Prevention of central venous line-related thrombosis by continuous infusion of low-dose unfractionated heparin, in patients with haemato-oncological disease. A randomized controlled trial

We have conducted a prospective randomized controlled trial to evaluate the role of low-dose unfractionated heparin prophylaxis in preventing central venous line-related thrombosis in patients with haemato-oncological disease. Patients were randomly assigned to receive either prophylactic intravenous unfractionated heparin (continuous infusion of 100 IU/kg/daily) or 50 ml/daily of normal saline solution as a continuous infusion. CVLs were externalized, non tunneled, double lumen catheters. All CVLs were placed percutaneously by the same physician in the subclavian vein. Upper limb veins were systematically examined by ultrasonography just before, or <24 hours after, catheter removal, and in case of clinical signs of thrombosis. One hundred and twenty-eight CVLs were inserted. Catheter-related thrombosis occurred in 1.5% of the catheters inserted in patients of the heparin group, and in 12.6% in the control group (p = 0.03). No other risk factors were found for the development of catheter-related thrombosis. Two and three patients experienced severe bleeding in the heparin group, and in the control group, respectively (p = 0.18). There were no other side-effects clearly ascribable to the use of unfractionated heparin. This is the first prospective, randomized study, which shows that low-dose of unfractionated heparin is safe and effective to prevent catheter-related thrombosis in patients with haemato-oncological disease.     

The absence of factor V Leiden mutation in Malays with recurrent spontaneous abortions

OBJECTIVES: The objectives of this study were to investigate the prevalence of factor V Leiden mutation in Malay women with recurrent spontaneous abortion and to clarify the contribution of the factor V Leiden mutation to recurrent miscarriages in these women. DESIGN: A prospective case control study between June 1999 and April 2000. SETTING: Hospital University Science of Malaysia, Kubang Kerian, Kelantan, and Maternal and Child Health Clinic, Pasir Mas, Kelantan, Malaysia. SAMPLES: A total of 46 Malay women with a history of three or more first or second trimester miscarriages were studied. The control group consisted of 46 parous women without obstetric complications. METHODS: Diagnosis of factor V Leiden mutation was made by examination of factor V Leiden allele product following Mnl I digestion of factor V Leiden alleles amplified by polymerase chain reaction. RESULTS: None of the 46 women with recurrent spontaneous abortion carried the mutation. Also, we found no subject carrying the factor V Leiden alleles in the control group. CONCLUSION: These results suggest that that there is no association between the factor V Leiden mutation and recurrent spontaneous abortion in the Malay population.     

Insulin levels measured with an insulin-specific assay in patients with fasting hypoglycaemia related to endogenous hyperinsulinism

OBJECTIVE: The finding of insulin levels above a minimum threshold at the time of symptomatic hypoglycaemia is crucial in the diagnosis of endogenous hyperinsulinism. The aim of this study was to evaluate insulin levels at the time of hypoglycaemia with an insulin-specific assay in such patients. DESIGN AND METHODS: We measured insulin levels in 15 patients with fasting hypoglycaemia related to endogenous hyperinsulinism using an insulin-specific immunoradiometric assay (IRMA) without any significant cross-reaction with intact proinsulin. RESULTS: Insulin levels were below 6 mIU/l in all the samples taken at the time of symptomatic hypoglycaemia in 6/15 patients, and in some of the samples in three patients; insulin levels were below 3 mIU/l in samples from 5 patients. C-peptide levels were above 0.6 ng/ml in all these samples. The lowest proinsulin level was 35 pmol/l. Insulin levels were measured with a less specific RIA (40% cross-reaction with proinsulin) in 8/15 patients and were above 6 mIU/l in all samples in seven patients, and all but one sample in the 8th patient. Mean concomitant C-peptide and insulinoma size were lower in those patients with insulin-IRMA levels below 6 mIU/l. CONCLUSION: Symptomatic hypoglycaemia below 0.45 g/l can result from insulin levels below 6 or even 3 mIU/l; lower insulin levels and secretion could be observed preferentially in small insulinomas. If an insulin assay devoid of any significant cross-reaction with intact proinsulin is employed, measuring C-peptide (and/or proinsulin) levels at the time of symptomatic hypoglycaemia is mandatory to make the diagnosis of endogenous hyperinsulinism.     

Enhanced generation of leukotriene B4 from calcium ionophore-stimulated rat peritoneal inflammatory cells: a possible clinical relevance

Leukotrienes (LTs) producing capacity was investigated in calcium ionophore A23187-stimulated peripheral white blood cells and peritoneal inflammatory cells suspension isolated from the same rat. A reverse phase high performance liquid chromatography technique and computerized UV spectroscopy were employed to isolate and quantitate the released LTs namely, LTC(4) and LTB(4). Preincubation of rat peritoneal inflammatory cells at 37 degrees C for 5 min followed by calcium ionophore A23187 stimulation for another 5 min produced significantly elevated amounts of LTB(4) as compared to peripheral white blood cells isolated from the same rat (103+/-12.7 versus 40+/-3.6 pmol/10(7) cells, respectively; mean+/-SEM). Enhanced generation of LTB(4) was associated with production of similar amounts of LTC(4) as compared with LTC(4) produced by peripheral white blood cells (15.2+/-4.2 versus 14.6+/-2 pmol/10(7) cells, respectively). In subsequent experiments, when peritoneal inflammatory cells and white blood cells suspension isolated from the same rats were stimulated with calcium ionophore A23187 (1 micro M) after preincubation with different concentrations of exogenous arachidonic acid (1, 3 and 10 micro M), significantly higher amounts of LTB(4) were produced by the peritoneal inflamed cells while a similar amounts of LTC(4)were produced by both types of cells. Increased LTB(4) formation by rat peritoneal inflammatory cells may prove to be of pathophysiological relevance, since this compound has been described to play an important role in acute inflammatory reaction.     

Abeta(1-42)-induced JNK and ERK activation in rabbit hippocampus is differentially regulated by lithium but is not involved in the phosphorylation of tau

Administration of Abeta(1-42) into the rabbit brain induces apoptosis and phosphorylation of tau. These Abeta effects correlate with the activation of JNK and ERK, but not of p38. Treatment with 7 mM lithium inhibits apoptosis, modulates JNK and ERK and does not affect the phosphorylation of tau. Our results demonstrate that lithium, at this dose, effectively inhibits the Abeta-induced apoptosis but has no effect on tau phosphorylation, and that MAP kinases are not involved in the phosphorylation of tau.     

Hyperthermic enhancement of the apoptotic and antiproliferative activities of paclitaxel

The antineoplastic agent paclitaxel (PTX), a microtubule-stabilizing agent, is known to arrest cell cycle progression and induce apoptosis. Mild hyperthermia (HT) also disrupts the microtubule system and triggers apoptosis. We therefore investigated whether concurrent exposure of murine breast cancer cells to 10 micromol/l PTX and 43 degrees C HT will promote improved anticancer effects. To do this, we exposed FM3A murine cancer cells to: (1) 10 micromol/l PTX for 1 h at 37 degrees C followed by exposure at 43 degrees C HT for 1 h; (2) 10 micromol/l PTX at 37 degrees C for 2 h; (3) 37 degrees C for 1 h followed by 43 degrees C HT for 1 h, and (4) untreated cells at 37 degrees C for 2 h which served as the control. Treatment No. 1 resulted in an enhanced cell cycle arrest, apoptosis and cytotoxicity. Exposure to 43 degrees C HT alone or 10 micromol/l PTX alone induced lesser apoptosis and cytotoxicity than the two treatments concurrently applied. The apoptotic cell death occurred in a time-dependent manner as follows: (1) concurrently applied 43 degrees C HT and 10 micromol/l PTX (5.6 +/- 0.5, 16.5 +/- 2 and 27.6 +/- 1%); (2) 43 degrees C HT alone (4.3 +/- 1, 6.6 +/- 0.3 and 12.7 +/- 1%) and (3) 10 micromol/l PTX alone (4.4 +/- 0.3, 8.6 +/- 1 and 12.8 +/- 1%) at 1, 6 and 24 h postexposure respectively compared to control of 2.0%. These data indicate that while both HT and PTX can individually induce apoptosis and antiproliferation in FM3A cancer cells, they may offer synergistic benefits when used concurrently.     

Hairy cell leukemia: report of 8 cases

Hairy cell leukemia haemopathy is a rare lympho?d haemopathy type B. 8 cases are reported and diagnosed at H?pital Aziza Othmana over a period of 20 years between 1979 and 1999, 7 men and one women. The mean age of the patients is 51 years, with externe ages from 42 to 81 years. 4 patients consulted for an infections and, or anaemia syndrome. The disease was revealed due to the presence of an isolated splenomegaly in other cases. At the clinical examination, the spleen is hypertrophied in 7 patients out of 8. Pancytopenia is observed in 50% of the patients. Only one patient has presented a moderated hyperleukocytosis at 11,000/mm3 related to the presence of moving on tricholeukocytes. The myelogramme is pocr. It allowed to mention the diagnosis in 6 cases out of 8. Bone Marrow biopsy revealed a diffuse infiltration by TCL with a reticulinic fibrosis in all patients. 4 patients out of 8 have been splenectomized. Cytopenies have been corrected in all patients. Only one patient has been treated by alpha Interferon for 3 years with a partial hematological response. A relapse was observed once the Interferon was stopped. With the introduction of new drugs such purine analogues. The HCL treatment has been revolutionarized thanks to the improvement of the rate of complete response (from 10% to 80% of CR). If splenectomy is still observed in HCL for splenomegalic and or severe cytopenia, our findings could be improved thanks to new purine analogues.     

Allogenic hematopoietic stem cell transplantation in acquired aplastic anemia: first experience of the National Center for Bone Marrow Grafting

Bone marrow transplantation from HLA-identical sibling offers cure and leads to restoration of normal hematopoiesis and long-term survival in 60-80% of recipients. From february 1998 to october 1999, seven patients with aplastic anemia (2 very severe aplastic anemia and 5 severe aplastic anemia), with a median age of 22 years (14-39), received a transplant from an HLA-identical sibling donor. All patients had sustained engraftment. Only one patient developed grade IV acute graft-versus-host disease. One patient died in the 22th day of systemic mycobacterial infection and one in the 79th day of acute graft-versus-host disease. The remaining 5 patients are alive and have a complete hematological recovery, with a median follow-up of 6 months (1,5-12). There are at least two reasons for the improved survival of patients with aplastic anemia who where treated by HLA-indentical bone marrow transplantation. One is the decreased incidence of graft rejection that has resulted from the more judicious use of transfusions before bone marrow transplantation, and improvements in the immunosuppressive qualities of the conditioning programs. Another reason for improved survival is the decrease in the incidence and severity of acute graft-versus-host disease.