Progression of renal insufficiency in the pre-end-stage renal disease setting

The rate of decline of renal function (RDRF) in the pre-end stage renal disease setting (pre-ESRD) is highly variable. Several factors have been involved as potential modifiers of renal failure progression. This retrospective study attempts to establish which were the main determinants of the RDRF in pre-ESRD patients followed in the predialysis consult. The study group consisted of 230 patients with pre-ESRD not yet on dialysis who were referred to the predialysis consult from January 1998 to July 2002. The mean follow-up time per patient was 356 days. RDRF was assessed as delta of the average of creatinine and urea clearances (CrCl-UCl). Data obtained at time of referral to the predialysis consult were analyzed as potential predictors of the subsequent RDRF. These independent variables included: demographics, comorbid conditions, main hematological and biochemical data, antihypertensive and statin treatment, mean blood pressure, and CrCl-UCl at time of referral. The predictors of delta CrCl-UCl were determined by multiple linear regression analysis. The determinants of the survival without dialysis were established by the Cox regression hazard model, adjusted to renal function at time of referral. Mean CrCl-UCl at time of referral was 10.98 +/- 2.58 ml/min/1.73 m2, and mean delta CrCl-UCl was -0.37 +/- 0.46 ml/min/1.73 m2/month. Patients with diabetic nephropathy and chronic glomerulonephritis had the fastest RDRF, while patients with ischemic nephropathy and chronic interstitial nephritis had the slowest RDRF. Seventy-five patients (46%) required EPO therapy. The best determinants of delta CrCl-UCl were: the 24-hour proteinuria (p < 0.0001), and the hematocrit at time of referral (p = 0.0024). The best determinants of the survival rate without dialysis during the study period were: the proteinuria (in g/24 hours) (R 1, 16; p < 0.0001), the hematocrit at time of referral (OR: 0.88; p < 0.0001), the treatment with EPO (OR: 0.59; p = 0.02), and the diagnosis of diabetes mellitus (OR: 1.59; p = 0.01). In conclusion, apart from the rate of proteinuria, which could represent the best marker of the RDRF in chronic renal diseases, the development of anemia was associated with faster decline in renal function.     

Proposal of a haemorheological profile for early detection of hypertensive gestational disorders

The objective of this study was to emphasise the potential power of simple and inexpensive haemorheological tests as predictors of hypertensive gestational disorders through a retrospective study. Blood samples of 195 primigravids with gestational age 18-23 weeks were studied. For data processing pregnant women were allocated into 3 groups, based on difference of SBP and DBP values measured at first and last consultation, and presence of proteinuria and oedema: Normotensive pregnants (n=149), hypertensive pregnants; n=26 and preeclamptic pregnants; n=20. Whole blood viscosity, plasma viscosity, erythrocyte rigidity and aggregability, haemoglobin, hematocrit, total protein, albumin and fibrinogen were assayed. Increased relative viscosity (eta(r)) (p<0.01), decreased erythrocyte deformability (p<0.05), lower O(2) release (p<0.01) and birth weight (p<0.01), showed a negative correlation with filterability index in preeclamptics. There was a decrease of erythrocyte deformability in hypertensive women. Erythrocyte deformability and blood viscosity could be an early indicator in preeclamptics, and erythrocyte deformability in hypertensive ones, therefore they could be considered alert factors in order to decide a thorough control in these patients to prevent further complications.     

Perfluorooctanoic acid disrupts gap junction intercellular communication and induces reactive oxygen species formation and apoptosis in mouse ovaries

Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acid family of compounds. Due to the presence of strong carbon–fluorine bonds, it is practically nonbiodegradable and highly persistent in the environment. PFOA has been detected in the follicular fluid of women, and positively associated with reduced fecundability and infertility. However, there are no reports concerning the experimental evaluation of PFOA on oocyte toxicity in mammals. The aim of the present study was to determine if PFOA is able to induce oxidative stress in fetal ovaries and cause apoptosis in oocytes in vitro. In addition, since inhibition of the gap junction intercellular communication (GJIC) by PFOA has been demonstrated in liver cells in vivo and in vitro, the effect of PFOA on the GJIC between the oocyte and its supportive cumulus cells was studied. Results show that PFOA induced oocyte apoptosis and necrosis in vitro (medium lethal concentration, LC₅₀ = 112.8 μM), as evaluated with Annexin‐V‐Alexa 508 in combination with BOBO‐1 staining. Reactive oxygen species (ROS) levels, as assessed by DCFH‐DA, increased significantly in fetal ovaries exposed to ¼ LC₅₀ (28.2 μM, a noncytotoxic and relevant occupational exposure concentration) and LC₅₀ PFOA ex vivo. This perfluorinated compound also caused the blockage of GJIC in cumulus cells‐oocyte complexes (COCs) obtained from female mice exposed in vivo, as evaluated by calcein transfer from cumulus cells to the oocyte. The ability of PFOA of disrupting the GJIC in COCs, generating ROS in the fetal ovary and causing apoptosis and necrosis in mammal's oocytes, might account for the reported association between increasing maternal plasma concentrations of PFOA with reduced fertility in women.     

Point prevalence of pressure ulcers in three second‐level hospitals in Mexico

Pressure ulcers (PU) are the source of multiple complications and even death. To our knowledge, there is no available data about PU prevalence in Mexico. The objective of this study was to determine the point prevalence of PU in three second‐level hospitals in Mexico. Every adult hospitalised patient was included in each hospital. Age, gender, hospitalisation ward, Braden score, and the number, location and stage of the ulcers encountered were recorded, as well as any pressure relief measures. In total, 294 patients were examined (127 were male); of these, 63 were considered to be at risk. The average age was 48·6 years. The overall prevalence of the PU was 17%. The service with the highest prevalence was the ICU. The most frequent stage was II (32%) and they were most commonly found in the sacrum (74%). The average Braden score of the patients with ulcers was 10, and 21·4% of the patients obtained moderate‐ to high‐risk Braden scores. Of them, 60·3% had ulcers and only 46% had any preventive measures. The prevalence of PU in three hospitals in Mexico is 17%. The most common stage is II and the most commonly affected site is the sacrum. Only 46% of patients with PU had at least one pressure release measure.     

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.     

Developments of prolonged exposure in treatment effect of post‐traumatic stress disorder and controlling dropout rate: A meta‐analytic review

Prolonged exposure (PE) has been proved as an efficacious psychological treatment for post‐traumatic stress disorder (PTSD). There are mainly two changed formats of PE: the modified PE (mPE) and the PE combined with drug (PE/d). Symptom reduction following these two PE training formats has been reported in the patients with PTSD. However, very little is focusing on the direct comparison of mPE + PE/d and PE. Therefore, this paper aims to compare the mPE + PE/d with PE on the PTSD treatment effect and the dropout rate directly through the meta‐analysis. Eighteen studies with total sample size of 1,397 met the final inclusion criteria. The results showed that mPE + PE/d had significantly lower posttreatment PTSD severity than control group (relaxation, wait list, etc.). There was no significant difference between mPE + PE/d and PE on the posttreatment, the follow‐up PTSD score, and the posttreatment dropout rate. Compared with PE, lower PTSD symptoms and marginally lower dropout rate following the treatment were observed in the PE/d group. PE/d yielded a significantly larger effect size than mPE when compared with PE on the posttreatment PTSD symptom severity. The significance of the above results would not be changed even if studies causing high heterogeneity were removed. Although PE/d enhanced treatment effect and lowered dropout rate when compared with PE, it was still insufficient to draw the conclusion that formats of adjustments would specifically improve the implementation of PE. Further studies are warranted to develop an easily accomplished and efficacy‐guaranteeing PE programme for PTSD patients.