Biomedical subjects
Publications and source records attributed to J G Allen.
Factors contributing to clinical recommendations for length of hospitalization for children and adolescents were investigated. Diagnosis, chronicity, severity of symptoms, response to prior treatment, and family resources were found to relate strongly to length-of-stay recommendations. Guidelines representing the consensus of experienced clinicians are proposed.
A lupinosis-associated myopathy occurred in 26 of 48 sheep given a crude toxic extract of Phomopsis leptostromiformis, and in 18 of 34 sheep that grazed a toxic lupin stubble. Treatment with selenium or alpha-tocopherol alone neither prevented nor cured the myopathy, but selenium and alpha-tocopherol together may have been partially effective. Among the group of 48 intoxicated sheep, those with myopathy had a significantly lower mean terminal concentration of alpha-tocopherol in their livers than those with no myopathy. There was no relationship between the severity of liver injury and the occurrence of the myopathy. It was considered that this lupinosis-associated myopathy may have a similar pathogenesis to nutritional myopathy. Data on plasma creatine phosphokinase and erythrocyte glutathione peroxidase activities, plasma alpha-tocopherol concentrations and terminal tissue concentrations of selenium and alpha-tocopherol are presented.
1. The pharmacokinetics of ticlopidine, a novel antithrombotic agent, have been investigated in 10 healthy volunteers dosed orally with the drug (250 mg 12 hourly for 21 days), to determine the basic pharmacokinetic parameters in humans, to investigate its accumulation during repeated administration, and to assess its effects on hepatic drug-metabolizing enzymes. 2. After the first dose, peak plasma concentrations (median 0.31, range 0.08-0.80 mg/l) were generally found at 2 h. The levels decreased rapidly to a median concentration of 0.087 mg/l by 4 h then declined to 0.022 (range less than 0.005-0.128) mg/l at 12 h after administration, with apparent half-lives of approx. 4 h. The median AUC value for this first dosage interval (AUC tau) was 0.97 (range 0.41-3.49) mg h l-1. 3. Pre-dose plasma concentrations indicated that steady state was reached after 5-10 days, and then remained essentially unchanged through to the end of the study. From 30 h after the final dose, drug levels declined exponentially with a median half-life of 28.8 (range less than or equal to 20-50) h. 4. Following the final dose, the median peak concentration and AUC tau were 0.99 (range 0.22-2.12) mg/l and 4.06 (range 0.90-15.2) mg h l-1 respectively. Based on AUC values, the mean accumulation factor +/- SD was 3.73 +/- 1.14. 5. The metabolic status of subjects was assessed by administration of single doses of antipyrine (700 mg orally) 7 days before the first dose of ticlopidine and 2 days after the final dose. Treatment with ticlopidine decreased antipyrine clearance, demonstrating that it inhibited drug-metabolizing enzymes. Significant correlations (r2 = 0.84, p less than 0.01) were found between the AUC values for ticlopidine and antipyrine, indicating that the interindividual variation in the pharmacokinetics of ticlopidine are explained by differences in metabolic clearance.
Formulating master treatment plans for the hospital treatment of psychiatric patients is especially challenging to psychodynamically oriented clinicians unaccustomed to reducing complex intrapsychic and interpersonal phenomena to specific observable behaviors. In collaboration with a wide cross section of hospital staff members, the authors developed a conceptual framework for treatment plans compatible with psychodynamic thinking. They describe the treatment evaluation research from which the format of the treatment plan evolved, as well as the guide they developed to facilitate its implementation .
Twenty-eight patients (median gestational age 17 weeks) referred for induction of second trimester abortion, were randomized to intracervical preliminary treatment by either 50 mg 17 beta-oestradiol or placebo. Abortion was then induced by 1 mg prostaglandin E1 vagitories. The preliminary treatment caused a significant rise in cervical score and a significant reduction in induction-abortion time especially by reducing the number of patients with prolonged induction-abortion time.
We report the case of a young man undergoing fixation of bilateral mandibular fractures, where the anaesthetist was unable to intubate. A Brain laryngeal mask was employed, thus enabling surgery to proceed. This relatively new device enabled the airway to be safeguarded whilst preserving reasonable surgical access for the attachment of Erich arch bars and a four hole osteosynthetic bone plate. The surgical and anaesthetic procedures are summarised. The laryngeal mask is described and its performance and limitations are discussed. We believe this to be the first report of mandibular fracture fixation performed with a Brain laryngeal mask in situ.
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The toxicities of up to four different toxic preparations containing metabolites of Phomopsis leptostromiformis were examined in two experiments with sheep and one with rats. It was shown that the different toxic preparations containing similar amounts of phomopsin A varied substantially in toxicity. Crystalline phomopsin A was the least toxic. It is suggested that the increased toxicity of the other three preparations was due to the presence of toxic metabolites additional to phomopsins A and B. Evidence to support this suggestion is presented.
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The authors developed scales to assess long-term hospital patients' collaboration in milieu treatment and their working relationships with various staff members. A factor analysis of patients' ratings of their collaboration in several areas of treatment yielded three dimensions: Goal Orientation, Involvement, and Use of Structure. While each dimension of collaboration correlated positively with working relationships and progress, Goal Orientation was the most substantial contributor. Patients' and staff members' perceptions of their working relationships corresponded to a statistically significant-but modest-degree. Only nurses' ratings of progress related significantly to patients' ratings. The authors highlight divergent perceptions of the treatment process, and advocate that different perspectives be openly discussed and clarified in the service of improved collaboration.
The authors draw attention to the problems of establishing and maintaining a therapeutic alliance in the psychotherapy of the borderline patient. They elaborate an extensive methodology designed to study the manner in which shifts in collaboration occur in response to therapist interventions. This report demonstrates how one particular borderline patient increased his ability to collaborate with the therapist in response to a transference focus in the psychotherapy. Methodological problems are noted as are directions for future research. Only a series of patients studied with this or with similar methodology will allow for a sophisticated and empirical rationale for choosing a particular form of psychotherapy for a particular kind of borderline patient.
Fifteen lupin stubble samples were tested for toxicity using a sheep bioassay and a chemical assay. A good association, in the functional form of a quadratic equation, existed between the results provided by the two assays. Only 16% of the variance of the chemical assay results was not associated with the sheep bioassay results.
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Twelve young and twelve elderly subjects received a single dose orally of midazolam 15 mg, nitrazepam 5 mg and placebo in a double-blind, crossover comparison. Midazolam acted rapidly, producing a deep sleep at 1 h in fifteen subjects compared to two after Nitrazepam and none after placebo. No comparison of psychomotor tests was possible at this time, but such tests showed that there was no detectable subjective or objective psychomotor impairment at 4 h postdose with either drug. However, the EEG scores strongly suggested that volunteers were more sleepy at 8 h after nitrazepam in comparison to placebo or midazolam. Both groups appeared to handle the drug in a similar manner, there being no significant differences between the groups in the plasma concentration time curves of nitrazepam, or midazolam. The elderly had higher concentrations of alpha-hydroxymidazolam. This accounted for a small proportion of the total plasma benzodiazepine concentration, and the mean area under the curve for midazolam and metabolite was not significantly different in the old from that in the young.
Pharmacokinetic studies in parkinsonian patients and healthy volunteers have shown that Madopar HBS behaves as a slow-release formulation of L-dopa and benserazide. In comparison with standard Madopar the rate of absorption is reduced, providing lower peak concentrations of L-dopa. The drug is released and absorbed over a period of 4-5 h, thus maintaining substantial plasma concentrations for 6-8 h after dosing. Although the bioavailability after oral dosing is reduced as compared with standard Madopar (60-70%), this difference seems to be due to incomplete absorption rather than altered disposition of the drug. The presence or absence of food in the stomach has no effect on the absorption of L-dopa from Madopar HBS, but administration of antacids further reduces the bioavailability (45%).
1. The clearance and elimination half-lives for i.v. doses of antipyrine were determined in 6 groups of 6 male CD rats with no prior treatment, then again following 7 days treatment with graded oral doses of midazolam, and finally after 3 i.p. doses of phenobarbitone. 2. Substantial increases in clearance and decreases in half-lives were observed following phenobarbitone treatment, demonstrating that antipyrine provides a reliable index of enzyme induction. 3. After treatment with midazolam, maximal induction was seen in animals dosed at 27 or 80 mg/kg per day; an intermediate effect was found with 9 mg/kg per day and no effect at 0.2 and 1.0 mg/kg per day. 4. The results indicate that there is a substantial margin of safety between the proposed human therapeutic doses (7.5 to 15 mg/day) and the minimum effective dose that leads to enzyme induction in laboratory animals.