Three-dimensional kinematics analysis of blind football kicking.

The purpose of this study was to identify critical technical points that lead to increased ball speed in a maximal toe kick with no run-up (a 'static kick') in blind football. Six visually impaired male players and eight sighted male players participated in the experiment. All participants wore a blindfold to fully remove visual information and performed the static kick. The motion was captured three-dimensionally using an optical motion analysis system. Our results demonstrated that ball speed, maximum linear velocity of the kicking-side thigh, and maximum angular velocity of the kicking-side shank for the sighted player group were significantly greater than those for the visually impaired player group. The sighted players tended to perform the static kick in a similar motion pattern, which was characterised by a backwards rotation of the torso to adequately extend the kicking-side hip joint during the back-swing phase and a stable posture of the lower torso on the frontal plane during the forward-swing phase. This motion pattern is critical to both acceleration of the kicking-side foot and orientation of the foot for a more precise ball contact position.

Effect of substituting allogenic blood transfusion with autologous blood transfusion on outcomes after radical oesophagectomy for cancer.

BACKGROUND: The oncologic benefit of avoiding allogenic blood transfusion in oesophageal cancer resection has not been studied. METHODS: The medical records of 68 patients (Auto group) who underwent a potentially curative oesophageal cancer resection without allogenic blood transfusion from 1996 to 1999 receiving 800 g of autologous blood donated preoperatively, and 97 patients (Allo group) who underwent the same operation with allogenic blood transfusion from 1990 to 1995 were compared. RESULTS: There were no differences in age, gender, stage of disease, number of retrieved nodes, or perioperative hemoglobin concentration between the two groups. The survival of the 45 patients with nodal involvement in the Auto group was better than that of the 59 patients in the Allo group (p=0.0435), and the survival of the 35 patients with T3 or T4 lesions in the Auto group was better than that of the 61 patients in the Allo group (p=0.0408). According to logistic regression analysis, allogenic blood transfusion correlated with tumour recurrence in patients with either nodal involvement or a T3-4 lesion. The natural killer cell activity remained higher in the Auto group than in the Allo group (p<0.05). CONCLUSION: Avoidance of allogenic blood transfusion favorably effected the survival of patients with oesophageal cancer at risk for recurrence.

Expression of bile duct-type cytokeratin in hepatocellular carcinoma in patients with hepatitis C virus and prior hepatitis B virus infection.

The clinicopathologic findings in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) positive for biliary markers, those related to the hepatic progenitor cells, were investigated. Cytokeratin (CK) 19 was reactive for HCCs only in patients with prior hepatitis B virus (HBV) infection. The proportions of patients with prior HBV infection and poorly differentiated HCC were significantly higher among those with CK 19-positive HCC than among those with CK 19-negative HCC. Some HCCs develop from the hepatic progenitor cells in patients with HCV infection and prior HBV infection, which may affect the clinicopathologic findings of HCV-related HCCs.

High susceptibility of p53 knockout mice to esophageal and urinary bladder carcinogenesis induced by N, N-dibutylnitrosamine.

In human cancer, alterations in the p53 tumor suppressor gene are the most common genetic alterations. The aim of the present study was to detect sensitivity of the p53 (+/-) mice and their littermates p53 (+/+) mice to N, N-dibutylnitrosamine (DBN) carcinogenicity. In experiment 1, 6-7-week-old p53 (+/-) and p53 (+/+) mice were treated with 0, 0.025 and 0.05% DBN, respectively, in drinking water for 20 weeks. Esophageal squamous cell and urinary bladder transitional cell carcinomas (TCCs) and fibrosarcomas were found to be significantly increased in p53 (+/-) mice treated with doses of DBN compared to p53 (+/+) mice administered similar doses. In experiment 2, 6-7-week-old p53 (+/-) and p53 (+/+) mice were administered 0 or 0.05 % DBN in drinking water for 8 weeks. Immunohistochemical staining revealed a significant increase in numbers of p53 and bromodeoxyuridine (BrdU) positive cells in the esophageal and urinary bladder epithelia of DBN-treated p53 (+/-) mice compared to p53 (+/+) mice administered DBN. Molecular analysis revealed point mutations in the residual p53 allele in four of eight (50%) esophageal mucosa of DBN-treated p53 (+/-) mice, and in three of eight (38%) of treated p53 (+/+) mice. The results show that p53 (+/-) mice were sensitive to DBN treatment with respect to esophageal and bladder tumor development, with a mechanism that could be confined to early mutations of the residual p53 allele and increased cellular proliferation in the target organs.

p53 null mutations detected by a p53 yeast functional assay predict a poor outcome in young esophageal carcinoma patients.

Esophageal carcinoma is one of the most common gastrointestinal malignant neoplasms in the world. Recent advances in treatment modalities as well as surgical resection techniques have improved the changes of survival of patients with esophageal carcinoma, although the prognosis is worse than for the other gastrointestinal carcinomas. A more precise stratification beyond clinicopathological classification may help determine optimal treatment. The importance of p53 gene mutations in the pathogenesis of human esophageal carcinoma is well established, but it is still controversial whether the presence of p53 mutations adversely affects individual patient prognosis. In this study, we investigated the p53 mutations of esophageal carcinomas and their correlation with clinicopathologic factors. We employed a p53 yeast functional assay because it is highly sensitive and can detect mutations based on the actual function of the p53 gene, clarifying more precisely the role of this gene in esophageal carcinomas. We also studied young patients (< or =65 years old), because our previous study raised the possibility of differences in the importances in esophageal carcinogenesis in young and old patients. Of 43 young esophageal carcinoma patients (42 squamous cell and 1 undifferentiated carcinoma), 38 (88.4%) harbored p53 mutations. Twenty-seven missense and 11 null mutations were detected, but the presence of p53 mutations did not correlate with any clinicopathologic factor. However, the null mutation was a significant indicator of a poor outcome (P=0.0278). All except one patient who harbored null mutation died within 3 years after a macroscopically curative resection. These data suggest that the type of p53 gene mutation may be predictive of outcome in young esophageal carcinoma patients. Furthermore, null mutations causing loss of function of the gene product may play a more important role than missense mutations in tumor progression.

Incidence and management of bile leakage after hepatic resection for malignant hepatic tumors.

BACKGROUND: Bile leakage is one of the frequent and disturbing complications of hepatic resection. STUDY DESIGN: Clinical records of the 363 patients who underwent hepatic resections without biliary reconstruction for hepatic cancers between January 1994 and June 2001 were reviewed. Postoperative bile leakage was defined as continuous drainage with a bilirubin concentration of 20 mg/dL or 1,500 mg/d lasting 2 days. Leakage that continued longer than 2 weeks or that required surgical intervention was defined as uncontrollable. Differences in incidence and frequency of uncontrollable leakage for the different types of hepatic resection, tumors, and underlying liver disease were investigated. Outcomes after treatment for uncontrollable bile leakage were also reviewed. RESULTS: Postoperative bile leakage occurred in 26 of 363 patients (7.2%). Although the incidence in patients with cholangiocellular carcinoma (3/9 [33%]) was higher (p = 0.03) than in patients with hepatocellular carcinoma, rates of occurrence were similar among the different types of hepatic resection and underlying liver disease. Eight of the 26 patients (31%) had uncontrollable leakage. Two patients required reoperation to control leakage; one of these developed hepatic failure and died 2 months after surgery. Four patients underwent endoscopic nasobiliary drainage 21 to 34 days after hepatectomy, and the leakage resolved within 3 to 21 days. Fibrin glue sealing was effective in two patients whose leaking bile ducts were not connected to the common bile duct. CONCLUSIONS: Although meticulous surgical technique can minimize the risk of postoperative bile leakage, some instances of leakage are unavoidable. Nonsurgical treatments, such as nasobiliary drainage or fibrin glue sealing, are preferable to reoperation.

Targeting superoxide dismutase to renal proximal tubule cells attenuates vancomycin-induced nephrotoxicity in rats.

Vancomycin hydrochloride (VCM), a glycopeptide antibiotic, has a broad spectrum against methicillin-resistant Staphylococcus aureus (MRSA). As it is known to induce renal dysfunction, the dose and the duration of its administration are limited. Moreover, the mechanism of VCM-induced renal dysfunction remains to be unclear. To evaluate the involvement of free radical on VCM-induced renal dysfunction, we carried out analysis with a hexamethylenediamine-conjugated superoxide dismutase (AH-SOD) which rapidly accumulates in renal proximal tubule cells and inhibits oxidative injury of the kidney. Male Wistar rats (weighing 200-210 g) were intraperitonealy administered with 200 mg/kg of VCM twice a day for 7 days. AH-SOD 5 mg/kg/day was subcutaneously injected 5 min before every VCM injection. VCM induced renal injury dose-dependently. Biochemical analyses revealed that plasma levels of blood urea nitrogen and creatinine significantly increased in the VCM-treated group by an AH-SOD-inhibitable mechanism. VCM simultaneously elicited an increase of 8-OHdG levels and chemiluminescence intensity of free radical generation in the kidney. Histological examination revealed that VCM also elicited a marked destruction of glomeruli and necrosis of proximal tubules. AH-SOD inhibited these phenomena in the kidney. These results suggested that oxidative stress might underlie the pathogenesis of VCM-induced nephrotoxicity and targeting SOD and/or related antioxidants to renal proximal tubules might permit the administration of higher doses of VCM sufficient for eradication of MRSA without causing renal injury.

Secondary hemocholecyst after radiofrequency ablation therapy for hepatocellular carcinoma.

A 65-year-old Japanese man underwent radiofrequency ablation (RFA) therapy of a hepatocellular carcinoma. Hemobilia from the intrahepatic bile ducts adjacent to the tumor developed on the fifth day after the RFA therapy. Ultrasonograms and computed tomograms showed swelling of the gallbladder, which was filled with a clot, suggesting the diagnosis of hemocholecyst. The hemobilia resolved with conservative therapy, but a cholecystectomy was performed to manage postprandial abdominal pain. The resected gallbladder was filled with a clot, but injury or ulceration of the gallbladder was absent, suggesting that the hemocholecyst developed secondary to the hemobilia. Secondary hemocholecyst is a rare complication of RFA therapy. The number of cases of secondary hemocholecyst is likely to increase as hepatocentestic therapy becomes more common. Cholecystectomy is indicated for hemocholecyst because spontaneous liquefication and drainage of a clot in the gallbladder usually does not occur.

Esophageal tuberculosis presenting with an appearance similar to that of carcinoma of the esophagus.

A case of esophageal tuberculosis presenting with an appearance similar to that of esophageal cancer is reported. The patient was an 82-year-old man with progressive dysphagia. Barium swallow and esophagoscopy revealed an elevated lesion with deep ulceration in the middle thoracic esophagus. Esophageal carcinoma, in particular, an undermining type of undifferentiated carcinoma, was suspected fluoroscopically and endoscopically. Histological examination of biopsy specimens revealed no malignancy, but there were epithelioid granulomas and a few Langhans' type multinucleated giant cells. Endoscopic ultrasonography clearly demonstrated an extramural lesion with calcification and direct infiltration of enlarged subcarinal lymph nodes into the esophageal wall. Ultrasonographic and histological findings indicated the possibility of esophageal tuberculosis. Although no bacteriological evidence was obtained, a therapeutic trial for tuberculosis, using antituberculous drugs, was started. After 2 weeks, the enlarged subcarinal lymph nodes were markedly reduced in size. The patient's symptoms improved gradually and had disappeared 8 weeks after he started treatment, when tubercle bacilli were isolated from sputum. A connection between the esophageal wall and its adjacent structures was clearly demonstrated by endoscopic ultrasonography. For patients with findings indicative of esophageal tuberculosis on endoscopic ultrasonography, a therapeutic trial for tuberculosis should be considered, even if polymerase chain reaction assay or culture is negative.

Surgical management of cystic hepatic neoplasms.

BACKGROUND: The clinicopathologic features of cystic neoplasms of the liver, such as cystadenoma and cystadenocarcinoma, are poorly defined because these lesions are extremely rare. METHODS: Clinicopathologic findings in six patients who underwent surgery for a cystic hepatic neoplasm were reviewed retrospectively to determine the best surgical strategy to treat this condition. RESULTS: Five patients had a multilocular cyst or elevated lesions detected on preoperative imaging studies. The remaining patient had elevated serum concentrations of carcinoembryonic antigen and carbohydrate antigen 19-9, even though preoperative imaging studies of the hepatic cystic lesion revealed no imaging features of cystadenocarcinoma. Cytology failed to detect malignant cells in the cyst contents of any patient. One patient underwent palliative resection because pleural dissemination was present, and five patients underwent curative resection. Three patients had cystadenoma diagnosed in the surgical specimen. One patient with cystadenocarcinoma has survived for more than 8 years after a curative resection that was limited to the cyst wall, and another patient died of recurrence 13 months after surgery. CONCLUSIONS: When a cystic neoplasm is suspected of being cystadenocarcinoma, hepatic resection should be considered, because reliable criteria for distinguishing cystadenoma from cystadenocarcinoma clinically do not exist.

Treatment with STI571, a tyrosine kinase inhibitor, for gastrointestinal stromal tumor with peritoneal dissemination and multiple liver metastases.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are usually refractory to standard chemotherapeutic agents. We successfully treated a patient with a tyrosine kinase inhibitor (STI571) for GIST with peritoneal dissemination and liver metastases. METHODS: In a 32-year-old man presenting with abdominal pain from diffuse peritonitis, a GIST and associated perforated small intestine were resected. Multiple liver metastases were present. After therapies with microwave coagulation, ethanol injection, and local and systemic antineoplastic drugs (fluorouracil, cisplatin, tegafur-uracil, and tegafur) failed, investigational treatment with a tyrosine kinase inhibitor was initiated (STI571, 300 mg, p.o. daily). RESULTS: Anorexia and abdominal fullness resolved within a few days. At 24 days after initiation, positron emission tomography showed a remarkable decrease in the abdominal uptake of [18F] fluorodeoxyglucose. Adverse effects of STI571, including mild alopecia and anemia, were minimal. CONCLUSIONS: The tyrosine kinase inhibitor STI571 may be effective against GISTs.

Ambulatory intraesophageal bilirubin monitoring in Japanese patients with gastroesophageal reflux.

BACKGROUND: The role of reflux of duodenal contents in gastroesophageal reflux in Japanese patients, which may be different from that in Western patients, was studied. METHODS: Intraesophageal pH and the bilirubin concentration were monitored, using the Bilitec 2000, in 43 patients with reflux symptoms and 10 normal volunteers. The percentage of the time that spectrophotometric absorbance was 0.15 or more and pH was less than 4.0 was defined as the holding times (HTs) of bilirubin and acid, respectively. Severity of esophagitis was classified using the Savary-Miller (S-M) classification. RESULTS: Esophagitis was present in 37 patients; 5, 10, 13, and 9 patients had S-M grades 1, 2, 3, and 4, respectively. Both HTs in the volunteers were less than 5%. Bilirubin HT was more than 5% in 3 of the 6 patients without esophagitis, but the acid HT was less than 5% in these 6 patients. Acid HT was less than 5% in 4, 2, 2, and 2 patients with S-M grades 1, 2, 3, and 4, respectively. Bilirubin HT was less than 5% in 1 patient with S-M grade 2 esophagitis. Bilirubin HT in patients with S-M grades 3 and 4 esophagitis (50.9 +/- 5.8%) was higher than that in grades 1 and 2 (14.9 +/- 2.9%) (P < 0.0001), but this was not so for acid HT. In 32 patients, bilirubin HT exceeded acid HT. Bilirubin HT did not correlate with acid HT. CONCLUSIONS: Duodenogastroesophageal reflux occurred independently of and exceeded acid reflux. The amount of duodenogastroesophageal reflux correlated with the severity of esophagitis.

Prognostic factors in patients with squamous oesophageal cancer associated with solitary lymph node metastasis after oesophagectomy and extended lymphadenectomy.

It is not fully understood whether oesophageal cancer, associated with solitary lymph node metastasis, is still a local disease or already a systemic one. Among 283 patients with squamous oesophageal cancer who underwent oesophagectomy and 3-field lymphadenectomy, 37 patients had single metastasized nodes. Clinicopathologic factors, following Japanese Guideline for the Clinical and Pathological studies on Carcinoma of the Esophagus, related to survival and pre-operative predictability of nodal involvement was studied. Five-year survival was 48%. Initial pattern of recurrence was mostly haematogenous. Among the factors related to survival, grade of lymph node metastasis (pN1 vs. pN2, pN3, p=0.006) was more closely related than depth of invasion (pT1, pT2 vs. pT3, pT4, p=0.037). Five-year survival was 71.7% for pN1 patients, whereas it was 22% for pN2 or pN3 patients. Of the metastasized nodes 65% were <10 mm, and 27% was <5 mm in the maximum diameter. Oesophageal cancer is still a local disease in half of the patients with a solitary metastasized node. For these patients, dissection along the recurrent laryngeal nerve is necessary to retrieve the node possibly metastasized.

Effect of duodenogastric reflux on N-methyl-N'-nitro-N-nitrosoguanidine-induced glandular stomach tumorigenesis in Helicobacter pylori-infected Mongolian gerbils.

Both Helicobacter pylori (Hp) and bile acids are gastric carcinogens. An experimental model of duodenogastric reflux in Mongolian gerbils was developed and was used to study the effects of Hp infection and duodenogastric reflux on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced glandular stomach tumorigenesis independently and synergistically. Male Mongolian gerbils underwent both inoculation with Hp, and had duodenogastric reflux (DR) induced, or neither, followed by MNNG administration. Animals were sacrificed at week 40, and histopathological examination of their excised stomachs and serological investigation were performed. Glandular stomach adenocarcinomas were observed in animals that underwent Hp inoculation and/or induction of DR after MNNG administration, and glandular stomach adenomas were found in animals inoculated with Hp after MNNG administration. The incidence of glandular stomach tumors was significantly higher in animals inoculated with Hp after MNNG administration and in animals undergoing combined Hp inoculation, DR induction and MNNG administration than in animals only administered MNNG. These findings indicate that Hp infection has a stronger tumorigenic effect than the exposure to duodenal contents, and duodenal contents may attenuate the effect of Hp on glandular stomach tumorigenesis.

Clinicopathologic and immunohistochemical features of surgically resected small cell carcinoma of the esophagus.

Esophageal small cell carcinoma (SmC) is considered an aggressive cancer carrying a poor prognosis, although the rarity of this tumor has impeded statistical evaluation. We reviewed records of 457 esophageal cancer patients treated in our department from 1986 to 2000, comparing clinicopathologic factors and post-treatment outcomes, for 9 patients with SmC, most undergoing esophagectomy including lymphadenectomy, with data from 128 patients with esophageal squamous cell carcinoma (SqC) invading to the muscular layer or beyond. Immunohistochemical features were compared between the SmC and 12 consecutive SqC. All patients studied had localized disease according to preoperative staging. SmC showed more ulcerative and infiltrative growth, and more aggressive lymphatic spread, than SqC. All SmC patients had lymph node metastasis (thoracic nodes, 9 patients: abdominal 6; cervical 1). All SmC specimens but no SqC were immunoreactive for neuron-specific enolase. Two and three SmC specimens were reactive for epithelial membrane antigen and keratin, respectively. Survival of SmC patients after esophagectomy (median, 11 months) was worse than for SqC patients (p=0.013). However, 1 SmC patient remains alive at 76 months. Survival was not related to any clinicopathologic or immunohistochemical features. While SmC shows aggressive behavior and worse outcomes than SqC, combining esophagectomy with chemotherapy or radiotherapy may prolong survival.

Oral fluoropyrimidine anticancer drug TS-1 for gastric cancer patients with peritoneal dissemination.

The survival of gastric cancer patients with peritoneal dissemination is dismal and surgical intervention is rarely indicated. The usefulness of TS-1, a novel oral anticancer drug, composed of tegafur, gimestat and otastat potassium at a molar ratio of 1:0.4:1, and the role of surgical intervention for this condition was studied. Among gastric cancer patients with peritoneal dissemination, 18 treated during September 1999 to March 2001, and 16 before March 1999, were classified into the TS-1 group and control group, respectively, and survival was compared. TS-1 was administered orally twice daily, at a dose of 80 mg/m2/day, for 28 days followed by 14 days without treatment. This cycle was repeated. There was no difference in clinicopathologic factors, including surgical intervention, between the two groups. Eleven patients of the control group had chemotherapy using fluoropyrimidine. Grade 3-4 adverse reactions caused by TS-1 occurred in 1 patient. Survival was better in the TS-1 group than control group (p=0.0008), with median survival of 257 vs. 118 days. The median discharged period of patients of the TS-1 group with a performance status 0-2 on the Zubor scale was 211 days. TS-1 was effective to prolong the survival of gastric cancer patients with peritoneal dissemination. In this series of cases, surgical intervention to establish the route of oral administration was essential for this treatment.

Weak enhancing effects of simultaneous ethanol administration on chemically induced rat esophageal tumorigenesis.

Excessive alcohol consumption is associated epidemiologically with an elevated risk of esophageal cancer. In this study, we examined the effects of simultaneous administration of ethanol on N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. Groups 1-3 were treated with NMBA at a dose of 0.5 mg/kg body weight (high dose), and groups 4-6 received a dose of 0.1 mg/kg body weight (low dose), by s.c.-injection, 3 times per week for the first 5 weeks. Groups 1 and 4 were given ethanol free water as controls. Groups 2 and 5 were treated with 10% ethanol in their drinking water only at the time of NMBA treatment, while groups 3 and 6 were administrated the supplement continuously up to the end of the experiment. Macroscopically, with high dose NMBA-initiation, simultaneous 5-week and continuous 24-week ethanol administration demonstrated a tendency to increase the incidence and multiplicity of tumors, and also microscopically the multiplicity of papillary hyperplasias. In low dose groups, the incidence of esophageal papillary hyperplasias was significantly increased by continuous 24-week ethanol administration. Immunohistochemistry, proliferating cell nuclear antigen (PCNA) positive indices tended to be increased in tumors by simultaneous 5-week and continuous 24-week ethanol administration, but cyclin D1 expression was not affected. These data suggest that simultaneous ethanol administration have weak enhancing effects, and also promoting effects in post-initiation phase is present on NMBA-induced rat tumorigenesis.

Causes of death and pattern of recurrence after esophagectomy and extended lymphadenectomy for squamous cell carcinoma of the thoracic esophagus.

Improved understanding of how esophageal cancer behaves following curative resection, including knowledge of other causes of death, is essential for informed decision making. The medical records of 246 consecutive patients with squamous cell carcinoma of the thoracic esophagus who had undergone esophagectomy and lymphadenectomy of the neck, chest, and abdomen that was deemed macroscopically curative, were reviewed. Patients who had had other malignancies or anticancer treatment were excluded. Median follow-up period was 1289 days (minimum, 730 days). The initial patterns of recurrence were classified as intramediastinal, hematogenous, or lymphatic. Forty-two patients died of a cause other than recurrence. The in-hospital death rate was 3.6%, and 19 patients died of pulmonary disease. Sixteen patients developed a second primary, most of which were in the upper aerodigestive tract; five of those patients died. Ninety-eight patients developed recurrence. Depth of invasion and number of nodal metastases predicted recurrence. The pattern of recurrence was intra-mediastinal, lymphatic, and hematogenous in 11, 21, and 67 patients, respectively. The patients with lymphatic recurrence survived longer than the patients with either of the other types of recurrences. Eighty-three percent of recurrences presented within 24 months. The time-to-recurrence correlated with survival after recurrence. The disease recurred earlier in patients with advanced stage than unadvanced disease at the time of esophagectomy. The time-to-recurrence, and anticancer therapy after the recurrence related to the survival. Meticulous care must be taken to detect hematogenous recurrence as early as possible so that adjuvant therapy may be started. Maintaining a good performance status permits the use of aggressive therapy should there be a recurrence. Pulmonary physiotherapy and treatment of metachronous primary tumors may improve overall survival.

Inhibition of vancomycin-induced nephrotoxicity by targeting superoxide dismutase to renal proximal tubule cells in the rat.

Vancomycin, a glycopeptide antibiotic, has a broad spectrum against methicillin-resistant Staphylococcus aureus (MRSA). Because vancomycin induces renal dysfunction, the dose and the duration of its administration are limited. The mechanism of vancomycin-induced renal dysfunction is not known. We recently synthesized a hexamethylenediamine-conjugated cationic superoxide dismutase (AH-SOD) which rapidly accumulates in renal proximal tubule cells and inhibits oxidative injury of the kidney. The present work reports the protective effects of AH-SOD against vancomycin-induced renal dysfunction. Male Wistar rats (200-210 g) were intraperitoneally administered with either 200 or 400 mg/kg of vancomycin twice a day for 7 days. Either 5 mg/kg/day AH-SOD or saline was subcutaneously injected 5 min before every vancomycin injection. Biochemical analysis revealed that plasma levels of blood urea nitrogen and creatinine increased significantly in vancomycin-treated group by an AH-SOD-inhibitable mechanism. Histological examination revealed that vancomycin also elicited a marked destruction of glomeruli and necrosis of proximal tubule by an AH-SOD inhibitable mechanism. These results suggest that oxidative stress underlies the pathogenesis of vancomycin-induced nephrotoxicity and that targeting SOD and/or related antioxidants to renal proximal tubule cells might permit the administration of higher doses of vancomycin sufficient for eradication of MRSA without causing renal injury.

Effects of alanine in patients with advanced primary biliary cirrhosis: preliminary report.

When rats given D-galactosamine are then treated with the glucogenic amino acid alanine, their alanine aminotransferase (ALT) activity, total bilirubin level, and survival rate improve compared with when other amino acids are used. Here, we report a preliminary study of the clinical and pharmacological effects of alanine given to three patients with primary biliary cirrhosis (PBC). The patients were jaundiced and were in the end-stage of the disease. The treatment they had been receiving was continued while they were given 18 g of alanine per day for a planned 8 weeks. For all three patients, test results for total bilirubin, alkaline phosphatase, and ALT decreased by 25% or more from the base line at some time during treatment. The arterial ketone-body ratio increased. Two of the patients reported that their itching and fatigue lessened. Except for one patient given a second course, who reported nausea, adverse effects were not found. In end-stage PBC, alanine administration decreased the total bilirubin level and improved symptoms, so this compound may decrease jaundice in this disease. A long-term study of a larger group of patients is needed.