Benefit of baseline cytometry for surveillance of patients with Barrett's esophagus.

BACKGROUND: The current gold standard for the surveillance of Barrett's esophagus is the Seattle four-quadrant biopsies protocol (4-QB). Using endoscopic brush cytology, this study prospectively investigated whether digital image cytometry (DICM) is of additional benefit over regular histology as a predictor for progression to high-grade dysplasia or cancer during a surveillance of at least 3 years. METHODS: The prospective cohort in this study included 93 patients (72% male) with Barrett's esophagus, baseline endoscopies, and at least one DICM in addition to 4-QB who had been followed up a minimum of 3 years at the time of analysis. High-grade dysplasia (HGD) and adenocarcinoma were defined as primary end points. The DICM was performed on Feulgen-restained cytology smears with a continuous collision detection (CCD) three-chip color video camera (Sony) and an AutoCyte QUIC DNA workstation. RESULTS: Of the 93 patients, 11 presented with the diagnosis of HGD and adenocarcinoma at baseline endoscopy. The remaining 82 patients were analyzed after a median follow-up time of 44 months (range, 36-65 months). Of these 82 patients, 9 (11%) had low-grade dysplasia (LGD) at baseline histology: One of two patients with LGD and aneuploid DICM showed HGD at follow-up assessment, whereas none of seven patients with LGD and diploid DICM had development of HGD. Of the 82 patients, 73 (89%) had either specialized intestinal metaplasia (SIM) without dyplasia or indefinite findings for dysplasia at baseline histology. Of the eight patients with SIM and intermediate/aneuploid DICM, two had development of HGD. None of those with negative or indefinite findings for dysplasia and diploid DICM had HGD at the follow-up evaluation. In summary, the three patients who had development of HGD showed a pathologic DICM at baseline, and no patient with diploid DICM had HGD. CONCLUSIONS: Cytometry from brush cytology as an add-on to histology appears to be of additional benefit during surveillance of Barrett's esophagus. Whereas an aneuploid/intermediate DICM warrants an early re-endoscopy, a diploid DICM underscores the low-risk status especially of patients with low-grade dysplasia.

Impaired cytotrophoblast cell-cell fusion is associated with reduced Syncytin and increased apoptosis in patients with placental dysfunction.

Preeclampsia (PE), Hemolysis Elevated Liver Enzymes and Low Platelets (HELLP)-syndrome, and intrauterine growth restriction (IUGR) are associated with abnormal placentation. In early pregnancy, placental cytotrophoblasts fuse and form multinuclear syncytiotrophoblasts. The envelope gene of the human endogenous retrovirus-W, Syncytin, is a key factor for mediating cell-cell fusion of cytotrophoblasts. This study investigated clinical parameters of PE and HELLP-associated IUGR and analyzed the cell-cell fusion index and beta-human chorionic gonadotropin (beta-hCG) secretion of cytotrophoblasts isolated and cultured from placentas of these patients. In addition, we performed absolute quantitation of Syncytin and determined the apoptosis rate in both cultured cytotrophoblasts and placental tissues. Cultured cytotrophoblasts from PE and HELLP-associated IUGR correlated with a pronounced lower cell-cell fusion index, 1.8- and 3.6-fold; less nuclei per syncytiotrophoblast, 1.4- and 2.0-fold; a significantly decreased beta-hCG secretion, 4.3- and 17.2-fold and a reduction of Syncytin gene expression, 8.1 (P = 0.019) and 222.7-fold (P = 0.011) compared with controls, respectively. In contrast, a significantly 2.3-fold higher apoptosis rate was observed in cultured PE/IUGR cytotrophoblasts (P = 0.043). Importantly, Syncytin gene expression in primary placental tissues of PE/IUGR was 5.4-fold lower (P = 0.047) and in HELLP/IUGR 10.6-fold lower (P = 0.019) along with a 1.8- and 1.9-fold significant increase in the apoptosis rate compared with controls, respectively. Low Syncytin expression in both cultured cytotrophoblasts and primary tissues from pathological placentas supports an intrinsic placenta-specific deregulation of cell-cell fusion in the formation of syncytiotrophoblasts leading to increased apoptosis. These processes could contribute to the development and severity of PE and HELLP-associated IUGR.

Self-reported management of pain in hospitalized patients: link between process and outcome.

PURPOSE: Hospitalized patients commonly experience pain. We investigated the association between patients' reported use of recommended pain management practices and overall pain relief. METHODS: All adult patients discharged during a 1-month period from a Swiss teaching hospital were invited to complete a mailed survey that included the Picker patient experience questionnaire, questions on pain relief during hospitalization, and questions on various procedures that are recommended as standards of pain management. RESULTS: Of 2156 eligible patients, 1518 (70%) participated. Sixty-nine percent (n = 1050) had experienced pain during their hospital stay, of whom 71% (n = 697/978) reported complete pain relief. After adjustment for sex, age, general health, and hospital department, pain relief was associated independently with availability of physicians (odds ratio [OR] = 11; 95% confidence interval [CI]: 3.3 to 36 for excellent vs. poor availability), having received information about pain and its management (OR = 2.8; 95% CI: 1.8 to 4.2), regular pain assessment (OR = 1.8; 95% CI: 1.2 to 2.8), modification of pain treatment when ineffective (OR = 3.0; 95% CI: 1.6 to 5.6), and waiting less than 10 minutes for pain medications (OR = 3.5; 95% CI: 1.9 to 6.6). CONCLUSION: Patient reports that recommended pain management procedures had been used were associated with better self-reported pain relief among hospitalized patients.

Effect of a comprehensive, multidisciplinary, educational program on the use of antibiotics in a geriatric university hospital.

OBJECTIVES: To assess the effect of a comprehensive, educational antibiotic management program designed to improve antibiotic use and reduce treatment costs in elderly patients with suspected urinary or respiratory tract infection. DESIGN: Interventional cohort study with 12 cross-sectional drug utilization reviews of antibiotic use before, during, and after the multifaceted intervention. SETTING: A 304-bed university hospital for geriatric patients. PARTICIPANTS: A total of 3,383 elderly patients. INTERVENTIONS: An educational program including distribution of guidelines on the diagnosis and treatment of urinary and respiratory tract infections; lectures on geriatric infectious diseases; weekly ward rounds for patients with suspected infection; and targeted, individual counseling on diagnosis and antibiotic treatment of infections. MEASUREMENTS: Antibiotic utilization data were collected from the patients' records. Antimicrobial costs were calculated using 1998 hospital wholesale prices. RESULTS: Of 3,383 screened patients, 680 (20%) received at least one antibiotic. During the study period, the mean number of prescribed drugs per patient increased from 5.9 to 7.6 (29%; P<.001). In contrast, a reduction of 15% was observed in the proportion of patients exposed to antibiotic agents (P=.08) and a drop of 26% in the number of antibiotics administered (P<.001). This resulted in a 54% decrease in cumulative daily antibiotic costs. In 83 (75%) of 110 surveyed patients, the guidelines were correctly implemented. The intervention had no measurable negative clinical effect. CONCLUSION: A comprehensive, multifaceted educational program for treating urinary and respiratory tract infections in the elderly was a safe and practical method to change physicians' antibiotic prescribing practice and significantly reduce the consumption and costs of antibiotics in a geriatric hospital.

Reduction of polypharmacy in the elderly: a systematic review of the role of the pharmacist.

Polypharmacy in the elderly complicates therapy, increases cost, and is a challenge for healthcare agencies. In the context of the evolving role of the pharmacist, this systematic review examines the effectiveness of interventions led by pharmacists in reducing polypharmacy. A computerised search was conducted using Medline, Embase geriatrics and gerontology (2001 edition), the Cochrane Library and International Pharmaceutical Abstracts (IPA) databases. A manual search of articles on polypharmacy and the role of pharmacists in the therapy of the elderly and of the reference sections of all retrieved articles was also carried out. Search terms used were 'polypharmacy', 'elderly', 'aged', 'intervention' and 'pharmacist(s)'. Articles that fulfilled the following criteria were included: only elderly people were included in the study, or all ages were included but the study gave separate results for the elderly; the outcome was expressed as a reduction in the number of medications; a pharmacist participated in the study; and the study was a controlled or a randomised controlled study. We initially identified 106 articles, but only 14 studies met our four inclusion criteria. Reduction in the number of medications was not the major purpose of most selected studies but often a secondary outcome. Objectives differed, the general aim being to enhance the quality of prescribing in elderly patients. These controlled studies argued in favour of the effectiveness of pharmacists' interventions, even though the number of medications eliminated was small. Most studies were not designed to demonstrate the impact of reducing the number of drugs on the clinical consequences of polypharmacy (nonadherence, adverse drug reactions, drug-drug interactions, increased risk of hospitalisation, and medication errors). The most frequently reported outcome related to cost savings. It was therefore difficult to assess whether the interventions benefited the patient. The methodological quality of many identified studies was poor. In particular, the study objectives were often very broad and ill-defined. Polypharmacy itself has been defined in different ways and the appropriate definition may differ according to the patient population and the study setting. Further studies are needed to find the most effective way to reduce polypharmacy, especially in the frail elderly population, and to quantify the real advantages of simplifying their drug regimens in terms of improved quality of life.

Upregulation of arginase expression in wound-derived fibroblasts.

BACKGROUND: Wound-derived fibroblasts (WFBs) are phenotypically different from normal dermal fibroblasts (NFBs). We have previously shown that the wound phenotype correlates with expression of the inducible isoform of nitric oxide synthase (iNOS) in fibroblasts. l-Arginine is the sole substrate for iNOS. Arginase is an alternative pathway of l-arginine metabolism in wounds. To clarify the role of l-arginine in wound healing, we investigated arginase expression and activity in WFB. METHODS: Male Lewis rats underwent dorsal skin incisions and subcutaneous PVA sponge implantation. WFBs were harvested from sponges retrieved at different days postimplantation. Normal fibroblasts were obtained from uninjured skin by an explant technique. Arginase activity was measured by newly formed urea (nmol/min/mg protein) and protein expression was detected by Western blotting using specific antibodies for type I (AI) and type II (AII). The effect of transforming growth factor beta1 (TGF-beta1), interleukin-4 (IL-4), lipopolysaccharide, and wound fluid on arginase activity was also investigated. RESULTS: WFB arginase activity was significantly elevated compared with NFB activity at all times postwounding. This was paralleled by increased AI protein expression by Western blotting. AII was not detectable. TGF-beta and IL-4 significantly increased arginase activity and protein expression whereas lipopolysaccharide and wound fluid did not affect it. CONCLUSIONS: The upregulation of the arginase expression in WFB underlines the distinct regulation of l-arginine metabolism in WFBs. Further work is needed to elucidate the functional implications.