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Biomedical subjects

M T Jones

Publications and source records attributed to M T Jones.

At least 19 recordsLinked to original sources

Retrospective analysis of serum valproate levels and need for an antidepressant drug.

We sought to determine whether patients receiving valproate plus an antidepressant had significantly lower serum valproate levels before initiation of the antidepressant than those patients receiving valproate without an antidepressant. We further sought to identify the prevalence of antidepressant-induced mania and to determine if valproate provided a protective effect against antidepressant-induced mania. A computer database search from January 1, 1990-June 30, 1998, identified patients with bipolar or schizoaffective disorder treated with valproate. Patients receiving an antidepressant during valproate therapy were identified as the treatment group (9 patients), and the remaining patients served as the control group (17 patients). Serum valproate levels were recorded just before starting the antidepressant for the treatment group and monthly during a comparable period for the control group. The mean time to antidepressant initiation was 15 +/- 8 weeks. The mean serum valproate level just before antidepressant initiation was significantly lower for the treatment group compared with the mean serum valproate level averaged over 16 +/- 6 weeks for the control group (54 +/- 24 vs 73 +/- 13 microg/ml, p<0.05). Four patients (44%) developed antidepressant-induced mania. Three required discontinuation of the antidepressant; their serum valproate levels were 54, 60, and 71 microg/ml. Patients requiring the addition of an antidepressant had significantly lower valproate serum levels than those who did not require an antidepressant. Further study is necessary to determine whether higher serum valproate levels are needed for prevention of depressive symptoms in bipolar and schizoaffective disorders.

Adult↗

Coronary surgery in Europe: comparison of the national subsets of the European system for cardiac operative risk evaluation database.

OBJECTIVE: To compare the national samples of patients who underwent isolated coronary artery bypass grafting (CABG) during the European System for Cardiac Operative Risk Evaluation (EuroSCORE) trial in order to evaluate national differences in epidemiology, patient risk profile and surgical methods. METHODS: From September to November 1995, 11731 patients had CABG in the six largest contributing nations to the EuroSCORE project: Germany, UK, Spain, Finland, France and Italy. The Chi-square and Kruskal-Wallis tests were applied to obtain an international comparison of patient general status, including pre-operative risk factors, cardiac status, critical pre-operative states, rare conditions, urgency of surgery, angina status, coronary lesions, procedures and EuroSCORE risk assessment. RESULTS: Large national samples (from 984 patients in Finland to 3138 in Germany) identified significant differences in epidemiology, risk profile and surgical practice. Regarding epidemiology, CABG accounted for 62.8% of adult cardiac surgery, with a range of 46.2 in Spain to 77.7% in Finland (P<0.001). The mean age was 62.9 years (61.4 in Britain to 64.4 in France, P<0.001). The mean body mass index was 26.8 (26 in France to 27.5 in Finland, P<0.001). With regard to risk profile, diabetes was present in 20.3% of patients (11.8% in Britain to 27.7% in Spain, P<0.001). Chronic renal failure was present in 8.3% (6.8% in Germany to 10.6% in Spain, P<0.001). Chronic airway disease affected 3.8% (1.9% in Italy to 5. 1% in Germany, P<0.001). The mean ejection fraction was 0.56 (0.48 in Britain to 0.58 in Finland, P<0.001). The mean predicted mortality (according to EuroSCORE) was 3.3% (2.8% in Finland to 3.6% in France, P<0.001). The prevalence of chronic congestive heart failure, unstable angina and recent myocardial infarction also showed statistically significant differences. No differences were found for some critical preoperative states (such as immediate preoperative cardiac massage and pre-operative intubation), or for surgery for catheter laboratory complication. Regarding surgical practice, major differences were noted in preoperative intra-aortic balloon use (mean 1%, Finland 0%, Spain 2.3%, P<0.001), the number of mammary artery conduits used (mean 0.9, Spain 0.7, France 1.1, P=0.0001) and the number of distal anastomoses (mean 3, France 2.7, Finland 3.8, P=0.001). CONCLUSION: There are important epidemiological differences in the national cohorts of CABG patients in the EuroSCORE database. Any international comparison of European surgical results must therefore take into account the risk profile of patients by using a compatible risk stratification system.

Aged↗

Pharmacist-designed and -implemented pharmaceutical care plan for antipsychotic-induced movement disorders.

We developed a systematic approach to assess the presence, severity, and management of extrapyramidal symptoms (EPS) in patients treated with antipsychotics. Patients were evaluated by the Modified Simpson-Angus scale, Abnormal Involuntary Movement Scale, and Dyskinesia Identification System: Condensed User Scale. We completed 235 sets of evaluations in 83 patients. A pharmaceutical intervention was proposed in 54% (130) of evaluations, of which 82% (107) were accepted and followed. In 93% (99) evaluations in which a recommendation was followed, clinical outcome was positive. The most common intervention was reducing the dosage or discontinuing the antidyskinetic agent, most often an anticholinergic (55% of cases). Our results show that detailed monitoring of EPS in a clinical pharmacist-operated clinic promotes rational drug therapy, limits unnecessary drugs, and improves clinical outcome of patients with EPS.

Algorithms↗

A critical review of published economic modelling studies in depression.

Depression is a very costly chronic disease. An important cost driver is treatment failure caused by patient noncompliance due, in part, to the adverse effects of medications. Additionally, inadequate duration of therapy and inappropriate medication switching contribute to the high cost of treatment. With the epidemiological data for depression demonstrating a rise in both incidence and prevalence over the last 20 years, and the fact that many of the newer antidepressants will see patent expiry in the near future, previous antidepressant cost-effectiveness scenarios are likely to change. As economic models play an increasingly important role in therapeutic decision-making, clinicians are encouraged to understand the strategies and methods involved in modelling antidepressant therapy. The aim of this review of the literature and synthesis of the various techniques important to the modelling of antidepressant therapies is for the practitioner to gain an increased understanding of the modelling methods previously utilised and be in a position to better evaluate future health economic models for the treatment of depression.

Antidepressive Agents↗

Risk factors and outcome in European cardiac surgery: analysis of the EuroSCORE multinational database of 19030 patients.

OBJECTIVE: To assess risk factors for mortality in cardiac surgical adult patients as part of a study to develop a European System for Cardiac Operative Risk Evaluation (EuroSCORE). METHODS: From September to November 1995, information on risk factors and mortality was collected for 19030 consecutive adult patients undergoing cardiac surgery under cardiopulmonary bypass in 128 surgical centres in eight European states. Data were collected for 68 preoperative and 29 operative risk factors proven or believed to influence hospital mortality. The relationship between risk factors and outcome was assessed by univariate and logistic regression analysis. RESULTS: Mean age (+/- standard deviation) was 62.5+/-10.7 (range 17-94 years) and 28% were female. Mean body mass index was 26.3+/-3.9. The incidence of common risk factors was as follows: hypertension 43.6%, diabetes 16.7%, extracardiac arteriopathy 2.9%, chronic renal failure 3.5%, chronic pulmonary disease 3.9%, previous cardiac surgery 7.3% and impaired left ventricular function 31.4%. Isolated coronary surgery accounted for 63.6% of all procedures, and 29.8% of patients had valve operations. Overall hospital mortality was 4.8%. Coronary surgery mortality was 3.4% In the absence of any identifiable risk factors, mortality was 0.4% for coronary surgery, 1% for mitral valve surgery, 1.1% for aortic valve surgery and 0% for atrial septal defect repair. The following risk factors were associated with increased mortality: age (P = 0.001), female gender (P = 0.001), serum creatinine (P = 0.001), extracardiac arteriopathy (P = 0.001), chronic airway disease (P = 0.006), severe neurological dysfunction (P = 0.001), previous cardiac surgery (P = 0.001), recent myocardial infarction (P = 0.001), left ventricular ejection fraction (P = 0.001), chronic congestive cardiac failure (P = 0.001), pulmonary hypertension (P = 0.001), active endocarditis (P = 0.001), unstable angina (P = 0.001), procedure urgency (P = 0.001), critical preoperative condition (P = 0.001) ventricular septal rupture (P = 0.002), noncoronary surgery (P = 0.001), thoracic aortic surgery (P = 0.001). CONCLUSION: A number of risk factors contribute to cardiac surgical mortality in Europe. This information can be used to develop a risk stratification system for the prediction of hospital mortality and the assessment of quality of care.

Adolescent↗

Treatment of mediastinitis: early modified Robicsek closure and pectoralis major advancement flaps.

BACKGROUND: The treatment of sternal wound complications is controversial. It is our practice to combine early aggressive debridement, a modified Robicsek sternal closure, and bilateral pectoralis major advancement flaps with or without closed irrigation in a single procedure. We reviewed our experience to determine the efficacy of this approach. METHODS: Grade II to IV mediastinitis (dehiscence and infection) developed in 47 patients 3 to 14 days after routine open heart operations between 1990 and 1995. Culture-positive infection was identified in 60% (n = 28); 62% (n = 29) had septicemia. Thirty patients underwent incision, drainage, and surgical assessment of the wound. Once systemic signs of infection were under control (no pyrexia, normal white blood cell count), formal single-stage debridement of all infected soft tissues and bones was performed. Sternal stability was achieved using a modified Robicsek closure and bilateral pectoralis major advancement flaps. Seventeen patients were treated with staged procedures. RESULTS: Early sternal closure and coverage with pectoralis major advancement flaps can be associated with a low mortality (0%), low morbidity (13%; n = 4: three superficial wound infections, one seroma), and shortened hospital stay (median, 22 days, compared with a median of 82 days in patients managed with conservative staged treatment; p < 0.05). Sternal stability with excellent functional and aesthetic results has been achieved in all patients. CONCLUSIONS: The combination of aggressive early surgical debridement, sternal closure, and the placement of bilateral pectoralis major advancement flaps is a simple procedure associated with a low mortality and morbidity and a short hospital stay.

Adult↗

Rotavirus RNA polymerase requires the core shell protein to synthesize the double-stranded RNA genome.

Rotavirus cores contain the double-stranded RNA (dsRNA) genome, RNA polymerase VP1, and guanylyltransferase VP3 and are enclosed within a lattice formed by the RNA-binding protein VP2. Analysis of baculovirus-expressed core-like particles (CLPs) has shown that VP1 and VP2 assemble into the simplest core-like structures with replicase activity and that VP1, but not VP3, is essential for replicase activity. To further define the role of VP1 and VP2 in the synthesis of dsRNA from viral mRNA, recombinant baculoviruses containing gene 1 (rBVg1) and gene 2 (rBVg2) of SA11 rotavirus were generated and used to express recombinant VP1 (rVP1) and rVP2, respectively. After purification, the proteins were assayed individually and together for the ability to catalyze the synthesis of dsRNA in a cell-free replication system. The results showed that dsRNA was synthesized only in assays containing rVP1 and rVP2, thus establishing that both proteins are essential for replicase activity. Even in assays containing a primer-linked mRNA template, neither rVP1 nor rVP2 alone directed RNA synthesis. Characterization of the cis-acting replication signals in mRNA recognized by the replicase of rVP1 and rVP2 showed that they were the same as those recognized by the replicase of virion-derived cores, thus excluding a role for VP3 in recognition of the mRNA template by the replicase. Analysis of RNA-protein interactions indicated that the mRNA template binds strongly to VP2 in replicase assays but that the majority of the dsRNA product neither is packaged nor stably associates with VP2. The results of replicase assays performed with mutant VP2 containing a deletion in its RNA-binding domain suggests that the essential role for VP2 in replication is linked to the protein's ability to bind the mRNA template for minus-strand synthesis.

Animals↗

The importance of work-up (verification) bias correction in assessing the accuracy of SPECT thallium-201 testing for the diagnosis of coronary artery disease.

Noninvasive testing is often evaluated by the sensitivity and specificity in comparison with a more invasive, but more definitive "gold" standard. However, work-up or verification bias, which occurs when the results of a noninvasive test impact the decision to perform the gold standard invasive test, increases the "observed" sensitivity and decreases the "observed" specificity of the noninvasive test. Most large clinical studies utilizing a noninvasive technique to diagnose coronary artery disease have biases, particularly work-up bias. To obtain more accurate measurements of sensitivity and specificity, we determined the observed sensitivity and specificity of stress (exercise and dipyridamole) single photon emission computed tomographic (SPECT) thallium testing for the detection of coronary artery disease by angiography, and then applied previously published equations to correct for work-up bias. From a computerized data base, reports of 4354 stress SPECT thallium studies from January 1, 1986 through December 31, 1992 were reviewed. All patients with a known history of myocardial infarction or prior coronary angiography were excluded, leaving 2688 patients. From this total, 471 patients underwent coronary angiography within 90 days following stress SPECT thallium testing. Coronary artery disease was defined as a visually assessed stenosis of a coronary artery or a major branch > 50%. Of the 2688 stress SPECT thallium studies, 1265 were normal and 1423 were abnormal. For the 471 patients who underwent catheterization within 90 days following stress SPECT thallium testing. the "observed" sensitivity and specificity were 98 and 14%, respectively. After correction for work-up bias, the corrected sensitivity and specificity were 82 +/- 6% and 59 +/- 2%, respectively. Most studies utilizing noninvasive technologies for the detection of coronary artery disease include patients with known coronary artery disease and have work-up bias as well. By knowing the thallium results of patients with and without catheterization, we were able to correct for work-up bias. These data provide better estimate of the sensitivity and specificity of stress SPECT thallium testing.

Bias↗

Aortic valve replacement for end-stage aortic valve disease.

To evaluate the outcome of surgical intervention for end-stage aortic valve disease, we carried out a retrospective, longitudinal survey of 85 patients (65 males, 20 females; mean age 53 period. All the patients presented in New York Heart Association (NYHA) class IV in cardiac failure (3 had cardiogenic shock and 27 had bacterial endocarditis). In-hospital mortality was 9.4% (8/85) overall. Those with endocarditis had a significantly higher mortality, 6/27 (22%) vs 2/58 (3.4%), p < 0.01. In-hospital mortality was not significantly increased in those with renal failure, reoperation, simultaneous coronary artery surgery, age > 65 years nor was it related to the predominance of aortic regurgitation or stenosis. After a mean follow-up period of 5.9 years (range 0 to 12.5 years), the overall actuarial survival was 82% and 74% at 5 and 10 years respectively. For 66 late survivors, the NYHA status improved to class I in 51, to II in 10, to III in 4 patients, and one patient remained in class IV. The incidence of paraprosthetic leak, reoperation, thromboembolism, anticoagulant-related haemorrhage, and endocarditis were respectively 0.8, 0.8, 1.6, 1.4, and 0.2 per 100 patient-years. Aortic valve replacement in the patient with end-stage aortic valve disease is a high-risk procedure, the risk being higher in the presence of endocarditis. The favourable long-term survival, long-term improvement in functional class and the relatively low incidence of valve-related complications justify surgical intervention in such patients, who would otherwise have a very poor prognosis.

Adolescent↗

Effect of increasing work rate on metabolic responses of the donkey (Equus asinus).

Oxygen consumption (VO2) and concentration of venous blood metabolites were measured in donkeys trained to run and to pull loads on a treadmill. VO2 in two donkeys running at maximal speed on a 9.8% slope was 110 +/- 2 ml.min-1.kg-1, approximately 22 times preexercise VO2. Average heart rate at maximal VO2 (VO2max) was 223 +/- 2 beats/min, five times the preexercise heart rate. Blood lactate increased 14-fold, and blood glucose did not change (P > 0.05). Animals running up a 4% incline and incremental draft loading of five donkeys walking on the level were also studied. The total energy cost of walking unloaded was 2.86 +/- 0.06 J.m-1.kg live wt-1. During low- to medium-intensity draft work for 25 min, glucose fell below preexercise values (P < 0.05), whereas plasma hematocrit and cortisol increased (P < 0.05). Blood lactate remained unchanged up to approximately 40% VO2 max but increased 170% at approximately 60% VO2max. The responses in donkeys are similar to those of exercising horses except for the rapid decline in blood glucose observed during low-intensity exercise and the lower lactate levels at both the high-intensity exercise and the apparent anaerobic threshold.

Animals↗

Histological examination of peroperative frozen sections in suspected lung cancer.

BACKGROUND: Despite extensive investigations some patients with suspected lung cancer may undergo thoracotomy without preoperative histological proof of malignancy. A questionnaire on the use of histological examination of peroperative frozen sections in such patients was sent to 50 thoracic surgeons. Replies were received from 41 surgeons and indicated an absence of consensus on the usefulness of histological examination of frozen sections in this context, confirming the need for this study. METHODS: During one year 60 consecutive patients undergoing thoracotomy for suspected lung cancer without a prior histological diagnosis were studied prospectively. At thoracotomy the surgeon assessed the lesion macroscopically and a verdict on whether it was malignant was recorded. A biopsy specimen was then taken for examination of a frozen section and the result recorded. The appropriate operation was performed and the surgeon's verdict and the report on the frozen section were compared with the definitive histological diagnosis based on a paraffin section. RESULTS: Of 50 malignant lesions, 43 were identified by the surgeon and 47 by examination of the frozen section (sensitivity 86% and 94% respectively). Of 10 benign lesions, four were identified by the surgeon and nine by examination of the frozen section (specificity 40% and 90% respectively). CONCLUSIONS: Clinical and macroscopic assessment at thoracotomy are inferior to examination of frozen sections in suspected lung cancer, particularly where the lesion is benign. Lung resection should not be performed without examination of peroperative frozen sections when thoracotomy is performed for suspected but unproved lung cancer.

Biopsy↗

Determination of maximal oxygen consumption in exercising pregnant sheep.

Previous work with pregnant ewes has shown that acute bouts of exercise may cause changes in plasma hormone concentrations, blood flow distribution, and maternal and fetal temperatures. However, most of these studies do not quantify the chosen exercise intensity through measurement of oxygen consumption (VO2). Therefore the purpose of this study was to statistically model the VO2 response of pregnant sheep to treadmill (TM) exercise to determine the exercise intensities (% maximal VO2) of previous studies. Ewes with either single (n = 9) or twin (n = 5) fetuses were studied from 100 to 130 days of gestation. After 1-2 wk of TM habituation, maximal VO2 (VO2max) was determined by measurements of VO2 (open flow-through method) and blood lactate concentration. VO2 was measured as a function of TM incline (0, 3, 5, and 7 degree) and speed (0.8-3.4 m/s). VO2max averaged 57 +/- 7 (SD) ml.min-1.kg-1, and peak lactate concentration during exercise averaged 22 +/- 2 mmol/l. The relationship between VO2 (ml.min-1.kg-1) and incline (INC) and speed (SP) [VO2 = 0.70(INC) + 13.95(SP) + 1.07(INC x SP) - 1.18] was linear (r2 = 0.94). Our findings suggest that most previous research used exercise intensities less than 60% VO2max and indicate the need for further research that examines the effect of exercise during pregnancy at levels greater than 60% VO2max.

Animals↗

Effect of regular voluntary exercise on resting cardiovascular responses in SHR and WKY pregnant rats.

The purpose of this study was to assess the influence of regular voluntary exercise in pregnant normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats on 1) uteroplacental perfusion and mean arterial pressure in the resting conscious condition and 2) fetal number, fetal weight, and number of fetal resorptions. WKYs and SHRs were randomly assigned to standard cages [CWKY (n = 10); CSHR (n = 6)] or cages with activity wheels [EWKY (n = 7); ESHR (n = 8)]. EWKYs and ESHRs exercised for 12 wk, and then all rats were bred and experiments were conducted on gestational day 17. Resting blood flow (microspheres), heart rate (HR), and mean arterial pressure (Pa) were measured. No significant difference was found in Pa, HR, uterine blood flow (ESHRs 52 +/- 8 ml.min-1.100 g-1; CSHRs 28 +/- 6 ml.min-1.100 g-1), or maternal placental blood flow (ESHRs, 122 +/- 31 ml.min-1.100 g-1; CSHRs 78 +/- 21 ml.min-1.100 g-1) among the groups. Exercise altered the relationship between maternal placental and uterine blood flow and Pa in the SHR; SHRs with lower Pa maintained higher placental and uterine blood flow after training. Before gestation ESHRs ran on average more kilometers per week than EWKYs (43 +/- 3 vs. 34 +/- 4), but during gestation ESHRs averaged fewer kilometers per week than EWKYs (16 +/- 4 vs. 22 +/- 4). Succinate dehydrogenase activity was higher in the white vastus lateralis (1.02 +/- 0.2 mumol cytochrome c reduced.min-1.g wet wt-1) and vastus intermedius (3.1 +/- 0.5 mumol cytochrome c reduced.min-1.g wet wt-1) muscles of ESHRs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Cocaine in pregnancy: the effect of maternal administration of cocaine on the maternal and fetal pituitary-adrenal axes.

The effects of cocaine on the maternal and fetal pituitary-adrenal axis in vivo during pregnancy have not been reported. Six pregnant ewes and their fetuses underwent instrumentation at 113 to 119 days' gestation. Ewes were assigned to receive an intravenous bolus injection of vehicle or cocaine (0.5, 1.0, or 2.0 mg.kg-1) at 124 to 136 days' gestation. Maternal arterial blood gases, fetal pH and fetal PCO2 were unchanged after injection of cocaine or vehicle. After administration of 2.0 mg.kg-1 cocaine, arterial fetal PO2 fell 3.2 +/- 1.72 mm Hg (p less than 0.05) at +5 minutes, returning to baseline by +15 minutes. Maternal and fetal adrenocorticotropin levels rose within 5 minutes after the highest cocaine dose (p less than 0.05). There was a significant (p less than 0.05) increase in maternal cortisol at all doses of cocaine and in fetal cortisol at +15 minutes after the 2.0 mg.kg-1.

Adrenocorticotropic Hormone↗

Comparison of ultrasonography and oral cholecystography in biliary lithotripsy. I. Screening patients.

Ultrasound and oral cholecystography (OCG) are both used to evaluate candidates for biliary lithotripsy. Some investigators have suggested abandoning the OCG, believing that sufficient screening information can be obtained from ultrasound. This study compares ultrasound and OCG in assessing the size and number of gallstones, both in vitro and in vivo. In the in vitro model, 35 gallstones, divided into 20 groups, were separately suspended in dilute contrast media in a phantom, and examined by ultrasound and simulated OCG by each of three gastrointestinal radiologists. In the in vivo study, the ultrasound and OCG examinations from 53 patients were independently reviewed by three radiologists. The number and size of the stones were recorded in both studies. In the in vitro study, the stone size was measured within 2 mm of the actual size by OCG in 23/35 stones (66%) and by ultrasound in 4/35 stones (11%). The correct number of stones was determined by OCG in 19/20 groups (95%), and by ultrasound in 14/20 (70%). In the in vivo study, all readers saw the same number of stones in 40/50 (80%) patients by OCG and 33/49 (67%) patients by ultrasound. Statistical analyses revealed correlation coefficients for OCG greater than those for ultrasound in each comparison. The size of the largest stone was within 2 mm by all readers in 26/51 (51%) of patients by OCG and 20/47 (43%) patients by ultrasound. Oral cholecystography is more reliable than ultrasound for the determination of size and number of stones in patients being screened for biliary lithotripsy.

Adult↗