Ellis‐van Creveld syndrome in a patient from Tanzania

We report an African infant with Ellis‐van Creveld (EVC) syndrome. EVC syndrome is a chondral and ectodermal dysplasia with autosomal recessive transmission. The baby presented with polydactyly, short limbs and atrioventricular septal defect, but was withdrawn from clinical follow up for the first year of life. Initial hematological abnormalities could not be explained and normalized later. EVC syndrome was confirmed by genetic analysis that showed two pathogenic mutations in the EVC2 gene, c.653_654del, p.Val218Glyfs*12 in exon 5, and c.2710C>T, p.Gln904* in exon 16. The variant c.653_654del; p.Val218Glyfs*12 in exon 5 has not been described before. Our review of medical literature suggested this is the first molecularly confirmed case of EVC syndrome in sub‐Saharan Africa.     

Protection of bronchoalveolar macrophages by granulocyte-macrophage colony-stimulating factor against dexamethasone suppression of fungicidal activity for Aspergillus fumigatus conidia.

The objectives of this study were to: (i) see if granulocyte macrophage colony-stimulating factor (GM-CSF) could protect bronchoalveolar macrophages (BAM) against suppression by dexamethasone (DEX) and (ii) test the combined effect of GM-CSF and DEX on lymphocyte responses. Murine BAM killed Aspergillus fumigatus conidia by 33 +/- 4% (mean +/- SD) in a 2.5-h assay, unaffected by GM-CSF treatment. Killing by BAM treated with DEX (10(-7) M) for 48 h in vitro was reduced to 13 +/- 6%; however, if GM-CSF (500 U ml(-1)) was present during DEX treatment of BAM, killing of conidia (33 +/- 2%) by BAM was preserved. By contrast, DEX suppression of lymphocyte responses to concanavalin A was maintained during co-culture with GM-CSF. In sequence treatment experiments, initial treatment of BAM with GM-CSF protected against subsequent treatment with DEX. When macrophages were pretreated with DEX, GM-CSF could reverse suppression even when added subsequently, provided DEX treatment was discontinued. These data suggest that it may be possible to suppress lymphocyte responses with DEX, yet at the same time maintain BAM defenses with GM-CSF against pulmonary infections by conidia of A. fumigatus.     

Pattern of ocular injuries in stone pelters in Kashmir valley

PurposeTo describe the pattern and types of ocular injuries in stone pelters in Kashmir valley during recent turmoil.DesignCross sectional study.MethodsSixty patients with different types of eye injuries were assessed between June–September 2010 and initial visual acuity was recorded. The injuries were classified according to Systems for Classifying Ocular Injuries (OTCS) and Ocular Trauma Score (OTS) was calculated in order to estimate the probability of follow-up visual acuity range.ResultsMost of the victims (75%) were young boys between 16–26 years with a mean age of 20.95, 95% of cases were males. The main cause of injury was stones (48.3%) and pellets (30%) besides rubber bullets, sling shots and tear gas shells.Most of the open-globe injuries due to stones were of Type B and A, Grade E, Zone II and III with Afferent Pupillary Defect (APD) in 30% of the cases. Closed-globe injuries were mostly of Type A, Grade C and D and Zone II and III.Most of the open-globe injuries due to pellets were of Type D, Grade D, Zone II and APD in 33.3%. Pellets Intra Ocular Foreign Body (IOFB) was in 41.6%. Most of the closed-globe injuries were of Type A, Grade D and E and of Zone III.Overall OTS of 1 was calculated in 16.6% and 3 in 53.3% of the cases.ConclusionIn stone pelting demonstrations eye injuries can result in visually significant trauma. Injuries due to pellets are mostly perforating and pellet IOFB, and both tend to have a very poor prognosis. OTS can be used to estimate visual prognosis.     

Abdominal Dermis-Fat Graft Versus Conventional Temporalis Myofascial Flap Interposition in Temporomandibular Joint Ankylosis: A Prospective Clinical Comparative Study

IntroductionTemporomandibular joint (TMJ) ankylosis is an extremely disabling condition with almost complete inability to open the jaws causing difficulty in chewing, speech, poor oral hygiene and cosmetic disfigurement. Temporalis myofascial flap still remains the most common interpositional material used; however, patients usually complain of pain during movement, unesthetic bulging in the temporal region and trismus due to scar contracture. The main aim of the study was to evaluate the efficacy of abdominal dermis-fat graft and compare it with temporalis myofascial flap as to see which of the two grafts offers more advantages and provides better postoperative results following TMJ ankylosis surgery. Materials and MethodsA total of 30 diagnosed cases of TMJ ankylosis were randomly divided into two groups of 15 patients each. All the patients underwent TMJ ankylosis release under general anesthesia followed by abdominal dermis-fat interposition in Group A and temporalis muscle in Group B. The patients were assessed for pre-operative and postoperative mouth opening (immediate and 6 month postoperative), pain during physiotherapy, donor and surgical site complications and recurrence of ankylosis.ResultsThe mean maximum inter-incisal opening in dermis-fat group was significantly higher than temporalis group both at immediate and 6 month postoperative periods (p = 0.041, 0.001). Physiotherapy was less painful in dermis-fat group than in temporalis group, and the differences in VAS scores among the 2 groups showed high statistical significance (p < 0.001). Hypertrophic scar developed at the donor site in 2 patients in dermis-fat group; however, it was located below the beltline and hardly noticeable. A total of 9 patients (4 in Group A and 5 in Group B) developed temporary facial nerve weakness, and no case of re-ankylosis was noted in either group.ConclusionDermis-fat graft in temporomandibular joint ankylosis showed better results than conventional temporalis myofascial flap in terms of postoperative mouth opening, physiotherapy and jaw function with esthetically acceptable results.     

Overexpression of FoxM1 offers a promising therapeutic target in diffuse large B-cell lymphoma

Background

FoxM1 has been shown to play a critical role in the pathogenesis of various epithelial malignancies. However, its role in lymphoid malignancies has not been fully clarified. We, therefore, investigated the role of FoxM1 expression in a large cohort of diffuse large B-cell lymphoma samples and panel of cell lines.

Design and Methods

FoxM1 expression was investigated in a large series of diffuse large B-cell lymphoma tissues in a tissue microarray format by immunohistochemistry. Apoptosis was measured by flow cytometry and protein expression was detected by immunoblotting using diffuse large B-cell lymphoma cell lines following treatment with either pharmacological inhibitor of FoxM1 or small interference RNA knockdown strategy. Invasion/migration and soft agar colony assays were also performed following treatment with FoxM1 inhibitor.

Results

FoxM1 expression was detected in 84.6% of diffuse large B-cell lymphoma tumors and found to be significantly associated with proliferative tumor marker Ki67 (P<0.0001), matrix metalloproteinases-2 (P=0.0008), matrix metalloproteinases-9 (P=0.0002), S-phase kinase associated protein-2 (P<0.0001) and inversely associated with p27 expression (P=0.0215). Expression of small interference RNA targeted against FoxM1 or treatment of diffuse large B-cell lymphoma cells with thiostrepton caused its downregulation accompanied by decreased expression of matrix metalloproteinases-2 and matrix metalloproteinases-9. Inhibition of FoxM1 in diffuse large B-cell lymphoma cells also decreased invasive and migratory capability, and induced caspase dependent apoptosis via activation of the mitochondrial apoptotic pathway. Finally, combined thiostrepton and bortezomib at sub-toxic doses led to efficient apoptosis in diffuse large B-cell lymphoma cells.

Conclusions

Altogether, these results suggest that FoxM1 is over-expressed in the majority of diffuse large B-cell lymphoma samples. These data also indicate that targeting FoxM1 signaling can serve as a potential therapeutic modality in the management of diffuse large B-cell lymphoma.     

Frequency and features of nocturnal enuresis in Pakistani children aged 5 to 16 years based on ICCS criteria: a multi-center cross-sectional study from Karachi,Pakistan

Background

Nocturnal enuresis (NE) is a common symptom in children worldwide. International Children’s Continence Society (ICCS) defines enuresis as either mono-symptomatic, NE with lower urinary tract symptoms and NE with co-morbid conditions. The objectives of this study were to determine the frequencies and types of NE and associated symptoms and conditions in children aged 5 to 16?years based on ICCS criteria.

Methods

A multi-center cross sectional study was conducted between November 2012 and December 2013 in the primary care clinics of four hospitals in Karachi. Children aged five to fifteen years were included through consecutive sampling. Informed consent was obtained from the parents and a pre-coded semi-structured questionnaire was used to obtain the information. Data was entered on SPSS version 20.0 and multivariable logistic regression analysis was used for data analysis.

Results

Out of 429 children aged between five and sixteen years, 243(56.9%) were boys and the remaining 186(43.1%) were girls. One hundred and eighty three children (43%) had nocturnal enuresis (NE). Forty four (10.3%), had mono-symptomatic NE, 57(31.1%) had associated lower urinary tract symptoms (NE-LUTS), whereas 30 (16.3%) had NE with a co-morbid condition. Fifty two (28.4%) NE’s had at least one of both LUTS and a co-morbid condition. Out of the 246(57%) non-enuretic’s, 31(12.6%) had a LUTS, 95(38.6%) had a co-morbid condition and 57(23.2%) had at least one of both LUTS and a co-morbid condition. The remaining 63 (25.6%) were symptom free. Increased voiding frequency, urgency, dysuria, suprapubic pain and daytime incontinence were the LUTS significantly associated with NE. Co-morbid conditions significantly associated with NE included constipation, congenital defects, developmental delay, and learning and sleep problems.

Conclusion

Although NE can be an only symptom, it is often associated with lower urinary tract symptoms like dysuria, urgency, suprapubic pain, and daytime incontinence. Children presenting with NE often have co-morbid conditions like constipation, urinary tract infection, sleep disorders, and developmental delay. Many children presenting with these conditions as the primary complaint may also have NE. It should be addressed as unrecognized and untreated NE can cause additional morbidity and distress.

     

Transcatheter aortic valve implantation under conscious sedation – the first Indian experience

Transcatheter aortic valve implantation (TAVI) is maturing strongly as an alternative to surgical aortic valve replacement (SAVR) in patients who are inoperable/high risk for open heart surgery. General anesthesia (GA) is the usual mode of anesthesia in these patients, but local anesthesia with conscious sedation (LACS) has recently been described as a safe alternative with some added advantages. We report 2 cases who were unfit for GA and were done successfully under LACS.