Angelo Tirelli

Magnesium Administration Reduces Platelet Hyperaggregability in NIDDM

OSullivan et al. (3-6) first reported reductions in perinatal losses and the frequency of macrosomia (birth weight >4000 g or >90th percentile value of a reference population of the same gestational age) in the offspring when fixed doses of intermediate-acting insulin were administered to randomly selected women with GDM. The subjects in this large population, studied more than two decades ago, were assigned to insulin treatment or control groups without regard to their degree of glucose intolerance (except for the exclusion of those with symptomatic diabetes or overt hyperglycemia). Limited documentation of metabolic rectification with treatment was available. Moreover, retrospective stratification of the subjects was needed to document that perinatal losses were reduced in obese women >25 yr of age in whom insulin therapy had been initiated by 32 wk of gestation. Roversi et al. (7) reported the virtual absence of macrosomia and perinatal loss among 280 women with GDM treated with maximal tolerated doses (MTDs) of short-acting insulin administered 3 times daily in subjects enrolled between 1963 and 1975. The lowest figures were seen in subjects with the least severe glucose intolerance, i.e., those with fasting plasma glucose (FPG) normal for pregnancy (<105 mg/dl; 1,2,8) or class A, (1,9).* Outcomes were contrasted with earlier pregnancy experiences of the same women in whom perinatal losses and macrosomia had been high. The fact that a past history of such events was used to select subjects for GDM case finding may have introduced some bias in this comparison. This value, which is commonly used to delineate normal and elevated FPG concentrations during pregnancy, has been extrapolated from whole blood glucose measurements in the original study reported by OSullivan and Mahan (8). As described in this study, some investigators use different values to define the normal limits for FPC based on 7) other formulas to extrapolate from the data cited earlier (8) or 2) determinations of FPG in other groups of pregnant women using different analytical techniques.

Macroamylasemia in a Patient with Multiple Myeloma

We report a rare case of a patient with multiple myeloma who developed hyperamylasemia not associated to hyperamylasuria and without symptoms of pancreatic or salivary disease. This condition suggested the occurrence of macroamylasemia, consisting of macromolecules of amylase bound with immunoglobulins, which are not filtered by the kidneys. Hyperamylasemia was not present at the diagnosis of myeloma and appeared at the relapse of the disease, simultaneously with the appearance of an additional γ -chain oligoclonal component, suggesting a possible role of these chains in producing macroamylasemia. To our knowledge, this is the first report of macroamylasemia in a patient with multiple myeloma.

C1 inhibitor infusion modifies platelet activity in hereditary angioedema patients.

CONTEXTnC1 inhibitor (C1-INH) is an alpha2-globulin that blocks esterolytic activity of the first component of the classic complement cascade. The alpha-granules of normal human platelets also contain C1-INH, which is expressed on the platelet surface during platelet secretion in healthy patients, but it is clearly reduced in patients with hereditary angioedema (HAE).nnnOBJECTIVEnTo evaluate the effects of in vivo C1-INH concentrate infusion on platelet responsiveness and coagulation system activity in patients with HAE.nnnDESIGNnAssessment of the platelet activity and plasma levels of C1-INH, activated factor XII (XIIa), and prothrombin fragment F1.2 (F1.2) before and after infusion of 15 U/kg of C1-INH concentrate.nnnPATIENTSnIn 6 patients (4 men and 2 women), HAE was diagnosed according to the accepted clinical and laboratory criteria.nnnMEASUREMENTSnPlatelet aggregation (final concentrations: adenosine diphosphate, 0.5, 1.25, and 2.5 microM; collagen, 5 microg/mL), C1-INH antigen (radial immunodiffusion), C1-INH activity (chromogenic substrates), and XIIa and F1.2 (enzyme-linked immunosorbent assay).nnnRESULTSnAfter C1-INH infusion, we observed a prompt increase of C1-INH level and a slow return toward its plasma preinfusion values within 4 to 7 days, a significant decrease of both adenosine diphosphate- and collagen-induced platelet aggregation versus preinfusion values (maximum after 1-2 days; P <.001), and a rapid decrease of high basal values of XIIa and F1.2 in 30 and 120 minutes, respectively.nnnCONCLUSIONSnThese data show a role of C1-INH in the control of platelet activity and that its deficiency increases platelet aggregability and plasma levels of XIIa and F1.2 in patients with HAE.

Decreased Hemoglobin Levels Are Associated with Higher Plasma Level of Fibrinogen, Irrespective of Age

Background:Increased plasma levels of fibrinogen are been associated with an increased risk of cardiovascular accident. We aimed at verifying whether the changes of fibrinogen levels are associated with red blood cell (and/or hemoglobin) concentration. Methods:A group of 381 carefully selected healthy volunteers (219 male and 162 female), aged from 18 to 101 years, were enrolled in this study. Fasting blood samples were taken and all measurements (fibrinogen plasma level, whole blood viscosity, hemoglobin concentration, hematocrit value, red blood cell and white blood cell count, platelet count, glucose, total cholesterol and triglycerides plasma concentration, and C-reactive protein level) were obtained with standardized methodology using appropriate equipment, procedures, and controls. Results and Conclusions:In the male but not in the female group, plasma fibrinogen concentration inversely correlated with hemoglobin (P < 0.0001) and hematocrit value (P < 0.01). In a post hoc analysis, plasma fibrinogen level inversely correlated with hemoglobin in the subgroup of the 93 premenopausal women and directly correlated with age and inversely correlated with platelet count in the subgroup of the 69 postmenopausal women. Results of multiple regression analysis revealed that in all the subjects, except in the postmenopausal women, hemoglobin level is an independent predictor of fibrinogen plasma level. Considering the physiopathologic role of increased plasma fibrinogen concentration and the scarcity of pharmacologic approaches to decrease its level, these findings could be important in designing a preventive therapy of cardiovascular disease.

A Case of Congenital Dyserythropoietic Anemia Type II, Gilbert's Syndrome and Malleolar Trophic Ulcers

Abstract A case of a woman with congenital dyserythropoietic anemia type II (CDA-II), Gilberts syndrome (GS) and trophic malleolar ulceration is described. The association of CDA-II and GS caused early gallstone formation that led the patient to undergo cholecystectomy at the age of 15. GS is typified by increased production of both unconjugated and monoconjugated bilirubin, which is more lithogenic. The development of ulcers is not typical of CDA-II, even though they are associated with many of the hemolytic anemias, and were thought in our patient to be due to a thrombophilic tendency which manifest with Antithrombin III and Protein C deficiency.

Development of a Transient Monoclonal Gammopathy after Chemotherapy in a Patient with Biphenotypic Acute Leukemia

The development of a IgGk monoclonal gammopathy after a phase of bone marrow aplasia following chemotherapy is described in a patient suffering from biphenotypic acute leukemia (BAL). Paraprotein was followed by the relapse of the disease and disappeared during a further chemotherapy. Paraprotein could have been caused by an additional chemotherapy-induced genetic mutation or by a dysfunction in T-B cooperation observed in the phase of reconstitution of the immune system after medullar aplasia.