Endothelin receptor blockade during hypothermic perfusion preservation mitigates the adverse effect of preretrieval warm ischemic injury on posttransplant glomerular filtration rate

BACKGROUND: Preretrieval warm ischemic injury predisposes to both short-term and long-term dysfunction of cadaveric renal allografts. We previously reported that the excretion of the vasoactive peptide, endothelin (ET), is significantly increased during hypothermic perfusion preservation (HPP) of kidneys subjected to preretrieval warm ischemia compared with nonischemic controls. As such, the purpose of this study was to determine if endothelin receptor (ET-R) blockade during HPP would improve glomerular filtration rate (GFR) of kidneys subjected to preretrieval warm ischemia when measured in situ at 2 weeks after transplantation (Tx). METHODS: The left kidney was retrieved from 300-g Lewis rats after in situ cold perfusion and transplanted after 2 hr of HPP. A 30-min period of preretrieval warm ischemia was induced. Kidneys were divided into four groups: nonischemic controls (n=9), ischemic (isch) kidneys not receiving ET-R blockade during HPP (n=7), isch kidneys receiving the ETA receptor antagonist (n=7), and isch kidneys receiving the ETA/B receptor antagonist (n=8). ET-R blockade was induced by adding the ETA, A-147627, or the ETA/B, A-182086, receptor antagonist (Abbott Laboratories, Abbott Park, IL) directly to the preservation solution (5x10-6M). The kidneys were then isografted into genetically identical Lewis rats and GFR, determined by measurement of urinary iohexol clearance, measured 2 weeks after Tx. RESULTS: Two-week GFRs (mL/min) for each of the study cohorts are as follows: nonischemic controls, 1.18+/-0.11; ischemic (isch) only, 0.57+/-0.08 (P< or =0.05 vs. nonischemic controls); isch + ETA blockade, 0.95+/-0.15 (P< or =0.05 vs. isch only); isch + ETA/B blockade, 0.90+/-0.08 (P< or =0.05 vs. isch only). CONCLUSION: Addition of an ETA, A-147627, or an ETA/B, A-182086, receptor antagonist to preservation solution used during HPP of kidneys subjected to preretrieval warm ischemia resulted in a normalization of GFR measured 2 weeks after Tx. The data provide a basis for further investigation of the impact of ET-R blockade on both the short- and long-term adverse effects of preretrieval warm ischemic injury in cadaveric renal Tx.     

Releasing pre-adoption birth records: a survey of Oregon adoptees

OBJECTIVE: In June 2000, Oregon implemented a citizen-initiated ballot measure that grants adult adoptees access to their birth records, which contain their birth parents' identifying information. Because other states are considering similar policy changes, the authors explored whether Oregon's new law is meeting the information needs of adoptees. METHODS: Birth records were abstracted for a 9% (221/2,529) random sample of adoptees who obtained their records from June 20, 2000, to July 20, 2000, to describe the population and the information they obtained. Telephone interviews documented their motivations, expectations, and whether they considered the birth record useful. RESULTS: The mean age of the adoptees was 41 years, 64% were female, and 97% were white. Virtually all received information about their birth mother; however, only one-third received information about their birth father. Of the 221 sampled, 123 (59%) participated in the telephone survey, 12 were ineligible, 84 could not be reached, and 2 refused. The most common motivations for requesting records were to find birth parents (29%) and to obtain medical information (29%). Twenty-nine percent received less information than they expected, with many expecting, but not receiving, birth father information. Thirty-three (47%) of the 70 adoptees who tried to find their birth mother were successful. The records were considered "very" useful by 52% of respondents, "somewhat" or "a little" useful by 42%, and "not at all" useful by 6%. CONCLUSIONS: The results indicate that many adoptees received less information than they expected, and many did not meet their goals of finding birth parents or obtaining medical information. Nonetheless, the majority considered their birth records useful and important.     

N-methyl-d-aspartate receptor-mediated processing of beta-amyloid precursor protein in rat hippocampal slices: in vitro--superfusion study

Abnormal proteolytic degradation of the beta amyloid precursor protein (beta-APP) may result in accumulation of potentially neurotoxic beta amyloid (betaA). The role of various receptors in the regulation of beta-APP processing has been suggested. This study aimed to determine how NMDA receptors and Ca2+ ions regulate proteolysis of beta-APP in rat hippocampus in vitro. Adult rat hippocampal slices were superfused with NMDA-containing media, and immunoreactivity of soluble beta-APP derivatives was detected in dialysates. Application of 100 microM and 250 microM NMDA for 20 min in Ca2+-containing medium induced dose-dependent release of aminoterminal beta-APP derivatives, and a fragment of Abeta sequence, whereas carboxy-terminal fragments of beta-APP were only slightly detected. This indicates activation of beta-APP processing, and release of its soluble cleavage products. This effect was inhibited by NMDA receptor antagonist 1 microM MK-801 and 100 microM CPP in Ca2+-free medium, thus indicating that NMDA receptors and calcium ions mediate proteolytic non-amyloidogenic degradation of the beta-APP.     

Snake oil, ethics, and the first amendment: what's a profession to do?

This article considers the appropriate legal and ethical response to those whose advocacy of "alternative" or unvalidated therapies places people at risk of harm. What are our professional responsibilities with respect to such advocacy, and what sorts of harm will justify government intervention?     

Liver function tests during treatment with antipsychotic drugs: a case series of 23 patients

Atypical antipsychotics represent a new class of medication for the treatment of schizophrenia and their use is associated with a reduction of neurological side effects. This article reports the result of the systematic clinical and biological supervision of hepatic enzymes on 23 schizophrenic inpatients treated by atypical antipsychotic during 2 weeks at Days 1 (D1), 7 (D7), and 14 (D14) in a naturalistic study during 6 months. The drug administrated was limited to four medications—risperidone, amisulpride, olanzapine, and clozapine—but other psychotropic agents were prescribed. Six cases of biological cytolytic hepatitis were observed. Due to the numerous risk factors and the frequency of “routine” conditions, careful supervision of the hepatic function is needed to prevent this kind of side effect.     

Culturally competent dietary education for southern rural African Americans with diabetes

PURPOSE: The purpose of this article is to describe a culturally competent, dietary self-management intervention designed to improve physiological outcomes, diabetes self-management, and costs of care for high-risk African Americans with type 2 diabetes. METHODS: A longitudinal, quasi-experimental design was used to evaluate the effectiveness of the intervention for 23 adult African Americans from a physician practice group in rural South Carolina. The intervention consisted of 4 low-fat dietary education classes, 6 discussion groups, and follow-up. Intervention sessions were provided by a dietitian and nurse case managers and framed as social events; families were encouraged to participate. RESULTS: Data suggest that the intervention significantly improved fat-related dietary habits, A1C values, fasting blood glucose, and frequency of acute care visits. A trend in reduction of lipids and weight also was observed. CONCLUSIONS: Culturally competent dietary self-management provides a meaningful approach to focused diabetes education for rural African Americans. Integrating nursing case management provides an innovative method of addressing the more global issues of delivery of care to underserved rural populations and decreasing the high costs of care.     

Tetrofosmin imaging in the detection of myocardial viability in patients with previous myocardial infarction: comparison with sestamibi and tl-201 scintigraphy

BACKGROUND: Technetium 99m tetrofosmin has been introduced as a myocardial perfusion agent, providing similar results to those of thallium 201 and sestamibi in the identification of patients with coronary artery disease. No data are available comparing tetrofosmin and sestamibi imaging in the identification of reversible left ventricular (LV) dysfunction in the same patients. This study compared the results of tetrofosmin, thallium, and sestamibi single photon emission computed tomography at rest in detection of myocardial viability in patients with previous myocardial infarction. METHODS AND RESULTS: Seventeen patients with previous myocardial infarction who were undergoing coronary revascularization were studied. Echocardiography was performed at baseline and 3 months after revascularization to evaluate recovery of LV function. The optimal threshold cutoffs to separate reversible from irreversible dysfunction, as determined by receiver operating characteristic analysis, were 55% of peak activity for both tetrofosmin and sestamibi and 60% for thallium. In all asynergic segments (n = 77) analyzed, tetrofosmin uptake correlated with both sestamibi (r = 0.90, P <.0001) and thallium (r = 0.85, P <.0001) activity. The sensitivity and specificity for reversible dysfunction were, respectively, 70% and 70% for tetrofosmin, 70% and 66% for sestamibi, and 60% and 68% for thallium imaging (all P = not significant). The areas under the receiver operating characteristic curves constructed for tetrofosmin, thallium, and sestamibi activity were 0.74 +/- 0.06 (mean +/- SD), 0.75 +/- 0.06, and 0.74 +/- 0.06, respectively (all P = not significant). Concordance for detecting myocardial viability between tetrofosmin and thallium imaging was found in 67 regions (87%) (kappa = 0.74), and concordance between tetrofosmin and sestamibi imaging was found in 69 regions (90%) (kappa = 0.79). CONCLUSIONS: The diagnostic performance of quantitative rest tetrofosmin single photon emission computed tomography in predicting functional recovery after revascularization is comparable to that of both thallium and sestamibi scintigraphy in patients with myocardial infarction and chronic LV dysfunction.     

Biomarkers in breast cancer

Breast cancer is one of the most frequently diagnosed cancers among women in the western world. Due to the aggressive behaviour of some specific types and the possibility of an early diagnosis, breast cancer has been constantly studied. Tumour size, histological type, cellular and nuclear characteristics, mitotic index, vascular invasion, hormonal receptors and axillary lymph node status are biomarkers routinely used. However, these parameters are not enough to predict the course of this disease. Molecular biology advances have made it possible to find new markers, which have already been incorporated to the clinical practice. Their ultimate goal is to reduce mortality by identifying women at risk for the development of this disease, help diagnosis, determine prognosis, detect recurrences, monitor and guide treatment, and in particular cancers they are suited for general screening. Tumour markers in breast cancer were ranked in categories reflecting their clinical utility, according to the American College of Pathologists. This article focuses on traditional and new molecular markers stratifying them into categories and emphasizing their relevance in the routine evaluation of patients with breast cancer.     

Adverse Reactions to Isosulfan Blue During Selective Sentinel Lymph Node Dissection in Melanoma

Background: Selective sentinel lymph node (SLN) dissection can spare about 80% of patients with primary melanoma from radical lymph node dissection. This procedure identifies the SLN either visually by injecting isosulfan blue dye around the primary melanoma site or by handheld gamma probe after radiocolloid injection.Methods: During selective SLN mapping, 1 to 5 ml of isosulfan blue was injected intradermally around the primary melanoma. From November 1993, to August 1998, 406 patients underwent intraoperative lymphatic mapping with the use of both isosulfan blue and radiocolloid injection. Three cases of selective SLN dissection, in which adverse reactions to isosulfan blue occurred, were reviewed.Results: We report three cases of anaphylaxis after intradermal injection with isosulfan blue of 406 patients who underwent intraoperative lymphatic mapping by using the procedure as described above. The three cases we report vary in severity from treatable hypotension with urticaria and erythema to severe cardiovascular collapse with or without bronchospasm or urticaria.Conclusions: In our series, the incidence of anaphylaxis to isosulfan blue was approximately 1%. Anaphylaxis can be fatal if not recognized and treated rapidly. Operating room personnel who participate in intraoperative lymphatic mapping where isosulfan blue is used must be aware of the potential consequences and be prepared to treat anaphylaxis.