Hemoglobin Rahere, a human hemoglobin variant with amino acid substitution at the 2,3-diphosphoglycerate binding site. Functional consequences of the alteration and effects of bezafibrate on the oxygen bindings.

We encountered an abnormal hemoglobin (Rahere), with a threonine residue replacing the beta 82 (EF6) lysine residue at the binding site of 2,3-diphosphoglycerate, which was responsible for overt erythrocytosis in two individuals of a Japanese family. Hemoglobin Rahere shows a lower oxygen affinity on the binding of 2,3-diphosphoglycerate or chloride ions than hemoglobin A. Although a decrease in the positive charge density at the binding sites of 2,3-diphosphoglycerate in hemoglobin Rahere apparently shifts the allosteric equilibrium toward the low affinity state, it greatly diminishes the cofactor effects by anions. The oxygen affinity of the patient's erythrocytes is substantially lowered by the presence of bezafibrate, which combines with sites different from those of 2,3-diphosphoglycerate in either hemoglobin Rahere or hemoglobin A.

A new electrophoretic variant of hemoglobin (Ogi) in which a leucine residue is replaced by an arginine residue at position 34 of the alpha-chain.

Hemoglobin Ogi, in which an arginine is substituted for a leucine residue at position 34 of the alpha-chain, was detected in a Japanese family. Although slightly increased oxygen affinity is associated with this amino acid substitution in the alpha 1 beta 1 contact, it is without obvious deleterious effect on the hematological parameters of the individuals heterozygous for this variant.

Multiple-dose study of imipenem/cilastatin in patients with end-stage renal disease undergoing long-term hemodialysis.

Multiple doses of imipenem/cilastatin were administered to patients with end-stage renal disease undergoing long-term hemodialysis. Schedules of 250 mg every six hours, 500 mg every six hours, and 500 mg every 12 hours were studied. Five hundred mg every 12 hours was the most efficient schedule that maintained effective trough antibiotic activity. Twelve volunteers including two patients with clinical infections using the dose schedule of 500 mg every 12 hours received imipenem/cilastatin for two to 14 days without any notable clinical side effects. Imipenem peak and trough concentrations averaged 29 +/- 5 micrograms/ml and 10 +/- 3 micrograms/ml, respectively. No accumulation of imipenem occurred during the trial. Cilastatin peak and trough concentrations were 89 +/- 38 micrograms/ml and 70 +/- 27 micrograms/ml, respectively. The plasma concentration of cilastatin increased with each dose until the next hemodialysis session.

Tetramer Bence Jones protein in the immunoproliferative diseases. Angioimmunoblastic lymphadenopathy, primary amyloidosis, and multiple myeloma.

The authors report the clinical features and the results of immunochemical studies of patients with angioimmunoblastic lymphadenopathy, primary amyloidosis, and multiple myeloma, each of whom had in the serum and urine multiple forms of Bence Jones protein (BJP). The BJPs were isolated and purified and were shown by electrophoretic, gel filtration, and ultracentrifugal analyses to exist as tetramers and dimers. The components in two cases were kappa type and in one lambda type. The kappa tetramers consisted of two covalent dimers and the lambda tetramer two noncovalently bound dimers present in both serum and urine.

Inflammatory pseudotumor of the liver with primary sclerosing cholangitis.

Inflammatory pseudotumor (IPT) of the liver is a rare benign variant of hepatic masses, and its exact etiology has not been elucidated. We report a case of IPT associated with primary sclerosing cholangitis (PSC). The patient was a 50-year-old man admitted to our hospital because of jaundice. Abdominal ultrasonography (US) and computed tomography showed multiple dilations of the intrahepatic bile ducts and multiple masses in the liver. On magnetic resonance imaging, the masses were slightly hypointense on T1-weighted images and slightly hyperintense on T2-weighted images. On T1-weighted images after the bolus infusion of Gd chelate, the masses had no contrast enhancement, and they were hypointense in the arterial phase and portal venous phase. However, they were slightly enhanced and became almost isointense relative to the surrounding normal liver parenchyma in the delayed phase. Endoscopic retrograde cholangiography demonstrated multiple irregular strictures and dilations of the intrahepatic bile ducts. Angiography demonstrated no abnormal findings, but, interestingly, subsequent dynamic CO2-enhanced US showed a strongly hyperechoic string, indicating that an artery had penetrated through the hypoechoic mass. A US-guided percutaneous needle biopsy revealed that the lesions were morphologically comparable to IPT. After cholangiography and microscopic analysis of the tumor, the final diagnosis was determined to be IPT of the liver with PSC. A number of previous reports have suggested a possible relationship between IPT and PSC, based on pathological findings. This report confirmed, based on clinical findings, that PSC is one of the causes of hepatic IPT.

Psychiatric liaison issues in cancer care in Japan.

To clarify the psychiatric liaison issues in Japan, this paper briefly introduces a survey of physician attitudes and practices regarding cancer care in Japan and preliminarily reports on an "active" liaison program developed at one Japanese general hospital. The survey of physicians from 31 teaching hospitals, including all cancer centers, revealed that 56% of physicians do not inform patients of a diagnosis of cancer. Thus, actual psychiatric consultation referrals were very few due to the physician's fear of harming his relationship with the cancer patient. One medical unit, in which about one-quarter of the cancer patients were told their diagnoses by the unit chief physician, showed significantly higher rates of psychiatric consultation after the introduction of an "active" liaison program in that hospital. These results suggest that the liaison program can positively influence the rate of psychiatric consultation referrals for cancer patients when the physician discloses the diagnosis to the patient. Consultation-liaison psychiatry in cancer care is expected to develop in Japan, because most physicians report a trend toward informing patients of their cancer diagnosis.

A case of undifferentiated carcinoma of the gallbladder with anomalous arrangement of the pancreaticobiliary ductal system.

Anomalous junction of the pancreaticobiliary duct (AJPBD) is a congenital anomaly associated with gallbladder carcinoma. Especially patients with noncystic dilatation and without dilatation of the biliary tract are at risk of gallbladder carcinoma. A 56-year-old woman with advanced gallbladder cancer associated with AJPBD but without dilatation of the biliary tract was treated at our hospital. Although histologically cancer cells remained in the layer of the proprial mucosa, extensive metastases to lymph nodes including the paraaorta and peripancreas were detected. According to the TNM classification this case was of Stage IVB. The cancer consisted of medullary round cells, and was diagnosed as undifferentiated carcinoma. After surgery poor prognosis was expected, but three years have elapsed with no recurrence. The case is of interest because of two points of discrepancy: the primary cancer did not show deep invasion but demonstrated extensive lymph node metastases; the cancer was histologically malignant but prognosis was relatively good.

Endoscopic papillary balloon dilatation for common bile duct stones: efficacy of combination with extracorporeal shockwave lithotripsy for large stones.

BACKGROUND: Endoscopic papillary balloon dilatation (EPBD) is generally considered a safe and effective technique for removal of common bile duct (CBD) stones. However, some reports have prompted concern about the risk of pancreatitis following the procedure, and it seems to be more difficult and to require adjunctive procedures more frequently in patients with large stones. AIMS: To analyse the factors influencing pancreatitis after the procedure, and to examine which is the more suitable adjunct for treating large stones, mechanical lithotripsy (ML) or extracorporeal shockwave lithotripsy (ESWL). PATIENTS AND METHODS: EPBD was performed in 92 patients, including 40 with large stones (> or = 12 mm). These 40 patients were randomly assigned to two groups receiving ML or ESWL to fragment stones (20 patients each). RESULTS: Complete ductal clearance was obtained in all 92 patients. Significant elevation of the serum amylase level compared with the prior value (> 300 IU/l) was observed in 26 (28%), and eight (8.7%) developed clinical pancreatitis. To assess the influence of various factors on the amylase level, multivariate analysis was used. The number of stones and the time required for treatment had a significant influence on the incidence of increased amylase level (P < 0.05), and ML also significantly increased it (P < 0.05). On the other hand, the amylase level remained low in the ESWL group. ML caused elevation of amylase level in 11 patients (55%), while three (15%) had elevation after ESWL. CONCLUSIONS: In patients with multiple stones, elevation of the amylase level is more frequent. This seems to be because repeated cannulation and much time is required for treatment. In patients with large stones, the rate was also high if ML was used, but was low when ESWL was used. ESWL may reduce the incidence of pancreatitis.

Therapeutic effect of balloon-occluded retrograde transvenous obliteration on portal-systemic encephalopathy in patients with liver cirrhosis.

OBJECTIVE: Balloon-occluded retrograde transvenous obliteration (B-RTO) has recently been introduced as a new interventional modality to prevent fatal bleeding from solitary gastric varices. A large portal-systemic shunt including gastric varices also causes severe encephalopathy in some cirrhotic patients. In this study, we evaluated the effect of B-RTO as a candidate therapeutic method to treat chronic recurrent hepatic encephalopathy due mainly to a portal-systemic shunt. PATIENTS AND METHODS: Since July 1995, we experienced 43 cirrhotic patients with chronic reccurent hepatic encephalopathy. Among them, six patients had anigographically proven large (>1 cm in diameter) portal-systemic shunt, and received B-RTO. B-RTO was carried out only once using 5% ethanolamine oleate with iopamidole to obliterate the portal-systemic shunt for 30 minutes. The median observation period after B-RTO was 29 months (range 23-46 months). RESULTS: In all 6 patients, encephalopathy had disappeared after B-RTO, and the patients were free of encephalopathy during the following 6 months. B-RTO significantly reduced blood ammonia levels at one month, 3 months, and 6 months later, without affecting serum aspartate aminotransferase activity, total bilirubin and albumin concentrations, and plasma prothrombin time. Encephalopathy relapsed in 4 patients between 6 and 30 months. Additional B-RTO was required and effective in 2 of them. CONCLUSION: B-RTO is an effective treatment for chronic recurrent hepatic encephalopathy with an angiographically proven portal-systemic shunt.

Rubidium (Rb) treatment of rats: biological effects and implications for psychiatry.

Experiments were carried out on rats in order to find out the implications for psychiatry of the basic biological effects of rubidium (Rb). The forced swimming test (FST), used to evaluate the effects on rats of treatment with Rb, was conducted after 1 or 3 mEq/kg Rb was given chronically or subacutely. The weight of rats treated with 1 or 3 mEq/kg Rb, once daily, was observed daily for two weeks. Rb levels in the blood and brain of rats treated with Rb chronically or subacutely were determined by atomic absorption spectrophotometry. The rectal temperature was observed at 30, 60, 90, 120, 180, and 240 min after injections of 1 or 3 mEq/kg Rb. The increase in the mean body weight of treated rats was almost the same as that of the control. The rectal temperature in rats treated with Rb showed a hyperthermic response. With both the 1 and 3 mEq/kg Rb treatments, Rb levels in the brains were significantly higher in the chronic experiments than in the subacute experiments. The experiments conducted to determine the effect of chronic and subacute treatment of Rb are hereafter termed 'chronic experiment' and 'subacute experiment' respectively. Almost the same significant difference was also observed in the Rb levels in the blood. In the FST, a decrease in the mean immobility time was not observed in either the subacute or the chronic experiments. Thus, antidepressant effects, as judged from the FST, were not observed although Rb did actually accumulate in both brain and blood.

[Follow-up study of obese pupils and their life styles in the lower grades of primary schools].

Physical examinations and a questionnaire survey of life style were carried out on all pupils (105 boys and 110 girls) at the first grade of primary school in Saigo town, Fuse village, Goka village, and Tsuma village of Shimane prefecture in 1992. In 1994, physical examinations and a questionnaire survey were again performed along with a newly-added blood examination on the same cohort. Parents of the pupils answered the questionnaire. The pupils who were included in both the first (in 1992) and the second (in 1994) examinations and surveys (89 boys and 101 girls, but 71 boys and 77 girls for blood examination) were subjects in this study to analyse the relationship between obesity and life style. The results showed (a) the proportional rates of obese boys and girls increased during the two years; (b) the obesity index of boys and girls in the third grades correlated with the obesity index of their mothers; (c) obese boys ate snacks frequently, had a higher speed in eating, and disliked physical exercise; and (d) the obesity index of boys and girls correlated with serum total cholesterol. These findings indicate that obesity occurs as early as the lower grades of primary schools and that it continues for at least two years.

First case report of spontaneous pulmonary hemorrhage following heparin therapy in acute myocardial infarction.

Since its discovery in 1916, heparin has been used extensively for treatment of thromboembolic disorders. Bleeding is its most well-known and frequent complication. We are describing the first case report of overt pulmonary hemorrhage in a patient who received heparin after emergent angioplasty for prevention of coronary artery rethrombosis.

[Determination and clinical significance of human hepatocyte growth factor in serum].

Hepatocyte growth factor (HGF) is the most potent mitogen for mature parenchymal hepatocytes in primary culture, and seems to be a hepatotrophic factor that acts as a trigger for liver regeneration after partial hepatectomy and liver injury. In the present study, we evaluated an enzyme-linked immunosorbent assay, using monoclonal antihuman HGF (h-HGF) antibody, for measuring serum h-HGF levels. Intra- and inter-assay coefficients of variation were 2.2-3.3% and 3.4-4.0%, respectively. Detection limit of this method was 0.1 ng/ml, determining by the dilution test. The substances tested did not interfere with this assay, except for high concentrations of hemoglobin. Furthermore, no interference was observed with plasminogen and lipoprotein (a), which show the structural homology to h-HGF, and with various kinds of cytokines. Reference ranges of serum h-HGF determined with 187 healthy subjects were 0.1-0.23 ng/ml. Serum h-HGF concentrations were increased in various kinds of liver diseases, in particular those were significantly higher in fulminant hepatic failure. Furthermore, prognosis of the patients with higher h-HGF values were strikingly worse than those with lower levels. We concluded that the determination of serum h-HGF plays important roles in the early diagnosis and prognosis of fulminant hepatic failure.

[Enzymatic determination of a molar ratio of free branched-chain amino acids to tyrosine (BTR) and its clinical significance in plasma of patients with various liver diseases].

A molar ratio of free branched-chain amino acids to tyrosine (BTR) was determined in the plasma of patients with liver diseases using a new enzymatic method. In addition, clinical significance of BTR was studied by comparing particularly with that of Fischer's ratio (a molar ratio of branched-chain amino acids to aromatic amino acids (tyrosine+phenylalanine], which was obtained by conventional HPLC (Amino acid autoanalyzer, Hitachi 835). Following results were obtained: 1) Enzymatically determined branched-chain amino acids and tyrosine showed significant correlations with respective results obtained by HPLC (r = 0.937, 0.972). 2) Significant correlation was also found between enzymatically determined BTR and Fischer's ratio obtained by HPLC. Changes of BTR in clinical courses were found to be in parallel with those of Fischer's ratio. 3) BTR as well as Fischer's ratio correlated significantly with ICG R15, KICG, prothrombin time (%) and serum albumin level. 4) BTRs in patients with decompensated liver cirrhosis or with fulminant hepatitis were significantly lower than those in patients with acute or chronic hepatitis. In conclusion, new enzymatic assay of branched-chain amino acids and tyrosine as described here is quite simple method, and is also considered to be very useful parameter of the clinical conditions of patients with liver diseases, particularly representing the severity of liver diseases and the protein nutritional status.

[Simultaneous coronary artery bypass grafting and cholecystectomy: a report of three cases].

The frequency of patients requiring non-cardiac surgery complicates ischemic heart disease (IHD) is increasing, however, there have been few reports of combined coronary revascularization and abdominal surgery. In this paper, we describe three patients with IHD and cholecystolithiasis in whom simultaneous coronary artery bypass grafting (CABG) and cholecystectomy was successfully performed. Initially, CABG was performed employing standard extracorporeal circulation through median sternotomy. After closure of chest, cholecystectomy was carried out through right pararectal laparotomy. Their postoperative course was uneventful. Relief of angina and freedom from epigastralgia were obtained in all patients. Combined CABG and cholecystectomy is beneficial for the selected patients.

[Complete disruption of cervical trachea, whose distal airways were migrated into the mediastinum].

The first case was a 55-year-old man, who suffered by a rope while driving his motor bicycle. On 7th day after injury, tracheotomy was scheduled due to progressive dyspnea. Following intubation of a endotracheal tube, his trachea was ruptured. The second case was a 16-year-old man, who was stabbed his trachea with a sword by his mother. His trachea completely separated following coughing during the examination of bronchoscopy. For 2 cases, we immediately excised their necks for tracheotomy but couldn't find their distal portion of trachea, because they were migrated into the mediastinum. We inserted our finger into the mediastinum for exploration and could draw it back. Both case's postoperative course was uneventful. Whenever cervical trachea is completely separated, tracheal distal end may be pulled down into the mediastinum. We invited new technique of exploration for migrated trachea using our finger.

[Correlation between pyrimidine nucleoside phosphorylase (PyNPase)/thymidine phosphorylase/platelet-derived endothelial cell growth factor and histological prognostic factor, and influence of 5'-deoxy-5-fluorouridine (5'-DFUR) administration on PyNPase activities and serum immunosuppressive acidic protein levels. A study group of oral anti-cancer drugs in Seiban/Tajima area].

PURPOSE: Among the pyrimidine nucleoside phosphorylases (PyNPase), thymidine phosphorylase (dThdPase) exists mainly in human tumor tissues, and is an enzyme which converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil. Recently, it was reported that dThdPase was identical to platelet-derived endothelial cell growth factor which was an antiogenetic factor, therefore. We think dThdPase may be a prognostic factor. METHODS: We investigated the possible correlation between PyNPase activities in tumor tissues and prognostic factors of histological findings, and examined influences of preoperative oral 5'-DFUR administration at a dose of 1,200 mg/body for 7 days on PyNPase activities and serum immunosuppressive acidic protein levels in patients with gastric cancer. RESULTS: Higher levels of PyNPase activities were especially observed in patients with v+ (p = 0.0161). PyNPase activities (p = 0.1668) and IAP (p = 0.0830) levels showed a decrease by 5'-DFUR administration. CONCLUSION: This study suggests that we must investigate in detail the possibility of PyNPase being prognostic factor, and 5'-DFUR administration may improve the prognosis of patients with gastric cancer.