[Evidence-based clinical practice guidelines development. From the bottom, to the top].
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Biomedical subjects
Publications and source records attributed to B Haynes.
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The human thymus is required for establishment of the T cell pool in fetal life, but postnatal thymectomy does not lead to immunodeficiency in humans. Because thymectomy in humans is performed for treatment of myasthenia gravis (MG), we have studied patients with MG for effects of thymectomy on peripheral blood (PB) naive (CD45RA(+), CD62L(+)) and memory (CD45RO(+)) T cells. We have also determined the effect of thymectomy on levels of PB cells containing signal joint TCR delta excision circles (TRECs), a molecular marker of thymus emigrants that have divided few times after leaving the thymus. In 17 nonthymectomized and 26 thymectomized MG patients studied at varying times after thymectomy (1 day to 41 years), we found no significant mean difference in PB T cell TREC levels between ages 40 and 80 years. However, both thymectomized and nonthymectomized MG patients had lower PB T cell TREC levels than did age-matched normal subjects (p < 0.0001 for both). These data demonstrated that MG itself or treatment for MG decreased thymopoiesis independent of thymectomy. Next, to control for disease activity and treatment, we prospectively studied 10 MG patients before and from 27 to 517 days after thymectomy. We found that thymectomy decreased CD4 or CD8 T cell TREC concentrations most when thymopoiesis was active before thymectomy (six of six patients), but had little effect in patients when thymopoiesis was minimal (four of four patients). In contrast, there was no significant effect of thymectomy on absolute numbers of naive PB T cells. Thus, in MG, removal of a thymus with active thymopoiesis resulted in a significant fall in PB TREC(+) T cells postthymectomy.
Membrane collection surfaces, developed and patented by researchers at Ohio University, were used to replace steel plates in a dry electrostatic precipitator (ESP). Such replacement facilitates tension-based rapping, which shears the adhered particle layer from the collector surface more effectively than hammer-based rapping. Tests were performed to measure the collection efficiency of the membranes and to quantify the potential improvements of this novel cleaning technique with respect to re-entrainment. Results indicate that even semiconductor materials (e.g., carbon fibers) collect ash nearly as efficiently as steel plates, potentially indicating that collection surface resistivity is primarily dictated by the accumulated ash layer and not by the underlying plate conductivity. In addition, virtually all sheared particles separated from the collecting membranes fell within the boundary layer of the membrane, indicating extremely low potential for re-entrainment.
OBJECTIVE: To document ocular penetration of oral tamoxifen in patients being administered systemic therapy by measuring intraocular and serum levels of the drug in a series of patients undergoing elective ocular surgery. DESIGN: Nonrandomized, prospective, comparative trial. PARTICIPANTS: Twenty-one eyes of 21 patients undergoing elective ocular surgery (cataract extraction or vitrectomy). Twenty patients were using the antiestrogen, tamoxifen, and one participant was not. Nine patients were excluded in the final analysis because of inadequate sample size. INTERVENTION: Preoperative serum samples and perioperative aqueous samples, vitreous samples, or both were obtained for each patient, and these were analyzed for tamoxifen and its metabolites. Dilated fundus examination was performed before surgery on all patients. MAIN OUTCOME MEASURES: Evidence of tamoxifen, its metabolites, or both in the samples. RESULTS: Tamoxifen was detected in all analyzed serum samples (range, 82.4-290.0 ng/ml.) from patients taking the medication and was found to have penetrated into both vitreous (range, 0.5-7.8 ng/ml) and aqueous (range, 0.5-3.9 ng/ml) cavities. No relationship was found between serum and intraocular levels. CONCLUSIONS: This study shows that tamoxifen penetrates intraocular fluids to varying degrees. The drug levels in aqueous and vitreous do not appear to correlate with serum levels. Evidence of tamoxifen retinopathy or keratopathy was not seen.
A grounded theory approach was used to explore the influence of peer relationships on adjustment to cystic fibrosis (CF) in 15 adolescents. Discovering the course was the core category that captured the influence of peers on adjustment to CF. Four subcategories were identified: (1) losing ground, (2) being out of the loop, (3) finding a new company of friends, (4) fighting a never-ending battle. The downward progression of CF and increasing social interactions with peers with CF during hospitalization helped them learn CF was a lifelong disease with relentless demands. Interventions should focus on strategies for promoting peer support, a positive attitude, and hope to create a sense of belonging, social competence, and well-being.
We report 2 cases of renal transplant recipients in whom hepatosplenic gamma-delta T-cell lymphoma (gamma-delta HSTCL) developed 5 and 10 years after transplantation. Both patients had marked hepatosplenomegaly, B symptoms (weight loss, fever, and night sweats), and abnormal peripheral blood findings, including anemia in both, thrombocytopenia and leukoerythroblastic changes in 1, and leukocytosis in the other. Markedly atypical lymphoid infiltrate of intermediate to large cells was observed in the spleen, liver, and bone marrow. The malignant cells showed typical immunophenotype of gamma-delta T cells (CD2+, CD3+, CD4-, CD8-, CD7+, gamma-delta T-cell receptor-positive, and alpha-beta T-cell receptor-negative) with clonal T-cell receptor gene rearrangement and were of the V-delta-1 subset. In addition, the cells contained a cytolytic granule-associated protein, TIA-1, and Fas ligand, indicating cytotoxic T-cell differentiation. The malignant T cells in both cases were of host tissue origin. Both cases were negative for Epstein-Barr virus genome using Southern blot analysis. The patients did not respond to reduction of immunosuppression. Despite initial response to chemotherapy, both patients died within 6 months of diagnosis. Our findings indicate that gamma-delta HSTCL can occur as a late complication in transplant recipients.
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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.
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.
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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.
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.
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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.
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.
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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.