Seizures can be triggered by stimulating non-cortical structures in the quaking mutant mouse

Mutant Quaking mice (C57BL/6J) display convulsive tonic-clonic seizures that can be either spontaneous or triggered by manipulation of the animal or by auditory stimulation. Several abnormalities have been found (especially in the noradrenergic system) in the brainstem of this mutant strain. We first verified by electrophysiological recording that the cerebral cortex was not involved in the generation or in the development of these fits. Then we showed that tonic-clonic seizures similar to those obtained in the freely moving animal were triggered by low-threshold (LT, 5-50 microA) or high-threshold (HT, 55-150 microA) stimuli performed during head restraint. LT stimuli were mostly efficient in a number of ponto-bulbar and mesencephalic structures, including several reticular nuclei, the locus coeruleus, the nucleus subcoeruleus and the red nucleus, whereas HT stimuli were generally necessary to trigger fits by stimulating the nuclei pontis, the substantia nigra, the central gray area and the cerebellar nuclei. Seizures were also provoked at the diencephalic level with LT stimulation delivered in the medial thalamic area, the nucleus reticularis thalami and some subthalamic regions (zona incerta, H field of Forel). In contrast, no fits were obtained by stimulating the cerebellar cortex and the inferior colliculus, the ventral and lateral groups of thalamic nuclei or the telencephalic regions (hippocampus, amygdala, caudate nucleus, putamen and cerebral cortex), with the exception of the globus pallidus.     

Mucous Gland Adenoma Simulating Bronchial Asthma: Case Report and Literature Review

We report a case of mucous gland adenoma arising in the left main bronchus which was initially misdiagnosed as asthma and review the previous reported cases of this rare tumor published in the available literature.     

Mechanisms of cold sensitivity of paramyotonia congenita mutation R1448H and overlap syndrome mutation M1360V

Missense mutations of the human skeletal muscle voltage-gated Na⁺ channel (hSkM1) cause a variety of neuromuscular disorders. The mutation R1448H results in paramyotonia congenita and causes cold-induced myotonia with subsequent paralysis. The mutation M1360V causes an overlapping syndrome with both K⁺-induced muscle weakness and cold-induced myotonia. The molecular mechanisms of the temperature dependence of these disorders are not well understood. Therefore we investigated physiological parameters of these Na⁺ channel mutations at different temperatures. Channel proteins were recombinantly expressed in human embryonic kidney cells and studied electrophysiologically, using the whole-cell patch-clamp technique. We compared the wild-type (WT) channel with both mutants at different temperatures. Both mutations had slower inactivation and faster recovery from inactivation compared to WT channels. This effect was more pronounced at the R1448H mutation, leading to a larger depolarization of the cell membrane causing myotonia and paralysis. The voltage dependence of activation of R1448H was shifted to more negative membrane potentials at lower temperature but not at the M1360V mutation or in the WT. The window current by mutation R1448H was increased at lower temperatures. The results of this study may explain the stronger cold-induced clinical symptoms resulting from the R1448H mutation in contrast to the M1360V mutation.     

Neuroendocrine Tumor Arising within Mature Cystic Teratoma of the Pancreas: Literature Review and Case Report

Cystic teratomas are germ cell tumors most commonly found in the ovaries and testes. The pancreas, however, is very rare as a site of occurrence. Moreover, only two cases of cystic teratoma with concomitant neuroendocrine tumor have been reported to date. We report the case of a 33-year-old female who presented with abdominal pain. Computed tomography and magnetic resonance imaging of the upper abdomen revealed an 85 mm cystic tumor in the head of the pancreas. Cystic teratoma and mucinous cystadenoma were suggested as differential diagnoses. Cytopathologic analysis of endoscopic ultrasound-guided fine needle aspiration was consistent with mucinous cystadenoma. Therefore, the patient underwent surgical resection. Histologic analysis revealed a mature cystic teratoma of the pancreas with a concomitant neuroendocrine tumor. The patient is in great condition at 8 months follow-up. Cystic teratoma of the pancreas with a concomitant neuroendocrine tumor is an extremely rare condition. Surgical resection remains the mainstay of treatment as it provides a definitive diagnosis and no recurrences have been reported to date.     

Relation of N-terminal pro B-type natriuretic peptide to progression of aortic valve disease.

AIMS: Recently an elevation of B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) in patients with aortic stenosis (AS) and aortic regurgitation (AR) has been described. The objective of this study was to evaluate the relation of NT-proBNP values to the progression of aortic valve disease. METHODS AND RESULTS: One hundred and sixty-eight patients were included. NT-proBNP was elevated in patients with AS (n=109) and AR (n=37) linked to disease severity. Values for NT-proBNP, pressure gradient, and left ventricular mass were identical in patients (n=22) after previous valve replacement and in those patients with mild AS. NT-proBNP levels decreased in 86 patients after valve replacement (2292+/-353 vs. 785+/-101 pg/ml; P<0.01) but increased in 82 patients who were treated conservatively (616+/-120 vs. 1155+/-432 pg/mL; P=0.029), related to the progression of disease. CONCLUSION: NT-proBNP is elevated in patients with aortic valve disease linked to disease severity and decreases after successful surgical therapy but increases in conservatively treated patients. These data underline the consistent relation of NT-proBNP to severity of aortic valve disease. Therefore, NT-proBNP should be considered as a biomarker for the monitoring of disease during follow-up, but further studies are warranted.     

Gastrin and antral G cells in course of Helicobacter pylori eradication： Six months follow up study

ABM: To assess long-term effects of Helicobacter pylori (H pylori) eradication on antral G cell morphology and function in patients with and without duodenal ulcer (DU). METHODS: Consecutive dyspeptic patients referred to the endoscopy entered the study. Out of 39 H pylori positive patients, 8 had DU (Hpylori+DU) and 31 gastritis (Hpylori +G). Control groups consisted of 11 uninfected dyspeptic patients (CG1) and 7 healthy volunteers (CG2). Basal plasma gastrin (PGL), antral tissue gastrin concentrations (ATGC), immunohistochemical and electron microscopic characteristics of G cells were determined, prior to and 6 mo after therapy. RESULTS: We demonstrated elevated PGL in infected patients compared to uninfected controls prior to therapy. Elevated PGL were registered in all H pylori+patients (H pylori +DU: 106.78±22.72 pg/mL, H pylori+G: 74.95±15.63, CG1: 68.59±17.97, CG2: 39.24±5.59 pg/mL, P<0.01). Successful eradication (e) therapy in H pylori+patients lead to significant decrease in PGL (H pylori+DU:59.93±9.40 and H pylori+Ge: 42.36±10.28 pg/mL, P<0.001). ATGC at the beginning of the study were similar in infected and uninfected patients and eradication therapy lead to significant decrease in ATGC in H pylori+gastritis, but not in DU patients. In the H pylori+DU patients, the mean number of antral G cells was significantly lower in comparison with all other groups (P<0.01), but after successful eradication was close to normal values found in controls. By contrast, G cell number and volume density were significantly decreased (P<0.01) in H pylori+Ge group after successful eradication therapy (294±32 and 0.31±0.02, respectively), in comparison to values before eradication (416±40 and 0.48±0.09). No significant change of the G cell/total endocrine cell ratio was observed during the 6 mo of follow up in any of the groups. A reversible increase in G cell secretory function was seen in all infected individuals, demonstrated by a more prominent secretory apparatus. However, differences between DU and gastritis group were identified. CONCLUSION: H pylori infection induces antral G cell hyperfunction resulting in increased gastrin synthesis and secretion. After eradication therapy complete morphological and functional recovery is observed in patients with gastritis. In the DU patients some other factors unrelated to the H pylori infection influence antral G cell morphology and function.     

Long-term prognosis of patients with early post-infarction angina.

BACKGROUND: Most studies have shown that early post-infarction angina (EPA) implies an unfavorable long-term prognosis among patients with acute myocardial infarction (AMI). However, some studies have failed to establish a link between the occurrence of EPA and increased mortality and recurrent infarction rates. METHODS AND RESULTS: In order to evaluate a long-term prognosis in patients with EPA, we assessed the 5-year prognosis of 80 patients with AMI by the presence or absence of EPA. During the 5-year follow up, the occurrence of death, cardiac death, recurrent infarction, unstable angina, heart failure, revascularization and cardiac events were recorded. A cardiac event was defined as an occurrence of any of the following events: cardiac death, recurrent infarction, unstable angina, heart failure and revascularization. Survival analysis showed no differences between patients with and without EPA in the probability of death (p=NS), cardiac death (p=NS), recurrent myocardial infarction (p=NS) and unstable angina (p=NS). Patients with EPA had a higher probability of developing cardiac events (p=0.0285) and undergoing revascularization procedures (p=0.0188). CONCLUSIONS: EPA increases the risk of patients developing cardiac events and undergoing revascularization procedures, and thereby implies a poor long-term prognosis for patients with AMI.     

Are There Differences in Arteriovenous Fistulae Created for Hemodialysis between Nephrologists and Vascular Surgeons?

ObjectiveMany studies have reported insufficient support from surgical services, resulting in nephrologists creating arteriovenous fistulas in many centers. The aim of this study was to compare risk factors of arteriovenous fistula dysfunction in patients whose fistulas were created by nephrologists versus vascular surgeons.MethodsThis was a retrospective, analytical study of interventions by nephrologists and vascular surgeons during a period of 15 years. Out of a total of 1,048 fistulas, 764 (72.9%) were created by nephrologists patients, while vascular surgeons were responsible for 284 (27.1%) fistulae. Laboratory, demographic, and clinical parameters which might affect functioning of these arteriovenous fistulae were analyzed.ResultsPatients whose arteriovenous fistula was formed by nephrologists differed significantly from those created by vascular surgeons in relation to the preventive character of the arteriovenous fistula (p = 0.011), lumen of the vein (p < 0.001) and systolic blood pressure (p = 0.047). Multivariate logistic regression of arteriovenous fistula dysfunction showed that risk factors were female gender (odds ratio [OR] = 1.56, 95% CI 1.16–2.07), whether the fistulae were created by vascular surgeons or nephrologists (OR = 1.38; 95% CI 1.01–1.89) and the site of the arteriovenous fistula (OR = 0.64; 95% CI 0.48–0.85).ConclusionsArteriovenous fistulae created by vascular surgeons, female gender, and the location are risk factors of dysfunction.     

Effect of single doses of SLV306, an inhibitor of both neutral endopeptidase and endothelin-converting enzyme, on pulmonary pressures in congestive heart failure

SLV306, a potent neutral endopeptidase (NEP) inhibitor with additional endothelin-converting enzyme (ECE)-inhibitory activity, in doses of 200, 400, and 800 mg reduced pulmonary and right atrial pressures, although there was not a clear dose response. Systemic blood pressure, heart rate, and cardiac output were unaffected. SLV306 increased plasma natriuretic peptides and big endothelin-1 levels in a dose-dependent manner, confirming NEP and ECE inhibition. The combined inhibition of NEP and ECE may be useful in heart failure by reducing right and left cardiac filling pressures.     

Relation of N-terminal pro-B-type natriuretic peptide to severity of valvular aortic stenosis

N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been shown to be a reliable biochemical marker for left ventricular wall stress and is increased in patients with aortic stenosis (AS). We evaluated the role of NT pro-BNP as a biochemical marker in the diagnosis of AS and whether it contributes to the optimal timing for aortic valve replacement (AVR). Included in this study were 146 patients who had AS, 31 who underwent AVR, and 32 who had "normal valve function" (controls). Increased NT pro-BNP was closely linked to severity of AS (mild AS 612 +/- 151 pg/ml, moderate AS 1,441 +/- 32 pg/ml, severe AS 2,579 +/- 13 pg/ml, AVR 593 +/- 148 pg/ml, controls 140 +/- 27 pg/ml; p <0,01) and to New York Heart Association functional class (class I 601 +/- 116 pg/ml, class II 1,119 +/- 216 pg/ml, class III 1,998 +/- 459 pg/ml, class IV 5,107 +/- 1,512 pg/ml; p <0.01). Area under the receiver-operating characteristic curve for NT pro-BNP as a predictor for AVR was 0.73. Using an optimized cutoff of 550 pg/ml for NT-proBNP, the positive predictive value was 85%. Thus, NT pro-BNP is linked to severity of AS and New York Heart Association class and is an indication for AVR. Therefore, it is a useful biochemical marker to evaluate severity of AS, monitor disease progression at an early stage, and decide on the optimal time for AVR.