Utilization of the validated Psoriasis Epidemiology Screening Tool to identify signs and symptoms of psoriatic arthritis among those with psoriasis: a cross-sectional analysis from the US-based Corrona Psoriasis Registry.

BACKGROUND: Despite increasing awareness of the disease, rates of undiagnosed psoriatic arthritis (PsA) are high in patients with psoriasis (PsO). The validated Psoriasis Epidemiology Screening Tool (PEST) is a five-item questionnaire developed to help identify PsA at an early stage. OBJECTIVES: To assess the risk of possible undiagnosed PsA among patients with PsO and characterize patients based on PEST scores. METHODS: This study included all patients enrolled in the Corrona PsO Registry with data on all five PEST questions. Demographics, clinical characteristics and patient-reported outcomes were compared in Corrona PsO Registry patients with PEST scores ≥3 and <3 using t-tests for continuous variables and chi-squared tests for categorical variables; scores ≥3 may indicate PsA. RESULTS: Of 1516 patients with PsO, 904 did not have dermatologist-reported PsA; 112 of these 904 patients (12.4%) scored ≥3 and were significantly older, female, less likely to be working, and had higher BMI than patients with scores <3. They also had significantly longer PsO duration, were more likely to have nail PsO and had worse health status, pain, fatigue, Dermatology Life Quality Index and activity impairment. CONCLUSIONS: Improved PsA screening is needed in patients with PsO because the validated PEST identified over one-tenth of registry patients who were not noted to have PsA as having scores ≥3, who could have had undiagnosed PsA. Appropriate, earlier care is important because these patients were more likely to have nail PsO, worse health-related quality of life and worse activity impairment.

The effect of bolus volume on laryngeal closure and UES opening in swallowing: Kinematic analysis using 320-row area detector CT study.

This study investigated the effects of three different volumes of honey-thick liquid on the temporal characteristics of swallowing. Twenty-six healthy subjects (15 males, 11 females) underwent 320-row area detector CT scan while swallowing 3, 10 and 20 mL of honey-thick liquid barium. Three-dimensional images were created at 10 images/s. Kinematic events involving six structures (velopharynx, hyoid bone, epiglottis, laryngeal vestibule (LV), true vocal cords (TVC), upper esophageal sphincter (UES)) and timing of bolus movement were timed using frame by frame analysis. The overall sequence of events did not differ across three volumes; however, increasing bolus volume significantly changed the onset and termination of events. The bolus head reached to pharynx and esophagus earlier and the duration of bolus passing through UES was significantly longer in 10 and 20 mL compared to 3 mL (P < .05). Consequently, the onset of UES opening was significantly earlier with increased volume (P < .05). LV and TVC closure occurred later in 20 mL compared to 3 mL (P < .05). These changes in motion of pharynx and larynx appeared to promote swallow safety by preventing aspiration, suggesting that anatomical structure movements adapt in response to bolus volume. Our findings also suggest that the pharyngeal swallow behaviours may be modified by afferents in the oral cavity. The three-dimensional visualization and quantitative measurements provided by 320-ADCT provide essential benchmarks for understanding swallowing, both normal and abnormal.

A questionnaire-based survey of perioperative blood conservation practice for revision hip arthroplasty in Scotland.

The aim of this study was to describe current blood conservation practice during revision hip surgery in Scotland and document practice variation. Revision hip surgery is associated with a high likelihood of blood transfusion. A decrease in the proportion of patients requiring blood transfusion has been documented, but the reasons for this are unclear. Various blood conservation practices are available to clinicians, but the extent to which these are used in Scottish hospitals is not known. A cross-sectional postal survey was sent to all consultant orthopaedic surgeons and consultant anaesthetists participating in revision hip surgery in Scottish hospitals. Responses were received from 92 of 120 (77%) surgeons, and 174 of 216 (81%) anaesthetists (62/92). A total of 62 of 92 (67%) surgeons and 78 of 174 (45%) anaesthetists surveyed participated in revision hip surgery. Blood conservation practice varied widely: 34 of 78 (44%) anaesthetists routinely assessed revision hip patients >or=1 week prior to surgery; 10 of 62 (16%) surgeons and 24 of 78 (31%) anaesthetists routinely used cell salvage; 7 of 78 (9%) anaesthetists and 2 of 62 (3%) surgeons routinely used tranexamic acid; and 45 of 62 (73%) surgeons use a transfusion protocol. A wide variation in the use of blood conservation strategies exists during revision hip surgery in Scotland.

Evaluation and treatment of swallowing impairments.

Swallowing disorders are common, especially in the elderly, and may cause dehydration, weight loss, aspiration pneumonia and airway obstruction. These disorders may affect the oral preparatory, oral propulsive, pharyngeal and/or esophageal phases of swallowing. Impaired swallowing, or dysphagia, may occur because of a wide variety of structural or functional conditions, including stroke, cancer, neurologic disease and gastroesophageal reflux disease. A thorough history and a careful physical examination are important in the diagnosis and treatment of swallowing disorders. The physical examination should include the neck, mouth, oropharynx and larynx, and a neurologic examination should also be performed. Supplemental studies are usually required. A videofluorographic swallowing study is particularly useful for identifying the pathophysiology of a swallowing disorder and for empirically testing therapeutic and compensatory techniques. Manometry and endoscopy may also be necessary. Disorders of oral and pharyngeal swallowing are usually amenable to rehabilitative measures, which may include dietary modification and training in specific swallowing techniques. Surgery is rarely indicated. In patients with severe disorders, it may be necessary to bypass the oral cavity and pharynx entirely and provide enteral or parenteral nutrition.

Developmental variation in stem-cell markers from human fetal liver and umbilical cord blood leukocytes.

Fetal tissues containing haematopoietic stem cells (HSC) are of potential value for allogeneic transplantation and gene therapy. Flow cytometry was used to investigate CD34+ cells from human fetal livers and umbilical cord (placental) blood (UCB). CD34+ cells, expressed as a proportion of CD45-positive leukocytes, were much more abundant in fetal livers (mean 38%) than in UCB (mean 0.3%), but fetal liver cells had lower proportions of CD34+HLA-DR+ and CD34+ CD38+ subsets. In fetal liver, there was a strong and highly significant inverse correlation between CD34+ cells (as a proportion of total leukocytes) and gestational age; no such relationship was found for subsets of CD34+ cells coexpressing CD38 or CDw90 (Thy-1), but CD34+HLA-DR+ cells were less abundant in first-compared to second-trimester livers. In UCB, a trend towards decreasing CD34+ cells (as a proportion of total leukocytes) with increasing gestational age in late pregnancy was also observed. The composition of fetal leukocytes changes during development, and therefore the timing of fetal HSC harvesting could be of relevance to transplantation outcome.

Multidrug resistance gene (MDR 1) expression in neuro-axial tumours of children and young adults.

Drug resistance in many cancers outside the CNS has been associated with over-expression of the multidrug resistance gene (MDR1), which codes for the transmembrane efflux pump P-glycoprotein (Pgp). To determine whether tumours of the neuroaxis over-express MDR1 and to identify the site of Pgp expression we examined 50 tumour specimens from 46 children and young adults using immunocytochemistry. Pgp was not expressed by any neoplastic cells, but was detected in the endothelium of tumour blood vessels in 35 of the 50 samples (70%). 11/35 (31%) were Pgp positive in the majority of vessels, 11/35 (31%) in a proportion, but < 50% of vessels, and 13/35 (37%) in one or two vessels. Pgp was also detected in surrounding normal brain capillaries. MDR1 may play a role in the chemoresistance of neuro-axial tumours either by its expression in the normal blood-brain barrier or by forming a blood-tumour barrier. The proportion of vessels expressing Pgp may determine the degree of resistance.

Twelve month comparison of salmeterol and salbutamol as dry powder formulations in asthmatic patients. European Study Group.

BACKGROUND: Salmeterol is a potent selective beta 2 agonist that has been shown to have a duration of action in excess of 12 hours. In this study salmeterol and salbutamol were compared over a three month period with a further extension of nine months. METHODS: Three hundred and eighty eight patients with mild to moderate reversible airways obstruction (forced expiratory volume in one second (FEV1) > 50% predicted) were randomised to receive salmeterol (50 micrograms) twice daily or salbutamol (400 micrograms) four times daily, both by dry powder, in a double blind parallel group study. During the first three months detailed assessment of efficacy was made with recording of morning and evening peak expiratory flow rates (PEF), asthma symptoms, and bronchodilator use when necessary for the relief of symptoms. Patients continued in the study for a further nine months with the salbutamol dose reduced to 400 micrograms twice daily. Lung function was measured at the clinic and safety data were collected during this period. RESULTS: Salmeterol produced a significantly higher mean morning PEF (mean difference compared with salbutamol 21 (95% CI 12-31) l/min), and a significant reduction in mean diurnal variation in PEF (from 30 l/min at baseline to 11 34 l/min at baseline to 32 l/min during salbutamol treatment). Salmeterol also reduced day and night symptoms and use of rescue bronchodilator. FEV1 increased with both salmeterol and salbutamol treatment over the 12 month treatment period. For both treatments the number of patients reporting exacerbations of asthma and the frequency of these exacerbations remained constant during the study. Thirty six patients in the salmeterol and 49 in the salbutamol group withdrew during the 12 months of the study. CONCLUSIONS: In this study salmeterol (50 micrograms twice daily) was more effective than salbutamol (400 micrograms four times daily) in the control of asthma over three months, and more effective than salbutamol (400 micrograms twice daily) over a further nine months. Neither salmeterol nor salbutamol was associated with any worsening of control of asthma.

Effects of pollution on swallowing: how little we know.

Swallowing is an essential function of the upper alimentary tract. It is highly complex, requiring precise coordination of numerous nerves and muscles of the oral cavity, pharynx, larynx, and esophagus. Swallowing is integrated with other physiologic functions, including mastication and respiration. Impairments of swallowing may result from many different structural or physiologic disorders. Little is currently known about the direct effects of pollution on swallowing. Structures critical to swallowing, however, are vulnerable to damage by environmental hazards such as exposure to ionizing radiation or intake of toxins by ingestion or inhalation. The relationship of swallowing to environmental lung disease is an area of particular interest because impaired swallowing may result in aspiration of food particles into the lung, and because pollutants may hamper airway defense mechanisms. In this article, we discuss the possible impact of selected environmental agents on swallowing and suggest future directions for research.

A clinical trial of red-cell concentrate prepared from blood collected in half-strength citrate anticoagulant.

Earlier studies have indicated that plasma from blood donations drawn into half-strength citrate anticoagulant (0.5 CPD-A2) may give improved yields of factor VIII:C after fractionation. It has also been shown previously that cellular components from blood donations drawn into 0.5 CPD-A2 have satisfactory in-vitro and in-vivo properties. The present study examines the clinical use of red cell concentrate (RCC) from 0.5 CPD-A2 blood donations. Forty-nine patients who were undergoing elective orthopaedic surgery and who required blood transfusion received 0.5 CPD-A2 RCC. A transfused control group of 107 patients received standard CPD-A1 RCC for their transfusion requirements. Patients in the two transfused groups had similar haemoglobin responses to transfusion. All patients experienced a moderate pyrexia following the operation. Both study groups showed similar responses to serum lactate dehydrogenase levels in the 2 weeks following surgery, and in postoperative peripheral blood platelet counts. Serious postoperative complications arose in both groups. In the 0.5 CPD-A2 group two patients had pulmonary emboli (one fatal) and one patient had a non-fatal myocardial infarction. Three patients had pulmonary emboli in the CPD-A1 transfused group. These incidences of major adverse events were within the expected range of these complications in patients who were undergoing major joint replacement surgery and did not differ significantly between the study groups. This study indicates that red cell concentrate prepared in half-strength citrate anticoagulant is comparable to that prepared in CPD-A1 for patients undergoing orthopaedic surgery.

Microglial cells in human brain have phenotypic characteristics related to possible function as dendritic antigen presenting cells.

The resting human microglia have previously been shown to be cells of dendritic morphology expressing class II MHC antigens and macrophage specific antigens by immunocytochemical techniques. To examine the relationship between the microglia and the family of dendritic antigen presenting cells (APC), normal white matter from eight normal adults with no neurological disease at autopsy was examined by immunocytochemical techniques to localize antibodies to leukocyte common antigen (LCA), HLA-DR, CD1 (T6), CD4 (T4), and glial fibrillary acidic protein. In addition, enzyme histochemical staining for ATPase, non-specific esterase (NSE), and acid phosphatase (ACP) was performed. The normal microglia are ATPase +ve, NSE -ve, ACP -ve, HLA-DR +ve, LCA +ve, CD1 (T6) +ve and weakly CD4 (T4) +ve. This specialized phenotype closely resembles that of Langerhans cells and suggests that microglia are not simply quiescent phagocytes, but may have a primary role as microenvironmentally specialized APC. The finding of weak anti-CD4 (T4) immunoreactivity supports suggestions for a central role for this cell in infection of the central nervous system by human immunodeficiency virus type 1.

VIP and PHM and their role in nonadrenergic inhibitory responses in isolated human airways.

There is increasing evidence in many species that vasoactive intestinal peptide (VIP) may be a neurotransmitter in nonadrenergic inhibitory nerves. We have studied the effect of electrical field stimulation (EFS), exogenous VIP, and isoproterenol (Iso) on human airways in vitro. We have also studied a related peptide, peptide histidine methionine (PHM), which coexists with VIP in human airway nerves, and in separate experiments studied fragments of the VIP amino acid sequence (VIP1-10 and VIP16-28) for agonist and antagonist activity. Human airways were obtained at thoracotomy and studied in an organ bath. In bronchi EFS gave an inhibitory response that was unaltered by 10(-6) M propranolol but was blocked by tetrodotoxin, whereas in bronchioles there was little or no nonadrenergic inhibitory response. VIP, PHM, and Iso all caused dose-dependent relaxation of bronchi, VIP and PHM being approximately 50-fold more potent than Iso. VIP, but not Iso, mimicked the time course of nonadrenergic inhibitory nerve stimulation. In contrast bronchioles relaxed to Iso but not to VIP or PHM. Neither propranolol nor indomethacin altered the relaxant effects of VIP or PHM, suggesting a direct effect of these peptides on airway smooth muscle. Neither of the VIP fragments showed either agonist or antagonist activity. We conclude that VIP and PHM are more potent bronchodilators of human bronchi than Iso and that the association between the relaxant effects of these peptides and nonadrenergic inhibitory responses suggests that they may be possible neurotransmitters of nonadrenergic inhibitory nerves in human airways.

Effect of infused vasoactive intestinal peptide on airway function in normal subjects.

Vasoactive intestinal peptide, one of the putative neurotransmitters of non-adrenergic inhibitory nerves in human airways, is a potent relaxant of human airways in vitro. Previous in vivo studies of infused vasoactive intestinal peptide in asthmatic subjects have shown only a small bronchodilator effect, which may have been secondary to the cardiovascular effects of the peptide. The effect on airway function of infused vasoactive intestinal peptide was studied in normal subjects, who readily develop bronchodilation in response to a beta agonist. Separate experiments were designed to assess whether there is any synergy between this peptide and the beta agonist isoprenaline. Incremental doses of 1, 3, and 6 pmol/kg/min of vasoactive intestinal peptide were infused for 15 minutes. At 6 pmol/kg/min it caused a mean fall in systolic blood pressure from 108 to 88 mm Hg and a rise in heart rate from 71 to 95 beats/min. There was no significant change in specific airways conductance (sGaw) at any dose of vasoactive intestinal peptide. No significant changes were found with placebo. Isoprenaline (400 microgram) given by inhalation at the end of the infusion produced a mean increase in sGaw of 50%. Infused peptide caused no significant change in the cumulative dose-response curve for inhaled isoprenaline. The lack of effect of vasoactive intestinal peptide on airway responses in vivo may be due to rapid enzymatic breakdown of the peptide or to the fact that dosage has to be limited by the cardiovascular effects.

Phosphatidylinositol response to cholinergic agonists in airway smooth muscle: relationship to contraction and muscarinic receptor occupancy.

Hydrolysis of membrane phosphatidylinositol (PI) and polyphosphonoinositides (PPI) may be the coupling mechanism between receptor stimulation and the rise in intracellular calcium concentration that leads to smooth muscle contraction. In bovine tracheal smooth muscle, we correlated PI/PPI turnover, contraction and muscarinic receptor occupancy by carbamoylcholine (10(-9) to 10(-2) M). Inositol monophosphate formation after agonist stimulation, in the presence of lithium, provided a direct measurement of PI/PPI breakdown, and receptor occupancy was determined by [3H]quinuclidinyl benzylate binding. Carbamoylcholine caused a concentration-dependent contraction (EC50 = 7.4 X 10(-8) M), PI/PPI response (EC50 = 3.8 X 10(-5) M) and [3H]quinuclidinyl benzylate displacement (with high and low affinity binding sites have dissociation constants (Kd) of 3 X 10(-7) and 6 X 10(-4) M, respectively). This indicates the presence of spare receptors as maximal contraction is obtained when less than 20% of receptors are occupied. The concentration of carbamoylcholine inhibiting 50% of the PI/PPI response and 50% of maximal receptor occupancy (IC50) were similar for atropine (IC50 = 1 X 10(-9) and 5.3 X 10(-9) M, respectively), and for pirenzepine (IC50 = 3 X 10(-6) and 2.3 X 10(-6) M, respectively); the pA2 of the contraction was 8.3 +/- 0.12 for atropine and 7.2 +/- 0.08 for pirenzepine, indicating that M2 receptors may be largely predominant among bovine tracheal smooth muscle muscarinic receptors. Bovine tracheal smooth muscle may be a useful model to study the effects of other spasmogens, as it allows comparison of functional effects, PI breakdown and receptor occupancy in the same preparation.

A randomised multicentre single blind comparison of a cannabinoid anti-emetic (levonantradol) with chlorpromazine in patients receiving their first cytotoxic chemotherapy.

One hundred and eight patients selected to receive combinations of highly emetic cytotoxic chemotherapy for malignant disease were included in a study of anti-emetic therapy. The patients were randomly allocated to receive levonantradol (0.5, 0.75 or 1 mg) or chlorpromazine (25 mg) prior to receiving their first course of cytotoxic therapy. The appropriate anti-emetic was administered 2 hr prior to the start of chemotherapy, 2 hr after chemotherapy and subsequently at 4-hourly intervals for a further 8 hr. The extent of anorexia, nausea and vomiting along with other side-effects were assessed at regular intervals by physicians and nursing staff during the 24 hr following chemotherapy. In addition, a self-assessment questionnaire was completed by the patients. Levonantradol (0.5 mg) was superior to chlorpromazine (25 mg) as an anti-emetic. Both were reasonably well tolerated, although at this dose of levonantradol 22% of patients experienced dysphoric reactions. At higher doses of levonantradol the proportion of patients experiencing these reactions rose to 50%, but without a concomitant increase in antiemetic activity. Neither drug achieved satisfactory control of vomiting in patients receiving combinations containing cis-platinum. We conclude that levonantradol (0.5 mg) is a more effective anti-emetic than chlorpromazine (25 mg) in patients receiving cytotoxic chemotherapy. However, its use cannot be recommended due to its high incidence of unacceptable central nervous system side-effects.

The heterogeneity of the 5q--chromosome marker in refractory anemia.

A patient presenting with an unusual case of refactory anemia is described in whom acquired markers originating from chromosomes No. 5 and 8 are identified by G- and sequential C-banding. Comparison with various published illustrations of chromosome No. 5 deletions in this general broad category of disease raises the possibility that karyotypic misclassification in cases of absent or substandard banding (typical of bone marrow) may help to explain the considerable variation in size and morphology of the 5q--marker.