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Biomedical subjects

P Bauer

Publications and source records attributed to P Bauer.

At least 73 records · Page 4Linked to original sources

Testing strategies in multi-dose experiments including active control.

Inferential test strategies for multi-arm trials are adapted or proposed for the special situation when more than one dose of a test treatment, placebo and active control(s) are compared. This includes between doses, dose-placebo and dose-active-control comparisons. The procedures refer to situations when detailed comparisons make sense only if the sensitivity of the trial has been shown, for example, if a dose-response relationship or a difference between active control and placebo has been established. Split strategies, hierarchical (assuming an order restriction among doses) or linked procedures are introduced. In linked procedures, equivalence to the active control will be established only if the dose is also shown to be effective as compared to placebo. All the inferential procedures control the experimentwise error rate in the strong sense for the respective sets of null hypotheses considered.

Alkylating Agents↗

Ceramide-independent CD28 and TCR signaling but reduced IL-2 secretion in T cells of acid sphingomyelinase-deficient mice.

Ceramide generated by lysosomal acid sphingomyelinase (aSMase) has been proposed to contribute to CD28 co-stimulatory signaling pathways. We used an aSMase-deficient mouse line (asmase-/-) to elucidate the role of the aSMase in splenocytes stimulated with either a combination of anti-CD3 and anti-CD28 antibodies, the lectin concanavalin A (Con A) or the superantigen staphylococcal enterotoxin B. All stimuli were shown to induce IL-2 expression, Con A additionally triggered the expression of high-affinity IL-2 receptor. However, in asmase-/- mice secretion of IL-2 was significantly reduced, whereas the intracellular IL-2 levels were elevated. Proliferation of anti-CD3/anti-CD28 or Con A-stimulated aSMase-deficient splenocytes was reduced up to 50% after 72 h in comparison to wild-type cells. We conclude that ceramide generated by aSMase is not involved in CD28 signal transduction, but rather a perturbation of the secretory system is responsible for the impaired proliferation of aSMase-deficient splenocytes.

Animals↗

The incidence of hyperthyroidism in Austria from 1987 to 1995 before and after an increase in salt iodization in 1990.

Between 1963 and 1990, Austria had iodized salt prophylaxis of endemic goitre with 10 mg KI (7.5 mg I) per kg. This was obviously insufficient, as urinary iodine excretion ranged from 42 to 78 microg I per g of creatinine and goitre in adults remained in the endemic range of 15%-30%. Therefore salt iodization was doubled in 1990. The aim of this study was to assess the annual incidence of different types of hyperthyroidism (HT) before and after this increase in salt iodization. The incidence of HT was recorded in 14 nuclear medicine centres from 1987 to 1995. In five additional centres data were available from 1992 onwards. Data prior to 1992 were documented retrospectively, while those after 1992 were recorded prospectively. The 14 centres drew patients from an area with a population of approximately 4.23 million while all 19 institutes were estimated to cover an area with a population of 5.4 million (the total population of Austria is 7.86 million). A total of 414232 persons were examined for the first time in the participating centres. HT and the type of HT were defined by clinical examination, serum TSH, thyroid hormone levels in blood, ultrasonography, scintigraphy and serum autoantibody titres. HT was classified into immunogenic HT (Graves' or Basedow's disease, GD) and HT with intrinsic thyroid autonomy (uni-, multinodular or disseminated Plummers' disease, PD). HT was also divided into overt (o) or subclinical (sc) disease. The following data were calculated: annual incidence per 100000 and the relative risk (RR) for HT with 95% confidence intervals (CI). In addition, linear trends were calculated for each type of HT by means of logistic regressions. In the 19 centres a total of 47834 patients with HT were registered from 1987 to 1995. PD accounted for 75% of all cases of HT and GD for 19%, while other types of HT were present in 6%. From 1987 to 1989 (time period T0), the annual incidence of oPD was 30.5 (95% CI 29.6-31.5) per 100000. The RR compared to the baseline period T0 was highest in 1992 (1.37; 1.3-1.45) and decreased to 1.17 (1.1-1.24) in 1995. The annual incidence of scPD in T0 was 27.4 (26.5-28.3) per 100000. The RR was highest in 1991 (1.64; 1.56-1.73) and was 1.60 (1. 51-1.69) in 1995. In oPD and scPD a higher RR was observed in persons older than 50 years of age, particularly in men. The incidence of oGD in T0 was 10.4 (9.8-10.9) per 100000; the maximum RR increased to 2.19 (2.01-2.38) in 1993 and decreased to 1.95 (1.78-2.13) in 1995. The incidence of scGD was 1.9 (1.6-2.1) in T0. The maximum RR was observed in 1994 (2.47; 2.04-3.0) and it was still 2.26 (1.85-2.77) in 1995. The increased incidence of oGD and scGD was evenly distributed in all ages and both sexes. The time course of different types of HT following the increase in salt iodization could be divided into two phases: an increase in the incidences of HT with peaks after 1-4 years and a subsequent decrease, the only exception being scGD. The effect was more pronounced in GD than in PD. PD showed an age and gender dependency over time, while GD did not.

Adult↗

Adjunctive daunorubicin in the treatment of proliferative vitreoretinopathy: results of a multicenter clinical trial. Daunomycin Study Group.

PURPOSE: To assess the efficacy and safety of adjunctive daunorubicin during vitrectomy surgery in eyes with idiopathic proliferative vitreoretinopathy (PVR). METHODS: Two hundred eighty-six eyes (286 patients) with stage C2 (Retina Society Classification, 1983) or more advanced preoperative PVR in which surgery with silicone oil was planned were enrolled in a multicenter, prospective, randomized, controlled clinical trial. Standardized surgery plus adjunctive daunorubicin perfusion was compared with surgery alone. Outcomes assessed were retinal attachment without additional vitreoretinal surgery 6 months after standardized surgery, number of and time until vitreoretinal reoperations within 1 year of standardized surgery, and change in visual acuity 1 year after standardized surgery, evaluated by photodocumentation, number of reoperations, and measurement of best-corrected visual function. Outcomes were determined 6 months after operation and reevaluated after 1 year of follow-up. RESULTS: Six months after standardized surgery, complete retinal reattachment without additional vitreoretinal surgery was achieved in 62.7% (89/142) of eyes in the daunorubicin group vs 54.1% (73/135) in the control group (P = .07, one-sided). However, in the daunorubicin group, significantly fewer vitreoretinal reoperations were performed within 1 year postoperatively (P = .005, one-sided) to achieve the same overall 1-year retinal reattachment rate (80.2% [105/131] vs 81.8% [103/126]). The rate of patients with no vitreoretinal reoperations was 65.5% (95/145) in the daunorubicin group vs 53.9% (76/141) in the control group. There was no difference in the best-corrected visual acuity. No severe adverse effect related to daunorubicin was identified. CONCLUSIONS: Although the rate of anatomic success after 6 months failed to show significance, some benefit of the adjunctive treatment exists, especially a tendency toward increased rate of reattachment and a significant reduction in the number of reoperations. This shows that human PVR is amenable to pharmacologic treatment.

Adult↗

Paediatric assessment in a residential child and adolescent psychiatry unit.

OBJECTIVE: To document the health status, comorbidity and functional impairments experienced by a group of psychiatrically disturbed children and adolescents. METHODOLOGY: A detailed study of consecutive admissions to a residential unit over a two-year period was undertaken. All admissions had a comprehensive paediatric, speech pathology and psychiatric assessment. RESULTS: Compared to the general population, there was a significant history of developmental delay and low birthweight, but only a slightly greater prevalence of antenatal problems. Clumsiness (37%), severe speech and language disorder (32%), and hearing loss (15%) were prominent. Only 25% had no history of comorbid medical or neurological disorders. CONCLUSION: Children and adolescents presenting with moderate to severe mental health morbidity may have pre-existing comorbid medical problems, as well as unrecognised difficulties and impairments in other skills areas. Multidisciplinary assessment and intervention should be an integral part of the residential programme.

Adolescent↗

Second-trimester measurements of placental volume by three-dimensional ultrasound to predict small-for-gestational-age infants.

OBJECTIVE: The objective of this study was to investigate the value of second-trimester three-dimensional sonographic placental volume measurements to predict infants who are below the 10th centile for birth weight. SUBJECTS AND METHODS: Placental volume measurements were performed using three-dimensional ultrasound in 382 women with normal singleton pregnancies at 16-23 weeks' gestation. Logistic multivariate regression consisting of variables considered to influence birth weight was used to predict infants with a birth weight below the 10th centile from the placental volume measurements. RESULTS: Prognostic influence could be shown for placental volume (p < or = 0.0001), gestational week at the time of measurement (p = 0.0002) and maternal weight at the time of registration (p = 0.0025). Values for specificity and sensitivity achieved by choosing an 'optimal' cut-off point of 0.16 for the estimation probability for a small-for-gestational-age (SGA) infant were low at 82.5% and 52.5%, respectively. CONCLUSIONS: Three-dimensional sonographic measurement of the placental volume alone is not a satisfactory technique for predicting SGA infants.

Adult↗

Recipient and provider perspectives of barriers to rural prenatal care.

Barriers to prenatal care have been linked to inappropriate service usage and poor health outcomes of mothers and infants. This study describes barriers to prenatal care, as identified by low-income recipients and providers of prenatal care in a small rural county in the Midwest. A prospective survey design and focus group were used. An unexpected finding occurred. Almost half of the recipients identified no barriers to prenatal care; however, these women still received less than adequate prenatal care. Providers identified the attitudinal barrier of women as not valuing prenatal care, but the women did not. Some women were found to need information about availability and eligibility for Medicaid and other services. Issues surrounding prenatal care for rural women are complex and subtle. Community health nursing can inform and influence community leaders and members about prenatal care services for rural low-income women.

Adolescent↗

[Possibilities of preliminary treatment of infected soft tissue defects by vacuum sealing and PVA foam].

The vacuum sealing technique is a simple and cost-effective method in the treatment of traumatic and chronic soft-tissue defects. Wound cavities are filled with polyvinyl alcohol foam with embedded drainage tubes. The tubes are either drawn transcutaneously through the tissue, or placed epicutaneously, depending on the condition of the wound. The wound including the adjacent skin and the drainage tubes are covered by a transparent vapor transmitting polyurethane film. When the drainage tubes are connected with a vacuum bottle, negative pressure of 60 to 80 kPa is established. The advantages of this vacuum sealing procedure are: protection against wound contamination, complete evacuation of wound fluids independent of gravity and rapid stimulation of dense, well vascularized granulation tissue. Relief of pain and early mobilisation improve the patients comfort. Between November 1994 and July 1996, 25 patients with 28 soft tissue defects underwent this procedure. Wound closure was performed in two cases with a free flap, in five cases by a loco-regional flap, in sixteen cases with mesh-grafts, in three cases by secondary closure of the wound. Two cases were definitively treated with the vacuum sealing technique.

Adolescent↗

The duration of antidiuretic response of two desmopressin nasal sprays.

The duration of antidiuretic response and pharmacokinetics of desmopressin were investigated in 16 healthy, male overhydrated volunteers after intranasal administration of 20 microg desmopressin (dDAVP). The antidiuretic activity was determined by measuring urine osmolality and diuresis over a period of 24 hours. Both study preparations were equally effective regarding a rapid onset of activity and a highly reproducible extent of effect. Urine osmolalities, analyzed as areas under the time curve (AUCosm) were similar for both nasal sprays. Urine volumes were comparable. Bioequivalence was assessed for the primary criterion AUCosm by a calculated mean ratio (test/reference) of 100.9% (90% confidence interval ranging from 88.0% to 115.6%). Plasma levels of desmopressin, measured by a specific and sensitive radioimmunoassay method, were already detectable 20 minutes after administration. The mean time courses showed a similar shape with increased concentration levels for the test preparation. Consequently maximum desmopressin plasma concentrations were different, showing high interindividual variability. However, the times of reaching maximum plasma concentrations were similar. AUC(0-24h) was significantly raised after treatment with the test preparation (mean ratio of 127.9%; 90% confidence interval ranging from 106.6% to 153.5%). A subanalysis of the 2 reference batches with the two-sided t-test procedure for parallel groups resulted in a mean ratio of 83.1% with a 90% confidence interval ranging from 67.2% to 102.7%. The estimated ratios of the 2 batches of the reference preparation were borderline to the equivalence range. In conclusion, both study preparations had the same pronounced biological effect with different desmopressin bioavailabilities.

Administration, Intranasal↗

Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease.

Flow-mediated vasodilation (FMD) of systemic arteries, a non-invasive parameter of endothelial function, is correlated with cardiovascular risk factors. The relationship between FMD and morphologically and clinically evident coronary artery disease has not been described. This study was performed to test the hypothesis that an impairment of FMD in the brachial artery is related to the presence and/or extent and severity of coronary artery disease (CAD). We examined 74 patients with angina pectoris and 14 control subjects (age 17 36 years). Angiography revealed coronary artery disease (> or = 30% diameter stenosis) in 44 patients (CAD, age 32 67 years) and smooth coronary arteries in 30 patients (non-CAD, age 22-73 years). Vasodilation following reactive hyperemia and after sublingual nitroglycerin (NTG) was assessed in the brachial artery using B-mode high resolution ultrasound. CAD patients showed markedly impaired FMD compared to the non-CAD group (5.7 +/- 4.8 versus 12.6 +/- 6.7%, P < 0.0001) and to controls (5.7 +/- 4.8 versus 15.7 +/- 3.9%, P < 0.00001). NTG induced similar degrees of vasodilation in the CAD and non-CAD groups but less vasodilation in the CAD patients compared to controls (12.2 +/- 6.3 versus 20.4 +/- 6.9%, P < 0.01). On univariate analysis, impaired FMD in CAD patients and non-CAD patients was related to the extent of coronary disease (1-, 2- or 3-vessel disease; r = -0.67, P < 0.0001), to the maximum percent diameter stenosis in one of the major coronary vessels (r = -0.52, P < 0.0001), brachial artery diameter (r = -0.46, P < 0.0001) and plasma cholesterol level (r = -0.34, P < 0.001). On multiple stepwise regression analysis the extent of coronary disease (r = -0.51, P < 0.0001) and the baseline brachial artery diameter (r = -0.37, P < 0.0001) were independently associated with FMD in CAD and non-CAD patients. The present findings suggest that the impairment of FMD in the brachial artery, a marker of systemic endothelial function, is closely related to the angiographic extent of CAD.

Adolescent↗

Myocardial angiotensin receptor type 1 gene expression in a rat model of cardiac volume overload.

To investigate the regulation of the angiotensin receptor type 1 (AT1) in different organs in cardiac volume overload, we measured AT1 mRNA content in the atria, left and right ventricle, kidney and liver of rats with an aortocaval shunt, produced by infrarenal aortocaval puncture 4 weeks earlier. For angiotensin receptor mRNA quantitation a novel quantitative PCR procedure based on liquid phase hybridization was used that allowed the determination of absolute AT1 mRNA copy numbers and its comparison in different organs. Glyceraldehydephosphate dehydrogenase (GAPDH) mRNA was measured by RT-PCR to control externally equal mRNA content and quality of RNA extraction in shunt animals and controls. Heart weight was increased in the shunt animals, with the greatest increase in the atria. Blood pressure, plasma renin activity, plasma angiotensin I and II and aldosterone concentrations were not significantly altered. The AT1 mRNA content was significantly increased in the atria (shunt: 1167 +/- 350 copies AT1 mRNA/ng RNA vs controls: 803 +/- 240; p < 0.05). No change was found in the right or left ventricle, in the kidney and liver. The findings document that atrial hypertrophy in cardiac volume overload parallel with a significant increase in atrial AT1 mRNA content.

Animals↗

Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study.

OBJECTIVES: To compare the effects of norepinephrine and dobutamine to epinephrine on hemodynamics, lactate metabolism, and gastric tonometric variables in hyperdynamic dopamine-resistant septic shock. DESIGN: A prospective, intervention, randomized clinical trial. SETTING: Adult medical/surgical intensive care unit in a university hospital. PATIENTS: 30 patients with a cardiac index (CI) > 3.51 x min(-1) x m(-2) and a mean arterial pressure (MAP) < or = 60 mmHg after volume loading and dopamine 20 microg/kg per min and either oliguria or hyperlactatemia. INTERVENTIONS: Patients were randomized to receive an infusion of either norepinephrine-dobutamine or epinephrine titrated to obtain an MAP greater than 80 mmHg with a stable or increased CI. MEASUREMENTS AND MAIN RESULTS: Baseline measurements included: hemodynamic and tonometric parameters, arterial and mixed venous gases, and lactate and pyruvate blood levels. These measurements were repeated after 1, 6, 12, and 24 h. All the patients fulfilled the therapeutic goals. No statistical difference was found between epinephrine and norepinephrine-dobutamine for systemic hemodynamic measurements. Considering metabolic and tonometric measurements and compared to baseline values, after 6 h, epinephrine infusion was associated with an increase in lactate levels (from 3.1 +/- 1.5 to 5.9 +/- 1.0 mmol/l;p < 0.01), while lactate levels decreased in the norepinephrine-dobutamine group (from 3.1 +/- 1.5 to 2.7 +/- 1.0 mmol/l). The lactate/pyruvate ratio increased in the epinephrine group (from 15.5 +/- 5.4 to 21 +/- 5.8; p < 0.01) and did not change in the norepinephrine-dobutamine group (13.8 +/- 5 to 14 +/- 5.0). Gastric mucosal pH (pHi) decreased (from 7.29 +/- 0.11 to 7.16 +/- 0.07; p < 0.01) and the partial pressure of carbon dioxide (PCO2) gap (tonometer PCO2-arterial PCO2) increased (from 10 +/- 2.7 to 14 +/- 2.7 mmHg; p < 0.01) in the epinephrine group. In the norepinephrine-dobutamine group pHi (from 7.30 +/- 0.11 to 7.35 +/- 0.07) and the PCO2 gap (from 10 +/- 3.0 to 4 +/- 2.0 mmHg) were normalized within 6 h (p < 0.01). The decrease in pHi and the increase in the lactate/pyruvate ratio in the epinephrine group was transient, since it returned to normal within 24 h. CONCLUSIONS: Considering the global hemodynamic effects, epinephrine is as effective as norepinephrine-dobutamine. Nevertheless, gastric mucosal acidosis and global metabolic changes observed in epinephrine-treated patients are consistent with a markedly inadequate, although transient, splanchnic oxygen utilization. The metabolic and splanchnic effects of the combination of norepinephrine and dobutamine in hyperdynamic dopamine-resistant septic shock appeared to be more predictable and more appropriate to the current goals of septic shock therapy than those of epinephrine alone.

Adrenergic beta-Antagonists↗

A carbonic anhydrase gene is induced in the nodule primordium and its cell-specific expression is controlled by the presence of Rhizobium during development.

Under nitrogen starvation, Rhizobium meliloti is able to induce nitrogen-fixing nodules on alfalfa roots. Certain alfalfa cultivars spontaneously develop pseudonodules in the absence of bacteria. A transcript, Msca1, expressed in spontaneous and R. meliloti-induced nodules, that codes for a carbonic anhydrase (CA), an enzyme catalyzing the hydration of CO2 has been identified. This is the first CA gene cloned from a non-photosynthetic tissue in plants. Msca1 was activated initially in all cells of the bacterium-induced nodule primordium and was also induced by cytokinin treatment of alfalfa roots. The presence of CA enzymatic activity in different nodule types was demonstrated. Thus, Msca1 is a new early nodulin gene with a function possibly related to the increased amyloplast deposition of the dividing cortical cells. Msca1 transcripts were subsequently found mainly in a peripheral envelope of cells in developing and mature nodules. This novel pattern of gene expression is controlled by the presence of the bacterium inside the nodule. Sucrose synthase and phosphoenol pyruvate carboxylase (PEPC), other genes of the carbon fixation metabolism, were expressed in the same peripheral cells and even more strongly in the nitrogen-fixing region. Analysis of expression patterns of these genes indicated that early CA function may not be related to carbon fixation through PEPC. CA might be acting in pH regulation and/or CO2/HCO3-transport during nodule initiation. Thus, carbonic anhydrase may play different roles at several stages of nodule development and function.

Amino Acid Sequence↗

The relationship between juxtapapillary duodenal diverticula and biliary stone disease.

OBJECTIVE: To assess the relationship between juxtapapillary duodenal diverticula (JDD) and common bile duct stones and biliary stone disease in general. DESIGN: A retrospective study. METHODS: We analysed 1115 patients who underwent consecutive endoscopic retrograde cholangiopancreatography examinations. The patients were subdivided into three groups: the first group (group I; n = 482) had no biliary stone disease, the second one (group II; n = 329) had common bile duct stones, and the third group (group III; n = 304) had biliary stone disease of the gallbladder but without evidence of common bile duct stones. Additionally, the patients were subdivided into age groups of < 50, 50-59, 60-69, 70-79, and > or = 80 years of age. Logistic regression was applied for statistical analysis. RESULTS: Juxtapapillary duodenal diverticula were diagnosed in 111 (10.0%) patients. The incidence of JDD was 6.9% in group I, 14.3% in group II and 10.2% in group III. Age was the most dominant influence factor for JDD, common bile duct stones, and biliary stone disease (P < 0.0001). Sex was also a factor, female patients having a higher risk for common bile duct stones (P = 0.01) and biliary stone disease (P < 0.0001). After adjustment for age and sex, JDD was found to have a noticeable, but not statistically significant (P = 0.073), influence on common bile duct stones and no influence on biliary stone disease (P = 0.15). CONCLUSION: Our data support only moderately the existence of a relationship, which had been conjectured in a part of the literature, between JDD and common bile duct stones. No noticeable influence on biliary stone disease was found.

Adolescent↗

Use of manganese in RT-PCR eliminates PCR artifacts resulting from DNase I digestion.

The precise quantification of rare mRNA copies from intronless genes by reverse transcription polymerase chain reaction (RT-PCR) requires the complete removal of genomic DNA because discrimination of cDNA and DNA amplification products by differing sizes of PCR products is not possible. Elimination of DNA is achieved by treating the RNA sample with RNase-free DNase I before RT-PCR. The lack of a PCR product from DNase-treated RNA samples before RT is usually accepted as a proof of efficient DNA destruction. However, this may vary depending on the metal cofactor used in the DNase I cleavage. Treating DNA-contaminated RNA samples with DNase I and magnesium as a cofactor creates a negative PCR control after digestion without further RT. Paradoxically, after additional RT-PCR, the original intron-containing DNA fragment size may be produced again. In the presence of manganese as cofactor, RT-created DNA fragments do not appear. This is because in the presence of manganese, DNase I cleaves both DNA strands at approximately the same site, yielding DNA fragments that are blunt-ended or that have protruding termini of only one or two nucleotides in length. However, overlapping fragments with the potential to recombine are created by DNase digestion with magnesium as cofactor. Because one cannot differentiate between a PCR signal produced by RNA and one produced by recombined DNA after DNase I digestion and RT, all such DNase I assays should be performed with manganese instead of magnesium.

Artifacts↗