Review article: Leukocyte-endothelial dysregulation in systemic small vessel vasculitis

Aberrant interaction between the leukocyte and the endothelial cell (EC) results in the uncontrolled inflammation seen in systemic small vessel vasculitis. This review discusses our current understanding of this process and includes consideration of the role of adhesion molecules, proteases and the neutrophil respiratory burst. The effects of anti-neutrophil cytoplasm antibodies and anti-endothelial cell antibodies and their pathogenic roles are examined, and we look at experimental disease models. Specificity of disease-targetted endothelial beds and the role of circulating EC are discussed.     

Comparison of transposed brachiobasilic fistulas to upper arm grafts and brachiocephalic fistulas

BACKGROUND: Renewed interest in transposed brachiobasilic fistulas has occurred since the release of the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) guidelines because it is an alternative method to achieve an upper arm fistula in patients who cannot achieve a functional brachiocephalic fistula. The objective of this study was to compare outcomes among transposed brachiobasilic fistulas, upper arm grafts, and brachiocephalic fistulas. METHODS: A cohort of patients with upper arm accesses was retrospectively identified. Access outcomes were determined from medical records and contact with physicians, dialysis providers, and patients. Primary outcome was thrombosis-free survival. Secondary outcomes were primary failure, time to use, risk of catheter-related bacteremia, need for intervention, incidence of access-related complications, cumulative, and functional patency. Group differences in age, sex, race, diabetes, peripheral vascular disease, and number of previous accesses were adjusted for in the analysis where appropriate. RESULTS: Transposed brachiobasilic fistulas, upper arm grafts, and brachiocephalic fistulas were compared in 59, 82, and 56 patients, respectively. Compared with transposed brachiobasilic fistulas, upper arm grafts were more likely to thrombose with an adjusted relative risk (RR) of 2.6 (95% CI, 1.3 to 5.3) excluding primary failures and 1.6 (95% CI, 1.0 to 2.7) when accounting for the lower risk of primary failure for grafts. Transposed brachiobasilic fistulas also required less intervention (0.7 vs. 2.4 per access-year, P < 0.01) and were less likely to become infected (0 vs. 13%, P < 0.05) than grafts. Mature brachiocephalic fistulas were less likely to fail (RR 0.3, 95% CI, 0.1 to 1.0) and showed a trend for less thrombosis (RR 0.3, 0.1 to 1.1) than mature brachiobasilic fistulas. There was no significant difference in cumulative patency (failure-free survival) among the three types of access if primary failure was included at the median follow-up of 594 days. Transposed brachiobasilic fistulas provided catheter-free access one month sooner than brachiocephalic fistulas and one month later than upper arm grafts. CONCLUSIONS: Transposed brachiobasilic fistulas provide cumulative patency equivalent to upper arm grafts and brachiocephalic fistulas. They are less likely to thrombose and become infected than upper arm grafts. Compared with brachiocephalic fistula, they are more likely to mature but are at increased risk of thrombosis after maturation. Transposed brachiobasilic fistulas should be considered before placing an upper arm graft for patients that cannot achieve a functional brachiocephalic fistula.     

Sex differences in essential hypertension

Abstract. A group of 41-year-old hypertensive men (n = 35, blood pressure (BP) 149.9 ± 2.1/ 98.9 ± 1.1 mmHg, mean ± SEM) who had never received treatment for their condition were compared with hypertensive women of the same age (n = 18, BP 155.9 ± 4.3/ 98.1 ± 1.6 mmHg) with comparable body mass index (BMI. 25.9 ± 0.5 vs. 24.9 ± 4.5 kg m^?2) who, also, had never received treatment. The lipid profile was more atherogenic in the men, with lower HDL cholesterol (1.21 ± 0.04 vs. 1.38 ± 0.06 mmol l^?1 P = 0.04), higher total cholesterol (6.04 ± 0.14 vs. 5.54 ± 0.18 mmol l^?1. P = 0.04) and triglycerides (1.80 ± 0.16 vs. 0.96 ± 0.10 mmol l^?1, P < 0.001). The hypertensive men had higher haemoglobin (P < 0.001) and haematocrit. Plasma catecholamines were inversely related to BMI in the women only (r = ?0.52, P < 0.05 for both noradrenaline and adrenaline). Women with BMI above 25 kg m^?2 had significantly lower arterial plasma adrenaline and noradrenaline than those with BMI below 25 kg m^?2 (28 ± 5 vs. 78 ± 16 pg ml^?1, P < 0.01 and 101 ± 17 vs. 206 ± 33 pg ml^?1, P < 0.01 respectively). A negative curvelinear relationship appeared between arterial adrenaline and insulin (r = 0.49, P= 0.05). These results suggest a male propensity for athero-thrombogenic risk factors in otherwise comparable hypertensive subjects. A close relationship between metabolic risk factors within the normal range seems to exist even in hypertensive women. The decreased sympathetic activity at rest in the obese hypertensive women indicates different pathophysiological mechanism for hypertension in lean and obese. Decreased sympathetic activity and thus reduced energy expenditure, promotes a risk for weight gain, and could explain the inverse relationship between insulin and adrenaline.     

Endothelialization of Nonapposed Stent Struts Located over the Origin of a Side Branch: Results with Different Carbofilm-Coated Stents

Objective: To evaluate the degree of endothelialization of the nonapposed struts located at the ostia of side branches.
Background: Endothelialization of coronary stents has got considerable relevance because of the phenomenon of late thrombosis. Bifurcation location and incomplete stent apposition have been linked to this complication.
Methods: Domestic pigs (n = 11; weight: 25 ± 3 kg) were anesthetized and had one stent per coronary artery implanted: one stainless steel (Tecnic^®), one cobalt-chromium (Chrono^®), and one tacrolimus-eluting stent (Janus^®), all of them being Carbofilm^®-coated (Sorin). One, three, or seven days postprocedure, the pigs were sacrificed, the hearts explanted, and longitudinal sections examined by surface electron microscopy to quantify the percentage of the strut endothelialized over the branches and in the total surface.
Results: Forty-four side branches (25 stents) that had stent struts over their origin were evaluated. Different patterns of endothelialization were observed, from the total absence to the complete endothelialization. There were no significant differences in relation to type of stent or to the artery treated. The predictors of higher percentage of endothelialization were the ratio of metal to branch diameter (P = 0.04) and better endothelialization in the rest of the stent (P = 0.0002), only this parameter maintaining significant correlation (P = 0.03) in multivariate analysis.
Conclusions: Carbofilm^®-coated stent struts located over the origin of side branches follow the pattern of endothelialization for the rest of the stent, even in the case of tacrolimus-eluting stent.     

Perinatal data reliability in a large teaching obstetric unit

Summary. In this inter-rater agreement study of antenatal and neonatal variables collected in a large teaching obstetric unit, information routinely collected by hospital staff was compared with that collected by a specially trained physician and a social worker. Agreement between the two sources of data was evaluated using kappa statistics and intraclass correlation coefficients. Excellent agreement was observed for some variables such as maternal and newborn anthropometric measures, and previous birthweight, but there was poor agreement for others such as indicators of physical activity, work during pregnancy and blood pressure measures. Some of the limitations are due to problems in phrasing questions, patients' recall, interviewer bias and abstracting data. We recommend that epidemiological studies should always include a reliability component, proper standardization of personnel and instruments and include, when published, validity data and examples of questions used.     

AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome

Background

Joubert syndrome (JS) is an autosomal recessive disorder characterised by hypotonia, ataxia, mental retardation, altered respiratory pattern, abnormal eye movements, and a brain malformation known as the molar tooth sign (MTS) on cranial MRI. Four genetic loci have been mapped, with two genes identified (AHI1 and NPHP1).

Methods

We screened a cohort of 117 JS subjects for AHI1 mutations by a combination of haplotype analysis and sequencing of the gene, and for the homozygous NPHP1 deletion by sequencing and marker analysis.

Results

We identified a total of 15 novel AHI1 mutations in 13 families, including nonsense, missense, splice site, and insertion mutations, with some clustering in the WD40 domains. Eight families were consanguineous, but no single founder mutation was apparent. In addition to the MTS, retinal dystrophy was present in 11 of 12 informative families; however, no subjects exhibited variable features of JS such as polydactyly, encephalocele, colobomas, or liver fibrosis. In contrast to previous reports, we identified two families with affected siblings who developed renal disease consistent with nephronophthisis (NPH) in their 20s. In addition, two individuals with classic NPH were found to have homozygous NPHP1 deletions.

Conclusions

Overall, 11% of subjects had AHI1 mutations, while ∼2% had the NPHP1 deletion, representing a total of less than 15% in a large JS cohort. Some preliminary genotype‐phenotype correlations are possible, notably the association of renal impairment, specifically NPH, in those with NPHP1 deletions. Subjects with AHI1 mutations may be at risk of developing both retinal dystrophy and progressive kidney disease.     

Intestinal ameliorative effects of traditional Ogi-tutu,Vernonia amygdalina and Psidium guajava in mice infected with Vibrio cholera

BackgroundCholera, a severe acute watery diarrhea caused by Vibrio cholerae is endemic in Nigeria with most cases occurring in the rural areas. In South West Nigeria, some individuals resort to alternative treatments such as Ogi-tutu, Psidium guajava and Vernonia amygdalina during infections. The effectiveness of these alternatives in the prevention and treatment of V. cholerae infection requires experimental investigation.ObjectiveThis study was designed to investigate the ameliorative effects of Ogi-tutu, Vernonia amygdalina and Psidium guajava on intestinal histopathology of experimental mice infected with V. cholerae.MethodsPreliminary investigation of in vitro vibriocidal activities of these alternatives were carried out using agar cup diffusion assay. For ameliorative effects, adult mice were inoculated with 100 µl (106 cells) of Vibrio cholerae and dosed at 0 h (immediate prevention) and 4 h (treatment of infection) and their intestines were histopathologically evaluated.ResultsThe histopathological changes were the same irrespective of the treated groups, but the lesions varied in extent and severity. The ameliorative effects in decreasing order were V. amygdalina > P. guajava > Ogi-tutu.ConclusionV. amygdalina gave the best ameliorative effects in the prevention and treatment of V. cholerae infection.     

Effect of <Emphasis Type="Italic">Citrullus vulgaris</Emphasis> on some functional indices of selected tissues of Wistar rats

Citrullus vulgaris (watermelon) is a fruit with prophylactic and therapeutic potentials. In an attempt to maximize these potentials, the seed and rind are now often consumed together with the pulp. This study aimed at evaluating the implications of such consumption. Study involved the use of 35 Wistar rats grouped into seven with a control group administered distilled water, and the other groups administered varying concentrations of the pulp and whole fruit for 28 days. Alanine and aspartate aminotransferase (ALT, AST) were assayed in the serum and liver. Total protein of the serum and selected tissues was determined and malondialdehyde (MDA) level measured. Phytochemical screening revealed the presence of steroids, saponin, alkaloids, flavonoids, and terpenoids in both whole fruit and pulp. Significant increases (p < 0.05) were seen in the liver ALT levels while there was a decreased (p < 0.05) intestinal total protein in the treatment groups. No significant (p ? 0.05) difference was seen in the serum and pancreas MDA levels while an increased (p < 0.05) intestinal MDA level was observed. Increased liver ALT levels in all the treatment groups might be due to high glutamate levels of C. vulgaris. Decreased (p ? 0.05) intestinal total protein might be indicative of protein loss, while elevated (p < 0.05) intestinal MDA levels in the groups administered whole fruit is suggestive of a defect in absorption at the intestinal epithelium. Hence, whole fruit consumption of C. vulgaris should be done with caution as it has potential to cause intestinal oxidative stress.     

Synthesis and excretion profile of 1,4- [14C]phenylenebis(methylene)selenocyanate in the rat

1,4-Phenylenebis(methylene)selenocyanate (p-XSC) inhibits chemically induced tumors in several laboratory animal models. To understand its mode of action, we synthesized p-[14C]XSC, examined its excretion pattern in female CD rats and also the nature of its metabolites. p- [14C]XSC was synthesized from alpha,alpha-dibromo-p-[ring-14C]xylene in 80% yield. The excretion profile of p-[14C]XSC (15.8 mg/kg body wt, 200 microCi/rat, oral administration, in 1 ml corn oil) in vivo was monitored by measuring radioactivity and selenium content. On the basis of radioactivity, approximately 20% of the dose was excreted in the urine and 68% in the feces over 3 days. The cumulative percentages of the dose excreted over 7 days were 24% in urine and 75% in feces, similar to excretion rates of selenium. According to selenium measurement, <1% of the dose was detected in exhaled air; radioactivity was not detected. Only 15% of the dose was extractable from the feces with EtOAc and was identified as tetraselenocyclophane (TSC). Most of the radioactivity remained tightly bound to the feces. Approximately 10% of this bound material converted to TSC on reduction with NaBH4. Organic soluble metabolites in urine did not exceed 2% of the dose; sulfate (9 % of urinary metabolites) and glucuronic acid (19.5% of urinary metabolites) conjugates were observed but their structural identification is still underway. Co-chromatography with a synthetic standard led to the detection of terephthalic acid (1,4- benzenedicarboxylic acid) as a minor metabolite. The major urinary conjugates contained selenium. Despite the low levels of selenium in the exhaled air, the reductive metabolism of p-XSC to H2Se cannot be ruled out. Identification of TSC in vivo indicates that a selenol may be a key intermediate responsible for the chemopreventive action of p- XSC.