Abnormal nucleotide pattern in the eosinophils of a patient with acute lymphoblastic leukemia associated with eosinophilia

In this article we present a patient with acute lymphoblastic leukemia (ALL) associated with eosinophilia, in which the eosinophilia preceded a meningeal and bone-marrow relapse of ALL. We analysed the purine and pyrimidine nucleotide content of the eosinophils (92% pure) and compared the nucleotide pattern with that of eosinophils from healthy donors and from patients with eosinophilia not associated with leukemia. The ratios of purine : pyrimidine and of uracil :cytosine nucleotides were decreased compared with those in eosinophils from healthy donors and from patients with eosinophilia with other aetiologies. The total nucleotide concentration was increased, especially the concentration of UDP-sugars and pyrimidine nucleotides.

The decrease in these ratios and the increase in concentration of the nucleotides and the UDPsugars were also detected in leukemic cells of patients with ALL (de Korte et al., Leukemia Res. 10, 389–396 (1986)) compared to normal lymphocytes. We suggest a malignant character of the eosinophils in our patient with ALL associated with eosinophilia, in contrast with the nonmalignant state suggested previously for these cells.     

Molecular genetic studies in alpha-thalassemia]

A group of 5,000 patients, suspected of haemolytic anaemia, were investigated with molecular genetic methods for deletion types of alpha-thalassemia. In 776 (15.6%) patients a deletion of one or more alpha-globin genes was found. The same group of patients was also investigated for abnormal haemoglobins and beta-thalassaemia. In about 30% of the patients either an alpha-thalassaemia, an abnormal haemoglobin, a beta-thalassaemia, or a combination was diagnosed. In a group of patients with a haemoglobinopathy, the frequency of alpha-thalassaemia was much higher (i.e. 33%) than in individuals without haemoglobinopathy. Preselection of the patients based on the presence of microcytic erythrocytes and/or a decreased ADW0.5 of the erythrocytes gave a high incidence of false-negative and false-positive results. Therefore, haemoglobin examination should not be restricted to protein chemistry, but should include molecular genetic investigations for deletion types of alpha-thalassaemia.     

Plasma hypercoagulability in haemodialysis patient: impact of dialysis and anticoagulation

Background: Thrombotic complications are common in patients with endstage renal disease and contribute substantially to the morbidity and mortality in this population. The aim of the present study was to: I) determine the prevalence and the extent of hypercoagulability in patients undergoing dialysis treatment by measuring parameters that directly reflect thrombin concentrations, ii) assess changes in coagulation status during haemodialysis (HD); iii) quantify the relative impact of heparin, dialysis and their combined effects on coagulation status and iv) detect factors that modify coagulation haemostasis in dialysis patients. Method: A total of 39 patients (HD: n=29, CAPD: n=10) was analysed for procoagulatory and fibrinolytic activity determined by measurements of partial thromboplastin time, prothrombin fragments F1+2, thrombin-antithrombin complexes and D-dimer concentrations. HD patients were investigated prior to and during dialysis. A subgroup of patients was infused heparin alone without dialysis or was dialysed without heparin administration. Furthermore, subgroup and correlation analyses were performed for the type of dialysis (HD vs CAPD), dialyzer and shunt, Kt/V, underlying disease and treatment with recombinant erythropoietin (rhEPO). Results: Baseline levels of all parameters-procoagulatory and fibrinolytic- were substantially elevated in all patients, but to a higher degree among those on CAPD. Moreover, haemodialysis treatment increased procoagulatory markers even further, suggesting stimulated coagulation and/or insufficient anticoagulation during dialysis. However, after 3 h of dialysis thrombin concentrations, determined by quantification of prothrombin fragments, were inversely correlated with Kt/V. Selective heparin infusion diminished procoagulatory activity only slightly and incompletely, whereas HD without heparin resulted in excess thrombin accumulation. Finally, subgroup analyses revealed more pronounced thrombin formation among patients treated with polysulfon dialyzers, whereas erythropoietin dosage was positively related with lower procoagulatory activity. Conclusion: A majority of patients on dialysis are in a hypercoagulable state, which is further aggravated by the haemodialysis procedure itself and may not be sufficiently controlled with current anticoagulation regimens. Intensified heparin treatment and the use of rhEPO are likely to improve coagulation haemostasis, whereas the type of dialyzer should be considered as a relevant procoagulatory factor.     

Alterations of lens metabolism with experimentally induced cataract in rats

Rat lenses with experimentally induced cataract (either by naphthalene or by streptozotocin) were analyzed biochemically. Both noxae had some effects in common. Water-soluble protein and aldose reductase activity decreased, and glucose-6-phosphate dehydrogenase, phosphofructokinase and glutathione reductase activity increased. A specific effect of streptozotocin was the rise in glucose, fructose and sorbitol. A specific effect of naphthalene was increased amounts of water-insoluble protein.     

Acute effects of lamotrigine (BW430C) in persons with epilepsy

Sixteen epileptic patients took single doses of lamotrigine, 120 mg or 240 mg. Six photosensitive patients showed reduction (with abolition in two) in photosensitivity after lamotrigine administration. Five subjects with frequent interictal spikes showed reduction in spike frequency over 24 h after lamotrigine administration. The half-life (t1/2) of lamotrigine in subjects taking sodium valproate was prolonged, whereas the t1/2 in subjects taking carbamazepine and/or phenytoin was reduced. The area under the curve of co-medication plasma levels was not affected by a single dose of lamotrigine. Five patients reported mild and generally transitory side effects; some of which represented exacerbation of preexisting complaints.     

Chicks from a high and low feather pecking line of laying hens differ in apomorphine sensitivity

Proactive rodents show a larger behavioral response to apomorphine (APO) than reactive copers, suggesting a more sensitive DA system in proactive individuals. Previously, chicks from a high feather pecking (HFP) and low feather pecking line (LFP) have been suggested to display a proactive and reactive coping strategy, respectively. Therefore, at approximately 4 weeks of age, the behavior of 48 LFP and 48 HFP chicks in response to an APO injection was studied using an open field. Another objective of the present study was to determine whether behavioral variation (in an open field) between HFP and LFP birds, after APO injection, is also reflected by variation of D(1) and D(2) receptor densities in the brain. Receptor binding capacities were assessed by measuring specific binding of tritiated D(1) and D(2) receptor ligands in different regions of the brain of control HFP and LFP chicks. In the present study, it is shown that indeed HFP chicks display a more enhanced behavioral response to acute APO treatment (0.5 mg/kg BW) than LFP birds in an open field. This difference was not reflected by variation of D(1) and D(2) receptor densities in the brain between both lines.     

Donor characteristics do not influence transfusion-related acute lung injury incidence in a secondary analysis of two case-control studies

Objective

To investigate the relation between donor characteristics and TRALI incidence.

Aldose reductase inhibitor--a new way for preventing diabetic lens changes?

Increased blood sugar levels may influence the refractive power of the lens in juvenile diabetics, and can lead to the rare true diabetic cataract ("snow-storm cataract"). Surplus glucose induces accumulation of the sugar alcohol within the cells, thus generating disturbances of the osmotic balance and finally causing cataract. The enzyme aldose reductase catalyzes the formation of sorbitol. Experiments with animals have shown that aldose reductase inhibitors can prevent the formation of such opacities with streptozotocin-induced diabetes in rats. Numerous aldose reductase inhibitors are now known, but we still have insufficient knowledge to determine whether systemic or local administration is preferable. The mechanisms reported here are not relevant with respect to the frequent occurrence of senile cataract in older diabetics, which has often been described.     

Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system

We used a modified version of the popliteal lymph node assay in rats to investigate the immunosuppressive potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In 10 months we conducted 3 experimental series. Animals were treated with single s.c. injections of TCDD and 7 days later human red blood cells (HRBC) were injected s.c. into the right hind footpad of the rat. Another 7 days later, both popliteal lymph nodes were prepared, weighed, the cell number was counted and the quotients (index) of these variables from the treated and the untreated side were determined. The doses applied in three experimental series were 600, 60, 6, 0.6, and 0.06 ng TCDD/kg body wt. In the first experimental series only the three highest doses were tested, in a second experimental series doses of 60, 6, 0.6, 0.06 ng TCDD/kg body wt were applied. Combining the results of these two experimental series, a statistically significant difference was found in the cell number index between the controls and the two highest doses tested (60 and 600 ng/kg body wt;p <0.01). This result was recently published as an abstract (Korte et al. 1990). However, with slight methodological changes in the third series of experiments (doses applied: 600, 60, 6, 0.6, and 0.06 ng TCDD/kg body wt) and using a greater number of animals we could not confirm these preliminary results. No difference was seen in the immune response to the antigen challenge in controls and in any of the treatment groups. We conclude that TCDD does not clearly influence the immune response as observed in the popliteal lymph node assay under our experimental conditions.