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ABSTRACT: For several decades, metformin has been used as an oral hypoglycaemic agent, where it is the first line of treatment in overweight and obese type 2 diabetic patients. This is because it decreases the hepatic glucose output and acts as an insulin sensitizer by increasing the glucose utilization by muscles and adipocytes. As a result of the improvement in glycaemic control, serum insulin concentrations decline slightly, thus improving hyperinsulinaemia and its signs. In addition, it has been shown that metformin has platelet anti-aggregating and antioxidant effects. These pharmacological properties have allowed metformin to be effective in non-diabetic situations including cutaneous conditions. This is an evidence-based review on the use of metformin in the treatment of skin disorders such as hirsutism, acne, hidradenitis suppurativa, acanthosis nigricans, psoriasis, skin cancer, among others. In addition, cutaneous side-effects such as leukocytoclastic vasculitis, bullous pemphigoid, psoriasiform drug eruption, lichen planus and acute alopecia have been associated with metformin use and are discussed in the article.
Journal of the European Academy of Dermatology and Venereology 02/2013; · 2.98 Impact Factor
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ABSTRACT: Background Scleroderma is a connective tissue disease that includes localized and systemic forms. Our recent encounter with a morphea case exhibiting prominent perineural inflammation microscopically prompted us to assess the features of all patients diagnosed with morphea/scleroderma at our institution. Objective/methods To describe the clinicopathological features of all patients diagnosed with morphea/scleroderma at American University of Beirut Medical Center (AUB-MC) between 1999 and 2010, and compare our findings with those published in the literature. Results A total of 81 cases (63 women and 18 men) were identified, of which 73 were localized (morphea) and eight were systemic scleroderma. Clinically, plaque type morphea was the most common variant both in adults and children, and seven (9%) cases of morphea were associated with lichen sclerosis et atrophicus (LSA). Histopathologically, perineural inflammation was observed in 49% of cases, and may serve, in addition to other features including lichen sclerosis-like changes (observed in exclusively nine cases of morphea), more diffuse dermal and less subcutaneous sclerosis, and intense inflammation, as clues favouring diagnosis of morphea over systemic sclerosis. Conclusion The features of morphea/scleroderma patients in this study are generally comparable to those published in the literature, with few differences. Clinically, plaque type morphea was the most common variant both in adults and children and LSA was a frequent association. Histopathologically, perineural inflammation was commonly observed and may serve in addition to lichen sclerosis-like changes and intense inflammation as clues favouring diagnosis of morphea over systemic sclerosis.
Journal of the European Academy of Dermatology and Venereology 05/2012; · 2.98 Impact Factor
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ABSTRACT: Hereditary leukonychia, also known as white or porcelain nails, is a rare genetic disease characterized by whitening of the nail plate of all 20 nails. The condition can be associated with other cutaneous or systemic manifestations, while an isolated leukonychia (MIM 151600) also exists, which can show either an autosomal dominant or recessive inheritance pattern.(1) We (M.K. and Y.S.) have recently identified mutations in PLCD1 gene on chromosome 3p22.2 in several Pakistani families with either autosomal dominant or recessive isolated leukonychia.(2) The human PLCD1 gene encodes a member of phospholipase C, and is abundantly expressed in the nail matrix.(2,3) Besides these findings, molecular basis of hereditary leukonychia in the other populations, as well as functional consequences resulting from PLCD1 mutations, remain largely unknown yet.
British Journal of Dermatology 03/2012; 167(4):946-9. · 3.67 Impact Factor
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ABSTRACT: Background Woolly hair (WH) belongs to a family of disorders characterized by hair shaft anomalies that clinically presents with tightly curled hair, which can be divided into syndromic and non-syndromic forms of WH. We have recently identified mutations in both LPAR6/P2RY5 and LIPH that are associated with autosomal recessive woolly hair (ARWH). Objective To study the underlying genetic causes of autosomal woolly hair in Pakistani population. Methods We studied 10 Pakistani families with ARWH for mutations in LPAR6/P2RY5 and LIPH and then performed haplotype analysis to confirm their segregation in the families. Results We identified five mutations in LPAR6/P2RY5, among which three were recurrent and two were novel in eight Pakistani families. We then showed that two of the mutations in LPAR6/P2RY5 are founder mutations in Pakistani families. Moreover, we identified two recurrent mutations in the LIPH gene in two Pakistani families. Conclusion Our study extends the spectrum of mutations in LPAR6/P2RY5 gene and underscores those mutations in LPAR6/P2RY5 and LIPH result in similar phenotypes.
Journal of the European Academy of Dermatology and Venereology 03/2012; · 2.98 Impact Factor
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ABSTRACT: Background Confluent and reticulate papillomatosis (CRP) is a rare disorder that has mostly been described in case reports and limited case series. Studies on this condition from our region are lacking. Objective/methods To describe the clinical and histopathological findings, as well as response to treatment of all patients diagnosed with CRP at the American University of Beirut Medical Center (AUB-MC) between 1999 and 2009, and to compare our findings with those published in the literature. Results Confluent and reticulate papillomatosis was diagnosed in 10 patients (five men, five women). Mean age at diagnosis was 19 years. Duration of lesions ranged from few months to several years. Skin lesions mainly consisted of reticulated, pigmented macules, patches and plaques. The most common area of involvement was the chest in five cases. The rash was asymptomatic in eight patients. Skin biopsy specimens from all patients revealed hyperkeratosis, papillomatosis and variable acanthosis. Whereas follicular plugging was observed in nine cases, anastomosis of the rete ridges was noted in three. Periodic acid Schiff stains highlighted yeast forms in six cases. Conclusion The clinical and histopathological features of the CRP patients in our study are generally comparable to those published in the literature, with minor differences. Clinically, one case had an atypical clinical presentation, and microscopically follicular plugging was seen in the majority of cases. Yeast-like spores were seen in six cases further supporting a role of Malassezia furfur in the pathogenesis of CRP.
Journal of the European Academy of Dermatology and Venereology 11/2011; · 2.98 Impact Factor
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ABSTRACT: Background Cutaneous leishmaniasis (CL) has been an endemic disease in Aleppo, Syria for many decades. During the past 12 years, there was a clear increase in the overall incidence of the disease in the region. Treatment using intralesional method of antimonial compounds became ineffective in a considerable proportion of cases and more patients developed the chronic form of the disease. Objectives To categorize chronic cutaneous leishmaniasis (CCL) into different subtypes that mimic a wide spectrum of skin diseases, and to analyse the cause of this increase in the incidence of the disease as a whole and of the chronic type in particular. Methods A total number of 6200 patients with CL were seen in our centre, among which 1880 were initially diagnosed with CCL. Inclusion criteria for CCL included CL for more than 1 year. The diagnosis of CCL was made based on the clinical presentation and a positive Giemsa smear test. Biopsies were performed whenever the Giemsa smear was negative. Patients who had immunosuppression due to a medical condition or intake of immunosuppressive medications were excluded. Results Of 1880 patients, 1750 patients fit the inclusion criteria. Based on the lesion morphology, three different types of CCL were defined, among which five subtypes were observed based on clinical pattern and distribution of lesions. The two most common types of CCL were the papulonodular and plaque forms. Around 80% of all CCL cases occurred in individuals under 16 years of age and the most common location was the face (88.6% of cases). Conclusions CCL due to Leishmania tropica can mimic many other dermatological conditions which might lead to a delay in making the correct diagnosis resulting in increased resistance to treatment. We have illustrated eight different clinical presentations of CCL and their differential diagnoses to make physicians more aware of the atypical presentations of CCL. A new treatment plan is suggested for the high-risk group of acute cutaneous leishmaniasis patients to decrease the likelihood of progressing to chronicity.
Journal of the European Academy of Dermatology and Venereology 09/2011; 26(10):1224-9. · 2.98 Impact Factor
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Clinical and Experimental Dermatology 04/2010; 35(3):e50-1. · 1.20 Impact Factor
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Clinical and Experimental Dermatology 04/2010; 35(3):e76-8. · 1.20 Impact Factor
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Clinical and Experimental Dermatology 03/2010; 35(3):e76 - e78. · 1.20 Impact Factor
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ABSTRACT: Hypotrichosis with juvenile macular dystrophy (HJMD; OMIM 601553) is a rare autosomal recessive disorder characterized by hypotrichosis with short scalp hair and progressive macular dystrophy leading to blindness between the second and the fourth decades of life. HJMD is caused by mutations in the P-cadherin gene (CDH3), a member of the family of classical cadherins.
We analyzed the DNA from members of 2 consanguineous Pakistani families with HJMD for mutations in the P-cadherin gene through direct sequencing.
We identified 2 splice site mutations in the P-cadherin gene in these families. One was a novel mutation, Ivs12-2A-->G and the other a recurrent mutation, Ivs10-1G-->T. A screening assay for the novel mutation ruled out the possibility of a polymorphism. Using haplotype analysis, we determined that the mutation, Ivs10-1G-->T, is a founder mutation in the Pakistani population.
We identified 2 splice site mutations in the CDH3 gene leading to HJMD, further enriching our understanding of HJMD versus ectodermal dysplasia, ectrodactyly and macular dystrophy syndrome.
Dermatology 03/2010; 220(3):208-12. · 2.05 Impact Factor
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ABSTRACT: Papillon-Lefevre syndrome (PLS; OMlM 245000) is an autosomal recessive disease caused by mutations in cathepsin C (CTSC) gene and is characterized by palmoplantar keratoderma, psoriasiform lesion over the extensor surfaces and gingivitis followed by loss of teeth. CTSC gene is expressed in several tissues including the skin and cells of the immune system. In the skin, CTSC plays a role in differentiation and desquamation, whereas in the immune system, it activates serine proteases.
We analysed the molecular basis of PLS in a Pakistani family.
Genomic DNA was isolated from the sample according to standard techniques. All exons of the CTSC gene with adjacent sequences of exon-intron borders were amplified by PCR and directly sequenced.
We identified a novel deletion mutation designated c.2ldelG (Leu7PhefsX57) in exon 1 of the CTSC gene, which probably results in the absence of CTSC protein.
Our data further expand the spectrum of mutations in the CTSC gene underlying PLS.
Journal of the European Academy of Dermatology and Venereology 03/2010; 24(8):967-9. · 2.98 Impact Factor
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Clinical and Experimental Dermatology - CLIN EXP DERMATOL. 01/2010; 35(3).
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Journal of dermatological science 11/2009; 57(2):132-4. · 3.71 Impact Factor
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Journal of the European Academy of Dermatology and Venereology 09/2009; 24(2):232-4. · 2.98 Impact Factor
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Clinical Genetics 09/2009; 76(3):300-2. · 3.13 Impact Factor
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ABSTRACT: The maintenance schedules of generating units attracts great attention in power system planning and designing, and also operation management. The power system maintenance schedule is a constrained optimization problem. In this paper, objective functions in power system maintenance are obtained and certain constraints are set up. The most used heuristic methods for maintenance schedule optimization are the levelized reserve method and the levelized risk method. They are discussed and used for the maintenance schedule optimization in an interconnected power system. The strategy in the maintenance scheduling of the generation units is also given.
Power Engineering, 2003 Large Engineering Systems Conference on; 06/2003
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ABSTRACT: Background: Congenital insensitivity to pain (CIP) (OMIM 243000) is a rare autosomal-recessive disorder. Clinically, CIP is characterized by insensitivity to all modalities of pain except neuropathic pain, and recurrent injuries frequently go unnoticed. CIP is caused by mutations in the SCN9A gene encoding for the Na1.7 channel. Methods: We analyzed the DNA from members of a consanguineous Pakistani family for mutations in the SCN9A gene through direct sequencing after performing linkage studies. Results: We identified a novel missense mutation designated R523X in all affected individuals. A screening assay ruled out the possibility of polymorphism. Conclusion: We identified a novel mutation in the Na1.7 channel leading to CIP, extending the spectrum of mutations in the Na1.7 channel, and enhancing our understanding of the physiology of pain.
Dermatology 08/1970; 221(2):179-183. · 2.05 Impact Factor
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ABSTRACT: Background: X-linked recessive hypohidrotic ectodermal dysplasia (XLHED; OMIM 305100) is a rare genodermatosis characterized clinically by developmental abnormalities affecting the teeth, hair and sweat glands. Mutations in the EDA-A1 gene have been associated with XLHED. Recently, mutations in the EDA-A1 gene have also been implicated in isolated X-linked recessive hypodontia (XLRH; OMIM 313500). Methods: We analyzed the DNA from members of 3 unrelated Pakistani families with XLRH for mutations in the EDA-A1 gene through direct sequencing and performed haplotype analysis. Results: We identified a common missense mutation in both families designated c.1091T→C (p.M364T). Haplotype analysis revealed that this is a founder mutation in the 3 families. Conclusion: XLHED is a syndrome with variable clinical presentations that contain a spectrum of findings, including hypodontia. We suggest that XLRH should be grouped under XLHED as both share several phenotypic and genotypic similarities.
Dermatology 08/1970; 221(3):243-247. · 2.05 Impact Factor
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ABSTRACT: Background: Autosomal recessive congenital ichthyosis (ARCI) can be divided into 3 types including lamellar ichthyosis (OMIM 242304), nonbullous congenital ichthyosiform erythroderma (OMIM 242100) and harlequin ichthyosis (OMIM 242500). The last type is uncommon since newborns with harlequin ichthyosis usually die shortly after birth. Several genes have been linked to ARCI, but these represent only 60% of the known genetic causes of this condition. Methods: After having performed a linkage analysis, we analyzed the DNA of 2 consanguineous Pakistani families with ARCI for NIPAL4 mutations and performed in situ hybridization (ISH) for NIPAL4 mRNA in the epidermis. Results: The haplotype analysis revealed a linkage to chromosome 5, and we identified a recurrent missense mutation, p.A176D, in affected individuals from both families. We also determined by ISH that NIPAL4 mRNA is highly expressed in the granular cell layer of the epidermis, consistent with the ARCI phenotype. Conclusion: Our results expand the spectrum of the clinical manifestations of the NIPAL4 gene and further extend our understanding of its molecular function.
Dermatology 08/1970; 220(1):8-14. · 2.05 Impact Factor
