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Biomedical subjects

M Weiss

Publications and source records attributed to M Weiss.

At least 289 records · Page 16Linked to original sources

The quality evolution in managed care organizations: shifting the focus to community health.

Community demand for high-quality, cost-effective health care is forcing many new changes for managed care organizations (MCOs). Competition among MCOs often prevents cooperative and comprehensive approaches to the enhancement of the health status of the community. MCOs are beginning to measure quality based on the health of enrolled populations, and communities are seeking communitywide quality of care indicators. To cope with the demands of capitated health care, MCOs need to shift their focus to managing the health status of specific community populations. Strategies for managing the health status of populations include community assessments, collaboration among competing players, and a focus on consumer health information.

Community Health Planning↗

Tumor necrosis factor-alpha modulates the selective interference of hypnotics and sedatives to suppress N-formyl-methionyl-leucyl-phenylalanine-induced oxidative burst formation in neutrophils.

OBJECTIVE: To clarify whether tumor necrosis factor (TNF)-alpha modulates the inhibitory effect of clinically applied hypnotics and sedatives on neutrophil function. DESIGN: Prospective, randomized, controlled, dose response, in vitro study. SETTING: A university research laboratory. SUBJECTS: Neutrophils from healthy human volunteers. MEASUREMENTS AND MAIN RESULTS: Neutrophils were primed by incubation with TNF-alpha (25 ng/mL) for 15 mins. Subsequently, TNF-alpha-primed neutrophils were incubated with two concentrations of commercially available drug preparations and drug-free solutions, respectively. The following commercially available preparations of hypnotics and sedatives as well as their corresponding drug-free solutions were tested: methohexital, thiopental, midazolam, diazepam, etomidate, and propofol. The production of oxygen radicals was initiated by adding N-formyl-methionyl-leucyl-phenylalanine (FMLP) 10(-7) mol/L and detected by luminol-enhanced chemiluminescence measurements for 15 mins. Within the range of therapeutic plasma concentrations, only thiopental, diazepam, and propofol suppressed chemiluminescence of unprimed neutrophils. Additionally, propofol alone suppressed TNF-alpha-primed neutrophils. Hypnotics and sedatives were unable to suppress oxygen radical production of TNF-alpha-primed neutrophils below the level of their control activity, measured in FMLP-induced unprimed neutrophils in the absence of the respective drug or drug-free solution. However, the effect of etomidate could not be evaluated secondarily to effects mediated by its drug-free solution. In a cell-free chemiluminescence system, thiopental and propofol demonstrated scavenging of oxygen free radicals. CONCLUSIONS: Priming with TNF-alpha counteracts the inhibitory effect by certain drugs for oxygen radical formation by FMLP-stimulated neutrophils. Thus, TNF-alpha plus FMLP mediate additive effects in stimulating oxygen radical formation in neutrophils. The following drugs dose-dependently interfere with these activating pathways: thiopental, diazepam, and propofol. Additionally, thiopental and propofol have efficient oxygen-scavenging properties and may attenuate radical-mediated tissue destruction in hyperinflammatory syndromes.

Free Radical Scavengers↗

Signifying the pandemics: metaphors of AIDS, cancer, and heart disease.

This article offers a symbolic analysis of the cultural construction and signification of three of the major "pandemics" of the late 20th century: AIDS, cancer, and heart disease. It is based on unstructured interviews conducted in Israel between 1993-94 with 75 nurses and 40 physicians and between 1993-95 with 60 university students. Two key symbols, "pollution" and "transformation," are shown to constitute AIDS and cancer within a symbolic space that I suggest is "beyond culture," where body boundaries are dissolved and cultural categories are dismantled. Heart disease, in contrast, is metaphorized as a defect in the "body machinery." The article concludes by arguing that heart attack is depicted as the pathology of the Fordist, modernist body, while AIDS/cancer are pathologies of the postmodern body in late capitalism.

Acquired Immunodeficiency Syndrome↗

Evaluation of pathologic criteria for acute renal allograft rejection: reproducibility, sensitivity, and clinical correlation.

This study was designed to evaluate the pathologic criteria used for acute renal allograft rejection that were developed by a panel of renal pathologists participating in the Cooperative Clinical Trials in Transplantation, a National Institutes of Health-supported, multicenter research group. The panel defined three categories of acute rejection. (1) Type I: mononuclear infiltrate in > or =5% of cortex, a total of at least three tubules with tubulitis in 10 consecutive high-power fields from the most severely affected areas, and at least two of the three following features: edema, activated lymphocytes, or tubular injury. (2) Type II: arterial, or arteriolar, endothelialitis with or without the preceding features. (3) Type III: arterial fibrinoid necrosis or transmural inflammation with or without thrombosis, parenchymal necrosis, or hemorrhage. Using these criteria, and without any knowledge of the clinical course or original diagnosis, a rotating panel of three pathologists agreed with the original study pathologist's diagnosis of the presence or absence of rejection in 259 of the 286 biopsies (91%) used for this analysis (kappa = 0.80). The sensitivity to establish the diagnosis of rejection was 91% for a single core and 99% for two cores. To validate the diagnostic criteria, the thresholds for number of tubules with tubulitis and the percent infiltrate were varied, and the pathologic diagnosis was compared with the clinical course. The greatest agreement occurred with a threshold of > or =1 tubule with tubulitis and > or =5% cortex with interstitial infiltrate (91%). Clinically severe rejection episodes were correlated with the type of rejection (type I, odds ratio [OR] 6.2; type II, OR 37.9). Type II rejection was more likely to be clinically severe than type I (OR 6.1). Analysis of other individual pathologic features revealed a correlation with clinical severity for endothelialitis (OR 13.2), interstitial hemorrhage (OR 13.2), and the presence of glomerulitis (OR 3.7) (all P < 0.05). The extent of tubulitis or of the interstitial infiltrate did not correlate with severity (P > 0.05). It is concluded that these criteria are simple, reproducible, and clinically relevant. These data should lead to further refinement of the diagnostic systems for renal allograft rejection.

Acute Disease↗

MR imaging of enhancing intraosseous disk herniation (Schmorl's nodes).

OBJECTIVE: This study was conducted to show vascularization of Schmorl's nodes with enhanced MR imaging and to correlate this finding with clinical complaints. MATERIALS AND METHODS: Retrospectively, 412 gadopentetate dimeglumine-enhanced MR imaging examinations of the lumbar and thoracic spine of 372 patients were reviewed for Schmorl's nodes, vascularization of Schmorl's nodes, and associated bone marrow edema. Sagittal T2-weighted spin-echo and unenhanced and enhanced T1-weighted spin-echo images with and without fat suppression were evaluated in symptomatic and asymptomatic patients. RESULTS: Of the 372 patients, 142 (38%) had 341 Schmorl's nodes. Gadopentetate dimeglumine-enhanced MR imaging revealed vascularized tissue in 30 Schmorl's nodes of 23 patients (mean age of patients, 53 years old). Associated bone marrow edema was found in nine of 30 vascularized Schmorl's nodes. The mean diameter (8.2 mm) of the nine vascularized Schmorl's nodes that were surrounded by bone marrow edema was significantly (p < .05) greater than the mean diameter (6.4 mm) of the 21 vascularized Schmorl's nodes that had no bone marrow edema. The vascularized Schmorl's nodes were significantly (p < .05) smaller in the seven asymptomatic patients (mean, 5.2 mm) than in the 23 patients with back pain (mean, 7.9 mm). We saw bone marrow edema adjacent to Schmorl's nodes less frequently in asymptomatic patients (one of seven) than in symptomatic patients (10 of 23). CONCLUSION: Vascularized Schmorl's nodes were larger and more frequently associated with bone marrow edema in patients with back pain than in asymptomatic patients. Enhanced MR images of Schmorl's nodes revealed vascularity, which was not shown on unenhanced MR images.

Adult↗

Vasoactive drugs inhibit oxygen radical production of neutrophils.

A concentration response study was performed to clarify whether vasoactive drugs, routinely used in intensive care patients, inhibit oxygen radical production of neutrophils. Moreover, in a cell-free system, it was investigated whether these drugs exert free radical scavenging properties. Vasoactive agents were incubated with neutrophils from healthy human volunteers, which were stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP) and by opsonized zymosan to produce oxygen radicals, detected by chemiluminescence measurements. Sympathomimetics (epinephrine greater than norepinephrine, dopamine and dobutamine) as well as phosphodiesterase-inhibitors (amrinone and enoximone) inhibited FMLP-induced and zymosan-induced oxygen radical production of neutrophils in a concentration-dependent and drug-specific fashion. With the exception of amrinone, FMLP-induced chemiluminescence of neutrophils was impaired nearly 10-fold more markedly than zymosan-induced chemiluminescence. Glyceryl trinitrate, nifedipine and prostacyclin had no effect on oxygen radical production of neutrophils. In the cell-free system, epinephrine, norepinephrine, dopamine, amrinone and enoximone demonstrated oxygen free radical scavenging properties. This study shows that vasoactive drugs, frequently used in the clinical setting, may suppress oxidative burst after FMLP-receptor stimulation. As demonstrated in the cell-free system, this suppression was, at least in part, due to oxygen radical scavenging.

Calcium Channel Blockers↗

The role of the alliance in the pharmacologic treatment of depression.

BACKGROUND: The purpose of this study was to determine the influence of the therapeutic alliance on the efficacy of pharmacotherapy for depression. METHOD: The sample consisted of 31 depressed outpatients treated with antidepressants. The alliance was measured by the patient and therapist versions of the California Pharmacotherapy Alliance Scale. Treatment outcome was measured by the Hamilton Rating Scale for Depression and the Beck Depression Inventory, and the Symptom, Sign, Side-Effect Checklist was also completed. RESULTS: The alliance measures accounted for between 21% and 56% of the variance in the three outcome measures. By averaging across outcome measures, therapist perceptions of the alliance predicted 41% of the variance in improvement in depressive symptoms, where patient perceptions predicted 25%. Scores on both alliance measures were lower than those reported in studies of psychotherapy. Patient attitude toward medication was correlated with somatic complaints, but not with depression scores. Therapist perception of patient hostility correlated with patient depression. Patients differed in the way their alliance and outcome interacted, so that the association might be positive or negative. CONCLUSION: Alliance is correlated with outcome in pharmacotherapy management of depression, although there may be interindividual variability across patients. In the pharmacotherapy of depression, therapist perception of alliance is a better predictor of symptom outcome than patient perception, while the reverse is usually found in psychotherapy.

Adult↗

A cost-effective approach to the use of selective serotonin reuptake inhibitors in a Veterans Affairs Medical Center.

In light of the tremendous expansion in the number of selective serotonin reuptake inhibitors available to the clinician, the Pharmacy and Therapeutics Committee of the Denver Veterans Affairs Medical Center considered the advantages and disadvantages of fluoxethine, paroxetine, and sertraline, to determine which agent or agents would be carried on the formulary. The committed recommended sertraline as the preferred agent for the treatment of depression, panic disorders, and obsessive-compulsive disorders. The purpose of this retrospective study was to assess the economic outcome of that decision. The study population consisted of patients at the medical center who were receiving selective serotonin reuptake inhibitors during January through March of 1994 and those were receiving these agents between September 1995 and January 1996. The expanded collection period in 1995-96 was due to a relatively new medical center policy to offer 90-day fills on medication to reduce costs. The extended collection period assured a 100% sample of patients receiving these agents. The 1994 fluoxetine to sertraline dosage equivalency ratio was 20 mg:55.6 mg, based on average daily doses of fluoxetine and sertraline of 32.7 and 90.9 mg, respectively. The cost to the medical center for an average daily dose of fluoxetine was $1.86; sertraline cost $1.22 per day. The 1996 fluoxetine to sertraline dosage equivalency ratio (20 mg:51.3 mg) had not changed significantly since 1994, indicating that the dose of 20 mg of fluoxetine remained very close to a 50-mg dose of sertraline. The average daily doses of fluoxetine and sertraline (34.9 mg and 89.7 mg, respectively) were not significantly different than the 1994 doses. Only 33 patients had been prescribed paroxetine (average daily dose, 32.4 mg). On the basis of these values, the average daily cost of fluoxetine to the medical center was $2.01, compared with $1.18 for sertraline and $1.24 for paroxetine. This $0.83 per patient per day drug acquisition cost difference between fluoxetine and sertraline results in a drug cost reduction of $302,674 per year.

Antidepressive Agents, Second-Generation↗

Thoracoscopic surgery of the oesophagus in rats: a training concept for the treatment of tracheo-oesophageal malformations in preterm infants.

In extremely preterm babies with type Vogt III b oesophageal atresia, the primary operative management can be restricted to a gastrostomy and ligation of the fistula. Some of these patients, however, may not even tolerate a thoracotomy or placement on the operating table. We developed a minimally invasive procedure to prepare and ligate the oesophagus thoracoscopically and perform laparoscopic gastrostomy in a rat model. In 15 operations we observed only one complication. This study implies that after adequate practice, thoracoscopic dissection of the oesophagus with ligation of a tracheo-oesophageal fistula could be performed even in every small infants.

Animals↗

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Attention Deficit Disorder with Hyperactivity↗

[The prognostic significance of impaired vocal cord motility in patients with stage II glottic cancer treated with radiotherapy].

Eighty-five patients with stage II glottic laryngeal cancer were treated with radiotherapy in Center of Oncology in Kraków between 1973 and 1989. Fifty-five patients were irradiated with 60Co unit, 30 with mixed photon--electron beam. The 5-year survival rates without evidence of disease after the radiotherapy only were 65.9%, after the radiotherapy and surgery for recurrences--76.5%. The sex, age, local extension of primay tumour and vocal cord mobility were evaluated in a uni- and multivariate analysis of prognostic factors. For the end-point of 5-year survival without evidence of disease no statistically significant relationship was found between results and analysis variables, especially between survival and impaired cord mobility.

Adolescent↗

[Prognostic factors in patients with early stages of supraglottic cancer treated by radiotherapy].

Three hundred patients with early stage supraglottic cancer were treated with radiotherapy in Center of Oncology in Kraków between 1973 and 1989. The 5-year NED survival rates after the radiotherapy only were 82.9% in stage I, and 70%in stage II cancer, after the radiotherapy and surgery for recurrences--90% and 75% respectively. The stage and tumor site were an important prognostic factors in the treated group of patients.

Adult↗

Detection of a secreted MUC1/SEC protein by MUC1 isoform specific monoclonal antibodies.

Although MUC1 proteins are known to be secreted by breast cancer cells, the mechanism of their release from the cell is still obscure. Our previously reported MUC1 cDNA sequences suggested the existence of a secreted MUC1 isoform, MUC1/SEC, that includes a sequence of intron 2, and terminates prematurely at a stop codon within this intron. It is thus devoid of a transmembrane domain. As no formal evidence for MUC1/SEC expression at the protein level had been provided, we generated monoclonal antibodies (mAbs) against a peptide sequence (sec peptide) that is unique for the MUC1/SEC protein. Two anti-sec peptide mAbs were obtained which reacted strongly with (a) the immunizing peptide, (b) recombinant MUC1/SEC protein, and (c) MUC1 proteins secreted from breast cancer cells. The immunoreactivity of the anti-sec peptide mAbs with MUC1 proteins secreted by breast cancer cells was specifically inhibited by the sec peptide-it was completely unaffected by a peptide sequence that represents a MUC1 repeat motif. Significantly, the anti-sec peptide mAbs also detected MUC1/SEC protein in sera of breast cancer patients. We have established here that these mAbs recognize the MUC1/SEC isoform via a peptide sequence which is unique for the MUC1/SEC protein. Our studies thus demonstrate that the MUC1/SEC protein is a bona-fide MUC1 isoform and that its expression may contribute to the secretion of MUC1 proteins by secretory epithelial cells in general and breast cancer cells in particular.

Animals↗

Effect of coronary artery size on the prevalence of atherosclerosis.

To investigate the effect of coronary artery size on the prevalence of atherosclerosis, we measured the diameters of the major coronary arteries prospectively in 884 consecutive patients referred for coronary arteriography. For each artery, we assigned patients to 3 groups: group S (small) and group L (large) with diameters >1SD smaller and larger, respectively, than the mean; and group A (average), with diameters within 1SD of the mean. As specified during study design, we compared the frequency of lesions > or = 50% diameter stenosis in groups S and L for each artery. We adjusted for relevant covariates by performing logistic regression on data from all 884 patients with coronary diameter entered as a continuous variable. In group S versus L, respectively, the frequency of > or = 50% lesion was 6.5% versus 2.4% (p = 0.13) in the left main artery; 61.3% versus 35.8% (p = 0.0001) in the right coronary artery; 58.1% versus 40.7% (p = 0.008) in the left anterior descending artery, and 47.4% versus 22.2% (p = 0.0001) in the circumflex artery. Multivariate analysis showed that coronary diameter was a significant independent predictor of lesions in the right coronary artery (p = 0.000001), left anterior descending artery (p = 0.001), and circumflex artery (p = 0.0002) and nearly significant in the left main artery (p = 0.077). Thus, small coronary artery size may be a risk factor for atherosclerosis.

Aged↗

[Diphtheria. An illness, which many physicians no longer see in personal experience].

Diphtheria is one of those diseases that the rigorous application of vaccination has rendered very rare in Western countries. However, as a result of being re-introduced from Eastern Europe, it may re-establish itself in the West. The incubation period is two to five days, and in the unprotected, infection may take place via a carrier who himself is not ill. The most feared form is the laryngeal form (croup) and the exotoxin-induced complications: myocarditis with arrhythmias and paresis affecting the muscles of the palate, throat and respiratory system. Once it is clinically suspected, antibiotic treatment and antitoxin therapy should be initiated without delay.

Adolescent↗

Evidence for a physical association between the Shc-PTB domain and the beta c chain of the granulocyte-macrophage colony-stimulating factor receptor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates the growth and function of several myeloid cell types at different stages of maturation. The effects of GM-CSF are mediated through a high affinity receptor that is composed of two chains: a unique, ligand-specific alpha chain and a beta common chain (beta c) that is also a component of the receptors for interleukin 3 (IL-3) and IL-5. Beta c plays an essential role in the transduction of extra cellular signals to the nucleus through its recruitment of secondary messengers. Several downstream signaling events induced by GM-CSF stimulation have been described, including activation of tyrosine kinases and tyrosine phosphorylation of cellular proteins (including beta c) and activation of the Ras/mitogen-activated protein kinase and the JAK/STAT pathways. A region within the beta c cytoplasmic tail (amino acids 517-763) has been reported to be necessary for tyrosine phosphorylation of the adapter protein, Shc, and for the subsequent GM-CSF-induced activation of Ras. In this paper, we describe a physical association between the tyrosine phosphorylated GM-CSF receptor (GMR)-beta c chain and Shc in vivo. Using a series of cytoplasmic truncation mutants of beta c and various mutant Shc proteins, we demonstrate that the N-terminal phosphotyrosine-binding (PTB) domain of Shc binds to a short region of beta c (amino acids 549-656) that contains Tyr577. Addition of a specific phosphopeptide encoding amino acids surrounding this tyrosine inhibited the interaction between beta c and shc. Moreover, mutation of a key residue within the phosphotyrosine binding pocket of the Shc-PTB domain abrogated its association with beta c. These observations provide an explanation for the previously described requirement for Tyr577 of beta c for GM-CSF-induced tyrosine phosphorylation of Shc and have implications for Ras activation through the GM-CSF, IL-3, and IL-5 receptors.

Adaptor Proteins, Signal Transducing↗