Genetic influences on pulmonary severity in cystic fibrosis.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
R Knight
Publications and source records attributed to R Knight.
Cystic fibrosis haplotype association and the delta F508 mutation in adult British CF patients.
The delta F508 mutation and cystic fibrosis (CF) haplotypes with the markers KM19, pMP6d-9 and J3.11 are described in 54 adult British CF patients. delta F508 was found on 70% of all CF chromosomes, on none of the normal chromosomes and on only 37.5% of pancreatic sufficient CF chromosomes. All patients with meconium ileus were homozygous for the deletion.
Adult↗
Comparison of bretylium and lidocaine in the prevention of ventricular fibrillation after aortic cross-clamp release in coronary artery bypass surgery.
The authors compared bretylium and lidocaine for reducing the incidence and persistence of ventricular fibrillation following aortic cross-clamp release performed during coronary artery bypass surgery. Thirty-three adult patients scheduled for elective bypass surgery were randomly assigned in a double-blind fashion to receive a bolus of bretylium, 10 mg/kg, lidocaine, 2 mg/kg, or saline, in equal volumes prior to the release of the aortic cross-clamp. Coronary artery bypass surgery was conducted using standard cardiopulmonary bypass (CPB) procedures with systemic cooling to 24 degrees to 28 degrees C. Temperature, arterial blood gases, and electrolytes were recorded. After clamp release, the first electrical rhythm was noted. Abnormal rhythms (ventricular fibrillation) were allowed to persist for 1 to 2 minutes, and if spontaneous conversion to a supraventricular rhythm did not occur, defibrillation with internal DC countershocks was applied. Patients were compared with respect to occurrence of ventricular fibrillation, need for DC countershocks, antiarrhythmic drugs, and inotropic support. There was no significant difference among the groups with respect to age, sex, preoperative medications, past medical histories, ejection fractions, average number of bypasses, cross-clamp times, or temperatures during bypass. The incidence of ventricular fibrillation after aortic cross-clamp removal was: saline 91%, lidocaine 64% (P less than 0.01), and bretylium 36% (P less than 0.01). The number of countershocks required to defibrillate, while lower in the bretylium group, did not reach statistical significance. After cardiopulmonary bypass, cardiac output and systemic vascular resistance were comparable. Bretylium warrants further study in this setting.
Aged↗
Geographical distribution of cases of Creutzfeldt-Jakob disease in England and Wales 1970-84.
Two hundred and sixty seven patients with a definite or probable diagnosis of Creutzfeldt-Jakob disease (CJD) were identified in an attempt to ascertain all cases of the disease in England and Wales in the period 1970-84. No evidence of space-time clustering of dates and places of onset was found for these cases. Two age- and sex-matched controls were selected for 72 of the 122 cases diagnosed in the period 1980-84 and life histories of places of residence were obtained for these cases and the controls. No evidence was found that cases had lived closer to each other than had controls at any time in their lives, except that there was an excess of cases born in London. The study does not provide supportive evidence for case-to-case transmission of CJD being an important component in the aetiology of the disease.
Adult↗
Chronic cerebral intracellular alkalosis following forebrain ischemic insult in rats.
We measured cerebral intracellular pH using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy during 1 week after forebrain ischemia or sham operation in eight and seven rats, respectively. Mean maximum pH was significantly higher (p less than 0.003) in the ischemic group than in the sham-operated group (7.34 +/- 0.03 and 7.19 +/- 0.02, respectively). The difference between mean maximum pH and baseline pH (7.08 +/- 0.01 in each group) was significantly greater (p less than 0.02) in the ischemic group than in the sham-operated group. In the ischemic group, alkalosis occurred primarily after 48-72 hours of recirculation. We speculate that brain tissue alkalosis occurring chronically after ischemia is associated with delayed ischemic neuronal death.
Alkalosis↗
Percutaneous toxicity of ethylene glycol monomethyl ether and of dipropylene glycol monomethyl ether in the rat.
The subacute percutaneous toxicity of dipropylene glycol monomethyl ether (DPM) in male rats dosed 5 days/week for 4 weeks under both occluded and unoccluded conditions has been assessed and compared to the percutaneous toxicity of ethylene glycol monomethyl ether (EGM). DPM caused no significant changes in the clinical chemistry, haematology, or pathology, whereas EGM caused changes in the haematology and clinical chemistry, and both testicular and bone marrow damage at doses of 1000 mg/kg per day.
Administration, Topical↗
The metabolic effects of mild hypothermia on global cerebral ischemia and recirculation in the cat: comparison to normothermia and hyperthermia.
The metabolic effects of graded whole body hypothermia on complete global cerebral ischemia and recirculation was investigated in the cat. Hypothermia was induced to one of three levels prior to ischemia; T = 26.8 degrees +/- 0.5 degrees C (n = 4), T = 32.1 degrees +/- 0.2 degrees C (n = 5), and T = 34.6 degrees +/- 0.3 degrees C (n = 6), and maintained constant throughout 16 min of ischemia and 1.5-2 h of recirculation. Intracellular cerebral pH and relative concentrations of high-energy phosphate metabolites were continuously monitored, using in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Except for the first 4 min of ischemia, no significant differences were detected in the response of adenylate intensities and intracellular pH to ischemia and recirculation between the hypothermic groups. The three hypothermic groups were then pooled into one group, and the data compared to previously published data from a normothermic group, T = 38.4 degrees +/- 0.6 degrees C (n = 14), and a hyperthermic group, T = 40.6 degrees +/- 0.2 degrees C (n = 9), subjected to the identical ischemic and NMR measurement protocols. The hypothermic animals exhibited a statistically significant reduction of cerebral intracellular acidosis, both during ischemia and recirculation, as well as a more rapid return of adenylate intensities during recirculation, compared to the normothermic or hyperthermic groups. The data thus suggest that mild hypothermia has an ameliorative affect on brain energy metabolism and intracellular pH under conditions of complete global cerebral ischemia and recirculation.
Animals↗
Reduction of hyperthermic ischemic acidosis by a conditioning event in cats.
We investigated the effects of multiple episodes of cerebral ischemia on intracellular brain pH using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy. Four cats were subjected to two 16-minute episodes of complete global cerebral ischemia 6 hours apart; the second episode occurred under hyperthermic conditions (mean +/- SD body temperature 40.8 +/- 0.4 degrees C). Intracellular pH in these four cats was compared with that in nine cats subjected to a single 16-minute episode of complete global cerebral ischemia under hyperthermic conditions (mean +/- SD body temperature 40.6 +/- 0.2 degrees C). Intracellular pH during hyperthermic recirculation was significantly (p less than 0.03) greater in cats subjected to a previous ischemic event than that in cats subjected to only a single hyperthermic ischemic event. We speculate that the induction of heat shock proteins by an initial ischemic event may protect brain tissue from further ischemic insult.
Acidosis↗
Creutzfeldt-Jakob disease.
Creutzfeldt-Jakob disease is a 'slow virus' illness usually presenting as a rapidly progressive dementia. Although rare, its laboratory and accidental transmission has given it great theoretical importance. However, the infective agent remains mysterious and it is not known how, or even whether, natural transmission occurs. Clinical diagnosis is difficult, treatment unfortunately unsuccessful and special precautions are necessary in dealing with potentially infectious material.
Chronic Disease↗
A study of knowledge, attitudes and practices (KAP) of a rural community on malaria and the mosquito vector.
A study of malaria on the Kano Plain, Kisumu District, Western Kenya, was carried out between April and August, 1985. The study included a knowledge, attitudes and practices (K.A.P.) survey on malaria illness and the mosquito vector. Overall knowledge about malaria illness was found to be good. However, treatment and prevention practices of malaria were found to be poor. Knowledge of the mosquito and its relationship to malaria was found to be high. Knowledge of methods of prevention of mosquito bites was also found to be high but actual use of the methods was low. Knowledge of traditional methods of prevention of mosquito bites was also found to be high. Actual use was again found to be low.
Gastric Acid↗
Interrelationship of Polyamine and Ethylene Biosynthesis during Avocado Fruit Development and Ripening.
Concentrations of polyamines (PA) and the activities of the PA-synthesizing enzymes ornithine decarboxylase (ODC) and arginine decarboxylase (ADC) extracted from the mesocarp tissue of avocado (Persea americana Mill, cv ;Simmonds') fruits at different stages of development were compared with DNA content and the activities of 5'-methylthioadenosine (MTA) nucleosidase and 5-methylthioribose (MTR) kinase. Putrescine, spermidine, and spermine were at their peak concentrations during the early stages of fruit development (362, 201, and 165 nanomoles per gram fresh weight, respectively, at 15 days from full bloom), then declined to 30% or less at full maturity. Agmatine showed only a slight change in concentration throughout the fruit development. The activity of ODC, which was low during flowering (8 nmoles per milligram protein per hour), increased more than threefold during the first 2 months then declined at the later stages of fruit development, while ADC activity showed only a slight increase. DNA content followed a similar pattern of change as that of PA and ODC. The decline in DNA and ODC activity suggest a lack of correlation between cell proliferation and PA at the later stages of the avocado fruit development. It is also possible that any cell division which may take place during the latter stages of the fruit development is not sufficient to alter the pattern of PA biosynthesis. MTA nucleosidase and MTR kinase activities increased during the first 15 days of fruit development followed by a slight decline at 60 and 90 days from full bloom. At 120 days (1 month before full maturity) both MTA nucleosidase and MTR kinase activities increased significantly. During maximum ethylene synthesis, MTA nucleosidase and MTR kinase activities were approximately fivefold and eightfold, respectively, higher than during maximum PA synthesis. The data indicate that the MTA molecules produced during PA and ethylene synthesis are actively metabolized to MTR and MTR-1-P, the two intermediates involved in the regeneration of S-adenosylmethionine from MTA. The data also suggest that the PA and ethylene biosynthetic pathways are not actively competing for the same substrates at any given stage of the avocado fruit development and ripening.
Journal Article↗
Creutzfeldt-Jakob disease in England and Wales, 1980-1984: a case-control study of potential risk factors.
An attempt was made to ascertain all cases of Creutzfeldt-Jakob disease occurring in England and Wales during the 5 year period 1980-1984. The mean annual mortality rate was 0.49/million; women were more frequently affected than men. The age-specific mortality rate reached a peak in the seventh decade. A case-control study involving 92 of the 122 definite and probable cases ascertained failed to confirm the reality of previously suspected aetiological agents in the environment. Although there was no confirmed instance of familial Creutzfeldt-Jakob disease in the case-control study, dementia in close relatives was significantly more common than in controls.
Adult↗
Effect of mild hyperthermia on recovery of metabolic function after global cerebral ischemia in cats.
We investigated the effect of mild whole-body hyperthermia before and after 16 minutes of global cerebral ischemia on metabolic recovery during recirculation in cats using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy. Hyperthermia (temperature 40.6 +/- 0.2 degrees C) was induced greater than or equal to 1 hour before ischemia and was maintained during 1.5-2 hours of recirculation in nine cats; four cats were subjected to hyperthermia without cerebral ischemia, six to hyperthermia during recirculation (after return of intracellular pH to preischemic values), and 14 to normothermic ischemia and recirculation. Our data indicate that preischemic hyperthermia results in an intracellular cerebral pH during recirculation significantly lower than that in normothermic cats. In hyperthermic cats beta-ATP and phosphocreatine (PCr) concentrations and the ratio of PCr to inorganic phosphate failed to return to preischemic levels during recirculation in contrast to normothermic cats. Hyperthermia without ischemia and hyperthermia during recirculation had no significant effect on intracellular pH. Thus, preischemic hyperthermia has a detrimental effect on metabolic recovery after transient global cerebral ischemia.
Acidosis↗
The importance of list size and consultation length as factors in general practice.
It is commonly believed that longer consultations are essential to better care and that this can only be achieved by lowering list sizes. The results of a survey of general practitioner trainers show that, on average, the time given to each patient was longer when general practitioners had lower list sizes, but that for a substantial minority of doctors list size played no part. Although the evidence is inconclusive, patients registered with lower list size general practitioners consulted more and received prompter attention. Doctors with smaller lists worked shorter hours and felt less overworked. However most of the correlates were weak owing to great individual differences of practice style between general practitioners. If a case for lower list sizes is to carry force, stronger evidence is needed that patients will receive more of their general practitioners' attention.
Appointments and Schedules↗
A diurnal rhythm in proopiomelanocortin messenger ribonucleic acid that varies concomitantly with the content and secretion of beta-endorphin in the intermediate lobe of the rat pituitary.
The present study investigated whether diurnal variations in the secretion of alpha MSH and beta-endorphin from the intermediate lobe (IL) of the pituitary are associated with parallel changes in the synthesis of mRNA specifically encoding proopiomelanocortin (POMC). The results demonstrate that concomitant diurnal variations occur in both plasma and IL concentrations of immunoreactive beta-endorphin and alpha MSH. Plasma and IL peptide levels were relatively constant during daylight hours (0600-1800 h), but increased after the onset of darkness and reached maximal concentrations at 0200 h. To examine the possibility that this diurnal rhythm in the content and secretion of POMC-derived peptides resulted from diurnal changes in the biosynthesis of POMC, the concentration and rate of synthesis of POMC mRNA were examined. POMC mRNA levels were elevated during the dark period, reaching a maximum level at 0200 h that was 2-fold higher than that occurring during the light period. POMC mRNA synthesis, determined by measuring the number of RNA polymerase II complexes transcribing the POMC gene in isolated cell nuclei, also varied diurnally, with maximum transcription rates occurring at 1800 h, thus preceding maximal increases in POMC mRNA content and POMC peptide secretion by 8 h. Together, these data indicate that diurnal variations in the content and secretion of POMC-derived peptides are associated with parallel changes in POMC mRNA concentrations and are preceded by similar changes in POMC gene transcription.
Animals↗
Ethological studies of depressed patients.
The use of ethological methods for characterising the non-verbal behaviour of depressed patients and quantifying change during treatment is described. Approximately 150 individual motor patterns--expressions, gestures and movements--have been defined and this element list provides the basis for encoding video-recordings of interactions. Data quality is controlled by inter- and intra-observer comparisons and by a split-screen technique which simultaneously displays a computer animation of a data file and the original video-recording. Two investigations of the characteristics of non-verbal behaviour in Depression are discussed. The first showed that the frequency and duration of many items of behaviour of depressed patients interviewed soon after admission to hospital differed significantly from matched controls. Recordings of an interview at an intermediate point in treatment showed a reduction in these differences and they had disappeared when examined shortly before discharge. The second study was of mothers suffering from Post Natal Depression who were interviewed once. This study provided evidence that quantification of non-verbal behaviour can distinguish between diagnostic subcategories and showed some of the fine detail of behaviour which can be revealed in this way.
Animals↗
Clearance-based oral drug interaction between verapamil and metoprolol and comparison with atenolol.
Explore the source record for details and available documents.
Administration, Oral↗
Effect of beta-blockers on psychomotor performance in normal volunteers.
The effects of beta-adrenergic receptor antagonists on psychometric tests including vehicle handling, choice reaction time, and kinetic visual acuity (KVA), are reviewed. The beta-blockers had little effect on the performance tests, with the unexplained but reproducible effect of enhanced KVA performance with atenolol. Although the beta-blockers had little effect on performance tests they were shown to have psychotropic effects in normal volunteers. The reasons for the conflicting evidence concerning the effect of these drugs on performance tests is discussed in relation to the present experiments and to variables that may influence response. It is concluded that one should use tests that are as independent as possible from potentially confounding variables. The use of evoked potentials in the electroencephalogram is one such test. A preliminary study is described in which the effects of beta-blockers were detected using visual evoked responses on the electroencephalogram.
Adolescent↗