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PubMed2000

Reciprocal social behavior in children with and without pervasive developmental disorders.

An invariant feature of pervasive developmental disorders (PDDs) is a relative deficit in the capacity for reciprocal social behavior (RSB). The authors acquired teacher reports of RSB in 287 schoolchildren and parent reports of RSB in 158 child psychiatric patients using a new research instrument, the Social Reciprocity Scale. Total scores on this measure of RSB were continuously distributed in all groups of subjects; children with PDDs scored significantly higher for the degree of deficits in RSB than did clinical or nonclinical controls. Latent class analysis and factor analysis failed to demonstrate separate categories of deficiency for core autistic symptomatology and more general impairments in RSB, consistent with the notion of a "broader autism phenotype." Assessments of RSB on a continuous scale may be useful clinically for characterizing the behavior of children whose social deficits fall below the threshold for a full diagnosis of autism. They may also be useful in genetic-linkage studies of autistic spectrum disorders.

Adolescent↗
PubMed1989

Type 3 fimbriae among enterobacteria and the ability of spermidine to inhibit MR/K hemagglutination.

The distribution of the gene cluster encoding type 3 fimbriae among various isolates of the family Enterobacteriaceae was investigated by using 112 clinical and nonclinical isolates. Closely related DNA sequences were detected in all Klebsiella strains, in most Enterobacter isolates, in a smaller number of Escherichia coli and Salmonella spp., and in a single isolate each of Yersinia enterocolitica and Serratia liquefaciens but not in isolates of Morganella or Providencia species or Serratia marcescens. Except for E. coli and Salmonella strains, the presence of gene sequences was correlated with the phenotypic expression of either the MR/K hemagglutinin or fimbriae that reacted with specific antibodies. In one isolate of Y. enterocolitica the expression of type 3 fimbriae was plasmid determined. The polyamine spermidine was identified as an inhibitor of MR/K hemagglutinating activity, exhibiting an MIC of 1.2 mM. Spermidine inhibited the hemagglutination of 37 MR/K-positive clinical isolates from various genera. However, one clinical isolate of Enterobacter cloacae and most (four of five) nonclinical Klebsiella isolates were not completely inhibited.

Antibodies, Monoclonal↗
PubMed2004

Too many, too few, too concentrated? A review of the pediatric subspecialty workforce literature.

OBJECTIVES: To summarize recent pediatric subspecialty workforce analyses and to highlight similarities and differences across studies. DESIGN: By using MEDLINE, we conducted a systematic search of the literature published from January 1, 1992, through December 31, 2002. We included research articles and task force reports, and abstracted author, year of publication, specialty, sample size, analytic perspective (eg, physician or academic department), inclusion of data on nonclinical activities, inclusion of an objective measure of demand, and workforce-related conclusions. RESULTS: We identified 41 relevant articles. Physician surveys provided data for most (n = 24) of these studies. Only 8 studies attempted to make future workforce projections; of these 8 studies, 1 explicitly accounted for nonclinical activities in its projections. An additional 16 studies presented data on involvement in nonclinical activities. While some studies suggest that additional pediatric subspecialists are not needed, these studies did not include objective assessments of demand in geographic areas where pediatric subspecialty physicians are not available. Of those studies that took a market perspective and attempted to account for demand, workforce recommendations varied considerably across specialties. CONCLUSIONS: We know little about the distribution of the pediatric subspecialty workforce relative to the demand for their services. Given concerns about the adequacy of the pediatric subspecialty workforce, future research should assess the availability of these physicians relative to need for their services and account for nonclinical activities in workforce projections.

Education, Medical↗
PubMed1996

Bacteriocin typing of Klebsiella spp. isolated from different sources.

To evaluate whether clinical Klebsiella isolates differ from nonclinical strains with respect to bacteriocin susceptibility patterns, a total of 452 Klebsiella pneumoniae and K. oxytoca strains isolated from different sources were examined. Bacteriocin typing was done by a modification of the scrape-and-point method, using a set of eight producer strains. 96% of the strains were typable. Forty-one different bacteriocin susceptibility patterns were observed. While two thirds of the K. oxytoca isolates belonged to only three different bacteriocin types, the K. pneumoniae strains showed a more heterogeneous distribution of patterns. No differences in pattern distribution were observed between isolates from clinical, fecal, or environmental sources. Certain bacteriocins showed a very broad spectrum of activity; e.g. 93% of all isolates were susceptible to bacteriocin type 3. The results suggest that nonclinical Klebsiella strains do not show other bacteriocin susceptibility types than clinical isolates do.

Bacteriocins↗
PubMed2001

Relative distribution and conservation of genes encoding aminoglycoside-modifying enzymes in Salmonella enterica serotype typhimurium phage type DT104.

PCR was used to identify genes encoding aminoglycoside-modifying enzymes in 422 veterinary isolates of Salmonella enterica serotype Typhimurium. The identities of extra-integron genes encoding resistance to streptomycin, gentamicin, kanamycin, and apramycin were evaluated. Gentamicin resistance was conferred by the aadB gene. Kanamycin resistance was encoded by either the aphA1-Iab gene or the Kn gene. Apramycin resistance was determined by the aacC4 gene. Analysis of gene distribution did not reveal significant differences with regard to phage type, host species, or region except for the Kn gene, which was found mostly in nonclinical isolates. The data from this study indicate that pentaresistant DT104 does not acquire extra-integron genes in species- or geography-related foci, which supports the hypothesis that clonal expansion is the method of spread of this organism.

Acetyltransferases↗
PubMed2001

BRCA1 germline mutations and polymorphisms in a clinic-based series of ovarian cancer cases: a Gynecologic Oncology Group study.

OBJECTIVE: The aims of this study were to determine the frequency of BRCA1 gene alterations in an unselected, clinic-based series of ovarian cancer cases; to evaluate the usefulness of family history in predicting the likelihood of a disease-causing mutation; and to document the occurrence of polymorphic variants in BRCA1 and to determine their distribution among families accordingly to history of breast and/or ovarian cancer. METHOD: Two hundred fifty-eight women with primary epithelial ovarian cancer, entered onto a nonclinical protocol of the Gynecologic Oncology Group, were analyzed for BRCA1 germline alterations by single-strand conformation polymorphism analysis. RESULTS: Protein-truncating mutations in BRCA1 were identified in 12 patients (4.6%). The median age of cancer diagnosis in BRCA1 mutation carriers was 47 years compared to 57 years in patients without mutations (P = 0.02). All but 1 of the patients with BRCA1 mutations reported a family history of breast and/or ovarian cancer and 8 had a first-degree relative with cancer. Twelve mutations of unknown significance were also identified. An association was also noted between the presence of common polymorphisms in BRCA1 and family history of cancer. Polymorphisms were present at higher frequency among women without a family history of cancer compared to women with positive family histories, suggesting they are associated with reduced risk. CONCLUSION: In a clinic-based series of ovarian cancer patients, germline BRCA1 mutations were detected in 12 of 258 (4.6%) patients. A strong correlation was noted between the presence of mutations and family history of breast and/or ovarian cancer, indicating that these women are most likely to benefit from genetic susceptibility testing.

Adult↗
PubMed2006

Novel probabilistic method for precisely correcting the QT interval for heart rate in telemetered dogs and cynomolgus monkeys.

INTRODUCTION: QT intervals are not regulated on a beat-to-beat cadence, but are strongly influenced by the preceding heart rate history (hysteresis). ECG sampling, when performed over sufficiently long periods, results in the detection of ranges of different QT values for each discrete RR interval. Given the potential impact of QT hysteresis in QT interval rate-correction procedures, we hypothesized that, physiologically, the QT interval exists as a probabilistic variable where the exact value corresponding to any RR interval is precisely estimated from the associated QT population. METHODS: Digital ECGs were collected for 18-21 h in telemetered dogs (n=7) and cynomolgus monkeys (n=7) employing epicardial ECG leads for accurate T(end) detection, and analyzed by computerized algorithms. Descriptive statistics were calculated for raw QT values in 10 ms RR increments. Individual rate-corrected QT (QTc) formulae were derived from the slopes of log-transformed QT-RR data where each QT point was the mean of >250 beats/RR increment. The aptness of this QTc model was assessed by residual analysis. RESULTS: Beat-to-beat ECG analysis demonstrated that for all discrete cycle lengths, the associated raw QT intervals were normally distributed populations, spanning approximately 30-40 and 45-100 ms in the dog and cynomolgus monkey, respectively. In both species, QTc was stable (< or =5 ms variation) over all physiological RR intervals. DISCUSSION: The probabilistic treatment of raw QT interval populations natively associated to any RR interval provides hysteresis-free raw QT estimates which can be accurately modeled, allowing the derivation of a precise QTc value. Previous unawareness of the probabilistic nature of the QT interval explains the historical failure of numerous QT rate-correction formulae to correctly solve this scientific issue. Importantly, QT distribution analysis has the potential to provide, for the first time, a universal and sensitive method for QT heart rate-correction, providing a robust method for nonclinical and clinical cardiac safety investigations of repolarization delay.

Algorithms↗
PubMed2005

Assessment of pharmacokinetic-pharmacodynamic target attainment of gemifloxacin against Streptococcus pneumoniae.

The treatment of community-acquired respiratory tract infections has been complicated by the emergence of multidrug-resistant Streptococcus pneumoniae. Although traditionally rare, a growing concern for fluoroquinolone-resistant pneumococci has surfaced. More pharmacodynamically potent antimicrobial agents are clearly needed, as the use of such agents may further optimize clinical and microbiological outcomes for patients and slow the emergence of fluoroquinolone resistance. For fluoroquinolones, the ratio of the 24-h area under the concentration-time curve of the agent to the minimum inhibitory concentration of the agent against the pathogen for the fraction of unbound drug is the major pharmacokinetic-pharmacodynamic (PK-PD) measure correlating with efficacy in nonclinical models and infected patients. A 2500-patient Monte Carlo simulation, utilizing a patient-population pharmacokinetic model derived from phase 3 registration trials and the minimum inhibitory concentration distribution for gemifloxacin against 3117 clinical strains of S. pneumoniae, was carried out to estimate the probability of gemifloxacin attaining exposures associated with efficacy. The overall probability PK-PD target attainment for gemifloxacin was greater than 0.99. Gemifloxacin is among the most pharmacodynamically potent fluoroquinolones and is more potent than ciprofloxacin, ofloxacin, and levofloxacin. Preferential use of pharmacodynamically potent agents over other alternatives may lead to improved clinical outcomes and decreased selection of fluoroquinolone-resistant pneumococci.

Anti-Bacterial Agents↗
PubMed2002

Serotype and phage type distribution of salmonella strains isolated from humans, cattle, pigs, and chickens in the Netherlands from 1984 to 2001.

We studied serotypes and phage types of Salmonella strains isolated from humans and animals in The Netherlands over the period 1984 to 2001. All human strains (n = 59,168) were clinical isolates. The animal strains (n = 65,567) were from clinical and nonclinical infections. All isolates were serotyped, and Salmonella enterica serovar Typhimurium and serovar Enteritidis strains were further phage typed. The most prevalent serotypes were as follows: in humans, serovars Typhimurium and Enteritidis; in cattle, serovars Typhimurium and Dublin; in pigs, serovar Typhimurium; and in chickens, serovars Enteritidis, Infantis, and Typhimurium. Serovar Enteritidis phage type 4 (pt 4) was the most common phage type in humans and chickens. Serovar Typhimurium pt 510 was the most prevalent serovar Typhimurium phage type in humans and pigs, pt 200 was the most prevalent serovar Typhimurium phage type in cattle, and pt 150 was the most prevalent serovar Typhimurium phage type in chickens. Analysis of the distribution of sero- and phage types during the study period indicated that types shifted over time in humans and animals. Serovar Typhimurium DT 104 emerged in 1991 in humans, cattle, pigs, and chickens and became the most common serovar Typhimurium phage type in 2001. In general, similar sero- and phage types were found in humans and animals, although distinct types were more common in animals. Between the animal species, the sero- and phage type distributions varied considerably.

Animals↗
PubMed1994

Racial differences in the use of total knee arthroplasty for osteoarthritis among older Americans.

The purpose of this study was to determine differences in the use of total knee arthroplasty for osteoarthritis among black and white older Americans and to determine whether clinical and economic factors contribute to these differences. Data on black and white Americans aged 65 years and older were gleaned from national Medicare hospitalization records for 1980 through 1988 and the Medicare enrollment file for 1987, the First National Health and Nutrition Examination Survey of 1971 through 1975, the National Hospital Discharge Survey of 1979 through 1988, the 1980 through 1988 US census counts and estimates, and 1980 census economic data. Information gathered includes prevalence of osteoarthritis of the knee among blacks and whites; rate of total knee arthroplasty use in the United States by race, sex, and age of subjects at the time of operations; use of competing procedures; and economic factors. Results showed that blacks were less often treated with total knee arthroplasty than were whites (white-to-black rate ratios = 3.0 to 5.1 for men and 1.5 to 2.0 for women) but had nonsignificantly higher rates of clinical osteoarthritis of the knee (white-to-black rate ratios = 0.39 for men and 0.78 for women). This racial difference in total knee arthroplasty rates was consistent across income levels and was unexplained by black patients' having operations at earlier ages or using competing procedures. Furthermore, the discrepancy occurred even among Medicaid-eligible Medicare recipients, who had no direct economic disincentive for surgery. These findings suggest that even though elderly blacks have higher rates of knee osteoarthritis, they do not receive total knee arthroplasty as often as do elderly whites. This discrepancy does not appear to have an economic explanation. Even if a comprehensive care system were in place to remove economic barriers, inequality in the use of this procedure would likely persist. Future studies should assess the nonclinical and noneconomic causes of these differences.

Black or African American↗
PubMed1997

Alexithymia: a right hemisphere dysfunction specific to recognition of certain facial expressions?

The most prominent features of alexithymic people are a demonstrated reduction in the ability to identify and to describe their own feelings. In recent years, these characteristics have been related to a functional disturbance of the right cerebral hemisphere. This should result in a number of other observable effects. The present study investigated whether high and low alexithymics from a nonclinical population differed in the degree of leftward perceptual bias on chimeric tasks. The chimeras consisted of pictures of faces made of up conjoined emotive and nonemotive halves as well as asymmetrically distributed stars. Differences between high and low alexithymics in the recognition of facial expressions of emotion of whole faces were also examined. High scorers on a test of alexithymia showed overall less leftward perceptual bias than low scores on the chimeric tasks and poorer recognition of facial expressions of whole faces. There was little evidence that the reduced left bias was specific to processing of emotional expressions only, or that differences in processing of facial expressions were emotion specific. These results are argued to support the right hemisphere dysfunction model of alexithymia.

Adult↗
PubMed1998

Twenty-year trends in the Ohio generalist physician workforce.

BACKGROUND: Many factors contribute to the variations seen in physician workforce projections, including assumptions about attrition, new physician entry, and geographic requirements. Our study offers data for bench-marking future research into this complex issue. METHOD: At 5-year intervals starting in 1975, data were collected for each Ohio county by local physician census takers. RESULTS: Total Ohio family physician rates per population did not increase appreciably during the 20-year period. A decrease in the number of allopathic family physicians was balanced by an increase in the number of osteopathic family physicians, many of whom were graduates of the state's first osteopathic medical school, which graduated its first class in 1980. Rates of general internists and general pediatricians increased. In 1975, the percentage of physicians older than 59 years was higher for family physicians than for general internists and general pediatricians. By 1995, this disparity in age distribution had greatly decreased. Rural family physician rates per 100,000 population decreased, and urban rates increased, while both urban and rural rates increased for general internists and general pediatricians. CONCLUSIONS: Variations in accounting for clinical time used for non-generalist clinical and nonclinical activities may explain a large part of the difference between generalist head count and full-time equivalency (FTE) study results; together these activities can be said to make up a "fourth compartment" contributing to improper specialty designation. The decrease in the percentage of family physicians older than 59 years indicates that the future supply of practicing family physicians is not in jeopardy. The rural family physician workforce is decreasing, while the general internist and general pediatrician rural workforce is increasing, but the total rural workforce is still well below the urban workforce. Neither component of the rural workforce appears to have stabilized.

Adult↗
PubMed2000

[Pharmacokinetics and tissue distribution of azithromycin in humans].

Azithromycin(AZM) is a new macrolides antibiotic developed by Pfizer Inc. of the US. It has a 15-membered ring structure obtainable by introducing methyl-substituted nitrogen into a 14-membered ring lactone of erythromycin(EM). An effective drug concentration is sustained long owning to its superiority in tissue distribution and long half life(T1/2). AZM is also demonstrated to be twice to three times more powerful than the existing macrolides owning to its reinforced antimicrobial activity against Gram-negative microorganisms including influenza virus. AZM is already used in clinical practice in foreign countries and its excellent clinical performance has been demonstrated by the data. As for the domestic basic and clinical studies of AZM, Phase I study was initiated in 1991 following completion of nonclinical studies, and general clinical studies, a dose-setting study and Phase III controlled studies were conducted between 1992 and 1994. Usefulness of AZM is substantiated by the data from those studies.

Anti-Bacterial Agents↗
PubMed2003

Methods of measuring asthma severity and influence on patient assignment.

BACKGROUND: There is a need for nonclinical measures in studies where objective clinical data used to determine asthma severity, such as spirometry and peak expiratory flow rate meter readings, are not available. OBJECTIVE: To determine whether different methods of defining asthma severity provide different distributions of patients across the categories of mild, moderate, and severe asthma. METHODS: Data were obtained from a mail survey and the database of a managed care organization located in Michigan. Seven methods of asthma severity that used either patient self-report or claims data were evaluated and divided into 3 categories: patient-perceived severity (1 method), symptom-derived severity (4 methods), and medication-derived severity (2 methods). To further evaluate the extent of the degree of agreement among the 7 severity methods, percent agreement and Cohen K scores were calculated. RESULTS: Surveys were sent to 1,139 persons, and 603 responses were usable. Substantial differences exist in the number of patients in each severity level for different methods of determining asthma severity. The proportion of persons identified as having mild, moderate, and severe asthma ranged from 48% to 82%, 16% to 38%, and 2% to 33%, respectively. The percent agreement and Cohen kappa scores were generally low among the 7 methods. CONCLUSIONS: Due to variations caused by the method of measuring asthma severity, comparability among studies using different methods of classifying asthma severity is limited. Although a uniform evaluation of asthma severity is needed, the results of this study do not identify one preferable method. Rather, investigators should know the limitations of the methods used.

Adolescent↗
PubMed1997

The relationship of distress to mood disturbance in primary care and psychiatric populations.

Disagreement remains as how to interpret elevated scores on measures of self-reported distress. This study compared elevated scores on the Center for Epidemiologic Studies-Depression Scale (CES-D) in 2 samples to mood disturbance as assessed in an interview. In a primary medical care sample, most distressed patients did not have a mood disturbance, and distress without mood disturbance was associated with little impairment. Primary care patients with elevated scores on the CES-D were less distressed and less likely to have mood disturbance, major depression, or impairment than distressed psychiatric patients. Few patients with mood disturbance in either sample failed to meet criteria for major depression. Implications are discussed for research on depression using self-report measures, for generalizations across clinical and nonclinical populations, and for screening for preventive interventions.

Adolescent↗
PubMed2005

A semiparametric two-component "compound" mixture model and its application to estimating malaria attributable fractions.

Malaria remains a major epidemiologic problem in many developing countries. Malaria is defined as the presence of parasites and symptoms (usually fever) due to the parasites. In endemic areas, an individual may have symptoms attributable either to malaria or to other causes. From a clinical viewpoint, it is important to correctly diagnose an individual who has developed symptoms so that the appropriate treatments can be given. From an epidemiologic and economic viewpoint, it is important to determine the proportion of malaria-affected cases in individuals who have symptoms so that policies on intervention program can be developed. Once symptoms have developed in an individual, the diagnosis of malaria can be based on the analysis of the parasite levels in blood samples. However, even a blood test is not conclusive as in endemic areas many healthy individuals can have parasites in their blood slides. Therefore, data from this type of study can be viewed as coming from a mixture distribution, with the components corresponding to malaria and non-malaria cases. A unique feature in this type of data, however, is the fact that a proportion of the non-malaria cases have zero parasite levels. Therefore, one of the component distributions is itself a mixture distribution. In this article, we propose a semiparametric likelihood approach for estimating the proportion of clinical malaria using parasite-level data from a group of individuals with symptoms. Our approach assumes the density ratio for the parasite levels in clinical malaria and nonclinical malaria cases can be modeled using a logistic model. We use empirical likelihood to combine the zero and nonzero data. The maximum semiparametric likelihood estimate is more efficient than existing nonparametric estimates using only the frequencies of zero and nonzero data. On the other hand, it is more robust than a fully parametric maximum likelihood estimate that assumes a parametric model for the nonzero data. Simulation results show that the performance of the proposed method is satisfactory. The proposed method is used to analyze data from a malaria survey carried out in Tanzania.

Animals↗
PubMed2001

U.S. nephrologists' attitudes towards renal transplantation: results from a national survey.

BACKGROUND: Renal transplantation is the optimal treatment for persons with end-stage renal disease (ESRD). A shortage of kidneys in the U.S. has focused increasing attention on the process by which kidneys are allocated. A national survey was undertaken to determine the relative importance of both clinical and nonclinical factors in the recommendation for renal transplantation by U.S. nephrologists. METHODS: We conducted a national random survey of 271 U.S. nephrologists using hypothetical patient scenarios to determine their recommendation for renal transplantation based on demographic, clinical, and social factors. Specifically, eight unique patient scenarios were randomly distributed to each survey respondent. RESULTS: According to responding nephrologists (response rate 53%), females were less likely than males to be recommended for renal transplantation [adjusted odds ratio (OR)=0.41; confidence interval (CI) 0.21, 0.79; for whites]. Asian males were less likely than white males to be recommended for transplantation (OR=0.46, CI 0.24, 0.91). Black-white differences in rates of recommendation were not found. Other factors associated with low rates of recommendation for renal transplantation included history of noncompliance (OR=0.17, CI 0.13, 0.23), <25% cardiac ejection fraction (OR=0.15, CI 0.10, 0.21), HIV infection (OR=0.01, CI 0.00, 0.01), and being >200 lbs (OR=0.73, CI 0.56, 0.95). CONCLUSIONS: Female gender, and Asian but not black race, were associated with a decreased likelihood that nephrologists would recommend renal transplantation for patients with end stage renal disease. The well-documented black-white disparities in use of renal transplantation may be due to unaccounted for factors or may arise at a subsequent step in the transplantation process.

Adult↗