FTY720 mediates apoptosis-independent lymphopenia in human renal allograft recipients: different effects on CD62L+ and CCR5+ T lymphocytes

BACKGROUND: The sphingolipid FTY720 (FTY), a novel immune modulator, induces lymphopenia and prevents allograft rejection. This study was designed to study the effect of FTY on lymphocyte subpopulations and apoptosis in stable renal allograft recipients. METHODS: Stable renal allograft recipients received a single oral dose of 0.25 to 3.5 mg of FTY (n= 13) or placebo (n= 3). Whole blood was drawn immediately before and at 4, 8, 12, 24, 72, and 96 hr after administration. The number of lymphocyte subpopulations, with an emphasis on surface markers involved in lymphocyte migration, was analyzed by flow cytometry. Apoptotic lymphocytes were detected following Annexin V-FITC/PI staining. Lymphocyte mobility was investigated in a modified Boyden chamber. RESULTS: FTY induced a transient lymphopenia by an apoptosis-independent mechanism. In vitro experiments with peripheral blood mononuclear cells (PBMC) confirmed that clinically relevant concentrations of FTY (0.1 microM) increased lymphocyte mobility, whereas only suprapharmacologic concentrations of FTY (10 microM) could induce apoptosis. FTY-treated patients had reversible changes in the composition of peripheral lymphocyte subpopulations. CD62L+ T cells decreased to the greatest extent (-57%). In contrast, CCR5+ T-cell counts declined only marginally (-10%). In vitro, treatment of PBMC with FTY (1 mM-10 microM) did not induce changes in the expression of these surface markers. CONCLUSIONS: The data indicate that FTY mediates apoptosis-independent lymphopenia in human renal allograft recipients. FTY-induced lymphopenia preferentially affects CD62L+ and CCR5- T-lymphocyte subpopulations.     

Early-stage cervical adenocarcinoma treated by surgical intent: the role of para-aortic lymph node dissection.

OBJECTIVE: Previous reports suggest that cervical adenocarcinomas have a unique pattern of spread and are more apt to metastasize to para-aortic lymph nodes. The purpose of this study was to further define the node of para-aortic lymph node dissection in early-stage cervical adenocarcinoma treated by surgical intent. METHODS: Institutional review board approval was obtained to perform a computerized search of the data of all women diagnosed with cervical adenocarcinoma between 1982 and 2000. Hospital charts were retrospectively reviewed. Follow-up was obtained from the tumor registry, medical records, and correspondence with health care providers. RESULTS: Three hundred (87%) of 345 early-stage (FIGO IA(1)-IIA) cervical adenocarcinoma patients were primarily treated by surgical intent. Two hundred seventy-six underwent pelvic and para-aortic node dissection (n = 69) or pelvic node dissection only (n = 207); 24 had no lymph node dissection. The median number of lymph nodes removed was 13 pelvic (range, 1-58) and 3 para-aortic (range, 1-17). Three (4%) of 69 patients had para-aortic nodal metastases. Each had either grossly evident para-aortic adenopathy (n = 2) or an adnexal metastasis. Thirty-six of 40 women developing recurrent disease had at least some component of pelvic recurrence; 4 had only extrapelvic disease. Three patients undergoing para-aortic node dissection developed an isolated extrapelvic recurrence despite originally negative para-aortic nodes (n = 2) or treatment by extended-field radiation for para-aortic metastases. One woman undergoing only pelvic node dissection had an isolated extrapelvic recurrence despite originally negative nodes. CONCLUSIONS: Early-stage cervical adenocarcinoma primarily treated by surgical intent has a very low risk of para-aortic metastases. These were detected only when there was gross evidence of nodal or adnexal disease.     

The pathophysiologic basis for the incorporation of 99mTc-pyrophosphate into myocardial infarct

The investigation studied the relation of 99mTc-pyrophosphate incorporation (99mTc-PYP) into experimental, 48-hours old myocardial infarction in dogs to tissue vascular supply and to the extent of necrotic tissue. The experimental myocardial infarction was induced in five animals during an operation by the ligation RIVA. The myocardial blood supply was measured in tissue samples, taken from transverse sections of the infarction by means of 86Rb captation. The extent of myocytolysis was measured by depletion of tissue creatine kinase (CK). In the subendocardial layer of the infarction it became obvious that 99mTc-PYP incorporation was proportional to the decrease of tissue blood supply. No relation between the extent of necrosis and the incorporation of the radioactive chemical was demonstrated. The accumulation of 99mTc-PYP requires the necrosis to be present, but its extent apparently does not influence the intensity of incorporation. In the subepicardial infarction layer there was neither a relation of the radioactive chemical cumulation to the blood flow, nor to the extent of the necrosis proved.     

Analysis of factors influencing nitrogen balance during acute starvation in obese subject with and without type 2 diabetes

BACKGROUND & AIMS: Patients with type 2 diabetes (T2DM) tend to loose more lean body mass during both long-term weight reduction and short-term very-low-calorie diet. We ask what factors influence protein loss during acute starvation in T2DM. METHODS: In a prospective in-hospital observational study, we compared 10 subjects with T2DM and 10 age-weight-sex matched obese controls (OB) during 60 h of fasting and used frequent blood sampling and indirect calorimetry to describe metabolic and endocrine response. We analyzed factors influencing nitrogen balance using stepwise multiple regressions. RESULTS: Despite comparable pattern of plasma insulin, free fatty acid, 3-hydroxybutyrate and almost identical behavior of growth hormone axis, our T2DM subjects remained hyperglycaemic and in contrast to OB subjects they failed to reduce the rate of protein oxidation, even though muscle protein breakdown rate declined similarly in both groups. Regression analysis revealed that protein oxidation rate in T2DM group was enhanced by hyperglycemia and sympathetic activity and suppressed by circulating insulin and 3-hydroxybutyrate. Liver insulin resistance increases peripheral insulin concentrations and enhances the conversion of non-esterified fatty acids (NEFA) to ketones and thus it might be a protein-saving factor. CONCLUSION: Relative deficiency of circulating insulin and hyperglycemia play a pivotal role in the impairment of protein sparing in T2DM during a short-term fasting.     

Clinically significant venous thromboembolism after gynecologic surgery.

OBJECTIVE: To review the incidence and outcome of clinically significant venous thromboembolism (VTE) following gynecologic surgery in a population receiving provider-specified prophylaxis. STUDY DESIGN: A computerized patient database was used to identify all patients diagnosed with VTE following gynecologic surgery from 1992 to 1997. Medical records were retrospectively reviewed. Clinically significant postoperative VTE was defined as pulmonary embolism or deep venous thrombosis, suggested by symptoms and physical findings, with subsequent confirmation by appropriate imaging study. Patients having VTE at the time of preoperative hospital admission and patients diagnosed with VTE after postoperative day 30 were excluded. RESULTS: Fifty-three patients developed postoperative VTE after > 30,000 gynecologic surgical procedures (incidence, < 1 event per 500 procedures). Forty-eight (91%) patients received some form of prophylaxis. Patients with benign disease, surgical anesthesia less than three hours and no history of prior VTE or factor V Leiden deficiency rarely developed postoperative VTE (incidence, < 1 event in 4,000 procedures). Thirteen (25%) patients had complications from anticoagulation therapy requiring prolonged hospital stay or readmission. CONCLUSION: Clinically significant VTE following gynecologic surgery is rare in the absence of malignancy, prolonged surgical anesthesia or hypercoagulation factors. Complications from anticoagulation therapy are common among gynecologic patients undergoing treatment for VTE.     

Incidence and prognostic factors for seroma development after MammoSite breast brachytherapy

PurposeDescribe the incidence and identify risk factors for seroma development after MammoSite breast brachytherapy (MBT).Methods and MaterialsMBT patient data were prospectively recorded into a quality assurance database. Departmental and electronic records were reviewed to extract patient-, treatment-, and outcome-specific data. Stepwise logistic regression analysis was performed to identify factors associated with development of any seroma including the subset of clinically significant seroma (CSS). CSS was defined as a symptomatic seroma requiring multiple aspirations, biopsy, and/or excision. Variables analyzed included age, weight, number of excisions, time from resection to catheter placement, placement technique, balloon volume, dosimetric factors, and postbrachytherapy infection.ResultsMBT was performed in 109 patients, of whom 97 had minimum 6 months (median, 36) post-MBT follow-up or earlier development of seroma. All patients received 34 Gy to 1 cm depth from balloon surface, delivered twice daily in 10 fractions. Seroma developed in 41% of patients at a median of 3 months (range, 0.1–25) post-MBT. One-third of seromas (13% of all patients) were CSS. The only factor identified as statistically significant for development of any seroma was catheter placement on day of resection vs. ≥1 day later (59% vs. 33%; p = 0.0066). Post-MBT infection was highly statistically significant for development of CSS (64% vs. 7%; p < 0.0001). Prophylactic antibiotics reduced the risk of post-MBT infection from 37.5% to 6% (p = 0.011).ConclusionsThe incidence of CSS after MBT is low. Post-MBT infection is statistically significantly associated with CSS development, the incidence of which is reduced with prophylactic antibiotics.     

U.S. publication trends in social and administrative pharmacy: Implications for promotion and tenure

BackgroundThere is no consensus on the preferred approach to assess journal quality. Procedures previously used include journal acceptance or rejection policies, impact factors, number of subscribers, citation counts, whether the articles were refereed or not, and journals cited in books within the discipline. This study built on the work of previous authors by using a novel approach to assess journal quality in social and administrative pharmacy (SAdP).ObjectivesTo determine U.S. SAdP faculty perceptions of prestigious journals for their research, SAdP faculty perceptions of prestigious journals by their promotion and tenure (P&;T) committees, and current research trends in SAdP.MethodsA census of U.S. colleges and schools of pharmacy was conducted using an e-mailed survey and an open-ended approach requiring respondents to list their preferred journals.ResultsSeventy-nine SAdP faculty reported that the 5 most prestigious journals were JAMA, New England Journal of Medicine, Health Affairs, Health Services Research, and Medical Care. These journals were selected because respondents wished to seek broad readership.ConclusionsResults of this study can be used as a guide by U.S. SAdP faculty and P&;T committees to assess the quality of publications by pharmacy administration faculty with the caveat being that pharmacy versus nonpharmacy journals will be chosen based on the fit of the article with the audience.