Lack of impact of radiologic septal measurements upon patient symptoms and performance of septoplasty during endoscopic sinus surgery.

BACKGROUND: Recent literature suggests that concurrent septoplasty during endoscopic sinus surgery (ESS) improves patient outcomes, however, the underlying indications for performing concurrent septoplasty are unknown. The objective of this study was to investigate the relationship between objective radiologic measures of nasal septal deviation with preoperative patient symptomatology and measures of CRS disease severity. We also sought to understand the association of objective radiologic measurements with surgeon performance of concurrent septoplasty during ESS. METHODOLOGY: Seventy-four patients with CRS undergoing ESS were prospectively enrolled. Angles of septal deviation, intranasal areas and volumes were assessed on preoperative computed tomography (CT) scans and correlated with a robust battery of patient reported outcomes measures (PROMs), objective measures of CRS severity including olfaction scores, radiologic and endoscopic staging, and performance of septoplasty. RESULTS: Intranasal areas and volumes demonstrated only weak linear associations with patient-reported nasal congestion, however, angles of septal deviation alone did not correlate with congestion or any other PROM measure. Meanwhile, radiologic septal-related measurements did not correlate with objective measures of CRS disease severity or the performance of a concurrent septoplasty. CONCLUSIONS: Though prior studies demonstrate improved patient outcomes in the setting of concurrent septoplasty during ESS, this study failed to establish an association between preoperative radiologic septal-related measurements and patient symptomatology or surgeon decision to perform septoplasty. Although objective factors to identify patients most likely to benefit from concurrent septoplasty remain unidentified, the potential improvement of surgical recommendations and patient outcomes makes this an important area of continued investigation.

Investigation of the changes in hydrogen bonding accompanying the structural reorganization at 103†K in ammonium iodate.

Neutron powder diffraction has been used to observe the changes in hydrogen bonding that occur as a function of temperature in ND4IO3 and, thus, determine the structural features that occur during the low-temperature (103 K) phase transition. It is shown that in the deuterated material the change is not a phase change per se but rather a structural reorganization in which the hydrogen bonding becomes firmly locked in at the phase transition temperature, and stays in this configuration upon further cooling to 4.2 K. In addition, both the differences and changes in the axial thermal expansion coefficients in the region 100-290 K can be explained by the changes involving both the hydrogen bonding and the secondary I...O halogen bonds.

Small hepatocellular carcinomas displayed as a ring enhancing mass on arterial phase MRI in the chronically diseased liver.

AIM: To assess the prevalence of arterial phase (AP) ring-enhancing small hepatocellular carcinomas (HCC) on magnetic resonance imaging (MRI); detail additional MRI features that enable HCC diagnosis; and examine arterial timing as one possible cause of this appearance. MATERIALS AND METHODS: Patients undergoing HCC screening with both computed tomography (CT) and MRI within 40 days were examined at a single institution over a 7- year time period ending in 2013. From this initial group, small (1-3 cm), (AP) ring-enhancing HCC on MRI were studied. RESULTS: From the initial group of 64 patients with 129 HCC, 20 patients with 78 HCCs had a small diameter with 32 (41%) having an AP ring at MRI. The mean age of this latter group was 63-years old, with the average tumour diameter of 1.9 cm. Histopathology and secondary imaging supported a diagnosis of HCC in 20 (100%) patients and 31 (97%) lesions. Most of the ringed lesions had early AP timing. CONCLUSION: This study revealed a high prevalence (41%) of small, AP ring HCC with MRI. The use of other MRI sequences adds support in making the proper diagnosis with this appearance. Early AP timing may help create this pattern.

Human gestation-associated tissues express functional cytosolic nucleic acid sensing pattern recognition receptors.

The role of viral infections in adverse pregnancy outcomes has gained interest in recent years. Innate immune pattern recognition receptors (PRRs) and their signalling pathways, that yield a cytokine output in response to pathogenic stimuli, have been postulated to link infection at the maternal-fetal interface and adverse pregnancy outcomes. The objective of this study was to investigate the expression and functional response of nucleic acid ligand responsive Toll-like receptors (TLR-3, -7, -8 and -9), and retinoic acid-inducible gene 1 (RIG-I)-like receptors [RIG-I, melanoma differentiation-associated protein 5 (MDA5) and Laboratory of Genetics and Physiology 2(LGP2)] in human term gestation-associated tissues (placenta, choriodecidua and amnion) using an explant model. Immunohistochemistry revealed that these PRRs were expressed by the term placenta, choriodecidua and amnion. A statistically significant increase in interleukin (IL)-6 and/or IL-8 production in response to specific agonists for TLR-3 (Poly(I:C); low and high molecular weight), TLR-7 (imiquimod), TLR-8 (ssRNA40) and RIG-I/MDA5 (Poly(I:C)LyoVec) was observed; there was no response to a TLR-9 (ODN21798) agonist. A hierarchical clustering approach was used to compare the response of each tissue type to the ligands studied and revealed that the placenta and choriodecidua generate a more similar IL-8 response, while the choriodecidua and amnion generate a more similar IL-6 response to nucleic acid ligands. These findings demonstrate that responsiveness via TLR-3, TLR-7, TLR-8 and RIG-1/MDA5 is a broad feature of human term gestation-associated tissues with differential responses by tissue that might underpin adverse obstetric outcomes.

Bioenergetic analysis of human peripheral blood mononuclear cells.

Leucocytes respond rapidly to pathogenic and other insults, with responses ranging from cytokine production to migration and phagocytosis. These are bioenergetically expensive, and increased glycolytic flux provides adenosine triphosphate (ATP) rapidly to support these essential functions. However, much of this work is from animal studies. To understand more clearly the relative role of glycolysis and oxidative phosphorylation in human leucocytes, especially their utility in a translational research setting, we undertook a study of human peripheral blood mononuclear cells (MNCs) bioenergetics. Glycolysis was essential during lipopolysaccharide (LPS)-mediated interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-α production, as 2-deoxy-D-glucose decreased significantly the output of all three cytokines. After optimizing cell numbers and the concentrations of all activators and inhibitors, oxidative phosphorylation and glycolysis profiles of fresh and cryopreserved/resuscitated MNCs were determined to explore the utility of MNCs for determining the bioenergetics health profile in multiple clinical settings. While the LPS-induced cytokine response did not differ significantly between fresh and resuscitated cells from the same donors, cryopreservation/resuscitation significantly affected mainly some measures of oxidative phosphorylation, but also glycolysis. Bioenergetics analysis of human MNCs provides a quick, effective means to measure the bioenergetics health index of many individuals, but cryopreserved cells are not suitable for such an analysis. The translational utility of this approach was tested by comparing MNCs of pregnant and non-pregnant women to reveal increased bioenergetics health index with pregnancy but significantly reduced basal glycolysis and glycolytic capacity. More detailed analysis of discrete leucocyte populations would be required to understand the relative roles of glycolysis and oxidative phosphorylation during inflammation and other immune responses.

Hepatoselectivity and the evolution of insulin.

In spite of major developments in insulin production, purification, pharmaceutical formulation and methods of delivery, problems remain both in the day to day management of insulin-treated diabetes and with regard to its long-term complications. The risks of hypoglycaemia and weight gain are major concerns particularly for the patient, and the persistence of microvascular and premature macrovascular complications as the main causes of morbidity and mortality in both type 1 and type 2 diabetes is a constant reminder that our therapeutic and management strategies are inadequate. One clear and striking difference between currently available insulin treatments and normal physiology is the relative difference in exposure to insulin of the liver versus peripheral tissues. Hepatoselective insulin analogues have the potential to restore the normal hepatic to peripheral gradient in insulin action. Here, we discuss the possible therapeutic potential that such analogues may have over currently available insulin preparations. These benefits could include a lower risk of hypoglycaemia, less weight gain and a potential reduction in microvascular and macrovascular complications. We explore the evolution of insulin with hepatoselectivity in mind and possible strategies to create hepatoselective insulins.

The management of benign salivary disease: a case series.

There are many causes for benign salivary gland disease but the most common relate to inflammation and infection. This usually revolves around duct obstruction and a reduction in the normal salivary flow from the gland into the mouth. This leads to retention of saliva, proximal to the obstruction and ascending infection from the mouth, usually because of the decrease in salivary flow. The increase in tension behind the obstruction causes significant pain and swelling, along with the inevitable infection if the obstruction is not relieved. This paper discusses the various treatments available for benign salivary gland disease, the traditional methods of treatment through to the use of endoscopic techniques which are currently available, including a discussion about the use of sialoendoscopy.

Temporomandibular joint reconstruction with total alloplastic joint replacement.

This paper is a preliminary paper which presents the early findings of an ongoing prospective trial on the use of the TMJ Concepts and Biomet Lorenz total joint replacement systems for the reconstruction of the temporomandibular joint (TMJ). Total alloplastic replacement of the TMJ has become a viable option for many people who suffer from TMJ disease where surgical reconstruction is indicated. Degenerative joint diseases such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, TMJ ankylosis, malunited condylar fractures and tumours can be successfully treated using this technique. There are a number of TMJ prostheses available. Two of the joint replacement products, which have been found to be most reliable and have FDA approval in the United States, are the TMJ Concepts system and the Biomet Lorenz system, and for this reason they are being investigated in this study. This study presents the findings of seven patients with a total of 12 joint replacements using either the TMJ Concepts system or the Biomet Lorenz joint system. Two patients (3 joints) had the TMJ Concepts system and five patients (9 joints) had the Biomet Lorenz system. Although still early, the results were generally pleasing, with the longest replacement having been in position for three years and the most recent six months. The average postoperative mouth opening was 29.7 mm (range 25-35 mm) with an average pain score of 1.7 (range 0-3, minimum score of 0 and maximum 10). Complications were minimal and related to sensory disturbance to the lip in one patient and joint dislocation in two patients.

Repair of the trigeminal nerve: a review.

Nerve surgery in the maxillofacial region is confined to the trigeminal and facial nerves and their branches. The trigeminal nerve can be damaged as a result of trauma, local anaesthesia, tumour removal and implant placement but the most common cause relates to the removal of teeth, particularly the inferior alveolar and lingual nerves following third molar surgery. The timing of nerve repair is controversial but it is generally accepted that primary repair at the time of injury is the best time to repair the nerve but it is often a closed injury and the operator does not know the nerve is injured until after the operation. Early secondary repair at about three months after injury is the most accepted time frame for repair. However, it is also thought that a reasonable result can be obtained at a later time. It is also generally accepted that the best results will be obtained with a direct anastamosis of the two ends of the nerve to be repaired. However, if there is a gap between the two ends, a nerve graft will be required to bridge the gap as the two ends of the nerve will not be approximated without tension and a passive repair is important for the regenerating axons to grow down the appropriate perineural tubes. Various materials have been used for grafting and include autologous grafts, such as the sural and greater auricular nerves, vein grafts, which act as a conduit for the axons to grow down, and allografts such as Neurotube, which is made of polyglycolic acid (PGA) and will resorb over a period of time.

The use of vein grafts in the repair of the inferior alveolar nerve following surgery.

Damage to the branches of the trigeminal nerve can occur as a result of a variety of causes. The most common damage to all divisions of this nerve occurs as a result of facial trauma. Unfortunately, iatrogenic damage to the inferior alveolar branch of the mandibular division of the trigeminal nerve is common because of its anatomical position within the mandible and its closeness to the teeth, particularly the third molar. It has been reported there is an incidence of approximately 0.5% of permanent damage to the inferior alveolar nerve following third molar removal. Extraction of other teeth within the mandible carries a lower incidence of permanent damage. However, damage can still occur in the premolar area, where the nerve exits the mandible via the mental foramen. Dental implants are a relatively new but increasing cause of damage to this nerve, particularly if the preoperative planning is inadequate. CT scanning is important for planning the placement of implants if this damage is to be reduced. Primary repair of the damaged nerve will offer the best chance of recovery. However, if there is a gap, and the nerve ends cannot be approximated without tension, a graft is required. Traditionally, nerve grafts have been used for this purpose but other conduits have also been used, including vein grafts. This article demonstrates the use of vein grafts in the reconstruction of the inferior dental branch of the mandibular division of the trigeminal nerve following injury, in this case due to difficulty in third molar removal, following sagittal split osteotomy and during the removal of a benign tumour from the mandible. In the five cases presented, this technique has demonstrated good success, with an acceptable return of function occurring in most patients.

Metabolic effects of intensive insulin therapy in critically ill patients.

Our aim was to investigate the effects of glycemic control and insulin concentration on lipolysis, glucose, and protein metabolism in critically ill medical patients. For our methods, the patients were studied twice. In study 1, blood glucose (BG) concentrations were maintained between 7 and 9 mmol/l with intravenous insulin. After study 1, patients entered one of four protocols for 48 h until study 2: low-insulin high-glucose (LIHG; variable insulin, BG of 7-9 mmol/l), low-insulin low-glucose (LILG; variable insulin of BG 4-6 mmol/l), high-insulin high-glucose [HIHG; insulin (2.0 mU . kg(-1).min(-1) plus insulin requirement from study 1), BG of 7-9 mmol/l], or high-insulin low-glucose [HILG; insulin (2.0 mU.kg(-1).min(-1) plus insulin requirement from study 1), BG of 4-6 mmol/l]. Age-matched healthy control subjects received two-step euglycemic hyperinsulinemic clamps achieving insulin levels similar to the LI and HI groups. In our results, whole body proteolysis was higher in patients in study 1 (P < 0.006) compared with control subjects at comparable insulin concentrations and was reduced with LI (P < 0.01) and HI (P = 0.001) in control subjects but not in patients. Endogenous glucose production rate (R(a)), glucose disposal, and lipolysis were not different in all patients in study 1 compared with control subjects at comparable insulin concentrations. Glucose R(a) and lipolysis did not change in any of the study 2 patient groups. HI increased glucose disposal in the patients (HIHG, P = 0.001; HILG, P = 0.07 vs. study 1), but this was less than in controls receiving HI (P < 0.03). In conclusion, low-dose intravenous insulin administered to maintain BG between 7-9 mmol/l is sufficient to limit lipolysis and endogenous glucose R(a) and increase glucose R(d). Neither hyperinsulinemia nor normoglycemia had any protein-sparing effect.

Differential effects of insulin detemir and neutral protamine Hagedorn (NPH) insulin on hepatic glucose production and peripheral glucose uptake during hypoglycaemia in type 1 diabetes.

AIMS/HYPOTHESIS: We compared the symptoms of hypoglycaemia induced by insulin detemir (NN304) (B29Lys(epsilon-tetradecanoyl),desB30 human insulin) and equally effective doses of neutral protamine Hagedorn (NPH) insulin in relation to possible differential effects on hepatic glucose production and peripheral glucose uptake. METHODS: After overnight intravenous infusion of soluble human insulin 18 participants with type 1 diabetes received subcutaneous injections of NPH insulin or insulin detemir (0.5 U/kg body weight) on separate occasions in random order. During the ensuing gradual development of hypoglycaemia cognitive function and levels of counter-regulatory hormones were measured and rates of endogenous glucose production and peripheral glucose uptake continuously evaluated using a primed constant infusion of [6,6-(2)H(2)]glucose. The study was terminated when plasma glucose concentration had fallen to 2.4 mmol/l or had reached a minimum at a higher concentration. RESULTS: During the development of hypoglycaemia no difference between the two insulin preparations was observed in symptoms or hormonal responses. Significant differences were seen in rates of glucose flux. At and below plasma glucose concentrations of 3.5 mmol/l suppression of endogenous glucose production was greater with insulin detemir than with NPH insulin, whereas stimulation of peripheral glucose uptake was greater with NPH insulin than with insulin detemir. CONCLUSIONS/INTERPRETATION: In participants with type 1 diabetes subcutaneously injected insulin detemir exhibits relative hepatoselectivity compared with NPH insulin, but symptoms of hypoglycaemia and hormonal counter-regulation are similar. TRIAL REGISTRATION: ClinicalTrials.gov NCT00760448.

Proactive integrated care improves quality of life in patients with COPD.

Self-management strategies improve a variety of health-related outcomes for patients with chronic obstructive pulmonary disease (COPD). These strategies, however, are primarily designed to improve chronic disease management and have not focused on early detection and early treatment of exacerbations. In COPD, the majority of exacerbations go unreported and treatment is frequently delayed, resulting in worsened outcomes. Therefore, a randomised clinical trial was designed to determine whether integration of self-management education with proactive remote disease monitoring would improve health-related outcomes. A total of 40 Global Initiative for Chronic Obstructive Lung Disease stage 3 or 4 COPD patients were randomised to receive proactive integrated care (PIC) or usual care (UC) over a 3-month period. The primary and secondary outcomes were change in quality of life, measured by the St George's Respiratory Questionnaire (SGRQ), and change in healthcare costs. PIC dramatically improved SGRQ by 10.3 units, compared to 0.6 units in the UC group. Healthcare costs declined in the PIC group by US$1,401, compared with an increase of US$1,709 in the UC group, but this was not statistically significant. PIC uncovered nine exacerbations, seven of which were unreported. Therefore, proactive integrated care has the potential to improve outcomes in chronic obstructive pulmonary disease patients through effects of self-management, as well as early detection and treatment of exacerbations.

Poor maternal nutrition followed by accelerated postnatal growth leads to telomere shortening and increased markers of cell senescence in rat islets.

Low birth weight (LBW) followed by accelerated postnatal growth is associated with increased risk of developing age-associated diseases such as type 2 diabetes. Gestational protein restriction in rats causes LBW, beta-cell dysfunction, and reduced longevity. These effects may be mediated by accelerated cellular aging. This study tested the hypothesis that LBW followed by rapid postnatal catch-up growth leads to islet telomere shortening through alterations in antioxidant defense capacity, stress/senescence marker proteins, and DNA repair mechanisms at the gene expression level. We used our rat model of gestational protein restriction (recuperated offspring) and control offspring. Southern blotting revealed shorter (P<0.001) islet telomeres in recuperated animals compared to controls. This was associated with increased expression of peroxiredoxin 1 (P<0.05), peroxiredoxin 3 (P<0.01), and heme oxygenase-1 (HO-1) (P<0.05), which are up-regulated under stress conditions. MnSOD expression was significantly (P<0.05) decreased in recuperated offspring, suggesting partial impairment of mitochondrial antioxidant defenses. Markers of cellular senescence p21 and p16 were also increased (P<0.01 and P<0.05, respectively) in the recuperated group. We conclude that maternal diet influences expression of markers of cellular stress and telomere length in pancreatic islets. This may provide a mechanistic link between early nutrition and growth and type 2 diabetes.

Chk1 deficiency in the mouse small intestine results in p53-independent crypt death and subsequent intestinal compensation.

Chk1 is a serine/threonine protein kinase that is activated by a wide range of DNA-damaging agents to slow the cell cycle during S phase and G2/M. Abrogation of these cell-cycle checkpoints using Chk1 inhibitors results in hypersensitivity to DNA-damaging agents in vitro and may provide a potential therapeutic tool to sensitize tumour cells in vivo. We have generated a Cre-Lox-based mouse model in which Chkl can be inducibly deleted from somatic epithelial cells in the adult mouse small intestine and liver. Loss of Chk1 in the liver is tolerated with no apparent phenotype. In contrast, the loss of Chk1 within the small intestine results in immediate DNA damage and high levels of p53-independent apoptosis leading to crypt death. However, the intestine is able to compensate for this death by undergoing complete re-population with Chk1-proficient cells. These data therefore show that Chk1 deficiency is cell lethal, but the intestine can tolerate such lethality at the organ level.

Clinical effectiveness of a rehabilitation program integrating exercise, self-management, and active coping strategies for chronic knee pain: a cluster randomized trial.

OBJECTIVE: Chronic knee pain is a major cause of disability and health care expenditure, but there are concerns about efficacy, cost, and side effects associated with usual primary care. Conservative rehabilitation may offer a safe, effective, affordable alternative. We compared the effectiveness of a rehabilitation program integrating exercise, self-management, and active coping strategies (Enabling Self-management and Coping with Arthritic Knee Pain through Exercise [ESCAPE-knee pain]) with usual primary care in improving functioning in persons with chronic knee pain. METHODS: We conducted a single-blind, pragmatic, cluster randomized controlled trial. Participants age >/=50 years, reporting knee pain for >6 months, were recruited from 54 inner-city primary care practices. Primary care practices were randomized to continued usual primary care (i.e., whatever intervention a participant's primary care physician deemed appropriate), usual primary care plus the rehabilitation program delivered to individual participants, or usual primary care plus the rehabilitation program delivered to groups of 8 participants. The primary outcome was self-reported functioning (Western Ontario and McMaster Universities Osteoarthritis Index physical functioning [WOMAC-func]) 6 months after completing rehabilitation. RESULTS: A total of 418 participants were recruited; 76 (18%) withdrew, only 5 (1%) due to adverse events. Rehabilitated participants had better functioning than participants continuing usual primary care (-3.33 difference in WOMAC-func score; 95% confidence interval [95% CI] -5.88, -0.78; P = 0.01). Improvements were similar whether participants received individual rehabilitation (-3.53; 95% CI -6.52, -0.55) or group rehabilitation (-3.16; 95% CI -6.55, -0.12). CONCLUSION: ESCAPE-knee pain provides a safe, relatively brief intervention for chronic knee pain that is equally effective whether delivered to individuals or groups of participants.

Economic evaluation of a rehabilitation program integrating exercise, self-management, and active coping strategies for chronic knee pain.

OBJECTIVE: To conduct an economic evaluation of the Enabling Self-Management and Coping with Arthritic Knee Pain through Exercise (ESCAPE-knee pain) program. METHODS: Alongside a clinical trial, we estimated the costs of usual primary care and participation in ESCAPE-knee pain delivered to individuals (Indiv-rehab) or groups of 8 participants (Grp-rehab). Information on resource use and informal care received was collected during face-to-face interviews. Cost-effectiveness and cost-utility were assessed from between-group differences in costs, function (primary clinical outcome), and quality-adjusted life years (QALYs). Cost-effectiveness acceptability curves were constructed to represent uncertainty around cost-effectiveness. RESULTS: Rehabilitation (regardless of whether Indiv-rehab or Grp-rehab) cost 224 pounds (95% confidence interval [95% CI] 184 pounds, 262 pounds) more per person than usual primary care. The probability of rehabilitation being more cost-effective than usual primary care was 90% if decision makers were willing to pay 1,900 pounds for improvements in functioning. Indiv-rehab cost 314 pounds/person and Grp-rehab 125 pounds/person. Indiv-rehab cost 189 pounds (95% CI 168 pounds, 208 pounds) more per person than Grp-rehab. The probability of Indiv-rehab being more cost-effective than Grp-rehab increased as willingness to pay (WTP) increased, reaching 50% probability at WTP 5,500 pounds. The lack of differences in QALYs across the arms led to lower probabilities of cost-effectiveness based on this outcome. CONCLUSION: Provision of ESCAPE-knee pain had small cost implications, but it was more likely to be cost-effective in improving function than usual primary care. Group rehabilitation reduces costs without compromising clinical effectiveness, increasing probability of cost-effectiveness.

Use of chaperones by obstetricians and gynaecologists: a cross-sectional survey.

The Royal College of Obstetrics and Gynaecologists (RCOG) recommends that a chaperone should be offered to every patient for an intimate examination. The use of chaperones has risen in primary care, but little is known about the practice of obstetricians and gynaecologists. Our aim was to determine the current attitudes and practices of Fellows and Members of the RCOG regarding chaperones during intimate examinations, both in public and private practice. A total of 800 Fellows and Members were asked to complete a 45-item questionnaire on their use of chaperones and how important a range of issues were in deciding whether or not to offer and provide a chaperone. A total of 449 questionnaires were returned. In summary, 23% of respondents never or occasionally offered a chaperone; 24% of NHS units have no agreed NHS policy and a further 16% did not know if a policy existed. In NHS practice, 77% used a chaperone with only 62% of women using a chaperone. Of those who did private practice, 34% never or occasionally offered a chaperone with 31% actually using a chaperone. In conclusion, obstetricians and gynaecologists use chaperones more than general practitioners but there is significant room for improvement. Chaperones are used more in NHS than private practice.