[Outpatient expectations in dermatology consultations: A pilot study]. / Attente des patients consultant un dermatologue «de ville¼: une étude pilote.

BACKGROUND: Understanding patients' expectations with regard to medical care is critical as it guarantees an efficient therapeutic process. Our aim was to determine outpatients' expectations concerning clinical encounters in a dermatology clinic and to study how these matched the opinions of dermatologists regarding them. PATIENTS AND METHODS: Consecutive outpatients consulting in five dermatology centres in the Paris suburbs between February 2013 and March 2013 were prospectively included. For this pilot cross-sectional study, we used two standardized forms to collect data from patients and dermatologists. Patients' answers were compared to those of their dermatologist, and the degree of matching was calculated to assess the ability of dermatologists to accurately identify their patients' expectations. RESULTS: Two hundred and sixty-five patients were included, with a median age of 41 years (interquartile range: 25; 62), of whom 166 were women (65.4%). Patient's principal expectations concerned diagnosis (51.7%) and medication (40.8%), with 32.1% of patients requiring reassurance. The rates of matching between patients' and dermatologists' answers ranged from 33.3% to 65.7% according to the type of expectations. The highest rate concerned expectation with regard to medications, being only 52.6% and 58.8%, respectively for expectations regarding diagnosis and the need for reassurance. CONCLUSION: This study highlights the need for improved identification of outpatient expectations in dermatology consultations.

Familial benign chronic pemphigus and doxycycline: a review of 6 cases.

BACKGROUND: Hailey-Hailey disease (HHD) or familial benign chronic pemphigus is a rare autosomal dominant inherited skin disorder, characterized by flaccid vesicles and erosions on the intertriginous areas. Current treatments are not particularly effective. We report 6 cases dramatically improving with doxycycline. CASE REPORTS: 6 patients, aged from 33 to 77 years old, presented with a variable 4 to 40 year history of severe treatment-resistant HHD. All 6 patients were then treated successfully with doxycycline 100 mg per day for at least 3 months. DISCUSSION: An improvement was observed in all 6 patients from 1 week to 3 months after the beginning of treatment. Relapses were observed after various periods. Maintenance half-dose therapy seemed to be beneficial in patients experiencing recurrence. Only one patient developed gastro-intestinal intolerance. No other side effects were reported. Currently, 2 patients have improved and present a decreased number of exacerbations, 2 others are in complete remission after more than 5 years of follow-up. Treatment efficiency is difficult to evaluate in HHD as it is a rare condition. No controlled studies have been published. Local treatments may improve inflammation but do not treat the underlying cause, targeted systemic therapies exist but there is little evidence supporting their use, physical treatments are cumbersome. Besides their antibiotic potential, tetracycline antibiotics also have anti-inflammatory properties and anticollagenase activity via inhibition of matrix metalloproteinases. CONCLUSIONS: Doxycycline appears to be an interesting therapeutic option in Hailey-Hailey disease.

Training-induced improvement in lipid oxidation in type 2 diabetes mellitus is related to alterations in muscle mitochondrial activity. Effect of endurance training in type 2 diabetes.

AIM: We investigated whether or not, in type 2 diabetic (T2D) patients, an individualized training effect on whole-body lipid oxidation would be associated with changes in muscle oxidative capacity. METHODS: Eleven T2D patients participated in the study. Whole-body lipid oxidation during exercise was assessed by indirect calorimetry during graded exercise. Blood samples for measuring blood glucose and free fatty acids during exercise, and muscle oxidative capacity measured from skeletal muscle biopsy (mitochondrial respiration and citrate synthase activity), were investigated in the patients before and after a 10-week individualized training program targeted at LIPOXmax, corresponding to the power at which the highest rate of lipids is oxidized (lipid oxidation at LIPOXmax). RESULTS: Training induced both a shift to a higher-power intensity of LIPOXmax (+9.1+/-4.2W; P<0.05) and an improvement of lipid oxidation at LIPOXmax (+51.27+/-17.93 mg min(-1); P<0.05). The improvement in lipid oxidation was correlated with training-induced improvement in mitochondrial respiration (r=0.78; P<0.01) and citrate synthase activity (r=0.63; P<0.05). CONCLUSION: This study shows that a moderate training protocol targeted at the LIPOXmax in T2D patients improves their ability to oxidize lipids during exercise, and that this improvement is associated with enhanced muscle oxidative capacity.

[Presenting skin disorders in black Afro-Caribbean patients: a multicentre study conducted in the Paris region]. / Motifs de consultation en dermatologie des sujets de peau noire d'origine africaine et antillaise: enquête multicentrique en région parisienne.

BACKGROUND: There have been few studies in France concerning the specific features of dermatological practice regarding dark skin (Fitzpatrick's phototype V and VI) or the special requirements of black African and Afro-Caribbean patients. AIM: To determine the principal reasons for dermatological consultation among black patients of African or Afro-Caribbean descent in the Paris region. METHODS: This was a prospective clinical study conducted between 15 February and 15 May 2004. The diagnoses of cutaneous conditions leading to dermatological consultation for all black patients of phototype V to VI were recorded by 10 dermatologists practicing in 14 centres within the Paris region. LIMITS: The method used did not allow any conclusions to be drawn regarding the incidence of the presenting conditions among the global population nor did it allow comparison between populations of different phototypes. The absence of any preset list of diagnoses or of precise inclusion criteria regarding evaluation of skin colour left individual investigators with a broad margin of interpretation. RESULTS: In 836 adults and 228 children (half of whom were from Africa and half from the West Indies), diagnoses were as follows: acne in 29.2% of adults and 13.2% in children, and eczema in 6.8% of adults and 27.2% of children. Among dermatoses more specific to black subjects, scalp conditions were frequently seen in both adults (alopecia 7% of diagnoses) and children (tinea capitis 9.6% and alopecia 3.6% of diagnoses). In at least 25% of cases, consultation was associated with dyschromia. Clinical signs suggesting the use of skin lightening products were seen in 95 patients. CONCLUSION: In France, as in other industrialized countries, black patients consult dermatologists essentially for common benign dermatoses also seen amongst white people. Nevertheless, it is important to emphasise the presence of skin problems specific to black patients such as dyschromia and pigmentary disorders, hair and scalp dermatoses, and side effects associated with the use of skin lightening products.

[Late diagnosis of a McArdle disease's case (type V glycogenosis)]. / Diagnostic tardif d'une maladie de McArdle (glycogénose de type V).

McArdle's disease is a metabolic myopathy characterized by a myophosphorylase deficiency resulting in an inability to degrade glycogen stores. We report the case of a 48 years old patient who complained since adolescence of rest and exercise myalgias and presented a chronic increased plasma creatine kinase activity. First, a maximal exercise test was performed. This test demonstrated a quasi lack of rise of respiratory exchange ratio and of blood lactate, possibly due to a glycogenolytic/glycolytic pathway deficiency. Second, a biopsy of vastus lateralis muscle was performed using Bergström needle. As expected, the analysis of mitochondrial function was normal. The in vitro screening test of the glycogenolysis/glycolysis pathway showed a lack of lactate production in presence of glycogen substrate. The study of muscular metabolism of glycogen revealed a glycogen accumulation and a decrease of active and total phosphorylase activities. These data allowed us to diagnose a type V glycogenosis, or McArdle's disease. The patient appeared heterozygous for the most frequent mutation (p.R50X).

Substrate oxidation during exercise: type 2 diabetes is associated with a decrease in lipid oxidation and an earlier shift towards carbohydrate utilization.

OBJECTIVES: Exercise is a recommended treatment for type 2 diabetes but the actual pattern of metabolic adaptation to exercise in this disease is poorly known and not taken in account in the protocols used. Metabolic defects involved in the pathways of substrate oxidation were described in type 2 diabetes. We hypothesized that type 2 diabetes, regardless of age, gender, training status and weight, could influence by its own the balance of substrates at exercise. METHODS: 30 sedentary type 2 diabetic subjects and 38 sedentary matched control subjects were recruited. We used exercise calorimetry to determine lipid and carbohydrate oxidation rates. We calculated two parameters quantifying the balance of substrates induced by increasing exercise intensity: the maximal lipid oxidation point (PLipoxMax) and the Crossover point (COP), intensity from which the part of carbohydrate utilization providing energy becomes predominant on lipid oxidation. RESULTS: Lipid oxidation was lower in the diabetic group, independent of exercise intensity. PLipoxMax and COP were lower in the diabetic group [PLipoxMax=25.3+/-1.4% vs. 36.6+/-1.7% %Wmax (P<0.0001)] - COP =24.2+/-2.2% vs. 38.8+/-1.9% %Wmax (P<0.0001). CONCLUSIONS: Type 2 diabetes is associated with a decrease in lipid oxidation at exercise and a shift towards a predominance of carbohydrate oxidation for exercise intensities lower than in control subjects. Taking into account these alterations could provide a basis for personalizing training intensity.

Relationships between maximal muscle oxidative capacity and blood lactate removal after supramaximal exercise and fatigue indexes in humans.

The present study investigated whether blood lactate removal after supramaximal exercise and fatigue indexes measured during continuous and intermittent supramaximal exercises are related to the maximal muscle oxidative capacity in humans with different training status. Lactate recovery curves were obtained after a 1-min all-out exercise. A biexponential time function was then used to determine the velocity constant of the slow phase (gamma(2)), which denoted the blood lactate removal ability. Fatigue indexes were calculated during all-out (FI(AO)) and repeated 10-s cycling sprints (FI(Sprint)). Biopsies were taken from the vastus lateralis muscle, and maximal ADP-stimulated mitochondrial respiration (V(max)) was evaluated in an oxygraph cell on saponin-permeabilized muscle fibers with pyruvate + malate and glutamate + malate as substrates. Significant relationships were found between gamma(2) and pyruvate + malate V(max) (r = 0.60, P < 0.05), gamma(2) and glutamate + malate V(max) (r = 0.66, P < 0.01), and gamma(2) and citrate synthase activity (r = 0.76, P < 0.01). In addition, gamma(2), glutamate + malate V(max), and pyruvate + malate V(max) were related to FI(AO) (gamma(2) - FI(AO): r = 0.85; P < 0.01; glutamate + malate V(max) - FI(AO): r = 0.70, P < 0.01; and pyruvate + malate V(max) - FI(AO): r = 0.63, P < 0.01) and FI(Sprint) (gamma(2) - FI(Sprint): r = 0.74, P < 0.01; glutamate + malate V(max) - FI(Sprint): r = 0.64, P < 0.01; and pyruvate + malate V(max) - FI(Sprint): r = 0.46, P < 0.01). In conclusion, these results suggested that the maximal muscle oxidative capacity was related to blood lactate removal ability after a 1-min all-out test. Moreover, maximal muscle oxidative capacity and blood lactate removal ability were associated with the delay in the fatigue observed during continuous and intermittent supramaximal exercises in well-trained subjects.

Large changes in Pluto's atmosphere as revealed by recent stellar occultations.

Pluto's tenuous nitrogen atmosphere was first detected by the imprint left on the light curve of a star that was occulted by the planet in 1985 (ref. 1), and studied more extensively during a second occultation event in 1988 (refs 2-6). These events are, however, quite rare and Pluto's atmosphere remains poorly understood, as in particular the planet has not yet been visited by a spacecraft. Here we report data from the first occultations by Pluto since 1988. We find that, during the intervening 14 years, there seems to have been a doubling of the atmospheric pressure, a probable seasonal effect on Pluto.

[Cosmetic use of skin depigmentation products in Africa]. / L'utilisation cosmétique de produits dépigmentants en Afrique.

The use of skin lightening products represents a real social phenomenon in many Sub-Saharan African countries. A few studies have been published on this subjects. An important proportion of the adult female population, estimated between 25 and 67% uses regularly and daily these creams. Today the products used are mainly dermocorticosteroids and hydroquinone. Their use over a long period of time is responsible for many cutaneous side effects mainly acne, pigmentary disorders, stretch marks and cutaneous infections. Systemic side effects have recently been reported, mainly related to the use of corticosteroids. The necessary control of the products by the local health authorities remains difficult.

Does growth hormone treatment alter skeletal muscle mitochondrial respiration in rats?

OBJECTIVE: Growth hormone (GH) has been shown to stimulate lipolysis and enhance lipid oxidation. We investigated whether GH could improve mitochondrial oxidative capacity. METHOD: Fourteen male Wistar rats received 14-day treatment with biosynthetic human GH (10 IU/kg/24 h) or placebo. Mitochondria were isolated from the total muscle of one hind limb of the rat. Mitochondrial oxygen consumption was measured in vitro using a Clark-type electrode with three substrates: palmitoyl-L-carnitine, pyruvate and succinate (+ rotenone). RESULTS: Muscle mitochondrial yield was not significantly different in the GH-treated group from that in controls. Neither the basal nor ADP-stimulated respiratory state reached a significant difference between the 2 groups with palmitoyl-L-carnitine, pyruvate, and succinate. CONCLUSION: GH treatment did not improve the oxidative capacity of skeletal muscle mitochondria.

Simplified measurement of insulin sensitivity with the minimal model procedure in type 2 diabetic patients without measurement of insulinemia.

This study aimed to evaluate a simplified minimal model protocol for measuring insulin sensitivity in mild and severe type 2 diabetes, considering that changes in serum insulin during an insulin-modified intravenous glucose tolerance test almost only reflect the insulin injection. Two groups of diabetics treated with high doses of antidiabetic agents were recruited. Mean insulin responses were calculated in group 1 (n = 30). In group 2 (n = 38), we compared insulin sensitivity (SI) obtained with reference protocol with SI calculated by a minimal model procedure including the theoretical average insulin profile determined in group 1, and with Homeostasis Model Assessment (HOMA-R). Additionally, the cost of each procedure was calculated. SI measured by the reference method strongly correlated with SI determined by the simplified protocol (r = 0.966, p < 0.0001), while no correlation was found with HOMA-R (r = - 0.349, NS). Reduction of cost for HOMA-R and simplified minimal model procedure were - 92 and - 81 %, respectively. This simplified and relative inexpensive protocol, using minimal model procedure without insulin measurement, accurately measures SI regardless of beta-cell defect degree. This approach could be of interest when limits of validity of simple indexes are reached.

Impaired sarcolemmal vesicle lactate uptake and skeletal muscle MCT1 and MCT4 expression in obese Zucker rats.

The present experiments were undertaken to characterize 1) the hindlimb muscle mass lactate uptake and 2) the expression of monocarboxylate transporter isoforms MCT1 and MCT4, as well as lactate dehydrogenase (LDH) isozyme distribution, in various skeletal muscles of Zucker fa/fa rats taken as a model of insulin resistance-related obesity. Initial lactate uptake at six different concentrations was measured in sarcolemmal vesicles (SV) by use of L-[U-(14)C]lactate. Compared with controls, the maximal rate of lactate uptake and affinity were decreased in SV of Zucker rats (approximately 30%) in which MCT4 content was significantly decreased (P < 0.05). MCT4 expression was decreased in soleus, extensor digitorum longus, and red tibialis anterior (RTA; P < 0.05), but not in white tibialis anterior, whereas MCT1 expression was decreased only in RTA of Zucker rats (P < 0.05). Obesity led to a shift toward type M-LDH isozyme in mixed muscles. We conclude that obesity leads to changes in muscular MCT1 and MCT4 expression, which, when associated with LDH isozyme redistribution, may contribute to the hyperlactatemia noted in insulin resistance.

Balance of substrate oxidation during submaximal exercise in lean and obese people.

OBJECTIVES: To compare fat and carbohydrate oxidation at different exercise intensities between overweight and normal-weight subjects, in order to analyze the influence of muscular metabolic abnormalities in obese people on substrate utilization during exercise. MATERIAL AND METHODS: 32 healthy sedentary overweight subjects (Body Mass Index (BMI): 30.8 +/- 0.8 kg/m(2); body fat: 37.4 +/- 1.1%; mean +/- SEM) and 26 controls (BMI: 23 +/- 0.4 kg/m(2); body fat: 22.7 +/- 1.1%) matched for age and sex were examined. The test consisted in four six-min. submaximal steady-state workloads with calculation of substrate oxidation rates and derived quantitative parameters, i.e., crossover point (defined as the power at which carbohydrate-derived energy becomes predominant) and maximal fat oxidation rate point. In addition, the accuracy of the test was analyzed and was found to be satisfactory. RESULTS: While exercise intensities were similar in both group, fat oxidation rates were significantly lower in overweight group (p<0.05). The crossover and the maximal fat oxidation rate points were significantly lower in overweight subjects than in controls: 33.3 +/- 2 vs 50.1 +/- 3.4% and 30.5 +/- 2.3 vs 44.6 +/- 3.3% of maximal aerobic power, respectively (p<0.001). CONCLUSION: Sedentary overweight subjects, compared to controls at the same exercise intensities, exhibited an alteration of the balance of substrate oxidation, reflected by lower rates of fat oxidation and a shift of quantitative parameters to lower intensities. The test appeared to be reliable and could be of interest to advise an individualized exercise prescription in obese people.

[Depigmentation for cosmetic purposes: prevalence and side-effects in a female population in Senegal]. / Dépigmentation cutanée à visée cosmétique.

BACKGROUND: Use of depigmenting agents by black women for cosmetic purposes is a long-standing practice. Most depigmenting agents contain topical steroids and hydroquinone. The purpose of this study was to clarify prevalence data on use of depigmenting agents in a female population in Senegal and to report the incidence and main features of adverse skin reactions in addition to possible associations with diabetes, hypertension and renal insufficiency. PATIENTS AND METHODS: A cross-sectional study was made in a representative sample of 147 hospitalized women aged from 15 to 60 years. The incidence of adverse skin reactions, diabetes, hypertension and serum creatinine in 41 women admitting use of depigmenting agents was compared to those found in 85 women who maintained they had never used depigmenting agents. Two patients who refused to participate in the study and 19 others who did use depigmenting products and had stopped their use for at least 3 months were excluded from the analysis. RESULTS: The prevalence of use of depigmenting agents was 27.9% (47/147). Adverse skin reactions were significantly more frequent among these patients. Effects observed were similar to those reported for prolonged use of topical steroids but also included periorbitary dyschromia, exogenous ochronosis, infectious dermatosis, and, in particular, extended dermatophytosis and necrotizing cellulitis, contact eczema, and certain hyperpigmentation when depigmenting agents were discontinued. Presence of relative hyperpigmentation of the dorsal phalanges identified use of depigmenting agents with a 100% specificity. Prevalence of diabetes and hypertension was significantly higher among the group of women using depigmenting agents (46.3% and 8.2%, versus 34.1% and 8.2% respectively). There was no difference for renal insufficiency. The risk increased independently of age depending on whether duration of use was less than 10 years or not with a relative risk that rose from 3.63 (1.2-10.47) to 6.47 (3.41-12.32) for diabetes and from 1.34 (0.45-3.96) to 2.65 (1.27-5.51) for hypertension, clearly suggesting a possible dose effect. DISCUSSION: The prevalence of use of depigmenting agents in this first published hospital series confirms the widespread nature of this phenomenon in Senegal. While certain patent skin signs are similar to those described in the literature, and excluding specific features related to the hospital setting, this is the first report of a dose-effect between use of depigmentation agents and diabetes and hypertension, probably via the effect of topical steroids.

Streptozotocin-induced diabetes decreases rat sarcolemmal lactate transport.

Impaired lactate metabolism is a metabolic disorder, which is not fully understood in the diabetic state including streptozotocin (STZ)-induced diabetes. We investigated whether STZ-induced diabetes results in altered lactate exchanges using the rat muscle sarcolemmal vesicles (SV) model. Fifteen days after diabetes onset (1 STZ-injection, 65 mg/kg, intraperitoneal [IP]), rats had higher blood and muscle lactate concentrations compared with normal rats (1.50 +/- 0.09 v 1.95 +/- 0.21 mmol/L (not significant [NS]) and 21.02 +/- 1.26 v 25.53 +/- 0.98 mmol/kg wet weight (ww); P < .05). The initial rate of lactate uptake was measured at various external lactate concentrations using SV of both group in zero-trans conditions. STZ-induced diabetes decreased the initial rate of total lactate influx at external lactate concentrations from 1 to 100 mmol/L (P < .05). This decrease in lactate transport was found in addition to an increased free radical production, as indicated by a significant increase in malonedialdehyde (MDA) concentration (64.3 +/- 8.7 v 100.3 +/- 13.5 nmol. g(-1) ww, P < .05), coupled with a higher glutathione peroxidase (Gpx) activity (48.03 +/- 3.13 v 84.7 +/- 15.01 micromol. min(-1). mg(-1) protein, P < .05) in red gastrocnemius. We concluded that STZ-induced diabetes decreases total lactate transport activity in rat SV and is associated with increased muscular oxidative stress.

Insulin resistance and associated metabolic abnormalities in muscle: effects of exercise.

Skeletal muscle is a major site of insulin resistance. In addition to glucose transport, oxidative disposal and storage defects, insulin resistant muscle exhibit many other metabolic abnormalities. After a brief review of insulin resistance determinants, we will focus on muscular abnormalities in obesity and type 2 diabetes. Glucose and lipid metabolism defects will be analysed and their interactions discussed. Exercise can improve many of these muscular abnormalities and the mechanisms underlying exercise-induced benefits have been clarified during the past decades. Therefore, exercise training has proved to be useful in the management of insulin resistant states, i.e. mainly obesity, especially in its truncal distribution, and type 2 diabetes. However, exercise prescription remains poorly codified, and results on glycaemic control are sometimes conflicting. In the last part of this review, we will emphasize the pathophysiological basis for an individualized exercise prescription in insulin resistant subjects.

Multivariate analysis of relationships between insulin sensitivity and blood rheology: is plasma viscosity a marker of insulin resistance?

We previously reported in populations exhibiting all the spectrum of insulin sensitivity (SI) values correlations between SI and blood viscosity eta suggesting that high eta is an additional symptom of the insulin resistance syndrome. However, due to the elevation of insulinemia (I) which is usually associated with insulin resistance it remained to determine whether this relationship was explained by SI or I. We analyzed SI with the minimal model procedure in 108 nondiabetic subjects and analyzed correlations of SI with blood rheology (eta, RBC aggregation and rigidity). Across quartiles of SI (defined after log transformation since distribution of SI was not normal), hematocrit and red cell rigidity remained stable, while aggregability and plasma viscosity (etap) increased in the lowest quartile. SI was correlated to only two rheological parameters: etap (r= -0.280, p=0.005) and Myrenne index M1 (r= -0.219, p=0.044). Among SI, I, age and BMI multivariate analysis selected only BMI as a determinant of either whole blood viscosity (etawb: r= -0.301, p=0.004) and RBC disaggregation threshold (gammaD: r= -0.331, p=0.013), only I as determinant of M1 (r=0.254, p=0.03), and a combination of BMI (p=0.009) and SI (p=0.007) for etap. Although age and obesity are factors of hyperviscosity, the hemorheological disturbances found in insulin resistance are not fully statistically "explained" by those two factors. While hyperaggregability (measured with M1) is rather related to hyperinsulinism, etap is influenced by SI and should be further investigated as a simple marker for the follow up of insulin-resistant states.