Zinc Gluconate Induces Potentially Cancer Chemopreventive Activity in Barrett's Esophagus: A Phase 1 Pilot Study.

BACKGROUND: Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett's esophagus (BE) in humans. AIMS: To determine if molecular evidence can be obtained potentially indicating zinc's chemopreventive action in Barrett's metaplasia. METHODS: Patients with a prior BE diagnosis were placed on oral zinc gluconate (14 days of 26.4 mg zinc BID) or a sodium gluconate placebo, prior to their surveillance endoscopy procedure. Biopsies of Barrett's mucosa were then obtained for miRNA and mRNA microarrays, or protein analyses. RESULTS: Zinc-induced mRNA changes were observed for a large number of transcripts. These included downregulation of transcripts encoding proinflammatory proteins (IL32, IL1ß, IL15, IL7R, IL2R, IL15R, IL3R), upregulation of anti-inflammatory mediators (IL1RA), downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT) (LIF, MYB, LYN, MTA1, SRC, SNAIL1, and TWIST1), and upregulation of transcripts that oppose EMT (BMP7, MTSS1, TRIB3, GRHL1). miRNA arrays showed significant upregulation of seven miRs with tumor suppressor activity (-125b-5P, -132-3P, -548z, -551a, -504, -518, and -34a-5P). Of proteins analyzed by Western blot, increased expression of the pro-apoptotic protein, BAX, and the tight junctional protein, CLAUDIN-7, along with decreased expression of BCL-2 and VEGF-R2 were noteworthy. CONCLUSIONS: When these mRNA, miRNA, and protein molecular data are considered collectively, a cancer chemopreventive action by zinc in Barrett's metaplasia may be possible for this precancerous esophageal tissue. These results and the extensive prior animal model studies argue for a future prospective clinical trial for this safe, easily-administered, and inexpensive micronutrient, that could determine if a chemopreventive action truly exists.

Serotonin receptor 2A (HTR2A) gene polymorphism predicts treatment response to venlafaxine XR in generalized anxiety disorder.

Generalized anxiety disorder (GAD) is a chronic psychiatric disorder with significant morbidity and mortality. Antidepressant drugs are the preferred choice for treatment; however, treatment response is often variable. Several studies in major depression have implicated a role of the serotonin receptor gene (HTR2A) in treatment response to antidepressants. We tested the hypothesis that the genetic polymorphism rs7997012 in the HTR2A gene predicts treatment outcome in GAD patients treated with venlafaxine XR. Treatment response was assessed in 156 patients that participated in a 6-month open-label clinical trial of venlafaxine XR for GAD. Primary analysis included Hamilton Anxiety Scale (HAM-A) reduction at 6 months. Secondary outcome measure was the Clinical Global Impression of Improvement (CGI-I) score at 6 months. Genotype and allele frequencies were compared between groups using χ(2) contingency analysis. The frequency of the G-allele differed significantly between responders (70%) and nonresponders (56%) at 6 months (P=0.05) using the HAM-A scale as outcome measure. Similarly, using the CGI-I as outcome, the G-allele was significantly associated with improvement (P=0.01). Assuming a dominant effect of the G-allele, improvement differed significantly between groups (P=0.001, odds ratio=4.72). Similar trends were observed for remission although not statistically significant. We show for the first time a pharmacogenetic effect of the HTR2A rs7997012 variant in anxiety disorders, suggesting that pharmacogenetic effects cross diagnostic categories. Our data document that individuals with the HTR2A rs7997012 single nucleotide polymorphism G-allele have better treatment outcome over time. Future studies with larger sample sizes are necessary to further characterize this effect in treatment response to antidepressants in GAD.

A double-blind parallel-group comparison of single bedtime doses of halazepam and placebo.

A single bedtime dose of 120 mg of halazepam was effective in the treatment of patients with mild to moderate anxiety. This dose was superior to both placebo and a 60 mg dose in this 2-week study, as shown by both physician and patient rating scales. The safety of single bedtime doses of halazepam was confirmed. All the reported side-effects were known adverse experiences to benzodiazepines in general.

An organizational model of a psychiatric hospital program for the elderly.

This article is a summary describing the program planning and initial experience of a new unit for geriatric psychiatry in a private psychiatric hospital. Elderly psychiatric patients, predominantly with diagnoses of depression, alcohol dependency, and dementia, but also other psychiatric illnesses, demonstrate more self-centeredness and less group awareness than do younger patients. Staff members often experience frustration, sadness, and anger in response to working with them. Major problems unique to a geriatric psychiatric unit include the paucity of adequate resources for post-discharge care and the necessity to plan an excellent medical support system.

Gastrointestinal complications of renal failure.

ESRD has well-documented effects on the esophagus, stomach, duodenum, and pancreas. Unless the supply of donor kidneys increases dramatically, these complications of ESRD will continue to be an important clinical issue for gastroenterologists given the large percentage of patients with symptoms. Further study of uremic retention products and abnormal gastrointestinal hormone profiles on the gastrointestinal tract should help provide additional insights into this complex group of patients.

Chronic pancreatitis: diagnosis, classification, and new genetic developments.

The utilization of recent advances in molecular and genomic technologies and progress in pancreatic imaging techniques provided remarkable insight into genetic, environmental, immunologic, and pathobiological factors leading to chronic pancreatitis. Translation of these advances into clinical practice demands a reassessment of current approaches to diagnosis, classification, and staging. We conclude that an adequate pancreatic biopsy must be the gold standard against which all diagnostic approaches are judged. Although computed tomography remains the initial test of choice for the diagnosis of chronic pancreatitis, the roles of endoscopic retrograde pancreatography, endoscopic ultrasonography, and magnetic resonance imaging are considered. Once chronic pancreatitis is diagnosed, proper classification becomes important. Major predisposing risk factors to chronic pancreatitis may be categorized as either (1) toxic-metabolic, (2) idiopathic, (3) genetic, (4) autoimmune, (5) recurrent and severe acute pancreatitis, or (6) obstructive (TIGAR-O system). After classification, staging of pancreatic function, injury, and fibrosis becomes the next major concern. Further research is needed to determine the clinical and natural history of chronic pancreatitis developing in the context of various risk factors. New methods are needed for early diagnosis of chronic pancreatitis, and new therapies are needed to determine whether interventions will delay or prevent the progression of the irreversible damage characterizing end-stage chronic pancreatitis.

Remote clinical assessment of gastrointestinal endoscopy (tele-endoscopy): an initial experience.

BACKGROUND: Gastrointestinal (GI) endoscopy is an effective tool to screen for cancers of the digestive tract. However, access to endoscopy is limited in many parts of South Carolina. This trial is a part of a prospective multi-part study for remote cancer screening in coastal South Carolina. This pilot study was to evaluate the quality of tele-endoscopy for cancer screening. METHODS: 10 patients scheduled for endoscopic procedures were observed simultaneously by the endoscopist and a remote observer connected over a 512 kbps ISDN line. Findings by both were compared for concordance on malignant or premalignant lesions. RESULTS: The image quality was adequate to support remote diagnosis of GI cancer and abnormal lesions by an experienced observer. However, assessment of the esophagogastric junction for Barrett's esophagus was equivocal. CONCLUSIONS: Overall, our tele-endoscopy setup shows great promise for remote supervision or observation of endoscopic procedures done by nurse endoscopists. Tele-endoscopy is both adequate and feasible for diagnosis of most gastrointestinal lesions. Subtle lesions still may be missed in our current setup. However, improvements are being made in our setup to address the problem with resolution prior to further evaluation.

The utility of EUS and EUS-guided fine needle aspiration in detecting celiac lymph node metastasis in patients with esophageal cancer: a single-center experience.

BACKGROUND: The aims of this study were to determine the utility of EUS and EUS-guided fine needle aspiration (EUS-FNA) in the detection and confirmation of celiac lymph node metastasis in patients with esophageal cancer and to define EUS features predictive of celiac lymph node metastasis in these patients. METHODS: The records of 211 patients with esophageal cancer who underwent EUS staging were reviewed. The operating characteristics of EUS were determined in patients where either surgery, EUS-FNA of a celiac lymph node, or both were performed (n = 102). The association between selected variables and the presence of celiac lymph node metastasis was evaluated by univariate and multivariable analyses. RESULTS: EUS in 48 patients provided a true-positive diagnosis of celiac lymph node involvement, a false-positive and false-negative result, respectively, in 6 and 14 patients, and a true-negative diagnosis in 34 patients. The sensitivity of EUS in detecting celiac lymph node was 77% (95% CI [67, 88]), specificity 85% (95% CI [74, 96]), negative predictive value 71% (95% CI [58, 84]), and the positive predictive value 89% (95% CI [81, 97]). EUS-FNA was performed in 94% (51/54) of patients with celiac lymph nodes. The accuracy of EUS-FNA in detecting malignant celiac lymph nodes was 98% (95% CI [90, 100]). Advanced T-stage, the need for dilation, detection of peritumoral lymph nodes, and black race were associated with celiac lymph node involvement. In multivariable analysis, advanced T-stage was the strongest predictor of celiac lymph node involvement. CONCLUSION: EUS and EUS-FNA are highly accurate in detecting and confirming celiac lymph nodes metastasis. Depth of tumor invasion as assessed by EUS is a strong predictor of celiac lymph node metastasis in patients with esophageal cancer.

Comparacion doble-ciega en grupos paralelos con dosis unicas nocturnas de halazepam y placebo. / Double-blind comparison in parallel groups with nightly single doses of halazepam and placebo

La dosis unica de 120 mg de halazepam al momento de acostarse fue eficaz en el tratamiento de pacientes con ansiedad leve a moderada. Esta dosis fue mas eficaz que el placebo o una dosis de 60 mg, en este estudio de dos semanas de duracion tal como lo indicaron las escalas de valoracion del medido y de los pacientes. Se confirmo la seguridad de la dosis unica de halazepam al momento de acostarse. Todos los efectos colaterales encontrados correspondieron a los efectos adversos conocidos de las benzodiacepinas en general