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Biomedical subjects

B Schmitt

Publications and source records attributed to B Schmitt.

At least 73 records · Page 4Linked to original sources
PubMed1999

Maximum androgen-blockade with medical or surgical castration in advanced prostate cancer: A meta-analysis of nine published randomized controlled trials and 4128 patients using flutamide.

With the recent Southwest Oncology Group (SWOG) publication of their metastatic prostate cancer clinical trial results, which concluded that orchiectomy and flutamide as maximal androgen blockade (MAB) therapy vs orchiectomy alone does not significantly improve survival (NCI 0105), and the 1989 publication from the same cooperative group indicating a 24% improvement in survival for MAB therapy with leuprolide and flutamide versus leuprolide alone (NCI 0036), clinicians may well be undecided about the likelihood of clinical benefits with flutamide in combination with medical or surgical castration. To better characterize this important therapeutic decision, we assessed the survival benefit of MAB therapy with flutamide through a meta-analysis of up-to-date information from studies reported/conducted from 1989 through 1998. All peer-reviewed published randomized controlled trials comparing treatment with flutamide plus either lutenizing hormone releasing hormone (LhRH) agonists or orchiectomy as MAB treatment with LhRH or orchiectomy alone were included. The primary objective of the study was to form a combined estimate and confidence interval for the hazard ratio (as measured by the relative risk (RR) of survival in a comparison of castration vs MAB) summarizing the effect of flutamide treatment on overall survival. Directly extracted estimates of the log hazard ratio were used if available (1 study); if not, either an estimate of the RR based on a reported P-value from a log rank test (7 studies) or a discrete proportional hazards approximation based on reconstructed annual life tables for the treatment arms (1 study) were used. Nine studies with 4128 patients with advanced prostate cancer were included in these analyses. Pooled estimates demonstrated a 10% improvement in overall survival with flutamide as MAB therapy (relative risk (RR)=0.90, 95% Confidence Interval=0.79, 1.00). The currently available updated evidence from randomized trials shows a 10% benefit in overall survival with flutamide as MAB therapy in comparison to conventional castration, almost identical to the estimate reported in the recently published Southwest Oncology Group Study (NCI 0105).

Journal Article↗
PubMed1999

Visual field constriction is not limited to children treated with vigabatrin.

Vigabatrin (GVG) is widely used in the treatment of complex partial seizures and infantile spasms. Persistent visual field constriction associated with GVG therapy in adults was reported as a rare but serious side-effect. Visual field examination in children is more difficult because of a lack of cooperation among very young or mentally handicapped patients. We performed Goldmann perimetry in 12 of 153 patients treated with GVG as mono- or as add-on therapy. The others would not cooperate, and two adolescents refused the examination. For comparison, we examined 12 age-matched patients with complex partial or generalized epilepsy who had never taken GVG. In five of 12 GVG-treated patients, and in one of the control group, we found a concentric visual field constriction. All patients were subjectively asymptomatic. The GVG-treated patients had taken the drug in combination with valproic acid (VPA) or oxcarbazepine (OCB). In four patients, GVG treatment was already stopped at the time of the ophthalmologic examination. Three patients had intracerebral lesions that could not account for the pathologic perimetric findings. The single patient from the control group with concentric visual field constriction had an absence epilepsy, treatment being performed with VPA and lamotrigine (LTG). In conclusion, GVG has a causal but not unique connection with visual field constriction in pediatric patients.

Adolescent↗
PubMed1998

Congenital ataxia of parietal origin? Report of two cases.

Congenital cerebellar ataxia is usually thought to be of cerebellar origin. We report two children with congenital cerebellar ataxia, in whom neuroimaging investigations suggest the possibility of a parietal etiology. The two boys showed hypotonia, delayed motor and cognitive development followed by marked, truncally pronounced ataxia. In one case infantile spasms were treated successfully with adrenocorticotropic hormone, although in follow-up the child suffered from occasional seizures. Magnetic resonance imaging showed in one case parieto-occipital pachygyria and in the other there was marked pachygyria, most pronounced over the parieto-occipital area. In both children cerebellar structures were normal. Cerebello-parietal connections are known to be responsible for acquired parietal limb ataxia. Although not proven, parietal lesions are the most likely etiology of congenital cerebellar ataxia in these two children. Therefore, cerebral, especially parietal pathology must be considered in children with congenital ataxia.

Brain Diseases↗
PubMed1998

Serum and CSF levels of neuron-specific enolase (NSE) in cardiac surgery with cardiopulmonary bypass: a marker of brain injury?

We investigated whether neuron-specific enolase (NSE) in serum or cerebrospinal fluid (CSF) reflects subtle or manifest brain injury in children undergoing cardiac surgery using cardiopulmonary bypass (CPB). NSE was measured in serum (s-NSE) before, and up to, 102 h after surgery in 27 children undergoing cardiac surgery with CPB. In 11 children, CSF-NSE was also measured 48 or 66 h post-surgery. As erythrocytes contain NSE, hemoglobin concentration in the samples was determined spectrophotometrically at 550 nm (cut-off limit: absorbance 0.4 = 560 mg/l) in 14 children and in a further 13 children by spectroscopic multicomponent analysis (cut-off limit 5 micromol/l = 80 mg/l). One hundred and one of 214 post-operative serum samples (47%) had to be discarded because of hemolysis (18% spectrophotometrically at 550 nm and 88% with spectroscopic multicomponent analysis). On the first and second post-operative day, the median s-NSE values were significantly higher when compared with samples taken after 54 h or longer (P = 0.008 and P = 0.002). All CSF-NSE levels were within the normal range and below the s-NSE measured in the same patient. Although in our study elevated s-NSE seems to indicate brain injury in CPB-surgery, the low concentration of NSE in the post-operative CSF of 11 children puts the neuronal origin of s-NSE in question. NSE from other non-neuronal tissues probably contributes to the elevated s-NSE. Additionally, normal post-operative CSF-NSE values in two children with post-operative neurological sequelae might question the predictive value of CSF-NSE with regard to brain injury.

Biomarkers↗
PubMed1998

D alpha3, a new functional alpha subunit of nicotinic acetylcholine receptors from Drosophila.

Nicotinic acetylcholine (ACh) receptors (nAChRs) are important excitatory neurotransmitter receptors in the insect CNS. We have isolated and characterized the gene and the cDNA of a new nAChR subunit from Drosophila. The predicted mature nAChR protein consists of 773 amino acid residues and has the structural features of an ACh-binding alpha subunit. It was therefore named D alpha3, for Drosophila alpha-subunit 3. The d alpha3 gene maps to the X chromosome at position 7E. The properties of the D alpha3 protein were assessed by expression in Xenopus oocytes. D alpha3 did not form functional receptors on its own or in combination with any Drosophila beta-type nAChR subunit. Nondesensitizing ACh-evoked inward currents were observed when D alpha3 was coexpressed with the chick beta2 subunit. Half-maximal responses were at approximately 0.15 microM ACh with a Hill coefficient of approximately 1.5. The snake venom component alpha-bungarotoxin (100 nM) efficiently but reversibly blocked D alpha3/beta2 receptors, suggesting that D alpha3 may be a component of one of the previously described two classes of toxin binding sites in the Drosophila CNS.

Amino Acid Sequence↗
PubMed1998

Vigabatrin as a first-line drug in West syndrome: clinical and electroencephalographic outcome.

The cessation of infantile spasms and the disappearance of hypsarrhythmia in sleep EEG are the criteria for successful treatment in West syndrome. In a prospective study at the Children's University Hospital, 28 children with West syndrome (17 symptomatic, 7 cryptogenic, 4 idiopathic) were treated with vigabatrin monotherapy for at least 2 weeks. Seven children received vigabatrin 150 mg/kg/day, and 21 children received 65-75 mg/kg/day. Patients were classified as responders, when infantile spasms and hypsarrhythmia in sleep EEG disappeared within 2 weeks. After 2 weeks, 18 patients were seizure-free, 14 without hypsarrhythmia. Fourteen children were responders (8 symptomatic, 3 cryptogenic, 3 idiopathic), and 14 non-responders. The follow-up encompassed 6 months to 5.3 years (mean 20.3 months). In the responder group, 12/14 patients (6 symptomatic, 3 cryptogenic and 3 idopathic) remained seizure-free, no relapse of West syndrome occurred. In the non-responder group, ACTH was efficient in 11, valproic acid in 2 children and clonazepam in 1 child. Relapse occurred in 4 children after discontinuation of ACTH. At last visit EEG was normal in 8/14 responders and 1/14 non-responders. The efficacy of vigabatrin monotherapy was comparable to ACTH and occurred within 2 weeks.

Adrenocorticotropic Hormone↗
PubMed1998

Electroencephalogram changes during inhalation with nitric oxide in the pediatric intensive care patient--a preliminary report.

OBJECTIVES: Although endogenous nitric oxide (NO) is an excitatory mediator in the central nervous system, inhaled NO is not considered to cause neurologic side effects because of its short half-life. This study was motivated by a recent case report about neurologic symptoms and our own observation of severe electroencephalogram (EEG) abnormalities during NO inhalation. DESIGN: Blind, retrospective analyses of EEGs which were registered before, during, and after NO inhalation. EEG was classified in a 5-point rating system by an independent electroencephalographer who was blinded to the patients' clinical histories. Comparisons were made with the previous evaluation documented at recording. Other EEG-influencing parameters such as oxygen saturation, hemodynamics, electrolytes, and pH were evaluated. SETTING: Pediatric intensive care unit of a tertiary care university children's hospital. PATIENTS: Eleven ventilated, long-term paralyzed, sedated children (1 mo to 14 yrs) who had EEG or clinical assessment before NO treatment and EEG during NO inhalation. They were divided into two groups according to the NO-indication (e.g., congenital heart defect, acute respiratory distress syndrome). MEASUREMENTS AND MAIN RESULTS: All 11 patients had an abnormal EEG during NO inhalation. EEG-controls without NO showed remarkable improvement. EEG abnormalities were background slowing, low voltage, suppression burst (n = 2), and sharp waves (n = 2) independent of patients' age, NO-indication, and other EEG-influencing parameters. CONCLUSIONS: These preliminary data suggest the occurrence of EEG-abnormalities after application of inhaled NO in critically ill children. We found no correlation with other potential EEG-influencing parameters, although clinical state, medication, or hypoxemia might contribute. Comprehensive, prospective, clinical assessment regarding a causal relationship between NO-inhalation and EEG-abnormalities and their clinical importance is needed.

Administration, Inhalation↗
PubMed1998

Adverse effects of vigabatrin in Angelman syndrome.

New antiepileptic drugs designed for enhancing GABAergic inhibition, such as vigabatrin (VGB) may be effective in Angelman syndrome (AS), because associated convulsions could be related to a reduced GABA-receptor density or receptor abnormality. From our preliminary experiences in four children with AS treated with VGB, we conclude that it may induce and increase seizures in patients with AS.

Adult↗
PubMed1997

Impact of medication nonadherence on coronary heart disease outcomes. A critical review.

A critical review of published literature was performed to assess the impact of medication adherence on morbidity and mortality among patients with or at risk for coronary artery disease and congestive heart failure. Twenty-one original research articles that met our inclusion criteria and related medication adherence to morbidity and mortality are summarized. No clinical trials that specifically tested the impact of a compliance-enhancing intervention on outcome in coronary heart disease were identified. Among 12 studies that compared hospitalization rates and mortality between adherers and nonadherers, 7 showed a significant relationship between medication adherence and outcomes. Three studies showed that adherence to placebo was associated with improved outcomes, suggesting that adherent behavior may be a marker of better prognosis or confers a protective effect on patients with coronary heart disease. Further study is necessary to determine whether adherent behavior can be taught and whether compliance-enhancing strategies improve outcomes in coronary heart disease.

Clinical Trials as Topic↗
PubMed1997

Insertional mutation of the Drosophila nuclear lamin Dm0 gene results in defective nuclear envelopes, clustering of nuclear pore complexes, and accumulation of annulate lamellae.

Nuclear lamins are thought to play an important role in disassembly and reassembly of the nucleus during mitosis. Here, we describe a Drosophila lamin Dm0 mutant resulting from a P element insertion into the first intron of the Dm0 gene. Homozygous mutant animals showed a severe phenotype including retardation in development, reduced viability, sterility, and impaired locomotion. Immunocytochemical and ultrastructural analysis revealed that reduced lamin Dm0 expression caused an enrichment of nuclear pore complexes in cytoplasmic annulate lamellae and in nuclear envelope clusters. In several cells, particularly the densely packed somata of the central nervous system, defective nuclear envelopes were observed in addition. All aspects of the mutant phenotype were rescued upon P element-mediated germline transformation with a lamin Dm0 transgene. These data constitute the first genetic proof that lamins are essential for the structural organization of the cell nucleus.

Animals↗
PubMed1997

Pharmacists on a primary care team at a Veterans Affairs medical center.

The role of pharmacists on a primary care team in the VA Chicago Health Care System--Lakeside Division is described. In 1990 the Veterans Affairs Lakeside Medical Center (now called the VA Chicago Health Care System--Lakeside Division) implemented the "Firm" system to improve the quality of patient care. This system split the original primary care clinics into three identical but smaller groups, or Firms. Each Firm provides three types of care: longitudinal care (ongoing care with a primary care physician), interim care (frequent care and close patient monitoring between primary physician visits), and un-scheduled care (acute care for complaints that may require immediate attention). Each Firm has a care team composed of physicians, a pharmacist, nurses, and other health care personnel. The pharmacist assists with interim care and, in conjunction with Firm physicians, is involved in follow-up and monitoring of drug therapy and identification of new problems. Originally it was expected that pharmacists would care for 30-40% of interim care patients, but Firm pharmacists have assisted in providing care to over 50% of these patients (plus 4% of un-scheduled care patients). The pharmacists have received high ratings from the internal medicine resident staff. Pharmacists on multidisciplinary care teams provided primary care to more than half of outpatient veterans in need of health care between regularly scheduled appointments.

Chicago↗
PubMed1997

In vitro studies of liposome-mediated gene transfer into head and neck cancer cell lines.

The 5-year survival rate of patients with squamous cell carcinoma of the head and neck (HNSCC) has remained poor despite innovative surgery and new radiation and chemotherapeutic strategies. In such patients, gene therapy relying on the modification of tumor cells by gene transfer may have great potential as a new treatment modality in the therapy of HNSCC. In the present study we developed an in vitro model to show the efficacy and technical feasibility of cationic liposome-mediated gene transfer into HNSCC. Five adherent squamous cell carcinoma cell lines were transfected with SV40- or CMV-promoter-driven CAT (chloramphenicol-acetyl-transferase)-expression plasmids using DOTAP as the liposome carrier. The level of CAT expression was shown to correlate directly with the amount of transfected DNA and could be measured by a CAT-enzyme-linked immunosorbent assay. The results of gene transfer by liposome-DNA complexes obtained for all cell lines showed a dose-dependent efficacy correlating to the amount of DOTAP employed. The data demonstrate the successful in vitro transfection of epithelial cell lines with DNA, suggesting its usefulness as a new tool for head and neck cancer therapy in vivo.

Carcinoma↗
PubMed1997

Systolic function, readmission rates, and survival among consecutively hospitalized patients with congestive heart failure.

We sought to describe the relation between left ventricular systolic function and rates of hospital readmission and survival among consecutively hospitalized patients with congestive heart failure. Medical records were reviewed for these patients at an academic medical center between Jan. 1, 1992, and Dec. 31, 1993. Left ventricular systolic function assessments performed within 6 months before discharge were used to classify left ventricular systolic function. Hospital readmission rates and survival through Dec. 31, 1994, were compared between patients with systolic dysfunction and those with preserved systolic function. Among 412 patients hospitalized with a primary diagnosis of congestive heart failure, 224 had undergone a left ventricular function assessment during the 6 months before hospital discharge. In-hospital mortality and readmission rates were higher among patients without a recent assessment of left ventricular systolic function. Of patients with systolic dysfunction, 55% versus 41% of patients with preserved systolic function were either readmitted or had an emergency room visit within 6 months after discharge (p = 0.06). At 27 months' follow-up, cumulative survival probabilities were 65% for patients with preserved systolic function, 65% for patients with systolic dysfunction, and 60% for patients without a left ventricular systolic function assessment (p = 0.24). Patients without a recent left ventricular systolic function assessment have significantly higher hospital readmission rates than patients with a recent systolic function assessment. Among hospitalized patients, mortality rates are comparable between patients with systolic dysfunction and those with preserved systolic function. However, patients with heart failure with systolic dysfunction may have higher readmission rates.

Aged↗
PubMed1997

Heart failure between 1986 and 1994: temporal trends in drug-prescribing practices, hospital readmissions, and survival at an academic medical center.

Since 1987, publications in widely circulated medical journals have reported improved survival and lower hospital readmission rates when patients with heart failure and systolic dysfunction are treated with angiotensin-converting enzyme (ACE) inhibitors. We describe changes in ACE inhibitor use among patients hospitalized with heart failure between 1986 and 1993. Simultaneous trends in readmissions and survival rates are reported. Subjects were 612 consecutive patients hospitalized with a principal diagnosis of heart failure at an academic medical center during the period of Sept. 1, 1986, to Dec. 31, 1987 (interval I) or during the period Aug. 1, 1992, to Nov. 30, 1993 (interval II). Medical records were reviewed for 434 patients, consisting of all patients hospitalized with heart failure during interval II and a randomly selected 50% subset of patients hospitalized during interval I. Among 145 patients with systolic dysfunction whose medical records were reviewed, ACE inhibitor prescriptions significantly increased between interval I and interval II (43% vs 71%, p < 0.01, odds ratio 3.22, 95% confidence interval 1.62 to 6.42). Prescriptions of ACE inhibitors combined with digoxin and a diuretic also increased (37% vs 56%, p = 0.02, odds ratio 2.22, 95% confidence interval 1.14 to 4.32). Among all 612 patients, 6-month heart failure readmission rates increased from 13% to 21% (p = 0.02, odds ratio 1.79, 95% confidence interval 1.10 to 2.82). There was no significant change in survival rate between interval I and interval II, however, survival rate was marginally significantly improved among patients with systolic dysfunction. Our results suggest that drug-prescribing practices have significantly changed between 1986 and 1993. The absence of observed improvement in outcomes may result from changes in hospital admission criteria for heart failure.

Aged↗
PubMed1997

Temperature-sensitive expression of Drosophila neuronal nicotinic acetylcholine receptors.

Heterologous expression of cloned Drosophila nicotinic acetylcholine receptor (nAChR) subunits indicates that these proteins misfold when expressed in mammalian cell lines at 37 degrees C. This misfolding can, however, be overcome either by growing transfected mammalian cells at lower temperatures or by the expression of Drosophila nAChR subunits in a Drosophila cell line. Whereas the Drosophila nAChR beta subunit (SBD) cDNA, reported previously, lacked part of the SBD coding sequence, here we report the construction and expression of a full-length SBD cDNA. We have examined whether problems in expressing functional Drosophila nAChRs in either Xenopus oocytes or mammalian cell lines can be attributed to an inability of these expression systems to assemble correctly Drosophila nAChRs. Despite expression in what might be considered a more native cellular environment, we have been unable to detect functional nAChRs in a Drosophila cell line unless Drosophila nAChR subunit cDNAs are coexpressed with vertebrate nAChR subunits. Our results indicate that the folding of Drosophila nAChR subunits is temperature-sensitive and strongly suggest that the inability of these Drosophila nAChR subunits to generate functional channels in the absence of vertebrate subunits is due to a requirement for coassembly with as yet unidentified Drosophila nAChR subunits.

Amino Acid Sequence↗
PubMed1997

The effect of the N-methyl-D-aspartate receptor antagonist dextromethorphan on perioperative brain injury in children undergoing cardiac surgery with cardiopulmonary bypass: results of a pilot study.

Experimental evidence indicates a role of the N-methyl-D-aspartate receptor in the pathogenesis of brain injury occurring during cardiac surgery with cardiopulmonary bypass (CPB). Dextromethorphan is a noncompetitive antagonist of this receptor with a favorable safety profile. Thirteen children age 3-36 months undergoing cardiac surgery with expected CPB of 60 minutes or more were randomly assigned to treatment with dextromethorphan (36-38 mg/kg/day) or placebo administered by naso-gastric tube. Dextromethorphan was absorbed well and reached putative therapeutic levels in blood and cerebrospinal fluid. Adverse effects were not observed. Mild hemiparesis developed after operation in one child of each group, and severe encephalopathy in one of the placebo group. Sharp waves were recorded in postoperative continuous electroencephalography in all placebo (n = 7) but only in 2/6 dextromethorphan treated children (p = 0.02). Pre- and postoperative cranial magnetic resonance imaging (MRI) revealed less pronounced ventricular enlargement in the dextromethorphan group (not significant). An increase of periventricular white matter lesions was visible in two placebo-treated children only. No elevations of cerebrospinal fluid enzymes were observed in either group. Although children with dextromethorphan showed less abnormalities in electroencephalography and MRI, dissimilarities of the treatment groups by chance diminished conclusions to possible protective effects of dextromethorphan at this time.

Brain Chemistry↗