[Women, forgotten by clinical research]. / Les femmes, oubliées de la recherche clinique.

For years, women were underrepresented in clinical studies. But the effect of many drugs differ among women and men, due to pharmacokinetic and pharmacodynamic differences. As a result, there is a lack of information on therapeutic or adverse effets of drugs and, more generally, a lack of knowledge on diseases, leading more frequently to sub-optimal medical care in women. This underrepresentation is due to various factors, including the social role of women or ethical issues about pregnancy. The need for adequate representation of women in clinical studies is a social as well as medical concern, that implies political and legal changes.

OS014. Which first-line drug to control severe hypertension in pregnancy? A pilot study.

INTRODUCTION: Severe hypertension is a common complication in pregnancy-associated hypertensive disorders and there is no clear consensus on which first-line antihypertensive drug to use in this setting. OBJECTIVES: To determine the efficacy and safety of four antihypertensive drugs (two intravenous and two oral) in pregnant women with severe hypertension. METHODS: Pilot prospective randomised study. INCLUSION CRITERIA: pregnant women with a gestational age >24weeks and admitted in the Obstetrics Department with severe hypertension defined as systolic blood pressure (SBP) ⩾165mmHg and/or diastolic blood pressure (DBP) ⩾105mmHg. The women were randomised in 4 groups to receive:-20mg intravenous labetalol;-5mg intravenous hydralazine;-10mg oral nifedipine tablets ;-10mg sublingual nifedipine. Treatment was repeated every 20mn until target SBP and DBP were reached (⩽150/⩽95mmHg). The primary endpoint was the time needed to achieve effective blood pressure control. Treatment failure was defined as the unability to reach the target BP within one hour. RESULTS: After giving informed consent, 41 pregnant women admitted with severe hypertension were randomised. Mean age was 35 years (SD 3.5), 65% were nulliparous and mean SBP and DBP at admission were 176 (SD 16) and 105 (SD 12)mmHg, respectively. Success to achieve target BP was reached in all patients within the oral 10mg nifedipine group (11 patients), in all but one patients with the 10mg sublingual group (12 patients), and only in 5 out of 9 patients and 6 out of 9 patients within the labetalol and hydralazine groups. They were only one hypotension (defined as SBP <120mmHg) in the two groups with intravenous drugs and 3 and 5 in the oral and sublingual nifedipine groups. CONCLUSION: These results indicate that oral nifedipine seems more effective than intravenous labetalol or hydralazine to reach BP control in pregnant patients with severe hypertension. A large scale randomized trial comparing oral nifedipine versus these commonly used intravenous antihypertensive drugs should be implemented in order to determine whether oral nifedipine is a more effective treatment in this population.

[Treating hypertension: a challenge for the general practitioner]. / Le traitement de l'hypertension artérielle: un défi pour le praticien.

Hypertension is associated with a greater risk of developing a stroke or a coronary heart disease, but remains, for the meanwhile, undertreated in a vast majority of patients. Non pharmacological interventions can reduce blood pressure and should be recommended to every patient suffering from hypertension. Nevertheless, a drug therapy must often be introduced. The threshold at which a treatment should be started depends mostly on the cardiovascular risk of each patient and the benefit of antihypertensive drug therapy depends primarily on the reduction of the blood pressure itself.

Parametric and quantitative analysis of MR renographic curves for assessing the functional behaviour of the kidney.

The aim of this study was to refine the description of the renal function based on MR images and through transit-time curve analysis on a normal population and on a population with renal failure, using the quantitative model of the up-slope. Thirty patients referred for a kidney MR exam were divided in a first population with well-functioning kidneys and in a second population with renal failure from ischaemic kidney disease. The perfusion sequence consisted of an intravenous injection of Gd-DTPA and of a fast GRE sequence T1-TFE with 90 degrees magnetisation preparation (Intera 1.5 T MR System, Philips Medical System). To convert the signal intensity into 1/T1, which is proportional to the contrast media concentration, a flow-corrected calibration procedure was used. Following segmentation of regions of interest in the cortex and medulla of the kidney and in the abdominal aorta, outflow curves were obtained and filtered to remove the high frequency fluctuations. The model of the up-slope method was then applied. Significant reduction of the cortical perfusion (Qc = 0.057+/-0.030 ml/(s 100 g) to Qc = 0.030 +/- 0.017 ml/(s 100 g), P < 0.013) of the medullary perfusion (Qm = 0.023 +/- 0.018 ml/(s 100 g) to Qm = 0.011 +/- 0.006 ml/(s 100 g), P < 0.046) and of the accumulation of contrast media in the medulla (Qa = 0.005 +/- 0.003 ml/(s 100 g) to Qa = 0.0009 +/- 0.0008 ml/(s 100 g), P < 0.001) were found in presence of renal failure. High correlations were found between the creatinine level and the accumulation Qa in the medulla (r2 = 0.72, P < 0.05), and between the perfusion ratio Qc/Qm and the accumulation Qa in the medulla (r2 = 0.81, P < 0.05). No significant difference was found in times to peak between both populations despite a trend showing Ta the time to the end of the increasing contrast accumulation period in the medulla, arriving later for renal failure. Advances in MR signal calibration with the building of quantitative model such as the up-slope allow to assess kinetic and haemodynamic and functional parameters of the diseased kidney.

Heterogeneous vascular response to vasopressin: radial artery versus forearm blood flow.

BACKGROUND: Arginine vasopressin (AVP) administered intra-arterially to normal volunteers exerts a biphasic effect on forearm blood flow when the effect is extrapolated from plethysmographic measurements. OBJECTIVE: To assess whether the high-dose AVP-induced increase in forearm blood flow could be confirmed when calculating blood flow from continuous radial artery diameter and flow velocity recordings obtained by using a high-resolution echotracking device combined with a Doppler system. METHODS: Increasing doses (0.04-0.8 ng/kg per min) of AVP were infused into a brachial artery of seven normal male volunteers (aged 21-33 years). Forearm blood flow derived from venous occlusion plethysmography was assessed simultaneously with proximal radial artery blood flow calculated from luminal area and flow velocity measurements. RESULTS: Confirming previous reports, plethysmography showed an increase in global forearm blood flow by > 100% with AVP concentrations > or = 0.2 ng/kg per min. In contrast, direct measurements of lumen diameter and blood flow velocity in the radial artery revealed a marked dose-dependent vasoconstriction with a > 30% decline in blood flow at the highest AVP concentration. CONCLUSIONS: The discrepancy between the two measurements suggests that AVP has a dual effect on forearm haemodynamics. At high AVP concentration, the muscle blood flow increase predominates over the vasoconstriction in the skin circulation. Furthermore, this study strongly suggests a heterogeneity of the vascular response to vasomediators by showing that opposing responses exist not only between resistive and conduit vessels but also between conduit arteries of a common vascular bed.

[Diagnosis and treatment of arterial hypertension in the elderly]. / Le diagnostic et le traitement de l'hypertension artérielle chez la personne âgée.

The incidence of hypertension increases with age and becomes very high in the seventh decade. The increase of the blood pressure may be systolic, diastolic or both. Various controlled studies have shown that the treatment of hypertension in the elderly reduces the incidence of myocardial infarction and of stroke. It appears today that also patients with isolated systolic hypertension benefit from antihypertensive treatment. All classes of antihypertensive agents, including beta-blocking drugs, may be used in the elderly.

Circulating soluble CR1 (CD35). Serum levels in diseases and evidence for its release by human leukocytes.

C receptor type 1 (CR1, CD35) is present in a soluble form in plasma (sCR1). Soluble CR1 was measured with a specific ELISA assay in normal individuals and in patients with different diseases. The mean serum concentration of sCR1 in 31 normal donors was 31.4 +/- 7.8 ng/ml, and was identical in plasma. An increase in sCR1 was observed in 36 patients with end-stage renal failure on dialysis (54.8 +/- 11.7 ng/ml, p < 0.0001), and in 22 patients with liver cirrhosis (158.3 +/- 49.9 ng/ml, p < 0.0001). The mean sCR1 levels dropped from 181 +/- 62.7 to 52.1 +/- 24.0 ng/ml (p < 0.001) in nine patients who underwent liver transplantation, and was 33.5 +/- 7.3 in 10 patients with functioning renal grafts, indicating that the increase in sCR1 was reversible. Soluble CR1 was elevated in some hematologic malignancies (> 47 ng/ml), which included B cell lymphoma (12/19 patients), Hodgkin's lymphoma (4/4), and chronic myeloproliferative syndromes (4/5). By contrast, no increase was observed in acute myeloid or lymphoblastic leukemia (10) or myeloma (5). In two patients with chronic myeloproliferative syndromes, sCR1 decreased rapidly after chemotherapy. The mean concentration of sCR1 was not significantly modified in 181 HIV-infected patients at various stages of the disease (34.8 +/- 14.4 ng/ml), and in 13 patients with active SLE (38.3 +/- 19.6 ng/ml), although in both groups the number of CR1 was diminished on E. There was a weak but significant correlation between sCR1 and CR1 per E in HIV infection and SLE (r = 0.39, p < 0.0001, and r = 0.60, p < 0.03 respectively). In vitro, monocytes, lymphocytes, and neutrophils were found to release sCR1 into culture supernatants. In vivo, sCR1 was detected in the serum of SCID mice populated with human peripheral blood leukocytes. The sCR1 levels correlated with those of human IgG (r = 0.97, p < 0.0001), suggesting synthesis of sCR1 by the transferred lymphocytes. The mechanisms underlining the increased levels of sCR1 and its biologic consequences remain to be defined.