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Biomedical subjects

M Schemper

Publications and source records attributed to M Schemper.

At least 19 recordsLinked to original sources

A meta-analysis of low dose aspirin for the prevention of intrauterine growth retardation.

OBJECTIVE: To determine more precisely the effect of prophylactic low dose aspirin on intrauterine growth retardation and perinatal mortality. DESIGN: Meta-analysis of 13 published randomised clinical trials. METHODS: We searched 18 medical databases, including MEDLINE since 1964 and EMBASE since 1974, review articles and the references from each retrieved report to identify all studies evaluating the effect of aspirin in pregnancy and including both intrauterine growth retardation and perinatal mortality as outcome measures. RESULTS: Among 13,234 women from 13 studies between 1985 and 1994, aspirin showed a significant reduction in intrauterine growth retardation (IUGR) (OR 0.82; 95% CI 0.72-0.93; P = 0.003) and a nonsignificant reduction in perinatal mortality (OR 0.84; 95% CI 0.66-1.08; P = 0.18). Subgroup analyses revealed that aspirin was effective at lower doses between 50 and 80 mg/day (IUGR: OR 0.87; 95% CI 0.76-0.99; mortality: OR 0.90, 95% CI 0.70-1.16), but that the preventive effect was greater at higher doses between 100 and 150 mg/day (IUGR: OR 0.36, 95% CI 0.22-0.59; mortality: OR 0.40, 95% CI 0.16-0.97) and among women entered before the 17th week of gestation (IUGR: OR 0.35, 95% CI 0.21-0.58; mortality: OR 0.43, 95% CI 0.17-1.06). We did not identify any specific subgroup of women most likely to benefit from aspirin treatment. CONCLUSION: The results of this meta-analysis showed that early aspirin treatment reduced the risk of intrauterine growth retardation. Low dose aspirin should not be used routinely in pregnant women until those most likely to benefit from aspirin treatment have been clearly identified.

Anti-Inflammatory Agents, Non-Steroidal

Explained variation for logistic regression.

Different measures of the proportion of variation in a dependent variable explained by covariates are reported by different standard programs for logistic regression. We review twelve measures that have been suggested or might be useful to measure explained variation in logistic regression models. The definitions and properties of these measures are discussed and their performance is compared in an empirical study. Two of the measures (squared Pearson correlation between the binary outcome and the predictor, and the proportional reduction of squared Pearson residuals by the use of covariates) give almost identical results, agree very well with the multiple R2 of the general linear model, have an intuitively clear interpretation and perform satisfactorily in our study. For all measures the explained variation for the given sample and also the one expected in future samples can be obtained easily. For small samples an adjustment analogous to Radj2 in the general linear model is suggested. We discuss some aspects of application and recommend the routine use of a suitable measure of explained variation for logistic models.

Likelihood Functions

Explained variation in survival analysis.

Several measures of explained variation have been suggested for the Cox proportional hazards regression model. We have categorized these measures into three classes which correspond to three different definitions of multiple R2 of the general linear model. In an empirical study we compared the performance of these measures and classified them by their adherence to a set of criteria which we think should be met by a measure of explained variation for survival data. We suggest that currently there is no uniformly superior measure, particularly as the concepts of either uncensored or censored populations may lead to different choices. For uncensored populations, a measure by Kent and O'Quigley and the squared rank correlation between survival time and the predictor from a Cox regression model appear recommendable choices. For the latter, censored survival times are terminated using a very recent data augmentation algorithm for multiple imputation under proportional hazards. With censored populations, Schemper's measure, V2, could be considered. We give an introductory example, discuss aspects of application and stress the desirability of routinely evaluating explained variation in studies of survival.

Humans

Adjunctive antibiotic treatment in preterm labor and neonatal morbidity: a meta-analysis.

OBJECTIVE: To estimate the effect of prophylactic antibiotics on neonatal mortality and morbidity in patients with preterm labor, based on a meta-analysis of seven published randomized clinical trials. DATA SOURCES: We searched 18 medical data bases, including MEDLINE from 1964 and EMBASE from 1974, to identify all literature included under preterm or premature labor and antibiotics. We scanned all abstracts from the computer printouts, the retrieved full-text reports, the references from each retrieved report, and review articles to determine whether studies met our inclusion criteria. METHODS OF STUDY SELECTION: The following criteria were used to select studies for inclusion: article-original published report written in English; study design-randomized controlled trial; population-patients with preterm labor, defined as labor before 37 weeks' gestation; intervention-antibiotic treatment; and one or more of the following outcomes-neonatal mortality, sepsis, pneumonia, respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. TABULATION, INTEGRATION AND RESULTS: We analyzed study patients and methods, and abstracted quantitative outcome data. For each outcome, both odds ratio (OR) and 95% confidence interval (CI) were calculated. Seven trials, published between 1989 and 1995 included a total of 795 patients. Adjunctive antibiotic therapy appeared to reduce the risk of pneumonia (OR 0.45, 95% CI 0.12-1.72) and necrotizing enterocolitis (OR 0.38, 95% CI 0.14-1.08) and to increase the risk of neonatal mortality (OR 3.25, 95% CI 0.93-11.38), but it had no effect on neonatal sepsis (OR 0.98, 95% CI 0.34-2.83), respiratory distress syndrome (OR 0.93, 95% CI 0.54-1.87), and intraventricular hemorrhage (OR 1.01, 95% CI 0.20-5.10). None of the effects observed reached a significance level of P < .05. CONCLUSION: The results of this meta-analysis do not support the routine use of adjunctive antibiotic treatment in patients with preterm labor diagnosed on the basis of subjective uterine contractions and the resulting cervical changes.

Anti-Bacterial Agents

Antibiotic treatment in preterm premature rupture of membranes and neonatal morbidity: a metaanalysis.

OBJECTIVE: We performed a metaanalysis of seven published randomized clinical trials to estimate more precisely the effect of prophylactic antibiotics on neonatal mortality, clinical sepsis of the neonate, respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. STUDY DESIGN: To evaluate the effect of antibiotic treatment unaffected by other forms of treatment such as tocolytics or corticosteroids, investigations in which these additional measures were used were not included. We analyzed study patients and methods and abstracted quantitative outcome data. For each outcome both odds ratios and 95% confidence intervals were calculated. RESULTS: Among the 657 patients from seven trials published between 1989 and 1994, antibiotic therapy significantly reduced the risk of neonatal sepsis by 68% (odds ratio 0.32, 95% confidence interval 0.16 to 0.65, p=0.001) and that of intraventricular hemorrhage by 50% (odds ratio 0.50, 95% confidence interval 0.28 to 0.89, p=0.019). In contrast, no significant effect of antibiotics on overall neonatal mortality (odds ratio 0.92, 95% confidence interval 0.46 to 1.81), respiratory distress syndrome (odds ratio 0.84, 95% confidence interval 0.58 to 1.22), or necrotizing enterocolitis (odds ratio 1.27, 95% confidence interval 0.61 to 2.62) was found. CONCLUSION: This metaanalysis supports an improvement of neonatal morbidity in mothers with preterm premature rupture of membranes treated prenatally with different antibiotic regimens.

Anti-Bacterial Agents

Topical versus peribulbar anesthesia in clear corneal cataract surgery.

PURPOSE: To evaluate the efficacy of topical anesthesia as an alternative to peribulbar anesthesia in clear corneal cataract surgery. SETTING: Department of Ophthalmology, University of Vienna, Austria. METHODS: In this prospective, double-blind clinical trial, 36 patients had bilateral cataract surgeries performed from 1 to 3 months apart. Half of the patients had topical anesthesia for the first surgery and peribulbar anesthesia for the second surgery. The other half had peribulbar first and then topical. All surgery was done using a temporal clear corneal approach and bimanual phacoemulsification followed by in-the-bag intraocular lens implantation. Subjective pain was assessed using a visual analog scale of no pain (0%) to worst pain imaginable (100%) and intraoperative motility using a rank scale of adverse motility (-5) to ideal patient cooperation (+5). RESULTS: Subjective pain was comparable whether topical or peribulbar anesthesia was used (mean 10.75 versus 10.97%; P > .6). Patient cooperation (motility) was significantly better when topical anesthesia was used (+2.16 versus +1.11; P = .03). There were no significant differences in complications. A peribulbar block was given in addition to the topical anesthesia in two cases. CONCLUSIONS: Topical anesthesia is a safe, effective alternative to peribulbar anesthesia in clear corneal cataract surgery.

Administration, Topical

Skin tumors in photochemotherapy for psoriasis: a single-center follow-up of 496 patients.

BACKGROUND: The significance of oral psoralen photochemotherapy (PUVA) for the development of nonmelanoma skin cancers (NMSC) is still controversial. OBJECTIVE: We evaluated 496 psoriatics, who received PUVA treatment according to the European PUVA protocol in order to reassess the influence of the cumulative UVA dose on the development of NMSC and to answer the question if there is a UVA threshold dose above which the carcinogenic risk is increased. METHODS: The study was conducted as a retrospective investigation. All patients were seen personally. Age, sex, skin type, cumulative UVA dose and carcinogenic risk factors (arsenic, X-rays, tar, UVB, methotrexate) were recorded and investigated by marginal (MA) and partial effects analyses (PA) according to the Cox regression model. RESULTS: In 14 patients (2.8%), one or multiple histologically confirmed NMSC were diagnosed. Nine patients (1.8%) had squamous cell carcinoma (SCC), 5 patients (1.0%) had basal cell carcinoma (BCC). No patient had both types of NMSC. None of the SCC had metastasized. By taking the appearance of BCC and SCC as the endpoint, arsenic [MA: relative risk (RR) = 7.62; PA:RR = 5.36], tar (MA:RR = 4.51; PA:RR = 3.83) and methotrexate (MTX; MA:RR = 4.97; PA:RR = 4.07) appear to produce strong and significant effects (p < 0.05), both in MA and PA. Using the endpoint SCC only, the effect of the natural logarithm of UVA (ln UVA; RR = 2.47), arsenic (RR = 11.2), tar (RR = 9.92) and MTX (RR = 7.1) is significant (p < 0.05) in MA. In PA, only the effect of arsenic (RR = 5.19) is strong and significant (p < 0.05) while the effects of tar (RR = 7.85), MTX (RR = 3.22) and ln UVA (RR = 2.77) are strong but of borderline significance (p = 0.05-0.11). Nonlinear effects of ln UVA on the risk of SCC were far from significant (p > 0.2). CONCLUSION: PUVA with the European treatment protocol appears to be only a weak carcinogen by itself for SCC with a linear increase in tumor risk but not for BCC development.

Administration, Oral

[Dilatation treatment of achalasia as initial therapy. Results of a prospective study].

From 1972 to 1991 primary dilatation therapy was investigated in a prospective study in 77 patients suffering from achalasia of the gastroesophageal sphincter. The patients were followed up continuously and the median follow-up period was ten years. 70% of patients were symptom-free after dilatation therapy at the time of the last follow-up examination, whereby 50% were cured of symptoms after a single dilatation. 27% required surgery after unsuccessful dilatation therapy. The probability of avoiding operation after dilatation therapy within 15 years of diagnosis of achalasia was 73%. The clinical symptomatology at diagnosis graded according to a scheme from I to IV, was significantly worse in patients requiring an operation (Wilcoxon test, p < 0.0005). The data of esophageal manometry were of no prognostic relevance.

Adult

EWS/FLI-1 antagonists induce growth inhibition of Ewing tumor cells in vitro.

Among primitive neuroectodermal tumors, Ewing tumors are characterized by a gene rearrangement recombining the 5'-EWS gene portion with one of two ETS-related proto-oncogenes, FLI-1 or ERG, in roughly 90 and 10% of cases, respectively. We attempted to antagonize EWS/FLI-1 function in Ewing tumor cell lines. As a control, a cell line derived from another small round cell tumor of neuroectodermal origin, neuroblastoma, was used. This cell line was found to express almost identical patterns of ETS proteins except for EWS/FLI-1 and a novel, ELF-related gene product. Stable expression of antisense EWS/FLI-1 cDNA resulted in decreased endogenous EWS/FLI-1 RNA levels and growth reduction of ET cells but not of neuroblastoma cells. DNA-binding FLI-1 derivatives localizing to the nucleus in which the 5'-EWS regulatory domain was replaced by bacterial beta-galactosidase dominantly modulated transcriptional transactivation from a degenerate ETS-binding motif. Transient transfection of these dominant-negative recombinants resulted in a significant decrease in the relative number of mitoses in four Ewing tumor cell lines tested but not in the neuroblastoma cell line. The presented evidence for modulation of tumor cell proliferation by EWS/FLI-1 antagonists suggests a causal role for EWS/FLI-1-mediated gene activation in the malignant transformation of the enigmatic Ewing tumor-precursor cell.

Blotting, Northern

Hemodynamic effects of prolonged abdominal insufflation for laparoscopic procedures.

Abdominal insufflation for laparoscopic procedures leads to numerous hemodynamic effects. We focused on blood flow distribution and arterial and venous pressure changes during CO2 insufflation at an intra-abdominal pressure of 12 mm Hg. Three segments of the vascular system were investigated (intrathoracic, cranial extrathoracic, caudal extrathoracic) in supine animals at insufflation, during a 90-minute period of pneumoperitoneum, and at desufflation. Except for instrumentation of the animals, no further surgery was performed. At insufflation (+5 minutes), cardiac output increased from 2.7 +/- 0.5 to 3.3 +/- 1.1 L/min while heart rate decreased from 138 +/- 26 to 128 +/- 17 beats per minute. Increases in jugular venous (from 6 +/- 1 to 11 +/- 4 mm Hg) and atrial (right, from 7 +/- 1 to 12 +/- 3; left, from 12 +/- 4 to 17 +/- 5 mm Hg) pressures occurred uniformly during inspiration. The great variance in atrial pressures during ventilation was not associated with changes in stroke volume, as the effective transmural filling pressures remained nearly constant. The increase in femoral venous pressure occurring during both inspiration and expiration (from 10 +/- 2 to 18 +/- 4 mm Hg) exceeded the increase in right atrial and jugular venous pressures during inspiration. Parallel increases were noted in arterial pressures (carotid, from 119 +/- 15 to 129 +/- 9; femoral, from 122 +/- 16 to 133 +/- 10 mm Hg), left ventricular pressure (from 133 +/- 17 to 143 +/- 10 mm Hg), and carotid and femoral flow (carotid, from 174 +/- 71 to 195 +/- 70; femoral, from 66 +/- 25 to 73 +/- 40 (NS) mL/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Resistance of nitrogen metabolism to growth hormone treatment in the early phase after injury of patients with multiple injuries.

OBJECTIVES AND DESIGN: Several studies have shown an anticatabolic effect of recombinant human growth hormone (rhGH) in surgical patients. We investigated, in a prospective, randomized, double blind, and placebo-controlled study, the effect of r-hGH on hormone and nitrogen metabolism in 14 patients with multiple injuries in the early phase of injury. MATERIALS AND METHODS: All patients were treated in the intensive care unit, had mechanical ventilation, and were highly catabolic, with a mean daily nitrogen loss of 13.2 +/- 1.8 g. r-hGH was given subcutaneously (once a day, at 8 PM) in a dosage of 0.2 IU/kg.d for seven days, starting on the second day after injury. RESULTS: Administration of r-hGH evoked a significant increase in plasma concentrations of GH, insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding-protein-3 (IGFBP-3). No significant differences were found for either daily or cumulative nitrogen balances (-103.1 +/- 14 g for patients receiving r-hGH and -92.1 +/- 18.1 for those with placebo). r-hGH therapy did not affect skeletal muscle extracellular water, nor did it affect plasma or muscle concentrations of total free amino acids or glutamine. Plasma albumin, prealbumin, and retinol-binding protein concentrations were also unchanged by r-hGH therapy, as were the urinary excretion of potassium and urea. CONCLUSIONS: We conclude that elevated plasma levels of GH, insulin, and IGF-I are unable to effect a protein anabolic drive in patients with multiple injuries during the early postinjury phase and assume that this r-hGH resistance to nitrogen metabolism takes place at the level distal to IGF-I.

Adult

Comparison of high dose therapy of rhEPO, given two or three times a week in premature infants.

We investigated the question whether there is a difference in the response to high dose human recombinant erythropoietin (rhEPO) given twice or three times weekly in premature infants. 48 premature infants were randomly assigned to receive 300 U/kg rhEPO three times a week or 450 U/kg two times a week for at least 4 weeks and up to 6 weeks. Concomitant oral iron supplementation was compulsory, median daily dosage reached 6.6 mg/kg, doses exceeding 8 mg/kg/d were not tolerated. Our data showed no differences in the two groups in regard to hematocrit (HCT), reticulocytes and ferritin levels. A marked increase in reticulocyte counts could be observed in both groups. Serum ferritin decreased as expected. Premature infants starting with a baseline HCT lower than 32% showed a steady increase in HCT without any initial decline. No adverse effects could be observed in either group. Since there is no difference in the response to high dose rhEPO given two or three times weekly, we therefore conclude that the twice weekly regimen is compatible with outpatient treatment.

Anemia

Shouldice is superior to Bassini inguinal herniorrhaphy.

The original Bassini and Shouldice methods for inguinal herniorrhaphy were tested against each other and against their respective variants that avoid permanent suturing of the internal oblique muscle. Seven hundred fifty inguinal hernia repairs were prospectively allocated to 1 of 4 groups: group A: Bassini with absorbable sutures (polyglycolic acid); group B: Bassini with nonabsorbable sutures (polyester); group C: Shouldice with four rows of polypropylene sutures; and group D: Shouldice with two rows of polypropylene sutures. Outcome was correlated to prospectively defined types and risk factors such as direct hernia, repair for recurrent hernia, hernial sac diameter greater than 8 cm, age greater than 70 years, overweight, and chronic bronchitis. Actual (not actuarial) recurrence rates were determined through clinical examination by hospital staff surgeons (not through information by letter or phone) for 93.6% of surviving patients. Local complications exclusive of recurrence, but including the redoubtable and litigious sequelae of testicular atrophy and chronic ilioinguinal pain, were significantly reduced from 6.3% (group B and C) to 2.3% by omitting permanent muscle sutures (groups A and D; P < 0.05). However, the use of slowly absorbable suture material resulted in a disproportionately high recurrence rate of 12.8% in the modified Bassini group A. The original Bassini method, ie, division of the transversalis fascia and repair with nonabsorbable sutures, as was used in group B, had an actual 2-year recurrence rate of 8.7%, still a highly significant difference compared with 3.6% and 2.3% for Shouldice groups C and D, respectively (P = 0.012). For repair of recurrent hernia, the superiority of the Shouldice technique was not statistically significant: re-recurrence rate 7.6% versus 13.5% for the original Bassini group B. Repair of recurrent hernia was the only patient-related risk factor of equal significance as the method of repair. The Shouldice technique is superior to and more than merely a reinvention of Bassini's original method. The omission of muscle sutures is physiologically sound and recommended for the Shouldice operation.

Actuarial Analysis

[The value of the "vascular invasion" factor for prognosis of breast cancer].

The histological sections of 106 patients, who underwent a primary breast cancer operation in the years 1986 and 1987, were inspected for the presence of tumour vascular invasion. With immunohistochemical methods, tumour vessels were tomographed and the paraffin sections were stained with an antibody, which is sensitive to factor VIII-antigen. A tumour embolus was considered present, if a malignant cell was established within a positively stained lumen. The question of possible influence on the pathogenesis of breast cancer was examined in case of vascular invasion in the histological preparation. In 46 of the 106 patients (43.4%), tumour emboli were found. After an average observation period of 59 months, no tumour progression was seen in 60 patients, 46 patients developed a recurrence of the tumour at the check-up date. The presence of vascular invasion correlates with undifferentiated tumour grading. The probability of relapse- free survival after 5 years was 83.9% within the group without vascular invasion, compared with 47.9% (p = 0.0001) within the group with established vascular invasion. In the multivariate analysis of the factors lymphonodular status, grading and vascular invasion, it was found, that the presence of tumour vascular invasion with a relative risk of 3.68 (95% CI 1.93-7.03) was the strongest statistically significant prognostic factor for relapse-free survival (p = 0.0001).

Adult

Prolonged preoperative prismatic treatment in alternating convergent squint.

Our 10-year retrospective study includes 178 children below the age of 10 years, operated for alternating convergent squint. Inclusion criteria were: Absence of amblyopia and an angle of squint less than 45 pdpt so that alignment of the eyes in only one operation could be expected. One hundred children received preoperatively a prismatic correction of the distance deviation for a period of 6-15 months; 78 cases were treated with glasses and occlusion. In the prism-treated group a significantly better alignment (p = 0.0001) with a motorial gain of 7-8 pdpt was observed 6 months after surgery; also better sensorial results with significantly (p = 0.0001) more cases of stable NRC or harmonious ARC and improved binocularity were achieved. Unlike the type of esotropia, the preexisting retinal correspondence significantly influenced the motorial outcome (p < 0.05). Fewer reoperations were necessary in the prism-treated group (p = 0.001). Our results indicate that a prolonged prismatic correction is an effective preoperative treatment in patients with alternating convergent squint.

Child

The relative importance of prognostic factors in studies of survival.

The relative importance of prognostic factors in regression can be measured either by standardized regression coefficients or by percentages of explained variation in a dependent variable. One advantage of using explained variation is the direct comparability of qualitative prognostic factors with others, or of groups of prognostic factors. The description of relative importance can be accomplished within marginal or partial effects analyses. It is demonstrated that it is possible not only to provide a descriptive ranking of prognostic factors according to their statistically determined importance, but also to make inferences concerning their relative importance, employing bootstrap techniques and procedures for multiple comparisons. The methods presented, which are new in the context of Cox regression, are exemplified by analyses of studies of lung cancer and breast cancer.

Adult

Differences in anti-Fab antibodies in adult and late onset rheumatoid arthritis.

In the present study the ratio of antigen-bound anti-IgG-Fab antibodies (hidden aFab) to free aFab was found to be significantly increased in patients with adult onset rheumatoid arthritis (AORA) as compared to late onset rheumatoid arthritis (LORA). The overall amount of aFab was similar in both groups. The difference was only seen in seropositive patients. Within the seropositive AORA group, the aFab ratio was correlated with the duration and the stage of disease but not with the patients' age at investigation. This might reflect a higher affinity of anti-Fab antibodies and/or a greater diversity of the idiotypic repertoire in adult onset disease resulting in the formation of immune complexes, the stability of which might be enhanced further by the presence of rheumatoid factors. Although a pathophysiological involvement of aFab cannot be concluded from our observations, it is conceivable that different immunoregulatory mechanisms could be operative in RA with onset at different ages.

Adult