Cutaneous leishmaniasis in Ouazzane and Sidi Kacem provinces, Morocco (1997-2012).

Cutaneous leishmaniasis (CL) is a major public health problem in Morocco. Three distinct parasites are involved; Leishmania tropica, Leishmania major and Leishmania infantum. The objective of this study is to investigate the epidemiological and the clinical features of endemic foci of CL in Sidi Kacem and Ouazzane provinces in the north of Morocco including molecular identification of parasites. We studied the evolution and the distribution of 1,656 CL cases coming from 39 sectors in these provinces between 1997 and 2012. The causative agents of CL in these areas were identified by using the ITS1-PCR-RFLP method. A tendency of seasonality in incidence was observed, showing a peak in April. Most infected patients were from Ouazzane province. The patients' ages ranged from 6 months to 85 years; 54% of them were females. The highest rate lesions were found in the age group of 9 years or less and most lesions were localized in the face (79.6%). The movement of populations from neighboring endemic areas and establishment of habitation in areas where housing conditions are unfavorable favored the emergence of the disease.

[State resistance of the mosquito Culex pipiens towards temephos central Morocco]. / État de la résistance du moustique Culex pipiens vis-à-vis du téméphos au centre du Maroc.

In Morocco, Culex pipiens plays a role in the high annoyance experienced by most urban cities, suburban and rural areas, especially since it was strongly suspected as the most likely vector in the transmission of West Nile virus epidemics that have hit Morocco in 1996. Chemical insecticides are generally the way in which they use the programs against harmful mosquitoes and disease vectors. However, the repeated and excessive use of these products regularly led to the emergence of the phenomenon of insect resistance. At the center of Morocco, information on the susceptibility or resistance to insecticides in mosquitoes (larvae and adults) vectors of diseases or pests, are almost nonexistent. This article reports the results of studies conducted between 2007 and 2010 with sensitivity tests WHO on larvae local populations of Culex pipiens collected in three lodging in the city of Fez, towards the insecticide mostly used by hygienic services: temephos. Five concentrations of insecticide (0.0025 mg/l, 0.005 mg/l, 0.0125 mg/l, 0.025 mg/l, 0.0625 mg/l) in addition to control, were used to determine the LC50 and LC 90 of Culex pipiens species towards temephos. Sensitivity tests were carried out at the entomology unit and monitoring of insect sensitivity towards insecticides installed at the Regional Diagnostic Laboratory Epidemiological and Environmental Hygiene (LRDEHM), Fez, under the Regional Directorate of Health in Fes Boulemane Region. The LC50 and LC90, concentrations corresponding to 50 and 90% mortality were determined graphically, by the linear relationship between the decimal logarithm of insecticide concentrations (x-axis) and the percentage of mortality transformed into probit values (ordinate) on logarithmic gausso paper. Resistance rates were determined on the basis of the sensitivity of a reference strain (S-Lab). The bioassay results affirmed the presence of resistance in larvae Culex pipiens towards temephos and that this species has also equally developed resistance levels similar and comparable in the three lodging studied, resistance rates recorded varying between 12.17 and 14.34. Facing such a situation, the surveillance of susceptibility of mosquitoes to insecticides used in mosquito control and anti-malarial fight has become imperative. This would undoubtedly allow a good management of the products available and consequently to adopt suitable measures for the best management of this resistance which must be an integral part of any program of vector control.

Idiopathic corporeal hemihypertrophy associated with hemihypertrichosis.

The hemihypertrophy or hemihyperplasy is a rare congenital abnormality, characterized by an asymmetric growth of the limbs, the trunk, and the face or half of the entire body. It may be isolated or be part of several syndromes including Beckwith-Wiedemann syndrome, Klippel-Trenaunay-Weber syndrome, Silver-Russell syndrome and Proteus syndrome. In its isolated form, it is called idiopathic. The latter may be associated with several anomalies including dermatological and urogenital abnormalities with increased risk of developing embryonal tumors. We report the case of a 22-month-old infant, who was referred by his pediatrician at the age of 15 months for a corporeal hemihypertrophy associated with hemihypertrichosis. In his medical history, a second degree parental consanguinity and a hypospadias in the father and a paternal uncle were found. Clinical examination found a weight and a size greater than chronological age (3 standard deviations), a hemihypertrophy of entire left side with a difference of length and diameter between the left and right limbs of 2 cm. The hemihypertrichosis was widespread in the left body and the genital examination found a hypospadias. Biological and radiological assessments did not show any abnormality, with the exception of an initially high plasma testosterone level, which gradually normalized. Thus, the diagnosis of idiopathic hemihypertrophy with congenital hemihypertrichosis was retained. This is the fourth case reported in the literature. Its management is similar to all hemihypertrophies, which consists of an initial assessment to detect an embryonic tumor, followed by a monitoring protocol including an abdominal and renal ultrasound every 6 months until the age of 8, determination of alpha-feto-protein every 6 to 12 weeks until the age of 4 years to track the development of the two most frequent tumors: Wilms tumor and hepatoblastoma. The hemihypertrophy associated with hemihypertrichosis has been exceptionally reported and the cause of this association has not been identified to date.

Cyclical sciatica: endometriosis of the sciatic nerve.

We describe a case of sciatic endometriosis in a 25-year-old woman diagnosed by MRI and histology with no evidence of intrapelvic disease. The presentation, diagnosis and management of this rare condition are described. Early diagnosis and treatment are important to prevent irreversible damage to the sciatic nerve.

Statewide demonstration of not on tobacco: a gender-sensitive teen smoking cessation program.

This study represented the largest statewide demonstration (n = 346) of the teen smoking cessation program Not On Tobacco (N-O-T) to date and one of the few systematically controlled teen smoking cessation trials reported in the literature. Results showed that N-O-T female teens were 4 times more likely to quit smoking almost 6 months after the program ended than female teens who received a brief intervention (BI). The quit rate for the N-O-T female groups was significantly higher than that for female brief intervention comparison groups. The study demonstrated that 2 times more N-O-T than BI teens quit smoking overall. Differences in the biochemically validated quit rate between the N-O-T groups and the brief intervention groups overall and for male participants were not statistically different, however. Furthermore, findings showed that N-O-T was more effective than the brief intervention in assisting youth with cigarette reduction. There was a significant difference in the reduction rate between the N-O-T and the BI groups on weekdays and weekends 6 months after the program ended. Overall, approximately 84% of N-O-T teens either quit or reduced smoking, compared with approximately 55% of BI teens. This study is 1 phase of an ongoing multiphase evaluation of N-O-T. This study resulted in several important findings that will help guide future teen cessation studies and tobacco cessation efforts of school health professionals.

Coaches' attitudes toward smokeless tobacco and intentions to intervene with athletes.

Smokeless tobacco use among athletes is alarming. Most of these athletes report beginning smokeless tobacco use in middle or high school. West Virginia has significantly higher rates of smokeless tobacco use among adolescent and adult males than the general population. Since West Virginia athletes may be particularly vulnerable to smokeless tobacco use, West Virginia coaches can be critical agents in smokeless tobacco prevention and intervention. This study surveyed West Virginia middle and high school coaches' 1) attitudes toward smokeless tobacco, 2) actions toward athletes who use smokeless tobacco, 3) intentions to provide intervention for users, and 4) tobacco use history. Results indicated coaches had unfavorable attitudes toward smokeless tobacco, perceived it as a problem, and were willing to help athletes quit. These findings provide support for development of training programs for middle and high school coaches to act as smokeless tobacco intervention agents.

Variable dose naltrexone-induced hypothalamic-pituitary-adrenal stimulation in abstinent alcoholics: a preliminary study.

Opiate antagonists have been found to stimulate the hypothalamic-pituitary-adrenal axis. However, despite established usefulness in the management of alcoholism, systematic, oral dose-titrated natrexone-induced hypothalamic-pituitary-adrenal stimulation has never been studied in alcoholics. Six patients (5 males, 1 female) with DSM-IV alcohol dependence, who were at least 4 weeks abstinent from any alcohol [mean 55 days (+/-SE 7.5)], were given four challenges of oral naltrexone (0, 25, 50, and 100 mg) in a randomized order at least 3 days apart, after an overnight fast. Naltrexone was administered at 9 AM; serum ACTH, cortisol, and prolactin were measured at time 0 and at 9 time points over the next 4 hr. Subjects also filled out a side effect questionnaire and an alcohol urge questionnaire. Physiological measurements of blood pressure and pulse rate were taken at the same time points. Repeated-measures ANOVA of the changes in serum ACTHs over time revealed a significant effect of drug (placebo vs. any dose of naltrexone) (p < 0.05). Post-hoc analysis revealed a significant difference between placebo and the 25 mg dose (p < 0.01), the 50 mg dose (p < 0.01), but no significance between the placebo and the 100 mg dose (p = 0.1). A repeated-measures ANOVA of the changes in serum cortisols over time revealed a significant effect of drug (p < 0.01). Post-hoc analysis revealed a significant difference between placebo and the 25 mg dose (p < 0.01), between placebo and the 50 mg dose (p < 0.05), and placebo and the 100 mg dose (p < 0.01). There was a significant between dose difference in pulse rate changes over baseline (p < 0.01), and post-hoc analysis revealed a significant diminution in pulse rate at the 100 mg dose relative to placebo (p < 0.001), and to the other doses. There were no significant differences in reported side effects, alcohol urge questionnaire scores, or in other physiological measurements between doses. These data suggest a significant rise in ACTH and cortisol in response to naltrexone in alcoholics compared with placebo, with no differences between 25 mg, 50 mg, and 100 mg doses, and a significant diminution in pulse rate responses at the 100 mg dose.

Nalmefene causes greater hypothalamic-pituitary-adrenal axis activation than naloxone in normal volunteers: implications for the treatment of alcoholism.

Among other actions, opioid antagonists modulate the control endogenous opioids exert on the hypothalamic-pituitary-adrenal (HPA) axis. Naloxone, nalmefene, and naltrexone are the opioid antagonists approved for use in man and are primarily mu-opioid selective. Naltrexone and nalmefene have been demonstrated to be useful in the treatment of alcoholism. Compared with naloxone, nalmefene has a longer half-life, is more potent at the mu-receptor, and has a higher affinity for kappa- and delta-opioid receptors. We conducted an inpatient study comparing the effects of 10 and 30 mg doses of intravenous naloxone and nalmefene in normal, nonsubstance nor alcohol-abusing, volunteers. Significant increases in ACTH and cortisol were observed after both antagonists, without an apparent dose-response relationship; however, both doses of nalmefene resulted in greater HPA axis activation than either dose of naloxone (ACTH: p <0.005). These results indicate that kappa- and delta-opioids may play important roles in the regulation of the HPA axis; nalmefene may be useful as both a probe to explore the HPA axis physiology and as a pharmacotherapeutic agent.

Growth hormone action is blunted by acidosis in experimental uremia or acid load.

The effects of rhGH (H) daily injection (2 IU/d) and of vehicle (V) during two weeks were studied in young (60 g) growing rats. Experiment I was performed in uremic rats (mean plasma creatinine: 65-71 mumol/l) either acidotic (mean HCO3-:11.5 mmol/l: UAH, n = 20; UAV, n = 18), or with corrected acidosis by addition of NaHCO3 in the diet (mean HCO3-:26 mmol/l: UBH, n = 25; UBV, n = 23). Experiment II used rats with normal renal function (plasma creatinine: 25 mumol/l), either non-acidotic but food restricted to the dietary intake of uremic rats (CRH: n = 18, CRV: n = 18), or rendered acidotic by NH4Cl (CAH: n = 16, CAV: n = 16). GH induced an augmentation of body weight and length gains in non-acidotic uremic rats (+33% and +41%: p < 0.01), and in non-acidotic food restricted rats (+13% and 42%: p < 0.05 and p < 0.0001). This was associated with increased protein synthesis rate in muscle and with little change of food intake as well as of plasma IGF 1. Plasma IGF 1 kept the same relationship to food intake, regardless of treatment, but length gain for each level of plasma IGF 1 was enhanced by GH in GH responding groups. In both acidotic rat groups, GH altered none of the parameters studied. Thus: 1) the presence of severe metabolic acidosis blunts the response to GH in uremic and non-uremic rats. 2) The increment of growth rate does not depend on a rise of plasma IGF 1.

Acidosis prevents growth hormone-induced growth in experimental uremia.

The effects of 2 weeks of a daily injection (2 IU/day) of recombinant human growth hormone (GH) were studied in young (60-g) growing rats in two experiments. Experiment 1 was performed in uremic animals (mean plasma creatinine 65-71 mumol/l) who were either acidotic (mean bicarbonate 11.5 mmol/l) or had acidosis corrected (mean bicarbonate 26 mmol/l) by addition of sodium bicarbonate to the diet. Experiment 2 used rats with normal renal function (plasma creatinine 25 mumol/l) who were either non-acidotic but restricted to the dietary intake of uremic rats or rendered acidotic by ammonium chloride. GH induced an increase in body weight and length in non-acidotic uremic (+33% and +41%) and in non-acidotic food-restricted (+13% and +42%) rats, associated with an increased rate of protein synthesis and little change in plasma insulin-like growth factor 1 (IGF 1). In both acidotic rat groups, GH altered none of the parameters studied. Thus: (1) the presence of severe metabolic acidosis blunts the response to GH in uremic and non-uremic rats and (2) the increment of growth rate does not depend on a rise in plasma IGF 1.

Continuous enteral feeding in uremic rats.

Because of constant uremia-induced anorexia, food restriction of normal rats is generally used to study the consequences of uremia. The effects of a normal food supply in uremic rats has never been tested, since no author has succeeded in providing normal intakes. Uremic rats either fed ad lib (U rats, n = 12) or force-fed through a gastric catheter (UF rats, n = 10), and sham-operated rats (C rats, n = 10) were compared from days 7 to 21 after surgery. U rats had lower food intake (13.8 vs. 17 g/day), weight gain (5.16 vs. 6.23 g/day), length gain (4 vs. 5 mm/day), nitrogen balance (228 vs. 279 mg/day) and muscle fractional protein synthesis rate (9.5 vs. 10.6%) measured in vivo by 3H-phenylalanine injection (p < 0.05 for all). All parameters were restored to normal values in UF rats, possibly due to correction of underhydration in addition to undernutrition. Such continuous enteral feeding may provide a model for normal nutritional supply in uremia.

Diagnosis of genetic defects by chromosomal analysis.

Of 901 karyotypes performed over a period of 4 years, genetic anomalies were detected in 162 cases. Down's syndrome (trisomy 21) was the most common (168.8%) genetic disorder followed by Turner's syndrome, Philadelphia chromosome, Klinefelter's syndrome, Edward's syndrome (trisomy 18) and Patau's syndrome (trisomy 13). All the three trisomies were detected very early in life. Mean age at the time of diagnosis for Turner's syndrome was 13.3 years, allowing a timely hormone replacement therapy to improve secondary sexual characters. Patients with Klinefelter's syndrome were diagnosed late (mean age 23.6 years), which greatly reduced their chances of an effective therapy to improve the clinical and social outcome.

In vivo unaltered muscle protein synthesis in experimental chronic metabolic acidosis.

Chronic metabolic acidosis (CMA) is a major cause of growth defect, implying disturbances of protein metabolism. Previously, in vivo studies performed in the fasting state showed enhanced whole body protein turnover, whereas in vitro studies showed unchanged muscle protein synthesis. The present study is the first to determine the effects of CMA on muscle protein synthesis and degradation in vivo. Two studies were performed in 60 g male rats fed a 30% casein diet. In study I, one group was sham-operated (C rats), and two groups underwent subtotal nephrectomy. One of them developed acidosis (UA rats) which was corrected in the other by NaHCO3 in the diet (UNA rats). Study II compared sham-operated rats rendered acidotic by NH4Cl in the drinking water (CA rats) and normal pair-fed (CNA) rats. Fractional protein synthesis rate (FSR) was determined in gastrocnemius muscle after injection of 3H-phenylalanine. Fractional protein degradation rate (FDR) was calculated as FSR minus fractional rate of muscle growth (FGR). In study I, UA rats had lower growth and N balance (163 +/- 12 vs. 216 +/- 11 mg N/day; P < 0.001) than UNA rats, despite identical food intake (11 g/day). This was associated with identical FSR (10.4 +/- 0.5 vs. 10.9 +/- 0.5%/day), but enhanced protein degradation (6.30 +/- 0.99 vs. 5.10 +/- 0.71%/day; P < 0.05). Plasma insulin, C peptide, PTH and corticosterone did not differ in UA and UNA rats, whereas plasma IGF-I was markedly reduced (147 +/- 21 vs. 283 +/- 27 ng/ml; P < 0.01) in UA rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced food intake is the main cause of low growth hormone receptor expression in uremic rats.

To examine the respective effects of reduced food intake and of uremia on the growth defect in uremic rats, we have studied the expression of GH receptors in three groups of male rats: Group 1, rats fed ad libitum; Group 2, food-restricted to be pair-fed with uremic rats; Group 3, uremic rats. Animals were studied for a time period of 9 days starting 1 week after surgery (sham operation in rats of Groups 1 and 2, 5/6 nephrectomy in rats of Group 3). The gain in body length and weight of pair-fed controls and of uremic rats was comparable and significantly lower than that of rats fed ad libitum. IGF-1 plasma levels were low in rats of groups 2 and 3. Low food intake (50% that of rats fed ad libitum) resulted in a reduced number of GH receptors in liver membranes and a low plasma level of GH-binding protein (GHBP); GH receptor gene expression in the liver, as analyzed by Northern blots, was not significantly lower in normal food-restricted animals. In uremic rats, the low level of GH binding to liver membranes was comparable to that found in pair-fed controls; but the level of GHBP activity was normal, not different from the values found in rats fed ad libitum. However, expression of the liver GHBP mRNA was reduced in uremic rats. In uremia, the GH receptor dysfunction is not only at a transcriptional level but also at a post-transcriptional level. These findings suggest that uremia, as such, is not primarily responsible for the growth failure.(ABSTRACT TRUNCATED AT 250 WORDS)

[Growth and protein metabolism in chronic metabolic acidosis from experimental renal insufficiency]. / Croissance et métabolisme protéique dans l'acidose métabolique chronique de l'insuffisance rénale expérimentale.

Two studies of uremia-induced chronic metabolic acidosis (CMA) were carried out to determine: 1) the level of acidosis beyond which growth failure occurs; 2) the protein metabolism anomalies which are associated with growth failure. Rats rendered uremic by subtotal nephrectomy were fed a diet containing sufficient protein amounts (30% casein) to induce CMA. CMA was left uncorrected in half the rats (group A) and was corrected by administration of bicarbonate in the other half (group B). 1) Fifty-two group A rats were compared with 52 group B rats matched for renal function. Results showed that a) CMA failed to reduce food intake; b) weight gain decreased only when CMA was profound (pH < 7.20) whereas reductions in length gain occurred at less severe levels of acidosis (pH < 7.25) suggesting that bone may be more susceptible to CMA than muscle mass. 2) Protein fractional synthesis rate was evaluated in skeletal muscle after a flooding dose of 3H-phenylalanine in group A rats (pH 7.22 +/- 0.01, HCO3-: 15.2 +/- 0.8 mmol/l) and group B rats matched for renal function. Values were identical in both groups (10.4 +/- 0.5 vs 10.8 +/- 0.5%/day). However, fractional muscle protein accretion rate was decreased in group A rats. These data demonstrate that CMA-associated growth failure in uremia is due to increased breakdown of protein with no change in protein production.

Nutritional effects of feeding a ketoanalogue mixture in growing and adult uremic rats.

Insufficient protein diets supplemented with ketoanalogue/essential amino acid (KA/EAA) mixtures are proposed to maintain nutrition and to retard renal deterioration. We compared in growing and in adult uremic rats diets containing limited or usual amounts of protein (12%, 20% for growing rats, and 10% and 16% for adult rats) with diets containing 50% or 60% less casein plus a KA/EAA mixture providing KA at an equimolar amount of removed EAA or at higher amounts. The latter supplement caused stunting, the former caused no anorexia, a slight growth deficit when added to the lowest basal casein diets, and almost normal growth when added to higher casein diets. Growth was normal with EAA supplements. The plasma EAA changes were unrelated to intake and to growth. Thus, KA utilization is maximal, provided that basal protein is sufficient and KA are not in excess.

Supplemented low-protein diets protect the rat kidney without causing undernutrition.

Low-protein diets supplemented with keto-analogues and essential amino acid (KA-EAA) mixtures or with EAA have been widely used to retard renal deterioration without affecting nutrition. These assumptions have recently been challenged in clinical studies and rest on little or no experimental data. The effects of EAA and KA-EAA supplementations have not been compared. We compared three groups of rats with subtotal nephrectomy that were fed (1) a 16% casein reference (R) diet, (2) a 6% casein plus EAA (A) diet, or (3) a 6% casein plus KA-EAA (K) diet with KA as amino acid salts. The three diets had the same energy and mineral contents, and they induced comparable growth. The two supplements had the same nitrogen content. The only difference found until month 3 was higher proteinuria and plasma urea levels in group R rats. Renal biopsies performed at month 3 showed more severe glomerular sclerosis and tubular changes in R rats than in A and K rats. From months 3 through 7, R rats developed higher plasma creatinine levels than did A and K rats (final median values: 167, 106, and 83 mumol/L; p < 0.04), had more proteinuria (232, 56, and 84 mg/day), and showed greater mortality rates. At the time the rats were killed, 2 R, 6 A, and 5 K rats had survived while receiving the diets. Examination of the remnant kidneys, regardless of time of death, showed that renal lesions were significantly worse in R than in A and K rats, with sclerosis affecting more than 50% of the glomeruli in 7 of 13 R, 4 of 14 A, and 4 of 15 K rats, and less than 25% glomeruli in 2 of 13 R, 10 of 14 A, and 10 of 15 K rats (A and K vs R: p < 0.03). In conclusion, restriction of nonessential amino acids compensated by EAA or by KA-EAA mixtures retards renal damage without affecting growth, but no real benefit of KA or EAA has been observed.

Zinc bone loss in chronic renal failure and chronic metabolic acidosis.

The effects of chronic metabolic acidosis (CMA) on zinc (Zn) bone content and urinary excretion were examined in the presence of normal or reduced renal function together with some aspects of calcium (Ca) metabolism. Four groups of rats were compared. All were fed a 30% protein and 9 mg Zn/100 g diet. Two were uremic (U): The first developed acidosis (UA), which was suppressed in the other (UNA) by NaHCO3 supplement. Two other groups had normal renal function: One was normal (CNA), and the other had NH4Cl in the drinking water and acidosis (CA). Femur total Zn and Ca content was markedly reduced by CMA and was not affected by uremia. Zn urinary excretion was increased by CMA and unaltered by uremia. Ca urinary excretion was markedly reduced in uremic rats, but was enhanced in both acidotic conditions. Urinary Ca and Zn showed a strong correlation in uremic and in control rats. Plasma parathormone and 1,25(OH)2D3 were unchanged by CMA. These data are in agreement with a direct primary effect of CMA on bone in releasing buffers. CMA induces bone resorption and a parallel decrease of mineral bone components, such as Ca and Zn, with little or no role of PTH, 1,25(OH)2D3 and of uremia itself.