Induction of apoptosis in neuroendocrine tumors of the digestive system during treatment with somatostatin analogs

The frequency of antibiotic resistance among bacteria in 4 intensive care units (ICUs) at a university hospital in Sweden was investigated annually from 1993 to 1996. An increase in ampicillin-resistant enterococci from 1993 to 1995 was seen which was due to a shift from Enterococcus faecalis to Enterococcus faecium. After a special infection control programme was instituted, the rate of ampicillin resistance among enterococci and the number of E. faecium isolates declined during 1996. The oxacillin resistance rates for Staphylococcus aureus were < or = 2%, while most of the coagulase-negative staphylococci (CNS) were oxacillin resistant. No vancomycin-resistant enterococci or staphylococci were seen. The ciprofloxacin resistance rate for CNS and Enterococci spp. were high. Relatively, high levels of resistance to cefotaxime and piperacillin/tazobactam among Enterobacter spp. were also seen. During 1995 and 1996 Pseudomonas aeruginosa showed increasing resistance to ceftazidime, ciprofloxacin and piperacillin/tazobactam. This was due to an outbreak among rather few patients. The overall resistance rates for Gram-negative bacteria were low for aminoglycosides and imipenem. From 1993 to 1996 the total antibiotic consumption decreased by 27% in the whole hospital and 16.5% in the ICUs. However, the reduced antibiotic consumption was paralleled with a 23% decrease in the total number of patients treated in the hospital from 1993 to 1996. In contrast there was an 11.5% increase in the number of ICU patients treated during this period. The conclusion is that all ICUs within a hospital should have a programme for 'on-line' antibiotic resistance surveillance of drugs used in that unit in order to change the empiric treatment when there is an increase in antibiotic resistance. It is also important to survey the antibiotic consumption in the ICUs in order to avoid further selective pressure on bacteria showing increased resistance rates.     

Congenital sodium diarrhoea in an Indian girl

BACKGROUND: Ecstasy is a synthetic amphetamine which causes a wide variety of adverse effects. Hepatic toxicity was only recently demonstrated but can be quite severe. CASE REPORT: A 27-year-old male with no past medical or surgical history developed jaundice without fever. He was a regular user of ecstasy and had recently increased the number of doses consumed. No evidence of a viral, alcoholic, metabolic or autoimmune mechanism was found which could explain the hepatitis. Complete cure was obtained by discontinuing ecstasy. DISCUSSION: Few cases of ecstasy hepatic toxicity have been reported. Ecstasy was undoubtedly the causal agent in this case since other known causes of acute hepatitis were excluded, confirming the hepatotoxicity of ecstasy reported in the literature. The liver disease has been reported to range form acute regressive hepatitis to fatal liver failure. Iterative exposure can lead to fibrosis. The pathophysiological mechanism of this toxic effect is not well elucidated. Ischemia alone cannot explain all the clinical forms described, particularly cases without hyperpyrexia. Ecstasy must be added to the list of potential causes of acute hepatitis. Exposure must always be searched for in cases of acute hepatitis in young subjects.     

Modeling two-state disease processes with random effects

Many chronic medical conditions are manifested by alternating sojourns in symptom-free and symptomatic states. In many cases, in addition to their relapsing and remitting nature, these conditions lead to worsening disease patterns over time and may exhibit seasonal trends. We develop a mixed-effect two-state model for such disease processes in which covariate effects are modeled multiplicatively on transition intensities. The transition intensities, in turn, are functions of three time scales: the semi-Markov scale involving the backward recurrence time for the cyclical component, the Markov scale for the time trend component, and a seasonal time scale. Multiplicative bivariate log-normal random effects are introduced to accommodate heterogeneity in disease activity between subjects and to admit a possible negative correlation between the transition intensities. Maximum likelihood estimation is carried out using Gauss-Hermite integration and a standard Newton-Raphson procedure. Tests of homogeneity are presented based on score statistics. An application of the methodology to data from a multi-center clinical trial of chronic bronchitis is provided for illustrative purposes.     

The ontological basis of strong artificial life

In 1973, the United States Congress enacted legislation requiring physicians to initiate Peer Review Organizations to monitor utilization and quality of hospital and physician services in the federally funded Medicare program. A hardly noticed provision of the statute intimated the desirability of formulating guidelines for medical treatment. What was originally intended to simplify and universalize general standards by which quality of care could be objectively measured has more recently escalated into formalized projects, subsidized by government, to create "practice parameters". The impetus to define clinical conditions and methods of treatment for specific medical conditions (practice parameters) and standards of practice to avoid or defend malpractice claims (risk management protocols) are part of the movement in the United States for tort reform. If the vague "reasonable man" standard of care in negligence law can be supplanted by a scientifically developed, particularized medical practice standard, it is anticipated that spurious claims and defensive medical practice will be discouraged, quality improved, iatrogenic injury and malpractice litigation diminished. Many U.S. states undertook tort reform in the last decade. A few have embarked on medical-legal reform. One state is conducting a five-year medical liability project that calls for the development of practice parameters and risk management protocols in four medical specialties. The parameters will have the effect of law and may be introduced as evidence in medical malpractice trials. How the parameters are established, their effect on the strategies of litigation, the resultant trial problems in the introduction of evidence and in the burden of proof and their potential for acceptance by a significant number of jurisdictions-are the issues to be explored in this paper.     

Immunohistochemical expression of the mucin-type glycoprotein A-80 and prognosis in human breast cancer

Immunohistochemical expression of the tumour associated mucin-type glycoprotein A-80 was investigated in a series of 173 breast cancer patients with a clinical follow-up between 13 and 19 years. A routine immunoperoxidase technique was used in formalin-fixed, paraffin-embedded surgical tumour specimens. One hundred and fifty of 173 tumours (87%) immunostained with MAb A-80. The degree of A-80 immunoreactivity was related to the tumour grade but not to lymph node status, tumour size, or nuclear DNA distribution pattern. In univariate analysis the degree of A-80 expression was found to be of significant prognostic value both in node negative and in node positive breast cancer patients (P = 0.03). Patients with non-A-80 immunoreactive tumours had significant longer distant metastases-free survival times and fewer relapses than women with carcinomas composed of A-80 immunoreactive tumour cells. This prognostic value was reduced in a multivariate analysis, including lymph node status, tumour size, and nuclear DNA distribution pattern, but retained borderline significance (P = 0.08). In conclusion, the findings of this study indicate that expression of the mucin-type glycoprotein A-80 as determined by immunohistochemistry seems to be related to clinical outcome in breast cancer patients.     

Regulation of hepatic cytochrome P450 2C11 by transforming growth factor-beta, hepatocyte growth factor, and interleukin-11

Injection of rats with bacterial lipopolysaccharide down-regulates P450 (P450) 2C11 (2C11) mRNA to about 20% of its control levels after only 6 hr, and this level is maintained for at least 48 hr. Although we and others have demonstrated that this effect may be at least partially mediated by the cytokines interleukin-1, interleukin-6, and tumor necrosis factor-alpha, as well as by glucocorticoids, the time courses and potencies of 2C11 repression by each single mediator suggested that no cytokine alone is responsible for the entire time course of 2C11 suppression during inflammation. Here, we show that transforming growth factor-beta, hepatocyte growth factor, and interleukin-11 are potent inhibitors of 2C11 expression. In all three cases, 0.1 ng/ml was enough to down-regulate 2C11 mRNA levels to 50% of control. Interleukin-8, a cytokine that is secreted during the acute phase response but does not influence the liver acute phase response, did not affect 2C11 expression. The various mediators have different time courses of 2C11 down-regulation, indicating that the roles of each may be different at different phases of the response.