Inheritance of moyamoya disease in a Caucasian family.

BACKGROUND AND PURPOSE: Moyamoya disease is a very rare occlusive cerebrovascular disorder characterized by progressive stenosis or occlusion of the intracranial portion of the internal carotid artery and proximal cerebral arteries with an extensive network of fine collaterals. The aetiology and genetic susceptibility of moyamoya disease, especially in Caucasians, still remains unclear. METHODS AND RESULTS: We describe the cases of affected German father, daughter and son with juvenile stroke because of idiopathic moyamoya disease. The rare existing literature is reviewed and discussed. CONCLUSIONS: This is the first report on a father-to-child inheritance pattern in Caucasian patients with idiopathic Moyamoya disease (MMD). Our cases indicate possible genetic risk factors for the genesis of Caucasian Moyamoya disease.

[New options in the therapeutic management of acute ischaemic stroke. Good results with combined i. v. and i. a. lysis and mechanical thrombectomy]. / Neue Wege bei der Akuttherapie des ischämischen Schlaganfalls. Behandlungserfolge mit kombinierter i. v. und i. a. Lyse sowie mechanischer Thrombektomie.

BACKGROUND: Standard therapy for acute ischaemic stroke is the intravenous thrombolysis with rtPA. A combined therapy with intravenous bridging and consecutive intraarterial thrombolysis and mechanical thrombectomy is a relatively new option in patients with proximal vessel occlusion. PATIENTS AND METHODS: 10 Patients with a CTA proven proximal vessel occlusion in the anterior circulation (ACI, carotis bifurcation, MCA) in CTA were treated with a combined therapy with i. v. and i. a. thrombolysis and thrombectomy with a Solitaire FR stent device. RESULTS: All Patients were recanalized, the NIHSS changed from 15.6 to 3.3. 8 out of 10 patients had nearly no symptoms when dismissed. There were no direct therapeutic complications. CONCLUSION: Combined therapy with i. v. and i. a. thrombolysis and thombectomy with the Solitaire FR stent device is a promising option in patients with acute proximal vessel occlusion in the anterior circulation.

Chronic bronchitis before age 50 years predicts incident airflow limitation and mortality risk.

BACKGROUND: Previous studies on the relationship of chronic bronchitis to incident airflow limitation and all-cause mortality have provided conflicting results, with positive findings reported mainly by studies that included populations of young adults. This study sought to determine whether having chronic cough and sputum production in the absence of airflow limitation is associated with onset of airflow limitation, all-cause mortality and serum levels of C-reactive protein (CRP) and interleukin-8 (IL-8), and whether subjects' age influences these relationships. METHODS: 1412 participants in the long-term Tucson Epidemiological Study of Airway Obstructive Disease who at enrolment (1972-1973) were 21-80 years old and had FEV(1)/FVC (forced expiratory volume in 1 s/forced vital capacity) > or = 70% and no asthma were identified. Chronic bronchitis was defined as cough and phlegm production on most days for > or = 3 months in two or more consecutive years. Incidence of airflow limitation was defined as the first follow-up survey with FEV(1)/FVC <70%. Serum IL-8 and CRP levels were measured in cryopreserved samples from the enrolment survey. RESULTS: After adjusting for covariates, chronic bronchitis at enrolment significantly increased the risk for incident airflow limitation and all-cause mortality among subjects <50 years old (HR 2.2, 95% CI 1.3 to 3.8; and HR 2.2, 95% CI 1.3 to 3.8; respectively), but not among subjects > or = 50 years old (HR 0.9, 95% CI 0.6 to 1.4; and HR 1.0, 95% CI 0.7 to 1.3). Chronic bronchitis was associated with increased IL-8 and CRP serum levels only among subjects <50 years old. CONCLUSIONS: Among adults <50 years old, chronic bronchitis unaccompanied by airflow limitation may represent an early marker of susceptibility to the effects of cigarette smoking on systemic inflammation and long-term risk for chronic obstructive pulmonary disease and all-cause mortality.

Importance of large conductance calcium-activated potassium channels (BKCa) in interleukin-1b-induced adhesion of monocytes to endothelial cells.

OBJECTIVE: The present study investigated the role of the large conductance calcium-activated potassium channels (BKCa) in interleukin-1b (IL-1b) induced inflammation. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were isolated and cultured. Endothelial cell membrane potential measurements were accomplished using the fluorescent dye DiBAC4(3). The role of BKCa was assessed using iberiotoxin, a highly selective BKCa inhibitor. Changes in the calcium intracellular calcium were investigated using Fura-2-AM imaging. Fluorescent dyes DCF-AM and DAF-AM were further used in order to measure the formation of reactive oxygen species (ROS) and nitric oxide (NO) synthesis, respectively. Endothelial cell adhesion tests were conducted with BCECF-AM adhesion assay and tritium thymidine uptake using human monocytic cells (U937). Expression of cellular adhesion molecules (ICAM-1, VCAM-1) was determined by flow cytometer. RESULTS: Interleukin-1b induced a BKCa dependent hyperpolarization of HUVECs. This was followed by an increase in the intracellular calcium concentration. Furthermore, IL-1b significantly increased the synthesis of NO and ROS. The increase of intracellular calcium, radicals and NO resulted in a BKCa dependent adhesion of monocytes to HUVECs. Endothelial cells treated with IL-1b expressed both ICAM-1 and VCAM-1 in significantly higher amounts as when compared to controls. It was further shown that the cellular adhesion molecules ICAM-1 and VCAM-1 were responsible for the BKCa-dependent increase in cellular adhesion. Additionally, inhibition of the NADPH oxidase with DPI led to a significant downregulation of IL-1b-induced expression of ICAM and VCAM, as well as inhibition of eNOS by L-NMMA, and intracellular calcium by BAPTA. CONCLUSIONS: Activation of the endothelial BKCa plays an important role in the IL-1b-induced monocyte adhesion to endothelial cells.

Effect of glibenclamide on insulin release at moderate and high blood glucose levels in normal man.

Insulin release occurs in two phases; sulphonylurea derivatives may have different potencies in stimulating first- and second-phase insulin release. We studied the effect of glibenclamide on insulin secretion at submaximally and maximally stimulating blood glucose levels with a primed hyperglycaemic glucose clamp. Twelve healthy male subjects, age (mean +/- SEM) 22.5 +/- 0.5 years, body mass index (BMI) 21.7 +/- 0.6 kgm-2, were studied in a randomized, double-blind study design. Glibenclamide 10 mg or placebo was taken before a 4-h hyperglycaemic clamp (blood glucose 8 mmol L-1 during the first 2 h and 32 mmol L-1 during the next 2 h). During hyperglycaemic clamp at 8 mmol L-1, the areas under the delta insulin curve (AUC delta insulin, mean +/- SEM) from 0 to 10 min (first phase) were not different: 1007 +/- 235 vs. 1059 +/- 261 pmol L-1 x 10 min (with and without glibenclamide, P = 0.81). However, glibenclamide led to a significantly larger increase in AUC delta insulin from 30 to 120 min (second phase): 16087 +/- 4489 vs. 7107 +/- 1533 pmol L-1 x 90 min (with and without glibenclamide respectively, P < 0.03). The same was true for AUC delta C-peptide no difference from 0 to 10 min but a significantly higher AUC delta C-peptide from 30 to 120 min on the glibenclamide day (P < 0.01). The M/I ratio (mean glucose infusion rate divided by mean plasma insulin concentration) from 60 to 120 min, a measure of insulin sensitivity, did not change: 0.26 +/- 0.05 vs. 0.22 +/- 0.03 mumol kg-1 min-1 pmol L-1 (with and without glibenclamide, P = 0.64). During hyperglycaemic clamp at 32 mmol L-1, the AUC delta insulin from 120 to 130 min (first phase) was not different on both study days: 2411 +/- 640 vs. 3193 +/- 866 pmol L-1 x 10 min (with and without glibenclamide, P = 0.29). AUC delta insulin from 150 to 240 min (second phase) also showed no difference: 59623 +/- 8735 vs. 77389 +/- 15161 pmol L-1 x 90 min (with and without glibenclamide, P = 0.24). AUC delta C-peptide from 120 to 130 min and from 150 to 240 min were slightly lower on the glibenclamide study day (both P < 0.04). The M/I ratio from 180 to 240 min did not change: 0.24 +/- 0.04 vs. 0.30 +/- 0.07 mumol kg-1 min-1 pmol L-1 (with and without glibenclamide, P = 0.25). In conclusion, glibenclamide increases second-phase insulin secretion only at a submaximally stimulating blood glucose level without enhancement of first-phase insulin release and has no additive effect on insulin secretion at maximally stimulating blood glucose levels. Glibenclamide did not change insulin sensitivity in this acute experiment.