[ANCA (antineutrophil cytoplasm antibodies)].
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Biomedical subjects
Publications and source records attributed to S Katz.
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A novel hybrid methodology for prediction of valve related complications in patients with implanted artificial heart valves is discussed. Artificial neural networks provided a mechanism for prediction of postoperative valve-related deaths based on preoperative patient information and valve parameters. Then bootstrap methodology was applied for estimating prediction errors and maximizing prediction accuracy. Data from a clinical trial with 10 years of follow-up on 789 patients implanted with Carpentier-Edwards Pericardial Bioprosthesis were used. A random subset of the data was reserved for validation of the final outcome. The remaining patients' records were repeatedly divided into two groups, using resampling strategy provided by the bootstrap methodology. One of the groups was used for training the neural net and the other one for testing the trained network and determining error rates. Patient information, such as sex, age, NYHA class and anticoagulation therapy, as well as valve parameters, such as size and the date of implant were used as the network inputs. Calculated error rates were then used for assessing the distribution of the error, further optimization of the neural network, and constructing confidence intervals for the error rates. Thus, reliable statistical estimation was obtained on the prediction accuracy. Additionally this new hybrid methodology allowed us to optimize the neural network even further, raising the accuracy of prediction to 78%.
OBJECTIVE: To identify potential barriers to the use of oral rehydration therapy (ORT) by pediatric practitioners. DESIGN: Cross-sectional, anonymous, self-administered survey of physicians' ORT knowledge, attitudes, and practice. SETTING: A national continuing medical education conference. PARTICIPANTS: One hundred four general pediatricians primarily in private practice (66%) who completed training after 1980 (76%). MEASUREMENTS AND RESULTS: Most respondents (83%) reported that ORT plays an important role in their management of dehydration. However, compliance with guidelines from the American Academy of Pediatrics for use of oral therapy is limited: 30% withhold ORT in children with vomiting or moderate dehydration, 50% fail to advise prompt refeeding, and only 3% advise use of a spoon or syringe. The degree of importance of ORT in physicians' practice was negatively associated with reported lack of convenience of ORT administration in the practice setting (P < .001), support staff preference for intravenous versus ORT (P < .001), need for additional training of support staff to implement ORT (P < .01), and likelihood of reimbursement for intravenous versus ORT (P = .07). Notably, degree of importance of ORT was not associated with physician ORT knowledge. CONCLUSION: Efforts to improve use of ORT should be expanded beyond physician education and focus on such barriers as support staff limitations and financial constraints.
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The effect of forskolin on platelet-activating factor (PAF) receptor was investigated. Rabbit platelets treated with forskolin showed approximately a 9-fold increase in cAMP levels over the control. After treatment of platelets with forskolin prior to PAF binding, a 30-40% (P < 0.005) decrease in PAF binding was observed. The decrease in PAF binding caused by forskolin was concomitant with a decrease in the physiological responses of platelets induced by PAF. However, this forskolin-induced decrease in PAF binding was not a consequence of cAMP formation as the addition of a cAMP analog could not mimic the action of forskolin. Additionally, the inactive analog of forskolin, dideoxyforskolin, which does not activate adenylyl cyclase, also reduced PAF binding to its receptor. Reduction of PAF binding by forskolin and dideoxyforskolin was also observed with isolated platelet membranes. To understand the mechanism of forskolin induced changes in PAF binding, the involvement of a G-protein in this process was investigated. Cells treated with GTP gamma S showed approximately a 25% reduction in PAF binding. Addition of forskolin to the GTP gamma S treated cells resulted in a further reduction in PAF binding, suggesting the action of forskolin was independent of G-protein activation. The data suggests that the action of forskolin was independent of adenylyl cyclase or G-protein involvement. It is speculated that the action of forskolin on PAF binding was due to a direct effect of this molecule and its analog on the PAF receptor itself or to components of the post-receptor signalling for PAF.
Retroviral oncogenes encode nuclear regulators of gene expression or signal transduction molecules, such as protein kinases, which stimulate the activity of cellular transcription factors. Here we describe the cloning of NF-M, a myeloid-specific transcription factor related to C/EBP beta, which is a target of activated protein kinases. NF-M stimulates the expression of the gene encoding cMGF, a myeloid cell-specific growth factor, creating an autocrine growth loop crucial to oncogene transformation of myeloid cells. The NF-M protein bound directly to the cMGF gene promoter and activated its transcription, even in erythroid cells where the promoter is usually inactive. In addition, a truncated, dominant-negative form of NF-M inhibited cMGF expression in macrophages, indicating that NF-M is required for the normal activation of the gene. When multipotent hematopoietic progenitor cells were stimulated to differentiate, NF-M expression was induced at a very early stage, suggesting that the transcription factor plays a role in lineage commitment. The stimulation of transformed myelomonocytic cells or of normal peripheral blood macrophages with kinases or LPS or TPA respectively, led to the rapid redistribution of NF-M protein from the cell bodies to the nucleus, consistent with the notion that NF-M was directly affected by such treatments. Our data indicate that NF-M plays a key role in myelomonocytic differentiation, in signal transduction during macrophage activation and in the development of myelogenous leukemia.
We report 5 cases of oat head aspiration in children that resulted in serious complications due to the unidirectional migration of the oat head to the periphery of the lung. The complications included pneumothorax, pneumomediastinum, recurrent hemoptysis, chronic lung disease, bronchiectasis, lobectomy, bronchopleural and bronchocutaneous fistulae, pleural effusion, empyema cavity, and, one not described before, osteomylitis of the rib. Physicians should be aware of the dangers with this particular foreign body aspiration.
Immunosuppressed prematures, cancer patients, and transplant recipients are susceptible to bacterial or fungal sepsis or both. This report evaluates whether the ability of the reticuloendothelial system (RES) to remove blood-borne viable radiolabeled 35S Escherichia coli and 3H-Leucine Candida albicans is adversely affected by a dual intravenous challenge of these organisms. Male Sprague Dawley rats (n = 150) weighing 175 to 180 g were placed in 5 experimental groups (n = 30). Group I received intravenous (IV) C albicans (10(7)/mL), group II received E coli (10(9)/mL), group III received a dual injection of C albicans and E coli, group IV received Candida 1 hour prior to E coli, and group V received E coli 1 hour prior to fungi. At 1, 4, and 24 hours, tissue samples (50 to 100 mg) of liver, spleen, kidneys, and lungs were processed for liquid scintillation counting. Organ distribution of bacteria and fungi was calculated and expressed as mean percent +/- SD of labeled organisms. The liver trapped 72% +/- 10% and the lungs 1.1% +/- 0.3% of E coli (group II) (P < .001). The organ distribution of Candida (group I), however, was similar in liver and lungs (42.5% +/- 10% and 41.4% +/- 6.4%, respectively). Liver localization of E coli was unaffected by simultaneous or staggered fungal injection (groups III, 4, and V). Lung distribution of E coli following dual injection (group III) was significantly higher than controls (group II) (3.6% +/- 0.7% v 1.1% +/- 0.3%; P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiac effects of omega-3 fatty acid treatment were studied in streptozocin (STZ)-induced (55 mg/kg intravenously [IV]) diabetic male Wistar rats. Nondiabetic control and STZ-diabetic animals were treated with Promega (0.5 mL/kg/d; Warner-Lambert, Morris Plains, NJ) for a period of 4 weeks beginning 2 weeks after either vehicle or STZ injection. Plasma glucose, triglyceride, and cholesterol concentrations were significantly (P < .05) elevated in diabetic animals; omega-3 fatty acid treatment did not significantly affect these parameters. An isolated working heart preparation was used to determine aortic and coronary flow rates in control, diabetic, treated control, and treated diabetic animals. Aortic and coronary flow rates of untreated STZ-diabetic rats were significantly (P < .05) lower than those of controls over a range of left atrial filling pressures (7.5 to 20 cm water). Both aortic and coronary flow rates of omega-3 fatty acid-treated diabetic animals were significantly (P < .05) increased above those of untreated diabetic rats. Aortic and coronary flow rates of treated diabetic rats paralleled those of control animals; omega-3 fatty acid treatment did not affect aortic or coronary flow rates of control animals. Cardiac phosphatidylcholine (PC) and phosphatidylethanolamine (PE) and sarcoplasmic reticulum (SR) total phospholipid were isolated and the acyl composition was determined. Stearic acid and C22:4, n-6 were significantly reduced in cardiac PE of diabetic animals. Relative to PE acyl species of untreated nondiabetic controls, treated diabetic PE had increased eicosapentaenoic acid (EPA) and decosahexaenoic acid (DHA) and reduced C22:4, n-6 levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal allograft glomerular filtration rate (GFR) was measured at 4-month intervals for up to 1 year in 43 CsA-treated patients using x-ray fluorescence determination of plasma iohexol clearance. Study patients were divided into cohorts based on time (years) after transplantation at study entry (0-1; 1-2; 2-3; and > 3 years) and entry GFR levels (20-29; 30-39; 40-49; and > or = 50 ml/min/1.73 m2). GFR at study entry was 42 +/- 2 and was comparable in CAD (n = 31) versus LRD (n = 12) allografts (42 +/- 2 and 44 +/- 4 ml/min/1.73 m2, respectively). Range of entry GFR levels was similar in each of the "time at entry" cohorts defined above. Serum creatinine concentrations of 1.5-2.5 mg% were associated with GFR levels of 20-60 ml/min/1.73 m2. Serial GFR levels obtained at 4-month intervals for 1 year (n = 34 patients) were not consistent with a pattern of progressively declining GFR occurring as a function of either time after transplantation or absolute GFR level at study entry (intraindividual coefficient of variation 10.3 +/- 1.0%). Patients in the lower quartile of "entry GFR" levels (< 34 ml/min/1.73 m2) were more likely than their counterparts to have had a history of acute rejection. Results are consistent with retrospective population studies of aggregate serum creatinine levels, indicating that long-term CsA use is not uniformly associated with accelerated loss of renal allograft function consequent to a progressive, toxic nephropathy. The data also suggest that neither absolute GFR level nor time after transplantation represent indications for routine dose reduction or conversion to AZA.
Immunosuppressive agents may initiate their pharmacologic action by disrupting phosphorylation cascades critical to T lymphocyte intracellular signaling after alloantigen recognition. Activator of DNA Replication (ADR), a transduction signal sensitive to CsA as well as rapamycin (RAPA) immunosuppression, seemed a likely candidate for phosphoregulation. This communication reports the development of a cell-free assay wherein CsA and RAPA inhibit ADR induction by protein kinase C (PKC). ADR and PKC are inactive in the cytosol of resting cells. Endogenous PKC activity in quiescent lymphocytes was triggered with the tumor promoter PMA, leading to the appearance of ADR, an event subsequently quantitated by the ability of ADR to trigger [3H]thymidine triphosphate incorporation into isolated nuclei. After PKC induction, ADR activity is increased (890 +/- 120 vs. 3910 +/- 345 cpm, P < 0.001). In the presence of the PKC inhibitor H7, ADR activity fails to increase (100 +/- 50 vs. 3910 +/- 345 cpm, P < 0.001). The high levels of ADR found in PHA-stimulated cells is marginally affected by in situ PKC induction, although the sustained impact of H7 throughout the cell cycle suggests that ADR is constantly being phosphorylated. Titration of CsA or RAPA into the cell-free system inhibited ADR induction in a dose-dependent fashion. The utility of ADR induction as a marker for immunosuppression was investigated by comparing ADR inducibility in resting cells that had been preloaded with CsA or RAPA with the proliferative index of cells cultivated with CsA or RAPA. ADR induction directly correlated with CsA or RAPA proliferative inhibition. The results suggested that ADR is a constituent of the PKC phosphoregulatory cascade essential for cell cycle progression. The correlation between cell-free ADR inducibility and proliferative inhibition by CsA or RAPA suggest that this procedure may be useful for in vitro prediction of allografted patient immunologic response.
The effect of hypothyroidism on isolated rat cardiac sarcoplasmic reticulum (SR) calcium transport activity was determined. Cardiac SR was studied 2, 4 and 6 weeks following surgical removal of the thyroid gland. Thyroidectomized rats had reduced body weight and left ventricular weight 4 and 6 weeks after thyroidectomy. The rate of SR calcium transport activity was not affected 2 weeks after thyroidectomy, but was reduced 4 and 6 weeks after thyroidectomy. To elucidate the mechanism responsible for altered calcium transport activity, the roles of endogenous SR acylcarnitine and SR calcium pump protein were determined. Thyroidectomy did not affect the level of endogenous acylcarnitine associated with the SR membranes isolated at the time points studied. The level of acylphosphoprotein, putatively the SR calcium pump protein, was not affected 2 weeks following thyroidectomy, but was significantly reduced in SR 4 weeks postthyroidectomy. These studies suggest that the quantity of SR calcium pump sites is reduced in hypothyroidism and that this reduction may explain the altered SR calcium transport activity observed.
OBJECTIVE: This study tested the impression that there have been significant shifts in the relative diagnostic frequencies of schizophrenia and major affective disorders. METHOD: Data on discharge diagnoses from 1972 to 1988 were gathered from six North American psychiatric teaching hospitals (data from one extended through 1991), and rates for schizophrenia and major mood disorders were evaluated. RESULTS: Total annual discharges increased by 6.6% during the study period. Large reciprocal shifts in the frequencies of diagnoses of schizophrenia and major affective disorders were found; schizoaffective disorder was a minor diagnosis. Beginning in the early 1970s, a gradual increase in the frequency of diagnoses of major affective disorders at all sites was accompanied by a corresponding decrease in diagnoses of schizophrenia at five of the six centers. Schizophrenia diagnoses decreased from a peak of 27% in 1976 to 9% in 1989 (a threefold decrease), and diagnoses of major affective disorders rose from a low of 10% in 1972 to 44% in 1990 (a fourfold increase). CONCLUSIONS: Several forces may have influenced these changes. 1) DSM-III narrowed the definition of schizophrenia and broadened the category of major affective disorders. 2) Treatment-oriented diagnostic bias associated with the availability of lithium and other mood-altering agents may have encouraged consideration of affective disorders. 3) Economic and social forces, including better third-party reimbursement rates, may have favored affective diagnoses. 4) True increases in the incidence of affective disorders may have occurred. 5) Although a real decrease in new cases of schizophrenia may have occurred, this effect was probably minor and dominated by a larger shift of such diagnoses to affective categories.
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The article compares characteristics of the residential and non-residential mental health services in Israel and in New York State and considers their influences on extent of service utilization. The data is based on special surveys covering all patients seen in public mental health services in New York State and in Israel during one week in 1986. The results indicate similar overall residential prevalence rates in both systems (1.9 per 1,000 population). Israeli males aged 45-64 show much higher residential prevalence rates than males of this group in NYS. The Israeli non-residential rates are much lower, 3.5 per 1,000 as compared to 5.5 in NYS. These differences are seen in both sexes and across all age groups. Overall diagnostic distributions show a greater percentage of patients with major affective disorder in NYS and a somewhat greater percentage of patients with the diagnosis of schizophrenia in Israel. Three Service Dependency Levels (SDL) are defined and their distribution by loci of care are presented. A greater proportion of patients belong to the highest SDL (1) in Israel as compared to NYS. Both in New York State and in Israel, the development of public mental health services is generally oriented to a preference for the non-residential, community treatment model over the residential, institutional model. However, Israel is less advanced than New York in developing its non-residential psychiatric services, as reflected by the relative low rate of psychiatric referrals to community facilities and clinics. Analysis and explanation of these survey differences are presented.
A novel approach to the prediction of valve-related complications in patients with implanted artificial heart valves is discussed. Adaptive artificial neural networks were used to identify patients at high risk of valve-related events based on preoperative data. Data from a clinical trial on 789 subjects with Carpentier-Edwards pericardial bioprostheses were used. Patients' records were divided into two groups, one of which was used for training the neural network and the other for testing the trained network and determining error rates. Patient information such as age, sex, NYHA class and anticoagulation therapy, as well as valve information such as size and the date of implant, were used as the network inputs. The neural net had a single output variable indicating the risk that an individual patient would develop a valve-related complication resulting in death. The results show that a trained neural network was able to predict valve-related deaths in the specified time interval of 1981-1991 with a high degree of accuracy. The neural network was also successful in classifying patients into high and low risk categories.
The standard regimen for prophylaxis in bilary surgery consists of three doses of a first- or second-generation cephalosporin (one pre- and two postoperatively). The purpose of our study was to compare a single dose of cefuroxime (1.5 gi.v. on call to surgery) with the standard regimen (1.5 gi.v. on call to surgery followed by two additional doses of 750 mg i.v. each, 8 and 16 h after surgery). One hundred patients participated in the study, 44 in the single-dose group and 56 in the triple-dose group. These two groups did not differ with regard to sex, risk factors, duration of surgery, etc. The incidence of infection was 9% in the single-dose group and 7% in the triple-dose group. We conclude that one dose of cefuroxime is as effective as three for biliary surgery. This regimen would reduce the risk of side effects and/or suprainfections and the emergence of resistant strains of bacteria. It is also more convenient for the nursing staff and reduces the cost by one-half.