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Biomedical subjects

C Clark

Publications and source records attributed to C Clark.

At least 91 records · Page 5Linked to original sources

Rapid tryptophan depletion, sleep electroencephalogram, and mood in men with remitted depression on serotonin reuptake inhibitors.

BACKGROUND: In previous studies, depletion of brain serotonin by administration of a tryptophan-free amino acid drink (TFD) (1) temporarily reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) in euthymic patients who had a history of major depression, and (2) enhanced rapid eye movement (REM) sleep in normal volunteers. In this study, we hypothesized that the TFD would not only increase depressive symptoms but also the propensity for REM sleep in euthymic patients treated with SSRIs. METHODS: Ten fully remitted, medicated male patients who had a history of major depressive episode ingested a 100-g TFD (the experimental dose) or a 25-g TFD (designed to be the control drink) in double-blind, random order on separate days. The effects were assessed with mood ratings, plasma tryptophan concentrations, and an all-night sleep electroencephalogram. RESULTS: The TFDs produced a dose-dependent reduction in plasma tryptophan concentrations, sleep latency, and REM latency, as well as increased REM percentage, REM minutes, REM density, and total sleep time. Neither strength of TFD altered mood to a clinically significant degree. CONCLUSIONS: Although the TFD affected plasma tryptophan concentrations and various sleep measures, our study did not confirm previous reports that TFD temporarily reversed the antidepressant effects of SSRIs in euthymic patients. Our patients, however, had been treated for a longer period with SSRIs and were more fully remitted at the time of the study. Our results suggest that TFD-induced relapse in SSRI-treated patients in remission decreases as a function of treatment duration, degree of remission, or both.

Amino Acids↗

The use of an oligonucleotide that hybridizes to DNA sequences interspersed in the genome of members of the genus Phytophthora as an adjunct to morphological criteria in species identification.

An oligonucleotide (primer), designed from a conserved region of the multi-allelic b locus of the basidiomycete fungus Ustilago maydis, generated reproducible PCR fingerprints in Phytophthora species. The primer hybridized in a species-specific manner to nucleotide sequences interspersed in the genome of the closely related members of Phytophthora taxonomic group IV. We recommend the use of this PCR procedure as an alternative method for resolving the close taxonomic affinity of some members of the genus Phytophthora.

DNA↗

The Genome Sequence DataBase version 1.0 (GSDB): from low pass sequences to complete genomes.

The Genome Sequence DataBase (GSDB) has completed its conversion to an improved relational database. The new database, GSDB 1.0, is fully operational and publicly available. Data contributions, including both original sequence submissions and community annotation, are being accomplished through the use of a graphical client-server interface tool, the GSDB Annotator, and via GIO (GSDB Input/Output) files. Data retrieval services are being provided through a new Web Query Tool and direct SQL. All methods of data contribution and data retrieval fully support the new data types that have been incorporated into GSDB, including discontiguous sequences, multiple sequence alignments, and community annotation.

Animals↗

Differential effects on TNF alpha production by pharmacological agents with varying molecular sites of action.

This study describes the activation conditions for tumor necrosis factor-alpha (TNF alpha) production in myelomonocytic U937 cells and human primary peripheral blood monocytes in response to lipopolysaccharide (LPS) and/or phorbol 12-myristate 13-acetate (PMA). PMA itself induced only low levels of TNF alpha production with delayed kinetics (e.g. 0.758 +/- 0.128 ng/ml from U937 cells after 48 h) while LPS induced greater levels of TNF alpha production in less time (e.g. 2.083 +/- 0.96 ng/ml from monocytes in 24 h). Pharmacological agents with various molecular sites of action were used to validate the two systems, with the protein serine-threonine kinase inhibitors staurosporine and Ro-31-8220, the protein tyrosine kinase inhibitor herbimycin A (HBA) and dexamethasone exhibiting the greatest potency (IC50S 5-350 nM). In contrast to the effect on TNF alpha production, PMA induced strong phosphorylation/activation of p42/p44mapk in monocytes by 10 min determined in a mobility shift assay, while LPS was a weaker inducer. Additionally, staurosporine (to LPS and PMA) and HBA (to LPS only) inhibited the activation of these mitogen-activated protein kinase (MAPK) isoforms at doses 10-100 fold higher than those required to inhibit maximal TNF alpha production. These data indicate the involvement of the p42/p44mapk signalling pathway in LPS-induced pro-inflammatory cytokine production but suggest that other signalling pathways are also implicated in this phenomenon.

Benzoquinones↗

Measurement of gastric mucosal carbon dioxide tension by saline and air tonometry.

PURPOSE: This study compares the balloon air tonometry method of measuring gastric mucosal CO2 to standard saline tonometry. Also, this study investigates the effect of histamine-2 receptor blockade on the precision of tonometric measures of gastric mucosal PCO2 (PtCO2). MATERIALS AND METHODS: We obtained hourly measurements of PtCO2 from two gastric tonometers inserted orally in 19 healthy volunteers. One tonometer measured PtCO2 by the intermittent saline method, whereas the other measured PtCO2 using a newer continuous air method. Subjects received intravenous 5% dextrose during the first 6 hours of the experiment followed by a continuous infusion of a solution of ranitidine in 5% dextrose for another 6 hours. The ranitidine infusion was titrated to maintain gastric fluid pH > or = 4. RESULTS: Comparison of air to saline tonometry yielded a bias of -1.3 mm Hg with a limit of agreement of 6.6 mm Hg under optimal conditions of optimal gastric fluid pH (gastric fluid pH > or = 5.0). Measures of PtCO2 were lower with ranitidine for either group, 45.3 +/- 1.3 mm Hg versus 39.7 +/- 0.5 mm Hg for saline (P < .01) and 45.9 +/- 1.0 versus 41.3 +/- 0.5 for air (P < .01). The mean PCO2 gap (PtCO2-P(arterial)CO2) at gastric fluid pH > or = 5.0 was 1.4 mm Hg, with a standard deviation of 2.7 mm Hg. A span of three standard deviations yields a normal limit for PCO2 gap of 9.5 mm Hg. CONCLUSION: Measures of PtCO2 with the air tonometer method are similar to those obtained with saline tonometry. The reliability of PtCO2 measurements with either method improved with the use of ranitidine to maintain gastric fluid pH > or = 5.

Adult↗

Assessment of CSF levels of tau protein in mildly demented patients with Alzheimer's disease.

CSF levels of tau protein are increased in many patients with Alzheimer's disease (AD). Studies disagree on whether the increase is found in moderate or severe AD to a greater extent than in mild AD, and in two reports there was an inverse correlation between tau levels and cognitive scores. To readdress this question, we measured CSF tau in a group of mildly impaired patients with AD (Mini-Mental State Examination [MMSE] scores > or =20/30) and compared their tau levels with those in age-comparable normal and neurologic controls. We found that the mean level of CSF tau was significantly increased in the AD group compared with the controls, and 29 of 36 patients with AD had levels that exceeded a cutoff determined in a previous study. CSF tau levels did not correlate with MMSE scores. These findings and those of previous studies show that elevated CSF tau levels are found in most patients with AD, occur early in the course of dementia, and may be useful in supporting the diagnosis of AD.

Aged↗

Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer's Disease Assessment Scale that broaden its scope. The Alzheimer's Disease Cooperative Study.

The cognitive assessment protocol of the Alzheimer's Disease Cooperative Study (ADCS) was designed to evaluate the reliability and validity of cognitive assessment measures that might be valuable additions to the Alzheimer's Disease Assessment Scale (ADAS) or other concise batteries used in antidementia drug trials. As part of an overall ADCS protocol to develop new instruments to be used in trials of treatments for Alzheimer's disease (AD), patients with mild to moderate AD and cognitively normal elderly were administered a battery of five tests at least three times over 1 year. The tests included word list learning with delayed free recall, a recognition memory test for faces, a series of letter and digit cancellation tests to measure concentration, tests of praxis, and a series of maze completion tasks designed to assess planning and executive function. A version of the digit cancellation task was reliable and sensitive to a broad range of dementia severity so that it could provide a useful addition to the present version of the ADAS. Performance on the word learning task with delayed recall and a subset of the mazes task were impaired even in mild AD, so these tasks may be useful in trials involving mild or at-risk subjects. Performances on the facial recognition task and on the praxis tasks were not related to dementia severity, so these tasks would not be useful to evaluate treatments. Therefore, the major outcome of this investigation was the identification of some potential additions to the present ADAS that extend both the cognitive domains and the range of symptom severity covered.

Aged↗

Health promotion and screening services reported by older adult patients of urban primary care physicians.

BACKGROUND: Adult preventive services provided at intervals recommended by expert panel guidelines may reduce morbidity and mortality. As part of an intervention trial to increase primary preventive services in urban primary care practices, baseline data were collected on primary prevention and screening test rates in older adults and on patient characteristics associated with provision of these services. METHODS: A questionnaire on preventive services offered or provided over the past 2 years was completed by patients aged 52 to 77 years and another by their 42 participating physicians. Logistic regression was used to identify patient characteristics associated with increased provision of these services. RESULTS: Usable questionnaires were completed by 1457 (80.9%) patients. Patient age and sex were not associated with the provision of primary preventive and counseling services. The presence of two or more chronic diseases was predictive of primary preventive services (P < .02), but was not associated with an increase in screening tests or procedures. Age was positively associated with delivery of prostate-specific antigen blood tests (P < .001) and rectal examinations (P < .001) in men, but was negatively associated with mammography (P < .001) and Papanicolaou (Pap) tests (P = .02) in women. The negative trend in screening mammography was evident even for women aged 50 to 65 years despite the national consensus regarding the benefits of screening for this age group. Patients with health management organization insurance reported significantly more mammography (P = .002), cervical Pap tests (P = .050), sigmoidoscopies (P = .002), and fecal occult blood tests (P = .035). CONCLUSIONS: In our study patients, the provision of primary preventive and screening services was closer to consensus guidelines than is typically reported in the literature. The data suggest that future investigations and interventions to improve primary prevention and screening services in older adults who have access to primary care do not need to be directed at fundamental changes in the way preventive services are delivered, but rather should target procedures of proven benefit, such as mammography, where rates remain below recommended guidelines.

Age Factors↗

OTC prescribing.

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Drug Costs↗

Trust in time.

Educator Ray Brown once said, ¿I never want to hire anyone who hasn't been fired at least once.¿ Well, we all know a few of the ¿right¿ reasons for being fired, or those that occur entirely beyond our control. You may be asked to perform an unethical or even illegal act, for instance, or one that violates your personal values, and refuse. But you want to keep your job. How can you be sure you do?

Chief Executive Officers, Hospital↗

Cranial desmoid tumor associated with homozygous inactivation of the adenomatous polyposis coli gene in a 2-year-old girl with familial adenomatous polyposis.

BACKGROUND: Familial adenomatous polyposis (FAP) is a dominantly inherited disorder characterized by the presence of more than 100 adenomatous polyps in the colon and rectum starting in the second decade of life. FAP is associated with extra colonic manifestations, including desmoid tumors. METHODS: A 2-year-old girl presented with a rapidly enlarging tumor of the forehead and a family history of FAP. The tumor was cultured for cytogenetic studies. A DNA linkage study using flanking and intragenic polymorphisms of the adenomatous polyposis coli (APC) gene was performed to identify the allele loss in the tumor. Germline mutation identification was by single strand conformation polymorphism analysis of exon 15 of the APC gene, with subsequent double stranded sequencing of fragments with conformational changes. A mutation-induced loss of a restriction site was used to confirm allele loss in the tumor. RESULTS: Microscopically, the tumor had desmoid features. Cytogenetic analysis of the tumor demonstrated loss of chromosome region 5(q21q22). A truncating adenomatous polyposis coli (APC) gene mutation was identified in the leukocyte DNA from the child and her affected father. Linked DNA markers suggested that the tumor had lost the maternal, wild-type allele. A mutation-induced restriction endonuclease site alteration demonstrated hemizygosity of the mutant sequence in the tumor DNA. CONCLUSIONS: These findings are compatible with the presence of a "second hit" inactivation of the APC gene and implicate this gene in the pathogenesis of desmoid tumors.

Adenomatous Polyposis Coli↗

Boerhaave's syndrome and children: a rare and unexpected combination.

Boerhaave's syndrome, or the spontaneous rupture of the esophagus, appears most commonly in males between the ages of 40 and 60. Severe vomiting followed by excruciating chest pain are the classic clinical signs, often in conjunction with a history of over indulgence in food and alcohol. The authors describe a case of Boerhaave's syndrome in a child, the result of missed appendicitis.

Appendicitis↗

Pulmonary lactate release in patients with sepsis and the adult respiratory distress syndrome.

PURPOSE: Elevated arterial lactate concentrations in patients with sepsis have been interpreted as evidence of peripheral, nonpulmonary tissue hypoxia. These patients often develop pulmonary failure manifested by the acute respiratory distress syndrome (ARDS). As the result of tissue hypoxia or inflammation, the lungs of patients with sepsis and ARDS may become a source of lactate release into the circulation. MATERIALS AND METHODS: Pulmonary lactate release was measured in 19 patients with sepsis, arterial lactate > or = 2.2 mm, and gastric mucosal pH > 7.30. A normal gastric mucosal pH served as a marker of adequate splanchnic oxygenation. Pulmonary lactate release was computed as the product of the cardiac index and the difference in plasma L-lactate concentration in simultaneously obtained arterial and mixed venous blood samples. Lung injury was graded with the Lung Injury Score using radiographic and physiologic data. RESULTS: The lungs of patients with minimal or no lung injury (lung injury score <1) produced significantly less lactate than those with moderate or severe lung injury (lung injury score > or = 1) (P < .005). The Lung Injury Score correlated with pulmonary lactate release (r2 = .73; P < .0001). This relationship resulted primarily from increases in mixed venous-arterial lactate differences (r2 = .59). The Lung Injury Score correlated weakly with the cardiac index (r2 = .32). Arterial lactate concentration did not correlate with pulmonary lactate release, systemic oxygen transport, or systemic oxygen consumption. CONCLUSIONS: The lungs of patients with sepsis and ARDS may produce lactate. Pulmonary lactate release correlates with the severity of lung injury. The contribution of pulmonary lactate release should be considered when interpreting arterial lactate concentration as an index of systemic hypoxia.

Acidosis, Lactic↗