A Reproducible Technique for Arthroscopic Acromioclavicular Joint Excision

Arthroscopic acromioclavicular joint excision is a commonly performed but technically demanding procedure. Incomplete excision can leave residual symptoms. We present a simple, reproducible technique ensuring satisfactory excision of the joint.     

Comparison of Sawchuk-Zaske and Bayesian forecasting for aminoglycosides in seriously ill patients.

1. Individual pharmacokinetic parameters and predicted steady-state serum concentrations of aminoglycosides were calculated by Sawchuck-Zaske (SZ) and Bayesian methods. 2. Predicted concentrations were compared with observed steady-state concentrations for 36 seriously ill patients with systemic infections. Four aminoglycoside concentrations were used for the SZ method. Differing numbers of serum aminoglycoside samples were used in the Bayesian parameter estimation: one sample Bayesian used one post-infusion concentration, two sample Bayesian used a trough plus one post-infusion concentrations and four sample Bayesian used a trough plus three post-infusion concentrations. 3. 79% of the SZ predictions were with +/- 2 mg l-1 of the observed peak concentrations, and 72% of the two sample Bayesian predictions were within the same range. 82% of SZ and the two sample Bayesian predictions were within +/- 1 mg l-1 of the observed trough concentrations. 4. A confidence interval comparison of estimated pharmacokinetic parameters and precision for the predicted concentrations showed no important differences between the SZ and the two sample Bayesian. The four sample Bayesian was the most precise method. 5. We conclude that the Bayesian forecasting method utilizing a trough plus one post-infusion concentrations is as useful as the SZ method which requires three to four serum concentrations in individualizing aminoglycoside therapy for seriously ill patients.     

A quick, sensitive high-performance liquid chromatography assay for monoethylglycinexylidide and lignocaine in serum/plasma using solid-phase extraction.

Recent advances in the investigation of liver disease and transplantation have seen the introduction of lignocaine as a probe of liver function. For this purpose, an assay that is sensitive and rapid is required for the major metabolite of lignocaine, monoethylglycinexylidide (MEGX). We have developed an accurate, low-cost high-performance liquid chromatography (HPLC) method using Bond-Elut phenyl (1 cc) cartridges for sample preparation. The total preparation time for five samples is less than 10 min and the run time is approximately 10 min/sample. Each cartridge can be used at least four times. Simultaneous measurement of another metabolite of lignocaine, glycinexylidide (GX), can be achieved by adjustment of the mobile phase and flow rate. The chromatogram is monitored with an UV detector at 210 nm. The inter- and intra-assay coefficients of variation for MEGX (10-250 micrograms/L) and lignocaine (100-2,000 micrograms/L) are less than 9.5 and less than 2%, respectively, with recoveries for MEGX, trimethoprim (internal standard), and lignocaine all greater than 85%. This method offers a rapid, sensitive assay that is clinically useful in the new role for lignocaine/MEGX in dynamic liver function testing.     

Mutations in protein N-arginine methyltransferases are not the cause of FTLD-FUS

The nuclear protein fused in sarcoma (FUS) is found in cytoplasmic inclusions in a subset of patients with the neurodegenerative disorder frontotemporal lobar degeneration (FTLD-FUS). FUS contains a methylated arginine–glycine–glycine domain that is required for transport into the nucleus. Recent findings have shown that this domain is hypomethylated in patients with FTLD-FUS. To determine whether the cause of hypomethylation is the result of mutations in protein N-arginine methyltransferases (PRMTs), we selected 3 candidate genes (PRMT1, PRMT3, and PRMT8) and performed complete sequencing analysis and real-time polymerase chain reaction mRNA expression analysis in 20 FTLD-FUS cases. No mutations or statistically significant changes in expression were observed in our patient samples, suggesting that defects in PRMTs are not the cause of FTLD-FUS.     

Metformin increases insulin sensitivity and basal glucose clearance in Type 2 (non-insulin dependent) diabetes mellitus

Abstract The effects of metformin on glycaemia, insulin and c-peptide levels, hepatic glucose production and insulin sensitivity (using the euglycaemic, hyperinsulinaemic clamp) were evaluated at fortnightly intervals in 9 Type 2 diabetic patients using a stepwise dosing protocol: Stage 1 - no metformin for four weeks; stage 2 - metformin 500mg mane; stage 3 - metformin 500mg thrice daily; stage 4 – metformin 1000mg thrice daily. Results are expressed as Mean ± SEM. Fasting blood glucose decreased from basal values (9.7 ±1.0 mmol/L) by 13% at stage 2, 34% at stage 3 and 41% at stage 4 (p<0.02 vs basal for all stages; p<0.02 stage 2 vs stage 3). Post-prandial glycaemia was significantly improved only with metformin 3000mg/day (p<0.05). Fasting, meal-stimulated and total insulin and c-peptide levels showed no change. Hepatic glucose output did not change significantly with metformin. Insulin sensitivity, measured as total glucose utilisation during hyperinsulinaemia, increased from stage 1 (10.3 ± 2.1 μmoL/kg/min) by 23% at stage 3 (p < 0.05) and by 29% at stage 4 (p < 0.02). Basal metabolic clearance of glucose increased compared to stage 1 (1.69 ±0.16 mL/kg/min) by 30% at stage 2, 53% at stage 3 and 44% at stage 4 (all p <0.02). This study demonstrates that improved efficiency of glucose utilisation, both basally and under conditions of euglycaemic hyperinsulinaemia, is the basis of metformin's antihyperglycaemic action.     

Intestinal permeability in subjects from two different race groups with diverse stone-risk profiles

It is well established that calcium oxalate stones may be caused by colonic or ileum oxalate (Ox) hyperabsorption (secondary to intestinal dysfunction). Studies have reported that increased intestinal permeability (IP) can cause hyperabsorption of nutrients culminating in passive diffusion of Ox. In South Africa, renal stones occur in the white population (W) but are extremely rare in the black population (B). Previous studies have shown that despite B having a hyperoxalurogenic diet relative to W, urinary Ox in the former is not higher. It has been suggested that different Ox handling mechanisms in the groups are the cause of this disparity. The present study was undertaken to examine whether the IP index, a reliable and accurate measure of intestinal integrity, plays a role in this anomaly. Ten healthy males from each group ingested a dual-sugar isotonic solution containing 5 g lactulose (LA) and 2 g mannitol (MA). IP was assessed by comparing the LA:MA ratio in 5 h urine samples using high performance anion exchange chromatography coupled with pulse amperometric detection to measure the concentration of each sugar. 24 h dietary intake and urine composition were also determined. LA excretion was identical in both groups (0.03 %) while MA excretion was 8.3 % in B and 11.3 % in W. IP index was 0.004 for B and 0.003 for W. It is concluded that IP is not a contributory factor in the apparent different handling of dietary Ox in B and W South Africans. It is speculated that differences in renal transporters may play a role.     

Skeletal muscle α-actin diseases (actinopathies): pathology and mechanisms

Mutations in the skeletal muscle α-actin gene (ACTA1) cause a range of congenital myopathies characterised by muscle weakness and specific skeletal muscle structural lesions. Actin accumulations, nemaline and intranuclear bodies, fibre-type disproportion, cores, caps, dystrophic features and zebra bodies have all been seen in biopsies from patients with ACTA1 disease, with patients frequently presenting with multiple pathologies. Therefore increasingly it is considered that these entities may represent a continuum of structural abnormalities arising due to ACTA1 mutations. Recently an ACTA1 mutation has also been associated with a hypertonic clinical presentation with nemaline bodies. Whilst multiple genes are known to cause many of the pathologies associated with ACTA1 mutations, to date actin aggregates, intranuclear rods and zebra bodies have solely been attributed to ACTA1 mutations. Approximately 200 different ACTA1 mutations have been identified, with 90 % resulting in dominant disease and 10 % resulting in recessive disease. Despite extensive research into normal actin function and the functional consequences of ACTA1 mutations in cell culture, animal models and patient tissue, the mechanisms underlying muscle weakness and the formation of structural lesions remains largely unknown. Whilst precise mechanisms are being grappled with, headway is being made in terms of developing therapeutics for ACTA1 disease, with gene therapy (specifically reducing the proportion of mutant skeletal muscle α-actin protein) and pharmacological agents showing promising results in animal models and patient muscle. The use of small molecules to sensitise the contractile apparatus to Ca²⁺ is a promising therapeutic for patients with various neuromuscular disorders, including ACTA1 disease.     

Evaluation of cardiovascular events and progression to end-stage renal disease in patients with dyslipidemia and chronic kidney disease from the North-Eastern area of Romania

International Urology and Nephrology - The aim of this prospective cohort study was: to identify the association between different biomarkers [proprotein convertase subtilisin/kexin 9-PCSK9,...