Stress test of the skin: The cutaneous permeability barrier treadmill

Studying skin barrier function is central to our understanding of many skin disorders. The past decade has seen a surge of skin barrier related investigative work. Genetic, biochemical and cell biology experiments have added much evidence to the importance of the barrier in disease pathogenesis of a variety of disorders including ichthyosis, atopic dermatitis and psoriasis. However, functional assays prove ever more important to demonstrate relevance of any of these findings. A paper published by Monash and Blank 60 years ago describes a stress test of the skin barrier, measuring skin barrier recovery, a functional test of tremendous implications. This seminal paper has not been cited for almost 15 years, time to acknowledge its critical importance and to review the relevance of this method today.     

Does monthly native arteriovenous fistula blood-flow surveillance detect significant stenosis--a randomized controlled trial.

BACKGROUND: Clinical practice guidelines recommend that the preferred method of surveillance for arteriovenous fistula (AVF) is the measurement of AVF blood flow (Qa). As these recommendations are based on observational studies, we conducted a randomized, prospective, double-blind, controlled trial to assess whether Qa surveillance results in an increased detection of AVF stenosis. METHODS: A total of 137 patients were randomly assigned to receive either continuing AVF surveillance using current clinical criteria (control, usual treatment) or usual treatment plus AVF blood-flow surveillance by ultrasound dilution (Qa surveillance group). The primary outcome measure was the detection of a significant (>50%) AVF stenosis. RESULTS: There were 67 and 68 patients assigned to the control and Qa surveillance groups, respectively. Patients in the Qa surveillance group were twice as likely to have a stenosis detected compared with the control hazard ratio (HR) confidence interval (CI) group (2.27, 95% 0.85-5.98, P = 0.09), with a trend for a significant stenosis to be detected earlier in the Qa surveillance group (P = 0.09, log rank test). However, using the Qa results alone prior to angiography, the area under the receiver operating characteristic curve demonstrated, at best, a moderate prediction of (>50%) AVF stenosis (0.78, 95% CI 0.63-0.94, P = 0.006). CONCLUSION: This study demonstrates that the addition of AVF Qa monitoring to clinical screening for AVF stenosis resulted in a non-significant doubling in the detection of angiographically significant AVF stenosis. Further, large multi-centre randomized trials are feasible and will be necessary to confirm whether Qa surveillance and the correction of detected AVF stenosis will lead to a reduction in AVF thrombosis and increased AVF survival.     

PINK1 mutations in sporadic early-onset Parkinson's disease.

Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.     

Agenesis of the Gallbladder Revisited Laparoscopically

Gallbladder agenesis is an extremely rare disease. Necropsy incidence has been reported to be 0.016%. Failure lo locate the gallbladder at the time of a planned cholecystectomy can be very challenging. We report such a case during a laparoscopic cholecystectomy. The indication for surgery in these patients are complaints of gallbladder symptoms along with a false-positive ultrasound study. During exploration, an abnormal location of the gallbladder has to be excluded. Ectopic gallbladder locations include intrahepatic, lesser omentum, retroperitoneal, retrohepatic, within the falciform ligament, retroduodenal, and retrohepatic areas. Thorough exploration and cholangiography are essential. Embryologically, the gallbladder and cystic duct arise from the caudal portion of the hepatic bud. All of the previously reported cases of gallbladder agenesis have shown an absence of both the gallbladder and cystic duct. We report an embryological oddity wherein a patent cystic duct was found along with an agenetic gallbladder. This is the first case report of this finding, along with this being the first absent gallbladder discovered laparoscopically.