Resolution of Diabetes Following Vertical Gastroplasty in Morbidly Obese Patients

Case reports are presented on three patients treated for morbid obesity by vertical gastroplasty. Prior to surgery the patients had diabetes which required insulin, up to 200 units per day, or oral hypoglycaemics for its control. Six months after surgery the diabetes had been resolved in all three patients, and they were no longer dependent on medication. Subjective reports from the patients suggests that their quality of life improved significantly.     

Biochemical Changes after Vertical Banded Gastroplasty for Morbid Obesity

A prospective study of biochemical changes after vertical banded gastroplasty for morbid obesity, in 94 patients (10 males and 84 females, ages ranging from 18 to 59 years) has been carried out. Liver function tests and electrolyte estimations were performed preoperatively, during hospitalisation for surgery, at 6 weeks and at 6 months postoperatively, and demonstrated no significant changes in liver function in these patients 6 months after surgery. The study concludes that there is no increase in the risk of liver damage or electrolyte disturbance after vertical gastroplasty, but that there may be subtle hepatic changes present as gall bladder disease developed in 18 patients postoperation (19%).     

Pharmacokinetics and pharmacodynamics of prolonged oral etoposide in women with metastatic breast cancer

The pharmacokinetics and pharmacodynamics of prolonged oral etoposide chemotherapy were investigated in 15 women with metastatic breast cancer who received oral etoposide 100 mg as a single daily dose for up to 15 days. There was considerable interpatient variability in the day 1 pharmacokinetic parameters: area under the plasma concentration time curve (AUC) (0–24 h) 1.95±0.87 mg/ml per min (mean ± SD), apparent oral clearance 60.9±21.7 ml/min per 1.73 m², peak plasma concentration 5.6±2.5 g/ml, time to peak concentration 73±35 min and half-life 220±83 min. However, intrapatient variability in systemic exposure to etoposide was much less with repeated doses. The intrapatient coefficient of variation (CV) of AUC for day 8 relative to day 1 was 20% and for day 15 relative to day 1 was 15%, compared to the day 1 interpatient CV of 45%. Neutropenia was the principal toxicity. Day 1 pharmacokinetic parameters were related to the percentage decrease in absolute neutrophil count using the sigmoidal E_max equation. A good fit was found between day 1 AUC and neutrophil toxicity (R ²=0.77). All patients who had a day 1 AUC>2.0 mg/ml per min had WHO grade III or IV neutropenia. The predictive performance of the models for neutrophil toxicity was better for AUC (percentage mean predictive error 5%, percentage root mean square error 18.1%) than apparent oral clearance, peak plasma concentration, or daily dose (mg/m²). A limited sampling strategy was developed to predict AUC using a linear regression model incorporating a patient effect. Data sets were divided into training and test sets. The AUC could be estimated using a model utilizing plasma etoposide concentration at only two time points, 4 h and 6 h after oral dosing (R ²=98.9%). The equation AUC_pr=–0.376+0.631×C_4h+0.336×C_6h was validated on the test set with a relative mean predictive error of –0.88% and relative root mean square error of 6.4%. These results suggest monitoring of AUC to predict subsequent myelosuppression as a strategy for future trials with oral etoposide.Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Locked Bag 1, A'Beckett St, Melbourne 3000, Australia     

Students conducting consultations in general practice and the acceptability to patients

OBJECTIVES: The General Medical Council has recommended that medical students should gain more experience in general practice. The study set out to determine patients' reactions to consultations conducted by a medical student alone prior to seeing their GP. DESIGN: A random sample of patients attending general practice surgeries in the Oxford area completed a questionnaire following consultation with a medical student. SETTING: Six general practice teaching surgeries. SUBJECTS: Fifth-year medical students. RESULTS: Of 130 responders 98% experienced no disadvantage in seeing the student; 35% considered that there were advantages in seeing the student; 98% said that they would be prepared to consult with a student again; 85% expressed no concerns about the gender of the student. CONCLUSIONS: The results of this study are very reassuring concerning the acceptability to patients of consulting with medical students and are more favourable than those reported for studies of students being present in consultations by GPs.     

Collagen production by human smooth muscle cells isolated during intestinal organogenesis

Summary The extracellular matrix influences organogenesis by modulating cell behavior. In humans, collagen is the major matrix constituent of the adult intestinal wall and is synthesized by smooth muscle cells. The objective of the current study was to examine collagen production by fetal human intestinal smooth muscle cells isolated during intestinal morphogenesis. Techniques were developed for the isolation and culture of human fetal intestinal smooth muscle cells. The cultured cells were confirmed as muscle by immunohistochemical stains for cytoskeletal filaments and documentation of contractile behavior. In culture, these cells stained for mesenchymal and muscle cytoskeletal proteins: vimentin, actin, and desmin, and did not stain for neural or epithelial markers. The muscle cells contracted in response to acetylcholine, in contrast to human fetal dermal fibroblasts which did not contract appreciably. Collagen production was assayed by the uptake of [³H]-proline into collagenase-digestible protein. Collagen production was greatest at 11 weeks gestation, the youngest age studied. By 20 weeks gestation, collagen production had decreased to adult levels. However, when compared to another matrix-producing fetal mesenchymal cell, the dermal fibroblast, intestinal smooth muscle cells produced twice as much collagen. Collagen types were determined by polyacrylamide slab gel electrophoresis. Smooth muscle cells predominantly produced types I and III collagen chains. Therefore, collagen production is a significant function of human fetal intestinal smooth muscle cells, and probably plays a major role in the development of intestinal structure. The in vitro model presented here provides a means of studying the regulation of this collagen production throughout intestinal organogenesis.     

Scopolamine Effects on Visual Information Processing, Attention, and Event-Related Potential Map Latencies

We measured performance and event-related brain potential (ERP) map latencies in 12 subjects during four visual discrimination tasks to compare the timing of scopolamine effects on information processing and attention. "Topographic component recognition" found ERP map latencies at times of best fit with a component model map. This "common topography" criterion minimized topographic differences among conditions to facilitate latency interpretations. Scopolamine slowed N1 latency in all tasks, and P3 and reaction time in some tasks. The drug delayed responses to easy targets more than to hard targets. It also induced a disproportionate N1 delay for unilateral high spatial frequency gratings. Both effects reflect a scopolamine-induced impairment when processing targets that usually capture attention. Scopolamine also impaired accuracy for unilateral high spatial frequency gratings, and for gratings presented at probable locations, confirming and extending previous findings. Scopolamine-induced P1 and N1 delays showed that visual processing was affected. Several results were inconsistent with a serial stage model. We suggest that scopolamine both delays selected processes and impairs a processing mode based on automatic capture of attention, inducing more serial processing.     

The effect of the nitric oxide donor glyceryl trinitrate on global and regional cerebral blood flow in man

Despite their potential use as cerebral vasodilatory agents there are few studies of the effect of nitric oxide (NO) donors on the cerebral circulation in non-anaesthetised man. We determined the effect of the NO donor glyceryl trinitrate (GTN) at clinically relevant doses on global and regional cerebral blood flow (CBF) in healthy non-anaesthetised volunteers, using H(2)(15)O PET, ultrasonic colour velocity flow imaging of carotid artery flow, and transcranial Doppler (TCD) of middle cerebral artery velocities (MCAv). Three rates of GTN infusion (0.1, 0.4, 1.0 microg/kg/min) were used. There was no significant change in common or internal carotid artery flow following GTN administration although a dose dependent fall in MCAv post GTN was observed. There was no significant change in either global or regional CBF following GTN. Thus intravenous GTN at therapeutic doses in awake humans does not alter global or regional CBF. However it does produce basal cerebral artery vasodilatation as evidenced by a fall in MCAv in the absence of a change in internal carotid artery flow.