Primary psychosis with comorbid drug abuse and drug-induced psychosis: Diagnostic and clinical evolution at follow up.

The study reports a follow-up assessment of 48 patients with concomitant drug abuse at the first admission for psychosis. We focused on the diagnostic distinction between primary psychosis with concomitant drug abuse and drug induced psychosis, to observe whether the diagnoses are stable over time and whether the clinical course significantly differs. The study examined 25 primary psychotic disorder with comorbid drug abuse and 23 drug-induced psychotic disorder patients. Diagnostic and psychopathological assessments were made at baseline and at follow-up. Mean follow-up period was 4.96 years. Patients with comorbid Drug Abuse exhibited higher scores in the item Unusual Content of Thought at baseline than drug-induced psychotic disorder patients: 5.48 vs 4.39 while the two patients groups did not differ in any of the BPRS items evaluated at follow-up. The primary psychosis with comorbid drug abuse and the substance induced psychosis groups were similar regarding diagnostic stability, and a diagnosis of schizophrenia at follow-up occurred similarly. There was no evidence that Drug Induced psychotic patients' symptoms tend to improve more after cessation of drug abuse. An earlier age of onset was found in primary psychotic patients, particularly for patients diagnosed as affected by schizophrenia at follow up. These results might reflect the uncertainty of the distinction between Primary and Drug Induced Psychosis and the difficulties in applying the DSM IV-TR criteria for diagnosing comorbid drug use disorders and psychotic disorders.

Paliperidone for the treatment of schizophrenia and schizoaffective disorders - a drug safety evaluation.

INTRODUCTION: Paliperidone, the major active metabolite of risperidone, is a second-generation antipsychotic that has been developed as an extended-release (ER) oral formulation and a long-acting injectable paliperidone palmitate (PP) formulation. Paliperidone has demonstrated efficacy in the reduction of acute schizophrenia symptoms and clinical benefits were maintained also in the long-term treatments. Paliperidone ER and PP are generally well tolerated with a predictable adverse event profile. Areas covered: Data from studies evaluating safety and tolerability in the acute and maintenance treatment of schizophrenia with paliperidone are reviewed. The reported treatment-emergent adverse events of these formulations are discussed. Expert opinion: In the treatment of schizophrenia and schizoaffective disorders the safety profile has a central role because it can enhance patient compliance. In fact treatment-emergent adverse events are one of the main causes of discontinuation in these patients. In particular the main limitation in the administration of paliperidone could be represented by the onset of hyperprolactinemia (especially in women) and of mild parkinsonism. Paliperidone has a high impact on current long-term drug strategies, especially given the new 3 month long-acting injectable formulation of PP.

Clinical pharmacology of atypical antipsychotics: an update.

This review will concentrate on the clinical pharmacology, in particular pharmacodynamic data, related to atypical antipsychotics, clozapine, risperidone, paliperidone, olanzapine, que¬tiapine, amisulpride, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone and cariprazine. A summary of their acute pharmacokinetics properties are also reported. Four new second-generation antipsychotics are available: iloperidone, asenapine, lurasidone and in the next future cariprazine. Similar to ziprasidone and aripiprazole, these new agents are advisable for the lower propensity to give weight gain and metabolic abnormalities in comparison with older second-generation antipsychotics such as olanzapine or clozapine. Actually lurasidone seems to be best in terms of minimizing unwanted alterations in body weight and metabolic variables. Therapeutic drug monitoring is not strictly necessary for all of the new antipsychotic drugs because there are no unequivocal data supporting a relationship between plasma drug levels and clinical outcomes or side effects. The exception can be represented by clozapine for which plasma levels of 350-420 ng/ml are reported to be associated with an increased probability of a good clinical response. Also for olanzapine an established therapeutic range (20-50 ng/ml) is proposed to yield an optimal response and minimize side effects.

Cancer of the ampulla of Vater: chromosome 17p allelic loss is associated with poor prognosis.

BACKGROUND: Cancer of the ampulla of Vater kills 60% of affected patients. Local spread of the tumour (T stage) is the only reliable prognostic factor. Nevertheless, any cancer stage includes long term survivors and patients dying from the disease. The molecular anomalies involved in this process have the potential to serve as additional prognostic markers. AIM: To evaluate if allelic losses (LOH) of chromosomes 17p and 18q may be of prognostic value in multivariate survival analysis. METHODS: We examined 53 ampullary cancers for chromosome 17p and 18q LOH using microsatellite markers and DNA from paraffin embedded tumours. All patients were treated by surgery alone (pancreaticoduodenectomy). Multivariate survival analysis included age, sex, tumour size, macroscopic appearance, grade of differentiation, T stage, lymph node metastasis, and chromosome 17p and 18q status. RESULTS: Chromosome 17p and 18q LOH were detected in 28 (53%) and 18 (34%) cancers, respectively. Multivariate survival analysis indicated chromosome 17p status as an independent prognostic factor together with T stage. The five year survival for chromosome 17p retention and 17p loss was 80% and 7%, respectively. The risk of death from cancer within the five year follow up period for patients with cancers harbouring chromosome 17p LOH was 11 times higher than that of patients with cancers retaining chromosome 17p (p<0.0001), regardless of the tumour stage at diagnosis. CONCLUSIONS: Chromosome 17p status is an independent prognostic factor among ampullary cancers at the same stage. The combined use of T stage and chromosome 17p status may help in deciding whether ampullary cancer patients require additional therapy other than surgery alone.

Chromosome 5 allelic losses are early events in tumours of the papilla of Vater and occur at sites similar to those of gastric cancer.

During our studies of DNA fingerprinting of tumours of the pancreas and papilla (ampulla) of Vater, using arbitrarily primed polymerase chain reaction (AP-PCR), we noticed two bands showing a decreased intensity in six of ten ampullary tumours with respect to matched normal tissues. Those bands were both assigned to chromosome 5. Such a finding was somewhat in contrast with the reportedly low frequency of APC gene mutations in ampullary cancers, located at chromosome 5q21, and suggested that loci different from that of APC might be the target of chromosome 5 allelic losses (LOH) in these tumours. Therefore, we analysed chromosome 5 LOH in a panel of 27 ampullary tumours, including eight adenomas, four early- and 15 advanced-stage cancers, using 16 PCR-amplified CA microsatellite polymorphic markers spanning the entire chromosome. Nineteen cases (70%) showed LOH, and the interstitial deletions found in these tumours described two smallest common deleted regions, in which putative suppressor genes might reside. They were at 5q13.3-q14 and at 5q23-q31 respectively, which correspond to those found in gastric tumours. In addition, the presence of 5q LOH in six of eight adenomas and in three of four early-stage cancers suggests that such phenomena occur at early stages of neoplastic progression of the ampullary epithelium.

Prevalence of upper gastrointestinal lesions and Helicobacter pylori infection in Crohn's disease.

Crohn's disease can affect the upper gut with reported variable frequency, although concurrent Helicobacter pylori infection has been reported to be low. We prospectively investigated the prevalence of esophageal, gastric, and duodenal lesions and Helicobacter pylori infection in 67 Crohn's disease, 41 ulcerative colitis patients, and 43 controls. Symptoms, esophagogastroduodenoscopy, and multiple biopsies were performed on all patients consecutively. Endoscopic lesions were found in 63% of Crohn's disease patients, with a Helicobacter pylori prevalence of 28%. Granulomas were found in three patients. Twenty-two percent of the ulcerative colitis patients had lesions, with a 29% prevalence of Helicobacter pylori infection. Half of the controls had pathological endoscopy, and Helicobacter pylori was positive in 40% of the cases. Subjective symptoms did not predict the presence of endoscopic lesions or Helicobacter pylori infection in inflammatory bowel disease patients. Chronic gastritis and duodenitis are common in Crohn's disease patients, and the majority are not associated with Helicobacter pylori infection.