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Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

Background The pathophysiology of adhesion formation after abdominal and pelvic surgery is still largely unknown. The aim of the study was to investigate the role of macrophage polarization and the effect of peroxisome proliferator-activated receptor (PPAR) γ stimulation on adhesion formation in an animal model. Methods Peritoneal adhesion formation was induced by the creation of ischaemic buttons within the peritoneal wall and the formation of a colonic anastomosis in wild-type, interleukin (IL) 10-deficient (IL-10−/−), IL-4-deficient (IL-4−/−) and CD11b-Cre/PPARγfl/fl mice. Adhesions were assessed at regular intervals, and cell preparations were isolated from ischaemic buttons and normal peritoneum. These samples were analysed for macrophage differentiation and its markers, and expression of cytokines by quantitative PCR, fluorescence microscopy, arginase activity and pathological examination. Some animals underwent pioglitazone (PPAR-γ agonist) or vehicle treatment to inhibit adhesion formation. Anastomotic healing was evaluated by bursting pressure measurement and collagen gene expression. Results Macrophage M2 marker expression and arginase activity were raised in buttons without adhesions compared with buttons with adhesions. IL-4−/− and IL-10−/− mice were not affected, whereas CD11b-Cre/PPARγfl/fl mice showed decreased arginase activity and increased adhesion formation. Perioperative pioglitazone treatment increased arginase activity and decreased adhesion formation in wild-type but not CD11b-Cre/PPARγfl/fl mice. Pioglitazone had no effect on anastomotic healing. Conclusion Endogenous macrophage-specific PPAR-γ signalling affected arginase activity and macrophage polarization, and counter-regulated peritoneal adhesion manifestation. Pharmacological PPAR-γ agonism induced a shift towards macrophage M2 polarization and ameliorated adhesion formation in a macrophage-dependent manner.Surgical relevancePostoperative adhesion formation is frequently seen after abdominal surgery and occurs in response to peritoneal trauma. The pathogenesis is still unknown but includes an imbalance in fibrinolysis, collagen production and inflammatory mechanisms. Little is known about the role of macrophages during adhesion formation.In an experimental model, macrophage M2 marker expression was associated with reduced peritoneal adhesion formation and involved PPAR-γ-mediated arginase activity. Macrophage-specific PPAR-γ deficiency resulted in reduced arginase activity and aggravated adhesion formation. Pioglitazone, a PPAR-γ agonist, induced M2 polarization and reduced postoperative adhesion formation without compromising anastomotic healing in mice.Pioglitazone ameliorated postoperative adhesion formation without compromising intestinal wound healing. Therefore, perioperative PPAR-γ agonism might be a promising strategy for prevention of adhesion formation after abdominal surgery.

These authors suggest there is no difference in postoperative complication rates in suture versus tack mesh fixation in laparoscopic umbilical hernia repair., Background and Objectives: Mesh fixation in laparoscopic umbilical hernia repair is poorly studied. We compared postoperative outcomes of laparoscopic umbilical hernia repair in suture versus tack mesh fixation. Methods: Patients who underwent laparoscopic umbilical hernia repair were separated by method of mesh fixation: sutures versus primarily tacks. Medical history and follow-up data were collected through medical records. The primary outcome of this study was the recurrence rates of hernias. Postoperative major and minor complications, such as surgical site infection, small-bowel obstruction, and seroma formation, were regarded as secondary outcomes. Additionally, a telephone interview was conducted to assess postoperative pain, recovery time, and overall patient satisfaction. Results: Eighty-six patients were identified: 33 in the suture group and 53 in the tacks group. The number of emergent cases was increased in the tacks group (6 vs 0; P = .022). Mean follow-up time was 2.7 years for both groups. Documented postoperative follow-up was obtained in 29 (90%) suture group and 31 (58%) tacks group patients. Hernia recurrence occurred in 3 and 2 patients in the sutures and tacks groups, respectively (P was not significant). No differences were found in secondary outcomes, including subjective outcomes from telephone interviews, between groups. Conclusions: There are no differences in postoperative complication rates in suture versus tack mesh fixation in laparoscopic umbilical hernia repair.

Background The aim of this study was to compare backs and forwards rugby union players recruited to a National team in the following physical and physiological indicators: anthropometrics, squat jump (SJ), countermovement jump (CMJ), 10- and 30-meter sprint, resting heart rate variability (HRV), Yo-Yo Test and heart rate (HR) at 2 minutes of test. Methods The measurements were performed on the first day of a training camp planned to finely select the players who would participate in the 2016 America's Rugby Championship. The magnitude-based inference was used in the comparisons. Results Backs demonstrated almost certainly greater distance in the Yo-Yo Test (backs: 2305.9±231.3 meters; forwards: 1802.4±361.2 meters), higher vertical jump height in both SJ and CMJ (SJ: 44.0±5.3 cm vs. 37.6±5.4 cm; CMJ: 46.1±5.0 cm vs. 40.0±5.5 cm, for backs and forwards respectively), and superior sprint velocity in 10- and 30-m (10-m: 6.02±0.23 m.s-1 vs. 5.51±0.34 m.s-1; 30-m: 7.46±0.25 m.s-1 vs. 6.89±0.37 m.s-1, for backs and forwards respectively) than the forwards. In contrast, forwards were almost certainly taller and heavier than backs, and displayed higher sprint momentum in 10- and 30-meters (10 meters: 513.0±51.6 kg.m.s-1 vs. 598.4±53.1 kg.m.s-1; 30 meters: 635.3±56.1 kg.m.s-1 vs. 749.0±70.5 kg.m.s-1, for backs and forwards respectively). The submaximal HR in the first 2-minutes of the Yo-Yo test was likely lower in the backs than in the forwards (77.6±5.1% of the maximal HR vs. 81.3±5.4% of the maximal HR for backs and forwards respectively), while HRV indices were not different between backs and forwards. Conclusions Playing position appears to be determined by the players' physical and physiological characteristics in top-level rugby union, and the submaximal HR measured during Yo-Yo test can be a simple alternative to discriminate backs and forwards.

Background To clarify the influence of hypertension and blood pressure ( BP ) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐ RHYTHM Registry was performed. Methods and Results A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05–2.21, P =0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73–1.52, P =0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up (Q1, CI 1.75–4.74, P CI 1.02–2.53, P =0.041) after adjustment for components of CHA 2 DS 2 ‐ VAS c score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage. Conclusions BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation. Clinical Trial Registration URL : http://www.umin.ac.jp/ctr . Unique identifier: UMIN 000001569.

Swimmers are often tested on both dry-land and in swimming exercises. The aim of this study was to test the relationships between dry-land, tethered force-time curve parameters and swimming performances in distances up to 200 m. 10 young male high-level swimmers were assessed using the maximal isometric bench-press and quarter-squat, mean propulsive power in jump-squat, squat and countermovement jumps (dry-land assessments), peak force, average force, rate of force development (RFD) and impulse (tethered swimming) and swimming times. Pearson product-moment correlations were calculated among the variables. Peak force and average force were very largely correlated with the 50- and 100-m swimming performances (r=− 0.82 and −0.74, respectively). Average force was very-largely/largely correlated with the 50- and 100-m performances (r=− 0.85 and −0.67, respectively). RFD and impulse were very-largely correlated with the 50-m time (r=− 0.72 and −0.76, respectively). Tethered swimming parameters were largely correlated (r=0.65 to 0.72) with mean propulsive power in jump-squat, squat-jump and countermovement jumps. Finally, mean propulsive power in jump-squat was largely correlated (r=− 0.70) with 50-m performance. Due to the significant correlations between dry-land assessments and tethered/actual swimming, coaches are encouraged to implement strategies able to increase leg power in sprint swimmers.

The aim of this study was to test the relationships between jump squat (JS) and Olympic push press (OPP) power outputs and performance in sprint, squat jump (SJ), countermovement jump (CMJ) and change of direction (COD) speed tests in elite soccer players. 27 athletes performed a maximum power load test to determine their bar mean propulsive power (MPP) and bar mean propulsive velocity (MPV) in the JS and OPP exercises. Magnitude-based inference was used to compare the exercises. The MPV was almost certainly higher in the OPP than in the JS. The MPP relative to body mass (MPP REL) was possibly higher in the OPP. Only the JS MPP REL presented very large correlations with linear speed (r>0.7, for speed in 5, 10, 20 and 30 m) and vertical jumping abilities (r>0.8, for SJ and CMJ), and moderate correlation with COD speed (r=0.45). Although significant (except for COD), the associations between OPP outcomes and field-based measurements (speed, SJ and CMJ) were all moderate, ranging from 0.40 to 0.48. In a group composed of elite soccer players, the JS exercise is more associated with jumping and sprinting abilities than the OPP. Longitudinal studies are needed to confirm if these strong relationships imply superior training effects in favor of the JS exercise.

Immunization involving a DNA vaccine prime followed by an adenovirus type 5 (Ad5) boost elicited a protective immune response against SHIV challenge in monkeys. However, the hepatocellular tropism of Ad5 limits the safety of this viral vector. This study examines the safety and immunogenicity of a replication-defective chimeric Ad5 vector with the Ad35 fiber (Ad5/35) in BALB/c mice and rhesus monkeys. This novel Ad5/35 vector showed minimal hepatotoxicity after intramuscular administration with the novel Ad5/35 vector. In addition, an Ad5/35 vector expressing HIV Env gp160 protein (Ad5/35-HIV) generated strong HIV-specific immune responses in both animal models. Priming with a DNA vaccine followed by Ad5/35-HIV boosting yielded protection against a gp160-expressing vaccinia virus challenge in BALB/c mice. The Ad5/35-HIV vector was significantly less susceptible to the pre-existing Ad5 immunity than a comparable Ad5 vector. These findings indicate that an Ad5/35 vector-based HIV vaccine may be of considerable value for clinical use.

Aims: Withdrawal of angiotensin-converting enzyme (ACE) inhibitors may affect the progression of chronic renal failure and an insertion/deletion (I/D) polymorphism of the ACE gene may influence it. Methods: We retrospectively collected patients with chronic glomerulonephritis and benign nephrosclerosis who discontinued ACE inhibitor use. The relationship between the decline of renal function after the withdrawal and the influencing factors such as ACE gene polymorphism, blood pressure and proteinuria were evaluated using multiple regression analysis. Results: Forty-two patients (initial serum creatinine 0.5 - 6.5 mg/dl) had been treated and discontinued ACE inhibitor use. Only patients with the II or DI genotypes of the ACE gene developed the deterioration of renal function, starting at 2 months after the withdrawal. Stepwise regression analysis revealed that the level of proteinuria after the withdrawal, presence of the insertion of ACE gene and serum creatinine level at the time of withdrawal mainly influenced the decline of renal function after the withdrawal (adjusted R 2 = 0.48). Conclusion: Withdrawal of ACE inhibitor causes the deterioration of renal function in patients with the II or DI genotypes, high proteinuria after the withdrawal, and high serum creatinine level at the withdrawal, which probably causes the rebound increase in serum ACE activity.

The objective of this open trial was to investigate the efficacy and safety of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin in hypercholesterolemic patients already receiving probucol. All of the participants had hypercholesterolemia. i.e. serum total cholesterolor = 220 mg/dl, despite administration of probucol, 500 mg/day, for more than 4 weeks. After this, fluvastatin, 30 mg/day, was added to probucol treatment for 12 weeks. Twenty-seven patients were recruited into this study; all were evaluated for safety, and 22 were evaluated for efficacy. The addition of fluvastatin to the probucol regimen produced a significant further reduction in serum total and low-density lipoprotein cholesterol concentrations (of 18 and 20%, respectively; p0.001); these effects were fully established within 4 weeks of treatment and were maintained throughout the treatment. Fluvastatin did not affect the serum high-density lipoprotein cholesterol concentration. Fluvastatin treatment decreased serum triglyceride concentrations slightly in all patients (not significant); in patients with hypertriglyceridemia, triglyceride levels were decreased significantly by 34% (p0.01; serum triglyceridesor = 150 mg/dl). In addition, fluvastatin significantly decreased serum apolipoprotein B, C-II, C-III and E levels, whereas serum apolipoprotein A-I and A-II levels were unaffected. One patient complained of slight abdominal discomfort during fluvastatin administration, but relationship to fluvastatin remains unclear. One patient had slight elevation of the serum alanine aminotransferase level, and another patient had an elevated gamma-glutamyl transferase level. The addition of fluvastatin to probucol treatment can be considered to be an effective and well tolerated treatment in hypercholesterolemic patients.

The optimal method of umbilical hernia repair (UHR) in the obese population, laparoscopic vs open, is not standardized. The purpose of this study was to determine the optimal surgical option for UHR in the obese population.A retrospective chart review was conducted on 123 obese patients (body mass index [BMI]30) who underwent UHR from 2003 to 2009 at a single institution. Patients were grouped by surgical approach (open vs laparoscopic). Intraoperative and postoperative courses were compared. Follow-up in the postoperative period was obtained from patient records and telephone interviews.Of the 123 patients undergoing UHR, 40 and 83 patients were operated on with the laparoscopic and open approach, respectively. Patients were well matched by demographics as well as comorbidities. No difference in the mean BMI was shown between the laparoscopic and open groups (37 vs 35, P = not significant, respectively). The operative time was significantly prolonged in the laparoscopic group (106 vs 71 minutes, P.01). Intraoperatively, no complications occurred in either group. In the immediate postoperative period, 1 patient who underwent laparoscopic UHR was readmitted for small bowel obstruction, and 2 patients in the open group were readmitted, 1 for pain control and 1 for wound infection. Follow-up was achieved in 63% of the laparoscopic group and 58% of the open group with a mean follow-up of 15 months in the laparoscopic group and 20 months in the open group (P = not significant). A significant increase in wound infection was reported in the open group with mesh insertion when compared with the laparoscopic procedure (26% vs 4%, P.05, respectively). No hernia recurrence was shown in the laparoscopic vs the open group with mesh insertion (0% vs 4%, P = not significant, respectively).In obese patients, the laparoscopic approach was associated with a significantly lower rate of postoperative infection and no hernia recurrence. Laparoscopic hernia repair may be the preferred option in the obese patient.

The authors illustrate a new method to identify the pre- and postcentral gyri on computed tomographic (CT) and magnetic resonance (MR) images of the brain on the basis of the pattern of the medullary branches of the cerebral white matter. The most commonly used method to identify the gyri depends on recognition of the central sulcus by surface arrangement of the sulci. The two methods were compared by analysis of CT images of 104 subjects who had normal findings (age range, newborn to 60 years; 57 males and 47 females). The usefulness of the new method was also determined in angiographic studies of nine patients with space-occupying lesions. The method is especially helpful for identification of gyri on the lower level of the centrum semiovale and if space-occupying lesions are present that may result in a blurred depiction of sulci. Since MR imaging depicts the medullary branches more clearly than does CT, this new method should facilitate identification of the gyri with either modality.

Clinical charts, radiological features, macroscopic and microscopic findings, and clinical follow-up data were retrospectively reviewed in 11 patients with papillary cystic neoplasm of the pancreas (PCNP). The patients were nine women and two men, aged from 13 to 51 years with a mean age of 25 years. The greatest diameter of the PCNPs ranged from 2·5 cm to 14·0 cm with a mean size of 7·5 cm. Six tumours were located in the tail of the pancreas, two in the body and three in the head. Most patients complained of abdominal pain or a mass. Ultrasonographic and/or computed tomography findings showed five solid, four mixed (solid and cystic) and two cystic types of tumour. Angiographically, PCNP was either a hypovascular or mild hypervascular mass with a displacement of the surrounding vessels. No vascular encasement was seen. Macroscopically all 11 tumours consisted of a well defined solid mass with degenerative change of various widths, including haemorrhage, necrosis or dystrophic calcification, and were represented by three radiological types of PCNP. The 11 patients with PCNP survived for from 3 to 253 months after curative resection without any signs of local recurrence or remote metastasis. PCNP usually affects the distal portion of the pancreas of young women. Despite its huge size, PCNP should be explored with aggressive surgical intent because of the inherently good prognosis.

Bioavailabilities of morphine after rectal administration of three different morphine.HCl suppositories were evaluated in dogs, whose rectum was lavaged or non-lavaged. The suppositories were prepared with three fatty bases (Witepsol H-15, Witepsol W-35, Suppocire AT) by the fusion method. The release of morphine from the suppositories was examined after stored for two weeks at 30 degrees C. The plasma concentrations of morphine and its metabolites, morphine-3-glucuronide and morphine-6-glucuronide, were determined by high-performance liquid chromatography. The bioavailabilities of morphine after rectal administration were compared with those after intravenous and oral administration of morphine++.HCl solution. In the case of rectal lavaged dogs, the plasma levels of morphine after rectal administration of morphine.HCl solution were higher than those after oral administration of morphine.HCl solution. The release of morphine from Witepsol H-15 suppository was more rapid than those from other suppositories. Morphine after rectal administration of Witepsol H-15 suppository was rapidly absorbed in the rectum, and the inter-animal variation of its plasma levels was smaller than those of other suppositories. In rectal non-lavaged dogs, the bioavailabilities of morphine after rectal administration of morphine.HCl solution and suppositories decreased more than those of rectal lavaged dogs. Although the bioavailability of morphine after rectal administration of morphine.HCl was decreased by the influence of contents in the rectum, morphine from Witepsol H-15 suppository was more rapidly absorbed in the rectum, and the inter-animal variation of its plasma levels was smaller. These results indicate that, among their suppositories, Witepsol H-15 suppository is available for the terminal care of malignant disease.

Adrenomedullin is a recently discovered peptide that was first purified from phaeochromocytoma tissue and has marked vasodilatory activity, causing hypotension. In thyrotoxicosis, various haemodynamic changes are observed, including an increase in cardiac output and heart rate with a concomitant decrease in peripheral vascular resistance. To evaluate the mechanism underlying these haemodynamic changes in thyrotoxicosis, we measured the plasma adrenomedullin concentration in thyrotoxic patients with Graves' disease. The plasma concentration of adrenomedullin was elevated in hyperthyroid patients (14.7 +/- 5.7 pmol L-1) compared with euthyroid control subjects (5.6 +/- 1.3 pmol L-1) (P < 0.001). The correlation between the plasma adrenomedullin concentration and serum free thyroid hormone levels was marginally significant. The mean blood pressure was relatively low in the face of an elevated plasma adrenomedullin level. Adrenomedullin may therefore be responsible for the vasodilatation observed in thyrotoxicosis.

Peritoneal dissemination is the most frequent type of recurrence in patients with gastric cancer with serosal exposure, irrespective of whether they have undergone curative gastrectomy. The purpose of this study was to establish a method to detect micrometastatic cells in the abdominal cavity and predict peritoneal recurrence in patients with such gastric carcinomas. A total of 86 patients with gastric carcinoma, undergoing gastrectomy, were examined. Reverse transcriptase-polymerase chain reaction (RT-PCR) assay was used to detect carcinoembryonic antigen (CEA) mRNA in abdominal lavage fluid. Twenty-four cases without serosal exposure were negative, while all 13 cases with macroscopic peritoneal dissemination were positive for CEA mRNA. Among the 49 cases with macroscopic serosal invasion and without peritoneal metastasis, cancer cells were detected in 27 cases with RT-PCR while in only 6 cases with conventional cytology. All cytologically-positive cases were also positive for CEA mRNA. Among the 27 CEA-positive cases, 15 patients (56%) relapsed with peritoneal metastasis within 12 months after gastrectomy. In contrast, none of the 22 CEA-negative cases had peritoneal recurrence within 16-60 months of observation, whereas in 43 cytologically-negative cases, 10 patients relapsed with peritoneal recurrence. As compared with conventional cytological examination, this method would be clinically more beneficial for detecting free cancer cells in the peritoneal cavity and for predicting peritoneal recurrence in gastric carcinoma with serosal invasion.

Elevated IgE responses and eosinophilia observed in patients with atopic dermatitis (AD) may reflect increased responses of type 2 T-helper (Th2) cytokines with a concomitant decrease in interferon-gamma (IFN-gamma) production. However, the cross-regulation of Th1/Th2 derivation and function in AD patients are incompletely characterized. Therefore, we investigated serum levels of several cytokines [interleukin (IL)-18, IL-12, IL-10, IL-2 and IFN-gamma] in patients with AD to assess their possible relationships to the severity of disease. Serum IL-18 levels in AD patients were significantly higher than those in healthy controls [207 pg/mL; 95% confidence interval (CI), 172-242 pg/mL vs. 144 pg/mL; 95% CI, 116-178 pg/mL; P = 0.026]. Those IL-18 levels significantly correlated with eosinophil counts and serum soluble IL-2 receptor (sIL-2R) levels, and showed a tendency to correlate with clinical severity scores and serum IgE levels. IL-2 levels showed a significantly inverse correlation with serum IgE levels, and IL-12 levels clearly correlated with IL-10 levels. These results suggest the value of serum IL-18 levels as a parameter of AD activity and may support a possible role for IL-18 in the pathogenesis of AD. The inverse correlation between IgE levels and IL-2 levels suggests that IgE production may be inhibited by IL-2 in patients with AD. Furthermore, the correlation of IL-12 levels with IL-10 levels may support the previous reports that show the induction of IL-10 production by human natural killer cells and/or T cells stimulated with IL-12 in vitro.

6-Sulfanilamidoindazole (6SAI) is known to induce not only an acute arthritis but also serositis and arteritis which resemble those induced by some vasodilators in rats. In this study, the recovery process of ankle lesions was examined histopathologically for up to 12 weeks of recovery period in rats bearing arthritis induced by administration of 6SAI (500 mg/kg) for 2 weeks. At 2 weeks of 6SAI-treatment, exudative synovitis and exudative/edematous periarthritis with marked formation of granulation tissues and periosteal reactive bone formation were noted in the ankles, but no remarkable neutrophil infiltration was detected in those lesions. The ankle swelling induced by 6SAI diminished by 4 weeks of recovery period, and the elevated plasma fibrinogen levels were normalized by 2 weeks of recovery period. Although fibrosis and newly-formed periosteal bone were still observed after 2 weeks of recovery period, no inflammatory lesion was detected at that point. At 4 or 12 weeks of recovery periods, the ankles showed an almost normal appearance. These results indicate that 6SAI-induced arthritis is reversible in nature and does not develop into chronic phase.

The goal of this study was to assess the management of failed or failing infrainguinal bypasses with distal correctable lesions. A retrospective analysis of 94 procedures was performed for 72 (77%) failed and 22 (23%) failing infrainguinal bypasses with distal correctable lesions in 94 patients. The 94 procedures included 50 (53%) balloon angioplasties and 44 (47%) distal vein graft extensions from the previous graft to the distal artery. Preprocedural thrombolytic therapy was performed in 62 of 94 limbs with a failed graft, and complete thrombolysis was achieved in 30 of 94. The results of thrombolytic therapy (complete or incomplete thrombolysis) or the means of revision procedure (balloon angioplasty or distal vein graft extension) did not affect the patency. Lower patency was observed for women, patients with a secondary bypass, and grafts with multiple episodes of revision. We conclude that the patency of failing infrainguinal bypasses after revision of distal lesions was affected not by means of therapy but by previous vascular procedures, the usual risk factors, and female gender.

A 72-year-old man had undergone surgical castration for metastatic prostate cancer (stage D2, the PSA value was 4,300 ng/ml) in September, 1997. He was well clinically for 16 months with undetected level of PSA. However, he presented with general malaise and gross hematuria in May, 1999. After admission to our hospital his condition rapidly deteriorated and he died one week later with respiratory failure. Autopsy revealed extensive involvement of the prostate and bladder by solid tumor with multiple metastases in lungs, liver, spleen, kidneys and bone. Histological examination revealed pure small cell carcinoma of the prostate.

Hyperthermo-chemo-radio (HCR) therapy has been found to be effective for rectal cancer. Biomarkers for predicting the effect of HCR therapy are important in determining optimum treatment regimens. Hyperthermo-chemo-radiotherapy (HCR therapy), consisting of hyperthermia at 42 degrees C to 45 degrees C for 40 minutes (twice per week for two weeks), a total of 60 Gy irradiation and administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU) (total 8400 mg), were prescribed pre-operatively for 29 patients with rectal cancer, using tissue specimens collected at pre-treatment biopsy. Apoptosis and overexpression of p53 protein were investigated histopathologically and immunohistochemically. On termination of HCR therapy, all the tumors were surgically resected and effectiveness of the therapy was evaluated histologically. Spontaneous apoptosis was evident in the pre-treatment cancer tissues of 14 patients (48.2%). In this apoptosis-positive group, the positive rate of expression of the p53 protein (21.4%, 3 out of 14) was lower as compared to findings in the apoptosis-negative group (66.7%, 10 out of 15). The response to HCR therapy was better in the apoptosis-positive group than in the apoptosis-negative group. We propose that spontaneous apoptosis is closely related to the function of wild-type p53 protein and is also a predictive biomarker of the effect of HCR therapy for patients with rectal cancer.

Liddle's syndrome is a rare form of autosomal-dominant salt-sensitive hypertension. Constitutive activation of the amiloride-sensitive distal renal epithelial sodium channel (ENaC) is essential for salt-sensitive hypertension. Recently, several DNA analysis studies have indicated that there is a mutation of C-terminus of either the beta or y subunit. We sequenced the C-termini of the beta and -gamma subunits of the ENaC in a Japanese family with hypertension and hypopotassemia without excess minerarocorticoids, clinically diagnosed as Liddle's syndrome. The mutation of the ENaC of this family was beta R564X. Since such case seem to be rare in the literature, detailed data are shown in this report.

Lymphocyte infiltration in esophageal cancer, especially when beneath intraepithelial carcinoma, is frequently seen. However, cases of esophageal cancer with a dense stromal infiltration of lymphocytes are rare and the pathogenesis of such cases has yet to be clearly demonstrated. The objective of this study is to clarify its pathogenesis.Four cases of esophageal squamous cell carcinoma with lymphoid stroma were investigated by immunohistochemical staining for the detection of Epstein-Barr virus, human papillomavirus, human leukocyte antigen-DR, as well as T and B cells in cancer tissue.In these four cases, neither positive staining of Epstein-Barr virus nor human papillomavirus infection was detected. On the other hand, the expression of human leukocyte antigen-DR antigen was evident in all cases with dense T-cell infiltration in the tumor tissue and moderate B-cell infiltration around the tumor.The expression of human leukocyte antigen-DR antigen without Epstein-Barr virus or human papillomavirus infection could thus be one possible pathogenesis of patients demonstrating esophageal squamous cell carcinoma with a lymphoid stroma.

The antiemetic effects of serotonin receptor antagonists during chemoradiotherapy for solid tumors have never been reported. We have developed hyperthermo-chemo-radiotherapy (HCR) for esophageal cancer. However, with this treatment, the more potent the chemotherapy was, the more frequently emesis was experienced.Fifteen patients with esophageal cancer underwent HCR (6 courses of hyperthermia, cisplatin 20 mg/m2 x 6, 5-FU 300 mg/m2 x 15 and radiation 1.5 Gy x 30). Ramosetron was administered intravenously (0.3 mg x 15). The emesis inhibition rate was defined as the rate of patients having neither vomiting nor severe nausea.The incidence of patients without nausea gradually decreased to 60% at the end of chemotherapy. However, vomiting was completely avoided except in one patient for two days. The emesis inhibition rates of weeks 1, 2, 3 and 4 were 100.0, 93.3, 89.5 and 95.2%, respectively. The overall inhibition rate was 94.5% and the rate of "well inhibited" was 79.0%. There were no ramosetron-related adverse reactions.These findings suggest that ramosetron is a useful antiemetic agent for nausea and vomiting induced by chemoradiotherapy for solid tumors.

1. The therapeutic effects of an orally active inhibitor of Na(+)-glucose cotransporter (SGLT), T-1095 (a derivative of phlorizin; 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-(6-O-methoxycarbonyl-beta-D-glycopyranoside)) were examined in C57BL/KsJ-db/db (db/db) mice, a genetic animal model of obese type 2 diabetes. 2. The higher renal SGLT activity in db/db mice than normoglycaemic C57BL/KsJ-db/+m (db/+m) mice may support the rationale for using an SGLT inhibitor in the treatment regimen for type 2 diabetes. Both T-1095 and its metabolite, T-1095A, which had approximately 10 times more potency, effectively inhibited renal SGLT activity of these mice in vitro. 3. Single oral administration of T-1095 (10, 30, 100 mg kg(-1), p.o.) to db/db mice caused a dose-dependent reduction in blood glucose levels and a concomitant increase in glucose excretion into urine. In contrast, T-1095 only slightly affected blood glucose levels in db/+m mice. 4. Chronic administration of T-1095 (0.1% w w(-1) pellet chow, for 12 weeks) decreased blood glucose and haemoglobin A(1C) levels, and improved glucose intolerance in db/db mice. The age-related decrease in plasma insulin levels was markedly inhibited and there was a 2.5 fold increase of insulin content in the pancreas of T-1095-treated db/db mice. Food consumption was not changed, while impaired body weight gain was ameliorated by T-1095 treatment. 5. Both the development of albuminuria and the expansion of glomerular mesangial area in db/db mice were significantly suppressed by chronic T-1095 treatment, indicating the prevention of the progression of diabetic nephropathy. 6. These results demonstrate that the SGLT inhibitor T-1095 is able to improve the metabolic abnormalities and inhibit the development of diabetic complications in db/db mice. Thus, T-1095 can be used for therapy of type 2 diabetic patients.

In eukaryotic cells, the kinase activity of the mitosis-promoting complex composed of cyclin B and Cdc2 (Cdk1) is negatively regulated by the phosphorylation of Cdk1 on threonine or tyrosine residues within its ATP binding domain.We identified human Wee1B by searching a sequence database. The predicted human Wee1B protein comprises 561 amino acids. Northern blot analysis revealed that human Wee1B mRNA is particularly abundant in testis. Interestingly, RT-PCR using early embryos revealed that the Wee1B product was readily detectable at the mature oocyte, but abruptly disappeared at embryonic day 2.5, suggesting that the amount of Wee1B mRNA is dependent on the maternal expression. GFP-Wee1B showed a predominantly nuclear localization in HeLa cells. Human Wee1B was able to rescue the lethal phenotype of the fission yeast wee1-50Deltamik1 mutant, and over-expression of the human protein in these cells resulted in cell elongation as a result of arrest of the cell cycle at the G2-M transition. Recombinant Wee1B effectively phosphorylated cyclin B-associated Cdk1 on tyrosine-15, resulting in an inactivation of the kinase activity of Cdk1.We identified human Wee1B as a novel Cdk1-inhibitory kinase. The identification of this new member of the Wee1 family suggests that inhibition of Cdk1 is mediated at multiple levels in mammals.

In acute myeloid leukemia (AML), p53 mutations are reportedly infrequent but associated with a poor prognosis. The majority of mutations are missense mutations, which generally lead to accumulation of nuclear p53 protein. However, the prognostic significance of the accumulation remains unknown in AML. In this study, we compared the prognostic value of p53 mutations versus accumulation of the product. p53 mutations were found in 9 (4.5%) of 200 patients with de novo AML. The p53 mutation detectable (mutation+) group had a worse prognosis (p = 0.0009) than the mutation not detectable (mutation-) group. Multivariate analysis showed that the p53 mutation was an independent factor (p = 0.005) for short overall survival as well as 60 yr or older (p = 0.001) and unfavorable karyotypes (p = 0.001). In 79 of the 200 patients, the expression of p53 was studied by immunocytochemistry (ICC) using anti-p53 monoclonal antibody (DO-7). All samples carrying missense mutations (N = 6) were positive for ICC in over 15% of nuclei of each sample, chosen as the optimized cutoff value of p53 accumulation. Accumulation was thus found in 14 of the 79 patients. However, there was no prognostic difference according to the accumulation, because the mutation-/accumulation+ group (N = 8) tended to have a good prognosis. These findings indicate that molecular detection of p53 mutations yields better prognostic information than ICC. In a subset of AML, p53 protein might be accumulated without mutation presumably due to upstream signals of p53.

Acute promyelocytic leukaemia (APL) with t(11;17)/PLZF-RARalpha responds poorly to all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3), in contrast to APL with t(15;17)/PML-RARalpha. Molecular studies have shown that histone deacetylase (HDAC) recruited by PLZF-RARalpha is associated with the ATRA resistance. Here, we analysed in vitro the differentiation of APL cells with t(11;17) using ATRA, As203, granulocyte colony-stimulating factor (G-CSF), HDAC inhibitor trichostatin A (TSA), or combinations of these. Although 1 microM ATRA, which stimulated the differentiation of APL cells with t(15;17), was insufficient to induce differentiation, 3 microM ATRA induced terminal differentiation into granulocytes. As203 alone or in combination with ATRA induced neither differentiation nor apoptosis. However, the combination of TSA and 1 microM ATRA had a potent differentiating effect, although TSA alone had little effect. The combination of 1 microM ATRA and G-CSF did not induce differentiation. These results indicate that APL cells with t(11;17) need a higher concentration of ATRA than those with t(15;17) to differentiate and suggest that HDAC inhibitor is a promising differentiation enhancer in APL with t(11;17).

The prediction of an effective adjuvant therapy is essential in order to increase the number of esophageal cancer cases demonstrating an excellent response. Correlation of the immunohistochemical expression of p53 protein and Ki-67 antigen were studied using biopsied specimens of advanced esophageal cancer. The combined staining status of both can help predict the efficacy of neoadjuvant therapy in patients with esophageal cancer.The overexpression of p53 protein and the Ki-67 labeling percentage were immunohistochemically investigated in 95 biopsied specimens of advanced esophageal carcinoma resected between 1988 and 1996. All patients preoperatively received 1 course of either chemoradiotherapy or hyperthermo-chemoradiotherapy.Thirty-nine specimens were positive for p53 protein staining (41.1%), and the treatment modalities were histopathologically effective in 71.8% of these 39 patients (28/39), while the efficiency rate was 58.9% (33/56) in patients with p53(-). On the other hand, the efficiency rate of patients with a high Ki-67 labeling percentage (or = 30%) was 73.9%, which was significantly higher than that of those with a low Ki-67 labeling percentage (30%) (38.5%, P = 0.0013). The efficacy rate of the patients with both a high Ki-67 labeling percentage and p53(+) was 80%, while that of the patients with a low Ki-67 labeling percentage and p53(-) was only 35.3% (P = 0.0098). The combination of a high Ki-67 labeling percentage and p53(-) particularly showed a high sensitivity to hyperthermo-chemoradiotherapy since the efficiency rate of these patients with hyperthermo-chemoradiotherapy was 81.5%, while the rate for those with chemoradiotherapy was 41.7% (P = 0.0129).An immunohistochemical analysis of p53 and the Ki-67 labeling percentage using biopsied specimens was thus found to effectively predict the efficacy of neoadjuvant therapies in patients with esophageal cancer.

We evaluated efficacy and safety of monotherapy with CZOP (1-2 g x 2/day) and combination therapy with CZOP (1-2 g x 2/day) and AMK (200 mg x 2/day) for infections in patients with hematological diseases. Efficacy was evaluated in 71 patients of monotherapy group and 70 patients of combination therapy group. Underlying diseases were mostly leukemia and lymphoma. Infections included sepsis, suspected sepsis, pneumonia and so on. Efficacy in CZOP monotherapy was excellent in 21 patients (31.3%), good in 23 patients (34.3%), fair in 5 patients (7.5%) and the efficacy rate was 65.7%. On the other hand, in combination therapy, each was 14 patients (21.2%), 23 patients (34.8%), 12 patients (18.2%) and the efficacy rate was 56.1%. Side effects such as eruption were noted in 2 patients. Abnormal laboratory findings were noted in 9 patients. All side effects as well as abnormal laboratory findings were minimal. It was concluded that CZOP monotherapy was effective in the treatment of various infections accompanying hematological diseases.

The purpose of this study was to analyze the transition of body mass index (BMI) by birth cohort and to determine the relationship between BMI and high blood pressure, for the health management of workers in an industry.The eligible study subjects were 3,043 male workers at printing and papermaking plants who were 20 to 49 years of age in 1986 and whose annual health checkup information was available for both 1991 and 1996. First, we analyzed the transition of BMI by 5-year birth cohort. Second, we analyzed the relationship between BMI and high blood pressure (systolic blood pressure= 140 mmHg or diastolic blood pressure= 90 mmHg) using multiple logistic regression models. In this analysis, we excluded 596 subjects who were diagnosed as having high blood pressure in 1986 and 17 subjects whose alcohol drinking habits were unknown. Consequently, we had 2,430 study subjects.(1) All the birth cohorts showed that the proportion of obese subjects (BMI= 26.4) became higher as age advanced. The proportion was higher for younger cohort. (2) By multiple logistic regression models, age at the beginning of the study, BMI, change of BMI in 5 or 10 years, and alcohol drinking habits were related to the risk of having high blood pressure.In the health management of workers, it is necessary to evaluate the risk by birth cohort. Also, we consider that we need to initiate obesity counseling before the workers become 30 years of age.

The patient, a 60-year-old man, was diagnosed as having a protruding lesion in the upper thoracic esophagus on a routine endoscopic examination. Endoscopy showed a polyp with a pedicle in the upper esophagus. A biopsy indicated the presence of hemangioma. Since endoscopic ultrasonography showed the tumor to be located within the mucosa and submucosa, we chose an endoscopic resection as the most appropriate treatment for the esophageal hemangioma. After endoscopic resection, the patient has remained free of any symptoms or recurrence. Although an esophageal hemangioma is a benign tumor, a risk of severe hemorrhaging does exist. We conclude that the first choice of the treatment for esophageal hemangioma should thus be an endoscopic resection if the tumor is located within the mucosal or submucosal layer. However, if it is impossible to resect endoscopically, then either endoscopic injection sclerotherapy (EIS) or a surgical resection should be considered.

The mechanism for the effect of cisplatin (CDDP) as a modulator for 5-fluorouracil (5-FU) has already been described. The effective AUC of serum 5-FU concentration with oral administration of tegafur and uracil (UFT) has been revealed. We administered a dose of 200-600 mg/body of UFT orally every day, and 3.5-10 mg/m2 of CDDP by drip infusion 5 days a week. Hospitalized patients were administered these agents for 2-5 weeks. Eleven patients were enrolled, including 4 with untreated pharyngeal squamous cell carcinoma (SCC), 5 with locoregional recurrent SCC, and 2 with pulmonary multiple metastases. The mean age of the patients was 71 years, and all patients had a PS 3. Of the 4 patients with untreated pharyngeal SCC, PR was noted in 3 and NC in one, for a response rate of 75%. Of the 11 patients with locoregional recurrent and pulmonary metastatic SCC, PR was noted in only one patient for a response rate of 14%. Although on average these patients died of the primary disease 150 days after chemotherapy, 4 patients later showed an improved PS stage, and could were able to leave the hospital. These 4 patients could stay home with a PS 0 or PS 1 for an average of 133 days, and survived with the disease for an average of 240 days after chemotherapy. No side effects were observed in any patients. In side of the low response rate for locoregional recurrent and pulmonary metastatic SCC, the present therapy was thought to be useful from the viewpoint of the quality of life.

Twenty-five cases with unresectable metastatic liver cancers were experienced in our hospital over the past five years who underwent weekly 24-hour continuous hepatic arterial infusion chemotherapy using 5-FU and CBDCA. The response rate was 20%, the median survival was 23 months, and the one/two year overall survival rates averaged 81.3/45.5%. In 77% of patients, this therapy prevented death from hepatic metastases. Moreover, since adverse effects were limited compared with bolus infusion, weekly 24-hour continuous hepatic arterial infusion chemotherapy was thought to be a favorable method.

Adrenomedullin (AM), a novel vasodilator peptide, is produced by C-terminal amidation reaction of AM-glycine. AM-glycine, an intermediate form of AM (iAM), is processed from pro AM. AM circulating in the human blood stream was found to consist of an amidated mature form (mAM) and iAM. Biological activity is exerted only by mAM.To investigate the pathophysiological role of mAM in renal disease, we measured plasma concentrations of mAM as well as total AM (tAM), representing both mAM and iAM, in patients with various renal diseases. In addition, plasma ANP level was measured in all patients.The concentrations of plasma mAM in renal failure with dialysis (2.1 +/- 0.2 fmol/ml, mean +/- SEM) and without dialysis (1.2 +/- 0.2) were significantly (p0.05) higher than those in control group (0.5 +/- 0.1). However, the plasma ANP level was increased only in renal failure patients with dialysis. Plasma mAM levels were significantly correlated positively with serum creatinine levels and negatively with hematocrit. No significant difference was noted in the ratio of mAM/tAM between renal failure patients and healthy subjects.These results suggest that plasma mAM is increased in renal failure in relation to deterioration of renal function, while the amidation process of AM seems to be unaffected in patients with renal failure.

Objective and Design: To study the effect of cellular cAMP-increasing agents on Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS)-induced mouse hepatitis.¶Material: Male BALB/c mice were used. Macrophages/Kupffer cells isolated from P. acnes-primed murine liver were used for the in vitro study.¶Treatment: Type IV phosphodiesterase (PDE)-specific inhibitor, rolipram, was administered (10, 30 mg/kg, p.o.). Dibutyryl cyclic AMP (dbcAMP) was injected (10, 100 mg/kg, i.p.) into the mice.¶Method: Plasma TNFα estimated by the use of an L-929 cell cytotoxic assay and plasma transaminase activities were measured for the in vivo study. The LPS-induced production of TNFα in vitro from the cultured macrophage/Kupffer cells was determined by ELISA.¶Results: Rolipram suppressed the elevation of plasma transaminases induced by injection of LPS, and dbcAMP had a tendency to suppress them. Both agents attenuated the LPS-induced release of TNFα in vivo, and suppressed the TNFα production from the cultured macrophage/Kupffer cells.¶Conclusions: These results suggest that rolipram and dbcAMP have potential to inhibit TNFa production from activated macrophage/Kupffer cells, and it may be partially involved in the protecting effect in the P. acnes/LPS hepatitis model.

The aim of this study is to evaluate whether super-elderly patients (or = 80) with gastric cancer may be appropriate candidates for an R2/R3 (extended) gastrectomy.The study evaluated 1334 patients with gastric cancer treated over the past 15 years, who were over 40 years of age. They were divided into three groups according to age: Super-elderly patients who were over 80 (group A; n=60), those aged 60-79 (group B; n=703) and those aged 40-59 (group C; n=571).The incidence of concomitant systemic disorders was higher in group A than in either group B or group C (65% vs. 53.2% vs. 34%) (p0.0001). The resection rates were similar (88.3% vs. 93.7% vs. 96.1%), however, the incidence of a total gastrectomy, an R2/R3 dissection, or a combined resection of other organs was much lower in group A than those in the other groups (p0.005). The survival curves of patients after a curative resection were not significant, however, 34.4% of the super-elderly patients died of other causes and the 5-year survival rates including other cause of death were poorer in groups A and B than those in group C (p0.01). In group A, patients receiving an R2/R3 dissection had a two-fold higher incidence of post-operative complications over those receiving an R0/R1 (regional) dissection, however, they also had a better prognosis whether or not other causes of death were considered.We, therefore, conclude that an R2/R3 gastrectomy is basically appropriate for super-elderly patients, as long as they demonstrate a good risk. However, the short-term results should also be considered.

This study surveyed the sexual behaviour of commercial sex workers and their clients in an attempt to identify factors of transmission of STDs (including HIV/AIDS) and to control their epidemics in Cambodia and South-East Asia.Cross-sectional study.Trained questioners asked items of the questionnaires to each objective subject in December 1996. Data were analysed to show the descriptive status by risk group of each person.200 direct commercial sex workers, 220 indirect commercial sex workers, and 211 clients in Phnom Penh.Prostitution was widely accepted by both young males and females, and this was an easy way for young girls to obtain money. Although commercial sex workers and clients were knowledgeable about prevention methods against STDs, they seldom used condoms. Some commercial sex workers had been infected with STDs many times, and many of them incompletely treated the diseases by themselves. Social support from governmental and non-governmental organisation was poor.It is very important to support both commercial sex workers in practicing preventive methods against STDs and also visiting physicians when they notice symptoms of STDs. It is strongly recommended that not only governmental but also non-governmental organisations should be more active in this area.

A 32-year-old man with hemiconvulsions, hemiplegia, epilepsy (HHE) syndrome is described. He was well developed with a normal pregnancy and delivery, but at age 10 months, he had status epilepticus during a febrile illness. Thereafter, he was noted to have left hemiparesis and mental retardation with recurrent hemiconvulsions. Magnetic resonance (MR) images showed atrophy and degeneration of the right cerebral cortex and white matter, homolateral thalamus, caudate nucleus, and hippocampus, with hyperintensities in both T2-weighted (TR/2200, TE/90) and proton (TR/2200, TE/30) images. There were also slight bilateral cerebellar atrophies. Quantitative single photon emission computed tomographic (SPECT) images using technetium-99m-ethyl cysteinate dimer (99mTc-ECD) revealed markedly reduced cerebral blood flow (CBF) in the right cerebral hemisphere, homolateral thalamus, caudate nucleus and bilateral cerebellum. Bilateral putamen and the medial occipital lobe showed normal findings on MR images and normal regional CBF in SPECT images. We suppose these selective neuronal injures in this case of HHE syndrome will be mainly due to histotoxic factors in epileptic brain damage.

We report on a 31-year-old man with a mediastinal neurilemmoma originating in the right phrenic nerve. The patient was admitted because of abnormal chest X-ray shadows observed during a routine checkup. A preoperative diagnosis of bronchial cyst in the mediastinum was made. The tumor was resected by video-assisted thoracic surgery. It was 3 x 4 x 3 cm in size, weighted 15 g, and originated in the right phrenic nerve. The histopathologic diagnosis was mediastinal neurilemmoma. Only 14 cases have been reported in the Japanese literature.

The patient was a 60-year-old man with progressive neck recurrence of laryngeal squamous cell carcinoma. As a previous treatment, he had undergone irradiation (primary: 60 Gy; neck: 45 Gy) after two cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 daily; day 1:5-fluorouracil 1,000 mg/m2 daily; day 1-5) and planned neck dissection. For a neck recurrence, he had received five cycles of low-dose cisplatin (5 mg/body daily: day 1-5) with tegafur and uracil (600 mg/body daily: day 1-7) every week. As an outpatient, he then received ten cycles of low-dose cisplatin (10 mg/body daily: day 3, 6) with tegafur and uracil (600 mg/body daily: day 1-7) every week. The size of the tumor did not decrease with the above chemotherapy, but no remarkable growth of the cancer was seen, and no toxic effect of the chemotherapy was observed. He continued his job for 30 weeks just as before he had fallen sick. Chemotherapy of low-dose cisplatin with tegafur and uracil was suggested to be useful for the patient with recurrent laryngeal squamous cell carcinoma.

Pharmacokinetics, efficacy and safety of tazobactam/piperacillin (TAZ/PIPC), a new beta-lactamase inhibitor combined with a penicillin antibiotic, were studied in pediatrics and the following results were obtained. 1) Serum concentration and urinary excretion of TAZ/PIPC after intravenous administration at a dose of 46 mg/kg to one child were investigated. Serum half-lives were 0.5 hours for TAZ and 0.6 hours for PIPC, while the urinary recovery rates in the first 6 hours after administration, were 61.6% and 56.3% respectively. 2) TAZ/PIPC was administered at a dose of 46.0-73.5 mg/kg t.i.d. for 3-13 days to 10 patients, 6 with respiratory infection, 1 with pharyngotonsillitis, 1 with pertussis and 2 with soft tissue infection of skin. Clinical response were excellent in 5 cases and good in 5 cases, and the efficacy rate was 100%. Bacteriologically, 2 strains (Staphylococcus aureus and Streptococcus pyogenes) isolated from 2 patients were eradicated after the treatment. As for adverse reaction, mild skin rash was observed in 1 case but disappeared within 2 days after withdrawal of the drug. As for abnormal laboratory test results decrease in neutrophiles and increase in eosinophiles in each 1 case were observed, which were, however, normalized after administration. From the above results, tazobactam/piperacillin was considered to be a useful antibiotic in the pediatric field.