Preexposure prophylaxis (PrEP) of HIV infection in France: a nationwide cross-sectional study (PREVIC study).

Although preliminary studies showed that preexposure prophylaxis (PrEP) lowers the HIV transmission in individuals with HIV, confirmative trials are ongoing and PrEP is not routinely recommended. The aim of this study was to assess whether individuals with HIV share antiretroviral (ARV) drugs for PrEP and to describe awareness and discussion on PrEP in this population. A cross-sectional survey was conducted in France in 23 representative departments of infectious diseases and internal medicine. Physicians administered an anonymous standardized questionnaire to all individuals with HIV receiving ARVs and followed between 24 and 31 October 2011. The questionnaire included items regarding PrEP (awareness; discussion with their close circle, physician or patients' association; experience), personal sociodemographic characteristics, risk behaviors and HIV status of the participants. Five hundred and ninety three participants were recruited: male 74.2% (men who have sex with men 52.4%, heterosexuals 21.6%), member of patient's association 9.8%. Half of them (50.6%) lived with a stable partner and 35.2% with an HIV-negative partner. Almost half (41.8%) were aware and 29.5% had had discussion about PrEP. In logistic regression, awareness and discussion on PrEP were more frequent: (1) among males, in patients' association members (p< 0.001 for both) and in nonheterosexuals (p=0.023 and 0.057, respectively); (2) among women, in those not living with a stable partner (p=0.035 and p=0.03, respectively) or living with an HIV-negative partner (p=0.049 and p=0.083, respectively). One percent of the participants declared having shared ARVs with someone and 8.3% reported PrEP in their close circle. Men reporting PrEP in their close circle shared ARVs more frequently than those who did not (10.3% vs. 0.2%, p < 0.001). Today, individuals with HIV do not seem to widely share personal ARVs for PrEP with seronegative people. A significant number of individuals with HIV are aware of and commonly discuss PrEP.

[Impact of a stroke-unit on rtPA use in a community hospital: a 3-year prospective study]. / Impact de la création d'une unité neurovasculaire sur l'utilisation du rtPA dans l'infarctus cérébral en centre hospitalier général : étude prospective sur trois ans.

INTRODUCTION: Although intravenous thrombolysis has been used for ischemic strokes since 2004 in our community hospital located in Pau (southwest of France), a specifically dedicated stroke-unit (SU) was created only recently in June 2010. We decided to collect prospective data to compare the use and efficacy of intravenous thrombolysis before and after the opening of this dedicated stroke unit. METHODS: Stroke patients with internal carotid artery territory involvement treated with intravenous thrombolysis were compared between two similar periods. The first period (called pre-SU period) stretched from January 2009 to June 2010. The second period (called SU period) stretched from June 2010 to October 2011. We collected prospectively all morbidity/mortality data as well as a modified Rankin score (mRS) three months later. RESULTS: During the pre-SU period, 21 strokes were treated with a mean NIHSS score of 15. Three months later, the mRS score was less than or equal to 2 for five patients, and greater than or equal to 3 for 12. A total of four patients died. In addition, two-thirds of patients (14 of 21) had suffered from notable complications at the initial phase of their stroke. During the SU period, 27 strokes were treated with a mean NIHSS score of 14. At 3 months, the mRS score less than or equal to 2 for 15 patients, and greater than or equal to 3 for nine other patients. A total of three patients died. During this second period, less than 50% of the patients (13 of 27) were not affected by any complication at the initial phase. Statistically, the results also show a better short-term (24 hours with NIHSS) and medium-term (3 months with NIHSS and mRS) clinical outcome for patients treated during the SU period. CONCLUSIONS: Instituting a dedicated stroke-unit helped improve outcome after ischemic strokes treated by intravenous thrombolysis. It also increased the number of patients and reduced the complications at the initial phase.

Chronic edema of the lower extremities: international consensus recommendations for compression therapy clinical research trials.

Chronic edema is a multifactorial condition affecting patients with various diseases. Although the pathophysiology of edema varies, compression therapy is a basic tenant of treatment, vital to reducing swelling. Clinical trials are disparate or lacking regarding specific protocols and application recommendations for compression materials and methodology to enable optimal efficacy. Compression therapy is a basic treatment modality for chronic leg edema; however, the evidence base for the optimal application, duration and intensity of compression therapy is lacking. The aim of this document was to present the proceedings of a day-long international expert consensus group meeting that examined the current state of the science for the use of compression therapy in chronic edema. An expert consensus group met in Brighton, UK, in March 2010 to examine the current state of the science for compression therapy in chronic edema of the lower extremities. Panel discussions and open space discussions examined the current literature, clinical practice patterns, common materials and emerging technologies for the management of chronic edema. This document outlines a proposed clinical research agenda focusing on compression therapy in chronic edema. Future trials comparing different compression devices, materials, pressures and parameters for application are needed to enhance the evidence base for optimal chronic oedema management. Important outcomes measures and methods of pressure and oedema quantification are outlined. Future trials are encouraged to optimize compression therapy in chronic edema of the lower extremities.

The venous return simulator: comparison of simulated with measured ambulatory venous pressure in normal subjects and in venous valve incompetence.

BACKGROUND: To compare results of numerical simulation of lower limb venous return with those of in vivo measurements, in normal subjects, and those with venous incompetence. PATIENTS AND METHODS: the venous return simulator (VRS) is a mathematical model which takes into account architecture, dimensions, and compliance of the venous network, blood viscosity, valve function, and external pressures (muscular contraction, compression stockings). Using the laws of hydrodynamics, it provides calibres, pressures and flows throughout the network. Ambulatory venous pressure (AVP) computed for some theoretical examples of superficial and /or deep venous incompetence has been compared to in vivo values reported in literature. RESULTS: In a normal subject, computed AVP was 33 mmHg during walking and 30 mmHg with tiptoe exercise; the range of conventionally measured AVP is 20.6 - 27.9 mmHg during walking, and 29 - 32.5 mmHg during tiptoe exercise; In the case of great saphenous vein (GSV) incompetence, computed AVP was 34 or 57 mmHg, according to whether the distal GSV was competent or not. The range of AVP measured in superficial venous insufficiency is 27.6 - 61 mmHg, all but one of the published values lie between the low computed value corresponding to a short reflux and the high computed value due to a long distance reflux. AVP computed in two cases of deep venous incompetence was 44 and 71 mmHg, according to the extent of devalvulation, as compared with the 60 mmHg reported in one clinical study In patients with extensive combined incompetence, computed AVP was 75 mmHg, whilst the range of conventionally measured values was between 62 and 84 mmHg. CONCLUSIONS: the good agreement between computed and measured AVP in different cases of valve incompetence indicates that the VRS is quite a realistic model, with the potential to simulate the results of surgery or compression therapy.

[Digital simulation of venous and lymphatic edema and the effects of compression]. / Simulation numérique de l'œdème veinolymphatique et des effets de la compression.

OBJECTIVE: Compression therapy for venous and lymphatic edema of the lower limbs raises a major challenge concerning the optimal pressure ensuring both efficacy and patient compliance. We present a mathematical model of tissue fluid transfers which is aimed at determining the lowest pressure required to prevent edema. METHODS: The model is based on a set of equations, derived from published experimental data, which describe the fluid and solute transfers between blood, interstitium and lymphatics, and the mechanical properties of interstitial compartment. It enables us to compute the changes in tissue volume, at the ankle level, resulting from increases of capillary pressure in case of venous insufficiency, and from an impairment of lymph drainage; as well as the effect of various external pressures upon this volume. RESULTS: An increase of capillary pressure to 40 and 50 mmHg results in an ankle edema which is completely prevented by an external pressure of 10 mmHg. This result is in keeping with the observation by Partsch that vesperal leg swelling is reduced by low compression stockings. The dose effect reported in this study is also found by simulation. The complete blockade of lymphatic return leads to an edema, the prevention of which requires a counterpressure of at least 30 mmHg. When an increase of venous pressure to 60 mmHg, and a reduction by 2/3 of lymphatic drainage are combined, simulating chronic venous insufficiency, the resulting edema is prevented by a 25 mmHg counterpressure. CONCLUSION: These first results of simulation are in reasonable agreement with clinical experience. As nearly every combination of disturbances may be simulated, the computer model could help to understand and treat edemas, as long as their cause can be identified.

Area-pressure relationship of lower limb main veins in man.

BACKGROUND: The mechanical properties of human veins remain incompletely known. However they play an important part in number of physiological and pathological situations, as hemodynamic adjustment to orthostasis, deep venous thrombosis (DVP) and chronic venous insufficiency (CVI). The aim of the study was to describe the pressure/volume (area) relationship of some important conduit veins of the human's lower limb. PROBANDS AND METHODS: We investigated the area/pressure relationship of thefemoral vein (FV) at mid thigh, the great saphenous vein (GSV) at lower third of the leg, and a deep leg vein (DLV), either the peroneal or posterior tibial vein, in fifteen healthy young men. The cross section areas were measured with B-mode ultrasound while various positive and negative venous pressures were generated by body's tilting. RESULTS: Over the range of pressures investigated, the area/pressure relationship was roughly linear, the classical sigmoid relation did not emerge from our data. The relative compliance of FV, GSV and DLV was 0.0312, 0.0118, and 0.0147 mmHg(-1), respectively. CONCLUSIONS: The relative compliance of FV is more than two times higher than the relative compliance of both the DLV and the GSV.

Modeling of the deformation of flexible tubes using a single law: application to veins of the lower limb in man.

The topic of this study mainly concerns a representative model of the behavior of flexible ducts such as elastic tubes or veins. This model is based on a phenomenological approach of the inflation and collapse of the tube. It leads to a single "universal" analytical expression of the tube law, valid fir a wide range of' positive and negative transmural pressures, which presents a significant improvement compared to previous theoretical studies defined with different expressions on restricted ranges of pressure. Moreover, the theoretical approaches most often require simplif'ing hypotheses--no longitudinal tension, no surrounding tissues--which are quite unrealistic both in the physiological case and in the experimental setup. These theoretical models can therefore be expected only roughly to describe the actual behavior of such vessels. The representative model, on the contrary, allows one to account for the deformation--inflating as well as collapse--of elastic tubes or veins with better accuracy. The tube law is a function of six parameters chosen in order to fit the experimental data. A comparison between results obtained in our laboratory using silicone tubes and representative models is presented. The model is then applied to physiological data obtained in vivo on human leg veins.

[Coronary angiography by left radial approach. A bi-center prospective pilot study]. / Coronarographie par voie radiale gauche. Une étude pilote prospective bicentrique.

The aim of this study was to assess prospectively the feasibility, safety and quality of coronary angiography performed by a left radial arterial approach. The investigation was performed under local anesthesia with a Lidocaine gel using Judkins 5f catheter. A bolus of heparin was injected intravenously at the start of the procedure (no heparin in phase 0.2 to 3.000 IU during phase 1 and 5.000 IU in phase 2). Between March 1994 and January 1996, after exclusion of 108 patients (15.1%) mainly because of an abnormal Allen test, coronary angiography was carried out in 540 patients aged 58.4 +/- 11.7 years, 85% of whom were men. The failure rate was 8%. The quality of opacification of the left coronary artery (scale 1 to 3) was 2.91 +/- 0.27 and of the right coronary artery was 2.96 +/- 0.18. There were no complications during the procedure. Analysis of the learning curve showed a failure rate decreasing to less than 5% after 60 procedures/operator. In the last 100 procedures, the failure rate fell to 3%, the canulation time was 2.2 +/- 2.5 min, the duration of fluoroscopy was 6.5 +/- 3.9 min and the duration of the procedure was 17.5 +/- 4.7 min (14.7 +/- 3.8 min, p < 0.01, by the femoral approach). Clinical and Doppler ultrasonographic follow-up revealed one in-hospital complication (a spontaneously regressive compressive haematoma). No clinical complications were observed at 3 months. Doppler ultrasonography showed the radial artery occlusion rate to be 71% in phase 0.32% in phase 1 and 3.2% in phase 2 (p < 0.0001). These results show that the left radial arterial approach for coronary angiography is safe and effective but requires a period of training. A 5.000 IU dose of heparin limits the risk of radial artery occlusion to 3%. The absence of complications in this large series which included the training period and the patient comfort suggest that this technique may be an excellent alternative to the femoral approach and especially the brachial approach when the Allen test is normal.

Left radial approach for coronary angiography: results of a prospective study.

Although radial approach has been shown to be feasible for coronary angiography, angioplasty, and even stent placement, there have been no prospective evaluations of ease and safety of left radial approach for coronary angiogram. We examined procedural duration and success as well as complications in 415 consecutive patients. Radial artery occlusion was assessed immediately post-procedure and at 2 month follow-up using echo-Doppler measurements. Procedure failure rate was 9%, mean time for sheath insertion was 4.7 +/- 4.7 min, and mean procedure duration was 19.1 +/- 8.2 min. No major complications occurred. Asymptomatic radial artery occlusion was noted in 71% of the first 49 patients, decreased to 24% in the next 119 receiving 2,000-3,000 units of heparin, and to 4.3% in the last 210 receiving 5000 (p < 0.05). Comparison with the femoral approach in the same laboratory suggested that the radial approach took longer, but provided similarly high-quality results without great difficulty in coronary cannulation. Hence, the left radial approach for coronary angiography (with heparin administration) allows immediate ambulation and may be especially useful for outpatients and when the femoral approach is not possible.

Inhibition of substance P-induced microvascular leakage by inhaled methoxamine in rat airways.

1. The effect of the inhaled alpha-adrenoceptor agonist, methoxamine (MTX), was studied on experimental airway oedema induced by injection of substance P (SP) in the rat. Sprague-Dawley rats (300-350 g) were anaesthetized with sodium thiopentone, tracheotomized and artificially ventilated. 2. MTX or its vehicle was administered by inhalation. Airway resistance and blood pressure were monitored continuously. Evans Blue dye (EB, 20 mg kg-1) was injected through a jugular catheter 1 min before SP (14.8 nmol kg-1). Airways were dissected out, weighed and placed in formamide for EB extraction and determination by spectrophotometry. 3. EB extravasation induced by SP was significantly reduced in distal intraparenchymal bronchi by inhaled MTX at doses of 50 micrograms kg-1 (58 +/- 9 vs 96 +/- 9 ng EB mg-1 tissue after vehicle, P < 0.001) and 100 micrograms kg-1 (69 +/- 11 vs 137 +/- 26 ng EB mg-1 tissue after vehicle, P < 0.01). Inhaled MTX by itself (100 micrograms kg-1) increased blood pressure: 172 +/- 6 vs 132 +/- 10 mmHg baseline (P < 0.02), but neither induced extravasation nor increased airway resistance. 4. In another set of experiments without SP, MTX was administered intravenously 1 min after EB. At 100 micrograms kg-1, i.v. MTX increased blood pressure to a similar extent as inhaled MTX (180 vs 147 mmHg baseline, P < 0.01), increased airway resistance and caused leakage of plasma proteins in distal intraparenchymal bronchi (79 +/- 7 vs 47 +/- 1 ng EB mg-1 tissue, P < 0.02). 5 Similarly, after sequential i.v. injections of doubling doses of MTX (50-800 microg kg-1), a marked EB extravasation was found in the airways. This was abrogated by pretreatment with prazosin (100 microg kg-1)but not with propranolol (2 mg kg-1).6 These results suggest that microvascular leakage and airway oedema induced by i.v. MTX may be linked to an increase in pressure in the pulmonary circulation, resulting from vasoconstriction of the pulmonary vasculature and acute cardiac dysfunction due to systemic hypertension.7 Our results with inhaled MTX show that direct deposition of MTX at the bronchial vasculature induces a reduction in SP-induced microvascular leakage in rat airways and that inhaled MTX does not share the untoward effect of i.v. MTX inducing airway oedema.

[Drug treatments of chronic venous insufficiency: pharmaco-clinical evaluation]. / Traitements médicamenteux de l'insuffisance veineuse chronique: évaluation pharmaco-clinique.

There are many methods for the assessment of venotropic drugs. Clinical trials based on randomized comparison with placebo are essential. The different methodes used for the evaluation of the functional effects are chosen on the basis of their performance and pertinence for the study objectives. These include three aims which we feel are essential: increased venous tone, decreased capillary permeability and reversal of microcirculatory impairment. Calf plethysmography is highly adapted for the evaluation of venous tone. The mercury gauge works well, but the future will tell if air plethysmography is more adapted here. For capillary permeability, fluoresceine angioscopy is without a doubt the most sensitive and specific method. Unfortunately many laboratories do not have this equipment. If it is not available, the suction cup test or the Landis isotope test may be used although these tests have their limits. For impaired microcirculation, the most interesting test is the laser-Doppler; the results are well correlated with the severity of the chronic venous insufficiency and return to normal after treatment. TcPO2 and capillaroscopic measurements are less sensitive, but are useful in severe cases. Other investigations may be important in individual cases depending on the impact of the medication under study. Drug-induced serum fibrinolytic activity can be measured by the euglobulin lysis time. A haemorheologic effect can be assessed with routine assays (Haematocrit, serum fibrinogen) and measured with tests of red cell deformability and erythrocyte agreggation capacity.

Presence of anti-insulin reaginic auto-antibodies of the IgG4 class in insulin-dependent (type I) diabetic patients before insulin therapy.

The autoimmune aetiology of type I diabetes has been well documented. We studied whether anti-insulin anaphylactic antibodies were present on the membrane of basophils from type I diabetics by the toluidine blue method (detecting basophil activation after stimulation by insulin). We observed that basophils of recently diagnosed insulin-dependent diabetic patients (n = 13) were statistically more frequently activated by insulin than basophils from noninsulin-dependent diabetics (p < 0.002, n = 8) or non-diabetic subjects (p < 0.05, n = 9). Basophils from normal donors were passively sensitized with plasma from insulin-dependent diabetics and could then be activated by insulin. This sensitization still occurred when using plasma previously heated to 56 degrees C, indicating that the sensitizing antibodies were not of the IgE class. When basophils from type I diabetics were preincubated with anti-IgG subclasses, only anti-IgG4 monoclonal antibodies inhibited the insulin-induced basophil activation. By contrast, preincubation with blocking concentrations of anti-IgG1-3 antibodies or desensitization of the IgE pathway did not modify basophil activation. These experiments strongly suggest the presence of anti-insulin antibodies of the IgG4 subclass in insulin-dependent diabetics before any insulin administration and provide a simple tool to complement the usual method of detecting auto-antibodies in diabetes.

Bronchial provocation tests in small animals: a quantified and automated procedure.

Bronchial provocation tests using aerosols in laboratory animals are difficult to standardize and quantify, because the amount of drug actually reaching the airways is unknown. To improve the quantification of aerosolized inhaled stimuli, we designed an apparatus that allows, in anesthetized intubated ventilated animals, control of temperature and hygrometry of inspired air, computerized measurement of pulmonary resistance, and fully automated delivery of a known amount of aerosolized drug directly into the trachea. Calibration of the aerosol delivery involved direct measurement of liquid delivered at the tip of the tracheal cannula. Despite all our efforts at standardization and full automation of all steps, reproducibility of aerosol delivery was poor, with stroke-by-stroke differences of 26 or 42%, according to whether an air-jet or an ultrasonic nebulizer was used. Histamine dose-response curves performed in 15 guinea pigs with this device confirmed marked differences among animals and also disclosed large intraindividual changes in bronchial responsiveness.

Purification and Partial Characterization of Two Soluble NAD(P)H Dehydrogenases from Arum maculatum Mitochondria.

Two enzyme systems carrying out the oxidation of NAD(P)H in the presence of various electron acceptors have been isolated and partially characterized from the supernatant of frozen-thawed mitochondria from Arum maculatum spadices. The two systems contain flavoproteins and differ by their ability to oxidize NADH or NADPH, optimum pH and pI values, sensitivity to Ca(2+) and EGTA, denaturation by 4 molar urea, molecular mass, and number of subunits. These properties, together with methodological considerations, are compatible with the location of these enzyme activities on the outer surface of the inner mitochondrial membrane, and support the hypothesis of the existence of two separate dehydrogenases responsible for the mitochondrial oxidation of cytosolic NADH and NADPH.

[Vitamin D and the immune system]. / Vitamín D a imunitní systém.

The authors draw attention to the contemporary broad concept of the vitamin D endocrine system comprising in addition to the gut, bones and kidneys, some other tissues and cells incl. cells of the immune system. They give an account of findings on receptors for the active hormonal metabolite of vitamin D, 1,25-dihydroxycalciferol [1,25(OH)2D], in the cells of the immune system and summarized contemporary ideas on the mechanism of action of 1,25(OH)2D in these cells. They discuss the role of 1,25(OH)2D in non-specific and specific immune processes, and based on data from the literature and results of their own experimental work, they evaluate the possibility to apply the immunoregulating action of vitamin D in clinical practice.

Breathing dry air causes acute epithelial damage and inflammation of the guinea pig trachea.

Drying and cooling of the airways mucosa caused by respiratory water loss may be responsible for exercise- and hyperventilation-induced asthma. Therefore we designed this study to investigate whether breathing dry air is capable of causing structural changes of the airways mucosa. Anesthetized guinea pigs breathed spontaneously through a tracheostomy either dry (n = 15) or water-saturated (n = 12) air at approximately 38 degrees C for 30 or 60 min, during which time total pulmonary resistance (TPR) was measured. Immediately afterward, the animals were killed and the lungs and airways were prepared for histological examination (light microscopy, transmission electron microscopy, and scanning electron microscopy). With dry as well as humid air, there was no change in TPR or in the structure of the main bronchi and lung parenchyma. With humid air the tracheal mucosa was normal in six guinea pigs and exhibited minor changes of the ciliae in eight and localized epithelial damage on light microscopy in the remaining animal. With dry air we found widespread loss of the ciliae on scanning electron microscopy in 10 of 12 animals, associated with detachment or sloughing of the epithelium, subepithelial vascular congestion, edema, and cellular infiltration on light microscopy. Our data demonstrate that a short exposure of the trachea to dry air causes marked epithelial lesions and local inflammation.

The arteriovenous fistula in segmental pancreatic transplantation in dogs--a hemodynamic study.

Arterial and/or venous thrombosis is a frequent complication in experimental or human pancreatic transplantation. A canine experiment was used to study the hemodynamic effects of spleno-splenic arteriovenous fistula during segmental pancreatic transplantation. An increase in blood flow, without "steal" syndrome in the pancreatic blood supply or pressure increase, was found. Thus this technique can help prevent vascular thrombosis in pancreatic transplant in dogs.