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Biomedical subjects

C Graham

Publications and source records attributed to C Graham.

At least 55 records · Page 3Linked to original sources

Carers' knowledge of dementia, their coping strategies and morbidity.

OBJECTIVE: The main hypothesis was that carers of dementia sufferers who have a higher level of knowledge on the subject of dementia have lower rates of physical and psychological morbidity. We also wanted to examine whether a carer's level of knowledge bears any relation to their attributional style and coping mechanisms. DESIGN: Informal carers, caring for patients who fulfilled the CAMDEX criteria for mild or moderate dementia, were approached to participate in the study. SETTING: Old age psychiatry services in the West Midlands and Bristol. PARTICIPANTS: Informal carers, caring for relatives with dementia. MEASURES: Trained researchers administered the Geriatric Mental State Schedule, the Dementia Knowledge Questionnaire, the Pennebaker Inventory of Limbic-Languidness (an inventory of common physical symptoms) and the Carer Stress Scale. RESULTS: More knowledgeable carers experienced significantly lower levels of depression but also higher rates of anxiety. Carers' level of knowledge on the subject of dementia showed no association with their physical health. More knowledgeable carers were more likely to have 'reduced expectations' of their dependants' abilities and make 'positive comparisons'; they were also more likely to feel competent and confident as carergivers. CONCLUSION: The findings support the main hypothesis when considering carers' rates of depression but not when considering rates of anxiety or physical ill-health.

Adaptation, Psychological

A retinaldehyde dehydrogenase as a structural protein in a mammalian eye lens. Gene recruitment of eta-crystallin.

eta-Crystallin is a taxon-specific crystallin, a major component of the eye lens in elephant shrews (Macroscelidea). Sequence analysis of eta-crystallin from two genera of elephant shrews and expression of recombinant eta-crystallin show that the protein is a cytoplasmic (class 1) aldehyde dehydrogenase (ALDH1, EC 1.2.1.3) with activity for the oxidation of retinaldehyde to retinoic acid. Unlike many other mammals, elephant shrews have two ALDH1 genes. One encodes ALDH1/eta-crystallin which, in addition to its very high expression in lens, is also the predominant form of ALDH1 expressed in other parts of the eye. The second gene encodes a "non-lens" ALDH1 (ALDH1-nl) which is the predominant form expressed in liver. This pattern of tissue preference contrasts with other mammals which make use of the same major ALDH1 transcript in both ocular and non-ocular tissues. Thus the gene recruitment of ALDH1/eta-crystallin as a structural protein in elephant shrew lenses is associated with its collateral recruitment as the major form of ALDH1 expressed in other parts of the eye.

Aldehyde Oxidoreductases

Fluorescent multiplex microsatellites used to define haplotypes associated with 75 CFTR mutations from the UK on 437 CF chromosomes.

The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene contains three highly informative microsatellites: IVS8CA, IVS17bTA, and IVS17bCA. Their analysis improves prenatal/ carrier diagnosis and generates haplotypes from CF chromosomes that are strongly associated with specific mutations. Microsatellite haplotypes were defined for 75 CFTR mutations carried on 437 CF chromosomes (220 for delta F508, 217 for other mutations) from Northern Ireland and three English regions: the North-West, East Anglia, and the South. Fluorescently labelled microsatellites were amplified in a triplex PCR reaction and typed using an ABI 373A fluorescent fragment analyser. These mutations cover all the common and most of the rare CF defects found in the UK, and their corresponding haplotypes and geographic region are tabulated here. Ancient mutations, delta F508, G542X, N1303K, were associated with several related haplotypes due to slippage during replication, whereas other common mutations were associated with the one respective haplotype (e.g., G551D and R560T with 16-7-17, R117H with 16-30-13, 621 + 1G > T with 21-31-13, 3659delC with 16-35-13). This simple, fast, and automated method for fluorescent typing of these haplotypes will help to direct mutation screening for uncharacterised CF chromosomes.

Chromosomes, Human

Nocturnal melatonin levels in human volunteers exposed to intermittent 60 Hz magnetic fields.

Two double-blind laboratory-based studies were performed to determine whether a suppression of nocturnal melatonin similar to that observed in rodents occurs when humans are exposed to magnetic fields at night. In study 1, 33 men were exposed to sham, 10 mG, or 200 mG intermittent, circularly polarized magnetic fields from 2300 to 0700 h under controlled environmental and exposure test conditions. Overall, exposure had no effect on melatonin levels. Men with preexisting low levels of melatonin, however, showed significantly greater suppression of melatonin when they were exposed to light and also when they were exposed to the 200 mG magnetic-field condition. Study 2 directly tested the hypothesis that low-melatonin subjects show enhanced sensitivity when exposed to light and to 200 mG magnetic fields. After preexposure screening, each of 40 men slept in the exposure facility on two nights. On one night, the men were sham exposed. On the other night, they were exposed to the 200 mG field condition used previously. Again, exposure had no overall effect on melatonin levels. The original finding of enhanced sensitivity in low-melatonin subjects was not replicated in this study. We conclude that the intermittent exposure conditions used in these two studies were not effective in altering nocturnal melatonin release patterns in human volunteers. Further research is underway with regard to exposure parameters, hormonal and immune system measures, and individual differences.

Adolescent

Structure-activity relationships and computer-assisted analysis of respiratory sensitization potential.

The mechanism(s) underlying respiratory sensitivity to chemicals is uncertain but is assumed to involve immunologic components with pharmacologic and neurologic involvement. Predictive testing would be valuable to prevent occurrence of hypersensitivity. Several in vitro and in vivo approaches have been used for predictive purposes. In vitro methods have included assessment of the ability of the chemical to undergo reaction with proteins. Computational methods have investigated the relationship between structure and electrophilic potential of chemical allergens. We have initiated a structure-activity evaluation of chemicals associated with elicitation of respiratory sensitization and have utilized a computer-based expert system, MultiCASE. A preliminary database of 39 active chemicals has been established from a literature search of clinical case reports and animal test results. Evaluation of the model has indicated structural alerts for activity which consist of structural fragments as well as physicochemical properties. Further development of the model and evaluation of findings should enable mechanistic insight into the process of respiratory sensitization and recognition of factors which distinguish respiratory sensitizers mechanistically from other chemical allergens such as contact sensitizing chemicals.

Allergens

The determination of radioisotope levels in municipal sewage sludge.

Sludge samples from 25 municipal waste water treatment plants have been analyzed to determine the level of environmentally present, man-made, gamma-ray emitting radioisotopes. Samples were freeze dried and separated into dried sludge, liquid-soluble and liquid-insoluble components. These were counted in the low background level, whole body counter at Missouri University using a standard intrinsic-Germanium spectrometer. After freeze drying, the liquid effluents from the samples were not found to have statistically significant levels of radioactivity. Using log-normal analysis, the dried sludge was found to have 0.0016 +/- 0.0022 Bq g-1 (0.04 +/- 0.06 pCi g-1) of 137Cs and 0.001 +/- 0.003 Bq g-1 (0.03 +/- 0.08 pCi g-1) of 60Co. These data can be used to determine if sewage effluents from nuclear facilities have levels of radioactivity above that expected from the environment.

Sewage

Child life programs in the pediatric emergency department.

Child life (CL) programs have long been utilized in the inpatient setting to help in relieving the stress and anxiety associated with hospitalization. The objective of this study was to determine the current availability of such programs in pediatric emergency departments (ED) and what interventions were provided in one ED with a CL program. We conducted a telephone survey of EDs in 44 large children's hospitals in the United States as to their use of child life specialists (CLS). Also, a retrospective review was performed of the CL intervention in one large pediatric ED over a two-year period. Only 6/44 EDs (14%) had at least one full-time CLS, with three of those having two full-time workers. In these EDs the CLS prepared children for painful or anxiety-provoking procedures and provided developmentally appropriate activities in the ED. Another 6/44 (14%) had CL services available by consult. There were no CLS available in 32/44 (72%) EDs, where nursing staff prepared children for painful procedures. EDs with a higher census were more likely to have a full-time CLS (P = 0.02). Hospitals with certified pediatric trauma centers were less likely to have any CL services available in the ED (P = 0.04). A review of the records of the ED at Arkansas Children's Hospital revealed that 32% of patient contacts by the CLS were for invasive procedure teaching and support. Another 22% of interventions were for developmental stimulation. Family support (21.5%) and therapeutic intervention (17.5%) were the next most common contacts. Admission teaching accounted for 4%, while preoperative teaching and support accounted for only 3% of the total. There were more patient contacts made by the worker on evening shift. CL programs, while common in the inpatient setting, are currently underutilized in most pediatric EDs. CLS can provide a variety of services in the pediatric ED.

Adaptation, Psychological

Fatal bone marrow embolism in a patient with sickle cell beta + thalassaemia.

Sickle cell beta + thalassaemia is regarded as the mildest of the sickle cell haemoglobinopathy syndromes with a benign natural course. In contrast to sickle cell disease, severe life threatening complications are not usually associated with this genotype. A case of a 30 year old West Indian man who, previously asymptomatic for 10 years, sustained a fatal pulmonary bone marrow embolism, is reported. This case report illustrates that serious, even fatal, complications may occur in patients with this 'benign' condition and bone marrow embolism should be included in the differential diagnosis of acute crisis in these patients.

Bone Marrow Diseases

Evaluating clinical case report data for SAR modeling of allergic contact dermatitis.

Clinical case reports can be important sources of information for alerting health professionals to the existence of possible health hazards. Isolated case reports, however, are weak evidence of causal relationships between exposure and disease because they do not provide an indication of the frequency of a particular exposure leading to a disease event. A database of chemicals causing allergic contact dermatitis (ACD) was compiled to discern structure-activity relationships. Clinical reports represented a considerable fraction of the data. Multiple Computer Automated Structure Evaluation (MultiCASE) was used to create a structure-activity model to be used in predicting the ACD activity of untested chemicals. We examined how the predictive ability of the model was influenced by including the case report data in the model. In addition, the model was used to predict the activity of chemicals identified from clinical case reports. The following results were obtained: When chemicals which were identified as dermal sensitizers by only one or two case reports were included in the model, the specificity of the model was reduced. Less than one half of these chemicals were predicted to be active by the most highly evidenced model. These chemicals possessed substructures not previously encountered by any of the models. We conclude that chemicals classified as sensitizers based on isolated clinical case reports be excluded from our model of ACD. The approach described here for evaluating activity of chemicals based on sparse evidence should be considered for use with other endpoints of toxicity when data are correspondingly limited.

Allergens

The aetiology of depression in the carers of dementia sufferers.

OBJECTIVE: To examine the associations of depression in the carers of dementia sufferers, diagnosed on the basis of a semistructured interview. DESIGN: Case control study. SETTING: Referrals to clinical services. SUBJECTS: The informal carers of 109 dementia sufferers, 32 with depression and 77 without. MEASURES: Carers were interviewed using the Geriatric Mental State Schedule. The diagnosis of depression was made according to Research Diagnostic Criteria. Instruments used to assess associations included Carers' Stress Scale, Marital Intimacy Scale, Cornell Depression Scale and CAMCOG Schedule. RESULTS: Only increasing age was significantly associated with depression in the overall group of carers. The severity of cognitive impairment was significantly associated with depression in carers who lived with a dementia sufferer and a low level of premorbid marital intimacy was significantly associated with depression amongst carers who were marital partners. CONCLUSION: Few factors are clearly associated with depression in the carers of dementia sufferers. The pattern of associations was, however, different for carers in different situations.

Activities of Daily Living

The duck gene for alpha B-crystallin shows evolutionary conservation of discrete promoter elements but lacks heat and osmotic shock response.

The gene for alpha Beta-crystallin from a bird (the domestic duck, Anas platyrhynchos) has been cloned and sequenced to allow comparison with its mammalian homologues. The duck gene has the same general structure as those of humans and rodents although, unlike those of mammals, the duck gene has two polyadenylation signals at the 3' end. The most interesting comparisons are in the 5'flanking promoter regions. In contrast to the broad conservation of promoter sequence among mammals, only two significant blocks and a few smaller elements have been conserved during evolution in the more distantly related avian gene. Block 1 (-350/-308) corresponds to alpha BE-2, a functional element defined in the mouse gene. Further downstream, block 2 (-98/-65) shows 27/33 identity among all three species but does not correspond to any previously defined element. Other regions are less well-conserved. In particular, putative heat-shock response elements of the mammalian alpha B-crystallin genes are absent from the duck gene. In contrast to the heat and osmotic stress-inducibility of mouse alpha B-crystallin in NIH 3T3 cells, duck alpha B-crystallin showed no inducibility in duck cells in culture. Thus, although high expression in lens is common to alpha B-crystallin genes in birds and mammals, other modes of expression appear to be taxon-specific.

Amino Acid Sequence

Coping by the carers of dementia sufferers.

One hundred and nine of 125 patients from consecutive referrals to a clinical service had an informal carer in contact at least once a week. Thirty-two of the carers had major or minor depression. The active management strategy 'being firm in directing behaviour' was significantly inversely associated with depression amongst carers living with the dementia sufferers, whilst carers who prioritized their daily routines were significantly more likely to be depressed. The active psychological coping strategy 'constructing a larger sense of the illness' was also significantly inversely associated with depression amongst carers living with the patients and 'reduction of expectations' showed a trend in the same direction. There were no significant differences between the coping strategies used by men and women. The type of coping strategy used by carers has an important relationship with depression. Active practical and psychological strategies were of benefit to carers and this has important treatment implications.

Activities of Daily Living

Classification of psychotic symptoms in dementia sufferers.

Little attention has been payed to the classification of psychotic symptoms in dementia sufferers. This article compares the etiology of delusions, visual hallucinations and delusional misidentification and examines the value of factors generated from principal components analysis as a possible classificatory system in a group of 125 patients with DSM-III-R dementia in contact with clinical services who were prospectively evaluated using standardized instruments to describe in detail individual psychotic symptoms. The assessment also included the Geriatric Mental State Schedule, the History and Aetiology Schedule and the CAMCOG. Delusions and visual hallucinations had a distinct cognitive profile as did delusions and delusional misidentification, although there was an overlap between visual hallucinations and delusional misidentification. Four factors were generated from principal components analysis. Three of these closely mirrored the 3 symptom groups delusions, visual hallucinations and delusional misidentification, although the phantom-boarder delusion was correlated with the visual hallucination factor and not delusional misidentification. The fourth factor included visual hallucinations of relatives and delusions that relatives were in the house. This factor was strongly inversely associated with emotional distress and could perhaps best be seen as a comfort phenomena. The pattern of cognitive deficits and etiological associations of each of the factors were independent of one another, supporting the notion that it is useful to consider them as separate entities.

Aged

Associations of psychotic symptoms in dementia sufferers.

BACKGROUND: Psychotic symptoms in dementia have been considered as a single category which may have masked important associations. An exploratory analysis was undertaken to look separately at delusions, visual hallucinations and delusional misidentification. METHOD: Psychotic symptoms were assessed with the Burns' Symptom Checklist in 124 patients with DSM-III-R dementia. RESULTS: Eighty-three (66.9%) patients had psychotic symptoms. Deafness and life events were associated with delusions and visual impairment was associated with visual hallucinations, while senile dementia of Lewy body type and older age were associated with both. CONCLUSIONS: Differences are evident in the associations of delusions and visual hallucinations. Sensory impairments were associated with both symptoms.

Aged

Temporal distribution of rotavirus G-serotypes in the West Midlands region of the United Kingdom, 1983-1994.

Samples of rotavirus from cases of acute gastroenteritis, occurring in the West Midlands region of the United Kingdom during the winter months of 1983 to 1994, were tested by enzyme-immunoassay for G-serotype (VP7). Statistically significant changes in the relative prevalence of serotypes occurred each year (p-values in chi-square tests were: p < 0.05 or p < 0.01). No consistent pattern was associated with these changes. G1, G2, G3, and G4 were the most common serotypes detected throughout the study period, accounting for 93.2%. Serotypes G5, G8, and G10 were detected in 0.4% samples, and serotypes other than G1 to G4 were detected in 6.8% samples. Thus, the rotavirus serotypes are less diverse here compared to other locations. These data are important for the development of an appropriate rotavirus vaccine.

Chi-Square Distribution

Dose response study of human exposure to 60 Hz electric and magnetic fields.

This human exposure study examined the relationship between field strength and biological response and tested whether the exposure levels at which the greatest effects occur differ for different endpoints. Three matched groups of 18 men each participated in two 6 h exposure test sessions. All subjects were sham exposed in one session. In the other session, each group of subjects was exposed at a different level of combined electric and magnetic field strength (low group:6 kV/m, 10 microT; medium group:9 kV/m, 20 microT; and high group: 12 kV/m, 30 microT). The study was performed double blind, with exposure order counterbalanced. Significant slowing of heart rate, as well as alternations in the latency and amplitude of event-related brain potential measures derived from the electro encephalogram (EEG), occurred in the group exposed to the 9 kV/m, 20 microT combined field (medium group). Exposure at the other field strength levels had no influence on cardiac measures and differential effects on EEG activity. Significant decrements in reaction time and in performance accuracy on a time estimation task were observed only in the low group. These results provide support for the hypothesis that humans may be more responsive to some combinations or levels of field strength than to others and that such differences in responsivity may depend, in part, on the endpoint of interest.

Action Potentials

Discriminating translation of insulin-like growth factor-II (IGF-II) during mouse embryogenesis.

The problem is to discover which of the promoters of the insulin-like growth factor-II gene stimulate the transcription of mRNA which is translated into protein. Three alternative leader exons are attached to the coding sequences in RNA transcribed from this gene in other systems, and it is mainly the paternal allele which is expressed in mouse development. Transcripts bearing each of the three leader exons were found in the RNA from the chorio-allantoic placenta, visceral yolk sac, and embryo, starting at 9.5 days. A varying proportion of one abundant transcript was disengaged from the polysomes at different days of development. This transcript was prefixed by the longest of the three alternative untranslated 5' leader exons (exon 2), and it was consistently associated with polysomes in the choroid plexus and leptomeninges of the brain. Many exon 2 transcripts were abbreviated by endonucleolytic cleavage and lacked a poly(A) tail. In contrast, the transcripts with the shortest leader (exon 3) were mainly displayed on polysomes at all the stages of development which were examined. During mouse development, the production of IGF-II protein must be partly controlled by the mechanisms which regulate translation.

Animals