Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis.

Axon outgrowth during development and neurotransmitter release depends on exocytotic mechanisms, although what protein machinery is common to or differentiates these processes remains unclear. Here we show that the neural t-SNARE (target-membrane-associated-soluble N-ethylmaleimide fusion protein attachment protein (SNAP) receptor) SNAP-25 is not required for nerve growth or stimulus-independent neurotransmitter release, but is essential for evoked synaptic transmission at neuromuscular junctions and central synapses. These results demonstrate that the development of neurotransmission requires the recruitment of a specialized SNARE core complex to meet the demands of regulated exocytosis.     

L-Dopa-responsive Parkinson's syndrome in association with phenylketonuria: In vivo dopamine transporter and D2 receptor findings.

Reports of parkinsonism in phenylketonuria are exceedingly rare. We report on a patient who had received a delayed diagnosis of phenylketonuria as an infant and subsequently developed levodopa-responsive parkinsonism at the age of 33. Single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123))I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) used to measure dopamine transporter levels on two occasions, 7 and 9 years after the onset of neurological symptoms, were normal. Iodine-123-iodo-lisuride SPECT (IBZM) imaging, however, showed reduced caudate over putamen binding. This combination of imaging findings indicates a possible upregulation of postsynaptic D2 receptors in the context of intact presynaptic dopamine nerve terminal density.     

Fetal magnetic resonance imaging in the prenatal diagnosis of cerebellar hemorrhage.

We report the case of a fetus with a sonographic mid-gestation diagnosis of hyperechogenic cerebellum suspected to be of hemorrhagic origin on fetal brain magnetic resonance imaging (MRI). No etiological factors for fetal hemorrhage were found other than a maternal heterozygocity for factor V Leiden. Following termination of the pregnancy, autopsy confirmed the prenatal diagnosis of massive cerebellar hemorrhage without underlying vascular anomaly. As an additional tool to ultrasonography, fetal brain MRI can affirm the hemorrhagic origin of hyperechogenic cerebellar lesions, especially by showing a high signal on T1-weighted images.     

Spontaneous angina caused by spasm of the left coronary artery]

A 42 year old woman presented with a one year history of retrosternal chest pain and back pain on effort and at rest sometimes accompanied by minor syncopal attacks. Transient atrioventricular block was documented during one such episode associated with hypotension. Coronary angiography showed spontaneous spasm of the left main coronary artery with clinical symptoms but no electrocardiographic changes. The spasm was relieved by injection of SIN-1. The similarity between the previous clinical symptoms and those observed at coronary angiography was in favour of the diagnosis of spasm of the left main coronary artery without atherosclerotic coronary disease. Treatment with calcium atherosclerotic coronary disease. Treatment with calcium blockers and platelet antiaggregants led to total regression of her symptoms with a follow-up of 5 months.     

Serial angiographic follow-up of sirolimus-eluting stents for unprotected left main coronary artery revascularization.

OBJECTIVES: This study was performed to evaluate the clinical and serial angiographic outcomes of patients undergoing sirolimus-eluting stent (SES) implantation for unprotected left main coronary artery (LMCA) stenosis. BACKGROUND: The efficacy of SES has led to their expanded use for off-label indications, including LMCA disease. METHODS: Unprotected LMCA intervention with SES was attempted in 50 patients. Surveillance angiography was performed at three and nine months' follow-up. RESULTS: The target lesion involved the distal LMCA in 47 patients (94%). In-lesion restenosis occurred in 21 patients (42%), was focal in 85% of cases, and in 82% involved the branch ostia, sparing the LMCA itself. Target lesion revascularization (TLR) occurred in 19 patients (38%) over a mean follow-up of 276 +/- 57 days; TLR was ischemia-driven in 7 patients (14%). Late loss was significantly greater within the left circumflex (LCX) ostium compared to the parent vessel (PV) of the LMCA bifurcation (0.83 +/- 0.89 mm vs. 0.49 +/- 0.72 mm, p = 0.04). Late loss continued to increase between three- and nine-month follow-up. Final minimal luminal diameter and maximal balloon pressure were independent predictors of restenosis of the PV. CONCLUSIONS: Restenosis is a frequent finding when serial angiographic follow-up is performed after SES implantation for unprotected distal LMCA lesions. Restenosis is usually focal, most often involves the LCX ostium, and often occurs without symptoms.     

Morphological analysis of the acute effects of overdistension on the extracellular matrix of the rat urinary bladder wall.

PURPOSE: To investigate the morphological effects of acute overdistension in the structure of the extracellular matrix of the bladder wall in rats. MATERIALS AND METHODS: The bladders of a group of 6 male Wistar rats were transurethrally overdistended for 3 hours. Another identical group (the control group) was only submitted to a sham operation. Specimens from the bladder dome were analyzed with light microscopy (LM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). RESULTS: LM--The control group bladders had a 4 to 5 layer urothelium, a lamina propria, and a smooth muscle layer with longitudinal and transversal fibers. The overdistended bladders presented an intense interstitial infiltrate in the lamina propria, and a less intense infiltrate among the smooth muscle fibers. TEM--The cells of the overdistended bladders had a significant amount of vacuoles, unlike the control bladders, where such vacuoles were scarce or absent. SEM--A delicate three-dimensional mesh of collagen fibrils was observed in the lamina propria of the bladder walls from the control group. Whilst for the control group this mesh consisted of distinct geometric structures, with mostly circular cellular spaces surrounded by the fibrils, the overdistended group showed evidence of distortion of the mesh, with flattened and elongated cellular spaces. CONCLUSIONS: Acute bladder overdistension induces structural modifications, altering the arrangement and interaction of collagen fibrils, as well as incipient tissue damage as edema in the lamina propria and smooth muscle layers.     

Ethics roundtable debate: Patients and surrogates want 'everything done' – what does 'everything' mean?

Highly complex and specialized care plans sometimes overwhelm the comprehension of patients and families. Many optimistic surrogates of critically ill patients err on the side of desiring that everything be done but with a nebulous idea of what 'everything' entails. Physicians must work closely to educate surrogates as to the benefits versus the risks of treatment. Our roundtable experts ponder the question of whether providers possess the authority to interpret unilaterally the nature of requests for everything.     

Stability of skeletal Class III malocclusion after combined maxillary and mandibular procedures: titanium versus resorbable plates and screws for maxillary fixation.

PURPOSE: The aim of this study was to evaluate skeletal stability after double jaw surgery for correction of skeletal Class III malocclusion to assess if there were any differences between resorbable plate and screws and titanium rigid fixation of the maxilla. PATIENTS AND METHODS: Twenty-two Class III patients had bilateral sagittal split osteotomy for mandibular setback stabilized with rigid internal fixation. Low level Le Fort I osteotomy for maxillary advancement was stabilized with conventional titanium plate and screws in 12 patients (group 1) and with resorbable plate and screws in 10 patients (group 2). Lateral cephalograms were taken before surgery, immediately postoperatively, 8 weeks after surgery, and 1 year postoperatively. RESULTS: Before surgery both groups were balanced with respect to linear and angular measurements of craniofacial morphology. One year after surgery, maxillary stability was excellent in both groups. In group 1 no significant correlations were found between maxillary advancement and relapse. In group 2, significant correlations were found between maxillary advancement and relapse at A point and posterior nasal spine. No significant differences in postoperative skeletal and dental stability between groups were observed. CONCLUSION: Surgical correction of Class III malocclusion after combined maxillary and mandibular procedures appears to be a fairly stable procedure for maxillary advancements up to 5 mm independently from the type of fixation used to stabilize the maxilla. Resorbable devices should be used with caution for bony movements of greater magnitude until their usefulness is evaluated in studies with large maxillary advancements.     

Gastro-oesophageal and bile reflux--simultaneous quantitative assessment with gastric and gallbladder emptying evaluation: clinical applicability of a new computerized gammagraphic method.

The aim of this study was to develop a new computerized gammagraphic method to evaluate gastrooesophageal (GER), bileo-oesophageal (BER) and bileogastric reflux (BGR) simultaneously with gastric and gallbladder emptying: a long duration (60 min) and a dual energy detection (113Inm-sulphur colloid and 99Tcm-HIDA) test of the different refluxes during slow gastric emptying of an enteric feeding liquid meal. Forty patients with oesophagitis and 18 normal volunteers were evaluated. Good reproducibility of all the quantified parameters was found with r Spearman between 0.75 (P < 0.05) and 1.0 (P < 0.001). Patients with oesophagitis have a tendency for slower gastric emptying patterns (gastric emptying T1/2, GT1/2 P < 0.05). The calculated specificity for gallbladder emptying parameters was 77.8% for the gallbladder T1/2 BT1/2) and 94.4% for gallbladder residue at 60 min (BR60). The calculated accuracy for the GER index was 90%. The predictability for positive values was 95%, owing to a 90% sensitivity and 89% specificity. The predictability for negative values was 80%. The mean GER index in oesophagitis was greater than in controls (P < 0.001). The calculated specificity for BGR was 94.4% and reflux was detected in 12 out of 40 patients. The calculated specificity for BER was 83.3% for a '+' index and 94.4% for a '++' BER index. In 14 patients a positive BER index has been determined ('+' in three and '++' in 11 cases).(ABSTRACT TRUNCATED AT 250 WORDS)     

The brain as a target for adrenocortical steroids: cognitive implications.

It is well established that a reciprocal control exists between the brain and glucocorticoid hormones. The brain regulates adrenocortical function via hypothalamic corticotrophin releasing hormone-41 (CRH-41), glucocorticoids act at specific receptors in the hippocampus, thus promoting negative feedback mechanisms. Because the hippocampus is a major site for memory processes, a role for excessive/long-lasting plasma glucocorticoid levels has been suggested in conditions of mental impairment. Major depression, Cushing's disease, and dementia of the Alzheimer type are disorders which share hyperactivity of the hypothalamo-pituitary-adrenal axis, as well as symptoms of cognitive decline. Although the mechanisms leading to hypercortisolemia appear to be different in each case, the neuropsychological features of these three disorders accord with the hypothesis of glucocorticoid-associated brain damage. It therefore is important to find pharmacological strategies that will avert or reduce these potential consequences on brain function.