Long-term prognosis in patients with end-stage renal disease after coronary artery bypass grafting.

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Coronary artery bypass grafting (CABG) is beneficial in selected patients with ESRD. This study investigates the survival outcomes and prognostic factors in ESRD patients who underwent CABG. METHODS: A retrospective analysis was performed for 149 patients with ESRD who underwent isolated CABG between 2006 and 2015. RESULTS: Mean age was 59.4±8.7 years and 106 patients (71.1%) were male. Operative mortality occurred in 20 patients (13.4%). Overall survival was 81.1%±3.2% at 1 year, 41.5%±4.3% at 5 years and 19.2%±4.2% at 10 years. Median survival was 4.3 years. Multivariable analysis identified age [P=0.001, odds ratio (OR): 1.15 per 1-year increase, 95% confidence interval (CI): 1.06-1.25], preoperative left ventricular ejection fraction (LVEF) (P=0.020, OR: 0.94, 95% CI: 0.89-0.99) and non-elective status of operation (P=0.049, OR: 3.34, 95% CI: 1.00-11.1) as predictors of operative mortality. Cox regression analysis identified age [P<0.001, hazard ratio (HR): 1.05 per 1-year increase, 95% CI: 1.03-1.08], New York Heart Association (NYHA) class III or IV status (P=0.010, HR: 1.75, 95% CI: 1.15-2.67) and the use of a left internal mammary artery (LIMA) to left anterior descending artery (LIMA-LAD) graft (P=0.029, HR: 0.42, 95% CI: 0.19-0.92) as factors influencing long-term survival. CONCLUSIONS: CABG is associated with high operative mortality and poor long-term survival in ESRD patients. Age and NYHA class influenced late survival. LIMA-LAD grafting conferred a long-term survival advantage.

Reducing variability in apparent operative inclination during total hip arthroplasty: findings of a randomised controlled trial.

AIMS: To determine which of 3 methods of cup insertion most accurately achieved a target apparent operative inclination (AOI) of 35° ± 2.5°: (1) Freehand; (2) Modified Mechanical Alignment Guide (MAG); or (3) Digital Inclinometer assisted. METHODS: Using a cementless cup via a posterior approach in lateral decubitus 270 participants were recruited, with 90 randomised to each method. The primary outcome was the unsigned deviation from target AOI. The digital inclinometer was used to measure AOI in all cases, though the surgeon remained blinded to the reading intraoperatively for both the Freehand and MAG methods. RESULTS: Mean deviation from target AOI for the Freehand, Modified 35° MAG and Digital Inclinometer techniques was 2.9°, 1.8° and 1.3° respectively. When comparing mean deviation from target AOI, statistically significant differences between the Freehand / Inclinometer groups ( p < 0.001), the Freehand / Modified 35° MAG groups ( p < 0.001) and the Digital Inclinometer / Modified 35° MAG groups ( p < 0.023) were evident. The Digital Inclinometer technique enabled the surgeon to achieve a target AOI of 35° ± 2.5° in 88% of cases, compared to 71% of Modified 35° MAG cases and only 51% of Freehand cases. DISCUSSION: The Digital Inclinometer and the Modified 35° MAG techniques were both more accurate than the Freehand technique, with the Digital Inclinometer technique proving most accurate overall. Radiographic inclination (RI) is also influenced by operative anteversion; however, the greatest source of error with respect to RI occurs when the pelvic sagittal plane is not horizontal at the time of acetabular component insertion. Clinical Trial Protocol number: NCT01831401.

Correction of pelvic adduction during total hip arthroplasty reduces variability in radiographic inclination: findings of a randomised controlled trial.

INTRODUCTION: The study aims were to identify the incidence of pelvic adduction during total hip arthroplasty (THA) in lateral decubitus and to determine, when aiming for 35° of apparent operative inclination (AOI), which of 3 operating table positions most accurately obtained a target radiographic inclination (RI) of 42°: (1) horizontal; (2) 7° head-down; (3) patient-specific position based on correction of pelvic adduction. METHODS: With patients seated on a levelled theatre table, a ruler incorporating a spirit level was used to draw transverse pelvic lines (TPLs) on the skin overlying the pelvis and sacrum. Subsequently, when positioned in lateral decubitus these lines provided a measure of pelvic adduction. 270 participants were recruited, with 90 randomised to each group for operating table position. In all cases target AOI was 35°, aiming to achieve a target RI of 42°. The primary outcome measure was absolute (unsigned) deviation from the target RI of 42°. RESULTS: 266/270 patients demonstrated pelvic adduction (overall mean 4.4°, range 0- 9.2°). No patients demonstrated pelvic abduction. There were significant differences in RI between each of the 3 groups. The horizontal table group displayed the highest mean RI. The patient specific table position group achieved the smallest absolute deviation from target RI of 42°. DISCUSSION: In lateral decubitus, unrecognised pelvic adduction is common and is an important contributor to unexpectedly high RI. The use of preoperative TPLs helps identify pelvic adduction and its subsequent correction reduces variability in RI. Clinical Trial Protocol number: NCT01831401.

Ciliopathy Protein Tmem107 Plays Multiple Roles in Craniofacial Development.

A broad spectrum of human diseases called ciliopathies is caused by defective primary cilia morphology or signal transduction. The primary cilium is a solitary organelle that responds to mechanical and chemical stimuli from extracellular and intracellular environments. Transmembrane protein 107 (TMEM107) is localized in the primary cilium and is enriched at the transition zone where it acts to regulate protein content of the cilium. Mutations in TMEM107 were previously connected with oral-facial-digital syndrome, Meckel-Gruber syndrome, and Joubert syndrome exhibiting a range of ciliopathic defects. Here, we analyze a role of Tmem107 in craniofacial development with special focus on palate formation, using mouse embryos with a complete knockout of Tmem107. Tmem107-/- mice were affected by a broad spectrum of craniofacial defects, including shorter snout, expansion of the facial midline, cleft lip, extensive exencephaly, and microphthalmia or anophthalmia. External abnormalities were accompanied by defects in skeletal structures, including ossification delay in several membranous bones and enlargement of the nasal septum or defects in vomeronasal cartilage. Alteration in palatal shelves growth resulted in clefting of the secondary palate. Palatal defects were caused by increased mesenchymal proliferation leading to early overgrowth of palatal shelves followed by defects in their horizontalization. Moreover, the expression of epithelial stemness marker SOX2 was altered in the palatal shelves of Tmem107-/- animals, and differences in mesenchymal SOX9 expression demonstrated the enhancement of neural crest migration. Detailed analysis of primary cilia revealed region-specific changes in ciliary morphology accompanied by alteration of acetylated tubulin and IFT88 expression. Moreover, Shh and Gli1 expression was increased in Tmem107-/- animals as shown by in situ hybridization. Thus, TMEM107 is essential for proper head development, and defective TMEM107 function leads to ciliary morphology disruptions in a region-specific manner, which may explain the complex mutant phenotype.

Acetabular Liner Dissociation following Total Hip Arthroplasty: A Rare but Serious Complication That May Be Easily Misinterpreted in the Emergency Department.

Acetabular liner dissociation is a rare complication of Total Hip Arthroplasty (THA) which requires urgent revision surgery. A case is presented in which the correct diagnosis was not appreciated on two separate Emergency Department attendances. The typical symptoms, signs, and radiological features are outlined and the importance of considering a rare complication following a commonly performed procedure is highlighted.

Involvement of protein kinase C in 5-HT-stimulated ciliary activity in Helisoma trivolvis embryos.

1. During development, embryos of the pulmonate gastropod, Helisoma trivolvis, undergo a rotation behaviour due to the co-ordinated beating of three bands of ciliated epithelial cells. This behaviour is in part mediated by the neurotransmitter serotonin (5-HT) released from a pair of identified embryonic neurons. Using time-lapse videomicroscopy to measure ciliary beat frequency (CBF) in response to pharmacological manipulations, we determined whether protein kinase C (PKC) is involved in mediating 5-HT-stimulated ciliary beating. 2. Diacylglycerol (DAG) analogues sn-1,2-dioctanoyl glycerol (DiC8; 100 microM) and 1-oleoyl-2-acetyl-sn-glycerol (OAG; 100 microM), partially mimicked the 5-HT-induced increase in CBF. In contrast, application of OAG in the absence of extracellular Ca2+ did not result in an increase in CBF. 3. 5-HT-stimulated CBF was effectively blocked by PKC inhibitors bisindolylmaleimide (10 and 100 nM) and calphostin C (10 nM). In addition, bisindolylmaleimide (100 nM) inhibited DiC8-induced increases in CBF. At a higher concentration (200 nM), bisindolylmaleimide did not significantly reduce 5-HT-stimulated cilio-excitation. 4. Two different phorbol esters, phorbol 12-myristate 13-acetate (TPA; 0.1, 10 or 1000 nM) and phorbol 12beta, 13alpha-dibenzoate (PDBn; 10 microM) did not alter basal CBF. TPA (1 microM) did not alter 5-HT-stimulated CBF. Likewise, the synthetic form of phosphatidylserine, N-(6-phenylhexyl)-5-chloro-1-naphthalenesulphonamide (SC-9; 10 microM), did not increase CBF, whereas a strong increase in CBF was observed upon exposure to 5-HT. 5. The results suggest that a DAG-dependent, phorbol ester-insensitive isoform of PKC mediates 5-HT-stimulated CBF in ciliated epithelial cells from embryos of Helisoma trivolvis.

Pharmacological characterization of a serotonin receptor involved in an early embryonic behavior of Helisoma trivolvis.

In contrast to the abundance of information on the many physiological and developmental actions of serotonin in molluscan nervous systems, comparatively little is known about the serotonin receptors involved in these responses. Embryos of the pulmonate gastropod, Helisoma trivolvis, display a cilia-driven rotational behavior that is regulated by endogenous serotonin. In the present study, two functional assays were used to determine some of the pharmacological properties of the receptors that mediate the cilio-excitatory action of serotonin. Time-lapse video microscopy was used to measure whole embryo rotation rate and cilia beat frequency in isolated cells. In dose-response experiments, serotonin was approximately 10 times more potent in stimulating cilia beat frequency over embryo rotation. In rotation experiments, 5-carboxyamidotryptamine and methysergide had effective agonist activity in dose ranges similar to that of serotonin (1 to 100 microM). In contrast, 8-hydroxydipropylaminotetralin HBr (8-OH-DPAT) displayed agonist activity of lower potency and effectiveness. Several compounds displayed antagonist activity in the 1 to 100 microM dose range, including mianserin, spiperone, ritanserin, 1-(1-naphthyl)piperazine, and propranolol. alpha-Methylserotonin had mixed agonist-antagonist activity, and metoclopramide, MDL-72222, and ketanserin were inactive. Experiments on isolated cells suggested that the extremely effective antagonism displayed by mianserin in the embryo rotation assay was due to its specific activity at ciliary serotonin receptors. These results implicate the presence of a novel serotonin receptor on embryonic ciliated cells that is pharmacologically distinct from those previously characterized in vertebrate or invertebrate systems.

The use of low density lipoprotein receptor activity of lymphocytes to determine the prevalence of familial hypercholesterolaemia in a rural South African community.

The diagnosis of heterozygous familial hypercholesterolaemia in three rural South African communities in which hypercholesterolaemia is very prevalent could be confirmed by the measurement of low density lipoprotein (LDL) receptor activity in circulating lymphocytes. A nominal cut off point could be proposed which separated the LDL receptor activity of 24 clinically diagnosed heterozygous FH patients and 31 healthy people. LDL receptor activity was measured as total degradation of 125I-LDL and expressed as ng LDL/mg cell protein/6 hours. The cut off point was set at 970 ng/mg protein/6 hours. This proposed cut off point was tested by assaying the LDL receptor of three homozygous FH patients and seven of their obligate heterozygous FH first degree relatives. The three homozygous FH patients showed no receptor activity and the activity of the seven obligate heterozygous first degree relatives fell below the proposed cut off point. To determine the prevalence of FH in the study population, all persons aged 15 to 24 years whose total cholesterol levels fell above the 80th centile for their age and sex, as well as their families, were approached (n = 114). The LDL receptor activity in lymphocytes of 77 of these persons aged 15 to 24 years was determined after applying the exclusion criteria. Ten of the 77 participants had LDL receptor activity below 970 ng LDL/mg protein/6 hours and were therefore diagnosed as being heterozygous FH patients. The calculation of the prevalence (corrected for exclusions) revealed that one in 71 of the 15 to 24 year old permanent residents in the predominantly Afrikaans speaking community suffered from heterozygous FH. This is higher than any FH prevalence previously reported for any group.

The prevalence of smoking and its relationship to other coronary risk factors in a rural white community.

A cross-sectional study of tobacco-smoking habits and its relationship to other coronary risk factors in a large rural community of 7,188 white subjects aged 15-64 years, revealed that 48.1% of the men and 17.9% of the women were currently smoking; only 28.6% men and 74.1% women had never smoked. Heavy smoking prevailed, with a mean daily consumption of 21.4 g and 14.6 g tobacco among male and female smokers respectively. Only 16.5% of male and 27.7% of female smokers smoked less than 10 g tobacco per day. Smoking was associated with a high total cholesterol level, a low high-density lipoprotein cholesterol level, low blood pressure, a low body mass index, coronary-prone type A behaviour, and a high prevalence of coronary heart disease in men. Furthermore, smoking was associated with a high alcohol consumption and a low level of education and occupational class. These findings emphasise the high prevalence of smoking in whites and its harmful association with coronary heart disease, and indicate the need for effective anti-smoking programmes.

A comparison of the effects of soya-bean protein and casein on bile composition, cholelithiasis and serum lipoprotein lipids in the vervet monkey (Cercopithecus aethiops).

1. Two groups of vervet monkeys (Cercopithecus aethiops) were fed on high-cholesterol diets which differed only with respect to the protein source. In one group casein was the only protein source, while the other group received only soya-bean protein. 2. Samples of blood, bile and liver biopsy material were collected at the commencement of the study and at 3-monthly intervals until termination 12 months later. 3. At the end of the experimental period all the animals (n 19) had high plasma cholesterol levels and had developed pigment gallstones, the compositions and weights of which were not related to the protein source or to plasma cholesterol levels. Gallstone weight was related to the presence of acidic and sulphated mucins in gallbladder mucosa. We were also unable to confirm the hypocholesterolaemic effect of soya-bean protein which has been demonstrated previously in rhesus monkeys and hamsters. Bile composition and plasma lipids did not differ significantly between the casein-fed and soya-bean fed animals. Lithogenic index was below 1 for both groups and did not differ significantly between the two groups. 4. No significant difference was found in the severity of cholelithiasis between the casein-fed and the soya-bean-fed animals.