Study of urinary leukotriene E4 in atopic dermatitis: relation to disease severity

Background: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease prevalent in patients with a personal or family history of atopy. Cysteinyl leukotrienes (LTs) are inflammatory mediators which play a role in the pathogenesis of atopic diseases. Urinary leukotriene E4 (LTE4) has been used as an index of the whole body cysteinyl LTs production. Objective: This study was meant to evaluate the importance of LTs in atopic dermatitis (AD) and to study the correlation of urinary LTE4 with disease severity and some commonly altered parameters in AD. Methods: The study included 30 children and adolescents diagnosed to have atopic dermatitis. Ten age and sex matched healthy children and adolescents were enrolled for comparison. They were subjected to clinical evaluation and measurement of urinary LTE4, absolute eosinophilic count, serum IgE and IL-4 and IL-5 in peripheral blood mononuclear cell culture (PBMC) supernatant. The patients were categorized into mild (n=5), moderate (n=16) and severe (n=9) AD subgroups. Results: The study revealed a significant increase in absolute eosinophilic count, urinary LTE4, serum IgE and IL-4 and IL-5 in PBMC culture supernatant in the patients as compared to controls. Moreover, urinary LTE4 levels were significantly increased in moderate and severe cases of AD as compared to the control group, whereas mild cases had levels that were comparable to the controls. Urinary LTE4 levels were higher in severe (p < 0.01) and moderate cases (p < 0.05) when compared to mild cases. Significant positive correlations could be elicited between urinary LTE4 and PBMC IL-4, disease severity scale, absolute eosinophilic count and serum total IgE. However, urinary LTE4 could not be correlated statistically with PBMC IL-5. Conclusion: Elevation in urinary LTE4 excretion in AD patients was demonstrated reflecting increased production of cysteinyl LTs. Urinary LTE4 was correlated to clinical and laboratory markers of severity suggesting that it could be an easy, non invasive and objective prognostic test in AD. Trials of 5-lipoxygenase inhibitors and LT receptor antagonists as additional lines of therapy in AD could thus be suggested.Keywords: atopic dermatitis, urinary LTE4, IgE, IL-4, IL-5, eosinophilic countEgypt J Pediatr Allergy Immunol 2003; 1(2): 134-

Women’s health and well-being in low-income formal and informal neighbourhoods on the eve of the armed conflict in Aleppo

Objectives To explore how married women living in low-income formal and informal neighbourhoods in Aleppo, Syria, perceived the effects of neighbourhood on their health and well-being, and the relevance of these findings to future urban rebuilding policies post-conflict. Methods Semi-structured interviews were undertaken with eighteen married women living in informal or socioeconomically disadvantaged formal neighbourhoods in Aleppo in 2011, a year before the armed conflict caused massive destruction in all these neighbourhoods. Results Our findings suggest that the experience of neighbourhood social characteristics is even more critical to women’s sense of well-being than environmental conditions and physical infrastructure. Most prominent was the positive influence of social support on well-being. Conclusions The significance of this study lies, first, in its timing, before the widespread destruction of both formal and informal neighbourhoods in Aleppo and, second, and in its indication of the views of women who lived in marginalised communities on what neighbourhood characteristics mattered to them. Further research post-conflict needs to explore how decisions on urban rebuilding are made and their likely influence on health and well-being

A rare case of locally advanced fibrosarcoma of diaphysal humerus managed successfully with limb-sparing procedures after neoadjuvant chemotherapy

Fibrosarcomas (FS) of bone are a rare malignancy accounting for less than 5% of all primary malignant bone neoplasms. Diagnosis and treatment approaches of this entity are complex and require a skilled and experienced multidisciplinary team

Clinicopathological, therapeutic and prognostic features of the triple-negative tumors in moroccan breast cancer patients (experience of Hassan II university hospital in Fez)

<p>Abstract</p> <p>Introduction</p> <p>Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors (ER, PR) and Her2, we can distinguish between two groups: basal-like (ER-, PR-, Her2-, cytokeratin (CK) 5/6+ and/or Her1+) and unclassified subtype (ER-, PR-, Her2-, Her1- and CK5/6-).</p> <p>The aim of this study is to determine the clinicopathological, histological, therapeutic and prognostic features associated with this type of breast cancer.</p> <p>Methods</p> <p>This is a retrospective study of 366 female breast cancer patients, diagnosed between January 2007 and June 2010 at the Department of Pathology. Epidemiological, clinical, histological, therapeutic and evolutive data were analyzed. OS and DFS rates were estimated by Kaplan-Meier analysis and a log-rank test to estimate outcome.</p> <p>Results</p> <p>A total of 64 women were identified as having TNBC (17.5% of all female breast cancer patients), 12.6% were basal-like, 4.9% were unclassified subtype, with a median age of 45 years. The median histological tumor diameter was 4.3 cm. TNBC were most often associated with a high grade, 49.2% grade III (53% for unclassified subtype, 47.6% for basal-like). Vascular invasion was found in 26.6% of cases (22% for unclassified subtype and 28.3% for basal-like). For the lymph node involvement: 51% had positive lymph nodes, and 22.4% had distant metastases. Neoadjuvant chemotherapy was administered to 18% patients with 26% of complete pathologic response; therefore adjuvant chemotherapy was given to 82%. 98% received anthracycline based regimen and only 30% received taxanes.</p> <p>The Kaplan-Meier curves based showed the lowest survival probability at 3-years (49% of OS, and 39% of DFS).</p> <p>Conclusion</p> <p>TNBC is associated with young age, high grade tumors, advanced stage at diagnosis, difference chemo response compared to other subtypes, and shortest survival. Critical to optimal future management is accurate identification of truly triple negative disease, and adequately powered prospective TNBC trials to establish treatment efficacy and define predictive biomarkers.</p

Clonal diversity and detection of carbapenem resistance encoding genes among multidrug-resistant Acinetobacter baumannii isolates recovered from patients and environment in two intensive care units in a Moroccan hospital

Background Carbapenem-resistant Acinetobacter baumannii has recently been defined by the World Health Organization as a critical pathogen. The aim of this study was to compare clonal diversity and carbapenemase-encoding genes of A. baumannii isolates collected from colonized or infected patients and hospital environment in two intensive care units (ICUs) in Morocco. Methods The patient and environmental sampling was carried out in the medical and surgical ICUs of Mohammed V Military teaching hospital from March to August 2015. All A. baumannii isolates recovered from clinical and environmental samples, were identified using routine microbiological techniques and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Antimicrobial susceptibility testing was performed using disc diffusion method. The carbapenemase-encoding genes were screened for by PCR. Clonal relatedness was analyzed by digestion of the DNA with low frequency restriction enzymes and pulsed field gel electrophoresis (PFGE) and the multi locus sequence typing (MLST) was performed on two selected isolates from two major pulsotypes. Results A total of 83 multidrug-resistant A. baumannii isolates were collected: 47 clinical isolates and 36 environmental isolates. All isolates were positive for the bla OXA51-like and bla OXA23-like genes. The coexistence of bla NDM-1 /bla OXA-23-like and bla OXA 24-like /bla OXA-23-like were detected in 27 (32.5%) and 2 (2.4%) of A. baumannii isolates, respectively. The environmental samples and the fecally-colonized patients were significantly identified (p < 0.05) as the most common sites of isolation of NDM-1-harboring isolates. PFGE grouped all isolates into 9 distinct clusters with two major groups (0007 and 0008) containing up to 59% of the isolates. The pulsotype 0008 corresponds to sequence type (ST) 195 while pulsotype 0007 corresponds to ST 1089.The genetic similarity between the clinical and environmental isolates was observed in 80/83 = 96.4% of all isolates, belonging to 7 pulsotypes. Conclusion This study shows that the clonal spread of environmental A. baumannii isolates is related to that of clinical isolates recovered from colonized or infected patients, being both associated with a high prevalence of the bla OXA23-like and bla NDM-1genes. These findings emphasize the need for prioritizing the bio-cleaning of the hospital environment to control and prevent the dissemination of A. baumannii clonal lineages

Astrocytic αVβ3 Integrin Inhibits Neurite Outgrowth and Promotes Retraction of Neuronal Processes by Clustering Thy-1

Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to αVβ3 integrin in trans eliciting responses in astrocytes. Nonetheless, whether αVβ3 integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of αVβ3 integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous αVβ3 integrin restricted neurite outgrowth. Likewise, αVβ3-Fc was sufficient to suppress neurite extension in Thy-1(+), but not in Thy-1(−) CAD cells. In differentiating primary neurons exposed to αVβ3-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC). Moreover, αVβ3-Fc also induced retraction of already extended Thy-1(+)-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by αVβ3 integrin. Binding of αVβ3-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, αVβ3-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that αVβ3 integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage

Aberrant crossed corticospinal facilitation in muscles distant from a spinal cord injury.

Crossed facilitatory interactions in the corticospinal pathway are impaired in humans with chronic incomplete spinal cord injury (SCI). The extent to which crossed facilitation is affected in muscles above and below the injury remains unknown. To address this question we tested 51 patients with neurological injuries between C2-T12 and 17 age-matched healthy controls. Using transcranial magnetic stimulation we elicited motor evoked potentials (MEPs) in the resting first dorsal interosseous, biceps brachii, and tibialis anterior muscles when the contralateral side remained at rest or performed 70% of maximal voluntary contraction (MVC) into index finger abduction, elbow flexion, and ankle dorsiflexion, respectively. By testing MEPs in muscles with motoneurons located at different spinal cord segments we were able to relate the neurological level of injury to be above, at, or below the location of the motoneurons of the muscle tested. We demonstrate that in patients the size of MEPs was increased to a similar extent as in controls in muscles above the injury during 70% of MVC compared to rest. MEPs remained unchanged in muscles at and within 5 segments below the injury during 70% of MVC compared to rest. However, in muscles beyond 5 segments below the injury the size of MEPs increased similar to controls and was aberrantly high, 2-fold above controls, in muscles distant (>15 segments) from the injury. These aberrantly large MEPs were accompanied by larger F-wave amplitudes compared to controls. Thus, our findings support the view that corticospinal degeneration does not spread rostral to the lesion, and highlights the potential of caudal regions distant from an injury to facilitate residual corticospinal output after SCI

A Wasp Manipulates Neuronal Activity in the Sub-Esophageal Ganglion to Decrease the Drive for Walking in Its Cockroach Prey

BACKGROUND: The parasitoid Jewel Wasp hunts cockroaches to serve as a live food supply for its offspring. The wasp stings the cockroach in the head and delivers a cocktail of neurotoxins directly inside the prey's cerebral ganglia. Although not paralyzed, the stung cockroach becomes a living yet docile 'zombie', incapable of self-initiating spontaneous or evoked walking. We show here that such neuro-chemical manipulation can be attributed to decreased neuronal activity in a small region of the cockroach cerebral nervous system, the sub-esophageal ganglion (SEG). A decrease in descending permissive inputs from this ganglion to thoracic central pattern generators decreases the propensity for walking-related behaviors. METHODOLOGY AND PRINCIPAL FINDINGS: We have used behavioral, neuro-pharmacological and electrophysiological methods to show that: (1) Surgically removing the cockroach SEG prior to wasp stinging prolongs the duration of the sting 5-fold, suggesting that the wasp actively targets the SEG during the stinging sequence; (2) injecting a sodium channel blocker, procaine, into the SEG of non-stung cockroaches reversibly decreases spontaneous and evoked walking, suggesting that the SEG plays an important role in the up-regulation of locomotion; (3) artificial focal injection of crude milked venom into the SEG of non-stung cockroaches decreases spontaneous and evoked walking, as seen with naturally-stung cockroaches; and (4) spontaneous and evoked neuronal spiking activity in the SEG, recorded with an extracellular bipolar microelectrode, is markedly decreased in stung cockroaches versus non-stung controls. CONCLUSIONS AND SIGNIFICANCE: We have identified the neuronal substrate responsible for the venom-induced manipulation of the cockroach's drive for walking. Our data strongly support previous findings suggesting a critical and permissive role for the SEG in the regulation of locomotion in insects. By injecting a venom cocktail directly into the SEG, the parasitoid Jewel Wasp selectively manipulates the cockroach's motivation to initiate walking without interfering with other non-related behaviors

A UK wide cohort study describing management and outcomes for infants with surgical Necrotising Enterocolitis

The Royal College of Surgeons have proposed using outcomes from necrotising enterocolitis (NEC) surgery for revalidation of neonatal surgeons. The aim of this study was therefore to calculate the number of infants in the UK/Ireland with surgical NEC and describe outcomes that could be used for national benchmarking and counselling of parents. A prospective nationwide cohort study of every infant requiring surgical intervention for NEC in the UK was conducted between 01/03/13 and 28/02/14. Primary outcome was mortality at 28-days. Secondary outcomes included discharge, post-operative complication, and TPN requirement. 236 infants were included, 43(18%) of whom died, and eight(3%) of whom were discharged prior to 28-days post decision to intervene surgically. Sixty infants who underwent laparotomy (27%) experienced a complication, and 67(35%) of those who were alive at 28 days were parenteral nutrition free. Following multi-variable modelling, presence of a non-cardiac congenital anomaly (aOR 5.17, 95% CI 1.9-14.1), abdominal wall erythema or discolouration at presentation (aOR 2.51, 95% CI 1.23-5.1), diagnosis of single intestinal perforation at laparotomy (aOR 3.1 95% CI 1.05-9.3), and necessity to perform a clip and drop procedure (aOR 30, 95% CI 3.9-237) were associated with increased 28-day mortality. These results can be used for national benchmarking and counselling of parents