Choice of coronary heart disease risk factor variables in a cross-sectional study of white South Africans

This report explores the possibility of redefining risk factors so as to improve their observed associations with prevalent coronary heart disease (CHD). A large cross-sectional community study of 5,895 white males and females aged 25-64 years yielded 240 cases of confirmed angina pectoris and 361 of confirmed myocardial infarction. Odds ratios for CHD end-points by level of risk factors when risk factors were expressed in the conventional manner (e.g. total cholesterol, systolic and diastolic blood pressure or current smoking) were often low and not statistically significant. Redefinition of risk factor variables in a manner that improved their specificity or compensated to some extent for the decreased risk factor exposure as a result of a CHD event (e.g. stopping smoking after a myocardial infarct) improved the strength of association. In this study, the most useful cholesterol variable was total cholesterol minus high-density lipoprotein cholesterol; for blood pressure the most useful variable was a blood pressure of 160/95 mmHg or above and/or being on anti-hypertensive treatment; and for smoking the most useful variable was the total duration of smoking (previous and current). Strong associations with CHD end-points were also found for conventionally expressed serum uric acid, diabetes prevalence (females) and family history of CHD. The study suggests that appropriate redefinition of risk factor variables and CHD end-points in cross-sectional studies yields associations similar in strength and direction to those found in prospective studies.     

Recurrent hip dislocation in intermediate spinal atrophy

Recurrent hip dislocation after corrective orthopaedic surgery in children and teenagers with intermediate spinal atrophy has not been reported in the literature. Four cases with long-term follow-up are presented. These represent the only cases surgically treated in 30 years of following spinal atrophy patients. Thus, it seems significant that all hips redislocated after the surgical procedure. In addition, two patients had second operations with subsequent dislocation. Pelvic obliquity should not be the basis for the surgery, as spinal fusion is generally necessary for wheelchair users. The sagacity of performing surgery for hip dislocations is raised.     

The Relationship Between Quantitative MRI and Neuropsychological Functioning in Temporal Lobe Epilepsy

Summary: Purpose: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach. Methods: We examined the relationship between two MRI measures of hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy patients. Results: As a group, patients with left hippocampal sclerosis (LHS) performed more poorly that those with right hippocampal sclerosis (RHS) on immediate and delayed prose recall. In the group as a whole, right hippocampal volume was significantly correlated with the delayed recall of a complex figure. None of the verbal memory test scores were significantly correlated with the right or left HCvol or HCT2 measures. However, stepwise multiple regression analyses indicated that up to a third of the variation in specific test scores could be explained by the quantitative MRI hippocampal measures in conjunction with chronological age, and age at onset of habitual epilepsy. Left hippocampal measures explained 24% of the variance in the story-recall tasks, while right hippocampal measures explained 18% of the variance in a design-learning task and 32% of the variance in a figure-recall task. Conclusions: Our results provide some support for the lateralised model of material specific memory deficits, but suggest that a number of demographic and epilepsy-related factors may interact with the extent and laterality of hippocampal pathology in shaping the nature of the associated neuropsychological deficit.     

Synthesis and pharmacological evaluation of a series of dibenzo[a,d]cycloalkenimines as N-methyl-D-aspartate antagonists.

A series of 73 dibenzo[a,d]cycloalkenimines were synthesized and evaluated for their ability to displace (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]-(+)-10) from its specific binding site on rat cortical membranes. A number of the more active compounds (Ki ranging from 0.006 to 0.21 microM) were evaluated for N-methyl-D-aspartate (NMDA) antagonist activity in the rat cortical slice (Kb ranging from 0.08 to 0.9 microM) and anticonvulsant activity in the mouse against NMDA induced convulsions. The ED50 values ranged from 0.22 to 7.76 mg/kg and correlated reasonably well with the Kb determination. In the dibenzo[a,d]cyclohepten-5,10-imine series, the (+)-5S,10R enantiomer displayed consistently higher levels of biological activity. While substitution at the 3-position of (+)-10 with electronegative atoms generally increased in vitro activity, a loss of potency relative to (+)-10 (MK-801) was observed in vivo for all of the compounds tested.     

Islet cell carcinomas of the pancreas: a twenty-year experience

Unlike its lethal exocrine counterpart, islet cell carcinoma of the pancreas is an indolent neuroendocrine neoplasm. The majority of these tumors are hormonally active. When functioning, a number of clinical syndromes (for example, hyperinsulinism, Zollinger-Ellison and Cushing's syndromes) may be evident. Fifty-eight patients surgically treated between 1965 and 1984 were retrospectively analyzed. The purpose of this study was to determine the distribution of functioning versus nonfunctioning tumors and the response to type of therapy. Mean postoperative follow-up was 7.4 years. Survival and prognostic indices were calculated by the Kaplan-Meier method and compared with log-rank tests. Of the group, 54% had functioning and 46% nonfunctioning tumors. Gastrinomas were the most common functioning tumors encountered (19%). Of interest was the finding that nonfunctioning tumors increased steadily during the last 15 years of the study (25% to 65%). Curative resections were performed in 15 (26%) and noncurative procedures in 43 patients (74%), with an overall operative mortality rate of 3%. Symptomatic improvement was achieved in 90% (curative) and 51% (noncurative). Survival at 3 years was 87% and 66% for the curative and noncurative groups, respectively (p less than 0.1), with an overall 5-year survival of 42%. The absence of hepatic metastases was a major predictor of survival at 3 years (82% vs 56%, p less than 0.05). Survival was statistically better at 3 years in those patients with gastrinomas compared with patients with nonfunctioning tumors (91% vs 58%, p less than 0.05). Although surgical cure is rare, significant long-term palliation may be achieved in a large percentage of patients with an aggressive surgical approach, occasional total gastrectomy, combination chemotherapy, H2 blockade, when indicated, and, most recently, with the new long-acting analogue of somatostatin.     

Deliberating about Bioethics

In some sense, bioethics was built on conflicts. Abortion, physician-assisted suicide, patients’ demand for autonomy all are staple and contentious issues. And the controversies continue to proliferate. What forum best serves such debates? A look at political theories of democracy can help answer that question. The most promising for bioethics debates are theories that ask citizens and officials to justify any demands for collective action by giving reasons that can be accepted by those who are bound by the action. This conception has come to be known as deliberative democracy.     

Additive interactions of calcitonin gene-related peptide and calcitonin on pancreatic exocrine function in conscious dogs

By convention, establishing a physiologic role for a gut peptide requires demonstration of biologic activity that can be reproduced by exogenous administration of the peptide in amounts that yield plasma concentrations that are not higher than those found after a meal. We have tested the hypothesis that the combined action of two inhibitory peptides may lower the effective doses of each. We further hypothesize that combined peptide responses may be responsible for the action of peptide hormones that have been difficult to demonstrate as physiologically relevant mediators, when examined as independently acting substances. In conscious dogs prepared with chronic pancreatic cannulas, stimulated pancreatic exocrine secretions were depressed in a dose-related manner by intravenous infusions of calcitonin (CT) and calcitonin gene-related peptide (CGRP). Doses of 2.0 nmol/kg/hr of both CT and CGRP yielded maximal inhibition of stimulated secretions of both bicarbonate (greater than 85% inhibition) and protein (greater than 55% inhibition). The lowest effective dose for either CT or CGRP, given alone, was 0.75 nmol/kg/hr, but when infused simultaneously, each at the subthreshold dose of 0.50 nmol/kg/hr, significant inhibition of protein and bicarbonate secretion was achieved. Combined infusions of the submaximal dose of 0.75 nmol/kg/hr resulted in an enhanced inhibitory response. To prove that this effect is not simply combined activation of a common receptor, we tested peptide YY (0.1 to 0.5 nmol/kg/hr) combined with CGRP and obtained similar results. Because a meal simultaneously releases a large number of active peptides, we speculate that such potentiated responses do occur physiologically. Cooperative interaction with other agents may be the primary mode of action for certain gut peptides.     

Varicose vein surgery using a pneumatic tourniquet: reduced blood loss and improved cosmesis.

A prospective controlled randomised study has been performed of 100 consecutive patients undergoing varicose vein surgery. One group underwent saphenofemoral flush ligation and multiple lower leg avulsions with the leg exsanguinated with a Rhys-Davies cuff, and ischaemia maintained with a pneumatic tourniquet. The other group underwent identical surgery but with a 30 degree head down tilt only. Blood loss was significantly less (13.5 +/- 12 ml vs 133 +/- 78 ml; P less than 0.01) and postoperative cosmesis was significantly improved in patients in the tourniquet group. Operating time was similar (27 +/- 11 min vs 30 +/- 13 min) in the two groups.     

Carbon Monoxide Mass Exposure in a Pediatric Population

Abstract. Objectives:To describe the outcomes of a mass carbon monoxide (CO) intoxication, and to calculate the CO half-life in a pediatric school-aged population.
Methods:A retrospective chart review was performed based on Regional Poison Center database information, hospital laboratory data, and medical records of the pediatric patients who sought care at one of 3 St. Louis area hospitals, after exposure to high levels of CO. Exposures occurred on January 5, 1996, after evidence of a CO leak was discovered at an area elementary school. Charts were reviewed for major demographics, symptoms reported, carboxyhemoglobin (COHb) levels and times, and level of effect.
Results:Information about 177 (35%) of the 504 children in attendance at school that day was available. Mean age was 8.7 ± 1.8 years (range 4–12 years). Symptoms were present in 155 (88%) of the 177 children for whom data were available. Initial COHb levels were obtained for 147 (83.1%) of the 177 children. First mean COHb level was 7.0% (95% CI = 6.6–7.5%). Second COHb level was obtained for 26 children with a mean of 2.7% (95% CI = 2.2–3.2%). Calculated half-life of COHb, on 100% 0₂ at 1 atm, was 44.0 minutes (95% CI = 39.6–48.2 minutes).
Conclusion:Some children had symptoms at COHb levels that traditionally have been considered nontoxic. The elimination of COHb was found to be more rapid in this population of children than reported in other studies.     

Stricture and perforation of the esophagus: Overlooked threats in the Zollinger-Ellison syndrome

This study was undertaken to assess the frequency of significant esophageal involvement in the Zollinger-Ellison syndrome (ZES). In a consecutive series of 24 patients with this disease, 9 (37%) showed endoscopic evidence of acid-induced esophageal lesions ranging from erosive inflammation to ulceration with massive bleeding, severe stricture formation, and perforation. In 3 cases, pronounced esophagitis was known 1–5 years before the underlying disease was diagnosed. Severe esophageal complications developed despite treatment with antisecretory drugs. It is emphasized that the best way to limit such complications is by excision of the underlying gastrin-secreting tumor(s) when possible.

---

Resumen El presente estudio fue emprendido con el propósito de determinar la frecuencia de afección ácido péptica significativa del esófago en pacientes con síndrome de Zollinger-Ellison. En una serie de 24 pacientes consecutivos con esta enfermedad, 9 (37%) exhibieron evidencia endoscópica de lesiones esofágicas inducidas por ácido, las cuales variaron entre inflamación erosiva y ulceración con sangrado masivo, estrechez severa, y perforación. En 3 pacientes se conocía la existencia de esofagitis severa entre 1 y 5 años antes del diagnóstico de la enfermedad de base. Se desarrollaron graves complicaciones esofágicas a pesar del tratamiento con drogas antisecretorias en 3 pacientes. Se hace enfasis en que la mejor manera de disminuir tales complicaciones es mediante la resección del tumor(es) secretor de gastrina, cuando ello sea posible.

---

Résumé Nous avons entrepris cette étude pour établir la fréquence de participation oesophagienne dans le syndrome de Zollinger-Ellison. Pour une série de 24 patients présentant cette maladie, 9 (37%) avaient à l'endoscopie des lésions oesophagiennes dues à l'acidité allant de l'érosion inflammatoire à l'ulcération avec saignement important, sténose sévère, et perforation. Dans 3 cas, une oesophagite importante était connue 1–5 ans avant que la maladie sous-jacente soit diagnostiquée. Des complications oesophagiennes sévères se sont produites malgré le traitement antisécrétoire. Nous insistons sur le fait que le meilleur moyen de limiter ces complications est d'exciser chaque fois que possible la ou les tumeurs sous-jacentes sécrétant la gastrine.

---

---

Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989.

---

Supported by grants from the Swedish Medical Research Council, the Swedish Society of Medicine, the Anders Otto Swärd Foundation, and the Surgery Foundation of Skövde Central Hospital.