Cutaneous manifestations of hyper-IgE syndrome in twins: a case report from Saudi Arabia.

The hyper-IgE syndrome with recurrent infections is a rare immunodeficiency disorder characterized by very high levels of IgE in serum. It is inherited in most of the cases in a dominant fashion meaning that it can run in families with a high frequency. About 250 cases have been published in literature so far

Single nucleotide substitution mutations and polymorphisms in ECM1 gene in lipoid proteinosis in siblings of a Pakistani family

A number of mutations in extracellular matrix protein 1 (ECM1) that is a glycoprotein and expressed in skin and other tissues are reported to cause a rare, autosomal recessive disorder called lipoid proteinosis (LP). The peculiar manifestation of LP is hoarseness of voice caused by laryngeal infiltration in infancy. Skin and mucous membrane changes clinically become apparent, and the disease typically follows a slowly progressive, yet often benign, course. About 300 cases of LP have been reported, but occurrence in siblings is rare. In this study, two siblings (18 and 24-year-old) of a Pakistani family were reported to have LP. This study presents two brothers with scaly itchy lesions on whole body, hoarse voice and macroglossia. Their deceased father had similar clinical manifestations but mother, younger brother and sister were unaffected. Blood from affected and clinically unaffected family members were collected with informed consent. The ECM1 gene containing 10 exons were amplified and sequenced. Both patients showed non-pathogenic missense and silent mutations in exon 6 and 8. In exon 6, a nucleotide C was substituted to T (C→T) at codon 2, in patient 1. This nonpathogenic missense mutation causes appearance of amino acid cysteine instead of arginine that is part of normal ECM1 protein. In patient 2, polymorphism of nucleotide C to T (C/T) was observed observed in exion 6 that may lead to the appearance of cysteine and/or arginine in the resulting gene product. In exon 8, a nucleotide G was substituted to A (G→A) at codon 53, in patient 1. This substitution leads to a silent mutation as serine is coded by both forms of codon. In patient 2, polymorphism of nucleotide G to A (G/A) was observed in exion 8 that do not cause any change in the coded amino acid. These findings represent a set of missense and silent mutations supporting an unusual function of ECM1 protein, broadening the spectrum of disease-linked mutations in rare cases of LP.Key words: Lipoid proteinosis, extracellular matrix protein 1 (ECM1), missense, silent mutation, single nucleotide polymorphism, exons 6 and 8, genodermatosis

Tuberculosis in children in India-II: Chemotherapy for tuberculosis

Tubercle bacilli readily become resistant to the common drugs, and resistant bacilli are more likely to proliferate if they are present in the patient at the start of treatment. So always use more than one drug. The only possible exception is prophylaxis for an asymptomatic case with a normal X-ray. CAUTION! (1) Never give intermittent (twice or thrice weekly) treatment unless every dose can be supervised by a health worker. Daily treatment is usually mandatory. (2) When you give more than one drug, give them both at the same time, so that high blood levels coincide; do not give one drug daily and the other drug less often. THE DOSES of the commonly used drugs for daily and intermittent treatment in children and adults are: lsoniazid (H) 5 mg/kg/24 hours if he is moderately ill and 10 mg/kg/24 hours if he is severely ill. The dose for a twice weekly course is 15 mg/kg. CAUTION! Opinions on the dose of isoniazid vary. Some consider 10 mg/kg/24 hours too much for an Indian child and always give 5 mg. Rifampicin (R) 10 mg/kg/24 hours, or 10 mg/kg twice weekly. Pyrazinamide (Z) 35 mg/kg/24 hours, 75 mg/kg twice weekly or 50 mg/kg thrice weekly, is an important drug for short course treatment, so try to include it whenever it is mentioned in the regimes below. Streptomycin (S) 10-20 mg/kg/24 hours, or 40 mg/kg twice weekly, to a total of not more than 0.75 g. Streptomycin is painful, so avoid it if you can. If you give it, inject in different places each day, because repeated injections into the same site are painful. Ethambutol (E) 25 mg/kg/24 hours for 2 months, then 15 mg/kg/24 hours. Avoid ethambutol in younger children (under 12); they are unable to complain of the early symptoms of retrobulbar neuritis (blindness). Thiacetazone (T) 4 mg/kg/24 hours to a maximum Of 150 mg; unsuitable for intermittent treatment

Tuberculosis in children in India-I

Tuberculosis is different in children. It involves many organs, instead of being the predominantly respiratory disease that it usually is in adults. Fortunately, it readily responds to treatment–if you diagnose it early enough and treat it for long enough! This is the problem. Unfortunately, tuberculosis causes such non-specific symptoms and signs, and you are so seldom able to isolate bacilli, that you may never be sure of the diagnosis. Even experts sometimes disagree. In India particularly, it is a disease of the poorest of the poor, but even in them it causes only a small proportion of their burden of morbidity. The great problem is to reach those infected. Of every thousand Indians, seven children and about twenty adults have active tuberculosis, and five of these adults are sputum positive. Only about half the 9 million in the community at any one time are ever diagnosed, and of these only about 13% complete their treatment, so there is a huge pool of infectious cases, half a million of whom die each year. Fortunately, the incidence of tuberculosis among children reporting to hospital is slowly decreasing, probably largely due to improved coverage with BCG

Drug overdose: a wake up call! Experience at a tertiary care centre in Karachi, Pakistan

OBJECTIVE: To study the characteristics of patients admitted with drug overdose caused either by accidental overdose of the prescribed medications or as an act of deliberate self harm (DSH) at a tertiary care hospital in Karachi, Pakistan.METHODS: A retrospective case series review was conducted at the Aga Khan University Hospital from January 2002 to October 2006. Three hundred and twenty four adult patients admitted with drug overdose were included in the study.RESULTS: Our sample group revealed mean age of 36.2 +/- 17.0 years, more females (59%), housewives (34%), and students (20%). Fifty six percent of patients committing DSH were married (p = 0.001), 81% needed in-patient psychiatric services (p = 0.016) of whom a significantly high number (38%) refused it. Domestic and social issues were rated highest among DSH group (p = 0.003), depression among females was common (p = 0.028) and Benzodiazepines (41%) was the most frequently used drug (p = 0.021). Sub-group analysis of accidental overdoses revealed mean age of 45.6 +/- 19.6 years, single (75.4%) and males (54.1%). Drugs used were mainly Benzodiazepines (18%) followed by Opioids (11%), Antiepileptics (10%) and Warfarin (10%).CONCLUSION: Our study showed that depressed housewives are at greater risk for DSH. Domestic and social issues were rated highest and Benzodiazepines were the most commonly used agents. Most of our patients refused inpatient psychiatric treatment leading us to believe that general awareness of psychiatric illnesses is imperative in our community. High number of accidental overdoses is alarming in older, single males convincing us to believe that existing pharmacy system needs further evaluation and modification

Prognostic model for patient survival in primary anorectal mucosal melanoma:stage at presentation determines relevance of histopathologic features

Pathological staging of primary anorectal mucosal melanoma is often performed according to the American Joint Commission on Cancer (AJCC) guidelines for cutaneous melanoma, as an anorectal melanoma-specific staging system does not exist. However, it remains unknown whether prognostic factors derived for cutaneous melanoma also stratify risk in anorectal melanoma. We retrospectively determined correlations between clinicopathological parameters and disease-specific survival in 160 patients. Patients were grouped by clinical stage at presentation (localized disease, regional or distant metastases). Cox proportional hazards regression models determined associations with disease-specific survival. We also summarized the somatic mutations identified in a subset of tumors analyzed for hotspot mutations in cancer-associated gene panels. Most of the patients were white (82%) and female (61%). The median age was 62 years. With a median follow-up of 1.63 years, median disease-specific survival was 1.75 years, and 121 patients (76%) died of anorectal melanoma. Patients presenting with regional (34%) or distant metastases (24%) had significantly shorter disease-specific survival compared to those with disease localized to the anorectum (42%). Of the 71 anorectal melanoma tumors analyzed for hotspot genetic alterations, somatic mutations involving the KIT gene (24%) were most common followed by NRAS (19%). Increasing primary tumor thickness, lymphovascular invasion, and absence of regression also correlated with shorter disease-specific survival. Primary tumor parameters correlated with shorter disease-specific survival in patients presenting with localized disease (tumor thickness) or regional metastases (tumor thickness, absence of regression, and lymphovascular invasion), but not in patients presenting with distant metastases. Grouping of patients according to a schema based on modifications of the 8th edition AJCC cutaneous melanoma staging system stratified survival in anorectal melanoma. Our findings support stage-specific associations between primary tumor parameters and disease-specific survival in anorectal melanoma. Moreover, the AJCC cutaneous melanoma staging system and minor modifications of it predicted survival among anorectal melanoma patients

Mesenchymal Stem Cell Graft Improves Recovery after Spinal Cord Injury in Adult Rats through Neurotrophic and Pro-Angiogenic Actions

Numerous strategies have been managed to improve functional recovery after spinal cord injury (SCI) but an optimal strategy doesn't exist yet. Actually, it is the complexity of the injured spinal cord pathophysiology that begets the multifactorial approaches assessed to favour tissue protection, axonal regrowth and functional recovery. In this context, it appears that mesenchymal stem cells (MSCs) could take an interesting part. The aim of this study is to graft MSCs after a spinal cord compression injury in adult rat to assess their effect on functional recovery and to highlight their mechanisms of action. We found that in intravenously grafted animals, MSCs induce, as early as 1 week after the graft, an improvement of their open field and grid navigation scores compared to control animals. At the histological analysis of their dissected spinal cord, no MSCs were found within the host despite their BrdU labelling performed before the graft, whatever the delay observed: 7, 14 or 21 days. However, a cytokine array performed on spinal cord extracts 3 days after MSC graft reveals a significant increase of NGF expression in the injured tissue. Also, a significant tissue sparing effect of MSC graft was observed. Finally, we also show that MSCs promote vascularisation, as the density of blood vessels within the lesioned area was higher in grafted rats. In conclusion, we bring here some new evidences that MSCs most likely act throughout their secretions and not via their own integration/differentiation within the host tissue