P300 alterations in schizophrenic patients experiencing auditory hallucinations.

RATIONALE: Attentional deficits have been implicated in the pathophysiology of auditory hallucinations in schizophrenia. Since the latency of the P300 component of event-related potentials (ERPs) is considered to be a sensitive measure of stimulus classification speed, while its amplitude-a measure of attentional resource allocation when memory updating is engaged, the present study focuses on the comparison of P300 between healthy subjects and schizophrenic patients experiencing auditory hallucinations and treated with clozapine and olanzapine. METHODS: The auditory P300 was assessed during the anticipatory period of a short memory test, in 16 male hallucinated schizophrenic patients and 13 male normal subjects matched for age and educational level. The patients were reexamined under identical conditions when their hallucinations had resolved following treatment with clozapine (8 patients) and olanzapine (8 patients). RESULTS: The patients with hallucinations exhibited significantly reduced P300 amplitude at leads Fp1, F3, (C3-T5)/2, F4, Cz and Fz, when compared to the normal controls and at leads Fp1, F3, F4, (C4-T6)/2, C4, P4, Cz and Fz when compared to themselves during the remission phase. However logistic regression models revealed that the most important leads, differentiating the patient group before treatment either with the healthy controls, or with itself after treatment, were that at the left temporoparietal and at the left prefrontal area. Memory performance of the patient group, even after treatment and in spite of its significant improvement, remained significantly less than that of healthy controls. both antipsychotic agents had similar effects on the p300 amplitude and memory performance. CONCLUSIONS: These findings indicate that auditory hallucinations in schizophrenia manifest abnormal aspects of attention, mediated by a distributed network involving or affecting the left temporoparietal and left prefrontal area. Additionally, the present study points to an improvement of attentional function in schizophrenic patients experiencing auditory hallucinations, both in the clozapine group but also in the olanzapine group.     

Neurokinin-1 (NK-1) receptor is required in Clostridium difficile- induced enteritis.

Toxin A, a 308,000-Mr enterotoxin from Clostridium difficile, mediates antibiotic-associated diarrhea and colitis in humans. Injection of toxin A into animal intestine triggers an acute inflammatory response characterized by activation of sensory neurons and immune cells of the intestinal lamina propria, including mast cells and macrophages, and migration of circulating neutrophils in the involved intestinal segment. In this study we show that mice genetically deficient in the neurokinin-1 receptor are protected from the secretory and inflammatory changes as well as from epithelial cell damage induced by toxin A. The protective effect of neurokinin-1R deletion correlates with diminished intestinal levels of the cytokine TNF-alpha and its mRNA and the leukocyte enzyme myeloperoxidase. These results demonstrate a major requirement for substance P receptors in the pathogenesis of acute inflammatory diarrhea.     

Diphenhydramine for nausea and vomiting related to cancer chemotherapy with cisplatin

High dose metoclopramide and adjuvant drugs, such as corticosteroids, benzodiazepines, and drugs with antidopaminergic, anticholinergic, or antihistaminic effects, are the most widely used antiemetics in cancer patients receiving chemotherapy, particularly cisdichloro-diammine platinum II (cisplatin). The purpose of our prospective randomized study was to investigate the possible antiemetic efficacy of diphenhydramine as an adjuvant antiemetic drug when combined with metoclopramide (MCP). A total of 91 patients were assigned to either group A (N = 44) who received only MCP and group B (N = 47) who received the combination of MCP and diphenhydramine. All patients received cisplatin-based combination chemotherapy for the first time and were evaluated only once in order to exclude the effects of anticipatory nausea and vomiting. There were no statistically significant differences between the two groups except that patients treated with diphenhydramine presented more sedative effects and had more limited activity. Also diphenhydramine did not give absolute protection from the extrapyromidal side effects of MCP. Side effects of diphenhydramine were minimal and well tolerated. We conclude that diphenhydramine is not a useful adjuvant drug in the antiemetic therapy.     

Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury

Substance P, acting via the neurokinin 1 receptor (NK1R), plays an important role in mediating a variety of inflammatory processes. However, its role in acute pancreatitis has not been previously described. We have found that, in normal mice, substance P levels in the pancreas and pancreatic acinar cell expression of NK1R are both increased during secretagogue-induced experimental pancreatitis. To evaluate the role of substance P, pancreatitis was induced in mice that genetically lack NK1R by administration of 12 hourly injections of a supramaximally stimulating dose of the secretagogue caerulein. During pancreatitis, the magnitude of hyperamylasemia, hyperlipasemia, neutrophil sequestration in the pancreas, and pancreatic acinar cell necrosis were significantly reduced in NK1R−/− mice when compared with wild-type NK1R+/+ animals. Similarly, pancreatitis-associated lung injury, as characterized by intrapulmonary sequestration of neutrophils and increased pulmonary microvascular permeability, was reduced in NK1R−/− animals. These effects of NK1R deletion indicate that substance P, acting via NK1R, plays an important proinflammatory role in regulating the severity of acute pancreatitis and pancreatitis-associated lung injury.     

Hepatopancreatoduodenectomy for metastatic duodenal gastrointestinal stromal tumor

BACKGROUND: Duodenal gastrointestinal stromal tumors, which are rare, comprise 3%-5% of all gastrointestinal stromai tumors. We present a case of a metastatic duodenal gastrointestinal stromal tumor that was successfully treated by simultaneous tight hemihepatectomy and pancreaticoduodenectomy. METHODS: A 50-year-old woman was admitted to our department for the treatment of a possible metastatic duodenal gastrointestinal stromal tumor (GIST). At laparotomy a large duodenal tumor was found displacing the head of the pancreas. A 3 cm in diameter lesion in the posterior aspect of segment Ⅷ of the liver was also noted. Simultaneous right hepatectomy and pancreaticoduodenectomy were performed. RESULTS: Histological examination revealed a high grade metastatic duodenal GIST strongly positive for c-kit, CD34, and vimentin. The patient had no additional therapy. A follow-up of 21 months showed that the patient is very well and there is no evidence of recurrent diseases. CONCLUSIONS: Malignant stromai tumors of the duodenum are rarely encountered. They are usually slow growing, and may be amenable to curative surgery, even after occurrence of metastases. Resection of localized liver metastasis is still advocated when feasible, since imatinib does not provide a complete or long-term response. Combined surgical resection is an efficacious treatment for patients with metastatic duodenal gastrointestinal stromal tumor.     

Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea

BACKGROUND & AIMS: Recurrent C difficile -associated diarrhea (CDAD) is associated with a lack of protective immunity to C difficile toxins. A parenteral C difficile vaccine containing toxoid A and toxoid B was reported previously to be safe and immunogenic in healthy volunteers. Our aim was to examine whether the vaccine is also well tolerated and immunogenic in patients with recurrent CDAD. METHODS: Subjects received 4, 50-microg intramuscular inoculations of the C difficile vaccine over an 8-week period. Serum antitoxin antibodies were measured by ELISA, and toxin neutralizing activity was evaluated using the tissue culture cytotoxin assay. RESULTS: Three patients with multiple episodes of recurrent CDAD were vaccinated. Two of the 3 showed an increase in serum IgG antitoxin A antibodies (3-fold and 4-fold increases, respectively) and in serum IgG antitoxin B antibodies (52-fold and 20-fold, respectively). Both also developed cytotoxin neutralizing activity against toxin A and toxin B. Prior to vaccination, the subjects had required nearly continuous treatment with oral vancomycin for 7, 9, and 22 months, respectively, to treat recurrent episodes of CDAD. After vaccination, all 3 subjects discontinued treatment with oral vancomycin without any further recurrence. CONCLUSIONS: A C difficile toxoid vaccine induced immune responses to toxins A and B in patients with CDAD and was associated with resolution of recurrent diarrhea. The results of this study support the feasibility of active vaccination against C difficile and its toxins in high-risk individuals but must be validated in larger, randomized, controlled trials.     

Mismatch task conditions and error related ERPs

Background  

The N200 component of event related potentials (ERPs) is considered an index of monitoring error related responses. The aim of the present work was to study the effect of mismatch conditions on the subjects' responses in an auditory identification task and their relation to the N200 of stimulus-locked ERPs.