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The clinical safety and efficacy of imipenem/cilastatin in the treatment of intra-abdominal infections was compared with the combination of aztreonam and clindamycin in a randomized prospective trial. The severity of illness was determined by means of the Apache II score and a fixed outcome reporting scheme was used. One hundred and four patients were entered into the study, of whom 80 were evaluable. Forty-two patients were treated with imipenem/cilastatin (500 + 500 mg qds) and 38 with aztreonam (600 tds) and clindamycin (1000 mg tds). The study groups were comparable for age and sex. The imipenem/cilastatin group differed from the aztreonam and clindamycin group in having significantly more patients with the diagnosis of acute appendicitis (P < 0.01) and a significantly lower mean Apache score (P < 0.05). The predominate microorganisms isolated in both groups were Escherichia coli and Bacteroides fragilis. Treatment with imipenem/cilastatin proved successful in 71% and failed in 24%, and initial success only was seen in 5%. The numbers in the group treated with aztreonam and clindamycin were 64%, 29% and 7% respectively. Severity of illness, as measured by Apache II score, had no influence on the study outcome. Imipenem/cilastatin as well as the combination of aztreonam and clindamycin were effective in the treatment of abdominal infections and no major adverse reactions were seen. [ABSTRACT FROM AUTHOR]

Introduction: The effects of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) and conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) on body composition and muscle function in rheumatoid arthritis (RA) patients requiring treatment enhancement were compared., Methods: This multicenter, prospective, observational study (PRESENT Study) divided RA patients non-randomly into a csDMARD group (n = 100) and a b/tsDMARD group (n = 100). Changes in body composition and muscle function were examined in 80 patients in each group followed for 52 weeks. The percentages of new-onset and improved sarcopenia over 1 year were investigated. Patients in the b/tsDMARD group were divided into three groups by drug type: TNF inhibitors (n = 30), non-TNF inhibitors (n = 23), and JAK inhibitors (n = 27)., Results: Baseline median age and disease duration were 70.0 and 4.0 years, respectively. Changes in weight (24 and 52 weeks) and muscle mass (52 weeks) were significantly higher in the b/tsDMARD group (p = .035, p < .001, and p = .002, respectively). On multivariate logistic regression analysis, b/tsDMARD treatment (OR 3.21, p = .002), DAS28-ESR (OR 0.65 p = .011), and muscle mass (OR 0.90, p = .023) were independently associated with increased muscle mass at 52 weeks. The percentages of new-onset and improved sarcopenia were almost equal. There were no significant differences in the time-dependent changes (52 weeks) of clinical status, body composition, muscle function, and status of sarcopenia among TNF inhibitors, non-TNF inhibitors, and JAK inhibitors., Conclusions: Weight and muscle mass increased significantly more with b/tsDMARD than with csDMARD treatment. There were no differences in body composition changes by mode of action with b/tsDMARDs., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: This study evaluated the effectiveness of Janus kinase inhibitors (JAKi) in patients with difficult-to-treat rheumatoid arthritis (D2T RA)., Methods: This study included 220 patients with RA who were treated with JAKi. Sixty-two patients were naïve to biological disease-modifying anti-rheumatic drugs (bDMARDs)/JAKi (1st group), 57 patients were failure to one bDMARDs/JAKi (2nd group), and 101 patients were failure to ≥ 2 bDMARDs/JAKi. Of these 101 patients, 25 did not meet the D2T RA criteria (non-D2T RA group) and 76 met the D2T RA criteria (D2T RA group)., Results: : DAS28-ESR was improved in all groups at 24 weeks (1st: p<0.01, 2nd: p<0.01, non-D2T RA: p=0.01, D2TRA: p=0.02), and improvement ratio of DAS28-ESR was not different between DT2RA group and 2nd (p=0.73) or non-D2T RA group (p=0.68). Glucocorticoid use (odds ratios: 8.67; 95% CI: 1.23-60.90; P=0.03) and number of past bDMARD/JAKi uses ≥ 3 (odds ratios: 10.55; 95% CI: 1.39-80.30; P=0.02) were risk factors for DAS28-ESR ≥ 3.2 at 24 weeks in the D2T RA group., Conclusions: Clinical efficacy of JAKi in D2T RA group did not differ from that in 2nd and non-D2T RA groups. Glucocorticoid use and multiple bDMARD/JAKi failure were poor prognostic factors for D2T RA., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objectives: This study aimed to examine whether creatine kinase (CK) elevation occurs with interleukin (IL)-6 inhibitors, as in Janus kinase (JAK) inhibitors, which are reported to increase CK levels in rheumatoid arthritis., Patients and Methods: A multicenter database of JAK inhibitor and IL-6 inhibitor treatment was retrospectively searched between January 2016 to December 2022; 142 cases (117 females, 25 males, mean age: 63.8±13.0 years; range, 20 to 85 years), with 71 cases in each group, were extracted by propensity score matching using age, sex, body mass index, and CK at 0 weeks. The outlier rate was compared. Patients' background characteristics related to elevated CK levels at 24 weeks were investigated by univariate and multivariate analyses., Results: Creatine kinase levels at 4 and 12 weeks were significantly higher with JAK inhibitors than with IL-6 inhibitors (four weeks, 72 vs. 87.5 IU/mL, p=0.016; 12 weeks, 71 vs. 95.5 IU/mL, p=0.028). The outlier rate (Grade 1) with JAK inhibitors increased significantly over time (0 weeks, 4.2%; four weeks, 18.1%; 12 weeks, 21.7%; 24 weeks, 18.3%; p=0.015), whereas that with IL-6 inhibitors increased slightly (0 weeks, 5.6%; four weeks, 9.2%; 12 weeks, 8.6%; 24 weeks, 8.5%; p=0.745), with a significant difference between the groups (p=0.035). No patients discontinued treatment due to myalgia or renal dysfunction. The factors significantly positively related to elevated CK levels at 24 weeks were male sex and creatinine. Those significantly negatively related were Steinbrocker stage and class, modified health assessment questionnaire scores, estimated glomerular filtration rate, and glucocorticoid dose., Conclusion: Mild CK elevations with JAK inhibitors are not a particular clinical problem. CK elevation might be specific to JAK inhibitors., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2024, Turkish League Against Rheumatism.)

Objectives: The purpose of this study was to evaluate the new incidence of carotid plaques in rheumatoid arthritis (RA) patients over a 6-year prospective follow-up and to assess the risk factors., Methods: This is a 10-year prospective cohort study that included 208 RA patients and 205 age- and gender-matched controls. Ultrasound assessment of the bilateral carotid arteries was performed in 2011 and 2017., Results: There were no differences in the incidence of new carotid atherosclerotic plaques over 6 years between the two groups (35.5% vs. 37.0%, respectively; p = .936). The mean Disease Activity Score 28-C-reactive protein over 6 years in RA patients was 2.73 ± 0.95. Multiple logistic regression analysis showed that RA was not a risk factor for new carotid atherosclerotic plaques (odds ratios, 0.708; 95% confidence interval, 0.348-1.440; p = .340). An average glucocorticoid dose of >1.8 mg/day over 6 years was a risk factor for new carotid atherosclerotic plaques (odds ratios, 8.54; 95% confidence interval, 1.641-44.455; p = .011)., Conclusions: Incidence of new carotid atherosclerotic plaques was similar between well-controlled disease activity RA patients and control subjects. A mean glucocorticoid dose of >1.8 mg/day over 6 years was a risk factor for new carotid atherosclerotic plaques., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Currently, there are many challenges in the culture of human induced pluripotent stem (iPS) cell-derived intestinal organoids (HIOs) for use in drug discovery, disease research, and regenerative medicine. For example, the main culture method, embedding culture, makes industrial large-scale culture difficult, and Matrigel, which is used for almost all HIO cultures, is not respected for its application in regenerative medicine. To overcome these challenges, we herein propose a new culture method using low concentrations of natural polysaccharides in a suspension culture. In the present study, five natural polysaccharides free from heterologous animal-derived components were used, and HIOs were successfully cultured in suspension with FP001 and FP003, which are microbial exopolysaccharide analogs of gellan gum. The fabricated HIOs were similar to living intestinal tracts with respect to their gene expression, microstructure, and protein expression. The observed activities of the drug metabolizing enzymes and drug transporters in the generated HIOs suggested that they have pharmacokinetic functions. We believe that suspension culture of HIOs using FP001 or FP003 can be widely applied to not only drug discovery research but also disease research and regenerative medicine., Competing Interests: Declaration of competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction: Coronavirus disease (COVID-19) rapidly spread from Wuhan, China to other parts of China and other regions/countries around the world, resulting in a pandemic due to large populations moving through the massive transport hubs connecting all regions of China via railways and a major international airport. COVID-19 will remain a threat until safe and effective vaccines and antiviral drugs have been developed, distributed, and administered on a global scale. Thus, there is urgent need to establish effective implementation of preemptive non-pharmaceutical interventions for appropriate prevention and control strategies, and predicting future COVID-19 cases is required to monitor and control the issue., Methods: This study attempts to utilize a three-layer graph convolutional network (GCN) model to predict future COVID-19 cases in 190 regions and countries using COVID-19 case data, commercial flight route data, and digital maps of public transportation in terms of transnational human mobility. We compared the performance of the proposed GCN model to a multilayer perceptron (MLP) model on a dataset of COVID-19 cases (excluding the graph representation). The prediction performance of the models was evaluated using the mean squared error., Results: Our results demonstrate that the proposed GCN model can achieve better graph utilization and performance compared to the baseline in terms of both prediction accuracy and stability., Discussion: The proposed GCN model is a useful means to predict COVID-19 cases at regional and national levels. Such predictions can be used to facilitate public health solutions in public health responses to the COVID-19 pandemic using deep learning and data pooling. In addition, the proposed GCN model may help public health policymakers in decision making in terms of epidemic prevention and control strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Anno, Hirakawa, Sugita and Yasumoto.)

The evaluation of drug pharmacokinetics in the small intestine is critical for developing orally administered drugs. Caucasian colon adenocarcinoma (Caco-2) cells are employed to evaluate drug absorption in preclinical trials of drug development. However, the pharmacokinetic characteristics of Caco-2 cells are different from those of the normal human small intestine. Besides this, it is almost impossible to obtain primary human intestinal epithelial cells of the same batch. Therefore, human iPS cell-derived enterocytes (hiPSEs) with pharmacokinetic functions similar to human intestinal epithelial cells are expected to be useful for the evaluation of drug absorption. Previous studies have been limited to the use of cytokines and small molecules to generate hiPSEs. Dietary fibers play a critical role in maintaining intestinal physiology. We used gellan gum (GG), a soluble dietary fiber, to optimize hiPSE differentiation. hiPSEs cocultured with GG had significantly higher expression of small intestine- and pharmacokinetics-related genes and proteins. The activities of drug-metabolizing enzymes, such as cytochrome P450 2C19, and peptide transporter 1 were significantly increased in the GG treatment group compared to the control group. At the end point of differentiation, the percentage of senescent cells increased. Therefore, GG could improve the differentiation efficiency of human iPS cells to enterocytes and increase intestinal maturation by extending the life span of hiPSEs.

Objectives: This study aimed to compare median nerve stiffness measured by ultrasound real-time tissue elastography in patients with and without rheumatoid arthritis (RA and non-RA groups, respectively). Methods: Altogether, 402 hands of 201 RA group and 222 hands of 111 non-RA group were included in the study. Ultrasonography was performed to evaluate the circumference, cross-sectional area (CSA) and strain ratio as an elasticity of the median nerve at the inlet level of the carpal tunnel and the proximal portion of the carpal tunnel inlet. Using propensity score matching, the difference between RA and non-RA group were analyzed. Results: After propensity score matching, 135 hands in 104 RA group and 70 non-RA group were finally analyzed. There were no significant differences in the circumference and CSA of the median nerve between the two groups. The strain ratio of the median nerve was significantly higher in RA group than in non-RA group only at the inlet of the carpal tunnel level. Conclusions: The nerve stiffness in patients with RA measured by ultrasound real-time tissue elastography was higher than without RA. Inflammatory condition of the flexor tendon and wrist joint in patients with RA may generate fibrotic changes in the median nerve. Trial registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN000015314.

Early warning systems (EWS) have been proposed as a measure for controlling and preventing dengue fever outbreaks in countries where this infection is endemic. A vaccine is not available and has yet to reach the market due to the economic burden of development, introduction and safety concerns. Understanding how dengue spreads and identifying the risk factors will facilitate the development of a dengue EWS, for which a climate-based model is still needed. An analysis was conducted to examine emerging spatiotemporal hotspots of dengue fever at the township level in Taiwan, associated with climatic factors obtained from remotely sensed data in order to identify the risk factors. Machinelearning was applied to support the search for factors with a spatiotemporal correlation with dengue fever outbreaks. Three dengue fever hotspot categories were found in southwest Taiwan and shown to be spatiotemporally associated with five kinds of sea surface temperatures. Machine-learning, based on the deep AlexNet model trained by transfer learning, yielded an accuracy of 100% on an 8-fold cross-validation test dataset of longitudetime sea surface temperature images.

To evaluate work disability and associated factors in patients with rheumatoid arthritis (RA) who participated in the TOMORROW study, a 10-year cohort study in Japan. Subjects in this cross-sectional analysis comprised 191 RA patients and 191 age- and sex-matched non-RA individuals. Work-related outcomes were measured using the Work Productivity and Activity Impairment questionnaire by employment status (full-time worker (FTW), employed ≥ 35 h/week; part-time worker (PTW), < 35 h/week; home worker (HW), non-employed). In addition, we assessed the EuroQol-5 Dimensions (EQ-5D) and Health Assessment Questionnaire (HAQ) to evaluate quality of life and activities of daily living. No significant differences were evident between groups in percentages of participants in each employment status (p = 0.11), percentages of absenteeism (FTW, p = 1.00; PTW, p = 0.29), presenteeism (FTW, p = 0.23; PTW, p = 0.54), overall work impairment (FTW, p = 0.23; PTW, p = 0.73), or percentage of activity impairment (AI) (FTW, p = 0.62; PTW, p = 0.60). In the HW group, percentage of AI was higher in RA patients than that in non-RA patients (p < 0.01). Among RA patients, HW showed lower EQ-5D and higher HAQ than FTW or PTW (p < 0.001 each). Higher disease activity was observed in HW than FTW (p < 0.01). In terms of the effect of biological disease-modifying anti-rheumatic drugs, no significant differences in work-related outcomes, health status, or daily activity were evident between users and non-users. No significant differences in employment status or work impairment were seen between RA and non-RA groups among paid workers. HW with RA showed more impaired daily activity and higher disease activity compared to working RA patients., Trial Registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN000003876 . Registered 1 Jun 2010.

Although patients with rheumatoid arthritis (RA) are prone to osteoporosis, tight control of disease activity might have a positive effect on bone metabolism. We aimed to determine whether bisphosphonate use is still important to improve bone mineral density (BMD) in RA patients whose disease activity was tightly controlled and the dose of glucocorticoid was reduced. This study was a sub-analysis of the 10-year prospective cohort TOtal Management Of Risk factors in Rheumatoid arthritis patients to lOWer morbidity and mortality: the TOMORROW which started from 2010. We compared BMD between 192 patients with RA and age- and sex-matched volunteers between 2010 and 2013 using dual-energy X-ray absorptiometry (DXA) in whole body mode. We then determined ratios of changes in BMD (%ΔBMD) to assess factors influencing increases in BMD among the patients using multivariate logistic regression analysis. The BMD was significantly lower in the patients than in the controls at all sites surveyed during 2010 and 2013. The %ΔBMD of the total spine was significantly higher among the patients treated with, than without bisphosphonate (6.2 vs. 1.8%, P = 0.0001). Multivariate logistic regression analysis revealed that use of bisphosphonate was a significant factor contributing to BMD increase (odds ratio 2.13; 95% confidence interval, 1.03-4.38, P = 0.041). Meanwhile, use of biologic agents, reducing glucocorticoid dose, and control of disease activity were not significant factors for gain of BMD. The BMD was lower among patients with RA than non-RA controls. Use of bisphosphonate significantly increased the BMD of the spine in patients over a period of 3 years and was important for maintaining the BMD among patients with RA under the control of inflammation and disease activity.

The aim of the present study was to identify geographical areas and time periods of potential clusters of dengue cases based on ecological, socio-economic and demographic factors in northern Sri Lanka from January 2010 to December 2013. Remote sensing (RS) was used to develop an index comprising rainfall, humidity and temperature data. Remote sensing data gathered by the AVNIR-2 instrument onboard the ALOS satellite were used to detect urbanisation, and a digital land cover map was used to extract land cover information. Other data on relevant factors and dengue outbreaks were collected through institutions and extant databases. The analysed RS data and databases were integrated into a geographical information system (GIS) enabling space-time clustering analysis. Our results indicate that increases in the number of combinations of ecological, socio-economic and demographic factors that are present or above the average contribute to significantly high rates of space-time dengue clusters. The spatio-temporal association that consolidates the two kinds of associations into one can ensure a more stable model for forecasting. An integrated spatiotemporal prediction model at a smaller level using ecological, socioeconomic and demographic factors could lead to substantial improvements in dengue control and prevention by allocating the right resources to the appropriate places at the right time.

Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia., Design and Methods: Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling., Discussion: Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields.

Genetic and environmental factors are both part of an elaborate feedback mechanism whereby the human adaptive form reacts to environmental stimuli via internal adjustments. Human survival may ultimately depend on understanding two important components of future environmental adaptation. First, we must elucidate the dynamics of the human genome underpinning the complex human phenotype. Second, we must understand how the environment pressures and affects the genome, helping to determine human traits. This article reviews current approaches to detecting the natural selection of skin color variation in human populations. We include statistical methods for clarifying gene-environment interactions applicable to the interactions with UV radiation levels. We recommend spatial data mining as an efficient approach that applies environmental association rules, extending our knowledge of adaptation to the environment.

This study aimed to identify single nucleotide polymorphism (SNP) alleles at multiple loci associated with racial differences in skin color using SNP genotyping. A total of 122 Caucasians in Toledo, Ohio and 100 Mongoloids in Japan were genotyped for 20 SNPs in 7 candidate genes, encoding the Agouti signaling protein (ASIP), tyrosinase-related protein 1 (TYRP1), tyrosinase (TYR), melanocortin 1 receptor (MC1R), oculocutaneous albinism II (OCA2), microphthalmia-associated transcription factor (MITF), and myosin VA (MYO5A). Data were used to analyze associations between the 20 SNP alleles using linkage disequilibrium (LD). Combinations of SNP alleles were jointly tested under LD for associations with racial groups by performing a chi(2) test for independence. Results showed that SNP alleles at multiple loci can be considered the haplotype that contributes to significant differences between the two population groups and suggest a high probability of LD. Confirmation of these findings requires further study with other ethnic groups to analyze the associations between SNP alleles at multiple loci and skin color variation among races.

This study was undertaken to clarify the molecular basis for human skin color variation and the environmental adaptability to ultraviolet irradiation, with the ultimate goal of predicting the impact of changes in future environments on human health risk. One hundred twenty-two Caucasians living in Toledo, Ohio participated. Back and cheek skin were assayed for melanin as a quantitative trait marker. Buccal cell samples were collected and used for DNA extraction. DNA was used for SNP genotyping using the Masscode system, which entails two-step PCR amplification and a platform chemistry which allows cleavable mass spectrometry tags. The results show gene-gene interaction between SNP alleles at multiple loci (not necessarily on the same chromosome) contributes to inter-individual skin color variation while suggesting a high probability of linkage disequilibrium. Confirmation of these findings requires further study with other ethic groups to analyze the associations between SNP alleles at multiple loci and human skin color variation. Our overarching goal is to use remote sensing data to clarify the interaction between atmospheric environments and SNP allelic frequency and investigate human adaptability to ultraviolet irradiation. Such information should greatly assist in the prediction of the health effects of future environmental changes such as ozone depletion and increased ultraviolet exposure. If such health effects are to some extent predictable, it might be possible to prepare for such changes in advance and thus reduce the extent of their impact.

We present a conceptual framework for applying techniques of SNP genotyping as a molecular biological approach and remote sensing as an ecological approach to elucidation of the contribution of polygene and environmental factors to inter-individual variation in skin pigmentation phenotype. Additionally, we discuss the obstacles that frustrate our efforts to identify how the human genome encodes the complex phenotype and suggest the use of computational methods designed for knowledge discovery within hereditary database.

Remote Sensing (RS), a Global Positioning System (GPS) and a Geographic Information System (GIS) were used to analyze relationship between Anopheles subpictus larval densities and environmental parameters in the Sekotong district on Lombok Island, Indonesia. Distance from the coast to larval habitats, season and surface water were considered as environmental parameters for determining An. subpictus larval densities. Japanese Earth Resources Satellite (JERS) Visible and Near Infrared Radiometer (VNIR) satellite imagery for the area acquired by National Space Development Agency of Japan (NASDA) were used to detect water, which could be used to characterize larval habitats. Data on larval sampling sites obtained from a GPS were entered into a GIS for mapping larval habitats to measure distance between the coast and the larval habitats. A GIS was used for overlaying of data coverages (i.e., water distribution from RS data and larval habitats coupled with data on larval densities) to identify factors that may explain the spatial distribution patterns of larval densities. An. subpictus larval densities were significantly associated with season and distance from the coast to larval habitats. The rainy season and the distance from the coast to larval habitats were critical environmental determinants for presence of An. subpictus larvae in the study. In this paper, we investigated relationship between An. subpictus larval densities and the environmental parameters using RS/GPS/GIS to determine if these tools could be used to predict larval densities.

We report a rare case of idiopathic myelofibrosis transformed to acute myelomonocytic leukemia associated with non-Hodgkin's lymphoma. A 64-year-old woman was admitted to our department because of anemia and leukocytosis. On admission, anemia and hepatosplenomegaly were noted. The hemoglobin content was 6.8 g/dl, and WBC count was 26,200/microliters with an increased number of immature neutrophils. Bone marrow biopsy revealed an increased amount of reticulin fiber. Because she had no disease which causes secondary myelofibrosis, idiopathic myelofibrosis was diagnosed, and she was treated with prednisolone, anabolic steroid and blood transfusion. Fifteen months after the diagnosis of myelofibrosis, blast increased in her peripheral blood and her spleen and liver enlarged remarkably. A tumor of right parotid region was recognized at the same time. The pathological diagnosis of biopsied tumor was non-Hodgkin's lymphoma. The cytochemical study of blasts in her peripheral blood showed that she had acute myelomonocytic leukemia. In spite of intensive chemotherapy, she died from heart failure, respiratory failure and renal insufficiency.

We compared the effect of combined natural interferon-alpha (HLBI)/VCAP chemotherapy with VCAP chemotherapy alone on multiple myeloma. Sixteen previously untreated patients with multiple myeloma were treated with a combination of IFN-alpha and VCAP chemotherapy; nine of them were treated with HLBI-VCAP (I) regimen (HLBI 3 x 10(6) units/day, daily, 56 days) only for induction chemotherapy, and seven with continuous HLBI-VCAP (II) regimen (HLBI 3 x 10(6) units/day, twice a week) both for induction and maintenance chemotherapy. Thirty-one control patients were treated with a VCAP regimen only. HLBI-VCAP (II) regimen exhibited an 85.7% (6/7) response rate, while VCAP and HLBI-VCAP (I) regimen showed 74.2% (23/31) and 77.8% (7/9) response rates, respectively. The median duration of survival was 43 months in the control group, greater than 44 months in HLBI-VCAP (I) group and greater than 45 months in HLBI-VCAP (II) group. No significant difference in survival duration has yet been observed between the VCAP group and HLBI-VCAP groups. We conclude that continuous, long-term combination therapy with HLBI and VCAP regimen for induction and maintenance therapy may be most effective, and found that intensive HLBI-VCAP regimen, for only remission induction therapy, was not more effective than VCAP regimen alone.

From 1985 to 1989, we treated a total of 24 adult patients with acute lymphoblastic leukemia, 17 males and 7 females, median age 26 (range 16-70 yr), with a protocol consisting of remission induction with Adriamycin (ADR), vincristine (VCR), prednisolone (PDN) and 1-asparaginase (ASP), followed by two consolidation courses with ADR, VCR, cyclophosphamide, methotrexate and PDN (Ad-VEMP), combined with CNS-prophylaxis (intrathecal MTX and PDN). Cyclic chemotherapy with VMM (vindesine, 6-MP and MTX) and Ad-VEMP regimen or therapy with VMM regimen only was used to maintain remission. Twenty patients (83.3%) achieved complete remission. The median durations of overall survival and complete remission were 20 and 18 months respectively. The significant unfavorable prognostic factors associated with survival were old age (more than 50 yr), high WBC counts on admission (more than 20,000/microliters) and low nadir of WBC counts (less than 500/microliters). The responders who received ASP for a period of 10 days had longer survival durations than did other responders. Remission did not continue long enough with our protocol, although a high CR rate was achieved. We conclude that the design of consolidation and maintenance therapy must be improved in order to obtain a longer duration with our protocol.