Simultaneous fronto-orbital advancement and dynamic posterior cranial vault expansion in Apert syndrome

Craniosynostosis in Apert syndrome is routinely treated by wide frontal and bilateral supraorbital reshaping and posterior cranial decompression. Dynamic cranial vault expansion has proved to be useful in craniofacial surgery, and its use has extended to syndromic patients. Although a controversy remains between conventional osteotomy and application of the spring-mediated technique in surgical treatment of craniosynostosis, there have been several positive clinical reports on expansion techniques for nonsyndromic and syndromic craniosynostosis. Simultaneous fronto-orbital advancement and posterior cranial vault expansion have been applied successfully to 2 patients of Apert syndrome, without intraoperative complications or postoperative morbidity and improving final cranial shape.     

Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats

The ketogenic diet (KD) is a high fat and low carbohydrate and protein diet. It is used in the clinical treatment of epilepsy, in order to decrease cerebral excitability. KD is usually composed by long-chain triglycerides (LCT) while medium-chain triglycerides (MCT) diet is beginning to be used in some clinical treatment of disorders of pyruvate carboxylase enzyme and long-chain fatty acid oxidation. Our study aimed to analyze the effects of medium- and long-chain KD on cerebral electrical activity, analyzing the propagation of the phenomenon of cortical spreading depression (CSD). Three groups of weaned rats (21 days old) received, for 7 weeks, either a control (AIN-93G diet), or a MCT-KD (rich in triheptanoin oil), or a LCT-KD (rich in soybean oil). They were compared to another three groups (21 days old) receiving the same diets for just 10 days. CSD propagation was evaluated just after ending the dietary treatments. Results showed that short-term KD treatment resulted in a significant reduction of the CSD velocity of propagation (control group: 4.02 ± 1.04 mm/min; MCT-KD: 0.81 ± 1.46 mm/min and LCT-KD: 2.26 ± 0.41 mm/min) compared to the control group. However, long-term treatment with both KDs had no effect on the CSD velocity (control group: 3.10 ± 0.41 mm/min, MCT-KD: 2.91 ± 1.62 mm/min, LCT-KD: 3.02 ± 2.26 mm/min) suggesting that both short-term KDs have a positive effect in decreasing brain cerebral excitability in young animals. These data show for the first time that triheptanoin has an effect on central nervous system.     

ABCB4 variants in adult patients with cholestatic disease are frequent and underdiagnosed

BackgroundHeterozygous ABCB4 variants are not routinely tested in adults with cholestasis because of their supposed rarity and high costs.MethodsNineteen adult patients presenting with unexplained cholestasis, and/or recurrent gallstones were included; genotyping was not done in five due to lack of health insurance approval.Resultsheterozygous ABCB4 variants were identified in seven patients, followed by cascade testing of 12 family members: one patient underwent liver transplantation at age 40 for end-stage liver disease; one had compensated cirrhosis; all symptomatic adults had gallstones, including four with low phospholipid-associated cholelithiasis; four had intrahepatic cholestasis of pregnancy; all children and one 54-year old female were asymptomatic. Genotype: Families A and C: c.2211G>A (p.Ala737=) combined with c.959C>T (p.Ser320Phe) in one subject; Family B: c.1130T>C (p.Ile377Thr); Family D: large deletion removing ABCB4 exons 1-4 plus ABCB1, RUNDC3B, SLC25A40, DBF4, ADAM22 exons 1-3; Family E: c.1565T>C (p.Phe522Ser) ; Family F: c.1356+2T>C combined with c.217C>G (p.Leu73Val). All patients responded to ursodeoxycholic acid.ConclusionsWe found ABCB4 variants in half of the adults with unexplained cholestasis and/or recurrent gallstones presenting at our center, suggesting that this condition is underdiagnosed and undertreated, with serious consequences not only for the patients and their families, but also in terms of healthcare costs.     

Patient Perspectives on Buprenorphine/Naloxone: A Qualitative Study of Retention During the Starting Treatment with Agonist Replacement Therapies (START) Study

This study examines the barriers and facilitators of retention among patients receiving buprenorphine/naloxone at eight community-based opioid treatment programs across the United States. Participants (n = 105) were recruited up to three and a half years after having participated in a randomized clinical trial comparing the effect of buprenorphine/naloxone and methadone on liver function. Semi-structured interviews were conducted with 67 patients provided with buprenorphine/naloxone who had terminated early and 38 patients who had completed at least 24 weeks of the trial. Qualitative data were analyzed using the constant comparison method. Barriers to buprenorphine/naloxone retention that emerged included factors associated with: (1) the design of the clinical trial; (2) negative medication or treatment experience; and (3) personal circumstances. The facilitators comprised: (1) positive experience with the medication; (2) personal determination and commitment to complete; and (3) staff encouragement and support. The themes drawn from interviews highlight the importance of considering patients’ prior experience with buprenorphine/naloxone and methadone, medication preference, personal circumstances, and motivation to abstain from illicit use or misuse of opioids, as these may influence retention. Ongoing education of patients and staff regarding buprenorphine/naloxone, especially in comparison to methadone, and support from staff and peers are essential.     

Mononuclear leukocyte apoptosis in haemodialysis patients: the role of cell thiols and vitamin E.

BACKGROUND: An increased apoptotic rate of peripheral blood mononuclear leukocytes (PBMLs) in haemodialysis (HD) patients has been reported in several studies, but its underlying mechanisms remain poorly understood. Oxidant stress is a well known cause of cell damage, and several lines of evidence suggest that it might influence the induction and signalling steps of mononuclear cell apoptosis through different mechanisms so as to provoke disturbances of the intracellular pool of thiols (SHi). In this study, we investigated the in vitro apoptotic rate and SHi of PBMLs in end-stage renal disease (ESRD) patients on HD or peritoneal dialysis (PD). METHODS: Apoptosis and SHi were evaluated in vitro in PBMLs obtained from 40 ESRD patients (HD, n = 30 and PD, n = 10) and 10 healthy controls. A subgroup of HD patients was also studied before and after 1 month of treatment with a vitamin E-coated dialyser (CL-E). Cell thiols and viability were also assessed in the monocyte-like cell line U937 and PBMLs after incubation in the presence of uraemic plasma with or without supplementation of the antioxidants vitamin E (70 micro M) or N-acetyl-cysteine (NAC) (0.5 mM). RESULTS: After 24 h in culture, the PBMLs of HD patients, but not those of CAPD patients, showed an apoptotic rate twice that of healthy controls and a 40% decrease of SHi levels (P < 0.01 in both). A negative correlation between the apoptotic rate and SHi was observed in both patients and controls (r = 0.648, P < 0.001). Plasma and ultrafiltrate samples from HD patients contained solutes (mainly in the low-middle molecular weight range) able to trigger apoptosis and oxidative stress in U937 cells. The treatment of HD patients with CL-E, as well as the in vitro supplementation of U937 cells with vitamin E or NAC during the exposure to uraemic plasma, decreased the rate of apoptosis and partially restored SHi. CONCLUSIONS: This study showed an association between an increased apoptotic rate and decreased SHi in PBML of HD patients, but not of CAPD patients. These changes are partially due to different pro-apoptogens that accumulate in the plasma and are at least partially prevented by exogenous antioxidants able to restore SHi, such as vitamin E or thiol suppliers.     

A robust goodness-of-fit test statistic with application to ordinal regression models

We propose a goodness-of-fit test statistic for linear regression with heterogeneous variance, which is asymptotically chi-square if the given model is correct. The test statistic is computed as a quadratic form of observed minus predicted responses. We apply the method to a linear regression for an ordinal categorical response, the wheezing status of a child (no wheeze, wheeze with cold, wheeze apart from cold) as a function of maternal smoking and city of residence.     

Phosphatidylcholine and peritoneal transport during peritoneal dialysis

Peritoneal effluent of patients on chronic ambulatory peritoneal dialysis (CAPD) contains a surface-active material (SAM) made up of phospholipids and showing phosphatidylcholine on thin-layer chromatography. This substance drastically lowers surface tension, helps to repel water and has a lubricating effect. The presence of stratified phosphatidylcholine on the peritoneum might narrow the stagnant dialysate fluid layer and situations which can alter the quantity or composition of SAM may affect peritoneal transport and also, perhaps, the formation of adherences. This led us to verify, experimentally, the presence of phospholipids in basal conditions, after CAPD and during peritonitis and to check if addition of phosphatidylcholine to dialysis liquid is able to modify water transport in patients with low ultrafiltration and peritonitis. Phospholipids in the dialysis effluent of patients who have been on CAPD for a long time are lower than observed in the first days of peritoneal dialysis. A more drastic, significant decrease in phospholipids was observed in patients with low ultrafiltration and in patients with peritonitis. Mean ultrafiltration significantly increases in patients with low ultrafiltration and in those with peritonitis during dialysis exchanges containing phosphatidylcholine (50 mg/l) indicating that the latter is able to restore normal physiological conditions.     

Endogenous oestradiol but not testosterone is related to coronary artery disease in men

Objectives Men die of coronary artery disease (CAD) more often than women. There is evidence that testosterone either is neutral or has a beneficial effect on male cardiovascular disease. The role of oestrogens in male CAD has been less studied. This study was carried out with the purpose of evaluating the relationship between sex hormone levels and CAD. Design Case–control study. Participants Men (aged 40–70) submitted to coronary angiography. A 70% occlusion of at least one major coronary artery defined the cases; subjects with ≤50% occlusion constituted the control group. Measurements Blood samples were collected for total testosterone (TT), oestradiol, luteinizing hormone, follicle‐stimulating hormone, sex hormone‐binding globulin, lipid profile and albumin measurements. Bioavailable and free testosterone, free androgen index (FAI) and free oestrogen index (FEI) were calculated. Oestradiol and TT levels were examined as terciles, based on the whole study population. Results Of the 140 patients included, 72 were cases and 68 were controls. The baseline characteristics of the two groups were similar, except for the older age and lower LDL‐C in the cases. Oestradiol and FEI but not total, bioavailable and free testosterone and FAI correlated positively with CAD. After adjustments for potential confounders, oestradiol remained statistically significant. The prevalence of CAD was significantly higher in the 3rd than in the 1st tercile of oestradiol. Conclusion In this study, men with CAD had higher oestradiol and FEI levels. Additional studies are needed to clarify the direction of causality and possible underlying mechanisms.