Ropeway-type bile duct biopsy forceps with a side slit for a guidewire

BACKGROUND: Transpapillary procurement of bile duct biopsy specimens is an effective diagnostic technique in cases of biliary structure. The utility of new ropeway-type bile duct biopsy forceps with a side slit for a guidewire was investigated in this study. METHODS: The 12 patients in this study had bile duct cancer (n = 3), cancer of the head of the pancreas (n = 4), gallbladder cancer (n = 1), and benign bile duct stenosis (n = 4). After endoscopic retrograde cholangiography, a guidewire was placed in the bile duct across the stenosis. The new forceps (1.8-mm diameter clamshell-type biopsy forceps without needle) was then introduced through the intact papilla along the guidewire. RESULTS: In all patients, sufficient tissue for histopathologic evaluation was obtained without complication. In one patient, biopsy specimens were selectively obtained of the left hepatic duct, which was impossible with conventional forceps. In another patient, histologic examination of specimens obtained by using this new forceps showed adenocarcinoma, whereas specimens obtained with a conventional forceps did not contain adenocarcinoma. However, in another patient, biopsy specimens obtained with a conventional forceps contained adenocarcinoma that was not evident in specimens obtained with the new forceps. Dislodgement of the guidewire during procurement of biopsy specimens occurred in 1 patient. In the other 11 patients, an endoscopic biliary drain was inserted over the guidewire. CONCLUSION: The new ropeway-type biopsy forceps is useful for selectively obtaining biopsy specimens of the bile duct. With this system, access for subsequent endoscopic biliary drainage is maintained.     

Etoposide prevents apoptosis in mouse liver with D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure resulting in reduction of lethality

D-Galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury is an experimental model of fulminant hepatic failure in which tumor necrosis factor alpha (TNF-alpha) plays a pivotal role. We examined the effects of etoposide on GalN/LPS-induced fulminant hepatic failure. Mice were given an intraperitoneal dose of GalN (800 microg/g body weight)/LPS (100 ng/g body weight) with and without intraperitoneal etoposide (10 microg/g body weight) treatment. Liver injury was assessed biochemically and histologically. TNF-alpha levels in the serum, and apoptosis of hepatocytes and CPP32/caspase-3 in the liver, were determined. GalN/LPS treatment caused lethal liver injury in 87% of animals (13 of 15). The effect was associated with significant increases in TNF-alpha and alanine transaminase (ALT) levels in serum, the number of apoptotic hepatocytes, CPP32/caspase-3 activity, and TNF receptor 1 (TNFR1) mRNA expression in the liver. Etoposide (10 microg/g body weight) was given 3 times (at 50, 26, and 4 hours before GalN/LPS administration). Treatment of GalN/LPS-treated mice with etoposide reduced apoptosis of hepatocytes, resulting in reduction of lethality (13% [2 of 15]), while another topoisomerase II inhibitor, IRCF-193, showed no significant effect. The antilethal effect of etoposide was also confirmed in GalN/TNF-alpha-induced fulminant hepatic failure. Etoposide treatment reduced CPP32/caspase-3 activity in the liver, although it did not alter the serum TNF-alpha levels or hepatic TNFR1 mRNA expressions. In addition, etoposide treatment enhanced the mRNA and protein expression of Bcl-xL, an antiapoptotic molecule in the liver. The present findings suggest that etoposide prevents endotoxin-induced lethal liver injury by up-regulation of Bcl-xL, and that etoposide could be useful for the treatment of TNF-alpha-mediated liver diseases.     

Non-steroidal anti-inflammatory drug-induced small bowel injuries identified by double-balloon endoscopy

AIM: To clarify clinical features of the NSAID-induced small bowel lesions using a new method of endoscopy. METHODS: This is a retrospective study and we analyzed seven patients with small bowel lesions while taking NSAIDs among 61 patients who had undergone double-balloon endoscopy because of gastro-intestinal bleeding or anemia between September 2000 and March 2004, at Jichi Medical School Hospital in Japan. Neither conventional EGD nor colonoscopy revealed any lesions of potential bleeding sources including ulcerations. Double-balloon endoscopy was carried out from oral approach in three patients, from anal approach in three patients, and from both approaches in one patient. RESULTS: Ulcers or erosions were observed in the ileum in six patients and in the jejunum in one patient, respectively. The ulcers were multiple in all the patients with different features from tiny punched out ulcers to deep ulcerations with oozing hemorrhage or scar. All the patients recovered uneventfully and had full resolution of symptoms after suspension of the drug. CONCLUSION: NSAIDs can induce injuries in the small bowel even in patients without any lesions in both the stomach and colon.     

Water intoxication-a dangerous condition in labor and delivery rooms

Water intoxication, a form of acute hyponatremia, has been described in various clinical situations. Although hyponatremia is a common metabolic disorder in hospitalized patients, it is generally not well known as a hazard in the labor and delivery room. However, several factors predispose laboring women to develop hyponatremia. Moreover, because the fetus acquires water from the maternal circulation via the placenta, and there is a close correlation between maternal and cord blood serum sodium levels, the newborn infant of a hyponatremic mother is also at considerable risk of developing water intoxication. We review the epidemiology, pathophysiology, clinical features, and treatment of this hazardous disorder. We emphasize the need for awareness of this condition, and call attention to the risk of fluid overload during labor.     

Adjustment of Insulin Pump Settings in Type 1 Diabetes Management: Advisor Pro Device Compared to Physicians’ Recommendations

Aims:To compare insulin dose adjustments made by physicians to those made by an artificial intelligence-based decision support system, the Advisor Pro, in people with type 1 diabetes (T1D) using an insulin pump and self-monitoring blood glucose (SMBG).Methods:This was a multinational, non-interventional study surveying 17 physicians from 11 countries. Each physician was asked to provide insulin dose adjustments for the settings of the pump including basal rate, carbohydrate-to-insulin ratios (CRs), and correction factors (CFs) for 15 data sets of pumps and SMBG of people with T1D (mean age 18.4 ± 4.8 years; eight females; mean glycated hemoglobin 8.2% ± 1.4% [66 ± 11mmol/mol]). The recommendations were compared among the physicians and between the physicians and the Advisor Pro. The study endpoint was the percentage of comparison points for which there was an agreement on the direction of insulin dose adjustments.Results:The percentage (mean ± SD) of agreement among the physicians on the direction of insulin pump dose adjustments was 51.8% ± 9.2%, 54.2% ± 6.4%, and 49.8% ± 11.6% for the basal, CR, and CF, respectively. The automated recommendations of the Advisor Pro on the direction of insulin dose adjustments were comparable )49.5% ± 6.4%, 55.3% ± 8.7%, and 47.6% ± 14.4% for the basal rate, CR, and CF, respectively( and noninferior to those provided by physicians. The mean absolute difference in magnitude of change between physicians was 17.1% ± 13.1%, 14.6% ± 8.4%, and 23.9% ± 18.6% for the basal, CR, and CF, respectively, and comparable to the Advisor Pro 11.7% ± 9.7%, 10.1% ± 4.5%, and 25.5% ± 19.5%, respectively, significant for basal and CR.Conclusions:Considerable differences in the recommendations for changes in insulin dosing were observed among physicians. Since automated recommendations by the Advisor Pro were similar to those given by physicians, it could be considered a useful tool to manage T1D.     

Transdermal absorption of clindamycin and tretinoin from topically applied anti-acne formulations in man

The percutaneous absorption of clindamycin was studied in healthy male volunteers, comparing two investigative clindamycin (% w/v)/tretinoin (0.025% w/v) gels, containing clindamycin phosphate ester and clindamycin HCl, respectively, relative to a clindamycin phosphate lotion (1% clindamycin; Dalacin T®). Formulations were applied daily for 5 days on the face, according to a balanced complete block design. Redness of the skin was scored visually, and blood and urine were collected. Clindamycin plasma levels did not exceed the limit of quantification (5 ng mL⁻¹) with the clindamycin phosphate formulations, but one volunteer who received the clindamycin HCl/tretinoin gel showed plasma levels of up to 13 ng mL⁻¹. Clindamycin urinary excretion for 12 h after application of the clindamycin phosphate/tretinoin gel was comparable to the values of the reference lotion, whereas the clindamycin HCl/tretinoin gel gave significantly higher values. Erythema appeared to be associated with increased urinary excretion. The formulations were tolerated well. In a separate clinical pilot study in acne patients, the transdermal uptake of tretinoin and clindamycin from the clindamycin phosphate/tretinoin gel was monitored. Plasma samples were collected after 4 and 12 weeks of daily treatment. None of the study plasma samples contained measurable tretinoin levels. Clindamycin levels were not quantifiable in the majority (87%) of samples, the highest plasma level was 11 ng mL⁻¹. The chemical form of clindamycin proved to modulate skin irritation and percutaneous uptake of clindamycin from a gel formulation in healthy subjects. There was no indications for a notable transdermal uptake of tretinoin during daily application of the gel in patients, nor for an enhancing effect of tretinoin on clindamycin uptake. Copyright © 1998 John Wiley & Sons, Ltd.