Totally extra-peritoneal repair of inguinal hernia by a glove-balloon: technical innovation.

Totally extra-peritoneal (TEP) laparoscopic repair of an inguinalhernia involves the creation of an extra-peritoneal space by blunt dissection or the use of commercial balloons. This new technique demonstrates the use of a device to create this extra-peritoneal space, without the need for any commercial balloons. The extra-peritoneal space was created using a glove-balloon. A total of 107 consecutive TEP repairs were carried out using the glove-balloon technique, these included ten bilateral and 17 recurrent inguinal hernias. This method is simple, cost-effective and easy to teach.     

Social support, social pressures and psychological distress during unemployment

A sample of 1150 unemployed 17 year-olds, containing blacks and whites, males and females, was obtained from 11 urban regions in England. Social support was measured in respect of five different forms of help from others. Measures were also obtained of psychological distress, perceived pressure from others to obtain a job, employment commitment, contact with other young people, and contact with other unemployed young people. Two forms of social support (having someone to turn to for help with money, and having someone to suggest interesting things to do) were significantly associated with measures of distress, as were perceived pressure to obtain a job and employment commitment, but not contact with other unemployed young people. The association between distress and having someone to turn to for help with money was greater for those perceiving pressure from others to obtain a job than those not perceiving pressure. Also, the association between distress and having someone to turn to when feeling low was greater for those with a high employment commitment than for those with a low one. Other associations between support and distress were found to be affected by sex and ethnic differences in the sample. The results are discussed in the light of a stress-buffering model of social support; and the need to disaggregate social support into its component parts is emphasized.     

A genetic and clinical study of individuals with nonsyndromic retinopathy consequent upon sequence variants in HGSNAT,the gene associated with Sanfilippo C mucopolysaccharidosis

Pathogenic variants in the gene HGSNAT (heparan‐α‐glucosaminide N‐acetyltransferase) have been reported to underlie two distinct recessive conditions, depending on the specific genotype, mucopolysaccharidosis type IIIC (MPSIIIC)—a severe childhood‐onset lysosomal storage disorder, and adult‐onset nonsyndromic retinitis pigmentosa (RP). Here we describe the largest cohort to‐date of HGSNAT‐associated nonsyndromic RP patients, and describe their retinal phenotype, leukocyte enzymatic activity, and likely pathogenic genotypes. We identified biallelic HGSNAT variants in 17 individuals (15 families) as the likely cause of their RP. None showed any other symptoms of MPSIIIC. All had a mild but significant reduction of HGSNAT enzyme activity in leukocytes. The retinal condition was generally of late‐onset, showing progressive degeneration of a concentric area of paramacular retina, with preservation but reduced electroretinogram responses. Symptoms, electrophysiology, and imaging suggest the rod photoreceptor to be the cell initially compromised. HGSNAT enzymatic testing was useful in resolving diagnostic dilemmas in compatible patients. We identified seven novel sequence variants [p.(Arg239Cys); p.(Ser296Leu); p.(Phe428Cys); p.(Gly248Ala); p.(Gly418Arg), c.1543‐2A>C; c.1708delA], three of which were considered to be retina‐disease‐specific alleles. The most prevalent retina‐disease‐specific allele p.(Ala615Thr) was observed heterozygously or homozygously in 8 and 5 individuals respectively (7 and 4 families). Two siblings in one family, while identical for the HGSNAT locus, but discordant for retinal disease, suggest the influence of trans‐acting genetic or environmental modifying factors.     

Two‐ and Three‐Dimensional Transthoracic Echocardiography in the Assessment of Acquired Ascending Aortic Aneurysm to Pulmonary Artery Fistula

Aorta to pulmonary artery fistula is an uncommon and potentially fatal condition. This case is of a 48‐year‐old Caucasian male with congestive heart failure and multiple aortic valve replacement surgeries who presented with an acquired ascending aortic aneurysm to pulmonary artery fistula diagnosed using two‐dimensional transthoracic echocardiography via nonstandard imaging windows. Three‐dimensional transthoracic echocardiography using live/real time three‐dimensional color Doppler was used to assess the size of the opening of the fistula, providing additional value. This patient was surgically managed and is doing well 8 months postoperation.     

RAGE: a new frontier in chronic airways disease

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous inflammatory disorders of the respiratory tract characterized by airflow obstruction. It is now clear that the environmental factors that drive airway pathology in asthma and COPD, including allergens, viruses, ozone and cigarette smoke, activate innate immune receptors known as pattern-recognition receptors, either directly or indirectly by causing the release of endogenous ligands. Thus, there is now intense research activity focused around understanding the mechanisms by which pattern-recognition receptors sustain the airway inflammatory response, and how these mechanisms might be targeted therapeutically. One pattern-recognition receptor that has recently come to attention in chronic airways disease is the receptor for advanced glycation end products (RAGE). RAGE is a member of the immunoglobulin superfamily of cell surface receptors that recognizes pathogen- and host-derived endogenous ligands to initiate the immune response to tissue injury, infection and inflammation. Although the role of RAGE in lung physiology and pathophysiology is not well understood, recent genome-wide association studies have linked RAGE gene polymorphisms with airflow obstruction. In addition, accumulating data from animal and clinical investigations reveal increased expression of RAGE and its ligands, together with reduced expression of soluble RAGE, an endogenous inhibitor of RAGE signalling, in chronic airways disease. In this review, we discuss recent studies of the ligand–RAGE axis in asthma and COPD, highlight important areas for future research and discuss how this axis might potentially be harnessed for therapeutic benefit in these conditions.