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Biomedical subjects

B Stein

Publications and source records attributed to B Stein.

At least 55 records · Page 3Linked to original sources
PubMed1999

Ileoanal anastomosis with reservoirs: complications and long-term results.

OBJECTIVE: To determine the rate of complications of ileoanal pouch anastomosis, their treatment and their influence on a successful outcome. DESIGN: A computerized database and chart review. SETTING: Three academic tertiary care health centres. PATIENTS: All 239 patients admitted for surgery between 1981 and 1994 with a diagnosis of ulcerative colitis and familial adenomatosis coli. INTERVENTIONS: Sphincter-saving total proctocolectomy and construction of either S-type of J-type ileoanal reservoir. OUTCOME MEASURES: Indications, early and late complications, incidence of pouch excision. RESULTS: Of the 239 patients, 228 (95.4%) were operated on for ulcerative colitis and 11 (4.6%) for familial polyposis coli. One patient in each group was found to have a carcinoma not previously diagnosed. Twenty-eight patients had poor results: in 17 (7.1%) the ileostomy was never closed or was re-established because of pelvic sepsis or complex fistulas, sclerosing cholangitis or severe diarrhea; 11 (4.6%) patients required excision of the pouch because of anal stenosis, perirectal abscess-fistula or rectovaginal fistula. Three patients died--of suicide, and complications of liver transplantation and HIV infection. Thus, 208 patients maintained a functioning pouch. The early complication rate (within 30 days of operation) was 57.7% (138 patients) and the late complication rate was 52.3% (125 patients). Pouchitis alone did not lead to failure or pouch excision. Emptying difficulties in 25 patients with anal stenosis were helped in 2 by resorting to intermittent catheterization. Patients with indeterminate colitis had a higher rate of anorectal septic complications, and all patients having Crohn's disease after pouch construction had complicated courses. CONCLUSIONS: The complication rate associated with ileoanal pouch anastomosis continues to be relatively high despite increasing experience with this technique. Overall, however, a satisfactory outcome was obtained in 87% of patients.

Abscess↗
PubMed1998

The mitogen-activated protein kinase p38-2 is necessary for the inhibition of N-type calcium current by bradykinin.

Calcium influx via voltage-dependent calcium channels (ICa,V) links depolarization of excitable cells to critical cellular processes, such as secretion, contraction, and gene transcription. Fast regulation of ICa,V (<1 sec) by G-protein-coupled receptors is a relatively well-defined mechanism, whereas slow (30-60 sec) actions of transmitters and hormones on the same current remain poorly understood. In NG108-15 cells, the kinetically slow inhibition of N-type ICa,V by bradykinin (BK) requires the sequential activation of two G-proteins, heterotrimeric G13 and monomeric Rac1/Cdc42. We have now defined a role in this pathway for the relatively fast-acting p38 mitogen-activated protein kinase (MAPK). The slow inhibition of ICa,V by BK was suppressed specifically by SB203580, a compound that inhibits the p38 family of MAPKs. BK potently and selectively activated a newly discovered p38 family member, p38-2. These data provide the first evidence that a MAPK is involved in the regulation of ICa,V by a receptor-mediated process.

Animals↗
PubMed1998

Diminution of contractile response by kappa-opioid receptor agonists in isolated rat ventricular cardiomyocytes is mediated via a pertussis toxin-sensitive G protein.

Opioids directly decrease the contractile response of isolated ventricular cardiomyocytes to electrical stimulation. To investigate whether these effects are mediated via GTP-binding G(i/o) proteins we examined the influence of pertussis toxin on the effects of the kappa-opioid receptor agonist trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benz eneacetamide (U-50,488) methanesulphonate and on the as yet undescribed effects of the opioid peptide dynorphin A (1-8) on contraction. In isolated, electrically driven, rat ventricular cardiomyocytes both agents concentration dependently reduced cell shortening within 15 min, decreasing the contractile response by 79+/-4% (n=5) and 62+/-2% (n=6) of control values at maximal effective concentrations of 10 microM (U-50,488) and 1 microM [dynorphin A (1-8)], respectively. Pertussis toxin pre-treatment (200 ng/ml; 4.5-5 h) completely abolished the effects of U-50,488 and dynorphin A (1-8) on the contractile response, indicating that these effects are mediated via G(i/o) proteins. In addition, the non-selective opioid receptor antagonist (-)-naloxone and the kappa-opioid receptor antagonist nor-binaltorphimine antagonized the effects of U-50,488 and dynorphin A (1-8) on the contractile response. Furthermore, the mu- and delta-opioid receptor agonist (D-Ala2, D-Leu5)-enkephalin (DADLE) had no effects on contraction. These results indicate that the decrease in cell shortening is due to stimulation of kappa-opioid receptors. The direct effect of kappa-opioid receptor agonists on the contractile response thus represents an additional mechanism for decreasing cardiac contractility, besides the M-cholinoceptor- or adenosine receptor-mediated pathway. It is conceivable that increased release of endogenous dynorphins from the heart during hypoxia may protect the heart in a similar manner to adenosine.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1998

Outcome of coronary bypass surgery versus coronary angioplasty in diabetic patients with multivessel coronary artery disease.

OBJECTIVES: This study sought to compare the outcome of percutaneous transluminal coronary angioplasty (PTCA) (n = 834) and coronary artery bypass graft surgery (CABG) (n = 1805) in diabetic patients with multivessel coronary disease from an observational database. BACKGROUND: There is concern about selection of revascularization in diabetic patients with multivessel coronary artery disease. METHODS: Data were collected prospectively and entered into a computerized database. Follow-up was by letter or telephone or additional events resulting in readmission. RESULTS: After CABG there were more in-hospital deaths (0.36% vs. 4.99%, p < 0.0001) and a trend toward more Q wave myocardial infarctions than after PTCA. Five- and 10-year survival rates were 78% and 45% after PTCA and 76% and 48% after CABG, respectively (p = 0.47). At 5 and 10 years, insulin-requiring patients had lower survival rates of 72% and 31% after PTCA and 70% and 48% after CABG, respectively (p = 0.54). Multivariate correlates of long-term mortality were older age, low left ventricular ejection fraction, heart failure and hypertension. In the total group, insulin requirement was a correlate of long-term mortality. For the total group, choice of therapy had a multivariate hazard ratio close to 1. In the insulin-requiring subgroup, the multivariate hazard ratio was 1.35 (95% confidence interval 1.01 to 1.79) for PTCA versus CABG. Corrected for baseline differences, 5- and 10-year survival rates were 68% and 36% after PTCA and 75% and 47% after CABG, respectively, in the insulin-requiring subgroup. Nonfatal events were more common after PTCA, especially additional revascularization. CONCLUSIONS: This study reveals a high incidence of events in diabetic patients and raises further questions about angioplasty in insulin-requiring diabetic patients with multivessel disease.

Aged↗
PubMed1998

Increased expression of constitutive nitric oxide synthase III, but not inducible nitric oxide synthase II, in human heart failure.

OBJECTIVES: The purpose of the present study was to examine the expression of the endothelial-type nitric oxide synthase (NOS III) and the inducible-type NOS (NOS II) in human myocardium and their regulation in heart failure from patients with different etiologies. BACKGROUND: In heart failure, plasma levels of nitrates were found to be elevated. However, data on myocardial NOS expression in heart failure are conflicting. METHODS: Using RNase protection analysis and Western blotting, the expression of NOS III and NOS II was investigated in ventricular myocardium from nonfailing (NF) hearts (n=5) and from failing hearts of patients with idiopathic dilated cardiomyopathy (dCMP, n=14), ischemic cardiomyopathy (iCMP, n=9) or postmyocarditis cardiomyopathy (mCMP, n=7). Furthermore, immunohistochemical studies were performed to localize NOS III and NOS II within the ventricular myocardium. RESULTS: In failing human hearts, NOS III mRNA levels were increased to 180% in dCMP, 200% in iCMP and to 210% in mCMP as compared to NF hearts. Similarly, in Western blots (using constitutively expressed beta-tubulin as a reference) NOS III protein expression was increased about twofold in failing compared to NF hearts. Immunohistochemical studies with a selective antibody to NOS III showed no obvious differences in the staining of the endothelium of cardiac blood vessels from NF and failing human hearts. However, NOS III-immunoreactivity in cardiomyocytes was significantly more intense in failing compared to NF hearts. Low expression of NOS II mRNA was detected in only 2 of 30 failing human hearts and was not found in NF hearts. Inducible-type NOS protein was undetectable in either group. CONCLUSIONS: We conclude that the increased NOS III expression in the ventricular myocardium of failing human hearts may contribute to the contractile dysfunction observed in heart failure and/or may play a role in morphologic alterations such as hypertrophy and apoptosis of cardiomyocytes.

Adult↗
PubMed1998

Rapid skeletal turnover and hypercalcemia associated with markedly elevated interleukin-6 levels in a young black man.

A 24-year-old black man presented with diffuse musculoskeletal pain and shotty lymphadenopathy. Laboratory studies revealed hypercalcemia and hyperphosphatemia, very high serum alkaline phosphatase activity, diffuse but intense uptake of radionuclide on a bone scan, urinary N-telopeptide excretion 30 times the upper limit of normal, and serum interleukin-6 100 times the upper limit of normal. An extensive workup for etiologies of the disorder was negative. A bone biopsy revealed intense osteoclastic resorption coupled with rapid bone formation and/or remodeling. This case appears to represent a new entity. Treatment with bisphosphonates produced symptomatic and biochemical improvement.

Adult↗
PubMed1998

Receptor mechanisms involved in the 5-HT-induced inotropic action in the rat isolated atrium.

1. The effects of 5-hydroxytryptamine (5-HT) in rat cardiac preparations were studied. 5-HT up to 10 microM failed to affect contractility in papillary muscles. However, in electrically driven (1 Hz) left atria 5-HT exerted a positive inotropic effect that started at 1 microM and attained its maximum at 10 microM (312+/-50% of predrug value, n=8). 2. 5-HT 10 microM stimulated the content of inositol-1,4,5-trisphosphate but not of cyclic AMP in rat left atria. 3. Plasma and serum levels of 5-HT amounted to about 0.3 microM and 15 microM, respectively. 4. The selective 5-HT4 receptor antagonists GR 125487 (10 nM and 1 microM) and SB 203186 (1 microM) did not attenuate the positive inotropic effect of 5-HT in rat left atria. In contrast, the 5-HT2 receptor antagonist ketanserin (5 nM, 50 nM, 1 microM) resulted in a concentration-dependent diminution of the positive inotropic effect of 5-HT in rat left atria. 5. Reverse transcriptase polymerase chain reaction with specific primers detected mRNA of the 5-HT2A receptor in rat atria and ventricles, while expression of the 5-HT4 receptor was confined to atria. 6. It is suggested that the positive inotropic effect of 5-HT in electrically driven rat left atria is mediated by ketanserin-sensitive 5-HT2A receptors and not through 5-HT4 receptors.

Animals↗
PubMed1998

Transmission and serial propagation of Enterocytozoon bieneusi from humans and Rhesus macaques in gnotobiotic piglets.

For over a decade Enterocytozoon bieneusi infections in people with AIDS have been linked with chronic diarrhea and wasting. The slow scientific progress in treating these infections is attributed to the inability of investigators to cultivate the parasite, which has also precluded evaluation of effective therapies. We report here successful serial transmissions of E. bieneusi from patients with AIDS and from macaques with AIDS to immunosuppressed gnotobiotic piglets. One infected piglet was still excreting spores at necropsy 50 days after an oral challenge. Spores in feces were detected microscopically by trichrome stain and by PCR and within enterocytes by in situ hybridization and immunohistochemistry. E. bieneusi infection induced no symptoms. The development of an animal model for E. bieneusi will open up new opportunities for investigating this parasite.

AIDS-Related Opportunistic Infections↗
PubMed1997

p38-2, a novel mitogen-activated protein kinase with distinct properties.

Mitogen-activated protein (MAP) kinases are involved in many cellular processes. Here we describe the cloning and characterization of a new MAP kinase, p38-2. p38-2 belongs to the p38 subfamily of MAP kinases and shares with it the TGY phosphorylation motif. The complete p38-2 cDNA was isolated by polymerase chain reaction. It encodes a 364-amino acid protein with 73% identity to p38. Two shorter isoforms missing the phosphorylation motif were identified. Analysis of various tissues demonstrated that p38-2 is differently expressed from p38. Highest expression levels were found in heart and skeletal muscle. Like p38, p38-2 is activated by stress-inducing signals and proinflammatory cytokines. The preferred upstream kinase is MEK6. Although p38-2 and p38 phosphorylate the same substrates, the site specificity of phosphorylation can differ as shown by two-dimensional phosphopeptide analysis of Sap-1a. Additionally, kinetic studies showed that p38-2 appears to be about 180 times more active than p38 on certain substrates such as ATF2. Both kinases are inhibited by a class of pyridinyl imidazoles. p38-2 phosphorylation of ATF2 and Sap-1a but not Elk1 results in increased transcriptional activity of these factors. A sequential kinetic mechanism of p38-2 is suggested by steady state kinetic analysis. In conclusion, p38-2 may be an important component of the stress response required for the homeostasis of a cell.

Activating Transcription Factor 2↗
PubMed1997

Epidemiology of acute renal failure and outcome of haemodiafiltration in intensive care.

OBJECTIVE: To examine the epidemiology of acute renal failure (ARF) and to identify predictors of mortality in patients treated by continuous venovenous haemodiafiltration (CVVHDF). DESIGN: Uncontrolled observational study. SETTING: One intensive care unit (ICU) at a surgical and trauma centre. PATIENTS: A consecutive sample of 3591 ICU treatments. MEASUREMENTS AND RESULTS: Demographic data, indications for ICU admission, severity scores and organ system failure at the beginning of CVVHDF were set against the occurrence of ARF and ICU mortality. 154 (4.3% of ICU patients and 0.6% of the hospital population) developed ARF and were treated with CVVHDF. Higher American Society of Anaesthesiologists (ASA) status and higher Apache II score were associated with ICU incidence of ARF. However, these criteria were not able to predict outcome in ARF. A simplified predictive model was derived using multivariate logistic regression modelling. The mortality rates were 12% with one failing organ system (OSF), 38% with two OSF, 72% with three OSF, 90% with four OSF and 100% with five OSF. The adjusted odds ratio (OR) of death was 7.7 for cardiovascular failure, 6.3 for hepatic failure, 3.6 for respiratory failure, 3.0 for neurologic failure, 5.3 for massive transfusion and 3.7 for age of 60 years or more. CONCLUSION: General measures of severity are not useful in predicting the outcome of ARF. Only the nature and number of dysfunctioning organ systems and massive transfusion at the beginning of CVVHDF and the age of the patients gave a reliable prognosis in this group of patients.

Acute Kidney Injury↗
PubMed1997

QC Validator 2.0: a computer program for automatic selection of statistical QC procedures for applications in healthcare laboratories.

A computer program has been developed to help healthcare laboratories select statistical control rules and numbers of control measurements that will assure the quality required by clinical decision interval criteria or analytical total error criteria. The program (QC Validator 2.0 (QC Validator and OPSpecs are registered trademarks of Westgard Quality Corporation, which has applied for a patent for this automatic QC selection process. Windows is a registered trademark of Microsoft Corporation)) runs on IBM compatible personal computers operating under Windows. The user enters information about the method imprecision, inaccuracy, and expected frequency of errors, defines the quality required in terms of a medically important change (clinical decision interval) or an analytical allowable total error, then initiates automatic selection by indicating the number of control materials that are to be analyzed (1, 2, or 3). The program returns with a chart of operating specifications (OPSpecs chart) that displays the selected control rules and numbers of control measurements. The automatic QC selection process is based on user editable criteria for the types of control rules that can be implemented by the laboratory, total numbers of control measurements that are practical, maximum levels of false rejections that can be tolerated and minimum levels of error detection that are acceptable for detection of medically important systematic or random errors.

Biometry↗
PubMed1997

[Psychiatric consultation service at the Psychiatric Clinic of the Görlitz Municipal Clinic GmbH, ECLW].

The Psychiatric Hospital at the Municipal (General) Hospital in Görlitz, Germany, was the only Department of Psychiatry in a non-University (general) hospital in the newly integrated German provinces who were originally part of the so-called "German Democratic Republic" before the re-unification of Germany, to participate in the German collective study on "Psychiatric and Psychosomatic Consultation and Liaison Service in German General Hospitals-A Multicentre Empirical Study to Assess and Evaluate Existing Structures and Services". This study is an independent part project that includes specific questions forming part of the European collective study on "Effectiveness of Mental Health Consultation and Liaison Service Delivery in the General Hospital".

Adolescent↗
PubMed1997

Lumbar spine surgery in the obese patient.

A prospective study was performed in obese and nonobese patients undergoing lumbar spine surgery to report perioperative data and surgical outcomes. One hundred fifty-nine consecutive patients who underwent lumbar spine surgery by a single surgeon entered the study. Among 159 consecutive patients, 55 met the criteria for obesity (> 20% ideal body weight). The average weight was 226 lb in the obese group. There were 28 men and 27 women with ages ranging from 25 to 81 years, with a mean of 47.9 years. The diagnoses and procedures included 31% herniated nucleus pulposus with laminotomy and discectomy, 14% spinal stenosis with laminectomy, and 55% lumbar fusion procedures for other disorders. Twenty-nine percent had previous lumbar surgery that had failed. Results indicated that there were no significant differences between the obese and control groups in terms of duration of surgery (3.8 versus 3.2 h), blood loss (723 versus 605 ml), and duration of hospital stay (5.6 versus 5.8 days). The clinical results were 24% excellent, 40% good, 27% fair, and 9% poor in the obese group; and 27% excellent, 37% good, 19% fair, and 17% poor in the control group. This study found no significant differences between obese and control patients relative to blood loss, operative time, hospital stay, rate of complications, and functional outcome in lumbar spine surgery. Patient selection continues to be the most important factor in terms of operative success. We believe that lumbar spine surgery, including fusion, should not be withheld from obese patients who present with proper indications for surgery and fail an appropriate course of conservative treatment.

Adult↗
PubMed1996

Contributions of the mitogen-activated protein (MAP) kinase backbone and phosphorylation loop to MEK specificity.

To examine the specificity of MEKs for MAP kinase family members, we determined the abilities of several MEK isoforms to phosphorylate mutants of the MAP kinase ERK2 and the related kinase ERK3 which are modified in the phosphorylation loop. The ERK2 mutants included mutations of the two phosphorylation sites, mutations of the acidic residue between these two sites, and mutations that shorten the length of this loop. All mutants were tested for phosphorylation by six mammalian MEKs and compared with several wild type MAP kinases. MEK1 and MEK2 phosphorylate a majority of the ERK2 mutants. MEK2 but not MEK1 will phosphorylate ERK3. Alteration of the residue between the two phosphorylation sites neither dramatically affected the activity of MEK1 and MEK2 toward ERK2 nor conferred recognition by other MEKs. Likewise, reduction of the length of the phosphorylation loop only partially reduces recognition by MEK1 and MEK2 but does not promote recognition by other MEKs. Thus other yet to be identified factors must contribute to the specificity of MEK recognition of MAP kinases.

Amino Acid Sequence↗
PubMed1996

Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade.

Mitogen-activated protein kinases are members of a conserved cascade of kinases involved in many signal transduction pathways. They stimulate phosphorylation of transcription factors in response to extracellular signals such as growth factors, cytokines, ultraviolet light, and stress-inducing agents. A novel mitogen-activated protein kinase kinase, MEK6, was cloned and characterized. The complete MEK6 cDNA was isolated by polymerase chain reaction. It encodes a 334-amino acid protein with 82% identity to MKK3. MEK6 is highly expressed in skeletal muscle like many other members of this family, but in contrast to MKK3 its expression in leukocytes is very low. MEK6 is a member of the p38 kinase cascade and efficiently phosphorylates p38 but not c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) family members in direct kinase assays. Coupled kinase assays demonstrated that MEK6 induces phosphorylation of ATF2 by p38 but does not phosphorylate ATF2 directly. MEK6 is strongly activated by UV, anisomycin, and osmotic shock but not by phorbol esters, nerve growth factor, and epidermal growth factor. This separates MEK6 from the ERK subgroup of protein kinases. MEK6 is only a poor substrate for MEKK, a mitogen-activated protein kinase kinase kinase that efficiently phosphorylates the related family member JNKK.

Amino Acid Sequence↗