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Hematological
Terms modified by Hematological Selected AbstractsLong-term patient monitoring for clozapine-induced agranulocytosis and neutropenia in Korea: when is it safe to discontinue CPMS?HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2006Byung-Jo Kang Abstract Objectives This study documents the incidences of agranulocytosis and neutropenia, and the patterns of incidence of the side effects of long-term clozapine treatment in order to determine an appropriate time to stop the Clozaril Patient Monitoring System (CPMS). Methods Hematological, demographic, and other data from the CPMS for 6782 patients who took clozapine for the past 11 years in the Republic of Korea has been analyzed. Results Twenty-nine (53.7%) of fifty-four agranulocytosis cases occurred within the first 18 weeks. The cumulative incidence of agranulocytosis was 1.64% between 6 and 11 years and the crude incidence was 0.8%. Neutropenia occurred in 697 patients, and 365 (52.4%) of these cases occurred within the first 18 weeks. The cumulative incidence of neutropenia was 19.8% between 8 and 11 years, and the crude incidence was 10.3%. There were no cases of agranulocytosis or neutropenia after the 9th year of clozapine treatment. Conclusions The incidence of agranulocytosis in the Republic of Korea was similar to those in the rest of the world. While agranulocytosis began several years after clozapine treatment, long-term monitoring of white blood cells is necessary. We suggest that the CPMS should be stopped or less frequently after the 9th year of treatment. Copyright © 2006 John Wiley & Sons, Ltd. [source] Oro-facial granulomatosis: Crohn's disease or a new inflammatory bowel disease?INFLAMMATORY BOWEL DISEASES, Issue 9 2005FRCP, Jeremy Sanderson MD Abstract Background: Oro-facial granulomatosis (OFG) is a rare chronic inflammatory disorder presenting characteristically with lip swelling but also affecting gingivae, buccal mucosa, floor of mouth, and a number of other sites in the oral cavity. Histologically, OFG resembles Crohn's disease (CD), and a number of patients with CD have oral involvement identical to OFG. However, the exact relationship between OFG and CD remains unknown. Methods: Thirty-five patients with OFG and no gut symptoms were identified from a combined oral medicine/gastroenterology clinic. All underwent a standardized assessment of the oral cavity and oral mucosal biopsy to characterize the number of sites affected and the type of inflammation involved. Hematological and biochemical parameters were also recorded. All 35 patients underwent ileocolonoscopy and biopsy to assess the presence of coexistent intestinal inflammation. Results: Ileal or colonic abnormalities were detected in 19/35 (54%) cases. From gut biopsies, granulomas were present in 13/19 cases (64%). An intestinal abnormality was significantly more likely if the age of OFG onset was less than 30 years (P = 0.01). Those with more severe oral inflammation were also more likely to have intestinal inflammation (P = 0.025), and there was also a correlation between the histologic severity of oral inflammation and the histologic severity of gut inflammation (P = 0.047). No relationship was found between any blood parameter and intestinal involvement. Conclusions: Endoscopic and histologic intestinal abnormalities are common in patients with OFG with no gastrointestinal symptoms. Younger patients with OFG are more likely to have concomitant intestinal involvement. In these patients, granulomas are more frequent in endoscopic biopsies than reported in patients with documented CD. OFG with associated intestinal inflammation may represent a separate entity in which granulomatous inflammation occurs throughout the gastrointestinal tract in response to an unknown antigen or antigens. [source] Equivocal Colonic Carcinogenicity of Aloe arborescens Miller var. natalensis Berger at High-Dose Level in a Wistar Hannover Rat 2-y StudyJOURNAL OF FOOD SCIENCE, Issue 2 2009M. Yokohira ABSTRACT:, A 2-y carcinogenicity study of Aloe, Aloe arborescens Miller var. natalensis Berger, a food additive, was conducted for assessment of toxicity and carcinogenic potential in the diet at doses of 4% or 0.8% in groups of male and female Wistar Hannover rats. Both sexes receiving 4% showed diarrhea, with loss of body weight gain. The survival rate in the 4% female group was significantly increased compared with control females after 2 y. Hematological and biochemical examination showed increase of RBC, Hb, and Alb in the 4% males. The cause of these increases could conceivably have been dehydration through diarrhea. AST and Na were significantly decreased in the males receiving 4%, and Cl was significantly decreased in both 4% and 0.8% males. A/G was significantly increased in the 4% females, and Cl was significantly decreased (0.8%) in the female group. Histopathologically, both sexes receiving 4% showed severe sinus dilatation of ileocecal lymph nodes, and yellowish pigmentation of ileocecal lymph nodes and renal tubules. Adenomas or adenocarcinomas in the cecum, colon, and rectum were observed in 4% males but not in the 0.8% and control male groups. Similarly, in females, adenomas in the colon were also observed in the 4% but not 0.8% and control groups. In conclusion, Aloe, used as a food additive, exerted equivocal carcinogenic potential at 4% high-dose level on colon in the 2-y carcinogenicity study in rats. Aloe is not carcinogenic at nontoxic-dose levels and that carcinogenic potential in at 4% high-dose level on colon is probably due to irritation of the intestinal tract by diarrhea. [source] Hemostatic and hematological abnormalities in gain-of-function fps/fes transgenic mice are associated with the angiogenic phenotypeJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2004W. Sangrar Summary. The Fps/Fes tyrosine kinase has been implicated in the regulation of hematopoiesis and inflammation. Mice expressing an activated variant of Fps/Fes (MFps) encoded by a gain-of-function mutant transgenic fps/fes allele (fpsMF) exhibited hematological phenotypes, which suggested that Fps/Fes can direct hematopoietic lineage output. These mice also displayed marked hypervascularity and multifocal-hemangiomas which implicated this kinase in the regulation of angiogenesis. Here we explored the potential involvement of Fps/Fes in the regulation of hemostasis through effects on blood cells and the vascular endothelium. Hematological parameters of fpsMF mice were characterized by peripheral blood analysis, histology, and transmission electron microscopy. Hemostasis parameters and platelet functions were assessed by flow cytometry and measurements of activated partial thromboplastin time, prothrombin time, thrombin clot time, platelet aggregation, bleeding times and in vitro fibrinolytic assays. Hematological and morphological analyses showed that fpsMF mice displayed mild thrombocytopenia, anemia, red cell abnormalities and numerous hemostatic defects, including hypofibrinogenemia, hyper-fibrinolysis, impaired whole blood aggregation and a mild bleeding diathesis. fpsMF mice displayed a complex array of hemostatic perturbations which are reminiscent of hemostatic disorders such as disseminated intravascular coagulation (DIC) and of hemangioma-associated pathologies such as Kasabach,Merritt phenomenon (KMS). These studies suggest that Fps/Fes influences both angiogenic and hemostatic function through regulatory effects on the endothelium. [source] Development of fluridil, a topical suppressor of the androgen receptor in androgenetic alopeciaDRUG DEVELOPMENT RESEARCH, Issue 3 2003Allen L Seligson Abstract Nonsteroidal antiandrogens (AA) cannot be topically used for androgenetic alopecia (AGA) because of systemic resorption. A new class of androgen receptor (AR) suppressors designed for safe topical treatment of AGA was synthesized from (3-amino-2-hydroxy-2-methyl- N -(4-nitro-3-trifluoromethyl)phenyl) propanamide (BP-34), to contain perfluoroalkyl moieties. The trifluoromethyl derivative (fluridil) at 10 ,M decreased expression of the AR in LNCaP human cells by 95%, its serum half-life was 6 h; it decomposes hydrolytically to BP-34 and trifluoroacetic acid. Acute intraperitoneal maximum tolerated dose (MTD) of fluridil in mice is 270,300 mg/kg/d and the subacute MTD is 450 mg/kg/d. The oral LD50 in mice was 2,872 mg/kg in males, 2,232 mg/kg in females, and >2,500 mg/kg in rats. Fluridil solution in isopropanol was not cutaneously absorbed in rabbits, did not sensitize or show any phototoxic or photoallergic effects on guinea pig skin, and demonstrated no skin irritation potential in rabbits and humans. Fluridil solid induced only slight and reversible eye irritancy in rabbits and displayed no cytotoxicity to rabbit corneal fibroblasts in vitro. Fluridil demonstrated no significant mutagenicity potential by Ames method. In a double-blind study, 43 males with AGA, Norwood grade II to Va, used topical 2% fluridil in isopropanol or the vehicle daily for 12 months. Anagens (growing hairs) increased in the fluridil group from 76% to 89%. All hematological and biochemistry values remained within normal range, including testosterone, which varied but seasonally. No fluridil or its decomposition product (BP-34) was detected in serum. No adverse side effects were reported. Drug Dev. Res. 59:292,306, 2003. © 2003 Wiley-Liss, Inc. [source] Serum transferrin receptor, ferritin, and reticulocyte maturity indices during the first year of life in ,large' preterm infantsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2007Vassiliki Schiza Abstract Background:, Preterm infants are at risk of developing iron deficiency; among the iron status and hemopoiesis indices the serum transferrin receptor (sTfr) has been shown to be a useful indicator in assessing iron status, while immature reticulocyte production is regarded as an estimator of erythropoiesis. Objective:, To investigate age-related changes in iron status infants born ,moderately' preterm, with a gestational age (GA) of 32,36 wk, and identify associations between sTfr and other hematological and biochemical iron indices. Design:, Hospital-based prospective, longitudinal study in preterm infants. Methods:, Iron and erythropoiesis parameters were evaluated in 181 formula-fed preterm infants at 2 and 6 wk and 3, 6, 9, and 12 months chronological age. Hemoglobulin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), reticulocytes, serum iron (sFe), serum ferritin (sFer), sTfr, and reticulocyte subpopulations were measured. Results:, A total of 756 measurements were performed. After an initial decline, Hb rose from month 3 to 12 of life. SFe and sFer and immature reticulocyte count decreased from the second week to the third month and remained stable thereafter. STfr was lower up to 6 wk and stable from month 3 to 12. Iron deficiency anemia (IDA) was found in 5.5% of infants. In 76 measurements sFer was <12 ,g/L, implying storage iron deficiency (SID). A negative correlation was observed between sTfr and other indices of iron status such as Hb, Hct, MCV, sFe, and sFer. Infants with sFer <12 ,g/L had lower sTfr than those with sFer >12 ,g/L. Reticulocyte production was positively associated with STfr, but this association was dependent on the chronological age of the infant. Conclusion:, Iron depletion is common in formula-fed preterm (32,36 wk GA) infants between month 3 and 12 of life. STfr appears to be an indicator of iron status in preterm infants during the first year of life. [source] Protein deficiency balance as a predictor of clinical outcome in hereditary spherocytosisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2005S. Rocha Abstract:, Vertical and horizontal interactions between membrane constituents account for integrity, strength and deformability of the erythrocyte. Disruption of vertical interactions caused by membrane protein deficiencies in hereditary spherocytosis (HS), favor membrane vesiculation with development of spherocytic cells. Our aim was to evaluate the hematological and clinical presentation of HS according to the type and amount of protein deficiency. We studied 81 Portuguese individuals, 71 belonging to 21 families plus 10 unrelated subjects, and found that 51 of them were HS patients. Patients were classified as presenting mild, typical or severe HS, according to laboratory results and clinical follow-up. We performed screening tests and the standardized electrophoretic membrane protein analysis to identify and quantify protein deficiencies. We found band 3 and ankyrin deficiencies as the major causes for HS. The ratios between the value of the primary and/or secondary protein deficiencies showed significantly different values according to the severity of HS, and a significant inverse correlation with the severity of HS was observed. In mild HS, the ratios between protein deficiencies reflected equivalent protein deficiencies, while an unbalance was observed in typical HS, which was enhanced in severe HS. Our data suggest that the relative quantification of each major membrane protein and of the ratios between the values of protein deficiencies may be helpful in providing additional data about the clinical outcome of HS. [source] Assessment of peripheral blood lymphocyte subsets in idiopathic myelofibrosisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2000Francisco Cervantes Abstract: The objective of this study was to contribute to a better characterization of the immunological profile of idiopathic myelofibrosis (IM) at presentation by analysing the blood lymphocyte subsets and their possible correlations with other disease features. Absolute blood lymphocytes and lymphocyte subsets were assessed in 31 IM patients, compared with those from 34 healthy individuals, and correlated with the patients' main clinical, hematological and bone marrow histologic features. The mean lymphocyte count of the IM patients was 1.1 (SD 0.6)×109/L, versus 1.6 (SD 0.49)×109/L in controls (p=0.0006), with 24 of the 31 patients (77.4%) showing lymphocytopenia (<1.5×109/L). IM patients had significantly lower counts of CD3, CD4, CD8, and CD3,/CD56+ cells, and significantly higher CD3+/CD56+ lymphocyte counts. Although no significant differences were found between patients and controls with regard to CD19+/CD5+ cell counts, increased CD5+ B-cell lymphocytes were observed in three IM patients. In one of the latter patients, Ig gene rearrangement analysis of the heavy chain gene demonstrated such a subpopulation to be clonal, but the patient did not develop features of chronic lymphoid leukemia during a 5-yr follow-up. No correlation was found between the patients' blood lymphocyte counts and other disease features. We conclude that most IM patients have absolute lymphopenia, decreased T cells and increased cytotoxic T cells at diagnosis, and 10% of them show an increased CD5+ B-cell subpopulation. [source] Comparison of hematologic or biochemical parameters among elderly hospital patients, institution-dwelling residents, and health check-up examineesGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 3 2003Ryuichi Yamamoto Background: The purpose of the present paper was to examine the differences in the levels of hematological or biochemical parameters among elderly hospital patients, nursing home residents, and mass health check-up recipients. Methods: One hundred and 44 geriatric inpatients (aged , 65 years), 237 outpatients, 146 nursing home residents, 120 aged examinees from mass health check-ups, and 512 younger health check-up examinees (controls) were included in the present study. They were divided into five male and five female subgroups, respectively. The levels of hemoglobin (Hb), white blood cells (WBC), serum albumin (Alb), Ca, albumin-corrected Ca, Na, creatinine (Cr), and total cholesterol (TC) were determined and compared. Results: There were significantly lower levels of Hb, Alb, Ca, Na, and TC in inpatients than in other groups in both sexes. In contrast, higher levels of WBC and Cr were found in inpatients. Among women there was no difference in the level of any parameter between nursing home residents, health check-up examinees, and controls. Conclusion: The data indicate that the levels of these parameters are affected to a greater extent in inpatients, and that female nursing home residents and health check-up examinees show values similar to those of controls. [source] Recent role of splenectomy in chronic hepatic disordersHEPATOLOGY RESEARCH, Issue 12 2008Toru Ikegami For years splenectomy in hepatic disorders has been indicated only for the treatment of gastro-esophageal varices. However, with recent advances in medical and surgical treatments for chronic hepatic disorders, the use of splenectomy has been greatly expanded, such that splenectomy is used for reversing hypersplenism, for applying interferon treatment for hepatitis C, for treating hyperdynamic portal circulation associated with intractable ascites, and for controlling portal pressure during small grafts in living donor liver transplantation. Such experiences have shown the importance of portal hemodynamics, even in cirrhotic livers. Recent advances in surgical techniques have enabled surgeons to perform splenectomy more safely and less invasively, but the procedure still has considerable clinical outcomes. Splenectomy in hepatic disorders may become a more common procedure with expanded indications. However, it should also be noted that the long-term effects of splenectomy, in terms of improved hematological or hepatic function, is still not guaranteed. Moreover, the impact of splenectomy on immunologic status remains unclear and needs to be elucidated in both experimental and clinical settings. [source] Chronic effects of polychlorinated dibenzofurans on mink in laboratory and field environmentsINTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT, Issue 2 2009Matthew J Zwiernik Abstract Mink are often used as a sentinel species in ecological risk assessments of chemicals such as polychlorinated biphenyls (PCBs), dibenzo- p -dioxins (PCDDs), and dibenzofurans (PCDFs) that cause toxicity mediated through the aromatic hydrocarbon receptor. Considerable toxicological information is available on the effects of PCBs and PCDDs on mink, but limited toxicological information is available for PCDFs. Thus, exposure concentrations at which adverse effects occur could not be determined reliably for complex mixtures in which PCDFs dominate the total calculated concentration of 2,3,7,8-tetrachlorodibenzo- p -dioxin equivalent (TEQ). Two studies were conducted to evaluate the potential toxicity of PCDFs to mink. The first was a chronic exposure, conducted under controlled laboratory conditions, in which mink were exposed to 2,3,7,8-tetrachlorodibenzofuran (2,3,7,8-TCDF) concentrations as great as 2.4 × 103 ng 2,3,7,8-TCDF/kg wet-weight (ww) diet or 2.4 × 102 ng TEQ2006-WHO-mammal/kg ww diet. In that study, transient decreases in body masses of kits relative to the controls was the only statistically significant effect observed. The second study was a 3-y field study during which indicators of individual health, including hematological and morphological parameters, were determined for mink exposed chronically to a mixture of PCDDs and PCDFs under field conditions. In the field study, there were no statistically significant differences in any of the measured parameters between mink exposed to a median estimated dietary dose of 31 ng TEQ2006-WHO-mammal/kg ww and mink from an upstream reference area where they had a median dietary exposure of 0.68 ng TEQ2006-WHO-mammal/kg ww. In both studies, concentrations of TEQ2006-WHO-mammal to which the mink were exposed exceeded those at which adverse effects, based on studies with PCDD and PCB congeners, would have been expected. Yet in both instances where PCDF congeners were the sole or predominant source of the TEQ2006-WHO-mammal, predicted adverse effects were not observed. Taken together, the results of these studies suggest that the values of the mammalian-specific toxicity equivalency factors suggested by the World Health Organization overestimate the toxic potency of PCDFs to mink. Therefore, hazard cannot be accurately predicted by making comparisons to toxicity reference values derived from exposure studies conducted with PCBs or PCDDs in situations where mink are exposed to TEQ mixtures dominated by PCDFs. [source] The effects of telomerase inhibition on prostate tumor-initiating cellsINTERNATIONAL JOURNAL OF CANCER, Issue 2 2010Calin O. Marian Abstract Prostate cancer is the most common malignancy in men, and patients with metastatic disease have poor outcome even with the most advanced therapeutic approaches. Most cancer therapies target the bulk tumor cells, but may leave intact a small population of tumor-initiating cells (TICs), which are believed to be responsible for the subsequent relapse and metastasis. Using specific surface markers (CD44, integrin ,2,1 and CD133), Hoechst 33342 dye exclusion, and holoclone formation, we isolated TICs from a panel of prostate cancer cell lines (DU145, C4-2 and LNCaP). We have found that prostate TICs have significant telomerase activity which is inhibited by imetelstat sodium (GRN163L), a new telomerase antagonist that is currently in Phase I/II clinical trials for several hematological and solid tumor malignancies. Prostate TICs telomeres were of similar average length to the telomeres of the main population of cells and significant telomere shortening was detected in prostate TICs as a result of imetelstat treatment. These findings suggest that telomerase inhibition therapy may be able to efficiently target the prostate TICs in addition to the bulk tumor cells, providing new opportunities for combination therapies. [source] Systemic Inflammatory Response Syndrome in Nosocomial Bloodstream Infections with Pseudomonas aeruginosa and Enterococcus Species: Comparison of Elderly and Nonelderly PatientsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2006Alexandre R. Marra MD OBJECTIVES: To determine whether the systemic inflammatory response syndrome (SIRS), clinical course, and outcome of monomicrobial nosocomial bloodstream infection (BSI) due to Pseudomonas aeruginosa or Enterococcus spp. is different in elderly patients than in younger patients. DESIGN: Historical cohort study. SETTING: An 820-bed tertiary care facility. PARTICIPANTS: One hundred twenty-seven adults with P. aeruginosa or enterococcal BSI. MEASUREMENTS: SIRS scores were determined 2 days before the first positive blood culture through 14 days afterwards. Elderly patients (,65, n=37) were compared with nonelderly patients (<65, n=90). Variables significant for predicting mortality in univariate analysis were entered into a logistic regression model. RESULTS: No difference in SIRS was detected between the two groups. No significant difference was noted in the incidence of organ failure, 7-day mortality, or overall mortality between the two groups. Univariate analysis revealed that Acute Physiology And Chronic Health Evaluation (APACHE) II score of 15 or greater at BSI onset; adjusted APACHE II score (points for age excluded) of 15 or greater at BSI onset; and respiratory, cardiovascular, renal, hematological, and hepatic failure were predictors of mortality. Age, sex, use of empirical antimicrobial therapy, and infection with imipenem-resistant P. aeruginosa or vancomycin-resistant enterococci did not predict mortality. Multivariate analysis revealed that hematological failure (odds ratio (OR)=8.1, 95% confidence interval (CI)=2.78,23.47), cardiovascular failure (OR=4.7, 95% CI=1.69,13.10), and adjusted APACHE II , 15 at BSI onset (OR=3.1, 95% CI=1.12,8.81) independently predicted death. CONCLUSION: Elderly patients did not differ from nonelderly patients with respect to severity of illness before or at the time of BSI. Elderly patients with pseudomonal or enterococcal BSIs did not have a greater mortality than nonelderly patients. [source] Tunisian radish extract (Raphanus sativus) enhances the antioxidant status and protects against oxidative stress induced by zearalenone in Balb/c miceJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2008Jalila Ben Salah-Abbès Abstract Radish (Raphanus sativus) is a food plant known worldwide. From antiquity it has been used in folk medicine as a natural drug against many toxicants. Zearalenone (zen) is a non-steroidal estrogenic mycotoxin present in corn and food mixture for farm animals and it is hepatotoxic, hematotoxic, immunotoxic, nephrotoxic and genotoxic. The objectives of the present study were to assess the biological activity of radish extract and to evaluate the protective role of radish extract against the toxicity of zen in female Balb/c mice. Animals were divided into seven groups and treated orally for 10 days as follows: a control, an olive oil group, groups treated with radish extract alone (5, 10 and 15 mg kg,1 b.w.), a group treated with zen (40 mg kg,1 b.w.) and a group treated with zen plus the lowest dose of radish extract. The results indicate that radish extract improved the antioxidant status and had no significant effects on hematological and biochemical parameters tested or histology of the liver and kidney. Treatment with zen results in a significant increase in ALT, AST, ALP, BILT, BILD, CRE accompanied with significant changes in most of hematological parameters and the antioxidant enzyme activities, co-treatment of zen and the radish extract results in a significant reestablishment of hematological, serum biochemical parameters, and the histology of the liver and kidney. These findings suggest that radish extract is safe and can be overcome or, at least, significantly diminish zen effects. Copyright © 2007 John Wiley & Sons, Ltd. [source] Effects of an ethanol,gasoline mixture: results of a 4-week inhalation study in ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2005I. Chu Abstract The inhalation toxicity of an ethanol,gasoline mixture was investigated in rats. Groups of 15 male and 15 female rats were exposed by inhalation to 6130 ppm ethanol, 500 ppm gasoline or a mixture of 85% ethanol and 15% gasoline (by volume, 6130 ppm ethanol and 500 ppm gasoline), 6 h a day, 5 days per week for 4 weeks. Control rats of both genders received HEPA[sol ]charcoal-filtered room air. Ten males and ten females from each group were killed after 4 weeks of treatment and the remaining rats were exposed to filtered room air for an additional 4 weeks to determine the reversibility of toxic injuries. Female rats treated with the mixture showed growth suppression, which was reversed after 4 weeks of recovery. Increased kidney weight and elevated liver microsomal ethoxyresorufin- O -deethylase (EROD) activity, urinary ascorbic acid, hippuric acid and blood lymphocytes were observed and most of the effects were associated with gasoline exposure. Combined exposure to ethanol and gasoline appeared to exert an additive effect on growth suppression. Inflammation of the upper respiratory tract was observed only in the ethanol,gasoline mixture groups, and exposure to either ethanol and gasoline had no effect on the organ, suggesting that an irritating effect was produced when the two liquids were mixed. Morphology in the adrenal gland was characterized by vacuolation of the cortical area. Although histological changes were generally mild in male and female rats and were reversed after 4 weeks, the changes tended to be more severe in male rats. Brain biogenic amine levels were altered in ethanol- and gasoline-treated groups; their levels varied with respect to gender and brain region. Although no general interactions were observed in the brain neurotransmitters, gasoline appeared to suppress dopamine concentrations in the nucleus accumbens region co-exposed to ethanol. It was concluded that treatment with ethanol and gasoline, at the levels studied, produced mild, reversible biochemical hematological and histological effects, with some indications of interactions when they were co-administered. Copyright © 2005 John Wiley & Sons, Ltd. [source] One-year dog toxicity study of D-002, a mixture of aliphatic alcoholsJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2001Celia Alemán Abstract D-002 is a mixture of high-molecular-weight aliphatic alcohols, obtained from bees wax (Apis mellifera), with mild anti-inflammatory properties and effective anti-ulcer activities demonstrated in experimental models. This study investigated the oral toxicity of D-002 administered for 1 year to beagle dogs. Twenty-four beagle dogs (12 males and 12 females) were distributed randomly in three experimental groups (four animals per group): a control and two treated groups received D-002 at 50 and 250 mg kg,1 (7 days/week) by gastric gavage. Overall, D-002 was well tolerated throughout the study. No signs or symptoms of toxicity were observed, and no mortality occurred during the study. All groups showed similar weight gain and food consumption. No hematological, blood biochemical or histopathological disturbances attributable to treatment were observed. This study shows no drug-related toxicity induced by long-term administration of up to 250 mg kg,1 D-002 to beagle dogs. Copyright © 2001 John Wiley & Sons, Ltd. [source] Chronic toxicity/oncogenicity study of styrene in cd-1 mice by inhalation exposure for 104 weeksJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2001George Cruzan Abstract Groups of 70 male and 70 female Charles River CD-1 mice were exposed whole body to styrene vapor at 0, 20, 40, 80 or 160 ppm 6 h per day 5 days per week for 98 weeks (females) or 104 weeks (males). The mice were observed daily; body weights, food and water consumption were measured periodically, a battery of hematological and clinical pathology examinations were conducted at weeks 13, 26, 52, 78 and 98 (females)/104 (males). Ten mice of each gender per group were pre-selected for necropsy after 52 and 78 weeks of exposure and the survivors of the remaining 50 of each gender per group were necropsied after 98 or 104 weeks. An extensive set of organs from the control and high-exposure mice were examined histopathologically, whereas target organs, gross lesions and all masses were examined in all other groups. Styrene had no effect on survival in males. Two high-dose females died (acute liver toxicity) during the first 2 weeks; the remaining exposed females had a slightly higher survival than control mice. Levels of styrene and styrene oxide (SO) in the blood at the end of a 6 h exposure during week 74 were proportional to exposure concentration, except that at 20 ppm the SO level was below the limit of detection. There were no changes of toxicological significance in hematology, clinical chemistry, urinalysis or organ weights. Mice exposed to 80 or 160 ppm gained slightly less weight than the controls. Styrene-related non-neoplastic histopathological changes were found only in the nasal passages and lungs. In the nasal passages of males and females at all exposure concentrations, the changes included respiratory metaplasia of the olfactory epithelium with changes in the underlying Bowman's gland; the severity increased with styrene concentration and duration of exposure. Loss of olfactory nerve fibers was seen in mice exposed to 40, 80 or 160 ppm. In the lungs, there was decreased eosinophilia of Clara cells in the terminal bronchioles and bronchiolar epithelial hyperplasia extending into alveolar ducts. Increased tumor incidence occurred only in the lung. The incidence of bronchioloalveolar adenomas was significantly increased in males exposed to 40, 80 or 160 ppm and in females exposed to 20, 40 and 160 ppm. The increase was seen only after 24 months. In females exposed to 160 ppm, the incidence of bronchiolo-alveolar carcinomas after 24 months was significantly greater than in the controls. No difference in lung tumors between control and styrene-exposed mice was seen in the intensity or degree of immunostaining, the location of tumors relative to bronchioles or histological type (papillary, solid or mixed). It appears that styrene induces an increase in the number of lung tumors seen spontaneously in CD-1 mice. Copyright © 2001 John Wiley & Sons, Ltd. [source] Diphenyl diselenide protects against hematological and immunological alterations induced by mercury in miceJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 5 2008Ricardo Brandão Abstract Mercury is a heavy metal that can cause a variety of toxic effects on the organism, such as hematological and immunological alterations. In the present investigation, deleterious effects of mercury-intoxication in mice and a possible protective effect of diphenyl diselenide (PhSe)2 were studied. Male adult Swiss albino mice received daily a pretreatment with (PhSe)2 (15.6 mg/kg, orally) for 1 week. After this week, mice received daily mercuric chloride (1 mg/kg, subcutaneously) for 2 weeks. A number of hematological (erythrocytes, leukocytes, platelets, hemoglobin, hematocrit, reticulocytes, and leukocytes differential) and immunological (immunoglobulin G and M plasma concentration) parameters were evaluated. Another biomarker of tissue damage, lactate dehydrogenase (LDH), was also determined. The results demonstrated that mercury exposure caused a reduction in the erythrocyte, hematocrit, hemoglobin, leukocyte, and platelet counts and an increase in the reticulocyte percentages. (PhSe)2 was effective in protecting against the reduction in hematocrit, hemoglobin, and leukocyte levels. (PhSe)2 ameliorated reticulocyte percentages increased by mercury. However, (PhSe)2 was partially effective in preventing against the decrease in erythrocyte and platelet counts. Immunoglobulin G and M concentrations and LDH activity were increased by mercury exposure, and (PhSe)2 was effective in protecting against these effects. In conclusion, (PhSe)2 was effective in protecting against hematological and immunological alterations induced by mercury in mice. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:311,319, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20242 [source] Comparative evaluation of heating ability and biocompatibility of different ferrite-based magnetic fluids for hyperthermia applicationJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2007Pallab Pradhan Abstract In this study, lauric acid-coated, superparamagnetic, nanoparticle-based magnetic fluids of different ferrites (Fe3O4, MnFe2O4, and CoFe2O4) were prepared and compared in terms of heating ability and biocompatibility to evaluate the feasibility of use in hyperthermia treatment of cancer. All the magnetic fluids prepared had particles of average sizes 9,11 nm. Heating ability of these magnetic fluids was evaluated by calorimetric measurement of specific absorption rate (SAR) at 300 kHz frequency and 15 kA/m field. Fe3O4 and MnFe2O4 showed higher SAR (120 and 97 W/g of ferrite, respectively) than CoFe2O4 (37 W/g of ferrite). In vitro study on BHK 21 cell lines showed dose-dependent cell viability for all the magnetic fluids. Threshold-biocompatible ferrite concentration for all the magnetic fluids was 0.1 mg/mL. Above 0.2 mg/mL, CoFe2O4 was more toxic than the other magnetic fluids. On intravenous injection of different doses (50, 200, and 400 mg/kg body weight) of magnetic fluids in mice, no significant changes in hematological and biochemical parameters were observed for Fe3O4 and MnFe2O4. With CoFe2O4, an increase in SGPT levels at a dose rate of 400 mg/kg body weight was observed, indicating its mild hepatotoxic effect. However, histology of different vital organs showed no pathological changes for all the three magnetic fluids. Further, long term in vivo evaluation of biocompatibility of the lauric acid-coated ferrites is warranted. This study shows that lauric acid-coated, superparamagnetic Fe3O4 and MnFe2O4 may be used for hyperthermia treatment and are to be preferred over CoFe2O4. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006 [source] Granulocyte colony-stimulating factor produces a decrease in IFN, and increase in IL-4 when administrated to healthy donorsJOURNAL OF CLINICAL APHERESIS, Issue 4 2010Octavio Rodríguez-Cortés Abstract Hematopoietic stem cells transplantation (HSCT) is the leading curative therapy for a variety of hematological and hereditary diseases; however, graft versus host disease (GVHD), an immunologic phenomenon that is favored by Th1 cytokines and cytotoxic cells from donors, is present frequently and is one of the most important causes of transplant related mortality. Peripheral blood HSCT is the preferred source of stem cells in almost 100% of the cases of autologous HSCT and in 70% of allogeneic transplants. The best mobilizing agent to get the stem cells out from the bone marrow is the Granulocyte-Colony Stimulating Factor (G-CSF). In this work, our main objective was to study a possible correlation between the graft cell dose and the patient's clinical outcome. We evaluated the immunologic changes produced by G-CSF in the lymphocyte and cytokine profiles in allogeneic HSC donors. HSC from twelve donors were mobilized with G-CSF at 16 ,g/kg/day, for 5 days. Basal Peripheral Blood (BPB), Mobilized Peripheral Blood (MPB), and aphaeresis mononuclear cells (G-MNC) samples were taken from all donors. Using flow cytometry, we quantified CD19+, CD3+, CD3+CD4+, CD3+CD8+, NK, NKT, DC1, and DC2 cells. Cytokines were determined by ELISA in culture supernatants. CD19+ (p = 0.001), DC1 (p < 0.002) and DC2 (p < 0.001) cells were increased in MPB with respect to BPB. An increase in Th2 cytokines such as (IL-4) and a decrease in Th1 cytokines (IFN,, IL-2) were also found in MPB samples. In conclusion, Th1 and Th2 cytokines are relevant in predicting the clinical outcome after allogeneic peripheral blood HSCT. J. Clin. Apheresis 25:181,187, 2010. © 2010 Wiley-Liss, Inc. [source] Increased risk of citrate reactions in patients with multiple myeloma during peripheral blood stem cell leukapheresisJOURNAL OF CLINICAL APHERESIS, Issue 4 2010Jill Adamski Abstract The citrate based anticoagulant ACD is commonly used in apheresis procedures. Due to its ability to decrease ionized calcium, citrate may cause unpleasant symptoms, such as paresthesias and muscle cramps, in patients undergoing therapeutic and donor apheresis. We noticed that patients with multiple myeloma (MM) undergoing autologous stem cell leukapheresis appeared to have more citrate reactions when compared to other patients undergoing the same procedure. A retrospective chart review was performed to evaluate 139 (of 151) consecutive patients with MM, amyloidosis, hematological and solid malignancies who had autologous peripheral blood stem cell collection between January 2007 and February 2008. Citrate reactions, ranging from mild (e.g., perioral tingling and parasthesias) to severe (e.g., nausea/vomiting and muscle cramps) were noted for 35 patients. Twenty-three of 63 patients with MM had documented citrate reactions, which was significantly higher than those with other hematological and solid malignancies (37% vs. 20%; P < 0.05, Relative Risk (RR) = 1.9). The severities of citrate reactions were the same in both groups; approximately 50% of patients in each group received i.v. calcium gluconate for treatment of hypocalcemia. No correlation between bisphosphonate therapy and citrate reactions were noted in our study group. Examination of available laboratory values related to calcium homeostasis, liver, and renal function failed to reveal a mechanism for the increase in citrate reactions observed. In summary, this single institution retrospective study indicates that patients with MM are more sensitive to citrate-induced hypocalcemia during leukapheresis when compared to patients with other hematological and solid malignancies. Strategies for decreasing citrate reactions (e.g., supplemental calcium and slowing return rates) should be considered for patient safety and comfort, especially in the MM population, on a prophylactic rather than reactive basis. J. Clin. Apheresis 25:188,194, 2010. © 2010 Wiley-Liss, Inc. [source] The number of CD34+ cells in peripheral blood as a predictor of the CD34+ yield in patients going to autologous stem cell transplantationJOURNAL OF CLINICAL APHERESIS, Issue 2 2006A.L. Basquiera Abstract The number of CD34+ cells in peripheral blood (PB) is a guide to the optimal timing to harvest peripheral blood progenitor cells (PBPC). The objective was to determine the number of CD34+ cells in PB that allows achieving a final apheresis product containing ,1.5 × 106 CD34+ cells/kg, performing up to three aphereses. Between March 1999 and August 2003, patients with hematological and solid malignancies who underwent leukapheresis for autologous bone marrow transplantation were prospectively evaluated. Seventy-two aphereses in 48 patients were performed (mean 1.45 per patient; range 1,3). PBPC were mobilized with cyclophosphamide plus recombinant human granulocyte-colony stimulating factor (G-CSF) (n = 40), other chemotherapy drugs plus G-CSF (n = 7), or G-CSF alone (n = 1). We found a strong correlation between the CD34+ cells count in peripheral blood and the CD34+ cells yielded (r = 0.903; P < 0.0001). Using receiver-operating characteristic (ROC) curves, the minimum number of CD34+ cells in PB to obtain ,1.5 × 106/kg in the first apheresis was 16.48 cells/,L (sensitivity 100%; specificity 95%). The best cut-off point necessary to obtain the same target in the final harvest was 15.48 cells/,L, performing up to three aphereses (sensitivity 89%; specificity 100%). In our experience, ,15 CD34+ cells/,L is the best predictor to begin the apheresis procedure. Based on this threshold level, it is possible to achieve at least 1.5 × 106/kg CD34+ cells in the graft with ,3 collections. J. Clin. Apheresis 2005. © 2005 Wiley-Liss, Inc. [source] The effect of long-term streptozotocin-induced diabetes mellitus (STZ-DM) on cynomolgus (Macaca Fascicularis) monkeysJOURNAL OF MEDICAL PRIMATOLOGY, Issue 1 2009D. Wu Abstract Background, This study aimed to retrospectively analyze the effect of long-term streptozotocin-induced diabetes mellitus (STZ-DM) on adolescent cynomolgus monkeys. Methods, A total of 12 monkeys (six STZ-DM and six controls) were monitored for fasting glucose levels and locomotor activities, tested for hematological and serum parameters, measured for body weight and somatometric values. Results, Fasting glucose was maintained at high levels in STZ-DM monkeys. At the age when normal adolescent monkeys dramatically increased their weight, STZ-DM led to the retardation of weight increase in diabetic monkeys. Moreover, STZ-DM monkeys showed abnormal lipid levels and somatometric measurements. In locomotor activity test, STZ-DM monkeys were more active than control ones. Conclusions, Long-term STZ-DM disrupts the normal growth of young monkeys and interferes with some aspects of hormone, lipid metabolism and physical activities. Mean plasma glucose (MPG) appeared to be an important factor in physical activity abnormalities of STZ-DM monkeys. [source] Comparison of the efficacy between paclitaxel/carboplatin and doxorubicin/cisplatin for concurrent chemoradiation in intermediate- or high-risk endometrioid endometrial cancer: A single institution experienceJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2010Hee Seung Kim Abstract Aim:, We sought to compare survival and toxicity between paclitaxel/carboplatin (TC) and doxorubicin/cisplatin (AP) for concurrent chemoradiation (CCR) in intermediate- or high-risk endometrioid endometrial cancer. Methods:, The clinical data of 40 patients with intermediate- (FIGO stage IC-IIB, n = 12) or high-risk endometrioid endometrial cancer (FIGO stage IIIA-IVA, n = 28) were reviewed retrospectively between March 2000 and December 2007, who were treated with TC (n = 23, group 1) or AP (n = 17, group 2) for CCR after surgery. Results:, Progression-free survival (PFS) and overall survival (OS) were not different between groups 1 and 2 (median PFS and OS; 35 vs 24 and 76 vs 39 months, respectively, P > 0.05). However, ,6 cycles of chemotherapy improved PFS compared with 3,5 cycles of chemotherapy (51 vs 21 months, P = 0.04), suggesting that ,6 cycles of chemotherapy was an independent prognostic factor improving PFS (adjusted HR, 0.27; 95% CI, 0.08 to 0.91; P = 0.04). Grade 3 or 4 hematological and non-hematological, especially, gastrointestinal, toxicities related with chemotherapy during CCR were more common in group 2 than in group 1, whereas there was no difference in grade 3 or 4 late complication by CCR between the 2 groups. Conclusion:, These findings suggest that TC may have comparable efficacy to AP for CCR with lesser toxicity, and ,6 cycles of chemotherapy may be more beneficial than 3,5 cycles of chemotherapy in intermediate- or high-risk endometrioid endometrial cancer. However, large-scale randomized controlled trials are needed to support these results. [source] Recurrent pregnancy loss: A disease of inflammation and coagulationJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4 2009Joanne Kwak-Kim Abstract Recurrent pregnancy loss (RPL) is one of the most common obstetrical complications. Multiple etiologies, such as endocrine, anatomic, genetic, hematological and immunological causes have been reported for this devastating disease. However, over half of the cases remain unexplained. Thrombotic/inflammatory processes are often observed at the maternal-fetal interface as the final pathological assault in many cases of RPL, including those of unexplained etiologies. In the present paper, cellular immune responses (T, natural killer [NK], natural killer-T [NKT], regulatory T [Treg] cells and their cytokines) and autoimmune abnormalities of women with RPL are reviewed. In addition, metabolic diseases and hematological conditions which often lead to thrombotic/inflammatory conditions are discussed in association with RPL. Finally, current therapeutic options for RPL are reviewed. [source] Melatonin protects against cardiac toxicity of doxorubicin in ratJOURNAL OF PINEAL RESEARCH, Issue 4 2001Mei Feng Xu Doxorubicin (DOX) is commonly used for the treatment of hematological and solid tumors. However, there are serious toxic effects on the cardiovascular system, which limits the application of the drug. Recently, melatonin has been reported to have immunomodulatory effect in addition to lowering cholesterol levels as well as inhibiting malignant tumors. In this study, the effect of melatonin against the toxicity of doxorubicin was investigated in rats. Hemodynamic function, pathological and biochemical changes were determined in different treated hearts. Our findings showed that a significant protection by melatonin (6 mg kg,1 for 15 days, cumulative dose of 90 mg kg,1) against the DOX-induced toxicity was observed. Cardiac function was improved and lipid peroxidation decreased after melatonin treatment. It is concluded that melatonin provides protection against doxorubicin toxicity via an attenuation of lipid peroxidation. [source] Immune Response and Resistance to Stress and Edwardsiella ictaluri Challenge in Channel Catfish, Ictalurus punctatus, Fed Diets Containing Commercial Whole-Cell Yeast or Yeast SubcomponentsJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 1 2007Thomas L. Welker Dietary supplementation of yeast or yeast subcomponents (YYS) as commercial preparations of ,-glucan (MacroGard®; Biotec-Mackzymal, Tromsø, Norway; and Betagard A®; Aqua-In-Tech, Inc., Seattle, WA, USA), mannan oligosaccharide (Bio-MosÔ Aqua Grade; Alltech, Nicholasville, KY, USA), or whole-cell Saccharomyces cerevisiae (Levucell SB20®; Lallemand Animal Nutrition, Milwaukee, WI, USA) at the manufacturer's recommended levels was evaluated on the physiological performance of juvenile channel catfish, Ictalurus punctatus. Fish were fed YYS diets for 4 wk, followed by 2 wk of control diet. Fish were sampled at the end of each feeding period (4 and 6 wk) to measure hematological and immune parameters and growth and to determine the effects of dietary ,-glucan on resistance to Edwardsiella ictaluri infection and to low-water stress (6 wk). Supplementation of YYS in diets did not affect growth performance, hematology, or immune function. Survival from E. ictaluri infection was from 5 to 17.5% higher in fish fed YYS diets than in the control group, but the increases were not significant. Some improvement in stress resistance was observed in YYS-fed catfish after exposure to low-water stress. Stress reduction in fish fed diets supplemented with yeast subcomponents has been reported previously, but thus far, no explanation has been proposed for this effect. The present study and the previously published research suggest that dietary YYS supplementation does not appear to improve resistance of channel catfish to E. ictaluri. [source] Evaluation of hematological, chemistry and blood gas values in dogs receiving hemoglobin glutamer-200JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 1 2007DACVECC, DACVIM, Marie E. Kerl DVM Abstract Objective: To evaluate the degree of interference that administration of hemoglobin glutamer-200 (Hb-200) caused for complete blood counts (CBC), biochemical profiles, cooximetry, and point of care (POC) testing in healthy dogs. Design: Prospective, longitudinal experimental study. Setting: Veterinary medical teaching hospital. Animals: Six purpose-bred research hounds. Interventions: Dogs were administered FDA-approved hemoglobin-based oxygen carrier (Hb-200) intravenously at 7.5 mL/kg over 2 hours. Arterial and venous blood samples were obtained before administration (Time 0) and at 3, 8, 14, 26, 50, 74, 98, 122, and 146 hours following administration. Measurements and main results: No adverse health effects were observed in any of the dogs. Characteristic mucous membrane, serum, and plasma color changes occurred following administration of Hb-200. Laboratory values that were significantly lower than baseline included packed cell volume, red blood cell count, hemoglobin, hematocrit, creatinine, cholesterol, alanine aminotransferase, and alkaline phosphatase. Laboratory values that were significantly greater than baseline included mean corpuscular hemoglobin concentration, arterial pH, arterial total carbon dioxide, arterial bicarbonate, amylase, albumin, total protein, globulin, calcium, phosphorous, total bilirubin, carboxyhemoglobin, and methemoglobin. All values returned to baseline by the completion of the 146-hour monitoring period. Conclusions: In normal dogs, administration of Hb-200 resulted in statistically significant changes in multiple laboratory parameters; however, these changes are not likely to be clinically significant in the care of critically ill dogs. [source] Clinical, virological and histopathological features: long-term follow-up in patients with chronic hepatitis C co-infected with S. mansoniLIVER INTERNATIONAL, Issue 4 2000Sanaa Kamal Abstract:Background/Aims: Infection with Schistosoma mansoni is endemic in Egypt leading to hepatic schistosomiasis and eventually portal hypertension. The prevalence of antibodies against hepatitis virus C among Egyptians is 14,51%. The aim of the present study was to investigate the influence of schistosomiasis on chronic hepatitis C with respect to the natural course of the disease, immunology, virology and histology. Patients and Methods: One hundred and twenty-six Egyptian patients classified into three groups: group A: chronic hepatitis C (n=33); group B: chronic schistosomiasis (n=30) and group C: chronic hepatitis C and chronic schistosomiasis (n=63) were enrolled and prospectively followed for 62.7±22 months. Patients infected with other hepatic viruses and/or parasites were excluded. Detailed history, clinical examination, CD4+ and CD8+ lymphocyte counts in blood, hematological and blood chemical values, abdominal ultrasonography, upper endoscopy, HCV RNA titer by RT/PCR, genotype and histological activity index in the liver biopsy were determined. Results: Thirty patients (48%) with HCV and schistosomiasis had liver cirrhosis and Child-Pugh class C vs. five (15%) in HCV patients and none in the schistosomal group. HCV RNA levels ranged between 0.07 and 13×105 copies/ml in group A, and between 1 and 25×105 copies/ml in group C. HCV genotype 4 was detected in 58 patients with co-infection (92%) and 21 patients with HCV alone (64%). Patients with coinfection showed higher grading and staging scores in their liver biopsies. Hepatocellular carcinoma was detected only in patients with coinfection. During follow-up, the mortality rate was 12%, 3% and 48% in group A, B and C, respectively. Conclusions: Patients with concomitant HCV and schistosomiasis infection were characterized by more advanced liver disease, higher HCV RNA titers, predominance of HCV genotype 4, higher histologic activity, higher incidence of cirrhosis and hepatocellular carcinoma as well as a much higher mortality rate. [source] Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myelomaAMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2010Francesca Gay The objective of this case-matched study was to compare the efficacy and toxicity of the addition of clarithromycin (Biaxin) to lenalidomide/low-dose dexamethasone (BiRd) vs. lenalidomide/low-dose dexamethasone (Rd) for newly diagnosed myeloma. Data from 72 patients treated at the New York Presbyterian Hospital-Cornell Medical Center were retrospectively compared with an equal number of matched pair mates selected among patients seen at the Mayo Clinic who received Rd. Case matching was blinded and was performed according to age, gender, and transplant status. On intention-to-treat analysis, complete response (45.8% vs. 13.9%, P < 0.001) and very-good-partial-response or better (73.6% vs. 33.3%, P < 0.001) were significantly higher with BiRd. Time-to-progression (median 48.3 vs. 27.5 months, P = 0.071), and progression-free survival (median 48.3 vs. 27.5 months, P = 0.044) were higher with BiRd. There was a trend toward better OS with BiRd (3-year OS: 89.7% vs. 73.0%, P = 0.170). Main grade 3,4 toxicities of BiRd were hematological, in particular thrombocytopenia (23.6% vs. 8.3%, P = 0.012). Infections (16.7% vs. 9.7%, P = 0.218) and dermatological toxicity (12.5% vs. 4.2%, P = 0.129) were higher with Rd. Results of this case-matchedanalysis suggest that there is significant additive value when clarithromycin is added to Rd. Randomized phase III trials are needed to confirm these results. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. 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