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INTRODUCTION: People with haemophilia (PWH) experience end stage joint disease as a result of repeated hemarthrosis, commonly leading to total knee arthroplasty (TKA). AIM: The goal of this meta-analysis is to calculate expected outcomes for range of motion (ROM), functional mobility, and complication rates in PWH following TKA. METHODS: Studies published between 1980 and 2015 were identified. INCLUSION CRITERIA: PWH having TKA, reporting Hospital for Special Surgery Knee Score or Knee Society Score, knee ROM, and incidence of complications for more than 5 TKAs. Inhibitor status, haemophilia severity and HIV status were not criteria for inclusion or exclusion. Meta-analysis was performed using mean, standard deviation, or P-value data to create effect sizes (ES) and 95% confidence intervals for each variable. RESULTS: Twenty studies met inclusion criteria; ten had sufficient data for meta-analyses. A total of 336 TKAs in 254 PWH were analysed with mean follow-up of 6.3 years. Statistically significant ROM improvements were found with 9.72° improvement of flexion contracture (-0.73 effect size (ES) (-0.91 to -0.56)), and 15.69°increase into flexion (0.63 ES (0.34-0.91)). Knee scores showed statistically significant improvements: clinically, 37.9 point increase (3.21 ES [1.79-4.63]) and functionally, 13.50 point increase (1.50 ES [0.80-2.21]). A 31.5% complication rate was calculated with 106 reported in 336 TKAs. CONCLUSIONS: TKA is an effective procedure for improving ROM and decreasing functional deficits resulting from haemophilic arthropathy. Knee score data shows TKA improves overall function. This study guides clinicians regarding outcome expectations post-TKA in PWH.

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AIMS: Among people with diabetes, 10-25% will experience a foot ulcer. Research has shown that supplementation with arginine, glutamine and ß-hydroxy-ß-methylbutyrate may improve wound repair. This study tested whether such supplementation would improve healing of foot ulcers in persons with diabetes. METHODS: Along with standard of care, 270 subjects received, in a double-blinded fashion, (twice per day) either arginine, glutamine and ß-hydroxy-ß-methylbutyrate or a control drink for 16 weeks. The proportion of subjects with total wound closure and time to complete healing was assessed. In a post-hoc analysis, the interaction of serum albumin or limb perfusion, as measured by ankle-brachial index, and supplementation on healing was investigated. RESULTS: Overall, there were no group differences in wound closure or time to wound healing at week 16. However, in subjects with an albumin level of ≤ 40 g/l and/or an ankle-brachial index of < 1.0, a significantly greater proportion of subjects in the arginine, glutamine and ß-hydroxy-ß-methylbutyrate group healed at week 16 compared with control subjects (P = 0.03 and 0.008, respectively). Those with low albumin or decreased limb perfusion in the supplementation group were 1.70 (95% CI 1.04-2.79) and 1.66 (95% CI 1.15-2.38) times more likely to heal. CONCLUSIONS: While no differences in healing were identified with supplementation in non-ischaemic patients or those with normal albumin, addition of arginine, glutamine and ß-hydroxy-ß-methylbutyrate as an adjunct to standard of care may improve healing of diabetic foot ulcers in patients with risk of poor limb perfusion and/or low albumin levels. Further investigation involving arginine, glutamine and ß-hydroxy-ß-methylbutyrate in these high-risk subgroups might prove clinically valuable.

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A stable ternary complex formed with vesicle-associated membrane protein 2 (VAMP2) and plasma membrane proteins syntaxin 1A and synaptosome-associated protein of 25 kDa (SNAP-25) is proposed to function in synaptic vesicle exocytosis. To analyze the structural characteristics of this synaptic protein complex, recombinant binary (syntaxin 1A.SNAP-25), recombinant ternary, and native ternary complexes were subjected to limited trypsin proteolysis. The protected fragments, defined by amino-terminal sequencing and mass spectrometry, included a carboxyl-terminal region of syntaxin 1A, the cytoplasmic domain of VAMP2, and amino- and carboxyl-terminal regions of SNAP-25. Furthermore, separate amino- and carboxyl-terminal fragments of SNAP-25, when combined with VAMP2 and syntaxin 1A, were sufficient for stable complex assembly. Analysis of ternary complexes formed with full-length proteins revealed that the carboxyl-terminal transmembrane anchors of both syntaxin 1A and VAMP2 were protected from trypsin digestion. Moreover, the stability of ternary complexes was increased by inclusion of these transmembrane domains. These results suggest that the transmembrane domains of VAMP2 and syntaxin 1A contribute to complex assembly and stability and that amino- and carboxyl-terminal regions of SNAP-25 may function as independent domains.

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Biochemical analyses revealed that a thyroxine (T4)-binding protein (TBP) in the blood of some turtles exhibits a high degree of structural homology to mammalian vitamin D-binding protein (DBP), instead of mammalian T4-binding protein (TBG). Like DBP, TBP is rich in Cys (ca. 28/molecule). The 31 NH2-terminal amino acids of TBP show 68% identity to the corresponding region of mammalian (rat, mouse, and human) DBP and one peptide from Lys-C proteolysis shows similar homology to residues 35-49 of DBP (the predicted sterol binding domain). Another peptide shows a 75% identity to a sequence corresponding to residues 134-154 of DBP, but seven others showed no homology to any proteins in GenBank. Digestion with N-glycosidase F reduced the M(r) of TBP by only 4.5K compared with 14K for TBG; T4-binding activity of TBP was unaffected. TBP (and DBP) also behaves as a much smaller molecule (approximately 57 kDa) than TBG (> 70 kDa) by size-exclusion chromatography, despite similarities in their estimated sizes from sodium dodecyl sulfate electrophoresis (approximately 60 kDa). Binding studies confirm that the turtle T4-binding protein likely also represents the major blood DPB. Thus, in the turtle, a single binding protein resembling DBP performs two major transport functions which are normally served by proteins representing two different multigene families in mammals.

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Eight clinicians in a renal dialysis unit were asked to classify the suitability of 100 cases (some real, some simulated) for regulat haemodialysis. Seven categories were used, ranging from "excellent prospect: accept without reservation" to "unequivocal rejection," based on 18 items of information previously agreed on as sufficient for the purpose. The ways in which they classified the cases different considerably; only six cases were placed in the same category by all eight clinicians, and this was the "unequivocal rejection" category. Analysis of the extent to which they made effective use of the items showed that between three and nine items were used to a sufficient extent to reach significance for the 100 cases.

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