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1.
Eval Program Plann ; 66: 79-88, 2018 02.
Article in English | MEDLINE | ID: mdl-29053984

ABSTRACT

This mixed methods study content validated the Information Assessment Method for parents (IAM-parent) that allows users to systematically rate and comment on online parenting information. Quantitative data and results: 22,407 IAM ratings were collected; of the initial 32 items, descriptive statistics showed that 10 had low relevance. Qualitative data and results: IAM-based comments were collected, and 20 IAM users were interviewed (maximum variation sample); the qualitative data analysis assessed the representativeness of IAM items, and identified items with problematic wording. Researchers, the program director, and Web editors integrated quantitative and qualitative results, which led to a shorter and clearer IAM-parent.


Subject(s)
Parents/education , Program Evaluation/methods , Program Evaluation/standards , Adult , Female , Humans , Internet , Male , Psychometrics , Qualitative Research , Reproducibility of Results
2.
Osteoporos Int ; 28(11): 3107-3111, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28756457

ABSTRACT

This study compares four screening tools in their ability to predict osteoporosis. We found that there was no significant difference between the tools. These results provide support for the use of automated screening tools which work in conjunction with the electronic medical record and help improve screening rates for osteoporosis. INTRODUCTION: The purpose of this study is to compare the performance of four fracture risk assessment tools (FRATs) in identifying osteoporosis by bone mineral density (BMD) T-score: Veterans Affairs Fracture Absolute Risk Assessment Tool (VA-FARA), World Health Organization's Fracture Risk Assessment Tool (FRAX), electronic FRAX (e-FRAX), and Osteoporosis Self-Assessment Screening Tool (OST). METHODS: We performed a cross-sectional analysis of all patients enrolled in the VA Salt Lake City bone health team (BHT) who had completed a DXA scan between February 1, 2012, and February 1, 2013. DXA scan results were obtained by chart abstraction. For calculation of FRAX, osteoporosis risk factors were obtained from a screening questionnaire completed prior to DXA. For VA-FARA and e-FRAX, risk factors were derived from the electronic medical record (EMR). Clinical risk scores were calculated and compared against the gold standard of DXA-based osteoporosis. Sensitivity, specificity, and predictive values were calculated. Receiver operator characteristic (ROC) curves were plotted, and areas under the curve (AUC) were compared. RESULTS: A cohort of 463 patients met eligibility criteria (mean age 80.4 years). One hundred twelve patients (24%) had osteoporosis as defined by DXA T-score ≤-2.5. Sensitivity, specificity, and predictive values were calculated. ROC statistics were compared and did not reach statistical significance difference between FRATs in identifying DXA-based osteoporosis. CONCLUSIONS: Our study suggests that all FRATs tested perform similarly in identifying osteoporosis among elderly, primarily Caucasian, male veterans. If these electronic screening methods perform similarly for fracture outcomes, they could replace manual FRAX and thus improve efficiency in identifying individuals who should be sent for DXA scan.


Subject(s)
Electronic Health Records , Osteoporosis/diagnosis , Osteoporotic Fractures/etiology , Absorptiometry, Photon/methods , Aged , Aged, 80 and over , Bone Density/physiology , Cross-Sectional Studies , Humans , Male , Mass Screening/methods , Osteoporosis/physiopathology , Osteoporotic Fractures/physiopathology , ROC Curve , Risk Assessment/methods , Risk Factors , Sensitivity and Specificity , Veterans Health
3.
Bone ; 78: 174-85, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25896952

ABSTRACT

PURPOSE: Adherence and persistence with bisphosphonates are frequently poor, and stopping, restarting, or switching bisphosphonates is common. We evaluated bisphosphonate change behaviors (switching, discontinuing, or reinitiating) over time, as well as fractures and costs, among a large, national cohort of postmenopausal veterans. METHODS: Female veterans aged 50+ treated with bisphosphonates during 2003-2011 were identified in Veterans Health Administration (VHA) datasets. Bisphosphonate change behaviors were characterized using pharmacy refill records. Patients' baseline disease severity was characterized based on age, T-score, and prior fracture. Cox Proportional Hazard analysis was used to evaluate characteristics associated with discontinuation and the relationship between change behaviors and fracture outcomes. Generalized estimating equations were used to evaluate the relationship between change behaviors and cost outcomes. RESULTS: A total of 35,650 patients met eligibility criteria. Over 6800 patients (19.1%) were non-switchers. The remaining patients were in the change cohort; at least half displayed more than one change behavior over time. A strong, significant predictor of discontinuation was ≥5 healthcare visits in the prior year (11-23% more likely to discontinue), and discontinuation risk decreased with increasing age. No change behaviors were associated with increased fracture risk. Total costs were significantly higher in patients with change behaviors (4.7-19.7% higher). Change-behavior patients mostly had significantly lower osteoporosis-related costs than non-switchers (22%-118% lower). CONCLUSIONS: Most bisphosphonate patients discontinue treatment at some point, which did not significantly increase the risk of fracture in this majority non-high risk population. Bisphosphonate change behaviors were associated with significantly lower osteoporosis costs, but significantly higher total costs.


Subject(s)
Diphosphonates/therapeutic use , Osteoporosis, Postmenopausal/drug therapy , Aged , Aged, 80 and over , Body Mass Index , Bone Density Conservation Agents/therapeutic use , Cohort Studies , Female , Hospitals, Veterans , Humans , Medication Adherence , Middle Aged , Natural Language Processing , Osteoporotic Fractures/drug therapy , Osteoporotic Fractures/prevention & control , Patient Outcome Assessment , Proportional Hazards Models , United States , Veterans
4.
Genome Announc ; 3(1)2015 Feb 12.
Article in English | MEDLINE | ID: mdl-25676769

ABSTRACT

The genus Cellulophaga is composed of obligate aerobic Gram-negative bacteria commonly found in association with marine algae. We report the approximately 4.42-Mbp draft genome sequence of Cellulophaga sp. E6, which inhibits N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL)-mediated quorum sensing (QS), lasB transcription, and biofilm formation by Pseudomonas aeruginosa.

5.
Osteoporos Int ; 26(2): 581-7, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25288442

ABSTRACT

SUMMARY: Many of the clinical risk factors used in fracture risk assessment (FRAX) calculator are available in electronic medical record (EMR) databases and are good sources of osteoporosis risk factor information. The EPIC EMR database showed a lower prevalence of FRAX risk factors and, consequently, proportion of patients who would be deemed "high risk." INTRODUCTION: The FRAX tool is underutilized for osteoporosis screening. Many of the clinical risk factors for FRAX may be available in EMR databases and may enable health systems to perform fracture risk assessments. We intended to identify variables in an EMR database for calculating FRAX score in a cohort of postmenopausal women, to estimate absolute fracture risk, and to determine the proportions of women whose absolute fracture risks exceed the National Osteoporosis Foundation (NOF) thresholds. METHODS: Our cohort was selected using an EMR database with demographic, inpatient, outpatient, and clinical information for female patients age≥50 in a family practice, internal medicine, or obstetrics/gynecology clinic in 2007-2008. The latest physician encounter was the index date. Variables, problem and medication lists, diagnosis codes, and histories from the EMR were used to populate the 11 clinical risk factor variables used in the FRAX. These risk factor prevalence and treatment-eligible proportions were compared to those of published epidemiology studies. RESULTS: The study included 345 patients. Mean (SD) 10-year risk for any major fracture was 11.1% (6.8) when bone mineral density (BMD) was used and 11.2% (6.5) when BMI was used. About 10.1% of the cohort exceeded the NOF's 20% major fracture risk threshold and 32.5% exceeded the NOF's 3% hip fracture risk threshold when BMD was used. Overall, the number of treatment-eligible patients was slightly lower when FRAX was calculated using BMD versus BMI (13.6 and 36.8%). CONCLUSION: Our cohort using EMR data most likely underestimated the mean 10-year probability of any major fracture compared to other cohorts in published literature. The difference may be in the nature of EMRs for supporting only passive data collection of risk factor information.


Subject(s)
Electronic Health Records/statistics & numerical data , Mass Screening/methods , Osteoporosis, Postmenopausal/epidemiology , Osteoporotic Fractures/epidemiology , Aged , Algorithms , Female , Humans , Middle Aged , Osteoporotic Fractures/diagnosis , Risk Assessment/methods , Risk Factors , Sensitivity and Specificity
6.
Clin Microbiol Infect ; 20(12): 1343-51, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25366338

ABSTRACT

Clostridium difficile infection (CDI) is costly. Current guidelines recommend metronidazole as first-line therapy and vancomycin as an alternative. Recurrence is common. Faecal microbiota transplantation (FMT) is an effective therapy for recurrent CDI (RCDI). This study explores the cost-effectiveness of FMT, vancomycin and metronidazole for initial CDI. We constructed a decision-analytic computer simulation using inputs from published literature to compare FMT with a 10-14-day course of oral metronidazole or vancomycin for initial CDI. Parameters included cure rates (baseline value (range)) for metronidazole (80% (65-85%)), vancomycin (90% (88-92%)) and FMT(91% (83-100%)). Direct costs of metronidazole, vancomycin and FMT, adjusted to 2011 dollars, were $57 ($43-72), $1347 ($1195-1499) and $1086 ($815-1358), respectively. Our effectiveness measure was quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were conducted from the third-party payer perspective. Analysis using baseline values showed that FMT($1669, 0.242 QALYs) dominated (i.e. was less costly and more effective) vancomycin ($1890, 0.241 QALYs). FMT was more costly and more effective than metronidazole ($1167, 0.238 QALYs), yielding an incremental cost-effectiveness ratio (ICER) of $124 964/QALY. One-way sensitivity analyses showed that metronidazole dominated both strategies if its probability of cure were >90%; FMT dominated if it cost <$584. In a probabilistic sensitivity analysis at a willingness-to-pay threshold of $100 000/QALY, metronidazole was favoured in 55% of model iterations; FMT was favoured in 38%. Metronidazole, as the first-line treatment for CDIs, is less costly. FMT and vancomycin are more effective. However, FMT is less likely to be economically favourable, and vancomycin is unlikely to be favourable as first-line therapy when compared with FMT.


Subject(s)
Anti-Bacterial Agents/economics , Anti-Bacterial Agents/therapeutic use , Biological Therapy/economics , Biological Therapy/methods , Clostridium Infections/economics , Clostridium Infections/therapy , Clostridioides difficile/isolation & purification , Clostridium Infections/microbiology , Computer Simulation , Cost-Benefit Analysis , Humans , Metronidazole/economics , Metronidazole/therapeutic use , Quality-Adjusted Life Years , Vancomycin/economics , Vancomycin/therapeutic use
7.
Osteoporos Int ; 25(12): 2701-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25037601

ABSTRACT

UNLABELLED: This is a cost-effectiveness analysis of training rural providers to identify and treat osteoporosis. Results showed a slight cost savings, increase in life years, increase in treatment rates, and decrease in fracture incidence. However, the results were sensitive to small differences in effectiveness, being cost-effective in 70 % of simulations during probabilistic sensitivity analysis. INTRODUCTION: We evaluated the cost-effectiveness of training rural providers to identify and treat veterans at risk for fragility fractures relative to referring these patients to an urban medical center for specialist care. The model evaluated the impact of training on patient life years, quality-adjusted life years (QALYs), treatment rates, fracture incidence, and costs from the perspective of the Department of Veterans Affairs. METHODS: We constructed a Markov microsimulation model to compare costs and outcomes of a hypothetical cohort of veterans seen by rural providers. Parameter estimates were derived from previously published studies, and we conducted one-way and probabilistic sensitivity analyses on the parameter inputs. RESULTS: Base-case analysis showed that training resulted in no additional costs and an extra 0.083 life years (0.054 QALYs). Our model projected that as a result of training, more patients with osteoporosis would receive treatment (81.3 vs. 12.2 %), and all patients would have a lower incidence of fractures per 1,000 patient years (hip, 1.628 vs. 1.913; clinical vertebral, 0.566 vs. 1.037) when seen by a trained provider compared to an untrained provider. Results remained consistent in one-way sensitivity analysis and in probabilistic sensitivity analyses, training rural providers was cost-effective (less than $50,000/QALY) in 70 % of the simulations. CONCLUSIONS: Training rural providers to identify and treat veterans at risk for fragility fractures has a potential to be cost-effective, but the results are sensitive to small differences in effectiveness. It appears that provider education alone is not enough to make a significant difference in fragility fracture rates among veterans.


Subject(s)
Education, Medical, Continuing/economics , Osteoporosis/economics , Osteoporotic Fractures/economics , Physicians, Primary Care/education , Rural Health Services/economics , Aged , Aged, 80 and over , Cost-Benefit Analysis , Education, Medical, Continuing/methods , Health Care Costs/statistics & numerical data , Humans , Male , Markov Chains , Osteoporosis/diagnosis , Osteoporosis/drug therapy , Osteoporotic Fractures/prevention & control , Physicians, Primary Care/economics , Primary Health Care/economics , Quality-Adjusted Life Years , Sensitivity and Specificity , United States , Veterans Health/economics
9.
Aliment Pharmacol Ther ; 37(4): 473-81, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23289640

ABSTRACT

BACKGROUND: Chronic hepatitis C (HCV) treatment with pegylated-interferon (PEG-IFN)/ribavirin (RBV) is often limited by preexisting medical, psychiatric and psychosocial contraindications. However, limited data exist in general patient populations. AIM: To evaluate the percentage of HCV-infected patients in the general US population who may have contraindications to PEG-IFN/RBV. METHODS: The General Electric (GE) Centricity dataset was used to screen the US population between 2004 and 2009 for HCV infection and contraindications to PEG-IFN/RBV. HCV diagnosis and contraindications were identified using ICD-9-CM codes or laboratory values. Only patients with an encounter 180 days prior to HCV diagnosis were included. Demographic differences were calculated using Pearson's chi-squared test. Frequencies and percentages for absolute and relative contraindications to PEG-IFN and/or RBV were determined and proportions and rates/1000 person-months were calculated. RESULTS: A total of 15 561 021 patients were screened, and 45 690 (0.3%) were HCV-positive and were evaluated. Those with contraindications were significantly younger, female, White, not currently married and receiving Medicare or Medicaid coverage (all P < 0.0001). 17.3% had at least one contraindication to PEG-IFN/RBV (5.5 events/1000 person-months); bipolar disorder (6.5%), anaemia (Hgb < 10 g/dL; 5.9%), pregnancy (1.9%) and neutropenia (neutrophils <750 cells/mm(3) ; 1.2%) were most frequently cited. CONCLUSIONS: Approximately, 17% of HCV-infected patients in the general US population had at least one contraindication to PEG-IFN/RBV. Most contraindications were relative and potentially modifiable. Clinical assessment of contraindications as relative and/or modifiable should be considered and used to determine if patients could benefit from current PEG-IFN-containing triple therapy or future PEG-IFN- or RBV-free regimens.


Subject(s)
Antiviral Agents , Hepatitis C, Chronic/drug therapy , Interferon-alpha , Polyethylene Glycols , Ribavirin , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Child , Child, Preschool , Contraindications , Databases, Factual , Drug Therapy, Combination , Female , Humans , Infant , Interferon alpha-2 , Interferon-alpha/therapeutic use , Male , Middle Aged , Polyethylene Glycols/therapeutic use , Recombinant Proteins/therapeutic use , Ribavirin/therapeutic use , Treatment Outcome , United States , Young Adult
10.
Osteoporos Int ; 23(3): 1017-27, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21562876

ABSTRACT

UNLABELLED: Absolute risk assessment is now the preferred approach to guide osteoporosis treatment decisions. Data collected passively during routine healthcare operations can be used to develop discriminative absolute risk assessment rules in male veterans. These rules could be used to develop computerized clinical decision support tools that might improve fracture prevention. INTRODUCTION: Absolute risk assessment is the preferred approach to guiding treatment decisions in osteoporosis. Current recommended risk stratification rules perform poorly in men, among whom osteoporosis is overlooked and undertreated. A potential solution lies in clinical decision support technology. The objective of this study was to determine whether data passively collected in routine healthcare operations could identify male veterans at highest risk with acceptable discrimination. METHODS: Using administrative and clinical databases for male veterans ≥50 years old who sought care in 2005-2006, we created risk stratification rules for hip and any major fracture. We identified variables related to known or theoretical risk factors and created prognostic models using Cox regression. We validated the rules and estimated optimism. We created risk scores from hazards ratios and used them to predict fractures with logistic regression. RESULTS: The predictive models had C-statistics of 0.81 for hip and 0.74 for any major fracture, suggesting good to acceptable discrimination. For hip fracture, the cut-point that maximized percentage classified correctly (accuracy) predicted 165 of 227 hip fractures (73%) and missed 62 (27%). All hip fractures in patients with prior fracture were identified and 67% in patients without. For any major fracture, the maximal-accuracy cut-point predicted 611 of 987 (62%) and missed 376 (38%); the rule predicted all 134 fractures in patients with prior fracture and 56% in patients without. CONCLUSION: Data collected passively in routine healthcare operations can identify male veterans at highest risk for fracture with discrimination that exceeds that reported for other methods applied in men.


Subject(s)
Osteoporosis/diagnosis , Osteoporotic Fractures/etiology , Risk Assessment/methods , Aged , Aged, 80 and over , Decision Support Techniques , Epidemiologic Methods , Hip Fractures/epidemiology , Hip Fractures/etiology , Humans , Male , Middle Aged , Osteoporosis/epidemiology , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/prevention & control , Prognosis , Recurrence , United States/epidemiology
11.
Middle East J Anaesthesiol ; 21(6): 899-904, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23634577

ABSTRACT

A 63 year-old obese man with gastroesophageal reflux disease, hiatal hernia, and no known history of airway pathology was to undergo a total knee arthroplasty. After intubation, however, repeated cuff leaks, decreasing tidal volumes, and desaturations prompted five additional endotracheal tube placements. Findings on radiography, computed tomography, and fiberoptic laryngoscopy and tracheoscopy were equivocal. Factors contributing to this challenge of persistent and repeated cuff leaks in the absence of known airway pathology could include various laryngotracheal abnormalities.


Subject(s)
Intubation, Intratracheal/instrumentation , Larynx/pathology , Trachea/pathology , Humans , Intubation, Intratracheal/adverse effects , Male , Middle Aged , Tracheal Stenosis/pathology
12.
Int J Sports Med ; 31(6): 372-6, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20419621

ABSTRACT

Acetazolamide is useful for acclimatizing to high altitude. How long it should be taken, and the physiological consequences of stopping it have not been thoroughly studied. We investigated the effect of acetazolamide cessation on exercise oxygenation at different altitudes and durations of use. Three groups were studied: group 1 acclimatized to 4,060 m for 6 days while taking acetazolamide 250 mg three times a day. On day 7 acetazolamide was stopped, then resumed on day 8. Standardized exercise oximetry was performed each day. The protocol for group 2 was identical to group 1, except acclimatization occurred over 14 days to 4 120 m. The protocol for group 3 was identical to group 2, except subjects acclimatized to 4,770 m. Multivariate regression revealed a negative effect of stopping acetazolamide on exercise oxygenation (p=0.028). At 4,100 m cessation of acetazolamide after one week resulted in a 11% drop in exercise oxygenation (p=0.008); after two weeks acclimatization to this altitude there was an non-significant drop in exercise oxygenation (2.5% p=0.064). At 4 770 m acetazolamide cessation resulted in an increase in exercise oxygenation (7% p=0.027). We conclude that exercise oxygenation after acetazolamide cessation is dependent both on duration of acclimatization/drug administration, and acclimatization altitude.


Subject(s)
Acetazolamide/therapeutic use , Carbonic Anhydrase Inhibitors/therapeutic use , Exercise/physiology , Hypoxia/prevention & control , Acclimatization/drug effects , Adult , Female , Humans , Male , Middle Aged , Peru
13.
Int J Med Inform ; 78(5): 321-9, 2009 May.
Article in English | MEDLINE | ID: mdl-19117798

ABSTRACT

CONTENT AND OBJECTIVE: Health professionals now routinely use electronic knowledge resources (EKRs). Few studies have considered EKR-related tensions which may arise in a clinical decision-making context. The present study aims to explore three types of tension: (1) user-computer tension, (2) social tensions, and (3) organizational tensions (constraints associated with organizational routines and health policies). DESIGN, PARTICIPANTS, INTERVENTION, SETTING: We conducted a multiple case study, examining Family Medicine residents' searches for information in everyday life. Cases were defined as critical searches for information among 17 first year family medicine residents using InfoRetriever 2003/2004 on a PDA over 1.5 months at McGill University. InfoRetriever-derived information was used within a resident-patient decision-making context in 84 of 156 cases. For each case, residents were interviewed, and extracts of interview transcripts were assigned to themes using specialized software (presence of tension; type of tension). Further computer-assisted lexical-semantic analysis was performed on transcripts. Authors reached consensus on assignments. RESULTS: Twenty-five cases with tension were identified (one case had two types of tension), and illustrate the above mentioned types of tensions: (T1) tension between the resident and InfoRetriever (N=16); (T2) InfoRetriever-related tension between the resident and other social actors, specifically supervisors, other health care professionals and patients (N=7); (T3) InfoRetriever-related tension between the resident and the health organization/system (N=3). CONCLUSIONS: Results suggest EKR usage in a clinical decision-making context may have negative consequences when three types of tension arise in a clinical decision-making context. Illustrated types of tension are interrelated and not mutually exclusive. Awareness of EKR-related tensions may help clinicians to integrate EKRs in practice.


Subject(s)
Decision Making , Medical Informatics , Practice Patterns, Physicians' , Cohort Studies , Quebec
14.
Pediatr Dent ; 20(7): 395-403, 1998.
Article in English | MEDLINE | ID: mdl-9866143

ABSTRACT

PURPOSE: Baby bottle tooth decay (BBTD) affects 6% of children under three years of age and is associated with inappropriate bottle use. The objective of this study was to estimate the caries-related risk associated with 26 infant formulas and whole milk. METHODS: First, the plaque pH of adult volunteers was monitored before and after an oral rinse with infant formula to determine the minimum pH obtained in response to each formula. Second, Streptococcus sobrinus 6715 was cultured in each infant formula, and the increase in the number of colony forming units was measured. Third, each infant formula was incubated with powdered enamel and the solubility of enamel mineral was calculated in the absence of bacteria. Fourth, each formula was mixed with standardized concentrations of acid to determine the buffering capabilities. Finally, enamel windows were created on extracted permanent molars and exfoliated primary incisor crowns that were then colonized with mutans streptococci and incubated with infant formula. Caries was assessed visually and radiographically for 18 weeks. The length of time required for the development of enamel caries, dentinal caries and pulpal involvement was recorded. RESULTS: One-way or two-way ANOVA of these five assays demonstrated that 1. Plaque pH varied in response to oral rinsing with infant formula and most formulas did have the ability to reduce the pH significantly below the pH obtained after rinsing with water 2. Some infant formulas supported significant bacterial growth 3. Enamel mineral was dissolved by incubation with certain infant formula 4. The buffer capacity varied among the infant formulas tested 5. The length of time required for caries to reach dentin or pulp differed for the formulas, with some formulas causing dentinal caries by 3.4 weeks and pulpal involvement by 7.2 weeks.


Subject(s)
Cariogenic Agents/adverse effects , Dental Caries/etiology , Infant Food/adverse effects , Acids , Adult , Analysis of Variance , Animals , Buffers , Cariogenic Agents/metabolism , Child, Preschool , Colony Count, Microbial , Culture Media , Dental Caries/diagnostic imaging , Dental Caries/microbiology , Dental Caries/pathology , Dental Enamel/drug effects , Dental Enamel/microbiology , Dental Enamel/pathology , Dental Enamel Solubility/drug effects , Dental Plaque/physiopathology , Dental Pulp/microbiology , Dental Pulp/pathology , Dentin/microbiology , Dentin/pathology , Humans , Hydrogen-Ion Concentration , Infant , Milk , Radiography , Risk Factors , Streptococcus mutans/growth & development , Streptococcus sobrinus/growth & development , Time Factors
15.
J Mol Biol ; 281(5): 843-56, 1998 Sep 04.
Article in English | MEDLINE | ID: mdl-9719639

ABSTRACT

The recently inserted subfamilies of Alu retroposons (Ya5/8 and Yb8) are composed of approximately 2000 elements. We have screened a human chromosome 19-specific cosmid library for the presence of Ya5/8 and Yb8 Alu family members. This analysis resulted in the identification of 12 Ya5/8 Alu family members and 15 Yb8 Alu family members from human chromosome 19. The total number of Ya5/8 and Yb8 Alu family members located on human chromosome 19 does not differ from that expected based upon random integration of Alu repeats within the human genome. The distribution of both subfamilies of Alu elements along human chromosome 19 also appears to be random. DNA sequence analysis of the individual Alu elements revealed a low level of random mutations within both subfamilies of Alu elements consistent with their recent evolutionary origin. Oligonucleotide primers complementary to the flanking unique sequences adjacent to each Alu element were used in polymerase chain reaction assays to determine the phylogenetic distribution and human genomic variation associated with each Alu family member. All of the chromosome 19-specific Ya5/8 and Yb8 Alu family members were restricted to the human genome and absent from orthologous positions within the genomes of several non-human primates. Three of the Yb8 Alu family members were polymorphic for insertion presence/absence within the genomes of a diverse array of human populations. The polymorphic Alu elements will be useful tools for the study of human population genetics.


Subject(s)
Chromosomes, Human, Pair 19/genetics , Repetitive Sequences, Nucleic Acid/genetics , Retroelements/genetics , Animals , Base Sequence , Cell Line , Cloning, Molecular , Cosmids/genetics , Evolution, Molecular , Gene Library , Humans , Molecular Sequence Data , Mutation/genetics , Phylogeny , Polymerase Chain Reaction , Polymorphism, Genetic/genetics , Primates , Sequence Alignment , Sequence Analysis, DNA
16.
J Physiol ; 487 ( Pt 3): 761-72, 1995 Sep 15.
Article in English | MEDLINE | ID: mdl-8544137

ABSTRACT

1. Clarke's column neurons of the dorsal spinocerebellar tract (DSCT) were recorded intracellularly in anaesthetized cats during weak sustained contractions of triceps surae (TS) produced by direct electrical stimulation of the muscle. 2. Of 145 DSCT neurons, 77 (53%) were contraction sensitive suggesting that information about weak contraction of a limited number of muscles is widely distributed among DSCT neurons. Four types of effects were observed in individual neurons during TS contractions. 3. In the first group of 11 DSCT neurons (14% of the contraction-sensitive cells), the effect was excitation persisting throughout the duration of contractions. These responses were ascribed to actions of afferents from contraction-activated tendon organs. 4. In a second group of 15 neurons (20% of the contraction-sensitive cells), quickly declining excitatory potentials were recorded during sustained TS contractions. By analogy with previous observations of contraction-induced effects in motoneurons, the decline of excitation might be explained by contraction-induced presynaptic inhibition of group I afferents in Clarke's column. 5. Declining inhibitions, resembling those previously observed in homonymous and synergic motoneurons, were recorded in 49% of contraction-sensitive DSCT neurons. This appears in keeping with the fact that interneurons mediating Ib inhibition to motoneurons project axon collaterals to DSCT neurons. Presynaptic inhibition of Ib fibres might therefore cause parallel reductions of inhibitory potentials in motoneurons and in DSCT neurons. 6. In a final group of 13 neurons, mixed excitatory and inhibitory effects were observed during TS contractions. Such DSCT neurons might monitor the excitability of Ib interneurons by integration of information about input to and output from these neurons. 7. The non-uniform patterns of DSCT responses to TS contractions suggest complex processing of information on ankle extensor activity in cerebellum. Phasic signalling of contraction onset is observed in many DSCT neurons while others carry messages about duration and strength of contraction.


Subject(s)
Cerebellum/physiology , Muscle Contraction/physiology , Muscle, Skeletal/physiology , Neurons/physiology , Spinal Cord/physiology , Animals , Cats , Cerebellum/cytology , Chlorides/metabolism , Electric Stimulation , Membrane Potentials/physiology , Motor Neurons/physiology , Muscle, Skeletal/innervation , Nerve Fibers/physiology , Neural Pathways/physiology , Neurons, Afferent/physiology , Signal Transduction/physiology , Spinal Cord/cytology
17.
J Neurophysiol ; 70(5): 1797-804, 1993 Nov.
Article in English | MEDLINE | ID: mdl-8294954

ABSTRACT

1. Motoneurons of pretibial ankle flexor and knee flexor and extensor muscles were recorded intracellularly in chloralose- or pentobarbitone-anesthetized cats during sustained submaximal contractions of either ipsi- or contralateral gastrocnemius medialis muscle (GM). 2. In a majority of ipsilateral motoneurons, a sustained GM contraction elicited inhibitory potentials that quickly subsided before the end of the contraction. An abrupt increase in contractile force could elicit a new series of inhibitory potentials, which declined again in spite of a maintained force level. 3. Contraction-induced effects were only exceptionally detected in contralateral triceps surae and plantaris motoneurons. In a small number of pretibial flexor and knee flexor and extensor motoneurons, declining inhibitions were observed during sustained contractions of the contralateral GM muscle. 4. At the onset of GM contractions, a variety of motoneurons uniformly receive inhibitory inputs that are quickly filtered out. Although the functional significance of this widespread initial inhibition remains to be elucidated, its rapid decline seems useful to allow subsequent recruitment of motor units as may be required for coordination of posture and movement. 5. Tendon organs are activated during muscle contraction, but it is not certain whether Ib inputs from GM can account for all the effects observed. Contribution of other afferents was considered and tested using a different experimental approach. The companion paper reports observations suggesting that effects elicited by group II afferents may cooperate in the contraction-induced inhibition of motoneurons.


Subject(s)
Functional Laterality/physiology , Motor Neurons/physiology , Muscle Contraction/physiology , Muscles/innervation , Neural Inhibition/physiology , Spinal Cord/physiology , Afferent Pathways/physiology , Animals , Cats , Electric Stimulation , Hindlimb/innervation , Membrane Potentials/physiology , Recruitment, Neurophysiological/physiology
18.
J Neurophysiol ; 70(5): 1805-10, 1993 Nov.
Article in English | MEDLINE | ID: mdl-8294955

ABSTRACT

1. The aim of the present experiments was to verify whether group II inputs from gastrocnemius medialis (GM) muscle could elicit declining inhibitions similar to those observed during GM contractions in a variety of lumbar motoneurons of the cat spinal cord. Motoneurons were recorded intracellularly in chloralose- or pentobarbitone-anesthetized preparations during electrical stimulation of GM nerve with repetitive trains. 2. With strengths in the group I range, repetitive stimulation evoked the usual Ia excitation in homonymous motoneurons and excitatory postsynaptic potential (EPSP) amplitudes remained constant throughout the stimulation sequence. In synergic plantaris motoneurons lacking an excitatory connection with Ia afferents from GM, the same stimulation, kept at a constant strength throughout the stimulation sequence, elicited rapidly decreasing inhibitory potentials reminiscent of those evoked by GM contractions. 3. In motoneurons of pretibial flexors, quadriceps, and posterior biceps-semitendinosus, the stimulation strength required to observe declining inhibitions resembling those produced by GM contractions was 4-8 times group I threshold, engaging group II in addition to group I fibers. 4. These results show that input from GM group II plus group I afferents can elicit inhibitory effects in a variety of motoneurons. Such observations support the hypothesis that messages from spindle secondary endings and/or nonspecific muscle receptors activated during contraction might contribute to the widespread inhibition caused by GM contractions. 5. Inasmuch as constant input in group II and group I afferents evoked declining inhibitory potentials, the origin of the decline must be central, which suggests that the rapid reduction of contraction-induced inhibitions also depended on a central mechanism.


Subject(s)
Functional Laterality/physiology , Motor Neurons/physiology , Muscle Contraction/physiology , Muscles/innervation , Neural Inhibition/physiology , Spinal Cord/physiology , Afferent Pathways/physiology , Animals , Cats , Electric Stimulation , Joints/innervation , Membrane Potentials/physiology , Reaction Time/physiology , Recruitment, Neurophysiological/physiology
20.
J Physiol ; 445: 345-54, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1501138

ABSTRACT

1. Intra-axonal records from the intraspinal course of Ib and Ia afferent fibres innervating the gastrocnemius medialis muscle were obtained in chloralose or Nembutal-anaesthetized cats during submaximal contractions of the muscle. 2. Afferent fibres in continuity with their muscle of origin were functionally identified by their responses to muscle stretch or contraction. 3. In six out of eight Ib afferents, primary depolarizations (PADs) were recorded during contraction. They were independent of the presence of orthodromic impulses fired by tendon organs. 4. These observations support the assumption that the reduction of Ib autogenetic inhibition in homonymous and synergic motoneurones during GM contractions is due to presynaptic inhibition of transmission in Ib pathways.


Subject(s)
Muscle Contraction/physiology , Neurons, Afferent/physiology , Spinal Cord/physiology , Animals , Axons/physiology , Cats , Electrophysiology
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