Long-term behavioral and morphological consequences of nonconvulsive status epilepticus in rats

The aims of the present study were to ascertain whether nonconvulsive status epilepticus (NCSE) could give rise to long-term behavioral deficits and permanent brain damage. Two months after NCSE was elicited with pilocarpine (15 mg/kg i.p.) in LiCl-pretreated adult male rats, animals were assigned to either behavioral (spontaneous behavior, social interaction, elevated plus-maze, rotorod, and bar-holding tests) or EEG studies. Another group of animals was sacrificed and their brains were processed for Nissl and Timm staining as well as for parvalbumin and calbindin immunohistochemistry. Behavioral analysis revealed motor deficits (shorter latencies to fall from rotorod as well as from bar) and disturbances in the social behavior of experimental animals (decreased interest in juvenile conspecific). EEGs showed no apparent abnormalities. Quantification of immunohistochemically stained sections revealed decreased amounts of parvalbumin- and calbindin-immunoreactive neurons in the motor cortex and of parvalbumin-positive neurons in the dentate gyrus. Despite relatively inconspicuous manifestations, NCSE may represent a risk for long-term deficits.     

Prospective evaluation of two stimulation protocols for low responders who were undergoing in vitro fertilization-embryo transfer

OBJECTIVE: To compare two stimulation protocols designed for low responders undergoing IVF. DESIGN: Randomized, prospective study. SETTING: University hospital IVF unit. PATIENT(S): Sixty low responders who were recruited on the basis of results in previous cycles. INTERVENTION(S): Modified flare protocol in which a high dose of GnRH agonist was administered for the first 4 days, followed by a standard agonist dose, or a modified long protocol in which a standard agonist dose was used until pituitary down-regulation, after which the agonist dose was halved during stimulation. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved. RESULT(S): Twenty-nine cycles were performed with the modified flare protocol and 31 were performed with the modified long protocol. Significantly more oocytes were obtained with the modified long protocol than the modified flare protocol (4.42 +/- 2.6 vs. 3.07 +/- 2.15). The number and quality of embryos available for transfer was similar in both groups. One clinical pregnancy (3.4%) was achieved with the modified flare protocol, and 7 pregnancies (22.5%) were achieved using the modified long protocol. CONCLUSION(S): These preliminary results substantiate the poor prognosis and outcome for low responders undergoing IVF. A modified long "mini-dose" protocol appears to be superior to a modified mega-dose flare protocol in terms of oocyte yield and cycle outcome.     

Outcome of prenatally diagnosed trisomy 6 mosaicism

We report the prenatal diagnosis of trisomy 6 mosaicism via amniocentesis, in which trisomy 6 cells were identified in three of five culture vessels with 33% (5/15) of colonies showing trisomic cells. The pregnancy was electively terminated and examination revealed minor abnormalities (shortening of the femurs, micrognathia, posterior malrotation of the ears, and bilateral camptomelia of the second digit of the hands and fifth digits of the feet). Cytogenetic analysis of the placenta showed trisomy 6 in 100% of 20 cells studied. Karyotype was 46,XX in 100 cells examined from fetal skin. There are relatively few prenatally diagnosed cases of mosaic trisomy 6 at amniocentesis. Confined placental mosaicism (CPM) has been postulated in other cases where follow-up cytogenetic studies were not available. The present case differs from those previously reported, as it appears to represent CPM of chromosome 6 with phenotypic effects to the fetus.     

Gamma-amino-butyric acid immunoreactivity in intramucosal colonic tumors

BACKGROUND AND AIM: The level of gamma-amino-butyric acid (GABA) is reported to be increased in colon cancer. Moreover, data suggests that GABA plays a role in the proliferation or maturation of some types of cells. We examined the expression of GABA in intramucosal colonic tumors to clarify the relation between GABA and the degree of atypia. METHODS: Paraffin sections were prepared from 56 protruded-type colonic neoplasms, which were classified as intramucosal adenocarcinoma (AC), adenoma with severe atypia (ASA), or adenoma with mild to moderate atypia (AMA). Expression of GABA was investigated immunohistochemically, and GABA immunoreactivity was compared to the staining patterns of carcinoembryonic antigen (CEA) and cancer-associated antigen (CA19-9) which were classified into three categories. RESULTS: Intense GABA immunoreactivity was observed in 73.7%, 54.6%, 13.3%, and 5.4% of AC, ASA, AMA, and normal mucosa specimens, respectively. Kendall's correlation coefficient between GABA immunoreactivity and the degree of atypia was 0.447. Strong, positive CEA staining (pattern 3) was observed in 57.9%, 36.3%, and 13.3% of AC, ASA, and AMA specimens, respectively. Strong, positive CA19-9 staining was observed: 26.3%, 9.1% and 0%, respectively. In AC and ASA, the proportion of glands with strong GABA immunoreactivity was greater than the proportion of glands that were strongly positive for CA19-9. CONCLUSION: GABA may be useful as a tumor marker in combination with other tumor markers such as CEA and CA19-9.     

Influence of galvanic phenomena on the occurrence of algic symptoms in the mouth

The presence of more than one dental alloy in the oral cavity often causes pathological galvanic currents and voltage. Due to various and multi-faceted symptomathology, they tend to be a source of significant problems not only for the patient but also for the attending dentist. Very discreet and uncharacteristically objective diagnosis during a regular examination frequently causes this state to be ascribed to a completely different illness.     

Impact of subsidizing effective anti-osteoporosis drugs on compliance with management guidelines in patients following low-impact fractures

Early in 2000, proven-effective antiresorptive drugs (alendronate and raloxifene) were included in the national "health basket" in Israel. We carried out the present study to evaluate the effect of subsidizing antiosteoporosis drugs on the use of antiosteoporosis drugs in patients following low-impact fractures. The rates of dispensation of antiosteoporosis drugs, in the hospital and in the community, before and after an incident of a newly diagnosed low-impact fracture, respectively, were evaluated during January and February 1998 and 1999 ("pre-basket") and the corresponding months of 2000 and 2001 ("post-basket"). The study was carried out in a 950-bed teaching hospital, the only one serving the area, and the largest health maintenance organization in the area. Hospital charts of women and men age 50 years and older with new fractures following low- or moderate-impact trauma treated in the emergency room, or admitted to the orthopedic surgery and rehabilitation departments, were reviewed. A centralized pharmacy computerized database was used to follow antiosteoporosis drug dispensation in the community. A significant, approximately two-fold, increase in the baseline (before fracture) rate of osteoporosis drug dispensation was observed between the pre- and post-basket periods. The rate of patients treated after a fracture incident also increased significantly, 1.6 fold, in the post-basket period; however, even in the post-basket period, two-thirds of the patients remained untreated following a fracture incident, and most of those treated received only calcium and vitamin D; only 17% received potent antiosteoporosis drugs. In a multivariate analysis, female gender, hospitalization, having the incident of fracture in the post-basket period, and above all being treated for osteoporosis before the fracture incident, had the greatest effect on the likelihood of being treated following a low-impact fracture incident. The increase in the pooled use of antiosteoporosis drugs and/or calcium/vitamin D supplements was continuous, and subsidizing created no step-up effect, besides a transient increase in the use of potent antiosteoporosis drugs in the first year following the health-basket amendment. We conclude that while subsidizing may have a significant, positive effect on antiosteoporosis drug utilization, other factors may be even more important. There is an ongoing need to find ways to encourage the use of effective pharmacological interventions for primary and secondary prevention of osteoporotic fractures.     

Interference of mouse polyomavirus with the c-myc gene and its product in mouse mammary adenocarcinomas

In two tumour sublines (T.wt/BL and T.wt/Bc), established from mammary adenocarcinomas caused by mouse polyoma (Py) infection of nu/nu mice, integration of polyomavirus DNA sequences into the c-myc gene locus was mapped. A complete Py genome was found to be integrated just upstream from the c-myc gene in T.wt/BL cell line, while only a part of the early Py region coding for the early proteins was inserted in the chromosomal DNA of T.wt/Bc cells. An interference of Py sequences with the regulation of c-myc gene expression gives further significance to a Py-derived tumour system that appears to be similar to some human mammary cancers in the modifications of c-myc expression. Both cell lines were found to produce truncated large T antigen and entire middle and small T antigens. In addition, production of VP1 protein was observed in the T.wt/BL cell line. The integration of polyomavirus sequences and/or expression of viral proteins caused an elevation of c-myc expression. The level of the c-myc expression was higher in both tumour cell lines in comparison with control normal murine mammary gland (NMuMG) lines, but substantially lower than in NMuMG cells infected with polyomavirus. Possible co-operation of Py proteins with c-Myc was examined. Through GST fusion protein pull-down experiments, we evidenced, that c-Myc forms a complex with the common part of the Py early antigens in the two tumour cell lines. Co-localisation of the c-myc and LT was observed in cells overexpressing c-Myc and LT.     

Enhanced erythrocyte adhesiveness/aggregation in obesity corresponds to low-grade inflammation

OBJECTIVE: Previous studies have suggested that obesity enhances the inflammatory response, producing macromolecules involved in the induction and/or maintenance of increased erythrocyte aggregation. The objectives of this study were to evaluate the correlation between inflammation markers, erythrocyte adhesiveness/aggregation, and the degree of obesity and to assess phosphatidylserine expression on erythrocyte surface membrane of obese vs. nonobese individuals. RESEARCH METHODS AND PROCEDURES: Erythrocyte adhesiveness/aggregation in the peripheral venous blood was evaluated by using a new biomarker, phosphatidylserine expression was assessed by means of flow cytometry, and markers of inflammation were measured in 65 subjects: 30 obese [body mass index (BMI) = 41 +/- 7.7 kg/m(2)] and 35 nonobese (BMI = 24 +/- 2.7 kg/m(2)) individuals. Pearson correlations and Student's t test were performed. RESULTS: A highly significant difference was noted in the degree of erythrocyte adhesiveness/aggregation and markers of inflammation between the study groups. BMI correlated with erythrocyte adhesiveness/aggregation (r = 0.42, p = 0.001), erythrocyte sedimentation rate (r = 0.42, p = 0.001), high-sensitive C-reactive protein (r = 0.55, p < 10(-4)), fibrinogen (r = 0.37, p = 0.004), and white blood cell count (r = 0.45, p < 10(-4)). The degree of erythrocyte adhesiveness/aggregation correlated with erythrocyte sedimentation rate (r = 0.5, p < 10(-4)), high-sensitive C-reactive protein (r = 0.56, p < 10(-4)), fibrinogen (r = 0.54, p < 10(-4)), and white blood cell count (r = 0.32, p = 0.01). DISCUSSION: Our results suggest that obesity-related erythrocyte adhesiveness/aggregation is probably mediated through increased concentrations of adhesive macromolecules in the circulation and not necessarily through hyperlipidemia or phosphatidylserine exposure on erythrocyte's membrane.