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Background. DNA ploidy determination of carcinomas in radical prostatectomy specimens has shown significant correlation with patient outcome, but the predictive value of ploidy status of cancers obtained by transrectal ultrasound-guided needle biopsies has not been studied extensively. Methods. Eighty-nine paired needle biopsy specimens (NBX) and radical prostatectomy (RPX) specimens from patients with early clinical stage (A2-B2) prostate cancer were evaluated for DNA content by image analysis of Feulgen stained tissue sections. Findings were compared with Gleason grading on the same specimens by univariate and multivariate analyses for prediction of local tumor invasion, metastasis, disease recurrence, and serum prostate specific antigen concentration during a 0.9-6.0 year clinical follow-up period. Results. There was excellent correlation of ploidy status between NBX and RPX specimens (P < 0.0001); NBX and RPX grades did not correlate. On RPX specimens, aneuploid status correlated with high tumor grade (P < 0.0005). Aneuploidy in NBX specimens was associated with a twofold higher rate of extracapsular spread (ECS) (P = 0.04). Aneuploid NBX tumors featured a ten fold greater frequency of metastasis than did diploid NBX tumors (P < 0.005). Radical prostatectomy grade correlated with ECS (P < 0.001) and presence of metastatic disease (P = 0.04). On multivariate logistic regression analysis, aneuploidy in both NBX and RPX specimens was the most significant variable and independently predicted the presence of metastasis (P = 0.006 for NBX; P = 0.028 for RPX). Tumor grade of NBX and RPX specimens did not independently predict metastatic disease or disease recurrence, but RPX grade was associated independently with ECS (P = 0.005). Aneuploid NBX tumors recurred after RPX three times more often than did diploid cases, which was significant on univariate (P < 0.001) and multivariate (P = 0.018) analyses using the Cox proportional hazards model. There was no correlation with NBX or RPX Gleason score and disease recurrence. Preoperative serum PSA concentration did not correlate with tumor grade or ploidy status, but on multivariate analysis, when paired with ploidy status, independently contributed to the propensity for ECS, metastasis, and disease recurrence. Conclusions. DNA content analysis of early clinical stage prostate carcinoma needle biopsy specimens by im age analysis directly correlates with radical prostatectomy specimen ploidy status and is associated independently, with the presence of metastasis, postprostatectomy disease recurrence, and ECS. Needle biopsy tumor grading did not correlate with prostatectomy grade and did not predict disease outcome accurately.

Background. Genetic changes in the development of endometrial carcinoma have not been characterized, and little is known of tumor or metastatic suppressor gene status in these malignancies. The current study on endometrioid carcinoma was undertaken to examine the status of two tumor suppressor genes that frequently have been found to be altered in human malignancies (the p53 gene and the retinoblastoma [Rb] gene) and to examine the status of the candidate metastatic suppressor gene, nm23-H1. Methods. The status of the p53 gene was studied by immunohistochemistry of formalin-fixed paraffin-embedded biopsy samples from 72 patients with atypical endometrial hyperplasia or endometrioid carcinoma who underwent hysterectomy immediately after biopsy and from 5 patients with benign endometria. A search for loss of heterozygosity (LOH) of the nm23 gene after DNA extraction from frozen tissues and hybridization with nm23-H1 cDNA specific probe was made in 10 endometrial carcinomas. Rb gene status was evaluated by image analysis quantification of immunoreactive retinoblastoma protein in frozen sections of 10 carcinomas and 2 benign endometria. Results. p53 expression was low in all benign endometria, but high expression was found in 2 (15%) of 13 atypical hyperplasias and in 23 (39%) of 59 carcinomas. High levels of p53 expression in endometrioid carcinoma correlated with the spread of disease outside of the uterus and by logistic regression, the presence of squamous differentiation, nuclear grade, and high p53 expression in the biopsy all independently correlated with spread of disease outside of the uterus. Although 7 of the 10 carcinomas studied were informative, LOH for the nm23 gene was not seen in any, including a site of metastasis. Rb protein expression in endometrial carcinoma was similar to expression in benign endometria. Conclusions. Although this study found no evidence of nm23-H1 gene alteration or alterations in Rb protein levels in endometrial carcinoma, high expression of p53 protein was sporadically identified in biopsy specimens of atypical hyperplasia and frequently found in endometrioid carcinomas. Determination of p53 expression in combination with the presence or absence of squamous differentiation and nuclear grade in biopsy material may help predict spread of endometrioid carcinoma outside the uterus and facilitate therapeutic planning before hysterectomy.

Background. Recent advances in the early detection of prostatic adenocarcinoma have stimulated interest in the development of techniques for determining metastatic potential. Methods. One hundred cases of adenocarcinoma, including 66 biopsy and radical prostatectomy specimens; 20 biopsies alone; and 14 transurethral resection specimens, were evaluated for Gleason tumor grade, DNA content and HER-2/neu expression. DNA content was determined on Feulgen-stained touch preparations and tissue sections (18 cases) or tissue sections alone. HER-2/neu expression level was determined by image-analysis-assisted quantitative immunocytochemistry. Results. Tumor grade and ploidy status were independent significant predictors of metastasis. HER-2/neu overexpression was found in 16 (16%) of the 100 cases and significantly correlated with high-tumor grade and aneuploid status, but was not of independent value in the prediction of metastasis. Conclusions. HER-2/neu overexpression is not uncommon in prostatic adenocarcinoma and is associated with high-tumor grade, abnormal DNA content, and distant metastasis. Tumor grade and DNA ploidy values are of the greatest value in determining the presence of metastasis.

Electronic creation and processing of prescriptions (e-prescribing) is attractive for a number of reasons, including convenience for the prescriber, patient, and pharmacist. Other benefits include the ability to provide clinical-decision-support tools and prescription-benefit information; the

The epidemiology, mechanics, prevention, pharmacology, clinical manifestations, and treatment of snakebites are reviewed. Poisonous snakes bite approximately 8000 persons annually in the United States, causing approximately 12-15 deaths per year. Pit vipers (rattlesnakes, copperheads, cottonmouths, and massasaugas) are responsible for 99% of all snakebite poisonings; coral snakes and other foreign exotic species are responsible for the additional 1%. Envenomation is characterized by pain, edema, and ecchymoses at or near the site of venom injection, followed by cardiac, hematologic, neurologic, renal, and pulmonary toxicity. The major clinical finding in most snakebite poisonings is local tissue necrosis. Immediate treatment for snakebite includes limiting movement and placing a constriction band proximal to the site of venom injection. If medical care is more than 30 minutes away, the wound may be incised and suctioned. Antivenin therapy is the mainstay of medical treatment of snakebite, along with administration of plasma expanders, pain medication, diazepam, tetanus toxoid, antiseptics, and antibiotics. Patients who have pain, swelling, ecchymoses, systemic symptoms, or abnormal laboratory findings within 30 minutes to one hour of a bite are probable candidates to receive antivenin therapy. Before receiving antivenin therapy, the patient must be tested for hypersensitivity to the antivenin. Antivenin therapy is most effective when given within four hours of the snakebite. Pharmacists--especially those serving rural areas--should be familiar with current snakebite treatments, both local and systemic, and should be prepared to provide important information and dispel any myths about snakebite poisoning.

In the ambulatory care setting, studies indicate that between 1.5% and 4.0% of prescriptions are in error with potentially serious patient risk.[1][1]–[3][2] Adverse drug events (ADEs) occur in 5–18% of ambulatory patients and at a rate of 50.1 per 1000 patient years in older persons.[4][3],[5][

Medication therapy management (MTM) is an important new service delivered by pharmacists in ambulatory and institutional settings.[1][1],[2][2] MTM includes a comprehensive medication therapy review, the development of a fully reconciled personal medication record (PMR), the creation of a medication

OBJECTIVE: We previously described vascular invasion-associated changes, defined as the presence of vascular invasion or perivascular lymphocytic infiltrates, as key prognostic indicators in stage I endometrioid carcinoma. The current study was undertaken to examine the prognostic value of HER-2/ neu expression in relation to other factors, including vascular invasion-associated changes, in surgical stage I endometrioid carcinoma. STUDY DESIGN: Seventy-one patients with surgical stage I endometrioid carcinoma treated by hysterectomy and followed up were randomly chosen for retrospective analysis of prognostic indicators including standard clinicopathologic features, deoxyribonucleic acid ploidy, and HER-2/ neu expression. The latter was examined by an objective computerized quantitative immunohistochemical system. RESULTS: By univariate analysis many factors were found to correlate with outcome, including age, tumor grade, depth of invasion, ploidy, HER-2/ neu expression, and vascular invasion-associated changes. By multivariate analysis only vascular invasion-associated changes, aneuploidy, and HER-2/ neu overexpression were found to independently correlate with survival. Stratification of patients on the basis of these three features revealed survival rates of 100%, 92%, and 60% when none, one, and two or three features were present, respectively. CONCLUSION: This study suggests that HER-2/ neu expression correlated with outcome independent of other factors in endometrial carcinoma and may aid in estimating prognosis. The prognostic value of HER-2/ neu overexpression independent of vascular invasion suggests that this factor may operate by increasing the ability of tumor cells to grow at a distal site once vascular invasion occurs.

Amiodarone, an iodinated benzofuran derivative, is used for treatment of refractory cardiac arrhythmias. Certain features of the drug's structure resemble those of the biologically active thyroid hormone, triiodothyronine (T3). In addition, the drug has a variety of complex effects on thyroid hormone physiology, including a number of possible antagonistic effects on thyroid hormone function at the cellular level. The drug occasionally causes clinically overt hyperthyroidism and hypothyroidism. We review these effects and discuss their clinical implications.

Four developments in diabetes care and management have evolved over the last decade and are now routinely incorporated into clinical practice: (1) the introduction of recombinant human insulin; (2) the use of second generation oral agents; (3) home glucose monitoring and glycohemoglobin monitoring; and (4) a better understanding of the relationship between diabetic control and complications.

Nicotinic acid (niacin) is a water-soluble vitamin widely used for the treatment of lipid disorders. In pharmacologic doses (1 g or more/day), alone or in combination with other lipid-lowering drugs, nicotinic acid lowers very low-density (VLDL) and low-density lipoprotein (LDL) levels, while concurrently increasing high-density lipoprotein (HDL) levels. It may reduce long-term mortality in patients with known coronary artery disease and may slow or reverse the progression of atherosclerosis. A major consideration against using nicotinic acid is the occurrence of frequent, bothersome, adverse reactions such as cutaneous flushing, skin rash, and gastric upset. Careful dosing titration may, however, minimize these effects. The beneficial effects, taken together with the low cost of nicotinic acid therapy and the relative freedom from serious side effects, have made nicotinic acid the agent of choice for the treatment of many patients with hyperlipidemia.