Progression of phenotype in Leber's congenital amaurosis with a mutation at the LCA5 locus

BACKGROUND: Leber’s congenital amaurosis (LCA) accounts for 5% of inherited retinal disease and is usually inherited as an autosomal recessive trait. Genetic and clinical heterogeneity exist. Mutations have been described in the RPE65, CRB1, RPGRIP1, AIPL1, GUCY2D, and CRX genes and other pedigrees show linkage to the LCA3 and LCA5 loci. The latter is a new locus which maps to 6q11-q16. The ocular findings and the evolution of the macula staphyloma are described in five members of a Pakistani family with consanguinity and a mutation in the LCA5 gene. METHODS: 13 family members including five affected individuals consented to DNA analysis and ocular examination including fundal photography. RESULTS: Ocular abnormalities are described. The most striking feature was the progression of macula abnormalities in three brothers resulting in a colobomatous appearance in the eldest compared to only mild atrophy in the youngest. The phenotypic pattern of this mutation in this Pakistani family contrasts with the “Old Order River Brethren” who were of Swiss descent, in whom the mutation was first described. CONCLUSION: The evolution of a new phenotypic picture is presented to a mutation in LCA5

Histological analysis of motoneuron survival and microglia inhibition after nerve root avulsion treated with nerve graft implantation and minocycline: an experimental study

Motor vehicle accidents are the most common cause of injuries involving avulsion of the brachial plexus in humans, resulting in debilitating motor dysfunction. Lack of an established animal model to test drug treatments hinders the introduction of new pharmacological agents. Avulsion injury of cervical ventral roots can be replicated in rats, resulting in a progressive loss of the motoneurons and increase in neurotoxic expression of microglia. This is a report on the effect of prompt nerve implantation and minocycline treatment on the suppression of microglia activation and survival of motoneurons. 20 adult female Sprague-Dawley rats were used for this study, which was approved by the Animal Ethical Committee, USM (approval number /2011/(73)(346)). The animals underwent surgical avulsion of the C6 nerve root, followed by reimplantation with peripheral nerve graft and treatment with intraperitoneal minocycline. At 6 weeks postoperatively, immunohistochemistry using primary antibody Iba1 (microglia) and nicotinamide adenine dinucleotide phosphate diaphorase (NADPh) with neutral-red staining (motoneuron) under flourescence microscopy was performed at the C6 spinal cord segment and then quantified. This study showed signifi cant reduction of microglia expression in the study group; mean ranks of control and study group were 15.2 and 11.6, respectively; U=9.5, Z=3.02, p0.05. This may be due to the effect of the surgery; the surgery has the potential to cause additional trauma to the cord parenchyma, leading to further motoneuron loss and an increase in scarring around the avulsed region, thus impeding regeneration of the motoneuron

Studies on length-weight and length-length relationships of a catfish Eutropiichthyes vacha Hamilton (Schilbeidae: Siluriformes) from Indus River, Sindh, Pakistan

Present study describes the length-weight (LWR) and length-length (LLR) relationships of a freshwater catfish Eutropiichthyes vacha Hamilton from Indus River, Sindh, Pakistan. A total of 281 specimen of E. vacha were collected from fisherman’s catch from February 2005 to January 2006, are used for this study. The parameters a and b of the length-weight relationship were calculated as W= aLb are presented. The values for allometric coefficient b of the LWR were close to isometric value for male (b = 3.159) and combined values for both sexes (b = 3.053). However, it suggested negative allometric growth for females (b = 2.973). Results for LLRs indicated that these are highly correlated (r2 > 0.9) P< 0.0001

Subacute sclerosing panencephalitis – Current perspectives

Subacute sclerosing panencephalitis is a progressive neurodegenerative disease. It usually occurs 7–10 years after measles infection. The clinical course is characterized by progressive cognitive decline and behavior changes followed by focal or generalized seizures as well as myoclonus, ataxia, visual disturbance, and later vegetative state, eventually leading to death. It is diagnosed on the basis of Dyken’s criteria. There is no known cure for subacute sclerosing panencephalitis to date, but it is preventable by ensuring that an effective vaccine program for measles is made compulsory for all children younger than 5 years in endemic countries

Baseline and On-Treatment High-Density Lipoprotein Cholesterol and the Risk of Cancer in Randomized Controlled Trials of Lipid-Altering Therapy

ObjectivesWe sought to examine the relationship between high-density lipoprotein cholesterol (HDL-C) levels and the risk of the development of cancer in large randomized controlled trials (RCTs) of lipid-altering interventions.BackgroundEpidemiologic data demonstrate an inverse relationship between serum total cholesterol levels and incident cancer. We recently reported that lower levels of low-density lipoprotein cholesterol are associated with a significantly higher risk of incident cancer in a meta-analysis of large RCTs of statin therapy. However, little is known about the relationship between HDL-C levels and cancer risk.MethodsA systematic MEDLINE search identified lipid intervention RCTs with ≥1,000 person-years of follow-up, providing baseline HDL-C levels and rates of incident cancer. Using random-effects meta-regressions, we evaluated the relationship between baseline HDL-C and incident cancer in each RCT arm.ResultsA total of 24 eligible RCTs were identified (28 pharmacologic intervention arms and 23 control arms), with 625,477 person-years of follow-up and 8,185 incident cancers. There was a significant inverse association between baseline HDL-C levels and the rate of incident cancer (p = 0.018). The inverse association persisted after adjusting for baseline low-density lipoprotein cholesterol, age, body mass index (BMI), diabetes, sex, and smoking status, such that for every 10-mg/dl increment in HDL-C, there was a 36% (95% confidence interval: 24% to 47%) relatively lower rate of the development of cancer (p < 0.001).ConclusionsThere is a significant inverse association between HDL-C and the risk of incident cancer that is independent of LDL-C, age, BMI, diabetes, sex, and smoking

Prevalence of non-Helicobacter pylori duodenal ulcer in Karachi, Pakistan.

AIM: To determine the prevalence of non-Helicobacter pylori (H pylori)-related duodenal ulcer in patients with acid-peptic diseases. METHODS: Medical records of patients who attended the Gastroenterology Department at Aga Khan University Hospital from 1999 to 2001 and had endoscopic diagnosis of duodenal ulcers were reviewed. Duodenal ulcer associated with H pylori was diagnosed on the basis of endoscopy, rapid urease test and histopathology whereas histories of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) related duodenal ulcers. Non-H pylori, non-NSAID duodenal ulcers were those without H pylori infection and history of NSAID intake. Co-morbid conditions associated were noted. RESULTS: Of 2 260 patients, 10% (217/2 260) had duodenal ulcer. Duodenal ulcer related to H pylori infection accounted for 53% (116/217), NSAID-related 10% (22/217), non-H pylori non-NSAID 29% (62/217), and 8% (17/217) had both H pylori infection and histories of NSAID intake. Fifteen percent (18/116) patients had past histories of peptic ulcer disease in H pylori infection, while 8% (5/62) in non-H pylori non-NSAID ulcer. Co-morbid conditions in H pylori infection were seen in 23% (27/116) and 34% (21/62) in non-H pylori non-NSAID ulcer. CONCLUSION: Incidence of H pylori infection related with duodenal ulcer is common. In the presence of co-morbids, non-H pylori and non-NSAID duodenal ulcer is likely to be present

The Fermi level effect in III-V intermixing: The final nail in the coffin?

Copyright 1997 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. This article appeared in Journal of Applied Physics 81, 2179 (1997) and may be found at

Standardising neonatal and paediatric antibiotic clinical trial design and conduct: the PENTA-ID network view.

Antimicrobial development for children remains challenging due to multiple barriers to conducting randomised clinical trials (CTs). There is currently considerable heterogeneity in the design and conduct of paediatric antibiotic studies, hampering comparison and meta-analytic approaches. The board of the European networks for paediatric research at the European Medicines Agency (EMA), in collaboration with the Paediatric European Network for Treatments of AIDS-Infectious Diseases network (www.penta-id.org), recently developed a Working Group on paediatric antibiotic CT design, involving academic, regulatory and industry representatives. The evidence base for any specific criteria for the design and conduct of efficacy and safety antibiotic trials for children is very limited and will evolve over time as further studies are conducted. The suggestions being put forward here are based on the adult EMA guidance, adapted for neonates and children. In particular, this document provides suggested guidance on the general principles of harmonisation between regulatory and strategic trials, including (1) standardised key inclusion/exclusion criteria and widely applicable outcome measures for specific clinical infectious syndromes (CIS) to be used in CTs on efficacy of antibiotic in children; (2) key components of safety that should be reported in paediatric antibiotic CTs; (3) standardised sample sizes for safety studies. Summarising views from a range of key stakeholders, specific criteria for the design and conduct of efficacy and safety antibiotic trials in specific CIS for children have been suggested. The recommended criteria are intended to be applicable to both regulatory and clinical investigator-led strategic trials and could be the basis for harmonisation in the design and conduct of CTs on antibiotics in children. The next step is further discussion internationally with investigators, paediatric CTs networks and regulators