'Working together' - A new approach to Reviewing the Quality of Postgraduate Medical Training Posts in Northern Ireland?

Many of us are involved in the education and training of junior doctors. Maintaining and improving the quality of such training is the common goal of all medical educators, including those working in the Northern Ireland Medical and Dental Training Agency (NIMDTA) and within our hospitals - the Local Education Providers (LEPs). The development of NIMDTA's Placement Quality Initiative (PQI) aims to create a more collaborative working relationship between NIMDTA and the LEPs, working together, to achieve a shared goal and develop and implement strategies to improve current practice. We review the PQI process, from both a trainee and trainer's perspective, and ascertain if this approach has facilitated positive, reproducible changes in training programmes that are felt at ground level.

Correction to: Flow-mediated dilation and heart failure: a review with implications to physical rehabilitation.

The scholarship support information in Acknowledgement was missing.

Flow-mediated dilation and heart failure: a review with implications to physical rehabilitation.

Endothelial dysfunction plays as an important role on mismatch responses that occur during exercise in patients with congestive heart failure (CHF). However, cardiac rehabilitation, a core component of management of CHF patients, can improve endothelial function, contributing to reduce the morbidity and mortality of these patients. The primary aims of this review were to describe the importance of flow-mediated dilatation (FMD) as a non-invasive validation tool to assess endothelial dysfunction and to highlight the relevance of scientific studies that evaluated the effects of exercise interventions on peripheral vascular endothelial function as measured by FMD in patients with CHF with both preserved and reduced ejection fraction.

Resistance exercise training improves heart rate variability and muscle performance: a randomized controlled trial in coronary artery disease patients.

BACKGROUND: Resistance exercise (RE) is an important part of cardiac rehabilitation. However, it is not known about the low intensity of RE training that could modify the heart rate variability (HRV), muscular strength and endurance in patients with coronary artery disease (CAD). AIM: To investigate the effects of high repetition/low load resistance training (HR/LL-RT) program on HRV and muscular strength and endurance in CAD patients. DESIGN: Randomized and controlled trial. SETTING: Patients seen at the Cardiopulmonary Physical Therapy Laboratory between May 2011 and November 2013. POPULATION: Twenty male patients with CAD were randomized to a training group (61.3±5.2 years) or control group (61±4.4 years). METHODS: 1 repetition maximum (1-RM) maneuver, discontinuous exercise test on the leg press (DET-L), and resting HRV were performed before and after 8 weeks of HR/LL-RT on a 45° leg press. RMSSD, SD1, mean HR and ApEn indices were calculated. The HR/LL-RT program consisted of a lower limb exercise using a 45° leg press; 3 sets of 20 repetitions, two times a week. The initial load was set at 30% of the 1-RM load and the duration of the HR/LL-RT program was performed for 8 weeks. RESULTS: After 8 weeks of HR/LL-RT there were significant increases of RMSSD and SD1 indices in the training group only (P<0.05). There was a significant decrease in mean HR after HR/LL-RT in the training group (P<0.05). There was a significantly higher ApEn after in the training group (P<0.05). There were significantly higher values in the training group in contrast to the control group (P<0.05). CONCLUSION: These results show positive improvements on HRV, as well as muscle strength and endurance in CAD patients. CLINICAL REHABILITATION IMPACT: Eight weeks of HR/LL-RT is an effective sufficient to beneficially modify important outcomes as HRV, muscle strength and endurance in CAD patients.

Benefit of a low-fat over high-fat diet on vascular health during alternate day fasting.

BACKGROUND: Alternate day fasting (ADF) with a low-fat (LF) diet improves brachial artery flow-mediated dilation (FMD). Whether these beneficial effects can be reproduced with a high-fat (HF) diet remains unclear. OBJECTIVE: This study compared the effects of ADF-HF to ADF-LF regimens on FMD. The role that adipokines have in mediating this effect was also investigated. METHODS: Thirty-two obese subjects were randomized to an ADF-HF (45% fat) or ADF-LF diet (25% fat), consisting of two phases: (1) a 2-week baseline weight maintenance period and (2) an 8-week ADF weight loss period. Food was provided throughout the study. RESULTS: Body weight was reduced (P<0.0001) in the ADF-HF (4.4±1.0 kg) and ADF-LF group (3.7±0.7 kg). FMD decreased (P<0.05) by ADF-HF relative to baseline (7±1 to 5±2%) and increased (P<0.05) by ADF-LF (5±1 to 7±2%). Blood pressure remained unchanged in both groups. Adiponectin increased (P<0.05) in the ADF-HF (43±7%) and ADF-LF group (51±7%). Leptin and resistin decreased (P<0.05) in the ADF-HF (32±5%; 23±5%) and ADF-LF group (30±3%; 27±4%). Increases in adiponectin were associated with augmented FMD in the ADF-LF group only (r=0.34, P=0.03). CONCLUSION: Thus, improvements in FMD with ADF may only occur with LF diets and not with HF diets, and adipokines may not have a significant role in mediating this effect.

The instruments of the bonesetter.

Orthopaedic surgeons use a variety of instruments to help correct, treat, and heal bone disease. The development of these instruments mirrors the history of orthopaedic surgery. The history of bonesetting, the treatment and replacement of joints, and of those who performed these techniques, appears to originate deep in antiquity. Changing ideas within medicine and surgery over the last 200 years have shaped the discovery and evolution of orthopaedic instruments and of the bonesetters themselves. Advances have led to the use of computers as instruments in the navigational guidance of arthroplasty surgery, the use of robotics, the development of cordless drills and improvements in the design of blades to cut bone. Yet some of the old instruments remain; plaster of Paris bandages, the Thomas Splint, Liston's bonecutter, Gigli's saw, bone nibblers and Macewan's osteotomes are still in use. This paper presents a historical review of bonesetters and examines how orthopaedic instruments have evolved from antiquity to the 21st century.

Responses of the bed bug, Cimex lectularius, to temperature extremes and dehydration: levels of tolerance, rapid cold hardening and expression of heat shock proteins.

This study of the bed bug, Cimex lectularius, examines tolerance of adult females to extremes in temperature and loss of body water. Although the supercooling point (SCP) of the bed bugs was approximately -20 degrees C, all were killed by a direct 1 h exposure to -16 degrees C. Thus, this species cannot tolerate freezing and is killed at temperatures well above its SCP. Neither cold acclimation at 4 degrees C for 2 weeks nor dehydration (15% loss of water content) enhanced cold tolerance. However, bed bugs have the capacity for rapid cold hardening, i.e. a 1-h exposure to 0 degrees C improved their subsequent tolerance of -14 and -16 degrees C. In response to heat stress, fewer than 20% of the bugs survived a 1-h exposure to 46 degrees C, and nearly all were killed at 48 degrees C. Dehydration, heat acclimation at 30 degrees C for 2 weeks and rapid heat hardening at 37 degrees C for 1 h all failed to improve heat tolerance. Expression of the mRNAs encoding two heat shock proteins (Hsps), Hsp70 and Hsp90, was elevated in response to heat stress, cold stress and during dehydration and rehydration. The response of Hsp90 was more pronounced than that of Hsp70 during dehydration and rehydration. Our results define the tolerance limits for bed bugs to these commonly encountered stresses of temperature and low humidity and indicate a role for Hsps in responding to these stresses.

Can we improve dysphagia referrals?

We set out to examine whether a multidisciplinary out-patient dysphagia referral triage service would shorten the duration of a patient's referral process and direct patients to the correct specialty. A review was carried out of patients referred with dysphagia before and after the introduction of a multidisciplinary out-patient dysphagia service, from February 2001 to April 2001 and from January 2002 to March 2002, inclusive. One hundred and eight patients were referred in total. The length of time until the first appointment was reduced from four to three weeks (median; range one to 23; p<0.001). The number of instrumental investigations was reduced, with a median of one instrumentation per patient under the new service, compared with two in those under the standard service (p<0.001). Attendance to hospital was also reduced, with 45 per cent of patients under the new service requiring only one appointment, compared with 13 per cent in those under the standard service (p<0.001). The multidisciplinary out-patient dysphagia service was associated with significant reductions in waiting times, in the number of instrumental investigations and in the duration of the patient's referral process.

Radiation induced small bowel "web" formation is associated with acquired microvascular dysfunction.

BACKGROUND AND AIMS: Radiation therapy of abdominal and pelvic solid tumours results in late intestinal toxicity of a severe nature in approximately 5% of cases. These manifestations may include ischaemia and stricture formation, which may present as "webs". These webs are likely to play a role in the pathogenesis of recurrent bowel obstruction. The mechanisms of microvascular injury to the bowel in the setting of radiation have not been defined. We hypothesised that microvascular dysfunction with impaired vasodilation to acetylcholine (Ach) would be an acquired pathophysiological abnormality in radiation and "web" formation. METHODS: A 40 year old patient treated with radiation, two years previously, for an anal squamous cell cancer presented with recurrent small bowel obstruction. "Webs" in the distal ileum were detected using wireless capsule endoscopy, after small bowel barium radiographs failed to demonstrate a lesion. Following resection, freshly isolated 50-150 mum diameter arterioles from the "web" and adjacent normal calibre bowel were analysed with histology and microvessel physiological studies. RESULTS: After constriction (30-50%) with endothelin, dilation to graded doses of Ach (10(-9)-10(-4) M) was observed in vessels dissected from the stricture and the adjacent normal calibre area. Ach dilation was reduced in vessels from "web" (mean diameter 7 (2)%; n = 3, p < 0.01) compared with the adjacent unaffected bowel (mean diameter 85 (5)%). Dihydroethidine and dichlorofluorescein diacetate intravital staining demonstrated increased reactive oxygen species production in microvessels from "web" compared with adjacent normal calibre bowel. Histology from the strictured bowel demonstrated narrowing of the arterial lumen due to intimal and muscularis propria fibrosis, with endothelial preservation. CONCLUSIONS: External radiation is associated with acquired microvascular endothelial dysfunction and "web" formation in the small bowel.

Extreme thyroid hormone resistance in a patient with a novel truncated TR mutant.

Resistance to thyroid hormone (RTH) is a syndrome in which patients have elevated thyroid hormone (TH) levels and decreased sensitivity to its action. We describe a child with extreme RTH and a severe phenotype. A 22-month-old female presented to the NIH with goiter, growth retardation, short stature, and deafness. Additionally, the patient had hypotonia, mental retardation, visual impairment, and a history of seizures. Brain magnetic resonance imaging showed evidence of demyelination and bilateral ventricular enlargement. The patient had markedly elevated free T3 and free T4 levels of more than 2000 pg/dl (normal, 230-420 pg/dl) and more than 64 pmol/liter (normal, 10.3-20.6 pmol/liter), respectively, and TSH of 6.88 mU/liter (normal, 0.6-6.3 mU/liter). These are the highest TH levels reported for a heterozygous RTH patient. A T3 stimulation test confirmed the diagnosis of RTH in the pituitary and peripheral tissues. Molecular analyses of the patient's genomic DNA by PCR identified a single base deletion in exon 10 of her TRbeta gene that resulted in a frameshift and early stop codon. This, in turn, encoded a truncated receptor that lacked the last 20 amino acids. Cotransfection studies showed that the mutant TR was transcriptionally inactive even in the presence of 10(-6) M T3 and had strong dominant negative activity over the wild-type receptor. It is likely that the severely defective TRbeta mutant contributed to the extreme RTH phenotype and resistance in our patient.

The timing of reduction and stabilisation of the acute, unstable, slipped upper femoral epiphysis.

We reviewed the management of 100 cases of slipped upper femoral epiphysis treated over a period of 26 years. A total of 14 slips was identified as unstable on admission. These underwent reduction and stabilisation within 24 hours of the onset of severe symptoms. Of the 86 stable slips four progressed to avascular necrosis (AVN), which was not seen in the unstable slips. The literature on slipped upper femoral epiphysis suggests that the acute unstable slip is at higher risk of developing AVN. We recommend reduction and stabilisation of unstable slips within 24 hours of the onset of symptoms in order to reduce the risk of AVN.

Identification and characterization of SNX15, a novel sorting nexin involved in protein trafficking.

Sorting nexins are a family of phox homology domain containing proteins that are homologous to yeast proteins involved in protein trafficking. We have identified a novel 342-amino acid residue sorting nexin, SNX15, and a 252-amino acid splice variant, SNX15A. Unlike many sorting nexins, a SNX15 ortholog has not been identified in yeast or Caenorhabditis elegans. By Northern blot analysis, SNX15 mRNA is widely expressed. Although predicted to be a soluble protein, both endogenous and overexpressed SNX15 are found on membranes and in the cytosol. The phox homology domain of SNX15 is required for its membrane association and for association with the platelet-derived growth factor receptor. We did not detect association of SNX15 with receptors for epidermal growth factor or insulin. However, overexpression of SNX15 led to a decrease in the processing of insulin and hepatocyte growth factor receptors to their mature subunits. Immunofluorescence studies showed that SNX15 overexpression resulted in mislocalization of furin, the endoprotease responsible for cleavage of insulin and hepatocyte growth factor receptors. Based on our data and the existing findings with yeast orthologs of other sorting nexins, we propose that overexpression of SNX15 disrupts the normal trafficking of proteins from the plasma membrane to recycling endosomes or the trans-Golgi network.

Activation of serum- and glucocorticoid-induced protein kinase (Sgk) by cyclic AMP and insulin.

Sgk (serum- and glucocorticoid-induced protein kinase) is a serine/threonine-specific protein kinase that is transcriptionally regulated by serum, glucorticoids, and mineralocorticoids. Sgk regulates the amiloride-sensitive sodium channel in kidney principal cells. Insulin and insulin-like growth factor-1 stimulate activity of Sgk by a mechanism mediated by phosphoinositide-dependent kinases (PDK)-1 and -2. In this study, we demonstrate that incubation of transfected cells with 8-(4-chlorophenylthio)-cAMP (8CPT-cAMP; 0.2 mm) led to a 2-fold activation of recombinant Sgk expressed in COS7 cells. Furthermore, the combination of insulin plus 8CPT-cAMP elicited a larger response than either agent alone. The effect of insulin was inhibited by wortmannin (100 nm), but not by the cyclic AMP-dependent protein kinase (PKA) inhibitor, H89 (10 microm). As expected, the effect of 8CPT-cAMP was completely blocked by H89. Surprisingly, the effect of 8CPT-cAMP was also inhibited by wortmannin, suggesting that phosphorylation of Sgk by PDK-1 and/or -2 is required for activation by 8CPT-cAMP. Mutational analysis led to similar conclusions. The Thr(369) --> Ala mutant, lacking the PKA phosphorylation site, was activated by insulin but not 8CPT-cAMP. In contrast, the Ser(422) --> Ala mutant, lacking a PDK-2 phosphorylation site, was inactive and resistant to activation by either insulin or 8CPT-cAMP. In summary, Sgk is subject to complex regulatory mechanisms. In addition to regulation at the level of gene expression, the enzymatic activity of Sgk is regulated by multiple protein kinases, including PKA, PDK-1, and PDK-2. Cross-talk among these signaling pathways may play an important role in the pathogenesis of the hypertension associated with hyperinsulinemia, obesity, and insulin resistance.

Physical and chemical evidence remaining after the explosion of large improvised bombs. Part 1: firings of ammonium nitrate/sugar and urea nitrate.

Recent criminal acts in the United Kingdom, United States and other countries have demonstrated the dangers to public safety from the criminal use of improvised explosives on a large scale. Four sets of trials were carried out over four years, partly in collaboration with the United States Federal Bureau of Investigation, involving the firing of large bombs, mostly fertilizer based. The principal objectives of the firings were to measure the physical effects of the explosions upon objects representative of those that would be found at a real bomb scene and to recover any chemical traces deposited on these objects. The results are intended for use as an aid in determining the approximate size and type of an explosive employed in a terrorist attack. This paper describes the background behind the trials, the procedures for preparation of witness materials and charges, and the collection and analysis of physical and chemical evidence.

Overexpression of a novel sorting nexin, SNX15, affects endosome morphology and protein trafficking.

Sorting nexin (SNX) 15 is a novel member of the SNX family of proteins. Although the functions of most SNXs have not yet been determined, several family members (e.g., SNX1, SNX2, SNX3, and SNX8) are orthologs of yeast proteins involved in protein trafficking. Overexpression of myc-tagged SNX15 in COS-7 cells altered the morphology of several endosomal compartments. In transient transfection experiments, myc-SNX15 was first seen in small punctate spots and small ring structures. Later, myc-SNX15 was found in larger rings. Finally, myc-SNX15 was observed in large, amorphous membrane-limited structures. These structures contained proteins from lysosomes, late endosomes, early endosomes, and the trans-Golgi network. However, the morphology of the endoplasmic reticulum and Golgi was not affected by overexpression of myc-SNX15. In myc-SNX15-overexpressing cells, the endocytosis of transferrin was severely inhibited and endocytosis of tac-trans-Golgi network (TGN) 38 and tac-furin was slowed. In addition, the recycling of internalized tac-TGN38 and tac-furin was also inhibited. Both the morphological and biochemical data indicate that SNX15 plays a crucial role in trafficking through the endocytic pathway. This is the first demonstration that a mammalian SNX protein is involved in protein trafficking.

Novel technique for the combined recovery, extraction and clean-up of forensic organic and inorganic trace explosives samples.

This paper describes a simple processing and analysis scheme for explosives trace swab samples which deals both with organic and inorganic materials. Swabs, wetted with ethanol or ethanol/water mixture, were extracted with ethanol/water mixture. The extract was passed directly through a simple column containing an acrylonitrile/styrene copolymer adsorbent. The adsorbent retained common organic explosives, which were recovered with an efficiency of 30-50% as a relatively clean ethyl acetate solution. The concentrated ethyl acetate eluate was analysed using gas chromatography with chemiluminescence or mass spectrometric detection. The unretained inorganic ions and sugars, which were recovered with generally high efficiency as an ethanol/water solution, could be directly analysed using ion chromatography and/or capillary electrophoresis. Minor difficulties encountered in the analysis of sugars, fluoride and phosphate were examined.