Stigma in visible skin diseases - a literature review and development of a conceptual model.

The burden of visible skin diseases (VSDs) includes not only physical symptoms but also psychosocial consequences such as depression, anxiety, impaired quality of life and low self-esteem. Stigmatization was shown to play a major role in people with skin diseases. The aim of the study was to review the evidence for the components, drivers and impacts of (self-)stigma, and to organize the data into a series of conceptual models. A targeted literature search was conducted to identify studies on (self-)stigma in relation to VSD. Conceptual models of stigma in VSDs were developed from existing generic conceptual models for VSD and of generic conceptual models of stigma and were refined after discussion with a board of experts, patient advocacy groups, clinicians and researchers. A total of 580 references were identified, of which 56 references were analysed and summarized. Two conceptual models of stigma were identified: one with external stigma and self-stigma dimensions, the other for self-stigma in mental health. These models were adapted to allow a complete description of stigma in VSDs. For this, a distinction was made between 'discrimination' and 'impact'. Finally, five models were developed: macro-overview; stigma, impact and socio-demographics; stigma, impact and disease characteristics; stigma, impact and quality of life; and stigma, impact and coping. Gaps were identified in available quantitative evidence. To our knowledge, this is the first conceptual model of stigma in VSDs. The model will help to standardize evaluation of stigma and to enhance empirical evaluation of anti-stigma interventions in VSDs. Further research should be conducted to develop a more complete model in stigma due to significant gaps in existing evidence, particularly including the stigma in others (external stigma) and also to cover a broader range of VSDs as their impact on particular dimensions of stigma differs.

[Metabolic rhabdomyolysis during statin therapy]. / Rhabdomyolyse métabolique au cours d'un traitement par statine.

The occurrence of rhabdomyolysis during statin treatment for dyslipidemia is a well-known side effect. However, the differential diagnosis of rhabdomyolysis is large. We report on a patient treated with statin who presented a rhabdomyolysis. The persistence of laboratory abnormalities allowed to discover a metabolic rhabdomyolysis, namely a carnitine palmitoyltransférase II deficiency. The diagnosis of the genetic abnormality allows to modify the therapeutic care.

Reduced fibre size, capillary supply and mitochondrial activity in constitutional thinness' skeletal muscle.

AIM: Constitutional thinness (CT) is a rare condition of natural low body weight, with no psychological issues, no marker of undernutrition and a resistance to weight gain. This study evaluated the skeletal muscle phenotype of CT women by comparison with a normal BMI control group. METHODS: Ten CT women (BMI < 17.5 kg/m2 ) and 10 female controls (BMI: 18.5-25 kg/m2 ) underwent metabolic and hormonal assessment along with muscle biopsies to analyse the skeletal muscular fibres pattern, capillarity, enzymes activities and transcriptomics. RESULTS: Constitutional thinness displayed similar energy balance metabolic and hormonal profile to controls. Constitutional thinness presented with lower mean area of all the skeletal muscular fibres (-24%, P = .01) and percentage of slow-twitch type I fibres (-25%, P = .02, respectively). Significant downregulation of the mRNA expression of several mitochondrial-related genes and triglycerides metabolism was found along with low cytochrome c oxidase (COX) activity and capillary network in type I fibres. Pre- and post-mitochondrial respiratory chain enzymes levels were found similar to controls. Transcriptomics also revealed downregulation of cytoskeletal-related genes. CONCLUSION: Diminished type I fibres, decreased mitochondrial and metabolic activity suggested by these results are discordant with normal resting metabolic rate of CT subjects. Downregulated genes related to cytoskeletal proteins and myocyte differentiation could account for CT's resistance to weight gain.

[Retrospective study of anorexia nervosa: reduced mortality and stable recovery rates]. / Diminution de la mortalité et stabilité du taux de guérison dans le suivi de l'anorexie mentale.

OBJECTIVES: Anorexia nervosa is an eating disorder that combines malnutrition, amenorrhea, and distorted body image. To learn more about the course of this disease we undertook a retrospective study of girls diagnosed with anorexia nervosa in the Saint Etienne Endocrinology Department between 1979 and 2004. METHODS: Patients were diagnosed according to DSMIV criteria. Data collected to complete the Morgan-Russell outcome assessment schedule included chronology of illness, patients' morphological features, anorexia type, treatment choice, patient's gynecological history, and social status. RESULTS: The study included 206 cases. The average follow-up period was 8.3 +/- 5.3 years. Defining recovery as stable BMI>17.5 kg/m2 for at least one year and recovery of normal menstruation, full recovery was observed in 55.8% and partial recovery in 25.7%, while 18.5% remained chronically ill. Early onset (i.e., during adolescence) was associated with good prognosis, and advanced emaciation and delayed or insufficient medical care with poor prognosis. CONCLUSIONS: The seriousness of this disease is due more to the incidence of cases that become chronic than to the mortality rate. Prediction of severity would be improved by taking into account underlying personality traits, such as addictive tendencies and depression.

Surgical management of hyperthyroidism.

AIMS: Hyperthyroidism includes several clinical and histopathological situations. Surgery is commonly indicated after failure of medical treatment. The aim of this study was to analyze the indications and complications of surgery as well as endocrine results. MATERIALS AND METHODS: Patients operated on for hyperthyroidism between 2004 and 2012 were included in a retrospective study. Total thyroidectomy was performed for Graves' disease, toxic multinodular goiter and amiodarone-associated thyrotoxicosis; patients with toxic nodule underwent hemithyroidectomy. Pathologic analysis assessed surgical specimens; postoperative complications and resolution of hyperthyroidism were noted. RESULTS: Two hundred patients from 15 to 83 years old were included. One hundred and eighty-eight underwent primary surgery and 12 were re-operated for recurrent goiter (6 with subtotal thyroidectomy for multinodular goiter 25 years previously; 6 with hemithyroidectomy for solitary nodule 15 years previously). Eighty-two patients suffered from toxic multinodular goiter, 78 from Graves' disease, 35 from solitary toxic nodules and 5 from amiodarone-associated thyrotoxicosis. Fourteen papillary carcinomas (including 11 papillary microcarcinomas) and 34 healthy parathyroid glands (17%) were identified in the pathological specimens. Postoperative complications comprised 4% permanent recurrent laryngeal nerve palsy (1 year follow-up), 9% hematoma requiring surgical revision, and 3% definitive hypocalcemia. Normalization of thyroid hormone levels was observed in 198 patients. Two recurrences occurred due to incomplete resection (1 case of Graves' disease and 1 intrathoracic toxic goiter that occurred respectively 18 and 5 months after resection). Postoperative complications were more frequent in multinodular goiter (23%) than in Graves' disease (13%) (ns: P>0.05). CONCLUSION: Surgical management of hyperthyroidism enables good endocrinal control if surgery is complete. Patients need to be fully informed of all possible postoperative complications that could occur, especially vocal ones. Long-term follow-up is necessary to detect recurrence, which can occur more than 20 years after partial thyroidectomy surgery. Surgery allows early diagnosis of 12.5% of papillary carcinomas.

Prevention by the tachykinin NK2 receptor antagonist, SR 48968, of antigen-induced airway hyperresponsiveness in sensitized guinea-pigs.

The involvement of tachykinins in antigen-induced airway hyperresponsiveness (AHR) was characterized pharmacologically in guinea-pigs sensitized to ovalbumin with antagonists of tachykinin NK1 and NK2 receptors, namely SR 140333 and SR 48968, respectively. AHR was illustrated by increased sensitivity to bronchoconstriction provoked by aerosolized acetylcholine in anaesthetized, ventilated animals, administrated 48 h after ovalbumin aerosol challenge. SR 48968 (1 mg kg-1, i.p.), when given once 30 min before the antigen challenge, prevented AHR, whereas SR 140333 did not. These findings suggest that the tachykinin NK2 receptor antagonist, SR 48968, may be useful for investigating mechanisms of tachykinins in the development of airway hyperresponsiveness.

Reduction of matrix metalloproteinase-9 activity by the selective phosphodiesterase 4 inhibitor, RP 73-401 in sensitized mice.

Matrix metalloproteinases are particularly potent in degrading basement membrane collagen and other extracellular matrix components. We have investigated the effects of a selective phosphodiesterase 4 inhibitor, RP 73-401 [N-(3, 5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide], on gelatinase (matrix metalloproteinase-2 and matrix metalloproteinase-9) activity in ovalbumin-sensitized and -challenged mice. Twenty-four hours after the last challenge, matrix metalloproteinase activity was evaluated in the bronchoalveolar lavage fluids by a zymography technique, and a significant increase in matrix metalloproteinase-9, but not matrix metalloproteinase-2, activity was noted. When administered orally (0.3-3 mg/kg) 1 h before each ovalbumin challenge, the selective phosphodiesterase 4 inhibitor, RP 73-401, significantly reduced this increased matrix metalloproteinase-9 activity in bronchoalveolar lavage fluids. Our data suggest that RP 73-401 may modulate tissue remodelling associated with lung inflammatory processes including asthma.

Influence of fatty acid ethanolamides and delta9-tetrahydrocannabinol on cytokine and arachidonate release by mononuclear cells.

The effects of arachidonic acid ethanolamide (anandamide), palmitoylethanolamide and delta9-tetrahydrocannabinol on the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-4, interleukin-6, interleukin-8, interleukin-10, interferon-gamma, p55 and p75 TNF-alpha soluble receptors by stimulated human peripheral blood mononuclear cells as well as [3H]arachidonic acid release by non-stimulated and N-formyl-Met-Leu-Phe (fMLP)-stimulated human monocytes were investigated. Anandamide was shown to diminish interleukin-6 and interleukin-8 production at low nanomolar concentrations (3-30 nM) but inhibited the production of TNF-alpha, interferon-gamma, interleukin-4 and p75 TNF-alpha soluble receptors at higher concentrations (0.3-3 microM). Palmitoylethanolamide inhibited interleukin-4, interleukin-6, interleukin-8 synthesis and the production of p75 TNF-alpha soluble receptors at concentrations similar to those of anandamide but failed to influence TNF-alpha and interferon-gamma production. The effect of both compounds on interleukin-6 and interleukin-8 production disappeared with an increase in the concentration used. Neither anandamide nor palmitoylethanolamide influenced interleukin-10 synthesis. delta9-Tetrahydrocannabinol exerted a biphasic action on pro-inflammatory cytokine production. TNF-alpha, interleukin-6 and interleukin-8 synthesis was maximally inhibited by 3 nM delta9-tetrahydrocannabinol but stimulated by 3 microM delta9-tetrahydrocannabinol, as was interleukin-8 and interferon-gamma synthesis. The level of interleukin-4, interleukin-10 and p75 TNF-alpha soluble receptors was diminished by 3 microM delta9-tetrahydrocannabinol. [3H]Arachidonate release was stimulated only by high delta9-tetrahydrocannabinol and anandamide concentrations (30 microM). These results suggest that the inhibitory properties of anandamide, palmitoylethanolamide and delta9-tetrahydrocannabinol are determined by the activation of the peripheral-type cannabinoid receptors, and that various endogenous fatty acid ethanolamides may participate in the regulation of the immune response.

Involvement of cyclic AMP in the effects of phosphodiesterase IV inhibitors on arachidonate release from mononuclear cells.

The effects of selective phosphodiesterase inhibitors, cyclic AMP (cAMP) elevating agents and stable analogues of cyclic nucleotides, on the release of arachidonate induced by N-formyl-Met-Leu-Phe (fMLP) were investigated on human peripheral blood mononuclear cells. The selective phosphodiesterase IV inhibitors, rolipram and Ro 20-1724, and the non-selective phosphodiesterase inhibitor, theophylline, elicited a concentration-dependent inhibition of arachidonate release (EC50 = 1.3 x 10(-6) M, 3.2 x 10(-6) M and 3.7 x 10(-4) M respectively). The selective phosphodiesterase III inhibitor, milrinone (10(-5) M), only caused a slight effect while the phosphodiesterase V inhibitor, zaprinast (10(-5) M), the beta 2-adrenoceptor agonists, salbutamol and fenoterol (10(-5) M), failed to inhibit arachidonate release. Forskolin (10(-5) M) and N6,2'-O- dibutyryladenosine 3':5'-cyclic monophosphate (db-cAMP), 10(-3) M) elicited a moderate inhibition. Forskolin increased the effects of rolipram and Ro 20-1724 (EC50 = 4.5 10(-7) M and 4 x 10(-7) M respectively). Incubation of the cells with rolipram (10(-8) to 10(-5) M), Ro 20-1724 (10(-8) to 10(-5) M, forskolin (10(-5) M) or salbutamol (10(-5) M) alone, induced a moderate increase or no increase at all in intracellular cAMP. However, in the presence of forskolin, rolipram (10(-8) to 10(-6) M) and Ro 20-1724 (10(-8) to 10(-6) M) induced significant and concentration-dependent increase in intracellular levels of cAMP. These results suggest that the potent inhibition of arachidonate release from mononuclear cells by selective phosphodiesterase IV inhibitors may be due to increases in discrete pools of intracellular cAMP.

Inhibition of inflammatory cell recruitment by the tachykinin NK(3)-receptor antagonist, SR 142801, in a murine model of asthma.

Several observations suggest that tachykinins (substance P, neurokinin A and neurokinin B) are involved in the pathogenesis of pulmonary diseases and elicit several airway responses such as bronchoconstriction and neurogenic inflammation via interactions with specific receptors denoted NK(1), NK(2) and NK(3). We have investigated the effect of a selective antagonist for tachykinin NK(3) receptor, SR 142801 ((R)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)propyl)-4-phenylpiperidin-4-yl-N-methylacetamide), on the inflammatory cell recruitment in ovalbumin-sensitized and -challenged mice used as a model of allergic asthma. Twenty hours after the two-ovalbumin challenges, differential cell counts were calculated and indicated that SR 142801 caused a significant decrease in the number of neutrophils and eosinophils. Forty hours after the last ovalbumin exposure, SR 142801 induced a significant decrease in the recruitment of eosinophils. These results suggest that tachykinins and tachykinin NK(3) receptors can interfere with cell recruitment in inflammatory response.

Modulation of airway remodeling-associated mediators by the antifibrotic compound, pirfenidone, and the matrix metalloproteinase inhibitor, batimastat, during acute lung injury in mice.

Matrix metalloproteinases (MMPs) are potent to degrade basement membrane collagen associated with acute lung injury in inflammatory processes. We have investigated effects of pirfenidone, antifibrotic agent, and batimastat, inhibitor of MMPs, on gelatinase activities, on release of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), as well as on recruitment of inflammatory cells in bronchoalveolar lavage (BAL) fluid after aerosol administration of lipopolysaccharide (LPS) in mice. Pretreatment with pirfenidone reduced neutrophil recruitment, TNF-alpha and TGF-beta levels, and MMP-9 secretion. In contrast, pretreatment with batimastat (30 or 60 mg/kg, i.p.) only reduced TNF-alpha and TGF-beta levels. Batimastat did not reduce MMP secretion in BAL fluid but inhibited MMP-9 activity. The increase in tissue inhibitor of matrix metalloproteinase (TIMP)-1 induced by LPS was not modified by the two drugs. These findings demonstrate that the two drugs can inhibit the in vivo increase in MMP induced by LPS, batimastat with a direct inhibitor effect on MMP activity and pirfenidone as a consequence of its antiinflammatory effect.

Interactions between cAMP- and cGMP-dependent protein kinase inhibitors and phosphodiesterase IV inhibitors on arachidonate release from human monocytes.

The effects of specific inhibitors of cAMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG) on the inhibitory activity of phosphodiesterase (PDE) type IV inhibitors and of the cell permeable analogue of cAMP, db-cAMP, were investigated on fMLP-induced arachidonate release from human monocytes. When monocytes were preincubated with the combined PKA/PKG inhibitor H8 (10(-6) to 10(-4) M) or the selective PKG inhibitor Rp-8-cpt-cGMPs (10(-6) to 10(-4) M) a concentration-dependent reduction of the inhibitory effect of db-cAMP (10(-3) M), rolipram (10(-5) M) and Ro 20-1724 (10(-5) M) was noted. When monocytes were preincubated with the selective PKA inhibitor H89 (10(-6) to 10(-4) M), only a small inhibition of the effect of db-cAMP and no inhibition of the effects of rolipram and Ro 20-1724 were observed. The present data indicate that db-cAMP and PDE IV inhibitors elicit an in vitro anti-inflammatory activity by a PKA-independent mechanism, which do not appear to be mainly mediated via the PKG activation.

Effects of cannabinoid receptor ligands on LPS-induced pulmonary inflammation in mice.

The effects of cannabinoid receptor agonists WIN 55,212-2, delta9-tetrahydrocannabinol (delta9-THC), arachidonoylethanolamide (anandamide) and palmitoylethanolamide on lipopolysaccharide (LPS) -induced bronchopulmonary inflammation in mice were investigated. WIN 55,212-2 and delta9-THC induced a concentration-dependent decrease in TNF-alpha level in the bronchoalveolar lavage fluid (BALF) (maximum inhibition 52.7% and 36.9% for intranasal doses of 750 nmol x kg(-1) and 2.65 mmol x kg(-1), respectively). This effect was accompanied by moderately reduced neutrophil recruitment. Palmitoylethanolamide (750 nmol x kg(-1)) diminished the level of TNF-alpha in BALF by 31.5% but had no effect on neutrophil recruitment. Anandamide (7.5-750 nmol x kg(-1)) did not influence the inflammatory process but TNF-alpha level and neutrophil recruitment were decreased by 28.0% and 62.0%, respectively, with 0.075 nmol x kg(-1). These results demonstrate that the cannabinoid receptor ligands inhibited LPS-induced pulmonary inflammation and suggest that this effect could be at least in part mediated by the cannabinoid CB2 receptor.

Effects of interleukin-10 and modulators of cyclic AMP formation on endotoxin-induced inflammation in rat lung.

The aim of this study was to investigate the effects of IL-10, a cell permeable analogue of cyclic AMP, dibutyryl-cAMP (db-cAMP), modulators of intracellular cyclic AMP such as phosphodiesterase (PDE) inhibitors and a beta 2-adrenoceptor agonist, salmeterol, on pulmonary inflammation following acute lung injury induced by endotoxin exposure in rats. Pulmonary inflammation was induced in adult Wistar rats by a 60-min exposure to endotoxin (lipopolysaccharide, LPS, 100 micrograms/mL). 4 h later bronchoalveolar lavage (BAL) was performed. The PDE inhibitors, rolipram (3 and 5 mg/kg) and theophylline (30 and 100 mg/kg) inhibited neutrophil recruitment, TNF-alpha release and cellular activation in BAL. Salmeterol (0.5 mg/mL) and IL-10 (0.1 microgram) only inhibit TNF-alpha increase in the BAL fluid and db-AMPc (2.5 micrograms/rat) was ineffective. The present data show that the selective PDE4 inhibitor, rolipram, and the non-selective PDE inhibitor, theophylline, markedly reduced the pulmonary inflammation associated with acute lung injury in the rat. These effects may be mediated in part by IL-10 rather than by cyclic AMP, as demonstrated by the potent inhibitory activity of exogenous IL-10 on the increase in TNF-alpha release in BAL fluid of rats exposed to LPS.

Study of basement membrane formation in dermal-epidermal recombinants in vitro.

Two different dermal-epidermal recombinants were prepared in vitro and used to study the synthesis and formation of basement membrane. The first was obtained by culturing keratinocytes on the surface of a collagen lattice populated by fibroblasts. The second was prepared by coculture of both keratinocytes and fibroblasts in a collagen lattice. After 6 weeks of culture, the basal lamina was observed with electron microscopy only if keratinocytes were cultivated on top of the collagen lattice populated by fibroblasts. In the second model, however, type IV collagen, laminin, and pemphigoid bullosa antigen could be detected by immunofluorescence as well as synthesis of type IV collagen in the culture, but no basement membrane was observed by electron microscopy. These data demonstrate that, in vitro, basement membrane formation depends not only on the presence of the macromolecular components but also on the culture conditions.

[Behavior on de-epidermized human skin of unspecified reconstituted collagen tissue]. / Comportement sur peau humaine désépidermisée d'un tissu collagène reconstitué déspécifié.

The aim of our study was to assess the behaviour of a despecified collagen tissue laid on desepidermized human skin (taking area of skin graft). The collagen tissue was prepared according to Bell's method. The collagen was latticed, contracted by fibroblasts, chemically treated (formaldehyde or glutaraldehyde) to stabilize the fibrils and then despecified by cialit treatment. This tissue laid on superficial, non infected wounds very rapidly took a necrotic appearance and was totally lysed after 10 to 12 days without any modification of the healing course. No bacterial infection was observed. Histological and ultrastructural studies showed desorganization of collagen fibre bundles and tissue invasion by inflammatory cells. Circulating antibodies to collagen were absent at day 30. This model lacks interest as a substitute for superficial tissue replacement, but a healing function could be assigned to its high chemotactic power for polynuclears and macrophages and should allow its use in cases of deep tissue loss.

Specific appetite, energetic and metabolomics responses to fat overfeeding in resistant-to-bodyweight-gain constitutional thinness.

BACKGROUND: Contrasting with obesity, constitutional thinness (CT) is a rare condition of natural low bodyweight. CT exhibits preserved menstruation in females, no biological marker of undernutrition, no eating disorders but a bodyweight gain desire. Anorexigenic hormonal profile with high peptide tyrosine tyrosine (PYY) was shown in circadian profile. CT could be considered as the opposite of obesity, where some patients appear to resist diet-induced bodyweight loss. OBJECTIVE: The objective of this study was to evaluate appetite regulatory hormones in CTs in an inverse paradigm of diet-induced weight loss. METHODS: A 4-week fat overfeeding (2640 kJ excess) was performed to compare eight CT women (body mass index (BMI)<17.5 kg m(-)(2)) to eight female controls (BMI 18.5-25 kg m(-)(2)). Appetite regulatory hormones profile after test meal, food intake, bodyweight, body composition, energy expenditure and urine metabolomics profiles were monitored before and after overfeeding. RESULTS: After overfeeding, fasting total and acylated ghrelin were significantly lower in CTs than in controls (P=0.01 and 0.03, respectively). After overfeeding, peptide tyrosine tyrosine (PYY) and glucagon-like-peptide 1 both presented earlier (T15 min vs T30 min) and higher post-meal responses (incremental area under the curve) in CTs compared with controls. CTs failed to increase bodyweight (+0.22±0.18 kg, P=0.26 vs baseline), contrasting with controls (+0.72±0.26 kg, P=0.03 vs baseline, P=0.01 vs CTs). Resting energy expenditure increased in CTs only (P=0.031 vs baseline). After overfeeding, a significant negative difference between total energy expenditure and food intake was noticed in CTs only (-2754±720 kJ, P=0.01). CONCLUSION: CTs showed specific adaptation to fat overfeeding: overall increase in anorexigenic hormonal profile, enhanced post prandial GLP-1 and PYY and inverse to controls changes in urine metabolomics. Overfeeding revealed a paradoxical positive energy balance contemporary to a lack of bodyweight gain, suggesting yet unknown specific energy expenditure pathways in CTs.

Systematic screening for diabetic retinopathy with a digital fundus camera following pupillary dilatation in a university diabetes department.

AIMS: Screening for diabetic retinopathy (DR) is highly inadequate in France because of insufficient infrastructure and increasing disease prevalence. We describe the results of the first systematic DR screening programme established in a university diabetes department. METHODS: In this cross-sectional study conducted over 1 year, consecutive adult patients underwent three-field retinal photography with the Topcon TRC NW6S digital fundus camera following pupillary dilatation with Tropicamide 1%. A questionnaire provided information on patients' systemic and ocular history. Glycated haemoglobin (HbA1c) was measured at the screening visit. Two ophthalmologists graded the retinal photographs in a masked fashion. RESULTS: Of 1157 patients attending the diabetes department, 1153 (99.7%)underwent photographic screening. Images were gradable in 96% patients. Diabetic retinopathy was detected in 522 (45%) patients and sight-threatening DR in 167 (14%). Of 704 (61%) patients previously believed to have no DR,254 (34%) screened positive. The presence of DR was associated with age,insulin use and non-Caucasian ethnicity in Type 2 patients, and with duration of diabetes and HbA1c in Type 1 and Type 2 patients. Associated ocular pathologies were diagnosed in 612 (53%) patients. CONCLUSIONS: Our photographic screening programme using pharmacological mydriasis provided a high screening coverage feasible in a hospital setting. We obtained information regarding prevalence and associated risk factors of DR inpatients attending a tertiary care centre. Screening was well accepted by patients and met with no protest from city ophthalmologists. It generated considerable interest among endocrinologists and feedback of results is expected to improve optimization of glycaemic control.

Age-related differences in hormonal and nutritional impact on lean anorexia nervosa bone turnover uncoupling.

INTRODUCTION: In anorexia nervosa (AN) patients osteoporosis occurs within a framework of multiple hormonal abnormalities as a result of bone turnover uncoupling, with decreased bone formation and increased bone resorption. The aim of study was to evaluate the hormonal and nutritional relationships with both of these bone remodeling compartments and their eventual modifications with age. PATIENTS AND MEASUREMENTS: In a cohort of 115 AN patients (mean BMI:14.6 kg/m2) that included 60 mature adolescents (age: 15.5-20 years) and 55 adult women (age: 20-37 years) and in 28 age-matched controls (12 mature adolescents and 16 adults) we assessed: bone markers [serum osteocalcin, skeletal alkaline phosphatase (sALP), C-telopeptide of type I collagen (sCTX) and tartrate-resistant acid phosphatase type 5b (TRAP 5b)], nutritional markers [ body mass index (BMI, fat and lean mass), hormones (free tri-iodothyronine (T3), free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), 17 beta estradiol, free testosterone index (FTI), dehydroepiandrosterone (DHEAS), insulin-like growth factor 1 (IGF-1), growth hormone (GH) and cortisol], plasma methoxyamines (metanephrine and normetanephrine) and calcium metabolism parameters [parathyroid hormone (PTH), Ca, vitamin D3]. RESULTS: Osteocalcin reached similar low levels in both AN age subgroups. sCTX levels were found to be elevated in all AN subjects and higher in mature adolescents than in adult AN (11,567+/-895 vs. 8976+/-805 pmol/l, p<0.05). sALP was significantly lower only in mature adolescent AN patients, while there were no significant differences in the levels of TRAP 5b between AN patients and age-matched control groups. Osteocalcin correlated with sCTX in the control subjects (r=0.65) but not in the AN patients, suggesting the independent regulation of these markers in AN patients. Osteocalcin levels strongly correlated with freeT3, IGF-I, 17 beta estradiol and cortisol, while sCTX correlated with IGF-I, GH and cortisol in both age subgroups of the AN patients. Other hormones or nutritional parameters displayed age-related correlations with bone markers, leading to different stepwise regression models for each age interval. In mature adolescent AN patients, up to 54% of the osteocalcin variance was due to BMI, cortisol and 17 beta estradiol, while 54% of the sCTX variance was determined by GH. In adult subjects, freeT3 and IGF-I accounted for 64% of osteocalcin variance, while 65% of the sCTX variance was due to GH, FTI and methoxyamines. CONCLUSIONS: We suggest a more complex mechanism of AN bone uncoupling that includes not only "classical" influence elements like cortisol, IGF-I, GH or 17 beta estradiol but also freeT3, catecholamines and a "direct" hormone-independent impact of denutrition. Continuous changes of these influences with age should be considered within the therapeutic approach to AN bone loss.

Increase in macrophage elastase (MMP-12) in lungs from patients with chronic obstructive pulmonary disease.

OBJECTIVE AND DESIGN: Chronic obstructive pulmonary disease (COPD) is characterized by an inflammatory process and airway remodeling involving matrix metalloproteinases (MMPs). Thus, we analyzed the expression and release of MMP-12 (macrophage metalloelastase) in bronchoalveolar lavage (BAL) and lung tissue from COPD patients and control subjects. METHODS: Immunocytochemistry and immunochemistry were performed to analyze the expression of MMP-12 in BAL cells and bronchial biopsies. Western blotting was used for the evaluation of MMP-12 in BAL fluids. RESULTS: The number of MMP-12 expressing macrophages together with the staining intensity was higher in BAL samples from COPD patients than in controls subjects. Similar results were noted in bronchial biopsies with higher MMP-12 expression in COPD subjects than in controls. Enhanced MMP-12 level was also observed in BAL fluids from patient with COPD in comparison to control subjects. CONCLUSION: This study demonstrated that COPD patients produce greater quantities of MMP-12 than controls, which may be a critical step in the pathogenesis of COPD and emphysema.