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Biomedical subjects

G Davies

Publications and source records attributed to G Davies.

At least 19 recordsLinked to original sources

Crystallization and preliminary X-ray analysis of a fungal endoglucanase I.

An endoglucanase I (EG1) from a fungal source (Humicola insolens) has been crystallized in a number of forms suitable for X-ray diffraction analysis. Four crystal forms have been grown from various precipitants using vapour phase diffusion methods in hanging drops. Three of these crystal forms diffract to beyond 2.5 A resolution. Two forms, obtained from ammonium sulphate at pH 5.4, or 8.0, grow as tetragonal bipyramids in space group P4(1)22 or P4(3)22, with approximate cell dimensions a = b = 102 A, c = 282 A. The other crystal forms were grown from polyethylene glycol 8000 at pH 8.0. One grows as monoclinic plates, space group P2(1), with cell dimensions a = 66.9 A, b = 75.2 A, c = 86.9 A and beta = 102.9 degrees and the other as long hexagonal rods in space group P6(1)22 or P6(5)22, with cell dimensions a = b = 119 A, c = 83 A.

Cellulose 1,4-beta-Cellobiosidase

Preangioplasty complicated coronary stenosis morphology as a predictor of restenosis.

To assess whether complicated preangioplasty coronary stenosis morphology is associated with restenosis, 41 patients (47 stenoses) who underwent repeat angiography 6 to 8 months after percutaneous transluminal coronary angioplasty (PTCA) were studied. Stenosis diameter and morphology were assessed by computerized quantitative coronary angiography before and immediately after PTCA and at follow-up angiography. Before PTCA 18 stenoses were concentric (symmetric narrowings with smooth borders), 12 were eccentric (asymmetric narrowings with smooth borders), and 17 were complicated (asymmetric with rough borders and overhanging edges). Restenosis occurred in 18 lesions: two (11%) concentric, four (33%) eccentric, and 12 (70%) complicated (p less than 0.05), whereas 29 lesions remained unchanged. Stenosis diameter before and immediately after PTCA was not significantly different in the 18 patients with and the 23 patients without restenosis. Follow-up angiograms showed that 11 (61%) stenoses in the group with restenosis and 18 (63%) in the group without restenosis had morphology similar to that before PTCA. Restenosis occurred in seven (30%) patients who initially had chronic stable angina and in 11 (61%) who were first seen with unstable angina (p less than 0.05). In patients with stable angina 1 of 13 concentric stenoses, two of eight eccentric stenoses, and four of five complicated lesions restenosed. In patients with unstable angina one of five concentric, two of four eccentric, and 8 of 12 complicated lesions had restenosis. Stenoses that were complicated before PTCA tended to adopt an irregular morphology if they recurred, whereas concentric stenoses rarely occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Relation between stimulation site of cardiac afferent nerves by adenosine and distribution of cardiac pain: results of a study in patients with stable angina.

OBJECTIVES: The purpose of this study was to establish whether stimulation of cardiac sensory receptors in different myocardial regions results in different distributions of cardiac pain. BACKGROUND: Previous studies have shown that adenosine provokes cardiac pain through stimulation of sensory receptors in the absence of myocardial ischemia. In this study adenosine was used to obtain a regional stimulation of cardiac sensory receptors. METHODS: Increasing doses of adenosine (0.25, 0.5 and 1 mg/min) were selectively infused into the right and then into the left coronary artery in 26 patients with stable angina. RESULTS: No patient developed ischemic electrocardiographic changes during either adenosine infusion. Eighteen patients experienced cardiac pain during both infusions. Despite the stimulation of sensory receptors in different myocardial regions, 13 patients experienced cardiac pain in the same body area. Adenosine-induced pain was always similar to the anginal pain. By contrast, the remaining five patients experienced adenosine-induced cardiac pain in different body areas. In two of these patients, the distribution of anginal pain was similar to that experienced during one of the two adenosine infusions. In the remaining three patients, the distribution of anginal pain was similar to that experienced during adenosine infusion into the right coronary artery during some anginal episodes and to that experienced during adenosine infusion into the left coronary artery during other episodes. CONCLUSIONS: During stimulation by adenosine of sensory receptors in different myocardial regions, the majority of patients experience cardiac pain in the same body area; only a few experience pain in different areas. These differences might be caused by different organizations of the ascending neural pathways to the cortex. Our results suggest that in the same patient different distributions of pain during anginal attacks are probably due to ischemia in different myocardial regions.

Adenosine

Effects of recombinant granulocyte-macrophage colony-stimulating factor on bovine peripheral blood and mammary gland neutrophil function in vitro.

Modulation of peripheral blood and mammary gland neutrophil function following in vitro exposure to recombinant bovine granulocyte-macrophage colony-stimulating factor (rBoGM-CSF) was studied. Bovine blood and mammary gland neutrophils were cultured for 9 h in media containing 0.005, 0.05 or 0.5 microgram/mL rBoGM-CSF. Neutrophils treated with rBoGM-CSF exhibited significantly more chemotactic and bactericidal activities and tended to produce more superoxide anion than control cells. The effects of rBoGM-CSF on bovine neutrophil populations appeared to be dose-dependent. The production of superoxide anion and the bactericidal activity of mammary gland neutrophils were consistently higher than blood neutrophils. Only moderate increases in lipopolysaccharide-induced mammary gland neutrophil functions were observed following incubation with rBoGM-CSF which suggests that there may be a threshold of immunomodulation for these prestimulated cells. It may be possible to augment the functional capacity of bovine neutrophil populations in vivo through the therapeutic application of rBoGM-CSF and consequently enhance resistance of dairy cattle to bacterial infections.

Animals

Strain variation in Dermatophilus congolensis demonstrated by cross-protection studies.

Cross-protection studies were conducted with vaccines prepared from two isolates of Dermatophilus congolensis (designated strain 1 and strain 2). The vaccines were prepared as either heat-inactivated, washed, formalized filamentous phase bacterium, mixed with alum as an adjuvant, and inoculated intramuscularly (type A vaccine) or sedimented live filaments inoculated intradermally (type B vaccine). The vaccinated sheep were challenged with D. congolensis zoospores of one or other strain. Challenge sites were observed for the presence and severity of lesions. Serum antibody levels to D. congolensis were monitored after vaccination and challenge. Type A and B vaccines from both strains produced some reduction in the severity of lesions when sheep were challenged with strain 1 but not with strain 2. Unvaccinated control sheep developed more severe and persistent lesions when challenged with strain 2 than controls challenged with strain 1. Serum antibody levels to the type B vaccine prepared from strain 1 were significantly higher (P less than 0.05) than antibody levels to type B vaccine from strain 2. These findings showed there was significant variation in virulence and antigenicity between these two isolates of D. congolensis.

Actinomycetales

Understanding the mind as an active information processor: do young children have a "copy theory of mind"?

Most 4-, but no 3-year-olds, were able to understand the mind's active role in evaluating the truth of verbal information. They appreciated that a statement, whether true or false, will be disbelieved if the listener has existing beliefs to the contrary and that it will be believed if no such beliefs exist. Four- and 5-year-olds were equally competent in understanding the need for interpretation of pictorial material. They realized that an uninitiated person cannot make sense of a "droodle", which in itself is an uninterpretable section of a larger meaningful drawing. We discuss the impact of our findings on the question of whether children at this age entertain a copy theory of mind.

Attention

Preoperative localisation of the saphenopopliteal junction with duplex scanning.

The anatomy of the saphenopopliteal junction shows considerable variation, and clinical localisation of this junction is inaccurate. Duplex scanning in preoperative mapping of the saphenous vein system in bypass surgery has been shown to be highly effective. In 62 patients with clinical evidence of insufficiency of the saphenopopliteal junction, preoperative localisation with duplex scanning was performed in 66 extremities. In 62 extremities duplex localisation matched the operative findings and in four extremities a difference of 2 cm or more was found. There was 1 false negative surgical exploration. In 93% of the cases exact localisation of the junction enabled us to perform flush ligation of a small saphenous vein through minimal exposure. Preoperative duplex scanning of the saphenopopliteal junction is highly accurate.

Female

Retinal blood flow following a tyramine-induced increase in blood pressure.

The effect of increasing systemic blood pressure on retinal blood flow was investigated in anaesthetised miniature pigs. Blood pressure was increased by the infusion of the sympathomimetic amine, tyramine. Volume flow was determined from axial erythrocyte velocity, measured by laser Doppler velocimetry, and vessel diameter, measured from monochromatic retinal photographs. Measurements were taken when mean arterial pressures were elevated by a mean of 22 +/- 3% and 50 +/- 8% above resting values, which represented increases of 31 +/- 2% and 74 +/- 16% in ocular perfusion pressures. Retinal blood flow increased by 8.5 +/- 8% at the lower infusion rate and by 57 +/- 19% at the higher infusion rate. We conclude that tyramine infusion is a suitable method for the study of retinal autoregulation and that the upper limit of retinal autoregulation in miniature pigs lies between 22-50% above resting mean arterial pressure.

Animals

Interaction of neuropeptide Y and the sympathetic nervous system in vascular control in man.

BACKGROUND: There is increasing evidence that neuropeptide Y (NPY) contributes to the autonomic control of the circulation. NPY coexists with noradrenaline in perivascular nerve terminals, may be released during sympathetic stimulation, and is a potent constrictor of the human coronary circulation and other vascular beds. In vitro studies show that NPY can act either directly on vascular smooth muscle or indirectly by modulation of the presynaptic release or the postsynaptic actions of noradrenaline. It is unclear to what extent these mechanisms operate in vivo. METHODS AND RESULTS: The effect on forearm blood flow of intra-arterial NPY was studied in six volunteers during coinfusion of noradrenaline and during reflex sympathetic stimulation induced by lower-body negative pressure. NPY alone induced a dose-dependent reduction of forearm blood flow in all subjects studied, to a maximum of 49 +/- 6.1%. The reduction of flow during infusion of noradrenaline alone was 42 +/- 8%. The response to noradrenaline was unaffected by coinfusion of a threshold constrictor dose of NPY (50 pmol/min). Furthermore, the reflex sympathetic vasoconstrictor response to 20 cm H2O of lower-body negative pressure was similar in both the infused and control arms during the infusion of 50 pmol/min NPY. The response to noradrenaline was abolished by alpha-blockade with phentolamine, but the flow reduction induced by NPY was unaffected by alpha-blockade. CONCLUSIONS: NPY is a potent constrictor of human forearm resistance vessels and has a direct effect independent of alpha-receptors. NPY has no detectable modulating effect in vivo on the action of endogenous or infused noradrenaline.

Adult

A pilot study of low-dose zidovudine in human immunodeficiency virus infection.

BACKGROUND: Zidovudine delays the progression of human immunodeficiency virus (HIV) infection but is associated with hematologic toxicity at high doses. Regimens are needed that preserve or enhance efficacy and reduce toxicity. Acyclovir has been reported to potentiate the effect of zidovudine on HIV in vitro. METHODS: We conducted a Phase II open-label, dose-escalating trial to evaluate the clinical and antiviral effects of zidovudine at low (300 mg daily, 28 subjects), medium (600 mg, 24 subjects), and high (1500 mg, 15 subjects) doses, either with or without acyclovir (4.8 g) by random assignment. The subjects had the acquired immunodeficiency syndrome (AIDS)-related complex, but not AIDS. All of them had either HIV p24 antigenemia or plasma viremia and CD4-lymphocyte counts of 200 to 500 per cubic millimeter when they began treatment. RESULTS: Performance scores and fatigue improved the most in the low- and medium-dose zidovudine groups (both P less than or equal to 0.025). Those assigned to low-dose zidovudine gained the most weight and had the greatest improvement in the mean CD4-lymphocyte count (from 321 per cubic millimeter at base line to 412 per cubic millimeter after 12 weeks, P = 0.01). The proportion of subjects in whom HIV antigenemia resolved, the decrease in the level of antigenemia, and the reduction in the plasma virus titers were similar at all three doses. Subjects assigned to receive the low or medium dose who subsequently crossed over to the 1500-mg dose (n = 19) did not have an increase in CD4-cell counts or a decline in levels of HIV antigen, but they did have dose-related toxicity. The addition of acyclovir to zidovudine was well tolerated, but it did not enhance any of zidovudine's antiretroviral effects. CONCLUSIONS: In this pilot study a very low dose of zidovudine (300 mg) had clinical and virologic effects similar to those of higher daily doses (600 and 1500 mg). The minimal effective dose of zidovudine for the treatment of HIV infection has yet to be determined, and further studies of very low daily doses are warranted.

AIDS-Related Complex

Myocardial ischemia caused by distal coronary-artery constriction in stable angina pectoris.

BACKGROUND: In patients with stable coronary artery disease, the ischemic threshold for the production of effort-related angina is often quite variable. Although this feature is commonly attributed to changes in the caliber of coronary arteries at the site of stenosis, it could also be caused by the constriction of distal vessels, collateral vessels, or both. METHODS: In order to test this hypothesis, we studied 11 patients with stable angina, total occlusion of a single coronary artery that was supplied by collateral vessels, normal ventricular function, no evidence of coronary-artery spasm, and no other coronary stenoses. These conditions precluded the modulation of coronary flow by vasomotion at the site of the coronary stenosis. RESULTS: The ischemic threshold--assessed by multiplying the heart rate by the systolic blood pressure at a 1-mm depression of the ST segment during exercise testing--increased by 19 percent after the administration of nitroglycerin (P less than 0.05) and decreased by 18 percent after the administration of ergonovine (P less than 0.01). Ambulatory electrocardiographic monitoring of the patients when not receiving treatment detected 73 ischemic episodes that, in keeping with the history, showed variations of 25 to 52 beats per minute in the heart rate at a 1-mm depression of the ST segment; 12 episodes of sinus tachycardia exceeded the lowest ischemic heart rate by a mean (+/- SD) of 22 +/- 13 beats per minute without ST-segment depression. Furthermore, 21 ischemic episodes occurred at a heart rate more than 25 beats per minute below that at a 1-mm depression of the ST segment during exercise testing. Delayed and reduced filling of collateral and collateralized vessels associated with depression of the ST segment similar to that observed during ambulatory monitoring was detected on angiographic evaluation after the intracoronary administration of ergonovine in three patients. CONCLUSIONS: We propose that the constriction of distal coronary arteries, collateral vessels, or both may cause myocardial ischemia in patients with chronic stable angina.

Adult

Surgery for Crohn's disease in childhood: influence of site of disease and operative procedure on outcome.

Factors influencing outcome after surgery have been studied in 67 children requiring bowel resection or diversion of the faecal stream for Crohn's disease. Patients were divided into four groups on the basis of disease location at time of surgery, and mean follow-up was 4.5 years. All three children with panenteric disease (group 1) have relapsed. Best results were observed in cases with disease confined to the small bowel (group 2) and ileocaecal region (group 3), in whom surgery was followed by sustained remission in six out of seven and 24 out of 30 patients respectively. In the 27 children with colitis (group 4), results were mixed. Six of the seven patients who had staged colonic resections with a primary anastomosis relapsed, as did three out of four patients given a loop ileostomy to divert the faecal flow; in contrast, 15 out of 16 children who had a subtotal colectomy with ileostomy as the primary procedure have remained well, with only minor problems involving the rectal stump. An acceleration in growth velocity was observed during the first year after operation in 89 per cent of 40 children studied. Outcome after surgery for Crohn's disease in childhood depends mainly on disease location, but is influenced by the type of primary operation performed. In addition to symptomatic relief the principal early benefit of surgery is improved growth.

Adolescent

Peri-operative supraventricular arrhythmias in coronary bypass surgery.

One hundred consecutive admissions for coronary bypass surgery were studied to establish the incidence of peri-operative supraventricular arrhythmias, to monitor their evolution, and to identify their possible aetiological factors. No important arrhythmias were detected before the operation. Post-operatively, 24 patients (24%) developed supraventricular arrhythmias. Nineteen of them had atrial fibrillation or flutter (19%), 2 had supraventricular tachycardia (2%), and 3 had inappropriate sinus bradycardia (less than 45 min) (3%). Almost two-thirds of the arrhythmias occurred within the critical early post-operative period (63%). Haemodynamic compromise ushered the onset of arrhythmias in more than one-third of the patients in whom antiarrhythmic measures ensured prompt improvement (37.5%). Three-quarters of those with atrial fibrillation or flutter were back in sinus rhythm at the time of discharge from hospital (74%). The incidence of supraventricular arrhythmia was significantly higher in patients with demonstrable myocardial ischaemia prior to surgery, in patients who underwent adjunctive coronary endarterectomy, or in those in whom topical cardiac cooling was applied (50%, 45%, and 58%, respectively). Supraventricular arrhythmias are frequently encountered during the critical early post-operative period when serious but reversible haemodynamic compromise might be precipitated. Although the nature of the underlying myocardial insult remains obscure, supraventricular arrhythmia may be related more to defective myocardial preservation than to any specific underlying myocardial lesion.

Arrhythmias, Cardiac

Reperfusion arrhythmias are rare during acute myocardial infarction and thrombolysis in man.

Coronary arterial reperfusion is commonly associated, in anaesthetized animals, with severe arrhythmias, but the clinical relevance of this model remains uncertain. Continuous electrocardiographic ST-segment recording was performed immediately from admission in 38 patients who presented within six (mean 2.5) hours of the onset of acute myocardial infarction and had emergency coronary arteriography and thrombolysis with intracoronary streptokinase. All patients received high doses of isosorbide dinitrate but no prophylactic anti-arrhythmic drugs. In 19 patients, 36 occurrences of intermittent reperfusion were observed. Stable reperfusion was achieved in 32 patients. Only 14 episodes of arrhythmia (11 ventricular) were observed in 6 patients within five minutes of transient or stable reperfusion. No episodes of arrhythmia were documented within five minutes of the other 57 occurrences of reperfusion. In contrast, 215 episodes of arrhythmia (198 ventricular) not associated with reperfusion were recorded in 32 patients. Arrhythmias are commonly observed in patients during evolving acute myocardial infarction and thrombolysis but are an insensitive and rarely specific marker of reperfusion at the time when this occurs.

Adult