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.     

Blood flow acceleration in the carotid and brachial arteries of healthy volunteers: respective contributions of cardiac performance and local resistance

Summary— The influence of local resistance and cardiac performance on peripheral blood acceleration was investigated in 14 healthy male volunteers. Steady and pulsatile flow was studied in the brachial and in the common carotid arteries, ie, two territories that exhibit marked differences in resistive characteristics. Instantaneous blood velocity (V), mean blood velocity (V_m) and artery diameter (D) were evaluated at rest by an ultrasonic range-gated pulsed Doppler flowmeter using a double transducer probe, thus allowing the calculation of mean blood flow (Q). Mean local resistance (R) was obtained by dividing the mean arterial pressure by Q. The peak value of the local acceleration of the blood was obtained by computer-assisted calculation of the first derivative of instantaneous blood velocity (G_max = +dV/dt_max). Peak aortic blood acceleration (GAo) was simultaneously measured from the suprasternal notch using a pulsed Doppler velocity meter. In the brachial and the common carotid arteries, G_max was of a similar magnitude (551 ±30 and 555 ± 44 cm/s², respectively) despite major differences in the respective D, V_m, Q and R values. In neither artery was there a relationship between G_max and either resting Q or R. At the brachial artery level, G_max was positively related to GAo ( r = 0.79, P = 0.0008). At the common carotid artery level, there was a weak, although non significant relationship between G_max and GAo ( P = 0.08). Our results indicate that the local acceleration of peripheral blood flow in the brachial artery is related rather to upstream central impulse than to downstream hemodynamics, and suggest some regional differences in the hemodynamic determinants of the local acceleration of peripheral blood flow.     

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.

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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.

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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.

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

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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.     

The biology of breast tumor progression. Acquisition of hormone independence and resistance to cytotoxic drugs.

Many breast tumors appear to follow a predictable clinical pattern, being initially responsive to endocrine therapy and to cytotoxic chemotherapy but ultimately exhibiting a phenotype resistant to both modalities. Using the MCF-7 human breast cancer cell line as an example of an 'early' phenotype (estrogen and progesterone receptor positive, steroid responsive, low metastatic potential), we have isolated and characterized a series of hormone-independent but hormone-responsive variants (MIII and MCF7/LCC1). However, these variants remain responsive to both antiestrogens and cytotoxic drugs (methotrexate and colchicine). MIII and MCF7/LCC1 cells appear to mimic some of the critical aspects of the early progression to a more aggressive phenotype. An examination of the phenotype of these cells suggests that some hormone-independent breast cancer cells are derived from hormone-dependent parental cells. The development of a hormone-independent phenotype can arise independently of acquisition of a cytotoxic drug resistant phenotype.