Pacemaker-associated infection caused by ST81/SCCmec IV methicillin-resistant, vancomycin-intermediate Staphylococcus aureus in Japan.

A 76-year-old Japanese man was admitted to hospital for treatment of fever and skin lesion at the implantation site of his pacemaker. During his hospitalization, vancomycin-intermediate Staphylococcus aureus (MIC 4 µg/mL) with reduced susceptibility to daptomycin was isolated from venous blood. This isolate was identified as methicillin-resistant S. aureus with SCCmec IV and was genotyped as sequence type 81, coa VIIa and spa type t7044, harbouring blaZ, aac(6')-aph(2″) and enterotoxin(-like) genes sea, seb, sek, sel, selx and selw. The patient was successfully treated with daptomycin, minocycline and sulfamethoxazole/trimethoprim. We describe the identification of sequence type 81/SCCmec IV vancomycin-intermediate S. aureus from pacemaker-associated septicaemia.

Tongue-palatal contact changes in patients with skeletal mandibular prognathism after sagittal split ramus osteotomy: an electropalatography study.

The purpose of this study was to investigate the changes in tongue-palatal contact patterns using electropalatography (EPG) before and after sagittal split ramus osteotomy (SSRO) in patients with mandibular prognathism. Nine clients who underwent SSRO for mandibular setback and seven control subjects were participated in this study. Tongue-palatal contact patterns for /t/, /s/ and /k/ production were investigated using EPG before surgery and 3 months after surgery. The mean value of whole total of palate contact (WT) in the maximum contact frame was examined before and after SSRO. The correlation quantity between the change of center of gravity (COG) value and the amount of mandibular setback was also evaluated. The mean value of WT for /t/ and /s/ significantly increased after SSRO, and the EPG pattern became normal. However, a remarkable change in WT for /k/ was not observed, and the mean value was significantly larger in the SSRO group before and after surgery than in the control group. A negative correlation between COG variation and the amount of mandibular setback for /t/ and positive correlation for /s/ was observed. This study demonstrated that tongue-palatal contact patterns for /t/ and /s/ articulation improved clearly after SSRO. There was a significant correlation between COG variation and the amount of mandibular setback. However, no significant change was detected through perceptual assessment before and after SSRO. Further investigation is needed to determine whether these results will change over time.

The effect of magnetic field during freezing and thawing of rat bone marrow-derived mesenchymal stem cells.

Previous studies showed that a programmed freezer with magnetic field can maintain a high survival rate of mesenchymal stem cells (MSCs). The purpose of this study was to evaluate the influences of magnetic field during freezing and thawing on the survival of MSCs isolated from rat bone marrow. The cells were frozen by a normal programmed freezer or a programmed freezer with magnetic field (CAS-LAB1) and cryopreserved for 7 days at -150 °C. Then, the cells were thawed in the presence or absence of magnetic field. Immediately after thawing, the number of surviving or viable cells was counted. The cell proliferation was examined after 1-week culture. Cryopreserved MSCs which were frozen by a normal freezer or a CAS freezer were transplanted into bone defects artificially made in calvaria of 4-week-old rats. Non-cryopreserved MSCs were used as a control. The rats were sacrificed at 8, 16, or 24 weeks after transplantation and the bone regeneration area was measured. Proliferation rates of MSCs after 1 week were significantly higher in the CAS-freezing-thawing group than in the CAS-freezing group. The extent of new bone formation in the CAS-freezing-thawing group tended to be larger than in CAS-freezing group 24 weeks after transplantation. These results suggest that a magnetic field enhances cell survival during thawing as well as freezing.

Cranial suture-like gap and bone regeneration after transplantation of cryopreserved MSCs by use of a programmed freezer with magnetic field in rats.

Mesenchymal stem cells (MSCs) can be used for regeneration of various organs and tissues. A previous study revealed that cryopreserved MSCs, which were frozen by a programmed freezer with a magnetic field (Cells Alive System: CAS) and cryopreserved for 7 days in a -150°C deep freezer, can maintain high survival and proliferation rates while retaining both adipogenic and osteogenic differentiation abilities. The purpose of this study was to examine MSC viability and tissue regenerative ability after long-term cryopreservation using a CAS freezer. MSCs were isolated from rat femora bone marrow and cryopreserved in a -150°C deep freezer (CAS group) or directly cryopreserved in a deep freezer (Direct group). After 3 years, the cells were thawed and the number of viable cells was counted. Cell proliferation was also examined after 14 days in culture. For histological examination, forty 4-week-old Fischer 344 male rats received bone and sagittal suture defects with a diameter of 6.0mm, and MSCs (CAS or Direct group) cryopreserved for 1 year were grafted with membranes. Non-cryopreserved MSCs (Control group) were transplanted to an additional twenty rats. The rats were sacrificed at 4, 8, 16, and 24 weeks after surgery. The parietal bones, including the sagittal suture, were observed under a light microscope and the extent of bone regeneration was measured. Our results indicate that MSCs survival and proliferation rates were significantly higher in the CAS group than in the Direct group. In the Control and CAS groups, a large amount of new bone formation and a suture-like gap was identified 24 weeks after transplantation, whereas only a small amount of new bone formation was observed in the Direct group. These results suggest that the CAS freezer is amenable to long-term cryopreservation of MSCs, which can be applied to the regeneration of various tissues, including bone tissue with suture-like gap formation.

Cryopreservation of osteoblasts by use of a programmed freezer with a magnetic field.

In order to determine a suitable condition for osteoblasts cryopreservation, murine osteoblasts were freezed by programmed freezer with a magnetic field (CAS freezer). After 7 days cryopreservation at -150°, the number of survival cells immediately after thawing and the growth rate of cultured cells for 48 hours were examined. Gene and protein expression of alkaline phosphatase (ALP), osteopontin (OPN) and bone sialoprotein (BSP) were compared between cryopreserved and non-cryopreserved groups. As a result, a plunging temperature of -30°, a hold-time at -5° for 15 minutes and a 0.1 mT of magnetic field led to the largest survival and growth rate. Moreover, there was no significant difference in ALP, OPN and BSP mRNA and protein expression between cryopreserved and control groups. From these results, it was suggested that the CAS freezer is available for osteoblast cryopreservation and bone tissue banking can be established in the future.

Effects of cryopreservation with a newly-developed magnetic field programmed freezer on periodontal ligament cells and pulp tissues.

The purpose of this study was to evaluate the effects of long-term cryopreservation on the isolated human periodontal ligament cells (PDL) and pulp tissues. In the first part of study, 10 freshly extracted teeth were selected and divided into two groups. In the cryopreserved group, the teeth were frozen for 5 years using a programmed freezer combined with a magnetic field, known as Cells Alive System "CAS". As for the control group, freshly extracted teeth were used. In each group, extracted PDL tissues were cultured and gene expression and protein concentration of collagen type I, alkaline-phosphatase (ALP) and vascular endothelial growth factor (VEGF) was compared between the two groups. In the second part, pulp tissues were obtained from 10 mature and immature third molars which were freshly extracted or cryopreserved for three months. Expression of VEGF and nerve growth factor (NGF) mRNAs and the protein concentration in the supernatant were investigated. Results indicated that long-term cryopreservation with the use of CAS freezer cannot affect the growth rate and characteristics of PDL cells. There was no significant difference in VEGF expression and VEGF and NGF protein concentration of pulp cells derived from cryopreserved teeth with immature apex and control group with mature root formation. Finally, proper PDL regeneration and appropriate apexogenesis after transplanting magnetically cryopreserved immature tooth was clinically confirmed. These findings demonstrate that teeth banking with the use of magnetic field programmed freezer can be available for future autotransplantation as a treatment modality for replacing missing teeth.

Aberrantly spliced alpha-dystrobrevin alters alpha-syntrophin binding in myotonic dystrophy type 1.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by a CTG repeat expansion in the DMPK gene. Aberrant messenger RNA (mRNA) splicing of several genes has been reported to explain some of the symptoms in DM1, but the cause of muscle wasting is still unknown. By contrast, many forms of muscular dystrophy are caused by abnormalities of the dystrophin-glycoprotein complex (DGC). alpha-Dystrobrevin is a key component of the DGC in striated muscle and plays important roles in maturation and signal transduction by interacting with alpha-syntrophin. The goal of this study was to investigate alternative splicing of alpha-dystrobrevin in DM1 and examine alpha-syntrophin binding of different alpha-dystrobrevin splice isoforms. METHODS: Splicing patterns of alpha-dystrobrevin in DM1 muscle were studied by reverse-transcriptase PCR. Expression of the variant splice isoform was examined by immunoblotting and immunohistochemistry. Alternatively spliced isoforms were expressed in cultured cells to investigate interaction with alpha-syntrophin. alpha-Syntrophin expression was examined by immunoblotting. RESULTS: alpha-Dystrobrevin mRNA including exons 11A and 12 was increased in both skeletal and cardiac muscle of DM1 patients. The aberrantly spliced alpha-dystrobrevin isoform was localized to the sarcolemma, and showed increased binding with alpha-syntrophin. Furthermore, levels of alpha-syntrophin associated with the DGC were increased in DM1 muscle. CONCLUSION: Alternative splicing of alpha-dystrobrevin is dysregulated in myotonic dystrophy type 1 (DM1) muscle, resulting in changes in alpha-syntrophin binding. These results raise the possibility that effects on alpha-dystrobrevin splicing may influence signaling in DM1 muscle cells.

Topical application of the immunosuppressant tacrolimus accelerates carcinogenesis in mouse skin.

BACKGROUND: Tacrolimus, produced by the fungus Streptomyces tsukabaensis, is a potent macrolide immunosuppressant widely used in liver and kidney transplantation. Topical tacrolimus has recently been found to be an effective treatment for atopic dermatitis (AD). OBJECTIVES: Because of the well-known association between T-cell immunosuppression and an increased risk of carcinogenesis, we investigated the effect of topical tacrolimus on skin carcinogenesis in 117 mice. METHODS: Approximately 8 cm2 of the shaved dorsal skin of 7-week-old female CD-1 mice was treated with 7,12-dimethylbenz[alpha]anthracene (DMBA) dissolved in acetone, which is in general use as a tumour initiator, or acetone alone, on day 1 of the experiment, followed by promoting treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) with or without tacrolimus, or acetone with or without tacrolimus, for 20 weeks. The mice were divided into six treatment groups: (1) DMBA followed by acetone; (2) DMBA followed by TPA; (3) DMBA followed by acetone + tacrolimus; (4) DMBA followed by TPA + tacrolimus; (5) acetone followed by acetone + tacrolimus; and (6) acetone followed by acetone (control). RESULTS: The induction of skin tumours was significantly greater in the TPA-treated groups than in the absence of TPA. However, after 14 weeks there was marked synergy between tacrolimus and the DMBA/TPA regimen, with 0.47 +/- 0.13 (mean +/- SD) new tumours per mouse per week in group 4 vs. 0.10 +/- 0.025 in group 2 (P < 0.01), and 0.01 +/- 0.002 in group 3. A significant reduction in the CD4/CD8 ratio was found in axillary and inguinal lymph nodes in tacrolimus-treated mice, supporting the presumption that the immunosuppressive effect of the drug was responsible for its effect in promoting tumorigenesis. The major increase in tumours caused by topical tacrolimus was of papillomas, not squamous cell carcinomas. Papillomas are uncommon in humans, and are benign. However, 8.5% of the tumours found in the experiment were squamous cell carcinomas, and a considerable synergy between topical tacrolimus and conventional carcinogens was observed, raising the spectre of some risk of skin carcinogenesis in AD patients undergoing prolonged treatment with tacrolimus. CONCLUSIONS: Caution and careful surveillance are required with regard to skin lesions in patients treated with tacrolimus for prolonged periods.

Protein oxidative damage in the stratum corneum: Evidence for a link between environmental oxidants and the changing prevalence and nature of atopic dermatitis in Japan.

BACKGROUND: The incidence of atopic dermatitis (AD) has increased in Japan, along with the number of patients with severe and treatment-resistant AD in urban and industrial areas. We hypothesize that these changes could be due to increased reactive oxygen species (ROS) generated from environmental pollution and solar radiation. OBJECTIVES: To demonstrate whether direct oxidative protein damage of the stratum corneum of the biopsied skin from AD patients is increased when compared with controls. PATIENTS AND METHODS: Carbonyl moieties in skin biopsies from 75 patients with AD were assessed using both spectrophotometric and immunohistochemical detection of the formation of dinitrophenylhydrazone (DNP) from dinitrophenylhydrazine (DNPH). These were compared with diseased and normal controls. Lipid peroxidation was also assessed by staining with antibody to 4-hydroxy-2-nonenal (4-HNE), an aldehyde product of oxidized omega-6-fatty acids. In addition, the activity of superoxide dismutase (SOD), an effective scavenger of ROS, was assessed and compared with controls. RESULTS: The level of protein carbonyl moieties in patients' skin was elevated and correlated directly with the severity of the disease. In contrast, DNP formation was not significantly increased in diseased controls, when compared with healthy volunteers, and no statistical significance was found between the two control groups. SOD activity was increased except for those with extra-severe disease. Positive staining with anti-DNP antibody and anti-4-HNE antibody were found in the most superficial layers of the stratum corneum. CONCLUSIONS: This study has found an association between AD severity and markers of ROS-associated damage, adding weight to the hypothesis that environmentally generated ROS may induce oxidative protein damage in the stratum corneum, leading to the disruption of barrier function and exacerbation of AD.

Direct-antiglobulin-test-negative immune haemolytic anaemia and thrombocytopenia in a patient with Hodgkin's disease.

A case of direct-antiglobulin-test (DAT)-negative auto-immune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP) associated with Hodgkin's disease (HD) is reported. A 52-year-old male was admitted with anaemia, thrombocytopenia, and lymphadenopathy. The patient was DAT negative, although he exhibited the clinical features of warm-type AIHA and elevated levels of red-blood-cell-associated IgG (RBC-IgG). The serum level of platelet-associated IgG (PA-IgG) was markedly increased. A biopsy specimen of the inguinal lymph nodes showed HD of mixed cellularity. Marked improvement of subjective symptoms, normalization of haematological values and a decrease in the level of both RBC- and PA-IgG were observed after the start of combination chemotherapy for HD. Although the association of HD, ITP, and/or AIHA has been infrequently reported, the measurement of RBC-IgG is recommended in cases of HD with anaemia even though DAT is negative, since HD is known to be associated with various protean immunological abnormalities.

Treatable subsets in cancer of unknown primary origin.

The purpose of this study was to investigate the treatable subsets in cancer of unknown primary origin (CUP). Fifty patients (27 males and 23 females; median age, 53 years) with CUP diagnosed between April 1992 and June 1999 were analyzed retrospectively. Of the 50 patients, 39 received chemotherapy: platinum-based in 31, non-platinum-based in 4, and clinical trials of new agents in 4. Of the 39 patients, 13 (33.3%; 95% confidence interval: 19.1 - 50.2%) showed objective responses, with 4 complete responders. Patients with poorly differentiated carcinomas in whom beta-subunit of human chorionic gonadotropin (beta-HCG) was elevated more than 10 mIU / ml and female patients with peritoneal adenocarcinomatosis achieved high response rates (83.3% and 80%, respectively) with platinum-based chemotherapy, as compared with only a 15.3% response rate in the remaining patients. Platinum-based chemotherapy provided promising results in patients with poorly differentiated carcinomas and in female patients with peritoneal adenocarcinomatosis. Significantly elevated serum levels of beta-HCG in patients with poorly differentiated carcinoma might predict a better response to platinum-based chemotherapy. However, the investigation of novel chemotherapeutic approaches is warranted for other groups of patients with CUP.

A novel dimorphism in the human SRY gene: usefulness in human migration studies.

A nucleotide polymorphism of C or T was detected at position 465 in the sex-determining region Y (SRY) gene. To evaluate the utility of this dimorphism in human population studies, the frequency and the frequency of the haplotype combined with the two polymorphic loci YAP and M9 were examined in a total of 130 unrelated Japanese and 130 unrelated German males. The T nucleotide was found in 24.6% (32/130) of the Japanese but not in any of the 130 German males. Accordingly, four of the eight possible combination haplotypes of SRY/YAP/M9 were identified in the Japanese population, but one of the four haplotypes comprising SRY(T) was absent in the German samples. This suggests that the C to T transition may be more recent than the YAP insertion or the M9 transversion and the change might have occurred in an ancestral Asian population. These results imply that the dimorphism at the SRY gene is one of the Y-linked markers useful for human population studies and also for ethnic identification of forensic samples.

Reduction of metallothioneins promotes the disease expression of familial amyotrophic lateral sclerosis mice in a dose-dependent manner.

We previously reported that abnormal copper release from mutated Cu, Zn-superoxide dismutase (SOD1) proteins might be a common toxic gain-of-function in the pathogenesis of familial amyotrophic lateral sclerosis (FALS) [Ogawa et al. (1997) Biochem. Biophys. Res. Commun., 241, 251-257.]. In the present study, we first examined metallothioneins (MTs), known to bind copper ions and decrease oxidative toxicity, and found a twofold increase in MTs in the spinal cord of the SOD1 transgenic mice with a FALS-linked mutation (G93A), but not in the spinal cord of wild-type SOD1 transgenic mice. We then investigated whether the clinical course of FALS mice could be modified by the reduced expression of MTs, by crossing the FALS mice with MT-I- and MT-II-deficient mice. FALS mice clearly reached the onset of clinical signs and death significantly earlier in response to the reduction of protein expression. These results indicated that the copper-mediated free radical generation derived from mutant SOD1 might be related to the degeneration of motor neurons in FALS and that MTs might play a protective role against the expression of the disease.

Hepatic arterial infusion of 5-fluorouracil for liver metastases from pancreatic carcinoma: results from a pilot study.

BACKGROUND/AIMS: Liver metastasis is a common progression of pancreatic carcinoma, but an effective chemotherapy has not been established. The purpose of this study was to examine the efficacy and safety of a hepatic arterial infusion of 5-FU in patients with liver metastasis from pancreatic carcinoma. METHODOLOGY: Thirteen patients were enrolled in a pilot study of a hepatic arterial infusion of 5-FU therapy. They received 5-FU for 5 days at a dose of 500 mg/m2/day by continuous hepatic arterial infusion every 4 weeks. RESULTS: One patient showed a partial response, while 6 showed no change. Of these 6 patients, 2 showed a minor response. The overall response rate was 8% (95% confidence interval: 0-22%). Nausea and vomiting were the most common types of toxicity. Three patients (23%) had hepatic arterial occlusion. There were no life-threatening toxicities or complications. The overall median survival time was 15.9 weeks. CONCLUSIONS: Hepatic arterial infusion of 5-FU in patients with liver metastasis from pancreatic carcinoma is tolerable but is minimally effective at this dose and schedule. The schedule of administration should be modified.

Correlation of tissue and plasma RANTES levels with disease course in patients with breast or cervical cancer.

The beta-chemokine RANTES was measured in plasma in 43 patients with breast cancer and in 23 patients with cervical cancer, and the RANTES content in primary tumors, tumor metastatic to lymph nodes, and clinically normal skin or pelvic mucosa was measured. In addition, plasma levels were determined in all of the patients for the platelet-derived chemokine beta-thromboglobulin (beta-TG) and for IFN-gamma, interleukin (IL)-2, IL-4, IL-5, and IL-10, along with serum IgE levels and blood eosinophils. Plasma RANTES levels were found to be higher in order of stages IV, III, II, and I of each cancer except for stage I. A marked increase in plasma RANTES level (> 10,000 pg/ml) was found in 27% of patients with progressive malignancy but in none of those in clinical remission. The platelet RANTES content was correspondingly decreased in those patients with increased plasma RANTES levels. Beta-TG showed a pattern similar to RANTES both in plasma and platelets, but with much less dramatic differences between patients with different stages of disease. Other allergic parameters, IgE, eosinophils and plasma IFN-gamma, IL-2, -5, and -10, were not elevated in the cancer patients. The RANTES content was markedly elevated in the primary tumor and metastatic lesions (lymph node or skin) from all of the patients with breast or cervical cancer, irrespective of the plasma RANTES level. In addition, in patients with progressive breast or cervical cancer, but not in patients thought to be cured of these tumors, the RANTES content was markedly increased in clinically normal tissue taken from near the operative site several months postoperatively, as well as in intact skin or mucosa taken perioperatively near the excised tumor. This study suggests an as-yet-undefined but important role played by RANTES in carcinogenesis, as well as the possibility that a RANTES assay in tissue surrounding a tumor or postoperative tumor site may help predict prognosis in these patients.

Visualization of blood flow in hepatic vessels and hepatocellular carcinoma using B-flow sonography.

PURPOSE: A B-flow sonographic technique was recently developed to provide direct visualization of blood flow with gray-scale sonography. Compared with color Doppler sonography, B-flow imaging has wideband resolution and a high frame rate. The purpose of this study was to evaluate the usefulness of B-flow sonography for visualizing blood flow in hepatic vessels and tumor vascularity in patients with liver cirrhosis or hepatocellular carcinoma (HCC). METHODS: Twenty-five patients with liver cirrhosis, including 15 with HCC, were studied by B-flow and color Doppler sonography. Blood-flow detection rates in portal veins and hepatic arteries and tumor vascularity in HCC were analyzed, and the 2 methods were compared. RESULTS: Using B-flow, blood flow was visualized in the portal vein in 23 (92%) of 25 patients and was visualized in the hepatic artery separately from the portal vein in 9 (36%) of 25 patients. The blood-flow signals were visualized only within vessels, never "bleeding" outside the vessel's lumen. Blood flow in the portal vein was observed with color Doppler sonography in all 25 patients, but the hepatic artery was never clearly separated from the portal vein. Vascularity within the HCC tumor was detected in 9 (60%) of 15 nodules with B-flow imaging, and fine arteries flowing into the tumor were observed in 6 nodules. Color Doppler sonography detected blood flow in 13 (87%) of the 15 HCC nodules. CONCLUSIONS: Blood flow in hepatic vessels and tumor vessels of HCC were visualized with B-flow sonography. B-flow sonography is a potentially useful technique for the evaluation of liver vascularity and intratumoral vessels.

Bacterial photosynthesis begins with quantum-mechanical coherence.

In the antenna system of photosynthetic bacteria, pigments form circular aggregates whose excitations are excitons with quantum-mechanical coherence extending over many pigments. These excitons play crucial roles in light harvesting, storage, and excitation-energy transfer (EET). EET takes place rapidly to and/or from optically forbidden exciton states, without total transition dipole, within the antenna system and to the reaction center. Such EETs cannot be rationalized by Förster's formula, the traditional theory on EET, because it allows EET only between optically allowed states. The coherence in the excitons seems to prohibit rapid EET on this formula. The bacteria overcome this difficulty by circumventing the coherence, using the effects of the physical size of an aggregate that is larger than the shortest distance between pigments in the donor and pigments in the acceptor. The shortest-distance pair therein cannot detect whether the aggregate has a nonvanishing total transition dipole or not, since the pair see effectively only the transition dipole on the other pigment in themselves. The transition dipole facilitates rapid EET even to and/or from optically forbidden exciton states. Such EETs have enabled us to develop a general formula for the rate constant of EET. This is a formula in the weak-interaction limit, and so is Förster's formula, but it correctly takes into account the above size effect.

The dangers of snowboarding: a 9-year prospective comparison of snowboarding and skiing injuries.

We studied 2,552 snowboarding injuries and 5048 skiing injuries sustained during 1988-97. The number of snowboarding injuries had been increasing year by year and was 6 times as many as skiing injuries (2.0 versus 0.35 per 1,000 visits). The types of snowboarding injuries included fractures (39%), lacerations (21%), dislocations (17%), and contusions (15%). Upper extremity injuries were more frequent than those in the lower extremity in snowboarders. The commonest fractures involved the radius (48%), clavicle (11%), humerus (11%), and ulna (7-8%). The shoulder joint was most commonly dislocated (55%) followed by the elbow (27%), acromioclavicular (10%), finger (4%), and hip joints. In snowboarding accidents, the rates of fractures and dislocations were higher than those in skiing in almost every part of the body. Severe injuries were commoner in snowboarding accidents. We recommend the use of appropriate equipment and instructions for beginners to prevent such injuries.

A case of inoperable esophageal carcinoma with hepatic and nodal metastases which showed a long-term survival after chemoradiotherapy including nedaplatin.

We report a case of metastatic esophageal carcinoma successfully treated with chemoradiotherapy. A 61-year-old man, diagnosed as suffering from advanced esophageal carcinoma with liver and lymph node metastases, was treated with a combination of nedaplatin (90 mg/m2/day, 1 h drip infusion, day 1), 5-fluorouracil (800 mg/m2/day, continuous infusion, days 1-5), and radiotherapy (2 Gy/day, days 1-5, 8-12 and 15-19). The cycle was repeated twice every 5 weeks from July 2, 1997. He achieved a complete response 1 month after finishing two courses of chemoradiotherapy followed by an additional three courses of chemotherapy without radiation. Seven months after the completion of radiotherapy, pericardial effusion with negative cytology was recognized. The effusion was treated by pericardiocentesis and drainage for several days. After drainage, the effusion could be easily managed with diuretics. This patient is still alive with no evidence of disease more than 2.5 years after the initiation of the treatment.