Clinical, Hormonal and Pathological Findings in a Comparative Study of Adrenocortical Neoplasms in Childhood and Adulthood

The present study investigated the role of nitric oxide (NO) in the reflex changes in urethral outlet activity during micturition. Isovolumetric bladder contractions, urethral pressure and external urethral sphincter electromyogram (EUS EMG) activity were recorded independently in urethane-anesthetized rats. During reflex bladder contractions, the urethra exhibited reflex responses characterized by an initial decrease in urethral pressure in conjunction with a rise in bladder pressure. This was followed by a period of high frequency oscillations (HFOs) associated with maximal urethral relaxation and burst type EUS EMG activity. Administration of N-nitro-L-arginine (L-NOARG) 10 mg./kg. intravenously, a nitric oxide synthase inhibitor, reversibly decreased the magnitude (62 percent, p less than 0.05) and duration (40 percent, p less than 0.05) of reflex urethral relaxation (N = 7). In 4 additional experiments, L-NOARG (10 to 15 mg./kg. intravenously) completely eliminated reflex urethral relaxation during micturition, and this effect was reversed in all animals by the administration of L-arginine (100 to 150 mg./kg. intravenously). Administration of N-nitro-D-arginine (D-NOARG) (10 to 30 mg./kg. intravenously) had no effect on reflex urethral relaxation. Neuromuscular blockade (vecuronium bromide 5 mg./kg. intravenously) reversibly decreased resting urethral pressure and eliminated the HFOs. The urethral smooth muscle relaxation that remained after neuromuscular blockade was eliminated following administration of L-NOARG (10 mg./kg. intravenously) in 2 of 3 animals. These results suggest that reflex urethral responses during micturition involve changes in both smooth and striated muscle activity, and that the predominant neurotransmitter mechanisms that mediate reflex urethral smooth muscle relaxation involve NO.     

Polymorphisms of FAS and FAS ligand genes in preeclamptic women

Objectives

This study investigated the influence that Fas and Fas ligand gene polymorphisms might have on preeclampsia. The pathogenesis of preeclampsia is still enigmatic and several studies have proposed that it may, in part, be determined by genetic susceptibility. Therefore, the identification of a gene polymorphism associated with an increased risk of preeclampsia might well represent a useful tool in the identification of at risk pregnant women enabling the setup of preventive therapy.Apoptosis has also been implied in the pathogenesis of preeclampsia and since Fas and Fas ligand are the main apoptotic pathway members, they may represent candidate genes involved in the development of preeclampsia.A polymorphism at the 670 position (A–G) in the Fas gene has been found more frequently in Hungarian women with preeclampsia.

Study design

The study cohort was a group of 50 women with preeclampsia and 142 healthy control subjects from the general Italian population. They were studied, by RFLP analysis, to validate the role that the 670 G Fas gene polymorphism plays in preeclampsia, and to evaluate the Fas ligand IVS2nt 124 G polymorphism. The Fisher's exact test was used to compute the statistical difference between groups.

Results

The presence of the 670 G Fas gene variant was observed in 42 preeclamptic patients (84%) and 96 members of the general population control group (67.6%) (p = 0.029). Regarding the Fas ligand gene, the IVS2nt 124 G variant was present in 14 preeclamptic patients (28%) and in 47 of the general population control subjects (33.1%) (p = 0.6).

Conclusions

The present study validated the hypothesis that the Fas 670 G variant may have an influencing role in preeclampsia.     

Role of acute normovolemic hemodilution in treating retinal venous occlusions

The supposed state of retinal venous occlusions by a thrombus has led to the use of diverse antithrombotic treatments (heparin, fibrinolytic agents). This theory being considered at the moment as controversial, haemorheological theories being more particularly favoured, other treatments are proposed in an attempt to better retinal microcirculation, and this by changing the blood viscosity parameters. The study reported here compared the effects on recovery of visual acuity of retinal venous occlusion patients of anticoagulant treatment alone, haemodilution alone, or both together. After initial ophthalmic assessment, twenty-five patients were randomly assigned to one of three groups: group I (n = 5; mean age 62 +/- 14 yr) received heparin for 21 days, followed by antivitamin K drugs for a further 30 days; group II (n = 10; mean age 54 +/- 16 yr) were acutely hemodiluted with 40,000 daltons molecular weight dextran, bringing the haematocrit to between 0.25 and 0.30; on day 2, the same anticoagulant treatment as in group I was associated; group III (n = 10; mean age 58 +/- 18 yr) were only hemodiluted. The hemodiluted state was maintained for 21 days. A biological assessment was carried out for the three groups on days 1, 2, 7, 14, 21 and 30 (haematocrit, fibrinogen level, platelet count, kaolin-cephalin time, heparin level). The evolution of visual acuity was assessed on days 7, 14, 21, 30, 60 and 90. Mean visual acuity was assessed on days 7, 14, 21, 30, 60 and 90. Mean visual acuity was virtually the same for the three groups on day 0.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice

Context  In long QT syndrome (LQTS), disease severity and response to therapy vary according to the genetic loci. There exists a critical need to devise strategies to expedite genetic analysis. Objective  To perform genetic screening in patients with LQTS to determine the yield of genetic testing, as well as the type and the prevalence of mutations. Design, Patients, and Setting  We investigated whether the detection of a set of frequently mutated codons in the KCNQ1, KCNH2, and SCN5A genes may translate in a novel strategy for rapid efficient genetic testing of 430 consecutive patients referred to our center between June 1996 and June 2004. The entire coding regions of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 were screened by denaturing high-performance liquid chromatography and DNA sequencing. The frequency and the type of mutations were defined to identify a set of recurring mutations. A separate cohort of 75 consecutive probands was used as a validation group to quantify prospectively the prevalence of the recurring mutations identified in the primary LQTS population. Main Outcome Measures  Development of a novel approach to LQTS genotyping. Results  We identified 235 different mutations, 138 of which were novel, in 310 (72%) of 430 probands (49% KCNQ1, 39% KCNH2, 10% SCN5A, 1.7% KCNE1, and 0.7% KCNE2). Fifty-eight percent of probands carried nonprivate mutations in 64 codons of KCNQ1, KCNH2, and SCN5A genes. A similar occurrence of mutations at these codons (52%) was confirmed in the prospective cohort of 75 probands and in previously published LQTS cohorts. Conclusions  We have developed an approach to improve the efficiency of genetic screening for LQTS. This novel method may facilitate wider access to genotyping resulting in better risk stratification and treatment of LQTS patients.      

Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia is a genetic arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. The electrocardiographic pattern of this ventricular tachycardia closely resembles the arrhythmias associated with calcium overload and the delayed afterdepolarizations observed during digitalis toxicity. We speculated that a genetically determined abnormality of intracellular calcium handling might be the substrate of the disease; therefore, we considered the human cardiac ryanodine receptor gene (hRyR2) a likely candidate for this genetically transmitted arrhythmic disorder. METHODS AND RESULTS: Twelve patients presenting with typical catecholaminergic polymorphic ventricular tachycardia in the absence of structural heart abnormalities were identified. DNA was extracted from peripheral blood lymphocytes, and single-strand conformation polymorphism analysis was performed on polymerase chain reaction-amplified exons of the hRyR2 gene. Four single nucleotide substitutions leading to missense mutations were identified in 4 probands affected by the disease. Genetic analysis of the asymptomatic parents revealed that 3 probands carried de novo mutations. In 1 case, the identical twin of the proband died suddenly after having suffered syncopal episodes. The fourth mutation was identified in the proband, in 4 clinically affected family members, and in none of 3 nonaffected family members in a kindred with 2 sudden deaths that occurred at 16 and 14 years, respectively, in the sisters of the proband. CONCLUSIONS: We demonstrated that, in agreement with our hypothesis, hRyR2 is a gene responsible for catecholaminergic polymorphic ventricular tachycardia.     

17Beta-hydroxysteroid dehydrogenase 3 deficiency in women

In genetic males, mutation of the 17beta-hydroxysteroid dehydrogenase 3 (17HSD3)gene that is normally expressed in the testes impairs testosterone formation and causes development of male pseudohermaphroditism. We have ascertained seven women who are sisters of men with 17HSD3 deficiency and who are either homozygotes or compound heterozygotes for the same mutations as their affected brothers. Our findings confirm the concept that women with such mutations are asymptomatic.     

Exploring corrosion protection properties of alkyd@lanthanide bis-phthalocyanine nanocomposite coatings

Organic coatings have been widely used to protect carbon steel pipelines from external corrosion; however, they often suffer from permeability and weak adhesion. Here we show that synthetic lanthanide bis-phthalocyanine complexes, LnPc₂ (Ln = lanthanide metal, Pc = C₃₂H₁₆N₈ denotes the phthalocyanine ligand) can be used to form new nanocomposite coatings to provide corrosion protection to the underlying carbon steel pipelines. Electrochemical studies (EIS and potentiodynamic polarization) showed that the incorporation of LnPc₂ compound (PrPc₂, SmPc₂ and HoPc₂) additives with alkyd coating, leads to a significant increase in the corrosion resistance of carbon steel in 0.5 M HCl solution. The alkyd@LnPc₂ nanocomposite coatings absorb very low water volumes, when compared to the neat alkyd coating. LnPc₂ compounds allowed enhancing the pull-off adhesion of coatings performance from 3.34 MPa to 19.94 MPa. The efficiency of alkyd@HoPc₂ coating appears higher than that of alkyd@PrPc₂ and alkyd@SmPc₂ coatings. The protective properties of alkyd@LnPc₂ coatings were confirmed by SEM, TGA, scratch hardness, impact resistance, bend test and contact angle analysis.

Organic coatings have been widely used to protect carbon steel pipelines from external corrosion; however, they often suffer from permeability and weak adhesion.