A clinical molecular genetic service for United Kingdom families with choroideraemia

A diagnosis of choroideraemia (CHM) can be made clinically, based on the fundus examination and a family history consistent with X-linked inheritance. Molecular genetic testing offers a means of confirming the clinical diagnosis, establishing carrier status and allows presymptomatic diagnosis for families who wish to pursue these options. The aim of this study was to examine the uptake and assess the results from a diagnostic molecular genetics service for CHM.We have carried out a comprehensive audit of all molecular genetic results of UK NHS patients and families referred to the North West Regional Molecular Genetics Laboratory in Manchester, UK over a 55 month period.110 people were referred to this service for testing including diagnostic, carrier and predictive requests. Putative pathogenic mutations were identified in 65/83 (78%) of male index cases. The identification of a familial pathogenic change enabled carrier testing in 16 asymptomatic females and predictive testing in 3 males. Case examples illustrate the range of cases referred for testing and also reflect the need for genetic counselling that results from offering a molecular diagnostic service such as this.Clinical molecular testing for CHM is available clinically and can be used to support the clinical diagnosis and management of patients with choroideraemia as well as their families. Case studies demonstrate the need to provide genetic testing to families and the potential clinical utility of testing.     

Role of Qa-1(b)-binding receptors in the specificity of developing NK cells

NK cells acquire the ability to recognize MHC class I molecules during development. Studies with Qa-1(b) tetramers (Qa-1 tetramers) showed that nearly all NK1.1(+) cells from newborn C57BL/6 mice express Qa-1-binding receptors. Cytotoxic activity of these cells is fully inhibited by Qa-1 ligands on target cells. In contrast, neither receptors for H-2K(b) nor H-2D(b) were observed on NK1.1(+) cells from newborn mice. After birth, frequencies of Qa-1 tetramer(+)/ NK1.1(+) cells gradually decrease as the number of Ly49(+) /NK1.1(+) cells increases. Cell transfer studies showed that Qa-1 tetramer(+) cells from newborn mice do not lose expression of Qa-1 receptors, but that they further acquire expression of Ly49 molecules. Acquisition of Qa-1-binding receptors appears largely independent of host MHC class I molecules, as observed in studies using beta2-microglobulin-deficient (beta2m(-/-)) mice as well as K(b)/ D(b-/-) and K(b)/D(b)/beta2m(-/-) mice. The present results suggest that Qa-1-binding receptors play an important role in the specificity of developing NK cells, and suggest that these cells rely mainly on inhibitory receptors specific for non-classical MHC class I molecules to maintain self tolerance during the first weeks of life.     

The bacterial species associated with aspirated foreign bodies in children

Objective

Inhaled foreign bodies in children are common and may be complicated by secondary airway tract infection. The inhaled foreign body may act as carrier of infectious material and the aim of this study was to explore the bacterial species associated with aspirated foreign bodies in a cohort of children.

Endotoxaemia and acute pancreatitis: correlation between the severity of the disease and the anti-enterobacterial common antigen antibody titre

Enterobacterial common antigen is a highly immunogenic component of the Gram negative bacterial cell wall that is common to all enteric bacteria. In the present study, the humoral antibody response against enteric bacteria was investigated by measuring antibodies to enterobacterial common antigen in paired serum samples in 38 patients with acute pancreatitis and in 31 healthy subjects. In mild pancreatitis (11 patients), no changes in anti-enterobacterial common antigen titres were observed as compared with healthy controls. Nine of the 10 patients had a significant increase (greater than or equal to 8 times) in anti-enterobacterial common antigen titres during the disease. Similarly, in patients with fulminant (haemorrhagic) pancreatitis who survived, a significant increase in anti-enterobacterial common antigen titres occurred during the course of the disease (in nine of the 11 patients). Paradoxically, only one of the six patients with fulminant pancreatitis with fatal outcome showed a significant increase in his anti-enterobacterial common antigen titre. The results suggest that Gram negative bacterial components escape into the systemic circulation in acute pancreatitis. This may have pathophysiologic significance in this disease.     

Action capability constrains visuo-motor complexity during planning and performance in on-sight climbing

The capability to adapt to changing conditions is crucial for safe and successful performance in physical activities and sports. According to the affordance-based control perspective, individuals act in such a way as to take into account the limits of their capability to act. However, it is not clear how strength interacts with skill in shaping performer-environment interactions. We, therefore, determined whether fingertip strength influences patterns of gaze and climbing behavior on new routes of ever-increasing difficulty. We expected that comparatively weaker climbers would show less complex behavior because of an inability to perceive and act. Stronger climbers would show more complex visuo-motor behavior because more opportunities for action remain, even as route difficulty increases. For very strong climbers the route would not be challenging enough, and less complex patterns suffice. Twenty climbers, ranging from lower grade to elite level participated. Maximum fingertip strength was obtained. Participants previewed and then climbed two separate 3 m long traverses, gradually decreasing in edge depth. Gaze and hip positions were collected for subsequent computation of gaze transition entropy (during preview) and hip displacement entropy (during climbing). Data revealed statistically significant curvilinear relationships between both fingertip strength and gaze transition entropy, and fingertip strength, and hip displacement entropy. Visuo-motor complexity is scaled by how close the individual must act relative to boundaries of what the environment affords and does not afford for action given the individual constraints. Future research should examine in greater detail relationships between action capabilities and functional movement variability.     

A comparison of 2 methods of vaginal cuff closure during robotic hysterectomy

ObjectiveTo compare 2 methods of vaginal cuff closure with regard to safety, ease of use, and postoperative outcome.MethodsAll patients undergoing robotic-assisted total hysterectomy by a gynecologic oncologist from July 1, 2010, to July 1, 2011, at Northwestern Memorial Prentice Women's Hospital were included in a retrospective analysis. Providers used either 2–0 monofilament synthetic absorbable suture to close the vaginal cuff in a running fashion, secured with an absorbable suture clip at the angles and then knotted in the middle, or 2–0 absorbable unidirectional barbed suture with a welded-loop closure in a running fashion.ResultsA total of 134 patients underwent robotic-assisted total hysterectomy. The 2–0 tied monofilament closure was used in 58 patients, and the 2–0 barbed knotless closure was used in 76 patients. There were no instances of vaginal cuff dehiscence or vaginal cuff cellulitis. Rates of vaginal spotting and bleeding were comparable between the groups (12.0% spotting in the monofilament suture group vs 13.0% spotting in the barbed suture group). All vaginal cuff bleeding resolved on its own without significant intervention.ConclusionThe use of either a 2–0 welded-loop unidirectional barbed suture or a 2–0 monofilament absorbable suture to close the vaginal cuff is safe and well tolerated.     

Deconvoluting the Obesity and Breast Cancer Link: Secretome, Soil and Seed Interactions

Obesity is associated with increased risk of breast cancer in postmenopausal women and is linked with poor prognosis in pre- and postmenopausal breast cancer patients. The mechanisms underlying the obesity-breast cancer connection are becoming increasingly clear and provide multiple opportunities for primary to tertiary prevention. Several obesity-related host factors can influence breast tumor initiation, progression and/or response to therapy, and these have been implicated as key contributors to the complex effects of obesity on cancer incidence and outcomes. These host factors include components of the secretome, including insulin, insulin-like growth factor-1, leptin, adiponectin, steroid hormones, cytokines, vascular regulators, and inflammation-related molecules, as well as the cellular and structural components of the tumor microenvironment. These secreted and structural host factors are extrinsic to, and interact with, the intrinsic molecular characteristics of breast cancer cells (including breast cancer stem cells), and each will be considered in the context of energy balance and as potential targets for cancer prevention.     

The incidence and natural course of occult inguinal hernias during TAPP repair

Background

One of the proposed advantages of laparoscopic inguinal hernia repair is complimentary inspection of the contralateral side and possible detection of occult hernias. Incidence of occult contralateral hernias is as high as 50 %. The natural course of such occult defects is unknown and therefore operative rationale is lacking. This study was designed to analyze the incidence of occult contralateral inguinal hernias and its natural course.

Methods

A total of 1,681 patients were diagnosed preoperatively with unilateral inguinal hernia. None of these patients had complaints of the contralateral side preoperatively. All patients underwent laparoscopic inguinal hernia transabdominal preperitoneal (TAPP) repair. Operative details were analyzed retrospectively. Patients with occult contralateral defects were identified and tracked. Patients with an evident occult hernia received immediate repair. Patients with a smaller beginning or incipient hernia were followed.

Results

In 218 (13 %) patients, an occult hernia was found at the contralateral side during preoperative exploration. In 129 (8 %) patients, an occult true hernia was found. In 89 (5 %) patients, an occult incipient hernia was found. An incipient hernia was defined as a beginning hernia. All patients with an incipient hernia were followed. The mean follow-up was 112 (range 16–218) months. Twenty-eight (32 %) patients were lost to follow-up. In the 61 remaining patients, 13 (21 %) occult incipient hernias became symptomatic requiring repair. The mean time between primary repair and development of a symptomatic hernia on the contralateral side was 88 (range 24–210) months.

Conclusions

This study shows that the incidence of occult contralateral hernias is 13 % during TAPP repair of unilateral diagnosed inguinal hernias. In 5 % of the cases, the occult hernia consisted of a beginning hernia. Eventually, one of five will become symptomatic and require repair. These outcomes support immediate repair of occult defects, no matter its size.