The dystrophin gene and cognitive function in the general population

The aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included in the analysis. To determine the association between DMD variants and cognitive ability, linear (mixed) modeling with adjustment for age, sex and education was used. Moreover, Sequence Kernel Association Test (SKAT) was used to test the overall association of the rare genetic variants present in the DMD with cognitive traits. Although no DMD variant surpassed the prespecified significance threshold (P<1 × 10⁻⁴), rs147546024:A>G showed strong association (β=1.786, P-value=2.56 × 10⁻⁴) with block-design test in the ERF study, while another variant rs1800273:G>A showed suggestive association (β=−0.465, P-value=0.002) with Mini-Mental State Examination test in the RS. Both variants are highly conserved, although rs147546024:A>G is an intronic variant, whereas rs1800273:G>A is a missense variant in the DMD which has a predicted damaging effect on the protein. Further gene-based analysis of DMD revealed suggestive association (P-values=0.087 and 0.074) with general cognitive ability in both cohorts. In conclusion, both single variant and gene-based analyses suggest the existence of variants in the DMD which may affect cognitive functioning in the general populations.     

Fibrinogen as a predictor of mortality after acute myocardial infarction: a forty-two-month follow-up study.

BACKGROUND: Several studies suggest that fibrinogen may be considered an independent risk factor for coronary artery disease, but it is still on debate if we need its evaluation during an acute myocardial infarction (AMI) to prevent future fatal or non-fatal cardiovascular events. Therefore, we decided to investigate this field. METHODS: We studied 92 male patients with AMI, evaluating at admission age, body mass index, systolic blood pressure, cigarette smoking, ejection fraction, plasma levels of total cholesterol, triglycerides, fibrinogen, glycemia, and white blood cell count. All patients were followed up for 42 months to evaluate total mortality and cardiovascular morbidity. RESULTS: During the follow-up 5 patients died and 64 had one or more non-fatal cardiovascular events: angina (n = 78), heart failure (n = 17), re-AMI (n = 3), stroke (n = 3), or revascularization procedure (n = 16). A multivariate analysis revealed that fibrinogen plasma levels at admission (r = +0.213, p < 0.05) were independently associated with mortality, while systemic thrombolysis was negatively associated (r = -0.447, p < 0.0001). CONCLUSIONS: Plasma fibrinogen levels were the only independent predictor of mortality in a 42-month follow-up post-AMI. This finding, together with other observations from recent studies, suggest that fibrinogen evaluation during AMI may be useful in identifying patients at higher risk of acute event recurrence.     

Effect of BH4 on blood phenylalanine and tyrosine variations in patients with phenylketonuria

BackgroundIn patients with phenylketonuria, stability of blood phenylalanine and tyrosine concentrations might influence brain chemistry and therefore patient outcome. This study prospectively investigated the effects of tetrahydrobiopterin (BH4), as a chaperone of phenylalanine hydroxylase on diurnal and day-to-day variations of blood phenylalanine and tyrosine concentrations.MethodsBlood phenylalanine and tyrosine were measured in dried blood spots (DBS) four times daily for 2 days (fasting, before lunch, before dinner, evening) and once daily (fasting) for 6 days in a randomized cross-over design with a period with BH4 and a period without BH4. The sequence was randomized. Eleven proven BH4 responsive PKU patients participated, 5 of them used protein substitutes during BH4 treatment. Natural protein intake and protein substitute dosing was adjusted during the period without BH4 in order to keep DBS phenylalanine levels within target range. Patients filled out a 3-day food diary during both study periods. Variations of DBS phenylalanine and Tyr were expressed in standard deviations (SD) and coefficient of variation (CV).ResultsBH4 treatment did not significantly influence day-to-day phenylalanine and tyrosine variations nor diurnal phenylalanine variations, but decreased diurnal tyrosine variations (median SD 17.6 μmol/l, median CV 21.3%, p = 0.01) compared to diet only (median SD 34.2 μmol/l, median CV 43.2%). Consequently, during BH4 treatment diurnal phenylalanine/tyrosine ratio variation was smaller, while fasting tyrosine levels tended to be higher.ConclusionBH4 did not impact phenylalanine variation but decreased diurnal tyrosine and phenylalanine/tyrosine ratio variations, possibly explained by less use of protein substitute and increased tyrosine synthesis.     

Compliance measurement in respiratory distress syndrome: the prediction of outcome

Dynamic compliance (Cdyn) measurements within the first three days of life predicted survival in 60 preterm infants suffering from respiratory distress syndrome. Cdyn was measured in 47 survivors at 2.3 +/- 1.4 days of life and in 13 nonsurvivors on 2.7 +/- 1.7 days. All nonsurvivors died from respiratory failure within the first two weeks of life. Mean Cdyn of the survivors was 0.83 +/- 0.33 ml/cm H2O and of the nonsurvivors 0.35 +/- 0.19 ml/cm H2O (p less than 0.001). Cdyn values below 0.45 ml/cm H2O predicted 11 of 13 deaths in infants, and Cdyn measurements above this value predicted 45 of 47 survivals, with a specificity of 81% and a sensitivity of 89%. Eleven of the survivors, who subsequently developed bronchopulmonary dysplasia (BPD), had a mean Cdyn of 0.56 +/- 0.23 ml/cm H2O. When these infants were matched with infants of comparable weight without evidence of BPD, the BPD group had a significantly lower Cdyn (p less than 0.05). Cdyn measurements during the first three days of life are useful in predicting outcome of respiratory failure secondary to respiratory distress syndrome.     

Bacteriology of the anal wound after open hemorrhoidectomy

The purpose of this study is to analyze the size of the bacterial colonies in anal wounds after open hemorrhoidectomy. Twenty patients were studied during predetermined postoperative time periods. Material was collected from the surface and from within the tissue of each patient's three open wounds, intraoperatively, on the 6th, 13th and 20th postoperative days for bacteriologic examination in aerobic, microaerophilic, and anaerobic media. The bacterium most commonly identified was Escherichia coli,followed by Staphylococcus aureus and Staphylococcus epidermidis. Pseudomonas aeruginosa, Enterococcus faecalis, Klebsiella pneumoniae, Proteus vulgaris,and Proteus mirabilis were also identified. Critical indexes of colonization were present since the intraoperative stage (>10 ⁵ bacteria/g of tissue and >10 ⁶ bacteria/ml); obligate anaerobic bacteria were not identified; neither the species nor the number of bacteria, even when critical indexes were present, prevented proper healing. The same bacteria were not necessarily present on the surface and in the tissue; the bacterial load observed among the three wounds (left lateral, right posterior, and right anterior), was the same.Presented at the Postgraduate Course, Surgical Technique and Experimental Surgery, offered by the Escola Paulista de Medicina (Paulista Medical School) and the Department of Biomedical Sciences of the University of Taubaté, São Paulo, Brazil.     

The role of macrophage colony-stimulating factor in patients with acute myocardial infarction: a pilot study

We assessed whether macrophage colony-stimulating factor (M-CSF) levels are associated with left ventricular systolic dysfunction (LVSD) in patients with acute myocardial infarction (AMI). We studied 56 patients with AMI (mean age: 67 ± 12 years) and identified those with clinical (Killip class >II) or echocardiographic signs (ejection fraction ≤45%) of LVSD. We evaluated the established cardiovascular risk factors and measured several cardiovascular biomarkers, including M-CSF. Serum M-CSF concentrations (pg/mL) were significantly increased in patients with both clinical and echocardiographic signs of LVSD (460 ± 265 vs 290 ± 210, P = .0103 and 493 ± 299 vs 287 ± 174, P = .0028, respectively). We found a significant inverse association between M-CSF and ejection fraction (r = -.351, P = .0079). Logistic regression analysis revealed that, among all evaluated clinical and biochemical parameters, the stronger predictor of LVSD was M-CSF (odds ratios 2.1, 95% confidence interval 1.1-2.9, P = .0168). This is the first study reporting plasma M-CSF levels as independent determinants of low LV ejection fraction and clinical LV dysfunction in patients with AMI.