First Demonstration of an Increased Serum Level of Reactive Oxygen Species During the Peripartal Period in the Ewes

Reactive Oxygen Species (ROS) are produced during oxidative metabolism, and regulate many biological processes. The acute inflammation characterizing parturition induces many physiological changes. Among them, there is evidence that ROS affect the synthesis of many factors involved in parturition. Our study aims to determine serum levels of ROS in periparturient ewes, as well as to establish a value of reference of their physiological concentration.

ROS determination was performed on blood collected every 12 hours in periparturient twin pregnant ewes. Our results will show a significant increase in ROS concentrations from the beginning to the end of the experiment. This increase may be due to the inflammatory process establishing during parturition.     

Prior antiplatelet drug use and short-term mortality in older patients with acute ischemic stroke (AIS)

Some studies suggest that previous treatment with antiplatelet agents (AA) might reduce ischemic stroke severity and improve outcomes in terms of clinical deficits or mortality. We evaluated the effect of the prior chronic use of AA on short-term (30 days) mortality in a sample of consecutive patients with AIS. Four hundred thirty-nine older patients (>65 years) with “major” AIS (modified Rankin scale ≥ 3) consecutively admitted to the University ward of Internal Medicine or Geriatrics were enrolled. Stroke was classified according to Oxfordshire Community Stroke Project (OCSP). Data recorded included: (1) clinical features; (2) medical history including home therapies, and vascular risk factors; (3) routine clinical chemistry analyzes (verb)/analyses (noun). Short-term (30 days) mortality was 27.6%. One hundred fifteen subjects (26.2%) were taking AA before admission. Compared with subjects not treated, subjects taking AA were characterized by higher prevalence of recurrent stroke (35% vs. 22%). In this group, a trend toward a higher prevalence of congestive heart failure (CHF), smoking, and altered levels of consciousness (ALC) was noted. Stroke type and short-term mortality (33% vs. 26.2%; odds ratio = OR = 1.25; 95% confidence interval = CI = 0.75-2.10, age and gender adjusted) were not different between the two groups. Adjustment for glucose, CHF, previous stroke, smoking, and ALC did not change mortality risk (OR = 0.83; 95%CI = 0.40-1.72). We conclude that in older patients hospitalized for “major” AIS, prior use of AA was not associated with any benefit in terms of short-term mortality both in patients with first, as well as in those with recurrent ischemic stroke.     

Impact of the type of anthracycline and of stem cell transplantation in younger patients with acute myeloid leukaemia: Long-term follow up of a phase III study

We provide a long-term evaluation of patients enrolled in the EORTC/GIMEMA AML-10 trial which included a total of 2157 patients, 15-60 years old, randomized to receive either daunorubicin (DNR, 50 mg/m²), mitoxantrone (MXR, 12 mg/m²), or idarubicin (IDA, 10 mg/m²) in addition to standard-dose cytarabine and etoposide for induction chemotherapy and intermediate dose cytarabine for consolidation. Younger patients who reached complete remission with complete (CR) or incomplete (CRi) recovery were then scheduled to receive an allogeneic hematopoietic stem cell transplantation (HSCT). That was if they had a HLA-identical sibling donor; in all other cases, an autologous HSCT had to be administered. At an 11-year median follow-up, the 5-year, 10-year and 15-year overall survival (OS) rates were 33.2%, 30.1% and 28.0%, respectively. No significant difference between the three randomized groups regarding OS was observed (P = .38). In young patients, 15-45 years old, no treatment difference (P = .89) regarding OS was observed, while in patients 46-60 years old, MXR and IDA groups had a trend for a longer OS as compared to the DNR group (P = .029). Among younger patients without a favorable MRC cytogenetic risk subgroup who achieved a CR/CRi after induction chemotherapy, those with a HLA-identical sibling donor had higher 10-year and 15-year OS rates than those without. In older patients who reached CR/CRi, the long-term outcomes of those with or without a donor was similar. In conclusion, long-term outcomes of the study confirmed similar OS in the three randomized groups in the whole cohort of patients.     

CRAT missense variants cause abnormal carnitine acetyltransferase function in an early‐onset case of Leigh syndrome

Leigh syndrome, or subacute necrotizing encephalomyelopathy, is one of the most severe pediatric disorders of the mitochondrial energy metabolism. By performing whole‐exome sequencing in a girl affected by Leigh syndrome and her parents, we identified two heterozygous missense variants (p.Tyr110Cys and p.Val569Met) in the carnitine acetyltransferase (CRAT) gene, encoding an enzyme involved in the control of mitochondrial short‐chain acyl‐CoA concentrations. Biochemical assays revealed carnitine acetyltransferase deficiency in the proband‐derived fibroblasts. Functional analyses of recombinant‐purified CRAT proteins demonstrated that both missense variants, located in the acyl‐group binding site of the enzyme, severely impair its catalytic function toward acetyl‐CoA, and the p.Val569Met variant also toward propionyl‐CoA and octanoyl‐CoA. Although a single recessive variant in CRAT has been recently associated with neurodegeneration with brain iron accumulation (NBIA), this study reports the first kinetic analysis of naturally occurring CRAT variants and demonstrates the genetic basis of carnitine acetyltransferase deficiency in a case of mitochondrial encephalopathy.     

Evaluation of the appropriateness of hospital use: the case of IRCCS Ospedale Maggiore di Milano,Italy

In 1999 an Italian version of the AEP was applied to some units of the IRCCS Ospedale Maggiore di Milano and a modified AEP version was used to evaluate the day hospital activity. The main aims of the study were: to establish the appropriateness of the utilisation of beds and of day hospital activity and to calculate the costing of the misuse of hospital resources. 267 admission days were evaluated and 31.5% were not appropriated; whereas of 3,248 days of stay 37% were found not appropriated. The day hospital activity was evaluated through 300 record referred to 570 days of treatment and 13% of them were not appropriated. The cost of the 1,201 not appropriated hospital days was over 351.000. The not appropriated level of hospital utilisation in the IRCCS Ospedale Maggiore di Milano is similar to what is reported in national and international literature. Our study highlights some limits in the application of the AEP protocol at high specialised hospital units.     

Treatment with angiotensin-converting enzyme inhibitors is associated with a reduction in short-term mortality in older patients with acute ischemic stroke

BACKGROUND: Stroke is the third cause of death in older people living in Western countries. We tested the hypothesis that angiotensin-converting enzyme inhibitors (A-I) might affect short-term (30 day) mortality in older persons with severe acute ischemic stroke. METHODS: We analyzed data from a retrospective study including 475 consecutive older patients hospitalized for acute ischemic stroke. Mean age was 78.4 +/- 9.2 years; 58.2% were female. Stroke type was classified according to the Oxford Community Stroke Project (OCSP). RESULTS: Mortality rate was 28%. Thirty-two percent of patients were treated with A-I; mortality was 16.5% in patients treated compared with 33.3% in those not treated (chi(2) p =.001). The odds ratio for mortality in treated patients was: 0.47 (0.25-0.89) after full adjustment (age, sex, mean diastolic and systolic blood pressure, previous stroke and/or transient ischemic attack, congestive heart failure, atrial fibrillation, diabetes, hypertension, coronary heart disease, and previous treatment with A-I); 0.29 (0.09-0.89) in patients with altered level of consciousness after full adjustment; 0.60 (0.33-1.12) after adjustment for OCSP classification, age, and sex; and 0.30 (0.08-0.97) in total anterior circulation infarction stroke type after full adjustment. CONCLUSIONS: Our data suggest that treatment with A-I might reduce short-term mortality in older patients with acute ischemic stroke. Randomized clinical trials should confirm this possible specific effect of A-I.     

Delayed non-infectious lung disease in allogeneic bone marrow transplant recipients

BACKGROUND AND AIM OF THE WORK: The studies on late-onset non-infectious respiratory complications after allogeneic bone marrow transplantation (allo-BMT) have been mainly focused on bronchiolitis obliterans to date. The aim of this work was to analyze the incidence, clinico-pathologic characteristics and outcome of the entire spectrum of entities falling into the group of delayed non-infectious lung disease (DLD). METHODS: Retrospective chart review was carried out of 112 patients who underwent allo-BMT for hematologic malignancies between April 1995 and November 1998 at a single Institution. The categorization of the pulmonary disease was made by analyzing clinical data, bronchoalveolar lavage (BAL), high-resolution computed tomography (HRCT) and histology when possible. RESULTS: DLD occurred in 10 (10%) out of 97 recipients who survived at least 100 days following allo-BMT and was defined as bronchiolitis obliterans (BO; 4 cases), acute lung injury (ALI; 1 case) and subacute cellular interstitial pneumonia (SCIP; 5 cases). The BAL-profile was characterized by a marked increase of the neutrophil percentage in BO cases and of the lymphocyte (predominantly CD8+) percentage in parenchymal DLDs (SCIP, ALI). HRCT proved to be helpful to correctly identify BO cases, whereas histology was always needed to better define DLD presenting with an interstitial and/or alveolar pattern. The predominant airway involvement as well as the acute-onset of a respiratory illness with histological evidence of diffuse alveolar damage were associated with a worse prognosis because of a poor response to the immunosuppressive treatment. CONCLUSIONS: DLDs represent a group of entities heterogeneous in regard to variables such as onset and clinical behaviour (acute, subacute or chronic), predominant pattern of lung involvement (airway or parenchymal), response to treatment. Although immunopathologic mechanisms related to c-GVHD probably have a relevant pathogenic importance in this setting, the possible role of associated events (eg, drug toxicity and infections) at least in priming the lung damage need to be better clarified for its therapeutical implications.     

MEKC of desmosine and isodesmosine in urine of chronic destructive lung disease patients.

Degradation of extracellular matrix components is central to many pathological features of chronic destructive lung disorders. Desmosine and isodesmosine are elastin-derived cross-linked amino acids whose urine levels are considered representative of elastin breakdown. The aim of this study was to apply a novel methodology, based on high-performance capillary electrophoresis, to the quantification of desmosine and isodesmosine in 11 patients with stable chronic obstructive pulmonary disease (COPD), 10 with an exacerbation of COPD, nine with alpha1-antitrypsin deficiency, 13 with bronchiectasis, and 11 adults with cystic fibrosis, in comparison to 24 controls. It was found that, in patients with stable COPD, urinary desmosine levels were higher than in controls (p=0.03), but lower than in COPD subjects with an exacerbation (p< or =0.05). The highest desmosine levels were found in subjects with alpha1-antitrypsin deficiency, bronchiectasis and cystic fibrosis (p<0.001 versus stable COPD). In a short-term longitudinal study, five stable COPD patients showed a constant rate of desmosine excretion (mean coefficient of variation <8% over three consecutive days). In conclusion, the present method is simple and suitable for the determination of elastin-derived cross-linked amino acid excretion in urine, giving results similar to those obtained using other separation methods. In addition, evidence is presented that urinary desmosine excretion is increased in conditions characterized by airway inflammation, such as exacerbations of chronic obstructive pulmonary disease, bronchiectasis and cystic fibrosis. Results obtained in subjects with alphal-antitrypsin deficiency suggest that this method might be used to evaluate the putative efficacy of replacement therapy.