Plasma levels of neuropeptides in Alzheimer's disease.

BACKGROUND: In the central nervous system, several neuropeptides are believed to be involved in the pathophysiology of Alzheimer's disease (AD). Indeed, previous studies have documented that glucagon-like peptide 1 (GLP-1) possesses neurotropic properties and can reduce amyloid-beta peptide levels in the brain in vivo. Moreover, the concentrations of neuropeptide Y (NPY) seem to be altered in the cerebrospinal fluid of patients with AD and in subjects with major depression. Finally, among the modifications induced by aging, a dysregulation of the ghrelin-growth hormone (GH) system has been reported. METHODS: We investigated the plasma concentrations of these neuropeptides in 14 subjects with AD. Data obtained from these patients were compared with data from an age- and weight-matched healthy group. RESULTS: No significant differences were found between the two groups in relation to plasma levels of GLP-1, NPY, ghrelin and GH. Peripheral NPY concentrations were positively correlated with ghrelin levels in both groups, and with plasma GLP-1 concentration only in controls. CONCLUSION: On the basis of our results, peripheral levels of these neuropeptides seem not to serve as biochemical markers of AD.     

Patient comprehension and recall of laparoscopic surgery and outcomes in a non-English speaking population.

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine patient recall and comprehension after laparoscopic appendectomy in an underserved population. Laparoscopic surgery can lead to diagnostic uncertainty secondary to poor recall and variable port placement. METHODS: After institutional review board approval, we identified a cohort of patients who underwent laparoscopic appendectomy from 2000 to 2004 at a single institution. We then attempted to contact the patients to conduct a 10-question telephone survey, which determined whether the patient spoke English or Spanish as a primary language, ethnicity, educational level, and questions about recall of perioperative events and diagnoses. If we could not reach the patient, we tried to call back on 2 different occasions. RESULTS: Between 2000 and 2004, 186 patients underwent laparoscopic appendectomy. Of these, 65% were Hispanic. We found that only 17% of these patients returned for a postoperative visit. Only 19.3% could be contacted by phone. Forty-seven percent of the patients contacted by phone spoke Spanish exclusively. Overall 92% of patients contacted knew what operation they had, and gave their correct diagnosis. CONCLUSIONS: The low percentage of patients available to follow-up makes this study statistically insignificant. However, we believe that fact in itself is important. In Southwestern states, we see a large migrant population. This highlights the need to communicate effectively with the patients at the time of surgery, which we speculate we did based on the percentage of patients that knew their diagnosis.     

Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence.

Hepatitis B virus (HBV) recurrence after liver transplantation is significantly reduced by prophylaxis with hepatitis B immune globulins (HBIG) or antiviral drugs in nonreplicating patients and by the combination of both drugs in replicating patients. However, the load of HBV DNA, which defines replicating status in patients undergoing liver transplantation, remains unclear. This study analyzes the correlation between the viral load, tested with a single amplified assay, at the time of liver transplantation, and the risk of hepatitis B recurrence in 177 HBV carriers who underwent transplantation in a single center from 1990 to 2002. Overall, HBV relapsed after surgery in 15 patients (8.5%) with a 5- and 8-year actuarial rate of recurrence of 8% and 21%, respectively. After liver transplantation hepatitis B recurred in 9% of 98 selected subjects treated only with immune globulins and in 8% of 79 viremic patients who received immune globulins and lamivudine (P = NS). A linear correlation was observed between recurrence and viral load at the time of surgery. In transplant patients with HBV DNA higher than 100,000 copies/mL, 200-99,999 copies/mL, and DNA undetectable by amplified assay, hepatitis B recurred in 50%, 7.5%, and 0% of patients, respectively. Overall, a viral load higher than 100,000 copies/mL at the time of liver transplantation was significantly associated with hepatitis B recurrence (P = .0003). In conclusion, spontaneous or antiviral-induced HBV DNA viral load at the time of surgery classifies the risk of HBV recurrence after liver transplantation and indicates the best prophylaxis strategy.     

Empty Sella and Headache

SYNOPSIS
Empty sella is an anatomical condition caused by herniation of the subarachnoid space into the pituitary fossa through an incompetent seller diaphragm. Headache seems to be one of the most frequently reported symptoms. We studied 13 headache patients (12 females, 1 male) presenting with primary empty sella (PES) on CT scan. The characteristics of the headache were analyzed and plasma levels of pituitary hormones or cortisol assessed. We confirmed the nonspecific nature of the headache in PES even though the majority of our patients complained of daily headache, mostly localized anteriorly. Hormone plasma levels were within normal range in all the patients assessed. However, four patients reported earlier endocrine disorders and more than half of the patients presented with obesity.
In our opinion, PES should be suspected in middle-aged overweight women with daily headache even in the absence of endocrine symptomatology.     

Genetic variability in the Guahibo population from venezuela

Four communities from Guahibo of Venezuela were analyzed for the genetic variants of nine erythrocyte enzymes and five serum proteins. Of the 14 loci determined, four were monomorphic. Significant frequency differentiation among communities, was present for ESD and TF markers. In general, Guahibo allele frequencies are in the variation ranges described for South American groups. The analysis indicates a relatively higher affinity of Guahibos with other Venezuelan groups within an irregular pattern of genetic distances that are likely related to the complex demographic history of the South American groups. Genetic diversity estimates reveal a moderate degree of genetic structure between the four Guahibo communities. This intra‐tribal variability in Guahibo appears to be lower than in Venezuelan Piaroa but higher than in other Amerindians and could be attributed to a combined effect of low population size and relative isolation of communities. At a continental level, the distribution of genetic diversity is consistent with preferential population movements along the eastern and western coastal areas. Am. J. Hum. Biol. 14:21–28, 2002. © 2002 Wiley‐Liss, Inc.     

A new priority policy for patients with hepatocellular carcinoma awaiting liver transplantation within the model for end-stage liver disease system.

The best prioritization of patients with hepatocellular carcinoma (HCC) waiting for liver transplantation under the model for end-stage liver disease (MELD) allocation system is still being debated. We analyzed the impact of a MELD adjustment for HCC, which consisted of the addition of an extra score (based on the HCC stage and waiting time) to the native MELD score. The outcome was analyzed for 301 patients with chronic liver disease listed for liver transplantation between March 1, 2001 and February 28, 2003 [United Network for Organ Sharing (UNOS)-Child-Turcotte-Pugh (CTP) era, 163 patients, 28.8% with HCC] and between March 1, 2003 and February 28, 2004 (HCC-MELD era, 138 patients, 29.7% with HCC). In the HCC-MELD era, the cumulative dropout risk at 6 months was 17.6% for patients with HCC versus 22.3% for those patients without HCC (P = NS), similar to that in the UNOS-CTP era. The cumulative probability of transplantation at 6 months was 70.3% versus 39.0% (P = 0.005), being higher than that in the UNOS-CTP era for patients with HCC (P = 0.02). At the end of the HCC-MELD era, 12 patients with HCC (29.3%) versus 57 without HCC (58.8%) were still on the list (P = 0.001). Both native and adjusted MELD scores were higher (P < 0.05) and progressed more in patients with HCC who dropped out than in those who underwent transplantation or remained on the list (the initial-final native MELD scores were 17.3-23.1, 15.5-15.6, and 12.8-14.1, respectively). The patients without HCC remaining on the list showed stable MELD scores (initial-final: 15.1-15.4). In conclusion, the present data support the strategy of including the native MELD scores in the allocation system for HCC. This model allows the timely transplantation of patients with HCC without severely affecting the outcome of patients without HCC.     

Qualitative difference between the cytotoxic T lymphocyte responses to melanocyte antigens in melanoma and vitiligo

Vitiligo is a skin disorder characterized by depigmented macules secondary to melanocyte loss. An unusual facet is its relation to melanoma: cytotoxic T lymphocytes directed to melanocyte antigens are found in both conditions and imply a breakdown of tolerance, yet the resulting immune reaction is the opposite. The mechanisms at the basis of these opposite effects are not known. Here, we performed a direct comparison of whole melanocyte-specific T cell populations in the two diseases. We demonstrate that neither precursor frequencies of Melan-A/MART-1-specific T lymphocytes nor their status of activation differ significantly. However, by using a tetramer-based T cell receptor down-regulation assay, we documented a higher affinity of vitiligo T cells. We calculated that the peptide concentration required for 50% of maximal receptor down-regulation differed by 6.5-fold between the two diseases. Moreover, only vitiligo T cells were capable of efficient receptor down-regulation and IFN-gamma production in response to HLA-matched melanoma cells, suggesting that this difference in receptor affinity is physiologically relevant. The differences in receptor affinity and tumor reactivity were confirmed by analyzing Melan-A/MART-1-specific clones established from the two diseases. Our results suggest that the quality, and not the quantity, of the melanocyte-specific cytotoxic responses differs between the two pathologies.     

A comprehensive in vitro characterization of pancreatic ductal carcinoma cell line biological behavior and its correlation with the structural and genetic profile

There are a large number of stable pancreatic ductal carcinoma cell lines (PDCL) that are used by researchers worldwide. Detailed data about their differentiation status and genetic alterations are present in the literature, but a systematic correlation with cell biological behavior is often lacking. PDCL (n=12) were clustered by source of tumor cell (ascites, primary tumor, metastasis), and the data of functional cell biology were correlated with the reported structural and genetic profiles. Major histocompatibility complex expression, chemosensitivity and aneuploidia appeared to be related to the source of PDCL, and proliferative capacity appeared to be related to the grade of differentiation. No correlation between genetic/structural features of PDCL and biological behavior was found. All the cell lines appeared generally insensitive to in vitro treatment with 5-fluorouracil and showed variable degrees of susceptibility to gemcitabine, raltitrexed and oxaliplatin. All the PDCL showed resistance to Fas-mediated apoptosis but were significantly sensitive to the pro-apoptotic effect of inflammatory cytokines [interleukin (IL)-1, tumor necrosis factor (TNF) and interferon ]. PDCL were characterized for the secretion of several factors relevant to the tumor-immune cross talk. Vascular endothelial growth factor, CCL2, CCL5 and transforming growth factor were the factors most frequently released; less frequent was the secretion of CXCL8, CCL22, IL-6 and sporadically CXCL12, IL-10 and hepatocyte growth factor. The cytokines IL-1 and TNF were always undetectable. In conclusion, a clear correlation between structural/genetic features and function could not be detected, suggesting the weakness of a morphological classification for the in vitro studies of pancreatic cancer.