Temporal order memory assessed during spatiotemporal navigation as a behavioral cognitive marker for differential Alzheimer's disease diagnosis

Episodic memory impairment is a hallmark for early diagnosis of Alzheimer's disease. Most actual tests used to diagnose Alzheimer's disease do not assess the spatiotemporal properties of episodic memory and lead to false-positive or -negative diagnosis. We used a newly developed, nonverbal navigation test for Human, based on the objective experimental testing of a spatiotemporal experience, to differentially Alzheimer's disease at the mild stage (N = 16 patients) from frontotemporal lobar degeneration (N = 11 patients) and normal aging (N = 24 subjects). Comparing navigation parameters and standard neuropsychological tests, temporal order memory appeared to have the highest predictive power for mild Alzheimer's disease diagnosis versus frontotemporal lobar degeneration and normal aging. This test was also nonredundant with classical neuropsychological tests. As a conclusion, our results suggest that temporal order memory tested in a spatial navigation task may provide a selective behavioral marker of Alzheimer's disease.     

beta3-Adrenergic receptor polymorphism and metabolic syndrome in postmenopausal women

Objectives. Some studies indicate that the Trp64Arg polymorphism in the gene encoding the β₃-adrenergic receptor (ADRB3) is associated with obesity, insulin resistance and earlier onset of type 2 diabetes mellitus. The aim of the present study was to evaluate the frequency of ADRB3 polymorphism and its association with metabolic syndrome in postmenopausal women.

Methods. We performed the study on 284 randomly chosen postmenopausal women, aged 50–60 years, who were then selected to the study. Measurements of anthropometric parameters and biochemical estimations such as lipid profile, glucose and insulin level in serum were carried out using commercial kits. ADRB3 genotyping was performed by polymerase chain reaction and mini-sequencing.

Results. The frequency of the Trp64/Arg64 genotype in the investigated population was 13%, and of the Trp64/Trp64 genotype, 85%. The Arg64/Arg64 genotype was present in only 2% of women. Metabolic syndrome was recognized in 22% of women bearing Trp64/Arg64 genotype and in 14% of women bearing Trp64/Trp64 genotype, without a statistically significant difference between the two groups (p > 0.05 in the χ² test). Women bearing the Trp64/Arg64 genotype had lower serum levels of high-density lipoprotein cholesterol (HDL-C) than Trp64/Trp64 genotype women (63.2 ± 13.0 vs. 71.4 ± 17.4 mg/dl). Both groups did not differ in any other investigated parameter.

Conclusion. Trp64Arg polymorphism of the β₃-adrenergic receptor gene is not related to metabolic syndrome in postmenopausal Polish women; however, it seems to be associated with decreased HDL-C levels.     

Perioperative Complications After Neoadjuvant Chemotherapy With and Without Bevacizumab for Colorectal Liver Metastases

Purpose

Bevacizumab has been shown to increase progression free and overall survival in patients with metastatic colorectal cancer. Neoadjuvant bevacizumab is commonly used in patients undergoing liver resection. Our purpose was to evaluate whether bevacizumab is associated with increased rate of perioperative complications in patients undergoing hepatic resection for colorectal liver metastases (CRLM).

Methods

Retrospective analysis of patients undergoing hepatic resection for CRLM who received chemotherapy and bevacizumab (group 1, n?=?134), or chemotherapy alone (group 2, n?=?57). We compared demographics, surgical characteristics, and perioperative course.

Results

Perioperative complications developed in 35 % of patients in group 1, and 47 % in group 2 (p?=?0.11). Of those complications, 15 (11.2 %) in group 1, and 5 (8.8 %) in group 2 were considered major (p?=?0.617). Four patients, all of whom received preoperative bevacizumab, developed enteric leaks following combined liver and bowel resection. The rate of anastomotic leak in group 1 was 10 %, compared with 0 in group 2, p?=?0.56.

Conclusion

Neoadjuvant chemotherapy along with bevacizumab was not associated with an increased risk of postoperative complications after hepatic resection. Possible association of increased morbidity with simultaneous bowel and liver resections following bevacizumab administration was found and we recommend avoiding such treatment combination.     

Long-term changes in postnatal susceptibility to pilocarpine-induced seizures in rats exposed to gamma radiation at different stages of prenatal development

PURPOSE: To determine whether brains irradiated at different stages of prenatal development also have different postnatal susceptibility to seizures evoked by pilocarpine. METHODS: Pregnant Wistar rats were exposed to a single 1.0-Gy dose of gamma rays on gestation days 13, 15, 17, or 19 (E13, E15, E17, and E19, respectively). On postnatal day 60, their offspring received i.p. pilocarpine injections to evoke status epilepticus. Behavior of the animals was observed continuously for 6 h after the injection, and motor manifestations of seizure activity were rated, and survival times recorded. After 7-day survival, the animals were killed, and their brains were weighed. RESULTS: The average brain weight of animals exposed to irradiation at earlier prenatal stages (E13 or E15) was significantly lower than that after irradiation on E17 or E19. However, effects of the irradiation on the susceptibility to pilocarpine-induced seizures were quite opposite. The intensity of status epilepticus evoked in rats irradiated on E13 or E15 was significantly lower than that in nonirradiated controls or in those irradiated on E17 or E19. Moreover, after irradiation on E13 or E15, survival of the animals was significantly higher in relation not only to other irradiated groups but also to the controls. CONCLUSIONS: The results suggest than the extent of neuronal deficit, even if relatively greater, cannot always lead to higher susceptibility of the dysplastic brain to seizures. Functional consequences of the deficit, even if its magnitude is relatively smaller but involving specific brain areas, appear to be critical for the epileptogenesis.     

MRI for the evaluation of scleral invasion and extrascleral extension of uveal melanomas

AIM: To study the diagnostic value of MRI for the detection of scleral infiltration and extrascleral extension of uveal melanoma. MATERIALS AND METHODS: Twelve consecutive patients with clinically suspected large uveal melanoma were examined by MRI. All of the patients underwent enucleation or exenteration. The clinical and histopathological findings were compared. RESULTS: The clinical diagnosis of uveal malignant melanoma was confirmed by histology in each case. MRI allowed detection of scleral infiltration with a sensitivity of 100% and a specificity of 50%. For extrascleral extension, MRI had a sensitivity of 100% and specificity of 89%. CONCLUSIONS: Using fat suppression technique and enhancement with contrast medium, MRI proved to be a valuable ancillary method for the assessment of scleral infiltration and extrascleral extension.     

Role of R-(-)-deprenyl in adhesion of neuronal and non-neuronal cells

Role of R-(-)-deprenyl in adhesion of neuronal and non-neuronal cells. The beneficial effect of the anti-parkinsonian monoamine oxidase-B inhibitor, R-(-)-deprenyl has been shown in a number of different diseases, such as Parkinson's and Alzheimer's disease, atherosclerosis or tumor formation. The role of the cytoskeleton, the main component of cell adhesion, has been suggested in the development of these diseases. Nevertheless, the effect of the drug on cell adhesion has never been examined. In the present study, the authors studied the effect of R-(-)-deprenyl on cell-cell adhesion of neuronal (PC12, rat phaeochromocytoma) and non-neuronal (NIH3T3, NIH3T3/EGFR, NIH3T3/EGFR-e3B1 mouse embryo fibroblasts, and 5180 mouse sarcoma) cells using cell association assay. R-(-)-deprenyl treatment resulted in a cell type- and concentration-dependent increase in cell-cell adhesion of PC12 cells, which contain no monoamine oxidase-B, and we observed the same effect in NIH3T3 cells at concentrations lower than those needed for monoamine oxidase-B inhibition. Interestingly, R-(-)-deprenyl increased cell-cell adhesion of tumor cell lines as well. The effect of R-(-)-deprenyl was not reversible during a 24-hour recovery period. At the same time, the monoamine oxidase-B inactive isomer of the drug, S-(+)-deprenyl had no effect on cell-cell adhesion in PC12 and NIH3T3 cells. In this study, the authors described a new, monoamine oxidase-B independent effect of R-(-)-deprenyl on cell-cell adhesion both in neuronal and non neuronal cells. The authors' results with S-(+)-deprenyl suggest that the sterical structure of the drug is an important factor of the observed effect, which is probably a consequence of an irreversible change in the cells.     

Influence of smoking during pregnancy on children's health--overview of epidemiologic studies

The association between maternal smoking and retarded maternal condition and birth outcome is well know. Smoking during pregnancy increases risk of spontaneous abortion, placenta previa, abruptio placenta, preterm premature rupture of membranes, stillbirth, preterm delivery and sudden infant death syndrome. The recently conducted studies also indicate that prenatal exposure to tobacco smoke is a risk factor for respiratory infections, asthma, allergy, childhood cancer, and it has neurobehavioral consequences regarding children's health. The risk for most of these conditions has been found to increase with the number of cigarettes smoked. On the other hand women who stopped smoking during pregnancy are at lower risk for most of those pathologies.     

Effects of a malpractice crisis on specialist supply and patient access to care

OBJECTIVE: To investigate specialist physicians' practice decisions in response to liability concerns and their perceptions of the impact of the malpractice environment on patient access to care. SUMMARY BACKGROUND DATA: A perennial concern during "malpractice crises" is that liability costs will drive physicians in high-risk specialties out of practice, creating specialist shortages and access-to-care problems. METHODS: Mail survey of 824 Pennsylvania physicians in general surgery, neurosurgery, orthopedic surgery, obstetrics/gynecology, emergency medicine, and radiology eliciting information on practice decisions made in response to rising liability costs. RESULTS: Strong majorities of specialists reported increases over the last 3 years in patients' driving distances (58%) and waiting times (83%) for specialist care or surgery, waiting times for emergency department care (82%), and the number of patients forced to switch physicians (89%). Professional liability costs and managed care were both considered important contributing factors. Small proportions of specialists reported that they would definitely retire (7%) or relocate their practice out of state (4%) within the next 2 years; another third (32% and 29%, respectively) said they would likely do so. Forty-two percent of specialists have reduced or eliminated high-risk aspects of their practice, and 50% are likely to do so over the next 2 years. CONCLUSIONS: Our data suggest that claims of a "physician exodus" from Pennsylvania due to rising liability costs are overstated, but the malpractice situation is having demonstrable effects on the supply of specialist physicians in affected areas and their scope of practice, which likely impinges upon patients' access to care.     

X-linked myotubular and centronuclear myopathies

Recent work has significantly enhanced our understanding of the centronuclear myopathies and, in particular, myotubular myopathy. These myopathies share similar morphologic appearances with other diseases, namely the presence of hypotrophic myofibers with prominent internalized or centrally placed nuclei. Early workers suggested that this alteration represented an arrest in myofiber maturation, while other hypotheses implicated either failure in myofiber maturation or neurogenic causes. Despite similarities in morphology, distinct patterns of inheritance and some differences in clinical features have been recognized among cases. A severe form, known as X-linked myotubular myopathy (XLMTM), presents at or near birth. Affected males have profound global hypotonia and weakness, accompanied by respiratory difficulties that often require ventilation. Most of these patients die in infancy or early childhood, but some survive into later childhood or even adulthood. The responsible gene (MTM1) has been cloned; it encodes a phosphoinositide lipid phosphatase known as myotubularin that appears to be important in muscle maintenance. In autosomal recessive centronuclear myopathy (AR CNM), the onset of weakness typically occurs in infancy or early childhood. Some investigators have divided AR CNM into 3 subgroups: 1) an early-onset form with ophthalmoparesis, 2) an early-onset form without ophthalmoparesis, and 3) a late-onset form without ophthalmoparesis. Clinically, autosomal dominant CNM (AD CNM) is relatively mild and usually presents in adults with a diffuse weakness that is slowly progressive and may be accompanied by muscle hypertrophy. Overall, the autosomal disorders are not as clinically uniform as XLMTM, which has made their genetic characterization more difficult. Currently the responsible gene(s) remain unknown. This review will explore the historical evolution in understanding of these myopathies and give an update on their histopathologic features, genetics and pathogenesis.