Access to kidney transplantation in France of non-French patients and French patients living in overseas territories

BACKGROUND: In France, foreign patients, whether resident or not in France, can register on the national waiting list under certain conditions. We compared waiting time to kidney transplantation, the level of HLA matching and graft cold ischemia time between foreign patients and French patients living in mainland France or in French overseas territories (FOT). METHODS: We performed a retrospective cohort survey using the nationwide registry. Between 1996 and 2003, 18,595 patients were registered on the French waiting list. Of these, 9.9% were of non-French nationality (0.7% Greek, 1.4% Italian, 1.5% other European, 3.7% North African, 1.8% sub-Saharan African and 0.9% other), and 3.8% were French nationals living in FOT. RESULTS: Median waiting time differed significantly between groups, from 13.8 months for mainland French patients to 39.5 months for sub-Saharan African patients. After adjustment for other factors significantly linked to waiting time, French residents of FOT (RR=0.83; P<0.001) and patients from sub-Saharan Africa (RR=0.75; P<0.0001) were found to wait significantly longer than other patients. HLA matching level, particularly HLA-A and HLA-B, was worse for African patients. After adjustment for the transplant team, cold ischemia time was found to be longer for Greeks (30.4 hr, P<0.0001) and French patients living in FOT (33.3 hr, P<0.0001) than for mainland French patients (21.2 hr). CONCLUSIONS.: Programs promoting organ donation aimed at minorities of African origin should improve their access to transplantation in France. We also need to strengthen international cooperation programs in certain countries to assist access to transplantation and to increase graft quality.     

A novel type of familial proximal axonal dystrophy: three cases and a review of the axonal dystrophies

Three related infants of Roma ancestry, two of them siblings, showed hypotonia, predominantly axial, from birth, difficulty swallowing, myoclonic seizures, and respiratory difficulty. Dysmorphic features, principally micrognathia were present. EEGs showed focal epileptiform abnormalities. All three died in their 5th month from respiratory insufficiency complicated by pneumonia. Autopsy showed small brains without malformation. Microscopy revealed numerous axonal spheroids involving particularly the brain stem and spinal cord, with especial prominence in the middle cerebellar peduncle, the anterior part of the thalamic reticular nuclei, and the anterior horns and columns of the spinal cord. Spheroids that appeared to be on axons of lower motor neurons were especially large. No spheroids were seen in peripheral nerves; electron microscopy did not show spheroids in skin. By electron microscopy spheroids contained neurofilaments, sparse mitochondria, and electron dense granules. The material did not allow identification of microtubules. Closely packed vesicles excluded neurofilamanets from the center of many spheroids, especially in the middle cerebellar peduncle. Sprouting of axons from the surface of many spheroids was seen. This disease is distinct from the well described type of infantile neuroaxonal dystrophy (Seitelberger's disease) in view of the distribution of spheroids, presence of spheroids on proximal rather than distal parts of axons, sparing of the peripheral nerves, lack of staining for synuclein, presence of sprouting, and lack of membranous profiles in the spheroids. A review of reported types of axonal dystrophy has not shown identical cases.     

Alternative route for erythropoietin ocular administration

Purpose

This study aimed to find an alternative route for erythropoietin (EPO) ocular administration because of its neuroprotective and neuroregenerative known properties. Ocular penetration of EPO after subconjunctival injection was assessed, and potential side-effects on the haematocrit for a 28-day period were also evaluated.

Methods

Wistar Hannover female albino rats (n?=?42) divided into seven groups of six were used. One group (n?=?6) served as control. Six groups (n?=?36) received 1,000 UI of EPO through the subconjunctival route in one of the eyes. According to the group, animals were humanely killed at 12 h (n?=?6), 24 h (n?=?6), 36 h (n?=?6), 48 h (n?=?6), and 60 h (n?=?6), after EPO administration, in a total of 30 animals. Enucleation of both eyes was performed, and EPO protein distribution in the rat’s retina was analyzed by immunohistochemistry. Another group of animals (n?=?6) was used to collect blood samples and perform haematocrit analysis at 0, 7, 14, 21, and 28 days after unilateral EPO subconjunctival administration.

Results

The evaluation of EPO expression in the animals' retinas after subconjunctival administration yielded a strong immunostaining signal. Among the retina’s layers, EPO expression was more evident in the RGC layer 24 h after the administration, and was still present on that layer till the end of the study (60 h). When administered subconjunctivally EPO reached several neuronal cells, in all retinal layers. The subconjunctival EPO administration did not cause significant changes in the haematocrit values over a 28-day period.

Conclusion

In this study, it was demonstrated that EPO reached the retinal ganglion cell layers when administered subconjunctivally. EPO reached the retina 24 h after the subconjunctival administration, and was still present 60 h after the administration. Furthermore, it was also proved that EPO subconjunctival administration did not cause any haematopoietic significant side-effects. The subconjunctival route was shown to be a promising alternative for EPO ocular delivery.     

ORIGINAL ARTICLE: Female Genital Tract Secretions Inhibit Herpes Simplex Virus Infection: Correlation with Soluble Mucosal Immune Mediators and Impact of Hormonal Contraception

Citation Shust GF, Cho S, Kim M, Madan RP, Guzman EM, Pollack M, Epstein J, Cohen HW, Keller MJ, Herold BC. Female genital tract secretions inhibit herpes simplex virus infection: correlation with soluble mucosal immune mediators and impact of hormonal contraception. Am J Reprod Immunol 2010; 63: 110–119 Problem Female genital tract secretions inhibit herpes simplex virus (HSV) infection, however, the intra‐ and inter‐subject variability, contribution of specific mediators, and impact of reproductive hormones have not been defined. Method of study Cervicovaginal lavage (CVL) (n = 89) obtained from nine cyclers and seven women on hormonal contraception (HC), who completed between three and eight weekly visits, were examined for anti‐herpes simplex virus activity and concentrations of mediators. Results The CVL inhibited HSV infection by a mean value of approximately 57% during the follicular or luteal phase, but only by 36% in hormonal contraceptive users. Human neutrophil peptides 1–3 (HNP1‐3) (P = 0.03), IL‐8 (P = 0.003), lactoferrin (P = 0.005), lysozyme (P = 0.003), IgA (P = 0.002), and IgG (P = 0.02) correlated with antiviral activity. Intra‐subject and inter‐subject variability was observed, suggesting that factors other than hormones contribute to innate defense. Conclusion Endogenous antimicrobial activity may provide a biomarker of healthy mucosal immunity and may be reduced in the setting of HC. However, larger prospective studies are needed.     

Intranasal flunisolide treatment in children with adenoidal hypertrophy

Adenoidal hypertrophy (AH) represents one of the most frequent indications for surgery in children and it has been proposed that treatment with intranasal corticosteroids can decrease the size of AH. Therefore, the aim of the study is to evaluate the effect of the use of intranasal flunisolide among children affected by AH. 178 children with AH were evaluated in this randomised and controlled study. Inclusion criteria for the study required that each patient had to have a III or IV degree of AH on the initial endoscopic examination. Children were treated with intranasal flunisolide or isotonic saline solution for 8 weeks. After treatment, endoscopy was performed to re-evaluate AH degree. Flunisolide treatment was associated with significant (p less than 0.04) reduction of AH degree. There was moreover a consistent reduction of children (46 out of 58) proposed to adenoidectomy. No clinically important adverse events were reported. In conclusion, this preliminary study demonstrates that an 8-week treatment with intranasal flunisolide is significantly associated with reduction of AH, thus preventing the recurrence to adenoidectomy, and is safe.     

In Vitro Synthesis of Triglycerides and Cholesterol in Human Gallbladder Mucosa

Triglyceride and sterol synthesis was investigated in vitro in the gallbladder mucosa from control subjects and patients with acalculous cholesterolosis. The incorporation rate of ¹⁴C-acetate was 1.6 ± 0.2 nmol/g/h into cholesterol (sum of squalene, methyl sterols, and cholesterol) and 5.7 ± 0.8 nmol/g/h into triglycerides. The rates were significantly correlated with each other (r = 0.667). The conversion of ³H-mevalonate into cholesterol (49 ± 10 nmol/g/h) and triglycerides (4.7 ± 1.2 nmol/g/h) indicated a high activity in the postmevalonate cholesterol synthesis and an active shunt pathway of mevalonate metabolism. The synthesis rates of cholesterol, triglycerides, and sterol esters were closely interrelated, were unaltered in cholesterolosis, and were not correlated with the serum, biliary, and mucosal lipid concentrations. Thus, despite marked lipid accumulation the lipid synthesis proceeds effectively in the gallbladder mucosa with cholesterolosis.     

In-traffic air pollution exposure and CC16, blood coagulation, and inflammation markers in healthy adults

Background: Exposure to traffic-related air pollution is a risk factor for cardiovascular events, probably involving mechanisms of inflammation and coagulation. Little is known about effects of the short exposures encountered while participating in traffic.Objectives: The objective of the study was to examine effects of exposure of commuters to air pollution on cardiovascular biomarkers.Methods: Thirty-four healthy adult volunteers commuted for 2 hr by bus, car, or bicycle during the morning rush hour. During the commute, exposure to particle number, particulate matter (PM) ≤ 2.5 µm in aerodynamic diameter (PM_2.5), PM ≤ 10 µm in diameter (PM₁₀), and soot was measured. We estimated inhaled doses based on heart rate monitoring. Shortly before exposure and 6 hr after exposure, blood samples were taken and analyzed for CC16 (Clara cell protein 16), blood cell count, coagulation markers, and inflammation markers. Between June 2007 and June 2008, 352 pre- and postexposure blood samples were collected on 47 test days. We used mixed models to analyze the associations between exposure and changes in health parameters.Results: We observed no consistent associations between the air pollution exposures and doses and the various biomarkers that we investigated.Conclusions: Air pollution exposure during commuting was not consistently associated with acute changes in inflammation markers, blood cell counts, or blood coagulation markers.