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Nineteen non-small cell lung cancer patients admitted for chemotherapy were investigated for cognitive dysfunction and factors affecting cognitive function. The results showed that the patients experienced some decline in cognitive function, and fatigue affected cognitive function and quality of life. Cognitive function in cancer patients affects their treatment choices, employment, and social life. We need to be aware of the cognitive dysfunction of cancer patients, and at the same time, we need to intervene with consideration for cognitive function, as fatigue can easily lead to a sense of cognitive decline.

An 80-year-old female with fever, edema in the lower extremities, and marked eosinophilia was referred to our hospital. Based on the presence of the Philadelphia chromosome, she was diagnosed with chronic myeloid leukemia (CML). Although imatinib induced a complete cytogenetic response (CCyR), CML relapsed after 28 months of starting it. A CCyR was achieved again by nilotinib but was lost after about 14 months. Only transient response occurred to dasatinib, and the patient died. At relapse, neutrophilia was more predominant than eosinophilia. We reviewed 6 patients with CML whose eosinophil rate in the peripheral blood was >50%. Most patients were males with palpable splenomegaly and had cardiac disorders, peripheral vascular disease, or pleural effusion. Typically, CML causes neutrophil-predominant leukocytosis. However, a subgroup of CML with marked eosinophilia resembles chronic eosinophilic leukemia or idiopathic hypereosinophilic syndrome.

We report a case of aphasia after neck clipping of a ruptured aneurysm at the origin of the duplicated middle cerebral artery(DMCA). A 60-year-old woman had a sudden onset of headache and nausea. A computed tomography(CT)scan revealed diffuse subarachnoid hemorrhage. Head three-dimensional CT angiography(3D-CTA)showed a left DMCA with a saccular aneurysm at the origin. She became aphasic on the third day after aneurysmal neck clipping. A CT scan revealed a low-density area in the anterior portion of the left temporal lobe, which is perfused by the DMCA. The DMCA was patent on 3D-CTA, but the angle between the ICA and the DMCA changed steep. It is suspected that the clip changed the branching angle at the DMCA origin, which may have led to decreased blood flow in the DMCA. She received linguistic rehabilitation for dysnomia and was discharged with slight difficulty in naming objects. Six months later, she recovered from the aphasia. One year later, the DMCA was patent on 3D-CTA. We should pay attention to ischemic complications in clipping because DMCAs are easily deformed.

Thalidomide is a TNF-alpha inhibitor and has been administrated for erythema nodosum leprosum (ENL, Type II leprosy reaction) which is one of leprosy reactions and can cause serious illness to patients oflepromatous pole among the immune spectrum. Twenty live cases (at May, 2011) were identified to whom thalidomide had been administrated since 1978 for their ENL reactions. Data were collected from their clinical records in order to evaluate the usage and effectiveness of thalidomide in National Sanatorium Oku-Komyoen, Okayama, Setouchi-city, Japan. Individual data includes bacillary index (BI), total dose, average daily dose, maximum daily dose, minimum daily dose, methods of thalidomide administration and change of symptoms of ENL. Results: No adverse effect was found among 20 cases. Average daily dose of 20 cases was 19 mg. Regarding to the maximum daily dose, in 3 cases (15%) more than 100 mg, in 3 cases (15%) 50 mg, and in 14 cases (70%) less than 40 mg was administrated. Dose was gradually tapered in most cases. From clinical records, thalidomide was found effective for ENL in 19 cases and clinicians concerned were trying to adjust the proper dose of the drug carefully depending on the current symptoms, because there was no guideline of thalidomide administration for ENL. This data suggests that even less than 50-100 mg as the initial daily dose was still effective, though 50-100 mg daily dose is recommended in the current guideline of Japan (2011) and more dose had been administrated in USA and India.

Treatment of erythema nodosum leprosum (ENL, type 2 reaction) using thalidomide provides effective alternative choice to steroid therapy. Yet, the Japanese National Health Insurance approves thalidomide prescription only for the treatment of multiple myeloma under the Thalidomide Education and Risk Management System (TERMS). Benefit of thalidomide therapy for patients with ENL is already an established fact based on various reports from other countries, but limited experiences and standards in Japan have hindered application of the medication to our patients. This led us to compose a local guideline. Based on and following the TERMS, we suggest starting thalidomide from 50-100 mg/day and then onwards adjusting the dose according to the symptoms of each patient, not to exceed the maximum recommended dose of 300 mg/day, for the treatment of ENL.

A 74-year-old man was admitted to our hospital in order to treat a mediastinal mass and 2 ground-glass attenuations in the right upper lobe detected by chest X-ray and computed tomography (CT). Partial resection of right lung and thymectomy were performed. The mediastinal mass and 2 ground-glass attenuations in the right upper lobe proved to be thymoma and bronchioloalveolar carcinomas, respectively by pathology.

We report a long-term survival case treated by chemotherapy with new anticancer drugs such as S-1, CPT-11 and docetaxel after bilateral overiectomy for bilateral ovarian metastases of progressive gastric cancer. A 68-year-old female, who had undergone total gastrectomy with D2 lymphadenectomy for scirrhous gastric cancer of Stage IIIA, was admitted because of ovarian metastasis. Laparoscopic bilateral ovariectomy was performed for ovarian metastases of the gastric cancer (Krukenberg tumor) 6 months after gastrectomy. Seven months after gastrectomy, 11-course of S-1 treatment (80 mg/m2) for bilateral ovarian metastases of the gastric cancer was administered. CT scan revealed mediastinal lymphadenopathy 2 years and 5 months after gastrectomy. Then, the drug was changed to docetaxel (60 mg/m2). After 9-course of docetaxel treatment, the mediastinal lymphadenopathy disappeared. For a treatment of grade 3 neuropathy, a 12-course CPT-11 was started after gastrectomy 3 years and 6 months ago. CT scan and PET-CT showed no new metastasis in 4 years and 10 months after gastrectomy.

An 79-year-old man admitted our hospital for abdominal mass. Computed tomography showed a tumor measuring about 10 cm in diameter without any metastasis lesion and any sings of local infiltration. Gastroduodenal endoscopy revealed the presence of a submucosal tumor in the third portion of the duodenum, and biopsy revealed tumor cells stained positive for c-kit. These findings were consistent with a GIST and we performed a partial resection of the duodenum sparing the pancreas. Gastrointestinal stromal tumors (GIST) were mainly located in the stomach and the small intestine. Duodenal localization is rare. Surgical approach for GISTs should basically be a partial resection. However, for GISTs located in the duodenum, the partial resection was sometimes difficult and pancreaticoduodenectomy (PD) may be needed, depending on the tumor size and the location of the tumor close to the papilla Vater. Since GIST grew expansively, rarely involving lymph nodes, PD may be an excessive procedure to treat the disease. For this reason pancreas-sparing partial duodenectomy has been introduced for the treatment of duodenal GIST.

We encountered a case of dural arteriovenous fistula (AVF) in which a cortical venous drainage was successfully treated by direct surgery. A 68-year-old man complained of headache and visual disturbance. CT on admission revealed intracerebral hematoma in the left occipital lobe and subdural hemorrhage in the left temporooccipital region. Angiography showed dural AVF in the left occipital region, which was type IV classified by Cognard and a varix of the draining vein. We performed direct surgery to remove the hematoma and obliteration of the draining vein was observed 10 days after onset. Intraoperative angiography via the middle meningeal artery which fed the dural AVF was very useful in the identification of the dural AVF and the varix and also to certify the obliteration of the fistula. Postoperative angiography showed disappearance of dural AVF. The patient had a good clinical course. Early direct surgery in this type of dural AVF is necessary in order to prevent another hemorrhage from the varix.

A 72-year-old woman was reffered to our hospital for further examination of a tumor shadow in the left upper lung field which was detected in a mass screening chest X-ray. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a chest wall tumor located in the left 4th intercostal space. The lesion was suspected to be neurogenic tumor and CT-guided needle biopsy was performed. The tumor was consisted of spindle-shaped cells, but immunohistochemistry demonstrated no evidence of neurogenic tumor. As a possibility of malignant tumor could not denied, we performed tumor resection under video-assisted surgery. The lesion was not originated from nerves, but adhered to the intercostal muscle. Histologically, the tumor was consisted of spidle-shaped cells without atypia which sparsely proliferate in the myxoid stroma adjacent to intercostal muscle. In immunohistochemistry, tumor cells were positive for vimentin, and negative for desmin, S-100 protein, smooth muscle actin, CD34 and factor VIII. It was diagnosed as intramuscular myxoma. This histology in the intercostal muscle is extremely rare.

A 42-year-old woman was admitted to our hospital because of an abnormal shadow on chest X-ray. Chest computed tomography scan revealed a tumor 4.0 cm in diameter in the right segment S8. We resected the right lower lobe because of the possibility of lung cancer. Historical finding of the resected specimen revealed epithelial-myoepithelial carcinoma of the lung. The patient has remained disease-free for a year and 3 months postoperatively.

A 59-year-old man was admitted to our hospital for abdominal mass and found to have a gastric cancer with peritoneal dissemination. Three courses of neoadjuvant chemotherapy combined with S-1 and CDDP were performed. This chemotherapy showed a substantial reduction of the size of primary tumor and peritoneal dissemination by CT examination. Surgical resection consisted of distal gasterectomy and D2 lymph node dissection was performed, and an ip catheter was placed through the douglas pouch, and the catheter was attached to the subcutaneous portal delivery system for ip chemotherapy. Operative cytology of ascites proved positive and remnant neoplasm cells were identified in the peritoneum. The pathological stage was determined as T3 N2 H0 P1 CY1 M0, pStage IV. Following surgery, we selected the ip administration of paclitaxel at a dose of 100 mg per body. Finally, the peritoneal dissemination was re-grown. However, we continued the ip chemotherapy for twenty-five times on ambulant basis. Most gastric cancer patients with peritoneal dissemination die within a few months, and there is no standard treatment for peritoneal dissemination from gastric cancer. In conclusion, a condition of no progression has been achieved and maintained for more than three years by intraperitoneal administration of paclitaxel for patient with peritoneal dissemination due to advanced gastric cancer.

The authors presented a patient with non-traumatic tension pneumocephalus 12 years after initial ventriculo-peritoneal shunt. A 60-year-old man had a past history of subarachnoid hemorrhage. At ÿtime, he underwent clipping surgery and emplacement of a ventriculoperitoneal shunt with a low pressure valve, and was discharged from hospital in a bedridden condition. After 12 years, he was transferred to our hospital because of dysarthria and right hemiparesis. On admission, he had multiple dimples of the scalp in the left frontal area where craniotomy had been carried out 12 years before. Head CT scan revealed air located mainly in bilateral subdural space and collapsed ventricles. We suspected that he had a tension pneumocephalus through a scalp-subdural fistula induced by long-term low intracranial pressure. Operation for closure of the fistula was intended. During the operation a subdural abscess was found so, artificial bone and the shunt system was removed. We were able to detect the fistula from the defect of the scalp to the subdural space and closed it by repairing a scalp defect, using dural plasty. Postoperative clinical course was uneventful and the patient was discharged. About 6 month after the operation, cranioplasty and lumbo-peritoneal shunt was performed. We must recognize that appropriate management of intracranial pressure after installation of a ventriculo-peritoneal shunt is necessary for prevention of tension pneumocephalus.

Human parvovirus B19 infection causes erythema infectiosum in child, aplastic crisis in patients with chronic hemolytic anemia, chronic pure red cell aplasia in immunocompromised patients and hydrops fetalis. Human parvovirus B19 causes arthritis and acute glomerulonephritis due to immunological mechanism. Other disorders, rheumatoid arthritis, vasculitis and thrombotic microangiopathy, are linked in human parvovirus B19 infection. Parvovirus B19 infection causes choronic rheumatoid-like arthropathy. Autoantibody and low complement were seen in acute human parvovirus infection, and parvovirus B19 infection present clinically lupus like tableau.

Ofloxacin(OFLX) is often applied today as a substitution drug of MDT for drug resistance to dapsone, rifampicin or clofazimine. However, OFLX resistance is also becoming a great concern. Low and/or irregular administration are considered to be the major causes of OFLX resistance. OFLX should be used as a combined therapy, and minimal daily dose of 400 mg of OFLX or 200-300 mg of levofloxacin is required. Quinolone resistance should be considered when no improvement of clinical and/or bacterial index is observed after the treatment for 6 months. In such cases, resistance gene detection is necessary.

We analyzed the medical and social problems of newly registered leprosy patients in the past 8 years from 1993 to 2000 in a low endemic country, Japan. There were 56 registered Japanese patients (males, 32; females, 24), and 76 registered foreign patients (males, 56; females, 20). The number of Japanese patients in each year was between 5 and 9, and 2/3 of them were from Okinawa Prefecture, located in subtropical zone. But the number of foreign patients in each year was between 5 and 18, and 2/5 of them were from Brazil. The number of foreign patients was greater than that of Japanese patients. Male/female ratio has decreased among the Japanese.

In leprosy, the causative bacteria, Mycobacterium leprae, will not threaten the lives of the hosts directly because they proliferate only slowly in the Schwann cells of the peripheral nerves. It is the "reactions" which give the patients irreversible morbidity through the inflammatory damages to the peripheral nerves. Physicians should be aware of the possibility of the state of the "reaction" when they examine leprosy patients. They also should be aware of the possibility of leprosy and the state of the "reaction" when they examine patients with cutaneous lesions and/or peripheral nerve disturbances, because it may be the first presenting symptom of the disease. In this review, recent advances on the issue about the reactions are discussed including pathogenesis, immunology, clinical features, pathology, treatment and prevention.

The effect of a high fat diet (HFD) on renal function, renal mitochondrial function and intrarenal oxygen-free radial scavenging activity were examined in the ischemia-reperfusion model of the rat kidney. Whether of not a novel lipophilic antioxidant (BO653) could minimize this effect in vivo was also investigated. Thirty minutes renal ischemia was introduced by vascular clamp in rats with or without HFD (cholesterol 1.25%). Some of the HFD rats received BO653 by gastric gavage. Creatinine clearance (Ccr) was measured 24 hours following the injury. Mitochondrial oxygen consumption and thiobarbituric acid reactive substance (TBARS), superoxide dismutase (SOD), glutathione peroxidase (GPX) and alpha-tocopherol were measured in the kidney before, 30 min ischemia and 30 min after reperfusion. HFD significantly reduced Ccr after ischemia-reperfusion (45% decreased compared to normal diet), which was ameliorated by BO653. Thirty-minute ischemia deteriorated the mitochondrial function in the normal diet (ND) group, high fat diet (HFD) group and high fat diet + BO653 (HFD + BO) group. Thirty-minute reperfusion ameliorated the mitochondrial function in all those groups. The kidney content of TBARS was not increased after the ischemia-reperfusion in all these groups. In the HFD group, the kidney content of GPX was higher than in the ND group during ischemia-reperfusion, but in the HFD group, the kidney content of SOD was significantly decreased after the thirty-minute ischemia. Thirty-minute ischemia decreased the kidney content of alpha-tocopherol in the HFD group, which was recovered by the thirty-minute reperfusion. In conclusion, a high fat diet deteriorates ischemia-reperfusion injury of the rat kidney and BO653 ameliorated this effect judged by creatinine clearance and renal mitochondrial function. Reperfusion injury could not be confirmed in the present model based on the results of lipid peroxidation and oxygen-free radical scavenging enzyme activity.

Assessment was made on the serum protein binding of clarithromycin (CAM), a representative oral macrolide, using sera from healthy subjects (HS) and patients with chronic renal failure (CRF) applying equilibrium dialysis in vitro. The protein binding of CAM was 81.9 +/- 1.9%, 85.9 +/- 3.6%, 82.9 +/- 3.3% and 86.8 +/- 3.3% for sera from HS, from patients in conservative treatment (ND), from those receiving hemodialysis (HD) and from those with continuous ambulatory peritoneal dialysis (CAPD), respectively. There was no significant difference among these values. The protein binding of CAM was 82.9 +/- 3.3% and 68.8 +/- 3.5% for sera before and after HD, respectively. There was significant difference between these values. In the study of the protein binding in patients on HD at an albumin concentration of 0.5 mM, the protein binding of CAM for sera was found to be significantly decreased following HD as compared to that prior to HD. The addition of palmitic acid (PA), a common NEFA, to pooled sera from HS, the protein binding of CAM showed no change. These findings suggest that changes in the protein binding of CAM with HD have been possibly caused by an increase in a drug binding inhibiter other than NEFA (PA) or by an allosteric effect on the albumin binding capacity. At therapy using CAM, the possibility of enhanced pharmacological effects and increased adverse reactions of CAM due to decreased protein binding in patients on HD should be considered.

Ultrafiltration failure has been one of the major causes of drop out from CAPD treatment. The present study was designed to develop an ultrafiltration failure model in the rat and to assess whether various agents could prevent a decrease in ultrafiltration capacity in this rat model. Peritoneal hyperpermeability was induced by repeated intraperitoneal injection of 15 ml of 4.25% dextrose dialysate for 7 days. Some of the rats received agents, such as phosphatidylcholine, chondroitin sulfate, siliac acid, heparan sulfate, keratan sulfate, sodium sulfate, sodium phosphate, and heparin sodium, simultaneously administered with 4.25 % dextrose dialysate for the same duration. Ultrafiltration volume, D4/D0 ratio of glucose and peritoneal net fluid absorption were evaluated by 4-hour dwelling of 30 ml of 2.5% dextrose dialysate. Sodium phosphate and heparan sulfate prevented peritoneal hyperpermeability due to repeated injection of hypertonic dialysate. Sodium phosphate, sodium sulfate, heparin and heparan sulfate suppressed peritoneal net fluid absorption, resulting in an increase in ultrafiltration. These findings may be applicable to CAPD patients with ultrafiltration loss.

A microbiological assay method for measurement of T-3761 and its stability in body fluids were investigated. The paper disc method proved suitable for this assay using Escherichia coli Kp as a test organism and commercially available heart infusion agar as a test medium. When using the paper disc method, lower detection limit of T-3761 was approximately 0.05 microgram/ml and 0.1 microgram/ml for 1/15M phosphate buffer (pH 7.0) and human serum, respectively. T-3761 in human serum and urine was stable under freezing -20 degrees C for at least 28 days.

We studied the absorption, distribution, metabolism and excretion of T-3761, a new quinolone derivative, in experimental animals. The following results were obtained. 1. The peak serum levels of T-3761 after a single oral administration to various fasting animals at a dose of 5 mg/kg were high in the order of rats, dogs, mice and rabbits, showing favorable absorption in all animals except for rabbits. In mice and rats, T-3761 showed higher peak serum levels than ofloxacin and ciprofloxacin but T-3761 were more rapidly eliminated from serum than ofloxacin and ciprofloxacin. 2. Tissue concentrations of T-3761 in rats were similar to those of ofloxacin but its ratio of tissue to serum levels were lower than those of ofloxacin. 3. Urinary excretion of T-3761 as active form until 24 hours after oral administration was 27.3%, 63.1%, 41.0% and 63.3% in mice, rats, rabbits and dogs, respectively. Only unchanged T-3761 was detected as active form in urine of all animals tested. In rats, urinary concentrations until 2 hours after administration were higher than those of ofloxacin. 4. Biliary excretion of T-3761 in mice and rats were 2.9% and 1.4% as active form. 5. The absorption of T-3761 was not different in male and female rats or 8 and 14 weeks old rats. The meal lowered absorption of T-3761 in rats. There was no significant difference in serum levels, urinary excretion and distribution to tissues after multiple administration of T-3761 comparing with its single administration. 6. In rats with liver dysfunction induced by D-galactosamine, the serum levels and urinary excretion were slightly higher than in normal rats. On the other hands, in rats with kidney dysfunction induced by HgCl2, the serum levels were significantly higher and urinary excretion of T-3761 was significantly lower than in normal rats. Above results show that T-3761 has unique characteristics in absorption, excretion and distribution after oral administration to animals among new quinolones, i.e., T-3761 was eliminated rapidly and poorly distributed to tissues but showed superior absorption and high peak serum levels.

There is increasing interest in the examination of urine sediment to differentiate between glomerular and non-glomerular hematuria. A newly developed automated urinary sediment analyzer was used for this purpose. It clearly recognized red blood cells, white blood cells, epithelial cells, bacteria and crystals by their cell size and fluorescent intensity. Ninety-eight urine samples from 31 glomerular and 67 non-glomerular lesions were analyzed by the analyzer and 69 samples, by light microscopy. According to the analysis of their histograms, a forward scatter (FSC) intensity of less than 126, where 80% of the smaller red blood cells were observed, was diagnosed as glomerular hematuria. A FSC intensity of more than 84, where 80% of the large red blood cells were counted, was non-glomerular hematuria. An FSC intensity between 84 and 126 was considered to be the overlap zone of glomerular and non-glomerular hematuria. The sensitivity for glomerular red blood cells was found to be 100% and specificity, 92.54% by means of flow cytometric analysis. On the other hand, light microscopic analysis yielded 95.83% sensitivity and 93.33% specificity for glomerular lesions. Flow cytometric analysis of the urinary red blood cells was concluded to be a fast, simple and reliable method to differentiate glomerular and non-glomerular hematuria.

Continuous vibration of the abdominal wall with a small electric vibrator was conducted to enhance peritoneal mass transport in rats with normal kidney function. Thirty ml of either 2.5% or 4.25% dextrose dialysate containing creatinine, urea and dextran 70 was infused intraperitoneally and was allowed to dwell for 30-240 min with or without abdominal wall vibration at the rate of 80 Hz. The mass transfer area coefficient (KA) of small molecular solutes and peritoneal lymphatic absorption were investigated. Peritoneal dialysis with vibration for 60 min increased the KA of urea, creatinine and glucose by 12%, 15%, 27%, respectively, without changes in ultrafiltration and lymphatic absorption. This effect may be attributed to enhanced mixing of dialysate in the peritoneal cavity and the increased peritoneal effective blood flow. This concept can be applied to short-term dwell dialysis, such as automated peritoneal dialysis.

Endothelin (ET) has been suggested to be involved in acute graft rejection of kidney transplantation and cyclosporin A (CsA) nephrotoxicity. For clarification of the pathophysiological role of ET in the early post-transplantation period, plasma endothelin-1 (ET-1) was measured by specific radioimmunoassay in renal transplant recipients, patients on maintenance hemodialysis (HD) and healthy volunteers. Twelve transplant recipients were used in this study, 8 of whom were living related subjects and 4 cadaver. Plasma ET-1 and graft function were measured each day, from 1 day prior and 7 days following transplantation and every week up to 5 weeks postoperatively. Plasma ET was measured in 20 other transplant recipients with stable function (serum creatinine < or = 1.8 mg/dl), 20 maintenance HD patients with no residual renal function and 6 healthy volunteers. Mean plasma ET-1 was 13.0 +/- 4.5 pg/ml in 20 recipients with stable graft function, 21.7 +/- 6.5 in 20 HD patients and 1.5 +/- 0.4 in healthy volunteers. These differences are statistically significant (p < 0.02). Plasma ET-1 showed significant decrease from 21.8 +/- 7.2 pg/ml prior to transplantation to 12.8 +/- 4.0 when urinary output reached more than 1000 ml in living and cadaveric transplantation subjects. All three acute vascular rejections clearly indicated histologically increased plasma ET-1 accompanied by an increase in serum creatinine. A significant positive liner correlation was noted between plasma ET-1 and serum creatinine during the first week following living transplantation. Two patients with clinically and histologically suspected CsA nephrotoxicity showed transient increase in plasma ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)

The beneficial effect of UW solution may result from its ability to prevent tissue edema during cold storage. This study was conducted to determine which impermeant was effective in this regard during cold storage of a rat kidney in solution. Functional and morphological studies were made on a rat isolated perfused kidney (IPK) following 24 hour-cold storage in various tested solutions. Right nephrectomy was performed in 95 male rats by the method of Nishitsutsuji-Uwo et al and the kidney was perfused and stored at 4 degrees C for 24 hours as follows: glucose (194 mM) as a control, mannitol, sucrose, raffinose (140 mM in each), lactobionate (100 mM), raff + lact, hydroxyethyl starch 20, 40 (5%) with electrolyte composition essentially the same as that of Euro-Collins or UW solution. Kidneys stored for 24 hrs at 4 degrees C were perfused by the IPK apparatus. The perfusate flow rate was adjusted to maintain the renal arterial perfusion pressure at 100 mmHg. Raff, raff + lact or UW solution showed significantly higher fractional reabsorption of sodium than the control with no change in renal hemodynamics. The release of LDH into the perfusate was significantly less in raffinose than the control. Raffinose may thus be considered to function effectively as an impermeant for cold kidney preservation and molecule size would appear more important than negative charge for rat kidney preservation.

A peritoneal dialysis patient was reported who had ultrafiltration loss due to a marked increase in lymphatic absorption and peritoneal membrane permeability. A 33-year-old male was transferred from hemodialysis to peritoneal dialysis because of acute subdural hematoma. His complicated history included left testicular tumor with retroperitoneal lymph node metastasis in 1982. He was treated with CDDP, Etoposide, Bleomycin, Vinblastine sulfate and Vincristine and received operation of retroperitoneal lymph node dissection in 1982. He had been on hemodialysis since 1983 due to cisplatinum nephropaty. Ultrafiltration failure was found immediately following the insertion of Tenckhoff catheter without malfunction of peritoneal catheter. Peritoneal equilibrate test and lymphatic absorption measurement showed a high permeability peritoneum with a marked increase in lymphatic absorption rate (3.7 ml/min). These two factors were thought to result in ultrafiltration loss. CAPD with 4-6 times exchange daily did not maintain ultrafiltration, because it gave approximately 2000 ml negative water balance every day. He was well maintained on a short time exchange intermittent peritoneal dialysis (IPD) with cycler using 18 L for 8 hours. We concluded that increased lymphatic absorption is one of the important factors for ultrafiltration fafilure and IPD with frequent exchange by cycler is suitable for the patient with ultrafiltration loss.

An assessment was made of the serum protein binding of representative oral cephems (cefdinir, cefixime and ceftibuten) for sera from healthy subjects (HS) and patients with chronic renal failure (CRF) using an application of equilibrium dialysis under a same set of conditions in vitro. The protein binding capacity of oral cephems in CRF patients being treated with continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD) was significantly less than that in HS, and a marked increase in free drug concentration was observed. While examining the protein binding of oral cephems with heparin in patients on HD, binding capacity decreased significantly immediately following the completion of dialysis compared to that prior to dialysis. On the other hand, the protein binding of oral cephems did not change when used nafamostat mesilate as an anticoagulant. The addition of palmitic acid (PA), a common non-esterified fatty acid (NEFA), to pooled sera from HS caused the binding capacity of oral cephems to decrease, accompanied by increase in PA concentration. It appears from these findings that changes in the binding capacity of oral cephems with HD have possibly been caused by increase in NEFA due to activation of lipase when heparin was used as an anticoagulant. In conclusion, changes in the protein binding capacity of oral cephems in CRF patients should be taken into consideration in attempts to avoid possible side effects.

Ultrafiltration volume (UFV) in peritoneal dialysis is expressed as the difference between net transcapillary ultrafiltration (TCUF) and lymphatic absorption (LA) in peritoneal cavity. An increase in LA results in a decrease in UFV. Endogenous hormones may modulate peritoneal membrane permeability and LA. This study was conducted to assess the effect of angiotensin II(AII) on peritoneal permeability and LA in rat. Rats (BW, approximately 300g) with normal renal function were dialyzed for 4 hours using 30ml of hypertonic dialysate (dextrose concentration: 3.86%). AII was added in dialysate at the concentration of 10(-9)-10(-2) mol/30ml. Peritoneal membrane permeability and UFV were studied by clearance of urea N and inorganic phosphate, albumin excretion, glucose absorption and LA. LA was calculated by the concentration change of dextran 70 in dialysate. AII decreased UFV from 15.7 +/- 2.8ml/4hr(control) to 5.7 +/- 1.5(AII 10(-4) mol/dwell). LA was increased in a dose dependent fashion (ED50:0.25 x 10(-6)mol) with no change in TCUF and clearances of urea N and inorganic phosphate. Ten types of AII analogue were used to investigate the site of action for LA in 8 amino acids of AII. [beta-Asp1], [Val5], [Ile3, Val5] and [Sar1] AII showed agonistic action against LA. [Sar1, Thr8], [Sar1, Ile8], [Sar1, Leu8], [Sar1, Ala8], [Sar1, Val5, Ala8] and [Sar1, Gly8] AII had no effect on LA, which found the importance of the 8th amino acid of AII for LA. These actions of AII analogue against LA were similar to those for vascular smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

FK506, a newly developed immunosuppressive agent, has recently been used for human liver and kidney transplantation. The present study was carried out to assess the functional and morphological changes by acute or chronic administration of FK506 in heminephrectomized rats. FK506 was given intravenously at the dose of 0.384 mg/kg/hr for 90 min in acute experiment. FK506 was administered by gastric gavage at doses of 1, 2.5, 5 mg/kg for 21 days. Blood and urinary biochemistry were monitored every week. Inulin and PAH clearance studies were conducted during the infusion of FK506 for acute study, and at day 21 for chronic study. Some of the rats were treated with diltiazem (Dilt), captopril or prazosine for 21 days to prevent FK506 nephrotoxicity. Acute infusion of FK506 did not change renal and systemic hemodynamics. Creatinine clearance showed a dose dependent decrease by 10-20% in the rats with chronic administration of FK506. Inulin/PAH clearance indicated a decrease in glomerular filtration rate and renal plasma flow with an increase in renal vascular resistance. The renal histology showed vacuolization in proximal tubuli and media of smooth muscle cells of arterioles. The administration of Dilt functionally and morphologically improved renal impairment induced by FK506. In conclusion, FK506 induces a dose dependent decrease in renal function with significant histological changes in tubuli and arterioles in rat kidney. Intracellular calcium deregulation seems to be involved in FK506-induced nephrotoxicity.

Progression of renal insufficiency was evaluated in partially nephrectomized Sprague-Dawley rats at the age of 10 weeks, fed on the low (6%), usual (20%), and high (36%) protein diet (group 6C, 20C, and 36C). Effects of oral adsorbent AST-120 on these experimental uremic models were also examined (group 6A, 20A, 36A). All the rats underwent paired feeding, and survived during the experimental period of 3 weeks. GFR (inulin clearance) and RPF (para-amino hippurate clearance), as well as Ccr was measured before the sacrifice. Initial serum creatinine and Ccr were 1.7 mg/dl and 0.27 ml/min. The rats of group 36C showed progressive elevation of serum creatinine level and decrease in Ccr. At the end of the study, GFR was significantly lower in group 36C than in group 6C and 20C (0.19, 0.68, 0.87 ml/min respectively). Significant elevation of filtration fraction in group 36C suggested that the decrease in GFR mainly resulted from low RPF. Even in group 36C, no glomerular sclerosis was histologically demonstrated in the remnant kidney, and the mean planar area of the remnant glomeruli was significantly small, which might reflect low RPF. Tubulo-interstitial changes like dilatation of the urinary space and tubular epithelial flattening were prominent in group 36C. Beneficial effect of AST-120 was obvious in high protein diet groups. GFR and RPF were rather well preserved in group 36A (0.36 and 0.78 ml/min) with normal filtration fraction. Tubulo-interstitial damage was evidently mild in group 36A. These data suggested the presence of some humoral factors, which can be adsorbed by AST-120 in gastrointestinal tract, and responsible for the deterioration of renal function and tubulo-interstitial damage induced by high protein diet in the uremic condition. Besides hyperfiltration and glomerular hypertrophy, such humoral factors as suggested in this study may contribute to the progression of chronic renal failure to some extent.

Urea kinetic modeling was applied to 19 CAPD patients followed in our outpatient clinics. Serum beta 2-microglobulin was also measured as a marker of large molecular weight substances. Clinical conditions of patients were assessed by both doctors and patients. Patient's assessment were done by the questionnaire. Indices of urea kinetics (KT/V, PCR) and biochemical parameters were compared between well-treated and not well-treated patients judging from patient's and doctor's assessment scores. The rate of peritonitis was significantly higher in the latter group. None of the parameters were different between 2 groups except for serum albumin. There was a significant correlation between serum concentration of albumin and doctor's assessment score (gamma = 0.52). In conclusion, urea kinetic parameters is not a good indicator for adequacy of dialysis in our CAPD population. Serum albumin seems to be one of the indices for adequate dialysis. However, clinical symptoms and signs are more valuable than biochemical parameters for the assessment of adequacy of dialysis.

This study was employed to investigate whether the serum protein binding of various cephems [cefpiramide (CPM), cefalotin (CET), latamoxef (LMOX)] differ among healthy subjects and patients with chronic renal failure (CRF) by means of in vitro equilibrium dialysis. The protein binding capacities of cephems in patients with CRF (hemodialysis, continuous ambulatory peritoneal dialysis, non-dialysis) decreased significantly compared to those in healthy subjects. The binding capacities correlated directly with total protein, albumin concentration and correlated inversely with blood urea nitrogen and serum creatinine concentration. In the study of protein binding during and after hemodialysis, the binding capacities of CPM and LMOX decreased immediately after dialysis and then increased with the time. However, the binding capacities of CET increased immediately after dialysis and then decreased. The binding capacities of CPM and LMOX correlated inversely with non-esterified fatty acids (NEFA) and those of CET correlated directly with NEFA. In the study of protein binding in pooled sera from healthy subjects with or without palmitic acid (PA), the binding capacities of CPM and LMOX decreased by increasing the concentration of PA, while those of CET increased by increasing PA up to 3 mM. The changes in binding capacity of cephems during and after hemodialysis have been possibly caused by increase of NEFA due to activation of lipase in use of heparin as an anticoagulant. In conclusion, changes in protein binding capacity of cephems in sera from CRF, which should be taken into consideration to avoid possible side effects.

In order to evaluate the direct or indirect effect of AST-120 on chronic renal failure (CRF) in rats, histological and electron microscopical examinations were performed. A total of 30 Sprague-Dawley rats (aged 11 weeks and weighing 226 to 229 gm) with CRF induced by 5/6 nephrectomy were prepared. Rats were fed by a commercial diet (CE-2, Japan Kurea) and were divided into two groups: A (16 rats) and B (14 rats). AST-120 (5% content) was only administered to group B. After two months, kidneys were removed and prepared for the histological and electron microscopical examinations. On histological examination, group A kidneys showed severe glomerular hyalinization (more than 80%) and frequent crescents, as well as tubulo-interstitial fibrosis and many protein casts. In contrast, segmental glomerular lesions were identified in group B kidneys. Tubulo-interstitium were also well preserved. Furthermore, the ultrastructural findings of group B were milder than that of group A. The preservation of renal tissue in group B revealed the beneficial effect of AST-120 on CRF rats' kidneys. In conclusion, this beneficial effect is provided by the removal of the serum toxic metabolite (uremic toxin) and the precursor substance of the toxin by orally administered AST-120.

Donor specific blood transfusion (DST), given prior to living related kidney transplantation has resulted in significant improvement in graft survival. This improvement, however, has been accomplished with a high rate of adverse sensitization against the donor. In an attempt to reduce the incidence of sensitization, we have employed DST with intermittent coverage of cyclophosphamide. A comparative study was done between 2 methods of DST with or without the coverage of immunosuppressant for prospective kidney transplant recipients from living related donors. In addition, the beneficial effect of DST on graft survival was evaluated in our recent series of living related transplantation using cyclosporine A (CsA) as postoperative immunosuppression. Twenty-nine prospective kidney transplant patients received 200 ml of fresh whole blood 3 times at 2 week intervals from HLA one-haploidentical living related donors. The first 13 patients received DST alone, while the remaining 16 were given cyclophosphamide (CPM 1.5 mg/kg/day) for 3 days prior to each DST. In patients with CPM coverage, 6.3% (1 of 16) developed positive T-warm antibody against donor and 15% of patients (2 of 13) with DST alone developed it. Like-wise 19% (3 of 16) of the former and 38% (5 of 13) of the latter became positive B-warm crossmatch. The difference in sensitization rates between these 2 groups was not statistically significant. Nineteen patients receiving DST were compared to 21 non-DST patients in incidence of acute rejection, graft function and graft survival with the same immunosuppressive regimen, such as CsA, prednisolone, and mizoribine.(ABSTRACT TRUNCATED AT 250 WORDS)

The in vivo antibacterial activity and the penetration into inflammatory tissues of cefoperazone (CPZ) were compared with those of cefotiam (CTM) in local infection systems using mouse subcutaneous abscess and rat granuloma pouch. The serum levels of CPZ in subcutaneous abscess in mice caused by Staphylococcus aureus F-230 (penicillinase producing strain) were lower than that of CTM, but there was no significance between the therapeutic effects of both drugs. The same results were obtained using Staphylococcus aureus F-196 (penicillinase non-producing strain). When infected with Enterobacter cloacae H-27 (cephalosporinase producing strain) in rat granuloma pouch, the exudate levels of CTM were lower than those of CPZ. Judging from these results, it was suggested that CPZ was a useful antibiotic for the treatment of bacterial-inflammatory tissues.