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S Walter

Publications and source records attributed to S Walter.

At least 145 records · Page 8Linked to original sources

Structure of human parathyroid hormone 1-37 in solution.

Human parathyroid hormone (hPTH), amino acids Ser1 to Leu37, is biologically active with respect to both receptor binding and activation of adenylate cyclase to influence the serum calcium concentration. It induces DNA synthesis via an unknown signal pathway. We investigated the structure of hPTH(1-37) in H2O/buffer solution under near physiological conditions, that is pH 6.0 and 270 mM salt, by circular dichroism, ultracentrifugation, nuclear magnetic resonance spectroscopy, and molecular dynamics calculations. Complete sequence specific assignments of all 1H resonances were performed by using 1H two-dimensional NMR measurements (double quantum-filtered correlated spectroscopy, nuclear Overhauser effect spectroscopy (NOESY), and total correlation spectroscopy with suppression of NOESY-type cross-peaks spectra). hPTH(1-37) obtained helical structure and showed hydrophobic interactions defining a tertiary structure. The NH2-terminal four amino acids of hPTH(1-37) did not show a stable conformation. Evidence for an alpha-helical region between Ile5 and Asn10 was found. This region was followed by a flexible link (Gly12, Lys13) and a well defined turn region, His14 to Ser17. The latter was stabilized by hydrophobic interactions between Trp23 and Leu15. Ser17 through at least Leu28 formed an alpha-helix. Arg20 and Lys27 were involved in the core built by His14 to Ser17. Unrestrained molecular dynamics simulations indicated that the structure was stable on the 200 ps time scale.

Amino Acid Sequence↗

[The urethral plug--an alternative treatment of women with urinary stress incontinence].

A developed urethral plug was evaluated for the treatment of women with genuine urinary stress incontinence. The plug consists of an oval meatal plate, a soft stalk and one or two spheres along the stalk with fixed distances between the meatal plate and the spheres. Inside the stalk is a removable semi-rigid guide pin to ease insertion. Forty women were randomly allocated to treatment with either the two-sphere or the one-sphere plug during period one (two weeks). In period two (two weeks) the patients used the other plug. They then continued with what they judged to be the better plug in period three (two months). Eighteen patients (45%) completed period three with the "preference" plug and 17 were subjectively and objectively continent or improved. Fourteen of these women preferred the two-sphere device. The plugs were equally effective in patients with mild or severe incontinence. Six women developed urinary tract infections and two of these had a plug in the bladder. The urethral plug is an effective treatment in a group of women with stress incontinence. Removal by hand is advisable in order to avoid retention of plugs in the bladder.

Adult↗

Basic statistics for clinicians: 4. Correlation and regression.

Correlation and regression help us to understand the relation between variables and to predict patients' status in regard to a particular variable of interest. Correlation examines the strength of the relation between two variables, neither of which is considered the variable one is trying to predict (the target variable). Regression analysis examines the ability of one or more factors, called independent variables, to predict a patient's status in regard to the target or dependent variable. Independent and dependent variables may be continuous (taking a wide range of values) or binary (dichotomous, yielding yes-or-no results). Regression models can be used to construct clinical prediction rules that help to guide clinical decisions. In considering regression and correlation, clinicians should pay more attention to the magnitude of the correlation or the predictive power of the regression than to whether the relation is statistically significant.

Data Interpretation, Statistical↗

Basic statistics for clinicians: 3. Assessing the effects of treatment: measures of association.

In the third of a series of four articles the authors show the calculation of measures of association and discuss their usefulness in clinical decision making. From the rates of death or other "events" in experimental and control groups in a clinical trial, we can calculate the relative risk (RR) of the event after the experimental treatment, expressed as a percentage of the risk without such treatment. The absolute risk reduction (ARR) is the difference in the risk of an event between the groups. The relative risk reduction is the percentage of the baseline risk (the risk of an event in the control patients) removed as a result of therapy. The odds ratio (OR), which is the measure of choice in case-control studies, gives the ratio of the odds of an event in the experimental group to those in the control group. The OR and the RR provide limited information in reporting the results of prospective trials because they do not reflect changes in the baseline risk. The ARR and the number needed to treat, which tells the clinician how many patients need to be treated to prevent one event, reflect both the baseline risk and the relative risk reduction. If the timing of events is important--to determine whether treatment extends life, for example--survival curves are used to show when events occur over time.

Case-Control Studies↗

Basic statistics for clinicians: 2. Interpreting study results: confidence intervals.

In the second of four articles, the authors discuss the "estimation" approach to interpreting study results. Whereas, in hypothesis testing, study results lead the reader to reject or accept a null hypothesis, in estimation the reader can assess whether a result is strong or weak, definitive or not. A confidence interval, based on the observed result and the size of the sample, is calculated. It provides a range of probabilities within which the true probability would lie 95% or 90% of the time, depending on the precision desired. It also provides a way of determining whether the sample is large enough to make the trial definitive. If the lower boundary of a confidence interval is above the threshold considered clinically significant, then the trial is positive and definitive, if the lower boundary is somewhat below the threshold, the trial is positive, but studies with larger samples are needed. Similarly, if the upper boundary of a confidence interval is below the threshold considered significant, the trial is negative and definitive. However, a negative result with a confidence interval that crosses the threshold means that trials with larger samples are needed to make a definitive determination of clinical importance.

Clinical Trials as Topic↗

Basic statistics for clinicians: 1. Hypothesis testing.

In the first of a series of four articles the authors explain the statistical concepts of hypothesis testing and p values. In many clinical trials investigators test a null hypothesis that there is no difference between a new treatment and a placebo or between two treatments. The result of a single experiment will almost always show some difference between the experimental and the control groups. Is the difference due to chance, or is it large enough to reject the null hypothesis and conclude that there is a true difference in treatment effects? Statistical tests yield a p value: the probability that the experiment would show a difference as great or greater than that observed if the null hypothesis were true. By convention, p values of less than 0.05 are considered statistically significant, and investigators conclude that there is a real difference. However, the smaller the sample size, the greater the chance of erroneously concluding that the experimental treatment does not differ from the control--in statistical terms, the power of the test may be inadequate. Tests of several outcomes from one set of data may lead to an erroneous conclusion that an outcome is significant if the joint probability of the outcomes is not taken into account. Hypothesis testing has limitations, which will be discussed in the next article in the series.

Clinical Trials as Topic↗

Interaction of B and T lymphocyte subsets with high endothelial venules in the rat: binding in vitro does not reflect homing in vivo.

Lymphocytes continuously migrate through the body, and their efficient extravasation from the blood via high endothelial venules (HEV) is essential for initiating an appropriate immune response. Most investigations have focused on the lymphocyte/HEV interaction in vitro. However, to what extent such systems reflect the situation in vivo is not known. It is also unclear whether lymphocyte subsets immigrate into the HEV in proportion to their presence in the blood, and whether import capacity is limited by the HEV. When rat mesenteric lymph node lymphocytes were incubated in vitro on cryostat sections, the well-known preferential binding of B lymphocytes to HEV of Peyer's patches (PP) and T cells to HEV of axillary lymph nodes (axLN) was observed (axLN vs. PP: B lymphocytes 21.2 +/- 5.0% vs. 40.6 +/- 11.0%, T lymphocytes 84.6 +/- 6.3% vs. 56.5 +/- 12.9%). However, when labeled mesenteric lymph node lymphocytes were injected and their location within the HEV was analyzed 15 min later, no preferential interaction was seen. After injection of labeled thoracic duct lymphocytes, the percentage of labeled cells among B and T lymphocytes in the blood was significantly different (4.4 +/- 0.9% vs. 8.9 +/- 3.6%), whereas that in HEV of axLN (19.0 +/- 6.4% vs. 16.6 +/- 6.0%) and PP (30.6 +/- 6.1% vs. 33.9 +/- 4.4%) was comparable. Although the number of injected lymphocytes was similar in magnitude to the total blood lymphocyte pool, after injection there was no increase in lymphocyte numbers in the HEV. Thus, the adhesion assay in vitro does not completely reflect immigration into HEV in vivo. In addition, our data suggest that both the availability of lymphocyte subsets in small venules and the immigration rate into HEV are actively regulated in vivo.

Animals↗

The cellulolytic system of Streptomyces reticuli.

The bacterium Streptomyces reticuli produces an unusual mycelia-associated cellulase (Avicelase, Cel1) which is solely sufficient to degrade crystalline cellulose to cellobiose. The enzyme consists of a binding domain, one adjoining region with unknown function, and a catalytic domain belonging to the cellulase family E. During cultivation, the strain produces a specific protease which processes the Avicelase to a truncated enzyme lacking the binding domain. The cellulase synthesis is regulated by induction (Avicel) and repression (metabolizable sugars and glycerol).

Bacterial Proteins↗

The relative radiosensitivity of TK6 and WI-L2-NS lymphoblastoid cells derived from a common source is primarily determined by their p53 mutational status.

The lymphoblastoid cell lines WI-L2-NS and TK6 were derived from a non-clonal pool of cells taken from a human spleen. Despite their common background they exhibit marked differences in radiosensitivities; D0 values of 93 and 67 cGy have been reported for WI-L2-NS and TK6 cells respectively. We show here that this differential radiosensitivity is due to a decreased ability of the WI-L2-NS cell line to undergo radiation-induced apoptosis. Further, the WI-L2-NS cell line overexpresses the p53 gene product as a result of a mutation in codon 237 of the p53 gene. These data indicate that WI-L2-NS cells through disruption of normal p53 function are unable to engage the radiation-induced apoptosis program and so are relatively radioresistant.

Apoptosis↗

Recall bias in case-control studies: an empirical analysis and theoretical framework.

Previous work has suggested that recall bias in case-control studies may be more serious when the overall study quality is lower. This paper summarizes a systematic literature search to examine the question. All relevant studies published between 1966 and 1990 were included if they met the following criteria: (1) they represented original work, (2) they used a human population, (3) they used a case-control design, (4) they had a "validated" gold standard applied equally to cases and controls and (5) they reported at least one of crude agreement rates, chance-corrected agreement rates (kappa), sensitivity or specificity. Sixteen such studies were identified. No relationship was found between the absolute differences in agreement between cases and controls and the overall level of agreement, in contradiction to suggestions in previous literature. Comparisons of the data quality for cases and controls using either the crude agreement level, kappa, sensitivity, or specificity gave linear relationships with correlations of 0.81, 0.78, 0.58 and 0.62 respectively. Kappas were generally lower than the corresponding crude agreement levels and specificities were higher than sensitivities. When used together, these types of comparisons can give valuable information regarding (1) the possible existence of differential recall in a particular study and (2) the quality of that study, A theoretical framework is proposed for use in these areas.

Bias↗

Evaluation of diagnostic criteria for autism using latent class models.

OBJECTIVE: To illustrate the use of latent class models for comparing alternative diagnostic criteria for autism. The models are based on the notion that the "true" classification of an individual is unknown but does exist at some unobserved, or "latent," level. Estimates of sensitivity and specificity are obtained for each set of diagnostic criteria through maximum likelihood techniques in relation to the latent standard. METHOD: In this paper, latent class models are used to compare DSM-III, DSM-III-R, and ICD-10 criteria for autism in a sample of 342 individuals with autism or other developmental disabilities. The diagnoses were made by one or more child psychiatrists who evaluated each patient and assigned a diagnosis of autism based on their own expert clinical judgment. In addition, the raters also determined whether criteria were met for the various diagnostic systems. RESULTS: The results indicate that the ICD-10 criteria agree best with the latent standard and a diagnosis based on expert opinion. CONCLUSION: It is suggested that latent class models can be usefully applied to the evaluation of other psychiatric disorders as well and represent an important new tool in evaluating diagnostic criteria by providing a way of dealing with data lacking an observable gold standard.

Adolescent↗

Validation of the self-administered Danish Prostatic Symptom Score (DAN-PSS-1) system for use in benign prostatic hyperplasia.

OBJECTIVE: To validate the Danish Prostatic Symptom Score (DAN-PSS-1), a self-administered quality-of-life questionnaire comprising 12 questions related to voiding problems and the perceived bother of each individual symptom. METHODS: Using published results from several comparisons of other symptom scoring systems with DAN-PSS-1, the test-retest reliability, internal consistency, construct and content validity, and responsiveness of the DAN-PSS-1 system were assessed. RESULTS: The system was internally consistent (Cronbach's alpha = 0.73), the median test-retest reliability of answers to each question was 83.5% (range 0-99.7%) and the questionnaire was well understood by the patients. The DAN-PSS-1 system demonstrated a high degree of construct validity, correlating with the extensively used Madsen-Iversen score system (Spearman's correlation coefficient, rs = 0.51) and with the patients' answers to questions about how bothersome their symptoms were (rs = 0.71). The DAN-PSS-1 system discriminated clearly between patients with benign prostatic hyperplasia (BPH) and control subjects (an area under the receiver operating characteristic curve of 0.94). Finally, the DAN-PSS-1 was sensitive to changes following intervention, with scores decreasing from a median of 20 to zero 4 months after patients underwent transurethral prostatectomy and from a median of 11.5 to 7.5 (65%) after patients had received 4 months treatment with an alpha-blocker. CONCLUSIONS: The DAN-PSS-1 system is reliable, valid and responsive, and therefore can be recommended for assessing the severity of symptoms among patients presenting with lower urinary tract complaints suggestive of BPH and in the follow-up after intervention.

Adrenergic alpha-Antagonists↗

Studies of Streptomyces reticuli cel-1 (cellulase) gene expression in Streptomyces strains, Escherichia coli, and Bacillus subtilis.

Various streptomyces strains [Streptomyces lividans 66, Streptomyces vinaceus, and Strepotmyces coelicolor A3 (2)] acquired the ability to utilize crystalline cellulose (Avicel) after transformation with a multicopy vector containing the cel-1 gene from Streptomyces reticuli. The expression level in these hosts was two to three times lower than in S. reticuli, indicating the absence of positive regulatory elements. Like S. reticuli, they processed the Avicelase to its catalytic domain and to an enzymatically inactive part. The cel-1 gene with its original upstream region was not expressed within Escherichia coli. When cel-1 had been fused in phase with the lacZ gene, large quantities of the fusion protein were produced in E. coli. However, this protein was enzymatically inactive and proteolytically degraded to a series of truncated forms. As the cellulase (Avicelase) synthesized by S. reticuli is not cleaved by the E. coli proteases, its posttranslational modification is proposed. With Bacillus subtilis as host, the cel-1 gene was expressed neither under its own promoter nor under the control of a strong Bacillus promoter.

Amino Acid Sequence↗

Flavoxate treatment of micturition disorders accompanying benign prostatic hypertrophy: a double-blind placebo-controlled multicenter investigation.

To investigate the effect of flavoxate (Urispadol) treatment on patients with symptomatic benign prostatic hypertrophy (BPH), with the main weight on the irritative symptoms, a randomized, double-blind, parallel-group, placebo-controlled and multicenter investigation was carried out. Seventy patients entered the study, 37 were allocated to flavoxate treatment on a daily dose of 1,200 mg (400 mg t.i.d.) for 12 weeks, and 33 patients were allocated to placebo treatment. In spite of a sufficient power, the study did not discriminate the two treatment groups in a statistically significant way (p > 0.05), when considering the main endpoints: the irritative symptom score and the global patient evaluation. Conservative treatment of micturition disorders accompanying BPH with flavoxate in doses of 1,200 mg/day cannot be recommended for clinical use.

Aged↗

Interobserver variation in the computed tomographic evaluation of mediastinal lymph node size in patients with potentially resectable lung cancer. Canadian Lung Oncology Group.

OBJECTIVE: To measure the reliability of the assessment of mediastinal lymph node size in computed tomographic (CT) scans of the thorax. DESIGN: Observer agreement study in which radiologists, blinded to one anothers' interpretation, were randomized to read 30 scans each. POPULATION: Sixty scans from patients with apparently operable non-small cell carcinoma of the lung were read by radiologists responsible for clinical interpretation (clinical radiologists) and four radiologists with a special interest in thoracic CT (study radiologists). MEASUREMENTS: Radiologists measured the size of left and right superior mediastinal nodes, aortic nodes, and the subcarinal nodes and, on the basis of whether any nodes accessible to mediastinoscopy were greater than 1 cm, recommended whether mediastinoscopy be undertaken. Agreement was quantified using kappa, a measure of chance-corrected agreement. RESULTS: Among all radiologists, agreement on whether there were any nodes larger than 1 cm for right superior mediastinal nodes was 0.68; for left superior mediastinal nodes it was 0.28; for aortic pulmonary nodes it was 0.62; for subcarinal nodes it was 0.58; and for any node greater than 1 cm and accessible to mediastinoscopy it was 0.61. The agreement was very similar when the analysis was restricted to the study radiologists. CONCLUSION: Although the good level of overall agreement suggests that CT provides useful information in the evaluation of mediastinal lymph node size, the disagreement was sufficient that it likely contributes to suboptimal sensitivity and specificity of CT in detecting tumor spread reported in previous studies.

Carcinoma, Non-Small-Cell Lung↗

[Antibiotic prophylaxis in diagnostic and therapeutic urological interventions].

An enquiry into the use of antibiotic prophylaxis in conjunction with diagnostic or therapeutic urological procedures at hospitals in four Scandinavian countries showed manifest national differences to exist for most procedures. In transurethral resection, for instance, antibiotic cover was used at 79 percent of Finnish hospitals, but at only nine percent of Danish hospitals. Not only were dosage regimens characterized by wide national variation, but also the spectrum of antibiotics used, quinolones being most frequently used in Sweden, but ampicillin and pivampicillin in Denmark. For some procedures policy was more uniform in all countries, antibiotic cover rarely being used in connection with ureterocystoscopy (5 percent of hospitals), but often in conjunction with percutaneous stone surgery (72 per cent). In certain procedures where there is strong evidence suggesting the necessity of antibiotic prophylaxis, it was not always used-e.g., in transrectal prostate biopsy where it was used at only 62 per cent of hospitals. The interpretation of published findings and clinical experience would appear to differ markedly, and local traditions would seem to be strong determinants of clinical routines. The wide variation suggests that all patients do not receive optimal treatment. To improve routines, our knowledge of antibiotic preparations needs to be expanded by well executed studies, followed by general implementation of the results at the various centres. A series of consensus conferences should be arranged and the recommendations published as a first step toward a more uniform and probably better use of antibiotic prophylaxis in conjunction with diagnostic and therapeutic urological procedures.

Anti-Bacterial Agents↗