Reduced deformability of stored red blood cells is associated with generation of extracellular vesicles.

Throughout storage, red blood cells (RBCs) undergo detrimental changes in viability and their ability to effectively transport oxygen. RBC storage lesions are mediated, in part, by a progressive loss of cell deformability, and associated with the release of extracellular vesicles (EVs). Accumulation of EVs during the storage of RBCs correlates with a decrease in RBC surface area to volume ratio. Similarly, the loss of RBC-deformability is associated with loss of RBC surface area to volume ratio. In this study we thus tested whether loss of RBC-deformability is associated with increased RBC-EV production during blood storage. EVs obtained by differential centrifugation of stored RBCs (non-leukoreduced non-irradiated or leukoreduced γ-irradiated RBCs stored 35 or 28 days respectively) were enumerated by high-sensitivity flow cytometry. RBC deformability was quantified, using a cell-flow-properties-analyzer, by measuring the median cell elongation ratio (MER) and percentage of low and high deformable cells in the population (%, LDFC, and HDFC, respectively). The number of EVs was inversely correlated with the MER and positively correlated with the %LDFC with both measures showing highly significant logarithmic dependence with EV levels in stored RBCs. Considering how highly deformable cells did not correlate with EV formation as compared with low deformable RBCs we propose that the formation of EVs is a key factor leading to increased RBC-rigidity.

Effects of blood type and blood handling on feeding success, longevity and egg production in the body louse, Pediculus humanus humanus.

The effects of feeding different types of human blood to human body lice, Pediculus humanus humanus L. (Phthiraptera: Pediculidae), on feeding success, longevity and numbers of eggs laid were investigated using an artificial blood-feeding system in the laboratory. No significant differences were found between lice fed on different human blood types for any of the parameters tested. However, when lice were fed on human blood of one blood type followed immediately by a different blood type, they took significantly smaller bloodmeals, their longevity was reduced and they laid fewer eggs per female than control lice that had been fed twice on the same human blood type. When lice were fed human blood that had been stored for 1-26 weeks, the quantity of blood taken, the proportion of lice that became fully engorged and lice longevity diminished gradually as the storage time of the blood increased, but there was no effect of storage time on the mean number of eggs laid per female. However, lice would not feed on 26-week-old blood. The type of anticoagulant used had a significant effect on the proportion fed, longevity and number of eggs laid per female. Generally, EDTA (ethylenediaminetetraacetic acid)-treated blood reduced longevity and the number of eggs laid per female to a greater degree than heparinized or citrated blood. Lice fed on rabbit blood took significantly larger amounts of blood, lived longer and laid a higher mean number of eggs per female than lice fed on human blood.

Monotherapy with rituximab induces rapid remission of recurrent cold agglutinin-mediated hemolytic anemia in a patient with indolent lympho-plasmacytic lymphoma.

Cold agglutinin mediated immune hemolytic anemia secondary to lymphoproliferative disease (LPD), is primarily treated with measures directed to eliminate the malignant clone and as such, chemotherapy is usually given. The recent availability of monoclonal antibodies, has made it feasible to obtain both a clinical and molecular remission, as well as a remission on the functional level, such as elimination of secondary autoimmune phenomena. Recently we have administered a course of monotherapy with rituximab (4 weekly injections, x 375 mg/m2) to a patient with refractory and transfusion dependent cold agglutinin mediated hemolytic anemia secondary to indolent B-cell lymphoma. She achieved complete remission with a significant improvement in hemolysis and also became transfusion independent with a current follow-up of over one year. In individual cases, Rituximab has the potential of achieving not only a complete clinical remission (CR) but also a molecular CR, as well as a "functional" CR, by eliminating the clinical manifestations of autoimmunity; in this case, cold agglutinin mediated hemolytic anemia, secondary to NHL. Good results in autoimmunity secondary to lymphoma raises the possibility of future potential benefit of this agent in other primary autoimmune disorders.

Laboratory diagnosis of autoimmune cytopenias.

The past year's literature shows that little progress has been achieved in the laboratory diagnosis of autoimmune hemolytic anemia. The direct antiglobulin test is the only diagnostic test for autoimmune hemolytic anemia. Advantages of new techniques, such as the gel test, have to be determined. Today, cephalosporins are known to cause both drug-dependent and -independent autoantibodies. The diagnosis of idiopathic thrombocytopenic purpura is a clinical one. The new assays that measure antibodies against specific glycoproteins offer improved specificity. New laboratory advancements and accumulation of data on granulocytes' antigens and antibodies enabled us to recommend guidelines for the laboratory investigation of autoimmune neutropenia.

Candida abscess of the thyroid in a patient with acute lymphocytic leukemia.

A case of Candida abscess of the thyroid in a patient with acute lymphoblastic leukemia is described. The patient developed this rare complication after treatment with steroids and combination chemotherapy, during therapy with broad spectrum antibiotics for febrile neutropenia. Prior to the thyroiditis the patient had pulmonary aspergillosis. The abscess developed during treatment with high dose Amphotericin B. Unlike previous cases, the Candida was isolated to the thyroid, with no evidence of Candidemia or Candida infection in other sites.

Isradipine for the prevention of cyclosporine-induced hypertension in allogeneic bone marrow transplant recipients: a randomized, double-blind study.

BACKGROUND: Hypertension and nephrotoxicity frequently occur in patients who receive cyclosporine therapy after bone marrow transplantation (BMT). Isradipine, a calcium channel entry blocker, has been used successfully in cyclosporine-induced hypertension. METHODS: Thirty leukemic patients who received cyclosporine after BMT were randomized to receive isradipine (0.005 mg/kg) from 72 hr before commencement of cyclosporine therapy until day 100 after BMT or placebo. RESULTS: The placebo and isradipine groups were well matched. No differences were found between the isradipine and placebo groups in the level of blood pressure, renal function, marrow engraftment, or mortality. Hypertension incidence was surprisingly low (30% a week after hospital discharge and 10% by day 100 after BMT), and did not differ between the groups. CONCLUSIONS: Isradipine does not harm immunohematopoietic reconstitution after BMT; therefore, it may be used in this setting, although the previously reported incidence of hypertension has been exaggerated.

Hepatobiliary graft-versus-host disease manifested by common and hepatic biliary duct obstruction.

BACKGROUND: A 26-year-old patient presented with ascending cholangitis 8 months after allogeneic bone marrow transplantation for immunoblastic lymphoma. METHODS AND RESULTS: Endoscopic retrograde cholangiopancreatography showed common and hepatic biliary duct obstruction that was attibuted to chronic graft-versus-host disease. CONCLUSION: This case indicates that hepatobiliary disease related to chronic graft-versus-host disease may involve major bile ducts causing obstruction.

Microsatellite instability and p53 mutations in therapy-related leukemia suggest mutator phenotype.

During the last decade the frequency of therapy-related acute leukemia (t-leuk) and myelodysplastic syndrome (t-MDS) has been increasingly observed. Over the past 15 years, we treated 56 patients with t-leuk who had received prior chemotherapy (39%), radiotherapy (11%), or both (45%). The drugs received included alkylating agents and topoisomerase II inhibitors. The primary tumors included hematological malignancies (49%) and solid tumors such as breast or ovarian cancer. The median age at diagnosis of the primary tumor was relatively young (43 years +/- 18). Twelve patients had more than one primary tumor and 31 patients had a family history of malignancy. Karyotypic abnormalities were found in 91% of the patients. Prognosis was uniformly poor, with an overall median survival of 10 months. Twelve of the 18 patients examined (67%) had a multidrug resistance phenotype. P53 genes of the leukemic cells, as well as the original tumors, were analyzed in 21 patients using polymerase chain reaction (PCR) with single-stranded conformation polymorphism analysis followed by sequencing. P53 mutations were identified in 38% of these patients, a relatively high prevalence compared with other forms of MDS or de novo acute myeloid leukemia. Mutations were nongermline and restricted to the leukemic cells. We identified different p53 mutations in the various primary tumors of individual patients. The presence of a mutator phenotype was assessed by PCR analysis of microsatellites in eight loci (one trinucleotide repeat sequence, four dinucleotide, and three mononuclear repeat sequences). Microsatellite instability in two to seven loci were found in 15 of 16 (94%) of the patients. This instability is compatible with a mutator phenotype, which predisposes the patients to the development of malignancies including t-leuk.

Acute promyelocytic leukaemia with t(15;17) following treatment of Hodgkin's disease--a report of 4 cases.

BACKGROUND: Therapy-related acute myeloid leukemia (t-AML) is a recognized entity complicating successful therapy for Hodgkin's disease (HD) and other neoplasias after many years. This risk appears to be related to cumulative exposure to alkylating agents and procarbazine, while drugs affecting DNA--topoisomerase II, such as epipodophyllotoxins and anthracyclines, are also associated with t-AML developing after a much shorter latent period. PATIENTS AND METHODS: Of 56 patients with t-AML or myelodysplasia seen in our institutes during the period 1980-1994 we encountered 5 patients with acute promyelocytic leukemia (APL) all of whom had t(15;17). Four of these had been treated for HD with both chemotherapy and radiotherapy, and one with radiotherapy alone. RESULTS: To the best of our knowledge these appear to be the first cases of t-AML in HD with cytogenetically proven t(15;17). Similarly to other cases of t-APL reported after therapy for neoplasias other than HD, these patients also have a relatively favorable prognosis as seen in de-novo APL. CONCLUSIONS: Although rare, t-APL should be added to the list of late complications of therapy for HD.

Triphasic waves in myxedema coma.

Triphasic waves occur in metabolic and nonmetabolic encephalopathies. We report an elderly patient in whom triphasic waves were associated with myxedema coma and disappeared after thyroid replacement therapy was initiated. The association between myxedema coma and triphasic waves has not been previously reported.

Delayed onset of responses to single doses of L-dopa in parkinsonian fluctuators on long-term L-dopa therapy.

Dose-related fluctuations in response to L-Dopa such as the "wearing-off" phenomenon are a common side effect of long-term L-Dopa therapy. In a retrospective clinical analysis, 18 of 32 chronically treated parkinsonian fluctuators developed a delay in onset of a beneficial effect induced by single doses of L-Dopa. In these patients, there was a threefold increase in latency from ingestion of the first morning dose to "start-up" of a response (from 0.4 +/- 0.2 to 1.1 +/- 0.3 h) in parallel to a twofold decrease in its duration (from 4.2 +/- 1.1 to 1.7 +/- 0.8 h). Longer durations of illness and of L-Dopa therapy, occurrence of totally ineffective doses, poorer responsiveness to afternoon and evening doses, and early-morning dystonia were more prevalent in this group. In 14 of the 32 parkinsonian fluctuators, monitored "start up" of clinical effect occurred at about an hour after the first morning oral dose of L-Dopa. The dose-induced elevations in plasma L-Dopa levels started after a mean of about 0.5 h and were maximal at 1.25 h. The study suggests that prolongation of "start-up" latencies in response to single doses of L-Dopa is a rather common complication of chronic treatment and may increase patients' disability by further decreasing the duration of daily "on" periods. Causes for this phenomenon are unknown but retarded absorption of orally administered L-Dopa may be important.

Episodic unresponsiveness to single doses of L-dopa in parkinsonian fluctuators.

Episodic total unresponsiveness to single doses of L-dopa developed in 14 of 32 parkinsonians with declining efficacy and response fluctuations after chronic L-dopa therapy. Complete lack of clinical benefit after occasional doses was unpredictable, occurred at least once daily mostly in the afternoon, and differed from other response failures related to food intake. In two patients, total unresponsiveness after dose ingestion coincided with lack of increases in plasma L-dopa levels suggesting that phenomenon was due, in part, to failure of L-dopa absorption from the gut.