Immunophenotypic, genomic and clinical characteristics of blast crisis of chronic myelogenous leukaemia

We have studied phenotypic and clinical features in a consecutive series of 45 patients with chronic myelogenous leukaemia (CML) in blast crisis (BC). In addition, in 22 of these patients we have analysed the genotypic characteristics including immunoglobulin, T-cell receptor (TCR) and major breakpoint cluster region (M-bcr) gene organization. The granulomonocytic and megakaryoblastic lineages are the most commonly involved in these BC of CML (33% and 33% of cases, respectively); only 18% of our cases displayed a lymphoid phenotype. Moreover, both morphological and immunophenotypic studies revealed the frequent coexistence of two or three cell populations, especially when the megakaryoblast component is involved. The lymphoid BC displayed the highest incidence of complete remissions although this was not associated with a longer survival. Only minor differences between the different myeloid subgroups were observed. Immunoglobulin heavy chain (IgH) gene rearrangement was found in five of the six lymphoid BC and in one myeloid BC. Only one case showed k light chain gene rearrangement. In all but one myeloid BC the TCR-beta gene was in germline configuration. The TCR-gamma gene was rearranged in all lymphoid and one myeloid BC, while TCR-delta gene rearrangement was detected in 67% and 16% of the lymphoid and myeloid BC, respectively. Most of the lymphoid BC (4/5) had the M-bcr breakpoint in subregion 3, while the myeloid BC had the breakpoint either in subregion 2 or 3. No differences between the different myeloid phenotypic subgroups were observed in relation to breakpoint.     

Action of 2-hydroxy-4,6-dimethoxyacetophenone isolated from Sebastiania schottiana

The inhibitory action of the major constituent of Sebastiania schottiana (Euphorbiaceae), 2-hydroxy-4,6-dimethoxyacetophenone (xanthoxyline) on contractions induced by agonists and electrical stimulation of smooth and cardiac muscle preparations was analysed. Xanthoxyline (30 to 300 microM) inhibited contractions of the rat uterus, guinea-pig ileum, and urinary bladder induced by several agonists in a non-competitive, non-selective, concentration-related manner, with the IC50's ranging between 47 and 190 microM. Twitches evoked by electrical-stimulation of strips of guinea-pig longitudinal ileum, urinary bladder, dog ureter, and rat left atrium were also inhibited dose-dependently by cumulative additions of xanthoxyline (IC50's between 50 and 480 microM). Xanthoxyline was found to be a potent inhibitor of spontaneous contractions of the circular smooth muscle layer of the dog ureter, yielding an IC50 of 54 microM. Repeated washing of all preparations completely reversed the inhibitory effects of xanthoxyline. Therefore, it appears that xanthoxyline induces a direct and non-selective inhibition of contractions triggered by agonists or electrical stimulation of smooth and cardiac muscle preparations. The elucidation of the mechanism(s) by which xanthoxyline induced muscle relaxation requires further investigations.     

Lipoid Proteinosis: Case Report

A 20-month-old Kuwaiti girl had manifestations of lipoid proteinosis, a rare autosomal recessive disorder seen more commonly in Caucasians. This condition is diagnosed based on clinical, histopathologic, and ultrastructural criteria. Its biochemical and genetic aspects are still poorly understood.     

Hand rejuvenescence by fat filling.

The advantages of fat filling for hand rejuvenescence are discussed. Seventy-two patients treated by this method are presented, including their follow-up, complication rate, and details of combined operations. Preference is given to local anesthesia when no other major surgeries are associated with the method. A highly satisfactory rate was obtained (98.62%) with a low complication rate (4.15%).     

Therapy of post-renal transplantation hyperlipidaemia: comparative study with simvastatin and fish oil

Background: Recipients of renal transplantation (RT) exhibit disturbances of serum lipids and apoproteins that may contribute to their cardiovascular morbidity and mortality. In our renal transplant department the hypercholesterolaemia prevalence at the first and fifth year of RT is 70.0% and 81.2%, respectively. Lipid-lowering therapy has been utilized in many Transplant Units. The aim of our study was to evaluate post-RT hyperlipidaemia control with simvastatin or fish oil. Method: Forty-three RT patients (26 men and 17 women) with persistent hypercholesterolaemia and stable graft function which were resistant to a lipid-lowering diet (American Heart Association Step Two) were randomized into two groups and treated for 3 months with simvastatin (S) (10 mg/day; n=25) and fish oil (F) (6 g/day; n=18). Total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), lipoprotein a (Lp(a)), apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B) were monitored and at the study baseline they were similar between the two groups. Results: No side effects were detected after 3 months of therapy. In group S, the concentrations of TC (271±46 mg% vs 228±49mg%; P <0.001), TG (180±78 vs 134±45; P<0.01), LDL-C (177& plusmn;40 vs 144±43; P <0.01) and Apo B (96±18 vs 82±16; P <0.001) were significantly reduced, and Apo A1 concentration had increased (135±24 vs 149±30; P <0.01). In group F, the concentrations of TC (266±25 vs 240±31; P <0.001), TG (203±105 vs 156±72; P=0.02) and HDL-C (63±15 vs 53±12; P <0.01) were significantly reduced. Conclusion: We concluded that low-dose simvastatin and fish oil are both effective and safe in correcting post-RT hyperlipidaemia. Further prospective studies with larger follow-up are needed to clarify whether this therapy has an impact on cardiovascular morbidity and mortality in RT patients.     

Effect of the aromatase inhibitor 4-hydroxyandrostene-3,17-dione progesterone synthesis by human luteal cells

The authors studied the effects of 4-hydroxyandrostene-3,17-dione (4-OHA) on progesterone (P), 17 beta-estradiol (E2), and 20 alpha-hydroxy-4-pregnen-3-one synthesis and pregnenolone accumulation in cultured human midluteal cells. A dose-dependent inhibition with and without human chorionic gonadotropin (hCG) of E2 and P production was observed. The accumulation of pregnenolone was significantly enhanced three to fourfold by 4-OHA in this culture system, as compared with control value. In addition, a sevenfold increase on pregnenolone accumulation was observed in the presence of 4-OHA plus 10 IU of hCG as compared with control values and 2.2-fold as compared with the 4-OHA treatments. These in vitro findings indicate a direct effect of 4-OHA on luteal steroidogenesis. Nevertheless, the suppressive effect of 4-OHA on P and E2 production is located at different sites of the steroidogenic pathway. In addition, the results demonstrate that hCG in the presence of 4-OHA stimulated pregnenolone accumulation, suggesting that the inhibition of P synthesis is in some steps after the formation of pregnenolone. These data indicate that the actions of 4-OHA on P or E2 formation have different inhibitory mechanisms.     

Pulmonary embolism.

Pulmonary embolism (PE) is an important health problem and often a major clinical challenge, not only because of the low specificity of its clinical manifestations but also because of the increasing number of medical circumstances that are risk factors for this illness and the importance of early identification, since prompt and appropriate treatment can decrease mortality from this disease by about 25%. In recent years research on PE has been extensive, directed mainly at trying to determine and characterize its risk factors, establish new clinical probability algorithms, develop new diagnostic methods and put existing ones into perspective, seek new therapeutic approaches (pharmacological and non-pharmacological), and above all establish protocols that can guide the clinician from the stage of clinical suspicion to measures to prevent recurrence. It was the authors' aim to review the most significant literature on this subject, in order to produce a text that reflects the state of the art concerning PE and that can be used as a guide in the clinical approach to this pathology.