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Biomedical subjects

M Cole

Publications and source records attributed to M Cole.

At least 73 records · Page 4Linked to original sources
PubMed1998

Reliability and validity of a new measure of severity of delirium.

The objective of this study was to assess the psychometric properties of a new instrument, the Delirium Index (DI), to measure changes in the severity of the symptoms of delirium among patients previously diagnosed with delirium. Subjects were medical inpatients aged 65 and over diagnosed with delirium by the Confusion Assessment Method. Interrater reliability of the DI was .78 between research assistants (concordance coefficient) and was .88 between research assistants and geriatric psychiatrists. Criterion validity, assessed by the correlation between DI and Delirium Rating Scale scores (Spearman's correlation coefficient, r), was .84. Construct validity was assessed using correlations of the DI with two measures of current function for convergent validity (r = -.60, -.70) and two measures of function before admission for discriminant validity (r = .26,-.42). We conclude that the DI has acceptable levels of interrater reliability, criterion validity, and construct validity.

Aged↗
PubMed1998

A study of the feasibility and accuracy of pharmacokinetically guided etoposide dosing in children.

Pharmacokinetically guided dosing was performed in nine paediatric patients receiving etoposide. Doses on day 2 of a 2- or 3-day schedule were adapted on the basis of the day-1 area under the plasma etoposide concentration vs time curve (AUC). The day-1 AUC was estimated using a limited sampling model and the day-2 target AUC defined by the etoposide dose-AUC relationship observed in 33 children. Target AUC values (4.6-8.2 mg ml(-1) x min) were achieved with a high degree of precision and with little bias (mean error 11% and root mean squared error 15% respectively). Pharmacokinetic parameters were similar to those reported previously in children, although interpatient pharmacokinetic variability was less than that observed previously: plasma clearance, 23 (18-26) ml min(-1) m(-2); volume of distribution at steady state (Vdss), 6.0 (3.9-8.9) l m(-2); t(1/2) 254 (127-550) min (median and range). This study has demonstrated that pharmacokinetically guided dosing with etoposide is feasible. However, pharmacokinetically guided dosing is likely to be of most benefit in patients with abnormalities of renal or hepatic function, or in children with prior exposure to cisplatin.

Adolescent↗
PubMed1998

The management of coeliac disease.

One hundred children put on a gluten free diet because of suspected coeliac disease were followed for a mean period of 9.9 years. The diagnosis was eventually confirmed in 53. Under the age of two, 35 children showed subtotal villous atrophy in their initial biopsy but nine of these on subsequent gluten challenge and rebiopsy were found to tolerate gluten normally. Challenge and rebiopsy are also necessary for children over the age of two where the initial biopsy changes are less severe than subtotal villous atrophy. Such challenges can probably be carried out earlier than the recommended age of six given in the 1990 ESPGAN (European Society for Paediatric Gastroenterology and Nutrition) report with little risk of serious dental damage.

Biopsy↗
PubMed1997

Alcohol metabolism in Asian-American men with genetic polymorphisms of aldehyde dehydrogenase.

BACKGROUND: About half of certain Asians have a deficiency of the low-Km aldehyde dehydrogenase (ALDH2) isoenzyme. This deficiency results from inheritance of a mutant ALDH2*2 allele. OBJECTIVE: To determine whether Asian Americans with ALDH2*2 alleles differ from Asian Americans without this mutation in terms of blood levels of alcohol and acetaldehyde after ingestion of a moderate amount of alcohol. DESIGN: Double-blind, crossover study. SETTING: Private research institute. PARTICIPANTS: 35 healthy Asian-American men. Three men who became ill after alcohol ingestion and one who had outlying data were excluded. INTERVENTION: Alcoholic beverage, containing 0.56 g of alcohol per kg of body weight, or placebo beverage, containing 3 mL of alcohol, given orally on separate occasions. MEASUREMENTS: Blood levels of alcohol and acetaldehyde measured before and several times after ingestion of the alcoholic or placebo beverage. RESULTS: Participants with ALDH2*2 alleles had significantly higher blood acetaldehyde levels after ingesting alcoholic and placebo beverages than did participants with ALDH2*1 alleles, despite similar blood alcohol concentrations. CONCLUSIONS: Blood acetaldehyde levels rather than blood alcohol concentration may mediate enhanced alcohol sensitivity among Asians with ALDH2*2 alleles.

Acetaldehyde↗
PubMed1997

A C. elegans E/Daughterless bHLH protein marks neuronal but not striated muscle development.

The E proteins of mammals, and the related Daughterless (DA) protein of Drosophila, are ubiquitously expressed helix-loop-helix (HLH) transcription factors that play a role in many developmental processes. We report here the characterization of a related C. elegans protein, CeE/DA, which has a dynamic and restricted distribution during development. CeE/DA is present embryonically in neuronal precursors, some of which are marked by promoter activity of a newly described Achaete-scute-like gene hlh-3. In contrast, we have been unable to detect CeE/DA in CeMyoD-positive striated muscle cells. In vitro gel mobility shift analysis detects dimerization of CeE/DA with HLH-3 while efficient interaction of CeE/DA with CeMyoD is not seen. These studies suggest multiple roles for CeE/DA in C. elegans development and provide evidence that both common and alternative strategies have evolved for the use of related HLH proteins in controlling cell fates in different species.

Amino Acid Sequence↗
PubMed1997

Hsp30, the integral plasma membrane heat shock protein of Saccharomyces cerevisiae, is a stress-inducible regulator of plasma membrane H(+)-ATPase.

Saccharomyces cerevisiae has a single integral plasma membrane heat shock protein (Hsp). This Hsp30 is induced by several stresses, including heat shock, ethanol exposure, severe osmostress, weak organic acid exposure and glucose limitation. Plasma membrane H(+)-ATPase activities of heat shocked and weak acid-adapted, hsp30 mutant and wild-type cells, revealed that Hsp30 induction leads to a downregulation of the stress-stimulation of this H(+)-ATPase. Plasma membrane H(+)-ATPase activity consumes a substantial fraction of the ATP generated by the cell, a usage that will be increased by the H(+)-ATPase stimulation occurring with several Hsp30-inducing stresses. Hsp30 might therefore provide an energy conservation role, limiting excessive ATP consumption by plasma membrane H(+)-ATPase during prolonged stress exposure or glucose limitation. Consistent with the role of Hsp30 being energy conservation, Hsp30 null cultures give lower final biomass yields. They also have lower ATP levels, consistent with higher H(+)-ATPase activity, at the glucose exhaustion stage of batch fermentations (diauxic lag), when Hsp30 is normally induced. Loss of Hsp30 does not affect several stress tolerances but it extends the time needed for cells to adapt to growth under several stressful conditions where the maintenance of homeostasis will demand an unusually high usage of energy, hsp30 is the first yeast gene identified as both weak organic acid-inducible and assisting the adaptation to growth in the presence of these acids.

Adenosine Triphosphate↗
PubMed1996

Biparous: a novel bHLH gene expressed in neuronal and glial precursors in Drosophila.

Genetic studies have uncovered many genes that are involved in the first steps of neuronal development in Drosophila. Less is known about the intermediate steps during which individual precursor cells follow either the neuronal pathway or the glial pathway. We report the identification of a novel bHLH gene, biparous, expressed in neuronal and glial precursors in Drosophila. Unlike most bHLH genes, biparous expression continues to the final stages of neurogenesis in the embryo. Expression of biparous is not observed in end stage postmitotic neurons and precedes the expression of repo, a gene activated in later stages of glial differentiation. The bHLH domain is sufficiently different from previously described bHLH domains to imply a novel function.

Amino Acid Sequence↗
PubMed1996

Cyclophosphamide pharmacokinetics in children.

1. Cyclophosphamide pharmacokinetics were measured in 38 children with cancer. 2. A high degree of inter-patient variation was seen in all pharmacokinetic parameters. Cyclophosphamide half-life varied between 1.1 and 16.8 h, clearance varied between 1.2 and 10.61 h-1 m-2 and volume of distribution varied between 0.26 and 1.48 1 kg-1. 3. The half-life of cyclophosphamide was prolonged at high dose levels (P = 0.008). 4. Children who had received prior treatment with dexamethasone showed a mean increase in clearance of 2.51 h-1 m-2 (P = 0.001) presumably as a result of CYP450 enzyme induction. 5. Treatment with allopurinol or chlorpromazine was associated with a significant increase in cyclophosphamide half-life (P < 0.001 in both cases). 6. Dose and concurrent treatment may influence cyclophosphamide metabolism in vivo and thus potentially alter the drugs therapeutic effect.

Adolescent↗
PubMed1996

Alcohol elimination in Native American Mission Indians: an investigation of interindividual variation.

The high prevalence of alcohol abuse and alcohol dependence among Native Americans may be mediated by unique environmental and genetic factors in this population. One factor that may influence the development of alcoholism is variability in alcohol metabolism. To determine factors that contribute to differences in alcohol elimination rates within a Native American population, this study evaluated healthy southern California Mission Indian men between the ages of 18 and 25 years. Each man drank a dose of alcohol, 0.56 g/kg of body weight as a 20% by volume solution, at approximately 9:00 AM after eating a low-fat breakfast and having fasted overnight. The drink was consumed within 7 min, and the concentrations of alcohol in blood were determined before and at 15, 30, 60, 90, 120, and 150 min after beverage ingestion. Rates of alcohol elimination were calculated from the pseudolinear slope of the blood alcohol versus time curve. The influences of estimated body water, recent drinking history, recent smoking history, polymorphism at the ADH2 and ADH3 loci, family history of alcoholism, and percentage Native American heritage on alcohol elimination rate were determined using multiple regression analyses. Estimated body water accounted for a significant proportion of the variance in alcohol elimination rate. There was also a nonsignificant trend for subjects with an ADH2*3 allele (n = 6) to have faster rates of alcohol elimination than those with ADH2*1 alleles only (n = 33). Given the high prevalence of alcoholism and alcohol-related health problems among Native Americans, the results from this study suggest that evaluation of alcohol metabolism and genotypes of the alcohol-metabolizing enzymes in Native American populations merits further study.

Adolescent↗
PubMed1996

Intra-amygdala muscimol decreases operant ethanol self-administration in dependent rats.

Dependence is an important factor motivating continued alcohol use in human alcoholics. Development of a model of ethanol (EtOH) consumption in dependent animals would advance the understanding of reinforcement after chronic EtOH exposure and allow for the investigation of the neuropharmacological mechanisms mediating reinforcement in dependent versus nondependent animals. In the present study, rats were trained to lever press for 10% EtOH, surgically implanted with bilateral guide cannulae in the amygdala, and either made dependent on EtOH by exposure for 2 weeks to EtOH or exposed to air in identical vapor chambers. Upon removal, the rats were placed in operant boxes and allowed to respond on levers for 10% EtOH or water during a 12-hr period. Rats were removed briefly at approximately 6.5 hr for intra-amygdala injections of saline or the GABAA receptor agonist muscimol. After the test period, rats were returned to the vapor chambers for 4 days before retest. EtOH-dependent animals responded more for EtOH across the 12-hr test period than did air control nondependent rats; this difference became more pronounced with repeated test sessions. Intra-amygdala muscimol significantly decreased responding for EtOH in EtOH-dependent rats, but had no effect in nondependent controls. These data suggest that the reinforcing effects of EtOH and neurotransmitter pathways mediating reward are altered after the development of dependence, and they support the use of this paradigm for further investigations into the neuropharmacology of EtOH dependence.

Alcoholism↗
PubMed1995

An anti-murine CD3 monoclonal antibody with a low affinity for Fc gamma receptors suppresses transplantation responses while minimizing acute toxicity and immunogenicity.

145-2C11, a hamster mAb directed against the mouse CD3 complex, is a potent immunosuppressive agent. Upon initial treatment, 145-2C11 triggers a systemic release of multiple cytokines that is responsible for the acute toxicity of the mAb. This cellular activation is a consequence of the cross-linking between T lymphocytes and Fc gamma R-bearing cells, mediated by the high affinity of the hamster mAb for murine Fc gamma Rs. Repeated mAb injections result in the onset of a neutralizing humoral response. Therefore, there has been an increased interest in developing nonmitogenic forms of anti-CD3 mAbs, although it is not clear whether these Abs will retain immunosuppressive properties. To determine whether the initial cytokine production is necessary for the immunosuppressive properties and the immunogenicity of anti-CD3 mAbs in vivo, we have generated chimeric (hamster 145-2C11 F(ab')2 region/mouse Fc gamma portion) mAbs using murine isotypes with different affinities for Fc gamma Rs. The 145-2C11 and a chimeric IgG2a isotype, both of which bind murine Fc gamma Rs avidly, had similar activating, immunogenic, and immunosuppressive properties in mice. The administration of a chimeric IgG3 isotype with a very low affinity for murine Fc gamma Rs did not result in cytokine production, a humoral response against the mAb, or TCR desensitization. Nevertheless, prolongation of skin graft survival was similar in the IgG3, IgG2a, and 145-2C11-treated mice, indicating that Fc gamma R nonbinding anti-CD3 mAbs retain potent immunosuppressive properties in vivo while not being immunogenic. This enhanced therapeutic to toxic profile may be beneficial in clinical transplantation.

Amino Acid Sequence↗
PubMed1995

Decreased brain reward produced by ethanol withdrawal.

Abstinence from chronic administration of various drugs of abuse such as ethanol, opiates, and psychostimulants results in withdrawal syndromes largely unique to each drug class. However, one symptom that appears common to these withdrawal syndromes in humans is a negative affective/motivational state. Prior work in rodents has shown that elevations in intracranial self-stimulation (ICSS) reward thresholds provide a quantitative index that serves as a model for the negative affective state during withdrawal from psychostimulants and opiates. The current study sought to determine whether ICSS threshold elevations also accompany abstinence from chronic ethanol exposure sufficient to induce physical dependence. Rats prepared with stimulating electrodes in the lateral hypothalamus were trained in a discrete-trial current-intensity ICSS threshold procedure; subsequently they were subjected to chronic ethanol administration in ethanol vapor chambers (average blood alcohol level of 197 mg/dl). A time-dependent elevation in ICSS thresholds was observed following removal from the ethanol, but not the control, chambers. Thresholds were significantly elevated for 48 hr after cessation of ethanol exposure, with peak elevations observed at 6-8 hr. Blood alcohol levels were directly correlated with the magnitude of peak threshold elevation. Ratings of traditional overt signs of withdrawal showed a similar time course of expression and resolution. The results suggest that decreased function of reward systems (elevations in reward thresholds) is a common element of withdrawal from chronic administration of several diverse classes of abused drugs.

Alcoholism↗
PubMed1995

Urinary creatinine adjusted reference ranges for homovanillic and vanillylmandelic acid in children and adults.

The relationship between urinary homovanillic acid (HVA), vanillylmandelic acid (VMA) and creatinine is investigated and reference ranges are constructed for HVA and VMA. A total of 769 urine samples were obtained from children and adults. The ratios HVA/creatinine and VMA/creatinine were highly correlated with creatinine concentration; hence, reference to creatinine was found to be an inappropriate adjustment for urinary dilution. An alternative method based upon linear regression is proposed. After allowing for differing levels of creatinine, HVA and VMA were found to be significantly correlated with age, height and weight for individuals aged less than 20 years. In those aged over 20 years, HVA was significantly correlated with weight and VMA with age. Differences between sexes were found in the levels of HVA and VMA, the exception being VMA in the over 20 age group. Reference ranges were constructed for HVA and VMA which are variously dependent upon creatinine, age, sex and weight.

Adolescent↗