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Solitary fibrous tumour (SFT) is a rare mesenchymal tumour with intermediate malignant potential. Although this tumour arises in several sites, prostatic SFT is an extremely rare neoplasm and may prove confusing owing to the lack of clinical experience because of tumour rarity. The diagnosis may be further difficult because SFTs can manifest positive immunoreactivity for CD34 and progesterone receptor, which are known markers of prostatic stromal tumours. Herein, we describe a case of prostatic SFT that was difficult to differentiate from a prostatic stromal tumour of uncertain malignant potential because of positive immunoreactivity to CD34 and progesterone receptor.A 40-year-old Japanese man presented with lower abdominal pain. Computed tomography revealed a prostatic mass; furthermore, prostate core needle biopsy revealed proliferating bland spindle cells, without necrosis or prominent mitoses. Tumour cells were positive for CD34 and progesterone receptor on immunohistochemical analysis; thus, a prostatic stromal tumour of uncertain malignant potential was initially suspected. However, as the tumour cells showed positive immunoreactivity for STAT6, the final diagnosis was an SFT of the prostate. The patient underwent tumour resection, and at the 6-month postoperative follow-up, neither local recurrence nor distant metastasis occurred.For an accurate diagnosis of an SFT of the prostate, STAT6 immunohistochemistry should be conducted for all mesenchymal tumours of the prostate. When STAT6 immunohistochemical analysis is unfeasible, pathologists should be aware that the morphological and immunohistochemical characteristics of SFT variable from case to case and diagnose with combined analysis of several immunohistochemical markers.

In Japan, inguinal hernia repair is widely performed with local anesthesia. The objective of this study was to evaluate safety and efficacy of intravenous dexmedetomidine as a sedation agent with local anesthesia in inguinal hernia repair. We performed this randomized, single-blind study for 200 patients who were scheduled to undergo inguinal hernia repair with local anesthesia. Patients were randomly divided into two groups (dexmedetomidine group: Group D, midazolam group: Group M). The primary outcome was to evaluate the safety of intravenous dexmedetomidine. Secondary outcomes were to analyze results of operators’ surveys and patients’ questionnaires and evaluate implementation of conscious sedation. Incidence of respiratory depression was significantly higher in Group M than Group D (p = 0.03). Other adverse events examined did not differ significantly. All three operators’ questionnaires indicated that results were better in Group D than Group M. More than 70% of patients in both groups were satisfied with the surgery. More than 80% of Group D patients and 74% of Group M patients achieved a state of conscious sedation. This study demonstrated that intravenous dexmedetomidine during hernia repair with local anesthesia is safe and the results were satisfactory to both operators and patients.

Aims The EURO-ENDO registry aimed to study the management and outcomes of patients with infective endocarditis (IE). Methods and results Prospective cohort of 3116 adult patients (2470 from Europe, 646 from non-ESC countries), admitted to 156 hospitals in 40 countries between January 2016 and March 2018 with a diagnosis of IE based on ESC 2015 diagnostic criteria. Clinical, biological, microbiological, and imaging [echocardiography, computed tomography (CT) scan, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)] data were collected. Infective endocarditis was native (NVE) in 1764 (56.6%) patients, prosthetic (PVIE) in 939 (30.1%), and device-related (CDRIE) in 308 (9.9%). Infective endocarditis was community-acquired in 2046 (65.66%) patients. Microorganisms involved were staphylococci in 1085 (44.1%) patients, oral streptococci in 304 (12.3%), enterococci in 390 (15.8%), and Streptococcus gallolyticus in 162 (6.6%). 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in 518 (16.6%) patients and presented with cardiac uptake (major criterion) in 222 (42.9%) patients, with a better sensitivity in PVIE (66.8%) than in NVE (28.0%) and CDRIE (16.3%). Embolic events occurred in 20.6% of patients, and were significantly associated with tricuspid or pulmonary IE, presence of a vegetation and Staphylococcus aureus IE. According to ESC guidelines, cardiac surgery was indicated in 2160 (69.3%) patients, but finally performed in only 1596 (73.9%) of them. In-hospital death occurred in 532 (17.1%) patients and was more frequent in PVIE. Independent predictors of mortality were Charlson index, creatinine > 2 mg/dL, congestive heart failure, vegetation length > 10 mm, cerebral complications, abscess, and failure to undertake surgery when indicated. Conclusion Infective endocarditis is still a life-threatening disease with frequent lethal outcome despite profound changes in its clinical, microbiological, imaging, and therapeutic profiles.

BACKGROUND AND PURPOSE Diphenylarsinic acid (DPAA) intoxication caused by drinking contaminated well water was found in Kamisu, Japan. The symptoms indicated cerebellar-brainstem and temporo-occipital involvement. However, it remains unclear how it affects the human brain. To elucidate the effect of DPAA on the human brain, we analyzed cerebral blood flow (CBF) data after the drinking of DPAA-contaminated water was stopped and investigated the correlation between DPAA exposure level and CBF by single-photon emission computed tomography (CBF-SPECT). METHODS The DPAA-exposed inhabitants (n = 78) were divided into 35 symptomatic and 43 asymptomatic subjects and compared with 38 healthy controls. The DPAA concentration in nails or hair and well water was measured using a high-performance liquid chromatography system and coupled plasma mass spectrometry after adequate extraction treatment. CBF-SPECT data, obtained within 1 year after the drinking of contaminated well water was stopped, were analyzed by statistical parametric mapping. We also examined the relationship between variations in CBF-SPECT signals and variations in DPAA concentrations in the hair or nails of the subjects. RESULTS Compared with control subjects, CBF in symptomatic DPAA-exposed subjects was significantly lower in the occipital lobe, including the cuneus and inferior occipital gyri. The DPAA concentration in the nails or hair of subjects was inversely and significantly related to their CBF. CONCLUSION These data suggest that CBF-SPECT may be useful as a clinical marker to infer the effect of accumulated DPAA on the brain.

Background The peroneal tubercle is a small bony ridge located on the lateral wall on the calcaneus immediately inferior to the lateral malleolus and separates the peroneus brevis and peroneus longus tendons. The size and configuration of the peroneal tubercle has been implicated in the pathogenesis of peroneal tendon tears and tenosynovitis and is the increasing object of clinical interest. However, the morphology of the tubercle is difficult to assess with precision. Methods We utilized a new method to evaluate the three-dimensional (3D) geometry of 46 calcanei from 34 consecutive patients; average patient age was 48.0 years who underwent lower extremity computed tomography (CT) for clinical treatment of non-peroneal tubercle-related conditions. The 3D geometries of calcanei were reconstructed by using the computer software to calculate the surface 3D models. To measure the size of the peroneal tubercle, we virtually excised it from the 3D calcaneus model and made a precise measurement of the height. Results Peroneal tubercles with measured heights of 1mm or more were detected in 65% of the feet, with an average tubercle height of 2.59mm. Peroneal tubercles were larger and more frequent in middle-aged or older than younger patients.

Summary. We report the second case of neonatal alloimmune thrombocytopenia due to anti-human platelet antigen (HPA)-3b (Bakb) antibody. The infant was severely affected with intracranial haemorrhage. Most importantly, we were able to detect this antibody only by using fresh, unfixed platelets as antigen. This antibody was detectable neither by conventional mixed passive haemagglutination, platelet immunofluorescence test using fixed platelets, nor by monoclonal antigen immobilization of platelet antigen assay using solubilized platelets. We assume that this antibody reacts only with fresh platelets and that the antigen is a labile component of HPA-3b (Bakb).

Objective: To examine the expression and localisation of adrenomedullin in human coronary atherosclerotic lesions from patients with unstable angina (UAP) and stable angina (SAP), and to study the relation between adrenomedullin expression and plaque instability. Design: A retrospective observational study. Patients: Directional coronary atherectomy samples were obtained from 15 patients with UAP and 12 with SAP. Methods: The localisation of adrenomedullin was examined by immunohistochemistry, and adreno-medullin mRNA expression was measured by quantitative polymerase chain reaction. Results: Adrenomedullin immunoreactivity was preferentially localised in macrophages, intimal smooth muscle cells, and proliferated microvessels. The mean number of adrenomedullin positive cells in five high power fields (× 400) per specimen was higher in patients with UAP than in those with SAP (mean (SEM), 110 (13) v 76 (7); p < 0.05); and the ratio of adrenomedullin positive to total cells was higher in patients with UAP (43.0 (2.2)% v 34.2 (2.0)%; p < 0.01). More adrenomedullin mRNA was expressed in the plaque of patients with UAP than in those with SAP (60.4 (16.9)% v 9.7 (3.3)%; p < 0.01). Conclusions: The findings suggest that adrenomedullin is involved in the development of atherosclerosis and plaque instability in human coronary arteries, in an autocrine or paracrine manner.

There have been no reports that low serum cholesterol levels increase the risk of colorectal adenoma, although many studies have shown that they do increase the risk of colorectal cancer. Alcohol intake, which is associated with a risk of colorectal adenomas, and serum cholesterol levels are closely related. The purpose of this study was to evaluate the influence of alcohol consumption on the association between serum cholesterol levels and colorectal adenoma.The subjects were 1,349 male patients who underwent both barium enema examination and total colonoscopy. They answered a questionnaire regarding their alcohol consumption history, and their blood samples were analysed. The subjects were divided into three groups: those with no tumour (with neither adenoma nor adenocarcinoma), those with adenoma and those with adenocarcinoma. Among the groups, the serum total cholesterol and triglyceride levels were compared in all the patients, in the patients who did not drink daily and in the patients who did.In all the patients, the serum cholesterol and triglyceride levels did not differ between the patients with and those without adenoma. In the daily drinkers, the serum cholesterol and triglyceride levels were significantly lower in patients with adenoma than in those without.Significantly lower levels of serum cholesterol and triglycerides were found in daily drinkers with adenoma than in those without.

Because HTLV-I, HTLV-2, and HIV share identical modes of transmission, simultaneous or subsequent infections with these retroviruses are to be expected. The population of Santos, the largest port in Latin America, includes large numbers of female commercial sex workers and intravenous drug users, presumably having been exposed to retroviral infection. To evaluate the seroprevalence of HTLV infection and their associated risk factors, a cross-sectional survey was carried out in 499 HIV-infected individuals from Santos, Brazil. HTLV testing consisted of enzyme immunoassays for serologic screening and confirmatory Western blot testing. Overall HTLV-I and HTLV-2 seroprevalences were 6.0% (95% confidence interval [CI], 3.9-8.1) and 7.4% (95% CI, 5.1-9.7), respectively. Multivariate logistic regression for statistical analysis revealed HTLV-I infection to be independently associated with: intravenous drug use (IDU) (odds ratio [OR]. 2.99; 95% CI, 1.09-8.20), seropositivity to hepatitis C virus (HCV) (OR, 3.03; 95% CI, 1.02-9.01) and < 3 years of education (OR, 4.73; 95% CI, 1.56-14.41). HTLV-2 infection was associated with: IDU (OR, 3.22; 95% CI, 1.33-7.84), HCV seropositivity (OR, 5.40; 95% CI, 1.86-15.66) and nonwhite race (OR, 3.32; 95% CI, 1.58-7.00). Results indicate that HIV-infected individuals living in Santos are at similarly high risk of being exposed to HTLV- 1 and HTLV-2. IDU constitutes the main risk factor for HTLV acquisition in this population, and there is no significant risk associated with sexual practice.

Objective: Expression of CINCs was regulated differentially in lipopolysaccharide-stimulated rat macrophages. We examined whether the expression of CINCs in lipopolysaccharide-stimulated rat macrophages is similarly inhibited by anti-inflammatory drugs.¶Materials and Methods: Rat peritoneal macrophages were stimulated by lipopolysaccharide in the presence of anti-inflammatory steroids (dexamethasone, prednisolone and hydrocortisone) or non-steroidal anti-inflammatory drugs (indomethacin and piroxicam). The production and mRNA expression of three types of CINCs were measured using enzyme-linked immunosorbent assay and northern hybridization.¶Results: Anti-inflammatory steroids; dexamethasone, prednisolone and hydrocortisone, dose-dependently inhibited the production of CINC-1, -2 and -3, whose inhibitory patterns were similar to each other. Furthermore mRNA expression of each CINC was inhibited by dexamethasone in a dose-dependent manner. In contrast, non-steroidal anti-inflammatory drugs, indomethacin and piroxicam were without effect. Expression of each CINC was regulated differently; the production of CINC-1 reached a maximum at 12 h and then slightly decreased after lipopolysaccharide stimulation, whereas that of CINC-2 and CINC-3 increased up to 24 h. Dexamethasone inhibited the CINCs production and mRNA expression at 9 h after lipopolysaccharide stimulation.¶Conclusions: These results indicate no difference among CINC-1, -2 and -3 in the inhibition of production and mRNA expression of CINCs by anti-inflammatory steroids, although lipopolysaccharide differentially induces expression of each CINC expression in culture of rat macrophages.

Rabbits develop a toxic reaction similar to endotoxemia following inoculation with a Sarcocystis cruzi cyst extract. To analyze the pathophysiology of the reaction, serum tumor necrosis factor alpha (TNFalpha), nitric oxide (NO) and lipid-lipoprotein profiles were investigated in rabbits given the cyst extract and lipopolysaccharide (LPS) by subcutaneous inoculation. In animals given the cyst extract, overproduction of TNFalpha was detected, together with an increase in NO. The animals developed derangement of lipid metabolism, which was considered to have resulted from TNFalpha induction, consisting of elevated triglyceride and very low density lipoprotein levels and decreased high density lipoprotein (HDL) levels. Serum interleukin-6-like activity also increased transiently in the animals. Capability of the cyst extract to induce TNFalpha, NO and the lipid profile derangement were completely lost by boiling. In animals given LPS, TNFalpha was induced and HDL decreased moderately, without inactivation of those activities of LPS by boiling. These results indicated that S. cruzi cyst extract is a potent, but thermolabile inducer of TNFalpha and NO for rabbits. It is likely that TNFalpha and NO play important roles as mediators in the reaction associated with toxicity of the cyst extract in rabbits.

The objective of this study was to investigate the thyroid cancer incidence in a whole territory of Ukraine and to clear up its age and gender patterns depending on average regional (oblast) thyroid doses from radioactive iodine due to the Chornobyl accident. MATERIALS AND METHODS. On the basis of average accumulated thyroid doses from radioactive iodine the geographical regions of Ukraine with low and high average thyroid doses were identified for a comparative analysis performance. Methods of descriptive epidemiology were used.The level and dynamics of thyroid cancer incidence were analyzed in different gender and age groups (both for attained age and age at the moment of the Chornobyl accident). Results of this study confirmed the radiation excess of thyroid cancer in individuals who were children and adolescents in 1986. Some excess was observed in elder age groups too. Especial situation was observed in female age group 40-49 at the moment of the Chornobyl accident i.e. the age-specific thyroid cancer incidence rates were significantly higher in "high exposure" regions comparing with "low exposure" ones during all years of observation within 1989-2009.A probable radiation excess of thyroid cancer was suggested not only in children and adolescents but also in adult age groups. In elder age groups this excess was less expressed and manifested after a longer period of time. The origin of the phenomenon in female age group of 40-49 is unclear now. Hypothesis of combined effect of radiation and natural changing of hormonal status in this age should be checked in the future studies.Metoju c'ogo doslidzhennja bulo vyvchyty zahvorjuvanist' na rak shhytopodibnoi' zalozy na vsij terytorii' Ukrai'ny ta vyjavyty statevi ta vikovi osoblyvosti zalezhno vid seredn'ooblasnyh doz na shhytopodibnu zalozu vid radioaktyvnogo jodu vnaslidok avarii' na ChAES. Materialy ta metody. Na osnovi serednih nakopychenyh shhytopodibnoju zalozoju doz oprominennja radioaktyvnym jodom geografichni regiony Ukrai'ny dlja provedennja porivnjal'nogo analizu bulo podileno na dvi grupy - z „vysokymy” ta „nyz'kymy” dozamy. V doslidzhenni vykorystovuvalys' metody deskryptyvnoi' epidemiologii'. Rezul'taty. Proanalizovano riven' ta dynamiku zahvorjuvanosti na rak shhytopodibnoi' zalozy v riznyh statevo-vikovyh grupah (vidnosno jak viku na moment diagnozu, tak i pid chas avarii' na ChAES). Pidtverdzheno radiacijnyj eksces u osib, jaki buly dit'my ta pidlitkamy na moment avarii'. Pevnyj eksces sposterigavsja i v starishyh vikovyh grupah. Osoblyva sytuacija mala misce u zhinok vikom 40–49 rokiv na moment avarii', sered jakyh povikovi pokaznyky zahvorjuvanosti na terytorijah z „vysokymy” dozamy buly dostovirno vyshhymy uprodovzh vs'ogo periodu sposterezhennja 1989–2009 rr. Vysnovky. Okrim dytjachyh ta pidlitkovyh grup, rezul'taty doslidzhennja svidchat' pro virogidnyj radiacijnyj eksces u doroslyh. U starishyh vikovyh grupah cej eksces mensh vyrazhenyj ta projavljajet'sja pislja bil'sh tryvalogo chasu. Pohodzhennja zgadanogo fenomenu u zhinok vikom 40–49 rokiv na moment avarii' poky shho zalyshajet'sja nejasnym. U podal'shyh doslidzhennjah slid pereviryty gipotezu kombinovanogo vplyvu radiacii' ta pryrodnyh zmin gormonal'nogo stanu u c'omu vici.

To characterize the global composition of oral fungal populations in frail elderly adults and to investigate the relationship with their health status.We investigated the fungal populations on the tongue dorsum in 291 institutionalized elderly adults by molecular PCR-based techniques using internal transcribed spacer regions of nuclear ribosomal DNA.Quantitative PCR analysis showed that fungi were present on the tongue dorsum of 128 subjects at ≥10(4) CFU per sample, and 35 of them exceeded 10(5) CFU per sample. Length heterogeneity-PCR analysis and nucleotide sequence determinations showed that Candida albicans was most frequently detected in those subjects with fungi at ≥10(4) CFU per sample (105 subjects), followed by Candida dubliniensis (78), Malassezia restricta (57), and Candida tropicalis (45). Statistical analysis revealed that those subjects with ≥10(5) CFU of fungi other than C. albicans per sample had an increased risk of fever (≥7 febrile days per 12 months) compared with subjects with10(5) CFU per sample, after adjustment for other fever-associated confounding factors.These data demonstrate that the oral cavity of the elderly is inhabited by a diverse array of fungi not limited to typical Candida species and they suggest that the diversity in distribution is associated with health status.

Ad4BP, a zinc finger DNA-binding protein, was identified as a transcription factor regulating steroidogenic P-450 genes in a cAMP-dependent manner. Immunochemical and immunohistochemical studies with steroidogenic tissues, adrenal, ovary, and testis, were performed using the antiserum to Ad4BP. Ad4BP was expressed to the same extent in the three zones of the adrenal cortex. Immunohistochemical examination of ovarian follicle and corpus luteum showed the expression of Ad4BP. The granulosa and thecal cells, the two distinct types of the steroidogenic cells in the follicle, gave Ad4BP signals, which were stronger than in the latter cells than in the former. Immunoblot analyses of mature and regressed corpora lutea indicated a parallel expression of Ad4BP and side-chain cleavage P-450, and both proteins significantly decreased in the regressed tissues. Leydig cells surrounding seminiferous tubules gave clear immunostaining signals for Ad4BP. ELP, a mammalian counterpart of Drosophila FTZ-F1 detected in EC cells, and are isoforms transcribed from the same gene. The Ad4BP and ELP forms recognize same nucleotide sequences. Reverse transcriptase-polymerase chain reaction with specific primers for ELP revealed that steroidogenic tissues contained ELP as well as Ad4BP. The effects of the two proteins on the transcription of the CYP11B gene were compared using the expression vectors of Ad4BP and ELP. ELP did not activate transcription and showed a weak inhibitor effect on the Ad4BP-dependent transactivation of the CYP11B gene promoter when transfected simultaneously. A gel shift analysis using in vitro synthesized Ad4BP and ELP revealed that the binding activity of ELP is significantly weaker than that of Ad4BP.

Parathyroid hormone-related peptide (PTHrP) was originally characterized as a tumor product responsible for hypercalcemia of malignancy and was subsequently found to be produced in many normal tissues. PTHrP is now suggested to play a critical role in the local modulation of vascular smooth muscle function. To elucidate the involvement of PTHrP in coronary atherosclerosis, we immunohistochemically examined coronary arteries obtained from 76 patients with various grades of atherosclerosis and compared the correlation between PTHrP staining and the percent stenosis. Smooth muscle cells at sites of coronary atherosclerosis overexpressed PTHrP, while cells from normal coronary arteries did not. The in situ hybridization using PTHrP riboprobe has also proven the overexpression of PTHrPmRNA in the affected lesions following atherectomy. The intensity of PTHrP expression by smooth muscle cells was significantly correlated with the degree of coronary artery stenosis. Coronary arterial PTHrP overexpression is closely related to the severity and/or progression of coronary atherosclerosis.

Summary. The association between viral level and the long-term outcomes of hepatitis B virus (HBV) carriers who test negative for hepatitis B virus e antigen (HBeAg) but have persistently normal serum alanine aminotransferase levels (PNALT) remains unclear. We examined hepatocarcinogenesis, hepatitis reactivation, predictive factors and the time course of HBV DNA levels during follow-up in 104 HBeAg-negative Japanese carriers with PNALT. During a mean follow-up period of 6.4 ± 3.4 years, 5 patients (4.8%) had hepatocarcinogenesis and 14 (13.5%) had hepatitis reactivation. At 5 and 10 years, the cumulative rates of hepatocarcinogenesis were 2.4% and 9.9%, while those of hepatitis activation were 13.7% and 15.5%, respectively. An HBV DNA level of ≥5 log10 copies/mL was the sole predictor of hepatocarcinogenesis with a univariate analysis. An HBV DNA level of ≥5 log10 copies/mL and an alanine aminotransferase (ALT) level of >20 to ≤40 IU/L were independent predictors of hepatitis reactivation in a Cox model. Because there was no association between hepatocarcinogenesis and ALT activity, the HBV DNA level was considered an essential predictor. In addition, the baseline HBV DNA level was related to the future level and was not subject to wide fluctuations. Our results showed that an HBV DNA level of ≥5 log10 copies/mL predicts subsequent hepatocarcinogenesis and hepatitis reactivation in HBeAg-negative carriers with PNALT. As the baseline HBV DNA level reflects the future level, appropriate clinical management according to the viral level is expected to decrease future risk.

We tested the effect of etodolac on the development of type-II collagen-induced arthritis in DBA/1J mice. It was administered orally once daily for 35 days after the primary immunization with type-II collagen. Etodolac (10 mg/kg) significantly inhibited the development of signs of arthritis on day 28 to day 35. Indomethacin (1 mg/kg) also significantly inhibited it on day 29 to day 34. Radiographic examination showed that etodolac (10 mg/kg) significantly prevented the development of osteopenia, bone erosion and new bone formation of the joints on day 35, while indomethacin (1 mg/kg) significantly prevented only the development of bone erosion. Histopathological examination showed that both etodolac (10 mg/kg) and indomethacin (1 mg/kg) significantly prevented the development of synovitis, erosion of cartilage of the joints and bone destruction of the limbs on day 35. Etodolac and indomethacin did not affect the serum level of anti-type-II collagen antibodies. These results suggest that etodolac and indomethacin suppress type-II collagen-induced arthritis without affecting humoral immune responses.

Effects of bombesin on brown adipose tissue (BAT) thyroxine (T4) 5'-deiodinase (5'D) activity and rectal temperature were examined in male mice. Immediately following an intracerebroventricular (ICV) or intravenous (IV) injection of bombesin (0.1-100 ng/animal) or vehicle (20 mM bacitracin dissolved in 0.9% saline), the mice were placed in a room at 4 degrees C or 22 degrees C for 30, 60, 120 or 240 min. The ICV injection of bombesin dose-dependently lessened cold-induced increase in BAT 5'D activity and increased hypothermia determined at 120 min of cold exposure, whereas the IV injection of bombesin was without effect. Bombesin (ICV)-induced hypothermia preceded the inhibition of BAT 5'D activity by at least 30 min at 4 degrees C. BAT 5'D activity was not affected by ICV injection of bombesin in mice kept at 22 degrees C, although the rectal temperature was significantly decreased. Bombesin thus appears to prevent cold-induced increase in T4 5'D activity in mouse BAT by its central effect. Bombesin-induced excessive hypothermia itself and/or the decrease in sympathetic tone of BAT by bombesin might decrease cold-induced increase in BAT 5'D activity.

This study assessed the efficacy and toxicity of the FOLFOX4 (SWIFT1) and mFOLFOX6 (SWIFT2) regimens in Japanese patients with metastatic colorectal cancer (mCRC).Patients with mCRC were required to have ECOG performance status of 0 to 1, and to have adequate organ function. Two multicenter Phase II studies (SWIFT1/SWIFT2) were conducted in chemotherapy naive patients with mCRC.112 patients were enrolled in these studies (SWIFT1: 54 patients / SWIFT2: 58 patients). The disease sites for each study were the colon in 27 patients and 28 patients, and the rectum in 27 patients and 30 patients, respectively. All patients received a median of 8 courses. After a median follow-up period of 35 months, 54 patients and 58 patients were evaluable in the respective studies, and the overall response rate was 50.0% (CR:31 PR:53). The response rate according to the sites of metastasis were as follows: liver, 54.1% (46/85); lung, 17.4% (4/23); and lymph node, 23.3% (7/30). Grade 3/4 neutropenia occurred in 14 patients (12.5%), while Grade 3/4 non-hematological toxicities were observed in 16 patients (31.0%) and Grade 3 neurotoxicity was observed in 6patients (5.4%) and 5 patients (4.5%), respectively.FOLFOX4 (SWIFT1) and mFOLFOX6 (SWIFT2) regimens complying with the international standard dosage and schedule can also be administered safely and effectively in Japan.

Estrogens attenuate renal injury induced by ischemia/reperfusion (I/R), an effect that is related to nitric oxide production in the post-ischemic kidney. The compound 17beta-estradiol (E(2)-beta) acting via estrogen receptors (ERs) is known to activate endothelial nitric oxide synthase (eNOS) through the phosphatidylinositol-3 kinase (PI3K)/Akt pathway. We determined if this pathway contributes to the renoprotective effect of E(2)-beta in the uninephrectomized ischemia reperfusion rat model of acute renal injury. Treatment with E(2)-beta suppressed the I/R-induced increases in blood urea nitrogen, plasma creatinine, urine flow, and fractional excretion of sodium while augmenting creatinine clearance, renal blood flow, and urine osmolality, indicating attenuation of renal injury. Phosphorylation of Akt and eNOS protein was significantly increased 30-60 min after reperfusion in estradiol-treated compared to vehicle-treated rats. The protective effects of E(2)-beta and protein phosphorylation were reversed by the PI3K inhibitor wortmannin or the ER antagonist tamoxifen. Furthermore, the E(2)-beta-induced renoprotective effects were not seen in eNOS knockout mice with renal injury. We conclude that the E(2)-beta-induced renoprotective effect is due to activation of the PI3K/Akt pathway followed by increased eNOS phosphorylation in the post-ischemic kidney.

To evaluate the clinical importance of mixed mutans streptococci colonization in predicting caries in preschool children.Caries prevalence was examined twice, with a 6-month interval, in 410 preschool children aged 3-4 years at baseline. A commercial strip method was used to evaluate the mutans streptococci score in plaque collected from eight selected interdental spaces and in saliva. Mutans streptococci typing polymerase chain reaction (PCR) assays (Streptococcus sobrinus and Streptococcus mutans, including serotypes c, e, and f) were performed using colonies on the strips as template.Twenty variables were examined in a univariate analysis to predict caries development: questionnaire variables, results of clinical examination, mutans streptococci scores, and PCR detection of S. sobrinus and S. mutans (including serotypes c, e, and f). Sixteen variables showed statistically significant associations (P0.04) in the univariate analysis. However, when entered into a logistic regression, only five variables remained significant (P0.05): caries experience at baseline; mixed colonization of S. sobrinus and S. mutans including S. mutans serotypes; high plaque mutans streptococci score; habitual use of sweet drinks; and nonuse of fluoride toothpaste.'Mixed mutans streptococci colonization' is a novel measure correlated with caries development in their primary dentition.

To examine mesiodens with regard to their status, their influence on adjacent teeth and their alteration during the follow-up period.From retrospective reviews of all patients who visited our institution from 1990-2001, we identified 200 patients (256 mesiodentes) who were shown to have mesiodentes on the basis of a periapical radiograph, a panoramic radiograph or an axial radiograph.The number of supernumerary teeth was one in 146 cases (73%), two in 52 cases (26%) and three in 2 cases (1%). Of 256 mesiodentes, the direction of the crown of the mesiodens was inverted in 172 (67%), in a normal direction in 69 (27%) and in a horizontal direction with regard to the tooth axis in 15 (6%). Of the 147 mesiodentes for which axial radiography was performed, 131 (89%) were located at a palatal site against the dental arch, 16 (11%) overlapped the dental arch and none were at a labial site. Of our 200 cases, a delay of eruption of the permanent central incisor was seen in 12 (6%), malposition or rotation of the central incisor in 5 (2.5%) and dentigerous cyst formation arising from mesiodens in 22 (11%). Marked movement of the mesiodens was seen in 10 cases during the follow-up period of 5-7 years. Some complication arising from mesiodens was seen in 19.5% of all cases in our research.Although mesiodentes are not caused by malocclusion, they may cause it. A long period of impaction of mesiodentes may bring about dentigerous cyst formation or movement of the mesiodentes.

To examine radiographically the relationship between the deciduous tooth and dentigerous cyst of the permanent successor during the transitional dentition.From a retrospective review of all patients who visited our institution from April 1988 to August 2001, 70 patients under 16 years of age who had histologically confirmed dentigerous cysts that had developed from the central incisor to the second premolar were identified. These 70 patients were investigated using panoramic and periapical radiographs.In most cases (54 cases; 77.1%) the cyst was in the premolar region. Of the 54 premolars with dentigerous cysts, the overlying deciduous tooth had already been lost in 7 cases. Of the 47 remaining premolars with associated deciduous tooth, 35 (74.5%) had bone resorption of the periapical or bifurcation region, or irregular resorption of the associated deciduous tooth. Of the remaining 12 deciduous teeth with no periapical lesions, 9 had been treated with root canal therapy. Thus, 44 of these 47 cases (93.6%) had the possibility of inflammation at the deciduous tooth associated with the dentigerous cyst. Evidence from one case in the present study suggesting the process by which cyst development occurs is also given.Inflammatory change at the apex of the deciduous tooth may bring on a dentigerous cyst of the permanent successor.

This study was designed to examine the effects of recombinant human erythropoietin (rHuEPO) therapy on blood coagulation and fibrinolysis in patients scheduled for elective heart surgery and undergoing preoperative autologous blood donation. Twenty-seven patients were studied, of whom 16 patients received rHuEPO (group E) and 11 patients no rHuEPO therapy (group N). The patients in group E were given 6000 units of rHuEPO intravenously every other day, three times a week, beginning from two weeks prior to the operation. In both groups, 400 ml of blood was collected preoperatively for predeposit once a week for two weeks, and the self-donated blood was returned to the patient intra- and postoperatively. Blood samples were drawn at the beginning of the study, immediately before the operation and two weeks after the operation. They were analyzed to assess blood coagulation, fibrinolysis, platelet function and vascular endothelial cell function, in order to examine the effects of the administration of rHuEPO. No significant difference was observed between the two groups in the degree of changes in these parameters following the operation. As enhancement of blood coagulability and fibrinolytic activity was evident postoperatively in both groups, changes in these parameters during the preoperative autologous blood donation period were also assessed excluding the postoperative data. Again, there was no significant intergroup difference in any of the markers evaluated. It was concluded that the administration of rHuEPO during preoperative autologous blood donation is unlikely to affect coagulation and fibrinolysis.

The clinical features of myocarditis that developed during the influenza epidemic of winter 1998-1999 were investigated to emphasize the need for medical attention to this disease.Nine patients were treated under diagnoses of acute myocarditis during the winter of 1998-1999. Five (two males and three females, mean age 52 +/- 18 years) were examined with myocarditis associated with influenza A. The diagnosis of influenza A myocarditis was based on electrocardiographic and echocardiographic abnormalities, increased creatine kinase levels and at least a four-fold increase in influenza A virus titers using paired sera.All patients had preceding flu-like symptoms and fever. Cardiac involvement developed between 4 and 7 days after the onset of influenza symptoms. Dyspnea progressively worsened in three patients, one went into shock and one had persistent fever, cough and mild dyspnea without apparent cardiac symptoms. Three patients had ST elevation associated with Q waves and one had complete left bundle branch block. The creatine kinase levels were abnormally increased and global wall motion of the left ventricle on echocardiography was decreased in all patients. Two patients had diagnoses of fulminant myocarditis. One patient died of pneumonia following cerebral infarction, but the left ventricular dysfunction normalized in the remaining four patients.Cardiac involvement occurred between 4 and 7 days after the onset of influenza symptoms, and worsening dyspnea was the most common symptom. Electrocardiography, echocardiography and creatine kinase levels should be checked to determine the potential for cardiac involvement when patients present with suspected influenza associated with worsening dyspnea or prolonged weakness. Increasing the awareness of influenza myocarditis may help in the earlier identification and treatment of this disease during influenza epidemics.

Postnatal development of mammalian seminiferous tubules can be divided into three phases: spermatogonial mitosis, spermatocyte meiosis, and a postmeiotic phase in which drastic morphological changes occur in spermatids (spermiogenesis). In an attempt to elucidate the molecular mechanisms involved in spermiogenesis, we have applied a differential display method to identify genes that are developmentally up-regulated during rat testis development. One of the cDNA fragments isolated by differential display turned out to be iba1, an ionized calcium binding adapter molecule-1, that contains two EF hand-like motifs. Expression of iba1 mRNA in the rat testis was detected first at 4 wk in postnatal development and then increased up to adulthood. Using the antibody against a synthetic peptide corresponding to the N-terminal Iba1 protein, we discovered that Iba1 protein was not detectable by immunohistochemistry in spermatogonia, spermatocytes, and round spermatids in adult rat testis but was specifically expressed in the cytoplasm of elongate spermatids (steps 10-19) as well as in residual bodies that are ultimately engulfed by Sertoli cells. In situ hybridization, on the other hand, revealed that iba1 mRNA is present in round spermatids as well as early elongate spermatids (steps 1-12) but not in late spermatids, suggesting that iba1 mRNA undergoes post-transcriptional regulation. Because Iba1 protein is specifically expressed in the cytoplasm of elongate spermatids, which is finally engulfed as residual bodies into Sertoli cells, we suggest that Iba1 may be involved in the final stage of spermiogenesis (i.e., in elimination of the residual cytoplasm from spermatids).

We report 3 patients with acute epididymo-orchitis with abscess formation due to Pseudomonas aeruginosa, which is relatively unusual and difficult to treat. All patients presented with swollen testicles, pain and high fever. First, they were treated empirically with several antibiotics. After several weeks of antibiotics therapy, the swelling of scrotum still persisted. In one patient, dark yellow pus drained from a fistula of the scrotum. Finally, an orchiectomy was performed on all patients. During the operation, an abscess was found in each testis. Each culture of the pus yielded P. aeruginosa, which is susceptible to many antibiotics.

Fifteen patients who were performed a rotator cuff repair were subjected for the determination of a concentration of isepamicin sulfate (ISP), which was infused intravenously, in venous blood and bone marrow blood. The concentrations were measured at 0, 30, 60 minutes after the injection. There was no statistically significance between ISP concentrations in venous and bone marrow blood. This study revealed that the transference of ISP to the bone marrow was excellent.

We evaluated the influence of interval between prior coronary revascularization and subsequent noncardiac surgery on perioperative cardiac events. We retrospectively identified 162 consecutive patients with previous revascularization procedures who had undergone noncardiac surgery. Postoperative cardiac complications occurred in 10 (6.2%) patients, cardiac death in 1 patient, and significant arrhythmia in 3 patients. These patients had higher rates of unstable angina, myocardial infarction within 3 months, cerebrovascular disease, peripheral vascular disease, renal dysfunction (Cror = 1.9 mg.dl-1) and higher preoperative risk scores as described by the Cleveland Clinic (P0.05). Also, the incidence of cardiac complications increased when noncardiac surgery was performed within 1 week of previous percutaneous transluminal coronary angioplasty (PTCA) and in more than 5 years after coronary artery bypass grafting or PTCA (P0.05). Although PTCA is widely accepted, especially in Japan, early lesion progression was observed during the first several days and atherosclerotic progression was apparent in more than 5 years after the procedure. Therefore, the time between coronary revascularization and noncardiac surgery, as well as atherosclerotic risk factors, is important in evaluating patients with history of previous revascularization procedures.

A 62-year-old male presented with ruptured anterior communicating artery (ACoA) aneurysm manifesting as severe headache associated with the rare combination of median artery of the corpus callosum (MACC) and accessory middle cerebral artery (MCA). Computed tomography demonstrated diffuse subarachnoid hemorrhage. Left carotid angiography demonstrated an anomalous vessel originating from the ACoA complex and passing forward in the interhemispheric fissure between the two companion A2 segments. This vessel was identified as the MACC. Another anomalous vessel originated from the left A1-A2 segment and passed into the sylvian fissure. This vessel was identified as the accessory MCA. Left frontotemporal craniotomy was performed to clip the neck of the aneurysm. After identifying both A1 and A2 segments, accessory MCA, and the MACC, the aneurysm neck was occluded successfully. The ACoA complex is one of the most frequent sites of vascular anomalies. Preoperative and intraoperative care is required to identify the presence of anomalies of the ACoA complex prior to clip placement, to avoid accidental damage or clipping, which may result in severe neurological deficits.

A novel and convenient in vitro method for predicting in vivo metabolic clearance in the liver (CL(H)) was developed. The CL(H) of a drug is usually predicted by using both the unbound fraction in serum and the intrinsic hepatic clearance of the unbound fraction, but this procedure is labor-intensive. We simplified the method by directly measuring intrinsic hepatic clearance using isolated rat hepatocytes suspended in rat serum and called this "the serum incubation method". Sixteen commercially available compounds reported to be mainly excreted by liver metabolism were evaluated using our method. The remaining ratio of the unchanged drug after incubation was measured to calculate the rate of metabolism, and then CL(H) was predicted based on the dispersion model. The predicted CL(H) values of the drugs estimated by the serum incubation method were in good agreement with their in vivo plasma clearance values. In addition, the intrinsic hepatic clearance values obtained by the serum incubation method were comparable with those obtained by conventional methods. Furthermore, oral bioavailability values were equal to or lower than hepatic availability values predicted from the serum incubation method. These results indicate that compounds showing poor oral bioavailability can be excluded before in vivo pharmacokinetic study by using this method. In conclusion, the serum incubation method is a convenient and useful tool at the early stage of drug discovery.

Increase of ketone body concentration in plasma is induced by various factors such as onset of diabetes. Secretion of excessive stress hormone including catecholamine is responsible for stimulation of lipolysis which increases plasma ketone body concentration. Catecholamine levels reflect the severity of the neurologic insult, so this is a basis for the use of catecholamine measurements as a physiological marker of patient outcome. Twenty-seven patients with severe head injury and twenty-five healthy volunteers were enrolled in this study, but patients with diabetes or liver dysfunction were excluded. The patients with severe head injury consisted of 19 with focal injury and 8 with diffuse injury. The outcome was as follows; 14 patients died and 13 patients survived. We collected arterial blood samples as promptly as possible after onset of severe head injury and measured the following: 1, base excess; 2, beta-hydroxybutyrate; 3, acetoacetate; 4, lactate; 5, epinephrine; 6, norepinephrine. The ketone body (beta-hydroxybutyrate + acetoacetate) concentration in plasma was significantly elevated in patients with severe head injury. The increment of beta-hydroxybutyrate levels was greater than that of acetoacetate levels, resulting decreased arterial ketone body ratio (AKBR; acetoacetate/beta-hydroxybutyrate). We demonstrated that plasma ketone body concentrations were elevated and the AKBR decreased in severe head-injured patients. Elevation of catecholamine has been reported as a stress reaction in severe head injury. Catecholamine is most potent in stimulating lipolysis, and ketogenesis. Therefore, the ketonemia observed in severe head injury is most likely to be induced by elevation of catecholamine levels. The degree of ketonemia may be an index of the severity of severe head injury.

Dad1, the defender against apoptotic cell death, comprises the oligosaccharyltransferase complex and is well conserved among eukaryotes. In hamster BHK21-derived tsBN7 cells, loss of Dad1 causes apoptosis which cannot be prevented by Bcl-2.To determine the role of Dad1 function in vivo, we prepared by gene targeting, mice harbouring a disrupted Dad1 gene. Homozygous mutants died shortly after they were implanted with the characteristic features of apoptosis. In an in vitro blastocyst culture system, Dad1-null cells displayed abnormalities which were comparable to those obtained in vivo. However, oligosaccharyltransferase activity was apparently retained even after the Dad1-null cells were destined to die. Some live-born heterozygous mutants displayed soft-tissue syndactyly. Mild thymic hypoplasia was also indicated in heterozygotes.These results suggest the involvement of the Dad1 gene in the acquisition of a common syndactyly phenotype, as well as in the control of programmed cell death during development.

The authors evaluated the influence of the vagal pyloric branches on the gastrointestinal function in patients who underwent a pylorus preserving pancreatoduodenectomy (PPPD).Twenty-seven patients with pancreatobiliary and duodenal diseases underwent a PPPD between 1991 and 1994. We analyzed several variables including the daily volume of gastric juice, days of gastric suctioning, start of diet, gastric acid, and gastrin levels. In addition, a gastric emptying scintigram and gastrointestinal manometry were measured. These variables were compared between two groups, namely, those with retained superior pyloric branches of the vagus nerve (preserved group: n = 14), and those without these branches (non-preserved group: n = 13).There were no significant differences in basal acid output, maximum acid output, or plasma gastrin levels between the preserved group and the non-preserved group. In addition, a gastric emptying scintigram demonstrated no difference between the two groups. Finally, on gastrointestinal manometry, there was no significant difference between the two groups during gastric and jejunal phase III activity of migrating motor complex.Preservation of the vagal pyloric branches did not influence gastric exocrine and endocrine secretion, nor did it effect the gastric emptying of patients who underwent a PPPD.

We report a case of transient cortical blindness and convulsions during embolization of the cerebellar AVM. A 29-year-old man was admitted to our hospital with subarachnoid hemorrhage. Cerebral angiography showed the right cerebellar AVM fed by the right superior cerebellar artery. Preoperative embolization of the AVM was performed. During embolization, the patient lost consciousness suddenly and appeared to be in a decerebrate posture. About 15 minutes later, the patient came around and complained of total blindness. Cerebral angiography revealed the disappearance of the aneurysm and AVM. There were no abnormal findings in the vertebrobasilar system. Computed tomography obtained just after the procedure, showed considerable contrast enhancement of the occipital lobes. Two hours later, a repeat computed tomography showed clearance of contrast enhancement. Magnetic resonance imaging obtained 12 hours after the procedure, showed no evidence of infarction in the occipital lobes. Two days after, the patient's sight gradually returned. Seven days after the procedure, the patient recovered completely. We speculated that these clinical features might be convulsions due to contrast material. In the reported cases, convulsions and transient cortical blindness due to non-ionic low osmolar contrast materials is a rare complication. This case suggested disruption of the blood-brain barrier demonstrated by the computed tomography appearance of contrast enhancement in the occipital lobes.

We present a case of long-term survival in primary malignant lymphoma of the duodenum treated with a curative surgical resection and post-operative chemotherapy. A 72 year-old man was admitted to our hospital complaining of epigastric discomfort. Endoscopy revealed an ulcerative tumor in the duodenal bulb. The tumor was diagnosed histologically as malignant lymphoma by endoscopic biopsy. A distal gastrectomy and duodenal bulb resection were performed with lymph nodes dissection. The tumor was histologically classified as B-cell phenotype, large cell, immunoblastic lymphoma of high grade, according to the Working Formulation. The patient received CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy after the operation, and he has no sign of recurrence during a follow-up period of 6 years.

To accommodate optimal sized aortic valve, our experiences with supraan-nular aortic root enlargement (SAE) in 20 patients with small aortic annulus have been described.From June 1981 to April 1996, aortic valve replacement with a St. Jude Medical (SJM) valve had been performed in 46 patients with aortic stenosis consecutively. After August 1993, we employed SAE in patients to insert 23 mm or larger aortic prostheses (SAE group, n = 20; control group, n = 26). Patients were followed-up for a period of 1.7 to 8.3 years.There were no intra- or postoperative complications. The pressure gradient across the prosthesis was greater than 30 mmHg in 4 patients of the control group and in 1 patient of the SAE group. Only in nineteen patients (73%) of the control group, 23 mm or larger sized valves could be implanted by a conventional technique. By contrast, with SAE, 23 mm or larger sized SJM prostheses were possible to implant in 19 out of 20 patients (95%).To avoid valve-patient mismatch, SAE of aortic root is safe and effective.

PIVKA-II is well known as a tumor maker of hepatocellular carcinoma (HCC). We measured serum PIVKA-II concentrations with a commercially available PIVKA-II immunoassay kit (Picolumi PIVKA-II: Eisai Co., Ltd., Tokyo) using Electrochemiluminescence Immunoassay (ECLIA). ECLIA system is a novel immunoassay system using a Ruthenium (II) Tris (bipyridyl) luminesced by electric energy. Cut off value was 40 mAU/ml by receiver-operating characteristic curves as a tumor maker for HCC. Eighty-nine out of 142 (62.2%) patients with HCC had elevated serum PIVKA-II levels and seventeen out of 36 (47.2%) patients whose tumor size was below 2 cm in diameter showed high PIVKA-II levels. We determined the serial changes in serum PIVKA-II levels of two patients with HCC following initial therapy. In these patients, elevations of serum PIVKA-II levels determined by ECLIA system preceded the HCC relapse detected by imaging diagnostic procedures. In summary, this assay system is suitable for detecting small increases in PIVKA-II concentrations. Determination of PIVKA-II by this assay system is found to be useful for the early detection of HCC.

Clinical experience of autologous blood preservation on 83 patients and transfusion on 43 patients were reported. When drawing blood, 14 patients whose hemoglobin level was below 13 g/dl (body weight70 kg) or 14 g/dl (body weight70 kg) received subcutaneous recombinant human erythropoietin injection (s.c.) to facilitate erythropoiesis, according to the internal standard protocol. Hemoglobin levels of all the patients recovered to more than 10 g/dl by the time they were admitted to the hospital, which value would not interfere with general neurosurgical procedures. The injection of erythropoietin did not cause any side effects. Autologous blood transfusion was performed in 43 patients but, in 3 patients, additional homologous transfusion was required because of excessive bleeding. Except in cases with meningioma, postoperative hemoglobin values were identical with preoperative values, indicating that autologous blood transfusion was enough to replace intraoperative blood loss. Autologous fibrin glue was applied in 74 patients. In 70 cases including 55 with skull base surgery, the glue was applied to ensure dural closure. The incidence of cerebrospinal fluid leakage was 16.4% (5 patients) in skull base surgery. This incidence was identical to or less than that in previous reports. The glue was also effective in transposing and fixing offending vessels in 4 cases which received microvascular decompression. As a conclusion, procedures for autologous blood preservation and transfusion were safely performed in neurosurgical cases. Review of the literature was also presented to discuss the advantages and problems to be solved in the future.

The arterial ketone body ratio (AKBR) is considered to be an accurate index of the functional reserve of the liver, and the validity of this idea has been confirmed in the field of abdominal surgery. We found low AKBR value intracerebral hemorrhage patients and discussed the clinical significance of this finding in this paper. Twenty-five patients with intracerebral hemorrhage treated at our institution were included in this study. Their ages ranged from 42 to 86 years old (average 68.5 years). There were 13 cases of putaminal hemorrhage and 12 cases of thalamic hemorrhage. Evacuation of the hematoma or ventricle drainage was performed in 20 of these cases within 3 days after symptoms of intracerebral hemorrhage appeared. There were 12 cases with intraventricular hemorrhage. The outcome of these patients was as follows; 17 cases survived, eight cases died. We collected blood samples on days 1, 2, 3, 7 and 10 after the onset of symptoms (day 0) and measured the following: 1, beta-hydroxybutyrate; 2, acetoacetate; 3, epinephrine; 4, norepinephrine. On day 0 total ketone body levels were higher (246.3 +/- 231.7 mumol/l), AKBR values (0.60 +/- 0.18) were significantly lower than in the control group (2.05 +/- 1.35) (p0.001). However, both epinephrine and norepinephrine levels were significantly higher, 638.4 +/- 229.0 pg/ml and 1036.5 +/- 288.2 pg/ml, respectively. The AKBR value was 0.76 +/- 0.19 on day 1, 1.04 +/- 0.30 on day 2, and increased thereafter. In addition, the relation between sequential changes of AKBR in patients with intraventricular hemorrhage and outcome were also discussed. AKBR values are known to decrease not only in cases of hepatic failure, but in cases in which the liver energy charge is reduced, such as shock and hypoxemia, but no investigations have ever been performed to determine whether AKBR is altered in cerebrovascular disease. In this study, we found that AKBR values were lower in intracerebral hemorrhage, presumably due to reduced hepatic blood flow causes by increased levels of epinephrine and norepinephrine. In addition, our findings suggest that the fluctuations in AKBR values correlated with the outcome of intracerebral hemorrhage patients.

Excellent results of multiple burr-hole operation (MBHO) for child moyamoya disease are reported in this study. Three patients of moyamoya disease had MBHO. After MBHO, transient, ischemic attacks disappeared in a patient despite progressing stenosis of the major cerebral arteries, and remarkable neurological improvement was recognized in a patient who had encephaloduroarteriosynangiosis. Another patient slowly improved and became able to go to junior high school. N-isopropyl-p-[123I] iodoamphetamine (IMPSPECT) findings also improved in all patients. There was no mortality or morbidity, and no new neurological deficits or bleedings developed during the follow up period. The authors recommend the MBHO as the surgical treatment of choice for not only adult but also child moyamoya disease because of its safety and effectiveness, and also report the usefulness of MBHO for the patients who have already received other bypass operations.

We retrospectively studied subarachnoid hemorrhage (SAH) patients with delayed ischemic neurological deficit (DIND), and analyzed the factors causing extremely late onset of deficits occurring over 15 days after onset of the SAH. Among 605 patients with SAH, 201 (33%) developed DIND. Among DIND patients, 137 had undergone early aneurysm surgery. In these 137 patients, onset date of DIND was definite in 131 patients. Six patients (5%) developed DIND over 15 days after SAH. All 6 had asymptomatic angiographical vasospasm and infections, most often meningitis, before the onset of DIND. Compared with cases in which there was ordinary onset of DIND, other statistically significant factors among these 6 patients were intracerebral hemorrhage, sepsis and meningitis. We suspect that DIND were manifested subclinically in the early period because of the associated hyperdynamic hemodynamics resulting from sepsis in these patients.

Fluorescence in situ hybridization with biotinylated repetitive DNA probe specific for the centromeric region of chromosome 17 (p17H8: Oncor) was applied to suspended nuclei which were isolated by Shutte's method from formalin-fixed paraffin-embedded tissue. The tissues were obtained from surgically resected specimens from nine patients with non-small cell lung carcinoma. The isolated nuclei were prepared with 0.05% pepsin/0.1NHCl for 15 minutes at 37 degrees C. Subsequently, these were immersed in 70% acetic acid for 10 seconds at room temperature. After heat denature with hybridization mixture which contained 3 mu 1 DNA probe for 10 minutesat 70 degrees C, 1 x 10(6) nuclei were incubated overnight at 37 degrees C. After washing with 60% formamide/2 x SSC, the hybridized probes were labeled by FITC conjugated avidin. A number of centromeric signals of chromosome 17 wasevaluated by fluorescence microscopy (BH-2, Olympus). Furthermore, a probe-related FITC intensity was quantified using flow cytometry (FACScan, Becton Dickinson). As the results, there was good correlation between a relative fluorescence intensity determined by flow cytometry and a relative fluorescence signal by fluorescence microscopy (p0.05).

A rare case of epididymal sarcoidosis is reported. A 52-year-old man was admitted with a painless mass in the left scrotum. An operation revealed that a 1-cm mass was located at the epididymal head and well demarcated from the testis and the surrounding tissue. Epididymectomy was performed. Histopathological diagnosis was noncaseating granulomas consistent with sarcoidosis. Systemic examination showed bilateral hilar lymphadenopathy and bilateral peripheral anterior synechiae, but these lesions were diagnosed as inactive. Serum level of angiotensin-converting enzyme was normal.

ATN-10, Mn-metalloporphyrin, has been developed as a tumor selective contrast agent for magnetic resonance (MR) imaging. To investigate the tumor specificity of ATN-10, we produced three experimental in vivo models; rat bran tumor (9L glioma) model, vasogenic (cold injury) and cytotoxic brain edema (24-hour MCA occlusion) models. The time course of contrast enhancement was compared after intravenous injection of ATN-10 or Gd-DTPA, measuring the signal intensity of the region of interest. After ATN-10 administration, the 9L glioma model showed early (5 min) and delayed (24 hr-) peak enhancement whereas the cold injury model showed only early enhancement and the 24-hour MCA occlusion model did not show significant enhancement. After Gd-DTPA administration, all three models showed similar pattern of only early enhancement. As a contrast agent for MR imaging, ATN-10 showed different behavior than Gd-DTPA in demonstrating the blood-brain barrier disruption and moreover ATN-10 showed selective enhancement in experimental brain tumors.

I read with great interest the article by Hilario et al.[1][1] The authors retrospectively analyzed the MR imaging data from the first 30 days after injury in 108 patients with severe head trauma and found that the presence of posterior and bilateral brain stem injuries were poor prognostic signs.

Arterial fibrinoid lesions in major salivary glands and lingual minor salivary glands from four autopsied patients with primary Sjögren's syndrome were studied histologically and immunohistochemically. On a morphological basis, the preceding arterial fibrinoid necrosis was regarded as medial damage, particularly of smooth muscle cells. The medial smooth muscle cells underwent vacuolated degeneration and disappeared, and resulted in full-blown fibrinoid arteritis. By means of the immunoperoxidase method the distribution of the immunoglobulins, fibrin, complement (C3), transferrin, ferritin, vimentin and lysozyme was studied. The normal arterial wall reacted with the lambda light chain of immunoglobulin, transferrin and vimentin Vacuolated degeneration of medial smooth muscle cells, regarded as the initial change in cases of vascular fibrinoid lesion, was positive for IgG, C3 and vimentin. We suggest that IgG antibody is a useful marker to detect the initial phase of arterial fibrinoid necrosis. In the foci of fibrinoid necrosis, fibrin, C3 and vimentin were detected. Among these three antibodies, only fibrin was negative in the normal arterial wall and vacuolated degenerates of medial smooth muscle cells. Mononuclear cells surrounding areas of fibrinoid necrosis stained strongly with antisera to immunoglobulins, transferrin, ferritin and vimentin, and negatively with fibrin, C3 and lysozyme antibodies.

A hemophilia A patient with high responder inhibitor had been treated by (activated) prothrombin complex concentrates (A) PCC and activated factor VII until the occurrence of intracranial bleeding at the age of 6 years. Since the inhibitor titer was decreased less than 1 Bethesda Units/ml, high dose of factor VIII was given followed by the infusions of factor VIII concentrates (100 units/kg) three times a week. In spite of previous episodes of anamnestic responses by factor VIII products before, the inhibitor titer did not increase and disappeared completely 6 months after the FVIII infusion therapy. The specific anti-factor VIII IgG subclasses of the inhibitor were IgG2 and IgG4. The inhibitor recognized both light and heavy chains. He have no bleeding episode for 6 months since the beginning of the prophylactic with factor VIII concentrates.