Demonstration of the formation of hydroxyl radicals in acute myocardial infarction in man using salicylate as probe.

Dihydroxybenzoic acid (DHBA) derivatives of acetylsalicylic acid (ASA) are formed in vivo by the action of the hydroxyl radical (OH.). In order to evaluate the possible formation of OH(.) in acute myocardial infarction (AMI) in man, 9 consecutive patients with a first episode of AMI (8 males, 1 female, mean age 50.3 years), treated with rt-PA, and 8 healthy volunteers (7 males, 1 female, mean age 29.8 years) were studied. All subjects received 100 mg ASA p.o. daily; venous blood samples were taken 30 min after the first dose (time 0) and then at 3-, 6-, 12-, 24- and 48 h and 5 days. Serum was analyzed by HPLC and electrochemical detection for 2,3- and 2,5-DHBA contents. 2,3-DHBA was present in all subjects with AMI and undetectable in healthy volunteers at all time points studied. Serum levels of 2,5-DHBA did not show statistically significant differences between AMI patients and healthy volunteers. These data support the hypothesis that hydroxyl radicals are formed during AMI in man.     

Expanding indications for the treatment of pulmonary artery stenosis in children by using cutting balloon angioplasty.

OBJECTIVES: To evaluate the role of cutting balloon angioplasty in children with pulmonary artery stenosis. BACKGROUND: Pulmonary artery stenoses can be either congenital or secondary to postoperative scar formation. Isolated multiple small-vessel pulmonary artery stenoses are very rare. No surgical procedures for their treatment are currently available. METHODS: We report on four patients in whom standard and high-pressure balloon angioplasty had failed. Three of the four (2.5-, 3-, and 3.5-years-old; two girls) had isolated multiple peripheral pulmonary artery stenosis. The fourth patient was an 11-month-old girl (8 kg) with tetralogy of Fallot and hypoplastic pulmonary artery branches treated with the implantation of two stents in the pulmonary arteries. During the follow-up this patient developed severe intrastent restenosis and showed severely hypoplasic distal left pulmonary artery. RESULTS: We treated 11 vessels. The mean vessel diameter increased by 81% (P<0.0001) and RV/LV pressure ratio decreased from 1.15 to 0.75 (P=0.05). Patient treated for intrastent restenosis underwent successful complete tetralogy of Fallot repair. None of the patients suffered procedure-related complications. At a median follow-up of 18 months, results were stable and no late complications had occurred. CONCLUSIONS: Cutting balloon angioplasty is a promising technique for the treatment of highly challenging pathologies such as small vessel pulmonary artery stenoses and intrastent restenosis.     

Transcatheter closure of residual atrial septal defects after surgical closure

The repair of an ostium secundum atrial septal defects (ASDs) by an open heart operation is a safe procedure associated with low mortality and morbidity. Transcatheter closure of ASDs is a less invasive method of repairing ASDs and may also be the procedure of first choice in residual postsurgical ASD.     

Risk of Adverse Pregnancy Outcomes in Women with CKD

CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage (at referral) were assessed at baseline. The following outcomes were studied: cesarean section, preterm delivery, and early preterm delivery; small for gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of hypertension; new onset/doubling of proteinuria; CKD stage shift; “general” combined outcome (preterm delivery, NICU, SGA); and “severe” combined outcome (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased across stages (for stage 1 versus stages 4–5: “general” combined outcome, 34.1% versus 90.0%; “severe” combined outcome, 21.4% versus 80.0%; P<0.001). In women with stage 1 CKD, preterm delivery was associated with baseline hypertension (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63 to 8.36). However, stage 1 CKD remained associated with adverse pregnancy outcomes (general combined outcome) in women without baseline hypertension, proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of intrauterine death did not differ between patients and controls. Findings from this prospective study suggest a “baseline risk” for adverse pregnancy-related outcomes linked to CKD.     

Maturation of Schaffer collateral synapses generates a phenotype of unreliable basal evoked release and very reliable facilitated release

Short‐term synaptic plasticity undergoes important age‐dependent changes that have crucial implications during the development of the nervous system. Paired‐pulse facilitation is a form of short‐term synaptic plasticity by which the response to the second of two temporally‐paired stimuli is larger and more reliable than the response to the first stimulus. In this study, a paired‐pulse minimal stimulation technique was used to measure the probability and quantal amplitude of synaptic release at hippocampal synapses from 12–16‐day‐old (young) and 7–9‐week‐old (adult) rats. In order to assess the contribution of temperature‐dependent processes, we carried out experiments at both room temperature and at near physiological temperature. We report here that neither temperature nor maturation affected the low basal evoked release probability and quantal amplitude of release. However, the warmer temperature revealed a unique developmental increase in facilitated evoked release probability and quantal amplitude of release. As a result, although both basal evoked release and facilitated release are rather unreliable in synapses from young animals, the maturation process at near physiological temperature generates a phenotype with unreliable basal evoked release and highly reliable facilitated release.     

ATM protein and p53-serine 15 phosphorylation in ataxia-telangiectasia (AT) patients and at heterozygotes

ATM (ataxia-telangiectasia mutated) gene plays a central role in the DNA-damage response pathway. We characterized the ATM protein expression in immortalized cells from AT and AT-variant patients, and heterozygotes and correlated it with two ATM-dependent radiation responses, G1 checkpoint arrest and p53-Ser 15 phosphorylation. On Western blots, the full-length ATM protein was detected in eight of 18 AT cases, albeit at 1-32% of the normal levels, whereas a truncated ATM protein was detected in a single case, despite the prevalence among cases of truncation mutations. Of two ataxia without telangiectasia [A-(T)] cases, one expressed 20% and the other approximately 70% of the normal ATM levels. Noteworthy, among ten asymptomatic heterozygous carriers for AT, normal amounts of ATM protein were found in one and reduced by 40-50% in the remaining cases. The radiation-induced phosphorylation of p53 protein at serine 15, largely mediated by ATM kinase, was defective in AT, A(-T) and in 2/4 heterozygous carriers, while the G1 cell cycle checkpoint was disrupted in all AT and A(-T) cases, and in 3/10 AT heterozygotes. Altogether, our study shows that AT and A(-T) cases bearing truncation mutations of the ATM gene can produce modest amounts of full-length (and only rarely truncated) ATM protein. However, this limited expression of ATM protein provides no benefit regarding the ATM-dependent responses related to G1 arrest and p53-ser15 phosphorylation. Our study additionally shows that the majority of AT heterozygotes express almost halved levels of ATM protein, sufficient in most cases to normally regulate the ATM-dependent DNA damage-response pathway.     

Chromosome studies in patients with T-CLL chronic lymphocytic leukemia and expansions of granular lymphocytes

Chromosome analyses were carried out in eight patients with lymphoproliferative disorders of mature T and NK cells. Three cases were characterized by an abnormal expansion of granular lymphocytes (GL), one by a lymphoma of GL with leukemic spread, and four by an OKT4-T-CLL. In four patients cytogenetic studies were performed on bone marrow cells; in seven patients peripheral blood lymphocytes were examined by either direct preparations or PHA-stimulated cultures. Six patients displayed a normal karyotype. Two cases belonging to the OKT4-T-CLL group had a chromosome number ranging from 44 to 47, with multiple numerical and structural clonal anomalies. Clonal anomalies could be a feature of patients with the more aggressive clinical course.     

Cystic lymphangioma of the adult: our experience and review of literature

Cystic lymphangioma is an uncommon benign pathology, usually reported in children, rarely in adult. Its embryopathogenesis is still controversial: it seems to arise from the lymphatic vessels, mainly in the cervico-cranial district. It is macroscopically characterised by multiple cystic non-communicating concamerations. Definitive diagnosis used to be intraoperative and was usually an unexpected finding. Nowadays, with modern imaging technologies, CT and MRI, diagnosis can be assumed before intervention even though certain diagnosis can still be reached only with histological examination. Imaging techniques can help for a precise mapping of the lesion and definition of its limits with the other structures, improving therapeutic success. Various therapeutical options are reported in literature, but complete surgical excision is still considered the best approach and the most successful. The Authors report their experience and review the literature on cystic lymphangioma in adult.