PubMed HealthSearch

Biomedical subjects

J W Winkelman

Publications and source records attributed to J W Winkelman.

At least 19 recordsLinked to original sources

Restless legs syndrome in end-stage renal disease.

The aim of this study was to evaluate the prevalence of restless legs syndrome (RLS) in patients with end-stage renal disease (ESRD), and to determine its association with sleep disorders and premature discontinuation of dialysis ("sign-offs"). End-stage renal disease patients (N = 204) and a control group of patients with heart disease (N = 129) completed a self-administered questionnaire regarding symptoms of RLS, sleep habits, pruritus, and adherence to dialysis therapy. Laboratory measures and sensory nerve amplitudes were collected on the ESRD patients. Twenty percent of the ESRD patients and 6% of the cardiac patients reported moderate to severe RLS symptomatology. Sleep onset was delayed and total sleep time was diminished in ESRD patients compared with cardiac patients. Symptoms of RLS were directly correlated with all sleep measures as well as with pruritus. Symptoms of RLS, sleep onset latency, and transferrin saturation were independently associated with premature discontinuation of dialysis. Significantly increased risk for mortality was observed in patients with RLS at the 2.5-year follow-up. Restless legs syndrome is a common finding in patients with ESRD and is associated with substantial morbidity.

Female

Prediction of fetal lung maturity in infants of diabetic mothers using the FLM S/A and disaturated phosphatidylcholine tests.

The authors evaluated the performance of the amniotic fluid surfactant to albumin ratio (FLM S/A), and disaturated phosphatidylcholine (DSPC) tests in assessing fetal lung maturity in infants of mothers with insulin-dependent diabetes mellitus antedating pregnancy. The distribution of the study population (n = 180) by class of diabetes was class B (27%); class C (28%); class D (29%); class F, FR and T (8%); and class R patients (8%). The diagnosis of respiratory distress syndrome (RDS) was the standard for evaluating the performance of FLM S/A and DSPC. The mean estimated gestational age was 37.4 weeks. Three infants (1.7%) were diagnosed with RDS. All three were delivered before 36 weeks. FLM S/A at the cut-off for "maturity" of > or = 70 mg/g, had a sensitivity of 66.6%, specificity of 94.9%, positive predictive value (PPV) of 18.2%, and negative predictive value (NPV) of 99.4%. DSPC at the cut-off for "maturity" of 1,000 micrograms/dL, had identical sensitivity and NPV, but lower specificity (89.2%) and PPV (9.5%) than FLM S/A. Both tests mispredicted maturity in the same case of RDS. The false "mature" rate of FLM S/A was 0.6% (95% confidence interval 0.0%-3.2%). The FLM S/A result of > or = 70 mg/g, obtained at or near-term, is a reliable predictor of the absence of RDS in infants of mothers with diabetes mellitus antedating pregnancy.

Albumins

An electromyographic marker for neuroleptic-induced akathisia: preliminary measures of sensitivity and specificity.

Previous polysomnographic (PSG) investigations have reported a rhythmic electromyographic (EMG) pattern (0.5-3.0 cps) of leg movement activity in a subset of patients with neuroleptic-induced akathisia (NIA). It has been suggested that this EMG pattern may represent a pathophysiological correlate of NIA and thus have clinical utility as an objective marker for this condition. We present preliminary measures of sensitivity and specificity for this EMG pattern as a diagnostic marker for NIA for 26 neuroleptic-treated patients. The EMG marker yielded a diagnostic sensitivity of 68.9% and a specificity of 70.0%, falling just short of statistical significance (Fisher's exact test p = 0.06). Quantitative analysis of the EMG pattern revealed a significant positive correlation between the percentage of time the NIA marker occurred during wakefulness and corresponding chlorpromazine equivalent levels. Clinical demographic findings for true-positive, false-positive, true-negative, and false-negative groups are discussed. Overall findings suggest that this particular pattern of EMG marker activity observed in neuroleptic-treated patients during PSG and EMG studies is valuable in facilitating the diagnosis and monitoring treatment.

Adolescent

Screening for clinical laboratory errors with Medicare claims data: results for digoxin.

A statistical model is demonstrated for finding outpatient clinical laboratories having high frequencies of bad patient outcomes, after testing, that may indicate testing errors. A sample of Medicare Part A and Part B claims for 30,685 digoxin tests for 1985 through 1987 was analyzed. Deaths or digoxin-related hospitalizations within 14 days of digoxin testing are defined as "adverse events" potentially influenced by test information. Approximately 3.3% of digoxin tests were followed by adverse events with two-thirds resulting in hospitalization or death. Adverse events were (a) lower in states with stronger laboratory regulations, (b) 15% higher whenever the site of testing switched, (c) unrelated to testing in low volume physician office laboratories, and (d) unrelated to frequency of digoxin testing in previous 6 months. Results a and b are consistent with findings for prothrombin testing but c and d are not. Differences are consistent with technical characteristics of the tests.

Anti-Arrhythmia Agents

Effects of passive body heating on the sleep of older female insomniacs.

The purpose of this study was to evaluate passive body heating (PBH) as a treatment for insomnia in older adults. Polysomnographic recordings of older adults routinely show an increase in sleep fragmentation and a substantial decrease in slow-wave sleep (SWS) consistent with complaints of "lighter" more disturbed sleep. An increase in body temperature in young adults early in the evening by way of PBH has been shown to produce an increase in SWS in the early part of the sleep period. In a crossover design, nine female insomniacs (aged 60-72 yr) participated in two consecutive nights of PBH, involving hot (40-40.5 degrees C) and luke-warm (37.5-38.5 degrees C) baths 1.5 hours before bedtime. Significant improvement in sleep continuity and a trend toward an increase in SWS occurred after hot baths. Results of subjective measures showed that subjects experienced significantly "deeper" and more restful sleep after hot baths. In addition, hot baths resulted in a significant delay of temperature nadir in comparison to baseline nights.

Adult

Total serum calcium reference intervals in postmenopausal outpatients.

The distribution of values of serum calcium has been studied in the following four outpatient populations: premenopausal (n = 411) and postmenopausal women (n = 399), men less than 50 years old (n = 365) and men over 55 years old (n = 361). Their respective average total serum calcium values (mg/dl) were 9.42, 9.56, 9.53, and 9.45. The reference intervals derived for total serum calcium (mg/dl) were 8.4-10.3 (premenopausal women), 8.4-10.7 (postmenopausal women), 8.6-10.5 (men less than 50 years old), and 8.4-10.4 (men over 55 years old). Increased total serum calcium levels were observed in the postmenopausal women as compared with both premenopausal women (p < 0.001) and with men over 55 years old (p < 0.003). Eight percent of the values obtained in postmenopausal women were above the current reference interval, as compared to 1.7% in premenopausal women, and 3.3% in men over 55 years old. In conclusion, the age-related increase in total serum calcium in postmenopausal female outpatients warrants a higher upper limit of the reference interval for this subpopulation.

Calcium

Evolution beyond the shared services model of consolidated hospital clinical laboratories.

OBJECTIVE: To compare the operational and financial outcomes of the transition from shared laboratory services to a recentralized model, in a consolidated hospital system. SETTING: United Health Services Hospitals (Binghamton General, Wilson Memorial, and Ideal hospitals, New York State). INTERVENTION: Consolidation of hospital services and recentralization of laboratory testing to a single site (Wilson Memorial Hospital). MAIN OUTCOME MEASURES: Laboratory workload, testing efficiency, personnel and nonpersonnel expenses, analytic error rate, turnaround time, and proficiency-testing scores. RESULTS: The postintervention period (1988 to 1992) was characterized by a 51% and a 10% increase in the out- and inpatient workloads, respectively, with a concomitant 24% increase in testing efficiency. The salary expenses were 26% lower, while the total true cost savings ranged from $1,544,000 (11.6%) to $2,500,000 (21.9%) compared with the shared services model. The recentralization produced decreased analytic error rates and improved testing turnaround time. CONCLUSIONS: The total costs per test have been lowered in the recentralized model. Recentralization may provide further true cost savings over the shared services model while maintaining high-quality service.

Cost Control

Management training for pathology residents. I. Results of a national survey.

The professional activities of anatomic and clinical pathologists involve, to a large extent, management issues. To evaluate the management training received by pathology residents, the authors surveyed pathology residency training programs in the United States. Responses were collected from 138 of 187 programs (73.8% response rate). Of the 138 programs, 61 reported that they had a formal training program in management, with an average of 26.8 +/- 4.9 (standard error) hours/year devoted to this discipline. Directors of 64.5% of the programs felt that management training should be expanded. Lectures were used in 61% of the programs, some in combination with case studies. Elements of training in fiscal management were present in 52.8% of the programs, and the presence of fiscal management training was associated significantly with a greater number of hours spent in management training (P < .001). Training in traditional laboratory management and quality control was included in 91.5% of the programs. The principles of total quality management were discussed in only 31.7% of the programs, but 80.6% of the programs encouraged residents' participation in departmental or institutional total quality management activities. These data indicate that there are major differences in the quality of and emphasis on management training for pathology residents in the United States.

Administrative Personnel

Management training for pathology residents. II. Experience with a focused curriculum.

Data collected from a survey of pathology training programs in the United States indicate that fewer than 50% of the programs provide a formal training experience in management. Pathologists face the challenge of effectively managing increasingly complex laboratory operations in a rapidly changing regulatory and reimbursement environment. The authors describe the outline of a management training program that emphasizes general management theory and practice and focuses strongly on the following: legal and regulatory requirements, fiscal and operational matters, and human resources functions. The curriculum includes lectures and participative experiences that are integrated into the residents' rotations through each section of the clinical laboratories.

Administrative Personnel

Quantification of medical and operational factors determining central versus satellite laboratory testing of blood gases.

Blood gas measurements performed at the central laboratory and at a satellite laboratory of Brigham and Women's Hospital were studied to determine the differences in quality, turnaround time (TAT), and cost. The quality in both laboratories, as determined by results on proficiency and quality control samples, satisfactorily met current standards for patient care. The central laboratory receives specimens for blood gas measurements through a pneumatic tube system and broadcasts results to computer terminals at the originating site, with a mean TAT of 6 minutes. The satellite laboratory, which is within the neonatal intensive care unit that it serves, has a mean TAT of 4.5 minutes. The difference is attributable to transit time in the pneumatic tube and accessioning time in the central laboratory. The total cost per reportable result was substantially higher for the satellite laboratory than for the central laboratory. The minor difference in TAT can be considered in a cost-benefit analysis that weighs medical utility criteria against cost.

Blood Gas Analysis

A predictive model for fetal lung maturity employing gestational age and test results.

Most laboratory tests for fetal lung maturity (FLM) are optimized to exclude false-negative predictions of absence of respiratory distress syndrome (RDS), with a reciprocal low predictive value for maturity. The authors employed FLM Surfactant/Albumin Ratio (FLM S/A) test results to construct a predictive model for FLM that included the obstetric estimates of gestational age. The charts of 388 newborns were abstracted and reviewed. The clinical outcome was the gold standard of the multivariate logistic analysis. Both the obstetric estimates of gestational age and the test result were significant predictors of the clinical outcome (P values of < .0002 and .001, respectively). The prediction rule for RDS as a function of both of these variables allows for adjustment of the test cutoffs, so that there is a consistent probability of RDS at the cutoff FLM S/A result for different gestational ages. Fetal lung maturity probability reporting may facilitate clinical decision-making.

Albumins

Molecular genetic analysis of a prokaryotic transcriptional coactivator: functional domains of the bacteriophage T4 gene 33 protein.

The bacteriophage T4 gene 33 encodes a small, acidic RNA polymerase-binding protein that mediates enhancement of transcriptional initiation at T4 late promoters by the T4 DNA replication accessory proteins. A set of nested deletions in the gene 33 open reading frame was constructed by oligonucleotide site-directed mutagenesis. The resulting variant gene 33 proteins were radiolabeled during overexpression employing a T7 RNA polymerase-based system and substantially purified. Each variant was analyzed for three properties of gp33: RNA polymerase binding activity, ability to mediate enhancer-dependent transcriptional activation, and repression of unenhanced transcription. Two separate regions of gp33 were required to form stable complexes with RNA polymerase, whereas the extreme carboxyl terminus of gp33 was essential for mediating late gene activation. Variant gene 33 proteins lacking the carboxyl terminus nevertheless repressed nonenhanced transcription, demonstrating that the functional domains required for transcriptional activation and repression of unenhanced transcription are separable. The possible roles of gp33 in mediating late gene expression are discussed in the light of the identification of these functional domains.

Bacteriophage T4

The fiscal consequences of central vs distributed testing of glucose.

We have compared the operational, medical, and fiscal consequences of performing urgent glucose testing at the bedside vs in the central laboratory. The turnaround time (TAT) with bedside testing was only 1-2 min shorter than that from the central laboratory, to which specimens are sent by pneumatic tube and from which results are automatically broadcast by computer to the originating site. No significant adverse medical outcomes were associated with this difference in TAT. The cost of bedside testing is approximately twice that of central laboratory testing.

Blood Glucose

Searching for inaccuracy in clinical laboratory testing using Medicare data. Evidence for prothrombin time.

OBJECTIVE: To determine if the occurrence of health outcomes following clinical laboratory testing can be used to identify types of laboratories that may be having higher than expected error rates. DESIGN: Retrospective analysis of Medicare Part B outpatient claims, Part A hospitalization bills, and death records using a case-control study. SETTING: Medicare records from six carrier territories were sampled during the period 1985 through 1987. PATIENTS: A total of 14,755 Medicare patients receiving a prothrombin time test in either a physician office laboratory or a commercial laboratory. OUTCOME MEASURES: Occurrence of a hospitalization for stroke or acute myocardial infarction, death, or no adverse outcome within 6 days of a prothrombin time. RESULTS: In physician office laboratories where prothrombin time test volume is below 40 per month, the odds that a tested patient will experience a stroke or an acute myocardial infarction are up to 1.96 and 3.43 times greater, respectively, than for a similar patient tested in a commercial laboratory. Switching from one laboratory to another between successive prothrombin time tests increased the odds of a stroke or an acute myocardial infarction by 1.57 and 1.32, respectively. Patients in two states with strong laboratory regulatory programs had fewer adverse outcomes. CONCLUSION: Examining patient outcomes subsequent to clinical laboratory testing may be a useful tool for clinical laboratory quality assurance.

Case-Control Studies

Stereochemical factors in the transport and binding of photosensitizers in biological systems and in photodynamic therapy.

The uptake and biological activity of porphyrins and phthalocyanines in tumours were correlated with the geometrical features of the photosensitizer molecules. The data suggest that a critical distance of approximately 1.2 nm between oxygen atoms (originating in SO3-, COO- or OH substituents) characterizes a biologically active photosensitizer for photodynamic therapy. We propose that tubulin, which is available in large amounts during mitosis, is the main receptor molecule which binds these photosensitizers. Basic amino acid residues or tightly bound cations in tubulin or homologous proteins may act as binding sites on the receptor molecule.

Animals

DNA topology-mediated regulation of transcription initiation from the tandem promoters of the ilvGMEDA operon of Escherichia coli.

It is becoming increasingly clear that the intrinsic and protein-induced topological properties of the DNA helix influence transcriptional efficiency. In this report we describe the properties of two upstream activating regions that influence transcription from the non-overlapping tandem promoters of the ilvGMEDA operon of Escherichia coli. One 20 base-pair region between the promoter sites contains an intrinsic DNA bend that activates transcription from the downstream promoter. The other region contains an integration host factor (IHF) binding site that overlaps the upstream promoter site. IHF binding at this site represses transcription from the upstream promoter and enhances transcription from the downstream promoter. IHF also induces a severe bend in the DNA at its target binding site in the upstream promoter region. The activating property of the 20 base-pair DNA sequence located between the promoters is dependent upon the helical phasing of the sequence-directed DNA bend that it encodes. However, the IHF-mediated activation of transcription is not dependent upon the helical phasing (spatial orientation) of the upstream IHF and downstream promoter sites. The IHF-mediated activation of transcription is also uninfluenced by the presence or absence of the intrinsic DNA bend between its binding site and the downstream promoter site. These results suggest the interesting possibility that IHF activates transcription from the nearby downstream promoter simply by bending the DNA helix in the absence of specific IHF-RNA polymerase or upstream DNA-RNA polymerase interactions.

Bacterial Proteins

Synergistic effects of photoactivated tetra(4-sulfonatophenyl)porphine and nocodazole on microtubule assembly, accumulation of cells in mitosis and cell survival.

Human carcinoma cells of the line NHIK 3025 were incubated with meso-tetra(4-sulfonatophenyl)porphine (TPPS4) for 18 h and exposed to light in the absence or presence of nocodazole. Nocodazole (1 microgram ml-1) was applied to the cells 15 min prior to light exposure and washed off the cells immediately afterwards. The presence of nocodazole during photoactivation of TPPS4-loaded cells leads to a significantly reduced ability of tubulin to repolymerize after withdrawal of nocodazole, an increased accumulation of the cells in mitosis with a larger fraction in c-metaphase and a higher yield of photoactivated cells. A higher proportion of the cells accumulating in mitosis 6-12 h after exposure to light is unable to form colonies when exposed to light in the presence of nocodazole than in its absence. The present results are consistent with a specific TPPS4-induced photodamage to the unpolymerized form of the microtubule components.

Carcinoma in Situ

Downstream outcomes: using insurance claims data to screen for errors in clinical laboratory testing.

A methodology is described by which health insurance claims data might be used to discover the occurrence of systematic errors by clinical laboratories. False-positive results should generate a series of tests or treatments that are eventually abandoned as the false signal of the initial test is discovered while false-negative results may cause necessary tests or treatments to be unduly delayed. False results may also generate adverse outcomes such as an unusually high number of deaths or hospitalizations among persons who have received particular laboratory tests. Health insurance claims data may be used to discover these patterns and how the inclusion of laboratory results on claims would improve the precision of such inferences. Appropriate statistical tests are discussed.

Centers for Medicare and Medicaid Services, U.S.