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Biomedical subjects

S Walter

Publications and source records attributed to S Walter.

At least 109 records · Page 6Linked to original sources

Adjudicating ventilator-associated pneumonia in a randomized trial of critically ill patients.

PURPOSE: The purpose of this study was to evaluate an adjudication strategy for diagnosing ventilator-associated pneumonia (VAP) in a randomized trial. MATERIALS AND METHODS: In a double-blind trial of sucralfate versus ranitidine, one of four pairs of adjudicators examined each case of clinically suspected VAP. Nurse and physician notes and all relevant laboratory data were allocated to each adjudication pair in groups of five patients. Each reader in the pair decided whether the patient had VAP; differences were resolved by consensus discussion. RESULTS: The overall unadjusted study odds ratio for VAP was 0.82 (P = .21) representing a trend toward less pneumonia with sucralfate compared with ranitidine. The odds ratio adjusted for adjudication pair was 0.85 (P = .27). The proportion of charts adjudicated as VAP positive among pairs ranged from 50% to 92%; crude agreement between readers in each pair varied from 50% to 82%. When adjudicators disagreed, the final consensus was split evenly between the two adjudicators' initial opinions in two pairs; in the other two pairs, the final decision reflected one dominant initial opinion. Personnel time to adjudicate all patients with a suspicion of VAP was 74 days. CONCLUSIONS: Though adjudication of outcomes such as VAP is time-consuming, consistent decision-making requires strict criteria, training, and calibration. Patients should be assigned to adjudication teams through random allocation.

Anti-Ulcer Agents↗

Synchronous block in DNA synthesis initiation with change in chromatin topology mediated by VP16.

The impact of chromatin topology on the DNA synthetic process was studied in the human squamous-cell carcinoma cell line SQ-20B. A 1-h exposure < or = 10 microM VP16 produced an increase in DNA supercoil tension, measured by recording laser light scatter from salt-extracted nuclei. This change was precisely paralleled by a decrease in DNA synthesis. The effects on both DNA supercoiling and DNA synthesis were suppressed at VP16 concentrations between 10 and 20 microM. The changes in DNA supercoiling and synthesis at VP16 concentrations -10 microM were eliminated by coincubation with mimosine, a DNA synthesis initiator poison. We conclude that brief exposure to low concentrations of VP16 disturbs the balance of torsional energy within discrete replicon domains by affecting normal topoisomerase II activity at sites of replication initiation. The resultant increase in negative supercoil tension mediates a topologic checkpoint, limiting the initiation of DNA synthesis. Such a checkpoint may be a common pathway for control, both during the normal replicative cycle and subsequent to DNA damage.

Cell Nucleus↗

Evaluating motor function in children with Down syndrome: validity of the GMFM.

The Gross Motor Function Measure (GMFM) was developed and validated originally by Russell and colleagues as an evaluative assessment of gross motor function in children with cerebral palsy (CP). The present study reports the results of reliability and validity testing of the GMFM for use with children with Down syndrome (DS). One hundred and twenty-three children with DS were assessed twice over a 6-month period, using the GMFM and the motor scale of the Bayley Scales of Infant Development - second edition (BSID-II). In addition to the usual method of scoring the GMFM using only observed motor behaviours (standard score), parent reports of children's activities not seen by the assessor on the day of testing were also obtained and a second score (reported score) was calculated for each GMFM assessment. Test-retest and interrater reliabilities were excellent (all >0.90). Observed correlations between change on GMFM and judgements of change made independently by parents, intervenors, and masked video raters were lower than hypothesized. However, the pattern of change scores in predefined age and severity subgroups supported the contention that the GMFM was able to detect differential amounts of change as predicted. The GMFM was shown to be relatively more responsive to change in gross motor function than the motor scale of the BSID-II. The 'reported' scores on the GMFM demonstrated better evidence of reliability, validity, and responsiveness than the standard scoring method and this approach is recommended for use when assessing children with DS.

Child↗

The cell wall-anchored Streptomyces reticuli avicel-binding protein (AbpS) and its gene.

Streptomyces reticuli produces a 35-kDa cellulose-binding protein (AbpS) which interacts strongly with crystalline forms of cellulose (Avicel, bacterial microcrystalline cellulose, and tunicin cellulose); other polysaccharides are recognized on weakly (chitin and Valonia cellulose) or not at all (xylan, starch, and agar). The protein could be purified to homogeneity due to its affinity to Avicel. After we sequenced internal peptides, the corresponding gene was identified by reverse genetics. In vivo labelling experiments with fluorescein isothiocyanate (FITC), FITC-labelled secondary antibodies, or proteinase K treatment revealed that the anchored AbpS protrudes from the surfaces of the hyphae. When we investigated the hydrophobicity of the deduced AbpS, one putative transmembrane segment was predicted at the C terminus. By analysis of the secondary structure, a large centrally located alpha-helix which has weak homology to the tropomyosin protein family was found. Physiological studies showed that AbpS is synthesized during the late logarithmic phase, independently of the carbon source.

Amino Acid Sequence↗

Transfection of a vector expressing wild-type p53 into cells of two human glioma cell lines enhances radiation toxicity.

Replication-deficient adenovirus (Adv5)-based vectors containing either wild-type p53 or the beta-gal marker gene were introduced into cells of the T98G (p53 mutant) and U87MG (p53 wild-type) human glioma cell lines. The wild-type p53 gene was successfully expressed in each cell line as shown by flow cytometry and Western blotting. The presence of the p53-expressing vector was toxic in both cell lines compared to control cells or to those containing the beta-gal vector. At levels of Adv5p53 vector that produced detectable toxicity, the effect of irradiation was enhanced, producing a twofold increase in cell killing. In the T98G cells, the presence of the p53 vector resulted in an increase in the number of cells undergoing apoptosis after irradiation, whereas a smaller and only additive response was observed in the U87MG cells. Conversely, an increase in micronucleus formation, indicating corrupt mitotic activity, was observed in irradiated Adv5p53-positive U87MG cells but not in T98G cells. These data suggest that p53-expressing vectors effectively enhance radiation lethality in these human glioma cell lines, but that the mechanism of action cannot be simply related to activation of the p53-dependent pathway to apoptosis.

Apoptosis↗

[Interstitial granulomatous dermatitis and paraneoplastic rheumatoid polyarthritis disclosing cancer of the lung].

INTRODUCTION: Interstitial granulomatous dermatitis is a histological entity usually associated with systemic auto-immune conditions or malignant lymphoproliferation. Its spontaneous regression after surgical treatment of a lung cancer suggests an eventual paraneoplasic variant. OBSERVATION: A 62 year old male patient, a smoker, was hospitalized for weakness, pruritus and symmetrical arthritis of small and large joints. Numerous rheumatoid nodules were located on the extensor aspects of the involved joints. During hospitalization, he developed an inflammatory plaque located on a thigh, which showed histologic features consistent with the diagnosis of interstitial granulomatous dermatitis. He had elevated E.S.R., blood eosiniphilia, and the search for antinuclear antibodies and antineutrophilic leukocyte cytoplasm antibodies (ANCA), of the p-ANCA type, was positive. A lung C.T. scan showed a cavitary tumor. Surgical removal of this tumor evidenced a bronchial squamous cell carcinoma. Four week after surgery, clinical signs and eosinophilia disappeared. After 6 months, ANCA became undetectable. DISCUSSION: Parallelism between the evolution of the cutaneous and articular symptomatology and of the cancer are diagnosis of paraneoplastic rheumatoid arthritis and paraneoplastic interstitial granulomatous dermatitis. Paraneoplastic rheumatoid arthritis is very unusual and this is the first reported case of simultaneously occurring paraneoplastic interstitial granulomatous dermatitis.

Antibodies, Antineutrophil Cytoplasmic↗

[Continuing medical education via questionnaire studies. Three pilot projects for anesthesiology, cardiology and neurology].

The Danish Medical Association and the scientific societies have initiated three studies to evaluate the use of questionnaires for continuous medical education. One study was a questionnaire in anaesthesiology with 30 questions with answers yes/no/no answer, which was sent to 600 specialists in anaesthesiology. One study was in cardiology with a multiple choice questionnaire, sent to 300 general practitioners and 75 specialists in internal medicine outside cardiology. One study concerned the educational value of State-of-the-Art articles about neurology in Ugeskrift for Laeger (Journal of the Danish Medical Association) sent to 500 doctors outside neurology. All questionnaires were sent anonymously, with one general reminder. For the anaesthesiology study 234 questionnaires were returned (40.5%). In the cardiology study 195 questionnaires were returned (52%). For the study on neurology 278 answered (56%). Only about half of the questionnaires were returned for the three studies, and a lot of effort and resources were put into the studies. An extension from these small pilot studies to a general systematic continuous methodology with updated questionnaires in the postgraduate medical education seems troublesome. An optional self-registration for medical education such as The Canadian "Mocomp concept" might be a more realistic suggestion.

Anesthesiology↗

Combinations of the alpha-helix-turn-alpha-helix motif of TetR with respective residues from LacI or 434Cro: DNA recognition, inducer binding, and urea-dependent denaturation.

We constructed 10 different variants of TetR by substituting all or some of the residues in the alpha-helix-turn-alpha-helix (HTH) operator binding motif with the respective amino acids from LacI or 434Cro. The variants were soluble, negative transdominant over tetR in vivo, and as active as wild-type TetR in tetracycline binding in vitro. The urea-induced denaturation of the 10 variants occurs in single reversible transitions, which are centered around 4.3 M urea. Denaturation is concentration-dependent, supporting a simple two-state mechanism in which the folded dimeric protein is in equilibrium with unfolded monomers. An analysis according to the two-state model yields a Gibbs free energy of stabilization (at 0 M urea, 25 degrees C) of about 75 kJ/mol, typical for dimeric proteins of this size. Even a deletion of 24 residues from the reading head decreased the stability by only 2.7 kJ/mol. These results suggest that the DNA reading head of Tet repressor is a thermodynamically independent domain and that the thermodynamic stability of the Tet repressor dimer is determined by the association of the dimerization domains of the individual monomers. Variants containing replacements in the first alpha-helix of HTH did not show any DNA binding activity whatsoever. We attribute this to the alteration of the two N-terminal residues in this alpha-helix. TetR variants were active in nonspecific DNA binding, when either all or only the solvent-exposed residues in the recognition alpha-helix of HTH were exchanged to the respective LacI sequence. Replacement of the same residues by the respective amino acids from 434Cro yielded hybrid proteins that specifically recognize tetO in vitro. Taken together, these results establish that the similarity of operator recognition between 434Cro and TetR is greater than between TetR and LacI and confirm that prediction of the recognized DNA sequence is not obvious from the sequence of the respective HTH or recognition alpha-helix.

Amino Acid Sequence↗

[Validation of the patient-administered Danish Prostate Symptom Score Schedule].

The DAN-PSS-1 system, a self-administered quality-of-life questionnaire comprising 12 questions related to voiding problems and the perceived bother of each individual symptom, was compared to other extensively used score systems and furthermore included in different clinical situations so as to validate the system. The system was internally consistent (alpha cr = 0.73), the median test-retest reliability of answers to each question was 83.5% (range 0-99.7%). A high degree of construct validity demonstrated in the correlation with the Madsen-Iversen score system (rs = 0.51) and with the patients' answers to questions about how bothersome their symptoms were (rs = 0.71). The discriminant validity of the DAN-PSS-1 was excellent with an area under the ROC curve of 0.94. Finally, the DAN-PSS-1 was sensitive to changes following intervention, with scores decreasing 100% after transurethral prostatectomy and 65% after four months of treatment with an alpha-blocker. The DAN-PSS-1 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 during follow-up.

Denmark↗

Direct sputum analysis of Pseudomonas aeruginosa macrorestriction fragment genotypes in patients with cystic fibrosis.

The distribution of bacterial populations in the airways of 13 patients with cystic fibrosis who were colonized for 6-23 years with Pseudomonas aeruginosa was investigated by genotyping of bacterial chromosomes directly isolated from 21 sputa. After removal of host material from sputum by hypotonic cell lysis and repetitive washing and centrifugation steps, agarose-embedded bacterial cells were lysed, residual eukaryotic DNA separated by field inversion gel electrophoresis, and the purified bacterial chromosomes subjected to macrorestriction fragment pattern and Southern analyses. Bacterial populations consisted of a single P. aeruginosa clone in 17 sputa, of which more than one clonal variant was apparent in two SpeI fragment fingerprints. Two clones of P. aeruginosa and another species co-existed in four samples. Genomically homogeneous populations of P. aeruginosa are characteristic for chronically colonized lungs in most cases of cystic fibrosis.

Adolescent↗

The International Continence Society "Benign Prostatic Hyperplasia" Study: international differences in lower urinary tract symptoms and related bother.

PURPOSE: We investigated the international differences in the reporting of lower urinary tract symptoms and related bother in patients with symptoms suggestive of bladder outlet obstruction. MATERIALS AND METHODS: Multiple logistic regression analysis was used to evaluate international differences in the reporting of lower urinary tract symptoms and related bother in 1,271 patients from 12 countries who participated in the International Continence Society "benign prostatic hyperplasia" study. RESULTS: Country of origin was significantly associated with the prevalence of a large number of lower urinary tract symptoms (10 of 20), even after adjusting for potentially confounding variables, including physical and socio-demographic factors. Country of origin was also significantly associated with the reporting of bother but for a much smaller number of symptoms (2). CONCLUSIONS: In different countries lower urinary tract symptoms may be reported to different extents. Therefore, the results of studies in particular countries may not be generally applicable to other countries. It is likely that symptom scores will conceal this variation, necessitating consideration of individual symptoms (as in the International Continence Society "benign prostatic hyperplasia" study) or the development of country specific scoring systems. An alternative would be to focus on bother, which appeared to be much less sensitive to international differences.

Aged↗

A randomized trial of surgical scrubbing with a brush compared to antiseptic soap alone.

BACKGROUND: The difference between use of a scrub brush versus soap alone in reducing hand bacterial counts has never been established by a prospective, comparative study. METHODS: Fifteen volunteers were taught the 5-minute surgical scrub. Baseline specimens were obtained by the glove fluid sampling procedure. Subjects were randomized to (1) scrub with an inert scrub brush and 4% chlorhexidine soap with isopropyl alcohol or (2) wash with 4% chlorhexidine soap with isopropyl alcohol alone. Specimens were obtained immediately after the scrub was completed and 45 minutes later. The experiment was repeated by use of a cross-over design after a 1-week washout period. The data were analyzed by three methods that took into account the broad range of baseline hand counts (5 x 10(1) to 11.2 x 10(4): method 1, the discordance between presence/absence of hand bacterial counts within individuals at 45 minutes for soap versus soap and brush; method 2, the absolute reduction of bacteria (baseline vs 45 min.) for soap versus soap and brush; and method 3, the proportional change in bacterial counts at 45 minutes from baseline for soap versus soap and brush. RESULTS: Although there was no statistically significant difference for any method, the point estimates for the odds ratio (OR) showed that up to twice the number of subjects had a greater reduction in bacterial counts when they washed with soap than when they scrubbed with a brush, as evidenced by the following data: method 1, OR 2.3 (95% confidence interval [CI] 0.53, 13.99) for soap alone; method 2, OR 1.0 (CI 0.23, 4.35); and method 3, OR 2.0 (CI 0.54, 9.10) for soap alone. CONCLUSIONS: The effect of use of soap alone in reducing hand bacterial counts at 45 minutes was similar to use of soap and brush. Soap can be used alone and the surgical infection rate prospectively monitored.

1-Propanol↗

A comparison of intensive neurodevelopmental therapy plus casting and a regular occupational therapy program for children with cerebral palsy.

The purpose of this research was to evaluate the combined effect of intensive neurodevelopmental therapy (NDT) and casting in improving hand function, quality of upper-extremity movement and range of motion in children aged between 18 months and 4 years with cerebral palsy (CP). A randomized crossover design was used to evaluate the difference between intensive NDT plus casting and a less intensive regular occupational therapy (OT) program. Blinded assessments of hand function, quality of upper-extremity movement, and parents' perception of hand-function performance were carried out at baseline, 4 months (end of first intervention period), 6 months (after a 2-month 'washout' period), and 10 months (end of second intervention period). Analysis of the outcomes revealed no significant differences in hand function, quality of upper-extremity movement, or parents' perception of hand-function performance between the two treatment groups-intensive NDT plus casting or regular OT programs. There does not appear to be any beneficial effect of an increased amount of therapy for the children in this study.

Activities of Daily Living↗

Development and reliability of a system to classify gross motor function in children with cerebral palsy.

To address the need for a standardized system to classify the gross motor function of children with cerebral palsy, the authors developed a five-level classification system analogous to the staging and grading systems used in medicine. Nominal group process and Delphi survey consensus methods were used to examine content validity and revise the classification system until consensus among 48 experts (physical therapists, occupational therapists, and developmental pediatricians with expertise in cerebral palsy) was achieved. Interrater reliability (kappa) was 0.55 for children less than 2 years of age and 0.75 for children 2 to 12 years of age. The classification system has application for clinical practice, research, teaching, and administration.

Activities of Daily Living↗

Epidemiology of chronic Pseudomonas aeruginosa infections in the airways of lung transplant recipients with cystic fibrosis.

BACKGROUND: The source of airway colonisation with Pseudomonas aeruginosa is not well defined in patients with cystic fibrosis after lung transplantation. Using a DNA-based typing system a study was undertaken to investigate whether lung transplant recipients acquired new strains of P aeruginosa or retained those they had before transplantation. METHODS: Seventy four P aeruginosa isolates taken before and after transplantation were analysed from 11 patients with cystic fibrosis who had undergone lung transplantation in the Medical School of Hannover between 1988 and 1994. The genetic relatedness of the 74 P aeruginosa strains was evaluated from macrorestriction fragment pattern similarity. RESULTS: Each of the 11 lung transplant recipients harboured one identical P aeruginosa clone before and after transplantation. The airways of four of the 11 patients were preoperatively colonised by two or three different clones, but six months after transplantation only one clone was detectable. CONCLUSIONS: These results show that there is no change in the P aeruginosa population in the airways of lung transplant recipients before and after transplantation and it is assumed that the chronic drainage of P aeruginosa into the lung allografts is caused by the bacterial reservoir in the paranasal sinuses and the trachea.

Adolescent↗

Concomitant chemoradiotherapy followed, where feasible, by surgery for cancer of the esophagus.

PURPOSE: To conduct a multicenter phase II study of a concomitant combination of chemotherapy and radiotherapy followed by surgery, where feasible, in patients with nonmetastatic esophageal tumor, stratified on operability at diagnosis. METHODS: Each cycle consisted of fluorouracil (5FU) 800 mg/m2/d by continuous intravenous (IV) infusion on days 1 to 5, cisplatin (CDDP) 50 mg/m2/d IV bolus on days 1 and 8, hydroxyurea (HU) 1.5 or 2 g/d orally on days 8 to 12 and concomitant radiotherapy 20 Gy in 10 fractions over 12 days. All patients were to receive two cycles on days 1 and 22. If feasible, surgery was performed 3 to 6 weeks after cycle two completion. Otherwise, a third cycle was administered. RESULTS: Eighty-eight patients were included between September 1990 and September 1993. Of the 47 operable patients, 41 (87%) underwent surgery and 38 (81%) had a complete resection. No residual primary tumor was found in the surgical specimen in 17 cases (36%), and only microscopic foci in 13 (28%). Two-year overall and disease-free survival probabilities were 51% (95% confidence interval [CI]; 37 to 65) and 43% (95% CI, 28 to 57), respectively. Among the 41 inoperable patients, 12 (29%) became operable. Seven (17%) had complete resection, two incomplete resection, and three exploratory surgery. Two-year overall and disease-free survival probabilities were 29% (95% CI, 15 to 43) and 27% (95% CI, 13 to 40), respectively. Five deaths occurred during chemoradiotherapy, six postoperatively and four in patients with evidence of cancer. Five late complications (one myelopathy) were observed. CONCLUSION: Despite a high histologic response rate in initially operable patients, overall survival was similar to that observed in other preoperative chemoradiation series because of substantial toxicity.

Aged↗