Safety and long-term effects of renal denervation: Rationale and design of the Dutch registry.

BACKGROUND: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapy-resistant hypertension. Also, it has been suggested that RDN may be beneficial for other conditions characterised by increased sympathetic nerve activity. There are still many uncertainties with regard to efficacy, safety, predictors for success and long-term effects. To answer these important questions, we initiated a Dutch RDN registry aiming to collect data from all RDN procedures performed in the Netherlands. METHODS: The Dutch RDN registry is an ongoing investigator-initiated, prospective, multicentre cohort study. Twenty-six Dutch hospitals agreed to participate in this registry. All patients who undergo RDN, regardless of the clinical indication or device that is used, will be included. Data are currently being collected on eligibility and screening, treatment and follow-up. RESULTS: Procedures have been performed since August 2010. At present, data from 306 patients have been entered into the database. The main indication for RDN was hypertension (n = 302, 99%). Patients had a mean office blood pressure of 177/100 (±29/16) mmHg with a median use of three (range 0-8) blood pressure lowering drugs. Mean 24-hour blood pressure before RDN was 157/93 (±18/13) mmHg. RDN was performed with different devices, with the Simplicity™ catheter currently used most frequently. CONCLUSION: Here we report on the rationale and design of the Dutch RDN registry. Enrolment in this investigator-initiated study is ongoing. We present baseline characteristics of the first 306 participants.

No effects of acute hyperglycaemia and hyperinsulinaemia on skin microcirculation and endothelial markers in Type II diabetes mellitus.

BACKGROUND: Increased microvascular permeability is a hallmark of microangiopathy in Type I diabetes mellitus and is associated with endothelial dysfunction and haemodynamic alterations. Type II diabetes mellitus is characterized by insulin resistance and hyperinsulinaemia. The purpose of this study was to determine whether acute hyperinsulinaemia, under both normoglycaemic and hyperglycaemic conditions, increases skin capillary permeability through its effect on skin haemodynamics, capillary recruitment or circulating markers of endothelial dysfunction in Type II diabetes. METHODS: Nine Type II diabetic patients without microalbuminuria, (pre-) proliferative retinopathy or clinical neuropathy underwent three glucose clamps of 210 min., in random order, on separate days. A "standard" clamp (insulin-infusion rate 30 mU kg(-1) h(-1), glucose-target 5.0 mmol/L) was compared with a hyperinsulinaemic (insulin-infusion rate 150 mU kg(-1) h(-1), glucose-target 5.0 mmol/L) and a hyperinsulinaemic, hyperglycaemic (insulin-infusion rate 150 mU kg(-1) h(-1), glucose-target 12.0 mmol/L) clamp. Skin capillary permeability and density were measured using large-window sodium fluorescein videodensitometry, and skin blood flow by laser Doppler flowmetry. Endothelial dysfunction was estimated from increases in soluble intercellular adhesion molecule-1 (sICAM-1) and von Willebrand factor antigen (vWF). RESULTS: No differences were found in skin capillary permeability, skin haemodynamics and capillary density at the end of the three glucose clamp periods. sICAM-1 and vWF did not increase as compared to the standard glucose clamp. sICAM-1 (r=-0.76, p<0.05) and vWF (r=-0.71, p<0.05) correlated negatively with insulin sensitivity, but not with skin microcirculatory parameters. CONCLUSIONS: Acute hyperinsulinaemia, both with and without concomitant hyperglycaemia, does not increase skin microvascular permeability, haemodynamics or parameters of endothelial dysfunction in Type II diabetic patients. Furthermore, these data suggest that the coexistence of hyperinsulinaemia and endothelial dysfunction in Type II diabetes does not indicate a causal relationship, but may rather indicate decreased insulin sensitivity as a common underlying cause.

Acute hyperglycemia and hyperinsulinemia enhance vasodilatation in Type 1 diabetes mellitus without increasing capillary permeability and inducing endothelial dysfunction.

Uncomplicated Type 1 (insulin-dependent) diabetes mellitus is characterized by generalized vasodilatation. Its possible correlates, increased microvascular permeability and endothelial dysfunction, have been associated with long-term complications. The objective was to study the effects of acute hyperglycemia and hyperinsulinemia, both separately and in combination, on skin microvascular flow, capillary permeability, capillary recruitment, and endothelial dysfunction in Type 1 diabetes mellitus. Sixteen Type 1 diabetic patients (all normoalbuminuric, no (pre-)proliferative retinopathy) underwent a euglycemic (glucose target 5.0 mmol/L, insulin infused at 30 mU x kg(-1) x h(-1)), a hyperglycemic (glucose target 12.0 mmol/L, insulin 30 mU x kg(-1) x h(-1)), a hyperinsulinemic (glucose target 5.0 mmol/L, insulin 150 mU x kg(-1) x h(-1)), and a hyperglycemic-hyperinsulinemic (glucose target 12.0 mmol/L, insulin 150 mU x kg(-1) x h(-1)) clamp on separate days, in random order. Skin microvascular flow was measured by laser Doppler flowmetry. Capillary permeability and density were determined by large-window sodium-fluorescein videodensitometry. Increases in serum soluble intercellular adhesion molecule-1 (sICAM-1) and plasma von Willebrand factor antigen (vWF-Ag) were considered to represent abnormal endothelial function. Hyperglycemia (P < 0.01) and hyperinsulinemia (P < 0.05) as well as both interventions combined (P < 0.001) induced an increase in laser Doppler flow, without capillary recruitment. Transcapillary leakage of sodium-fluorescein and sICAM-1 and vWF-Ag levels were unaffected by hyperglycemia or hyperinsulinemia. Microvascular permeability appears to be determined primarily by properties of the capillary wall and not by acute changes in local hemodynamics. The acute hyperglycemia- and hyperinsulinemia-induced vasodilatation is not accompanied by changes in microvascular permeability or endothelial markers.

[Spondylodiscitis cause by Brucella suis]. / Spondylodiscitis door Brucella suis.

In a 72-year-old Dutchman Brucellae suis spondylodiscitis TXII-LI was diagnosed, complicated by a paraspinal abscess, for which surgical drainage was carried out. The patient failed to recover after the combined antibiotic regimen of doxycycline, rifampicin and trimethoprim-sulfamethoxazole. There was good clinical improvement after a course of doxycycline and streptomycin, however. After a symptom-free period of 9 weeks a relapse occurred. The patient refused treatment and died 6 weeks later at home. The infection had probably been contracted after handling wild boar carcasses from eastern Europe.