Influences of a future corporate health system on medical education

Corporate attention to problems in health care delivery has grown over the last decade. As this focus by the "purchasers" of medical care increases business and industry influence on health policy decisions, significant changes may come about in the delivery system, and eventually in medical education. Whether the evolving corporate design for health care best serves consumer interests is less clear than how the medical profession and medical educators will fare in the next twenty years.     

β-Adrenoceptors and resistance to stress: old problems and new possibilities

The commentators suggest that our approach may be too limited to account for many of the factors which influence stress-related behaviour, yet too general to help us interpret the neurochemical coding of behavioural responses to stress. In our reply we argue that the strategy described in our Critique both confronts the issues discussed in the Commentaries and is more objective and rigorous than approaches used currently.     

The Rationale and Results of Gastroplasty/Distal Gastric Bypass

A recent review of the results of gastroplasties done at the University of Alberta Hospital showed that there was a high incidence of late weight loss failure. Therefore a new operation, gastroplasty/distal gastric bypass, has been performed on 263 patients. This operation results in a profound (mean greatest percentage excess weight loss of 87% at approximately 2 years) and lasting weight loss (mean final percentage excess weight loss of 78%) at 4 years, range 2-7.5 years post-operatively. Only 0.9% of patients failed to maintain at least a 40% excess weight loss. The operation achieves its effect through a moderate restriction that permits patients to eat normal table food from the time of discharge and with a mild malabsorption that is not ordinarily associated with diarrhea or notable deficiencies. Certain patients required debanding of the stoma and others developed staple-line eventration. Neither of these events after long-term follow-up resulted in weight loss failure nor in other serious side-effects. It is concluded that moderate failure of the gastroplasty stoma and staple line does not necessarily result in weight loss failure, because the malabsorptive portion of the operation remains intact. Low hemoglobin occurred in 16% of cases and deficiency of serum iron in 34%; a much smaller number of patients had chronic or intermittent deficiencies of these entities. Correction was easily achieved with oral replacement. Deficiencies in albumin, calcium, phosphorus and folate were rarely seen and minimal elevation of serum AST values occurred in just over 1% of patients. Chronic deficiencies or elevations were not seen in these patients. Stomal ulcer occurred in 6% of patients and bleeding associated with stomal ulcer in 1%. Half the patients with ulcer were managed with H₂ blockers, the other half with vagotomy. Both forms of treatment when individualized effectively prevent re-ulceration.     

Marrow regeneration after mechanical depletion

The origin of marrow regeneration after mechanical depletion was reinvestigated in mouse chimeras. The results were compatible with the local origin of stem cells from remnants of incompletely removed marrow, but not with their origin from a common precursor of both bone and hemopoietic cell lines. In transplanted femurs depleted by a modified technique of in vivo evacuation of marrow, hemopoietic regeneration failed to occur. The presence of hemopoietic stem cells in the Haversian canals was thus excluded. The demonstration of ample hemopoiesis with minimal bone formation in nondepleted controls in which bone marrow initially became necrotic provided new evidence that osteogenesis was not a prerequisite of hemopoietic regeneration.     

Voxel-based analysis of confounding effects of age and dementia severity on cerebral metabolism in Alzheimer's disease

Alzheimer's disease is characterized by early hippocampal lesions, but neuropathological and functional imaging studies have also demonstrated involvement of associative cortices in patients suffering from this illness. New image-processing technologies have led to demonstration of predominant posteromedial cortical metabolic impairment in the disease. Confounding effects of both age and dementia severity on brain metabolism were assessed using categorical and correlational analyses performed with Statistical Parametric Mapping. Posterior cingulate and precuneus metabolism, assessed by positron emission tomography, was significantly correlated with age in a population of 46 patients with probable Alzheimer's disease. Metabolism in posterior cingulate and precuneus was higher in elderly than in younger patients with a diagnosis of Alzheimer's disease, even when dementia severity was taken as a confounding covariate. The data suggest that the sensitivity of positron emission tomography for the diagnosis of Alzheimer's disease is reduced in elderly cases, where less severe pathology is sufficient to induce clinical symptoms of dementia. Conversely, higher posteromedial metabolic impairment in early onset cases may reflect greater density of regional cerebral lesions or major decrease of functional afferences in a richly connected multimodal associative area. Posterior cingulate metabolism was also correlated to dementia severity, even when age was taken as a confounding covariate, whereas metabolism in the hippocampal formation was not shown to correlate with global cognitive deficit. Functional correlation was maintained between posterior cingulate and middle frontal cortex in demented patients as in elderly controls. The key role of posteromedial cortex in cognitive dysfunction assessed in Alzheimer's disease is probably related to its highly integrated position within attentional, visuospatial and memory neuronal networks.     

Safe retrieval of impacted central venous line.

Embolisation of impacted central venous lines is not uncommon in paediatric practice. We describe a method of preventing this complication and associated risks.     

Characterization of gastrin-induced proangiogenic effects in vivo in orthotopic U373 experimental human glioblastomas and in vitro in human umbilical vein endothelial cells.

PURPOSE: This study aims to investigate the role of gastrin-17 (G17) on angiogenesis features in gliomas both in vitro and in vivo. EXPERIMENTAL DESIGN: The influences of G17 and G17 receptor antagonists were characterized in vitro in terms of angiogenesis on human umbilical vein endothelial cell (HUVEC) tubulogenesis processes on Matrigel and in vivo with respect to U373 orthotopic glioma xenografts. The influence of phosphatidylinositol 3'-kinase, protein kinase C, and nuclear factor-kappaB inhibitors was characterized in vitro on G17-mediated HUVEC tubulogenesis. G17-mediated release of interleukin (IL)-8 from HUVECs and G17-induced modifications in nuclear factor-kappaB DNA binding activity were characterized by means of specific enzyme-linked immunosorbent assays. The influence of G17 on E- and P-selectin expression was determined by means of computer-assisted microscopy, whereas the influence of E- and P-selectin on HUVEC migration was approached by means of antisense oligonucleotides. The chemotactic influence of G17 and IL-8 on HUVEC migration was characterized by means of computer-assisted videomicroscopy with Dunn chambers. RESULTS: Messenger RNAs for cholecystokinin (CCK)A, CCKB, and CCKC receptors were present in HUVECs and microvessels dissected from a human glioblastoma. Whereas G17 significantly increased the levels of angiogenesis in vivo in the U373 experimental glioma model and in vitro in the HUVECs, the CCKB receptor antagonist L365,260 significantly counteracted the G17-mediated proangiogenic effects. G17 chemoattracted HUVECs, whereas IL-8 failed to do so. IL-8 receptor alpha (CXCR1) and IL-8 receptor beta (CXCR2) mRNAs were not detected in these endothelial cells. Gastrin significantly (but only transiently) decreased the level of expression of E-selectin, but not P-selectin, whereas IL-8 increased the expression of E-selectin. Specific antisense oligonucleotides against E- and P-selectin significantly decreased HUVEC tubulogenesis processes in vitro on Matrigel. CONCLUSIONS: The present study shows that gastrin has marked proangiogenic effects in vivo on experimental gliomas and in vitro on HUVECs. This effect depends in part on the level of E-selectin activation, but not on IL-8 expression/release by HUVECs.     

Relationship of mammographic parenchymal patterns to breast cancer risk factors and smoking in Alaska Native women.

The purpose is to determine breast cancer risk factors and correlates of mammographic parenchymal patterns among Alaska Native women. A retrospective review was performed of mammograms and mammogram records among 528 sequential screening mammogram examinations performed in Anchorage, Alaska. Mammogram density was classified by American College of Radiology (Breast Imaging Reporting and Data System) density patterns 1-4 (fat-->dense) and by percent density. Clinical data, including risk factors, ethnic group (Indian, Aleut, or Eskimo), and smoking status were obtained. Results were analyzed by univariate and multivariate analyses. Of 528 women, 164 were Indian, 155 were Aleut, and 209 were Eskimo. Mean age at first birth was lower and parity higher compared with published data in white women. Breast cancer risk factors were similar across ethnic groups. In multivariate analysis, patient age, parity, hormone replacement therapy, hysterectomy, and history of biopsy were associated, and smoking was not associated with density scores. Aleut and Indian women were less likely to have high-density mammograms than were Eskimo women (P = 0.0448). No significant differences were found between ethnic group for conventional breast cancer risk factors. Mammogram density was associated with age at screening, parity, hormone replacement therapy, hysterectomy, history of biopsy, and ethnicity but not smoking status. Eskimo women had higher mammogram density than Aleuts or Indians.