Medications used to treat Parkinson's disease and the risk of gambling.

Recent case-series studies indicated that a medication used to treat Parkinson's disease (PD), in particular Pramipexole, is associated with gambling. A case-series study cannot test this hypothesis; therefore, we need to design a case-control or cohort study to test the aforementioned hypothesis. Typical of a case-control design, we sampled on the dependent variable, which we defined as incident gambling in PD. A research neurologist, who was kept uninformed of the case-control status, retrospectively measured the exposure of interest (i.e. medications used to treat PD) by using the medical database system of Mayo Clinic Jacksonville. Eleven patients with PD without history of gambling, but had newly developed gambling, were matched by age and sex to the control group of 37 PD patients without gambling at a ratio of one case to at least three controls. Disease duration, age, and sex did not differ between cases and controls. Combined therapy with Pramipexole and levodopa did not increase the risk of gambling as compared to monotherapy with Pramipexole (OR, 0.15; 95% CI, 0.01-1.26). Treatment with Pramipexole was associated with increased risk of gambling and this association approached significance (OR, 3.6; 95% CI, 0.9-14.9). Patients with PD who newly developed gambling behavior were more likely to have been taking Pramipexole than other anti-PD medication. However, the association between Pramipexole and gambling behavior is not necessarily etiologic.

Phylogeny of the Colubroidea (Serpentes): new evidence from mitochondrial and nuclear genes.

The Colubroidea contains over 85% of all the extant species of snakes and is recognized as monophyletic based on morphological and molecular data. Using DNA sequences (cyt b, c-mos) from 100 species we inferred the phylogeny of colubroids with special reference to the largest family, the Colubridae. Tree inference was obtained using Bayesian, likelihood, and parsimony methods. All analyses produced five major groups, the Pareatidae, Viperidae, Homalopsidae, the Elapidae, and the Colubridae. The specific content of the latter two groups has been altered to accommodate evolutionary history and to yield a more stable taxonomy. We propose an updated classification based on the reallocation of species as indicated by our inferred phylogeny.

Atrophy of superior cerebellar peduncle in progressive supranuclear palsy.

BACKGROUND: Pathologic changes in the superior cerebellar peduncles (SCP) are common in progressive supranuclear palsy (PSP), but atrophy of the SCP has never been systematically studied. OBJECTIVE: To investigate the SCP width in PSP cases and controls with morphometric methods. METHODS: The mean width of the SCP in transverse sections of the pons at the level of trigeminal nerve was determined in 48 PSP cases (29 men, 19 women; mean age 72.5 +/- 8.2 years) and 29 age-matched control subjects, many with neurodegenerative disorders that can be clinically mistaken for PSP. As the origin of the SCP is the cerebellar dentate nucleus, correlations were sought between SCP atrophy and severity of grumose degeneration in the dentate nucleus. RESULTS: The average width of the SCP was less in PSP (range 0.09 to 0.24 cm) than in controls (range 0.21 to 0.43 cm; Mann-Whitney U test, p < 0.001), including control cases that had been clinically misdiagnosed as PSP (range 0.26 to 0.41 cm). Severity of SCP atrophy normalized by brain weight correlated with disease duration (Spearman rank order correlation, r = 0.367, p = 0.028), suggesting that SCP atrophy is a relatively early feature of PSP. No correlation was found between grumose degeneration and SCP width. CONCLUSIONS: SCP atrophy is common in PSP and correlates with disease duration. Given that measurements of the SCP are within the resolution of MRI, it remains to be determined if SCP atrophy can be used as a diagnostic marker of PSP.

Effect of phosphoramidon on brain tissue angiogenesis in the chronic phase of vasospasm after subarachnoid hemorrhage in the rat.

BACKGROUND: Subarachnoid hemorrhage (SAH) frequently leads to prolonged cerebral vasospasm resulting in vascular pathology due to endothelial cell ischemia and neuronal hypoxia. Posthemorrhagic vasospasm can be counteracted by the administration of phosphoramidon, which blocks the endothelin converting enzyme (ECE) responsible for the conversion of big endothelin into a fully active ET1 peptide. The aim of the study was to determine the effect of chronic vasospasm after SAH on angiogenesis and the effect on this process of endothelin-1, the main causative factor in vasospasm. MATERIAL AND METHODS: Male Wistar rats were examined. Seven days after cannulation of the cisterna magna, blood was administered to induce SAH. The ECE inhibitor phosphoramidon was administered in a dose of 40 nmol in 50 microl of cerebrospinal fluid three times: 20 min before SAH, 60 min after SAH, and 24 hours after SAH. The brains were removed 48 hours later for histological evaluation. The vascular surface density was measured in cerebral hemisphere sections (at the level of the dorsal part of the hippocampus) and brainstem sections (1/2 of the pons). CONCLUSION: Increased angiogenesis was observed in the cerebral hemispheres after SAH. The administration of phosphoramidon inhibits angiogenesis in cerebral hemispheres after SAH.

Multimodal sex therapy for the treatment of vulvodynia: a clinician's view.

Sex therapists are often challenged when treating women with the primary diagnosis of vulvodynia or subtypes of vulvar-vestibular pain. This article presents an overview of how a sex therapist can assess problem areas related to this diagnosis and approach treatment in a practical and comprehensive fashion. What follows is based on anecdotal clinical experience of the author. It outlines a multimodal approach that includes cognitive-behavioral techniques, both individual and conjoint therapy, as well as close cooperation with physicians who provide concurrent medical management.

Cerebral angiogenesis after subarachnoid hemorrhage (SAH) and endothelin receptor blockage with BQ-123 antagonist in rats.

The aim of the study was to determine the effect of chronic vasospasm after SAH on angiogenesis and the effect of endothelin-1, the main causative factor in vasospasm, on this process. Male Wistar rats, 220-250 g, were examined. Seven days after cannulation of the cisterna magna (CM), a 100 microl dose of non-heparinized blood was administered to induce SAH. Sham SAH (aSAH) was induced by intracisternal injection of 100 microl of artificial cerebrospinal fluid. Endothelin receptor antagonist BQ-123 in a dose of 40 nmol in 50 microl of cerebrospinal fluid was given three times: 20 min. before SAH and aSAH, 60 min and 24 hours after SAH and aSAH. The same pattern of BQ-123 administration was used in the nonSAH group. The brains were removed 48 hours later for histological evaluation. Vascular surface density was measured in cerebral hemisphere sections (at the level of the dorsal part of the hippocampus) and brain stem sections (1/2 of the pons). An increase in angiogenesis was observed after SAH, compared to control values. The administration of BQ-123, a specific endothelin receptor blocker inhibits angiogenesis in cerebral hemispheres after SAH.

Molecular polytomies.

This paper focuses on polytomies, especially molecular polytomies. The distinction between molecular and species polytomies is important, but is often not made. Likelihood ratio tests are an easier method for detecting molecular polytomies than other methods cited herein. Simulation shows that parsimony will generally falsely resolve molecular polytomies, which is worrisome because a simple mathematical model described herein predicts that molecular polytomies will occur often when the mean branch length is small. A test of the model using several real molecular data sets indicates that molecular polytomies may actually occur more often than predicted by the model. This suggests that at least some published molecular parsimony trees contain clades that are false resolutions of polytomies. Finally, a possible method for detecting species polytomies from molecular data is described.

Expression of vascular endothelial growth factor (VEGF) in rat brain after subarachnoid haemorrhage and endothelin receptor blockage with BQ-123.

Cerebral vasospasm is one of the most severe complications of subarachnoid haemorrhage (SAH), leading to pathological changes in the vessel wall itself and in the nervous tissue, due to ischaemia of endothelial cells and neurones. Amongst the known substances inducing vasospasm, the most potent spasmogenic effect is exerted by endothelin-1 (ET1). The constriction of cerebral arteries and obliteration of capillaries highly stimulates the secretion of growth factors by endothelial cells and induces compensatory formation of collateral circulation in response to brain ischaemia. Expression of vascular endothelial growth factor (VEGF), the main factor responsible for angiogenesis and vascular permeability, was found to be increased in hypoxic cells (irrespective of the cause of hypoxia) as well as in neoplastic cells in the brain. The aim of the study was to determine whether chronic vasospasm and hypoxia of endothelial cells stimulate expression of VEGF, and whether blockage of the endothelin receptor ET(A) reduces this expression. The SAH was induced experimentally in male Wistar rats and the ET(A) receptor antagonist--BQ-123 was administered into the cisterna magna. After 48 hours the brain was removed and expression of VEGF studied immunohistochemically on paraffin sections. We found that hypoxia of endothelial cells, induced by chronic vasospasm after SAH, caused increased expression of VEGF in brain vessels and neurones of the cerebral hemispheres, brain stem and cerebellum. After administration of the endothelin receptor antagonist BQ-123, no changes in VEGF expression in the brain were found.

BCL2 and BAX mRNA concentration profile in fibrillary astrocytoma.

A high level of the BCL2 protein and the lack of apoptosis promoting protein BAX are beginning to be treated as markers of cellular resistance to anti-neoplastic drugs. The object of the study were specimens from stereotactic biopsy of Astrocytoma fibrillare in the central brain area, inaccessible to conventional surgery. The cytological preparations have been evaluated with histopathological and immunohistochemical methods in order to determine the origin of the tumour and assess cell proliferation activity. The molecular analysis conducted in order to determine the sensitivity of the tumour to radio- or chemotherapy included the determination of the number of mRNA BCL2 alpha and beta molecules and of BAX in 1 microg total RNA obtained from microscope slides. A higher expression of BAX than of BCL2-alpha is a prognosis for a positive result of chemo- or radiotherapy. A trace number of mRNA BCL2-beta molecules and a smaller number of mRNA BCL2-alpha molecules than mRNA BAX is a good prognosis for therapy.

Effect of endothelin-1 receptor antagonist BQ-123 on basilar artery diameter after subarachnoid hemorrhage (SAH) in rats.

Aim of the study was to quantify cerebral vasospasm in rats after subarachnoid hemorrhage (SAH) by morphometric examination of basilar artery and to evaluate the influence of endothelin receptor blocker BQ-123 on basilar artery constriction. The rat cisterna magna (CM) was cannulated and after 7 days SAH was developed by administration of 100 microl autologic, non-heparinized blood to the CM. The sham subarachnoid hemorrhage was developed by intracisternal administration of 100 microl of artificial cerebrospinal fluid. Endothelin receptor blocker BQ-123 was injected into the CM in a dose of 40 nmol diluted in 50 microl of cerebrospinal fluid 20 min. before SAH, and 24h and 48 h after SAH. After perfusion fixation the brains were removed from the skull and histological preparations of basilar artery were done. The internal diameter and wall thickness of basilar arteries was measured by interactive morphometric method. The most severe vasospasm was found in rats after SAH. The presence of numerous infiltrations composed of neutrophils and macrophages correlated with advanced vasospasm (index of constriction 5 times lower than in normal), suggesting the role of other factors participating in the late phase of vasospasms after SAH. Administration of BQ-123 in the late phase after SAH caused the dilatation of basilar artery. Following the administration of BQ-123 in the late phase (48 h after SAH) the basilar artery dilated, its wall became thinner, and the number of leukocyte infiltrations in the subarachnoid space decreased compared to the values after SAH alone.

Phylogenetic relationships of elapid snakes based on cytochrome b mtDNA sequences.

Published molecular phylogenetic studies of elapid snakes agree that the marine and Australo-Melanesian forms are collectively monophyletic. Recent studies, however, disagree on the relationships of the African, American, and Asian forms. To resolve the relationships of the African, American, and Asian species to each other and to the marine/Australo-Melanesian clade, we sequenced the entire cytochrome b gene for 28 elapids; 2 additional elapid sequences from GenBank were also included. This sample includes all African, American, and Asian genera (except for the rare African Pseudohaje), as well as a representative sample of marine/Australo-Melanesian genera. The data were analyzed by the methods of maximum-parsimony and maximum-likelihood. Both types of analyses yielded similar trees, from which the following conclusions can be drawn: (1) Homoroselaps falls outside a clade formed by the remaining elapids; (2) the remaining elapids are divisible into two broad sister clades, the marine/Australo-Melanesian species vs the African, American, and Asian species; (3) American coral snakes cluster with Asian coral snakes; and (4) the "true" cobra genus Naja is probably not monophyletic as the result of excluding such genera as Boulengerina and Paranaja.

Mitochondrial DNA phylogeography of the polytypic North American rat snake (Elaphe obsoleta): a critique of the subspecies concept.

Subspecies have been considered artificial subdivisions of species, pattern classes, or incipient species. However, with more data and modern phylogenetic techniques, some subspecies may be found to represent true species. Mitochondrial DNA analysis of the polytypic snake, Elaphe obsoleta, yields well-supported clades that do not conform to any of the currently accepted subspecies. Complete nucleotide sequences of the cytochrome b gene and the mitochondrial control region produced robust maximum-parsimony and maximum-likelihood trees that do not differ statistically. Both trees were significantly shorter than a most parsimonious tree in which each subspecies was constrained to be monophyletic. Thus, the subspecies of E. obsoleta do not represent distinct genetic lineages. Instead, the evidence points to three well-supported mitochondrial DNA clades confined to particular geographic areas in the eastern United States. This research underscores the potential problems of recognizing subspecies based on one or a few characters.

Reactivity of cerebral arteries after subarachnoid hemorrhage in rats after phosphoramidon administered.

The aim of the study was to quantify cerebral vasospasm in rats after subarachnoid hemorrhage (SAH) by morphometric examination of basilar artery and to evaluate the influence of Phosphoramidon on basilar artery constriction. The rat cisterna magna (CM) was cannulated and after 7 days SAH was developed by administration of 100 microliters autologic, non-heparinized blood to the CM. The sham subarachnoid hemorrhage was developed by intracisternal administration of 100 microliters of artificial cerebrospinal fluid. After 60 min and after 24 h Phosphoramidon was injected into the CM in a dose of 40 nmol diluted in 50 microliters of cerebrospinal fluid. After perfusion, the brain was removed from the skull and histological preparations of the basilar artery were made. The internal diameter and wall thickness of basilar arteries were measured by interactive morphometric method. The most severe vasospasm was found in rats after SAH and the administration of Phosphoramidon in the late phase after SAH caused the dilatation of the basilar artery. The presence of numerous infiltrations composed of neutrophils and macrophages correlated with advanced vasospasm (index of constriction 5 times lower than normal), suggesting the role of other factors participating in the late phase of vasospasms after SAH.

Influence of chronic cadmium exposure during pregnancy on DNA synthesis in different organs of rat offspring.

Though partly bound by placental metallothionein, cadmium easily enters fetal circulation and exerts toxic effects in offspring tissues and organs. The synthesis of DNA in different organs of rat offspring, whose dams were exposed to cadmium during pregnancy was examined in this study. Scintillation technique was applied for quantification of tritiated thymidine incorporation. In most studied organs a significant increase of DNA synthesis was noted, pronounced especially in small intestine and bone marrow (over 2-fold increase in comparison with controls). In view of known carcinogenic effects of cadmium in animals, our data suggest alteration of cell cycle in selected organs, which may correspond to increase of proliferation rate typical of neoplastic conditions. Further studies are necessary for correlating these findings with proliferation indices and expression of protooncogenes in situ.

Secretory meningioma of the brain. Report of two cases.

Two cases of cerebral secretory meningioma, occurring in 57 and 33-year-old females are reported. The tumors were located in the tentorial and frontotemporal region, respectively. The general histologic appearance of the tumors was of meningothelial meningioma (case 1) and meningioma with microcystic and angiomatous features (case 2). The most striking histological finding in both tumors were numerous pseudopsammoma bodies, localized chiefly around blood vessels. The inclusions were slightly eosinophilic, stained strongly with PAS method and were differing in size from 3 to 30 microns. Tumor cells containing or surrounding pseudopsammomas were immunopositive for cytokeratin and epithelial membrane antigen. In the first case, individual pseudopsammomas were strongly positive for carcinoembryonic antigen. Some diagnostic aspects of this antigen and problems regarding differential diagnosis in secretory meningioma are briefly discussed.

Smear technique in the intra-operative brain tumor diagnosis: its advantages and limitations.

The role of intra-operative pathological diagnosis increases along with a development of minimally invasive neurosurgery, especially stereotactic and endoscopic techniques. The authors present their own experience with the cytological method and evaluate its usefulness in intra-operative diagnosis of brain tumors. Brain tumor biopsy specimens obtained during craniotomy from 217 patients were examined. The cytological preparations (smears) were stained with 1% toluidin blue and/or with May-Grünwald-Giemsa stain. In 199 cases (92%) the cytological diagnosis was consistent with the histopathological one. A 99% sensitivity and 69% specificity were obtained. The histogenesis of gliomas was correctly established in 90% and their grade in 73% of cases. The most frequent diagnostic errors were: undergrading of gliomas (20), incorrect assessment of their histogenesis (10), diagnosis of low grade astrocytoma in a case of gliosis (3) and diagnosis of glioblastoma multiforme instead of metastatic carcinoma (2 cases). The most important advantages of cytological examination are rapidity, simplicity and relatively high diagnostic efficacy. Even very tiny specimens, especially of soft consistency are suitable for this technique, which is extremely important in operations of brain tumors localized in functionally important brain areas. In the authors' opinion this method still merits wider popularization in neurosurgical centers.