Chimerism and T-cell receptor repertoire analysis after unrelated cord blood transplantation with a reduced-intensity conditioning regimen following autologous stem cell transplantation for multiple myeloma.

A 65-year-old Japanese male was diagnosed as multiple myeloma with Bence Jones kappa type, clinical stage IIIA. His disease status reached partial remission after chemotherapy. Thereafter, he received tandem transplantation, consisting of high-dose chemotherapy with autologous stem cell transplantation (ASCT), followed by unrelated cord blood transplantation (U-CBT). U-CBT with a reduced-intensity conditioning regimen (RI-CBT) was performed in August 2003. HLA mismatch between the patient and the CBT donor was present at two serological loci (B and DR). A total nucleated CBT cell dose of 2.45 x 10(7)/kg body weight was infused on day 0. Graft-vs.-host disease (GVHD) prophylaxis consisted of cyclosporine A and short-term methotrexate. Neutrophil engraftment (>0.5 x 10(9)/l) was obtained on day 46. He developed positive cytomegalovirus antigenemia, grade II acute GVHD involving skin and liver, varicella-zoster virus infection, septic shock, hemorrhagic cystitis caused by adenovirus and acute hepatitis B virus infection after U-CBT. We retrospectively analyzed T-cell receptor (TCR) repertoire diversity and found that TCR repertoire diversity decreased continuously after U-CBT. Therefore, low-TCR repertoire diversity in this patient appears to be associated with various infections caused by immunodeficiency.

Analysis of donor-type chimerism in lineage-specific cell populations after allogeneic myeloablative and non-myeloablative stem cell transplantation.

We analyzed donor-type chimerism in CD3+, CD14.15+ and CD56+ cells from 36 patients who had undergone conventional-intensity allogeneic stem cell transplantation (CST) and 34 patients who had undergone non-myeloablative allogeneic stem cell transplantation (NST) for hematological malignancies. On day 28 after transplantation, all fractions in NST patients and CD3+ cells in CST patients who received a non-total body irradiation (TBI) regimen showed more frequent mixed chimerism (<90% donor cells) than those in patients who had received TBI. NST patients with acute graft-versus-host disease (grade II-IV) frequently showed more than 50% donor-type chimerism in CD3+ cells on day 14 (P=0.029). NST patients with <50% donor-type chimerism on day 14 and with <90% donor-type chimerism on day 28 in CD56+ cells had significantly poor 1-year overall survival (0 vs 91%, P<0.001 and 20 vs 74%, P=0.002, respectively). Both NST and CST patients with <90% donor-type chimerism in CD14.15+ cells on day 28 had significantly poor 1-year overall survival (14 vs 70%, P=0.005 and 0 vs 66%, P=0.002, respectively). Our data show that the extent of donor-type chimerism in lineage-specific cells appears to have an impact on outcome after allogeneic stem cell transplantation.

[Syndrome of inappropriate secretion of antidiuretic hormone and neurotoxicity induced by vincristine and alkylating agents during chemotherapy for malignant lymphoma of thyroid gland].

We report a syndrome of inappropriate secretion of antidiuretic hormone (SIADH), neurotoxicity and facial erythema induced by several anti-cancer drugs in a case of malignant lymphoma of thyroid gland. A 68-year-old male was admitted, complaining of neck tumor and dyspnea. On admission, he was treated with vincristine (VCR) for bronchostenosis due to malignant lymphoma. Neck tumor and mediastinal lymph node swelling reduced. On the ninth day after chemotherapy of VCR, a consciousness disturbance was found and he was diagnosed as having SIADH. Following chemotherapy of cyclophosphamide, SIADH was also induced so he was treated with irradiation for neck and mediastinal field, instead of chemotherapy. During irradiation, however, enlargement of systemic lymph nodes appeared, and the chemotherapy was resumed. He achieved partial remission, but somnolence after ifosfamide and facial erythema after ranimustine were observed. In spite of the difference in the chemical structure of these anti-cancer drugs, several side effects occurred. It is suggested that the direct effects of drugs on the nervous system were SIADH and neurotoxicity.

Secondary aortoduodenal fistula complicating aortic grafting, as a cause of intermittent chronic intestinal bleeding.

Intermittent intestinal bleeding persisted in a 77-year-old male, who had undergone grafting for abdominal aortic aneurysm. Each attack lasted for a few weeks and spontaneously resolved. Only a minute abnormality was found in the third portion of the duodenum; barium studies showed a segmental narrowing, but endoscopy disclosed only a small erosion in that portion. Massive and fatal gastrointestinal hemorrhage broke out 6 months after the onset of bleeding. Autopsy revealed an adhesion area with a small fistula formation between the duodenum and aorta. Even slight endoscopic findings should be considered suggestive of aortoenteric fistula in patients after aortic surgery.

Combination chemotherapy of carboplatin and cytosine arabinoside for high-risk leukemia: a pilot study.

Fourteen patients with high-risk leukemia (six with relapsed AML, three with relapsed ALL, one with AML-M0, four with CML in myeloid blastic crisis) were treated with a combination chemotherapy of carboplatin (200-300 mg/m2/day) and cytosine arabinoside (100 mg/m2/day) by 24 h continuous infusion for 5-7 days. Five patients (35.7%) achieved complete remission including two patients complicated with myelofibrosis (one with AML-M0 and one with CML in myelo-megakaryocytic crisis). Thirteen patients had nausea and vomiting, five patients had severe, prolonged neutropenia for which it was necessary to administer granulocyte colony-stimulating factor and six patients had severe thrombocytopenia. We concluded that this regimen is effective for the treatment of high-risk leukemia.

Acute graft-versus-host disease of the gut.

A 28-year-old man with acute promyelocytic leukemia at first early relapse received HLA-matched allogenic bone marrow transplantation (BMT) at first early relapse. Cyclosporin A and methotrexate were administered at conventional doses as a prophylaxis for graft-versus-host disease (GVHD). He presented with severe bloody diarrhea on day 87 after BMT. Examination of the lower gastrointestinal tract revealed diffuse mucosal change of inflammation. A diagnosis of late onset of acute gut GVHD was made, in the absence of other manifestations such as skin and liver involvement. A further survey is needed to clarify the incidence and the pathogenesis of atypical gut GVHD.

Extracellular ATP promotes cellular growth of glomerular mesangial cells mediated via phospholipase C.

The present study was undertaken to determine whether extracellular ATP promotes cellular growth of glomerular mesangial cells. ATP increased inositol 1,4,5-trisphosphate (IP3) production and cellular free calcium concentration ([Ca2+]i) in a dose-dependent manner. None of ADP, AMP or adenosine caused an increase in IP3 production or [Ca2+]i mobilization. Also, ATP activated mitogen-activated protein (MAP) kinase and 3H-thymidine incorporation and increased the absorbance by colorimetric assay in a dose-dependent manner. Again, either of ADP, AMP or adenosine had no effect. These results indicate that extracellular ATP binds to P2 purinergic receptors and activates phospholipase C in glomerular mesangial cells. Such a signal transduction promotes cellular growth of mesangium.

[Clinical experience with cefixime in urinary tract infections].

Cefixime (CFIX, Cefspan), a new oral cephem, was used in the treatment of urinary tract infections, and was evaluated for its therapeutic effectiveness and safety at the Department of Urology, Osaka Rosai Hospital. In a total 129 cases, to which daily doses of 200 mg of CFIX were divided into 2 doses and administered clinical efficacies in 35 cases of women with acute uncomplicated cystitis treated for 3.9 days in average and 79 cases with complicated urinary tract infections (UTIs) treated for 5.9 days in average were assessed, according to the Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents on UTI (3rd ed.) recommended by the Japan UTI Committee with our own minimum modifications. Mid term urine and catheterized urine were examined as urine samples for bacteriological evaluation. Clinical efficacies in 35 cases with acute uncomplicated cystitis were excellent in 24 (69%) and moderate in 11 (31%), with an overall clinical efficacy rate of 100%. Clinical efficacies in 79 patients with complicated UTIs were excellent in 24 (30%), moderate in 26 (33%) and poor in 29 (37%), with an overall clinical efficacy rate of 63%. All of the 35 bacterial strains isolated from urine samples of uncomplicated UTIs patients were totally eradicated by the CFIX treatment, while 85 strains (79%) were eradicated among 107 strains isolated from urine samples of complicated UTIs patients. Subjective adverse reactions were observed in 4 cases (3.1%) out of a total of 128 patients, as general malaise in 1 and lower abdominal symptoms in 3 were recorded. All of them disappeared after the termination of CFIX administration.(ABSTRACT TRUNCATED AT 250 WORDS)

[Retroperitoneal plasmacytoma: a case report].

We have experienced a case of retroperitoneal plasmacytoma. A 47-year-old man was admitted to our hospital with the chief complaints of right lumbago and lower abdominal dull pain. Roentgenography revealed retroperitoneal tumors, and right nephrectomy and excision of left pararenal tumors were performed. The histological examination and urine immunoelectrophoresis showed retroperitoneal plasmacytoma. No signs or symptoms of multiple myeloma were recognized postoperatively. The literature is reviewed briefly concerning the diagnosis and treatment of retroperitoneal plasmacytoma.

[Clinical evaluation of cefixime (CFIX) in the treatment of urinary tract infection].

Cefixime (CFIX, Cefspan), a new oral cephem, was used in the treatment of urinary tract infections, and was evaluated for its therapeutic effectiveness and safety at the Department of Urology, Osaka University Hospital and 16 affiliated hospitals. A total of 238 patients were administered daily doses of 200 or 400 mg. Clinical efficacy was assessed on 92 female patients with acute uncomplicated cystitis and 42 patients with complicated UTI according to the Criteria for Clinical Evaluation of Antimicrobial Agents in UTI (3rd ed.) recommended by the Japan UTI Committee, to which we added our own minimum modification. Clinical efficacy was evaluated as excellent in 57 of the acute uncomplicated cystitis cases, moderate in 33 and poor in 2, with an overall clinical effectiveness rate of 98%. Clinical efficacy was evaluated as excellent in 12 of the complicated UTI cases moderate in 12 and poor in 18, with an overall clinical effectiveness rate of 57%. In one case of uncomplicated pyelonephritis, CFIX showed an excellent efficacy. Of the total of 102 bacterial strains isolated from uncomplicated UTIs, 95 (93%) were eradicated by CFIX, while 36 (72%) eradicated in 50 strains isolated from complicated UTIs. Subjective adverse reactions were seen in 4 cases (1.7%) of the 236 patients, as generalized pruritus and upper gastrointestinal discomforts. Abnormal laboratory findings were recorded in 6 out of 141 cases. They were increases in serum GPT, GOT, alkaline phosphatases, total bilirubin, as well as increases in peripheral leukocytes. These adverse symptoms and abnormal laboratory findings disappeared after the termination of CFIX administration. CFIX might therefore be considered as a clinically useful oral antibiotic in the treatment of UTI.

[Clinical evaluation of monotherapy with ceftazidime for severe infections complicating hematological disorders. Hyogo Cooperative Study Group of Infectious Diseases Complicating Hematological Disorders].

Clinical effects of the monotherapy with ceftazidime (CAZ) were evaluated in patients with severe infections associated with febrile granulocytopenia in hematological disorders in 10 institutions. CAZ (4-6g/day) was administered intravenously by drip infusion divided into 2 to 4 doses. 83% of the underlying diseases were hematological malignancies. Infections mainly consisted of documented sepsis (10%), presumed sepsis (60%). Overall efficacy rate was 65%, and that of septic patients was 83.3%. Adverse reactions were minimal, and this study revealed safety of CAZ.

A case of gastric cancer in which long-term administration of 5'-deoxy-5-fluorouridine proved effective.

A patient diagnosed with Borrmann type 4 gastric cancer (mucinous adenocarcinoma), who had refused surgery, was treated by oral administration of 1200 mg/day 5'-deoxy-5-fluorouridine for about 23 weeks. This resulted in substantial improvement of her condition, i.e. the tumour almost completely disappeared, distensibility improved between the central region of the corpus ventriculi and the angulus, and only small protrusions remained on the anterior and posterior walls and the pars pylorica of the lesser curvature. Mild anorexia and diarrhoea were noted as adverse reactions although these symptoms subsided by reducing the dose or temporarily stopping treatment, thereby allowing long-term treatment. Long-term use of 5'-deoxy-5-fluorouridine proved temporarily effective in this patient. The patient died about 3 years and 7 months after starting therapy. Examination showed that the cancer had been mainly in the stomach and that it had metastasized to the colon and pancreas. The liver was free of metastasis.

[A case of signet ring cell carcinoma of the urinary bladder].

A case of primary signet ring cell carcinoma of the urinary bladder is reported. A 52-year-old man was admitted with the complaint of gross hematuria. Cystoscopy showed non-papillary tumor on the right lateral wall. Abdominal CT, Ga scintigraphy, upper gastrointestinal series and barium enema, revealed no signs of a tumor other than the bladder carcinoma. The routine hematologic and chemistry profiles showed no abnormalities except for the serum level of carcinoembryonic antigen elevated to 210 ng/ml. Total cystectomy and right nephroureterectomy with left cutaneous ureterostomy was performed and the surgical specimen showed adenocarcinoma of the bladder. The patient died 5 months after the operation, and autopsy was performed. No tumors were found on the mucosa of the whole digestive tracts or pancreas. This case might be of primary adenocarcinoma originated from the bladder. The literature on the differential diagnosis of the cases reported as bladder adenocarcinoma are reviewed briefly.

[Retroperitoneal ganglioneuroma: report of 3 cases].

We have experienced 3 cases of retroperitoneal ganglioneuroma. One case was in a 5-year-old boy with the chief complaint of abdominal mass. The preoperative diagnosis was neuroblastoma due to excessive urinary excretion of vanillylmandelic acid. The other two cases were in adults, 40 and 28 years old, and were found incidentally. All three cases were doing well without any clinical signs of recurrence almost 10 years, 5 years, and 6 months, postoperatively. The literature is reviewed briefly concerning some cases in children under 5 years of age whose ganglioneuromas were sometimes confused with neuroblastoma because of excessive catecholamines.

[A case of gastric cancer in which long-term administration of 5'-deoxy-5-fluorouridine (5'-DFUR) proved effective].

A patient with gastric cancer (mucinous adenocarcinoma), classified as Borrmann Type 4, refused surgery and a chemotherapy regimen was applied. 5'-DFUR (5'-deoxy-5-fluorouridine) was administered orally at 1,200 mg/day for 23 weeks, for a total dosage of 110.8 g. The patient showed marked remission: the tumor nearly disappeared, distensibility reappeared from the central region of the corpus ventriculi to the incisura angularis, and only small protrusions classified by Yamada's criteria as Type I, remained on the anterior and posterior wall and pars pylorica of the lesser curvature. Side effects were slight anorexia and diarrhea. These could be avoidable by temporal interruption of administration or dosage reduction, to allow long-term treatment. This case can be considered to be one example in which 5'-DFUR proved effective against gastric cancer.

[Metastatic renal tumors: clinical report of three cases and review of 136 cases including 38 cases from the Japanese literature].

Three cases of metastatic renal tumor are reported. The first case was of a 61-year-old man, who had a Miles' operation for rectal adenocarcinoma 30 months before, and suffered from high fever and right flank pain. Right nephrectomy was carried out and the kidney was found to contain an adenocarcinoma identical to the one previously removed from the rectum. He died 1 year after nephrectomy. The second case was of a 35-year-old man, who had undergone left pneumonectomy for a squamous cell carcinoma of the bronchus. One month later, he was readmitted with cloudiness of consciousness and high fever. Investigations revealed right kidney, adrenal gland and brain malignancies, and which were ectomized totally. On pathological examination all ectomized tissues were metastatic squamous cell carcinoma. He died 1 month after the second operation. The third case was of a 48-year-old man, who had undergone left pneumonectomy for a squamous cell carcinoma of the bronchus. One year after pneumonectomy, abdominal CT showed a left renal tumor. Right nephrectomy was performed and pathological examination revealed a metastatic squamous cell carcinoma. He is now alive 4 months after nephrectomy without any sign of recurrence. A total of 136 cases of metastatic renal tumors including 38 cases from the Japanese literature, are reviewed.

Splenic vein thrombosis as a consequence of chronic pancreatitis: a study of three cases.

Splenic vein obstruction was found in three patients with chronic pancreatitis. All had suffered epigastric pain, but no specific findings which suggested obstruction of the splenic vein were evident on physical or laboratory examinations. Enlarged pancreatic contour with calculi and pseudocyst formation were observed by CAT scan in all three cases. Gastric varices were found in two patients who had episodes of gastric bleeding. The splenic vein was shown to be occluded in two patients in the venous phase of celiac angiography and was entirely nonvisualized by percutaneous portography in the third case. The first patient underwent elective surgery, while the second patient had emergency surgery due to intraabdominal abscess formation with gastric bleeding. The surgical procedure in both patients was splenectomy coupled with distal pancreatectomy. Thrombus formation was confirmed by venous dissection at surgery.