Gallbladder Findings after Cholecystectomy in Morbidly Obese Patients

Morbidly obese patients constitute a high risk group for the development of gallbladder disease. In our series 70 consecutive patients underwent vertical gastroplasty in an effort to manage morbid obesity. The mean age was 37 years (range 20-60), and the mean excess body weight was 92 kg (range 52-265). Six patients (8.5%) had undergone cholecystectomy before bariatric surgery because of symptomatic cholelithiasis. The remaining 64 patients underwent cholecystectomy at the time of vertical gastroplasty. Ninety-seven percent of the removed gallbladders had gross or histologic abnormalities, including cholelithiasis 18.5% (13 patients), and cholesterolosis 31% (22 patients). Histologically, chronic cholecystitis was present in all patients with cholelithiasis and cholesterolosis. Chronic cholecystitis alone was found in 27 patients (38.5%) and only two patients (3%) had normal findings. The mean excess body weight of the patients with cholesterolosis (96 kg) was not significantly greater than that of patients with cholelithiasis (89 kg) or chronic cholecystitis (88 kg). Our findings suggest that cholecystectomy should be performed in all morbidly obese patients concomitant with vertical gastroplasty.     

A neurotensin antagonist, SR 48692, inhibits colonic responses to immobilization stress in rats.

We previously reported that short-term immobilization stress of rats causes increased colonic mucin release, goblet cell depletion, prostaglandin E2 secretion, and colonic mast cell activation, as well as increased colonic motility. The purpose of this study was to investigate whether neurotensin (NT), a peptide expressed in both brain and digestive tract, participates in these responses. Rats were pretreated with SR 48692 (1 mg/kg, i.p.), an NT antagonist, 15 min before immobilization (30 min). The administration of the antagonist significantly inhibited stress-mediated secretion of colonic mucin, prostaglandin E2, and a product of rat mast cells, rat mast cell protease II (P < 0.05), but did not alter the increase in fecal pellet output caused by immobilization stress. Immobilization stress also resulted in a quantifiable decrease in the abundance of NT receptor mRNA in rat colon compared with that in colonic tissues from nonimmobilized rats as measured by densitometric analysis of in situ hybridization studies (P < 0.03). We conclude that the peptide NT is involved in colonic goblet cell release and mucosal mast cell activation after immobilization stress.     

Gastric phytobezoars may be treated by nasogastric Coca-Cola lavage

Large gastric phytobezoars may occur in patients with gastric dysmotility disorders. Treatment options include dissolution with enzymes, endoscopic fragmentation with removal or aspiration, and surgery. We report our experience with nasogastric cola lavage therapy. Over an 8-year period, five consecutive patients were referred to our unit for endoscopic treatment of large gastric phytobezoars. They included one patient with lobectomy for lung cancer and four patients with diabetic gastroparesis. An initial attempt of endoscopic fragmentation and removal was unsuccessful. Patients were treated with 3 l of Coca-Cola nasogastric lavage over 12 h. Nasogastric lavage was very well tolerated by the patients. Complete phytobezoar dissolution was achieved in one session in all cases. There were no procedure-related complications. The dissolution of large gastric phytobezoars with cola nasogastric lavage is a safe, rapid and effective method. Patients may be treated in the medical ward, avoiding therapeutic endoscopy or surgery.     

Human colonic aspirates containing immunoglobulin A antibody to Clostridium difficile toxin A inhibit toxin A-receptor binding.

Clostridium difficile toxin A, a 308-kilodalton protein exotoxin, is the principal causative agent of antibiotic-associated, C. difficile-induced colitis. In the current study, the prevalence of specific human serum and secretory antibody to toxin A and the possible protective effect of secretory, intestinal anti-toxin A antibody are examined. Serum (n = 35), colonic aspirates (n = 35), and duodenal aspirates (n = 20) were collected from adults at diagnostic endoscopy. Patients with evidence of colitis or a history of recent antibiotic use were excluded from the study. Specific serum immunoglobulin (Ig) A and IgG antitoxin A antibodies were detected in 60% and 57% of subjects, respectively, by enzyme-linked immunosorbent assay. Fifty-seven percent of colonic aspirates contained IgA antitoxin, whereas only 10% of duodenal aspirates were positive (P = 0.002). Binding of toxin A to its intestinal receptor was studied using [3H]toxin A and purified rabbit ileal brush border membranes. Toxin A binding was significantly inhibited by colonic aspirates with high IgA anti-toxin A antibody levels (0.503 +/- 0.055 pmol toxin A bound per milligram of brush border membrane protein, mean +/- SE) in comparison with antitoxin A-negative aspirates (0.778 +/- 0.089 pmol; P = 0.02) and control (0.766 +/- 0.004 pmol; P = 0.03). In the current study, a specific intestinal secretory IgA antibody response to C. difficile toxin A in humans is reported. This antibody response is more evident in the colon, the site of C. difficile infection, than in the upper intestinal tract. Our data suggest that human colonic IgA antitoxin may protect against C. difficile colitis by inhibiting the binding of toxin A to its intestinal epithelial cell receptor.     

Corticotropin-releasing hormone antagonists possess anti-inflammatory effects in the mouse ileum

BACKGROUND & AIMS: Corticotropin-releasing hormone (CRH) released at local sites of inflammation promotes inflammation in the periphery. We investigated its effects in the intestinal responses caused by toxin A from Clostridium difficile, the causative agent of antibiotic-associated colitis. METHODS: Ileal loops were injected with 10 microg of toxin A, and enterotoxic responses were measured at various time points. RESULTS: Pretreatment of mice with 2.5 microg/kg of the CRH receptor antagonist alpha-helical CRH((9-41)) that blocks both CRH receptor subtypes reduced toxin A-mediated ileal secretion, epithelial cell damage, mucosal edema, neutrophil infiltration, and mucosal content of interleukin 1 beta and tumor necrosis factor alpha. Pretreatment with the specific CRH(1) receptor antagonist antalarmin (20 mg/kg, IP) also inhibited toxin A-induced fluid secretion and toxin A-associated histologic changes. CRH messenger RNA and protein were increased in mouse ileum 30 minutes after intraluminal toxin A administration. In situ hybridization and immunohistochemistry demonstrated that toxin A at 1 hour caused a substantial increase in the expression of both CRH receptor subtypes in the ileal mucosa. CONCLUSIONS: Peripheral CRH may play a proinflammatory role in toxin A-induced intestinal secretion and inflammation and that CRH(1) receptor, at least in part, is important in the mediation of these responses.     

Efficacy and safety of high dose versus low dose furosemide with or without dopamine infusion: The Dopamine in Acute Decompensated Heart Failure II (DAD-HF II) Trial

Aims

The role of low-dose dopamine infusion in patients with acute decompensated heart failure (ADHF) remains controversial. We aim to evaluate the efficacy and safety of high- versus low-dose furosemide with or without low-dose dopamine infusion in this patient population.

Methods and results

161 ADHF patients (78 years; 46% female; ejection fraction 31%) were randomized to 8-hour continuous infusions of: a) high-dose furosemide (HDF, n = 50, 20 mg/h), b) low-dose furosemide and low-dose dopamine (LDFD, n = 56, 5 mg/h and 5 μg kg^− 1 min^− 1 respectively), or c) low-dose furosemide (LDF, n = 55, furosemide 5 mg/h). The main outcomes were 60-day and one-year all-cause mortality (ACM) and hospitalization for HF (HHF). Dyspnea relief (Borg index), worsening renal function (WRF, rise in serum creatinine (sCr) ≥ 0.3 mg/dL), and length of stay (LOS) were also assessed. The urinary output at 2, 4, 6, 8, and 24 h was not significantly different in the three groups. Neither the ACM at day 60 (4.0%, 7.1%, and 7.2%; P = 0.74) or at one year (38.1%, 33.9% and 32.7%, P = 0.84) nor the HHF at day 60 (22.0%, 21.4%, and 14.5%, P = 0.55) or one year (60.0%, 50.0%, and 47%, P = 0.40) differed between HDF, LDFD, and LDF groups, respectively. No differences in the Borg index or LOS were noted. WRF was higher in the HDF than in LDFD and LDF groups at day 1 (24% vs. 11% vs. 7%, P < 0.0001) but not at sCr peak (44% vs. 38% vs. 29%, P = 0.27). No significant differences in adverse events were noted.

Conclusions

In ADHF patients, there were no significant differences in the in-hospital and post-discharge outcomes between high- vs. low-dose furosemide infusion; the addition of low-dose dopamine infusion was not associated with any beneficial effects.     

Long-term abstinence syndrome in heroin addicts: indices of P300 alterations associated with a short memory task

Attentional deficits have been implicated in the pathophysiology of opioid addicts. The P300 component of event-related potentials (ERPs) is considered as a manifestation of attentional operations. The authors' goal was the comparison of P300 elicited during a short memory test between subjects with prolonged heroin abstinence and current heroin users as well as healthy controls. The P300 component was evaluated during the anticipatory period of a short memory task in 20 patients characterized by a past history of opioid dependence (6 months abstinence), in 18 current heroin users and in 20 healthy comparison subjects, matched for age, sex and educational level. Abstinent heroin addicts exhibited significant reduction of P300 amplitude at central frontal region, relative to the other two groups. The findings are discussed in connection to the aim of identifying psychophysiological indices, addressing issues in opioid use disorders, and suggest that knowledge about cognitive operations, such as those reflected by P300 component, could provide further insight into psychophysiological mechanisms underlying the long-term abstinence state of heroin addicts.     

Multicenter dose-finding study of concurrent capecitabine and radiotherapy as adjuvant treatment for operable rectal cancer

PURPOSE: 5-Fluorouracil-based chemotherapy with concurrent radiotherapy (RT) is the standard adjuvant treatment in rectal cancer. A Phase I study was conducted to determine the maximal tolerated dose and the dose-limiting toxicities of capecitabine combined with standard RT as adjuvant treatment in patients with rectal cancer. METHODS AND MATERIALS: Patients with Stage II-III rectal cancer after surgery were eligible. RT included a total dose of 50.4 Gy in fractions of 1.8 Gy/d, 5 d/wk, for 5.5 weeks. Capecitabine was administered twice daily in escalating doses during the entire period of RT. Dose-limiting toxicity included Grade 4 neutropenia or thrombocytopenia, febrile neutropenia, Grade 3 or greater nonhematologic toxicity, or treatment delay because of unresolved toxicity for >1 week. RESULTS: Thirty-one patients were enrolled at the following dose levels: 1000 mg/m(2)/d (3 patients), 1150 mg/m(2)/d (4 patients) 1300 mg/m(2)/d (6 patients), 1400 mg/m(2)/d (6 patients), 1500 mg/m(2)/d (3 patients), 1600 mg/m(2)/d (3 patients), and 1700 mg/m(2)/d (6 patients). Dose-limiting toxicities were observed in 2 patients at 1300 mg/m(2)/d (Grade 3 diarrhea), and 2 patients at 1400 mg/m(2)/d (skin toxicity in 1 and abdominal pain with fever in 1, resulting in treatment delay), and 3 patients at 1700 mg/m(2)/d (2 patients had Grade 3 diarrhea and 1 had hand-foot syndrome). Four patients presented with chronic postradiation colitis. CONCLUSIONS: The maximal tolerated dose of capecitabine given concurrently with RT was 1600 mg/m(2)/d in this study. This dose is recommended for additional use in Phase II-III studies.     

Do atypical antipsychotics fail to exert cognitive sparing effects?

The aim of the study was to investigate patterns of the P600 component of event-related potentials (ERPs) elicited during a working memory test in 16 male schizophrenic patients experiencing auditory hallucinations before and after treatment with clozapine and olanzapine, and 13 male normal subjects matched for age and educational level. Before treatment, patients showed significantly reduced P600 amplitudes on the right parietal region compared with controls, and when in remission also showed significantly reduced P600 amplitudes located on the right parietal and temporofrontal areas, compared both to themselves before treatment and to normal controls. The patient's memory performance before and after treatment remained significantly lower than that of healthy controls. These findings may indicate that auditory hallucinations in schizophrenia are associated with impaired synchronization of the processes related to target detection, as reflected by the P600. The present study also casts doubts regarding the cognitive sparing effect of atypical antipsychotics, despite the fact that they mediate symptom improvement.