Derepression of glomerular filtration, renal blood flow and antioxidant defence in patients with type 2 diabetes at high-risk of cardiorenal disease.

BACKGROUND: The role of antioxidant status on microvascular blood flow and glomerular filtration (eGFR) in patients with type 2 diabetes and hypertension whose risk of progressive renal disease varies by ethnicity is unknown. METHODS: Adult, non-Caucasian (n = 101) and Caucasian (n = 69) patients with type 2 diabetes, hypertension and/or microalbuminuria and an eGFR > 45 mL/min/1.73 m2 were randomised to receive 400 IU vitamin E and/or 20 µg selenium daily or matching placebo. eGFR (CKD-EPI) was measured at baseline, 3,6 and 12 months and renal blood flow by contrast-enhanced ultrasonography in a sub-group (n = 9) at baseline and 3 months by assessing the area under the time intensity curve (TIC). Circulating glutathione peroxidase 3 (GPx-3) activity was measured as a biomarker of oxidative defence status. RESULTS: The time to change in eGFR was shortest with combined vitamin E and selenium than usual care (5.6 [4.0-7.0] vs 8.9 [6.8-10.9 months]; p = 0.006). Area under the TIC was reduced compared to baseline (38.52 [22.41-90.49] vs 123 [86.98-367.03]dB.s; P ≤ 0.05 and 347 [175.88-654.92] vs 928.03 [448.45-1683]dB.s; P ≤ 0.05, respectively] at 3 months suggesting an increase in rate of perfusion. The proportional change in eGFR at 12 months was greater in the group whose GPx-3 activity was above, compared with those below the cohort median (360 U/L) in the non-Caucasian and the Caucasian groups (19.1(12.5-25.7] % vs 6.5[-3.5 to 16.5] % and 12.8 [0.7 to 24] % vs 0.2 [-6.1 to 6.5] %). CONCLUSION: In these patients with type 2 diabetes and early CKD, antioxidant treatment derepresses renal blood flow and a rise in eGFR correlated directly with GPx-3 activity. SIGNIFICANCE: Diabetes mellitus is the world's leading cause of end-stage renal disease which has a predilection for black and minor ethnic groups compared with Caucasians. The differences in risk despite the benefits of conventional care may be related to oxidative stress. We found that glomerular filtration and renal blood flow is suppressed when renal function is preserved in high-risk patients with type 2 diabetes. Conventional care supplemented with selenium - the co-factor for glutathione peroxidase-3 (GPx-3) - improves renal perfusion and increase glomerular filtration according to host antioxidant defence determined by GPx-3 activity. Circulating GPx-3 activity warrants further investigation as a novel biomarker of reversible haemodynamic changes in early diabetic kidney disease to better enable targeting of renoprotective strategies.

Photographic smile tracking: Evidence of asymmetric crying faces over time improvement: Case report.

INTRODUCTION: Congenital hypoplasia of the depressor anguli oris muscle is a rare mimic disorder depicted by a lower lip asymmetry apparent when laughing or crying. PRESENTATION OF CASE: A 10-year-old boy consulted our department for an asymmetry when opening his mouth. According to the family, this asymmetry was present since birth. Perinatal characteristics and childhood medical history were investigated with no abnormalities. Physical exam revealed an inability to draw down the right lower lip unilaterally. At rest position, facial asymmetry was not noticeable. Several investigations were done: A CT scan of the petrous part of the temporal bone, an MRI of soft tissues, an electromyography and a heart ultrasound. No anomalies were found. DISCUSSION: This condition has stimulated great interest because of its potential association with congenital anomalies but also in order to reassure families often worried by the situation. A large therapeutic armamentarium is described in literature. CONCLUSION: Among the large armamentarium of therapeutic options, we opted for a wait and see strategy through photographic smile tracking leading to an evidence of Asymmetric crying faces over time improvement.

Sex Differences in Glutathione Peroxidase Activity and Central Obesity in Patients with Type 2 Diabetes at High Risk of Cardio-Renal Disease.

Women with type 2 diabetes (T2DM) have an increased susceptibility of developing cardio-renal disease compared to men, the reasons and the mechanisms of this vulnerability are unclear. Since oxidative stress plays a key role in the development of cardio-renal disease, we investigated the relationship between sex, plasma antioxidants status (glutathione peroxidase (GPx-3 activity), vitamin E and selenium), and adiposity in patients with T2DM at high risk of cardio-renal disease. Women compared to men had higher GPx-3 activity (p = 0.02), bio-impedance (p ≤ 0.0001), and an increase in waist circumference in relation to recommended cut off-points (p = 0.0001). Waist circumference and BMI were negatively correlated with GPx-3 activity (p ≤ 0.05 and p ≤ 0.01, respectively) and selenium concentration (p ≤ 0.01 and p ≤ 0.02, respectively). In multiple regression analysis, waist circumference and sex were independent predictors of GPx-3 activity (p ≤ 0.05 and p ≤ 0.05, respectively). The data suggest that increased central fat deposits are associated with reduced plasma antioxidants which could contribute to the future risk of cardio-renal disease. The increased GPx-3 activity in women could represent a preserved response to the disproportionate increase in visceral fat. Future studies should be aimed at evaluating if the modulation of GPx-3 activity reduces cardio-renal risk in men and women with T2DM.

Lipopolysaccharide-Induced VEGF Production and Ambient Oxidative Stress in Type 2 Diabetes.

Context: Oxidative stress is implicated in the development of vascular disease and is associated with an upregulation of vascular endothelial growth factor (VEGF), which is pathogenetically linked to the microvascular complications of diabetes. Patients of African origin have an increased susceptibility to microvascular kidney disease compared with white patients; the reasons and mechanisms that contribute to this vulnerability are unclear. Objectives: To investigate whether there are ethnic differences in lipopolysaccharide-induced monocyte VEGF production in whole blood cell cultures. In addition, to assess whether stimulated VEGF production is related to prevailing oxidative stress assessed by plasma lipid hydroperoxides (LOOHs) and α-tocopherol. Design and Setting: Cross-sectional study at a secondary care center in North London, United Kingdom, serving an inner-city community of 154,000 adults. Patients: African-Caribbean and white patients with type 2 diabetes mellitus [(T2DM); n = 52]. Results: Lipopolysaccharide-induced production of VEGF in whole blood cultures [61.8 (31.9) pg/mL to 78.4 (6.0) pg/mL; P < 0.001] correlated positively with LOOH levels (r = 0.3, P = 0.04) and was significantly higher in African-Caribbean than white patients with T2DM [404 (207.5) vs 268.8 (137.0)] pg/mL ×109/L monocytes; P = 0.018]. Plasma α-tocopherol concentration was higher in Caucasian (white) patients [40.3 (18.3) vs 30.0 (9.6)] µmol/L; P = 0.04] compared with African-Caribbean patients. Conclusions: This study suggests that the redox environment influences VEGF production in response to proinflammatory stimuli in T2DM. The differential responsiveness by ethnic origin may be of relevance in the variations in susceptibility to the long-term microvascular complications.

Residual renal and cardiovascular disease risk in conventionally-treated patients with type 2 diabetes: the potential of non-traditional biomarkers.

Diabetes is a leading cause of chronic kidney disease (CKD) in the developed world. Promoters of the progression of kidney disease include the traditional profile of cardiovascular risk factors. However, the development of CKD and vulnerability to end-stage renal disease (ESRD) is highly variable. Determinants of the susceptibility to ESRD may include non-traditional risk factors such as gene-environment interactions, socio-geographic factors and/or treatment strategies. We review the conflicting clinical relevance of studies implicating pathways related to oxidative stress. These pathways are strongly implicated in the phenotype of some groups of high-risk patients and could assume importance in clinical care. Recent clinical trial evidence has shown that newer glucose-lowering agents also have beneficial effects on reducing the incidence of renal dysfunction and cardiovascular events in high-risk patients. Research is required to identify which patients will benefit most from newer approaches to managing diabetes. Understanding the relationship of non-traditional risk factors to renal and cardiovascular disease could help clinicians targeting new therapeutic approaches in the management of type 2 diabetes.

Ethnic differences in the +405 and -460 vascular endothelial growth factor polymorphisms and peripheral neuropathy in patients with diabetes residing in a North London, community in the United Kingdom.

BACKGROUND: There are marked ethnic differences in the susceptibility to the long-term diabetic vascular complications including sensory neuropathy. The vascular endothelial growth factor (VEGF) +405 (C/G) and -460 (T/C) polymorphisms are associated with retinopathy and possibly with nephropathy, however no information is available on their relationship with peripheral neuropathy. Therefore, we examined the prevalence of these VEGF genotypes in a multi-ethnic cohort of patients with diabetes and their relationship with evident peripheral diabetic neuropathy. METHODS: In the current investigation, we studied 313 patients with diabetes mellitus of African-Caribbean, Indo-Asian and Caucasian ethnic origin residing in an inner-city community in London, United Kingdom attending a single secondary care centre. Genotyping was performed for the VEGF +405 and VEGF -460 polymorphisms using a pyrosequencing technique. RESULTS: Forty-nine patients (15.6%) had clinical evidence of peripheral neuropathy. Compared to Caucasian patients, African-Caribbean and Indo-Asian patients had lower incidence of neuropathy (24.6%, 14.28%, 6.7%, respectively; P = 0.04). The frequency of the VEGF +405 GG genotype was more common in Indo-Asian patients compared to African-Caribbean and Caucasian patients (67.5%, 45.3%, 38.4%, respectively; p ≤ 0.02). The G allele was more common in patients with type 2 diabetes of Indo-Asian origin compared to African-Caribbean and Caucasian origin (p ≤ 0.02). There was no difference between the ethnic groups in VEGF -460 genotypes. The distributions of the VEGF +405 and VEGF -460 genotypes were similar between the diabetic patients with and without neuropathy. CONCLUSIONS: In this cohort of patients, VEGF +405 and VEGF -460 polymorphisms were not associated with evident diabetic peripheral neuropathy, however an association was found between VEGF +405 genotypes and Indo-Asian which might have relevance to their lower rates of ulceration and amputation. This finding highlights the need for further investigation of any possible relationship between VEGF genotype, circulating VEGF concentrations and differential vulnerability to peripheral neuropathy amongst diabetic patients of different ethnic backgrounds.

Sex differences in vascular stiffness and relationship to the risk of renal functional decline in patients with type 2 diabetes.

BACKGROUND: Recent data suggest that the higher risk of end-stage renal disease in women compared with men is associated with waist circumference. We investigated whether vascular stiffness which is linked to visceral fat accumulation is gender specific and associated with a loss in renal function. METHODS: We studied 166 patients with type 2 diabetes at high risk of progressive renal disease. A vascular stiffness index was derived from measurement of the peripheral arterial pulse waveform using infrared finger photoplethysmography. Multiple regression analysis was used to examine the relationship between vascular stiffness and traditional clinical and biochemical renal disease risk factors. RESULTS: Women were of similar mean (standard deviation) age [61.6 (6.8) vs 60.0 (8.3) years; p = 0.444] and duration of diabetes [9.8 (7.2) vs 10.9 (8.1) years; p = 0.885] compared to men. Waist circumference was significantly associated with vascular stiffness [regression coefficient B = 0.15 (95% confidence interval: 0.06-2.24); p = 0.001]. There was a negative slope parameter for the relationship between glomerular filtration rate and vascular stiffness [ B = -0.15 (95% confidence interval: -0.22 to -0.09); p < 0.001] in women only. CONCLUSION: In this cohort, early renal functional decline in women is linked to increased vascular stiffness which may be associated with visceral fat accumulation as determined by waist circumference.

Modulation of endogenous antioxidant defense and the progression of kidney disease in multi-heritage groups of patients with type 2 diabetes: PRospective EValuation of Early Nephropathy and its Treatment (PREVENT).

BACKGROUND: Diabetes is the western world's leading cause of end-stage renal disease. Glucose-dependent, oxidative stress is linked to the development of renal inflammation and sclerosis, which, in animal models of diabetes, can be prevented by anti-oxidative treatment. Patients of non-Caucasian heritage have low activity of the selenoprotein, antioxidant enzyme, glutathione peroxidase (GPx) and its co-factor vitamin E, which may be linked to their increased propensity to developing end-stage renal disease. RESEARCH DESIGN AND METHODS: We have designed a double-blind, randomized, placebo controlled study with selenium and/or vitamin E versus placebo as the interventions for patients with type 2 diabetes and chronic kidney disease (CKD) stages 1-3. A 2 × 2 factorial design will allow a balanced representation of the heritage groups exposed to each intervention. The primary biochemical outcome is change in GPx activity, and clinical outcome measure is the actual, rate of-and/or percentage change in estimated glomerular filtration rate (eGFR) from baseline. Analysis will be with a marginal model for longitudinal data using Generalized Estimating Equations corrected for measures of baseline serum antioxidant enzyme activities (GPx, superoxide dismutase and catalase), micronutrient levels (vitamins E and C), measures of inflammation (interleukin 6, c-reactive protein and monocyte chemoattractant protein-1) and markers of oxidative damage (plasma 8-isoprostaglandin F2α and urinary 8-hydroxydeoxyguanosine). EXPECTED RESULTS: The study will assess the relationship between GPx activity, oxidative stress, inflammation and eGFR. It will test the null hypothesis that antioxidant therapy does not influence the activity of GPx or other antioxidant enzymes and/or alter the rate of change in eGFR in these patient groups. CONCLUSIONS: Outcome data on the effect of antioxidants in human diabetic renal disease is limited. Previous post hoc analyses have not shown a beneficial effect of vitamin E on renal function. A recent trial of a pharmaceutical antioxidant agent, improved eGFR, but in patients with advanced diabetes-related chronic kidney disease its use was associated with an increased incidence of cardiovascular events. We will explore whether the nutritional antioxidants, vitamin E and selenium alone, or in combination in patients at high risk of renal disease progression, forestalls a reduction in eGFR. The study will describe whether endogenous antioxidant enzyme defenses can be safely modified by this intervention and how this is associated with changes in markers of oxidative stress. Trial registration ISRCTN 97358113. Registered 21st September 2009.

Mobile telemonitoring for achieving tighter targets of blood pressure control in patients with complicated diabetes: a pilot study.

BACKGROUND: Hypertension is a major risk factor for the long-term complications of diabetes. Mobile, self-measurement of blood pressure is emerging as a method to manage blood pressure in general, but its impact in patients with diabetes is unclear. METHODS: We randomized 137 patients with diabetes and hypertension to either mobile telemonitoring (n = 72) or usual care (n = 65). Clinic blood pressure was recorded at baseline and after 6 months. Patients in the intervention arm transmitted weekly blood pressure readings wirelessly, using adapted sensors via mobile phones to a central server. Clinicians received the data in real-time and using a web-based application provided management advice to the patient and their physicians. RESULTS: Systolic blood pressure fell significantly in the patients in the intervention group (mean [95% confidence interval], -6.5 [-0.8 to -12.2] mm Hg; P = 0.027) and remained unchanged in the control group (2.1 [9.3 to -5.0] mm Hg; P = 0.57). Patients within the intervention arm of African origin seemed to benefit more from the intervention. In addition, those who achieved a systolic blood pressure of <120 mm Hg had lower average blood sugars than those with higher readings (7.8 [SD 1.6] vs. 8.9 [SD 2.2] mmol/L; P = 0.02). CONCLUSIONS: In patients with diabetes, mobile telemonitoring has potential for delivering intensified care to improve blood pressure control, and its use may be associated with reduced exposure to hyperglycemia.

[Experience of a multidisciplinary team in the management of superficial venous malformations: 99 cases]. / Les malformations veineuses superficielles et leur prise en charge par un comite multidisciplinaire: 99 cas.

BACKGROUND: Vascular malformations are heterogenous angiodysplasias. AIM: The aim of this work is to study the epidemiological and clinical features of venous malformations (VM) as well as their multidisciplinary management. METHODS: It is a retrospective study of patients having simple VM, seen at the multidisciplinary consultation of angiodysplasias of our hospital, over a 10 year period. RESULTS: This study included 99 patients having VM. A female predominance was noticed. Average age was 18.5 years. VM had mainly cephalic location. All VM were treated with percutaneous sclerotherapy. Aesthetic results were excellent in the cases of small VM size. CONCLUSION: VM are most frequent in cephalic region and cause aesthetic and functional handicaps. Percutaneous sclerotherapy is the treatment of choice for such a venous malformations, especially for small VM. VM are anomalies which can have serious complications. Their management has to be multidisciplinary in order to better precise the diagnosis and to take the adequate therapeutic decision.

Evaluation of a mobile phone telemonitoring system for glycaemic control in patients with diabetes.

We conducted a randomized controlled trial using mobile health technology in an ethnically diverse sample of 137 patients with complicated diabetes. Patients in the intervention group (n = 72) were trained to measure their blood glucose with a sensor which transmitted the readings to a mobile phone via a Bluetooth wireless link. Clinicians were then able to examine and respond to the readings which were viewed with a web-based application. Patients in the control arm of the study (n = 65) did not transmit their readings and received care with their usual doctor in the outpatient and/or primary care setting. The mean follow-up period was 9 months in each group. The default rate was higher in the patients in the intervention arm due to technical problems. In an intention-to-treat analysis there were no differences in HbA(1c) between the intervention and control groups. In a sub-group analysis of the patients who completed the study, the telemonitoring group had a lower HbA(1c) than those in the control group: 7.76% and 8.40%, respectively (P = 0.06).

Nitric oxide bioavailability and its potential relevance to the variation in susceptibility to the renal and vascular complications in patients with type 2 diabetes.

OBJECTIVE: We compared the renal and systemic vascular (renovascular) response to a reduction of bioavailable nitric oxide (NO) in type 2 diabetic patients without nephropathy and of African and Caucasian heritage. RESEARCH DESIGN AND METHODS: Under euglycemic conditions, renal blood flow was determined by a constant infusion of paraminohippurate and changes in blood pressure and renal vascular resistance estimated before and after an infusion of L-Ng-monomethyl-L-arginine. RESULTS: In the African-heritage group, there was a significant fall in renal blood flow (Delta-46.0 ml/min per 1.73 m(2); P < 0.05) and rise in systolic blood pressure (Delta 10.0 mmHg [95% CI 2.3-17.9]; P = 0.017), which correlated with an increase in renal vascular resistance (r(2) = 0.77; P = 0.004). CONCLUSIONS: The renal vasoconstrictive response associated with NO synthase inhibition in this study may be of relevance to the observed vulnerability to renal injury in patients of African heritage.

B-cell lymphoma of the mandible: a case report.

INTRODUCTION: The mandible is an infrequent localisation of primary osseous non-Hodgkin's lymphomas. Few cases of mandibular non-Hodgkin's lymphomas (NHL) have been reported. CASE REPORT: A rare condition of primary malignant non-Hodgkin's lymphoma of the mandible in 53-year-old man, was reported at the Department of Maxillofacial and Plastic Surgery in Charles Nicolle Hospital (Tunis, Tunisia). Histologic and Immunohistochemical (IHC) examination Confirmed a B-Cell lymphoma. DISCUSSION: The purpose of this report is to describe this rare case of NHL of the mandible, explore the diagnosis and workup, and discuss treatment strategies. In this localisation, neither the clinical features nor the radiologic appearances are often pathognomonic. CONCLUSION: Particular care must be taken to consider lymphoma in the differential diagnosis because this uncommon lesion can pose significant diagnostic problems and is frequently misdiagnosed.

[Place of the precocious surgical treatment in facial hemangioma]. / Place du traitement chirurgical précoce dans les hémangiomes périorificiels de la face.

Infantile cutaneous hemangioma is a benign vascular tumour present at 10% of the infants. It forms part of the group of the vascular tumours in the classification of international society for vascular anomalies (ISSVA). Usual surgical attitude is abstention and surgery is proposed only in order to treat sequelae. But some particular situations require early surgery to avoid functional impairment, deformation or growth delay due to the lesion's development. Using our observations, we recall the epidemiology, the physiopathology, the clinical aspects, the particularities of the facial localizations and their treatments. In these localizations the time intervenes like a fourth dimension that is going to modify, to improve or to aggravate the prognosis. Treatment requires a strategy and precocious surgery. We insist on the fact that the dogma of the therapeutic abstention remained true for a majority of children with small size hemangioma and that a precocious surgery must be proposed for some localizations in the face.

Circulating cholesterol as a modulator of risk for renal injury in patients with type 2 diabetes.

Amelioration of albuminuria may be related to specific constellations of risk factors including race and dyslipidaemia. Circulating cholesterol could mitigate the beneficial effect of antihypertensive therapy. We assessed whether cholesterol affected the remission of urinary albumin in patients with type 2 diabetes of white, Caucasian and non-white origin. We studied 100 patients (African and Asian: n=57 and Caucasian: n=43) with type 2 diabetes and newly diagnosed microalbuminuria who received intensified and structured care for a median (IQ range) of 41 (32-48) months. Microalbuminuria remitted in 20% and progressed in 12% of patients. In those with uncontrolled systolic hypertension (>140 mmHg) systolic blood pressure fell by a mean (95% CI) of -9.4 (-3.8 to -15.11)mmHg; p=0.002. The change in urinary albumin excretion with time varied inversely with baseline systolic blood pressure (r=-0.25; p=0.04). At 3 years follow-up the decrement in blood pressure was significant for those patients in the regression group (-19.6[16.8]mmHg; p=0.005). In patients of African origin, systolic blood pressure was higher than in the other groups and correlated with cholesterol concentrations (r=0.44; p=0.04). Baseline systolic blood pressure and total cholesterol (odds ratio [95%CI]) were independent determinants of remission and progression of microalbuminuria (1.04[1.006-1.064]; p=0.02 and 1.75[1.03-2.95]; p=0.04). Patients with higher total cholesterol and baseline urinary albumin excretion were less likely to go into remission. Blood pressure correlated with cholesterol concentrations in patients of African origin. Specific cholesterol lowering strategies may benefit certain patients groups at high risk of renal disease.

[Arteriovenous malformations: study about 54 patients]. / Malformations arterioveineuses: etude de 54 patients.

BACKGROUND: Arteriovenous malformation (AVM) are vascular anomalies that may threaten functional and vital prognosis. The aim of this study was to assess the managment of Arteriovenous malformation METHODS: It is a retrospective study about 54 patients, having AVM, collected over a 7-year period. RESULTS: Sex ratio MJF was 1.25; average age at the diagnosis was 25.4 years. Puberty, pregnancy and trauma, were the most important favoring factors for the development of AVM. Location was the head in 75% of the cases. Doppler ultrasound was the most indicated examination to confirm the diagnosis. In over than 70% of our patients, therapeutic abstention and follow-up were indicated. In the other cases, embolization, with or without surgery was the treatment. A patient died of massive haemorrhage. Treatment is necessary in complicated AVM. Follow-up (if abstention or after treatment) is mainly based on clinical and Doppler data. CONCLUSIONS: AVM are anomalies that may be serious and their management must be multidisciplinary, to allow better therapeutic indications.