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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
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

A controlled investigation of current and premorbid personality: characteristics of Parkinson's disease patients.

It has been suggested that before development of motor symptoms, Parkinson's disease (PD) patients with idiopathic display a specific cluster of personality traits consisting of increased rigidity, conscientiousness, industriousness, orderliness, and cautiousness. The idea of such a distinctive premorbid personality profile remains controversial. This hypothesis was reexamined using a methodology that expands on previous studies. Patients with idiopathic PD, probable Alzheimer's Disease (AD), and medical controls with nonneurological chronic progressive motor disorders were rated by a close relative on the NEO-Personality Inventory (PI) to compare current and premorbid personality profiles. For PD and control subjects, current and past self-ratings were also obtained. Results do not support the postulated distinctive PD personality either premorbidly or following onset of symptoms. Both in terms of the premorbid personality profile and perceived changes in personality post-dating the onset of illness, PD patients are similar to AD patients. Though not differing from medical controls premorbidly, after developing symptoms, PD patients were described as less extroverted; less exploratory and curious; and less organized, goal directed, and disciplined.

Age Factors↗
PubMed1995

Association of apolipoprotein epsilon 4 allele and neuropathologic findings in patients with dementia.

Apolipoprotein E (APOE) is a lipoprotein expressed in liver and brain as one of three isoforms (APOE 2, APOE 3 and APOE 4). Recent findings suggest that the presence of APOE 4 is associated with an increased risk for both familial Alzheimer's disease and late-onset Alzheimer's disease. We extended these observations by determining the frequency of APOE alleles in patients with pathologically confirmed Alzheimer's Disease (AD), Parkinson's disease (PD), diffuse Lewy Body disease (DLBD), AD with concomitant PD pathology, demented PD patients without or with concomitant AD pathology and in schizophrenics with a progressive dementia (SCHIZ+DEM). The APOE genotype was determined by restriction digestion of polymerase chain reaction-amplified DNA isolated from frozen brain samples. The frequency of the APOE epsilon 4 allele was highest among sporadic AD and DLBD patients (0.30 and 0.38, respectively) and lowest in the SCHIZ+DEM and non-demented PD patients (0.06 and 0.1, respectively). Thus, the APOE epsilon 4 allele is over-represented selectively in patients with dementias associated with plaques and tangles and/or cortical Lewy bodies, but not in demented schizophrenics or non-demented PD patients.

Aged↗
PubMed1995

Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest.

Human cytomegalovirus (HCMV) infection stimulates cellular DNA synthesis and causes chromosomal damage. Because such events likely affect cellular proliferation, we investigated the impact of HCMV infection on key components of the cell cycle. Early after infection, HCMV induced elevated levels of cyclin E, cyclin E-associated kinase activity, and two tumor suppressor proteins, p53 and the retinoblastoma gene product (Rb). The steady-state concentration of Rb continued to rise throughout the infection, with most of the protein remaining in the highly phosphorylated form. At early times, HCMV infection also induced cyclin B accumulation, which was associated with a significant increase in mitosis-promoting factor activity as the infection progresses. In contrast, the levels of cyclin A and cyclin A-associated kinase activity increased only at late times in the infection, and the kinetics were delayed relative to those for cyclins E and B. Analysis of the cellular DNA content in the infected cells by flow cytometry showed a progressive shift of the cells from the G1 to the S and G2/M phases of the cell cycle, leading to an accumulation of aneuploid cells at late times. We propose that these HCMV-mediated perturbations result in cell cycle arrest in G2/M.

Cell Cycle↗
PubMed1995

Ascertainment of myotonic dystrophy through cataract by selective screening.

Myotonic dystrophy (DM) almost always results from the expansion of an unstable (CTG)n repeat. The mutation can be detected directly. Affected patients with cataracts may have minimal additional signs of the disorder, but all are at risk of life threatening complications. We have studied the efficacy of detecting new families with myotonic dystrophy by selectively screening cataract patients. Selection criteria were: age under 60 with no obvious precipitating factor (except non-insulin dependent diabetes mellitus (NIDDM)); patients of any age with other signs suggestive of myotonic dystrophy detected by the ophthalmologist. Ninety-six patients were tested prospectively; 17 others under 55 were screened retrospectively. All patients were counselled by a clinical geneticist before testing. The patients' DNA was analysed using the DNA probe/restriction enzyme combinations GB2.6/EcoRI, KB1.4/BglI and polymerase chain reaction (PCR). Six patients have been found to have a mutation, three (3.1%) in the prospective group and three (17.6%) in the retrospective group. Three of these patients had minimal myotonic dystrophy and three had classical DM.

Adolescent↗
PubMed1995

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part IX. A prospective cliniconeuropathologic study of Parkinson's features in Alzheimer's disease.

Although extrapyramidal signs such as rigidity, bradykinesia, and postural impairment frequently occur in patients with Alzheimer's disease (AD), the correlation of these parkinsonian manifestations with the neuropathologic changes of Parkinson's disease (PD) has not been well established. Previous clinicopathologic studies addressing this issue have been largely retrospective or have consisted of relatively small numbers of cases. We examined the neuropathologic correlates of clinical parkinsonism in 78 cases with autopsy-confirmed AD prospectively enrolled in the Consortium to Establish a Registry for Alzheimer's Disease. Sixteen (20.5%) of the 78 AD cases showed concomitant PD pathology (AD/PD) as evidenced by the presence of nigral degeneration and Lewy bodies at any site. There were neocortical Lewy bodies in eight of these 16 cases. Two or more clinical manifestations of extrapyramidal dysfunction were present in eight (50.0%) of the 16 cases of AD/PD versus 11 (17.7%) of the 62 cases of AD alone (p < 0.01). Although semiquantitative ratings of the frequency of neuritic plaques showed no differences between the two groups, neurofibrillary tangles in the AD/PD group were less frequent in the midfrontal (p < 0.001) and superior temporal cortex (p < 0.05). These findings support previous reports that AD/PD cases are more likely to manifest extrapyramidal dysfunction and show plaque predominance at autopsy.

Aged↗
PubMed1995

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part XI. Clinical milestones in patients with Alzheimer's disease followed over 3 years.

The rate of cognitive decline, measured by psychometric testing, is widely used to track the progression of Alzheimer's disease (AD). As an alternative approach, we studied clinical measures as markers of the progression of dementia in 343 community-dwelling patients with probable AD enrolled in the multi-center Consortium to Establish a Registry for Alzheimer's Disease (CERAD) project. Subjects received standardized evaluations at entry and at annual follow-up. Decline on the Clinical Dementia Rating, loss of instrumental activities of daily living, failure to recall three words on the Mini-Mental State Examination (MMSE), and decline of the total MMSE score to below 10 were high-risk milestones, with cumulative frequencies exceeding 50% at 3 years. Loss of dressing and toileting activities occurred at intermediate rates, while loss of eating ability was rare. The risk of reaching clinical milestones and the annual rate of cognitive decline on the MMSE were directly correlated. Clinical milestones are useful indices of the progression of dementia in patients with AD.

Activities of Daily Living↗