PubMed Health⌕ Search

Biomedical subjects

L Cook

Publications and source records attributed to L Cook.

At least 19 recordsLinked to original sources

A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms.

We describe a map of 1.42 million single nucleotide polymorphisms (SNPs) distributed throughout the human genome, providing an average density on available sequence of one SNP every 1.9 kilobases. These SNPs were primarily discovered by two projects: The SNP Consortium and the analysis of clone overlaps by the International Human Genome Sequencing Consortium. The map integrates all publicly available SNPs with described genes and other genomic features. We estimate that 60,000 SNPs fall within exon (coding and untranslated regions), and 85% of exons are within 5 kb of the nearest SNP. Nucleotide diversity varies greatly across the genome, in a manner broadly consistent with a standard population genetic model of human history. This high-density SNP map provides a public resource for defining haplotype variation across the genome, and should help to identify biomedically important genes for diagnosis and therapy.

Chromosome Mapping↗

Diaphragm versus diaphragm with spermicides for contraception.

BACKGROUND: The diaphragm is usually used with a spermicide. However, some practitioners have suggested that spermicides offer no additional contraceptive protection and have advocated alternative guidelines for the use of diaphragms. OBJECTIVES: The objective of this review was to compare the effectiveness, safety and acceptability of the diaphragm with and without spermicide. SEARCH STRATEGY: We searched MEDLINE, EMBASE, POPLINE, CINAHL, the Cochrane Controlled Trials Register, and reference lists of relevant articles. In addition, we contacted experts in the field to identify unpublished studies. SELECTION CRITERIA: Randomized controlled trials comparing women of reproductive age using the diaphragm with and without spermicide as the sole contraceptive method that reported clinical outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data on outcomes and trial characteristics and any discrepancies were resolved by consensus or by consultation with the third reviewer. The results of the one identified study are presented descriptively. MAIN RESULTS: We identified only one study. No significant difference was found in the pregnancy rates (with typical use or consistent use) or discontinuation rates between the diaphragm-with-spermicide and diaphragm-without-spermicide groups. There was a trend towards higher pregnancy rates in the diaphragm-without-spermicide group. However, this study failed to recruit the planned number of participants and was consequently underpowered. REVIEWER'S CONCLUSIONS: As only one underpowered study was identified, we cannot distinguish between the contraceptive effectiveness of the diaphragm with and without spermicide. We cannot draw any conclusion at this point, further research is needed.

Contraception↗

Randomized crossover trial comparing the eZ.on plastic condom and a latex condom.

This randomized crossover trial compared the breakage and slippage rates, safety, and acceptability of the recently developed polyurethane bi-directional eZ.on condom with a marketed latex condom. Three hundred sixty couples were asked to use 4 eZ.on condoms and 4 latex condoms. Like several other non-latex condoms tested to date, the eZ.on condom had a higher clinical breakage rate than its latex comparator, while the slippage rates were similar. The clinical breakage rate for the eZ.on condom was 5.6%, compared with 0.9% for the latex condom (difference = 4.76%, with upper 95% confidence bound on the difference = 6.26%). Thus, based on an a priori definition of a 2% clinically acceptable difference, the study failed to conclude equivalence relative to clinical breakage. The complete slippage rate for eZ.on was 1.6%; compared to 0.7% for latex (difference = 0.87%, with upper 95% confidence bound = 1.55%). Thus, based on an a priori definition of a 2% difference we concluded equivalence relative to complete slippage. The safety profile of the eZ.on condom was good and similar to the latex condom. The eZ.on was also found to be easier to don and remove than the latex condom. Although no overall preference existed for either condom, nearly 30%women and men strongly preferred the eZ.on condom to the latex condom. The eZ.on condom may be an acceptable alternative for couples unable or unwilling to use latex condoms.

Adult↗

Probabilistic linkage of computerized ambulance and inpatient hospital discharge records: a potential tool for evaluation of emergency medical services.

STUDY OBJECTIVES: Emergency medical services (EMS) is an important part of the health care system. The effect of EMS on morbidity, mortality, and costs of illness is difficult to evaluate because hospital information is not available in out-of-hospital databases. We used probabilistic linkage to create such a database from ambulance and inpatient data and demonstrate the potential for linkage to facilitate evaluation of EMS responses resulting in hospital admission. METHODS: Statewide ambulance and inpatient hospital discharge records were available for 1994 through 1996. Ambulance records indicating admission to the emergency department or hospital (165,649 records) were linked to inpatient hospital records indicating emergency admission (146,292 records) by using probabilistic linkage. Out-of-hospital data (dispatch code, treatments rendered, and ages), linkage rates, and inpatient data (discharge status, charges, length of stay, and payer category) were analyzed. RESULTS: We linked 24,299 (14.7%) ambulance events to inpatient hospital discharges. If we had used exact linkage methods, we would have only linked 14,621 record pairs, a loss of nearly 40%. Linkage rates were relatively constant between years (approximately 15%) but differed by ambulance dispatch codes. Out-of-hospital dispatch codes with high linkage rates included breathing problems (22.6%), chest pain (21.5%), diabetic problems (16.9%), drowning incidents (14.9%), falls (19.2%), strokes (32.8%), and unconsciousness or fainting episodes (16.1%). Linkage to the hospital record provided access to hospital outcome data. Inpatient mortality was 6.8%. Survivors were discharged home (60.7%), transferred to other acute-care facilities (3.6%) or intermediate-care facilities (23.3%), or discharged with home health care provision (4.9%). The median length of stay was 3 days, and median charges were $6,620; total inpatient charges were $286,737,067. CONCLUSION: Probabilistic linkage enables ambulance and hospital discharge records to be linked together and potentially increases our ability to critically evaluate EMS by providing access to hospital-based outcomes. Such evaluation will be further improved by linking to ED, other outpatient, and other public health data sources.

Adolescent↗

Characterization of osteoblast-like behavior of cultured bone marrow stromal cells on various polymer surfaces.

The creation of novel bone substitutes requires a detailed understanding of the interaction between cells and materials. This study was designed to test certain polymers, specifically poly(caprolactone) (PCL), poly(D,L-lactic-CO-glycolic acid) (PLGA), and combinations of these polymers for their ability to support bone marrow stromal cell proliferation and differentiation. Bone marrow stromal cells were cultured from New Zealand White rabbits and were seeded onto glass slides coated with a thin layer of PCL, PLGA, and combinations of these two polymers in both a 40:60 and a 10:90 ratio. Growth curves were compared. At the end of 2 weeks, the cells were stained for both matrix mineralization and alkaline phosphatase activity. There was no statistically significant difference in growth rate of the cells on any polymer or polymer combination. However, there was a striking difference in Von Kossa staining and alkaline phosphatase staining. Cells on PCL did not show Von Kossa staining or alkaline phosphatase staining. However, in the 40:60 and 10:90 blends, there was both positive Von Kossa and alkaline phosphatase staining. These data indicate that PCL alone may not be a satisfactory material for the creation of a bone substitute. However, it may be used in combination with PLGA for the creation of a bone substitute material.

Animals↗

Development of the antinuclear and anticytoplasmic antibody consensus panel by the Association of Medical Laboratory Immunologists.

The Association of Medical Laboratory Immunologists (AMLI) have developed a panel of antinuclear and anticytoplasmic antibody consensus sera that can be useful for enzyme immunoassay (EIA), Ouchterlony, and immunofluorescence assay methods. It was developed to assist in the evaluation of newly available EIA methods for the detection of autoantibodies. The panel of sera was evaluated in several clinical laboratories and a large number of laboratories owned by manufacturers of clinical autoantibody testing kits. The majority of sera performed well for the EIAs in both the clinical laboratories and the manufacturers' laboratories, but some samples had discrepant results. A major source of discrepancy is the current inability of the EIA results to be directly compared in a quantitative way as no standardization exists. The evaluation demonstrated lower sensitivity of detection by the Ouchterlony method. The limited evaluation of the sera with immunoblotting and Western blotting did not show good agreement with other methods. Further work must be done to standardize blotting methods prior to their use in routine clinical testing. The sera are now available to vendors and clinical laboratories for use in the detection of SS-A, SS-B, Sm, U1-RNP, Scl-70, Jo-1, double-stranded DNA, and centromere antibodies. The availability of the consensus sera will help evaluate and improve the EIA methods currently being used.

Antibodies, Antinuclear↗

Use of whole blood specimens for routine clinical quantitation of hepatitis C virus RNA does not increase assay sensitivity.

The measurement of hepatitis C virus (HCV) RNA levels in the blood has, in the last few years, become a critical component in the therapy of patients with HCV infections. Initially, extraction methods for serum and plasma were used, but a newer method that uses Catrimox-14 as the extraction agent for whole blood has been reported. Because the whole blood extraction method may yield higher virus levels if significant levels of virus are present in the white blood cells (WBC), the method was evaluated for use in our clinical diagnostic laboratory despite its higher reagent costs and more time-consuming methodology. RNA was simultaneously extracted from 39 clinical samples by four different methods: Catrimox-14-Trizol extraction from whole blood, Trizol extraction from whole blood, Trizol extraction from serum, and a commercial serum extraction method, the EZNA total RNA kit. In addition, in an effort to quantitate the amount of HCV RNA virus in the WBC, Trizol extraction from isolated WBC was also performed. Quantitative results for samples from which RNA was extracted by all four methods were essentially the same; the Catrimox-14-Trizol method did not yield increased virus levels. Insignificant levels of virus were found in the WBC. The results did not demonstrate a clinical usefulness for the Catrimox-14-Trizol method.

Hepacivirus↗

Effect of seating position and restraint use on injuries to children in motor vehicle crashes.

OBJECTIVE: To determine the effect of restraint use and seating position on injuries to children in motor vehicle crashes, with stratification by area of impact. METHODS: Children <15 years old involved in serious automobile crashes in Utah from 1992 through 1996 were identified from statewide motor vehicle crash records. Serious crashes are defined as those resulting in occupant injuries with broken bones or significant bleeding or property damage exceeding $750. Probabilistic methods were used to link these records with hospital records. Analysis used logistic regression controlling for age, restraint use, occupant seating position, and type of crash. RESULTS: We studied 5751 children and found 53% were rear seat passengers. More than 40% were unrestrained. Sitting in the rear seat offered a significant protective effect (adjusted odds ratio: 1.7; 95% confidence interval: 1.6-2.0), and restraint use enhanced this effect (adjusted odds ratio: 2.7; 95% confidence interval: 2.4-3.1). Mean hospital charges were significantly greater for front seat passengers. CONCLUSIONS: Rear seat position during a motor vehicle crash provides a significant protective effect, restraint use furthers this effect, and usage rates of restraint devices are low. The rear seat protective effect is in addition to and independent of the protection offered from restraints.

Accidents, Traffic↗

The effects of high-intensity intermittent exercise on saliva IgA, total protein and alpha-amylase.

The aim of this study was to assess the effect of an acute bout of high-intensity intermittent exercise on saliva IgA concentration and alpha-amylase activity, since this type of training is commonly incorporated into the training programmes of endurance athletes and games players. Eight well-trained male games players took part in the study. They reported to the laboratory after an overnight fast and performed a 60-min cycle exercise task consisting of twenty 1-min periods at 100% VO2max, each separated by 2 min recovery at 30% VO2max. Unstimulated whole saliva was collected over a 5-min period into pre-weighed tubes and analysed for total protein, saliva IgA and alpha-amylase. The saliva flow rate ranged from 0.08 to 1.40 ml x min(-1) at rest and was not significantly affected by the exercise. The performance of the intermittent exercise bout did not affect the saliva IgA concentration, but caused a five-fold increase in alpha-amylase activity (P<0.01 compared with pre-exercise) and a three-fold increase in total protein concentration (P<0.01). These returned to pre-exercise values within 2.5 h post-exercise. It has been suggested that IgA concentration should be expressed as the ratio to total protein concentration, to correct for any concentrating effect due to evaporative loss of saliva water when breathing through the mouth (as in strenuous exercise). The present study clearly demonstrates that this is not appropriate, since there is an increase in salivary protein secretion rate immediately after exercise (571+/-77 microg x min(-1) compared with 218+/-71 microg x min(-1) pre-exercise; P<0.05). The increased saliva alpha-amylase activity after exercise may improve the protective effect of saliva, since this enzyme is known to inhibit bacterial attachment to oral surfaces. The saliva alpha-amylase secretion rate was lower immediately pre-exercise than at any other instant, which may have been due to anticipatory psychological stress, although the subjects were all familiar with interval exercise. This emphasizes the need for true resting non-stressed control conditions in future studies of the effects of exercise on saliva constituents.

Adult↗

Pre-hospital emergency medical services: a population based study of pediatric utilization.

OBJECTIVES: To examine emergency medical services (EMS) usage by children in one state. METHODS: Dispatch of an EMS vehicle in response to a call in the US is referred to as a "run". Runs for Utah for 1991-92 were linked to corresponding hospital records. Abbreviated injury severity scores (AISs) were assigned using ICDMAP-90 software. RESULTS: For the two year period there were at least 15 EMS runs per 100 children per year, with incomplete reporting from rural areas. EMS response and scene times were similar for all age groups, but interventions were less frequent for children under 5 years of age. When the principal AIS region of injury was the head, neck, or face, cervical immobilization was less frequent for children less than 5 years of age (54%) than for older children (76%) and immobilization was associated with improved outcome, using the crude measure of lower hospital charges. There was a similar association between splinting of upper extremity fractures and reduced hospital charges. Both associations did not appear to be due to differences in injury severity. CONCLUSIONS: The majority of EMS use by children is for trauma. Children less than 5 years of age are less likely to have an EMS intervention than older children. Whether the lower frequency of interventions is due to the lack of properly sized equipment on the vehicle, or to other factors, is undetermined.

Adolescent↗

De novo 10q22 interstitial deletion.

We describe a 4 month old male with a de novo interstitial deletion of chromosome 10q22. His clinical features included growth deficiency, developmental delay, ocular hypertelorism, posteriorly rotated ears, retrognathia, and fifth finger clinodactyly. He later developed dental lamina cysts of the alveolar ridge. To our knowledge, this is the first reported case of an interstitial deletion of 10q22.

Abnormalities, Multiple↗

Tuberculin skin test screening practices among US colleges and universities.

CONTEXT: Concern about transmission of Mycobacterium tuberculosis on college campuses has prompted some schools to institute tuberculin skin test screening of students, but this screening has never been evaluated. OBJECTIVE: To describe tuberculin skin test screening practices and results of screening in colleges and universities in the United States. DESIGN AND SETTING: Self-administered mail and telephone questionnaire in November and December 1995 to a stratified random sample of US 2-year and 4-year colleges and universities. MAIN OUTCOME MEASURES: Type of tuberculin screening required; types of schools requiring screening; number and rate of students with positive skin test results and/or diagnosed as having tuberculosis. RESULTS: Of the 3148 US colleges and universities, 624 (78%) of 796 schools surveyed responded. Overall, 378 schools (61%) required tuberculin screening; it was required for all new students (US residents and international students) in 161 (26%) of 624 schools, all new international students but not new US residents in 53 (8%), and students in specific academic programs in 294 (47%). Required screening was more likely in 4-year vs 2-year schools, schools that belonged to the American College Health Association vs nonmember schools, schools with immunization requirements vs schools without, and schools with a student health clinic vs those without (P<.001 for all). Public and private schools were equally likely to require screening (64% vs 62%; P=.21). In the 378 schools with screening requirements, tine or multiple puncture tests were accepted in 95 (25%); test results were recorded in millimeters of induration in 95 (25%); and 100 (27%) reported collecting results in a centralized registry or database. Of the 168 (27%) of 624 schools accepting only Mantoux skin tests and reporting results for school years 1992-1993 through 1995-1996, 3.1% of the 348 368 students screened had positive skin test results (median percentage positive, 0.8%). International students had a significantly higher case rate for active tuberculosis than US residents (35.2 vs 1.1 per 100000 students screened). CONCLUSIONS: Widespread tuberculin screening of students yielded a low prevalence of skin test reactors and few tuberculosis cases. To optimize the use of limited public health resources, tuberculin screening should target students at high risk for infection.

Adolescent↗

Weaver syndrome: autosomal dominant inheritance of the disorder.

Weaver syndrome (WS), a condition first described in 1974 by Weaver et al., consists of macrosomia, advanced skeletal age, characteristic pattern of facial and radiographic anomalies, and contractures. Although there have been three reports of close relatives (sibs or both parent and offspring) affected with this condition, the syndrome generally occurs sporadically, and the recurrence risk in sporadic cases appears to be low. We report here on a family in which the propositus and his sister were born with the facial phenotype, club feet, and macrosomia characteristic of WS. Their father had macrosomia and macrocephaly as an adult, and childhood photos show clearly that he has WS. Two sisters of the propositus have had normal growth and development. The syndrome in this family appears to be inherited in an autosomal dominant fashion.

Craniofacial Abnormalities↗

Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors: a prospective controlled multicenter study.

CONTEXT: Although a large number of women of reproductive age use new selective serotonin reuptake inhibitors (SSRIs) and half of all pregnancies are unplanned, no data exist on the safety of these agents for the human fetus. OBJECTIVE: To assess fetal safety and risk of fluvoxamine, paroxetine, and sertraline. DESIGN: A prospective, multicenter, controlled cohort study. SETTING: Nine Teratology Information Service centers in the United States and Canada. PATIENTS: All women who were counseled during pregnancy following exposure to a new SSRI and followed up by the participating centers. Controls were randomly selected from women counseled after exposure to nonteratogenic agents. MAIN OUTCOME MEASURES: Rates of major congenital malformations. RESULTS: A total of 267 women exposed to an SSRI and 267 controls were studied. Exposure to SSRIs was not associated with either increased risk for major malformations (9/222 live births [4.1%] vs 9/235 live births [3.8%] in the controls, relative risk, 1.06, 95% confidence interval, 0.43-2.62) or higher rates of miscarriage, stillbirth, or prematurity. Mean (SD) birth weights among SSRI users (3439 [505] g) were similar to the controls (3445 [610] g) as were the gestational ages (39.4 [1.7] weeks vs 39.4 [1.9] weeks). CONCLUSION: The new SSRIs, fluvoxamine, paroxetine, and sertraline, do not appear to increase the teratogenic risk when used in their recommended doses.

1-Naphthylamine↗

New methods for detection of anti-nuclear antibodies.

Many different autoantibodies which react with a variety of different nuclear and cytoplasmic antigens have been described. Detection of some these antibodies has been shown to be clinically useful in a number of different autoimmune diseases. For many years, the detection of most of the clinically relevant antibodies was done with by immunofluorescence on tissue substrates and human cultured cell lines. Within the past few years, a number of technical advances has now made it possible to convert to enzyme immunoassay. The paper reviews the clinically relevant antibodies and discusses the variety of new methods which are now available for ANA detection in diagnostic laboratories.

Antibodies, Antinuclear↗

The effects of high-intensity intermittent exercise on the plasma concentrations of glutamine and organic acids.

Glutamine is an essential substrate for the proper functioning of cells of the immune system. Falls in plasma glutamine concentration after exercise may have deleterious consequences for immune cell function and render the individual more susceptible to infection. The purpose of the present study was to examine changes in plasma glutamine concentration (measured using a validated enzymatic spectrophotometric method) following an acute bout of intermittent high-intensity exercise. Eight well-trained male games players took part in the study. Subjects reported to the laboratory following an overnight fast and performed a 1-h cycle exercise task consisting of 20 1-min periods at 100% maximal O2 consumption (VO2max) each separated by 2 min of recovery at 30% VO2max. Venous blood samples were taken before exercise and at 5 min, 1 h, 2.5 h, 5 h and 24 h post-exercise. Glutamine was measured by enzymatic spectrophotometric determination of the ammonia concentration before and after treatment of the plasma with glutaminase (EC 3.5.1.2). Plasma glutamine concentration did not fall in the immediate post-exercise period [pre-exercise 681 (23) microM compared with 663 (46) microM at 5 min post-exercise, mean (SEM)], but fell to 572 (35) microM at 5 h post-exercise (P < 0.05 compared with pre-exercise). Plasma lactate concentration rose to 8.8 (1.0) mM at the end of exercise and fell to 1.8 (0.4) mM at 1 h post-exercise, but plasma concentrations of free fatty acids and beta-hydroxybutyrate both rose substantially in the post-exercise period (to 240% and 400% of pre-exercise levels, respectively). The circulating leucocyte count increased significantly during exercise (P < 0.01), continued to increase in the hours following exercise and peaked at 2.5 h post-exercise (mainly due to a neutrophilia). The fall in the plasma glutamine concentration at 5 h post-exercise could be due to increased renal uptake of glutamine, which generally occurs in conditions of metabolic acidosis or due to a greater removal of glutamine from the plasma resulting from the elevated circulating leucocyte count.

3-Hydroxybutyric Acid↗

The effect of severe eccentric exercise-induced muscle damage on plasma elastase, glutamine and zinc concentrations.

The aim of this study was to determine if severe exercise-induced muscle damage alters the plasma concentrations of glutamine and zinc. Changes in plasma concentrations of glutamine, zinc and polymorphonuclear elastase (an index of phagocytic cell activation) were examined for up to 10 days following eccentric exercise of the knee extensors of one leg in eight untrained subjects. The exercise bout consisted of 20 repetitions of electrically stimulated eccentric muscle actions on an isokinetic dynamometer. Subjects experienced severe muscle soreness and large increases in plasma creatine kinase activity indicative of muscle fibre damage. Peak soreness occurred at 2 days post-exercise and peak creatine kinase activity [21714 (6416) U x l(-1) mean (SEM)] occurred at 3 days post-exercise (P < 0.01 compared with pre-exercise). Plasma elastase concentration was increased at 3 days post-exercise compared with pre-exercise (P < 0.05), and is presumably indicative of ongoing phagocytic leucocyte infiltration and activation in the damaged muscles. There were no significant changes in plasma zinc and glutamine concentrations in the days following eccentric exercise. We conclude that exercise-induced muscle damage does not produce changes in plasma glutamine or zinc concentrations despite evidence of phagocytic neutrophil activation.

Adult↗