Interferon and cyclosporin A in the treatment of fulminant viral hepatitis.

The prognosis of fulminant hepatitis due to non-A, non-B virus infection and acute reactivation of hepatitis B virus in HB carriers is generally poor, and the treatment of choice in Western countries is recognized as liver transplantation. In countries such as Japan where liver transplantation is not readily available, however, these intractable types of fulminant hepatitis have to be treated medically. Based on the assumption that persistent replication of causal viruses and enhanced host immune responses, especially cellular immunity, to eradicate the viruses are the key mechanism in progressive liver cell destruction and the poor prognosis, we attempted a combination treatment with interferon and cyclosporin A for these types of fulminant viral hepatitis. Subjects in the present study consisted of 1 patient with acute severe hepatitis without coma and 13 patients with coma (13 with fulminant hepatic failure) due to non-A, non-B virus and acute reactivation of hepatitis B virus. The patients were given interferon-beta, 300 x 10(4) U daily, and cyclosporin A, at an initial dose of 3 mg/kg, with tapering. Fourteen patients with coma received artificial liver support that we devised. The patient with acute severe hepatitis survived, showing histologically remarkable liver regeneration. Eight of the 14 patients with hepatic coma, all of whom were indications for liver transplantation according to the criteria of the King's College group, survived. Decreased transaminase level, increased liver volume, and histological liver regeneration were observed in all the survivors. The combination of interferon and cyclosporin A is worth attempting in fulminant hepatitis caused by non-A, non-B virus and acute reactivation of hepatitis B virus in HB carriers.

[A close association of prognosis with effect of interferon in HBV carriers developing acute severe exacervation].

We have treated 19 HBV carriers who developed acute severe exacerbation using interferon and immunosuppressive agents. Of these 14 patients developed fulminant hepatic failure. Of 10 patients with positive result for serum HBV DNA polymerase before the start of te treatment, five patients in whom HBV DNA polymerase turned negative and one patient whose HBV DNA polymerase level fluctuated in a low abnormal range after the start of the treatment survived. While, four patients whose HBV DNA polymerase level remained high after the start of interferon treatment died. Thus, it is suggested that suppression of HBV virus replication is closely related to prognosis in HB carriers developing acute severe exacervation of hepatitis.

[Serial hepatic and splenic volumetry in acute severe hepatitis].

In this study, we elucidate a relationship between final outcome and changes in hepatic and splenic volume in patients with acute severe hepatitis. The subjects were 40 patients: 10 with sever acute hepatitis (prothrombin time < 40%) and 30 with fulminant hepatic failure (acute type in 12 and subacute type in 18). Liver and spleen volume were measured by CT initially on hospitalization and subsequently 1 to 40 days after hospitalization, and the scans were analyzed retrospectively. Liver volume decreased in 15 of 26 survivors, and all 14 non-survivors. Among 15 survivors and 14 non-survivors whose liver volume decreased, spleen volume increased in none of the survivors, whereas it increased in 11 of the 14 non-survivors. In survivors there was a close parallelism between changing rates of the liver volume and that of the spleen volume (r = 0.82, p < 0.0001). These observations suggest that the decrease of liver volume accompanied by that of spleen volume implies a good prognosis, while the decrease without such accompaniment implies a bad prognosis.

[Mental rotation of kinesthetic hand images and modes of stimulus presentation].

Three experiments on mental rotation were carried out to investigate conditions under which hand images are operated kinesthetically. In Experiment 1 a, either a left or right hand was presented in a photographic slide, and subjects' task was left-right identification. In Exp. 2, each slide consisted of two hands, identical hands or mirror-imaged hands, and same-different judgment was required. In Exp. 3, two hands were presented successively, requiring same-different (mirror-reversed) judgement. On the other hand, subjects in Exp. 1 b were asked to rate physical difficulty of actual hand movements to imitate stimuli. Six to 12 undergraduate students served as subjects in each experiment. The results suggested that subjects' mental operations of hand images were kinesthetic in Exp. 1 a but visual in Exp. 2 and 3, on the basis of comparison between reaction times in the three experiments and the ratings in Exp. 1 b. Conditions which give rise to kinesthetic image processes were argued in relation with task structures.

[Interferon treatment of type C fulminant hepatitis].

On the contrary to Western countries, there are a substantial number of patients with type C fulminant hepatitis (FH) including coinfection on type A and type B hepatitis in Asian countries. The pathogenesis of FH is not fully understood, however, recent clinical observations suggest that enhanced host immune responses contribute to hepatocyte destruction in type C FH. In contrast to type B FH, type C FH is characterized by gradual and continuous liver necrosis probably duo to persistent infection of hepatitis C virus. Administration of interferon with immunosuppressive agents is the treatment of choice. Prognosis may be improved if the treatment is started in the early stage of the disease.

[Causal relationship between GBV-C and fulminant hepatitis].

GBV-C is recently discovered RNA virus which appeared to be member of Flaviviridae. We previously reported the possible involvement of GBV-C in the etiology of fulminant hepatitis(FH). It is still controversial whether GBV-C cause FH. So far, the only reliable tool for the diagnosis of GBV-C is the detection of the viral genome using PCR. Detection of GBV-C in serum of patient with FH dose not necessarily mean that GBV-C is causal virus. Serial quantification of serum GBV-C RNA in patient with FH may reveal a pathogenetic role of GBV-C. Further study is needed to elucidate the relationship between FH and a specific strain of GBV-C.

Immunological responses of astroglia in the rat brain under acute stress: interleukin 1 beta co-localized in astroglia.

In previous studies, we demonstrated that acute stress induces microglial activation, without inducing any inflammatory responses; however, the effect of acute stress on astroglia, another glial cell subtype in the brain, remains to be elucidated. We determined the effect of acute stress on astroglia, particularly in terms of morphological changes and inflammatory properties. In contrast to microglia, the morphology of astroglia was not altered following a 2-h period of acute stress. Interestingly, the number of astroglia immunoreactive to interleukin 1 beta (IL-1ß) significantly increased in several brain regions including the hippocampus, hypothalamus, amygdala, and periaqueductal gray following the acute stress. Confocal microscopy revealed that IL-1ß is exclusively co-localized in astroglia, and not in neurons or microglia. The present study demonstrates that exposing rats to acute stress increases IL-1ß immunoreactivity in astroglia in specific regions of the brain, and the mechanism of astroglial response to acute stress clearly differs from that of microglial response. Thus, astroglia may play important roles in neuroimmunomodulation through IL-1ß during times of acute stress.

Numerical evaluation method for catheter prototypes using photo-elastic stress analysis on patient-specific vascular model.

BACKGROUND: To date, no quantitative analysis has been developed to evaluate catheter performance inside the vascular lumen. METHODS: An evaluation system for endovascular tools was built with a polyurethane elastomer vascular model inside a polariscope and a catheter driving system. This robotic system reproduced a catheter insertion trajectory inside the vascular model, using a surgical catheter and three catheter prototypes used for motion capture on endovascular surgery simulation. Birefringence is produced by photo-elastic characteristics of the polyurethane elastomer when the material is submitted external stress. The birefringence produced by the catheter on the vascular model wall was recorded and represented numerically by the correlation between consecutive frames of the registered video. RESULTS: Correlation values between frames showed that the performance of the prototypes was lower than that of the medical use catheter. The performance of prototypes was reduced by microcoils on their tips. CONCLUSIONS: This methodology opens new options to evaluate medical catheters and physicians skills. opyright

Importance of head axes in perception of cutaneous patterns drawn on vertical body surfaces.

The "disembodied eye" phenomenon (Corcoran, 1977), that is, the observation that a cutaneous (tactile) pattern is perceived as right-left reversed or not, depending on whether it is presented on the forehead or the back of the head, was extended by incorporating a top-bottom axis into a model of the frame of reference in cutaneous-pattern perception. In two experiments, 21 and 15 subjects were asked to report the letter perceived when one of four letters (p, q, b, or d) was tactually presented. The sites studied were vertical body surfaces (Experiment 1) and hands alongside the body (Experiment 2). The positions for the presentations varied according to the height (head, shoulder, waist, thigh, and calf levels) and the orientation of the surface: forward-, backward-, and side-facing. Although the results for the head and back surfaces supported the notion of a "disembodied eye" behind the individual, other frames were needed: On the forward-facing surfaces below the waist, the prevailing perception was 180 degrees rotated, as if the subjects were looking at the surface by bending forward. An additional frame of reference was introduced for the forward-facing surfaces in lower positions and was described as head axes projected onto body surfaces within the possibility of actual body movements.

Cultural and linguistic factors in audiovisual speech processing: the McGurk effect in Chinese subjects.

The "McGurk effect" demonstrates that visual (lip-read) information is used during speech perception even when it is discrepant with auditory information. While this has been established as a robust effect in subjects from Western cultures, our own earlier results had suggested that Japanese subjects use visual information much less than American subjects do (Sekiyama & Tohkura, 1993). The present study examined whether Chinese subjects would also show a reduced McGurk effect due to their cultural similarities with the Japanese. The subjects were 14 native speakers of Chinese living in Japan. Stimuli consisted of 10 syllable (/ba/, /pa/, /ma/, /wa/, /da/, /ta/, /na/, /ga/, /ka/, /ra/) pronounced by two speakers, one Japanese and one American. Each auditory syllable was dubbed onto every, visual syllable within one speaker, resulting in 100 audiovisual stimuli in each language. The subjects' main task was to report what they thought they had heard while looking at and listening to the speaker while the stimuli were being uttered. Compared with previous results obtained with American subjects, the Chinese subjects showed a weaker McGurk effect. The results also showed that the magnitude of the McGurk effect depends on the length of time the Chinese subjects had lived in Japan. Factors that foster and alter the Chinese subjects' reliance on auditory information are discussed.

McGurk effect in non-English listeners: few visual effects for Japanese subjects hearing Japanese syllables of high auditory intelligibility.

The McGurk effect is a phenomenon that demonstrates a perceptual fusion between auditory and visual (lip-read) information in speech perception under the condition of audio-visual discrepancy, created by dubbed video tapes. This paper investigated whether or not the McGurk effect could be extended to Japanese subjects listening to Japanese syllables of different auditory intelligibility. The audio and video signal of a female talker's speech for ten Japanese syllables (/ba/, /pa/, /ma/, /wa/, /da/, /ta/, /na/, /ra/, /ga/, /ka/) was combined on videotapes, giving 100 audio-visual stimuli. These stimuli were presented to ten Japanese subjects who were required to identify the stimuli as heard speech in both noise-added and noise-free conditions. For both conditions, the intelligibility of the auditory stimuli was measured, by presenting the audio-alone stimuli. The results showed that, in the noise-free condition, the McGurk effect was small and almost limited to auditory stimuli of which the intelligibility was less than 100%. In the noise-added condition, the McGurk effect was very strong and widespread. These results indicate that the "Japanese McGurk effect" is less easily induced than the English one, and that it depends on the auditory intelligibility of the speech signal.

Prognostic value of hepatic volumetry in fulminant hepatic failure.

Serial hepatic volumetry calculated from the liver area on abdominal computed tomography was performed in 19 patients with fulminant hepatic failure to determine a relationship between liver volume and prognosis. All patients received intensified artificial liver support comprised of plasma exchange and hemodiafiltration using high-performance membranes, and 10 patients survived. Liver volume was significantly larger in survivors than in nonsurvivors, both in an initial volumetry performed at the onset of coma and in subsequent volumetry performed 10-20 days after the onset of coma. The difference became more significant in the subsequent volumetry because of the recovery of liver size in some of the survivors and progressive liver shrinkage in all nonsurvivors. All patients with a liver volume greater than 656 ml at 10-20 days after the onset of coma survived, whereas all but one patient with a liver volume less than that died. Multivariate analysis revealed only liver volume in subsequent volumetry had discriminatory power upon prognosis among six prognostic factors. These observations imply that in order to obtain an accurate prediction of fulminant hepatic failure by hepatic volumetry, serial studies at least until 10-20 days after the onset of coma are necessary.

Possible association between serum GB virus C RNA level and disease activity in fulminant hepatitis type G.

BACKGROUND/AIMS: Whether GB virus C causes serious liver diseases remains controversial. The aim of the present study was to determine whether there is an etiological relationship between GB virus C and fulminant hepatitis. METHODS: The level of GB virus C RNA in the sera of three patients with fulminant hepatitis was quantitatively determined using the newly developed real-time detection polymerase chain reaction method, which is based on Taq Man chemistry. The NS 3 region of the viral genome isolated from the sera was sequenced at several time points to confirm whether the same virus was responsible for fulminant hepatitis during the patients' clinical courses. RESULTS: The sensitivity of the PCR was comparable to that of nested PCR and a linear relationship between RNA copy number and threshold cycle was observed for 10(1) and 10(6) RNA copies/ml (r = 0.99). The serum level of GB virus C RNA closely paralleled that of ALT in all patients. Sequence analysis of the NS3 region isolated from the patients' sera revealed that the same GB virus C strain infected the patients during their entire clinical courses, despite plasma exchange therapy. CONCLUSIONS: These observations suggest that GB virus C may be etiologically associated with fulminant hepatic failure, and is not merely an inactive bystander introduced by therapeutic plasma exchange.

Development of reliable artificial liver support (ALS)--plasma exchange in combination with hemodiafiltration using high-performance membranes.

A new artificial liver support system (ALSS) consisting of plasma exchange (PE) in combination with hemodiafiltration (HDF) using high-performance membranes of polymethyl methacrylate (PMMA) and cellulose triacetate (CTA) was developed to efficiently remove middle molecules from plasma and treat fulminant hepatic failure (FHF) complicated by the onset of hepatic coma. Twenty-seven patients with FHF due to viral hepatitis, two with type A (HA), nine with type B (HB), and 16 with type non-A, non-B (NANB) underwent therapy with this new ALSS over the last five years. Three patients with an exacerbation of chronic HB and 15/16 with type NANB hepatitis were treated with interferon (IFN) also. Of these, 25 patients (92.6%) regained consciousness and 15 (55.6%) [1/2 (50%) with type A, 6/9 (66.7%) with type B and 8/16 (50%) with type NANB hepatitis] survived. Including four patients who survived with intensive care and plasma exchange alone, 19/31 (61.3%) patients survived. Because of its biocompatibility, both survivors and nonsurvivors could be sustained with the ALSS without complications for long periods (19.3 days for the survivors and 32.4 days for nonsurvivors). With this ALSS the ability to sustain life for such prolonged periods allows hepatic regeneration to occur and result in patient survival. It is anticipated that this new ALSS will not only be of value in cases of fulminant hepatic failure but that it may also play a role in sustaining life for those awaiting liver transplantation.