Mutations in the core and NS5A region of hepatitis C virus genotype 1b and correlation with response to pegylated-interferon-alpha 2b and ribavirin combination therapy.

Mutations in two regions of hepatitis C virus (HCV) have been implicated in influencing response to interferon (IFN) therapy. Substitutions in the NS5A region of HCV have been associated with response to IFN therapy, and this region has been known as the IFN sensitivity-determining region (ISDR). The mutations in the core region of HCV have also been reported to predict IFN response. The aim of this study was to investigate whether amino acid substitutions in the core region and ISDR among patients with HCV genotype 1b affect the response to IFN therapy. A total of 213 patients who completed IFN treatment were randomly selected. All patients received pegylated-IFN-alpha 2b once each week, plus oral ribavirin daily for 48 weeks. Of the 213 patients, 117 (54.9%) showed early virologic response (EVR), with HCV-negativity, at 12 weeks. Factors related to EVR on multivariate analysis were non-Gln70 and Leu91 in the core region, and ISDR mutant-type. One hundred and two (47.9%) showed a sustained virologic response (SVR). SVR occurred more frequently in patients without Gln70 (55.4%) than in those with Gln70 (21.3%) (P < 0.0001). SVR was achieved in 43.6% of patients with wild-type ISDR and 62.5% of patients with mutant-type (P = 0.0227). Of the 34 patients who simultaneously had non-Gln70 and mutant-type ISDR, 26 (76.5%) achieved SVR. Factors related to SVR on multivariate analysis were non-Gln70 and ISDR mutant-type. In conclusion, amino acid substitutions in the core region and ISDR were useful for predicting the response to IFN in patients with HCV genotype 1b.

Four novel mutations of the connexin 32 gene in four Japanese families with Charcot-Marie-Tooth disease type 1.

DNA-based mutation analysis on the connexin 32 gene was performed in 49 families with Charcot-Marie-Tooth disease (CMT) type 1 but without duplication involving the chromosomal region, 17p12-p11.2. Mutations were identified in five of the 49 families, and four of the five mutations were hitherto undescribed: Va137Met, Glu57His, Arg142Glu, Val177Ala. X-linked CMT sometimes lacks evidence for X-linked transmission and cannot be differentiated from CMT type 2, especially in females with mildly decreased nerve conduction velocity. Therefore, molecular analysis is useful for molecular pathology of their disease.

A survey of filling methods, intracanal medications, and instrument breakage.

The present survey was conducted to obtain answers to some basic questions regarding the use of intracanal medications, root canal filling methods, and the intracanal breakage of instruments. A letter was sent to 300 endodontists listed in the 1995-1996 membership roster of the American Association of Endodontists. Eighty-five replies were received. Calcium hydroxide as an intracanal medication was used by 91.7% of the responding endodontists. With regard to the root canal filling technique, 52.9% used the lateral condensation method. When intracanal breakage occurred, 95.3% of the respondents informed the patient. The results of this survey provide useful information for the education of undergraduate dental students.

[Trans-arterial embolization or transarterial infusion of anti-cancer drugs suspended in a lipid contrast medium against unresectable metastatic liver cancer].

We had 84 patients with unresectable metastatic liver cancer from May, 1980 to December 1987 in the National Matsudo Hospital. Eighteen of them had no treatment; 26 of them had serial transarterial embolization (TAE) with or without infusion of anti-cancer drug dispersed in lipiodol; 7 of them had only serial trans-arterial infusion (L-TAI) of an anticancer drug suspended in lipiodol. A significant survival advantage of patients with TAE or L-TAI was noted when compared with no treatment, but there was no difference between the survival rate of patients with TAE and L-TAI. There were some 82 patients with unresectable metastatic liver cancer from October 1984 to March 1988 in Kyto Prefectural University of Medicine Hospital. Thirteen of them had L-TAI using one anti-cancer drug (one-drug group); 8 of them had L-TAI using two drugs (two-drug group); 22 of them had L-TAI with three drugs (three-drug group). The survival rate of the three-drug group was superior to the one- and two-drug groups. It was concluded that TAE was not necessary for metastatic liver cancer, but L-TAI must be undertaken, because combined cancer chemotherapy enhanced the effect of L-TAI.

Amperometric detection studies of Nafion/indium hexacyanoferrate film for the determination of electroinactive cations in ion chromatography.

An amperometric detector based on the chemical modification of Nafion and indium (III) hexacyanoferrate (II, III) thin film (Nafion/In-CN-Fe) onto a glassy carbon (GC) electrode, was first successfully used for the determination of electroinactive cations (Li+, Na+, K+, Rb+, Cs+, NH4+) in single column ion chromatography (IC). A set of well-defined peaks of electroinactive cations was obtained. The detection limits of the cations are 8.9 x 10(-6) mol/L for Li+, 2.3 x 10(-6) mol/L for Na+, 5.2 x 10(-6) mol/L for K+, 4.8 x 10(-6) mol/L for Rb+, 4.0 x 10(-6) mol/L for Cs+ and 5.3 x 10(-6) mol/L for NH4+ at a single-to-noise ratio of 3. The proposed method was quick, sensitive and simple. The cations in rainwater and mineral water were successfully analyzed by this method.

Preparation of agglomerated crystals for direct tabletting and microencapsulation by the spherical crystallization technique with a continuous system.

Adhesive and cohesive properties of chlorpromazine hydrochloride (CP) crystals were modified to improve their powder processing, e.g., direct tabletting and microencapsulation, by agglomeration. Moreover, sustained-released gelling microcapsules of CP were devised to prolong the pharmacological effect. The spherical crystallization technique was applied to prepare agglomerates for direct tabletting and microencapsulation to use them as core materials. The ethanolic solution dissolving CP was poured into a stirred cyclohexane, yielding spherically agglomerated crystals. The resultant agglomerates were free-flowing and easily packable spheres with average diameters of 200 to 1000 microns. The agglomerates reserved the high compressibility of the original powder having a small particle size (14 microns). The compression behavior represented by Heckel's equation suggested that the agglomerates were disintegrated to individual primary crystals at low compression pressures, and then they were closely repacked and plastically deformed at higher pressures. After agglomeration, microencapsulation was continuously performed in the same batch by a phase separation method. Coacervate droplets produced by pouring cyclohexane into a dichloromethane solution, dissolving polyvinyl acetate as a coating polymer, were added to the crystallization system under stirring, to prepare the microcapsules. By filling the microcapsules in gelatin hard capsules or tabletting them, their drug release rates became retarded compared with the physical mixture treated in the same way, having the same formulation as the microcapsules. This phenomenon was due to the gelation of polyvinyl acetate of the microcapsules in the dissolution medium, whose glass transition temperature is very low. This novel sustained-release dosage form is termed "gelled microcapsules."