Oxytocin‐induced PGF2α Release in Mares With and Without Post‐breeding Delayed Uterine Clearance

The aim of the present study was to evaluate within 24 h post‐ovulation oxytocin‐induced PGF_2α release in mares with and without post‐breeding delayed uterine clearance (DUC). Twenty‐one of 34 mares with a variable amount of intrauterine fluids accumulation were considered to be affected by delayed uterine clearance (DUC group), while the other 13 mares did not show any uterine fluid accumulation, and were considered as controls (WDUC group). Both DUC and WDUC mares were administered with 20 IU oxytocin i.m. 90 min after the ultrasound examination performed 24 h after breeding. Immediately before, 5 and 10 min after oxytocin administration, blood samples were collected for 15‐ketodihydro‐PGF_2α (PG‐metabolite), 17β‐estradiol, and progesterone analysis. Ultrasonography performed 24 h after oxytocin treatment showed a complete uterine clearance in all DUC mares. The oxytocin‐induced PG‐metabolite increase was detected in 71.4% DUC mares compared with 38.5% in WDUC group, with a positive trend of release, as evidenced from 5 min after oxytocin administration. In WDUC mares, no significant differences in oxytocin‐induced PG‐metabolite trend of release were observed. In conclusion, the results of the present study showed the importance of PGF_2α involvement in the pathogenesis of post‐breeding DUC in the mare.     

Good and poor CD34+ cells mobilization in acute leukemia: analysis of factors affecting the yield of progenitor cells

Summary:The factors possibly affecting the collection of peripheral blood stem cells (PBSC) were evaluated in 104 de novo acute leukemia patients (66 myeloid and 38 lymphoblastic leukemias) in first cytological complete remission (CR); all patients achieved CR after first-line induction chemotherapy. The acute myeloid leukemia patients (AML) were given consolidation-mobilization chemotherapy with cytarabine, and daunoblastin or mitoxantrone or idarubicin; the acute lymphoblastic leukemia patients (ALL) were given consolidation-mobilization chemotherapy with cytarabine and etoposide. In all patients, the collection of PBSC was performed during recovery after giving consolidation chemotherapy and granulocyte colony-stimulating factor (G-CSF). Two main groups were considered according to the CD34+ cells x 10(6)/kg b.w. collected, that is, poor mobilizers (PM), with a collection of <2 x 10(6)/kg and good mobilizers, with a collection of >2 x 10(6)/kg. Of 104 patients, 27 (25.9%) were PM; 20/27 had AML and 7/27 had ALL. At multivariate analysis, a lower CD34+ cells count premobilization chemotherapy (CD34 steady state), the presence of FUO (fever of unknown origin) or infection, and a lower number of CD34+ cells on the first day of collection correlated with poor mobilization. These results may enable early recognition of patients who may have poor mobilization, and aid selection of patients for different mobilization regimens.     

Usefulness of the severity and extent of wall motion abnormalities as prognostic markers of an adverse outcome after a first myocardial infarction treated with thrombolytic therapy

The prognostic value of wall motion score index (WMSI), assessed at predischarge after a first acute myocardial infarction (AMI) in the thrombolytic era, is still not well known. One-hundred forty-four consecutive patients with a first AMI treated with thrombolytic therapy underwent exercise testing and echocardiography at rest before discharge and were followed-up for a mean period of 18 months. During follow-up, there were 32 cardiac events (12 patients had cardiac deaths, 8 had unstable angina pectoris, 1 had nonfatal reinfarction, and 11 patients had congestive heart failure). The patients who experienced any cardiac event had a higher WMSI (1.67+/-0.15 vs. 1.30+/-0.16, p<0.0001), a higher end-systolic volume (75.1+/-34 vs. 59.5+/-22 ml, p<0.01), and a lower ejection fraction (47+/-16% vs. 55+/-10%, p<0.001) at predischarge than patients without events. The incidence of a positive predischarge exercise testing did not differ between patients with and without cardiac events (22% vs. 24%, p = NS). Multivariate Cox regression analysis, including clinical, exercise results, and echocardiographic parameters, showed that the most powerful predictor of a subsequent event was a resting WMSI > or =1.50 before discharge (chi-square 17.8, p<0.0001). Thus, in patients with a first AMI who underwent thrombolysis, the severity and extent of echocardiographically detected wall motion abnormalities are important independent predictors of cardiac events.     

Atrial fibrillation in hypertension: predictors and outcome

Incidence, determinants, and outcome of atrial fibrillation in hypertensive subjects are incompletely known. We followed for up to 16 years 2482 initially untreated subjects with essential hypertension. At entry, all subjects were in sinus rhythm. Subjects with valvular heart disease, coronary artery disease, preexcitation syndrome, thyroid disorders, or lung disease were excluded. During follow-up, a first episode of atrial fibrillation occurred in 61 subjects at a rate of 0.46 per 100 person-years. At entry, subjects with future atrial fibrillation differed (all P<0.05) from those without by age (59 versus 51 years), office, and 24-hour systolic blood pressure (165 and 144 versus 157 and 137 mm Hg, respectively), left ventricular mass (58 versus 49 g/height[m](2.7)), and left atrial diameter (3.89 versus 3.56 cm). Age and left ventricular mass (both P<0.001) were the sole independent predictors of atrial fibrillation. For every 1 standard deviation increase in left ventricular mass, the risk of atrial fibrillation was increased 1.20 times (95% CI, 1.07 to 1.34). Atrial fibrillation became chronic in 33% of subjects. Age, left ventricular mass, and left atrial diameter (all P<0.01) were independent predictors of chronic atrial fibrillation. Ischemic stroke occurred at a rate of 2.7% and 4.6% per year, respectively, among subjects with paroxysmal and chronic atrial fibrillation. These data indicate that in hypertensive subjects with sinus rhythm and no other major predisposing conditions, risk of atrial fibrillation increases with age and left ventricular mass. Increased left atrial size predisposes to chronicization of atrial fibrillation.     

Low-dose dipyridamole infusion acutely increases exercise capacity in angina pectoris: a double-blind, placebo controlled crossover stress echocardiographic study

OBJECTIVES: The aim of this study was to assess whether endogenous accumulation of adenosine, induced by low-dose dipyridamole infusion, protects from exercise-induced ischemia. BACKGROUND: Adenosine is a recognized mediator of ischemic preconditioning in experimental settings. METHODS: Ten patients (all men: mean age 63.4 +/- 7.3 years) with chronic stable angina, angiographically assessed coronary artery disease (n = 7) or previous myocardial infarction (n = 3) and exercise-induced ischemia underwent on different days two exercise-stress echo tests after premedication with placebo or dipyridamole (15 mg in 30 min, stopped 5 min before testing) in a double-blind, placebo controlled, randomized crossover design. RESULTS: In comparison with placebo, dipyridamole less frequently induced chest pain (20% vs. 100%, p = 0.001) and >0.1 mV ST segment depression (50% vs. 100%, p < 0.05). Wall motion abnormalities during exercise-stress test were less frequent (placebo = 100% vs. dipyridamole = 70%, p = ns) and significantly less severe (wall motion score index at peak stress: placebo = 1.55 +/- 0.17 vs. dipyridamole = 1.27 +/- 0.2, p < 0.01) following dipyridamole, which also determined an increase in exercise time up to echocardiographic positivity (placebo = 385.9 +/- 51.4 vs. dipyridamole = 594.4 +/- 156.9 s, p < 0.01). CONCLUSIONS: Low-dose dipyridamole infusion increases exercise tolerance in chronic stable angina, possibly by endogenous adenosine accumulation acting on high affinity A1 myocardial receptors involved in preconditioning or positively modulating coronary flow through collaterals.     

Outcomes of Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation for Hodgkin Lymphomas: A Retrospective Multicenter Experience by the Rete Ematologica Pugliese (REP)

Background

Hodgkin lymphoma (HL) is a potentially curable disease, and modern therapy is expected to successfully cure more than 80% of the patients. However, patients progressing after intensive treatments, such as autologous stem cell transplantation (SCT), have a very poor outcome. Allogeneic SCT offers the only strategy with a curative potential for these patients. This study reports a retrospective multicenter experience of the Rete Ematologica Pugliese (REP) over the past 17 years, aiming to define the impact of each patient’s disease and transplant-related characteristics on outcomes.

The first Italian family with tibial muscular dystrophy caused by a novel titin mutation

Tibial muscular dystrophy (TMD) or Udd myopathy is an autosomal dominant distal myopathy with late onset, at first described in the Finnish population. We report here the first Italian cases of TTN mutated titinopathy. The proband, a 60 year-old female, had the first muscular signs at the age of 59 years, with difficulty in walking and right foot drop. Muscle imaging showed selective fatty degenerative change in the anterior compartment of leg muscles. Her 67 year-old brother, started to show muscle weakness, pain at lower limbs and hypertrophy of calf muscles at the age of 66 years. Their mother began to show foot drop and impaired walking from the age of 60 years. Other relatives are reported to be affected in a similar way. Because the phenotype appeared compatible with TMD, we analyzed the TTN gene in the DNA of the proband and we identified a heterozygous mutation 293326A>C. This mutation is also present in the brother and in the other affected individuals of the same family. The mutation predicts a His33378Pro change located next to the previously known Belgian TMD mutation. The mutation was not found in 100 Italian control DNA samples. Then, since the introduction of a proline in the last domain of titin was previously known to cause TMD in French families, we can conclude that this missense mutation is the obvious pathogenetic mutation in the affected patients. No other disease causing mutations in the TTN gene have so far been reported in the Italian population.