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Biomedical subjects

M Schuster

Publications and source records attributed to M Schuster.

At least 73 records · Page 4Linked to original sources
PubMed2000

Hypothermia-induced coagulopathy during hemorrhagic shock.

A porcine model of hemorrhagic shock was used to study the effect of hypothermia on hemodynamic, metabolic, and coagulation parameters. The model was designed to simulate the events of severe blunt injury with hemorrhage occurring initially, to a systolic blood pressure of 30 mm Hg, followed by simultaneous hemorrhage and crystalloid volume replacement, followed by cessation of hemorrhage and blood replacement. Half of the animals were rendered hypothermic by external application of ice, and half remained normothermic. There was seven pigs in each group. Two deaths occurred in each during the hemorrhage phase. The hypothermic pigs demonstrated larger reduction in cardiac output than normothermic pigs. Volume replacement in the normothermic group restored cardiac output to baseline values. In the hypothermic group, cardiac output remained depressed despite volume replacement. Prothrombin times and partial thromboplastin times showed significantly more prolongation in the hypothermic group. Furthermore, this was not corrected by replacement of shed blood in the hypothermic group, as was seen in the normothermic group. We conclude that when shock and hypothermia occur together, their deleterious effect on hemodynamic and coagulation parameters are additive. The effects of hypothermia persist despite the arrest of hemorrhage and volume replacement. Thus, it is necessary to aggressively address both shock and hypothermia when they occur simultaneously.

Animals↗
PubMed2000

The carina as a landmark in central venous catheter placement.

Location of the tip of a central venous catheter (CVC) within the pericardium has been associated with potentially lethal cardiac tamponade. Because the pericardium cannot be seen on chest x-ray (CXR), an alternative radiographic marker is needed for correct placement of CVCs. The anatomy of the region was studied in 34 cadavers. The carina was a mean (SEM) distance of 0.4 (0.1) cm above the pericardial sac as it transverses the superior vena cava (SVC). In no case was the carina located below the pericardial sac. The carina is a reliable, simple anatomical landmark for the correct placement of CVCs. In almost all cases, the carina is radiologically visible even in poor quality, portable CXRs. CVC tips should be located in the SVC above the level of the carina in order to avoid cardiac tamponade.

Aged↗
PubMed1999

Quantitative changes in T-cell populations after left ventricular assist device implantation: relationship to T-cell apoptosis and soluble CD95.

BACKGROUND: Left ventricular assist devices (LVADs) are currently being evaluated as permanent therapy for end-stage heart failure. Because life-threatening infections limit successful long-term device implantation, we investigated the relationship between quantitative T-cell defects in LVAD recipients and CD95-mediated T-cell apoptosis. METHODS AND RESULTS: Immunological studies were performed in NYHA class IV patients awaiting cardiac transplantation who received either a TCI Heartmate left ventricular assist device (LVAD) or medical management. Fluorochrome-labeled Mabs were used in T-cell phenotypic analyses. T-cell apoptosis was measured by annexin V binding of T cells cultured in medium for 24 hours. Circulating serum levels of soluble CD95 were measured by ELISA. LVAD recipients had a relative lymphopenia and reduction in CD4 T-cell levels compared with NYHA class IV heart failure controls. These observations were confirmed in a longitudinal study in LVAD recipients, which showed that device implantation was accompanied by progressive and sustained reductions in circulating CD4 T-cell levels. These abnormalities in LVAD recipients were accompanied by increased levels of circulating soluble CD95 and by excessive CD4 and CD8 T-cell apoptosis. Susceptibility to induction of apoptosis was >2-fold greater for CD4 T cells than for CD8 T cells. CONCLUSIONS: These results suggest that the reduction in CD4 T-cell levels accompanying LVAD implantation is a consequence of an augmented pathway of CD95-mediated apoptosis. The clinical consequences of these abnormalities may include increased prevalence of systemic infections.

Apoptosis↗
PubMed1999

Mosaicism in a fragile X male including a de novo deletion in the FMR1 gene.

In most cases the fragile X syndrome is caused by an amplification of the CGG trinucleotide repeat in the 5' untranslated region of the FMR1 gene, in combination with the hypermethylation of the proximal CpG island. Recently, also a few cases with deletions or a mosaic of a deletion and a full mutation in the FMR1 gene, leading to the same phenotype, have been described. Here we report the molecular analysis of a patient with typical fragile X phenotype and mosaicism of the FMR1 genomic region consisting of a premutation, a full mutation of the CGG repeats, and a 215 bp deletion, diagnosed by Southern blot hybridisation and polymerase chain reaction (PCR). Sequence analysis of the deletion demonstrated that the 5' breakpoint of the deletion is located within a putative hotspot region 75-53 bp proximal to the CGG repeat.

Adult↗
PubMed1999

Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group.

BACKGROUND: In patients with persistent fever and neutropenia, amphotericin B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections. However, breakthrough fungal infections can develop despite treatment, and amphotericin B has substantial toxicity. METHODS: We conducted a randomized, double-blind, multicenter trial comparing liposomal amphotericin B with conventional amphotericin B as empirical antifungal therapy. RESULTS: The mean duration of therapy was 10.8 days for liposomal amphotericin B (343 patients) and 10.3 days for conventional amphotericin B (344 patients). The composite rates of successful treatment were similar (50 percent for liposomal amphotericin B and 49 percent for conventional amphotericin B) and were independent of the use of antifungal prophylaxis or colony-stimulating factors. The outcomes were similar with liposomal amphotericin B and conventional amphotericin B with respect to survival (93 percent and 90 percent, respectively), resolution of fever (58 percent and 58 percent), and discontinuation of the study drug because of toxic effects or lack of efficacy (14 percent and 19 percent). There were fewer proved breakthrough fungal infections among patients treated with liposomal amphotericin B (11 patients [3.2 percent]) than among those treated with conventional amphotericin B (27 patients [7.8 percent], P=0.009). With the liposomal preparation significantly fewer patients had infusion-related fever (17 percent vs. 44 percent), chills or rigors (18 percent vs. 54 percent), and other reactions, including hypotension, hypertension, and hypoxia. Nephrotoxic effects (defined by a serum creatinine level two times the upper limit of normal) were significantly less frequent among patients treated with liposomal amphotericin B (19 percent) than among those treated with conventional amphotericin B (34 percent, P<0.001). CONCLUSIONS: Liposomal amphotericin B is as effective as conventional amphotericin B for empirical antifungal therapy in patients with fever and neutropenia, and it is associated with fewer breakthrough fungal infections, less infusion-related toxicity, and less nephrotoxicity.

Adolescent↗
PubMed1999

Organic brain disease in psychogeriatric patients: impact of symptoms and screening methods on the diagnostic process.

Psychogeriatric patients are mentally affected by a heterogeneous group of diseases, traditionally classified as functional or organic brain disorders (OBDs). Here, we evaluate screening procedures with respect to revelation of underlying OBD. Fifty consecutive patients admitted to a psychogeriatric unit dedicated to late-onset psychiatric disease were included. Diagnosis at admission, symptoms, and time of onset of disease were determined blindly by an independent, experienced psychiatrist on the basis of referral documents and the interview written at admission. Subsequently, consensus established a clinical diagnosis (after psychiatric and neurologic evaluations) and a final diagnosis after the screening procedures (Cognistat and MMS-tests, electroencephalograms, computed tomography, and SPECT). Conventional criteria (ICD-10, ICPC) were used for diagnostic classification. Only 10 of the 50 patients were diagnosed with OBD at admission and an additional 7 patients following full clinical evaluations. At final diagnosis, 34 (of 46) patients were diagnosed with significant OBD. The Cognistat test had the largest diagnostic impact, with sensitivity/specificity values of 81%/60% for OBD.

Aged↗
PubMed1999

Randomized, double-blind, placebo-controlled trial to evaluate the hematopoietic growth factor PIXY321 after moderate-dose fluorouracil, doxorubicin, and cyclophosphamide in stage II and III breast cancer.

PURPOSE: To measure the effect of PIXY321 (granulocyte-macrophage colony-stimulating factor/interleukin-3 S. cerevisiae fusion protein) on the incidence, duration, and complications of neutropenia and thrombocytopenia after moderate-dose fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 750 mg/m(2) (FAC) chemotherapy in patients with stage II and III breast cancer. PATIENTS AND METHODS: In this multicenter, randomized, double-blind placebo-controlled trial, 71 women were to receive four 21-day cycles of treatment with moderate-dose FAC chemotherapy by short intravenous infusion on day 1, followed by either placebo or PIXY321 (375 microg/m(2) subcutaneously twice a day) on days 3 to 15. All patients were to receive prophylactic oral ciprofloxacin when the absolute neutrophil count was less than 1,000/microL. RESULTS: PIXY321 significantly reduced the incidence and duration of grade 3 and grade 4 neutropenia in cycles 1 and 2 and the duration of grade 3 neutropenia in cycles 1 through 4. In cycles 3 and 4, grade 3 thrombocytopenia was significantly more common with PIXY321 (P <.05). Two patients, both in the PIXY321 group, required platelet transfusions. Fever and hospitalization for intravenous antibiotics were significantly more common in the PIXY321 group during cycle 1 only. More patients in the PIXY321 group achieved hematologic recovery by day 22 in cycles 1 through 3, and time to recovery was significantly shorter with PIXY321 in all cycles. FAC dose intensity was roughly 2% higher in the PIXY321 group (P = NS). Nonhematologic events of any intensity occurring with significantly greater overall frequency in the PIXY321 group included injection-site reactions, fever, chills, abdominal pain, and arthralgia. No patient died on study or within 30 days of her last dose of study drug. CONCLUSION: PIXY321 decreased the incidence and duration of FAC-induced grade 3 and 4 neutropenia in cycles 1 and 2 and significantly shortened the time to hematologic recovery in all cycles. However, it produced more systemic toxicity as well as thrombocytopenia in cycles 3 and 4.

Adenocarcinoma↗
PubMed1999

Lymphocyte dynamics in the pulmonary microenvironment: implications for the pathophysiology of pulmonary sarcoidosis.

It is generally accepted that lymphocytes play a role in sarcoidosis. Lymphocyte numbers and in particular certain subsets are increased in the bronchoalveolar lavage fluid, and these parameters have been used as indicators for prognosis. To understand the pathophysiology of sarcoidosis the localisation and kinetics of lymphocytes in the normal lung have to be known. Lymphocytes are found in different compartments of the lung: the pulmonary vascular bed with the marginal lymphocyte pool, intraepithelial lymphocytes, the lamina propria of the bronchial tree, at a young age and under certain pathological conditions the bronchus-associated lymphoid tissue, the interstitial lymphocyte pool and the lymphocytes in the bronchoalveolar space as recovered by bronchoalveolar lavage. The lymphocyte subsets differ in these compartments. The number and subset composition are influenced by the balance of immigration, regulated by adhesion molecules, local proliferation, apoptosis and migration. In sarcoidosis lymphocyte proliferation and cell death in the bronchoalveolar space are increased several fold in the lung. More studies on regulatory factors of lymphocyte kinetics are needed in the lung of sarcoidosis patients before new therapeutic strategies can be tested.

Apoptosis↗
PubMed1998

CD95 ligand-induced apoptosis of human medulloblastoma cells.

CD95 ligand (CD95L) is a cytotoxic cytokine that induces apoptosis in susceptible target cells. Medulloblastoma is the most common non-glial intrinsic malignancy of the brain. In this study, we have studied CD95-mediated apoptosis of human medulloblastoma cell lines. We found that DAOY, MED-1 and D-283 cells are susceptible to CD95L-induced apoptosis when RNA and protein synthesis are inhibited. Preexposure of D-283, but not DAOY or MED-1 cells, to interferon-gamma or tumor necrosis factor-alpha enhances CD95 expression and primes these cells for CD95-mediated apoptosis. Inhibitors of interleukin 1-converting enzyme (ICE)-like protease (caspase) activity block CD95L-induced cytotoxicity, suggesting that caspases mediate the death signal induced by CD95L in human medulloblastoma cells. Interestingly, medulloblastoma cells belong to an increasing number of tumor cell types that coexpress CD95 and CD95L. We conclude that CD95 may be a promising target of immunochemotherapy for human medulloblastoma.

Animals↗
PubMed1998

Acetylation at Lys-92 enhances signaling by the chemotaxis response regulator protein CheY.

When Escherichia coli cells lacking all chemotaxis proteins except the response regulator CheY are exposed to acetate, clockwise flagellar rotation results, indicating the acetate stimulus has activated signaling by CheY. Acetate can be converted to acetyl-CoA by either of two different metabolic pathways, which proceed through acetyl phosphate or acetyl-AMP intermediates. In turn, CheY can be covalently modified by either intermediate in vitro, leading to phosphorylation or acetylation, respectively. Either pathway is sufficient to support the CheY-mediated response to acetate in vivo. Whereas phosphorylation of Asp-57 is a recognized mechanism for activation of CheY to stimulate clockwise flagellar rotation, acetylation of CheY is less well characterized. We found evidence for multiple CheY acetylation sites by mass spectrometry and directly identified Lys-92 and Lys-109 as acetylation sites by Edman degradation of peptides from [14C]acetate-labeled CheY. Replacement of CheY Lys-92, the preferred acetylation site, with Arg has little effect on chemotaxis but completely prevents the response to acetate via the acetyl-AMP pathway. Thus acetylation of Lys-92 activates clockwise signaling by CheY in vivo. The mechanism by which acetylation activates CheY apparently is not simple charge neutralization, nor does it involve enhanced binding to the FliM flagellar switch protein. Thus acetylation probably affects signal generation by CheY at a step after switch binding.

Acetate-CoA Ligase↗
PubMed1998

Surviving social assistance: 12-month prevalence of depression in sole-support parents receiving social assistance.

BACKGROUND: Although it is generally recognized that poverty and depression can coexist among single parents receiving social assistance, there is insufficient research on this topic. The goals of this study therefore were to investigate the prevalence, correlates and health care expenditures associated with depression among sole-support parents receiving social assistance. METHODS: Sole-support parents who had applied for social assistance in 2 regions of southwestern Ontario were included in the study. Depression was diagnosed with the 1994 University of Michigan Composite International Diagnostic Interview short forms. RESULTS: The 12-month prevalence rate of depressive disorder among the parents interviewed was 45.4% (345/760). A total of 247 (32.5%) had major depressive disorder alone, 19 (2.5%) had dysthymia, and 79 (10.4%) had both major depressive disorder and dysthymia ("double depression"). Those with major depressive disorder, particularly double depression, had significantly higher rates of coexisting psychiatric disorder than those without depressive disorders. Parents with depression reported higher rates of developmental delay and behaviour problems in their children than parents without depression. Expenditures for health care services were higher for parents with depression and for their children than for parents without depressive disorder and their children. INTERPRETATION: Single parents receiving social assistance have high rates of depression. Such parents with depression also have higher rates of other psychiatric disorders and higher expenditures for health care services, and their children have higher rates of developmental delay and behaviour problems.

Adaptation, Psychological↗
PubMed1998

Increasing immunization rates among inner-city, African American children. A randomized trial of case management.

CONTEXT: Immunization rates in the inner city remain lower than in the general US population, but efforts to raise immunization levels in inner-city areas have been largely untested. OBJECTIVE: To assess the effectiveness of case management in raising immunization levels among infants of inner-city, African American families. DESIGN: Randomized controlled trial with follow-up through 1 year of life. SETTING: Low-income areas of inner-city Los Angeles, Calif. PATIENTS: A representative sample of 419 African American infants and their families. INTERVENTIONS: In-depth assessment by case managers before infants were 6 weeks of age, with home visits 2 weeks prior to when immunizations were scheduled and additional follow-up visits as needed. MAIN OUTCOME MEASURES: Percentage of children with up-to-date immunizations at age 1 year, characteristics associated with improved immunization rates, and cost-effectiveness of case management intervention. RESULTS: A total of 365 newborns were followed up to age 1 year. Overall, the immunization completion for the case management group was 13.2 percentage points higher than the control group (63.8% vs 50.6%; P=.01). In a logistic model, the case management effect was limited to the 25% of the sample who reported 3 or fewer well-child visits (odds ratio, 3.43; 95% confidence interval, 1.26-9.35); for them, immunization levels increased by 28 percentage points. Although for the case management group intervention was not cost-effective ($12022 per additional child immunized), it was better ($4546) for the 25% of the sample identified retrospectively to have inadequate utilization of preventive health visits. CONCLUSIONS: A case management intervention in the first year of life was effective but not cost-effective at raising immunization levels in inner-city, African American infants. The intervention was demonstrated to be particularly effective for subpopulations that do not access well-child care; however, currently there are no means to identify these groups prospectively. For case management to be a useful tool to raise immunizations levels among high-risk populations, better methods of tracking and targeting, such as immunization registries, need to be developed.

Black or African American↗
PubMed1998

Reducing missed opportunities to vaccinate during child health visits. How effective are parent education and case management?

BACKGROUND: At child health visits, immunizations that are due are frequently not given. Increased parent understanding of and demand for immunizations may influence providers to not miss these opportunities. OBJECTIVE: To assess, as part of a larger study of effectiveness of parent education and case management (CM) in raising immunization rates, the intervention's effectiveness at reducing missed opportunities to vaccinate during child health visits. METHODS: A representative sample of African American newborns and their families from south central Los Angeles, Calif, were randomly assigned to a control or a CM group and observed during the first year of life. Case managers visited and telephoned parents, educating them on the benefits and safety of immunizations, and encouraging them to request immunizations from providers. When the children were at least 1 year of age, parents were interviewed and provider records were abstracted. RESULTS: Complete records were abstracted for 126 controls and 129 CM group children. For these children, 1092 visits were documented where immunizations were due. Missed opportunities to vaccinate occurred at more than 50% of visits. Case management was associated with a modest reduction in the percentage of visits with missed opportunities in the bivariate analysis but not after adjustment for other covariates. In a logistic regression model, missed opportunities were more frequent at visits with private than public physicians and at acute illness than well-child visits. Missed opportunities were less frequent among children with a history of at least 1 cancelled appointment, and for visits of children with mothers who smoked. CONCLUSIONS: Missed opportunities were minimally influenced by a home visitation and parent education program. They are primarily determined by issues under the control of the provider. Family- and child-related characteristics, however, do influence the likelihood of a missed opportunity occurring independent of provider factors.

Black or African American↗
PubMed1998

Solvent production by Clostridium beijerinckii NRRL B592 growing on different potato media.

Very good solvent formation rates were observed when Clostridium beijerinckii NRRL B592 was cultivated on different whole potato media. The increase in whole potato concentration contributed to the increased final solvent concentrations, while the addition of yeast extract or mineral salts gave negative effects. To obtain good solvent productivities and high final solvent concentrations during batch fermentation, no enzymatic hydrolysis of the potato starch was necessary, indicating high activity of the clostridial amylases produced by the strain applied.

Amylases↗
PubMed1998

Massachusetts Weapon-Related Injury Surveillance System.

CONTEXT: Surveillance data on nonfatal weapon-related injuries--particularly those treated only in the emergency department (ED)--have been largely unavailable. OBJECTIVE: To develop a surveillance system for fatal and nonfatal gunshot wounds and sharp instrument assaults. DESIGN: The Massachusetts Department of Public Health (DPH) developed an ED-based reporting system for weapon-related injuries. Inpatient discharges and mortality data were linked to ED data, and police data sources were evaluated. SETTING: Statewide. PARTICIPANTS: All 84 acute care hospital emergency departments. Uniform Hospital Discharge Data Set (UHDDS), mortality, and police data were obtained from existing systems. MAIN OUTCOME MEASURES: System sensitivity, predictive value positive (PVP), representativeness, flexibility, usefulness, acceptability, and sustainability. RESULTS: The ED reporting system captured 82% of firearm-related injuries and 74% of reportable sharp instrument wounds from 1994 to 1996. Case reporting by demographic characteristics of the victim was representative and largely complete. Reporting by characteristics of the incident (e.g., type of gun) was less reliable. Police data were used to augment the system. From 1994 to 1996, ED-treated gunshot wounds dropped 41%, from 662 in 1994 to 393 in 1996. Unintentional and self-inflicted gunshot wounds showed no declines. For every firearm-related homicide, 4.7 nonfatal firearm assaults were treated; 85% of self-inflicted gunshot wounds were fatal. CONCLUSIONS: The system has proven timely (1996 ED data were available for release in March 1997), flexible (the reporting form has been revised several times), useful (DPH responds to 150 weapon injury data requests annually), acceptable (reporting is voluntary and no hospital declined participation), and sustainable (state funding is currently supporting the ED reporting system).

Adolescent↗
PubMed1998

Soluble CD95 (Fas/APO-1) in malignant glioma: (no) implications for CD95-based immunotherapy?

CD95 targeting is a novel approach of immunotherapy for malignant glioma that might be antagonized by the release of soluble CD95 by the tumor cells. An alternatively spliced CD95 mRNA that encodes a secreted CD95 variant has been detected in glioma cell lines in vitro and in human tumors in vivo. Here, we report that the levels of soluble CD95 in the serum of malignant glioma patients do not differ from those of lumbar disk disease patients. Soluble CD95 was detected in the CSF in 2 of 20 malignant glioma patients by ELISA. Bioassay studies indicate that these low levels of soluble CD95 in the CSF of some patients with malignant glioma cells are unlikely to interfere with CD95-based immunotherapy of malignant gliomas in vivo.

Apoptosis↗