Detailed anatomy of the intracranial segment of the hypoglossal nerve: neurovascular relationships and landmarks on magnetic resonance imaging sequences

OBJECT: The thin hypoglossal nerve can be very difficult to distinguish on magnetic resonance (MR) images. The authors used a combination of sequences to increase the reliability of MR imaging in its demonstration of the 12th cranial nerve as well as to assess the course of the nerve, display its relationships to adjacent vessels, and provide landmarks for evaluating the nerve in daily practice. METHODS: The study group consisted of 34 volunteers (68 nerves) in whom a three-dimensional (3D) Fourier-transformation constructive interference in steady-state (CISS) sequence and a 3D T1-weighted contrast-enhanced magnetization-prepared rapid-acquisition gradient-echo (MPRAGE) sequence were applied. Two trained neuroradiologists collaboratively identified the hypoglossal trigone, preolivary sulcus, 12th cranial nerve, posterior inferior cerebellar artery, vertebral artery, 12th nerve root sleeve, and the hypoglossal canal on each side. The 3D CISS sequence successfully demonstrated the hypoglossal trigone (100% of images), 12th nerve root bundles (100% of images), and 12th nerve sleeves (88.2% of images). The canalicular segment was exhibited with the aid of plain 3D CISS sequences in 74% of images and by using contrast-enhanced 3D CISS sequences and contrast-enhanced MPRAGE sequences in 100% of images. The landmarks that proved useful to identify the cisternal segment of the 12th cranial nerve included the hypoglossal trigone, preolivary sulcus, and 12th nerve root sleeve. Neurovascular contact was identified in 61% of root bundles. The roots were distorted in 44% of these contacts. CONCLUSIONS: The contrast-enhanced 3D CISS sequence consistently displayed the cisternal segment as well as the canalicular segments of the hypoglossal nerve and is, therefore, the best sequence to visualize the complete cranial course of this nerve. Landmarks such as the 12th nerve sleeves can assist in the identification of this nerve.     

Gender identity disorder and eating disorders

We report three cases of transsexual patients who are suffering from an eating disorder: a biological male patient diagnosed with anorexia nervosa (AN), a biological male patient with bulimia nervosa (BN), and a biological female patient with AN as well as a severe alcohol dependence. The relationship between eating behavior, gender identity, sexual orientation, and body dissatisfaction is discussed.     

Enhanced microtubule-dependent trafficking and p53 nuclear accumulation by suppression of microtubule dynamics

The tumor suppressor protein p53 localizes to microtubules (MT) and, in response to DNA damage, is transported to the nucleus via the MT minus-end-directed motor protein dynein. Dynein is also responsible for MT-mediated nuclear targeting of adenovirus type 2 (Ad2). Here we show that treatment with low concentrations of MT-targeting compounds (MTCs) that do not disrupt the MT network but are known to suppress MT dynamics enhanced p53 nuclear accumulation, and the activation of the p53-downstream target genes. p53 nuclear accumulation required binding of MTCs to MTs and enhanced the induction of p53-up-regulated modulator of apoptosis (PUMA) mRNA and apoptosis on challenging cells with the DNA-damaging drug adriamycin. Low concentrations of MTCs enhanced the rate of movement of fluorescent Ad2 to the nucleus and increased the nuclear targeting efficiency of Ad2. We propose that suppression of MT dynamics by low concentrations of MTCs enhances MT-dependent trafficking toward the minus ends of MTs and facilitates nuclear targeting.     

No association between high-altitude tolerance and the ACE I/D gene polymorphism

PURPOSE: The absence (deletion allele [D]) of a 287 base-pair fragment in the ACE gene is associated with higher ACE tissue activity than its presence (insertion allele [I]) and, as such, may enhance vasoconstriction and fluid retention through increased levels of angiotensin II and aldosterone. Because fluid retention is found in acute mountain sickness (AMS) and exaggerated pulmonary hypertension is essential in the pathophysiology of high-altitude pulmonary edema (HAPE), we hypothesized that the DD genotype is associated with increased susceptibility to these illnesses. METHODS: ACE genotype was thus determined in 83 mountaineers staying over night at 4559 m and related to AMS symptoms. Genotype was similarly determined in 76 mountaineers who had participated in previous studies at 4559 m; 38 of the latter group had a history of HAPE, and 25 had developed HAPE again during these studies. RESULTS: The allele frequency was in Hardy-Weinberg equilibrium in both investigations. Neither the history nor the observed episodes of HAPE nor the prevalence of AMS defined as an AMS-C score >/= 0.70 (environmental symptom questionnaire) in the first study or in both studies taken together were significantly different between the genotypes DD, ID, and II. CONCLUSION: We conclude that I/D-ACE gene polymorphism has no important effect on susceptibility to AMS or HAPE.     

Effect of oral creatine supplementation on human muscle GLUT4 protein content after immobilization

The purpose of this study was to investigate the effect of oral creatine supplementation on muscle GLUT4 protein content and total creatine and glycogen content during muscle disuse and subsequent training. A double-blind placebo-controlled trial was performed with 22 young healthy volunteers. The right leg of each subject was immobilized using a cast for 2 weeks, after which subjects participated in a 10-week heavy resistance training program involving the knee-extensor muscles (three sessions per week). Half of the subjects received creatine monohydrate supplements (20 g daily during the immobilization period and 15 and 5 g daily during the first 3 and the last 7 weeks of rehabilitation training, respectively), whereas the other 11 subjects ingested placebo (maltodextrine). Muscle GLUT4 protein content and glycogen and total creatine concentrations were assayed in needle biopsy samples from the vastus lateralis muscle before and after immobilization and after 3 and 10 weeks of training. Immobilization decreased GLUT4 in the placebo group (-20%, P < 0.05), but not in the creatine group (+9% NS). Glycogen and total creatine were unchanged in both groups during the immobilization period. In the placebo group, during training, GLUT4 was normalized, and glycogen and total creatine were stable. Conversely, in the creatine group, GLUT4 increased by approximately 40% (P < 0.05) during rehabilitation. Muscle glycogen and total creatine levels were higher in the creatine group after 3 weeks of rehabilitation (P < 0.05), but not after 10 weeks of rehabilitation. We concluded that 1) oral creatine supplementation offsets the decline in muscle GLUT4 protein content that occurs during immobilization, and 2) oral creatine supplementation increases GLUT4 protein content during subsequent rehabilitation training in healthy subjects.     

Inhibition of growth-factor-activated proliferation by anti-estrogens and effects on early gene expression of mcf-7 cells

Recently, it was reported that the anti-estrogen tamoxifen not only inhibits estradiol-stimulated growth of MCF-7 cells but also significantly reduces the proliferation rate of cells stimulated by growth factors. We have confirmed this finding and also shown that the new anti-estrogen droloxifene inhibits the proliferation of epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I)-stimulated MCF-7 cells. The growth-factor-induced proliferation was inhibited in a dose-dependent manner by the anti-estrogens in the complete absence of estrogen and FCS. Of the anti-estrogens, droloxifene was considerably more potent than tamoxifen. Because the exprersion of the proto-oncogenes c-fos and c-myc has been considered a key event in development of the mitogenic response, we examined the effects of anti-estrogens on c-myc and c-fos gene expression. We included in these investigations the steroidal anti-estrogen ICI 164,384 because this compound has no or very little estrogenic activity. The studies revealed that all 3 antiestrogens transiently induced c-myc mRNA expression. However, the anti-estrogens inhibited estradiol-induced c-myc mRNA expression, although with different potencies. Pre-incubation of MCF-7 cells with droloxifene and tamoxifen resulted in elevated levels of growth-factor-induced c-myc mRNA expression. In contrast, the anti-estrogens did not induce c-fos mRNA or affect the expression of c-fos mRNA induced by growth factors. In conclusion, non-steroidal anti-estrogens inhibit growth-factor-stimulated proliferation of MCF-7 cells without inhibitinggrowth-factor-induced c-myc or c-fos mRNA expression.     

Fatal reactivation of hepatitis B post-chemotherapy for lymphoma in a hepatitis B surface antigen-negative, hepatitis B core antibody-positive patient: potential implications for future prophylaxis recommendations

In the absence of prophylaxis, the reactivation of hepatitis B in oncology patients who are hepatitis B carriers is a well-known and often fatal complication of chemotherapy. The current recommendations in Canada and the USA are that patients who are positive for hepatitis B surface antigen (HBsAg) receive antiviral prophylaxis prior to chemotherapy. We report a 67-year-old man with B-cell lymphoma who developed hepatitis B reactivation following chemotherapy with cyclophosphamide, adriamycin, vincristine, prednisone and rituximab. Pre-chemotherapy, the patient was negative for HBsAg, positive for hepatitis B core antibody (anti-HBc) and weakly positive for hepatitis B surface antibody. Despite treatment with lamivudine, the patient died of fulminant hepatic failure. Our experience indicates that patients who are negative for HBsAg but positive for anti-HBc are still at risk for reactivation of latent hepatitis B during and after chemotherapy and may be considered for prophylaxis.     

Increased level of phosphorylated akt measured by chemiluminescence-linked immunosorbent assay is a predictor of poor prognosis in primary breast cancer overexpressing ErbB-2

Introduction  

Akt1, Akt2 and Akt3 kinases are downstream components of phosphoinositol 3-kinase derived signals from receptor tyrosine kinases, which influence cell growth, proliferation and survival. Akt2 overexpression and amplification have been described in breast, ovarian and pancreatic cancers. The present study was designed to investigate the prognostic significance of activated Akt in primary breast cancer and its association with other tumour biomarkers.     

Preserved pharmacological activity of hepatocytes-treated extracts of valerian and St. John's wort

The two herbal extracts valerian (Valeriana officinalis L.) and St. John's wort (Hypericum perforatum L.) were studied for their metabolic changes upon incubation with freshly prepared rat hepatocytes and subsequently analysed phytochemically as well as pharmacologically in vitro. Quantitative HPLC analysis of valerian extracts revealed considerable metabolic activities with regard to sesquiterpenes and iridoids. The amount of acetoxyvalerenic acid decreased 9-fold, while that of hydroxyvalerenic acid correspondingly increased 9-fold due to O-deacetylation. The valepotriates didrovaltrate, isovaltrate and valtrate decreased 2-, 18- and 16-fold, respectively. However, the binding affinities of the incubated extracts to the benzodiazepine and picrotoxin binding site of the GABA (A) receptor were quite similar to those of the non-incubated extracts. Neither valerenic acids nor valepotriates exhibited any significant effect on the two binding sites when tested as single compounds. Therefore, either other constituents represent the active ones or multiple compounds are necessary for the observed inhibitory and allosteric effects at the GABA (A) receptor. Extracts of St. John's wort were less potently metabolised than valerian. The amount of pseudohypericin and the main flavonoids (hyperoside, rutin, isoquercitrin, quercitrin, quercetin and I3,II8-biapigenin) slightly decreased during the 4-h incubation period. Both the antagonist effect at the corticotropin-releasing factor (CRF) type 1 receptor and the binding inhibition at the 5-HT transporter were attenuated during the metabolic treatment. The reduced antagonist effect correlates with the decreasing amount of pseudohypericin known to be a CRF (1) receptor antagonist. In conclusion, the incubation of plant extracts with freshly prepared rat hepatocytes represents a useful approach to study the pharmacological action of metabolised plant extracts. The consistent pharmacological activity of both valerian and St. John's wort is concordant with the known clinical efficacy of pharmacological activities.     

Decline of ambient air pollution levels and improved respiratory health in Swiss children

The causality of observed associations between air pollution and respiratory health in children is still subject to debate. If reduced air pollution exposure resulted in improved respiratory health of children, this would argue in favor of a causal relation. We investigated whether a rather moderate decline of air pollution levels in the 1990s in Switzerland was associated with a reduction in respiratory symptoms and diseases in school children. In nine Swiss communities, 9,591 children participated in cross-sectional health assessments between 1992 and 2001. Their parents completed identical questionnaires on health status and covariates. We assigned to each child an estimate of regional particles with an aerodynamic diameter < 10 microg/m3 (PM10) and determined change in PM10 since the first survey. Adjusted for socioeconomic, health-related, and indoor factors, declining PM10 was associated in logistic regression models with declining prevalence of chronic cough [odds ratio (OR) per 10-microg/m3 decline = 0.65, 95% confidence interval (CI), 0.54-0.79], bronchitis (OR = 0.66; 95% CI, 0.55-0.80), common cold (OR = 0.78; 95% CI, 0.68-0.89), nocturnal dry cough (OR = 0.70; 95% CI, 0.60-0.83), and conjunctivitis symptoms (OR = 0.81; 95% CI, 0.70-0.95). Changes in prevalence of sneezing during pollen season, asthma, and hay fever were not associated with the PM10 reduction. Our findings show that the reduction of air pollution exposures contributes to improved respiratory health in children. No threshold of adverse effects of PM10 was apparent because we observed the beneficial effects for relatively small changes of rather moderate air pollution levels. Current air pollution levels in Switzerland still exceed limit values of the Swiss Clean Air Act; thus, children's health can be improved further.