIb, and IV. Particularly, gemfibrozil is effective when dietary management or available therapeutic control fail to reduce serum cholesterol and triglycerides as well as normalizing the lipoprotein pattern. Percutaneous liver biopsies of 9 patients on long-term gemfibrozil therapy were evaluated by light microscopy, interference contrast optics and transmission electron microscopy. The distribution of patients according to lipoprotein phenotype was 3 Type IIa, 3 Type IIb, and 3 Type IV. Their lipoprotein patterns approached normal and the serum lipids were controlled during gemfibrozil therapy. By light microscopy, the lobular architecture and other parameters were within normal limits. Varying degrees of fatty change were found as would be expected. No preferential lobular disposition of the fat globules was evident. Coalescence of fat droplets, nuclear displacement and fatty cysts were noted. Differential interference contrast microscopy revealed several degrees of contrast amplitude in these droplets suggesting a heterogeneous lipid deposition in hepatocytes. The subcellular analysis revealed a moderate degree of glycogen deposition, absence of nuclear abnormalities and unremarkable mitochondria; the rough endoplasmic reticulum was not significantly altered and smooth surfaced membranes appeared proliferated. Detailed analysis of the peroxisome population showed matrix rarefaction, marginal plate formation and spurious densities though no significant proliferation occurred. Distribution of peroxisomes in hepatocytes varied widely from cell to cell and in different lobular areas. This study confirmed the association of hepatic fatty change with hyperlipoproteinemia irrespective of the pattern observed in circulating lipoproteins. Peroxisome proliferation, as seen in rodents when receiving gemfibrozil, did not occur and the structure of these subcellular organelles was not compromised. It was concluded that the long-term administration of this compound did not show adverse effects on the hepatocyte in hyperlipoproteinemia.

Gemfibrozil↗
PubMed1982

Phenytoin metabolism in subjects with long and short plasma half-lives.

Normal adult men with long and short phenytoin plasma half-lives were given 300-mg oral doses of phenytoin once daily for 15 days. Plasma levels of phenytoin (DPH) and its major metabolite (p-HPPH) were measured during the period of drug administration and for 5 days thereafter. Average steady-state plasma levels of DPH rose to 13.4 micrograms/ml in the long half-life group, compared with 3.6 micrograms/ml in the short half-life group. HPPH levels in the long half-life group were about one half of those observed in the short half-life group. The DPH/HPPH ratios in plasma specimens showed excellent correlation with the plasma half-lives of DPH and average steady-state levels, suggesting that this ratio could provide guidance in the selection of optimum dosage regimens for problem patients.

Adult↗
PubMed1981

Investigations on the galvanic corrosion of multialloy total hip prostheses.

Total hip prostheses combining cobalt and titanium alloys in direct physical contact are currently being used. The purpose of this paper was to investigate the possibility of an accelerated corrosion occurring due to the coupling of these alloys. Electrochemical corrosion studies based on mixed potential and protection potential theories were used to study the in vitro effects of coupling the titanium and cobalt alloys. Verification of these studies was made by direct coupling experiments. Macroscopic examination of' surface features of four retrieved total hip prostheses ranging from 0-6 years implantation were conducted. The electrochemical studies predicted coupled corrosion potentials of -0.22 V and low coupled corrosion rates of 0.02 microA/cm2. Direct coupling experiments verified these results. Cobalt-titanium interfaces on the implants were macroscopically examined, and no instances of extensive corrosion were found. Overall, the in vitro corrosion studies and the examination of retrieved prostheses predicted no exaggerated in vivo corrosion due to the coupling of these cobalt and titanium alloys.

Alloys↗
PubMed1981

Methsuximide for refractory complex partial seizures.

The efficacy and safety of methsuximide were evaluated for 12 weeks in 21 patients with complex partial (psychomotor) seizures refractory to conventional anticonvulsants. After addition of methsuximide to the previous anticonvulsant regimens, the number of complex partial seizures per patient decreased from a weekly average of 5.8 to 0.9 seizures. A 90 to 100% control of complex partial seizures was achieved in 15 (71%) of the patients. Dose reduction or discontinuation of one or more previous medications was possible in 42%. Seizure control was optimal at methsuximide doses of 9.5 to 11.0 mg per kilogram per day and plasma levels of 20 to 24 micrograms per milliliter. Adverse experiences, particularly somnolence and lethargy, were reported by 12 patients. Methsuximide appeared to be an effective and generally well tolerated adjunct medication in the management of complex partial seizures.

Adolescent↗
PubMed1980

Plasma levels and urinary excretion of vidarabine after repeated dosing.

Vidarabine (Vira-A) was given intravenously for 5 days to 5 immunosuppressed patients with herpes zoster. The daily dose, 10 mg/kg, was given by slow infusion over 12 hr. Blood samples were taken at 0, 1, 2, 4, 8, and 12 hr on days 1, 3, and 5. Twenty-four-hour urine specimens were collected before treatment and on days 1, 3, and 5. Blood and urine specimens were assayed for vidarabine and its principal metabolite, hypoxanthine arabinoside (ara-Hx), by high pressure liquid chromatography. The results showed that vidarabine is quickly deaminated; virtually all of the drug present in the plasma and urine was in the form of ara-Hx. The highest plasma level, approximately 3 microgram/ml, was at the end of the infusion period. The urinary excretion of ara-Hx accounted for between 40% and 50% of the dose. The renal clearance values varied, but were close to the expected glomerular filtration rate of 125 ml/min. The plasma levels and the excretion levels were much the same on days 1, 3, and 5, indicating that drug did not cumulate. The results of the study were consistent with those observed in single-dose studies. The results indicated that the infusion of vidarabine is clinically appropriate, since therapeutic plasma levels are reached promptly, drug is rapidly excreted, and there is no cumulation.

Biotransformation↗
PubMed1980

Pharmacology, tolerance, and antiviral activity of vidarabine monophosphate in humans.

Vidarabine (adenine arabinoside) is a purine nucleoside useful in humans for therapy of herpes simplex virus encephalitis and herpes zoster virus infections in immunocompromised patients. However, the potential usefulness of vidaribine is limited by its poor solubility, which requires continuous infusion in relatively large volumes of intravenous fluid. Vidarabine 5'-monophosphate is highly soluble and has the advantage that it can be administered intermittently intramuscularly or intravenously. In a clinical, pharmacokinetic study, plasma levels and urinary excretion of vidarabine 5'-monophosphate were determined after intravenous and intramuscular administration in 29 immunosuppressed patients with herpes simplex or zoster virus infections at dosages of 15 to 30 mg/kg per day administered for 5 days. As determined by high-pressure liquid chromatography, vidarabine 5'-monophosphate was metabolized in a fashion comparable to the metabolism of vidarabine and its major metabolite in plasma was arabinosyl hypoxanthine. After administration, 40 to 50% of the vidarabine 5'-monophosphate was recovered from the urine as arabinosyl hypoxanthine, and 3 to 4% was recovered as vidarabine. Determinations of areas under the curve for arabinosyl hypoxanthine were not statistically different by dosage for intramuscular or intravenous routes of administration. At all dosages studied, viral clearance appeared to occur with therapy. The advantage of increased solubility will lead to controlled clinical investigations in which vidarabine 5'-monophosphate is administered by intramuscular or intravenous routes against targeted human herpesvirus infections.

Antiviral Agents↗
PubMed1979

In vitro corrosion of Ti-6Al-4V and type 316L stainless steel when galvanically coupled with carbon.

In vitro corrosion experiments were conducted employing potentiostatic polarization techniques, a saline environment and candidate biomaterial alloy/carbon combinations. Corrosion currents and potentials of carbon/metal couples were predicted by mixed-potential theory utilizing the polarization curves generated. The alloys examined were annealed ELI grade Ti-6A1-4V and cold-worked 316L stainless steel while the types of carbon examined were LTI pyrolytic carbon and vapor-deposited carbon. It was determined that galvanic couples of carbon to cold-worked 316L stainless steel with carbon/metal area ratios of 10:1 to 100:1 produced coupled corrosion potentials in the range of the observed breakdown potential of the stainless steel. It was therefore predicted that localized corrosion in the form of pitting could occur on the cold-worked stainless steel when coupled to carbon with area ratios of 10:1 or greater. The titanium alloy did not exhibit a breakdown potential up to a potential of 1.2 V. Therefore, accelerated corrosion was not predicted for the titanium alloy to carbon galvanic couples under these experimental conditions. Direct carbon/alloy coupling experiments were conducted to verify the corrosion currents and potentials predicted from mixed-potential theory and polarization curve analysis. The experimental and theoretical values showed good agreement.

Alloys↗
PubMed1979

A clinical trial of topically applied 3 percent vidarabine against recurrent herpes labialis.

Seventy-six participants were enrolled in a clinical trial to determine therapeutic effectiveness of 3 percent vidarabine applied topically to recurrent perioral herpetic lesions. Following a 6- to- 12-month natural history phase, a 12-month clinical trial was conducted. Seventy participants developed 463 lesions during 361 episodes. Three percent vidarabine in a water-miscible gel was applied six times daily for 7 days to each lesion in the experimental group. Identically packaged placebo was used by the control group. Group assignment was by computer-generated randomization. Lesion size was reduced when vidarabine, rather than placebo, was applied. The difference was statistically significant (Student's t test, P = 0.02). Vesiculation followed tingling more rapidly when vidarabine, rather than placebo, was applied prior to vesiculation (P = 0.05). No significant difference between the two groups was found in episode frequency or lesion duration. Adverse reactions to vidarabine were not experienced.

Administration, Topical↗
PubMed1976

Ethosuximide dosage regimens.

A study was conducted in 9 children with petit mal epilepsy to compare the plasma levels of ethosuximide after divided daily administration with those after single daily administration. The children received their previously established dose in divided doses for 4 wk, single morning doses for 4 wk, and again in divided doses for 4 wk. None of the children suffered petit mal seizures during the study. Three had grand mal seizures but the frequency did not differ between the dosage regimens. Plasma levels during the single-dose period peaked more rapidly and fell more quickly than during the other periods, but mean levels remained in the therapeutic range. The mean half-life of the drug in these children was 29 hr. For reasons not understood, plasma levels generally were lower in the second divided dose period than in the other two periods. No adverse experiences were reported during the study. The data indicate that ethosuximide is clinically effective when given in a single daily dose. This regimen offers advantages in convenience and possibly in patient compliance.

Adolescent↗
PubMed1976

A clinical study for the control of facial mucocutaneous herpes virus infections. I. Characterization of natural history in a professional school population.

One thousand thirty-one dental and dental hygiene students, faculty and staff at The University of Michigan School of Dentistry were interviewed in order to identify those with a past history of perioral mucocutaneous herpetic infection. Subsequently, the population was followed for 9 (+/- 3) months in order to determine various parameters of disease expression. Analysis of the results indicate the following: 1. In this professional population, 20.5 per cent described prior experience with perioral herpes. No sex difference was noted. 2. Prevalence increased with age. In the faculty-staff group (mean age 32.9 years +/ 11.8) prevalence was 30.7 per cent, whereas in the student -roup (mean age, io.6 years+/- 3.8) prevalence was 17.7 per cent. Occupational and/or socioeconomic factors did not appear to account for the age-related difference in prevalence. 3. Only 40 per cent of those who related prior disease experience developed lesions within the observation period of 9 (+/-3) months. 4. The recurrence rate, based upon an observation period of 9 (+/-3) months, in those persons who related prior disease experience was found to be 1.3 episodes per year (0.1 per month). 5. Duration of lesions ranged between 3 and 17 days, with a mean of 9 days. 6. The lower lip was the most common site of a lesion. 7. Triggering factors associated with development of a lesion in order of decreasing frequency were found to be; emotional stress, exposure to sun, and illness.

Adult↗
PubMed1976

Myocardial infarction in patients less than 45 years old: acute course, angiographic findings, and long-term follow-up.

The clinical courses of 57 patients who had an acute myocardial infarction when less than 45 years of age were reviewed to identify descriptors which might be useful in selecting candidates for coronary artery surgery. Follow-up for the subgroup of 45 patients seen initially with acute myocardial infarction was 98% (44/45) complete. Those patients referred to the medical center because of complications for specifically for coronary artery surgery following recent infarction were not followed. Average duration of follow-up for survivors without coronary surgery was 45 months and ranged from 10 to 105 months. The hospital mortality for the above group was 16% (7/45). During the follow-up period, 11% (4/37) died, 51% (19/37) had angina, 19% (7/37) had congestive heart failure, 51% (19/37) returned to work, and only 43% (16/37) remained asymptomatic. Angiographic assessment of coronary artery lesions by the Friesinger method indicated moderately severe disease in these young patients. Multiple regression analysis did not reveal a reliable predictor of hospital or late death or subsequent morbidity.

Acute Disease↗
PubMed1975

Treatment of variola major with adenine arabinoside.

A double-blind study of the efficacy of adenine arabinoside in the treatment of patients with variola major was conducted. Adenine arabinoside (20 mg/kg of body weight) was given to patients intravenously every 24 hr for seven days in a 8-hr infusion. Five of the nine patients receiving adinine arabinoside died, and four of 11 patients receiving placebo died. Mortality was related to the severity of illness for both groups of patients. No difference was found between the drug and control groups in number of febrile days after initiation of therapy or in the period during which it was possible to isolate virus from skin lisions, throat swabs, and sources of clotted blood. Formation of scabs on skin lesions was complete 8.3 days after the initiation of therapy for the drug group and after 11.3 days for the control group. The findings suggest that adenine arabinoside is not effective in the chemotherapy of smallpox.

Adenine↗
PubMed1975

Treatment of varicella-zoster virus infections with adenine arabinoside.

Twenty-three patients with complicated varicella-zoster virus infections were treated with adenine arabinoside. Of 14 patients with herpes zoster, 13 had malignancy treated with irradiation and cytotoxic agents or steroids. Although the duration of active vesicle formation in these patients ranged from two to 14 days before therapy, no new lesions appeared after the fourth day of treatment with adenine arabinoside. Zoster encephalitis developed in one patient on the third day of treatment, and severe postherpetic neuralgia was seen in three patients. Of nine treated patients with primary varicella, six improved, including five with evidence of varicella pneumonia. Two of the three patients with varicella who died were immunosuppressed and had progressive viral pneumonia with persistently high titers of virus in vesicular fluid; the third pateint was a child with Reye's syndrome. Double-blind controlled studies will be necessary to demonstrate the efficacy of adenine arabinoside in the treatment of infections with varicella-zoster virus.

Adult↗