Liver support systems as perioperative care in liver transplantation-historical perspective and recent progress in Japan.

A meta-analysis of the efficacy of artificial liver support (ALS) systems for fulminant hepatic failure (FHF) by the Cochrane Hepato-Biliary Group suggested that all ALS systems previously developed are ineffective for FHF. This supports the view that the only treatment of choice for FHF is immediate liver transplantation. Plasma exchange, in combination with high-volume hemodiafiltration or high-flow continuous hemodiafiltration using large pore membranes, which was excluded from the Cochrane meta-analysis because of the lack of randomized control trials, has become a standard ALS system in Japan. This system is safe, and it efficiently removes more low and middle molecular weight toxic substances than other methods by using a large volume of buffers (more than 200 L per session), resulting in recovery from coma in patients with severe FHF comparable to an ahepatic state. These artificial liver support systems are effective tools for sustaining patients with FHF in a favorable condition until liver function recovers or liver transplantation becomes available.

Induction of allogeneic unresponsiveness in adult dogs. Role of non-DLA histocompatibility variables in conditioning the outcome of bone marrow, kidney, and skin transplantation in radiation chimeras.

Exposure to supralethal total body irradiation and transplantation of bone marrow from a DLA- and pedigree-identical donor have regularly produced successful engraftment and the establishment of stable long-term chimerism in beagles of the Cooperstown colony. Bone marrow allografts performed in pairs of dogs bearing identical DLA haplotypes derived from different pedigree origins (i.e., different classes of the same haplotype) yielded two different results. Depending upon the particular haplotype pedigree combination used, such transplants either led to long-term chimerism or to failures of engraftment, secondary disease, and death of the recipients (i.e., pedigree-incompatible combinations). Radiation chimeras given bone marrow from a DLA-and pedigree-identical donor were challenged within 8-12 h after marrow transplantation with a renal allograft obtained from another DLA- and pedigree-identical donor. The recipients have remained unresponsive to such renal allografts and have survived indefinitely with normal renal function. In contrast, renal allografts obtained from donors bearing the same DLA haplotypes derived from pedigree-incompatible sources were rejected within 25-50 days after transplantation. The long-term surviving recipients have also been unresponsive to skin allografts obtained from their donor of marrow and the kidney donor. Skin grafts obtained from other DLA- and pedigree-identical dogs were rejected within 13-41 days, and grafts from DLA-incompatible donors survived for 10-25 days. These results highlight the potential importance of genetically controlled histocompatibility determinants other than DLA in conditioning allograft reactivity. The determinants uncovered in the present study appear to be linked to the DLA complex, as demonstrated by the ability of the pedigree origins of DLA haplotypes present in individual dogs to serve as an effective marker system for such non-DLA antigen(s). The results also point to the potential usefulness of the early postirradiation period for the induction of allogeneic unresponsiveness in large adult mammals.

Direct hemoperfusion with a cytokine-adsorbing device for the treatment of persistent or severe hypercytokinemia: a pilot study.

BACKGROUND/AIMS: Cytokine overproduction has been noted during the aggravation of clinical conditions. Countermeasures to control hypercytokinemia are therefore important in critical care. We investigated the clinical efficacy of hemoadsorption therapy using a new cytokine-adsorbing device in critically ill patients with persistent or severe hypercytokinemia. METHODS: Direct hemoperfusion using the CYT-860, a cytokine-adsorber column (CYT-860-DHP), was performed in critically ill patients with hypercytokinemia. To evaluate the efficacy of CYT-860-DHP, changes in pathological and clinical parameters were examined. RESULTS: Seven patients with hypercytokinemia and a SOFA score of > or = 5 underwent CYT-860-DHP treatment. Four patients survived 28 days after CYT-860-DHP treatment. Significant decreases in blood levels of cytokines were observed. PaO2/F(I)O2 improved significantly. CONCLUSION: The possibility that CYT-860-DHP treatment can reduce blood cytokine levels and thereby improve the general condition of patients was suggested. These findings warrant the initiation of a prospective randomized trial to evaluate the clinical efficacy of CYT-860-DHP treatment.

Alzheimer's disease and 5-HTTLPR polymorphism of the serotonin transporter gene: no evidence for an association.

Recently two independent research groups consistently reported a significant association between the serotonin transporter (5-HTT) gene and late-onset sporadic Alzheimer's disease (AD). They found that the "short" allele of the 5-HTT gene-linked polymorphic region (5-HTTLPR), which is associated with reduced transcriptional activity of the gene, increases the risk of developing late-onset AD. The present study tried to replicate this finding in a Japanese sample. We genotyped 41 patients with early-onset AD (<65 years), 82 with late-onset AD, and 336 controls. There was no significant difference in genotype or allele distribution between either patient group and controls in our sample, suggesting that the 5-HTTLPR does not play a major role in the pathogenesis of AD in Japanese.

Comparison of Sepsis-related Organ Failure Assessment (SOFA) score and CIS (cellular injury score) for scoring of severity for patients with multiple organ dysfunction syndrome (MODS).

OBJECTIVE: To evaluate the usefulness of cellular injury score (CIS) and Sepsis-related Organ Failure Assessment (SOFA) score for determination of the severity of multiple organ dysfunction syndrome (MODS). DESIGN: A prospective observational study. SETTING: A medical and surgical intensive care unit (ICU) of a teaching hospital. PATIENTS: Forty-seven consecutive MODS patients. MEASUREMENTS AND RESULTS: SOFA score and CIS were measured every day for 12 months for 47 MODS patients. Comparison was made of the SOFA score and CIS for usefulness in the scoring of severity of MODS in 26 survivors and 21 non-survivors. In addition, receiver operating characteristics (ROC) analysis was used to determine the usefulness of these two indexes as predictors of prognosis. No significant differences were found on admission between the survivors and non-survivors, but significant differences between the two subgroups (p < 0.001) were found in maximum value within 1 week after admission and maximum value during the course of treatment for both indexes. Analysis of changes after admission indicated that significant differences between survivors and non-survivors began to appear on day 3 of admission for both indexes; at that time SOFA score began to deteriorate in the non-survivors while CIS began to improve in the survivors. ROC analysis demonstrated that the area under the ROC curve was 0.769 for SOFA scores and 0.760 for CIS. CONCLUSIONS: Both SOFA score and CIS sequentially reflected the severity of MODS. Furthermore, they were comparable in diagnostic value as predictors of prognosis. These findings may indicate the possibility that MODS is a summation of effects of cellular injury. In addition, sequential evaluation of both SOFA score and CIS would provide a more accurate prediction of prognosis than conventional methods.

Blocking AMPA receptor desensitization prolongs spontaneous EPSC decay times and depolarizes H1 horizontal cells in carp retinal slices.

Desensitization of H1 horizontal cell (H1 HC) glutamate receptors was investigated in carp retinal slices using cyclothiazide (CTZ), an inhibitor of AMPA receptor desensitization. 100 microM CTZ depolarized H1 HCs and increased the amplitude of light responses, without any prominent changes in their kinetics. Spontaneous EPSCs (sEPSCs) in H1 HCs were observed in the presence of 2.5 mM heptanol, an uncoupling agent of gap junctions. 20 microM GYKI52466 (an AMPA receptor antagonist) blocked the sEPSCs, consistent with the sEPSCs being mediated by AMPA receptors. 100 microM cobalt suppressed the frequency of sEPSCs without changing their mean peak amplitude, suggesting that calcium-dependent transmitter release from cones was not affected by heptanol. CTZ increased the total inward charge transferred per sEPSC by increasing the sEPSC decay time constant twofold, without any significant change in their frequency and mean peak amplitude. This suggests that the depolarizing effect of CTZ on H1 HCs was due to blocking desensitization of AMPA receptors, increasing the inward current induced by glutamate released from cone synaptic terminals. The desensitization of glutamate receptors may function to extend the dynamic range of H1 HC light responses.

Analysis of spontaneous EPSCs in retinal horizontal cells of the carp.

Spontaneous excitatory postsynaptic currents (sEPSCs) were recorded under Whole-cell voltage clamp from carp type 1 horizontal cells (H1 cells) uncoupled by dopamine in retinal slices. Red light steps, which hyperpolarise cones and reduce glutamate release, induced outward current responses accompanied by a suppression of sEPSCs. sEPSCs decayed exponentially with a mean time constant of 0.71+/-0.07 ms and had a reversal potential near 0 mV. Power spectral analysis of sEPSCs revealed a similar decay time constant. They were suppressed by a non-NMDA receptor antagonist, CNQX at 10 microM, and a relatively specific AMPA receptor antagonist, GYKI52466 at 20 microM. The presence of sEPSCs suggests that the release of glutamate from cone synaptic terminals is vesicular. The reduction in mean sEPSC frequency with red light was not accompanied by a significant change in the mean sEPSC conductance increase (482+/-59 pS), suggesting that a decrease in the vesicular release rate from cones does not alter the vesicular glutamate concentration (quantal contents). The results suggest that the spontaneous events in H1 cells were contributed by non-NMDA (possibly AMPA) type glutamate receptors modulated by the red cone input.

Effects of nitric oxide, light adaptation and APB on spectral characteristics of H1 horizontal cells in carp retina.

The spectral characteristics of cone-driven horizontal cells of H1 subtype (H1 HCs) receiving main synaptic input from red-sensitive cones were studied in light- and dark-adapted retinae of carp. The spectral sensitivity profile of H1 HCs in dark-adapted retinae was practically the same as the absorption spectrum of red-sensitive cones. Light-adaptation decreased the sensitivity preferentially in the short-wavelength (blue/green) region, resulting in a relative enhancement of the 617 nm peak. Application of nitric oxide (NO) donors, sodium nitroprusside (SNP) and S-nitrosoglutathione (SNOG or GSNO), or dopamine to dark-adapted retinae decreased the sensitivity preferentially in blue/green region, an effect similar to that of light-adaptation. Application of haemoglobin (Hb, an NO scavenger) or 2-amino-4-phosphonobutyrate (APB, a metabotropic glutamate receptor agonist), to light-adapted retinae increased the sensitivity preferentially in the blue/green region, an effect similar to dark-adaptation. The photoresponses of H1 HCs were univariant in dark-adapted retinae as well as Hb-treated light-adapted retinae. In light-adapted retinae with normal Ringer, however, the univariance did not hold. These results suggested that the photoresponses of H1 HCs to short-wavelength stimuli contain a depolarising (sign-reversing) component, which can be activated by light-adaptation or application of NO and dopamine, and inactivated by dark-adaptation or deprivation of NO or application of APB.

Myoclonus in Alzheimer's disease.

Myoclonus was studied electrophysiologically in seven patients with clinically diagnosed Alzheimer's disease. There seem to be at least two physiological types of myoclonus in Alzheimer's disease. Cerebral cortical structures might participate in the generation of myoclonus in one type, while the other type is probably generated by subcortical structures.

Possible association of missense mutation (Gly[-63]Glu) of the neurotrophin-3 gene with Alzheimer's disease in Japanese.

Several lines of evidence have suggested a possible involvement of neurotrophic factors in the pathogenesis of neurodegenerative disease. We examined whether a missense mutation (Gly[-63]Glu) of the neurotrophin-3 (NT-3) gene is associated with Alzheimer's disease (AD) in a Japanese sample of 123 patients and 215 controls. We found that homozygotes or heterozygotes for the mutated type (Glu[-63]) were significantly more common among the patients than the controls (P = 0.013, odds ratio 1.77, 95% CI 1.12-2.79). The mutated type was more frequent among the patients than the controls (P = 0.011, odds ratio 1.63, 95%CI 1.11-2.38). This association between NT-3 and AD was more prominent among those who did not carry the epsilon4 allele of the apolipoprotein E gene than those who carried the epsilon4 allele. Our results suggest that the Glu(-63) allele of the NT-3 gene by itself or another mutation nearby which would be in linkage disequilibrium to the mutation is a risk factor for AD.

Activation of the visual cortex imaged by 24-channel near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) is a noninvasive technique for continuous monitoring of the amounts of total hemoglobin (total-Hb), oxygenated hemoglobin, (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb). The purpose of the present study was to demonstrate the utility of NIRS in functional imaging of the human visual cortex. A new NIRS imaging system enabled measurements from 24 scalp locations covering a 9 cm sq area. Topographic images were obtained from interpolations of the concentration changes between measurement points. Five healthy subjects between 25 and 49 years of age were investigated. After a resting baseline period of 50 s, the subjects were exposed to a visual stimulus for 20 s, followed by a 50 s resting period in a dimly lit, sound attenuating room. The visual stimulus was a circular, black and white, alternating checkerboard. In four of five subjects the visual cortex was the most activated area during visual stimulation. This is the first reported use of a NIRS-imaging system for assessing hemodynamic changes in the human visual cortex. The typical hemodynamic changes expected were observed; the total-Hb and oxy-Hb increased just after the start of stimulation and plateaued after 10 s of the stimulation period.

Hydrostatic pressure versus osmotic pressure in the development of vasogenic brain edema induced by cold injury.

The role of hydrostatic pressure and osmotic pressure gradient in the development of vasogenic brain edema induced by cold lesion made in the parietal cortex was studied in cats under ketamine anesthesia and blood pressure monitoring. The animals were divided into a hypertensive group and a normotensive group and were kept alive for 6 hr. The brain was removed and cut coronally at the lesion for tissue sampling from various areas of edematous white matter to measure both the SG and the amount of extravasated serum albumin in the same samples. Our result showed that the edema confined in the area containing extravasated serum albumin and the increase of water content correlated linearly with the amount of extravasated serum albumin both in the normotensive group and hypertensive group. However, the slope of the regression line indicated albumin content in the edema fluid was significantly different between the two groups. The slope became lower as the MABP during the experiment became higher, indicating that protein concentration in the edema fluid became lower when hypertension sustained. Thus, both hydrostatic and osmotic pressure gradient regulate the extravascular accumulation of edema fluid in the cold lesion edema.

Quantitative EEG correlates of normal aging in the elderly.

To clarify the effect of normal aging on the EEG in the elderly, relative EEG power and coherence were studied in 68 elderly subjects (age range 61-90 years) as well as in 20 young subjects (age range 23-38 years). Relative beta power was significantly higher in the elderly subjects, while no significant differences were seen among the elderly groups. Therefore it may be assumed that EEG power in the centrooccipital region among the normal elderly remains almost unchanged. Also, age had no effect on interhemispheric coherence. However, intrahemispheric coherence was found to decrease with age in all bands almost linearly. Thus, intrahemispheric coherence is a more sensitive indicator of normal aging than relative power.

New equations to calculate temperature correction factors for PO2 in human blood.

Effects of hemoglobin concentration (Hb), pH, and body temperature (T) on the relationships between delta log PO2/delta T and PO2 were studied by means of a mathematical model using a Newton-Raphson iteration method. The functions between delta log PO2/delta T and PO2 were affected by the above three factors. New equations considering the effects of Hb, pH, and T were proposed by modifying the equation reported by Severinghaus: delta log PO2/delta T = (L +(U-L)/(A(vPO237)B + 1))(10(-2) where U = 3.15-0.45(7.4-pH37) L = 0.68-0.09(7.4-pH37) A = 5.86(exp10(0.074(T)-0.294(7.4-pH37)-11))((Hb)0.913) B = 6.33(exp10(-0.0051(T)))((Hb)-0.113) + 0.24(7.4-pH37) and vPO237 is virtual PO237 which may exist when PO237 is corrected to standard conditions (pH = 7.4, BE = 0) by the following equations: vPO237 = PO237(exp10(fB(7.4-pH37)-0.0013(BE))) fB = (PO237/26.6)0.08-1.52 where fB is the Bohr factor. The above equations provided values of delta log PO2/delta T which fit closely to those obtained by the complex iteration method with maximum differences of less than 1.3 X 10(-3) at T = 27, indicating that maximum % errors for PO2 at T (PO2T) are less than 3.0% at T = 27 and that our equations can be applied over a wide range of Hb, pH37 and T.

Bony entrapment of ulnar nerve after closed forearm fracture: a case report.

We report a case of ulnar nerve palsy following forearm fracture in a 13-year-old girl. Significant anterior angulation and displacement of the ulna were noted. Operation was performed 3 months after the injury, when no recovery of numbness and claw hand deformity were demonstrated. Intra-operatively the ulnar nerve was found to be embedded between fragments of the fractured ulna, which showed lack of callus formation on the preoperative radiograph. The patient achieved complete recovery of sensory and motor functions 4 months after the surgery.

Kienböck disease treated by excisional arthroplasty with a palmaris longus tendon ball: a comparative study of cases with or without bone core.

We hypothesised that using a palmaris longus tendon ball (PLTB) with bone core (w bc) after excisional arthroplasty for Kienböck disease would maintain post-operative carpal height compared to a PLTB without bone core (w/o bc). Seventeen hands of 16 consecutive patients with Kienböck disease at Lichtman stage IIIA or IIIB were treated by replacement of the lunate with a PLTB w bc or w/o bc. We evaluated the clinical and radiological outcomes at one, three and 12 months after surgery. According to Dornan and Lichtman criteria respectively, there were no significant differences between the two groups. In the w bc group, the post-operative values of the carpal height ratio (CHR) were maintained at the same level as pre-operative values for one year, while the post-operative CHR values in the w/o bc group were significantly lower than those in the w bc group. Our results indicate that in Kienböck disease, arthroplasty using a PLTB w bc can maintain CHR at one year after surgery compared to arthroplasty using a PLTB w/o bc.

[Nosocomial infections and clinical microbiology].

Hospital-acquired infection with strains of methicillin-resistant Staphylococcus aureus (MRSA) have considerably increased in recent years. In addition to being resistant to methicillin, these strains are resistant to practically all forms beta-lactams, aminoglycosides and many other antibiotics. There appears no cost-effective control and preventive measures for this common but also potentially life-threatening disease. Although not clearly presented, the overall cost for the treatment of patients infected with MRSA should be enormous. Can laboratory medicine (or clinical microbiology) contribute to this global medical problem? Multiple strains of MRSA circulate within a hospital and some strains are even localized within specific wards. These facts suggest yet undisclosed routes of transmission and/or foci of infection. Triumph over these versatile organisms may have to await the development of new antibiotics effective for MRSA.

[Methicillin-resistant Staphylococcus aureus infection in the Akita University Hospital: surveillance and microbiology data].

In order to control the nosocomial infections by methicillin-resistant Staphylococcus aureus (MRSA) in the Akita University Hospital, the systematic surveillance for MRSA-infection has been done since October in 1991. We reviewed MRSA-isolation numbers, MRSA-detected patient numbers, risk factors of nosocomial infection and patient's basic diseases with the data of a total 336 cases, and then examined the microbiological characteristics of MRSA strains which had been isolated in our hospital in 1986 approximately 1994. The results obtained are as follows; 1) MRSAs were isolated at 13 per month on the average and the detection rate was 0.81 to 1,000 inpatients per day. 2) MRSAs were isolated more in the surgical ward. 3) Patients with 0 year old and more than 60 years old were more infected. 4) MRSA was isolated more from the immunocompromised patients with underlying diseases such as malignant tumors but half of the diseases were not affected by MRSA. 5) Seventy percent of patients had the risk factors of MRSA-transmission such as surgical operation and IVH-cathetering. 6) All isolates of MRSA strains in our hospital showed type II in coagulase type analysis and resistance to minocycline and ofloxacin. 7) It was suggested that one strain expanded throughout the hospital by several DNA analysis with the mecA gene in MRSA. These surveillance and microbiology data will be useful for our nosocomial mecA gene in MRSA. These surveillance and microbiology data will be useful for our nosocomial infection control.

[A study on the utility of flumazenil for patients in the ICU].

Flumazenil, a specific antagonist of benzodiazepines, was administered to adult patients receiving treatment at ICU, and its utility to hasten recovery from sedation was evaluated in 40 patients and its usefulness for differential diagnosis of sedated conditions was also evaluated in 5 patients. The efficacy rate for recovery from sedation induced by benzodiazepines was 85.0%. Moreover, flumazenil was considered to be useful for differentiation of sedated conditions when causes were unknown. Depression of respiration improved in association with improvement of consciousness level. In some patients an elevation in blood pressure was also observed with improved consciousness.

[Evaluation of the therapeutic effect of HCFU (1-hexylcarbamoyl-5-fluorouracil) on non-resectable stomach cancer].

The present study was aimed at investigating the efficacy of a new oral anticancer agent, HCFU, that is, (1-hexylcarbamoyl-5-fluorouracil), against 14 cases of unresectable gastric cancers which were confirmed by the laparotomy. The daily dose was 600mg and given continuously as long as the patients could take the drug orally. The efficacy was examined by X-ray photographs according to the criteria for the judgement of direct effect of the chemotherapy for solid malignant tumor. For the diffuse invasive type of gastric cancer, the changes in the X-ray finding such as stiffness and poor elasticity of gastric wall and malignant relief were also taken into consideration for the judgement. Among 9 patients, in whom the efficacy was measurable, two cases showed "partial response (PR)", two cases were diagnosed as "no change (NC)" and other 5 cases were diagnosed as "progressive disease (PD)". Among 2 partial responders, 1 case showed 85.3% decrease of the tumor size on the X-ray film and the other, who had diffuse invasive gastric cancer, showed much improvement on the X-ray film described above. The survival was around 5 months in "progressive disease" group. On the other hand, the patients with the good response to HCFU such as PR patients and NC patients could obtain a relatively longer survival period.