Systemic activation of integrin alphaVbeta3 in donors with spontaneous intracerebral hemorrhage is associated with subsequent development of vasculopathy in the heart transplant recipient.

BACKGROUND: Recipients of hearts from donors with spontaneous intracerebral hemorrhage (ICH) are at increased risk of allograft vasculopathy compared with trauma donors. We have recently shown that the vitronectin receptor (integrin alpha(V)beta3) is upregulated in transplant vasculopathy. We hypothesized that donor ICH is associated with systemic activation of alpha(V)beta3 in the donor before transplantation. METHODS: We evaluated mRNA expressions of alpha(V)beta3 (TaqMan PCR) in endomyocardial biopsy samples at 1-week post-transplant in 20 recipients from ICH donors and 20 recipients from trauma donors. To investigate whether systemic activation of alpha(V)beta3 was present in the donor before transplantation, alpha(V)beta3 expression was also evaluated in the corresponding donor spleen lymphocytes. All patients underwent serial coronary intravascular ultrasound to evaluate for coronary vasculopathy. The baseline characteristics were similar except for increased donor age in the ICH Group. RESULTS: The ICH Group showed significant increased mRNA expression of alpha(V)beta3 in the heart biopsy samples (3.8-fold, p = 0.012) and in the corresponding donor spleen lymphocytes (3.5-fold, p = 0.014) compared with the Trauma Group. At 1 year, the ICH Group also showed increased progression of coronary vasculopathy. Multivariate regression analysis found that donor lymphocytic alpha(V)beta3 mRNA expression was independently associated with increased risk of vasculopathy (odds ratio, 1.9; 95% CI, 1.21-3.98, p = 0.03). CONCLUSIONS: Our report demonstrates the presence of systemic activation of alpha(V)beta3 in donors with spontaneous intracerebral hemorrhage and its association with the subsequent development of allograft vasculopathy in the recipient.     

GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma.

Glucose is provided to cells by a family of glucose transport facilitators known as GLUTs. These transporters are expressed in a tissue specific manner and are overexpressed in many primary tumors of these tissues. Regulation of glucose transport facilitator expression has been demonstrated in endometrial tissue and endometrial adenocarcinoma. The following experiments were conducted to quantify and localize the expression of GLUT1 and GLUT8 in benign endometrium and compare this expression to endometrial cancer. Endometrial tissue samples were obtained from random hysterectomy specimens of patients with benign indications for surgery and endometrial cancer. Immunoblot and immunolocatization studies were performed using GLUT1 and GLUT8 specific antisera. Endometrial samples from 65 women who had undergone hysterectomy were examined (n=38 benign, n=27 malignant). A 44 and a 35.4 kDa immunoreacive species was demonstrated in endometrium and endometrial cancer for GLUT1 and GLUT8, respectively. Upregulation of GLUT1 expression was demonstrated with increasing grade of tumors (P<0.002). GLUT8 expression was increased in all tumor subtypes compared to atrophic endometrium (P<0.001). Apical localization by GLUT1 and GLUT8 was demonstrated in endometrial glands. GLUT1 and GLUT8 demonstrated diffuse intracellular localization in the cancer subtypes. GLUT1 and GLUT8 are expressed in both human endometrium and endometrial cancer. There appears to be a step-wise progression in GLUT1 and GLUT8 expression as tumor histopathology worsens. GLUT1 and GLUT8 may be important markers in tumor differentiation, as well as providing energy to rapidly dividing tumor cells.     

Screening for major depression in persons with HIV infection: the concurrent predictive validity of the Profile of Mood States Depression‐Dejection Scale

Major Depressive Disorder (MDD) is among the most prevalent but underdiagnosed psychiatric disorders in persons with HIV infection. Given the known adverse impact of comorbid MDD on HIV disease progression and health‐related quality of life, it is important both for research and for efficient, effective clinical care, to validate existing screening measures that may discriminate between MDD and the somatic symptoms of HIV (such as fatigue). In the current study, we evaluated the concurrent predictive validity of the Profile of Mood States (POMS) Depression‐Dejection scale in detecting current MDD in 310 persons with HIV infection. The Structured Clinical Interview for DSM‐IV (SCID) diagnosis of MDD and the Cognitive‐Affective scale from the Beck Depression Inventory (BDI‐CA) served as comparative diagnostic and severity measures of depression, respectively. Results demonstrated that the POMS Depression‐Dejection scale accurately classified persons with and without MDD SCID diagnoses, with an overall hit rate of 80%, sensitivity of 55%, specificity of 84%, and negative predictive power of 91% using a recommended cutpoint of 1.5 standard deviations above the normative mean. Moreover, the POMS performed comparably to the BDI‐CA in classifying MDD. Findings support the predictive validity of the POMS Depression‐Dejection scale as a screening instrument for MDD in persons with HIV disease. Copyright © 2006 John Wiley & Sons, Ltd.     

The effect of skin surface warming during anesthesia preparation on preventing redistribution hypothermia in the early operative period of off-pump coronary artery bypass surgery.

OBJECTIVE: Redistribution hypothermia adversely affects hemodynamics and postoperative recovery in patients undergoing cardiac surgery. In off-pump coronary bypass surgery (OPCAB), maintaining the temperature is important because warming by cardiopulmonary bypass is omitted. Pre-warming studies reported earlier showing pre-warming as an effective means of preventing redistribution hypothermia was time consuming since it required at least 1-2h to pre-warm the patients before the surgery. Because pre-warming for such a long time is impractical in clinical practice, this study evaluated the efficacy of active warming during the preanesthetic period for the prevention of redistribution hypothermia in the early operative period of OPCAB. METHODS: After gaining the approval of Institutional Review Board and informed consent from the patients, 40 patients undergoing OPCAB were divided into control and pre-warming groups. The patients in control group (n=20) were managed with warm mattresses and cotton blankets, whereas patients in pre-warming group (n=20) were actively warmed with a forced-air warming device before the induction of anesthesia. Hemodynamic variables and temperature were recorded before anesthesia (Tpre) and at 30 min intervals after anesthesia for 90 min (T30, T60, and T90). RESULTS: Active warming duration was 49.7+/-9.9 min. There were no statistically significant differences in skin temperature, core temperature and hemodynamic variables between the two groups at preinduction period except for mean arterial pressure and central venous pressure. The core temperature at T30, T60, and T90 was statistically higher in pre-warming group than that in control group. Core temperature of six (30%) and seven patients (35%) in control group was reduced below 35 degrees C at T60 and T90, respectively, whereas core temperature of only one patient (5%) in pre-warming group was reduced below 35 degrees C at T90 (P=0.02). CONCLUSIONS: Active warming using forced air blanket before the induction of anesthesia reduced the incidence and degree of redistribution hypothermia in patients undergoing OPCAB. It is a simple method with reasonable cost, which does not delay the induction of anesthesia nor the surgery.     

Future direction of nanomedicine in gastrointestinal cancer]

Cancer is one of the leading causes of death in human, and among various cancers, gastrointestinal cancers occupy more than 55%. Gastric cancer is the first leading cause of cancer-related mortality in the world and the number of pancreas and colon cancers are increasing remarkably during last two decades which will continue to increase in the future. Even though the clinical importance of gastrointestinal cancers is very high and endless efforts has been made to develop novel diagnostic and therapeutic methods to improve the patient's quality of life and survival, the realistic advance in the actual survival benefit of the cancer patients are still strongly required. Nanotechnology has the power to radically change the way of cancer diagnosis and treatment. Currently, there is a lot of researches on novel nanodevices capable of detecting cancer at its earliest stage, pinpointing its location within the body, and delivering anticancer drugs specifically to the malignant cells. Nanoscale devices can readily interact with biomolecules both on the cell surface and within the cell. In addition, nanoscale devices are already proven that they can deliver therapeutic agents to target cells even within specific organelles. Major areas in which nanomedicine is being developed in cancer include early detection and proteomics, imaging diagnostics and multifunctional therapeutics. Because nanotechnology would provide a technical power and tool that enable new diagnostics, therapeutics, and preventives to keep pace with today's explosion in knowledge in the future, it would be very useful to know the perspectives in the direction of nanotechnology as a major clinician responsible for the patients with gastrointestinal malignancies.