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Biomedical subjects

J Thornton

Publications and source records attributed to J Thornton.

At least 91 records · Page 5Linked to original sources
PubMed1993

Protein fold recognition.

An important, yet seemingly unattainable, goal in structural molecular biology is to be able to predict the native three-dimensional structure of a protein entirely from its amino acid sequence. Prediction methods based on rigorous energy calculations have not yet been successful, and best results have been obtained from homology modelling and statistical secondary structure prediction. Homology modelling is limited to cases where significant sequence similarity is shared between a protein of known structure and the unknown. Secondary structure prediction methods are not only unreliable, but also do not offer any obvious route to the full tertiary structure. Recently, methods have been developed whereby entire protein folds are recognized from sequence, even where little or no sequence similarity is shared between the proteins under consideration. In this paper we review the current methods, including our own, and in particular offer a historical background to their development. In addition, we also discuss the future of these methods and outline the developments under investigation in our laboratory.

Amino Acid Sequence↗
PubMed1993

Randomized trial of dapsone and aerosolized pentamidine for the prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis.

PURPOSE: Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis are the most frequent pulmonary and central nervous system opportunistic infections associated with human immunodeficiency virus (HIV) infection. We designed a prospective study to compare the effects of aerosolized pentamidine and dapsone in the prophylaxis of these infections in HIV-infected persons with CD4+ lymphocyte counts less than 250/mm3. PATIENTS AND METHODS: Two hundred seventy-eight patients seropositive for HIV who had acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex were randomly assigned to receive intermittent dapsone (100 mg twice weekly) or aerosolized pentamidine (100 mg every 2 weeks). The proportion of patients remaining free of PCP or toxoplasmosis was analyzed with the log-rank test as a function of time, as were the effects of zidovudine or prophylaxis on survival. RESULTS: Dapsone and aerosolized pentamidine demonstrated similar efficacy in the primary and secondary prophylaxis of PCP, with 15 (18%) failures among patients receiving dapsone compared to 15 (14%) among those receiving aerosolized pentamidine (p = 0.4), after a mean length of follow-up of 42 and 44 weeks, respectively. Dapsone was more effective in the primary prophylaxis of toxoplasmic encephalitis, with six toxoplasmic encephalitis events occurring among those receiving aerosolized pentamidine, compared to none among those taking dapsone (p = 0.01). Primary prophylaxis for PCP was more effective than secondary prophylaxis with either therapy. Zidovudine therapy did not prevent PCP yet prolonged the PCP-free interval for those in whom either prophylactic therapy failed. Kaplan-Meier estimates did not show a difference in survival between the patients receiving either therapy, yet zidovudine use was associated with improved survival, independent of race and risk factor (Cox proportional hazards model, p = 0.001). The 1-month survival for patients developing PCP despite prophylaxis was better with those in whom dapsone failed than it was for those in whom aerosolized pentamidine failed (p = 0.08). CONCLUSION: Dapsone is as effective as aerosolized pentamidine in preventing PCP and has the advantage of a lower cost, easier administration, and possibly an additional preventive effect against toxoplasmosis. Zidovudine prolongs the PCP-free interval for patients receiving prophylaxis, regardless of which prophylactic agent is used.

AIDS-Related Opportunistic Infections↗
PubMed1993

Sternal blood flow during mobilization of the internal thoracic arteries.

A laser Doppler tissue perfusion monitor was used to measure sternal blood flow before, during, and after mobilization of the internal thoracic arteries in 24 patients undergoing coronary artery bypass grafting. To minimize chest wall injury, a narrow pedicle was mobilized. Bilateral flow data were available from 15 of the 24 patients. Analysis of these 39 studies showed no significant reduction of sternal blood flow as a consequence of mobilization of the internal thoracic arteries except in 2 patients who were both diabetic and obese.

Aged↗
PubMed1992

Effect of using protocols on medical care: randomised trial of three methods of taking an antenatal history.

OBJECTIVE: To compare the effectiveness of three methods of taking an antenatal history on the quality of obstetric care. DESIGN: Randomised controlled trial. SETTING: Antenatal clinic of St James's University Hospital, Leeds. SUBJECTS: 2424 women attending the hospital for the first (booking) visit. INTERVENTIONS: Histories were taken by midwives using an unstructured paper questionnaire, a structured paper questionnaire (incorporating a checklist), or an interactive computerised questionnaire (incorporating 101 clinical reminders). MAIN OUTCOME MEASURES: The number of clinical responses to factors arising from the antenatal booking history according to method of taking the history. Actions were categorised as medical and surgical, obstetric, personal, current symptoms and treatment, related to maternal age, and related to two common actions (cervical smear testing and dental hygiene) and were weighted for clinical importance by 10 obstetricians. RESULTS: Overall the unstructured questionnaire generated 1063 actions, the structured questionnaire 1146, and the computerised questionnaire 1122. The clinical importance of these actions was lowest for the unstructured questionnaire (overall total value score 1987 v 2182 and 2110 for the structured and computerised questionnaires respectively). The structured questionnaire was better than the computerised questionnaire in the medical and surgical (total value score 191 v 184), obstetric (275 v 241), and personal (430 v 360) categories but inferior in the current symptoms category (179 v 191). CONCLUSION: Structured questionnaires (computerised or paper) provide more and better information, and their use improves clinical response to risk factors. Computerised systems offer no further advantage in antenatal clinics.

Clinical Protocols↗
PubMed1992

Adenosine is an endogenous protectant against stunning during repetitive ischemic episodes in the heart.

To investigate whether adenosine receptor blockade alters the response to serial coronary occlusions in the rabbit heart, we measured changes in segment length with ultrasonic dimension gauges placed in the field of a coronary branch. The coronary branch was subjected to four 5-minute occlusions, each separated by 10 minutes of reperfusion. In control hearts, the percentage of segment shortening fell from 15.7% to 9.3% after release of the first occlusion with no further deterioration after each of the subsequent three occlusions. In hearts in which adenosine receptors were blocked with PD 115,199, a potent blocker of both A1 and A2 receptors, segment shortening again recovered to about two thirds of the preischemic value during the reperfusion period after the first occlusion. Each subsequent occlusion, however, resulted in a further deterioration of function to the extent that shortening was less than 20% of the preischemic value during reperfusion after the fourth occlusion. Therefore the first occlusion of a series of four occlusions, while mildly stunning the heart, also preconditions the myocardium against further stunning by subsequent occlusions. Because that protection was when adenosine receptors were blocked, adenosine must play an important role in the mediation of this protective effect.

Adenosine↗
PubMed1992

Body-fat measurement in patients with acquired immunodeficiency syndrome: which method should be used?

Malnutrition is common in patients with acquired immunodeficiency syndrome (AIDS), which distorts the chemical contents in the fat-free mass (FFM) and alters the assumptions underlying the traditional methods for calculating body-fat content so that such measurements may not be accurate. In vivo neutron-activation analysis (IVNA) measures FFM independently of the traditional assumptions, thereby providing more accurate measurements of body fat. We compared seven methods for measuring body fat in 18 male patients with AIDS: IVNA, total body water (TBW by 3H2O dilution), total body potassium (TBK by 40K counting), dual-photon absorptiometry (DPA), bioelectrical impedance analysis (BIA), and two well-calibrated anthropometric methods. FatTBW and fatDPA were not significantly different from fatIVNA. FatTBW gave the highest correlation with fatIVNA and the smallest SEE of +/- 1.8% (1.1 kg). The traditional and widely available TBW and the newer DPA method provide reliable estimates of fatIVNA in patients with AIDS.

Absorptiometry, Photon↗
PubMed1992

Protection from reperfusion injury by preconditioning hearts does not involve increased antioxidant defenses.

Preconditioning the heart with 5 min of ischemia renders the heart very resistant to infarction from subsequent ischemia by an unknown mechanism. We investigated whether the protective effect of preconditioning might be related to an increase in rabbit heart antioxidant defenses. The antioxidant activities of catalase, glutathione peroxidase, Mn superoxide dismutase, Cu,Zn superoxide dismutase, glucose-6-phosphate dehydrogenase, glutathione reductase, and total glutathione were measured in ischemic and normal regions from both control and preconditioned rabbit hearts. All hearts experienced 30 min regional ischemia and 5 min reperfusion. None of the antioxidant enzymes changed in activity when comparing nonischemic and postischemic zones in either nonpreconditioned or preconditioned hearts. Total glutathione, however, was reduced in reperfused zones and showed better preservation in preconditioned hearts. To determine whether this preservation resulted from a higher value at the onset of reperfusion or slower washout during reperfusion, we analyzed a second group of nonreperfused hearts after 30 min ischemia. The hearts had normal glutathione content in both ischemic and nonischemic zones of either preconditioned or control hearts. The most likely explanation is that preconditioned hearts experienced less washout of glutathione simply because they were less injured. We therefore conclude that enhancement of antioxidant defenses is not the mechanism of preconditioning.

Adaptation, Physiological↗
PubMed1992

Needs of well siblings of persons with schizophrenia.

The practical concerns of well siblings of persons with schizophrenia were examined in a descriptive study that included a needs assessment survey and a workshop designed to increase well siblings' knowledge about schizophrenia. A questionnaire focusing on needs for information, support, and practical skills was completed by 88 well siblings and 19 of their spouses. The results indicated a desire for more specific information about schizophrenia, particularly prognosis, and difficulties in communicating and problem solving with siblings with schizophrenia. Although respondents to the questionnaire were neutral about the need for support from other well siblings, participants at the workshop indicated that they found the opportunity to meet and share experiences with other well siblings to be the workshop's strongest feature. The study indicates that well siblings of persons with schizophrenia have specific needs that may differ from those of other family members.

Activities of Daily Living↗
PubMed1992

A prospective randomized trial of laparoscopic versus open appendectomy.

BACKGROUND: Laparoscopic appendectomy is feasible, but whether it confers any advantage to patients with acute appendicitis is not known. We performed a randomized controlled trial to compare results of laparoscopic and open appendectomy in patients with signs and symptoms suggesting acute appendicitis who were seen by one surgical team. METHODS: Sixty-two consecutive patients were randomized, 30 to laparoscopy and 32 to a classical open appendectomy. Postoperative recovery, complications, and return to normal activities were compared in the two groups. RESULTS: The laparoscopy group were discharged earlier (2.5 vs 3.8 days, p less than 0.01). Postoperative complications were more frequent after open appendectomy. Follow-up showed less pain, shorter bed stay at home, and faster return to work and sport after laparoscopic appendectomy. CONCLUSIONS: This prospective randomized study shows that laparoscopic appendectomy is superior to open appendectomy in terms of hospital stay, postoperative complications, and return to normal activities and is recommended as the approach of choice in the management of acute appendicitis.

Adult↗
PubMed1991

Comparison of dual-photon absorptiometry systems for total-body bone and soft tissue measurements: dual-energy X-rays versus gadolinium 153.

A total of 81 subjects (41 males and 40 females) were scanned by dual-photon absorptiometry by 153Gd source (DPA; Lunar DP4) and by dual-energy x-ray absorptiometry (DEXA; Lunar-DPX) within a 24 h period. Total-body bone mineral density (TBMD), calcium content (Ca), and soft tissue mass (ST) were determined with a precision of about 1-1.5% using DPA and 0.5-1.0% using DEXA. Measurements of TBMD, Ca, ST, bone area (area), percentage fat, and regional bone mineral densities (BMD) were compared. Paired t-tests showed small but significant differences between all measurements. Correlations (r) for TBMD, Ca, area, ST, percentage fat, arm BMD, leg BMD, and trunk BMD were 0.99, 0.99, 0.97, 0.99, 0.97, 0.99, 0.99, and 0.98. There were small systematic differences for TBMD (less than 1%), calcium (3%), bone area (3%), soft tissue mass (7%), and percentage fat (9%) between the two approaches. Regression equations are given relating these measurements.

Absorptiometry, Photon↗
PubMed1991

Bone mineral density and mass by total-body dual-photon absorptiometry in normal white and Asian men.

Total body bone mineral density, total body bone mineral mass (TBBM), and bone mineral densities (BMD) in seven different regions of the body were measured in 238 normal men (154 Whites and 84 Asians), age 22-94, using dual-photon absorptiometry. Although Asian men had lower TBBM and BMD in all regions (p less than 0.05) except the arms, when multiple regression was done with body weight, height, and age, no significant differences were found between Asians and Whites for bone measurements. Thus lower bone mineral densities and bone mineral mass in Asian males compared to White males appear to be due to differences in height and weight rather than to ethnic differences. The two groups were combined to derive multiple regression equations for TBBM, total-body BMD, and regional BMD. Age, weight, and height were significant in the multiple regression equations for TBBM, ribs BMD, and legs BMD. Age and weight, but not height, were significant for total-body BMD, trunk BMD, spine BMD, arm BMD, and pelvis BMD. Weight, but neither height nor age, was significant for head BMD. These reference normal bone mineral density and bone mineral mass standards are appropriate for both Asian and White males when adjusted for weight, height, and age.

Absorptiometry, Photon↗
PubMed1991

Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart.

BACKGROUND: Preconditioning (5 minutes of ischemia followed by 10 minutes of recovery) renders the heart very resistant to infarction from subsequent ischemia. This study tests whether adenosine receptors might mediate preconditioning protection. METHODS AND RESULTS: We examined the effect on infarct size of pretreatment with either of two adenosine receptor antagonists in both control and preconditioned in situ rabbit hearts. Hearts underwent 30 minutes of regional ischemia plus 3 hours of reperfusion, and infarct size was measured with tetrazolium. Infarct size averaged 39% of the zone at risk in controls but only 8% in preconditioned hearts. Preconditioned and nonpreconditioned hearts receiving either blocker had infarcts not different in size from the controls. A 5-minute intracoronary infusion of adenosine was as effective as 5 minutes of ischemia in protecting parabiotically perfused isolated hearts against infarction from a 45-minute ischemic insult. Similarly, intracoronary infusion of N6-1-(phenyl-2R-isopropyl)adenosine, an A1-selective adenosine receptor agonist, at a dose that delayed conduction but did not dilate the coronary vessels, also limited infarct size. The protection disappeared when we reduced the coronary concentration of drug by intravenous infusion of adenosine, indicating that cardiac rather than peripheral receptors were involved in the protection. CONCLUSIONS: We conclude that adenosine released during the preconditioning occlusion stimulates cardiac A1 receptors, which leaves the heart protected against infarction even after the adenosine has been withdrawn.

Adenosine↗