Search

The pathophysiological link between adiposity and blood pressure is not completely understood, and evidence suggests an influence of sex and genetic determinants. We aimed to identify the relationship between adiposity and blood pressure, independent of a robust set of lifestyle and metabolic factors, and to examine the modulating role of sex and Angiotensin-Converting Enzyme (ACE) insertion/deletion (I/D) polymorphisms. In the Relationship Between Insulin Sensitivity and Cardiovascular Disease (RISC) study cohort, 1211 normotensive individuals, aged 30 to 60 years and followed-up after 3.3 years, were characterized for lifestyle and metabolic factors, body composition, and ACE genotype. Body mass index (BMI) and waist circumference (WC) were independently associated with mean arterial pressure, with a stronger relationship in women than men (BMI: r =0.40 versus 0.30; WC: r =0.40 versus 0.30, both P ID and II ACE genotypes in both sexes ( P ACE genotype only in women ( P =0.03). A 5 cm larger WC at baseline increased the risk of developing hypertension at follow-up only in women (odds ratio, 1.56 [95% CI, 1.15–2.10], P =0.004) and in II genotype carriers (odds ratio, 1.87 [95% CI, 1.09–3.20], P =0.023). The hypertensive effect of adiposity is more pronounced in women and in people carrying the II variant of the ACE genotype, a marker of salt sensitivity.

The affiliation details for Geltrude Mingrone are corrected below.

International audience; We assessed the risks of bleeding, acute kidney injury (AKI) and kidney failure associated with the prescription of antithrombotic agents (oral anticoagulants and/or antiplatelet agents) in patients with moderate-to-advanced CKD. CKD-REIN is a prospective cohort of 3022 nephrology outpatients with CKD stages 2-5 at baseline. We used cause-specific Cox proportional hazard models to estimate hazard ratios (HRs) for bleeding (identified through hospitalizations), AKI and kidney failure. Prescriptions of oral antithrombotics were treated as time-dependent variables. At baseline, 339 (11%) patients (65% men; 69 [60-76] years) were prescribed oral anticoagulants only, 1095 (36%) antiplatelets only, and 101 (3%) both type of oral antithrombotics. Over a median [IQR] follow-up period of 3.0[2.8-3.1] years, 152 patients experienced a bleeding event, 414 patients experienced an episode of AKI and 270 experienced kidney failure. The adjusted HRs [95%CI] for bleeding associated with prescriptions of antiplatelets only, oral anticoagulants only, and antiplatelet + oral anticoagulant were respectively 0.74[0.46; 1.19], 2.38[1.45; 3.89], and 3.96[2.20; 7.12]. An increased risk of AKI risk was associated with the prescription of oral anticoagulants (adjusted HR [95%CI]: 1.90[1.47; 2.45]) but not the prescription of antiplatelets (1.24[0.98; 1.56]). Kidney failure was not associated with the prescription of oral antithrombotics of any type. This study confirms the high risk of AKI associated with oral anticoagulants prescription in CKD patients and also highlights the potential aggravating effect of combining VKA and antiplatelets on the risk of bleeding.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Background: Uremic toxins have emerged as potential mediators of morbidity and mortality in patients with chronic kidney disease (CKD). Indole-3-acetic acid (IAA, a tryptophan-derived uremic toxin) might be a useful biomarker in patients with CKD. The objectives of the present study were to (i) describe IAA concentrations in a cohort of non-transplanted patients with CKD and a cohort of transplanted patients with CKD, and (ii) investigate the possible relationship between IAA levels and adverse outcomes in the two cohorts. Methods: Levels of free and total IAA were assayed in the two prospective CKD cohorts (140 non-transplanted patients and 311 transplanted patients). Cox multivariate analyses were used to evaluate the association between IAA levels and outcomes (mortality, cardiovascular events, and graft loss). Results: In the non-transplanted CKD cohort, free and total IAA increased progressively with the CKD stage. In the transplanted CKD cohort, free and total IAA levels were elevated at the time of transplantation but had fallen substantially at one-month post-transplantation. Indole acetic acid concentrations were lower in transplanted patients than non-dialysis non-transplanted patients matched for estimated glomerular filtration rate (eGFR), age, and sex. After adjustment for multiple confounders, the free IAA level predicted overall mortality and cardiovascular events in the non-transplanted CKD cohort (hazard ratio [95% confidence interval]: 2.5 [1.2&ndash, 5.1] and 2.5 [1.3&ndash, 4.8], respectively). In the transplanted CKD cohort, however, no associations were found between free or total IAA on one hand, and mortality, CV event, or graft survival on the other. Conclusion: We demonstrated that levels of IAA increase with the CKD stage, and fall substantially, even normalizing, after kidney transplantation. Free IAA appears to be a valuable outcome-associated biomarker in non-transplanted patients, but&mdash, at least in our study setting&mdash, not in transplanted patients.

International audience; AIMS: Long-term use of proton pump inhibitors (PPIs) has been associated with adverse kidney events in the general population, but their impact among chronic kidney disease (CKD) patients is unclear. We studied the prevalence and incidence (new users) of PPI prescriptions and their relation to kidney outcomes and mortality in CKD patients. METHODS: We collected drug prescriptions prospectively in a cohort of 3023 nephrology outpatients with CKD stages 2-5 at inclusion. Hazard ratios (HR, 95% confidence intervals [95% CI]) for acute kidney injury (AKI), end-stage kidney disease (ESKD), and mortality associated with new PPI prescriptions as a time-dependent variable were estimated with cause-specific Cox models in 1940 non-users with eGFR ≥ 15 mL/min/1.73 m(2) at baseline, adjusted for comorbidities, laboratory data and drugs. RESULTS: There were 981/3023 (32%) prevalent users (67 ± 13 years, 65% men) at baseline, and 366/3023 (12%) were prescribed PPI (new users) over a median follow-up of 3.9 years (interquartile range, 3-4.2). Among these new users, their median cumulative duration of prescription was 1 year (interquartile range: 0.4-2.3). During follow-up, 354 patients developed ESKD and 216 died before ESKD. The adjusted HRs associated with PPI prescription were 1.74 (95% CI, 1.26-2.40) for ESKD and 2.42 (95% CI, 1.73-3.39) for all-cause mortality. Over the first 3 years of follow-up, 211 AKI events had occurred. The adjusted HR for AKI associated with PPI prescription was 2.89 (95% CI, 1.91-4.38). CONCLUSIONS: Long-term PPI prescription was common in CKD patients. Our results call attention to its potential risks of both acute and chronic kidney failure.

Background For patients with recurrent flares of gout, tophi, urate crystal arthropathy, and renal stones, urate-lowering therapies (ULTs, including allopurinol and febuxostat) are the first-line treatment. Due to the widespread use of these ULTs (especially in patients with impaired renal function), assessment of the associated renal risk is essential. Accordingly, we performed a disproportionality analysis of reported cases of acute renal failure (ARF) associated with allopurinol and febuxostat. Methods We carried out a case/non-case study of the World Health Organization’s VigiBase® pharmacovigilance database between January 1, 2008, and December 31, 2018. The frequency of reports of ARF as a standardized Medical Dictionary for Regulatory Activities query for allopurinol and febuxostat was compared with that of all other reports for the two drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval (CI)]. The results’ stability was assessed in a series of sensitivity analyses (notably after the exclusion of putative competing drugs). Results Among 3509 “suspected drug” notifications for febuxostat and 18,730 for allopurinol, we identified respectively 317 and 1008 cases of ARF. Acute renal failure was reported significantly more frequently for febuxostat and allopurinol than for other drugs (ROR [95%CI] 5.67 [5.05–6.36] and 3.25 [3.05–3.47], respectively). For both drugs, the ROR was higher in women than in men, respectively 11.60 [9.74–13.82] vs. 3.14 [2.69–3.67] for febuxostat and 4.45 [4.04–4.91] vs. 2.29 [2.11–2.50] for allopurinol. The sensitivity analyses confirmed the disproportionality for these two ULTs. Conclusions Acute renal failure was reported respectively 5.7 and 3.3 times more frequently for febuxostat and for allopurinol than for other drugs. Due to the potential consequences of ARF, physicians should take account of this disproportionality signal when prescribing the ULTs febuxostat and allopurinol.

Background The recommended treatment duration in neonates with developmental dysplasia of the hip (DDH) varies depending on whether prolonged Pavlik harness therapy is believed to favourably affect the course of the acetabular dysplasia. According to one theory, several months of additional Pavlik harness therapy after achieving hip reduction contributes to correct the acetabular dysplasia. Another theory holds that hip dislocation induces the acetabular dysplasia, which corrects spontaneously once the femoral head is properly seated in the acetabulum. Here, we evaluated this second theory by studying outcomes after early brief Pavlik harness therapy. Hypothesis Acetabular dysplasia associated with neonatal hip instability undergoes self-correction provided stable hip reduction is achieved very early after birth. Therefore, the duration of Pavlik harness therapy can be substantially shortened. Materials and methods We defined hip instability as either reducible hip dislocation or a very easily dislocatable hip with a soft clunk precluding determination of spontaneous hip position as dislocated or reduced. Static and dynamic ultrasound scans were obtained. Patients with ultrasonographic instability (pubo-femoral distance > 5 mm with less than 50% of coverage) underwent a second physical examination and received treatment. We re-evaluated 42 abnormal hips in 30 patients after a mean follow-up of 6.7 years (range, 5–14 years). Mean age at treatment initiation was 5 days (range, 1–15 days) and mean treatment duration was 34 days (range, 15–75 days). Results Mean acetabular angle was 20° (range, 12°–30°) and mean Wiberg's lateral centre-edge angle was 30° (range, 22°–35°). Blunting of the lateral angle of the bony roof was noted in 8 hips at last follow-up. In 1 patient whose hip was stable clinically but unstable by ultrasonography at 21 days of age, recurrent dislocation occurred at 5 months of age. The Severin class was 1a in all patients. Discussion Despite continuing controversy about whether hip dislocation induces dysplasia or vice versa, the need for early treatment is universally recognised. The optimal treatment duration, however, remains debated. Proponents of the familial determinism of DDH consider that acetabular shaping is genetically programmed when the femoral head is centred in the acetabular socket. Others advocate routine prolongation of Pavlik harness therapy for 2 months or longer, based on the opinion that this strategy decreases the dislocation recurrence rate and that mechanical hip unloading may promote correction of the dysplasia. Mean treatment duration in our population was 34 days and our sole objective was to treat the instability. The hip was reduced and held in its proper position long enough to allow sufficient capsule and ligament tightening to stabilise the hip. Under these conditions, the acetabular dysplasia underwent self-correction that was not related to treatment duration. Conclusion Very early Pavlik harness therapy to ensure rapid hip reduction and stabilisation optimises the potential of the acetabulum for spontaneous remodelling. Level of evidence Level IV, retrospective study.

International audience; We found for the first time that in maintenance hemodialysis patients, higher sclerostin serum level was associated with severe abdominal aortic calcification (AAC). In addition, cortical bone microarchitecture (density and thickness) assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at tibia was also independently associated with severe AAC. These results suggest that sclerostin may be involved in the association of mineral and bone disorder with vascular calcification in hemodialysis patients. INTRODUCTION: Severe abdominal aortic calcifications are predictive of high cardiovascular mortality in maintenance hemodialysis (MHD) patients. In patients with end-stage renal disease, a high aortic calcification score was associated with lower bone turnover on bone biopsies. Thus, we hypothesized that sclerostin, a Wnt pathway inhibitor mainly secreted by osteocytes and acting on osteoblasts to reduce bone formation, may be associated with vascular calcifications in MHD patients. METHODS: Fifty-three MHD patients, aged 53 years [35-63] (median [Q1-Q3]) were included. Serum was sampled before the MHD session to assay sclerostin. Framingham score was computed and the abdominal aortic calcification (AAC) score was assessed according to Kauppila method on lateral spine imaging using DEXA. Tibia bone status was evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Patients were distributed into two groups according to their AAC score: patients with mild or without AAC (score below 6) versus patients with severe AAC (score of 6 and above). RESULTS: In multivariate analysis, after adjustment on age, dialysis duration and diabetes, serum sclerostin and cortical thickness were independently associated with severe AAC (odds ratio (OR) = 1.43 for each 0.1 ng/mL increase [95 % confidence interval (CI) 1.10-1.83]; p = 0.006 and 0.16 for 1 SD increase [0.03-0.73]; p = 0.018, respectively). A second cardiovascular model adjusted on Framingham score and the above mentioned confounders showed similar results. CONCLUSIONS: Elevated sclerostin serum level and poorer tibia cortical bone structure by HR-pQCT were positively and independently associated with higher odds of severe AAC in MHD patients. Serum sclerostin may become a biomarker of mineral and bone disorder and vascular risk in MHD patients.

Objective : This study was designed to assess the changes in fetal oxygen saturation (FSp o 2 ) using fetal pulse oximetry when the fetal heart rate (FHR) monitoring became abnormal during stage II of labour. Study design : FSp o 2 was recorded with the Nellcor N400 Oximeter (FS-14 sensor) and was averaged over the last 10 min of the second stage of labour. Second stage FHR patterns were assessed according to Melchior's classification. Results : In terms of FHR patterns, FSp o 2 -10″ measured 41.4% in type 0 ( n =5), 42.4% in type 1 ( n =19), 43.3% in type 2 ( n =6), 34.0% in type 3 ( n =4) and 27.6% in type 4 ( n =7) ( P =0.03). Conclusions : FSp o 2 -10″ decreases in cases of severe FHR abnormality during the second stage of labour and could help to decide whether to perform an instrumental extraction. © 1997 Elsevier Science Ireland Ltd.

Summary Introduction Closed reduction of secondary displacements of distal metaphyseal radius fractures is an easy procedure only when performed within the first ten to fifteen days post-trauma, prior to the occurrence of malunion. When a hard bony callus prevents proper reduction, an open osteotomy is generally advocated. Hypothesis We suggest the use of a less invasive technique which aims at correcting early malunion when closed reduction is made impossible: the percutaneous callus osteoclasis. Materials and methods Callus osteoclasis consists in a series of multiple bone-drilling in a postage stamp pattern performed under image intensifier using a large diameter pin, at a distance from the growth plate. Once the bone has been weakened, reduction is obtained by using the pin as an intrafocal lever. The pin is then pushed through the opposite cortex to ensure postero-lateral stabilization. Results Twenty-one patients were managed using this technique and reported good results with no complications. Discussion This technique offers a low aggressive management of malunions and may be performed within two to six weeks after trauma. Level of evidence Level IV. Multicenter retrospective study.

Granulomatous interstitial nephritis (GIN) are identified in 0.5 to 1,3% of all renal biopsies. Renal outcome and treatment modalities are not clearly established in the literature.We retrospectively analyzed a case series of 44 GIN identified among all renal biopsies performed between 1984 and 2005 in the Rhône-Alpes area.The study population included 25 men and 19 women with a mean age of 56 years, and mean diagnostic delay was 11 months. Renal function was severely impaired (mean creatinine clearance 24mL/min). Proteinuria was observed in 77% (mean value 0,9 g/24h) of the patients and associated with microscopic hematuria and leukocyturia in 30% and 25%, respectively. The most common diagnosis was sarcoidosis (25%, n = 11), followed by drug-induced GIN (9%, n = 4), tuberculosis (6,8%, n=3), hemopathy-related paraneoplastic GIN (6,8%, n = 3), HIV infection (n = 1) and chronic renal allograft rejection (n = 1). In other patients, no aetiology was found (48%, n = 21). Severity of renal failure justified hemodialysis in 34% (n = 15) of the patients. Three patients underwent renal transplantation. Nonetheless, renal outcome was generally favorable: renal function improved in 41% (n = 18) and stabilized in 34% (n = 15) of patients.Sarcoidosis, drug-induced and infections represent the main causes of GIN. Histologic features are not specific enough to determine the aetiology. Corticosteroids is the gold standard in sarcoidosis, drug-induced, and idiopathic GIN. Treatment is etiologic in the other cases.

The prognostic of uremic syndrome had been improved by the development of renal replacement therapy. Uremic syndrome remains a dramatic medical concern in African sub-saharan countries. Nephrology practice has been introduced recently in Burkina Faso and epidemiological data on acute renal failure is not available. We conducted this study with the aim to describe the clinical profile of hospitalized patients. One hundred and twenty-one patients (18.4% of all admissions) with acute renal failure (creatinine240micromol/L, abrupt onset) were included (age: 38.6+/-16.3y; creatinine: 1246.1+/-870.5micromol/L; urea: 40.2+/-18.3micromol/L), 75 men (age: 41.2+/-16.4) and 46 women (age: 34.2+/-15.2y). Acute renal failure was of medical cause in 91 cases, surgical cause in 16 cases and gyneco-obstetrical in 14 cases. Many pathophysiological factors have been identified like volume depletion, infections and obstruction. Acute renal failure was renal in 57 cases (age: 38.2+/-14.6y), prerenal in 43 cases (age: 36.8+/-16.7y) counting acute tubular necrosis in 21 cases, obstructive in 15 cases (age: 50.5+/-15.6y) and unclassified in six cases. Comorbidities have been identified: heart failure (13 cases), hepatocellular failure (eight cases), tumours (four cases) and severe hypertension (13 cases). Dialysis was justified in 84 cases but only accomplished in 14 cases. Hospital length of stay was 20.4+/-14.9 days. Twenty-nine patients died and causes were uraemia in 13 cases, hepatic in three cases, sepsis in 10 cases, malignant tumour in two cases and associated in one case.

Classical surgical treatments for Legg-Calvé-Perthes (LCP) disease are pelvic or femoral osteotomies, which are not without complications and inconvenience for the patient.An effective, relatively undamaging surgical alternative would improve this disease treatment.Augmentation acetabuloplasty using shelf acetabuloplasty is a recognized treatment for LCP disease, but its results have never been assessed in view of Herring's lateral pillar classification, the current reference in determining the prognosis of this disease. Assessment of its efficacy based on this system is therefore needed.Over 15 years, 21 patients underwent shelf acetabuloplasty. Included in the study were children with a progressively subluxating femoral head and classified minimum grade B in the lateral pillar classification. The last follow-up had to be at least 12 months after surgery and include a clinical examination as well as an AP pelvic X-ray.The mean follow-up was 4 years and 3 months. Only two complications occurred, one of which required surgical revision. Shelf acetabuloplasty was considered effective (contained and Stulberg 1 or 2) in 13 cases and ineffective (lysed or Stulberg 3, 4, or 5) in eight cases.The lateral pillar classification demonstrated its high value in LCP disease in correlation with symptom onset. This series shows that at the medium term, shelf acetabuloplasty is as effective as pelvic or femoral osteotomies for children of any age and any level of disease severity, with fewer complications and less inconvenience for the patient.: Level IV. Therapeutic retrospective study.

Summary Introduction Multiple surgical options are available in the treatment of severe Sprengel's deformities and vary according to the selected muscle disinsertion site. We report here the functional and cosmetic results of the Green's operative technique. Material and methods We retrospectively reviewed cases of congenital elevation of the scapula operated on, between 1999 and 2007, at Saint-Denis Regional Hospital Center. Clinical and radiographic examinations along with parents questioning were performed. Results This study included eight children with a mean follow-up of 4.5 years. Improvement occurred in all cases: the appearance was improved by one grade in three children and two grades in three other children, according to the Rigault's classification system. Cosmetically, all families were satisfied with the final result of the treatment. A case of complete brachial plexus palsy (BPP) that resolved spontaneously within 7 months was observed. Discussion Sprengel's deformity is an unusual skeletal abnormality. The Green's operative technique allows both lowering and rotation of the scapula. Muscle attachment is distally, rather than proximally, modified which provides a better biomechanical effect: muscles are reattached higher than the acromiothoracic junction's rotation center. The Green's scapuloplasty has been rarely reported in literature, whereas the Woodward procedure remains the reference standard. However, both techniques report similar results. Our choice was based on a better impression in terms of operative approach and improved muscle levers’ distance adjustment to the fulcrum. Finally, resection of the superomedial portion of the scapula which is fixed to the rib cage into a pocket of the latissimus dorsi seems to provide a more efficient correction. Level of evidence Level IV, retrospective therapeutic study.

The purpose of this work was to study early short-term treatment of reducible dislocated or very unstable dislocated hips using the Pavlik harness. This approach is based on the theory of that dislocation favors dysplasia and that spontaneous correction occurs if the hip is reduced and stable. Very easily dislocated hips have been qualified as "major instability" if voluntary dislocation was easily achieved. In this case, it is very difficult to predict whether postnatal capsuloligamentary retraction will occur in the reduced or dislocated position.We retained for study 34 patients with 44 pathological hips; 15 hips presented reducible dislocation and 29 major instability. Treatment began early at 3.4 days of life on average and lasted 27.9 days.Outcome was very good for 39 hips with stabilization and spontaneous correction of the acetabular dysplasia, good in four with late correction of the dysplasia, and a failure in one. There were no major complications, none of the patients presented post-reduction osteochondritis.Two different entities can be distinguished: dislocation producing dysplasia which is symptomatic neonatally and would imply pathogenic in utero events, and primary dysplasia which can be asymptomatic at birth and for which correction is not spontaneous. If the hip is symptomatic at birth, treatment should begin immediately and be continued to confirmation that the reduced hip is stable, i.e. about three to five weeks on average. Simple dysplasia of dislocatable hips should be excluded from this strategy because of their favorable spontaneous course. Likewise for irreducible dislocated hips because of the higher risk of complications. Under these conditions, this therapeutic strategy is effective for the reduction, stability, and correction of dysplasia achieved in 97.7% of cases without increasing the rate of complications.

The purpose of this study was to ascertain whether immediate weight bearing after surgery for chronic or stable epiphysiolysis treated with a single percutaneous screw increases the risk of greater displacement.Epiphysiolysis procedures (n=30) performed in 25 patients were reviewed retrospectively. One percutaneous screw was inserted under fluoroscopic control in all cases. For ten patients (from 2002), weight bearing was allowed immediately after surgery. The Southwick grading system was applied to classify each epiphysiolysis into one of three stages according to the cervicoepiphyseal angle measured on the lateral radiograph. Clinical and radiographic controls were obtained in all children at 1, 3, 6, and 12 months. Outcome was assessed using the Heyman and Herndon criteria.The study population included 17 boys and 8 girls (mean age 12 years 18 months). The left side was involved in 12, the right in 8 and both in 5. Weight bearing was allowed immediately after surgery in 10 patients with a stable epiphysiolysis (4 stage I, 5 stage II, 2 stage III). Time to weight bearing was 3 months on average for the others. Mean follow-up was 4 years (range 1-8 years). Clinically, none of the ten patients presented pain or limping at last follow-up. Abduction was limiting in 9 and internal rotation in 19. There was no increase in the displacement for patients with immediate weight bearing.Most teams advise against weight bearing for 6 weeks to 3 months. We were unable to find any pathophysiological reason for this attitude. It would be more logical to wait until complete fusion of the subcapital growth cartilage before authorizing weight bearing. This raises the question of the effect of this practice on postoperative displacement For stable epiphysiolysis, there is no evidence that not allowing weight bearing had an effect on the evolution if the screw is correctly positioned and at least 4 or 5 spires are engaged within the epiphysis.

Obesity and insulin resistance are directly associated with the presence of microalbuminuria. However, the prospective relationship between abdominal adiposity and the occurrence of micro-albuminuria has been little studied in a non-diabetic population. From the DESIR cohort, we examined whether waist circumference was associated with the incidence of micro-albuminuria at 6 years (D6). The study evaluated 2738 non-diabetic subjects without micro-albuminuria at inclusion who were then followed prospectively. At 6 years, 254 individuals (9.3%) had developed pathological micro-albuminuria (or =20 mg/l) measured at micturation. In both sexes, the incidence of micro-albuminuria was associated with increased waist circumference and blood pressure, but not with blood glucose levels, lipid parameters or body mass index. Subjects with a higher waist circumference at inclusion were at a higher risk of having micro-albuminuria at 6 years compared to those with a normal waist circumference. Logical regression analysis showed that waist circumference as a continuous value, or greater than 94 cm for males and 88 cm for females, were predictive factors for the incidence of micro-albuminuria, after adjustment for age, hypertension, ACE inhibitor usage, fibrinogen, and blood glucose level. Abdominal adiposity is thus linked in both sexes to the development of microalbuminuria, which underlines the importance of measuring waist circumference when assessing risk factors for renal lesions in non-diabetic hypertensives.

Physeal distraction or chondrodiastasis uses the growth plate as a zone of least resistance. Application of force thus provokes distraction and opening of the plate (Salter and Harris type I epiphyseal detachment). Progressive lengthening allows room for regenerate bone and enables limb lengthening and correction of angular deformations.Twenty chondrodiastasis procedures were performed in fifteen patients. Mean age was 14.4 years (10.3-15.7). The underlying causes were trauma (n = 6), constitutional deformation (n = 8), infection (n = 2, distal lateral femoral epiphysiodesis), and malformation (n = 4). The localizations were: proximal tibia (n = 11), distal tibia (n = 4), distal femur (n = 4), distal radius (n = 1). The surgical procedure involved installation of an external fixator on either side of the physis after planification of the desired correction and taking into account the remaining growth potential of the physis. The distraction was performed by the patient at the rate of 1 mm per day. A one-sided external fixator was used for eleven patients (distal femoral correction and proximal tibial hemichondrodiastasis for angular deformation) and a circular fixator (to control 3D correction) in nine. Complications were noted according to the four grades of severity described by Caton.Mean follow-up was 26.1 months. Epiphyseal detachment was achieved in all patients, even in the presence of an epiphysiodesis bridge, in 7.7 days on average (2-15 days). Mean lengthening was 4.75 cm, mean angular correction was 22.2 degrees (mean preoperative angle 20.5 degrees ). For chondrodiastasis (symmetrical physeal distraction), the mean duration of correction was 4.6 months (1-9), mean time to healing was 8.3 months (4-13) and mean healing index was 55.6 days/cm (Verone). For hemichondrodiastasis (asymmetrical physeal distraction), mean duration of correction was 1.3 months (1-3), and mean time to healing was 2.7 months (2-5). The healing index was different and was 3 days per degree. Complications were studied using the Caton classification. There were 17 (85%) benign complications (not requiring revision under anesthesia) and 6 (30%) serious complications (requiring anesthesia and unplanned revision). There were 2 (10%) severe complications (knee flexion, ankle equinus).Chondrodiastasis has specific complications, mainly involving the distal femur (stiff knee, risk of septic arthritis). It provides rapid in situ correction resulting from epiphysiodesis bridges. The resection step proposed by Bollini is not necessary, but the growth plate is definitively sterilized. This implies that the procedure be used for preventive lengthening, depending on the predicted limb length discrepancy. This notion limits indications to older children. Besides the fact that several deformations can be corrected simultaneously, this technique does not require osteotomy and respects vascular supply to the regenerative tissue. It involves the physis responsible for the angular deformation or limb length discrepancy. It does not require internal fixation nor bone grafting and can be performed with weight bearing. Finally, the procedure can be adjusted as needed during the correction phase, with the patient in the standing position.

High job strain has been reported to be associated with higher blood pressure. Job strain could lead to hypertension if individual perception of stress or cardiovascular reactivity to stress are high. We report the results of the first five-year follow up study, which aimed to assess the respective influences of perception of professional strain and cardiovascular reactivity to a mental stress test on BP. A cohort of 292 healthy subjects (mean +/- SEM, 38 +/- 1 years) was followed for progression to hypertension outcome which was defined as an increase in SBP or DBP higher than 7 mmHg or a DBP higher than 95 mmHg during the follow-up. The high strain (HS) group representing 20.9% of the subjects was compared with the remaining subjects (NHS). Similarly the 20.9% subjects with the highest BP stress reactivity (HR) were compared with the remaining subjects (NHR). The Kaplan-Meier survival estimates revealed that neither high job strain, nor high stress reactivity, increased incidence of progression to hypertension. Age, alcohol, salt diet, BMI, and occupation did not interfere with our results. In conclusion, high stress cardiovascular reactivity and high job strain do not appear to be major risk markers for future high BP in healthy young adults. Stress could be associated with high BP at a short term and could explain high blood pressure in a long run only in stress-sensible subjects.

Elastic sliding centromedullary nailing (ESCN) proposed by Métaizeau in 1987 for the prevention and treatment of limb fractures in osteogenesis imperfecta has never been evaluated. A multicentric serie was studied in order to evaluate results of these procedure.Thirty-six ESCN procedures were performed in fourteen patients. Percutaneous pinning was used for the femur and distal tibia and arthrotomy for the distal femur as needed and in all cases for the proximal tibia. The pins were bent in compliance with the principles of the ESCN system. The ends of the pins were bent back to form a U pushed into the epiphysis. Reaxing osteotomies required minimal incisions. Age at the first procedure, the number of procedures and complications, and time between procedures were recorded. Pin overlap and the angle formed were also recorded. Pin gliding was evaluated. Ability to walk with or without assistance was noted.The medullary canal measured 4 to 10 mm. The first procedure was performed at a mean age of four years (range 15 days to 10 years). Follow-up was eight years (range 1-12). There were 2.5 procedures per patient (range 1-5). Pins had to be changed in 75% of the bone segments. Mean time between two procedures was 3.2 years. There were no cases of defective sliding or infection. There were four cases of secondary fracture with a mean 30% pin overlap, two pin migrations, one nonunion, and one shortening. The majority of the complications occurred after the age of five years. At last follow-up, three patients could not walk, four walked with aids, and eight without aids.The advantages of the technique (size of the pins, nailing without reaming, pin sliding in all cases, low cost) must not overshadow the drawbacks (risk of pin deformation and migration, secondary fracture). Secondary fractures might be limited by discrete valgus of the femoral shaft and preventive pin change when the angle formed approaches 30 degrees and when there is only 30% overlap left. Use of telescopic nails before the age of five years increases the risk of complications while most of the complications observed with ESCN occur after the age of five years. Twenty-five percent of the ESCN complications involved only the femur. The percent of secondary fractures was less than with telescopic nailing (3.6% versus 11%) but there were more cases of nail migration. All pins slid, compared with 6% failure of elongation with telescopic nails. Although proof is not available, surgical treatment of osteogenesis imperfecta before the age of five years appears to provide more rapid functional progress.Sliding centromedulary nailing is an attractive alternative before the age of five years. In older children and to the end of growth, telescopic nail or pinning should be discussed although pinning may permit more secondary fractures which can be limited by rigorous surveillance of pin position.

The parallel investigation of the renal and cardiac complications of recent and never treated systemic hypertension has only rarely been undertaken. The aim of this study was to define the renal function of never treated hypertensive subjects, separated into white coat hypertensives (HTbb: n = 19, BP at consultation 153/97 mmHg) or permanent hypertensives (HT: n = 49, BP at consultation 169/104 mmHg) as a function of their 24 hour BP. Their renal functions were then compared with those of normotensive subjects (NT: n = 10). The 68 hypertensive subjects seen consecutively underwent renal function investigation (DFG: glomerular filtration rate, DPR: renal plasmatic debit, and muAlb: microalbuminuria over 24 hours), and myocardial echography (measurement of the left ventricular mass index, IMVG). The white coat hypertensives had a normal renal function, while the permanent hypertensives had a significant decrease in DPR and a significantly higher muAlb compared to the normotensives. Compared to the white coat hypertensives, the permanent hypertensives had a significantly lower DFG and DPR, as well as a higher muAlb and IMVG. In all the hypertensives (white coat and permanent) the 24 hour systolic BP was significantly correlated with muAlb (r = 0.51, p0.001), filtration fraction (r = 0.30, p0.05), and IMVG (r = 0.52, p0.001). The renal and myocardial parameters were not significantly correlated. In conclusion, there seems to be a continuum between the level of ambulatory BP and the effect on target organs without a parallel progression of the renal and myocardial effects. From a practical point of view, only ambulatory BP measurement allows differentiation of permanent hypertensives who have a very early renal and/or myocardial effect, while white coat hypertensives are spared.

Four prospective randomised long-term studies have been recently completed and published (Diabetes Prevention Study, Diabetes Prevention Program, STOP-NIDDM trial, XENDOS Study). Both of them clearly demonstrate the possibility to delay and/or prevent the onset of type 2 diabetes in at high-risk subjects with impaired glucose tolerance, through changes in lifestyle (dietary intervention, weight reduction, increased physical activity) or drug treatment (metformin, acarbose, orlistat). These studies are reviewed and practical implications of their results are discussed.

The purpose of this study was to demonstrate the contribution of shelf acetobuloplasty for the treatment of Legg-Perthes-Calve disease.Eighteen children with Legg-Perthes-Calve disease were operated on between 1992 and 2001. Mean age at diagnosis was 7 years 2 months, and mean age at surgery was 8 years 5 months (range 5-13 years). Mean motion was limited -25 degrees in abduction and internal rotation preoperatively. The radiological classification was: 2 Catterall II Herring B with signs of risk for the head, 8 IIB, 1 III C, 2 IV B, 3 IV C, and 2 at the sequelar stage. Mean excentration was 6.5 mm and mean overhang was 10.2 mm.The indication for surgery was aggravation of the excentration or advanced revascularization. An iliac graft was embedded in the supralimbic and covered with a rectus femoris tendon which, left continuous, provided elastic support. A bermuda cast was used in 17 cases and immediate weight-bearing in 11. The patients were hospitalized 36 hours.Sixteen patients were reviewed at mean follow-up of 3 years 2 months (2 lost to follow-up). There were no complications. Clinically, the patients were pain free. Three patients had persistent limping 10 moderate limitation of motion, and three had severe stiffness. Radiologically, head covering was good in 15 cases, and joint congruency was achieved in 15 (11 of which were concentric). Shelf acetabuloplasty was considered useful in 12 cases, not useful in 1 after complete lysis of a poorly positioned graft, and of uncertain usefulness in 3 (including 2 cases treated at the sequalar stage).Femoral osteotomy for varisation and pelvic osteotomy for reorientation or enlargement of the acetabulum are effective but have certain drawbacks (limitation of abduction, leg length discrepancy, reintervention to remove material). The excellent integration of the shelf graft at mid-term is a good sign of correct head-acetabulum adaptation, with radiological and clinical results similar to other techniques. Joint stiffness and limping are observed in very severe forms where the prognosis depends on the stage of the disease.The patients in this series have not yet all reached maturity. Shelf plasty is a rapid, easily-performed, and safe means of enabling weight-bearing in Legg-Perthes-Calve hips undergoing excentration and beginning revascularization.

We report a series of percutaneous lengthenings of the Achilles tendon in cerebral palsy children with equinus deformity in 25 patients due to retraction of the triceps surae. This technique has several advantages over open procedures. Based on our results and data reported in the literature, we emphasize the minimally invasive nature of this technique, the low rate of complications and recurrence, and the absence of secondary deformation of the calcaneus since over-lengthening is not compatible with the technique.

The regulation by insulin of the expression of the p85alpha regulatory subunit of phosphoinositide 3-kinase (PI 3-kinase) is impaired in skeletal muscle and adipose tissue of type 2 diabetic patients. The gene encoding p85alpha (named grb-1) can generate several variants by alternative splicing, all being able to activate the p110 catalytic subunits of PI 3-kinase. Our aims were (i) to determine the mRNA expression profiles of these variants in human skeletal muscle and adipose tissue; (ii) to investigate the effect of insulin on their expression in vivo and in vitro in muscle and (iii) to verify whether this regulation is defective in type 2 diabetes. We determined the human genomic organization of grb-1 and set up reverse transcriptase competitive PCR assays for the quantification of each mRNA variant. In muscle, p85alpha and p50alpha mRNAs were the most abundant, and p55alpha represented less than 20% of all grb-1-derived mRNAs. In adipose tissue, p85alpha was expressed predominantly and p55alpha mRNA was not detectable. These expression profiles were not different in type 2 diabetics. During a 3 h hyperinsulinaemic clamp, insulin increased the mRNA expression of the three variants in muscle of control subjects. In diabetic patients, the effect of insulin on p85alpha and p50alpha mRNAs was blunted, and largely reduced on p55alpha transcripts. In cultured human myotubes, up-regulation of p85alpha, p55alpha and p50alpha mRNAs by insulin was abolished by LY294002 (10 microM) and by rapamycin (50 nM), suggesting that the PI 3-kinase/protein kinase B/p70 S6 kinase pathway could be involved in the stimulation of grb-1 gene expression by insulin in human muscle cells.

Defective regulation of gene expression may be involved in the pathogenesis of type 2 diabetes. We have characterized the concerted regulation by insulin (3-h hyperinsulinemic clamp) of the expression of 10 genes related to insulin action in skeletal muscle and in subcutaneous adipose tissue, and we have verified whether a defective regulation of some of them could be specifically encountered in tissues of type 2 diabetic patients. Basal mRNA levels (determined by reverse transcriptase-competitive polymerase chain reaction) of insulin receptor, insulin receptor substrate-1, p85alpha phosphatidylinositol 3-kinase (PI3K), p110alphaPI3K, p110betaPI3K, GLUT4, glycogen synthase, and sterol regulatory-element-binding protein-1c (SREBP-1c) were similar in muscle of control (n = 17), type 2 diabetic (n = 9), type 1 diabetic (n = 9), and nondiabetic obese (n = 9) subjects. In muscle, the expression of hexokinase II was decreased in type 2 diabetic patients (P0.01). In adipose tissue, SREBP-1c (P0.01) mRNA expression was reduced in obese (nondiabetic and type 2 diabetic) subjects and was negatively correlated with the BMI of the subjects (r = -0.63, P = 0.02). Insulin (+/-1,000 pmol/l) induced a two- to threefold increase (P0.05) in hexokinase II, p85alphaPI3K, and SREBP-1c mRNA levels in muscle and in adipose tissue in control subjects, in insulin-resistant nondiabetic obese patients, and in hyperglycemic type 1 diabetic subjects. Upregulation of these genes was completely blunted in type 2 diabetic patients. This study thus provides evidence for a specific defect in the regulation of a group of important genes in response to insulin in peripheral tissues of type 2 diabetic patients.

KIDNEY DISEASE AND HYPERTENSION: Hypertension is increasingly associated to renal insufficiency leading to end stage renal damage (ESRD), through several mechanisms involving renal vasculature. Ten to 25% of new ESRD patients are now categorized as hypertensive nephropathy and vascular renal disease.Besides the risk of spontaneously evolving atheromatous stenoses of renal arteries, the individual risk of ESRD in essential hypertension is relatively low, except in selected genetic backgrounds such as black people especially in the USA. In long term studies, the risk of ESRD in treated hypertensives is between 1.5 and 3% at 15 years, and approximately 3% of French hypertensives have plasma creatinine levels above 150 mumol/l. The risk of significant creatinine increase is doubled each 20 mmHg increment in diastolic BP, but long term studies suggest that the influence of systolic BP is even greater.Animal models have extended our pathophysiological view of hypertensive nephropathy, in which renal ischemia and nephron loss will induce preglomerular vasodilation and glomerular hypertension. In the future, the evaluation of the renal prognosis in essential hypertension could benefit from indirect renal hemodynamic explorations, genetic progress, determination of microalbuminuria which is the renal probe of a more generalized microvascular disease, these indices should be useful to adapt the antihypertensive therapy, with the goal of normalizing blood pressure at a lowest albumin excretion rate.

Much work has focused on the short-term outcome after external fixation with the Ilizarov apparatus for treatment of severe recurrent or neglected foot deformity. No series has provided sufficient follow-up to allow an analysis of long-term stabilization.We reviewed a series of 17 patients (21 feet) treated with the Ilizarov apparatus between 1988 and 1998 and reexamined after a mean 6-year follow-up. We assessed the risk of degradation of the initial result and quantified the need for secondary arthrodesis surgery. This series included 18 congenital clubfeet and 3 cases of acquired talipes equinus. Mean patient age was 15 years.Pain, morphology, weight bearing attitude and quality of shoe fit were assessed. Results at treatment end were very good in 16 cases, good in 4 and poor in 1. Two early recurrences required arthrodesis. At last follow-up, results were very good in 17 cases, good in 3, and poor in 1 (late recurrence with arthrogryposis).With 3 recurrences among 21 cases, results were maintained well over time in this series. Most of the recurrences were observed during the first year and never completely reproduced the initial deformation. In 2 out of 3 cases, the recurrence occurred on a secondary talipes equinovarus. Age was not a risk factor (only 2 feet have not reached maturity to date). The lack of over-correction at treatment end is a factor predictive of poor outcome.Long-term outcome demonstrated the stability of the results and the absence of severe complications and foot shortening, emphasizing the important contribution of Ilizarov fixation for severe foot deformity.

The consequences of physical inactivity on fuel homeostasis were evaluated during 7 days of head-down bed rest (HDBR), a model mimicking weightlessness. Eight men (32.4 +/- 1.9 yr; body mass index, 23.9 +/- 0.7 kg/m2) and eight women (27.9 +/- 0.9 yr; body mass index, 20.9 +/- 0.6 kg/m2) underwent an oral glucose tolerance test (OGTT; 1 g/kg) before and after HDBR. The glucose load was labeled with 13C and associated with D-[6,6-2H2] glucose infusion, indirect calorimetry, breath tests, and plasma measurements to determine the glucose turnover and biodisponibility, substrate oxidation, and endocrine responses. Body composition was assessed using H2(18)O dilution. In addition, hormones were measured in daily blood and 24-h urine samples. No change in body composition was noted. Daily fasting insulin increased during HDBR (men, 34%; women, 26%), as did the insulin to glucose ratio (men, 30%; women, 25%). The normetanephrine level dropped (men, 30%; women, 16%), but metanephrine was unchanged. During OGTTs, the insulin response was increased after HDBR (men, 47%; women, 67%), whereas plasma glucose levels were similar. Nonesterified fatty acids and beta-hydroxybutyrate levels were lower. Endogenous glucose production dropped (28%), and exogenous glucose oxidation increased (28%) only in men. Resting energy expenditure was unchanged, but nonproteic respiratory quotient increased (men, 10%; women, 14%). Basal levels of lipid oxidation dropped in both sexes (approximately 90%), but those of carbohydrate oxidation increased in men (40%); as did lipogenesis in women (570%). In response to OGTTs, lipid oxidation was 80% reduced in both sexes after HDBR, but carbohydrate oxidation increased (25%) in men. Lipogenesis occurred in men (304%) and women (74%), but the latter had higher absolute levels. Therefore, 7 days of HDBR resulted in 1) reduced sympathetic activity, 2) insulin resistance suggested at the muscle level in men and at both the muscle and liver levels in women, 3) no changes in glucose biodisponibility, suggesting no alterations in the gastrointestinal function, and 4) a shift toward carbohydrate oxidation in men and a net lipogenesis in women. Such results suggest gender differences in response to sedentary life style and warrant further analysis.

An association with subcutaneous adipose tissue TNFalpha expression and insulin resistance has been suggested in obesity/type-2 diabetes, but this has not been examined directly. In the first part of the study we investigated whether this association is present in 7 lean, 10 obese nondiabetic and 9 type-2 diabetic men. In the second part of the study we examined the relationship between adipose tissue TNFalpha mRNA levels and BMI in 81 nondiabetic subjects spanning a wide range of BMIs.Subcutaneous adipose tissue TNFalpha mRNA levels and insulin sensitivity were determined with quantitative RT-competitive PCR and hyperinsulinaemic clamp, respectively.Subcutaneous adipose tissue TNFalpha mRNA levels were similar in 7 lean and 10 obese nondiabetic and 9 type-2 diabetic men (P = 0.68), and did not change in response to 240-min hyperinsulinaemia. TNFalpha mRNA levels and insulin sensitivity were not correlated. Unexpectedly, no correlation between TNFalpha mRNA and BMI was found. The relationship between adipose tissue TNFalpha mRNA and BMI was examined further in 31 male and 50 female nondiabetic subjects. The subcutaneous adipose tissue TNFalpha mRNA level correlated with BMI in all subjects (rS = 0.32, P0.01), and in a subgroup analysis in men (rS = 0.55, P0.01) but not in women (rS = - 0.08). The correlation in men was dependent on a fourfold higher TNFalpha mRNA level in 5 morbidly obese men while there was no difference in TNFalpha mRNA levels in lean or obese men.Subcutaneous adipose tissue TNFalpha expression does not correlate with insulin sensitivity in nondiabetic or type-2 diabetic men; is not regulated by acute hyperinsulinaemia; and is increased only in morbidly obese men.

Forty-three tibia vara in 27 patients were analyzed retrospectively in two centers. The criteria for diagnosis of the child form are discussed. A simple classification is suggested to facilitate the choice of treatment. In stage 0 (possible Blount's disease), the patient is younger than 2 1/2 years, and an observation period is indicated for gathering data. In stage 1 (confirmed Blount's disease and absence of medial metaphyseal bony bridge), known as physis+, a valgization osteotomy is proposed. In stage 2 (evidence of a medial metaphysoepiphyseal bony bridge) known as physis-, valgization osteotomy with lateral epiphysiodesis and treatment of the lower limb discrepancy is proposed. For stages 1 and 2, there are two possibilities: normal medial tibial plateau or sloping of the medial tibial plateau, indicating a transphyseal elevation osteotomy. When one-step correction is proposed for stage 2 disorder, external fixators such as Orthofix or Ilizarov devices are useful.

Marijuana is known to affect learning and memory in humans, and cannabinoids block long-term potentiation in the hippocampus, a model for the synaptic changes that are believed to underlie memory at the cellular level. We have now examined the physiological properties of the Schaffer collateral-CA1 synapses in mutant mice in which the CB1 receptor gene has been invalidated and found that these animals exhibit a half-larger long-term potentiation than wild-type controls. Other properties of these synapses, such as paired-pulse facilitation, remained unchanged. This indicates that disrupting CB1 receptor-mediated neurotransmission at the genome level produces mutant mice with an enhanced capacity to strengthen synaptic connections in a brain region crucial for memory formation.

Membranous nephropathy in adults causes 20% of nephrotic syndromes. Spontaneous outcome of this glomerulopathy is difficult to evaluate from clinical and histological data. Some patients can achieve complete remission, while others develop progressive renal failure. In this study we assessed alpha-smooth muscle actin (alpha-SMA) expression in renal interstitial myofibroblasts as a marker to predict the outcome of membranous nephropathy.Renal function tests in tandem with alpha-SMA immunolabelling were performed on 25 patients with a mean follow-up of 7.2+/-5.6 years. The intensity of interstitial alpha-SMA (ialpha-SMA) immunostaining was compared to changes in glomerular filtration rate (GFR) evaluated by inulin clearance, between the time of diagnosis (GFR1) and the end of follow-up (GFR2).A significant correlation (r = 0.62, p0.001) was found, between the intensity of interstitial myofibroblasts, immunolabeling and GFR at the end of follow-up. Moreover, the annual GFR variation and the annual percentage of GFR variation were correlated to interstitial myofibroblast labeling (respectively r = 0.62, p0.001; r = 0.67, p0.001). In addition, the importance of proteinuria, initial GFR impairment and fibrosis were confirmed as prognostic criteria.This study strongly shows that ialpha-SMA expression is a useful and early prognostic marker in the evolution of membranous nephropathy.

Despite the severity and the prognosis value of undernutrition in haemodialysed patients, no large study is available as yet in Europe. Hence, this French National Cooperative Study aimed to determine the prevalence of undernutrition and its relationship to dialysis efficacy.Nutritional status was determined in 7123 patients (i.e. one-third of the French haemodialysis population) using body mass index (BMI), predialysis haemoglobin, albumin, pre-albumin, cholesterol, and also normalized protein catabolic rate (nPCR) and lean body mass (LBM) calculated from pre- and postdialysis urea and creatinine. Dialysis treatment was estimated from weekly dialysis time and KtV determination.Dialysis time was 12.4+/-2.7 h/week and KtV 1.36+/-0.36. BMI was below 20 kg/m2 in 24% and the observed/expected LBM ratio below 90% in 62%. Albumin, pre-albumin and nPCR were below the high-risk thresholds of 35 g/l, 300 mg/l and 1g/kg/day in 20%, 36% and 35% of patients, respectively. Pre-albumin was the most representative nutritional parameter. Albumin, pre-albumin and LBM correlated with nPCR. A dialysis time above 12 h/week was associated with higher BMI, albumin, pre-albumin and LBM. LBM was higher in patients with a KtV value1.1.This study showed life-threatening undernutrition in 20-36% of the studied population, according to nutritional parameters. Protein intake (estimated by nPCR) and dialysis efficacy (estimated by dialysis time and KtV) appeared to be major determinants of nutritional status in this population.

PPAR gamma, leptin and TNF alpha are three major factors that play a key role in influencing adipocyte differentiation and both adipose tissue function and metabolism. However, the regulation of these three genes during a dynamic period of weight loss is unknown. We therefore investigated the concomitant regulation of the mRNA expression of PPAR gamma, leptin and TNF alpha in adipose tissue during a 21-day very low calorie diet (VLCD) in 12 non-diabetic obese women.The mRNA levels of PPAR gamma, leptin and TNF alpha were quantified by quantitative RT-competitive PCR in abdominal subcutaneous adipose tissue before and during VLCD (940 kcal/day).VLCD induced weight loss (approximately 6 kg) and improved insulin sensitivity. Simultaneously, VLCD induced the reduction in the adipose tissue mRNA abundances of PPAR gamma (-13%, p0.05) and of leptin (-58%, p0.005), whereas TNF alpha mRNA levels increased (+78%, p0.005). PPAR gamma and leptin mRNA levels were correlated before (r = 0.778, p0.01) and after VLCD (r = 0.797, p0.01). Serum HDL-cholesterol concentrations were positively associated with PPAR gamma (r = 0.696, p0.03) and leptin (r = 0.806, p0.01) mRNA levels.The increase in TNF alpha mRNA levels suggested that a local increased expression of this cytokine in adipose tissue might play a role in the control of the fat mass during weight loss. PPAR gamma and leptin mRNA levels were positively associated both before and after VLCD, suggesting that common regulatory mechanism(s) might control their expression. More strikingly, we found strong positive correlations between circulating HDL-cholesterol and both PPAR gamma and leptin mRNA levels, suggesting the existence of physiological links between circulating lipoprotein metabolism and adipose tissue function.

The authors report 24 cases of revision in recurrent club foot deformity. They assessed Cahuzac's procedure for treatment of the residual forefoot adduction. This procedure (opening of the first cuneo-metatarsal joint and proximal abduction osteotomy of the second, third, and fourth metatarsals) was generally associated with postero-medial, plantar release, and split tibialis anterior tendon transfer.Twenty four procedures for 20 children at mean age of five years have been performed. The revision chart comprised 12 clinical and radiological items as proposed by Seringe.Seven feet were considered as excellent, 14 as good, 2 as fair, and 1 as poor. The mean follow-up was four years.Treatment of the adduction component with Cahuzac procedure is focused on the fore part of the foot, and on the calcaneo-pedal block by postero medial release, but never on the midfoot, as no Evans or Lichtblau's procedure has been performed. This series was compared to others procedures, and morphological results were equivalent. Cahuzac's operation is riskless for foot growth, and needs two approaches which can be useful for simultaneous procedures as split lateral transfer of tibialis anterior tendon.Metatarsal osteotomies (Cahuzac's procedure), associated with soft tissues release and split anterior tibial transfer, seems to be effective in surgical treatment of relapsed clubfeet, but the debate concerning the location of the adduction component of the deformity remains still open.

We identified 174 cases of chronic severe renal failure (blood creatinine650 mumol/l) and/or blood urea35 mmol/l) in a retrospective study of patients admitted to hospital between January 1989 and June 1996. Of these patients, 110 were men and 64 were women. The mean age was 36 +/- 15 years. Fifty three patients had a history of hypertension before admission, 3 patients had diabetes and 3 had gout. The most frequent clinical signs were dyspnea (55.2% of all patients), fatigue (78.2%), vomiting (63.2%) and edema (66.1%). The prevalence of hypertension was 64.9%. Glomerulonephritis was found in 42.5% of patients, chronic interstitial nephritis in 16.1%, polycystic kidney disease in 2 cases, congenital renal hypoplasia in 4 cases and unclassified kidney disease in 14.4% of cases. End-stage renal failure was complicated by heart failure in 40.2% of patients, pericarditis in 31.6%, hemorrhage of the gastrointestinal tract in 15% and infections in 22.4%. 47.7% of the patients died following admission.

Our purpose was to evaluate the feasibility of intrapartum fetal pulse oximetry, the distribution of fetal oxygen saturation values, and the relationship with the neonatal outcome in a population with an abnormal fetal heart rate.A prospective multicenter observational study was performed from June 1994 to November 1995. Fetal oxygen saturation was continuously recorded with use of a Nellcor N-400 fetal pulse oximeter in case of an abnormal fetal heart rate during labor. Simultaneous readings of fetal oxygen saturation and fetal blood analysis were obtained at inclusion and before birth. Feasibility, adverse effects, distribution of fetal oxygen saturation values, and relationship with neonatal outcome were assessed.One hundred seventy-four patients were included. From 172 attempted sensor placements, the procedure was impossible in three cases and fetal oxygen saturation values were obtained in 164 cases (95.3%). Physicians considered sensor placement an easier task than an attempt at fetal blood analysis (easy in 87.5% vs 78.9% for fetal blood analysis, p = 0.03). The mean reliable signal time (+/- SD) was 64.7% +/- 32% during the first stage. There were no serious adverse effects in the study population. The mean fetal oxygen saturation during the first stage of labor was 42.2% +/- 8.0% (10th to 90th percentile range 30% to 53%). Fetal oxygen saturation was significantly correlated with scalp pH (r = 0.29, p = 0.01) but not with neonatal umbilical artery pH or gas values. There was a significant association between low fetal oxygen saturation (30%) and poor neonatal condition.The feasibility of fetal pulse oximetry is satisfactory in clinical practice. It is easy to use and provides a fair rate of recorded values, even in a population with suspicion of fetal distress. A low fetal oxygen saturation is significantly associated with an abnormal neonatal outcome.

Our purpose was to compare the predictive value of intrapartum fetal pulse oximetry with that of fetal blood analysis for an abnormal neonatal outcome in case of an abnormal fetal heart rate.A prospective multicenter observational study was conducted from June 1994 to November 1995. Fetal oxygen saturation was continuously recorded with a Nellcor N-400 fetal pulse oximeter in case of an abnormal fetal heart rate during labor. Simultaneous readings of fetal oxygen saturation and fetal blood analysis obtained before birth (i.e., either at full dilatation or before cesarean section when indicated) were compared with the neonatal status. The criteria for an abnormal neonatal outcome were (1) an umbilical arterial blood pHor = 7.15 and (2) a combined variable including 5-minute Apgar scoreor = 7, umbilical arterial pHor = 7.15, secondary respiratory distress, transfer in a neonatal care unit, or neonatal death.At a 7.20 threshold for fetal scalp pH and 30% for fetal oxygen saturation (i.e., the 10th percentile in the study population), the predictive value of fetal pulse oximetry was similar to that of fetal blood analysis for an arterial umbilical pHor = 7.15 and for an abnormal neonatal outcome (positive predictive value 56% vs 55%, negative predictive value 81% vs 82%, sensitivity 29% vs 35%, and specificity 93% vs 91%, respectively). The receiver-operator characteristic curve showed similar performance of either technique for cutoff valuesor = 7.20 for fetal blood pH andor = 30% for fetal oxygen saturation, whereas fetal pulse oximetry became superior at higher thresholds.The predictive value of intrapartum fetal pulse oximetry can be favorably compared with that of fetal blood analysis. Randomized controlled management trials can now be performed to assess potential clinical benefits of this new tool.

This study compares the loop diuretic piretanide 6 mg in a slow-release formulation (PIR) with hydrochlorothiazide 25 mg (HCT) and the fixed combination altizide 15 mg-spironolactone 25 mg (ALT-SP) in hypertension. 1105 mild to moderate hypertensive patients entered a three-week placebo wash-out period; 899 were randomized in a 6-month, double-blind, parallel group treatment phase; 800 completed the study. Primary end-points; serum potassium concentration and quality of life at one month; secondary end-points: ionic, renal and metabolic variables; blood pressure (BP) measurements. HCT and ALT-SP were compared only to PIR using Dunnett's or chi 2 tests.No difference was found for the overall quality of life. No change of serum potassium concentration at one month was found in PIR while small decreases were detected with ALT-SP (-0.1 mM) and HCT (-0.26 mM). Serum creatinine concentration increased significantly in ALT-SP when compared to PIR. All the drugs were effective in reducing BP: HCT had a higher rate of responders than PIR with similar mean BP falls and ALT-SP induced greater falls in blood pressure.PIR proves to be a potent antihypertensive drug without significant effect on serum electrolytes, plasma glucose and lipids. HCT was slightly more potent but induced a fall in serum potassium concentration with a significant risk of hypokalaemia. The addition of SP to ALT led to a more potent diuretic with a higher level of serum potassium and plasma creatinine disturbances.

We designed a short-term randomized controlled study in 12 adult patients with chronic renal failure to assess the metabolic effects of a low-protein diet (LPD) supplemented or not with ketoacids (Cetolog, Clintec Corp., France). Dietary survey included a monthly 3-day food record and a 24-hour urinary urea measurement. After a baseline period (1.11 g protein, 31.7 kcal/kg BW/day), patients reduced their protein intake (PI) to 0.71 g/kg BW/day. Energy intake (EI) was kept constant (31.4 kcal/kg BW/day) during the 3-month period. Baseline plasma lipids did not show overt hyperlipemia. After reducing PI, a significant increase in apolipoprotein AI and the Apo-AI/Apo-B ratio was observed. Plasma Lp(a) levels were elevated at baseline and did not change during the 3-month LPD period. There was no difference between groups receiving ketoacids or not. Thus, in adult chronic renal failure, under a sufficient EI, reducing PI by 40% had a beneficial effect on plasma lipid profile. This improvement in lipid profile might reduce the high cardiovascular risk in these patients.

We report the renal and metabolic effects of a 40 day administration of recombinant human growth hormone in a 31 years old diabetic and GH-deficient patient who underwent a kidney and pancreas transplantation. The data show an increase in glomerular filtration rate, tubular reabsorption of phosphate, and plasma hemoglobin level. Anabolism is suggested from a decrease in serum urea nitrogen and an increase in muscle mass (increase in plasma creatinine). These positive effects might be partly explained by an overcome of endogenous growth hormone resistance when administering pharmacological doses of recombinant growth hormone.

A stress test was performed before (S1) and after a 1-month treatment period (S2) in patients with essential hypertension, randomly allocated to receive either an angiotensin-converting enzyme inhibitor (ACEI), lisinopril (n = 10), or placebo (n = 10). The two groups were similar with regard to systolic and diastolic blood pressure (SBP, DBP), body weight, renal function, and 24-h sodium excretion. At S1, stress induced a significant increase in SBP of 18 +/- 9 mm Hg and in DBP of 10 +/- 6 mm Hg and a significant reduction in sodium excretion from 258 +/- 105 to 204 +/- 72 mumol/min. Stress-induced sympathetic stimulation was assessed by a significant increase in urinary norepinephrine (NE) excretion from 21 +/- 10 to 26 +/- 10 micrograms/g creatinine. One-month treatment by placebo did not change stress-induced BP reactivity, sodium retention, or urinary NE excretion. In the lisinopril group, rest and stress BP were significantly reduced by the treatment. Stress-induced sodium retention was higher after 1-month placebo treatment (72 +/- 78 vs 48 +/- 67 mumol/min), whereas this retention was significantly reduced by lisinopril (13 +/- 27 vs 69 +/- 60 mumol/min).

Thirty-eight cases of Larsen's syndrome in patients living on Reunion Island were analyzed, with an average follow-up of 13 years. Fourteen of these patients died of early complications secondary to dislocation of the cervical spine, tracheomalacias, heart disease, and severe respiratory infection. These children pose a problem of planning early treatment. Clubfeet must be treated conservatively early, and operation should be postponed until after knee deformities are corrected by plaster cast and/or early operation. Unilateral hip dislocations should be treated surgically in the second year of life. Treatment of bilateral hip dislocations is best neglected. Finally, the spinal status of these children must be monitored throughout their life.

Detection of subjects from a multiple endocrine neoplasia type 1 family must rest on clinical, biochemical and radiological data, since study of the genome is unable to detect these subjects. In the new family described here, 6 out of the 14 subjects explored were affected. One had a confirmed pancreatic endocrine tumour and in 3 others a pancreatic endocrine tumour was highly probable, since insulin and glucagon levels, as well as ultrasonic exploration of the pancreas were pathological. Measurements of gastrointestinal hormones gave normal results in all cases. We conclude that to detect this endocrine neoplasia in subjects at risk it seems necessary to measure plasma insulin levels and perform an abdominal ultrasonography.

Massive obesity is defined by a body mass index [weight (kg)/height (m)2] greater than 40. It corresponds to an increase in mortality ratio. Its frequency differs among countries and its incidence is important in USA (13 million subjects), Finland, and South Africa. Obesity is now a serious, emerging problem in developing countries. Frequency of obesity is influenced by age, sex, race and has increased during the last 30 years. Importance of heredity has been highlighted. Recently an increase in superobesity in childhood has been observed, especially in the United States. Finally, besides people with stable obesity throughout their life, there are subjects with weight cycling. These subjects have higher cardio-vascular risks than the others.

Five ulnar palsies with spontaneous improvement, from the medial percutaneous pinning, have been analysed out of thirty two displaced supracondylar fractures of the humerus. These findings allow us to discuss this technique, despite the advantages provided by the mechanical stability of this fixation.