Telaprevir impairs renal function and increases blood ribavirin concentration during telaprevir/pegylated interferon/ribavirin therapy for chronic hepatitis C

We aimed to examine the relationship between renal dysfunction and anaemia that may develop during combination therapy involving pegylated interferon, ribavirin and telaprevir (PEG‐IFN/RBV/TVR) for the treatment of chronic hepatitis C. Sixty‐eight patients with genotype 1b high viral loads were treated with PEG‐IFN/RBV/TVR. Peg‐IFN and RBV doses were administered according to body weight. TVR was prescribed at 2250 mg/day for 44 patients and at 1500 mg/day for 24 patients who had low haemoglobin level (<12 g/dL). When anaemia had developed, the RBV dose was decreased. The serum TVR concentration at day 8 was measured, and the serum RBV concentration was measured serially. The estimated glomerular filtration rate (eGFR) was estimated to assess renal function. At week 1, serum TVR concentration was not correlated with a decrease in eGFR; however, the TVR dose, on a weight basis (mg/kg), and eGFR were correlated (r = 0.2691; P = 0.0265). Moreover, there was a negative correlation between eGFR and RBV serum concentration (r = −0.3694; P = 0.0025), and the serum RBV concentration and decrease in the haemoglobin were significantly correlated from week 1 to week 8. In triple therapy, the TVR dose per weight is correlated with a decline in renal function. Thus, the serum concentration of RBV increases, with a concomitant decrease in haemoglobin. It is important to adjust the doses of TVR and RBV to avoid excessive serum RBV levels and the development of severe anaemia, to achieve a good clinical effect.     

Combination of hepatitis B viral antigens and DNA for prediction of relapse after discontinuation of nucleos(t)ide analogs in patients with chronic hepatitis B

Aim: The factors associated with hepatitis recurrence after discontinuation of nucleos(t)ide analogs (NAs) in patients with chronic hepatitis B were analyzed to predict the risk of relapse more accurately. Methods: A total of 126 patients who discontinued NA therapy were recruited retrospectively. The clinical conditions of a successful discontinuation were set as alanine aminotransferase (ALT) below 30 IU/L and serum hepatitis B virus (HBV) DNA below 4.0 log copies/mL. Results: Relapse of hepatitis B were judged to occur when maximal serum ALT became higher than 79 IU/L or when maximal serum HBV DNA surpassed 5.7 log copies/mL following NA discontinuation since these values corresponded with mean values of ALT (30 IU/L) and HBV DNA (4.0 log copies/mL), respectively. At least 90% of patients with either detectable hepatitis B e antigen or serum HBV DNA higher than 3.0 log copies/mL at the time of NA discontinuation relapsed within one year. In the remaining patients, higher levels of both hepatitis B surface and core‐related antigens at the time of discontinuation, as well as a shorter course of NA treatment, were significantly associated with relapse by multivariate analysis. Conclusions: It appears that negative results for hepatitis B e antigen and serum HBV DNA lower than 3.0 log copies/mL are essential for successful NA discontinuation, which may be attained by a longer treatment period. Levels of hepatitis B surface and core‐related antigens are also significant factors independently associated with relapse of hepatitis.     

Endoscopic band ligation for refractory gastric antral vascular ectasia associated with liver cirrhosis

An 84-year-old woman with unknown liver cirrhosis was admitted to our hospital in October 2008 with anemia due to recurrent gastric antral vascular ectasia (GAVE). At 78 years of age, argon plasma coagulation (APC) was performed for GAVE, and between 79 and 83 years of age, APC was carried out five times for recurrent episodes of GAVE presenting as anemia. Upon hospitalization, she was found to have anemic conjunctivae and the laboratory findings were red blood cells 245 × 10⁴/mm³ and hemoglobin 7.7 g/dL. During this period, endoscopic band ligation (EBL) was performed for the recurrent refractory GAVE. EBL was first applied to the most distal antrum, and subsequent EBLs were performed more proximally. Two weeks after initial EBL treatment, endoscopy revealed both ulcers and shrinking of GAVE in the stomach. Fourteen months later, no further recurrence of GAVE was observed by endoscopy. This patient had no episodes of bleeding during the 20 month period since she was treated with EBL, and has a hemoglobin value of 10.1 g/dL. The histologic changes that occur with GAVE exist in the mucosal and submucosal region of the stomach; therefore, EBL may be effective for refractory GAVE because of obliterating submucosal vascular plexus.     

Resistance of germinal nucleus to aging in Paramecium: Evidence obtained by micronuclear transplantation

A diversity of time when increase in mortality after conjugation occurs during the lifespan was found in subclones of three stocks of Paramecium caudatum. A possible micronuclear contribution to the increase in sterility has been investigated by micro-nuclear transplantation. We found two classes of micronuclei in aged clones: those that can function normally if the cytoplasmic environment is young, and those that cannot, even in a young cytoplasmic environment. The results indicate that in the former, the age-dependent increase in sterility is due to a deleterious macronucleus and/or cytoplasm, and in the latter it is due to micronuclear damage. The micronuclear damage in aged clones is probably induced by a deleterious cytoplasmic environment because aged clones with transplanted young micronuclei showed an abrupt decrease in progeny survival between 14 and 42 cell divisions after transplantation. Overall, the micronucleus seems not to be a source of age-related damage but rather is subjected to damage from macronuclear and/or cytoplasmic sources.     

Extent of lesions in idiopathic sudden hearing loss with vertigo: study using click and galvanic vestibular evoked myogenic potentials

OBJECTIVE: To clarify the extent of the vestibular lesions in idiopathic sudden hearing loss with vertigo using vestibular evoked myogenic potentials (VEMPs) in response to click (click-VEMP) and galvanic (galvanic-VEMP) stimulation, as well as caloric tests. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: We enrolled 22 patients with idiopathic sudden hearing loss with vertigo in this study. All patients underwent audiometry and click-VEMP and caloric tests. Eight patients underwent a galvanic-VEMP test. RESULTS: Among the 22 patients, 17 (77%) showed an absence of click-VEMPs on the affected side. In response to caloric testing, 10 patients (45%) showed a decreased response on the affected side. All 8 patients who underwent galvanic-VEMP testing showed normal responses. Most patients with decreased caloric responses (9 [90%] of 10 patients) showed an absence of click-VEMPs, whereas 9 (53%) of the 17 patients who showed abnormal click-VEMPs showed decreased caloric responses. Initial hearing level and hearing outcome significantly correlated with abnormalities on the vestibular test results. CONCLUSIONS: The lesion site of vestibular disorders in idiopathic sudden hearing loss with vertigo appeared to be within the labyrinth on the basis of galvanic-VEMP findings. Results of the click-VEMP and caloric tests suggested that the saccule could be involved more frequently than the semicircular canals. The combined use of click-VEMP and caloric tests is useful for evaluating vestibular functions in idiopathic sudden hearing loss with vertigo because the extent of vestibular abnormalities correlated well with hearing outcome.     

Perceptual categorization of sound spectral envelopes reflected in auditory-evoked N1m

Magnetic responses to periodic complex sounds with equivalent acoustic parameters except for two different fundamental frequencies (F0) and 12 different spectral envelopes of vocal, instrumental, and linear shapes were recorded to determine the cortical representation of timbre categorization in humans. Responses at approximately 100 ms (N1m) to vocal and instrumental (nonlinear) sounds were localized significantly anterior to linear sound responses. N1m source strength for nonlinear sounds was significantly larger than that for linear sounds, and this difference was more marked in the left hemisphere than in the right. N1m peak latency only for vocal sounds was not affected by F0. Perceptual categorization was reflected in N1m source strength and location (linear or nonlinear), and in N1m latency (vocal or nonvocal).     

Microscopic structure of disturbed flows in the arterial and venous systems, and its implication in the localization of vascular diseases

A novel technique to prepare isolated transparent natural blood vessels was developed and used to investigate the connection between blood flow and the localization of vascular diseases in man. Transparent segments of arteries and veins were prepared from dogs and humans postmortem, and the flow patterns in various regions of the circulation were studied in detail by means of flow visualization and cinemicrographic techniques. It was found that under normal physiological conditions, complex spiral secondary flows and recirculation zones form in various regions of the arterial and venous systems such as the aortic arch, aortic T-junctions, carotid artery bifurcations, the major branching sites of the intracranial cerebral arteries and venous valve pockets. Incipient saccular aneurysms were found at the flow divider of the anterior communicating-anterior cerebral artery junction where the flow directly impinged on the vessel wall. In human cerebral arteries, atherosclerotic thickenings of the vessel wall were found to be localized on the outer wall (hip) of one or both daughter vessels at bifurcations and T-junctions, and at the inner wall of arterial bends, at the very places where secondary and recirculation flows were dominant and wall shear stress was low. The results clearly indicate that there is a strong correlation between the sites of flow disturbance and the preferred sites for the genesis and development of vascular diseases clinically found in man.     

Characteristic distribution of HTLV type I and HTLV type II carriers among native ethnic groups in South America.

To confirm the geographic and ethnic segregation of HTLV-I and HTLV-II carriers in native populations in South America, we have conducted a seroepidemiological study of native populations in South America, including HTLV-I carriers distributed among seven ethnic groups in the Andes highlands of Colombia, Peru, Bolivia, Argentina, and Chile, and two ethnic groups on Chiloe Island and Easter Island; and HTLV-II carriers distributed among seven ethnic groups of the lowlands along the Atlantic coast of Colombia, Orinoco, Amazon, and Patagonia, and one ethnic group on Chiloe Island. The incidence rate of HTLV-I and HTLV-II carriers varied among the ethnic groups, ranging from 0.8 to 6.8% for HTLV-I seropositivity and from 1.4 to 57.9% for HTLV-II seropositivity. A new HTLV-I focus was found among the Peruvian Aymara (1.6%), the Bolivian Aymara (5.3%) and Quechua (4.5%), the Argentine Puna (2.3%), and the Chilean Atacama (4.1%), while on HTLV-II focus was found among the Brazilian Kayapo (57.9%), the Paraguayan Chaco (16.4%), and the Chilean Alacalf (34.8%) and Yahgan (9.1%). The distribution of HTLV-I/II foci showed a geographic clustering of HTLV-I foci in the Andes highlands and of HTLV-II foci in the lowlands of South America. It was thus suggested that South American natives might be divided into two major ethnic groups by HTLV-I and HTLV-II carrier state.