Effect of Force of Microneedle Insertion on the Permeability of Insulin in Skin

Many experiments conducted in the literature have investigated the effect of microneedles (MNs) on insulin permeation across skin. There are also a number of articles that deal with the effect of MN insertion force in skin. However, there is little known on quantifying the relationship between the effect of MN insertion force and the amount of insulin permeated for given MNs. This issue is addressed in this article. MNs of 1100 µm and 1400 µm are used to conduct in vitro permeability experiments on porcine skin, using insulin. Histological images of MN treated skin are obtained from a microtome and the viscoelastic properties of the skin sample are measured using a rheometer. An in-house insertion force device is utilized that can reproducibly apply a specified force on MNs for a set period of time using compressed air. It is deduced that when porcine skin was pretreated with an applied force of 60.5 N and 69.1 N, the resultant amount of insulin permeated was approximately 3 µg and 25 µg over a 4-hour period for the MNs used. The amount of MN force applied to porcine skin was shown to be related to the amount of insulin permeated. An increase in insertion force increase the amount of insulin permeated. It was also demonstrated that using insufficient force may have reduced or prevented the amount of insulin passing through the skin, regardless of the geometry of the MNs.     

The anti‐inflammatory effect of celecoxib does not prevent liver fibrosis in bile duct‐ligated rats

Background/Aims: Celecoxib was used in the treatment of inflammation in patients with cirrhosis. However, data on the progression of liver fibrosis after treatment by celecoxib are not available. This study aims to elucidate the effects of celecoxib on cholestatic liver fibrosis in rats. Methods: Rats underwent bile duct ligation (BDL) for 1 or 2 weeks to induce hepatic fibrosis. Celecoxib was introduced on day 1 after operation. The effects of celecoxib were assessed by comparison of the severity of hepatic fibrosis. Results: Infiltration of inflammatory cells and proliferation of bile ducts was seen after 1 week of BDL and fibrosis was induced after 2 weeks. Reduced alanine aminotransferase (ALT) levels and blunted expression of inflammatory factors [tumour necrosis factor‐α, interleukin (IL)‐1β and IL‐6] were seen in the liver of BDL‐treated rats that received celecoxib at week 1. Although celecoxib was sufficient in suppressing the cyclo‐oxygenase (COX)‐2 expression in the control organ (kidney), it failed to suppress the enhanced hepatic COX‐2 expression. At week 2, celecoxib did not alter the ALT level, the severity of fibrosis and hepatic collagen contents. This was associated with unchanged α‐smooth muscle actin protein expression and tissue inhibitor of metalloproteinase‐2 (TIMP‐2), matrix metalloproteinase (MMP)‐2 and MMP‐9 mRNA expressions in the liver. Celecoxib had no effect on the BDL‐dependent increase in bilirubin levels at any time point. Conclusions: The present study provides morphological and molecular biological evidences for the role of celecoxib in cholestatic liver fibrosis. Celecoxib protects against hepatic inflammation in the early stage of BDL rats, but does not have an effect on liver fibrosis.     

Outcome of surgical treatment for recurrent pyogenic cholangitis: a single-centre study

Background

Recurrent pyogenic cholangitis (RPC) is still a common disease in East Asia. The present study reviews the operative results for this disease in a single centre.

Methods

The records of 85 patients who underwent surgical treatment for RPC from August 1995 to March 2008 were retrospectively reviewed.

Results

Patients included 35 men and 50 women with a median age of 61 years. Types of surgery included: hepatectomy (65.9%); hepatectomy plus drainage (9.4%); drainage alone (14.1%), and percutaneous choledochoscopy (10.6%). There was no operative mortality. Complications occurred in 40% of patients and half the complications involved wound infections. The overall incidences of residual stone, stone recurrence and biliary sepsis recurrence were 21.2%, 16.5% and 21.2%, respectively, over a median follow-up of 45.4 months. The drainage-alone group and percutaneous choledochoscopy group had higher incidences of residual stone, stone recurrence and biliary sepsis recurrence. In hepatectomy patients, regardless of whether or not a drainage procedure had been performed, rates of residual stone, stone recurrence and biliary sepsis recurrence were 15.6%, 7.8% and 9.4%, respectively, over a median follow-up of 42.7 months.

Conclusions

Hepatectomy is safe and yields the best treatment outcome for RPC. It should be considered as the treatment of choice for suitable patients with RPC.     

Modified Epworth Sleepiness Scale in Chinese children with obstructive sleep apnea: a retrospective study

Background and objective  The purpose of this study is to assess whether Chinese children with high apnea–hypopnea index (AHI) are sleepier by a modified Epworth Sleepiness Scale (ESS). Materials and methods  Records were retrospectively reviewed. We included children who were between 3 and 12 years old, admitted for overnight polysomnogram because of suspected obstructive sleep apnea syndrome (OSAS). A modified ESS was used to assess excessive daytime sleepiness (EDS) of the children. Results  One hundred ninety-two Chinese children were included. Children with high AHI, defined as AHI > 5.0, were sleepier than children with AHI less than or equal to 5. After adjustment by age, gender, and obesity, children with high AHI remained significantly sleepier. Modified ESS was significantly correlated with AHI (rho = 0.124, 95% CI = 0.004–0.281). Modified ESS score of >8 was the best cutoff point with the sensitivity and specificity of 0.29 and 0.91, respectively. The odds ratio of children with modified ESS > 10 having high AHI was 4.231 (95%CI = 1.248 to 14.338) and children with modified ESS > 8 had the highest odds ratio, 4.295(95%CI = 1.66 to 11.1), of having high AHI. Conclusion   Chinese children with high AHI appear to be sleepier than children with low AHI. Children with suspected OSAS and high modified ESS, i.e., ESS > 8, had significantly higher odds ratio of having high AHI. Increased sleepiness is a specific but not a sensitive symptom in snoring children with high AHI. Screening for EDS in snoring children may help us identify those with high AHI and prioritize the management of those children. All authors worked and the study was carried out in Kwong Wah Hospital in Hong Kong. There was no conflict of interest and no specific source of funding for the study.     

Detection of inadvertent catheter movement into a pulmonary vein during radiofrequency catheter ablation by real-time impedance monitoring

Introduction: During radiofrequency ablation to encircle or isolate the pulmonary veins (PVs), applications of radiofrequency energy within a PV may result in stenosis. The aim of this study was to determine whether monitoring of real-time impedance facilitates detection of inadvertent catheter movement into a PV.
Methods and Results: In 30 consecutive patients (mean age 53 ± 11 years) who underwent a left atrial ablation procedure, the three-dimensional geometry of the left atrium, the PVs, and their ostia were reconstructed using an electroanatomic mapping system. The PV ostia were identified based on venography, changes in electrogram morphology, and manual and fluoroscopic feedback as the catheter was withdrawn from the PV into the left atrium. Real-time impedance was measured at the ostium, inside the PV at approximately 1 and 3 cm from the ostium, in the left atrial appendage, and at the posterior left atrial wall. There was an impedance gradient from the distal PV (127 ± 30 Ω) to the proximal PV (108 ± 15 Ω) to the ostium (98 ± 11 Ω) in each PV (P < 0.01). There was no significant impedance difference between the ostial and left atrial sites. During applications of radiofrequency energy, movement of the ablation catheter into a PV was accurately detected in 80% of the cases (20) when there was an abrupt increase of ≥4 Ω in real-time impedance.
Conclusion: There is a significant impedance gradient from the distal PV to the left atrium. Continuous monitoring of the real-time impedance facilitates detection of inadvertent catheter movement into a PV during applications of radiofrequency energy. (J Cardiovasc Electrophysiol, Vol. 15, pp. 1-5, June 2004)     

Twenty-four-hour ambulatory BP in snoring children with obstructive sleep apnea syndrome

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a known risk factor for hypertension in adults. This relationship is less clear in childhood OSAS. OBJECTIVE: This study examined the relationship between OSAS and 24-h ambulatory BP (ABP), a more accurate assessment than casual BP, in children with snoring. METHODS: Snoring children aged 6 to 15 years who underwent polysomnography in the sleep laboratory were recruited. Measurement: Twenty-four-hour ABP monitoring was initiated a few hours before polysomnography. The children were classified into two groups: a high apnea-hypopnea index (AHI) group (obstructive AHI > 5/h), and a low-AHI group (AHI < or = 5/h). Mean sleep, wake, and 24-h systolic BP (SBP) and diastolic BP (DBP) were recorded. A child was considered a "nondipper" if his or her mean SBP and DBP did not decrease by >/= 10% during sleep. RESULTS: Ninety-six children (mean age +/- SD, 9.4 +/- 2.8 years) were recruited. Forty-one children were obese. When awake, the high-AHI group children had a significantly higher SBP. When asleep, both SBP and DBP were higher in the high-AHI group. Age, body mass index (BMI) z score, and desaturation index (DI) were significant predictors for elevated sleep DBP. BMI z score was the only significant predictor for wake and sleep SBP. Sixteen children (17%) had hypertension, and all were nondippers. Obese children in the high-AHI group had a significantly higher prevalence of hypertension than obese children in the low-AHI group. This relationship was not found in nonobese children. CONCLUSION: The current study shows that increased DI contributed to the elevation of sleep DBP elevation.