Effect of preoperative supplementation with alpha-tocopherol and ascorbic acid on myocardial injury in patients undergoing cardiac operations

Augmentation of antioxidant defenses may help protect tissues against ischemia-reperfusion injury associated with operations involving cardiopulmonary bypass. In this study we examined the effect of pretreating patients with alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C) or placebo on injury to the myocardium. Seventy-six subjects undergoing elective coronary artery bypass grafting participated in a prospective, double-blind, placebo-controlled randomized trial, receiving either placebo or both 750 IU dl-alpha-tocopherol per day for 7 to 10 days and 1 gm ascorbic acid 12 hours before the operation. Plasma alpha-tocopherol concentrations, raised fourfold by supplementation, fell by 70% after the operation in the supplemented group and to negligible levels in the placebo group. There were no significant differences between the groups with respect to release of creatine kinase MB isoenzyme over 72 hours, nor in the reduction of the myocardial perfusion defect determined by thallium 201 uptake. Electrocardiography provided no evidence of a benefit from antioxidant supplementation. Thus the supplementation regimen prevented the depletion of the primary lipid soluble antioxidant in plasma, but provided no measurable reduction in myocardial injury after the operation.     

Risk factors for a medically inappropriate admission to a Department of Internal Medicine

OBJECTIVE: To identify patient- and admission-related risk factors for a medically inappropriate admission to a department of internal medicine. METHODS: Cross-sectional study of a systematic sample of 500 admissions to the department of internal medicine of an urban teaching hospital. The appropriateness of each admission and reasons for inappropriate admissions were assessed using the Appropriateness Evaluation Protocol. Risk factors included the time (day of week and holidays) and manner (through emergency department or direct admission) of admission, patient age and sex, health status of patient and spouse, living arrangements, formal home care services, and informal support from family or friends. RESULTS: Overall, 76 (15.2%) hospital admissions were rated as medically inappropriate by the Appropriateness Evaluation Protocol. In multivariate analysis, the likelihood of an inappropriate admission was increased by better physical functioning of the patient (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1-2.1 [for 1 SD in Physical Functioning scores]), lower mental health status of the patient's spouse (OR, 2.6; 95% CI, 1.3-5.6), receipt of informal help from family or friends (OR, 3.3; 95% CI, 1.5-7.2), and hospitalization by one's physician (OR, 3.6; 95% CI, 1.7-7.5). Receiving formal adult home care was not associated with inappropriateness of hospitalization. CONCLUSIONS: Inappropriate admissions to internal medicine wards are determined by a mix of factors, including the patient's health and social environment. In addition, the private practitioners' discretionary ability to hospitalize their patients directly may also favor medically inappropriate admissions.     

Cervical disk disease and the keyhole foraminotomy: proven efficacy at extended long-term follow up

Eighty-four consecutive patients with posterolateral cervical disk herniation treated by keyhole foraminotomy between 1980 and 1987 were reviewed. Radicular pain was the most common presenting complaint. Weakness was present in 59 patients. Sixty patients were available for long-term follow up, averaging 6.1 years. Fifty-six patients' results were graded as excellent. Three patients had good results and one fair result was noted. There were no poor results. Preoperative pain symptoms were relieved in all patients. There were no significant complications. The posterolateral keyhole foraminotomy is an efficient means of decompressing lateral soft disk herniations, without the risk of an anterior approach or iliac crest bone harvest. Careful patient selection and use of an operative microscope are essential in obtaining consistent, excellent results.     

Bioethics in the medical subspecialty literature

The high affinity growth hormone-binding protein (GHBP) circulates in human blood and represents the extracellular domain of the growth hormone (GH) receptor. It is well known that repetitive bouts of endurance type exercise result in increased integrated GH secretion. As the effects of chronic exercise on plasma GHBP levels have never been studied systematically, we investigated the effect of 2 weeks of intense endurance training on plasma GHBP as well as on plasma insulin-like growth factor (IGF)-I levels in 10 healthy, young, non-obese men. IGF-I was measured as an indicator of the effects of GH release. We also studied 10 control subjects matched for sex, age and activity, who were instructed not to change their customary activities. GHBP was determined by FPLC size exclusion chromatography and subsequent Scatchard plot analysis of the binding data; IGF-I levels were measured by RIA. The results showed that plasma IGF-I and GHBP levels were increased in the subjects who followed the training program. IGF-I and GHBP changed from 252 +/- 56 ng/ml and 912 +/- 59 pmol/l before training, to 344 +/- 61 ng/ml (p < 0.01) and 1020 +/- 48 pmol/l (p < 0.01), respectively. Another effect of the training was that the aerobic capacity of these subjects was better utilized and endurance was improved. In contrast, plasma IGF-I, GHBP, utilization of aerobic capacity and endurance did not change significantly in the control subjects. We conclude that two weeks of strenuous endurance training lead to increased plasma IGF-I and high affinity GHBP levels.     

Neuropathology of bovine herpesvirus type 5 (BHV-5) meningo-encephalitis in a rabbit seizure model

CI-994 (acetyldinaline) is an orally active anticancer drug currently in Phase 1 clinical trials. To assess its preclinical toxicity, CI-994 was administered orally as suspensions to Wistar rats (10/sex/dose) and in capsules to beagle dogs (3/sex/dose) once daily for two weeks. Doses were 1.5, 5, and 15 mg/kg for rats (9, 30, and 90 mg/m2, respectively), and 0.5, 2, and 5 mg/kg for dogs (10, 40, and 100 mg/m2, respectively). Systemic exposure was dose-proportional based on toxicokinetic analysis in dogs. Severe clinical signs and mortality occurred at the highest dose in both species beginning on Day 10. Neutropenia, lymphocytopenia, thrombocytopenia, lymphoid depletion, bone marrow hypocellularity, and testicular degeneration were observed in both species, primarily at the mid- and high-doses. Despite continued treatment, neutrophil counts in dogs returned to control levels in Week 2. Other microscopic findings in rats included splenic hematopoietic depletion at all doses and epithelial cell necrosis in various tissues at 15 mg/kg. Additional bone marrow changes in dogs involved myeloid and megakaryocyte hyperplasia at 2 mg/kg and abnormal myeloid and megakaryocyte maturation at 2 and 5 mg/kg. Except for the testicular effects in both species, all changes were reversible within a 4-week (rat) or 9-week (dog) recovery period. The results of these studies show that target organ effects of CI-994 principally involve tissues with rapidly dividing cell populations and that bone marrow suppression is the dose-limiting toxicity. CI-994 also seems to interfere with the release and/or maturation of cells in the bone marrow.     

Plastic changes in the cholinergic innervation of the rat cerebral cortex after unilateral lesion of the nucleus basalis with alpha-amino-3-OH-4-isoxozole propionic acid (AMPA): effects of basal forebrain transplants into neocortex

Since the beginning of the twentieth century, different methods to control the quality of analyses have been in use. The advent of modern analytical instruments has prompted the need for such controls. In a modern clinical chemistry laboratory, quality control is an important tool to maintain the high predictive value of the methods in use. In this article the most important aspects of quality control are outlined. For further study, I recommend the references listed at the end of this article.     

Influence of fat source and sorghum grain treatment on performance and digestibilities of high yielding dairy cows

Forty-eight lactating Holstein cows averaging 81 d in milk were allotted to eight blocks based on milk yield during the 14-d pretreatment period and randomly assigned to six treatment groups in a 2 x 3 factorial arrangement of treatments for 64 d. Factors were type of sorghum grain processing [dry-rolled vs. steam-flaked; fed at 34% of dry matter (DM) in a total mixed ration (TMR) based on alfalfa] and type of supplemental fat (2.5% of DM as cottonseed oil, tallow, or prilled fatty acids). Compared with dry-rolled sorghum, steam-flaked sorghum did not affect milk yield, fat percentage, or fat yield but did increase milk protein percentage, body weight gains, and estimated net energy for lactation (22%). Fat source did not affect lactational response, but, compared with tallow, prilled fatty acids tended to decrease DM intake. Steam-flaked sorghum, compared with dry-rolled sorghum, increased digestibilities of DM, organic matter, crude protein, and starch, regardless of fat source. The TMR containing prilled fat had lower digestibilities of DM and organic matter than did TMR containing cottonseed oil or tallow; and TMR containing prilled fat had lower digestibilities of crude protein and total fatty acids than did TMR containing tallow. This study showed that steam-flaking of sorghum grain increased milk protein content, body weight gains, and estimated net energy for lactation, regardless of dietary fat source.     

Glycogenolysis stimulation by non-steroidal anti-inflammatories in the perfused rat liver is not accompanied by Ca2+ release

To better understand the characteristics of amyloid deposition in the choroid plexus, we examined autopsied brain by routine histology, immunohistochemistry, and electron microscopy in three group of patients: primary systemic amyloidosis (n = 7), cerebral amyloid angiopathy (CAA, n = 6), and controls (n = 3). Three of the CAA patients had Alzheimer's disease. Congophilic, birefringent amyloid deposits of the choroid plexus were seen in six of the seven cases of systemic light chain amyloidosis. Immunohistochemistry revealed that the deposited amyloids had reactivity for immunoglobulin light chain and amyloid P component. Accumulation of macrophages labeled with monoclonal antibodies against CD 68 and major histocompatibility complex class II antigens were observed around the massive amyloid deposits. The presence of approximately 10 nm amyloid fibrils along the epithelial basement membrane as well as in the vascular walls was ascertained by electron microscopy. In CAA, Congo red-positive amyloid deposits were consistently present in meningeal blood vessels and were often found in senile plaques of the cerebral parenchyma; congophilic amyloid deposits were absent in the choroid plexus. Choroid plexus epithelial cells exhibited immunostaining for beta amyloid precursor protein (APP) with N-terminal- and C-terminal-specific antibodies; in particular, consistent staining was obtained for the latter antibody. Immunoreactivity for amyloid beta protein (A beta) with monoclonal antibodies (6E10, 4G8) was often found in choroid plexus epithelial cells. These findings suggest that amyloid deposition of the choroid plexus depends on the major component protein in amyloidosis, and that the choroid plexus may produce APP and A beta protein although A beta amyloidosis is not evident in the choroid plexus.     

The HIV/AIDS epidemics among drug injectors: a study of contact structure through a mathematical model

Numerical results of a model with variable infectivity for the dynamics of HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome) have been compared with the data of AIDS cases among intravenous drug users in Italy, especially in the Latium region. We examined several hypotheses about the dynamics of the epidemics; for each we obtained, mainly through a least-square approach but also minimizing a different quantity, a best-fit estimate of the parameters. In the simplest model, the population is assumed to be homogeneous, and we estimate contact rate and year of start of the epidemics, obtaining a good fit up to 1989, less so after. A substantial increase in fit is obtained in assuming either a decrease of the contact rate over time or a heterogeneous population with a smaller active group. We have also compared models with different infectivity curves during the incubation period: the assumption of constant infectivity is untenable, whereas the often suggested hypothesis of a peak in infectivity shortly after infection seems to be in agreement with data.