Capsular Management in Direct Anterior Total Hip Arthroplasty: A Randomized,Single-Blind,Controlled Trial

BackgroundThe direct anterior approach (DAA) is a popular approach to total hip arthroplasty (THA). Unlike the posterior approach, the importance of anterior capsular management is unknown. This randomized controlled trial compares capsular repair versus capsulectomy.MethodsThis single-surgeon, single-blinded, parallel-group randomized controlled trial occurred between 2013 and 2016. Patients undergoing unilateral, primary THA for osteoarthritis consented to undergo blinded, simple randomization to anterior capsulotomy with repair or anterior capsulectomy. Primary outcome measures included hip range of motion, hip flexion strength, and pain with seated hip flexion. Secondary outcome measures included surgical time, estimated blood loss, postoperative complications, and hip disability and osteoarthritis outcome score. Data were prospectively collected intraoperatively, six weeks, six months, an average of over 5 years postoperatively.ResultsNinety-eight patients were ultimately enrolled in the trial; 50 received capsulectomy and 48 received capsulotomy. No significant differences were seen in preoperative demographics or in primary or secondary outcomes during this study. No difference was seen in pain at final follow-up at average > 5 years postoperatively.ConclusionThis study demonstrates that capsular management in DAA THA does not affect postoperative pain or range of motion. The anterior capsule’s role in prosthetic stability after DAA THA remains uncertain, but it does not currently appear that repair provides benefit and may lead to increased surgical time and blood loss. As such, capsular management in DAA THA is at surgeon discretion.     

Genetic manipulation of mammary epithelium by transplantation

Genes can be introduced into mammary epitheliumin vivo by the tissue reconstitution method. Primary cultures of mammary epithelial cells are prepared, a gene introduced using retrovirus vectors, and the cells transplanted into a mammary fat pad from which the normal epithelium has been removed. The cells reform an epithelium in which some cells express the introduced gene. The technique is reviewed and compared with the mammary-specific expression of genes in transgenic mice. To model the development of neoplasia, particularly the preneoplastic changes caused by a single oncogene alone, several oncogenes have been expressed this way—myc, Ha-ras, erbB, erbB2,Wnt-1, andhst/FGF-4. Each caused a different alteration to the growth pattern of the epithelium, such as altered branching, premature alveolus development, distorted duct structure, or altered hormone sensitivity. Insights into normal development have also been obtained by inappropriate expression of genes such asWnt-4.     

Screening for medium chain acyl-CoA dehydrogenase deficiency using electrospray ionisation tandem mass spectrometry

OBJECTIVE: To establish criteria for the diagnosis of medium chain acyl-CoA dehydrogenase (MCAD) deficiency in the UK population using a method in which carnitine species eluted from blood spots are butylated and analysed by electrospray ionisation tandem mass spectrometry (ESI-MS/MS). DESIGN: Four groups were studied: (1) 35 children, aged 4 days to 16.2 years, with proven MCAD deficiency (mostly homozygous for the A985G mutation, none receiving carnitine supplements); (2) 2168 control children; (3) 482 neonates; and (4) 15 MCAD heterozygotes. RESULTS: All patients with MCAD deficiency had an octanoylcarnitine concentration ([C8-Cn]) > 0.38 microM and no accumulation of carnitine species > C10 or < C6. Among the patients with MCAD deficiency, the [C8-Cn] was significantly lower in children > 10 weeks old and in children with carnitine depletion (free carnitine < 20 microM). Neonatal blood spots from patients with MCAD deficiency had a [C8-Cn] > 1.5 microM, whereas in heterozygotes and other normal neonates the [C8-Cn] was < 1.0 microM. In contrast, the blood spot [C8-Cn] in eight of 27 patients with MCAD deficiency > 10 weeks old fell within the same range as five of 15 MCAD heterozygotes (0.38-1.0 microM). However, the free carnitine concentrations were reduced (< 20 microM) in the patients with MCAD deficiency but normal in the heterozygotes. CONCLUSIONS: Criteria for the diagnosis of MCAD deficiency using ESI-MS/MS must take account of age and carnitine depletion. If screening is undertaken at 7-10 days, the number of false positive and negative results should be negligible. Because there have been no instances of death or neurological damage following diagnosis of MCAD deficiency in our patient group, a strong case can be made for neonatal screening for MCAD deficiency in the UK.     

Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors.

Histone deacetylase inhibitors (HDIs) are a new class of drugs with significant antileukemic activity. To explore mechanisms of disease-specific HDI activity in acute myeloid leukaemia (AML), we have characterised expression of all 18 members of the histone deacetylase family in primary AML blasts and in four control cell types, namely CD34+ progenitors from umbilical cord, either quiescent or cycling (post-culture), cycling CD34+ progenitors from GCSF-stimulated adult donors and peripheral blood mononuclear cells. Only SIRT1 was consistently overexpressed (>2 fold) in AML samples compared with all controls, while HDAC6 was overexpressed relative to adult, but not neo-natal cells. HDAC5 and SIRT4 were consistently underexpressed. AML blasts and cell lines, exposed to HDIs in culture, showed both histone hyperacetylation and, unexpectedly, specific hypermethylation of H3 lysine 4. Such treatment also modulated the pattern of HDAC expression, with strong induction of HDAC11 in all myeloid cells tested and with all inhibitors (valproate, butyrate, TSA, SAHA), and lesser, more selective, induction of HDAC9 and SIRT4. The distinct pattern of HDAC expression in AML and its response to HDIs is of relevance to the development of HDI-based therapeutic strategies and may contribute to observed patterns of clinical response and development of drug resistance.