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Biomedical subjects

B Haynes

Publications and source records attributed to B Haynes.

At least 19 recordsLinked to original sources

Comparison of performance of interns completing the old (1993) and new interactive (1997) Advanced Trauma Life Support courses.

BACKGROUND: The 1997 edition of the Advanced Trauma Life Support (ATLS) course emphasized interactivity as its major change. The impact of this change is assessed in this study. METHODS: We compared two matched groups of 16 interns completing either the old (group I) or new (group II) ATLS course. Cognitive skills (40 standard ATLS questions plus 10 additional questions on airway and shock) and clinical trauma management skills (four trauma objective structured clinical examinations [OSCEs] on simulated trauma patients) were tested. OSCE station scores (standardized to a maximum of 20), priority scores (graded 1-7), organized approach global passing grades (graded 1-5), and initial assessment test station scores (graded 1-5) were compared. RESULTS: Using ATLS criteria, three interns failed in each group. Post-ATLS examination question scores were similar (84.5+/-6.9 for group I, 85.9+/-7.1 for group II); scores for the airway and shock questions were higher but not different between the two groups. The four OSCE station mean scores varied between 13.9+/-2.0 and 15.4+/-2.1 for group I and were higher (p < 0.05) for group II (17.9+/-1.6 to 19.1+/-1.0). Priority scores were similar (group I, 6.3+/-1.1; group II, 6.4+/-1.2), but approach scores (3.9+/-0.1 for group I and 4.9+/-0.8 for group II) were lower in group I, as were the initial assessment test scores (2.9+/-0.2 for group I and 4.9+/-0.8 for group II). There were 8 honors grades in group I and 40 (p < 0.05) in group II. Interactive teaching, adult education principles, opportunities for discussion, provision of feedback, and stimulation of self-learning were rated more highly in the new course. CONCLUSION: Using standard ATLS pass criteria, performance after the new and old ATLS courses was similar. Superior performances were measured using OSCE methodology for clinical trauma management skills after the new compared with the old ATLS course in this population of interns.

Clinical Competence

Clinical pharmacology of selective estrogen receptor modulators.

Observations of the pharmacology of tamoxifen and related compounds have lead to the concept of selective estrogen receptor modulators (SERMs). This new class of drug displays estrogen agonist or antagonist effects in a tissue-dependent manner and appears to offer an alternative to hormone replacement therapy for the prevention and treatment of osteoporosis and cardiovascular disease in postmenopausal women. Moreover, the estrogen antagonist actions of SERMs on breast tissue may also provide a protective effect against breast cancer. Although tamoxifen therapy reduces plasma cholesterol levels and maintains bone density, it is also associated with an increased risk of endometrial cancer, pulmonary embolism and deep vein thrombosis. This has lead to the development of newer SERMs which will hopefully lack these adverse effects of tamoxifen. These compounds promise a new era of disease prevention in the aging woman and their therapeutic potential is currently being evaluated in large-scale clinical trials.

Animals

Effect of basic prehospital trauma life support program on cognitive and trauma management skills.

We tested the effectiveness of a basic prehospital trauma life support (PHTLS) program by assessing cognitive performance and trauma management skills among prehospital trauma personnel. Fourteen subjects who completed a standard PHTLS course (group I) were compared to a matched group not completing a PHTLS program (group II). Cognitive performance was assessed on 50-item multiple choice examinations, and trauma skills management was assessed with four simulated trauma patients. Pre-PHTLS multiple choice questionnaire scores were similar (45.8 +/- 9.4% vs. 48.8 +/- 8.9% for groups I and II, respectively), but the post-PHTLS scores were higher in group I (80.4 +/- 5.9%) than in group II (52.6 +/- 4.9%). Pre-PHTLS simulated trauma patient performance scores (standardized to a maximum total of 20 for each station) were similar at all four stations for both groups, ranging from 7.9 to 10.4. The post-PHTLS scores were statistically significantly higher at all four stations for group I (range 16.0-19.0) compared to those for group II (range 8.0-11.1). The overall mean pre-PHTLS score for all four stations was 8.3 +/- 2.1 for group I and 8.8 +/- 2.0 (NS) for group II; the group I post-PHTLS mean score for the four stations was 17.1 +/- 2.7 (p < 0.05) compared to 9.1 +/- 2.3 for group II. Pre-PHTLS Adherence to Priority scores on a scale of 1 to 7 were similar (1.1 +/- 0.9 for group I and 1.2 +/- 1.0 for group II). Post-PHTLS group I Priority scores increased to 5.9 +/- 1.1. Group II (1.1 +/- 1.0) did not improve their post-PHTLS scores. The pre-PHTLS Organized Approach scores in the simulated trauma patients on a scale of 1 to 5 were 2.1 +/- 1.0 for group I and 1.9 +/- 1.2 for group II (NS) compared to 4.2 +/- 0.9 (p < 0.05) in group I and 2.0 +/- 0.8 in group II after PHTLS. This study demonstrates improved cognitive and trauma management skills performance among prehospital paramedical personnel who complete the basic PHTLS program.

Emergency Medical Services

Hodgkin's disease diagnosed by endoscopic ultrasound-guided fine needle aspiration of a periduodenal lymph node.

Hodgkin's disease rarely presents as obstructive jaundice. We report a case of Hodgkin's disease arising in periduodenallymph nodes, presenting with biliary obstruction, definitively diagnosed on cytologic material obtained by endosonographically-guided real-time fine needle aspiration biopsy and confirmed at laparotomy. The medical literature pertaining to the use of endosonography and fine needle aspiration biopsy for pancreatic lesions and abdominal lymphoma is reviewed. Currently available data support the use of fine needle aspiration biopsy in establishing the diagnosis of lymphoma. This case highlights the utility of endoscopic ultrasonography with endosonographically guided real-time fine needle aspiration biopsy in diagnosing and managing patients with extrahepatic biliary obstruction or suspected abdominal lymphoma. Pairing endosonographically guided real-time fine needle aspiration biopsy with on-site cytologic assessment and immediate specimen triage can lead to definitive diagnosis of abdominal lymphoma, avoiding surgical intervention in many cases.

Adult

Tirapazamine with cisplatin in patients with advanced non-small-cell lung cancer: a phase II study.

PURPOSE: A phase II study was conducted to evaluate the safety and efficacy of tirapazamine combined with cisplatin for the treatment of patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-four patients with stage IIIB/IV NSCLC were treated with a combination of tirapazamine and cisplatin. Patients received tirapazamine 260 mg/m2 administered intravenously over 2 hours, followed 1 hour later by cisplatin 75 mg/m2 administered over an additional hour, repeated every 21 days. The duration of therapy was meant to be limited to four cycles for nonresponders and eight cycles for responders. RESULTS: Ten of 44 patients (23%) showed a partial response. The estimated median survival for all patients was 37 weeks. Toxicities were treatable and included grade 3 nausea or vomiting (25%), fatigue (27.3%), and muscle cramps (4.5%). No dose reductions were necessary. CONCLUSION: The results show that tirapazamine can safely be added to cisplatin. Both the median survival and response rate observed strongly suggest that tirapazamine with cisplatin is more active than cisplatin alone.

Adult

A comparative study of six commercial lipoprotein(a) assays in seventeen laboratories within the British Isles.

Seventeen laboratories in the British Isles participated in a study to compare six different commercially available immunoassays for serum lipoprotein(a) (Lp(a)) and to establish reasons for the variations in the measurement of serum Lp(a) concentrations. Pooled serum was distributed neat and after dilution at a central laboratory. In addition, the central laboratory sent unpooled serum sampled monthly from six healthy volunteers to each of the participating laboratories for 12 months. The assays all gave linear dilution curves which were parallel, although the reported values varied twofold. There were major differences in the values assigned to different manufacturers' calibrants which was not explained by whether the units employed were whole Lp(a), the protein moiety of Lp(a) or simply apolipoprotein(a). The coefficient of variation for the reported value of Lp(a) over 12 months was 33%. The component variation was 10% after adjustment for inter-laboratory and intra-laboratory variation. Some individuals clearly had a greater tendency to variable serum Lp(a) concentrations than others, but all the assays responded to this in the same way. Thus, the assays tested probably measured the same analyte. The problem of calibration could largely be addressed if agreement were reached by the manufacturers. Even with improvements in analytical precision it should be realized that multiple measurements of serum Lp(a) levels are necessary if the true mean value is to be appreciated. Individuals showing wide variation in serum Lp(a) may reward further study if its role is to be established.

Clinical Laboratory Techniques

Reporting, updating, and correcting systematic reviews of the effects of health care.

The recent growth in the numbers of published systematic reviews reflects growing recognition of their importance for improving knowledge about the effects of health care. In Britain the NHS R&D Programme has established two centres to prepare systematic reviews of existing information, and the Cochrane Collaboration--an international network of individuals and institutions--evolved to produce systematic, periodically updated reviews of randomised controlled trials. The large amount of existing evidence that needs to be considered creates a problem for the reporting of systematic reviews: the need to ensure that methods and results of systematic reviews are adequately described has to be reconciled with the limited space available in printed journals. A possible solution is the use of electronic publications: reviews could be published simultaneously in a short, printed form and in a more detailed electronic form. Electronic publications also have the advantage of the ease with which reviews may be updated as new evidence becomes available or mistakes are identified.

Health Services Research

Biodistribution and kinetics of radiolabelled pyrrolidino-4-iodo-tamoxifen: prospects for pharmacokinetic studies using PET.

With a view to evaluating the role of PET imaging in early clinical studies of new anticancer drugs, we are investigating the recently developed antiestrogen compound pyrrolidino-4-iodo-tamoxifen (idoxifene). Preliminary experimental studies have been undertaken using [125,131I]idoxifene, following synthesis of a tributyl-stannyl-idoxifene precursor to facilitate radioiodination. We have investigated the tissue biodistribution and kinetics of [125I]idoxifene following i.v. infusion in hooded rats bearing the hormone-dependent transplantable mammary tumour OES.HR1. Clearance of idoxifene from the circulation is accompanied by an increase in uptake by tumour and uterus, to peak levels after 24 hours (0.33 +/- 0.037% dose/g (mean +/- 1 SD) and 0.40 +/- 0.033% dose/g, respectively). Highest uptake of idoxifene was found in the liver (11.0 +/- 0.8% dose/g), with a progressive fall after 24 hours consistent with hepatobiliary excretion of the radiotracer. No evidence of idoxifene metabolism was found in tissue extracts taken up to 48 hours. Whole body clearance of [131I]idoxifene was characterised by a single exponential decay (t1/2 = 140 hours) up to 350 hours post administration. We conclude that 124I-labelled idoxifene combined with PET imaging would facilitate human in vivo pharmacokinetic studies of this new anticancer drug and provide an opportunity to investigate relationships between drug uptake and tumour response.

Animals

Effects of a new fish oil concentrate on plasma lipids and lipoproteins in patients with hypertriglyceridaemia.

OBJECTIVES: The effect of a fish oil preparation, K-85, in which the omega-3 fatty acid content was concentrated to 92% of total fat, on serum lipid and lipoprotein concentrations was investigated in patients with primary hypertriglyceridaemia. DESIGN: The study was a randomized, double-blind, placebo-controlled study. SETTING: Seven centres participated in the study, five secondary referral centres and two general practices. SUBJECTS: Men and women aged 18-70 years with fasting serum triglyceride concentrations between 2 and 10 mmol/l and fasting serum cholesterol concentrations > 5.2 mmol/l were studied. Patients with diabetes mellitus, hypothyroidism, serious illness in the previous 3 months or severe concurrent illness were excluded from the study, as were drug or alcohol abusers and pregnant and lactating women. Ninety-five subjects entered the study, 79 completed the study. INTERVENTIONS: Patients were randomized to receive K-85 2 g twice daily or corn oil 2 g twice daily for 14 weeks. MAIN OUTCOME MEASUREMENTS: The serum concentrations of triglycerides and cholesterol, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and lipoprotein (a). Fasting blood glucose and blood pressure. RESULTS: Serum triglycerides and VLDL-cholesterol were significantly lower in the group treated with K-85 than in the placebo group after 6, 10 and 14 weeks (all P < 0.01) and there was a decrease in the serum triglyceride concentration from 3.99 (2.94-9.47) to 2.87 (1.2-9.93) mmol/l (P < 0.001) and in VLDL-cholesterol from 1.47 (0.77-3.63) to 1.12 (0.21-3.67) mmol/l (P < 0.01) in patients receiving K-85. Serum HDL-cholesterol increased from 0.98 (0.95-1.01) to 1.11 (1.07-1.15) mmol/l (P < 0.01) in the patients with type IV hyperlipoproteinaemia but did not change in those with type IIb. Serum LDL-cholesterol, lipoprotein (a) and fasting blood glucose were unaffected by K-85. Diastolic blood pressure decreased from 86 +/- 11 to 80 +/- 12 mmHg (P < 0.02) and was also lower than in the placebo group (P < 0.05). The corn oil placebo did not affect any of the parameters. CONCLUSION: K-85 is effective in lowering serum triglycerides and VLDL in patients with primary hypertriglyceridaemia and may have utility as a triglyceride-lowering agent.

Adult

Mechanism of decreased arachidonic acid in the renal cortex of rats with diabetes mellitus.

The purpose of this study was to investigate the roles of decreased synthesis and increased consumption in the depression of arachidonic acid levels in renal cortex and glomeruli of rats with streptozotocin-induced diabetes mellitus. In diabetic rats, arachidonic acid was depressed 33.2% in renal cortex, 47.4% in liver and 66.1% in heart compared to values of control rats. delta 6 Desaturase activity was depressed in renal cortex, liver and heart of diabetic rats to 53.3, 55.5 and 63.7%, respectively, of control values. delta 5 Desaturase activity was also depressed 43.7, 55.5 and 47.6% in renal cortex, liver and heart of diabetic rats, respectively. In other rats the activities of five enzymes involved in the synthesis and esterification of arachidonic acid were measured in renal cortex and in isolated glomeruli. Both tissues from diabetic rats showed depressed activities of delta 5 and delta 6 desaturases, increased activities of long-chain acyl-CoA synthetase and 1-acyl-sn-glycero-3-phosphocholine acyltransferase and no change in the activity of elongase as compared to those in control tissues. Malondialdehyde, an end product of lipid peroxidation, was lower in the renal cortex of diabetic rats than in control rats, whereas beta-oxidation of linoleic acid and arachidonic acid were similar in diabetic and in control rats. Basal and stimulated prostaglandin E2 synthesis were significantly higher in isolated glomeruli from diabetic rats compared to those in control rats. In isolated tubules, prostaglandin E2 synthesis was similarly low in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyl-CoA Dehydrogenase, Long-Chain

Immediate hypersensitivity in colon of children with chronic Trichuris trichiura dysentery.

There are few data on mucosal immune responses to intestinal helminths in human beings, especially those involving the IgE system, which is thought to be important in parasite expulsion. We sought evidence of an immediate hypersensitivity reaction in the colon of children with chronic dysentery due to Trichuris trichiura. 28 children with Trichuris dysentery syndrome (TDS) were compared with 16 control children (with no TDS or worms visible on colonoscopy). All children were aged 1-11 years. Rectal biopsy samples were taken before and after expulsion of the worms by means of mebendazole treatment. Children with TDS had significantly greater numbers than controls of mast cells (mean [SD] 10.9 [1.3] vs 3.9 [0.6]% of all cells; p less than 0.0003) and of cells with surface IgE (median [range] 11.1 [7.5-11.6] vs 1.0 [0-1.5]%; p less than 0.001) in the subepithelial region of the mucosa. On electronmicroscopy, degranulating mast cells were prominent in parasitised children. In culture, rectal biopsy samples from parasitised children showed high rates of spontaneous histamine release, but only low rates of antigen-specific release. After treatment, spontaneous histamine release was significantly reduced and antigen-specific histamine release could be provoked. Thus, an IgE-mediated immune mucosal response to a helminth infection does occur in human beings but is not sufficient to cause appreciable parasite expulsion.

Anaphylaxis