Antenatal antipsychotic exposure induces multigenerational and gender-specific programming of adiposity and glucose tolerance in adult mouse offspring.

Second-generation antipsychotics (SGAs) are well known for their metabolic side effects in humans, including obesity and diabetes. These compounds are maintained during pregnancy to prevent the relapse of psychoses, but they readily diffuse across the placenta to the fetus, as documented with the widely-prescribed drug olanzapine (OLZ). However, observational studies have provided conflicting results on the potential impact of SGAs on fetal growth and body weight, and their effects on metabolic regulation in the offspring. For this reason, our study has tested whether antenatal exposure of CD1 mice to OLZ influenced metabolic outcomes in the offspring of the first (F1) and second (F2) generations. In F1 mice, OLZ antenatal treatment caused a decrease in neonatal body weight in both genders, an effect that persisted throughout life only in male animals. Interestingly, F1 female mice also displayed altered glucose homoeostasis. F2 mice, generated by mating normal males with F1 female mice exposed to OLZ during antenatal life, exhibited higher neonatal body weights which persisted only in F2 female animals. This was associated with expansion of fat mass and a concordant pattern of adipose tissue gene expression. Moreover, male and female F2 mice were glucose-intolerant. Thus, our study has demonstrated that antenatal OLZ exposure induces multigenerational and gender-specific programming of glucose tolerance in the offspring mice as adults, and points to the need for careful monitoring of children exposed to SGAs during pregnancy.

A retrospective analysis of the results of p(65) + Be neutrontherapy for the treatment of prostate adenocarcinoma at the cyclotron of Louvain-la-Neuve. Part I: Survival and progression-free survival.

PURPOSE: To retrospectively evaluate survival, progression-free survival (PFS) and biological response in a series of patients irradiated with mixed neutron/photon beams for locally advanced prostate cancer in our institution. PATIENTS AND METHODS: Three hundred and eight patients were treated between January 1990 and December 1996. Fifty-five of these were recruited for pT3 or pN1 tumors after radical prostatectomy. Neoadjuvant androgen deprivation was given in 106 patients. The treatment protocol consisted of a mixed photon/neutron irradiation in a two-to-three proportion, up to a total equivalent dose of 66 Gy (assuming a clinical RBE value of 2.8). Pre- and post-treatment PSA determinations were available in practically all cases. Study endpoints were overall survival (OAS) and progression-free survival (PFS). The Cox proportional hazard regression model was used to investigate the prognostic value of baseline characteristics on survival and progression-free survival were a progression was defined as local, regional, metastatic or biological progression. Mean age was 69 years (49-86); mean pretreatment PSA was 15 (0.5-330) in all patients and 14 (0.5-160) in those receiving neoadjuvant hormonotherapy; seven patients only had an initial PSA < or = 4 ng/mL; 15% were T1, 46% were T2, 28% were T3 or pT3 and 4% were T4 (7% unspecified); WHO grade of differentiation was I in 38%, II in 38% and III in 14% (5% unspecified). RESULTS: The median follow-up was 2.8 years (0-7.8). Five-year overall survival (OAS) was 79% (95% CI: 71-87%) and 5-year progression-free survival (PFS) was 64% (95% CI: 54-74%) for the entire series. PFS in patients with an initial PSA > or = 20 ng/mL was the same. PFS could be predicted by two optimal Cox regression models, one including histological grade (p = 0.003) and initial PSA (p = 0.0009) as cofactors, the other including histological grade (p = 0.003) and T stage (p = 0.02). The main prognostic factors for overall survival were PSA and age. Biological responses with PSA < 1.5 ng/mL, < 1 ng/mL and < 0.5 ng/mL at any time after treatment were documented in 70%, 61% and 47% of the patients, respectively. CONCLUSION: Five-year OAS was 79%, PFS was 64%, and biological response was 70% for prostate cancer patients treated with mixed photon/neutron beams as applied at Louvain-la-Neuve, which are good results as compared with the literature. The usual prognostic factors were confirmed.

[Uncommon cause of mitral insufficiency: pacemaker lead malpositioning in the left ventricle. Case report]. / Cause inhabituelle d'insuffisance mitrale: implantation involontaire d'une sonde de stimulation endocavitaire dans le ventricule gauche. A propos d'un cas.

Cardiac pacemakers' insertions may be associated with different types of complications such as lead's malposition. The authors report the observation of lead's malposition in the left ventricular chamber through the interatrial septum. This malposition is potentially dangerous because of the potent risk factor for stroke and thromboembolism that the patient might run. The diagnosis of this malposition can be done by surface electrocardiogram and thorax X-ray. However, we do insist on the importance of echocardiography and furthermore of transesophageal echocardiography which can lead to a much better choice in the treatment.

Discrimination between chronic pancreatitis and pancreatic adenocarcinoma using artificial intelligence-related algorithms based on image cytometry-generated variables.

The incidence of pancreatic adenocarcinomas (PA) is increased in the setting of chronic pancreatitis. Distinguishing chronic pancreatitis from pancreatic adenocarcinomas is often difficult, and is based on routine brush cytological specimens provided during endoscopic retrograde cholangiopancreatography (ERCP). Reactive epithelial changes in chronic pancreatitis may appear similar to those of a well-differentiated cancer. Brush cytology specimens were obtained during ERCP from 49 patients with diseases for which the differential diagnosis included chronic pancreatitis and/or pancreatic adenocarcinoma Image cytometry was performed involving the assessment of between 200-400 Feulgen-stained nuclei per case; for each case, 40 quantitative cytometric variables were generated. Data analysis was performed using artificial intelligence methods of data classification that produced decision trees and production rule systems. Different classification models were produced for a subset of 34 patients. The best models were identified by the use of a sampling technique (leave-one-out), and were tested on the remaining 15 patients. These models were based on 5 of the 40 variables associated with a significant discriminatory function. Pancreatic adenocarcinoma was diagnosed in the training data set of 34 patients during a leave-one-out process with an estimated sensitivity of 91% and specificity of 87%. Both sensitivity and specificity were 80% in the independent test set of 15 patients. We conclude that inflammatory and malignant pancreatic epithelia exhibit distinct morphological features that can be distinguished by decision tree-based classifiers employing image-cytometric numerical data.

Financial costs of alcoholism treatment programs: a longitudinal and comparative evaluation among four specialized centers.

BACKGROUND: Alcoholism is a worldwide problem. Many strategies for alcohol detoxification and relapse prevention exist, but each alcohol treatment center has its own program. The objective of this study was to analyze and compare the financial cost and effectiveness of alcohol treatment programs from inpatient stay to follow-up 1 year later. This was a prospective, open, nonrandomized study of 4 specialized alcohol treatment centers and 267 patients admitted for alcohol detoxification. METHODS: We recorded all medical and nonmedical interventions related to the program during patient stay in the hospital and every 3 months after discharge for 1 year and recorded the occurrence of alcohol relapse. Financial evaluation was based on the prices of refund from the French national health insurance service. RESULTS: The mean cost of hospitalization ranged from 1326 euros to 1917 euros(p = 0.001), a variation mainly due to the difference in the length of hospital stay but also to the cost of the inpatient program, routine medical checkups, and drugs administered. The mean cost of 1 year of follow-up per patient ranged from 419 euros to 1704 euros (p = 0.001). The efficiency, corresponding to the money spent to prevent the relapse of one patient during 1 month, was approximately 500 euros/month in three centers and 658 euros in the fourth. However, for a similar efficiency, the effectiveness, assessed by the mean time without relapse, was significantly (p = 0.001) different; center 1, which had the highest total cost, had an effectiveness 1.56 times higher than center 3, which had the lowest cost. CONCLUSIONS: This work emphasizes the heterogeneity of the costs and effectiveness of alcoholism treatment programs and suggests that research should be conducted to determine which program is the most rational, cost-efficient, and beneficial for patients and the public health office economy.

Image cytometry as a discriminatory tool for cytologic specimens obtained by endoscopic retrograde cholangiopancreatography.

BACKGROUND: Routine brush cytology is relatively insensitive for the diagnosis of biliary and pancreatic malignancy. Sensitivity can be improved by measuring DNA and proliferation. The goal of this study was to assess the discriminatory capacity of image cytometry using pancreaticobiliary brush cytology specimens obtained during endoscopic retrograde cholangiopancreatography (ERCP). Analysis included morphometry, DNA quantification, and characterization of nuclear chromatin distribution and condensation. METHODS: Brush cytology specimens were obtained during ERCP from 22 chronic pancreatitis specimens, 11 pancreatic adenocarcinoma specimens, 13 primary sclerosing cholangitis specimens, and 11 cholangiocarcinoma specimens and contrasted with 25 normal epithelia specimens. A SAMBA 2005 image processor was used to analyze Feulgen stained chromatin density and distribution. Discriminant analysis of 37 morphonuclear variables was performed to characterize differences between: 1) chronic pancreatitis and pancreatic adenocarcinoma, and 2) primary sclerosing cholangitis and cholangiocarcinoma. RESULTS: Chronic pancreatitis was distinguished from pancreatic adenocarcinoma (P < or = 0.001); sensitivity and specificity were both estimated to be 82%. Primary sclerosing cholangitis was distinguished from cholangiocarcinoma (P < or = 0.01); sensitivity and specificity were estimated to be 82% and 85%, respectively. CONCLUSIONS: Multiparameter image cytometry has potential as an adjuvant diagnostic technique in patients with pancreaticobiliary malignancy.