[Screening for diabetic retinopathy by non-mydriatic fundus photography: First national campaign in Lebanon]. / Dépistage de la rétinopathie diabétique par rétinographie non mydriatique : première campagne nationale au Liban.

INTRODUCTION: Diabetic retinopathy (DR) is a leading cause of blindness worldwide. Non-mydriatic fundus photography (NMFP) has been adopted as a screening tool for this disease. We aim to determine the prevalence of DR through this method in Lebanese diabetic patients and to evaluate the impact of such screening in this population. MATERIALS AND METHODS: This study explores data from an awareness and screening campaign conducted in Lebanon. Diabetic patients from multiple regions were referred by their endocrinologists to undergo NMFP using the Optomed SmartScope® handheld fundus camera. Photographs were interpreted by a remote observer, and recommendations were given accordingly. The prevalence of DR was calculated, and statistical analyses were performed on the clinical characteristics, fundus findings and number of referrals to ophthalmologists. RESULTS: The campaign lasted 11 months, during which 2205 patients were examined in 37 screening locations. Out of the 97.41% of patients with type 2 diabetes mellitus, 12.56% had signs of DR, with no significant difference between the regions. 6.28% of the photos were uninterpretable. Positive results were associated with a longer duration of diabetes (P<0.01), treatment with insulin (P<0.01), as well as the presence and chronicity of systemic hypertension (P=0.01). 25% of patients with positive testing were retrospectively asked about their follow-up; only one third had an ophthalmologic examination as per the recommendation, among whom 68.18% underwent treatment for proliferative DR and/or diabetic macular edema. CONCLUSION: Tele-ophthalmology is useful in mass screening for DR. The importance of dilated fundus examinations still needs to be highlighted for diabetic patients, and better collaboration between endocrinologists and ophthalmologists is required to improve screening outcomes.

Relation of the Mediterranean diet with the incidence of gestational diabetes.

BACKGROUND/OBJECTIVES: Some studies document relationships of the incidence of gestational diabetes mellitus (GDM) with individual components of the diet, but studies exploring relationships with patterns of eating are lacking. This observational study aimed to explore a possible relationship between the incidence of GDM and the Mediterranean diet (MedDiet) pattern of eating. SUBJECTS/METHODS: In 10 Mediterranean countries, 1076 consecutive pregnant women underwent a 75-g OGTT at the 24th-32nd week of gestation, interpreted both by the ADA_2010 and the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)_2012 criteria. The dietary habits were assessed by a previously validated questionnaire and a Mediterranean Diet Index (MDI) was computed, reflecting the degree of adherence to the MedDiet pattern of eating: a higher MDI denoting better adherence. RESULTS: After adjustment for age, BMI, diabetes in the family, weight gain and energy intake, subjects with GDM, by either criterion, had lower MDI (ADA_2010, 5.8 vs 6.3, P=0.028; IADPSG_2012, 5.9 vs 6.4, P<0.001). Moreover, the incidence of GDM was lower in subjects with better adherence to the MedDiet (higher tertile of MDI distribution), 8.0% vs 12.3%, OR=0.618, P=0.030 by ADA_2010 and 24.3% vs 32.8%, OR=0.655, P=0.004 by IADPSG_2012 criteria. In subjects without GDM, MDI was negatively correlated with both fasting plasma glucose and AUC glucose, P<0.001 for both. CONCLUSIONS: Adherence to a MedDiet pattern of eating is associated with lower incidence of GDM and better degree of glucose tolerance, even in women without GDM. The possibility to use MedDiet for the prevention of GDM deserves further testing with intervention studies.

A cyclic peptide targeted against PSD-95 blocks central sensitization and attenuates thermal hyperalgesia.

Post-synaptic density protein PSD-95 is emerging as a valid target for modulating nociception in animal studies. Based on the key role of PSD-95 in neuronal plasticity and the maintenance of pain behavior, we predicted that CN2097, a peptide-based macrocycle of nine residues that binds to the PSD-95 Discs large, Zona occludens 1 (PDZ) domains of PSD-95, would interfere with physiologic phenomena in the spinal cord related to central sensitization. Furthermore, we tested whether spinal intrathecal injection of CN2097 attenuates thermal hyperalgesia in a rat model of sciatic neuropathy. Results demonstrate that spinal CN2097 reverses hyperexcitability of wide dynamic range (WDR) neurons in the dorsal horn of neuropathic rats and decreases their evoked responses to peripheral stimuli (brush, low caliber von Frey and pressure), whereas CN5125 ("negative control") has no effect. CN2097 also blocks C-fiber long-term potentiation (LTP) in the dorsal horn, which is linked to neuronal plasticity and central sensitization. At a molecular level, CN2097 attenuates the increase in phosphorylated p38 MAPK, a key intracellular signaling pathway in neuropathic pain. Moreover, spinal injection of CN2097 blocks thermal hyperalgesia in neuropathic rats. We conclude that CN2097 is a small molecule peptide with putative anti-nociceptive effects that modulates physiologic phenomena related to central sensitization under conditions of chronic pain.

Activated polymorphonuclear cells promote injury and excitability of dorsal root ganglia neurons.

Therapies aimed at depleting or blocking the migration of polymorphonuclear leukocytes (PMN or neutrophils) are partially successful in the treatment of neuroinflammatory conditions and in attenuating pain following peripheral nerve injury or subcutaneous inflammation. However, the functional effects of PMN on peripheral sensory neurons such as dorsal root ganglia (DRG) neurons are largely unknown. We hypothesized that PMN are detrimental to neuronal viability in culture and increase neuronal activity and excitability. We demonstrate that isolated peripheral PMN are initially in a relatively resting state but undergo internal oxidative burst and activation by an unknown mechanism within 10 min of co-culture with dissociated DRG cells. Co-culture for 24 h decreases neuronal count at a threshold<0.4:1 PMN:DRG cell ratio and increases the number of injured and apoptotic neurons. Within 3 min of PMN addition, fluorometric calcium imaging reveals intracellular calcium transients in small size (<25 microm diam) and large size (>25 microm diam) neurons, as well as in capsaicin-sensitive neurons. Furthermore, small size isolectin B4-labeled neurons undergo hyperexcitability manifested as decreased current threshold and increased firing frequency. Although co-culture of PMN and DRG cells does not perfectly model neuroinflammatory conditions in vivo, these findings suggest that activated PMN can potentially aggravate neuronal injury and cause functional changes to peripheral sensory neurons. Distinguishing the beneficial from the detrimental effects of PMN on neurons may aid in the development of more effective drug therapies for neurological disorders involving neuroinflammation, including painful neuropathies.

Neutrophils invade lumbar dorsal root ganglia after chronic constriction injury of the sciatic nerve.

To test whether neutrophils (PMN) target lumbar dorsal root ganglia (DRG) following axonal injury leading to neuropathic pain, we visualized PMN infiltration in DRG tissue sections and estimated PMN count by flow cytometry following sciatic chronic constriction injury (CCI). Seven days after CCI, results show PMN within DRG where their count increased by three fold ipsilateral to injury compared to contralateral or sham, concomitant with peak neuropathic pain behavior. Superoxide burst in PMN isolated from rats d7 after CCI was elevated by 170% +/-18 compared to naïve and MCP-1 mRNA expression in DRG increased by 8.9+/-2.9 fold, but that of MIP-2, CINC-1, and RANTES did not change. We conclude that CCI causes PMN invasion of the DRG whereby the functional implication of their close proximity to neuronal axon and soma remains unknown.

Cerebellar stimulation modulates the intensity of a visceral nociceptive reflex in the rat.

The cerebellum modulates different nociceptive phenomena and influences visceral functions. This study shows cerebellar modulation of an abdominal reflex elicited by a visceral noxious stimulus (colorectal distension, CRD). The intensity of the reflex was measured by electromyographic (EMG) recording from the rectus abdominus muscle, and the cerebellar cortex (vermis, lobule VIII), the fastigial nucleus, or the dentate nucleus was stimulated using D, L-homocysteic acid (0.1 M, 1 micro l). To release the fastigial nucleus from inhibition by the Purkinje cells, bicuculline (GABA(A) receptor antagonist, 100 micro M, 1 micro l) was used. Stimulation of the cerebellar cortex enhanced, whereas stimulation or disinhibition of the fastigial nucleus decreased, the responses to CRD measured by EMG. Stimulation of the dentate nucleus did not have an obvious effect on the intensity of the reflex. These results are in agreement with the hypothesis that the cerebellum modulates visceral nociceptive functions, whereby the cerebellar cortex and the fastigial nucleus, respectively, play a pro-nociceptive and an anti-nociceptive role.

Stimulation in the rat fastigial nucleus enhances the responses of neurons in the dorsal column nuclei to innocuous stimuli.

The cerebellum was recently proposed to play a role in cognition and sensation in addition to motor phenomena. We have shown that the cerebellum is involved in the processing of sensory nociceptive information. In this study, the activity of neurons in the dorsal column nuclei (DCN) was tested following stimulation in the rat fastigial nucleus. The results showed an enhancement of the extracellularly recorded responses of DCN neurons to somatic non-noxious stimuli following injection of D,L-homocysteic acid (0.1 M, 1 microl) into the area of the fastigial nucleus. We conclude that the cerebellum influences the processing of non-noxious somatosensory information at the level of the DCN, an important relay and a center for the processing of fine tactile and vibratory information. This observation is not yet supported by clinical data.

Bone mineral density in beta - thalassemic Lebanese children.

Osteoporosis has been described extensively in adult thalassemics. Fewer studies have been reported in thalassemic children. In this article, we measured the bone mineral density (BMD) of Lebanese beta-thalassemic children before institution of a balanced transfusion-chelation regimen, in comparison with that of healthy controls, and studied its correlation with various demographic and biological parameters. Both groups, controls and thalassemics were comparable with respect to age, sex, socioeconomic and regional distribution. On the other hand, thalassemics had a significantly lower height age (p<0.001), lower bone age (p=0.001), lower sexual maturation (p=0.004), lower absolute BMD values and larger negative BMD-Z scores (p<0.001). Within the thalassemic group, BMD correlated significantly with luteinizing hormone (LH) and follicle stimulating hormone (FSH), estradiol and testosterone values, as well as with the pretransfusion hematocrit, but not with other endocrine or bone metabolism parameters. We conclude that Lebanese beta-thalassemic children have a significantly lower BMD than their healthy counterparts due, in part, to their slower physical development. A major contributor seems to be the low-transfusion regimen followed by these patients, as well as the endocrine dysfunction which was detected in about 25% of them.

Nociceptive visceral stimulation modulates the activity of cerebellar Purkinje cells.

The cerebellum is a system with various input and output functions that influence motor, sensory, cognitive, and other processes. In a previous study, we showed that cerebellar cortical stimulation increases spinal neuronal responses to visceral noxious stimulation by colorectal distension (CRD). However, the neuronal network underlying the cerebellar modulation of nociceptive phenomena is largely unknown. Purkinje cells of the cerebellar cortex receive ascending and descending inputs and exert a major inhibitory control over neurons in the underlying cerebellar nuclei that constitute the cerebellar output. Therefore, in this study, we tested the effect of CRD and other somatic stimuli on the firing rate of Purkinje cells using in vivo extracellular recording techniques. The results suggest that Purkinje cells respond to nociceptive visceral and somatic stimulation in the form of early and delayed changes in activity. Based on these and previous findings, we propose a negative feedback circuitry involving the cerebellum for the modulation of peripheral nociceptive events.

Cerebellar cortical stimulation increases spinal visceral nociceptive responses.

The role of the cerebellum in modulating nociceptive phenomena is unclear. In this study, we focus on the effects of cerebellar cortical stimulation on the responses of midline neurons of the lumbosacral spinal cord to graded nonnoxious and noxious visceral (colorectal distension) as well as somatic (brush, pressure, pinch) stimuli. Extracellular recording was used for the isolation and recording of spinal nociceptive neurons, while electrical current pulses and chemical injection of D, L-homocysteic acid were used to stimulate the cortex of the posterior cerebellar vermis. Cerebellar cortical stimulation increased the responses of all isolated cells to colorectal distension, whereas the effect on the responses to somatic stimuli was variable. These findings indicate that the posterior cerebellar vermis may exert a pro-nociceptive effect on spinal visceroceptive neurons.

Preemptive intrathecal ketamine injection produces a long-lasting decrease in neuropathic pain behaviors in a rat model.

BACKGROUND AND OBJECTIVES: Ketamine is an N-Methyl-D-Aspartate (NMDA) receptor antagonist, which has been found to effectively treat somatic and neuropathic pain. This study examines the effect (on neuropathic pain) of preemptive ketamine using different routes of administration (intrathecal versus intraperitoneal). METHODS: The Institutional Animal Care and Use Committee approved the study. Thirty male Sprague-Dawley rats (250-275 g) were divided into three treatment groups [intrathecal saline/intraperitoneal saline or Control (CTL), intrathecal ketamine/intraperitoneal saline (ITK), and intrathecal saline/intraperitoneal ketamine (IPK)] prior to undergoing surgery to induce neuropathic pain by tight ligation of the left L5 and L6 spinal nerves. All drugs were given 15 minutes before nerve ligation. The ITK group received intrathecal ketamine (0.5% solution, 1 mg/kg), the IPK group received intraperitoneal ketamine (0.5% solution, 1 mg/kg), saline was given in equal volume (approximately 0.05 mL). Mechanical allodynia, cold allodynia, and ongoing pain behaviors indicative of neuropathic pain were assessed on postoperative days 1, 3, 7, and 14 using validated methods. RESULTS: Compared with the CTL group, the ITK group showed a state of decreased mechanical allodynia, cold allodynia, and ongoing pain as revealed by the von Frey hair, acetone, and cold plate testing, respectively. Further, this decrease was sustained for at least 2 weeks. The IPK group showed intermediate results between the CTL and ITK. CONCLUSIONS: Neuropathic pain behaviors were significantly reduced for at least 2 weeks after intrathecal ketamine was preemptively administered to animals undergoing surgery to induce neuropathic pain. The mechanism of action is thought to be prevention of spinal cord sensitization.

[Turner syndrome: spontaneous growth of stature, weight increase and accelerated bone maturation]. / Syndrome de Turner: croissance staturopondérale et maturation osseuse spontanées.

BACKGROUND: Since growth hormone is effective in increasing the height of girls with Turner's syndrome, it is important to dispose of growth and bone maturation curves in a large number of untreated patients. POPULATION AND METHODS: Data on growth and bone maturation were collected from 160 patients with Turner's syndrome (50 have reached final height), born 1965-1991, untreated with growth hormone or anabolic steroids. X monosomy was found in half of the patients, mosaicism or X abnormality was present in the other half. Spontaneous puberty occurred in 25% (n = 25) of patients older than 13 years, 38 patients received estrogen after 13 years. Final heights were compared to predicted height according to Lyon's method. RESULTS: Forty-five percent of patients were small for date. Height velocity decreased from 2 years of age and decreased faster during adolescence, when gonadal dysgenesis occurred. Bone maturation velocity decreased also during adolescence. Excessive weight appeared after the age of 5 years. Patients with partial deletion of the long arm of X (n = 6) were taller than the other girls (n = 44) (mean +/- DS) 152.5 +/- 3.1 cm, range 150-158 cm versus 142.5 +/- 4.9 cm, 130-150 cm (P < 0.0001). Final height was not modified by spontaneous puberty. Final height was correlated with birth weight (r = 0.7), maternal height (r = 0.5) and mid parental height (r = 0.5). Finally, the Lyon's method for predicted final height seemed to be suitable for this population, (r = 0.8, P < 0.001). CONCLUSION: Appropriate growth curve is an essential clinical tool in evaluating treatment aimed at increasing final stature in patients with Turner's syndrome.

Nutritional status and growth hormone-binding protein.

To study the effects of nutrition on growth hormone (GH) receptor status, the plasma GH-binding protein was evaluated under conditions of poor nutrition, anorexia nervosa, celiac disease, and obesity. Nine patients, aged 12-30 years, presented anorexia nervosa and had a mean weight loss of -19% of their initial weight at the time of the study. Ten patients with celiac disease, aged 3-14 years, had a mean height at -4.2 SD, and normal body weight for height. Fourteen severely obese children, aged 3-10 years, had a mean body mass index (BMI) of 25.7 +/- 0.9. GH-binding protein was low in patients with anorexia nervosa (16.8 +/- 1.9% of radioactivity) and in patients with celiac disease (16.1 +/- 2.2%) whereas it was very high in obese children (57.2 +/- 3.3%). A strong correlation was found between GH-binding protein and BMI. GH-binding protein was also correlated with insulin-like growth factor-1 plasma levels. Nutrition is an important regulator of the GH receptor/binding protein. The growth failure presented by undernourished children is associated with partial GH resistance and low GH receptor level. On the contrary, children with obesity and normal growth have a high GH receptor level.

[Solidarity-Psychiatry inc.]. / Solidarité-Psychiatrie Inc.

The authors, after explaining what it is to suffer a depression and the consequences involved, then follow with a criticism of the psychiatric institution. They describe their project : <> inspired by D. W. Winnicott's experience and M. Mannoni's concept of institution. The aim of this project is to provide a meeting place for people concerned with the reality of mental illness where they would reflect on different aspects of mental illness and learn how to read to its manifestations in everyday life. The project became operational in April 1979, since then more than 110 persons have benefited from it. They have weekly meetings, ongoing activities such as a theatrical play, regular discussions on various themes; three committees have been formed 1) a committee for a theatrical workshop; 2) a committee of reflexion; 3) a committee to deal with emergencies. They are also working on the procedures necessary for the request of a chart.