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Stereotactic surgery for Parkinson's disease can be performed using different neuroimaging methods. Ventriculography has been used to locate the coordinates of the structures close to the third ventricle. Although it has several potential disadvantages related to the intraventricular injection of iodine contrast, it is considered a precise method. Computed tomography and magnetic resonance imaging have been used in some centers. In order to compare their efficacy, 50 stereotactic thalamotomies for Parkinson's disease were performed using either ventriculography (VE) (25) or magnetic resonance imaging (MRI) (25). In 14 out of 25 VE procedures, computed tomography (CT-scan) was also used and showed a significant mean difference of coordinate Y and Z. The clinical results employing either VE or MRI were similar, with 80% abolition of tremor in the VE group, and 84% in the MRI group, after a follow up period of at least 3 months. Another 12% of VE and 16% of MRI group showed significant improvement of tremor. Complication rate was 4% in both groups. MRI-guided stereotactic thalamotomy in Parkinson's disease has shown good clinical results, comparable to VE-guided stereotaxis. A cirurgia estereotáxica para doença de Parkinson (DP) pode ser realizada com diferentes métodos de neuroimagem. A ventriculografia (VE) tem sido empregada para determinar as coordenadas estereotáxicas das estruturas próximas ao terceiro ventrículo. Apesar de várias desvantagens relacionadas com a injeção intraventricular de contraste iodado, é considerada como uma técnica precisa. A tomografia computadorizada (TC) e a ressonância magnética (RM) têm sido utilizadas em alguns centros. Para comparar a eficácia dos diferentes métodos, 50 talamotomias estereotáxicas para DP foram realizadas utilizando VE (25 casos) e RM (25 casos). Em 14, dos 25 casos com VE, o emprego concomitante de TC demonstrou diferença média importante nas coordenadas Y e Z. Os resultados clínicos utilizando-se VE ou RM foram similares, com 80% de abolição de tremor no grupo com VE e 84% com RM durante seguimento mínimo de 3 meses. Além disso, 12% do grupo com VE e 16% do grupo com RM apresentaram significativa melhora do tremor. índice de 4% de complicações foi encontrado em ambos os grupos. Não houve mortalidade. A talamotomia estereotáxica guiada por RM para DP demonstrou resultados comparáveis aos obtidos com VE.

The heterosexual transmission of hepatitis C virus (HCV) remains controversial, and data from general populations are scanty. In this cross-sectional study, we assessed the seroprevalence of antibodies to hepatitis C virus (anti-HCV) and the presence and genotype of HCV-RNA among 109 married couples within an endemic, community-based Japanese population. Overall, 25% of the husbands and 32% of the wives had anti-HCV. Spouses with anti-HCV-positive partners were around 2 times more likely to have anti-HCV than spouses with anti-HCV-negative partners (p = 0.01). Of 6 couples in which both spouses had HCV-RNA, however, 3 presented discordant HCV genotypes (type 1b vs. 2b). The couples' anti-HCV concordance status was not significantly influenced by the presence or absence of HCV-RNA among anti-HCV-positive partners (odds ratio [OR]: 0.8 for wives, 0.6 for husbands), nor by the length of marriage, the number of pregnancies or the use of contraceptives. No significant associations with anti-HCV were observed for serum markers of sexually transmitted agents, including human T-lymphotropic virus (OR = 1.1, 95% confidence interval [CI] 0.5-2.3), Treponema pallidum (OR = 0.7; CI 0.1-6.1) and hepatitis B virus (OR = 1.6; CI 0.9-3.0). Our results suggest that the clustering of HCV infection among specific couples within this endemic population may not be attributable to heterosexual transmission. Follow-up studies are necessary to determine the risk of heterosexual transmission of HCV in endemic areas.

The efficacy and safety of oral placebo or odanacatib 10, 25, or 50 mg once weekly for 52 weeks were evaluated in a double-blind, randomized, multi-center study in Japanese female and male patients with osteoporosis.Odanacatib is a selective and reversible cathepsin K inhibitor that decreases bone resorption and increases bone mineral density (BMD).The primary efficacy endpoint was percent change from baseline to week 52 in lumbar spine BMD. Secondary endpoints included percent change in total hip, femoral neck, and trochanter BMD and in bone biomarkers after treatment for 52 weeks.In this study, 286 patients [94% female, mean age (SD) 68.2 (7.1) years] were included in the analysis. The least-squares mean percent changes from baseline to week 52 in the groups receiving placebo, 10, 25 and 50 mg of odanacatib for lumbar spine (L1~L4) BMD were 0.5, 4.1, 5.7, and 5.9% and for total hip BMD were -0.4, 1.3, 1.8, and 2.7%, respectively. The changes in femoral neck and trochanter BMD were similar to those at the total hip. Bone turnover markers were reduced in a dose-dependent manner. However, the effects of odanacatib on bone formation markers were less compared with the effects on bone resorption markers. Tolerability and safety profiles were similar among all treatment groups with no dose-related trends in any adverse events.Weekly odanacatib treatment for 52 weeks increased BMD at the lumbar spine and at all hip sites in a dose-dependent manner and was well tolerated in Japanese patients with osteoporosis.

We analyzed the cranial computerized tomography scans (CT) of 1000 consecutive patients with the history of seizures. The seizures were classified in generalized tonic-clonic seizures (GS) and partial seizures (PS) on the basis of the clinical semiology, as it was described by the patients and family members. Seizure types were correlated with age group, sex and CT findings. GS were observed in 70.7% of the patients and PS in 29.3 %. An increased incidence of GS was noted among the age groups 0 to 10 yrs (31%) and 11 to 20 yrs (21.8%). For PS the 0 to 10 yrs (24.5 %), 21 to 30 yrs (16.7%) and 31 tp 40 yrs (18.5%) age groups were the most prevalent groups. The CT scan findings for the GS group were the following: normal studies 48.8 % of the patients, calcifications/cysticercosis (14.0%), neurocysticercosis/cysts (9.6 %), hydrocephalus (4.3%), ischemia (4.2 %), non-definite lesions (4.1 %), tumor (2.5%), and others (12.5%). In the PS group we found 37.4% of normal studies, calcifications/cysticercosis (11.2%), neurocysticercosis/cysts (12.2%), tumor (10.5%), ischemia (5.4%), hydrocephalus (3.7%), non-definite lesions (8.1%) and others (11.6%). We emphasize the importance of CT scan imaging in patients presenting with seizures, particularly in the diagnosis of cysticercosis.

Cyclin D1, one of the G(1) cyclins, is frequently overexpressed in several types of carcinomas and is thought to play an important role in tumorigenesis and tumor progression including hepatocellular carcinoma. We constructed a retrovirus vector-carrying rat cyclin D1 cDNA in the reverse orientation, resulting in expression of antisense (AS) cyclin D1 mRNA. For efficient transduction of this recombinant retrovirus, two-step gene transfer was performed. The rat hepatoma cell line (dRLh84) was infected with this recombinant retrovirus after preinfection with adenovirus expressing the retrovirus receptor. In the rat hepatoma cells, AS cyclin D1 mRNA was expressed, inducing a decrease in the expression of endogenous cyclin D1 mRNA and an inhibition of cell growth. Moreover, two-step gene transfer of AS cyclin D1 into s.c. hepatoma xenografts resulted in inhibition of tumor growth and prolonged animal survival. In the virus-infected tumor xenografts, expression of cyclin D1 was immunohistochemically inhibited, and apoptosis of hepatoma cells was detected. These findings suggest that transduction of AS cyclin D1 is useful as an adjunct to standard treatments for hepatocellular carcinoma.

Surgical treatment of pancreatic adenocarcinoma has failed to produce many cures secondary to high rates of intraperitoneal relapses and liver metastases. The aim of this ex vivo study was to evaluate the inherent chemosensitivity, radiosensitivity and hyperthermic sensitivity of pancreatic adenocarcinoma and to investigate the usefulness of a 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay utilized in each sensitivity test.Nine human pancreatic adenocarcinomas were tested ex vivo after growth in nude mice. After 72 hr of chemotherapy, radiotherapy and hyperthermia, efficacy was assessed using MTT assay to determine the ratio of surviving fraction of treated cells-to-that of untreated control cells (TIC ratio).Tumor sensitivities as measured by the IC50 (drug concentration producing 50% growth inhibition) varied largely between drugs, ranging larger than 3 x 10(5) ng/mL for 5-FU, larger than 1.5 x 10(2) ng/mL for MMC, 20 ng/mL to 1.4 x 10(3) ng/mL for ADM, and 80 ng/mL to 2.4 x 10(3) ng/mL for CDDP. D0 (dose of radiation reducing the surviving fraction to 37%) ranged from 3.2 to 8.3 Gy (mean +/- standard deviation; 5.8 +/- 1.6 Gy). For hyperthermia, the mean T50 (duration of hyperthermia reducing the surviving fraction to 50%) at 43 degrees C was 9.4 +/- 3.3 min 4.8 to 14.2 min). The T/C ratio at 43 degrees C for 12 min was less than that at 41 degrees C for 30 min (p = .01; the Wilcoxon signed-ranks test). No clear relationship among chemosensitivity, radiosensitivity, hyperthermic sensitivity and pathologic features could be established.Nine human pancreatic adenocarcinomas varied widely in their sensitivity to chemotherapies, especially for 5-FU. These results suggested that MTT assay may be useful in excluding some less sensitive cases of pancreatic cancer. For hyperthermia, sufficient therapeutic time and temperature may realize enough effect against pancreatic adenocarcinoma.

We previously reported that the retroviral vector expressing the herpes simplex virus-thymidine kinase gene under the control of 0.3-kb human alpha-fetoprotein (AFP) gene promoter (AF0.3) provided the cytotoxicity to ganciclovir (GCV) in high-AFP-producing human hepatoma cells but not in low-AFP-producing cells. Therefore, specific enhancement of AFP promoter activity is likely to be required to induce enough cytotoxicity in low-AFP-producing hepatoma cells. In this study, we constructed a hybrid promoter, [HRE]AF, in which a 0.4-kb fragment of human vascular endothelial growth factor 5'-flanking sequences containing hypoxia-responsive element (HRE) was fused to AF0.3 promoter. By means of the reporter gene transfection assay, hypoxia-inducible transcriptions that were mediated by [HRE]AF promoter were detected in low- and non-AFP-producing human hepatoma cells, but not in nonhepatoma cells. When the herpes simplex virus-thymidine kinase gene controlled by [HRE]AF promoter was transduced into hepatoma and nonhepatoma cells by a retroviral vector, the exposure to 1% O2 induced GCV cytotoxicity specifically in the hepatoma cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors consisting of the virus-infected hepatoma cells gradually disappeared by GCV administration. These results indicate that the hypoxia-inducible enhancer of the human vascular endothelial growth factor gene, which is directly linked to human AFP promoter, involves selective and enhanced tumoricidal activity in gene therapy for hepatocellular carcinoma.

We report the use of laryngeal mask airway (LMA) to facilitate smooth emergence from anesthesia in 3 patients who underwent lung volume reduction surgery (LVRS) for severely symptomatic emphysema. To prevent coughing during emergence we replaced the endotracheal tube with LMA while patient was still in deep anesthesia. Emergence was smooth without coughing in all three patients, and ventilation with facemask was not needed after removal of LMA. We believe this technique is safe and beneficial for anesthetic management of LVRS.

Visceral larva migrans (VLM) is a disease usually observed in children in which the larvae of animal parasites invade and reside in human tissues for long periods. Although the common causal species of VLM are Toxocara canis and T. cati, we identified three adult patients with VLM, probably due to Ascaris suum, whose diagnosis was made by specific immunoserological tests. The patients complained of respiratory symptoms, and laboratory tests showed pronounced eosinophilia, but neither larvae nor eggs were detected in stool samples. We present the findings of various imaging studies of the patients. Multiple small hypoechoic mass lesions were demonstrated by ultrasound tomography, which disappeared after anti-helminthic therapy. Hepatic mass lesions were detected as low-density areas on computed tomography, as high signal intensities on T2-weighted magnetic resonance images, as space-occupying regions in liver scintigraphy, and as yellow-white nodules in laparoscopy. Although biopsied liver tissue specimens showed marked infiltrations of eosinophiles in the portal tracts and hepatic sinusoids, neither larvae nor eggs could be identified.

We report 2 adult cases where the diagnosis of acute plastic bowing of the forearm was either delayed or missed. In a 21-year-old man, ulnar bowing was missed and fixation was not performed because the patient had no limitation to his range of movement or pain. In a 24-year-old woman, the presentation of bowing in both the ulna and radius was delayed and corrective osteotomy was necessary for restoration of full range of movement. Prompt diagnosis enables manual reposition for easy restoration of full range of movement.

Human T-lymphotropic virus type I (HTLV-I) carriers often have abnormal lymphocytes (Ably) that resemble malignant cells of adult T-cell leukemia (ATL). To identify predictors of the level of Ably in a longitudinal study of asymptomatic HTLV-I carriers, we analyzed data from 215 subjects (67 men and 148 women) with multiple Ably measurements on blood smears. Ably+ (those having Ably0.6% of leukocytes counted on a blood smear at least once) was strongly associated with a high proviral load (OR 8.9; 95% CI 4.1, 19.5). The association among those defined as Ably++ (Ably0.6% at all screens or Ably1.6% at least once) was higher (19.7; 6.9, 56.1). Ably++ was also significantly associated with male gender (2.8; 1.0, 7.8). Multivariate analysis of Ably level indicates that men with a high proviral load, high anti-HTLV-I titer and low anti-Tax reactivity have the highest Ably level.

Human hepatocyte growth factor (hHGF), now known to be identical with scatter factor and tumor cytotoxic factor, is thought to be involved in the regeneration of the liver in humans.We measured the levels of immunoreactive hHGF levels in peritoneal fluid before and after partial hepatectomy in 37 patients, 10 with and 27 without cirrhosis. The presence of hHGF was confirmed in human peritoneal fluid with rat hepatocytes in primary culture and Western blot.Levels of hHGF increased significantly in peritoneal fluid after surgery, with its total concentration being correlated with the weight of resected liver 168 hours postoperatively.Findings suggest that the hHGF levels in peritoneal fluid may indicate the extent of hepatic damage following partial hepatectomy and other liver diseases.

Mutations in the precore region are not always detected in hepatitis B virus (HBV) from patients with chronic hepatitis B who respond to interferon and lose hepatitis B e antigen (HBeAg) from serum. The other mutations may also be responsible for the loss of HBeAg and response.Forty six consecutive patients with HBeAg-positive chronic hepatitis B received recombinant-alpha 2 a interferon (total dose: 702 MU). The mutation for stop codon 28 in the precore region was determined by restriction fragment length polymorphism, and mutations in the core promoter were searched for in five HBV DNA clones propagated from each patient.HBeAg was cleared at 6 months after interferon in 11 (61%) of 18 patients with the precore mutation and in 12 (43%) of 28 without it. Of these 28 patients, 19 with mutations in the core promoter in all five HBV DNA clones lost HBeAg more frequently than the remaining nine who had at least one clone among the five that lacked such mutations (58 vs 11%, p0.05).HBeAg-positive patients infected with HBV variants having mutations for an HBeAg-negative phenotype would respond better to interferon by clearing HBeAg from serum. Such mutations may not necessarily be in the precore region but also in the core promoter, which would interfere with the synthesis and secretion of HBeAg either at the translation or transcription level.

The purpose of mass screening is to decrease the mortality rate of diseases which are fatal if advanced by detecting them at an early and curable stage. From this point of view, we describe here the present state of mass screening, its problems, and the future of mass screening for esophageal and gastric cancer in Japan. The conventional X-ray examination commonly used to detect esophageal cancer does not seem to be effective in detecting the malignancy at an early stage. Therefore, endoscopic examination with Lugol staining for high-risk groups is recommended for the purpose. In contrast, mass screening for gastric cancer by X-ray examination, which has been applied until now, has reduced the mortality rate of gastric cancer. At the same time, however, as various problems are pointed out, some additional investigations have been undertaken to further reduce the mortality rate of gastric cancer. As social circumstances change, and therapy as well as diagnosis for the disease improves, it is necessary to evaluate the accuracy, problems, and limits of the present system to conduct effective and functional mass screening program. The present system must be adapted it to reflect improvements and changes.

The authors present a study about 50 stereotactic procedures for intracranial lesions. In 12 cases stereotaxis was used as a treatment: stereotactic surgical resection (5 patients) and aspiration of lesions (7 patients). This study confirms the great accuracy and low morbidity of the stereotactic techniques. Computed tomography and magnetic resonance imaging determinate the precise stereotactic coordinates, but in some cases it is necessary to perform stereo-angiography. The stereotactic surgical resection of brain tumors allows the treatment of deep lesions or located at functional areas and considered to be inoperable before. The related literature is discussed.

Various side effects of interferon (IFN) therapy have been reported. In this study, we examined retinal change during IFN therapy.We performed ophthalmological examinations before, during, and after therapy on 63 patients with chronic hepatitis C who were receiving either natural IFA-alpha or recombinant IFN-alpha 2a or 2b.No retinal lesion was detected before IFN therapy, but, during therapy, retinal abnormality or retinopathy developed in 36 (57.1%) of 63 patients, including retinal hemorrhage in 25 patients and cotton-wool spots in 28 patients. They were noted early in the course of IFN therapy, within the first 4 wk in 67% (24/36) and within 8 wk in 86% (31/36). The incidence was not influenced by the type of IFN but was higher among diabetic (11/12, 92%, p0.05) or hypertensive patients (4/5, 80%, not significant) than among patients without either diabetes or hypertension (24/49, 49%). There was no relation between the incidence of retinopathy and the level of ALT activity or white blood cell or platelet counts. However, retinopathy occurred in most patients receiving IFN therapy after white blood cell count and platelet count reached a nadir. The levels of LDL-cholesterol and the atherosclerotic index in patients with retinopathy were slightly higher than those in the patients without retinopathy.These results suggest that retinopathy often occurs in patients with chronic hepatitis C who are receiving IFN and that we should closely monitor patients for retinal complications during IFN therapy.

A 38 year-old man presented fever and a clinical picture of intracranial hypertension and ataxic syndrome. A CT-scan disclosed an expanding lesion of the cerebellum. Surgical excision of the lesion was performed and pathological examination made the diagnosis of an actinomycotic abscess. The probable primary source of infection were the lungs and/or oral cavity. The postoperative course was uneventful, with complete recovery after a long period of treatment with penicillin (IV and PO). The authors review some aspects about central nervous system involvement in actinomycosis.

A 63-year-old man with smoldering adult T-cell leukemia (ATL) which became acute was admitted. During chemotherapy, he experienced epigastric pain and fever due to neutropenia. The combination therapy of antimicrobials and rhG-CSF was ineffective and he died. Autopsy revealed systemic invasion of ATL cells. The stomach findings resembled those of phlegmonous gastritis, a rare form of bacterial gastritis, along with diffuse, mucosal necrosis with hemorrhage. The pathogenesis of necrotizing gastritis remains to be elucidated. The patient had also received histamine H2 antagonist for gastric ulceration, which might have influenced the gastric bacterial flora.

Twenty-five consecutive patients with myelodysplastic syndrome (MDS) were followed in the Second Department of Internal Medicine, Miyazaki Medical School from 1984 to 1993. The diagnosis of MDS was morphologically based on the criteria of FAB. At the time of diagnosis, 9 patients had refractory anemia (RA), 1 had RA with ring sideroblasts (RARS), 6 had RA with excess blasts (RAEB), 6 had RAEB in transformation (RAEB-t), and 3 had chronic myelomonocytic leukemia (CMMoL). Prognostic factors involved in survival times and progression to leukemia were analyzed in these patients; FAB classification of MDS, age, sex, peripheral blood cell counts, bone marrow examination, karyotype, numbers of blasts. None of these prognostic factors had a significant effect on the prognosis of MDS patients. Study of the therapeutic effects on MDS patients revealed no significant increase of survival time in treated MDS patients compared to non-treated patients. Further, no significant difference in survival time was found between MDS patients treated with or without anticancer drugs. These results indicated that MDS patients were pathologically and therapeutically heterogeneous.

A 49-year old male with chronic myelogenous leukemia (CML) and psoriasis was admitted for interferon treatment. He was given 6 MU of human lymphoblastoid interferon (HLBI), a natural alpha-interferon, daily for 1 month followed by 3 MU every other day for 1.5 months and twice a week for 1 month. Because HLBI administration showed no favorable effects on the hematological findings and because of the exacerbated psoriasis of the patient, it was discontinued. Subsequently his psoriasis improved to the initial findings observed at the admission. We reported a case of CML in which psoriasis was exacerbated during interferon therapy.

A 42 year-old man with subarachnoid hemorrhage was admitted in our Service (HuntHess grade II). CT-scan disclosed predominantly perimesencephalic subarachnoid hemorrhage. Digital subtraction angiographic study did not disclose either cerebral aneurysm or any other potential site of intracranial bleeding. The evolution was uneventful. A DSA was repeated one month later and was negative. Four months later, the patient was asymptomatic. The authors review the literature and emphasize the importance in recognizing this benign clinical form of nonaneurysmatic subarachnoid hemorrhage.

The human T-lymphotropic virus type I (HTLV-I) antibody profile of 216 asymptomatic carriers in Miyazaki, Japan, was analyzed in conjunction with the HTLV-I proviral DNA levels in their peripheral blood mononuclear cells (PBMC) determined by the semiquantitative polymerase chain reaction (PCR) method. The geometric mean HTLV-I titer by particle agglutination assay (PA) of 58 subjects (27%) with a high DNA level was 1:1, 240; 94 (44%) with a medium DNA level, 1:740; 38 (18%) with a low level, 1:476; and, 26 (12%) with an undetectable level, 1:263. Moreover, when the subjects were divided into four groups according to titer from high to low, the correlation between DNA level and antibody titer level was highly significant (p0.0001). HTLV-I antibody subclass by Western blot (WB) was determined for 78 randomly selected samples from these carriers. Immunoglobulin (Ig) M antibody was detected in 35 (45%). The mean PA antibody titer was higher in carriers with IgM antibody than in those without, at each detectable proviral DNA level. These findings suggest that HTLV-I antibody titer is related to proviral DNA level and also to the presence of IgM antibodies among those with proviral DNA of the same level. Seven carriers (9%) were negative for IgG antibody by WB, among whom the proviral DNA level was low or undetectable and the PA titer was also low. Three of these were positive only for IgM antibody.