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Biomedical subjects

C Graham

Publications and source records attributed to C Graham.

At least 37 records · Page 2Linked to original sources
PubMed1998

Nocturnal exposure to intermittent 60 Hz magnetic fields alters human cardiac rhythm.

Heart rate variability (HRV) results from the action of neuronal and cardiovascular reflexes, including those involved in the control of temperature, blood pressure and respiration. Quantitative spectral analyses of alterations in HRV using the digital Fourier transform technique provide useful in vivo indicators of beat-to-beat variations in sympathetic and parasympathetic nerve activity. Recently, decreases in HRV have been shown to have clinical value in the prediction of cardiovascular morbidity and mortality. While previous studies have shown that exposure to power-frequency electric and magnetic fields alters mean heart rate, the studies reported here are the first to examine effects of exposure on HRV. This report describes three double-blind studies involving a total of 77 human volunteers. In the first two studies, nocturnal exposure to an intermittent, circularly polarized magnetic field at 200 mG significantly reduced HRV in the spectral band associated with temperature and blood pressure control mechanisms (P = 0.035 and P = 0.02), and increased variability in the spectral band associated with respiration (P = 0.06 and P = 0.008). In the third study the field was presented continuously rather than intermittently, and no significant effects on HRV were found. The changes seen as a function of intermittent magnetic field exposure are similar, but not identical, to those reported as predictive of cardiovascular morbidity and mortality. Furthermore, the changes resemble those reported during stage II sleep. Further research will be required to determine whether exposure to magnetic fields alters stage II sleep and to define further the anatomical structures where field-related interactions between magnetic fields and human physiology should be sought.

Adolescent↗
PubMed1997

Alternative splicing of Pax6 in bovine eye and evolutionary conservation of intron sequences.

Pax-6 is essential for eye development and for tissue-specific gene expression within the eye. Splicing of an alternative exon (5a) leads to variant DNA binding specificity in Pax6. Here we show that in the mature bovine eye the relative abundance of the alternative Pax6-5a mRNA varies markedly, particularly between the lens and iris. Additional alternative splicing products were identified which may lead to "domain swapping" or truncation of Pax6 proteins. Comparison of amphibian (Xenopus) and mammalian (bovine) Pax-6 genes revealed highly conserved intronic sequences flanking exon 5a, including potential lariat sites which may have a role in the mechanism of alternative splicing.

Alternative Splicing↗
PubMed1997

Efficacy of laser-assisted uvulopalatoplasty.

BACKGROUND AND OBJECTIVE: Laser-assisted uvulopalatoplasty (LAUP) is being used increasingly as a surgical treatment for snoring and obstructive sleep apnea (OSA). There is limited evidence for the success of LAUP in eliminating OSA. This study assesses the efficacy of LAUP in eliminating snoring and OSA and addresses which patients may be the best candidates for LAUP treatment. STUDY DESIGN/MATERIALS AND METHODS: From January 1994 to January 1996, 297 patients were evaluated for snoring, with 190 (64%) exhibiting some degree of OSA documented by a PSG: 41/ 190 (22%) mild OSA; 33/190 (17%) moderate OSA; 85/190 (45%) severe OSA; 31/190 (16%) severity unknown. Ninety patients (90/ 297) have undergone LAUP treatment: 58/90 (64%) with OSA and 32/90 (36%) with snoring only. RESULTS: Our results indicate a significant reduction of snoring in patients without OSA, but diminishing success in patients with increasing degrees of OSA. Additionally, LAUP was not efficacious in treating OSA: pre-op respiratory disturbance index (RDI) of 10.8 vs. post-op RDI of 19.5 for mild OSA (P = 0.14); pre-op RDI of 22.9 vs. post-op RDI of 25.4 for moderate OSA (P = 0.43); pre-op RDI of 56.8 vs. post-op RDI of 46.3 (P < 0.05), which is statistically but not clinically significant (i.e., RDI remained in the severe range). CONCLUSION: We conclude that LAUP is an effective treatment for nonapneic snoring, but does not provide sufficient resolution of OSA, and based on our results, LAUP should be considered as an adjunctive therapy rather than a sole treatment for OSA in most cases.

Adult↗
PubMed1997

Structure-activity model of chemicals that cause human respiratory sensitization.

We report a structure-activity model of chemicals with the potential to cause respiratory allergy developed through the CASE/MultiCASE systems. Chemicals documented to elicit a decrease in FEV1 of > or = 20% within 24 h of inhalation provocation challenge were used to form a learning set. Additional requirements for inclusion in the learning set were that chemicals had at least two contiguous nonhydrogen atoms and were nonmetallic. Forty chemicals met these criteria. The model identified several "structural alerts" including the isocyanate functionality (N = C = O), primary and secondary amines, substituted aromatic moieties, and distance descriptors. An external data-withholding exercise used to validate the model yielded a sensitivity of 0.95 and a specificity of 0.95. This model is applicable to initial prediction of the sensitizing ability of untested chemicals and may provide mechanistic insight into the process(es) of respiratory sensitization.

Administration, Inhalation↗
PubMed1997

Automated fed-batch fermentation with feed-back controls based on dissolved oxygen (DO) and pH for production of DNA vaccines.

A fermentation process in Escherichia coli for production of supercoiled plasmid DNA for use as a DNA vaccine was developed using an automated feed-back control nutrient feeding strategy based on dissolved oxygen (DO) and pH. The process was further automated through a computer-aided data processing system to regulate the cell growth rate by controlling interactively both the nutrient feed rate and agitation speed based on DO. The process increased the total yield of the plasmid DNA by approximately 10-fold as compared to a manual fed-batch culture. The final cell yield from the automated process reached 60 g L-1 of dry cell weight (OD600 = 120) within 24 h. A plasmid DNA yield of 100 mg L-1 (1.7 mg g-1 cell weight) was achieved by using an alkaline cell lysis method. Plasmid yield was confirmed using High Performance Liquid Chromatography (HPLC) analysis. Because cells had been grown under carbon-limiting conditions in the automated process, acetic acid production was minimal (below 0.01 g L-1) throughout the fed-batch stage. In contrast, in the manual process, an acid accumulation rate as high as 0.36 g L-1 was observed, presumably due to the high nutrient feed rates used to maintain a maximum growth rate. The manual fed-batch process produced a low cell density averaging 10-12 g L-1 (OD600 = 25-30) and plasmid yields of 5-8 mg L-1 (approximately 0.7 mg g-1 cells). The improved plasmid DNA yields in the DO- and pH-based feed-back controlled process were assumed to be a result of a combination of increased cell density, reduced growth rate (mu) from 0.69 h-1 to 0.13 h-1 and the carbon/nitrogen limitation in the fed-batch stage. The DO- and pH-based feed-back control, fed-batch process has proven itself to be advantageous in regulating cell growth rate to achieve both high cell density and plasmid yield without having to use pure oxygen. The process was reproducible in triplicate fermentations at both 7-L and 80-L scales.

Acetic Acid↗
PubMed1997

A controlled family study of late-onset non-affective psychosis (late paraphrenia).

BACKGROUND: The relationship between those schizophrenia-like conditions that have their onset in late life and early-onset schizophrenia is unclear. Very few family history studies of patients with late-onset psychosis have been reported, and it is not known whether their relatives have an increased risk of psychosis. METHOD: Information was collected on the psychiatric morbidity of 269 first-degree relatives of patients with schizophrenia or delusional disorder with an onset after the age of 60 (late paraphrenia), and 272 first-degree relatives of healthy elderly control subjects, using a research diagnostic instrument. RESULTS: With a narrow age range (15-50 years) at risk, the estimated lifetime risk of schizophrenia was 1.3% in the relatives of both cases and controls. With a wider age range (15-90 years) at risk, estimated lifetime risk of schizophrenia was 2.3% for the relatives of cases and 2.2% for the relatives of controls. However, depression was significantly more common among the relatives of cases than controls. CONCLUSIONS: Those schizophrenia-like psychoses with onset in late life are not genetically associated with schizophrenia.

Adult↗
PubMed1997

The expression and activity of prostaglandin H synthase-2 is enhanced in trophoblast from women with preeclampsia.

Preeclampsia is associated with altered biosynthesis of vasoactive prostanoids in placental villi. The two isozymes of prostaglandin H synthase (PGHS) are essential for prostanoid synthesis. We tested the hypothesis that PGHS-2 expression is elevated in trophoblast from preeclamptic women, compared with trophoblast from healthy women. Using immunofluorescent staining, we demonstrated a higher PGHS-2 expression in villi from preeclampsia, compared with normal pregnancy. Cytotrophoblasts cultured from placentas of preeclamptic women expressed higher levels of PGHS-2 compared with cytotrophoblasts from normal placentas. This enhanced expression of PGHS-2 correlated with increased media levels of both thromboxane and prostaglandin E2, two products of PGHS activity. The increased prostanoid production by trophoblast from preeclamptic women was markedly reduced by NS-398, a specific inhibitor of PGHS-2. We conclude that both expression and activity of PGHS-2 are enhanced in trophoblasts from preeclamptic women compared with trophoblast from normal pregnancies. The increased production of prostanoids may contribute to the clinical syndrome of preeclampsia. Our data suggest that a selective inhibitor of PGHS-2 might provide a therapeutic alternative to prophylactic low-dose aspirin in modifying the prostanoid profile in preeclampsia.

Blotting, Northern↗
PubMed1997

Prioritizing testing of organic compounds detected as gas phase air pollutants: structure-activity study for human contact allergens.

Organic compounds that are used or generated anthropogenically in large quantities in cities can be identified through their presence in the urban atmosphere and in air pollutant source emissions. Compounds identified by this method were screened to evaluate their potential to act as contact allergens. The CASE and MULTICASE computer programs, which are based on the detection of structure-activity relationships (SAR), were used to evaluate this potential. These relationships first are determined by comparing chemical structures to biological activity within a learning set comprised of 458 compounds, each of which had been tested experimentally in human trials for its sensitization potential. Using the information contained in this learning set, CASE and MULTICASE predicted the activity of 238 compounds found in the atmosphere for their ability to act as contact allergens. The analysis finds that 21 of 238 compounds are predicted to be active contact allergens (probability >0.5), with potencies ranging from mild to very strong. The compounds come from chemical classes that include chlorinated aromatics and chlorinated hydrocarbons, N-containing compounds, phenols, alkenes, and an S-containing compound. Using the measured airborne concentrations or emission rates of these compounds as an indication of the extent of their use, together with their predicted potencies, provides an efficient method to prioritize the experimental assessment of contact sensitization of untested organic compounds that can be detected as air pollutants.

Air Pollutants↗
PubMed1997

Airway isocyanate-adducts in asthma induced by exposure to hexamethylene diisocyanate.

OBJECTIVES: The clinical features, airway histology, and detection of hexamethylene diisocyanate (HDI) protein adducts in endobronchial biopsies from a patient with HDI asthma are described. METHODS: Isocyanate asthma was diagnosed by history, methacholine challenge, and workplace HDI challenge. Bronchoscopy was performed 24 h after challenge and immunohistochemical staining was performed. RESULTS: Airway biopsies obtained at bronchoscopy demonstrated inflammatory changes typical for asthma, including increased airway eosinophils and T cells. Immunohistochemical staining with specific anti-HDI antibodies demonstrated the presence and localization of HDI adducts in human bronchial biopsies. CONCLUSIONS: These studies confirm epithelial exposure to HDI following workplace challenge and demonstrate the feasibility of detecting and localizing isocyanate adducts in human lung tissue. Identifying and characterizing the airway macromolecules to which isocyanates bind in vivo are probably crucial to the understanding of how isocyanates cause sensitization and asthma. The ability to detect isocyanate adducts may also help characterize isocyanate exposure patterns and exposure-disease relationships.

Adult↗
PubMed1997

Human melatonin during continuous magnetic field exposure.

This report describes the third in a series of double-blind, laboratory-based studies that were aimed at determining the effects of nocturnal exposure to power frequency magnetic fields on blood levels of melatonin in human volunteers. Our two earlier studies evaluated effects on melatonin of intermittent exposure to 60 Hz circularly polarized magnetic fields at 10 and 200 mG. No overall effects on melatonin levels were found. In the present study, men were exposed continuously rather than intermittently through the night to the same 200 mG magnetic field condition that was used previously; again, no overall effects on melatonin levels were found. We conclude that the intermittent and continuous exposure conditions used in our laboratory to date are not effective in altering nocturnal blood levels of melatonin in human volunteers.

Adolescent↗
PubMed1997

Variables which distinguish patients fulfilling clinical criteria for dementia with Lewy bodies from those with Alzheimer's disease.

OBJECTIVES: To compare patients fulfilling clinical criteria for Lewy body dementia with those meeting clinical criteria for Alzheimer's disease. DESIGN: Prospective cohort study. SETTING: Psychiatric services and a memory clinic. SAMPLE: 124 patients with DSM-III-R dementia. MEASURES: The assessment included the GMS/HAS/SDS package, the CAMCOG, the Cornell Depression scale and the Burns Symptom Checklist. Dementia was diagnosed according to DSM-III-R, NINCDS ADRDA, McKeith, Byrne, Hachinski and HAS AGECAT criteria. RESULTS: Patients meeting McKeith et al. criteria for senile dementia of Lewy body type were significantly more likely to have clouding of consciousness, significant Parkinsonian symptoms and less severely impaired recent memory than patients with NINCDS ADRDA Alzheimer's disease. Each of these variables also distinguished patients meeting Byrne et al.'s criteria for dementia with Lewy bodies from those with a diagnosis of Alzheimer's disease. CONCLUSIONS: It is suggested that one set of criteria could encompass those overlapping groups of patients. Work is needed to further develop the diagnostic criteria for Lewy body dementia.

Aged↗
PubMed1997

Carers' knowledge of dementia and their expressed concerns.

OBJECTIVE: The authors wished to determine how much carers from different settings caring for patients with dementia knew about the disorder and elicit their main concerns about the disease. DESIGN: A survey questionnaire was administered to 136 carers. SETTING: Two old age psychiatric services and an Alzheimer's support group in urban areas of the UK. PARTICIPANTS: The carers came from one of three categories: (1) carers with no prior contact with elderly mental health services (preassessment group); (2) carers who had been in contact with mental health care professionals (postassessment group); (3) carers in contact with an Alzheimer's Disease Society support group. MEASURES: A questionnaire on the subject of dementia. Carers' worries about the disorder were also recorded. RESULTS: Carers in contact with an Alzheimer's support group were the most knowledgeable and carers in the preassessment group were the least knowledgeable on the subject of dementia. While carers in the postassessment group had a level of knowledge above that of the preassessment group, this difference failed to reach statistical significance. CONCLUSION: The study highlights the need for elderly mental health teams to evaluate their methods of dissemination of knowledge to carers, develop educational packages for carers and evaluate their effectiveness.

Aged↗
PubMed1997

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↗
PubMed1996

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↗