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The FIB-4 index is a simple formula to predict liver fibrosis based on the standard biochemical values (AST, ALT and platelet count) and age. We here investigated the utility of the index for noninvasive prediction of progression in liver fibrosis. The time-course alteration in the liver fibrosis stage between paired liver biopsies and the FIB-4 index was examined in 314 patients with chronic hepatitis C. The average interval between liver biopsies was 4.9 years. The cases that showed a time-course improvement in the fibrosis stage exhibited a decrease in the FIB-4 index, and those that showed deterioration in the fibrosis stage exhibited an increase in the FIB-4 index with a significant correlation (P0.001). Increase in the ΔFIB-4 index per year was an independent predictive factor for the progression in liver fibrosis with an odds ratio of 3.90 (P = 0.03). The area under the receiver operating characteristic curve of the ΔFIB-4 index/year for the prediction of advancement to cirrhosis was 0.910. Using a cut-off value of the ΔFIB-4 index/year0.4 or ≥ 0.4, the cumulative incidence of fibrosis progression to cirrhosis at 5 and 10 years was 34% and 59%, respectively in patients with the ΔFIB-4 index/year ≥0.4, whereas it was 0% and 3% in those with the ΔFIB-4 index/year0.4 (P0.001). In conclusion, measurement of the time-course changes in the FIB-4 index is useful for the noninvasive and real-time estimation of the progression in liver fibrosis.

There is an increasing need for accurate prediction methods of assessing individual risk for breast cancer for both clinical and research purposes. The purpose of this study is to compare the Gail and Claus model risk estimates of breast cancer among women with a family history of breast cancer. This study presents risk estimates from two models of breast cancer risk in 491 women 18 to 74 years of age with a family history of breast cancer who were recruited to risk counseling clinical trials in Seattle, Washington between 1996 and 1997. These trials included women from the general population and additional samples of Ashkenazi Jewish, African-American, and lesbian women. We estimated and compared lifetime (to age 79) and 5-year risk for developing breast cancer using the National Surgical Adjuvant Breast and Bowel Project adaptation of the Gail model and the Claus model. About one-quarter of participants fell into the Gail "high" risk category (or =1.7% risk of developing breast cancer in the next 5 years). The average lifetime risk was estimated at 13.2% by the Gail model and 11.2% by the Claus model. Estimates from the two models were moderately and positively correlated (r = 0.55) with the Gail model yielding a higher estimate than the Claus model for most participants. If women with a family history of breast cancer are being counseled regarding decisions on genetic testing, tamoxifen use, or other preventive measures, presenting both Claus and Gail estimates may be the best option.

Our aim was to describe and identify factors associated with breast cancer screening among Cambodian American women. We conducted a cross-sectional survey of 1,365 households using bilingual and bicultural interviewers. We found that low proportions of Cambodian American women were up to date on their clinical breast examinations (CBE; 42%) and mammograms (40%). More than 80% of women with female physicians have had at least one prior screening, and 52% have had the tests recently. Women with male Asian American physicians were less likely to have had screening as compared to women with female non-Asian physicians: ever had CBE (odds ratio [OR], 0.26); recent CBE (OR, 0.39); ever had mammogram (OR, 0.36); and recent mammogram (OR, 0.22). Breast cancer screening among Cambodian American women lags behind the general U.S. population. Tailored promotion efforts should address barriers and promote cancer screening by physicians, staff, and organizations serving this population.

Parallel to its established causal association with both infectious mononucleosis (IM) and young adulthood Hodgkin disease (YAHD), we propose a hypothesis that "delayed" primary EBV infection (i.e., primary infection occurring during adolescence or adulthood) is associated with elevated breast cancer risk. We evaluated this hypothesis with two investigations, one descriptive and the other analytic. The descriptive study used international/United States cancer registry data to assess the association between incidence rates of breast cancer and those of YAHD. The incidence rates of the seemingly unrelated neoplasms were strongly correlated (correlation coefficients of 0.74 and 0.88 for international and United States data, respectively; these were higher than the correlation coefficients of YAHD with two other cancers that we considered). Populations with higher incidence rates corresponded to those with higher likelihood of delayed primary EBV infection. The analytical study was based on a population-based case-control study of breast cancer in middle-aged women. Age-adjusted odds ratios of breast cancer in women who reported a history of IM, relative to women who did not, increased monotonically from 0.55 [95% confidence interval (CI), 0.05-6.17] for women with 0-9 years of age at IM onset to 2.67 (CI, 1.04-6.89) for women withor =25 years of age at IM onset (P = 0.016). An older age at tonsillectomy, another surrogate of delayed EBV exposure, was also associated with increased risk of breast cancer: odds ratios, 0.92 (CI, 0.57-1.48) and 1.76 (CI, 1.15-2.69) for women with tonsillectomy at 0-4 years of age andor =15 years of age, respectively (P = 0.018). Adjusting for additional potential confounders did not modify the associations appreciably. The implications of the findings and a potential biological mechanism are presented.

Colorectal hyperplastic polyps are benign lesions that share many risk factors with colorectal adenomas and cancers. Low folate intakes are associated with an increased risk of colon cancer. The enzyme 5,10-methylene-tetrahydrofolate reductase (MTHFR) may be linked to DNA methylation and nucleotide synthesis and thus play a role in the etiology of colorectal neoplasia. We investigated an association between the common MTHFR polymorphism (C677T) and colorectal hyperplastic polyps within the Minnesota Cancer Prevention Research Unit case-control study. Cases (n = 200) were diagnosed with colonoscopically confirmed hyperplastic polyps; controls (n = 645) were derived from the same gastroenterology practice and were polyp-free at colonoscopy. Dietary intakes were estimated from a self-administered food-frequency questionnaire prior to colonoscopy. Multivariate adjusted odds ratios (ORs) and 95% confidence intervals for MTHFR status were 0.8 (0.6-1.2; CT versus CC wild-type) and 0.9 (0.5-1.6; TT versus CC). In subgroup analyses stratified on dietary intakes of folate, vitamin B12, vitamin B6, or methionine, those with the TT genotype and either low intakes of folate or vitamin B6 were at increased risk relative to those with normal or high vitamin intake. However, most 95% confidence intervals included 1.0, and no consistent trends were observed. In contrast to our findings on colorectal adenomas, increasing alcohol consumption was associated with an elevated risk of colorectal hyperplastic polyps, regardless of genotype. The MTHFR (C677T) variant genotype does not appear to be related to risk of colorectal hyperplastic polyps, and there is no convincing evidence that MTHFR shows a different relation to risk, dependent on dietary intakes of nutrients related to its pathway.

5,10-Methylene-tetrahydrofolate reductase (MTHFR), an enzyme in folate metabolism, may play a role in the etiology of colorectal adenomas via effects on DNA methylation and nucleotide synthesis. We investigated the association between a common polymorphism (C677T, reduced MTHFR activity) and colorectal adenomas within the Minnesota CPRU case-control study. Cases (n = 527) were diagnosed with colonoscopically confirmed adenomas; controls (n = 645) were derived from the same gastroenterology practice and were polyp free at colonoscopy. Dietary intakes were obtained from a self-administered food-frequency questionnaire prior to colonoscopy. Age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals for the MTHFR genotype were 0.9 (0.7-1.2; CT versus CC wild-type) and 0.8 (0.6-1.3; TT versus CC). The associations between dietary intakes of folate, vitamin B12, vitamin B6, or methionine and risk of adenomas showed consistent patterns dependent upon MTHFR genotype. Individuals with the TT genotype and intakes of any of these nutrients in the lowest tertile were at elevated risk for adenomas (about 2-3-fold when compared with TT genotype with high intakes). These trends were more pronounced among individuals over age 60, resulting in a 3-6-fold increase for low intakes of folate, B12, and B6. An increased risk with increasing alcohol consumption was observed only among those with the CC genotype (P-trend = 0.005); among those with the TT genotype, those with moderate alcohol consumption were at lowest risk (P for interaction P = 0.02). In conclusion, nutrients involved in the MTHFR metabolic pathway may modify the relationship between the MTHFR C677T polymorphism and colorectal adenomas. Low intakes of folate, vitamin B12, and vitamin B6 increase risk among those (particularly the elderly) with the MTHFR TT genotype.

Vietnamese have higher liver cancer rates than any other racial/ethnic group in the United States. Approximately 80% of liver cancers are etiologically associated with hepatitis B virus (HBV) infection, which is endemic in Southeast Asia.A telephone survey of randomly selected Vietnamese households (n = 75) was conducted during 1998 to examine HBV knowledge among Seattle's Vietnamese community. The questionnaire included items related to the transmission of HBV, the possible sequelae of infection, and disease prevention.The response rate was 70% among reachable and eligible households. Prior to being provided with a description of the disease, two thirds of our respondents had heard of HBV infection. Less than 60% knew that asymptomatic individuals can transmit the disease to others. Most thought that HBV infection can cause liver cancer (63%) and death (80%). However, only a minority knew that infection can be lifelong (38%) and incurable (22%). Finally, 28% had never heard of the HBV vaccine. There were significant associations between knowledge and educational level as well as home ownership.The findings suggest that Vietnamese immigrants have low levels of knowledge about HBV infection, and indicate a need for targeted educational interventions aimed at reducing HBV-related liver cancer mortality.

To improve the response and decrease toxicity of the treatment non-Hodgkin's lymphomas, a prospective single-arm trial was initiated using cyclophosphamide, epirubicin, vincristine, prednisone, bleomycin, eoposide (CEOP-BE). From March 1994 to August 1997, 29 previously untreated patients with intermediate- or high-grade non-Hodgkin's lymphomas, stage II to IV, were included in the study. Complete remissions (CR) were observed in 26 patients. The 4-year overall survival (OS) was 71.3%, and the 4-year disease free survival (DFS) was 61.8%. Recurrences occurred in 11 of 26 patients. Seven of 11 patients with recurrences showed bone marrow or other extranodal lesions. CEOP-BE is an active and feasible regimen for most patients with intermediate- and high-grade non-Hodgkin's lymphomas.

The goal of this paper is to provide a preliminary description of the marital status for a large number of childhood cancer survivors participating in the Childhood Cancer Survivor Study (CCSS).This report includes children and adolescents (21 years of age) diagnosed with cancer between 1970 and 1986 at 25 oncology centers in the United States and Canada who survived at least 5 years from diagnosis. Self-reported data from 10,425 survivors are used in this preliminary descriptive summary. The proportion of survivors ever married and divorced/separated is compared to the U.S. population according to age-specific groups. The median age of the survivor population at diagnosis was 7 years and 26 years at the time martial status was ascertained. Excluded from this assessment are children15 years of age at the time of study, those whose martial status was unknown, and those married prior to diagnosis. Data for marital status of the U.S. population, as tabulated in the Bureau of Census 1995 Update, is used as a general comparison to the survivor population.Overall, 32% of the survivors reported being married or living as married, 6% being divorced or separated, 0% being widowed, and 62% having never been married. In general, compared to the U.S. population, survivors were less likely to have ever married, particularly females and whites, but, once married, were less likely to divorce/separate, again particularly females and whites. Black survivors were generally found to be more likely to have married, with males and blacks more likely to divorce/separate once married. Comparison of childhood tumor types suggested that survivors of CNS tumors, particularly males, were less likely to have ever married and more likely to divorce/separate compared to those with other cancer diagnoses and the general U.S. population.This interim evaluation of the CCSS cohort provided preliminary data describing a suggested decreased likelihood of marriage, which may be influenced by gender and/or race. These patterns must be confirmed within the entire CCSS cohort and comparisons made with an appropriate sibling comparison group before making final conclusions.

Southeast Asian women have higher invasive cervical cancer incidence rates and lower Pap testing frequencies than most other racial/ethnic groups in the United States. However, there is little information about the cervical cancer screening behavior of Cambodian-American women. Cambodian residents of Seattle were surveyed in person during late 1997 and early 1998. The PRECEDE model was used to guide the development of items that assessed predisposing, reinforcing, and enabling factors associated with cervical cancer screening participation. The estimated overall survey response was 72%. Four hundred thirteen women completed our questionnaire. Approximately one-quarter (24%) of the respondents had never had a Pap test, and over one-half (53%) had not been screened recently. The following variables were positively associated with a history of at least one Pap smear: younger age, greater number of years since immigration, belief about Pap testing for postmenopausal women, prenatal care in the United States, and physician recommendation. Women who believed in karma were less likely to have ever been screened for cervical cancer than those who did not. Six variables independently predicted recent screening: age; beliefs about regular checkups, cervical cancer screening for sexually inactive women, and the prolongation of life; having a female doctor; and a previous physician recommendation for Pap testing. The study findings indicate that culturally specific approaches might be effective in modifying the cervical cancer screening behavior of immigrant women. Programs targeting Cambodian-Americans are likely to be more effective if they are multifaceted and simultaneously address predisposing, reinforcing, and enabling factors.

OBJECTIVE: To examine the impact of a policy restricting reimbursement for Medicaid anti-ulcer drugs on anti-ulcer drug use and peptic-related hospitalizations. DATA SOURCES/STUDY SETTING: In addition to U.S. Census Bureau data, all of the following from Florida: Medicaid anti-ulcer drug claims data, 1989-1993; Medicaid eligibility data, 1989-1993; and acute care nonfederal hospital discharge abstract data (Medicaid and non-Medicaid), 1989-1993. STUDY DESIGN: In this observational study, a Poisson multiple regression model was used to compare changes, after policy implementation, in Medicaid reimbursement for prescription anti-ulcer drugs as well as hospitalization rates between pre- and post-implementation periods in Medicaid versus non-Medicaid patients hospitalized with peptic ulcer disease. PRINCIPAL FINDINGS: Following policy implementation, the rate of Medicaid reimbursement for anti-ulcer drugs decreased 33 percent (p < .001). No associated increase occurred in the rate of Medicaid peptic-related hospitalizations. CONCLUSIONS: Florida's policy restricting Medicaid reimbursement for anti-ulcer drugs was associated with a substantial reduction in outpatient anti-ulcer drug utilization without any significant increase in the rate of hospitalization for peptic-related conditions.

Efficiency of urine sediment analysis was evaluated in 423 specimens including 86 documented renal disorder ones using three methods; a traditional centrifugal and microscopic one, an image-scanning one and a flow cytometric one. Among the three methods, good correlations were observed in white blood cells and epithelial cells. Between white blood cells and bacterial counts a good correlation was observed only in the flow cytometry one. Female specimens usually demonstrated high values in white blood cells except with the microscopic method. Casts in patients with renal disorder exhibited significantly high in the flow cytometric method. In all methods, proteinuria specimens showed high cast count in the sediment. From these results we concluded that the flow cytometric method was clinically useful, especially in urinary tract disorder specimens.

To evaluate the pain experience of seriously ill hospitalized patients and their satisfaction with control of pain during hospitalization. To understand the relationship of level of pain and dissatisfaction with pain control to demographic, psychological, and illness-related variables.Prospective, cohort study.Five teaching hospitals.Patients for whom interviews were available about pain (n = 5,176) from a total of 9,105 patients in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT).None.Patients were interviewed after study enrollment about their experiences with pain. When patients could not be interviewed due to illness, we used surrogate (usually a family member) responses calibrated to patient responses (from the subset of interviews with both patient and surrogate responses). Ordinal logistic regression was used to study the association of variables with level of pain and satisfaction with its control. Nearly 50% of patients reported pain. Nearly 15% reported extremely severe pain or moderately severe pain occurring at least half of the time, and nearly 15% of those patients with pain were dissatisfied with its control. After adjustment for confounding variables, older and sicker patients reported less pain, while patients with more dependencies in activities of daily living, more comorbid conditions, more depression, more anxiety, and poor quality of life reported more pain. Patients with colon cancer reported more pain than patients in other disease categories. Levels of reported pain varied among the five hospitals and also by physician specialty. After adjustment for confounding variables, dissatisfaction with pain control was more likely among patients with more severe pain, greater anxiety, depression, and alteration of mental status, and lower reported income; dissatisfaction with pain control also varied among study hospitals and by physician specialty.Pain is common among severely ill hospitalized patients. The most important variables associated with pain and satisfaction with pain control were patient demographics and those variables that reflected the acute illness. Pain and satisfaction with pain control varied significantly among study sites, even after adjustment for many potential confounders. Better pain management strategies are needed for patients with the serious and common illnesses studied in SUPPORT.

A 23-year old woman was admitted to our hospital because of fever, leukocytopenia, thrombocytopenia and cervical lymphadenopathy. From pathological findings of the cervical lymphnode she was diagnosed as subacute necrotizing lymphadenitis (SNL). Bone marrow aspiration was hypocellular with proliferation of mature histiocytes with hemophagocytosis. Lactate dehydrogenase was elevated to 1863 IU/l and mild liver dysfunction was observed. Hepatosplenomegaly, lymphnode swelling in abdominal cavity, pleural effusion and pericardial effusion were detected. After glucocorticoid therapy all such disorders were normalized. In this course, Epstein-Barr (EB) virus genome was detected by a polymerase chain reaction method from peripheral mononuclear cells. After normalization, EB virus genome became not to be detected. From present case we concluded that EB virus was expanded in clinical course and was associated with pathogenesis of SNL.

Clinicopathological analysis was performed in 19 patients diagnosed clinically with malignant histiocytosis. Ultimately, 9 patients died and 10 are still alive. All 19 had fever of unknown origin. Among the 10 surviving patients, 6 recovered with only supportive therapy such as antibiotic treatment. One recovered with steroid therapy and 2 with VP (vincristine and prednisolone) therapy. Complications due to immunodeficiency were detected in one surviving patient and 2 who died. All 9 patients who died had anemia, and 8 had thrombocytopenia. However, among survivors, only one had anemia and only 2 had thrombocytopenia. Chromosomal abnormality was detected in one patient who died. Histiocytic cells were classified morphologically into 3 types: immature, intermediate and mature. In 4 patients who died, histiocytic cells were immature, but in 4 others mature histiocytic cells were detected. In 5 of the 10 surviving patients, histiocytic cells were of the immature type. Immuno-histochemical analysis of the origin of histiocytic cells in 8 deceased patients showed T-zone histiocytes in one, T cells in one, monocyte phagocytic system (MPS) in 5, and histiocytes of unknown origin in one. Thus, malignant histiocytosis is a heterogenous entity including reactive histiocytic disorder, lymphocytic neoplasm and true histiocytic neoplasm. In histiocyte proliferative disorders, red blood cell counts and platelet counts are useful for assessing prognosis, while cytological findings only confuse this evaluation.

The efficacy and safety of a combination regimen using flomoxef (FMOX) and tobramycin (TOB) were evaluated in the treatment of infections complicated with hematological disorders. The primary diseases in 40 patients included acute leukemia, malignant lymphoma and others. Complicated infections included 35 cases with suspected septicemia, 4 cases with septicemia and 1 case with pleuritis. Clinical responses were excellent in 10 (25.0%), good in 14 (35.0%), fair in 2 (5.0%) and poor in 14 (35.0%). The efficacy rate was 73.1% in patients with neutrophil counts higher than 501/microliters after administration, but it was 35.7% in patients with counts less than 501/microliters; the difference was statistically significant. No side effects were observed in any of the 40 patients. Abnormal laboratory data in liver functions were identified in 1 patient (2.5%). Degree of this abnormality was very slight, and the continuation of treatment was not disturbed. In conclusion, this combination therapy of FMOX and TOB thus appears to be useful and safe in therapies for infections complicated with hematological disorders.

Forty-three patients with severe infections which were complicating hematological disorders were treated with panipenem/betamipron, and the efficacy and the safety of the drug were evaluated. The results obtained are summarized below. 1. Out of 40 patients in whom efficacies are evaluable, the clinical responses were excellent in 17 patients, good in 4, fair in 7 and poor in 12, and the total clinical efficacy rate was 52.5%. 2. The efficacy rate in 7 patients who had failed to respond to prior treatment with other antibiotics was 57.1%. Thus, no significant difference was observed in efficacy rates between the patients who had failed to respond to prior treatment with other antibiotics and the patients who received no preceding antibiotics therapy. 3. Out of the 43 patients in whom the safety was evaluable, no side effects nor abnormal laboratory findings were found.

We studied the effects of granulocyte-colony stimulating factor (G-CSF) on human erythropoiesis in vivo. Changes in the peripheral blood were analyzed in 9 subjects; 3 healthy volunteers, 3 patients with pancytopenia and hypersplenism and 3 patients with chronic renal failure and severe anemia being treated with hemodialysis. We monitored erythropoiesis according to the number of highly fluorescent cells (HFC) present in the peripheral blood after staining with Auramine 0. These cells are relatively immature reticulocytes that contain much RNA. All subjects received recombinant human G-CSF at a daily dose of 100 micrograms/m2 administered intravenously for 3 to 5 days. Plasma erythropoietin was measured in patients receiving dialysis before and several times after its administration. The number of HFC increased significantly in all subjects. In 1 of 3 patients receiving dialysis, the plasma erythropoietin increased transiently but insignificantly. These findings show that G-CSF affects human erythropoiesis in vivo, but that the mechanism of its effect did not involve an increase in plasma erythropoietin.

A 33-year-old man was hospitalized because of thrombocytopenia and severe splenomegaly. On admission 78% of peripheral lymphoid cells were abnormally large, with pale cytoplasm. Flow cytometry of the abnormal lymphocytes showed that they expressed CD 2, CD 3, CD 11, CD 16, and CD 56, but not CD 4 nor CD 8, so they were T-cell large granular lymphocytes (T-LGL). Abnormal lymphocytes obtained from a lymph node expressed CD 2, CD 16, CD 38, and CD 56, but not CD 3, CD 4, and CD 8, so they were natural killer(NK) cells. Splenectomy was performed and the operative specimen showed diffuse infiltration of pleomorphic lymphocytes, probably chronic lymphocytic leukemia cells. After splenectomy, the platelet count returned to normal but the lymphocytosis continued. Two years after discharge, chemotherapy was done because of thrombocytopenia and hepatomegaly. The patient died of disseminated intravascular coagulation arising from sepsis. The differences and similarities between peripheral and lymph-node lymphocytes suggest that LGL and NK cells may be differentiated from the same kind of cell, somewhat differentiated from stem cells.

It is generally difficult to treat patients with ovarian cancer. A Tenckhoff catheter was implanted in eighteen patients for intraperitoneal chemotherapy and drainage of ascites. Sixteen cases including 5 recurrent cases were treated with anticancer drug. It could not be used in two cases by bowel adhesion, so immediately catheters were removed. CDDP (100-150 mg/body) with or without Etoposide (180-300 mg/body) in 2 liters of saline was administered via Tenckhoff catheter over 30 minutes with a dwell time of 4 hours. We have studied the kinetics of CDDP and Etoposide in ascites and blood after intraperitoneal chemotherapy. High concentrations of free-CDDP and Etoposide were reached for 4 hours in the ascites but concentrations in the blood varied. These results showed obviously high values and direct effects on the tumor cells in the abdominal cavity and the peritoneal clearance depended on the severity of carcinomatous peritonitis in each case. Twelve cases showed decrease, but 4 cases increase of ascites. Five recurrent cases and one patient of stage IV died. Seven cases are outpatients and the disease free duration of their ranges are from 1 to 24 months. Three patients are now under treatment. Intraperitoneal chemotherapy elicited only mild nausea, myelosuppression and no significant changes of renal function. No patients had signs of catheter infection and peritonitis. These findings suggested that a Tenckhoff catheter was valuable to treat and manage ovarian cancer patients with little side effect.

We evaluated the effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) given to 30 patients with hematological malignancies after cytotoxic chemotherapy. The first course of chemotherapy was not treated with rhG-CSF (control), and in the second to fourth courses, rhG-CSF was given by one of the following three ways to the patients (not necessarily in this order): 1) 10 days of administration starting 48 hr after chemotherapy, 2) 5 days of administration starting 48 hr after chemotherapy, and 3) 5 days of administration after the leukocyte counts reached to less than 2,000/microliters. The leukocyte nadirs were significantly higher in the course with 10 days of administration compared with the control course. The time needed for recovery from the leukocyte nadir was significantly shorter in 10-day course and 5-day course after the leukocyte counts reached to less than 2,000/microliters. The therapy spans became significantly shorter with all of the three patterns of administration of rhG-CSF compared with the control course. The number of days on which the leukocyte counts became less than 2,000/microliters were significantly fewer in 10-day course and 5-day course after the leukocyte counts became less than 2,000/microliters. These findings showed that rhG-CSF prevented severe neutropenia after cytotoxic chemotherapy, and (or) assisted the rapid recovery from neutropenia. These effects depend on the timing of its administration.

Twenty cases of myelodysplastic syndrome (MDS) were treated with ubenimex. Seventeen cases were treated with the drug over 90 d. Among these, 10 showed improvement of anemia, 12 an increase in platelet count which had decreased before treatment and 10 an increase in neutrophil count; however, 14 showed an increase in blast percentage in bone marrow aspirate. CD4/CD8 ratio was increased in 4 cases and shifted to a normal from an abnormal range in 6 cases. When the MDS cases were observed in refractory anemia (RA) and refractory anemia with excess blasts (RAEB), great improvement was seen, but in RAEB increase in blast percentage was also observed. CD4 increased mostly in RA and CD8 increased in RAEB. Ten cases of chronic myelocytic leukemia (CML) were first treated with ubenimex and cytostatics, then with ubenimex only. Six cases attained partial remission within 3 months, but one case showed a marked increase in white cell count and blast count and in another case a progression of splenomegaly associated with increase in white cell count. From these findings we conclude that ubenimex could be utilized in MDS or CML if the patient was at risk for strong chemotherapy.

We did a retrospective statistical study of 117 patients with non-Hodgkin's lymphoma admitted to our hospital from January 1979 to December 1988. Five-year survival was 83% for patients in stage I at diagnosis, which was significantly better than the 55% in stage II, 37% in stage III, and 34% in stage IV. Five-year survival was 74% for patients with B-cell lymphoma (74%), which was significantly better than with the 32% for T-cell lymphoma. For patients in stage I or II, five-year survival was 46% for those with nasal lymphoma, which was significantly worse than the 72% with nodal lymphoma and the 82% for those with Waldeyer's lymphoma. Sixty-eight patients were treated initially with radiation only. The relapse frequency was 20% in stage I and 40% in stage II. All of the relapses occurred outside the irradiated area treated on the other side of the diaphragm. Of all 48 patients with combination chemotherapy such as vincristine, cyclophosphamide, predonisolone, and Adriamycin (VEPA), mitoxantrone, cyclophosphamide, vincristine, and predonisolone (MCOP), and mitoxantrone, ifosfamide, vindesine, and predonisolone (MIFP), 33 (69%) achieved complete remission.

Nephrotoxicity is the major side effect of cisplatinum (CDDP) and it is often the dose limiting factor. We have studied the effect of urinastatin (US) to decrease the nephrotoxicity of CDDP administration. 28 patients with gynecological cancer treated by chemotherapy including CDDP (13 mg/m2 daily for 5 days) were assigned to two groups, the group with US (n = 14) and the group without US (n = 14). The former was added each 150,000 units of US before and after administration of CDDP. The BUN, serum creatinine (Cre), creatinine clearance (Ccr) and the excretion of beta 2-microglobulin (beta 2-MG) index and N-acetyl-beta-glucosaminidase(NAG)index were measured. The BUN, Cre and Ccr were within normal range during four cycles. However NAG index rose remarkably when CDDP was treated by CDDP. And the increase in NAG index, which reflect the magnitude of renal tubal damage, was less in the group with US than in the group without US. It was suggested that US had effects to reduce nephrotoxicity of CDDP in chemotherapy, and that we could treat patients by high dose CDDP.

The efficacy and safety of a combination regimen using cefmetazole (CMZ) and netilmicin (NTL) were evaluated in the treatment of infections complicated with hematological disorders. Primary diseases in 31 patients included in the evaluation were acute myelocytic leukemia (3 cases), acute lymphocytic leukemia (2 cases), malignant lymphoma (14 cases), chronic myelocytic leukemia (2 cases), chronic myelocytic leukemia blast crisis (4 cases), myelodysplastic syndrome (2 cases), aplastic anemia (3 cases), and malignant histiocytosis (1 case). Complicated infections included 29 cases of suspected septicemia, 1 case of septicemia and 1 case of pneumonia. Clinical responses were excellent in 6 (19.4%), good in 12 (38.7%), fair in 1 (3.2%) and poor in 12 (38.7%). The total clinical efficacy rate was 58.1%. No significant effect of initial neutrophil counts was observed on response rates. Patients who showed increasing neutrophil counts during therapy had higher response rates than those in whom the neutrophil count decreased or remained unchanged at levels less than 500/mm3 in after neutrophil counts. No side effects were observed in any of the 31 patients. In conclusion, this combination therapy of CMZ and NTL thus appears to be useful and safe in therapies for infections complicated with hematological disorders.

A 20-year-old woman was hospitalized because of abdominal distention. She had developed facial edema about one year earlier, and recently amenorrhea and red verrucae on the chest and abdomen. Neurological examination disclosed hypesthesia, paresthesia, and diminished tendon reflexes in the arms and legs. The level of serum immunoglobulin A (IgA) was elevated and an M protein was detected. Examination of the bone marrow disclosed abnormal increase in plasma cells. Results of glucose tolerance test were mildly abnormal. The patient was diagnosed as Crow-Fukase syndrome. Plasma exchange was done four times and melphalan was given orally for two weeks, but the level of serum IgA increased further. Then one bolus injection of methylprednisolone decreased the serum IgA with improvement in other signs. The disorder is now controlled satisfactory with a low dose of prednisolone.

An intraarterial high-dose CDDP, using a balloon catheter, has been infused into five patients with a recurrent ovarian cancer. The dose of CDDP was 150 mg-200 mg/body. Two patients experienced a partial tumor regression, whereas three showed no change. With regard to the toxicity, the NAG index (NAG activity/urinary creatinine) rose markedly in all patients, but toxicity was almost similar to that seen from a systemic administration. No significant catheter complication occurred.

In our series of investigations concerning immunopotentiators, we evaluated the host immunocompetence of patients triggered by PSK. Our subjects for screening consisted of seven patients with malignant tumors of female reproductive organs chosen at random from our patients. Four of them were treated with chemotherapy (CAPF) alone and served as controls, whereas the other three were administered PSK, 3.0 g/day, plus chemotherapy as above. Cellular and humoral immunities were measured at three points. Firstly prior to chemotherapy, secondly, two weeks after the start of chemotherapy, and thirdly, prior to next chemotherapy. The results indicated higher values of T-cell subset ratio OKT-4/8 of 2.73 +/- 0.56 on the average for cellular immunocompetence as compared to 1.35 +/- 0.45 for normal subjects in the PSK-administered group, whereas there was no increase in the non-PSK-administered group, in which the value was 1.28 +/- 0.30. Thus, PSK was considered to extert an immunopotentiating effect on the T-lymphocytes.

A continuous subcutaneous infusion of peplomycin was performed on 15 patients with cervical cancer. Eight patients received 5 mg of peplomycin a day and 7 patients received 2.5 mg a day. The peplomycin concentrating in the serum after infusion for 24 hours thus were 0.094 microgram/ml and 0.056 microgram/ml, respectively. The concentration of peplomycin in the tumor was found to be higher than in normal cervical tissue, and in the lymph nodes it was equal or higher than in the serum. Histological changes were minimum. A Grade IIa determination, however, was found in one patient, which may have been due to the total dose and/or the time of the examination. No pulmonary toxicity developed in any patients.

Pharmacokinetic and clinical studies on a new cephalosporin antibiotic, cefodizime (THR-221, CDZM), were performed and the results obtained are summarized as follows: 1. At about 84 minutes after a bolus injection of 1 g dose of CDZM, the drug was transferred well into tissues of internal genital organs and remained there at therapeutic levels for 285 minutes. The drug was also transferred quickly and sufficiently into exudate from pelvic dead space and its levels were still kept at high levels at 6 hours after administration. 2. CDZM was given to 8 women affected with gynecologic infections. The outcome of CDZM therapies showed that the drug was effective in all 8 of patients (100%) clinically and bacteriologically. 3. Notable adverse effects or abnormal laboratory test results were not observed except for 2 patients with transient and slight elevation of transaminase levels. Based on these results, it may be concluded that CDZM is a highly effective and a very safe antibiotic for the treatment on infectious diseases in gynecologic field.

A case of advanced cancer of the vulva that was treated by cisplatin with good result, is reported. This case was adenocarcinoma of Bartholin gland, and the clinical stage was third stage. The method of administration was intravenous injection of cisplatin (150 mg/body) in hypertonic saline (3%) for the decrease of nephrotoxicity. After administration (450 mg/body), the tumor markedly reduced. Additional operation, one course of CDDP and irradiation were carried out. After discharge, there has been no sign of recurrence for one year and five months. In this case, we used CDDP in hypertonic saline to decrease the nephrotoxicity. During these courses, the nephrotoxicity was moderate. This shows that patients can be treated by higher-doses of cisplatinum by this method.

Eight patients with gynecologic cancer (cervix: 6, corpus: 1 and vulva: 1) were treated with combination chemotherapy, PPM therapy consisting of continuously infused PEP 4mg/m2 days 1-5, CDDP 13 mg/m2 days 1-5, and MMC 3mg/m2 day 1. This was repeated every three to five weeks. Six of the eight patients were evaluable, two had a complete response and one had a partial response, for an overall response rate of 50%. Because of hematological toxicity, blood transfusion was carried out in four patients. Nephrotoxicity and pulmonary toxicity were slight. Nausea and vomiting were controlled with dexamethasone and domperidone. PPM therapy is considered to be an effective and useful combination chemotherapy for patients with gynecologic cancer.

Serum CA125 levels were measured by radioimmunoassay patients with various gynecological tumors. Elevated levels of CA125 were detected in the serum of patients with malignant ovarian tumors. Among patients with uterine tumors, CA125 levels were elevated in those with malignant uterine tumors, but not with uterine myomas. The correlations between tumor markers (CA125, IAP, ferritin, PTA) and malignant ovarian tumors were measured, and only CA125 levels were found to correlate with progression or regression of the disease in patients with malignant ovarian tumors. These results suggest that CA125 may be a useful marker for monitoring the response to treatment in patients with malignant ovarian tumors.

A rare case of complete thoracic aortic occlusion secondary to blunt trauma was reported. The patient was a 27-year-old policeman who was involved in an automobile accident while driving a patrol car. Hypertension of the upper extremities, edema of the upper body and anuria were found at emergency room examination. Emergent aortogram demonstrated traumatic occlusion of the aorta at the level of isthmus. Urgently an axillo-femoral bypass was performed, and two days later radical aortic repair was carried out. At the radical operation, disruption of the aortic intima was encountered in the area of ligamentum arteriosum. The distal torn edge was enfolded and completely occluded the aortic lumen. The lacerated intima was sutured, and the intimal defect of the aorta was restored with woven Dacron patch. Postoperative course was uneventful. On subsequent follow-up 3 years after injury, the patient was asymptomatic showing normal thoracic aortogram.

During spinal anesthesia for appendectomy (sensory level: -Th7), apnea occurred for about 20 minutes by intravenous administration of diazepam. Since the patient showed hyperventilation sign before the incident, this apnea might be caused by low PaCO2 and stopping respiratory stimulation from psychological unrest when diazepam, pentazocine and droperidol were administered. In the postoperative period, this patient showed normal neurologic and psychosomatic functions. In such a case as this, long duration of apnea might damage brain by severe hypoxia. Apnea after hyperventilation during spinal anesthesia as observed in this case could lead to a serious accident.