A431 cell variants lacking the blood group A antigen display increased high affinity epidermal growth factor-receptor number, protein-tyrosine kinase activity, and receptor turnover.

The epidermal growth factor receptor (EGF-R) of human A431 cells bears an antigenic determinant that is closely related to the human blood group A carbohydrate structure. Labeling studies with blood group A reactive anti-EGF-R monoclonal antibodies and various lectins revealed that A431 cultures are heterogeneous with respect to blood group A expression. We have isolated clonal variants of these cells that either express (A431A+ cells) or completely lack (A431A- cells) the blood group A specific N-acetyl-D-galactosamine (GalNAc) residue. We show that this difference is due to the absence of a UDP-GalNAc:Gal transferase activity in A431A- cells. Subsequently, we have compared EGF-R functioning in these cell lines. Scatchard analysis of EGF-binding shows that in A431A- cells 6.3% of the EGF-R belongs to a high affinity subclass (Kd = 0.4 nM) while in A431A+ this subclass represents only 3.2% of the total receptor pool. The elevated level of high affinity receptors in A431A- cells is accompanied by a parallel increase in receptor protein- tyrosine kinase activity. In membrane preparations of A431A- cells, receptor autophosphorylation as well as phosphorylation of a tyrosine-containing peptide substrate is 2-3-fold higher as compared with A431A+ cells. In intact A431A-cells, the difference in receptor activity is measured as a 2-3-fold elevated level of receptor phosphorylation and a 2-3-fold higher abundance of phosphotyrosine in total cellular protein in A431A- cells. In addition, [35S]methionine pulse-chase experiments showed a ligand-independent increase in turnover of EGF-R in A431A- cells: the receptor's half life in these cells is 10 h as compared with 17 h in A431A+ cells. Our results suggest a possible involvement of GalNAc residue(s) in determining EGF-R affinity, protein-tyrosine kinase activity and turnover in A431 cells. Furthermore, our results indicate that high affinity EGF-R are the biologically active species with respect to protein-tyrosine kinase activity.

Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acids.

BACKGROUND: Crohn's disease is a chronic inflammatory condition affecting the gastrointestinal tract. Polyunsaturated omega-3 fatty acids given orally may reduce the secretion of proinflammatory cytokines and hereby downregulate the inflammatory process. AIM: To assess the effects of enteral fatty acids, in the form of Impact Powder (Novartis, Switzerland), as adjuvant therapy to corticosteroid treatment on the proinflammatory and anti-inflammatory cytokine profiles in patients with active Crohn's disease. METHODS: The proinflammatory and anti-inflammatory cytokines were measured in plasma from 31 patients with active Crohn's disease. Patients were randomized for oral intake of omega-3 fatty acid (3-Impact Powder) or omega-6 fatty acids (6-Impact Powder). Clinical and biochemical markers of inflammation were studied at baseline and after 5 and 9 weeks. RESULTS: Within the 3-Impact Powder group, no significant changes in concentrations of interleukin-6, interferon-gamma, monocyte chemoattractant protein-1, interleukin-2, interleukin-5 and interleukin-10, whereas a significant differences in concentration of interleukin-1beta and interleukin-4 were observed during therapy. Within the 6-Impact Powder group a significant changes in concentrations of interleukin-1beta, interleukin-6, interferon-gamma, monocyte chemoattractant protein-1, interleukin-2, interleukin-4, interleukin-5 and interleukin-10 were observed. CONCLUSIONS: The 3-Impact Powder showed immunomodulatory properties and might inhibit an increase of proinflammatory cytokines in contrast to the 6-Impact Powder.

Effects of pure ethanol and alcopops on glucose, insulin, and the insulin-like growth factor system in healthy subjects.

INTRODUCTION: Alcohol induces disturbances in insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) levels. The aim of the present study was to compare pure ethanol and alcopop effects on total and free IGF-I, IGFBP-1, IGF-I:IGFBP-1 complex, insulin and plasma glucose levels in healthy subjects. METHODS: Five males and seven females (21-51 years) consumed pure ethanol and alcopops with identical alcohol content in a cross-over design after 6h fasting. Blood samples were obtained for determination of serum ethanol and plasma glucose at 0, 30, 60, 90, 120 and 180 min. Serum total and free IGF-I, IGFBP-1, IGF-I:IGFBP-1 complex, and insulin were measured at 0, 60 and 180 min. RESULTS: Area under the curve for serum ethanol concentration was significantly less following alcopop compared to pure ethanol (1124+/-201 vs. 1691+/-359 mmol/Lh, P<0.01). Serum insulin and glucose levels were unchanged by ethanol while alcopop intake was followed by a transient increase in glucose and insulin levels (P<0.05). Pure ethanol and alcopop reduced free IGF-I levels by the end of the study period (P=0.05). IGFBP-1 and the IGF-I:IGFBP-1 complex increased following ethanol intake (P<0.05) while only a small transient IGFBP-1 increase was observed following alcopop intake. No change in total IGF-I was observed. CONCLUSION: Both drinks resulted in reduced free IGF-I levels, however, only pure ethanol increased IGFBP-1 and the IGF-I:IGFBP-1 complex. Alcopop intake was associated with a transient increase in IGFBP-1 and unchanged IGF-I:IGFBP-1 complex levels probably due to marked changes in insulin and glucose levels.

Factors influencing cardiac auscultation proficiency in physician trainees.

INTRODUCTION: We assessed the accuracy of physician trainees in identifying different cardiac sounds and examined the factors influencing their cardiac auscultation proficiency. METHODS: A total of 106 physicians in the Family Medicine Training Programme were asked to identify 10 cardiac sounds played sequentially on the Littmann electronic stethoscope, which functioned as a surrogate patient. Their auscultation accuracy was scored numerically out of a maximum of 10. Demographical data of the physicians was collected prospectively. RESULTS: The mean (+/-SD) auscultation proficiency score of the study population was 4.0 +/- 1.7. Physicians who graduated in 1994 or earlier fared significantly poorer than those who obtained their Bachelor of Medicine and Bachelor of Surgery degrees between 1995 and 2000 (p-value equals 0.02). Auscultation proficiency was not related to current practice, previous years of primary care, cardiology, internal medicine or paediatric medicine postings, or cumulative years of postings. Normal heart sounds were most accurately identified. Prosthetic cardiac sounds were better identified than other extra-cardiac sounds while systolic murmurs were more accurately identified than diastolic murmurs. Tachycardia had the lowest identification rate. CONCLUSION: Our data suggest that cardiac auscultation skill declined with time, being significantly impaired eight years after graduation. We suggest that there is a need for retraining in the form of continuing medical education to address not only new knowledge and skills, but also basic skill competency.

The effect of protein supplementation on quality of life, physical function, and muscle strength in patients with chronic obstructive pulmonary disease.

BACKGROUND: The combination of protein supplementation with exercise is successful in increasing weight and energy intake, as well as exercise capacity and health-related quality of life in sarcopenic patients diagnosed with chronic obstructive disease (COPD). However, the potential benefit of protein supplementation for non-sarcopenic patients with COPD has yet not previously been examined. AIM: The aim of this trial was to evaluate the effect of protein supplementation on quality of life, physical function, muscle strength and biochemical blood markers in patients diagnosed with COPD undergoing nine weeks of pulmonary rehabilitation. DESIGN: A prospective, parallel group randomised clinical trial. SETTING: Patients referred from their general practitioners to the COPD rehabilitation outpatient programme at the local community rehabilitation centre. POPULATION: Patients (N.=53) with stable moderate to severe COPD diagnosed with COPD, 40 years or older and with a BMI<30. METHODS: The participants were assigned to one of two groups to receive either twice daily protein supplementation (9.3 g of protein/566.4 KJ) plus exercise or exercise only. Before and after nine weeks of rehabilitation, mental state was measured by means of St George Respiratory Questionnaire, physical performance was evaluated by shuttle walking test and maximal muscle strength test, and fasting blood samples were analyzed. RESULTS: Supplementing exercise with protein had no additional effect on any of the outcome measures. However, shuttle walk time, St George total score and subscore for impact improved as effect of time. CONCLUSION: This trial was unable to provide evidence for the effect of protein supplementation on quality of life, physical function, and muscle strength in non-sarcopenic patients with moderate to severe COPD. CLINICAL REHABILITATION IMPACT: The role of protein supplementation in COPD-rehabilitation should focus on identifying patients to receive supplement with protein and from those who will not benefit.

Clinically relevant heterotopic ossification after elbow fracture surgery: a risk factors study.

BACKGROUND: Heterotopic ossification (HO) is a common complication of elbow fracture surgery that can significantly impair function and range of motion (ROM). Whereas numerous studies have assessed HO after hip trauma or replacement surgery, few data have been reported on the prevalence and risk factors of HO after elbow fractures. HYPOTHESIS: Our objective was to investigate the prevalence and risk factors of clinically relevant HO after elbow fracture surgery under the hypothesis that the ability to identify high-risk patients would improve treatment tailoring and assist in meeting patient expectations. MATERIALS AND METHODS: We retrospectively included consecutive patients who had surgery for elbow injuries between January 2007 and December 2011. Patient demographics, operative details, and radiographs were reviewed. RESULTS: Of 124 elbows in 122 patients, 38 (30.6%) had HO and 26 (21%) clinically relevant HO. The prevalence of clinically relevant HO was highest in floating elbow injury, followed by combined olecranon and radial head fractures, types A and B distal humerus fractures, and terrible triad injury. By multiple logistic regression, factors that independently predicted clinically relevant HO were fracture-dislocation (OR, 4.87; 95%CI, 1.78-13.29; P=0.002) and longer time to surgery (P<0.05). Of the 26 patients with clinically relevant HO, 6 (23%) eventually required revision elbow surgery to improve ROM. DISCUSSION: HO of the elbow occurred in almost one-third of our patients with surgically treated elbow fractures. Fracture-dislocation of the elbow and longer time to surgery independently predicted HO responsible for ROM loss. Clinically relevant HO was associated with significant morbidity. LEVEL OF EVIDENCE: Level IV, retrospective study.

Evaluation of the ulcerogenic effect of potassium chloride by endoscopy and fecal blood loss.

In a blinded-observer crossover study, 16 volunteers ingested equimolar doses of three different potassium chloride preparations and placebo for nine days in a random order. The irritating effect on the mucosa was evaluated by means of upper gastrointestinal endoscopy and fecal blood loss, measured by reference to the amount of radioactivity in three 24-hour samples after previous injection of 51Cr-tagged autologous red cells. The microencapsulated KCl capsule preparation induced three ulcers, but the total endoscopic group score was not significantly higher than the score with placebo. The total endoscopic group score for the wax-matrix formulation was significantly higher than the score for placebo (P less than .05) and for a new microencapsulated KCl tablet preparation containing a potent disintegrant (P less than .10). We did not find any significant differences in mean fecal blood loss during the four different treatments. A correlation between endoscopic score and fecal blood loss was found in the placebo group (r = .54) and the microencapsulated KCl capsule preparation (r = .56) group.

The economics of an intensive education programme for asthmatic patients: a prospective controlled trial.

The costs and benefits of a planned patient education programme for patients with asthma were evaluated in a controlled trial. The patient education group received a planned patient education programme, performed by a physician, a pharmacist and a nurse over a 6-month period. Changes in the use of resources, productive output and in health status were measured for the patient education group and the control group. The total cost for planning, implementation and evaluation of the programme was 14074 British pounds sterling. The patient education group increased its contacts to general practitioners and the extra costs totalled 252 British pounds sterling. The increased costs of drugs used by the patient education group in the 6-month period was 2313 British pounds sterling compared with costs in the control group. The number of days lost through sickness decreased in the patient education group, corresponding to a 4528 British pounds sterling saving of otherwise lost earnings. The quality of life increased in the patient education group by 3.2 points on the Psychosomatic Discomfort Scale (2.9%). Health status increased by 38.9%. The study shows that the patient education programme has a positive clinical effect on the patient's quality of life and health status. The economic consequences of the implementation programme depend on the specific setup of the local healthcare system, where the programme is applied.

Antibiotic activity in serum following single and repeated oral administration of sodium fusidate in volunteers.

The pharmacokinetics of antibiotic activity were investigated in 10 healthy, female volunteers receiving a single oral dose of sodium fusidate (500 mg) followed after 48 h by repeated oral dosing of 250 mg b.i.d. for 5 consecutive days. By use of turbidimetry, drug-related antibiotic activity in serum was determined and expressed as fusidic acid equivalents. After a single dose and repeated dosing, the peak concentrations were (mean +/- SE): 30 +/- 3 micrograms/ml and 27 +/- 3 micrograms/ml, respectively (NS), and the trough concentration at steady state was 8.4 +/- 1.8 micrograms/ml. The experimental and predicted accumulation ratios were 2.1 +/- 0.1 versus 1.6 +/- 0.2, respectively (P < 0.16). By use of a model independent method, the terminal elimination half-lives were estimated to be 11 +/- 1 h and 13 +/- 2 h after a single dose and repeated doses, respectively (NS). The total clearances of antibiotic activity were 2.0 +/- 0.4 l/h after a single dose and 1.6 +/- 0.2 l/h after repeated doses (P < 0.11). Model dependent pharmacokinetic parameters were also obtained by fitting a two-compartment open model to the median serum concentrations which, with respect to half-life and clearance, gave values close to those observed by use of the model independent approach. Safety-wise, biochemical parameters were within the normal range. However, a statistically significant increase in ASAT and a decrease in leucocytes were observed. The tolerability of the drug was good and only minor adverse events were reported.

[A clinical evaluation of three different quantitative fibrin D-dimer analyses in the diagnosis of deep venous thrombosis]. / Den kliniske anvendelighed af tre kvantitative fibrin D-dimer-analyser ved diagnostik af dyb venetrombose.

The trial included ninety-five consecutive outpatients admitted with symptoms and signs suggesting deep venous thrombosis. Blood samples were collected on admission and analysed when the trial was ended. The three different D-dimer methods were BC D-dimer, Tinaquant D-dimer (both quantitative latex agglutination methods) and VIDAS D-dimer, based on the ELISA principle. Ultrasound was used as the reference method, but the outcome evaluated at three month follow up was the gold standard. The sensitivities of the three different methods were 66% (95% confidence interval 55-75%), 93% (88-98%) and 98% (94-100%) respectively. The negative predictive values were respectively 71% (62-80%), 88% (81-95%) and 95% (91-99%). This trial confirms that VIDAS D-dimer has a high sensitivity and negative predictive value that makes it suitable for clinical use. The same conclusion can be drawn for the Tinaquant D-dimer. The trial also emphasizes the importance of testing new methods under routine clinical conditions.

Short-term results of physiotherapy in patients with newly diagnosed degenerative cervical spine disease.

INTRODUCTION: Degenerative cervical spine diseases are common, and physiotherapy is widely used as an initial form of treatment. We aimed to analyse the effects of the initial sessions of physiotherapy for patients who were newly diagnosed with degenerative cervical spine disorders. METHODS: A prospective series of 30 patients with newly diagnosed degenerative cervical spine disease were referred to our department and followed up for the initial two sessions of physiotherapy. The patients were assessed after each session. Outcome parameters studied included pain using a visual analogue scale (VAS), neck range of movements and activities of daily living (ADL). RESULTS: Our study subjects comprised mainly females (60%) in their fifties (46.7%) who worked as clerks or secretaries (53.3%). There was an improvement in the patients' pain score (VAS) from a median of 8 to 4 after two visits to the physiotherapists. Slight improvement in the neck range of movements was also observed. Marked improvement was seen in ADL, especially in the ability to carry heavy objects. CONCLUSION: Physiotherapy is an effective initial option for patients with newly presented degenerative cervical spine disease. The results of this study can be used to advise patients on the short-term benefits of physiotherapy.