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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 469 records · Page 26Linked to original sources
PubMed1996

Confirmation of association between expanded CAG/CTG repeats and both schizophrenia and bipolar disorder.

Recent studies have suggested that expanded CAG/CTG repeats contribute to the genetic aetiology of schizophrenia and bipolar disorder. However, the nature of this contribution is uncertain and difficult to predict from other known trinucleotide repeat diseases that display much simpler patterns of inheritance. We have sought to replicate and extend earlier findings using Repeat Expansion Detection in an enlarged sample of 152 patients with schizophrenia, 143 patients with bipolar disorder, and 160 controls. We have also examined DNA from the parents of 62 probands with schizophrenia or bipolar disorder. Our results confirm our earlier, preliminary findings of an association between expanded trinucleotide repeats and both schizophrenia and bipolar disorder. However, our data do not support the hypothesis that trinucleotide repeat expansion can alone explain the complex patterns of inheritance of the functional psychoses neither can this mechanism fully explain apparent anticipation.

Adult↗
PubMed1996

A multicentre inter-rater reliability study using the OPCRIT computerized diagnostic system.

We examined the reliability of the OPCRIT system from ratings produced by 30 USA and European clinicians involved in molecular genetic research. The OPCRIT system facilitates a polydiagnostic approach to research on severe psychiatric disorders. OPCRIT comprises a 90-item checklist of signs and symptoms and a suite of computer programs, which together generate diagnoses according to the operational criteria of 12 major classificatory systems (e.g. DSM-III, DSM-III-R, RDC, ICD-10). Thirty summaries of actual cases ranging in signs and symptoms, taken from independent sources, were rated by participants from research centres across Europe and the USA using the OPCRIT system. Each rating was then compared to a standard rating using a kappa statistic. Good levels of reliability were observed within all classifications (e.g. DSM-III-R, kappa = 0.73, RDC, kappa = 0.71; ICD-10, kappa = 0.70) and a similar pattern of ratings was found in both the European and USA samples. We conclude that the OPCRIT system, is both flexible and practicable retaining the 'top-down' advantage of operational definitions as well as the 'bottom-up' potential offered by well defined signs, symptoms and other component items. Within the limitations of an international, multicentre design this study shows that the OPCRIT system affords good reliability with raters from a variety of geographical and theoretical backgrounds.

Diagnosis, Computer-Assisted↗
PubMed1996

The design of agents to control DNA methylation adducts. Enhanced major groove methylation of DNA by an N-methyl-N-nitrosourea functionalized phenyl neutral red intercalator.

An N-methyl-N-nitrosourea (MNU) moiety [CH3N(N=O)C(=O)NH-] linked to the C4'-position of the 5-substituted phenyl ring of phenyl neutral red (PNR), 2-methyl-3-amino-5-[p-[[2-[(N-nitroso-N-methylcarbamoyl)amino]ethy l] carbamoyl]phenyl]-7-(dimethylamino)phenazenium chloride (MNU-PNR), has been synthesized as an approach to design a molecule that will deliver alkylating agents with some preference to guanine (Gua) in the major groove of DNA. The PNR nucleus was chosen because previous studies suggested the following: (1) PNR binds with a slight preference for G/C rich sequences; and (2) PNR intercalates into DNA from the major groove with the 5-phenyl ring pointing out into the major groove (Müller, W., Bünemann, H., and Dattagupta, N. (1975) Eur. J. Biochem. 54, 279-291). It is demonstrated that MNU-PNR yields 2.6 and 6.0 times more N7-methylguanine (7-MeGua) than MNU at low salt (10 mM Tris buffer) and high salt (10 mM Tris buffer + 200 mM NaCl), respectively. It is also shown that the ratio of 7-MeGua (a major groove adduct) to N3-methyladenine (a minor groove adduct) is approximately 5 times higher for MNU-PNR than for MNU. The yield of the 7-MeGua adduct is decreased by the coaddition of a nonmethylating analogue of MNU-PNR or NaCl, but increased in the presence of the minor groove intercalator, ethidium bromide. Using a 32P-end-labeled restriction fragment, the enhanced methylation by MNU-PNR at 7-Gua is confirmed, and it is demonstrated that the sequence-dependent formation of 7-MeGua from MNU-PNR is the same as that seen with MNU. UV, circular dichrosism, and viscosity studies are consistent with MNU-PNR binding to DNA via an intercalation-based process.

Adenine↗
PubMed1996

Reproducibility of a self-administered diet history questionnaire administered three times over three different seasons.

The reproducibility of the widely used Health Habits and History Questionnaire (HHHQ) for estimating "usual past-year" nutrient intake was examined. The HHHQ was self-administered on three occasions during three different seasons; 68 women (avg age 43 yrs) provided usable data for all three questionnaires in the appropriate seasons. Intraclass correlations (ICC) among the three administrations ranged from 0.56 (carotene) to 0.82 (fat as percentage of energy), with a median of 0.72. Thus, reliability was moderate to good, and season of administration/ordinality generally had little impact on ranking of individuals. The point estimates of intake of energy and a number of nutrients were higher in the first administration (winter). Except for dietary fiber and possibly carotene, most differences disappeared when adjusted for energy using a nutrient density approach, as well as using repeated-measures regression models. The higher intake in the first administration may be due more to either learning or fatigue effect rather than an effect of seasonal food availability on perceptions of "usual" intake. These data should be used in conjunction with validity data in the future to help evaluate the gain in precision of group means (and changes in these means) and improved estimates of odds ratios and correlations between nutrients and factors such as serum values, if a questionnaire is administered more than once.

Adult↗
PubMed1996

Liver function and morphology after resuscitation from severe hemorrhagic shock with hemoglobin solutions or autologous blood.

OBJECTIVE: To test the effects of three hemoglobin solutions on liver function and hepatic morphology after resuscitation from severe hemorrhagic shock. DESIGN: Prospective study. SETTING: Laboratory. SUBJECTS: Thirty-three beagle dogs. INTERVENTION: Hemorrhagic shock was induced in anesthetized dogs by removal of blood at a rate of 2 mL/kg/min until systolic blood pressure (BP) reached 50 mm Hg. BP was maintained at this level 2 hrs by further withdrawing 5 to 10 mL aliquots whenever BP increased > 50 mm Hg. Resuscitation was then initiated with autologous whole blood (n = 7), 4% pyridoxalated-hemoglobin-polyoxyethylene conjugate (4% PHP [n = 6]), 8% pyridoxalated-hemoglobin-polyoxyethylene conjugate (8% PHP [n = 9], or 8% stroma-free hemoglobin (n = 7). Four dogs were managed identically but were not resuscitated. Gross necropsy and histologic examination of the liver were performed on all dogs after 7 days, or earlier if death occurred. MEASUREMENTS AND MAIN RESULTS: In vitro interferences of PHP and stroma-free hemoglobin with liver function tests were determined and recommendations for interpretation of results from blood samples containing PHP and stroma-free hemoglobin were made. Blood was collected before, during, and after resuscitation from hemorrhagic shock. The dogs were then awakened and survivors were monitored daily with blood sampling until they were killed and necropsy was performed. After 7 days, the survival rate following hemorrhagic shock was 100% for whole blood and 4% PHP, 86% for stroma-free hemoglobin, and 33% for 8% PHP. Of the resuscitated dogs not surviving 7 days, all but one died within 27 hrs from coagulopathy. All dogs not resuscitated died within 1.75 hrs after 2 hrs of shock. Bilirubin, alkaline phosphatase, and lactic dehydrogenase concentrations could not be measured due to interferences of stroma-free hemoglobin and PHP. Aspartate (AST) and alanine (ALT) aminotransferase concentrations could be measured after dilution to overcome the interferences. Significant increases in AST and ALT values in all groups 24 hrs after resuscitation were attributed to hypoxic hepatocellular damage associated with the severity of the shock model rather than to the resuscitation fluid. Liver histology showed no changes attributed to toxic damage of hepatocytes in dogs resuscitated with stroma-free hemoglobin or PHP. However, changes, were less severe in dogs resuscitated with 4% PHP than in other groups. CONCLUSION: Morphologic studies at necropsy and liver function tests in dogs receiving hemoglobin solutions, compared with autologous blood, support the conclusion that the PHP and stroma-free hemoglobin solutions tested did not produce hepatic toxicity when used as resuscitation fluids in this model of severe shock.

Acute Disease↗
PubMed1996

Prevention of anaemia in inner city toddlers by an iron supplemented cows' milk formula.

There are few data to support the use of follow-on formulas in infants from the age of 6 months. In a prospective trial in a deprived inner city area of Birmingham 100 infants who were already receiving pasteurised cows' milk by 6 months of age were enrolled and randomised either to receive a follow-on formula or to continue on cows' milk from 6 months until 18 months. At 18 months of age the follow-on formula group returned to cows' milk and both groups were followed up until 24 months. Iron status, growth, and nutritional status were analysed at intervals of six months. At enrollment, no differences in haematological status were evident. However, by 12 months of age, 31% of the cows' milk group were anaemic (haemoglobin concentration < 110 g/l) compared with only 3% of those receiving follow-on formulas. At 18 months, 33% of the cows' milk group were anaemic compared with only 2% of the follow-on formula group and by 24 months of age none of the follow-on formula group was anaemic, whereas 26% in the cows' milk group still had a haemoglobin of < 110 g/l. Mean corpuscular volume was significantly smaller and ferritin significantly lower in the cows' milk group at 12, 18, and 24 months. Dietary iron intake was higher in the follow-on formula group at 12 and 18 months but not at 24 months, when both groups were back on cows' milk. Infants and toddlers at high risk of iron deficiency are therefore unlikely to become anaemic if receiving a follow-on formula, although the relative merits of follow-on formula compared with an ordinary infant formula remain uncertain.

Anemia, Iron-Deficiency↗
PubMed1996

No evidence for allelic association between schizophrenia and a polymorphism determining high or low catechol O-methyltransferase activity.

OBJECTIVE: Catechol O-methyltransferase (COMT) inactivates catecholamines by methylating their m-hydroxy group. Some previous studies using biochemical methods have found higher levels of COMT activity in schizophrenic patients. Recently, the genetic polymorphism that underlies variation in COMT activity, which results in the creation of a NlaIII restriction site in the low-activity allele, has been elucidated. METHOD: This study investigated this polymorphism in 78 unrelated schizophrenic patients and 78 comparison subjects matched for age and ethnicity. High-molecular-weight DNA was isolated from lymphocytes with routine procedures, and each individual was typed for high and low COMT activity. RESULTS: The frequency of the NlaIII polymorphism was 0.51 in the schizophrenic patients and 0.53 in the comparison subjects, and no significant allelic or genotypic associations were observed. CONCLUSIONS: There was no evidence for variation in COMT activity between a group of schizophrenic patients and matched comparison subjects.

Alleles↗
PubMed1996

Behavioral descriptors that differentiate between seizure and nonseizure events in a pediatric population.

The diagnosis and treatment of epilepsy relies heavily on descriptions of behavioral changes noted during seizure episodes. A pilot study was completed to determine the frequency of occurrence of behaviors commonly associated with seizures in a pediatric population (n = 153). Caretakers of the children (ages = 4 months to 19 years) were asked to respond to a checklist containing 40 behavioral descriptors. Thirteen descriptors were found to differentiate between seizure and nonseizure events. Twelve of these behaviors were endorsed significantly more frequently by caretakers of children with seizures including the following: does not remember what happened, moves mouth funny, drools, jerking/twitching, becomes stiff, changes in breathing, stares off, bites or chews tongue, eyes look glassy, will not respond, mumbles or slurs words, and eyes or head turn to one side. One behavior, fidgets in seat, was significantly more associated with nonseizure episodes. The behavioral descriptors may be presented in a checklist format or incorporated within a clinical interview in primary care settings for initial screening of children with possible seizure disorders.

Adolescent↗
PubMed1996

Concurrent validity of the OPCRIT diagnostic system. Comparison of OPCRIT diagnoses with consensus best-estimate lifetime diagnoses.

BACKGROUND: OPCRIT (a suite of computer programs that allow data entry and generate diagnoses according to 12 operational diagnostic systems) is used in a wide range of psychiatric research including both European Science Foundation and NIMH research initiatives in the molecular genetics of mental disorders. We examined its concurrent validity in 100 subjects collected for linkage studies of Bipolar Disorder and Schizophrenia. METHOD: We compared diagnoses generated by OPCRIT from data rated by two trained clinicians with diagnoses made according to consensus, best-estimate, lifetime procedures by the same two raters according to DSM-III-R and RDC classifications. RESULTS: Good to excellent agreement was achieved between OPCRIT diagnoses and those made by consensus best-estimate procedures. CONCLUSIONS: OPCRIT provides a convenient, reliable, rapid and valid approach to polydiagnostic assessment that can be used as an adjunct to conventional (but time consulting) best-estimate consensus diagnostic procedures.

Bipolar Disorder↗
PubMed1996

The initiation of basal disc formation in Dictyostelium discoideum is an early event in culmination.

We have analysed expression of the ecmA and ecmB genes of Dictyostelium by enzymatic double staining using beta-galactosidase and beta-glucuronidase reporter gene constructs. Cells expressing the ecmA gene first appear as scattered cells at the mound stage of development and we show that this is also true for cells expressing the ecmB gene. During tip formation the ecmA-expressing cells move to the apex of the mound, while the ecmB-expressing cells accumulate in the base. The ecmB-expressing cells constitute part of the basal disc if the culminant is formed in situ but are discarded if a migratory slug is formed. During slug migration they are replaced by a band of ecmB-expressing cells, situated in the front half of the prespore zone and tightly apposed to the substratum. When culmination is triggered these cells rapidly move to the back half of the prestalk zone, possibly acting as a point of attachment to the substratum. Ultimately, they are joined by cells at the back of the slug, the rearguard cells, to form the basal disc. Thus, contrary to previous belief, basal disc formation is initiated very early during culmination and occurs by the forward movement of cells located in the anterior of the prespore zone.

Animals↗
PubMed1996

Retreatment of patients surviving cancer-free 2 or more years after initial treatment of small cell lung cancer.

STUDY OBJECTIVE: To assess the outcome after retreatment of patients with small cell lung cancer (SCLC) who redevelop small cell cancer (SCC) 2 or more years after initial therapy. DESIGN: Retrospective analysis. SETTING: Single government institution: the National Cancer Institute. PATIENTS: Twenty patients who redeveloped SCC among 65 patients who survived 2 or more years after starting treatment for their initial cancer. MEASUREMENTS: The response rate of patients after retreatment, the survival duration from the time of redevelopment of SCC, and the toxicities of retreatment. RESULTS: Twenty patients redeveloped SCC: 18 with a relapse and 2 with a second primary cancer. Sixteen received treatment after they redeveloped SCLC while four did not. Eleven patients were retreated with chemotherapy alone, two patients received chemotherapy plus chest radiotherapy, one patient received radiotherapy alone, one patient underwent lobectomy, and one patient was treated with a monoclonal antibody followed by chemotherapy. Nine of 16 patients (56%) treated after they redeveloped SCLC had an objective response (3 complete and 6 partial). The median survival of all 20 patients after they redeveloped SCC was 3.9 months (range, 0 to 46 months). The median survival of the patients who were retreated was 6.5 months (range, 1 to 46 months). CONCLUSIONS: Patients who suffer relapses with SCLC 2 or more years from diagnosis are candidates for retreatment.

Adult↗
PubMed1996

Left-handedness increases injury risk in adolescent girls.

In a self-report survey of a representative national sample of 4081 Scottish schoolchildren, injuries requiring medical assistance were more common in left-handers; these were also more severe and likely to involve an overnight stay in hospital. Particularly at risk were adolescent girls with a 32% greater chance of being injured if they were left-handed compared with their right-handed peers. The corresponding relative risk for boys was not significant.

Adolescent↗
PubMed1996

Agenda for training.

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Education, Nursing, Continuing↗
PubMed1996

Measuring management potential.

This article provides a brief introduction to instruments that may be used to measure management potential in persons being considered for administrative positions. Instruments that measure aspects of leadership, power, personality, conflict, and organizational climate are discussed. An overview of each instrument is provided as well as data on the type of test, time to complete, cost, and purchasing information. While objective tests such as these are useful in assessing individual suitability for management positions, we advise that they be used prudently and judiciously.

Administrative Personnel↗