Japanese-style intensive medical care improves prognosis for acute liver failure and the perioperative management of liver transplantation.

The Japanese style of intensive medical care for acute liver failure has yielded high survival rates. The care system comprises artificial liver support (ALS) together with treatment for the underlying disease. Plasma exchange in combination with high-volume hemodiafiltration using an high performance membrane has become the standard ALS system. It is safe, efficiently removing more low and middle molecular weight toxic substances than other methods because of the large volumes of buffer (more than 200 L per session), resulting in recovery from coma in patients with severe fulminant hepatitis, a status comparable with the ahepatic state. This ALS is therefore an effective tool to sustain patients with fulminant hepatitis in a favorable condition until liver function recovers or liver transplantation becomes available. The accompanying treatment for underlying disease serves to limit the liver destruction that hampers regeneration. The treatment has remarkably improved the prognosis for patients with subacute types of fulminant hepatitis, which generally carry a less favorable prognosis than the acute type. This treatment system thus provides more time for physicians to assess the indications for liver transplantation as well as giving the patient a greater chance of undergoing transplantation.

Neuroprotective effect of chronic lithium treatment against hypoxia in specific brain regions with upregulation of cAMP response element binding protein and brain-derived neurotrophic factor but not nerve growth factor: comparison with acute lithium treatment.

OBJECTIVES: We evaluated the neuroprotective effect of chronically or acutely administered lithium against hypoxia in several brain regions. Furthermore, we investigated the contribution of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and cAMP response element binding protein (CREB) to the neuroprotective effect of lithium. METHODS: Brain slices were prepared from rats that had been treated chronically or acutely with lithium. The cerebral glucose metabolic rate (CMRglc) before and after hypoxia loading to brain slices was measured using the dynamic positron autoradiography technique with [(18)F]2-fluoro-2-deoxy-D-glucose. The changes of expression of proteins were investigated using Western blot analysis. RESULTS: Before hypoxia loading, the CMRglc did not differ between the lithium-treated and untreated groups. After hypoxia loading, the CMRglc of the untreated group was significantly lower than that before hypoxia loading. However, the CMRglc of the chronic lithium treatment group recovered in the frontal cortex, caudate putamen, hippocampus and cerebellum, but not in the thalamus. In contrast, the CMRglc of the acute lithium treatment group did not recover in any analyzed brain regions. After chronic lithium treatment, the levels of expression of BDNF and phospho-CREB were higher than those of untreated rats in the frontal cortex, but not in the thalamus. However, the expression of NGF did not change in the frontal cortex and thalamus. CONCLUSIONS: These results demonstrated that lithium was neuroprotective against hypoxia only after chronic treatment and only in specific brain regions, and that CREB and BDNF might contribute to this effect.

Topological and chronological features of the impairment of glucose metabolism induced by 1-methyl-4-phenylpyridinium ion (MPP+) in rat brain slices.

1-Methyl-4-phenylpyridinium (MPP(+)) was added directly to fresh rat brain slices and the dynamic changes in the cerebral glucose metabolic rate (CMRglc) were serially and two-dimensionally measured with [(18)F]2-fluoro-2-deoxy-D-glucose as a tracer. MPP(+) dose-dependently increased CMRglc, reflecting enhanced glycolysis compensating for the decrease in aerobic metabolism. While the CMRglc enhancement induced by MPP(+) (<10 microM) was restricted to the striatum, MPP(+) (>or=10 microM) induced a significant CMRglc enhancement in all brain regions. MPP(+) at high concentration (1 mM) eventually initiated rapid metabolic collapse, with failure to sustain anaerobic glycolysis.

Region-specific induction of hypoxic tolerance by expression of stress proteins and antioxidant enzymes.

We examined the induction of hypoxic tolerance after hypoxic preconditioning in the frontal cortex, caudate putamen and thalamus using the dynamic positron autoradiography technique and [18F]2-fluoro-2-deoxy-D-glucose with rat brain slices. Hypoxic tolerance induction was confirmed in the frontal cortex, but not in the caudate putamen and thalamus. Next, we compared the gene expression in the frontal cortex and caudate putamen using the ATLAS Rat Stress Array, and found that the expression of 150-kDa oxygen-regulated protein and mitochondrial heat shock protein 70 as stress proteins, and copper-zinc-containing superoxide dismutase and manganese-containing superoxide dismutase as antioxidant enzymes was elevated only in the frontal cortex. These results suggest that the induction of hypoxic tolerance after hypoxic preconditioning is region-specific, and stress proteins and antioxidant enzymes participate in this phenomenon.

Thirty cases of bronchial asthma associated with exposure to pet hamsters.

BACKGROUND: The identification, isolation, and elimination of allergen(s) causing bronchial asthma are the most efficient form of treatment. The pet industry has diversified recently, increasing the risk of exposure of pet owners to many unknown antigens. We clinically studied the characteristics of asthma associated with exposure to pet hamsters. METHODS: The study group comprised 30 adults in whom the onset, recurrence, or exacerbation of asthma was triggered by contact with pet hamsters. Clinical characteristics such as sex, age, period required for symptom onset, species of hamster, treatment and disease course, smoking status, and hamster-specific IgE antibodies in serum were studied. RESULTS: The male: female ratio of the study group was 1:1.3, and mean age was 37.7 years. Patients with no previous history of asthma initially presented with cough, progressing to episodes of asthma. Asthmatic symptoms were associated with hamster contact and ranged in severity from mild to severe. Three patients required hospital admission for treatment. The mean period from the start of hamster exposure to the onset of asthmatic episodes was 15.7 months. Dwarf hamsters were responsible for most cases. The CAP-RAST score for hamster-specific IgE antibodies was 1 to 4 in 22 patients and 0 in 8 patients. Eight patients with a score of 1 or higher for hamster-specific IgE antibodies had a CAP-RAST score of 0 for mite antigen. In these patients, terminating hamster contact resulted in a rapid improvement in symptoms, with no need for further treatment. Twenty-three of the 30 subjects (76.7%) were smokers. CONCLUSION: Exposure to pet hamsters is an important risk factor for the onset, recurrence, or exacerbation of asthma. Smoking may also increase the risk of asthmatic symptoms in patients exposed to hamsters.

Clinical evaluation of response to long-term treatment with Pranlukast in patients with bronchial asthma.

BACKGROUND: Short-term treatment with pranlukast, a leukotriene receptor antagonist, has shown to be effective for the management of asthma. The effectiveness and safety of long-term treatment with pranlukast remains to be established. OBJECTIVES: The aim of this study was to determine the effects of pranlukast on morning peak expiratory flow rates (PEFRs), the diurnal variation of these values, and disease severity. METHODS: Fifteen men with bronchial asthma were studied for 5 years. During the first year, the subjects were treated with a bronchodilator; some also received inhaled and oral corticosteroids. During the next 4 years, the subjects received pranlukast in addition. RESULTS: Mean PEFR increased after the start of treatment with pranlukast. The increase in PEFR occurred later in subjects with more severe disease. Diurnal variation of PEFR was unchanged, but subsequently decreased. The condition of all subjects improved, but the greatest improvement was obtained in patients with mild to moderate asthma. CONCLUSIONS: Long-term treatment with pranlukast is effective for the management of bronchial asthma, particularly in patients with mild to moderate disease. Our results suggest that the effectiveness of antiasthmatic drugs should be evaluated over a period of years, rather than on a short-term basis.

Greater resistance and lower contribution of free radicals to hypoxic neurotoxicity in immature rat brain compared to adult brain as revealed by dynamic changes in glucose metabolism.

Seven-day-old rat brain slices were incubated at 36C in oxygenated Krebs-Ringer solution containing [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG), and serial two-dimensional time-resolved images of [(18)F]FDG uptake by the slices were obtained. The Gjedde-Patlak graphical method was applied to the image data, and the duration limit of hypoxia loading that allowed recovery of the fractional rate constant (k3*) of [(18)F]FDG (proportional to the cerebral glucose metabolic rate) after hypoxia loading to the unloaded control level was 50 min, and MK-801 as an N-methyl-D-aspartate antagonist had neuroprotective effects, but PBN as a free radical scavenger was ineffective. In our previous study in adult (7-week-old) rat brains [Murata et al., Exp Neurol 2000, 164:269-279], the limit of the hypoxia loading time was 20 min, and both MK-801 and PBN were effective. In the immature rat brains, the ratio of aerobic glucose metabolism to the total glucose metabolism was low compared with the adult rat brains, suggesting only a slight involvement of free radicals in hypoxic neurotoxicity. These data suggest that the higher resistance of immature brains to hypoxia compared to that of adult brains is attributable to a lower involvement of free radicals due to a lower aerobic glucose metabolic rate.

alpha-actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells.

Voltage-gated K(+) (Kv) channels are particularly important in the physiology of excitable cells in the heart and the brain. PSD-95 is known to cluster Shaker channels and NMDA receptors and the latter is known to couple through alpha-actinin-2 to the post-synaptic cytoskeleton [Wyszynski et al. (1997) Nature 385, 439-442], but the mechanisms by which Kv channels are linked to the actin cytoskeleton and clustered at specific sites in the heart are unknown. Here we provide evidence that Kv1.5 channels, widely expressed in the cardiovascular system, bind with alpha-actinin-2. Human Kv1.5 interacts via its N-terminus/core region and can be immunoprecipitated with alpha-actinin-2 both after in vitro translation and from HEK cells expressing both proteins. The ion channels and alpha-actinin-2 co-localize at the membrane in HEK cells, where disruption of the actin cytoskeleton and antisense constructs to alpha-actinin-2 modulate the ion and gating current density.

Preparation of detergent-lipase complexes utilizing water-soluble amphiphiles in single aqueous phase and catalysis of transesterifications in homogeneous organic solvents.

A novel method of preparing detergent-enzyme complexes that can be employed in organic media was developed utilizing newly synthesized water-soluble nonionic gemini-type detergents, N,N-bis(3-D-gluconamidopropyl)-3-(dialkyl-L-glutamatecarbonyl)propanamides (BIG2CnCA: n = 10,12,14,16,18) and N,N-bis(3-D-lactonamidopropyl)-3-(dialkyl-L-glutamatecarbonyl)propanamides (BIL2CnCA: n = 16,18), and nonionic twin-headed detergents, N,N-bis(3-D-gluconamidopropyl)alkanamides (BIG1Cn: n = 12,14,16,18,delta9). This method simply entails mixing a selected enzyme with an appropriate detergent in an aqueous solution followed by lyophilization, and it offers the advantages of enhanced enzymatic activity in organic solvents and eliminates both enzyme loss and the necessity for an organic solvent in the preparation stage. Using various modified lipases originating from Aspergillus niger (Lipase A), Candida rugosa (Lipase C), Pseudomonas cepacia (Lipase P), and porcine pancreas (PPL), prepared using the novel method and detergents, including conventional synthesized nonionic detergents such as dialkyl N-D-glucona-L-glutamates (2CnGE: n = 12,18delta9) and octanoyl-N-methylglucamide (MEGA-8), enantioselective transesterifications of 6-methyl-5-hepten-2-ol (sulcatol) and 2,2-dimethyl-1,3-dioxolane-4-methanol (solketal) with a vinyl or isopropenyl carboxylate were carried out in an organic solvent. The modified lipase activity was influenced by both the lipases and the structure of the detergents. The value for the hydrophile-lipophile balance (HLB) of the detergent provided a means of correlating the structure and the obtained modified lipase activity. For detergents of the same class with a HLB value of approximately 9 and 12, the highest activity was obtained for Lipase A and Lipase P, and Lipase C and PPL, respectively. Among detergents of the same HLB value tested, the gemini-type detergents possessing the most bulky head and tail were most effective as a modifier for lipases of all types. The preparation and reaction conditions for these novel gemini-type detergent-modified lipases were optimized using BIG2C12CA (HLB = 9.4) by studying the effect of the detergent/lipase ratio and the nature of organic solvents on the complex formation. The high enzymatic activities of the BIG2C12CA-modified lipases were independent of the solubility of the lipases in organic solvents, unlike in the case of 2CnGE-modified lipases prepared using the conventional suspension system.

Modulation of slow inactivation in human cardiac Kv1.5 channels by extra- and intracellular permeant cations.

1. The properties and regulation of slow inactivation by intracellular and extracellular cations in the human heart K+ channel hKv1.5 have been investigated. Extensive NH2- and COOH-terminal deletions outside the central core of transmembrane domains did not affect the degree of inactivation. 2. The voltage dependence of steady-state inactivation curves of hKv1.5 channels was unchanged in Rb+ and Cs+, compared with K+, but biexponential inactivation over 10 s was reduced from approximately 100 % of peak current in Na+ to approximately 65 % in K+, approximately 50 % in Rb+ and approximately 30 % in Cs+. This occurred as a result of a decrease in both fast and slow components of inactivation, with little change in inactivation time constants. 3. Changes in extracellular cation species and concentration (5-300 mM) had only small effects on the rates of inactivation and recovery from inactivation (tau recovery approximately 1 s). Mutation of residues at a putative regulatory site at R487 in the outer pore mouth did not affect slow inactivation or recovery from inactivation of hKv1.5, although sensitivity to extracellular TEA was conferred. 4. Symmetrical reduction of both intra- and extracellular cation concentrations accelerated and augmented both components of inactivation of K+ (Kd = 34.7 mM) and Cs+ (Kd = 20.5 mM) currents. These effects could be quantitatively accounted for by unilateral reduction of intracellular K+ (K+i) (Kd = 43.4 mM) or Cs+i with constant 135 mM external ion concentrations. 5. We conclude that inactivation and recovery from inactivation in hKv1.5 were not typically C-type in nature. However, the ion species dependence of inactivation was still closely coupled to ion permeation through the pore. Intracellular ion modulatory actions were more potent than extracellular actions, although still of relatively low affinity. These results suggest the presence of ion binding sites capable of regulating inactivation located on both intracellular and extracellular sides of the pore selectivity filter.

[Agenesis of the right internal carotid artery with intracerebral hemorrhage: case report].

A 45-year-old woman was admitted to our department because of intracerebral hemorrhage. Neurological examination showed upward gaze palsy, right hemihypesthesia including face and nuchal rigidity. CT scan demonstrated a high density spot in the left quadrigeminal plate. Postcontrast CT scan demonstrated an abnormal vessel in the left midbrain. We suspected the presence of an arterio-venous malformation (AVM) and angiography was performed. Left vertebral angiography demonstrated early filling as far as the basal vein of Rosenthal with the contrast medium. However, no nidus suggesting AVM was observed. The right middle cerebral artery was fed via an anastomotic vessel (anomalous posterior communicating artery) from basilar bifurcation. Right carotid angiography demonstrated only the right external carotid artery indicating the absence of the right internal carotid artery. The bone target image of thin slice CT scan of the cranial base also disclosed the absence of the right carotid canal. 123I-IMP SPECT demonstrated no hypoperfusion area in the right cerebral hemisphere. The usefulness of the thin slice CT scan in the cranial base was discussed.

Ruptured intracranial aneurysm in a 19-day-old infant--case report.

The authors describe the case of a 19-day-old infant with a ruptured intracranial aneurysm. She had suddenly become lethargic after drinking milk. Cerebral angiography demonstrated a large aneurysm arising from the right middle cerebral artery. Because the aneurysm was fusiform, the parent artery was clipped. Histological examination of a specimen taken from the aneurysmal dome showed an organized thrombus with deposition of a calcium-like substance in the wall, which appeared on histochemical examination to be pseudolime. The postoperative course was uneventful and she was discharged without neurological deficits.

Cavernous hemangioma of the optic nerve. Case report.

A case of cavernous hemangioma of the optic nerve of a 24-year-old pregnant woman is reported. The visual disturbance with subacute onset was thought to be related to the delivery of a child. The lesion was totally removed through the subfrontal approach, resulting in satisfactory recovery of visual symptoms. Cavernous hemangioma involving the optic nerve and chiasm is extremely rare. Only two similar cases have been reported previously.

[AUFRAP therapy: combined modality treatment of malignant gliomas with intraarterial infusion of ACNU].

A method of combination therapy was proposed for the treatment of malignant gliomas, and the clinical results were reported. This combination consisted of ACNU (nimustine), UFT (tegafur + uracil), Radiation, vitamin A and PSK (krestin), and was named AUFRAP therapy. Intracarotid infusion of ACNU (100 or 150 mg/body) was done after the administration of vitamin A (100,000 units), in the first and last week of radiation therapy with a total dose of 60-70 Gy. UFT (400-600 mg/day) and PSK (3g/day) were also given orally. After the induction of remission, patients were treated in the outpatient clinic under a similar maintaining protocol. Two patients who received 150 mg of ACNU and daily 600 mg of UFT in combination with radiation therapy showed severe myelosuppression in the early stage of treatment, and the combination therapy was aborted. Two of four patients who received 100mg of ACNU and daily 400mg of UFT did not show such severe side effects and two showed transient, moderate myelosuppression and vomiting. The serum phenitoin concentration doubled and was thought to be a side effect of tegafur. All four patients completed the induction protocol and follow-up CT scans disclosed shrinkage of the remained tumors, decreased contrast enhancement or no evidence of recurrence. Interactions of these drugs and radiation were discussed and the literature was reviewed.

[Spinal cord injury by a broken acupuncture needle--a case report].

Acupuncture has been widely performed for the treatment of many different disorders in Japan. Several complications of acupuncture such as pneumothorax, cardiac tamponade, serum hepatitis have been reported. Accidentally broken needle is also one of the causes of complications of acupuncture. Usually it produces little problem, but may cause spinal cord injury, as presented by this report. The patient was a 49-year-old man who received an acupuncture procedure in his left nuchal region for shoulder pain. During acupuncture the needle was accidentally broken. The needle was tried to be removed by a surgeon on the same day but it could not be found. He was seen at our hospital with no neurological deficit 3 month later. Plain X-ray films and CT scan revealed a 4 cm long needle between C2 and C3 vertebrae penetrating into the cord. The needle was removed to prevent the possible neurological deficit which might be produced by the moving needle. The operative procedure was done under operating microscope with the aids of X-ray monitoring and injected dye. The direction to reach the tail of the broken needle is most important for avoiding further spinal cord injury during procedure. The post-operative course of the patient was uneventful and he was discharged with no deficit.