Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology that is frequently associated with inflammatory bowel disease. It is characterized by diffuse inflammation and fibrosis of the biliary tree, and it usually leads to biliary cirrhosis and portal hypertension. PSC is most commonly diagnosed with endoscopic retrograde cholangiopancreatography, although magnetic resonance cholangiography (MRC) is rapidly emerging as a first choicediagnostic test. MRC has the advantage of being non-invasive, does not require radiation, and is cost-effective in that it does not carry the risk of pancreatitis associated with retrograde studies. 2 Percutaneous cholangiography is seldom performed anymore. 相似文献
Recent data suggest that Alzheimer's patients who discontinue treatment with cholinesterase inhibitors have a significantly delayed cognitive decline as compared to patients receiving placebo. Such observations suggest cholinesterase inhibitors to provide a disease-modifying effect as well as symptomatic relief and, moreover, that this benefit remains after drug withdrawal. Consistent with this suggestion, we now demonstrate that chronic administration of tacrine, nefiracetam, and deprenyl, drugs that augment cholinergic function, increases the basal frequency of dentate polysialylated neurons in a manner similar to the enhanced neuroplasticity achieved through complex environment rearing. While both drug-treated and complex environment reared animals continue to exhibit memory-associated activation of hippocampal polysialylated neurons, the magnitude is significantly reduced suggesting that such interventions induce a more robust memory pathway that can acquire and consolidate new information more efficiently. This hypothesis is supported by our findings of improved learning behavior and enhanced resistance to cholinergic deficits seen following either intervention. Furthermore, the level of enhancement of basal neuroplastic status achieved by either drug or environmental intervention correlates directly with improved spatial learning ability. As a combination of both interventions failed to further increase basal polysialylated cell frequency, complex environment rearing and chronic drug regimens most likely enhanced cognitive performance by the same mechanism(s). These findings suggest that improved memory-associated synaptic plasticity may be the fundamental mechanism underlying the disease modifying action of drugs such as cholinesterase inhibitors. Moreover, the molecular and cellular events underpinning neuroplastic responses are identified as novel targets in the search for interventive drug strategies for the treatment of neurodegenerative and neuropsychiatric disorders. 相似文献
The adequate treatment of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis has intrigued clinicians for some time. As the resistance of these pathogens, coupled with the increase in community-acquired cases, continues steadily to rise, clinicians are finding it useful to employ multi-modal approaches for efficacious treatment. The authors present a single case report of a patient with recurrent MRSA osteomyelitis, lumbar paraspinal and epidural abscess. He was found to have decreased muscle strength and was hyporeflexic in the involved extremity. Serum testing demonstrated MRSA bacteremia. Neuroimaging studies revealed evidence of paraspinal abscess and a presumed herniated nucleus pulposus at the L5/S1 interspace with significant nerve root compromise. Despite antimicrobials, his symptoms persisted, necessitating surgical exploration. At surgery, paraspinal and epidural abscesses were encountered and debrided; however, no herniated disc was visualized. This case demonstrates the diagnostic and therapeutic dilemmas with which these lesions present. We postulate that the MRSA osteomyelitis/discitis pathogens were walled off in the disc space and subsequently inoculated the soft tissues with ensuing bacteremia. We concur that antimicrobial treatment should be the first line of therapy for these patients; however, surgical debridements and cautious spinal instrumentation should be employed where appropriate. 相似文献
A case of primary malignant melanoma in the mediastinum presenting as recurrent laryngeal nerve palsy is reported. Tissue biopsy at mediastinotomy yielded a diagnosis of malignant melanoma. The mass was fixed to the left aspect of the trachea and to the upper border of the left main bronchus and could not be removed surgically. Further extensive clinical and radiological investigations revealed no evidence of tumor elsewhere in the body. 相似文献
The development of intrinsic, N-methyl-D-aspartate (NMDA) receptor-mediated voltage oscillations and their dependence on co-activation of 5-hydroxytryptamine (5HT) receptors was explored in motor neurons of late embryonic and early larval Xenopus laevis. Under tetrodotoxin, 100 μM NMDA elicited a membrane depolarization of around 20 mV, but did not lead to voltage oscillations. However, following the addition of 2–5 μM 5HT, oscillations were observed in 12% of embryonic and 70% of larval motor neurons. The voltage oscillations depended upon co-activation of NMDA and 5HT receptors since they were curtailed by selectively blocking NMDA receptors with D-2-amino-5-phosphonovaleric acid (APV) or by excluding Mg2+ from the experimental saline. 5HT applied in the absence of NMDA also failed to elicit oscillations. Oscillations could be induced by the non-selective 5HT1a receptor agonist, 5-carboxamidotryptamine (5CT) and both 5HT- and 5CT-induced oscillations were abolished by pindobind-5HT1, a selective 5HT1a receptor antagonist. To test whether 5HT enables voltage oscillations by modulating the voltage-dependent block of NMDA channels by Mg2+, membrane conductance was monitored under tetrodotoxin. Although 5HT caused membrane hyperpolarization of 4–8 mV, there was little detectable change in conductance. NMDA application caused an approximate 20 mV depolarization and an ‘apparent’ decrease in conductance, presumably due to the conductance pulse bringing the membrane into a voltage region where Mg2+ blocks the NMDA ionophore. 5HT further decreased conductance, which we propose is due to its enhancement of the voltage-dependent Mg2+ block. When the membrane potential was depolarized by ~20 mV via depolarizing current injection (to mimic the NMDA-induced depolarization), 5HT increased rather than decreased membrane conductance. Furthermore, 5HT did not affect the increase in membrane conductance following NMDA applications in zero Mg2+ saline. The results suggest that intrinsic, NMDA receptor-mediated voltage oscillations develop in a brief period after hatching, and that they depend upon the co-activation of 5HT and NMDA receptors. The enabling function of 5HT may involve the facilitation of the voltage-dependent block of the NMDA ionophore by Mg2+ through activation of receptors with 5HT1a-like pharmacology. 相似文献
Summary A simple technique of stereotactic craniotomy and intraoperative lesion localisation that uses the Brown-Robert-Wells (BRW) stereotactic frame is presented. The method optimises craniotomy placement and facilitates localisation of small intracerebral lesions. Using the system, 16 patients have had resection of intracranial neoplasms from deep and/or eloquent areas of the brain with no neurological morbidity. 相似文献
Diagnostic accuracy has been addressed previously for Parkinson's disease in a brain bank collection, but accuracy of progressive supranuclear palsy (PSP) has not been addressed in a similar setting. Clinical and genetic features of pathologically confirmed cases of PSP were compared with misdiagnosed cases to determine ways to improve diagnostic accuracy. Medical records were reviewed for 180 cases sent to the Society of Progressive Supranuclear Palsy Brain Bank that had standardized neuropathologic evaluations as well as determination of apolipoprotein E and tau genotypes. Of the 180 cases studied, 137 had PSP and 43 had other pathologic diagnoses. Corticobasal degeneration (CBD), multiple system atrophy (MSA), and diffuse Lewy body disease (DLBD) accounted for 70% of the misdiagnosed cases. History of tremor, psychosis, dementia, and asymmetric findings were more frequent in misdiagnosed cases. The frequency of H1 tau haplotype (93 vs. 80%) and H1H1 genotype (86 vs. 66%) were significantly greater and APOE epsilon4 carrier state was significantly less (17 vs. 41 %) in PSP compared with misdiagnosed cases. Pathologic evaluation of clinically diagnosed PSP remains important for definitive diagnosis, and CBD, MSA, and DLBD are the disorders most likely to be misdiagnosed as PSP. Tremor, psychosis, early dementia, asymmetric findings, absence of H1 haplotype, and presence of APOE epsilon4 should raise questions about a diagnosis of PSP. 相似文献
Background: Contraction of airway smooth muscle is regulated by receptor-coupled mechanisms that control the force developed for a given cytosolic calcium concentration (i.e., calcium sensitivity). Halothane antagonizes acetylcholine-induced increases in calcium sensitivity by inhibiting GTP-binding (G)-protein pathways. The authors tested the hypothesis that hexanol, like halothane, inhibits agonist-induced increases in calcium sensitivity in airway smooth muscle by inhibiting G-protein pathways.
Methods: Calcium sensitivity was assessed using [alpha]-toxin-permeabilized canine tracheal smooth muscle. In selected experiments, regulatory myosin light chain phosphorylation was also determined by Western blotting in the presence and absence of 10 mm hexanol and/or 100 [mu]m acetylcholine.
Results: Hexanol (10 mm) and halothane (0.76 mm) attenuated acetylcholine-induced calcium sensitization by decreasing regulatory myosin light chain phosphorylation during receptor stimulation. Hexanol also inhibited increases in calcium sensitivity due to direct stimulation of heterotrimeric G-proteins with tetrafluoroaluminate but not with 3 [mu]m GTP[gamma]S, consistent with prior results obtained with halothane. In contrast, in the absence of receptor stimulation, both compounds produced a small increase in calcium sensitivity by a G-protein-mediated increase in regulatory myosin light chain phosphorylation that was not affected by pertussis toxin treatment. 相似文献