Percutaneous sclerotherapy for intractable external biliary fistula after hepatectomy

A 59-year-old man was diagnosed with cholangitis and a liver abscess caused by intrahepatic stones and underwent a hepatectomy of the left lobe and a side-to-side hepaticojejunostomy. After the operation, the patient developed an intractable external biliary fistula in the left remnant medial region. For the purpose of closing the fistula as a conservative treatment, an injection of 95% dehydrated ethanol was started after confirming the absence of any communication with the central bile duct; 1.5-5 ml was used for each injection, and the tube was clamped for 2 hours after injection. The excretion of bile juice decreased from the second injection, the excretion became serous, and the fistula completely closed after about 2 months without any particular complications. Percutaneous sclerotherapy by the injection of ethanol was found to be useful for closing a noncommunicating external biliary fistula.     

Radiation Enterocolitis: Overview of the Past 15 Years

n = 18) or an intestinal resection in addition to decompression ( n = 36). The clinical factors contributing to survival after irradiation were retrospectively reviewed by a multiple variate proportional hazards model. As a result, patients treated with decompression procedures alone had an 11 times higher risk for death than those treated with the addition of intestinal resection. In the former group, 5 of 18 patients died of bleeding from the remaining intestine after operation. We concluded that surgical resection of the diseased intestine is a useful procedure for treating radiation enterocolitis to reduce intestinal bleeding from the irradiated intestine.     

Intranasal l-threo-3,4,-dihydroxyphenylserine in Treating Diarrhea Associated With Familial Amyloidotic Polyneuropathy

We evaluated the absorption disturbance of the gastrointestinal tract in patients with familial amyloidotic polyneuropathy (FAP). Ursodeoxycholic acid (UDCA) 300 mg was administered orally to 10 patients with FAP and 11 control subjects. Serum levels of total bile acid were determined as an indicator of absorption. The patients had lower serum levels of total bile acid than controls, suggesting an absorption disorder. To attempt to treat the diarrhea commonly associated with FAP, l-threo-3,4-dihydroxyphenylserine (l-threo-DOPS), a synthetic precursor of norepinephrine, was administered 100 mg/dose by the oral and 8 mg/0.4 ml by the intranasal route and their effects on the elevation of serum norepinephrine levels were compared. The 3–0-monohemiphthalate salt of glycyrrhizinic acid and sodium ascorbate were used as vehicles for the intranasal preparation to enhance drug absorption and prevent oxidation. Increased serum levels of norepinephrine, the converted metabolite of l-threo-DOPS in serum, was observed 2 hours after intranasal administration, but not after administration of the oral preparation or vehicle alone. Intranasal administration of 8 mg 3 times/day for 1 week resulted in reduction of the daily frequency of diarrhea as well as a decrease in the severe orthostatic hypotension in three patients with FAP. Thus, an intranasal delivery system for l-threo-DOPS, which acts by stimulating adrenergic receptors, may be considered in treating patients with FAP with severe diarrhea.     

Varicella-zoster virus-specific cell-mediated immunity in subjects with herpes zoster

Though cell-mediated immunity (CMI) against varicella-zoster virus (VZV) is critical for prevention of the onset of herpes zoster (HZ), clinicians currently lack a simplified procedure to monitor CMI. We have recently developed an assay, called the IFN-γ release assay, and showed that it is a simple and reliable method to determine VZV-specific CMI. In the present study, we applied an IR assay to measure the VZV-specific CMI of patients with HZ. VZV-specific CMI levels were significantly high at the onset of the disease, but were decreased several weeks later. In contrast, CMI VZV-specific antibody titers increased in convalescent phase compared to those in acute phase. Thus, this technology is likely to be very useful in monitoring ongoing VZV-specific immune status.     

Formulation development of inhalation powders for FK888 with carrier lactose using Spinhaler and its absorption in healthy volunteers.

(4R)-4-Hydroxy-l-[(l-methyl-lH-indol-3-yl)carbonyl]-L-prolyl-N-benzyl-N-methyl-3-(2-naphthyl)-L-alaninamide (FK888) is a candidate selective NK1 receptor antagonist, and it exhibits poor absorption from the gastrointestinal (GI) tract in healthy volunteers. The objective of this study was to develop an optimized DPI formulation with carrier lactose using a Spinhaler, and thereby improve the systemic absorption of FK888. The fine particles of FK888 were blended with various carrier lactoses, and in vitro deposition properties were investigated using a twin impinger. The mixture using 100 M and 325 M lactoses [Sieved lactoses (SLs)] exhibited a higher emitted dose (Em) than 200 M, 450 M and micronized lactoses [Milled lactoses (MLs)]. The flowability of carrier lactose had an influence on the Em. On the other hand, the respirable particle (RP) fraction in the formulations with MLs was much higher than that of SLs, in spite of the blended ratios of lactose. It was also observed that the mixture of 325 M with the micronized lactose particles had the same RP as 200 M, although the 325 M alone had a low RP. Considering the Em and RP obtained, we chose 200 M for FK888 dry powder inhaler (DPI). The proportional absorption was found up to the 12.5% of the FK888 ratio (5 mg as unit dose) for the Cmax and AUC in healthy volunteers. In conclusion, 200 M, which has fine lactose particles and a better flowability than other MLs, is an extremely suitable carrier for maximizing the fine particle dose as far as FK888 is concerned. Furthermore, an improvement in the systemic absorption of FK888 was achieved using the dry powder formulations.     

Improvement of pulmonary absorption of cyclopeptide FK224 in rats by co-formulating with beta-cyclodextrin.

FK224 is a cyclopeptide drug with a low aqueous solubility. Following oral administration to rats, poor absorption was observed due to proteolysis in the gastrointestinal tract. The objective of this study was to investigate the effect of the pulmonary route on the systemic absorption of FK224 in comparison with other administration routes, and to determine the bioavailability (BA) of FK224 following pulmonary administration in rats using various dosage forms. From absorption studies on the Polyethylene Glycol 400 solution given by various routes (intranasal, subcutaneous, intratracheal and intravenous as reference), it was shown that pulmonary administration was a potentially attractive route for FK224. In the pulmonary absorption studies, after administration of the aqueous suspension, the BA was reduced to 2.7% compared with 16.8% for the solution. However, beta-cyclodextrin (beta-CyD) was found to be an effective additive as far as improving the solubility of FK224 was concerned. The BA of the aqueous suspension containing beta-CyD was increased to 19.2%. Pressurized metered dose inhalers were prepared by formulating beta-CyD with various molar ratios of 1:0, 1:1 and 1:7 (FK224/beta-CyD), and the resulting BAs were 4.3%, 29.0% and 91.2%, respectively. It was observed that both the C(max) and AUC of FK224 were increased as the amount of beta-CyD increased. The plasma profiles showed sustained absorption. In conclusion, we have seen that the lung is a suitable route for absorption of FK224, and beta-CyD is an extremely effective additive as far as improving the pulmonary absorption of FK224 is concerned. beta-CyD or derivatives with various degrees of aqueous solubility are potential drug carriers for controlling pulmonary absorption.