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Biomedical subjects

S Schmitz

Publications and source records attributed to S Schmitz.

At least 37 records · Page 2Linked to original sources
PubMed2000

Intracranial haemorrhage and use of selective serotonin reuptake inhibitors.

AIMS: In the past few years an increasing number of bleeding disorders have been reported in association with the use of selective serotonin reuptake inhibitors (SSRIs), including serious cases of intracranial haemorrhage, raising concerns about the safety of this class of drugs. The present study was performed to test the hypothesis of an increased risk of intracranial haemorrhage associated with the use of SSRIs. METHODS: We carried out a case-control study nested in a cohort of antidepressants users with the UK-based General Practice Research Database (GPRD) as the primary source of information. The study cohort encompassed subjects aged between 18 and 79 years who received a first-time prescription for any antidepressant from January, 1990 to October, 1997. Patients with presenting conditions or treatments that could be associated with an increased risk of intracranial haemorrhage were excluded from the cohort. Patients were followed-up until the occurrence of an idiopathic intracranial haemorrhage. Up to four controls per case, matched on age, sex, calendar time and practice were randomly selected from the study cohort. We estimated adjusted odds ratios and 95% confidence intervals of intracranial haemorrhage with current use of SSRIs and other antidepressants as compared with nonuse using conditional logistic regression. RESULTS: We identified 65 cases of idiopathic intracranial haemorrhage and 254 matched controls. Current exposure to SSRIs was ascertained in 7 cases (10. 8%) and 24 controls (9.7%) resulting in an adjusted OR (95%CI) of 0. 8 (0.3,2.3). The estimate for 'other antidepressants' was 0.7 (0.3,1. 6). The effect measures were not modified by gender or age. No effect related to dose or treatment duration was detected. The risk estimates did not change according to the location of bleeding (intracerebral or subarachnoid). CONCLUSIONS: Our results are not compatible with a major increased risk of intracranial haemorrhage among users of SSRIs or other antidepressants at large. However, smaller but still relevant increased risks cannot be ruled out.

Adolescent↗
PubMed2000

Gender-specific characteristics of 5-year-olds' play narratives and associations with behavior ratings.

OBJECTIVES: To examine the content and structure of children's play narratives in a large sample of 5-year-olds in order to replicate previous findings, explore the role of gender differences, and identify a pattern that can provide useful information about children's behavior. METHOD: The MacArthur Story Stem Battery and coding system was used to code content themes and coherence from play narratives of 652 twins in a nonclinical sample. To measure behavior problems, parents completed the Child Behavior Checklist when their children were aged 5 and 7 years; teachers completed the Teacher's Report Form when the children were aged 7 years. RESULTS: Girls told more coherent narratives with less aggression than boys. Aggressive themes were found to correlate with behavior problems as in previous studies. Upon further examination, this correlation held for girls but not boys. Children who told repeated aggressive/incoherent narratives had more behavior problems than those who did not show this narrative pattern. CONCLUSIONS: The Story Stem methodology is useful for gaining access into the young child's inner world. The gender of the child, content of the story, and coherence of the story all provide useful information in identifying narratives that may indicate more risk for behavior problems.

Aggression↗
PubMed2000

Contrast sensitivity and glare disability by halogen light after monofocal and multifocal lens implantation.

BACKGROUND: Standard examination of contrast sensitivity under conditions of glare disability is performed with incandescent light. A new halogen glare test that simulates glare as seen with oncoming vehicle headlights was used to measure glare disability in patients implanted with multifocal and monofocal intraocular lenses (IOLs). METHODS: 28 patients with an average age of 69 years (SD 12 years) were implanted with a monofocal IOL (SI-40NB, Allergan) and 28 patients with an average of 66 years (12 years) were implanted with a refractive multifocal IOL (Array-SA-40N, Allergan). All patients were followed for 5 months postoperatively. Contrast sensitivity at four spatial frequencies (3, 6, 12, and 18 cycles per degree, cpd) with and without a glare source were measured using the halogen glare test (CSV-1000 HGT). Statistical analysis was performed using the two sample Wilcoxon test. The local significance level was set at 0.05. RESULTS: When tested at the lowest spatial frequency (3 cpd) without halogen glare, contrast sensitivity was lower in the multifocal group than in the monofocal group (p=0.0292). With additional glare, there was no difference between both groups. At all other spatial frequencies (6, 12, and 18 cpd), when tested without halogen glare (6 cpd, p=0.5250; 12 cpd, p=0.8483; 18 cpd, p=0.9496) and with moderate (3 cpd, p=0.7993; 6 cpd, p=0.4639; 12 cpd, p=0.7456; 18 cpd, p=1.0) and high halogen glare (3 cpd, p=0. 1513; 6 cpd, p=0.2016; 12 cpd, p=0.3069; 18 cpd, p=0.9933), there was no statistically significant difference between groups. Patients in both groups of age 70 or older had reduced contrast sensitivity without halogen glare and with moderate and strong glare. When monofocal and multifocal patients older than 70 years of age were analysed separately, there was no statistically significant difference in contrast sensitivity with and without glare. Astigmatism >1 dioptre had no significant influence on contrast sensitivity and glare disability when monofocal and multifocal eyes were compared. CONCLUSION: Reduced contrast sensitivity was found in the multifocal group only at the lowest spatial frequency without halogen glare. The monofocal and multifocal groups had no statistically significant differences in contrast sensitivity with moderate and strong glare. These results suggest no difference in glare disability induced by halogen light similar to oncoming vehicle headlights for patients implanted with monofocal and multifocal IOLs.

Adult↗
PubMed1999

Actin residue glu(93) is identified as an amino acid affecting myosin binding.

Many mutants have been described that affect the function of the actin encoded by the Drosophila melanogaster indirect flight muscle-specific actin gene, Act88F. We describe the development of procedures for purification of this actin from the other isoforms expressed in the fly as well as in vitro motility, single molecule force/displacement measurements, and stop-flow solution kinetic studies of the wild-type actin and that of the E93K mutation of the Act88F gene. We show that this mutation affects in vitro motility of F-actin, in both the presence and absence of methylcellulose, and the ability of the ACT88F actin to bind the S1 fragment of rabbit skeletal myosin. However, optical tweezer measurements of the actomyosin working stroke and the force transmitted from the rabbit heavy meromyosin to and through F-actin are unchanged by the mutation. These results support the proposal (Holmes, K. C. (1995) Biophys J. 68, (suppl.) 2-7) that actin residue Glu(93) is part of the secondary myosin binding site and suggest that myosin binding occurs first at the primary myosin binding site and then at the secondary site.

Actins↗
PubMed1999

Expression of neurofilament L-promoter green-fluorescent protein constructs in immortalized Schwann cell-neuron coculture.

The neurofilament L/68 protein (NF-L/68) gene is expressed in the immature Schwann cell phenotype but suppressed after myelin-formation. We have investigated conditions which regulate the activity of the NF-L/68 promoter in green fluorescent protein reporter constructs expressed in the immortal rat Schwann cell strain SCL4.1/F7 in coculture with neurons. Constructs expressed in a plasmid vector containing both the full-length promoter and the 3' proximal 107 bp sequence which includes the cyclic AMP response element (CRE), were active in SCL4.1/F7 cells, but were suppressed as the cells underwent spontaneous growth-arrest. Interaction of SCL4.1/F7 with axons accelerated downregulation of expression from both constructs, however expression of the full-length promoter continued in some cells until the onset of myelin-formation. Expression of the NFL/68 construct recommenced when demyelination was induced in culture by exposure to human sera from patients with paraproteinemic gammopathy. We have demonstrated a method to study the regulation of gene expression patterns in single Schwann cells interacting with neurons and shown that different promoter regions may be controlled by axon-related and -unrelated factors.

Animals↗
PubMed1999

Endophthalmitis in cataract surgery: results of a German survey.

OBJECTIVE: To document perioperative prophylactic treatment and to evaluate the risk factors for endophthalmitis after cataract surgery. DESIGN: Cross-sectional study via anonymous survey. PARTICIPANTS: Four hundred sixty-nine centers in Germany were queried. RESULTS: A total of 311 (67%) questionnaires were received, with each center reporting an average of 900 cataract surgeries per year (total, 340,633 surgeries in 1996). Respondents reported a total of 267 cases of endophthalmitis, which resulted in a mean responder-specific endophthalmitis rate of 0.148% versus a median rate of 0%. Statistical analysis via Poisson regression suggested that sclerocorneal incisions were associated with a reduced incidence of endophthalmitis (odds ratio, 0.35; 95% confidence interval, 0.24-0.51). Antibiotics used intraocularly (odds ratio, 0.65; 95% confidence interval, 0.43-0.98) and the preoperative application of diluted povidone-iodine on the conjunctiva (odds ratio, 0.59; 95% confidence interval, 0.36-0.99) were associated with a reduced risk of postoperative infection. Immune deficiencies (66%), diabetes mellitus (62%), occlusion of the lacrimal system (40%), and skin diseases (33%) were regarded as risk factors for endophthalmitis by the respondents. When cataract surgery is performed solely under inpatient conditions, the use of systemic antibiotics as well as the periocular injection of antibiotics at the end of the operation were associated (although not significantly) with a trend toward reducing the incidence of postoperative infection. Conversely, flushing the lacrimal drainage system, using eye shields, and cutting the eyelashes had no demonstrable effect in preventing endophthalmitis. The use of preoperative topical antibiotics (odds ratio, 2.38; 95% confidence interval, 1.21-4.68) and the performance of more than 20% of the surgeries in an outpatient center (odds ratio, 2.0; 95% confidence interval, 1.24-3.21) were associated with a detrimental effect on the development of endophthalmitis. CONCLUSIONS: Although the appropriate antibiotic agent and dosage are not yet established, the administration of intracameral antibiotics and the application of povidone-iodine on the conjunctiva significantly reduced the relative risk of postoperative endophthalmitis in this survey. Because the study was not individual based but rather on aggregate questionnaire, the results have to be interpreted with care.

Ambulatory Care↗
PubMed1999

Differential memory span--abnormal lateralization pattern in schizophrenic patients and their siblings?

The recurring digit span test is hypothesized to assess consolidation memory and hypothetically addresses neuropsychological left-temporohippocampal functioning, an area of the brain which is presumed to play a crucial role in schizophrenia. The present study applied the recurring digit span memory test and the recurring block span memory test (assumed to be an indicator of right-temporohippocampal functioning) to 106 acute schizophrenic patients (DSM-III-R), 49 siblings of these patients without DSM-III-R lifetime diagnoses as well as 53 non-related control subjects without DSM-III-R lifetime diagnoses. Results of our investigation indicate that schizophrenic patients differ from control subjects regarding recurring digit span in a reduced number of correct reproductions of recurring trials. Since performance of schizophrenic patients was only non-significantly different from control subjects regarding recurring block span memory, our findings point to a task-specific memory impairment in schizophrenia and argue against a generalized deficit in this disease. Furthermore, individuals at risk for schizophrenia also differed from control subjects concerning the recurring digit span memory test but not with regard to the recurring block span test. Therefore we conclude that the reduced cumulative learning curve of verbal material (reduced number of correct reproduction of recurring digit trials) in schizophrenic patients and their healthy siblings might represent a marker for the liability to schizophrenia and parallels neuroimaging findings concerning left-sided temporohippocampal abnormalities in this disease, which presumably play a key role in the etiology of schizophrenia.

Adult↗
PubMed1999

How many myeloid post-progenitor cells have to be transplanted to completely abrogate neutropenia after peripheral blood progenitor cell transplantation? Results of a computer simulation.

Although hematopoietic recovery following high-dose chemotherapy (HD-CT) and peripheral blood progenitor cell (PBPC) transplantation is rapid, there is still a 5- to 7-day period of severe neutropenia which, theoretically, might be abrogated by an additional transplantation of more differentiated myeloid post-progenitor cells (MPPC). However, both the number of MPPC required to abrogate neutropenia as well as the optimum scheduling of MPPC infusions are currently unknown. Therefore, these questions were addressed by applying a computer model of human granulopoiesis. First, model calculations simulating varying levels of chemotherapy dose intensity were performed and compared with typical clinical neutrophil recovery curves. Using this approach, the data for HD-CT without PBPC transplantation could be reproduced by assuming a reduction of stem cells, committed granulopoietic progenitors and proliferating precursors to about 0.001% of normal. PBPC-supported HD-CT was reproduced by increasing the starting values to at least 0.1%, which corresponded to about 1 to 2 x 10(5)/kg transplanted CFU-GM. Interestingly, reproduction of PBPC-supported HD-CT data could be observed for a wide range of starting values (0.1%-10% of normal), thus confirming the clinical observation that hematopoietic recovery after PBPCT cannot be improved by increasing the dose of transplanted cells over a certain threshold. Using the same simulation model, we then studied the effects of an additional MPPC transplantation. The results showed, that at least 5.7 X 10(8) MPPC/kg have to be provided in addition to the normal PBPC graft to avoid neutropenia <100/microL, and that MPPC are best transplanted on days 0 and 6 after HD-CT. Assuming a 100- to 120-fold cellular ex-vivo expansion rate and MPPC representing about 70% of total expanded cells, 5.7 X 10(8) MPPC/kg could be generated starting from 1 to 2 leukapheresis preparations with about 7 to 8 x 10(6) CD34+ PBPC/kg. Considering furthermore, that only a fraction of ex-vivo generated cells will seed and effectively produce neutrophils in-vivo, the required number of MPPC is most likely even higher and, therefore, might be difficult to be achieved clinically. However, the validity of the model results remains to be proven in appropriate clinical studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

A new concept for melatonin deficit: on pineal calcification and melatonin excretion.

Even though exogenous melatonin has proven to influence sleep and circadian parameters, low endogenous melatonin is not related to sleep disturbances, nor does it predict response to melatonin replacement therapy. In this manuscript, we present a new concept towards a definition of a melatonin deficit. The purpose of the study was to introduce a marker for an intra-individual decrease in melatonin production. Therefore, we developed a method to quantify the degree of pineal calcification (DOC) using cranial computed tomography. Combining pineal DOC with the organs's size, we estimated the uncalcified pineal gland volume. This estimation was positively and significantly associated with 6-sulfatoxymelatonin (aMT6s), collected over 24 hours in urine, in 26 subjects. Data yielded evidence that the decline in aMT6s excretion with age can be sufficiently explained by an increased pineal calcification. These results suggest that DOC might be useful as an indicator of an intra-individual, decreased capability of the pineal gland to produce melatonin. DOC might prove to be a response-marker for melatonin replacement therapy and a vulnerability marker of the circadian timing system.

Adolescent↗
PubMed1999

Endogenous thrombopoietin serum levels during multicycle chemotherapy.

Little is known about the behaviour of endogenous thrombopoietin (TPO) serum levels during rapid sequences of dose-intensified chemotherapy. To characterize the relationship between TPO levels and platelet counts in this setting we serially measured both parameters over the entire treatment period of patients receiving multicycle polychemotherapy. We found TPO and platelet responses to be generally antagonistic through all cycles. However, a cross-correlation analysis indicated that TPO responses preceded platelet responses by approximately one day in all patients. The cumulative severity of thrombocytopenia observed over successive cycles was accompanied by an increasing TPO response which tended to grow overproportionally in relation to the degree of peripheral thrombocytopenia. These findings are consistent with a model suggesting that both platelet and megakaryocyte mass contribute to a receptor-dependent consumption process regulating the endogenous TPO level. In order to develop optimal schedules for exogenous TPO administration it might be important to consider endogenous TPO response characteristics.

Adult↗
PubMed1999

The effects of an intervention campaign to enhance seat belt use on campus.

The national health objectives for the year 2000 called for an increase in the use of safety restraints to 85% of motor vehicle occupants. An assessment on one campus indicated that only 79% of those observed were wearing seat belts. Nursing faculty and students undertook a multimodal intervention campaign to increase seat belt use in the campus community. Observed use of seat belts increased to 81% after the week-long intervention consisting of reminder banners, media coverage, permanent reminder signs, roll-over demonstrations, a presentation on the need for seat belt use, and distribution of seat belt use pledge cards. Although the increase was small, it was statistically significant and could represent considerable savings in healthcare costs if even 2% of the population could be saved from serious injury by using seat belts. In addition, the change in seat belt use represented a decline of nearly 10% in the number of nonusers.

California↗
PubMed1999

Personality dimensions and substance misuse: relationships in adolescents, mothers and fathers.

The research addressed the question of whether relationships exist between personality dimensions, antisocial behavior, and alcohol or other substance misuse (AOSM) in adolescents and in their fathers and mothers, who often also have histories of AOSM. One hundred male adolescents (mean age 15.8 years) entering a residential treatment center for youths with AOSM, their mothers (n = 88, mean age 39.4 years), their fathers (n = 36, mean age 44.9 years), and community controls (n = 100 adolescents, mean age 16.5 years; n = 96 mothers, mean age 43.8 years; n = 87 fathers, mean age 45.9 years) were recruited. All participants completed a personality questionnaire and were interviewed on several measures, including structured interviews for psychopathology and substance misuse. The findings indicated that novelty seeking (NS), one of the personality dimensions, was significantly correlated with substance misuse in adolescent probands, adolescent controls, and proband fathers and mothers, but not in control fathers and mothers. Regression analyses that included conduct disorder (CD) or antisocial personality disorder (APD) symptoms indicated that both NS and CD or APD symptoms made significant contributions to the prediction of substance misuse in treatment group probands and in their fathers and mothers. The findings further suggest that NS and antisocial behaviors contribute independently to substance misuse in severely impaired adolescents and their fathers, but not in their mothers.

Adolescent↗
PubMed1999

Behavioral genetic analyses of self-reported anxiety at 7 years of age.

OBJECTIVE: To conduct behavioral genetic analyses of self-reported childhood anxiety at 7 years of age. METHOD: Three hundred twenty-six same-sex twin pairs (174 monozygotic, 152 dizygotic) completed the Revised Children's Manifest Anxiety Scale at 7 years of age. Behavioral genetic analyses were conducted on the total and subscale scores. RESULTS: Monozygotic within-pair correlations were higher than dizygotic correlations for physiological and social anxiety symptoms, suggesting heritable influences on these aspects. These results were found to be statistically significant with structural equation modeling. CONCLUSION: Certain symptoms of self-reported anxiety in children 7 years of age seem to result, at least in part, from genetic factors. Physiological and social anxiety symptoms, which may be related to behavioral inhibition, appear to be genetically influenced. These results are linked to previous findings in older children and adults.

Anxiety Disorders↗
PubMed1999

Growth arrest and spontaneous differentiation are initiated through an autocrine loop in clonally derived Schwann cells by alpha1-procollagen I C-propeptide.

Schwann cells cloned from rat sciatic nerve survive and display self-induced growth suppression, or undergo spontaneous apoptosis, on long-term serum-free subconfluent culture. Strain SCL4.1/F7 sustained the capacity to growth arrest for up to 40 generations. A soluble activity transmitted between neighbouring cells of this strain suppresses DNA synthesis within three cell cycles. Autocrine Schwann cell growth-inhibitory factor (SGIF) operates during the G1 phase of the cell cycle, overcomes the mitogenic action of Schwann cell/serum-associated (platelet-derived growth factor-BB) and axon-associated (axolemma-enriched fraction) stimuli in serum-free conditions, and suppresses DNA synthesis in sciatic nerve Schwann cell cultures in a stage-specific manner. A 35-kDa protein with N-terminal sequence and approximate molecular mass of the C-propeptide of rat alpha1-procollagen I makes a major contribution to SGIF. Growth suppression in the SCL4.1/F7 strain is mediated by the ras/extracellular signal-regulated kinase pathway, is accompanied by down-regulation of erbB2/erbB3 and of tetraethylammonium-sensitive K+ currents, and is followed by transition of cells within 5-10 days from O4+, p75 nerve growth factor receptor (p75NGF-R)+, glial fibrillary acidic protein (GFAP)+ to O4+, p75NGF-R-, GFAP-, periaxin+ phenotypes. Oct-6/SCIP mRNA is present in both proliferating and growth-arrested SCL4.1/F7 cells. These results demonstrate an autocrine/ paracrine loop for the growth arrest of clonally derived Schwann cells in the absence of axons linked in part to the metabolism of collagen. Schwann cells thus appear to self-regulate growth in a negative as well as a positive direction through characterized molecular mechanisms and signal pathways.

Animals↗
PubMed1998

Cloning of conserved genes from Zymomonas mobilis and Bradyrhizobium japonicum that function in the biosynthesis of hopanoid lipids.

The squalene-hopene cyclase (SHC) is the only enzyme involved in the biosynthesis of hopanoid lipids that has been characterized on the genetic level. To investigate if additional genes involved in hopanoid biosynthesis are clustered with the shc gene, we cloned and analyzed the nucleotide sequences located immediately upstream of the shc genes from Zymomonas mobilis and Bradyrhizobium japonicum. In Z. mobilis, five open reading frames (ORFs, designated as hpnA-E) were detected in a close arrangement with the shc gene. In B. japonicum, three similarly arranged ORFs (corresponding to hpnC-E from Z. mobilis) were found. The deduced amino acid sequences of hpnC-E showed significant similarity (58-62%) in both bacteria. Similarities to enzymes of other terpenoid biosynthesis pathways (carotenoid and steroid biosynthesis) suggest that these ORFs encode proteins involved in the biosynthesis of hopanoids and their intermediates. Expression of hpnC to hpnE from Z. mobilis as well as expression of hpnC from B. japonicum in Escherichia coli led to the formation of the hopanoid precursor squalene. This indicates that hpnC encodes a squalene synthase. The two additional ORFs (hpnA and hpnB) in Z. mobilis showed similarities to enzymes involved in the transfer and modification of sugars, indicating that they may code for enzymes involved in the biosynthesis of the complex, sugar-containing side chains of hopanoids.

Amino Acid Sequence↗
PubMed1998

Interaction of positively charged amino acid residues of recombinant, cyanobacterial ferredoxin:NADP+ reductase with ferredoxin probed by site directed mutagenesis.

The petH genes encoding ferredoxin:NADP+ reductase (FNR) from two Anabaena species (PCC 7119 and ATCC 29413) were cloned and overexpressed in E. coli. Several positively charged residues (Arg, Lys) have been implicated to be involved in ferredoxin binding and electron transfer by cross-linking, chemical modification and protection experiments, and crystallographic studies. The following substitutions were introduced by site-directed mutagenesis: R153Q, K209Q, K212Q, R214Q, K275N, K430Q and K431Q in Anabaena 29413 FNR, and R153E, K209E, K212E, R214E, K275E, R401E, K427E, and K431E in Anabaena 7119 FNR. Comparison of the diaphorase activities, the specific rates of ferredoxin dependent NADP(+)-photoreduction and cytochrome c reduction catalyzed by FNR showed that all these amino acid residues were required for efficient electron transfer between FNR and ferredoxin. Replacement of any one of these basic residues produced a much more pronounced effect on the cytochrome c reductase activity, where FNR, reduced by NADPH, acted as electron donor, than in the reduction of NADP+ by photosystem I via FNR. A mutation involving the replacement of positive charge by a neutral amide produced in all cases a smaller inhibitory effect on the activity than a charge reversal mutation. In addition, it has been found that R214 was necessary for stable integration of the non covalently bound FAD-cofactor.

Amino Acids↗
PubMed1998

Increase in power through multivariate analyses.

Power to detect genetic and environmental influences increases not only with sample size but also with the number of measurements through longitudinal and/or multivariate designs, if those measurements correlate with each other. Power simulations are presented for uni- through quadrivariate cases, with differing genetic and environmental parameters. Even though subject attrition is a problem for most longitudinal studies, the gain in power available may more than make up for this shortcoming in many situations. In terms of planning studies to examine genetic and environmental influences, power calculations should not only consider sample size but number of measurements on particular phenotypes and their intercorrelations.

Genotype↗