Search PubMed⌕ Search

Biomedical subjects

C Clark

Publications and source records attributed to C Clark.

At least 73 records · Page 4Linked to original sources

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.

Explore the source record for details and available documents.

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↗

Phenylalanine 30 plays an important role in receptor binding of verotoxin-1.

The homopentameric B subunit of verotoxin 1 (VT1) binds to the glycosphingolipid receptor globotriaosylceramide (Gb3). We produced mutants with alanine substitutions for residues found near the cleft between adjacent subunits. Substitution of alanine for phenylalanine 30 (Phe-30) resulted in a fourfold reduction in B subunit binding affinity for Gb3 and a 10-fold reduction in receptor density in a solid-phase binding assay. The interaction of wild-type and mutant B subunits with Pk trisaccharide in solution was examined by titration microcalorimetry. The carbohydrate binding of the mutant was markedly impaired compared with that of the wild type and was too weak to allow calculation of a binding constant. These results demonstrate that the mutation significantly impaired the carbohydrate-binding function of the B subunit. To ensure that the mutation had not caused a significant change in structure, the mutant B subunit was crystallized and its structure was determined by X-ray diffraction. Difference Fourier analysis showed that its structure was identical to that of the wild type, except for the substitution of alanine for Phe-30. The mutation was also produced in the VT1 operon, and mutant holotoxin was purified to homogeneity. The cytotoxicity of the mutant holotoxin was reduced by a factor of 10(5) compared to that of the wild type in the Vero cell cytotoxicity assay. The results suggest that the aromatic ring of Phe-30 plays a major role in binding of the B subunit to the Galalpha1-4Galbeta1-4Glc trisaccharide portion of Gb3. Examination of the VT1 B crystal structure suggests two potential carbohydrate-binding sites which lie on either side of Phe-30.

Amino Acid Sequence↗

Outcome measures, pooled index and quality of life instruments in rheumatoid arthritis.

BACKGROUND AND OBJECTIVE: A variety of outcome measures are used in evaluating disease activity and therapeutic efficacy in rheumatoid arthritis (RA) studies, and this makes comparisons of drug efficacy difficult. Some of the endpoints used are not standardized and/or are insensitive to change. The purpose of this report is to present a critical appraisal of outcome measures and quality of life assessments in RA studies. METHOD: An overview of the literature was undertaken to determine the extent to which there is consensus among experts in this area of research. RESULTS: The data suggest that the core set of endpoints in RA clinical studies should include tender joint count swollen joint count, patients' assessment of pain, patients' and physicians' global assessments, patients' assessment of physical function and acute phase reactant level. When trials of disease-modifying antirheumatic drugs (DMARD) last for more than a year, radiography may be useful. A 'pooled index' may be valuable, and its construction is discussed. Quality of life (QoL) instruments facilitate a fuller examination of the effects of health care interventions and these should be used to complement the more traditional clinical endpoints in the core set. The instruments most commonly used in RA research are identified. CONCLUSIONS: We conclude that randomized clinical trials of treatments in RA should now ideally use the core set of clinical endpoints and validated QoL instruments for assessing safety and efficacy.

Arthritis, Rheumatoid↗

Kinaesthetic acuity and fine motor skills in children with attention deficit hyperactivity disorder: a preliminary report.

Two groups of 9-year-old children (24 children with attention deficit hyperactivity disorder [ADHD] and 24 controls) were assessed for kinaesthetic acuity and fine motor skills with medication withdrawn. Results showed significantly poorer performance on both tasks for children with ADHD, but only a weak association between fine motor and kinaesthetic performance. The implications are discussed, particularly the role of attention to proprioceptive signals in children with the diagnosis of ADHD.

Attention Deficit Disorder with Hyperactivity↗

Sump bay fever: inhalational fever associated with a biologically contaminated water aerosol.

OBJECTIVE: To investigate the clinical, serological, and environmental features of a work related inhalational fever associated with exposure to an aerosol generated from a biologically contaminated 130,000 gallon water pool in a building used for testing scientific equipment. METHOD: Cross sectional survey of all exposed subjects (n = 83) by symptom questionnaire, clinical examination, spirometry, and serology for antibody to Pseudomonads, pool water extract, and endotoxin. In symptomatic patients diffusion capacity was measured, and chest radiology was performed if this was abnormal. Serial peak flow was recorded in those subjects with wheeze. Bacterial and fungal air sampling was performed before and during operation of the water pool pump mechanism. Endotoxin was measured in the trapped waters and in the pumps. Serum cotinine was measured as an objective indicator of smoking. RESULTS: Of the 20 symptomatic subjects, fever was most common in those with the highest exposure (chi 2 42.7, P < 0.001) in the sump bay when the water was (torrentially) recirculated by the water pumps. Symptoms occurred late in the working day only on days when the water pumps were used, and were independent of the serum cotinine. Pulmonary function was normal in most subjects (spirometry was normal in 79/83, diffusion capacity was low in five subjects, chest radiology was normal). Peak flow recording did not suggest a work relation. The bacterial content of the aerosol rose from 6 to > 10,000 colony forming units per cubic metre (cfu/m3) (predominantly environmental Pseudomonads) when the pumps were operating. High endotoxin concentrations were measured in the waters and oil sumps in the pumps. Low concentrations of antibody to the organisms isolated were detected (apart from two subjects with high antibody) but there was no relation to exposure or the presence of symptoms and similar antibody was found in the serum samples from a non-exposed population. The fever symptoms settled completely with the simple expedient of changing the water and cleaning the pumps. CONCLUSION: Given the results of our study, the development of inhalational fever in this unique environment and clearly restricted cohort was closely related to the degree of exposure to contaminated aerosol and mainly occurred in the absence of distinct serological abnormality and independent of cigarette smoking.

Adult↗

Clinical and neuropsychological differences between patients with earlier and later onset of Alzheimer's disease: A CERAD analysis, Part XII.

To determine whether the age of the onset of Alzheimer's disease (AD) is related to the expression and rate of decline of this disorder, we examined the clinical and neuropsychological performance of 421 patients entered into the Consortium to Establish a Registry for Alzheimer's Disease and followed annually for up to 4 years. Statistical analyses were based on multivariable logistic regression analysis for dichotomous clinical measures and multivariable linear regression analysis for psychometric measures. All analyses examined the effect of age after controlling for gender, education, and stage of dementia. Clinical information obtained on entry into the study indicated that younger patients performed more poorly on measures of language and concentration, and older patients performed more poorly on measures of memory and orientation. On neuropsychological measures at entry, younger patients, performed more poorly on praxis and had significantly higher scores of confrontation naming. Younger age predicted a significantly faster rate of progression for all neuropsychological measures. These findings support the concept of age-related clinical subtypes of AD.

Age of Onset↗

The effects of relaxation response training on menopausal symptoms.

The specific aim of this study was to investigate the efficacy of elicitation of the relaxation response for the treatment of menopausal hot flashes and concurrent psychological symptoms. The volunteer sample consisted of 33 women, between the ages of 44 and 66 years, who were in general good health, with a minimum of 6 months without a menstrual period, experiencing at least five hot flashes per 24-h, and not using hormone replacement therapy. The setting was an outpatient clinic in a tertiary care teaching hospital. The interventions used were relaxation response training and an attention-control group and a daily symptom diary measuring both the frequency and intensity of hot flashes, the Spielberger State-Trait Anxiety Inventory (STAI), and the Profile of Mood Scale (POMS) were the measures used. This was a randomized, controlled, prospective study. Subjects were randomly assigned to one of three groups (relaxation response, reading, or control) for the 10-week study. The first 3 weeks of baseline measurement of frequency and intensity of hot flash symptoms, and the preintervention psychological scores were compared with the final 3 weeks measurement of frequency and intensity and the postintervention psychological scores for symptomatic improvement. The relaxation response group demonstrated significant reductions in hot flash intensity (p < 0.05), tension-anxiety (p < 0.05) and depression (p < 0.05). The reading group demonstrated significant reductions in trait-anxiety (p < 0.05) and confusion-bewilderment (p < 0.05). There were no significant changes for the control group. Daily elicitation of the relaxation response leads to significant reductions in hot flash intensity and the concurrent psychological symptoms of tension-anxiety and depression.

Affect↗

Improving physicians' preventive health care behavior through peer review and financial incentives.

We assessed improvement of preventive health care behaviors by physicians in an independent practice association-health maintenance organization. A before-after, 3-year study of a defined cohort measured changes through chart audit, accompanied by peer review, feedback, and financial incentives. Outcome measures consisted of rates of mump-measles-rubella (MMR) immunization, screening for cholesterol levels, and charting adequacy. Offices meeting MMR vaccination standards over 3 years increased from 78% to 96% (P < .05); those meeting standards for screening for cholesterol levels, from 92% to 95%. The average scores for charting adequacy rose from 87% to 92% (P < .05). The percentage of practices not in compliance with a standard of 90% decreased as follows: for MMR vaccination, from 57% to 12%; for screening for cholesterol levels, from 21% to 11%; and for charting adequacy, from 53% to 29% (P < .05).

Cholesterol↗

Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease.

In this clinical study the cerebrospinal fluid (CSF) level of a novel form of the beta-amyloid peptide (A beta) extending to position 42 (A beta 42) was determined in patients with Alzheimer's disease (AD) as well as controls. In addition to measurement of CSF A beta 42 levels, total A beta peptides, microtubule-associated protein tau, and apolipoprotein E (ApoE) genotype were also assessed. It is interesting that CSF A beta 42 levels were found to be significantly lower in AD patients relative to controls, whereas total A beta levels were not. A beta 42 has recently been shown to preferentially deposit in the brain tissue of patients with AD, suggesting that diminished clearance may account for its reduction in CSF. As previously reported, tau levels were increased in AD patients; however, neither A beta 42 nor tau levels were apparently influenced by the ApoE genotype.

Aged↗