Vascular endothelial dysfunction in Duchenne muscular dystrophy is restored by bradykinin through upregulation of eNOS and nNOS

Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscular dystrophy (GRMD) dogs with left ventricular dysfunction (measured by echocardiography) and in isolated coronary arteries. eNOS and nNOS proteins in carotid arteries were measured by western blot and cyclic guanosine monophosphate (cGMP) content was analyzed by radioimmunoassay. Compared with controls, GRMD dogs had an impaired vasodilator response to acetylcholine. In isolated coronary artery, acetylcholine-elicited relaxation was nearly absent in placebo-treated GRMD dogs. This was explained by reduced nNOS and eNOS proteins and cGMP content in arterial tissues. Chronic bradykinin infusion (1 μg/min, 4 weeks) restored in vivo and in vitro vascular response to acetylcholine to the level of control dogs. This effect was NO-mediated through upregulation of eNOS and nNOS expression. In conclusion, this study is the first to demonstrate that DMD is associated with NO-mediated vascular endothelial dysfunction linked to an altered expression of eNOS and nNOS, which can be overcome by bradykinin.     

The clinical differences between dengue and scrub typhus with acute respiratory failure in southern Taiwan

Background

For both dengue and scrub typhus, acute respiratory failure (ARF) is a serious complication. The present study was carried out in order to investigate the clinical courses and outcomes of adult dengue and scrub typhus patients with ARF, and to identify the clinical differences between adult dengue and scrub typhus patients with ARF.

Methods

We conducted a retrospective study of the serologically confirmed adult dengue or scrub typhus patients admitted between 1998 and 2008 at Kaohsiung Chang Gung Memorial Hospital. A total of 980 dengue and 102 scrub typhus adult patients were included in our study.

Results

Eighteen of the 980 adult dengue patients and 8 of the 102 adult scrub typhus patients had ARF. There were significant differences that existed for eschar (P?=?0.001; dengue 0%; scrub 62.5%), cough (P?=?0.016; dengue 55.6%; scrub typhus 100%), white blood cell (WBC) count [P?=?0.026; dengue 7.40?±?5.74; scrub typhus 11.84?±?4.95 (×10³/??L)], platelet count [P?=?0.008; dengue 42.2?±?33.9; scrub typhus 104.1?±?93.3 (×10⁹/L)], prothrombin time (PT) [P?=?0.007; dengue 12.82?±?1.36; scrub typhus 10.74?±?0.98 (s)], activated partial thromboplastin time (APTT) [P?=?0.002; dengue 50.81?±?10.08; scrub typhus 37.44?±?4.06 (s)], blood urea nitrogen (BUN) [P?P?P?=?0.027; dengue 2.9?±?1.3; scrub typhus 5.4?±?2.6 (days)], and ventilator duration [P?=?0.022; dengue 9.4?±?14.0; scrub typhus 14.8?±?10.4 (days)] between both groups.

Conclusions

This study provides relatively rare data regarding the clinical differences between adult dengue and scrub typhus patients with ARF.     

A case of adenocarcinoma in situ of the distal common bile duct diagnosed by percutaneous transhepatic cholangioscopy

Extrahepatic cholangiocarcinoma is often clinically challenging to diagnose. Even multidisciplinary approaches which include computed tomography, magnetic resonance imaging, and endoscopic retrograde cholangiography are unsatisfactory in some cases, especially with biliary stricture. Percutaneous transhepatic cholangioscopy (PTCS) with its direct visualization for biopsy appears to be a promising technique for detecting cholangiocarcinoma at an early stage. We report a case of adenocarcinoma in situ of the distal common bile duct (CBD) that was confirmed by PTCS. This case suggests the useful role of PTCS in the differential diagnosis of a distal CBD obstruction, particularly when other diagnostic modalities do not provide definitive information.     

Monitoring complex secundum atrial septal defects percutaneous closure with real time three-dimensional echocardiography

Background: Atrial septal defect (ASD) is one of the most common congenital heart diseases. Nowadays, percutaneous closure is considered the treatment of choice in most of secundum ASDs. Assessment of the defect and procedure monitoring have been usually performed by angiographic balloon‐sizing and/or two‐dimensional (2D) transesophageal echocardiography. However, in complex ASDs these techniques might be inaccurate. Methods: From January 2009 to January 2011 all adult patients with complex ASDs submitted for percutaneous closure were selected. Those defects, where shunts were present through a device previously implanted on the atrial septum or through multiperforated septums, were considered complex ASDs. Two‐dimensional transesophageal echocardiography and real time three‐dimensional (3D) echocardiography were performed simultaneously during the percutaneous closure procedure. Number of orifices, relationships between the defect, catheter, and device, as well as residual shunt were assessed. Results: Seven patients were included. Five patients had a multiperforated septum and in two cases the defect in the septum was through a previously implanted device. In all cases, 3D echocardiography was superior to 2D echocardiography in relation to the assessment of the relationship between the defect and the catheter or the device. Mechanisms responsible for residual shunts through a device were also better assessed by 3D echocardiography. Conclusion: Three‐dimensional echocardiography is a safe and useful technique when monitoring percutaneous closure of ASDs, showing relevant advantages over 2D echocardiography. (Echocardiography 2012;29:729‐734)