Real-life rilpivirine resistance and potential emergence of an E138A-positive HIV strain in north-eastern France.

OBJECTIVES: To assess the prevalence of resistance to rilpivirine and mutations at position 138 in reverse transcriptase and to identify associated epidemiological and biological characteristics. METHODS: This retrospective study included 238 patients with available HIV-1 nucleotide sequences analysed at the Laboratory of Virology at the University Hospital of Nancy between January 2011 and June 2013. Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was evaluated according to the ANRS algorithm (version 23) and correlated with clinico-epidemiological and therapeutic data. The virus strains were analysed by evaluating the distance and distribution of the phylogenetic tree (MEGAv5). RESULTS: Among previously treated patients (111/238, 46.6%), 68/111 (61.3%) had received NNRTIs; all were rilpivirine-naive. The prevalence of rilpivirine resistance in the whole cohort was 12.6% (30/238), and was 10.2% (13/127) and 15.3% (17/111) in naive and pre-treated patients, respectively. The E138A mutation was the most frequent mutation associated with resistance to rilpivirine (P < 0.0001). The prevalence of the E138A mutation tended to increase over time, from 3.6% (2/55) during the first half of 2011 to 9.3% (4/43) during the first half of 2013 (P = 0.0614). Seven viral strains from seven naive male patients positive for the E138A mutation appeared in the same cluster. CONCLUSIONS: In our cohort of patients, we observed significantly increased resistance to rilpivirine, mostly because of the E138A mutation, probably due to an E138A strain circulating in newly diagnosed men who have sex with men. Taken together, our results emphasize the need to investigate the prevalence of rilpivirine resistance-associated mutations in the coming years both in France and abroad.

[Update on SENLAT syndrome: scalp eschar and neck lymph adenopathy after a tick bite]. / Les nouveautés sur le syndrome SENLAT : Scalp Eschar and Neck LymphAdenopathy after Tick bite.

SENLAT syndrome, also known as TIBOLA/DEBONEL, is an emerging disease in France. The major symptoms are necrotic eschar on the scalp associated with painful cervical lymphadenopathy. It occurs mainly in women and children during the cold seasons after a bite by a Dermacentor tick, responsible for transmitting Rickettsia slovaca or Rickettsia raoultii. Cutaneous swabs are safe, easy and reliable tools that should be used routinely by physicians to confirm diagnosis. In this particular disease, they should be preferred to serology, which is less sensitive. Doxycycline is the antibiotic of choice for this syndrome.

[Lymphangitis-associated rickettsiosis caused by Rickettsia sibirica mongolitimonae]. / "Lymphangitis-associated rickettsiosis" due à Rickettsia sibirica mongolitimonae.

Rickettsia sibirica mongolitimonae was first isolated 20 years ago in Asia but has now been identified on three continents. Hyalomma spp. and Rhipicephalus pusillus ticks are vectors but only a small number of cases have been reported to date, mainly on the Mediterranean coast. This bacterium induces the lymphangitis-associated rickettsiosis, a still unfamiliar rickettsiosis that is mainly characterized by fever with a rope-like lymphangitis and/or lymphadenopathy and skin eschar occurring after tick bites. These features are especially evocative if they occur in spring. Sequellae are very rare and treatment with doxycycline is recommended.

Effects of different pedalling techniques on muscle fatigue and mechanical efficiency during prolonged cycling.

The present study aimed to test the influence of the pedalling technique on the occurrence of muscular fatigue and on the energetic demand during prolonged constant-load cycling exercise. Subjects performed two prolonged (45 min) cycling sessions at constant intensity (75% of maximal aerobic power). In a random order, participants cycled either with their preferred technique (PT) during one session or were helped by a visual force-feedback to modify their pedalling pattern during the other one (FB). Index of pedalling effectiveness was significantly (P<0.05) improved during FB (41.4 ± 5.5%); compared with PT (36.6 ± 4.1%). Prolonged cycling induced a significant reduction of maximal power output, which was greater after PT (-15 ± 9%) than after FB (-7 ± 12%). During steady-state FB, vastus lateralis muscle activity was significantly (P<0.05) reduced, whereas biceps femoris muscles activities increased compared with PT. Gross efficiency (GE) did not significantly differ between the two sessions, except during the first 15 min of exercise (FB: 19.0 ± 1.9% vs PT: 20.2 ± 1.9%). Although changes in muscular coordination pattern with feedback did not seem to influence GE, it could be mainly responsible for the reduction of muscle fatigue after prolonged cycling.

HDL particles from type 1 diabetic patients are unable to reverse the inhibitory effect of oxidised LDL on endothelium-dependent vasorelaxation.

AIMS/HYPOTHESIS: In healthy individuals, HDL can counteract the inhibition of vasorelaxation induced by oxidised LDL. Several abnormalities such as increased size, glycation and decreased paraoxonase activity have been reported for HDL from type 1 diabetic patients. Thus, we hypothesised that the ability of HDL to protect vessels against impairments of vasorelaxation would be decreased in these patients. METHODS: We compared the ability of HDL from 18 type 1 diabetic patients and 12 control participants to counteract the inhibition of endothelium-dependent relaxation induced by oxidised LDL on rabbit aorta rings. RESULTS: Serum triacylglycerol and total cholesterol, LDL- and HDL-cholesterol were similar in type 1 diabetic and control participants. Fasting glycaemia and the HDL-fructosamine level were higher in diabetic patients than in controls (9.06 +/- 3.55 vs 5.27 +/- 0.23 mmol/l, p < 0.005; and 10.2 +/- 3.2 vs 7.7 +/- 2.5 micromol/g protein, p < 0.05, respectively). HDL composition, size and paraoxonase activity were similar in both groups. HDL from controls reduced the inhibitory effect of oxidised LDL on maximal relaxation (E (max); 79.3 +/- 11.8 vs 66.4 +/- 11.7%, p < 0.05), whereas HDL from type 1 diabetic patients had no effect (E (max) = 70.6 +/- 17.4 vs 63.9 +/- 17.2%, NS). In type 1 diabetic patients, E (max) was not correlated with glycaemia or the HDL-fructosamine level. CONCLUSIONS/INTERPRETATION: HDL particles from type 1 diabetic patients do not protect against inhibition of endothelium-dependent vasorelaxation induced by oxidised LDL, in contrast to HDL particles from healthy individuals. This defect cannot be explained by abnormalities in HDL composition, size or paraoxonase activity, and may contribute to the early development of atherosclerotic lesions in type 1 diabetic patients.

Inability of HDL from type 2 diabetic patients to counteract the inhibitory effect of oxidised LDL on endothelium-dependent vasorelaxation.

AIMS/HYPOTHESIS: In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by oxidised LDL. In type 2 diabetic patients, HDL are glycated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by oxidised LDL. SUBJECTS AND METHODS: Using rabbit aorta rings, we compared the ability of HDL from 16 type 2 diabetic patients and 13 control subjects to suppress the inhibition of vasodilation that is induced by oxidised LDL. RESULTS: Oxidised LDL inhibited endothelium-dependent vasodilation (maximal relaxation [Emax] = 58.2+/-14.6 vs 99.3+/-5.2% for incubation without any lipoprotein, p < 0.0001). HDL from control subjects significantly reduced the inhibitory effect of oxidised LDL on vasodilatation (Emax = 77.6+/-12.9 vs 59.5+/-7.7%, p < 0.001), whereas HDL from type 2 diabetic patients had no effect (Emax = 52.4+/-20.4 vs 57.2+/-18.7%, NS). HDL triglyceride content was significantly higher in type 2 diabetic patients than in control subjects (5.3+/-2.2 vs 3.1+/-1.4%, p < 0.01) and was highly inversely correlated to Emax for oxidised LDL+HDL in type 2 diabetic patients (r = -0.71, p < 0.005). CONCLUSIONS/INTERPRETATION: In type 2 diabetes mellitus, the ability of HDL to counteract the inhibition of endothelium-dependent vasorelaxation induced by oxidised LDL is impaired and is inversely correlated with HDL triglyceride content. These findings suggest that HDL are less atheroprotective in type 2 diabetic patients than in control subjects.

Urinary lithiasis in children. A review of 155 cases.

155 children presenting with lithiasis have been studied. The study confirms other recent analyses: (1) Urinary lithiasis in the child is far more frequent than was previously thought. It is not always easy to diagnose because of the limited opacity of the calculi. (2) Its secondary nature is shown in 25% of the cases. (3) Its cause is still debated in spite of the evident part played by Proteus infection. (4) The prognosis is generally favourable.