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Biomedical subjects

C Holmes

Publications and source records attributed to C Holmes.

At least 73 records · Page 4Linked to original sources
PubMed1997

Ethical aspects of phenomenological research with mentally ill people.

Given the dramatic rise in the frequency of nursing research that involves eliciting personal information, one would expect that attempts to maintain the balance between the aspirations of researchers and the needs and rights of patients would lead to extensive discussion of the ethical issues arising. However, they have received little attention in the literature. This paper outlines and discusses some of the issues associated with qualitative research. The discussion converges on the specific case of phenomenological research, which involves the invasion of participants' personal worlds, and draws attention to some of the ethical issues that arise when the participants are psychiatric patients.

Behavioral Research↗
PubMed1997

Sequential therapy with cefuroxime followed by cefuroxime axetil in community-acquired pneumonia.

STUDY OBJECTIVES: To compare the efficacy of two sequential therapy regimens of IV cefuroxime followed by oral cefuroxime axetil for the treatment of community-acquired pneumonia (CAP). DESIGN: Prospective, multicenter, randomized, open-label, parallel-group study. SETTING: Sixty-six centers in 11 countries (Belgium, Canada, Czech Republic, Germany, Hungary, Ireland, Israel, Poland, Portugal, South Africa, and the United Kingdom). PATIENTS: Six hundred thirty-six adults with CAP requiring hospitalization and initial IV antibiotic treatment. INTERVENTIONS: Cefuroxime, 1.5 g IV tid or bid for 48 to 72 h followed by oral cefuroxime axetil, 500 mg bid for 7 days. MEASUREMENTS AND RESULTS: For clinically evaluable patients, the clinical response rates were equivalent for cefuroxime tid and bid groups posttreatment (cure/improvement, 79% and 84%, respectively) and at follow-up (maintained cure, 87% and 82%, respectively). All signs and symptoms of pneumonia showed improvement at the time of switch from IV to oral therapy. A total of 111 pathogens were isolated, the most common being Streptococcus pneumoniae (23%), Haemophilus influenzae (18%), and Enterobacteriaceae (15%). Bacteriologic clearance was obtained posttreatment in 47 of 49 and 36 of 42 of bacteriologically evaluable patients in the cefuroxime tid and bid groups, respectively. Both regimens were well tolerated with a low incidence of drug-related adverse events, the most common being GI. CONCLUSIONS: Twice daily IV cefuroxime followed by oral cefuroxime axetil is a simple and effective sequential therapy regimen for the treatment of CAP. It offers potential cost savings and can replace the current tid regimen in this indication.

Administration, Oral↗
PubMed1997

Prevention of heat strain by immersing the hands and forearms in water.

The effectiveness of hand immersion in water at 10 degrees C, 20 degrees C and 30 degrees C as a technique for reducing heat strain in Royal Navy (RN) personnel has been investigated at the Institute of Naval Medicine (INM). Four subjects exercised at a moderate work rate, whilst wearing fire fighting clothing in an environmental chamber at 40 degrees C. The subjects reached heat strain safety limits within 45 minutes of commencing work at which point they rested in the heat for 30 minutes whilst they underwent one of four experimental conditions: without intervention (control); or with their hands immersed in water at 10 degrees C, 20 degrees C or 30 degrees C. The experiment was repeated on a further three days so that the subjects undertook each experimental condition in a balanced randomised order. During the control condition without hand immersion the subjects were unable to cool. Immersion of the hands in water (at 10 degrees C, 20 degrees C or 30 degrees C) significantly (P < 0.05) lowered body core (auditory canal) temperature within ten minutes. Assessing the effectiveness of this technique by the initial rates of core temperature reduction, revealed that immersion of the hands was more effective the colder the water. Following 20 minutes of hand immersion mean core temperature had dropped from 38.5C to: 36.9(standard deviation 0.19) degrees C, 37.3(0.18) degrees C, and 37.8(0.10) degrees C, in 10 degrees C, 20 degrees C and 30 degrees C water respectively. Cooling powers estimated from changes in mean body temperature were 334, 307 and 113 watts using 10 degrees C, 20 degrees C and 30 degrees C water respectively. These results indicate that hand immersion in water at a temperature of between 10 degrees C and 30 degrees C is an efficient means of cooling heat stressed personnel who have been exercising. This simple and effective technique may be applied to many industrial and military tasks to reduce heat strain, lower the risk of heat injury, and increase safe total work times in the heat. For the RN, hand immersion could be used in fire fighting, damage control and NBC operations where personnel alternately work and rest.

Adult↗
PubMed1996

In vivo morphometry of the intrasulcal gray matter in the human cingulate, paracingulate, and superior-rostral sulci: hemispheric asymmetries, gender differences and probability maps.

Volumes of the intrasulcal gray matter were measured in three cerebral sulci located on the medial wall of the human frontal lobe: cingulate sulcus (CS), paracingulate sulcus (PCS), and superior-rostral sulcus (SRS). The measurements were carried out on T1-weighted 3-D high-resolution magnetic-resonance (MR) images acquired in 105 young right-handed volunteers (42 female and 63 male). Before the measurement, the images were transformed into a standardized stereotaxic space (Talairach and Tournoux [1988] Human Brain: 3-Dimensional Proportional System. An Approach to Cerebral Imaging. Stuttgart, New York: Georg Thieme Verlag), thus removing inter-individual differences in brain size. The intrasulcal gray matter was segmented in a semi-automatic manner. Significant gender differences were found in the volume of the CS (female > male) and the PCS (male > female). Hemispheric asymmetries were observed between the left and right volumes of the intrasulcal gray matter in the anterior (right > left) and posterior (left > right) segments of the CS, as well as between the left and right volumes of the PCS (left > right). There was no interaction between the asymmetries and gender. In addition, significant positive correlations were found between the left and right gray-matter volumes in the anterior (r = 0.43) and posterior (r = 0.66) segments of the CS, whereas significant negative correlations were observed between the gray-matter volumes of the anterior segment of the CS and those of the PCS (left hemisphere: r = -0.48; right hemisphere: r = -0.42). The observed hemispheric asymmetries in the CS and PCS gray-matter volumes are consistent with the proposed role of these structures in the integration of emotions with cognition (CS) and in the control of speech/vocalization (PCS). The pattern of inter-hemispheric correlations in the sulcal gray-matter points to an increasing asynchrony in the foetal development of primary (CS), secondary (SRS), and tertiary (PCS) sulci, respectively. The presence of negative correlations between the two neighbouring sulci (CS and PCS) suggests that a process of compensation could underlie interactions between adjacent primary and tertiary sulci. Besides the above volumetric analysis, we also provide average (probability) maps of the three sulci; the use of such maps for the parcellation of the medial frontal lobe and localization of "peaks" obtained in blood-flow activation studies is discussed.

Brain Mapping↗
PubMed1996

Association between a PS-1 intronic polymorphism and late onset Alzheimer's disease.

Previous work suggests an association between allele 1 and the 1-1 genotype of an intronic polymorphism in the presenilin-1 (PS-1) gene and late onset Alzheimer's disease. We found an excess of the 1-1 genotype in our late onset clinical sample (p = 0.006, one-tailed) but not in our postmortem confirmed sample, which instead exhibited an excess of allele 1 (p = 0.02, one-tailed). No interaction between PS-1 and ApoE genotype was detected and the findings remained significant when the effects of ApoE were taken into account (p = 0.03, one-tailed). These results suggest that the PS-1 polymorphism, or a locus in linkage disequilibrium with it, acts as a risk factor for late onset AD.

Age of Onset↗
PubMed1996

Pattern of plasma levels of catecholamines in familial dysautonomia.

This report extends previous investigations of endogenous catecholamine levels in patients with orthostatic hypotension due to familial dysautonomia (FD), to define better the neurochemical phenotype and elucidate possible pathophysiological mechanisms. Ten FD patients (age 26.1 +/- 2.6 (SEM) years) and eight control subjects (age 29.5 +/- 3.7 years) were studied. Heart rate, blood pressure and venous blood samples were obtained while supine and after 5 min in the upright position. Plasma levels of dihydroxyphenylalanine (DOPA), noradrenaline (NA), adrenaline (A), dopamine (DA), dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) were measured. When supine, the FD group had greater NA and DOPA levels, and lower DHPG levels. Plasma NA did not increase with erect posture in FD patients. Individual FD mean blood pressures were correlated positively with plasma NA levels when supine and with plasma DA and DOPAC when upright. In FD, DOPA:DHPG ratios were above the range found in normal subjects or that reported in patients with acquired forms of dysautonomia regardless of posture, whereas DOPAC:DHPG ratios remained normal. Thus FD patients have a characteristic neurochemical pattern which probably reflects either decreased vesicular storage of catecholamines or limited oxidative deamination despite normal or increased tyrosine hydroxylation.

Adolescent↗
PubMed1996

Autoimmune autonomic failure in a patient with myeloma-associated Shy-Drager syndrome.

We report here the case of a patient with the Shy-Drager syndrome and multiple myeloma who had evidence consistent with a central neural autoimmune basis for sympathetic autonomic failure. Autonomic function testing showed no recordable peroneal skeletal muscle sympathoneural traffic, normal arterial norepinephrine (NE) spillover during supine rest and no increment in NE spillover during exposure to lower body negative pressure. The patient's cerebrospinal fluid and serum contained an immunoglobulin G that bound to rat locus ceruleus (LC) in an in vitro test system. The myeloma protein was of the lambda subtype and bound in the rat LC, without binding in the substantia nigra, as demonstrated with anti-lambda antiserum. Since in this case the monoclonal antibody produced by the myeloma bound specifically to LC cells, the results are consistent with the hypothesis that in this patient the Shy-Drager syndrome may have had an immune-mediated basis.

Animals↗
PubMed1996

Neurotoxic and neurotrophic effects of chronic N-methyl-D-aspartate exposure upon mesencephalic dopaminergic neurons in organotypic culture.

Current theories regarding the mechanisms of degeneration of dopaminergic nigrostriatal neurons in Parkinson's disease suggest a pivotal role for excitotoxicity. In this study, the effects of chronic exposure of rat ventral mesencephalic slice cultures to the excititoxin N-methyl-D-aspartate, were investigated. Chronic (18 day) exposure to N-methyl-D-aspartate produced widely varying, dose-dependent effects. High doses (100 mu M) caused a pronounced toxicity upon tyrosine hydroxylase-positive neurons, with the surviving neurons possessing shrunken somata and stunted neurites: co-administration of the N-methyl-D-aspartate receptor antagonist MK-801, inhibited N-methyl-D-aspartate-induced toxicity. In contrast, exposure to a low concentration of N-methyl-D-aspartate (0.1 mu M), stimulated the outgrowth of tyrosine hydroxydase-positive neurites from the culture; this effect was abolished by MK-801. Chronic application of glutamate had similar, though not as pronounced, growth-promoting actions. However, the concentration of glutamate required was 1000 times that of N-methyl-D-aspartate, due to the presence ot high-affinity glutamate transport mechanisms. Cultures exposed to a submicromolar concentration of N-methyl-D-aspartate exhibited a significant resistance to subsequent exposure to a lethal (300 mu M) concentration of the toxin. It would thus appear that N-methyl-D-aspartate may have both trophic and toxic actions upon dopaminergic neurons in culture. Moreover, the ability of low doses of N-methyl-D-aspartate to protect neurons in this critical brain region may be of relevance to future attempts to arrest the degeneration associated with Parkinson's disease. The putative mechanisms of these phenomena are discussed.

Animals↗
PubMed1996

Carer informants for dementia sufferers: carer awareness of cognitive impairment in an elderly community-resident sample.

By comparing data obtained from the carers of 170 community-resident dementia sufferers with the results of objective cognitive testing, we assessed carer awareness of a range of cognitive deficits in their dependents. Spouses living with demented patients were the best at estimating the overall severity of cognitive impairment, whereas both first-degree (particularly if living with the dementia sufferer) and second-degree relatives were better at identifying and reporting the severity of memory impairment and topographical disorientation. Only one carer was aware of problems with object recognition, although a definite problem was detected in at least 40% of the study group. The testing instruments used (MMSE and CAMCOG) probably under-detected dysnomia and appeared to be inconclusive when compared with carer reports of difficulties that could be attributable to dyspraxia, highlighting the problem of sole reliance on either these instruments or informant accounts to obtain accurate clinical information.

Activities of Daily Living↗
PubMed1996

International comparison of baccalaureate nursing degrees: collaboration in qualitative analysis.

This paper describes a study which investigated the perceived similarities and differences of a selection of baccalaureate nursing degrees from different continents. An international research team was formed, and by using a modified version of the Delphi process and nominal group techniques the group undertook a qualitative analysis of curriculum documents. The major areas analysis were: aims, content, methods and assessment. Under these headings the group produced a list of key issues supported by a number of indicative statements by collating the independent analyses undertaken by each of the team members. Examples of findings are that critical thinking and personal development are most obvious in aims but that the progression of curricula may not achieve this, there are differences in 'western' and 'asian' orientations to the concept of personal autonomy. Sciences are valued more than arts or humanities. The lecture method as well as practice placement dominate the teaching methods. Transcultural nursing is not significant except where there are two therapeutic ideologies in existence. Assessment methods are largely summative. The findings have application in the development of credit transfer and international exchange schemes. The conclusions highlight areas of special considerations when designing such schemes.

China↗
PubMed1996

A single amino acid change in Escherichia coli glycerol kinase abolishes glucose control of glycerol utilization in vivo.

Escherichia coli glycerol kinase (EC 2.7.1.30; ATP:glycerol 3-phosphotransferase) is a key element in glucose control of glycerol metabolism. Its catalytic activity is inhibited allosterically by the glycolytic intermediate, fructose 1,6-biphosphate, and by the phosphotransferase system phosphocarrier protein, IIIGlc (also known as IIAGlc). These inhibitors provide mechanisms by which glucose blocks glycerol utilization in vivo. We report here the cloning and sequencing of the glpK22 gene isolated from E. C. C. Lin strain 43, a strain that shows the loss of glucose control of glycerol utilization. DNA sequencing shows a single missense mutation that translates to the amino acid change Gly-304 to Ser (G-304-S) in glycerol kinase. The effects of this substitution on the functional and physical properties of the purified mutant enzyme were determined. Neither of the allosteric ligands inhibits it under conditions that produce strong inhibition of the wild-type enzyme, which is sufficient to explain the phenotype of strain 43. However, IIIGlc activates the mutant enzyme, which could not be predicted from the phenotype. In the wild-type enzyme, G-304 is located 1.3 nm from the active site and 2.5 nm from the IIIGlc binding site (M. Feese, D. W. Pettigrew, N. D. Meadow, S. Roseman, and S. J. Remington, Proc. Natl. Acad. Sci. USA 91:3544-3548, 1994). It is located in the same region as amino acid substitutions in the related protein DnaK which alter its catalytic and regulatory properties and which are postulated to interfere with a domain closure motion (A. S. Kamath-Loeb, C. Z. Lu, W.-C. Suh, M. A. Lonetto, and C. A. Gross, J. Biol. Chem. 270:30051-30059, 1995). The global effect of the G-304-S substitution on the conformation and catalytic and regulatory properties of glycerol kinase is consistent with a role for the domain closure motion in the molecular mechanism for glucose control of glycerol utilization.

Allosteric Regulation↗
PubMed1996

Apolipoprotein E: non-cognitive symptoms and cognitive decline in late onset Alzheimer's disease.

OBJECTIVES: To determine the association between the epsilon2 and epsilon4 alleles of apolipoprotein E (ApoE) and independent measures of cognitive decline and non-cognitive symptomatology in late onset Alzheimer's disease. METHODS: The frequency of the epsilon2 and epsilon4 alleles of ApoE and their association with measures of cognitive decline and non-cognitive symptomatology were assessed in a population based case register study of 164 patients with late onset Alzheimer's disease from the east Lambeth and south Southwark districts of south London. RESULTS: Analysis of a wide range of non-cognitive symptoms against ApoE epsilon4 genotype showed no significant association but a positive relation was found between ApoE epsilon2 genotype and depressive symptomatology (P = 0.004). No relation was found between measurements of cognitive decline and the presence of the ApoE epsilon4 allele. A trend for decreasing age at onset of 3 to 4 years in carriers of the ApoE epsilon4 allele was found, confirming earlier studies. CONCLUSION: Presence of the epsilon4 allele of ApoE is associated with an earlier age at onset but does not seem to be related to either a more severe psychopathology or a more rapid progression of the illness. The epsilon2 allele of ApoE is associated with depressive symptomatology in late onset Alzheimer's disease.

Age of Onset↗
PubMed1995

Lung cancer risk in African-Americans in relation to a race-specific CYP1A1 polymorphism.

The possible association between lung cancer and a polymorphism of the CYP1A1 gene specific to African-Americans was examined using peripheral blood DNA from 144 incident cases of lung cancer and 230 population controls with detailed data on smoking and other risk factors for the disease. The CYP1A1 variant allele was present in 15.2% of controls and 16.7% of cases. The smoking-adjusted odds ratio for the presence of the variant allele in relation to lung cancer risk overall was 1.3 (95% confidence interval, 0.7-2.4). According to histological type, the strongest association was observed for squamous cell carcinoma (odds ratio, 2.1), but this result was compatible with chance (95% confidence interval, 0.8-5.9). Adenocarcinoma was not materially associated with the presence of the variant allele (odds ratio, 1.3; 95% confidence interval, 0.5-3.2). No important associations were observed upon stratification by several risk factors for lung cancer, including smoking history, occupational exposures to asbestos and motor vehicle exhaust, or low intake of the micronutrient antioxidants beta-carotene, vitamin E, or vitamin C. These results do not confirm an earlier report that this CYP1A1 polymorphism may be an important risk factor for adenocarcinoma of the lung in African-Americans.

Aged↗
PubMed1995

The influence of target and non-target brain regions on the development of mid-brain dopaminergic neurons in organotypic slice culture.

The development and regeneration of rat dopaminergic neurons of the ventral mesencephalon was studied in organotypic slice cultures. Single ventral mesencephalon cultures and co-cultures of ventral mesencephalon with striatum (a target region) or cerebellum (a non-target region) were prepared from postnatal day 1 Wistar rats. Cultures were processed for tyrosine hydroxylase and glial fibrillary acidic protein immunoreactivity, at two day intervals, for an overall incubation period of 20 days. Analysis of these cultures revealed that the striatal target tissue, exerted neither a trophic nor a tropic influence on the tyrosine hydroxylase immunoreactive neurons. In both single and co-cultures, tyrosine hydroxylase immunoreactive neurites projected radially from the ventral mesencephalon slice. However, in striatal co-cultures, tyrosine hydroxylase immunoreactive neurites were seen penetrating the striatal slice, whereas in cerebellar co-cultures no tyrosine hydroxylase immunoreactive neurites entered the cerebellar tissue. Glial fibrillary acidic protein positive cells actively migrated from the tissue sections, however tyrosine hydroxylase immunoreactive neurite outgrowth was not guided by these glial cells. Tyrosine hydroxylase immunoreactive neurites terminated once they had penetrated the striatal slice. This retardation of neurite growth by a target region could be important in establishing and reinforcing synaptic connections in the developing nigro-striatal pathway.

Animals↗
PubMed1995

The effect of acetylcholinesterase on outgrowth of dopaminergic neurons in organotypic slice culture of rat mid-brain.

This study has investigated the possibility that acetylcholinesterase could play a non-classical role as an adhesion factor or growth factor in the development of dopaminergic neurons in organotypic slice culture of postnatal day 1 rats. When the culture medium was supplemented with acetylcholinesterase (3 U/ml), outgrowth of tyrosine hydroxylase-immunoreactive neurites was significantly enhanced. Addition of a specific inhibitor of acetylcholinesterase, BW284c51, caused a decrease in the number of tyrosine hydroxylase neurons and a reduction in the cell body size and extent of neurite outgrowth of remaining neurons. However, echothiophate which also inhibits AChE activity, did not produce these effects. Therefore acetylcholinesterase could act as a growth enhancing factor for dopaminergic neurons, and disruption of an as yet unidentified site on the acetylcholinesterase molecule by BW284c51 could decrease the survival and outgrowth of these neurons.

Acetylcholinesterase↗
PubMed1995

Monoaminergic effects of folinic acid, L-DOPA, and 5-hydroxytryptophan in dihydropteridine reductase deficiency.

Plasma and CSF concentrations of endogenous L-DOPA, catecholamines, and metabolites of monoamines were assayed in a patient with atypical phenylketonuria due to absent dihydropteridine reductase (DHPR), before and during treatment with folinic acid, Sinemet, and 5-hydroxytryptophan. The patient had low but detectable levels of L-DOPA, 3,4-dihydroxyphenylacetic acid (DOPAC), and 3,4-dihydroxyphenylglycol (DHPG) in plasma and low but detectable levels of these compounds and of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in CSF, with approximately normal plasma and CSF levels of norepinephrine [noradrenaline (NA)]. Folinic acid treatment approximately doubled plasma levels of L-DOPA, NA, DOPAC, and DHPG, compared with values during dietary phenylalanine restriction alone. Detection of L-DOPA, catecholamines, and monoamine metabolites in this patient indicates that monoamine synthesis in humans does not absolutely require DHPR. The results are consistent with the existence of an alternative biochemical pathway, with folinic acid treatment augmenting activity along this pathway. Low plasma levels of L-DOPA, DOPAC, and DHPG may reflect decreased catecholamine synthesis and turnover in sympathetic nerves, with compensatory increases in exocytotic release normalizing plasma NA levels.

5-Hydroxytryptophan↗