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Biomedical subjects

C Siebert

Publications and source records attributed to C Siebert.

At least 19 recordsLinked to original sources

Measuring the perceptual magnet effect in the perception of /i/ by German listeners.

In a study of the internal category structure of the vowel /i/, Kuhl found a "perceptual magnet effect": Discrimination sensitivity was poorer for category instances that were acoustically similar to the category prototype than it was for category instances that were not. The typicality of category exemplars was determined by goodness judgments and was found to correlate with the acoustics of average production. Analysis and interpretation of discrimination performance relied on two important assumptions: that listeners perceived all stimuli presented as exemplars of the same vowel category and that, apart from the influence of phonetic coding, discrimination sensitivity was the same across the investigated part of the vowel space. In the present study, it is shown that production and perception estimates of the category prototype may diverge, possibly because listeners seem to prefer hyperarticulated variants of vowel categories. An approach towards measurement of intra-category discrimination minima is put forward and tested that protects against intercategory confounds and avoids the isosensitivity assumption.

Germany↗

Surfactant abnormalities in idiopathic pulmonary fibrosis, hypersensitivity pneumonitis and sarcoidosis.

Bronchoalveolar lavage fluids (BALF) from patients with idiopathic pulmonary fibrosis (IPF; n=36), hypersensitivity pneumonitis (HP; n=32) and sarcoidosis (n=44) were investigated for their surfactant properties and compared to healthy control subjects (n=29). The phospholipid (PL) and protein concentration, the PL:protein ratio, PL subclasses, and the surfactant apoproteins (SP)A and SP-B were quantified in BALF. Large surfactant aggregates (LSA) were measured by means of ultracentrifugation and assayed for surface activity using the pulsating bubble surfactometer. As compared to controls, SP-A concentrations, LSA content and PL:protein ratios were significantly decreased in all groups, whereas PL and SP-B concentrations remained unchanged. Changes in the phospholipid profile, with reduced percentages of phosphatidylcholine (not significant) and phosphatidylglycerol and increased fractions of phosphatidylinositol and sphingomyelin (p<0.05), occurred more in IPF than in HP, and not in sarcoidosis. Surface activity was found to be severely impaired in IPF (minimum surface tension (gamma min) approximately 15-20 mN x m(-1)), but only modestly affected in HP and sarcoidosis (gamma min approximately 5 mN x m(-1)) compared to controls (gamma min approximately 0 mN x m(-1)). Reconstitution of pelleted surfactant material with soluble BALF proteins further increased gamma min values. In conclusion, moderate changes in biochemical and physical surfactant properties are encountered in hypersensitivity pneumonitis and sarcoidosis, but pronounced disturbances occur in idiopathic pulmonary fibrosis.

Adolescent↗

[Injury and exertion patterns in football on artificial turf].

This controlled non-selected cross-sectional study supplies a basic survey on the topic analysing 1783 injuries in 433 of 736 athletes out of a closed collective. Aged 11 to 40 years and having played an average of 3.7 years an artificial turf the players had sustained 38% skin injuries (58% in the legs), 28% sprains (64% in the ankle joints, 21% in the knee joints) and 17% muscle injuries. 76% of all injuries were minor, i.e. leading to an interruption of under one week, only 8% were severe with a break of over 3 weeks. The average risk of injury was 6 per 1000 hours of participation, similar to that in football on natural grass. More than half of the players protocol pain in the joints, muscles or column persisting even one day after the game, which only led to medical assistance in 3% of all cases. Playing football on artificial grass displays a specific pattern of injuries and exertion syndromes without a higher rate or grade of injuries and therefore shows no medical need for restriction.

Adolescent↗

Biochemical separations by continuous-bed chromatography.

Innovations in column-packing media for biomolecule purification have progressed from large spherical, porous polysaccharide beads to advanced polymeric supports. Continuous-bed technology is a radical new technology for chromatography based on the polymerization of advanced monomers and ionomers directly in the chromatographic column. The polymer chains form aggregates which coalesce into a dense, homogeneous network of interconnected nodules consisting of microparticles with an average diameter of 3000 A. The voids or channels between the nodules are large enough to permit a high hydrodynamic flow. Due to the high cross-linking of the polymer matrix, the surface of each nodule is nonporous yet the polymeric microparticles provide a very large surface area for high binding capacity. This paper will demonstrate the properties and advantages of using a continuous bed support for high resolution biomolecule separations at high flow-rates without sacrificing capacity.

Animals↗

The relationship between parameters of serotonin metabolism and emetogenic potential of platinum-based chemotherapy regimens.

Evaluation of the relationship between parameters of serotonin (5-HT) metabolism and emesis in platinum-based chemotherapy. Female patients receiving chemotherapies containing either cisplatin (35 patients; 80 courses) or carboplatin (65 patients; 102 courses) were recruited. Recording of emesis and measurements of urinary 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of 5-HT, was performed over 3 days. Comparisons were performed for single-agent cisplatin (DDP) versus single-agent carboplatin (CBDCA), single-agent high-dose DDP (> or = 75 mg/m2) versus high-dose DDP combined with cyclophosphamide, high-dose versus low-dose DDP (< or = 50 mg/m2), and single-agent CBDCA versus a combination with alkylating agents. Cisplatin induced both a significantly higher frequency of emesis and a significantly higher increase of 5-HIAA excretion than carboplatin. The velocity of 5-HIAA increase may correlate better with emetogenic potential than peak 5-HIAA excretion levels. The increase of 5-HIAA excretion induced by cisplatin was limited to day 1. Higher cisplatin doses showed both a higher emetogenic potential and a more pronounced increase in urinary 5-HIAA on day 1. No significant difference was found when single-agent cisplatin was compared with cisplatin combined with cyclophosphamide. In contrast, a combination of carboplatin with alkylating agents induced a larger increase in urinary 5-HIAA and showed a higher emetogenic potential than single-agent carboplatin. Low-dose cisplatin induced less emesis than carboplatin combination therapy, but induced a larger increase in urinary 5-HIAA. Our findings provide evidence for a relationship between emetogenic potential and patterns of 5-HIAA excretion following platinum-based chemotherapy.

Antineoplastic Agents, Alkylating↗

Oligonucleotide analysis by capillary polymer sieving electrophoresis using acryloylaminoethoxyethanol-coated capillaries.

Capillary polymer sieving electrophoresis using dynamic sieving polymer solutions provides size-based separations of oligonucleotides. The polymer sieving system described here resolves single-stranded oligonucleotides with single-base resolution up to lengths of 30 bases within 10 min. The effect of temperature on the separation of synthetic oligonucleotide standards was examined between 20 degrees C and 40 degrees C, with optimal performance at 35-40 degrees C. By adding urea to the sieving buffer single-base resolution could be extended to 60 bases in about 40 min. Best performance was achieved with capillaries coated with a new monomer, acryloylaminoethoxyethanol. This coating provides the necessary stability to ensure long lifetimes.

Acrylic Resins↗

Surfactant alterations in severe pneumonia, acute respiratory distress syndrome, and cardiogenic lung edema.

Bronchoalveolar lavage fluids (BALF) were analyzed for surfactant abnormalities in 153 patients with acute respiratory failure necessitating mechanical ventilation. Diagnoses were acute respiratory distress syndrome (ARDS) in the absence of lung infection (n = 16), severe pneumonia (PNEU; n = 88), ARDS and PNEU (n = 36), and cardiogenic lung edema (CLE; n = 13). The PNEU group was subdivided into groups with alveolar PNEU (n = 35), bronchial PNEU (n = 16), interstitial PNEU (n = 18) and nonclassified PNEU (n = 19). Comparison with healthy controls (n = 20) was undertaken. Total phospholipids (PL), proteins, PL classes (HPTLC) and surfactant apoproteins SP-A and SP-B (ELISA) were quantified in the original BALF. The 48,000 x g pellet from centrifugation of the BAL was used to assess the percentage of large surfactant aggregates (LSA) and the biophysical properties of the surfactant (pulsating bubble surfactometer). All groups with inflammatory lung injury (PNEU and/or ARDS) showed some decrease in the lavageable PL pool, a reduced LSA content in BALF, and a manifold increase in alveolar protein load. Marked changes in the PL profile were noted throughout the groups (a decrease in phosphatidylcholine (PC) and phosphatidylglycerol (PG) and an increase in phosphatidylinositol [PI] and sphingomyelin [SPH]). Concentrations of SP-A but not of SP-B in BALF were reduced. Minimum surface-tension values approached 0 mN/m in controls, and ranged from 10 to 25 mN/m in the absence of supernatant protein and from 20 to 35 mN/m in recombination with leaked protein in the groups with ARDS and/or PNEU. Abnormalities in alveolar PNEU surpassed those in bronchial PNEU, and interstitial PNEU presented a distinct pattern with extensive metabolic changes. All surfactant changes were absent in CLE except for a slight inhibition of surface activity by proteins. We conclude that pronounced surfactant abnormalities, comparable to those in ARDS in the absence of lung infection, occur in different entities of severe PNEU, but not in CLE.

Acute Disease↗

Bronchoalveolar and systemic cytokine profiles in patients with ARDS, severe pneumonia and cardiogenic pulmonary oedema.

The aim of this study was to investigate whether bronchoalveolar lavage (BAL) and serum levels of proinflammatory cytokines discriminate between different entities of patients with acute respiratory failure. BAL and circulating concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) were measured in 74 mechanically-ventilated patients and 17 healthy controls. Patients were classified as cardiogenic pulmonary oedema (CPO), acute respiratory distress syndrome (ARDS), primary severe pneumonia (PN) and a combined group (PN+ARDS). In all patients with ARDS and/or PN, markedly elevated BAL levels of IL-6 and IL-8 were detected, which were significantly greater than levels in CPO and healthy controls. Absolute quantities and time-course of these cytokines did not differentiate between the absence and presence of lung infection, or different categories of PN. Similarly, circulating IL-6 levels were comparably elevated in patients with ARDS and/or PN, whereas circulating IL-8 concentrations were inconsistently increased. TNF-alpha was rarely detected in BAL samples, but increased serum concentrations were measured in ARDS and/or PN patients. Bronchoalveolar lavage levels of interleukin-6 and interleukin-8, but not tumour necrosis factor-alpha, and serum concentrations of interleukin-6 are consistently elevated in acute respiratory distress syndrome and/or severe pneumonia, discriminating these entities from cardiogenic pulmonary oedema. Alveolar and systemic cytokine profiles do not differentiate between acute respiratory distress syndrome in the absence of lung infection and states of severe primary or secondary pneumonia, which evidently present with comparable local and systemic inflammatory sequelae.

Acute Disease↗

The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.

BACKGROUND: Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications. METHODS: A total of 1441 patients with IDDM--726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly. RESULTS: In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of > or = 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of > or = 300 mg per 24 hours) by 54 percent (95 percent confidence interval 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia. CONCLUSIONS: Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.

Adolescent↗

Operational and policy considerations of data monitoring in clinical trials: the Diabetes Control and Complications Trial experience.

Many clinical trials incorporate a system for monitoring emerging data that utilizes a committee composed of individuals who are independent of the investigators conducting the study. Although this is a common practice, there is a paucity of publications examining the operating methods of these groups. This paper describes the composition, functions, and procedures of the Data, Safety and Quality Review Group (DSQ) of the Diabetes Control and Complications Trial (DCCT). The DSQ is not masked to emerging data and the voting membership is made up of individuals with a wide diversity of expertise that reflects the needs of the trial. There are also nonvoting exofficio members who represent other components of the study organization. In addition to data monitoring, the DSQ provides external review of coordinating center operations. A distinctive aspect of the DCCT's DSQ is the creation of a free-standing operations manual for the DSQ's use during the trial and the involvement of the study investigators in developing certain sections of this document. Utilizing a process that allowed participation of the investigators was considered critical to achieving a mutual understanding regarding the planned uses and interpretations of the study data prior to the study's completion so as to minimize the chances of major disagreements regarding the conclusions drawn. Equally important, the existence of such a manual provides documentable reassurance to all interested parties that both scientific integrity and patient safety are being closely watched and gives the study investigators confidence that the results of the study will be scientifically credible and clinically important.

Clinical Trials as Topic↗

Glomerular filtration rate measurements in clinical trials. Modification of Diet in Renal Disease Study Group and the Diabetes Control and Complications Trial Research Group.

To assess the utility and precision of GFR measurements in multicenter trials, the test performance and variability of GFR were analyzed in 2,250 patients enrolled in 44 clinical centers participating in either the Modification of Diet in Renal Disease (MDRD) Study or the Diabetes Control and Complications Trial (DCCT). GRF was measured as the renal clearance of [125I]iothalamate after an sc injection without epinephrine. The studies used similar protocols for obtaining blood and urine, training clinical center staff, and processing specimens in central laboratories. The performance of GFR measurements, assessed from adherence to protocol and quality control analyses, was excellent. The variability among the four clearance periods (intratest coefficient of variation [CV]) was acceptable; the median intratest CV for GFR was 9.4% in the MDRD Study and 11.7% in the DCCT. The pattern of decline in serum counts was better approximated by an exponential rather than a linear relationship. The cause of the intratest variability in GFR measurements was explored by univariate and multivariate analysis. The intratest CV was highest at the extremes of GFR. Among patients with a high GFR (> 90 mL/min per 1.73 m2), most of whom were participants in the DCCT, the higher intratest GFR was due, in part, to a systematic decline in GFR during the test. Among patients with a very low GFR (< 13 mL/min per 1.73 m2), technical difficulties in urine collections contributed substantially to the higher intratest CV. Other patient characteristics, including age, gender, weight, serum glucose, renal diagnosis, and use of diuretics, were not strongly correlated with the intratest CV. The precision of GFR measurements was assessed from the variability from measurement to measurement (interest CV). Among MDRD Study subjects, in whom two measurements of GFR were performed over a 3-month interval, the median interest CV was relatively low (6.3%) and was only weakly related to the intratest CV. Thus, GFR measurements are reasonably precise, even if the intratest CV is high. Given the relatively high intratest CV that is characteristic of GFR measurements, the estimate of GFR in an individual is more precise if multiple clearance periods, rather than a single period, are included. Similarly, the estimate of mean GFR for a population is also more precise if multiple clearance periods are included. In conclusion, by the use of standardized methods, an acceptable precision of GFR results can be obtained in multicenter trials. The same methods can be applied in clinical practice.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Survey of physician practice behaviors related to diabetes mellitus in the U.S. I. Design and methods.

OBJECTIVE: To conduct a survey among a representative sample of primary care physicians in the U.S. to assess practice behaviors, treatment goals, and beliefs related to management of diabetes mellitus and prevention of its complications. RESEARCH DESIGN AND METHODS: A mail survey with telephone follow-up was conducted among 3481 primary care physicians in active practice in the continental U.S. A stratified probability sample was selected using the files of the American Medical Association and American Osteopathic Association. Four specialties were selected to be included in the study: family physician, general practitioner, internist, and pediatrician. Two versions of a questionnaire were constructed: one for pediatricians containing questions about IDDM only and one for the other three specialties containing questions about both IDDM and NIDDM. Physicians who were not actively engaged in practice or did not see patients with diabetes were excluded. RESULTS: Completed questionnaires were received from 1502 of 3481 sampled physicians. Based on various assumptions of eligibility among nonresponders, an overall response rate to the survey was estimated to be between 65.7 and 86.5%. Discrepancies between specialty identifications as noted on the American Medical Association/American Osteopathic Association files and as self-designated were noted. CONCLUSIONS: This report describes the methodology used in the design and conduct of the survey, and data are provided to document the technical success of survey execution. This report provides the methodological basis for a series of separate reports on demographic characteristics of the physicians, their practices and their patients, and on specific attitudes, beliefs, and practice behaviors of primary care physicians in the U.S. with regard to diabetes mellitus.

American Medical Association↗

Capillary electrophoresis of hemoglobins and globin chains.

Capillary isoelectric focusing (cIEF) and free zone capillary electrophoresis were evaluated for separation of native hemoglobins and globin chains. High-resolution separations of adult human hemoglobin A, fetal human hemoglobin F, and hemoglobin variants S and C were obtained using cIEF with cathodic mobilization. Absorbance detection in the UV and visible regions were compared, and on-line fast UV or visible-wavelength scanning detection was used to obtain spectral information on separated components. Globin chain analysis was performed on the same hemoglobin species by free zone capillary electrophoresis following precipitation of the protein with acidic acetone. Free zone separations were carried out at low pH in the presence of 7 M urea.

Electrophoresis↗

[Undesirable side effects of contrast media during i.v. DSA--a comparison of 2 nonionic contrast media].

For the first time a controlled double-blind study was performed to compare side effects and complications of i.v. DSA with central venous application of iopamidol and iopromide. 200 consecutive patients 15-85 years of age were studied. The randomisation brought up two homogeneously structured groups of 100 patients each. Using a given protocol, 66% of the patients were classified as high-risk patients. Side-effects and complications were registered by an extensive, standardised protocol. In 71 (35.5%) of 200 patients contrast-media related side effects and complications were noted. 37 reactions in 24 patients (9 iopamidol, 15 iopromide group) were classified as clinically relevant. In four patients (4%) of each group a drug therapy was initiated. Contrast-media related reactions occurred with delay in 5.5% of initially symptom-free patients. In no case intensive care or hospital admission became necessary. There were no significant differences between the two non-ionic contrast media in the incidence of side effects and complications. Both substances were well tolerated in i.v. DSA. In the total population patients with diseases known as auto-immune diseases and prior drug reactions demonstrated clinically relevant reactions significantly more often.

Adolescent↗