Gray platelet syndrome: Management of perioperative bleeding in redo cardiac surgery

Gray platelet syndrome (GPS) is a rare (<1/1 000 000) and inherited platelet function disorder characterized by macrothrombocytopenia, α-granule deficiency, and hemorrhages. Bleeding intensity does not correlate with platelet count nor with functional test results. We hereby describe the perioperative bleeding prevention and management of a patient with GPS requiring multiple redo cardiac surgeries.     

MEMRI and tumors: a method for the evaluation of the contribution of Mn(II) ions in the extracellular compartment

The purpose of the work was to set‐up a simple method to evaluate the contribution of Mn²⁺ ions in the intra‐ and extracellular tumor compartments in a MEMRI experiment. This task has been tackled by “silencing” the relaxation enhancement arising from Mn²⁺ ions in the extracellular space. In vitro relaxometric measurements allowed assessment of the sequestering activity of DO2A (1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid) towards Mn²⁺ ions, as the addition of Ca‐DO2A to a solution of MnCl₂ causes a drop of relaxivity upon the formation of the highly stable and low‐relaxivity Mn‐DO2A. It has been proved that the sequestering ability of DO2A towards Mn²⁺ ions is also fully effective in the presence of serum albumin. Moreover, it has been shown that Mn‐DO2A does not enter cell membranes, nor does the presence of Ca‐DO2A in the extracellular space prompt migration of Mn ions from the intracellular compartment. On this basis the in vivo, instantaneous, drop in SE% (percent signal enhancement) in T₁‐weighted images is taken as evidence of the sequestration of extracellular Mn²⁺ ions upon addition of Ca‐DO2A. By applying the method to B16F10 tumor bearing mice, T₁ decrease is readily detected in the tumor region, whereas a negligible change in SE% is observed in kidneys, liver and muscle. The relaxometric MRI results have been validated by ICP‐MS measurements. Copyright © 2015 John Wiley & Sons, Ltd.     

Patients with Fabry disease on dialysis in the United States.

BACKGROUND.: Fabry disease results from an X-linked deficiency of lysosomal alpha-galactosidase A and is a rare cause of end-stage renal disease. Little is known about the characteristics of patients with Fabry disease that initiate dialysis in the United States, although data from Europe suggests these individuals have a poor survival. METHODS.: Using the United States Renal Disease System database, we first studied in detail 42 Fabry patients who initiated dialysis between April 1995 (following the introduction of the new detailed HCFA 2728 form) and July 1998. To examine crude survival in a larger cohort, 95 Fabry patients were studied who initiated dialysis between 1985 and 1993, similar to the European Registry. Diabetic and non-diabetic controls matched by age, gender, race, year of dialysis initiation, and initial dialysis modality were examined for comparison. RESULTS.: During the years 1995 to 1998, the mean age of Fabry patients that initiated dialysis was 42 years, 83% were Caucasian, and 10% were African American. Despite the X-linked inheritance of Fabry disease, 12% of Fabry patients on dialysis were female. At initiation of dialysis mean serum albumin and creatinine were significantly higher and mean body mass index was significantly lower among Fabry patients, but mean glomerular filtration rate was similar to controls. Fabry patients tended to have a lower three-year survival compared to non-diabetic controls, but the results were not significantly different. In a larger cohort of Fabry patients who initiated dialysis between 1985 and 1993, the three-year survival of Fabry patients was significantly lower than non-diabetic controls: 63% (95% CI, 50 to 75%) versus 74% (95% CI, 67 to 80%; P=0.03). CONCLUSION.: End-stage renal disease is associated with significant morbidity and mortality among patients with Fabry disease. Recent evidence that progression of Fabry disease may be attenuated by enzyme replacement therapy necessitates increased awareness of Fabry disease and its comorbidities.     

Postpartum acute myocardial infarction

We report a postpartum acute myocardial infarction that occurred during the first week after cesarean section delivery. We also calculated the rate of postpartum myocardial infarction as related to all women with myocardial infarctions seen in our hospital.(Am J Obstet Gynecol 1997;177:1553-5.)     

Urethral closure function in women with prolapse

In 19 patients with different types of severe descensus, all without clinical evidence of stress incontinence, urethral stress pressure profiles and stress tests were done before and after repositioning of the prolapse. In 13 of the 19 patients, continence was artificial, because during repositioning they showed leakage of urine; however, 6 of the patients remained continent. The pressure transmission ratios decreased in different parts of the urethra in all the patients when repositioning with a gynecological speculum was done. The drop was most significant in those patients who lost urine after repositioning, showing poor urethral function. In women with genito-urinary prolapse, a test of urethral function is essential, even if there is no clinical evidence of incontinence after removal of the descensus. In cases of severe stress incontinence under this condition, a procedure for bladder neck stabilization should be added to routine prolapse surgery.     

Significance of extractable nuclear antigens in childhood autoimmune liver disease.

The relative virulence of different isolates of Mycobacterium avium has been linked to their capacity to trigger the secretion of TNF from the macrophages they infect. Smooth opaque (SmOp) variants of Myco. avium have been shown to trigger higher expression of TNF-alpha by macrophages in vitro than the smooth transparent (SmTr) variants. To analyse the role of TNF in resistance to infection by Myco. avium, we studied the infection by two different morphotypes of strain 2.151 of Myco. avium both in vitro and in vivo in the presence or absence of neutralizing antibodies to TNF. No effects were found in vitro regarding the growth of either isolate of Myco. avium. In vivo, only the virulent SmTr morphotype showed enhanced growth in the presence of the neutralizing antibodies. This enhancement occurred relatively late when priming for TNF secretion in vivo was evident. Among four isolates of Myco. avium, three virulent ones induced a marked priming for TNF release and one avirulent strain did not. Mycobacterium tuberculosis H37Ra, which is very active in inducing TNF release due to its lipoarabinomannan moiety, was used to compare with the previous results. The growth of H37Ra in macrophages was increased in vitro by the neutralization of TNF and neutralization of either TNF and/or interferon-gamma (IFN-gamma) enhanced the in vivo proliferation of this microbe in the spleen and liver of infected animals, whereas only the combination of both anti-TNF and anti-IFN-gamma enhanced bacterial proliferation in the lung. We conclude that resistance to the avirulent strains of Myco. avium did not involve TNF, but rather antimicrobial mechanisms expressed constitutively in the mononuclear phagocytes. In contrast, TNF plays an important role in the control of Myco. tuberculosis H37Ra infection.     

Altered long-term corticostriatal synaptic plasticity in transgenic mice overexpressing human CU/ZN superoxide dismutase (GLY(93)-->ALA) mutation

Apart from the extensive loss of motor neurons, degeneration of midbrain dopaminergic cells has been described in both familial and sporadic forms of amyotrophic lateral sclerosis (ALS). Mice overexpressing the mutant human Cu/Zn superoxide dismutase (SOD1) show an ALS-like phenotype in that they show a progressive death of motor neurons accompanied by degeneration of dopaminergic cells. To describe the functional alterations specifically associated with this dopaminergic dysfunction, we have investigated the corticostriatal synaptic plasticity in mice overexpressing the human SOD1 (SOD1+) and the mutated (Gly(93)-->Ala) form (G93A+) of the same enzyme. We show that repetitive stimulation of the corticostriatal pathway generates long-term depression (LTD) in SOD1+ mice and in control (G93A-/SOD1-) animals, whereas in G93A+ mice the same stimulation generates an N-methyl-D-aspartic acid receptor-dependent long-term potentiation. No significant alterations were found in the intrinsic membrane properties of striatal medium spiny neurons and basal corticostriatal synaptic transmission of G93A+ mice. Bath perfusion of dopamine or the D(2) dopamine receptor agonist quinpirole restored LTD in G93A+ mice. Consistent with these in vitro results, habituation of locomotor activity and striatal-dependent active avoidance learning were impaired in G93A+ mice. Thus, degeneration of dopaminergic neurons in the substantia nigra of G93A+ mice causes substantial modifications in striatal synaptic plasticity and related behaviors, and may be a cellular substrate of the extrapyramidal motor and cognitive disorders observed in familial and sporadic ALS.