Myeloid progenitor cells in the peripheral blood of patients with hairy cell leukemia and other "leukemic" lymphoproliferative disorders

We assayed granulocyte-macrophage committed progenitor cells (CFU-GM), erythroid committed progenitor cells (BFU-E) and pluripotent hemopoietic progenitor cells (CFU-MIX) in the peripheral blood of patients with hairy cell leukemia (HCL), acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). In 8 HCL patients retaining their spleens, the number of circulating CFU-GM, BFU-E and CFU-MIX were under the lower limits of normal controls in 6, 6 and 5 cases, respectively, and were in the lower normal ranges in the remaining cases. Six splenectomized HCL patients had generally more circulating progenitor cells than their nonsplenectomized counterparts. In the peripheral blood of 2 patients with ALL and 3 patients with CLL, progenitor cells of all types were markedly increased compared to their respective values in the blood of control subjects. Hairy cells from 2 HCL patients failed to inhibit CFU-GM, BFU-E and CFU-MIX derived colony growth from control peripheral blood mononuclear cells. In 3 HCL patients previously low circulating progenitor cells did not rise 5-7 months after RC-alpha 2-IFN treatment despite normalization of peripheral blood counts. Our results suggest that a reduction of the committed and pluripotent progenitor cell compartment might be at least in part responsible for the pancytopenia in the majority of patients with HCL.     

A study of enterotoxigenic Escherichia coli, serogroup 0126, by bacterial restriction endonuclease DNA analysis (BRENDA).

Sixteen isolates of Escherichia coli were subjected to bacterial restriction endonuclease DNA analysis (BRENDA). Nine of these isolates were from an outbreak of human diarrhoea and produced stable toxin, the remaining seven were non-toxigenic strains from animal and human sources. The isolates from the outbreak produced indistinguishable DNA electrophoretic patterns in spite of their assignment to seven different H serotypes. Their BRENDA patterns were markedly different from the other isolates examined. These results support the epidemiological evidence that a single-strain outbreak had occurred, and they cast doubt on the value of H typing for this particular investigation.     

Impact of the factor II: G20210A variant on the risk of venous thromboembolism in relatives from families with the factor V: R506Q mutation

OBJECTIVES: Factor V: R506Q mutation and the prothrombin G20210A variant (factor II: G20210A variant) are associated with an increased risk of venous thromboembolism (VTE). In cohorts of unrelated patients a cosegregation of both mutations has been shown to be associated with an increased risk of developing VTE. The aim of this study was to investigate the impact of the coinheritance of both mutations on the risk of VTE in relatives of symptomatic carriers of the factor V: R506Q mutation and the factor II: G20210A variant. PATIENTS AND METHODS: Four families with 48 family members were investigated for the presence of the factor V: R506Q mutation and the factor II: G20210A mutation, and their clinical history was evaluated. RESULTS: VTE was more frequent in family members with a combined defect (3/10; 30%) compared to those with a single mutation (1/16; 6%) or without a defect (1/12; 8%). The probability for VTE for 40-yr-old individuals with both mutations, a single mutation and no mutation was 56%, 12% and 20%, respectively. CONCLUSIONS: These data suggest that the G to A transition at position 20210 of the prothrombin gene leads to an increase in the risk of VTE in carriers of the factor V: R506Q mutation. The determination of the factor II: G20210A variant in index patients carrying a factor V: R506Q mutation and, if present, in family members may help to identify individuals who are at high risk for VTE.     

Ophthalmodynamographic and ophthalmodynamometric findings following irreversible loss of cerebral function (author's transl)]

In 12 patients with irreversible cessation of cerebral function (so-called "brain death") ophthalmodynamographic (ODG) measurements were made. In 8 of these ophthalmodynamometric (ODM) investigations were also made. ODG results were abnormal in all cases, pulsation volumes showing a deep decrease (x:16.8 mm3;x of mean arterial pressure 79,1 mm Hg). ODM measurements revealed highly scattered results, ophthalmic artery pressure being normal in 3, increased in 1, severely reduced in 2 patients.--In 2 other cases mere touching of the eye bulb by the ophthalmodynamometer caused a sudden complete collapse of the central retinal artery. Whereas the ODG results might already be considered as useful auxiliary findings, for definite evaluation of the clinical significance of ODG and ODM in diagnosing an intracranial circulatory, additional comparative investigations may be necessary.     

The effect of acetyl-salicylic-acid pretreatment on re-formed aqueous humor

Aqueous humor (a.h.) was sampled in 67 patients operated on for cataract by intracapsular lens extraction at the start and finish of surgery. Twenty eight of these patients received pretreatment with acetyl-salicylic acid (ASA), to a total of 2.5 g, beginning 18 hours prior to surgery. A serum sample was drawn immediately following the operation from 55 patients. Using radial immunodiffusion, albumin and IgG were measured in primary and secondary a.h. and in serum.The group pretreated with ASA showed a significantly smaller relative increase of IgG (P<0.05).The increase of the proteins, however, showed no dependence on their serum-level and the only side-effect of the treatment was an unexplained rise in serum-albumin.The possible clinical application for patients with a high risk of postoperative complications is briefly summarized.

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Zusammenfassung Bei insgesamt 67 Patienten, die einer intracapsulären Extraktion der getrübten Augenlinse unterzogen wurden, konnte am Beginn der Operation primäres und vor dem endgültigen Wundverschluß neugebildetes sekundäres Kammerwasser entnommen werden. Bei 28 dieser Patienten wurde eine Vorbehandlung mit Acetyl-Salicylsäure (insgesamt 2,5 g, beginnend 18h vor der Operation) durchgeführt. Unmittelbar nach Beendigung der Operation wurde bei 55 Patienten eine Serumprobe abgenommen.In allen Proben wurden mit Hilfe der radialen Immundiffusion Albumin und IgG bestimmt. In der Gruppe der vorbehandelten Patienten fand sich ein signifikant geringerer relativer Anstieg des Proteins mit höherem Molekulargewicht (P<0.05). Der Anstieg der Proteine zeigte jedoch keine Abhängigkeit von ihrem Serumspiegel.Die einzige beobachtete Nebenwirkung dieser Behandlung war eine signifikante Erhöhung des Serum-Albumin-Spiegels, deren Ursache unbekannt ist.Der mögliche klinische Anwendungsbereich einer Behandlung mit Prostaglandin-Synthese-Inhibitoren bei Risikopatienten wird kurz zusammengefaßt.

     

First‐trimester fetal heart rate in mothers with opioid addiction

Aim To investigate the difference in fetal heart rate of opioid‐dependent mothers compared to non‐dependent mothers in the first trimester of pregnancy. Design The data of 74 consecutive singleton pregnancies of mothers enrolled in a maintenance programme for opioid‐dependent women was matched to 74 non‐exposed singleton pregnancies by maternal age, crown–rump length, smoking status, ethnic background and mode of conception. Measurement Fetal heart rate measured as part of first‐trimester screening by Doppler ultrasound between 11+0 and 13+6 gestational weeks was compared retrospectively. Findings The mean fetal heart rate in opioid‐dependent mothers was 156.0 beats per minute (standard deviation 7.3) compared to 159.6 (6.5) in controls. The difference in fetal heart rate was significant (P = 0.02). There was a significant difference in mean maternal body mass index (P = 0.01) but not in mean nuchal translucency (P = 0.3), gestational age (0.5), fetal gender (P = 0.3) and parity (P = 0.3) between both groups. Fifty‐five per cent (41 of 74) of cases were taking methadone, 30% (22 of 74) buprenorphine and 15% (11 of 74) were taking slow‐release morphines throughout the pregnancy. Conclusions In fetuses of opioid‐dependent mothers a decreased fetal heart rate can already be observed between 11+0 and 13+6 gestational weeks. The effect of opioid intake needs to be taken into consideration when interpreting fetal heart rate in opioid‐dependent mothers at first‐trimester screening.     

Acquired thrombasthenia due to GPIIb/IIIa-specific platelet autoantibodies

An otherwise healthy woman developed a hemorrhagic diathesis with fluctuating clinical symptoms and laboratory findings, but without thrombocytopenia, over 8 years. In periods of bad clinical condition, a platelet defect, characteristic of thrombasthenia, was found. In contrast to classic thrombasthenia, electrophoresis of the patient's platelet membranes revealed normal amounts of glycoproteins IIb alpha, IIb beta, and IIIa in the normal positions. Monoclonal antibodies, specific for GPIIIa and GPIIb/IIIa, respectively, bound normally to the P1A1-positive platelets from the patient. Although no antibody and no platelet function inhibitor were evident in the autologous plasma, an IgG1 antibody that was bound to the patient's platelets and was directed against GPIIb/IIIa could be demonstrated. After elution from the patient's platelets, this antibody immunoprecipitated GPIIb (both subunits), IIIa, and a 200-kilodalton (kd) band (probably undissociated GPIIb/IIIa complex) from solubilized normal platelets, but did not react with thrombasthenic platelets. Adding the eluate from the patient's platelets to normal platelet-rich plasma immediately caused concentration-dependent inhibition of adenosine diphosphate (ADP)-induced and collagen-induced aggregation and also strong inhibition of ADP-stimulated fibrinogen binding. Because it was very unlikely from the patient's medical history that the antibody was caused by alloimmunization, the hemorrhagic diathesis must be interpreted as acquired thrombasthenia due to an anti-GPIIb/IIIa autoantibody.     

Granulocyte colony-stimulating factor (G-CSF) as an adjunct to induction chemotherapy of adult acute lymphoblastic leukemia (ALL)

Summary Our purpose was to evaluate the ability of re-combinant human granulocyte colony-stimulating factor (r-metHuG-CSF) as an adjunct to induction chemo-therapy of acute lymphoblastic leukemia (ALL) to ameliorate chemotherapy-induced neutropenia and thus allow patients to receive full doses of chemotherapy on time. Sixteen consecutive patients with adult ALL (13 de novo, three relapsed) were treated with induction chemo-therapy according to the BMFT protocol and received in addition r-metHuG-CSF (200g/m²/day). Patients who were treated with the same induction chemotherapy but without G-CSF between 1982 and 1990 served as controls. Fifteen of the 16 patients achieved complete hematological remission. One patient died because of fungal septicemia. Compared with historical controls, G-CSF-treated patients had a significantly faster neutrophil recovery in phase I, resulting in neutrophil counts > 1000/l at day 17 vs day 26 (in median) in controls. In phase II, the onset of severe leukocytopenia (< 1500/l) was significantly (p = 0.01) delayed and the degree of leukocytopenia less pronounced (mean nadir 3300/l) in G-CSF-treated patients compared with controls (1880/l). The number of days of febrile neutropenia was not different in phase I. In phase II it was lower in study patients (0 vs 1.1 days), but the difference did not reach statistical significance (p = 0.09). Full doses of chemo-therapy could be given on time to 11/13 (85%) G-CSF pa-tients but to only 7/30 (23%) controls. These data indicate that (a) G-CSF can be given along with chemotherapy in induction treatment of ALL without compromising efficacy; (b) the duration of neutropenia in phase I is markedly shortened and the degree of leukocytopenia in phase II ameliorated; (c) these beneficial effects allow patients to receive full doses of chemotherapy on time.     

Interleukin-3 is a differentiation factor for human basophils

The effect of recombinant human (rh) cytokines, interleukin-1 alpha (IL- 1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL- 4), granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), monocyte/macrophage colony stimulating factor (M-CSF), interferon-alpha (IF-alpha), interferon-gamma (IF-gamma), and the tumor necrosis factor-alpha (TNF- alpha) on differentiation and function of metachromatic cells (MCS) was studied. Among all cytokines tested, rh interleukin-3 (rhIL-3) selectively induced a significant formation of MCS (IL-3: 1.1 +/- 0.6 x 10(5) v control: 0.02 +/- 0.15 x 10(5) MCS/mL suspension) and dose dependent increase in formation of intracellular histamine (IL-3, 100 U/mL: 95 +/- 23 ng/mL v control: 1.8 +/- 0.8 ng/mL) in a bone marrow suspension culture system (analyzed on day 14 of culture). Besides MCS, formation of eosinophils was observed in this culture system in the continuous presence of rhIL-3, whereas IL-3 pulse-stimulation for three hours and subsequent exposure to control medium induced growth of MCS but not of eosinophils. By combined immunofluorescence/toluidine blue staining, MCS were found to express a cell surface marker profile that corresponds to the immunological phenotype of peripheral blood basophils (MY-7(CD13)+, VIM12(CD11b)+, VIM2+, MAX1-, MAX24- and YB5B8- ). Furthermore, cultured MCS expressed surface membrane receptors for IgE and could be triggered for nontoxic histamine release by a monoclonal anti-IgE antibody. To evaluate a possible influence of IL-3 on basophil function, studies were extended to freshly obtained blood basophils (healthy volunteers, n = 3). However, like all other cytokines tested, rhIL-3 failed to induce basophil histamine release. Taken together, our studies demonstrate that IL-3 is a differentiation factor for human basophils.