Prevention of bacteremia caused by α-hemolytic streptococci by roxithromycin (RU-28 965) in granulocytopenic patients receiving ciprofloxacin

Summary We previously demonstrated that ciprofloxacin prevents infections caused by gram-negative bacilli in patients with granulocytopenia. However, in patients with intensive cytotoxic treatment leading to severe mucosal damage a high incidence of bacteremias caused by -hemolytic streptococci was seen. In the present study 45 consecutive patients undergoing intensive cytotoxic treatment received a short course of roxithromycin (10 days) in addition to ciprofloxacin for prevention of bacteremias caused by -hemolytic streptococci. The results of this study were compared with the results obtained in previous comparable patients receiving ciprofloxacin alone. During the days with addition of roxithromycin no infections caused by -hemolytic streptococci occurred, while in the control group of 80 patients 16 bacteremias (20%) were seen. Although roxithromycin was shown to antagonize bactericidal action of ciprofloxacin on gram-negative bacilliin vitro, in vivo study based on serum bactericidal titers and on results of surveillance cultures showed no antagonistic interactions.

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Roxithromycin (RU-28 965) zur Prävention der Bakteriämie durch alpha-hämolytische Streptokokken bei granulozytopenischen Patienten unter Ciprofloxacin-Prophylaxe

Zusammenfassung In früheren Studien konnte die präventive Wirksamkeit von Ciprofloxacin gegen Infektionen durch gramnegative Bakterien bei granulozytopenischen Patienten belegt werden. Jedoch traten bei Patienten, die mit intensiven Zytostatikaschemata behandelt wurden, häufig Bakteriämien durch alpha-hämolytische Streptokokken auf. In der vorliegenden Studie erhielten 45 Patienten, die nacheinander eingewiesen wurden und eine hochdosierte Zytostatikatherapie durchmachten, zehn Tage lang Roxithromycin als Zusatz zu einer Prophylaxe mit Ciprofloxacin, um das Auftreten septischer Infektionen durch alpha-hämolytische Streptokokken zu verhüten. Die Ergebnisse dieser Studie wurden denjenigen einer vorausgegangenen Studie mit vergleichbaren Patienten unter Prophylaxe mit Ciprofloxacin allein gegenübergestellt. Während in der Vergleichsgruppe bei 16 von 80 Patienten Bakteriämien durch alpha-hämolytische Streptokokken aufgetreten waren, kam es bei den Patienten, die Roxithromycin erhielten, zu keiner einzigen solchen Infektion, solange dieses Antibiotikum verabreicht wurde. Im Gegensatz zuIn vitro-Beobachtungen, die darauf schließen lassen, daß Roxithromycin die bakterizide Aktivität von Ciprofloxacin gegen gramnegative Bakterien antagonisiert, waren antagonistische Interaktionen in einerIn vivo-Studie anhand der Serumbakterizidietiter und Ergebnisse von Überwachungskulturen nicht festzustellen.

     

Shwachman syndrome: Exocrine pancreatic dysfunction and variable phenotypic expression

BACKGROUND & AIMS: Shwachman syndrome is an inherited condition with multisystemic abnormalities, including exocrine pancreatic dysfunction. The aim of this study was to evaluate the occurrence and progression of features in a large cohort of patients. METHODS: Clinical records of 25 patients with Shwachman syndrome were reviewed. RESULTS: Mean birth weight (2.92 +/- 0.51 kg) was at the 25th percentile. However, by 6 months of age, mean heights and weights were less than the 5th percentile. After 6 months of age, growth velocity was normal. Severe fat maldigestion due to pancreatic insufficiency was present in early life (fecal fat, 26% +/- 17% of fat intake; age, < 2 years). Serial assessment of exocrine pancreatic function showed persistent deficits of enzyme secretion, but 45% of patients showed moderate age-related improvements leading to pancreatic sufficiency. Neutropenia was the most common hematologic abnormality (88%), but leukopenia, thrombocytopenia, and anemia were also frequently encountered. Patients with hypoplasia of all three bone marrow cellular lines (n = 11) had the worst prognosis; 5 patients died, 2 of sepsis and 3 of acute myelogenous leukemia. Other findings included hepatomegaly and/or abnormal liver function test results and skeletal abnormalities. CONCLUSIONS: A wide and varied spectrum of phenotypic abnormalities among patients with Shwachman syndrome is described. Pancreatic acinar dysfunction is an invariable abnormality. Patients with severe bone marrow involvement may have a guarded prognosis. (Gastroenterology 1996 Dec;111(6):1593-602)     

Red cell membrane stiffness in iron deficiency

The purpose of this study was to characterize red blood cell (RBC) deformability by iron deficiency. We measured RBC deformability to ektacytometry, a laser diffraction method for determining the elongation of suspended red cells subjected to shear stress. Isotonic deformability of RBC from iron-deficient human subjects was consistently and significantly lower than that of normal controls. In groups of rats with severe and moderate dietary iron deficiency, RBC deformability was also reduced in proportion to the severity of iron deficiency. At any given shear stress value, deformability of resealed RBC ghosts from both iron-deficient humans and rats was lower than that of control ghosts. However, increase of applied shear stress resulted in progressive increase in ghost deformation, indicating that ghost deformability was primarily limited by membrane stiffness rather than by reduced surface area-to-volume ratio. This was consistent with the finding that iron-deficient cells had a normal membrane surface area. In addition, the reduced mean corpuscular hemoglobin concentration (MCHC) and buoyant density of the iron-deficient rat cells indicated that a high hemoglobin concentration was not responsible for impaired whole cell deformability. Biochemical studies of rat RBC showed increased membrane lipid and protein crosslinking and reduced intracellular cation content, findings that are consistent with in vivo peroxidative damage. RBC from iron-deficient rats incubated in vitro with hydrogen peroxide showed increased generation of malonyldialdehyde, an end-product of lipid peroxidation, compared to control RBC. Taken together, these findings suggest that peroxidation could contribute in part to increased membrane stiffness in iron- deficient RBC. This reduced membrane deformability may in turn contribute to impaired red cell survival in iron deficiency.     

Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial

We evaluated the role of rituximab during remission induction chemotherapy in relapsed aggressive CD20+ non-Hodgkin lymphoma. Of 239 patients, 225 were evaluable for analysis. Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable). Patients in complete remission (CR) and partial remission (PR) after 2 chemotherapy courses were eligible for autologous stem-cell transplantation. After the second chemotherapy cycle, 75% of the patients in the R-DHAP arm had responsive disease (CR or PR) versus 54% in the DHAP arm (P=.01). With a median follow-up of 24 months, there was a significant difference in failure-free survival (FFS24; 50% vs 24% vs, P<.001), and progression free survival (PFS24; 52% vs 31% P<.002) in favor of the R-DHAP arm. Cox-regression analysis demonstrated a significant effect of rituximab treatment on FFS24 (HR 0.41, 95% confidence interval [CI] 0.29-0.57 versus 0.51, 95% CI 0.37-0.70) and overall-survival (OS24: HR 0.60 [0.41-0.89] vs 0.76 [0.52-1.10]) when adjusted for time since upfront treatment, age, World Health Organization performance status, and secondary age-adjusted international prognostic index. These results demonstrate improved FFS and PFS for relapsed aggressive B-cell NHL if rituximab is added to the re-induction chemotherapy regimen.     

Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983--93 and 1994--8 at European Group for Blood and Marrow Transplantation centres

Out of 690 allogeneic matched sibling donor transplants for multiple myeloma reported to the European Group for Blood and Marrow Transplantation (EBMT) registry, 334 were performed during the period 1983-93 (all with bone marrow) and 356 during 1994-98 [223 with bone marrow and 133 with peripheral blood stem cells (PBSCs)]. The median overall survival was 10 months for patients transplanted during the earlier time period and 50 months for patients transplanted with hone marrow during the later period. The use of PBSCs was associated with earlier engraftment but no significant survival benefit compared to bone marrow transplants during the same time period. The improvement in survival since 1994 with the result of a significant reduction in transplant-related mortality, which was 38%, 21% and 25% at 6 months and 46%, 30% and 37% at 2 years during the earlier period, and the later period with bone marrow and PBSCs respectively. Reasons for the reduced transplant-related mortality appeared to be fewer deaths owing to bacterial and fungal infections and interstitial pneumonitis, in turn a result of earlier transplantation and less prior chemotherapy. Better supportive treatment and more frequent use of cytokines may also play a role. The improvement in survival was not directly related to the increased use of PBSCs.