Autosomal recessive microcephaly, mental retardation with nonpigmentary retinopathy and a distinctive electroretinogram

The association of microcephaly and mental retardation with a non-pigmentary retinopathy is described in three siblings of consanguineous parents. The electroretinogram showed the distinctive appearance of markedly attenuated "b" wave but normal "a" wave suggestive of a retinal dystrophy primarily affecting post-receptoral elements in the inner retina. This appears to be an autosomal recessive condition which has not been previously reported.     

Intratracheal administration of liposomal clodronate accelerates alveolar macrophage reconstitution following fetal liver transplantation

To facilitate study of alveolar macrophages in vivo, we developed a method to rapidly and efficiently replace resident alveolar macrophages with macrophages of a different (donor) genotype. Chimeric mice were generated by lethal irradiation followed by fetal liver transplantation (FLT) using green fluorescent protein (GFP) transgenic reporter mice as donors. Kinetics of peripheral blood monocyte (PBM) and alveolar macrophage reconstitution was determined 4 and 10 weeks post-FLT by quantifying the percentage of GFP+ cells. To enhance the recruitment of donor monocytes into the lung after FLT, mice were treated with intratracheal administration of liposomal clodronate to deplete host alveolar macrophages at 6 weeks post-FLT. PBM reconstitution occurred by 4 weeks after FLT (85.7+/-1.6% of CD11b+/Gr-1+ monocytes were GFP+), and minimal alveolar macrophage repopulation was observed (9.5% GFP+). By 10 weeks following FLT, 48% of alveolar macrophages were GFP+ by immunostaining of macrophages on lung tissue sections, and 55.1 +/- 1.6% of lung lavage macrophages were GFP+ by fluorescein-activated cell sorter analysis. Clodronate treatment resulted in a significant increase in GFP+ alveolar macrophages 10 weeks after FLT. By immunostaining, 90% of macrophages were GFP+ on lung tissue sections and 87.5 +/- 1.1% GFP+ in lung lavage (compared with GFP-transgenic controls). The ability of newly recruited alveolar macrophages to clear Pseudomonas aeruginosa and activate nuclear factor-kappaB in response to Eschericia coli lipopolysaccharide demonstrated normal macrophage function. Optimizing this methodology provides an important tool for the study of specific genes and their contribution to alveolar macrophage function in vivo.     

Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming

Naive T cells are stimulated by antigen-presenting dendritic cells (DCs) in secondary lymphoid organs, but whether other types of cell participate in T cell priming is unclear. Here we show in mice that natural killer (NK) cells, which are normally excluded from lymph nodes, are rapidly recruited in a CCR7-independent, CXCR3-dependent manner to lymph nodes on stimulation by the injection of mature DCs. Recruitment of NK cells is also induced by some, but not all, adjuvants and correlates with the induction of T helper cell type 1 (T(H)1) responses. NK cell depletion and reconstitution experiments show that NK cells provide an early source of interferon-gamma (IFN-gamma) that is necessary for T(H)1 polarization. Taken together, our results identify an induced pathway of NK cell migration in antigen-stimulated lymph nodes and a mechanism by which some adjuvants may facilitate T(H)1 responses.     

Nitric oxide is not permissive for cutaneous active vasodilatation in humans

The precise role of nitric oxide (NO) in cutaneous active vasodilatation in humans is unknown. We tested the hypothesis that NO is necessary to permit the action of an unknown vasodilator. Specifically, we investigated whether a low-dose infusion of exogenous NO, in the form of sodium nitroprusside (SNP), would fully restore vasodilatation in an area of skin in which endogenous NO was inhibited during hyperthermia. This finding would suggest a 'permissive' role for NO in active vasodilatation. Eight subjects were instrumented with three microdialysis fibres in forearm skin. Sites were randomly assigned to (1) Site A: control site; (2) Site B: NO synthase (NOS) inhibition during established hyperthermia; or (3) Site C: NOS inhibition throughout the protocol. Red blood cell flux was measured using laser-Doppler flowmetry (LDF) and cutaneous vascular conductance (CVC; LDF/mean arterial pressure) was normalized to maximal vasodilatation at each site. In Site B, N ^G-nitro- l -arginine methyl ester ( l -NAME) infusion during hyperthermia reduced CVC by ∼32 % (65 ± 4 % CVC_max vs. 45 ± 4 % CVC_max; P < 0.05). Vasodilatation was not restored to pre-NOS inhibition values in this site following low-dose SNP infusion (55 ± 4 % CVC_max vs. 65 ± 4 % CVC_max; P < 0.05). CVC remained significantly lower than the control site with low-dose SNP infusion in Site C ( P < 0.05). The rise in CVC with low-dose SNP (ΔCVC) was significantly greater in Site B and Site C during hyperthermia compared to normothermia ( P < 0.05). No difference in ΔCVC was observed between hyperthermia and normothermia in the control site (Site A). Thus, NO does not act permissively in cutaneous active vasodilatation in humans but may directly mediate vasodilatation and enhance the effect of an unknown active vasodilator.     

Characterizing fibroblast migration on discrete collagen threads for applications in tissue regeneration

Collagen threads with mechanical properties and fibrillar substructure similar to native tissue have been synthesized for the repair of injured tendon and ligament. While these scaffolding materials have demonstrated the potential for inducing tissue regeneration, one limitation has been an insufficient rate of tissue ingrowth for complete regeneration. We hypothesize that the structural hierarchy and biochemical cues on the surfaces of these threads will enhance the rate of cell migration and ultimately the rate of new tissue ingrowth. We developed an in vitro assay to measure the effects of various collagen sources and crosslinking on the rate of fibroblast migration on the surfaces of collagen threads. Threads were suspended from elevated platforms and seeded with fibroblast-populated collagen lattices. Cell migration rates ranging from 0.75 to 1.25 mm/day were measured as the fibroblasts left the lattices and migrated onto various thread types. Threads self-assembled from type I collagen were found to have migration rates similar to native tendon threads while crosslinking by severe dehydration decreased the rate. This novel in vitro model system allows examination of cell migration from a wound margin onto biomaterials to determine the effects of various cell types, matrix materials, and surface biochemistries on cell-matrix interactions. Ultimately, this assay will allow us to identify design parameters that will be most effective for enhancing the rate of tissue ingrowth on fiber-based collagen scaffolds for soft tissue regeneration.     

Re-thinking “I”dentity in medical education: genealogy and the possibilities of being and becoming

Advances in Health Sciences Education - Professional identity formation has emerged as a key topic for medical education research, with contributions from perspectives of psychological development...     

Increased Operative Time Impacts Rates of Short-Term Complications After Unicompartmental Knee Arthroplasty

BackgroundPrevious evidence has demonstrated an exacerbating effect of increased operative time on short-term complications in total joint arthroplasty. While the same relationship may be expected for unicompartmental knee arthroplasty (UKA), supporting evidence remains sparse. The purpose of this study is to determine the impact of operative time on short-term complication rates after UKA and determine a critical threshold in operative times after which complications may increase.MethodsThe American College of Surgeons National Surgical Quality Improvement Project was queried from 2007 to 2018 to identify 11,633 UKA procedures that were included in the final analysis. The effect of operative time on complications within 30 days was evaluated using multivariate logistic regression models. Receiver operating characteristics curves and spline regression models were used to identify critical thresholds in operative time that increase the likelihood of short-term complications.ResultsLonger operative times (in minutes) were associated with higher rates of surgical site infection (90.4 ± 26.7 vs 84.8 ± 25.5, P = .003), blood transfusions (94.9 ± 28.6 vs 84.9 ± 25.5, P = .007), as well as reoperation rates (90.8 ± 27.9 vs 84.9 ± 25.5, P = .01), extended hospital length of stay (93.4 ± 29.8 vs 84.5 ± 25.2, P < .001), and mortality (110.4 ± 35.5 vs 84.9 ± 25.5, P = .008). Following multivariate logistic regression, operative time was found to independently predict increased surgical site infection, blood transfusion, myocardial infarction, extended length of stay, and mortality (odds ratio: 1.09 – 1.45, CI: 1.01 – 1.91, all P values <0.02). Receiver operating characteristics curves found an increase in mortality risk during the 30-day postoperative period after 88.5 minutes of operative time, a finding supported by spline regression plots.ConclusionThe present study found a positive correlation between increased operative times and short-term postoperative complication rates after UKA. Despite a statistically significant association with increasing operative time, odds ratios of reported complications are relatively low.     

The canine eye: in vitro dissolution of the barriers to aqueous outflow.

Facility of aqueous outflow and time-dependent changes in its hyaluronidase-sensitive and hyaluronidase-resistant components were evaluated in freshly excised canine eyes by constant pressure quantitative aqueous perfusion. Mean baseline facility of outflow was 0.24 microliter/min/mm Hg. With prolonged perfusion at constant intraocular pressure, facility of outflow was observed to increase almost linearly for at least 3 hr and continued to increase for up to 10 hr, reaching a maximum several times the initially measured facility. Perfusion with pooled dog aqueous humor did not prevent the time-dependent increase in measured facility. Rapid exchange of anterior chamber contents with perfusion solution alone produced an immediate threefold increase in facility, again followed by a gradual time-dependent facility increase. Rapid exchange of anterior chamber contents with hyaluronidase produced an immediate fivefold increase in facility with stabilization of measured facility over 3 hr and subsequent perfusion. The time-dependent changes in measured facility of outflow or "washout phenomenon" appeared to result from the gradual dissolution of the hyaluronidase-sensitive component of the barriers to aqueous outflow in the canine eye.     

Flying squad to the rescue

Set up following a serious train crash at Sutton Coldfield in January 1955, the accident and emergency department at the Derbyshire Royal Infirmary was the first such department to organise and operate an accident flying squad. On its 25th anniversary Tim Brett, deputy administrator at the hospital, looks at its development and the role it plays today.