Management of peri-prosthetic joint infection and severe bone loss after total hip arthroplasty using a long-stemmed cemented custom-made articulating spacer (CUMARS).

BACKGROUND: There is little evidence on techniques for management of peri-prosthetic infection (PJI) in the context of severe proximal femoral bone loss. Custom-made articulating spacers (CUMARS) utilising cemented femoral stems as spacers was described providing better bone support and longer survival compared to conventional articulating spacers. We retrospectively report our experience managing PJI by adaptation of this technique using long cemented femoral stems where bone loss precludes use of standard stems. METHODS: Patients undergoing 1st stage revision for infected primary and revision THA using a cemented long stem (> 205 mm) and standard all-polyethylene acetabulum between 2011 and 2018 were identified. After excluding other causes of revision (fractures or aseptic loosening), Twenty-one patients remained out of total 721 revisions. Medical records were assessed for demographics, initial microbiological and operative treatment, complications, eradication of infection and subsequent operations. 2nd stage revision was undertaken in the presence of pain or subsidence. RESULTS: Twenty-one patients underwent 1st stage revision with a cemented long femoral stem. Mean follow up was 3.9 years (range 1.7-7.2). Infection was eradicated in 15 (71.4%) patients. Two patients (9.5%) required repeat 1st stage and subsequently cleared their infection. Three patients (14.3%) had chronic infection and are on long term suppressive antibiotics. One patient (4.8%) was lost to follow up before 2 years. Complications occurred in seven patients (33%) during or after 1st stage revision. Where infection was cleared, 2nd stage revision was undertaken in 12 patients (76.5%) at average of 9 months post 1st stage. Five (23.8%) CUMARS constructs remained in-situ at an average of 3.8 years post-op (range 2.6-5.1). CONCLUSIONS: Our technique can be used in the most taxing of reconstructive scenarios allowing mobility, local antibiotic delivery, maintenance of leg length and preserves bone and soft tissue, factors not afforded by alternative spacer options.

Outcomes of surgery for chronic exertional compartment syndrome in a military population.

AIM: To determine the outcome following fasciectomy for chronic exertional compartment syndrome (CECS) in the UK military, and the association between presurgical intramuscular pressure (IMP) and outcome. METHODS: All patients who underwent fasciectomy for anterior CECS were identified between 2007 and 2010. Presurgery and postsurgery military medical grading for leg function was extracted from the medical records system. The Wilcoxon signed-rank test compared grades before and after surgery. Spearman's rank correlation examined the relationship between IMP and outcome. RESULTS: Presurgery and postsurgery grading was available for 63% of patients. These patients had significantly better leg function after surgery (Z=-3.63, p<0.001). Of these, 49% improved by at least one grade, 36% showed no improvement in grading and 15% had a poorer outcome. There were no significant correlations between IMP and outcome. CONCLUSIONS: A large proportion of patients do not return to full fitness following fasciectomy in the military population. This is in line with a recent study in the US military, but conflicts with most civilian reports. The reasons for these differences are not clear. Furthermore, the lack of a relationship between IMP and outcome questions the role of pressure in this condition. These results suggest that the role of postoperative rehabilitation protocols and other conservative options should be explored.

Implementation and scalability of a digital intervention to reduce depressive symptoms in people with diabetes, hypertension or both in Brazil and Peru: a qualitative study of health system's stakeholders' perspectives.

Two randomized controlled trials (RCTs) in Brazil and Peru demonstrated the effectiveness of CONEMO, a digital intervention supported by trained nurses or nurse assistants (NAs), to reduce depressive symptoms in people with diabetes and/or hypertension. This paper extends the RCTs findings by reflecting on the conditions needed for its wider implementation in routine care services. A qualitative study using semi-structured interviews and content analysis was conducted with nurses/NAs, clinicians, healthcare administrators, and policymakers. Informants reported that CONEMO would be feasible to implement in their health services, but some conditions could be improved before its scale-up: reducing workloads of healthcare workers; raising mental health awareness among clinicians and administrators; being able to inform, deliver and accompany the intervention; assuring appropriate training and supervision of nurses/NAs; and supporting the use of technology in public health services and by patients, especially older ones. We discuss some suggestions on how to overcome these challenges.

A pre-hospital technique for controlling haemorrhage from traumatic perineal and high amputation injuries.

Perineal trauma resulting from the adaptive use of improvised explosive devices (IEDs) has become an increasingly common problem during current operational conflicts in Afghanistan. Control of haemorrhage from the perineum and high amputations is a particular challenge due to the bony anatomy, rich pelvic vascular supply and the difficulty in achieving haemostasis by direct pressure. In this article, the authors describe a potential pre-hospital solution for controlling haemorrhage from perineal and high amputation injuries.

Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle.

Vasodilators are used clinically for the treatment of hypertension and heart failure. The effects of some vasodilators seem to be mediated by membrane hyperpolarization. The molecular basis of this hyperpolarization has been investigated by examining the properties of single K+ channels in arterial smooth muscle cells. The presence of adenosine triphosphate (ATP)-sensitive K+ channels in these cells was demonstrated at the single channel level. These channels were opened by the hyperpolarizing vasodilator cromakalim and inhibited by the ATP-sensitive K+ channel blocker glibenclamide. Furthermore, in arterial rings the vasorelaxing actions of the drugs diazoxide, cromakalim, and pinacidil and the hyperpolarizing actions of vasoactive intestinal polypeptide and acetylcholine were blocked by inhibitors of the ATP-sensitive K+ channels, suggesting that all these agents may act through a common pathway in smooth muscle by opening ATP-sensitive K+ channels.

Intravenous fluid and electrolyte administration in elective gastrointestinal surgery: mechanisms of excessive therapy.

INTRODUCTION While clinical guidelines stress the importance of the judicious perioperative intravenous fluid administration, data show that adherence to these protocols is poor. The reasons have not been identified. We therefore audited the magnitude and indications of fluid and electrolyte administration in a teaching hospital. We hypothesised that epidural analgesia is associated with excessive fluid therapy. MATERIALS AND METHODS Intravenous fluid and electrolyte administration during the day of surgery and the subsequent 2 days in consecutive patients undergoing elective gastrointestinal surgery between November 2013 and May 2014 were retrospectively audited. Timing, volumes and indications were recorded. RESULTS One hundred patients undergoing elective gastrointestinal resection were studied. Patients received 9030 ml ± 2860 ml (mean ± standard deviation) intravenous fluids containing a total of 1180 ml ± 420 mmol sodium and resulting in a cumulative fluid balance of +5120 ml ± 2510 ml; 44% ± 14% of total volumes were given in theatre. Nearly all fluid was given for maintenance, 100% (96-100%, interquartile range), with 17 patients only receiving replacement or resuscitation. Independent predictors of increased volumes included open surgery, upper gastrointestinal surgery, increased duration and epidural analgesia but not body weight. Postoperative fluid volume was the only independent predictor of postoperative complication grade (P = 0.0044). CONCLUSIONS Despite published guidelines, perioperative fluid and electrolyte administration were excessive and were associated with postoperative morbidity. Substantial volumes were administered in theatre. Nearly all administration was for maintenance, yet patients received approximately five times the amount of sodium required. Epidural analgesia was an independent predictor of fluid volumes but body weight was not.

LATIN-MH: a model for building research capacity within Latin America.

BACKGROUND: Latin America Treatment and Innovation Network in Mental Health (LATIN-MH) is a research hub located in Brazil and Peru that conducts a research project to help reduce the treatment gap in mental health in Latin America (LA). Besides its research core, LATIN-MH has a Capacity Building (CB) component that aims to help young researchers receive the specific training to contribute to the growing scientific production in mental health in LA. METHODS: LATIN-MH proposal in CB includes a series of actions to prepare professionals in the research area. The main proposals are described here, which include online study groups, promotion of scientific meetings, hands-on training in different levels and sharing of information. RESULTS: LATIN-MH CB activities are at its initial stages but the proposed activities were well evaluated by the participants. The first participating fellows who finished their fellowships are contributing elsewhere in the mental treatment and human resources formation area. CONCLUSION: The repercussion of LATIN-MH actions in CB and its evaluation, particularly on the formation of human resources and dissemination of information, show that the hub is contributing to the critic formation of young researchers and the circulation of important information.

KATP channels in vascular smooth muscle.

ATP sensitive potassium channels (KATP channels) appear widely distributed in the vascular system. At the single channel level, channels with both small and large conductance have been described, though the former appear to be activated by potassium channel openers or ATP depletion in whole cell studies. KATP channels are inhibited by cytoplasmic ATP, and may be activated by intracellular nucleotide diphosphates. Regulation by intracellular metabolites confers a degree of sensitivity of the channel to the metabolic status of the cell, and there is evidence that KATP currents are activated during metabolic inhibition. In general, activation of KATP channels will lead to membrane hyperpolarisation and so to vasorelaxation. The functional role of the channel is being intensively studied at present. The channel may form a target for a number of endogenous vasodilators, and may be inhibited by some vasoconstrictors. It may be involved in the vasodilator response to hypoxia, and may contribute to the resting membrane potential of smooth muscle in some blood vessels.

Caveolar disruption causes contraction of rat femoral arteries via reduced basal NO release and subsequent closure of BKCa channels.

Background and Purpose. Caveolae act as signalling hubs in endothelial and smooth muscle cells. Caveolar disruption by the membrane cholesterol depleting agent methyl-ß-cyclodextrin (M-ß-CD) has various functional effects on arteries including (i) impairment of endothelium-dependent relaxation, and (ii) alteration of smooth muscle cell (SMC) contraction independently of the endothelium. The aim of this study was to explore the effects of M-ß-CD on rat femoral arteries. Methods. Isometric force was measured in rat femoral arteries stimulated to contract with a solution containing 20 mM K(+) and 200 nM Bay K 8644 (20 K/Bay K) or with one containing 80 mM K(+)(80 K). Results. Incubation of arteries with M-ß-CD (5 mM, 60 min) increased force in response to 20 K/Bay K but not that induced by 80 K. Application of cholesterol saturated M-ß-CD (Ch-MCD, 5 mM, 50 min) reversed the effects of M-ß-CD. After mechanical removal of endothelial cells M-ß-CD caused only a small enhancement of contractions to 20 K/Bay K. This result suggests M-ß-CD acts via altering release of an endothelial-derived vasodilator or vasoconstrictor. When nitric oxide synthase was blocked by pre-incubation of arteries with L-NAME (250 µM) the contraction of arteries to 20 K/Bay K was enhanced, and this effect was abolished by pre-treatment with M-ß-CD. This suggests M-ß-CD is inhibiting endothelial NO release. Inhibition of large conductance voltage- and Ca(2+)-activated (BKCa) channels with 2 mM TEA(+) or 100 nM Iberiotoxin (IbTX) enhanced 20 K/Bay K contractions. L-NAME attenuated the contractile effect of IbTX, as did endothelial removal. Conclusions. Our results suggest caveolar disruption results in decreased release of endothelial-derived nitric oxide in rat femoral artery, resulting in a reduced contribution of BKCa channels to the smooth muscle cell membrane potential, causing depolarisation and contraction.

Fading and rebound of P2X2 currents at millimolar ATP concentrations caused by low pH.

When ATP is applied at high concentrations (above 1 mM) to PC12 cells, it produces a rapidly desensitizing peak current followed by a rebound of the current after termination of the ATP application. We expressed P2X2 receptors, which are thought to mediate the ATP currents of PC12 cells, in HEK293 cells and studied the effects of acidification on this 'fading and rebound' phenomenon. We found that the desensitization disappeared after adjusting the low pH (<5.0) of the millimolar ATP concentrations to a more physiological value (pH 7.3). Furthermore, the fading and rebound could also be induced at much lower ATP concentrations by decreasing the pH of the ATP containing application solutions. Thus, it appears this phenomenon is not caused directly by high concentrations of ATP, but is due to a concomitant acidification that occurs when high concentrations of ATP are dissolved in only moderately buffered application solutions.

Molecular analysis of the subtype-selective inhibition of cloned KATP channels by PNU-37883A.

1. In this study, we have used Kir6.1/Kir6.2 chimeric proteins and current recordings to investigate the molecular basis of PNU-37883A inhibition of cloned K(ATP) channels. 2. Rat Kir6.1, Kir6.2 and Kir6.1/Kir6.2 chimeras were co-expressed with either SUR2B or SUR1, following RNA injection into Xenopus oocytes, and fractional inhibition of K(ATP) currents by 10 microm PNU-37883A reported. 3. Channels containing Kir6.1/SUR2B were more sensitive to inhibition by PNU-37883A than those containing Kir6.2/SUR2B (mean fractional inhibition: 0.70, cf. 0.07). 4. On expression with SUR2B, a chimeric channel with the Kir6.1 pore and the Kir6.2 amino- and carboxy-terminal domains was PNU-37883A insensitive (0.06). A chimera with the Kir6.1 carboxy-terminus and Kir6.2 amino-terminus and pore was inhibited (0.48). These results, and those obtained with other chimeras, suggest that the C-terminus is an important determinant of PNU-37883A inhibition of Kir6.1. Similar results were seen when constructs were co-expressed with SUR1. Further chimeric constructs localised PNU-37883A sensitivity to an 81 amino-acid residue section in the Kir6.1 carboxy-terminus. 5. Our data show that structural differences between Kir6.1 and Kir6.2 are important in determining sensitivity to PNU-37883A. This compound may prove useful in probing the structural and functional differences between the two channel subtypes.

Inhibition of vascular K(ATP) channels by U-37883A: a comparison with cardiac and skeletal muscle.

1 The aim of this study was to investigate the selectivity of the ATP-sensitive potassium (K(ATP)) channel inhibitor U-37883A (4-morpholinecarboximidine-N-1-adamantyl-N'-1-cyclohexyl). Membrane currents through K(ATP) channels were recorded in single muscle cells enzymatically isolated from rat mesenteric artery, cardiac ventricle and skeletal muscle (flexor digitorum brevis). K(ATP) currents were induced either by cell dialysis with 0.1 mM ATP and 0.1 mM ADP, or by application of synthetic potassium channel openers (levcromakalim or pinacidil). 2 U-37883A inhibited K(ATP) currents in smooth muscle cells from rat mesenteric artery. Half inhibition of 10 microM levcromakalim-induced currents occurred at a concentration of 3.5 microM. 3 Relaxations of rat mesenteric vessels caused by levcromakalim were reversed by U-37883A. 1 microM levcromakalim-induced relaxations were inhibited at a similar concentration of U-37883A (half inhibition, 1.1 microM) to levcromakalim-induced KATP currents. 4 K(ATP) currents activated by 100 microM pinacidil were also studied in single myocytes from rat mesenteric artery, skeletal muscle and cardiac ventricle. 10 microM U-37883A substantially inhibited K(ATP) currents in vascular cells, but had little effect in skeletal or cardiac myocytes. Higher concentrations of U-37883A (100 microM) caused a modest decrease in K(ATP) currents in skeletal and cardiac muscle. The sulphonylurea K(ATP) channel antagonist glibenclamide (10 microM) abolished currents in all muscle types. 5 The effect of U-37883A on vascular inward rectifier (KIR) and voltage-dependent potassium (KV) currents was also examined. While 10 microM U-37883A had little effect on these currents, some inhibition was apparent at higher concentrations (100 microM) of the compound. 6 We conclude that U-37883A inhibits K(ATP) channels in arterial smooth muscle more effectively than in cardiac and skeletal muscle. Furthermore, this compound is selective for K(ATP) channels over KV and KIR channels in smooth muscle cells.

Activation of human neutrophils by soluble immune complexes: role of Fc gamma RII and Fc gamma RIIIb in stimulation of the respiratory burst and elevation of intracellular Ca2+.

Activation of control, unprimed neutrophils with soluble immune complexes fails to generate a respiratory burst. However, if the cells are primed with either tumor necrosis factor-alpha or granulocyte-macrophage colony-stimulating factor prior to addition of soluble immune complexes, then a rapid and transient burst of reactive oxidant secretion is observed. In unprimed neutrophils the soluble immune complexes stimulate an intracellular Ca2+ transient that arises from the mobilization of intracellular Ca2+. However, in primed cells, an "extra" intracellular Ca2+ signal is observed that arises from Ca2+ influx. After removal of Fc gamma RIIIb by treatment with pronase or PI-PLC, the soluble immune complexes fail to activate a respiratory burst in unprimed neutrophils and the "extra" Ca2+ signal is not observed. These results indicate that during priming Fc gamma RIIIb becomes functionally activated and thence its ligation leads to stimulated Ca2+ influx and the generation of intracellular signals that lead to NADPH oxidase activation. Experiments using Fab/F(ab')2 fragments to specifically crosslink either Fc gamma RII or Fc gamma RIIIb and experiments with neutrophils from an individual with Fc gamma RIIIb gene deficiency confirm this important function for Fc gamma RIIIb in neutrophil activation.

Cytokine expression by inflammatory neutrophils.

Bloodstream neutrophils do not express mRNA for interleukin-1 beta (IL-1 beta), but transcripts for this cytokine are rapidly induced following exposure to recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) in vitro. Levels of IL-1 beta mRNA reach maximal values 1 h after exposure to rGM-CSF and then decline to near basal levels by 4 h. Similarly, rGM-CSF treatment of blood neutrophils in vitro induced increases in levels of mRNA for IL-6 and tumour necrosis factor-alpha (TNF-alpha). RNA extracted from neutrophils isolated from the synovial fluid of patients with rheumatoid arthritis expressed low, but significant levels of IL-1 beta mRNA that were between 0.5 and 3% of the levels that could be maximally induced by rGM-CSF treatment of blood neutrophils. However, transcripts for TNF-alpha and IL-6 were not detected in these synovial fluid neutrophils. mRNA for transforming growth factor-beta (TGF-beta) was constitutively expressed in blood and synovial fluid neutrophils and transcripts for this cytokine were not altered by rGM-CSF exposure. Because of the transient nature of IL-1 beta expression by activated neutrophils, we propose that the low levels of expression of mRNA for this cytokine in the synovial fluid neutrophils represents expression by a small, perhaps newly-recruited and activated, sub-population of cells. IL-1 beta expression by this sub-population may thus contribute to the pathogenesis of rheumatoid disease.

Retention of young general practitioners entering the NHS from 1991-1992.

BACKGROUND: The supply of general practitioners (GPs) in the National Health Service (NHS) is dynamic and there are fears that there will be an inadequate number of doctors to meet the needs of the NHS. There are particular concerns about changes in the career trajectory of young GPs and what they mean for overall supply. AIM: To identify predictors of retention among young, new entrant GPs entering the NHS between 1 October 1991 and 1 October 1992. METHOD: Two-year retention rates of young (35 years of age or less) new entrant GPs have been modelled using a multilevel logit model. Retention is defined as young, new entrant GPs remaining in their initial health authority for two years or more. RESULTS: Two hundred and fifty-two (13.0%) members of the study group left general practice within two years of entry (i.e. were not retained). Sex (females had lower retention [95% CI = 0.43-0.75]), practice size (young GPs in larger practices had higher retention [95% CI = 1.10-1.29]), and belonging to a practice in one of 16 Greater London Health Authorities (which had lower retention [95% CI = 0.39-0.82]) were identified as major predictors of retention. Deprivation, measured at the individual GP patient list level, had a very slight association with retention (P = 0.097; 95% CI = 1.00-1.02). Deprivation measured at the health authority level (95% CI = 0.99-1.01) was not found to be a statistically significant predictor of retention (P = 0.83). CONCLUSION: None of the statistically significant predictors of retention suggest any policy panacea to end this phenomenon. The challenge for policy is to learn to deal with the dynamic nature of the GP workforce with a non-crisis mentality.

An operation for chronic prepatellar bursitis.

An operation for chronic prepatellar bursitis is described in which only the posterior wall of the bursa is excised, thus preserving, undamaged, healthy and normally sensitive skin. This procedure is easier and less traumatic than complete excision of the bursa and results in fewer complications. It is suggested that removal of tha anterior wall of the bursa results in unnecessary and harmful interference with the underlying skin. The operation described gives a good functional and structural result; leaving the anterior wall of the bursa does not predispose to recurrence.

Sexual function after bilateral lumbar sympathectomy and aorto-iliac by-pass surgery.

Sexual function has been assessed in 44 patients under 60 years old after bilateral lumbar sympathectomy. 21 had lumbar sympathectomy alone, but in 23 it was combined with by-pass aorto-iliac surgery. Half these patients produced seminal fluid for analysis and spermatozoa were present in all. In those patients who also had aorto-iliac surgery, sexual function was impairedin 40%, ejaculation and erection difficulties occurring in the same proportion. In patients who had only bilateral sympathectomy, these complications occurred in 24% and mainly consisted of ejaculation disturbances. Only three patients became impotent, each having had aortic surgery. Serious sexual complications caused by lumbar sympathectomy alone seem relatively rare and should only preclude its use in young men wishing to reproduce.

Oesophageal varices: evaluation of injection sclerotherapy without general anesthesia using the flexible fibreoptic gastroscope.

A technique of injecting oesophageal varices through a flexible fibreoptic gastroscopic is described and its value in controlling haemorrhage and eradicating varices in 34 patients is considered prospectively. Twenty-five per cent of the patients re-bled during the first emergency admission after injections, but control was achieved in all. Subsequent re-bleeding occurred in 46% and varices were ultimately eradicated in 59%. It ic concluded that the procedure is associated with fewer serious complications compared with rigid oesophagoscopic techniques and may be as effective.

Bascom's operation for pilonidal sinus.

During 1985 in England and Wales, 7000 patients were treated for pilonidal disease with an average hospital stay of 5 days. The aim of this paper is to report our early experience with Bascom's operation for pilonidal sinus--a procedure relatively untried in the UK.

A low energy paediatric clavicle fracture associated with acute brachial plexus injury and subclavian artery compression.

Paediatric clavicle fractures are common injuries presenting to orthopaedic surgeons. The majority of these represent midshaft low energy fractures, which in the vast majority of cases are treated non-operatively and recover rapidly. The main indications to consider operative intervention include high energy of injury, >2 cm shortening, open fractures and associated vascular or neurological injuries. Brachial plexus (BP) injuries are uncommon with variable outcomes. They often result from high energy motorcycle related accidents with potentially fatal associated injuries such as vascular disruption. Their management is complex, requiring expertise, and they are therefore usually managed in supraregional centres. We present a unique case of a low energy midshaft clavicle fracture in a paediatric patient in whom there was an acute BP injury and subclavian artery compression that has not been described previously.