A simple assessment method for auditing multi-centre unilateral cleft lip repairs.

The aim of a cleft lip repair is to achieve a functional and aesthetically acceptable upper lip and nose appearance. However, the methods of assessing severity and outcome are still very subjective. Fortunately, it is recognised that human judgement can act as a very reliable tool in assessing facial attractiveness. Therefore, using a simple subjective assessment method, a multi-centre comparison study was performed. Following the Clinical Standards Advisory Group review (1998) and subsequent reconfiguration of the cleft services in the UK a tri-centre comparative audit, involving three out of the nine designated UK cleft centres, was set up. Photographs of 37 patients (consecutive where possible), with complete unilateral cleft lip defects from six regional cleft units (seven surgeons), taken preoperatively and then taken 5 years postoperatively were examined by 10 medical and 10 laypersons to rate the severity and perceived difficulty of repair preoperatively and aesthetic outcome postoperatively. This was repeated after 2 weeks. A five-point scale was used for the assessment. Weighted kappa scores were used to assess agreements within and between rater reliability. Results showed high levels of intra- and inter-rater reproducibility in both groups of raters. This technique was used as a ranking tool to assess the aesthetic outcomes of surgical repair and thereby rank surgeons within our supra-regional audit. This technique can be employed to aid education, stimulate research and also coordinate national inter-centre comparisons following cleft lip repairs.

A randomized trial to investigate the effects of functional electrical stimulation and therapeutic exercise on walking performance for people with multiple sclerosis.

BACKGROUND: Functional electrical stimulation (FES), is a means of producing a contraction in a paralyzed or weak muscle to enable function through electrical excitation of the innervating nerve. OBJECTIVE: This two-group randomized trial assessed the effects of single channel common peroneal nerve stimulation on objective aspects of gait relative to exercise therapy for people with secondary progressive multiple sclerosis (SPMS). METHODS: Forty-four people with a diagnosis of SPMS and unilateral dropped foot completed the trial. Twenty patients were randomly allocated to a group receiving FES and the remaining 24 to a group receiving a physiotherapy home exercise program for a period of 18 weeks. RESULTS: The exercise group showed a statistically significant increase in 10 m walking speed and distance walked in 3 min, relative to the FES group who showed no significant change in walking performance without stimulation. At each stage of the trial, the FES group performed to a significantly higher level with FES than without for the same outcome measures. CONCLUSION: Exercise may provide a greater training effect on walking speed and endurance than FES for people with SPMS. FES may provide an orthotic benefit when outcome is measured using the same parameters. More research is required to investigate the combined therapeutic effects of FES and exercise for this patient group.

Reduced access aortic exposure (RAAE) technique for infrarenal abdominal aortic aneurysm (AAA) repair.

OBJECTIVE: A reduced access aortic exposure (RAAE) technique for repair of infrarenal AAA repair has been evaluated and the short-term surgical outcomes are compared with conventional open repair (OPEN). METHODS: All consecutive patients having repair of infrarenal AAA over a period of 3 years were included in this study. A group of these patients had AAA repair using the RAAE technique with a small midline incision (<8 cm). Patient characteristics and peri-operative outcomes were compared with the other group treated with the traditional full-length midline incision (OPEN). RESULTS: Sixty patients underwent AAA repair in this study (38 in the RAAE group and 22 in the OPEN group). The age, sex distribution and co-morbidities were similar across the two groups (median age 76 and 75 years respectively). The RAAE group had a significantly shorter Intensive care stay (2 vs. 4 days, p=0.041) and a shorter total hospital stay (9 vs. 14 days, p=0.004). Significant postoperative chest infection was recorded in 13% (5/38) in the RAAE group as compared to 41% (9/21) in the OPEN group (p=0.025). CONCLUSIONS: The RAAE technique for infra renal AAA repair is feasible and safe, and allows quicker postoperative recovery with comparable morbidity and mortality to the conventional technique.

X chromosome loss and ageing.

The detection of a low level 45,X cell line during routine cytogenetic analysis in an adult female can be difficult to interpret. In the absence of recent information regarding loss of the X chromosome and ageing, we undertook a prospective study. A total of 19,650 cells from 655 females aged from birth to 80 years were screened cytogenetically. The frequency of X chromosome loss ranged from 0.07% at age <16 years to 7.3% at >65 years of age and showed a highly significant quadratic relationship between X chromosome loss and ageing (P < or = 0.00001). We have produced a graphic representation that provides a minimum baseline age-related rate of X chromosome loss. This should assist diagnostic cytogenetics laboratories to determine the significance of 45,X cell lines detected in women of all ages. We also compared the frequency of 45,X cells in women referred with at least one spontaneous abortion with those referred for other reasons and found no significant difference. Thus, in our population, an excess of 45,X cells is not associated with pregnancy loss.

Triggering of acute coronary syndromes by physical exertion and anger: clinical and sociodemographic characteristics.

OBJECTIVE: To investigate the role of vigorous physical exertion and anger as triggers of acute coronary syndromes (ACS) and to identify the clinical and sociodemographic correlates of triggering. DESIGN: Prospective observational clinical cohort study. SETTING: Four coronary care units in the London area. PATIENTS: 295 men and women with electrocardiographically and biochemically verified ACS. MAIN OUTCOME MEASURES: Physical exertion in the 1 h and anger in the 2 h before symptom onset were assessed with structured interviews. Control periods were the equivalent hours one day earlier and usual rates over the past six months. Data were analysed by case-crossover methods. RESULTS: Physical exertion was reported by 10% and anger by 17.4% of patients in the hazard period. The risk of ACS onset after physical exertion compared with light or no activity was 3.50 (95% confidence interval (CI) 1.37 to 10.6). The risk of onset with anger was 2.06 (95% CI 1.12 to 3.92). Physical exertion during the hazard period was related to an absence of premonitory symptoms, presentation with an ST elevation myocardial infarction (STEMI), low socioeconomic deprivation and higher future cardiovascular risk. Anger during the hazard period was more common in younger, socioeconomically deprived patients who presented with a STEMI. CONCLUSIONS: Triggers are relevant across the spectrum of ACS. The distinct clinical and sociodemographic factors associated with physical exertion and anger suggest that different pathophysiological processes may be involved.

Post-traumatic stress disorder in patients with cardiac disease: predicting vulnerability from emotional responses during admission for acute coronary syndromes.

OBJECTIVES: To assess frequency and predictors of post-traumatic stress disorder (PTSD), measured by the Post Traumatic Stress-self report version, at three months after admission for acute coronary syndromes (ACS). DESIGN: Two-phase prospective study. SETTING: Four coronary care units. PATIENTS: 135 patients admitted to hospital with ACS confirmed by ECG and cardiac enzyme changes. RESULTS: 20 patients (14.8%) showed a symptom pattern characteristic of PTSD at three months assessed by a conservative scoring criterion. Severity of chest pain and psychological factors during admission were predictive of PTSD severity. Acute stress symptoms, depression, negative affect, hostility, and pain scores were independent predictors of three-month PTSD symptoms (R(2) = 0.495, p < 0.001). In contrast, demographic factors (age, sex, education level and income) were unrelated to post-traumatic symptoms, as were markers of clinical disease severity. CONCLUSIONS: Patient vulnerability to PTSD three months after ACS is predictable on the basis of psychological state and chest pain at the time of admission. This may be valuable to the clinician, as PTSD after myocardial infarction is associated with poorer quality of life, reduced adherence to drug treatment and increased likelihood of cardiovascular morbidity.

Age has a profound effect on the incidence and significance of chromosome abnormalities in myeloma.

A simple high throughput micro-fluorescence in situ hybridisation technique (FISH) was used to detect chromosome 13 deletions (delta13), immunoglobulin heavy chain (IgH) rearrangements, t(11;14)(q13;q32), t(4;14)(p16;q32), t(14;16)(q23;q32), p53 loss, and numerical changes of chromosomes 3, 6, 7, 9, 10, 11 and 17 in 228 cases of multiple myeloma (MM), including 33 asymptomatic/smouldering MM (SMM). The patients were not part of a clinical trial and were from 30 different hospitals. In all, 98.4% of cases were abnormal, with 43% having IgH rearrangements and 42% Delta13. The low incidence of IgH rearrangements was due to a decrease in this finding with age (P = 0.001) and the relatively high proportion of elderly patients in our study population (41% >70 years old). The incidence of specific IgH translocations was t(4;14) 11%, t(11;14) 16% and t(14;16) 3%. Univariate statistical testing showed delta13 (P = 0.002), and t(14;16) (P = 0.005) to be associated with shorter survival. This effect was exaggerated for patient's aged 70 years or under but no effect on survival was seen for those over 70 years. In younger patients t(4;14) (P = 0.044) and p53 deletion (P < 0.001) were also significant poor prognostic indicators. Multivariate analysis showed delta13 and t(14;16) to be independent prognostic variables when considered with age and clinical parameters.

Acute inflammation and negative mood: mediation by cytokine activation.

Inflammatory diseases are commonly associated with depressed mood. This association may be influenced by the production of proinflammatory cytokines. Accordingly, we assessed whether cytokine levels and mood (measured with the profile of mood states) could be altered by a mild, non-sickness inducing, acute inflammatory stimulus. Using a randomised placebo-controlled, double-blind design, 30 healthy male volunteers were injected with Salmonella typhi vaccine or placebo. Assessments of mood, symptoms of illness and temperature were made at baseline and at 1.5, 3, and 6 h post-injection. Plasma concentrations of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and tumour necrosis factor-alpha (TNF-alpha) were assessed at baseline and 3 h post-injection. No significant symptoms of illness were reported in either group. Mood was more negative following injection in the vaccine than the placebo group, and the vaccine group experienced a 106% increase in IL-6 concentration. Negative changes in mood following injection were significantly correlated with increases in IL-6 production. No changes in TNF-alpha or IL-1Ra concentration were recorded in either group. It is concluded that S. typhi vaccination may be a useful model of mild inflammatory challenge, producing a significant transient cytokine-induced decrease in mood in the absence of any febrile response. Implications for depressed mood in physical illness are discussed.

A pilot study to investigate the effects of electrical stimulation on recovery of hand function and sensation in subacute stroke patients.

Objectives. 1) To compare the effect of cyclic neuromuscular electrical stimulation (NMES) of the forearm and elbow extensor muscles with passive stretching exercises on hand function and sensation following stroke. 2) To inform sample size for a larger randomized controlled trial (RCT). Materials and Methods. Twenty-two subjects with hemiplegia resulting from a stroke during the previous 12 months were randomly allocated into stimulation (treatment) and exercise (control) groups. Stimulation was applied to the elbow, and forearm extensor muscle groups of the hemiplegic arm for 12 weeks. Subjects in the control group were taught passive stretching exercises for the same period. The primary outcome measure was the Action Research Arm test (ARAT). Sensation was tested using two-point discrimination. Statistical analysis applied nonparametric analysis of covariance (ancova). Results. Statistically significant between-group differences in change in ARAT scores were shown between the two groups after 12 weeks of treatment (p = 0.003) and following 12 further weeks without intervention (p = 0.012). There were no significant differences in sensation. Conclusions. 1) A significant treatment effect of electrical stimulation over passive exercise has been demonstrated in a group of 22 subacute stroke patients, randomized into two equal groups and further work identified which may help to improve recovery of hand function and sensation following stroke. 2) A sample size of 24 subjects in each group has been estimated assuming a two-sided test significance level of 5% with 80% power, primary outcome variability SD = 6.75, a minimum difference of ten ARAT score units, and a 10% dropout rate.

Prospective randomised double-blind comparative study of rocuronium and pancuronium in adult patients scheduled for elective 'fast-track' cardiac surgery involving hypothermic cardiopulmonary bypass.

The majority of cardiac anaesthetists in the UK use pancuronium for fast-track cardiac surgery. We compared the duration of action of pancuronium and rocuronium in patients undergoing fast-track hypothermic cardiopulmonary bypass and cardiac surgery. We determined whether patients would have had residual neuromuscular blockade at extubation. Twenty patients were randomly allocated to receive either pancuronium 0.1 mg x kg(-1) or rocuronium 1 mg x kg(-1). Neuromuscular function was assessed by acceleromyography; spontaneous recovery was evaluated by the train-of-four ratio measured at the adductor pollicis longus muscle. Median times to recover train-of-four ratio of 0.9 were 3 h 38 min for rocuronium and 7 h 52 min for pancuronium. The median difference in recovery times was 4 h 15 min (95% CI 2 h 30 min to 6 h 20 min; p = 0.0003 by Mann-Whitney test). None of the patients in the rocuronium group and seven of 10 patients in the pancuronium group had their extubations delayed because of residual neuromuscular blockade. Unless fast-track patients have neuromuscular function assessed before extubation, pancuronium should not be used.

See one, do one, teach one--is this still how it works? A comparison of the medical and nursing professions in the teaching of practical procedures.

A survey of 80 junior doctors and nurses was performed to compare the methods of teaching medical and nursing students in eight common practical procedures. Nurses were more likely to have received formal teaching and to be supervised when first performing a procedure. Some 42% percent of doctors felt inadequately trained to carry out a practical procedure safely when performing it alone for the first time compared with 7% of nurses. This study confirms that much of the training of doctors in practical procedures is still received on an informal basis, compared with that of nurses. It also reveals that many doctors view this training as insufficient.

Cell-cell interactions influence resistance and survival of Salmonella serotype Typhimurium to environmental stress.

AIMS: The aim of this work was to study the effects of prolonged nutrient stress on survival, cell interactions and resistance to inimical processes in Salmonella serotype Typhimurium. METHODS AND RESULTS: Salmonella Typhimurium cells were subjected to prolonged incubation in the stationary phase of growth and the properties of starved cells (old) were investigated with reference to those of exponentially-growing cells (young). Competition experiments between old and young cells revealed cell-cell interactions that influenced stationary phase survival and response of the bacterium to heat stress. During prolonged incubation of cells, cycles of resistance and sensitivity to heat stress were identified. Competition experiments between old and young cells revealed that the resistance of young cells to heat increased to levels more like those of stationary phase cells than growing cells. The presence of old cells influenced the phenotype of young cells, possibly by means of cell-cell interactions. There was no evidence for the involvement of any extracellularly-produced factors in this phenomenon, but a requirement that the old competitor cells be viable could be demonstrated. CONCLUSIONS: It is proposed that the complex interactions within stationary phase cultures of Salm. Typhimurium may be due to cycles of mutation in concert with an as yet undefined interaction between old cells and growing ones. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides evidence for active and diverse responses to nutrient stress within populations of Salm. Typhimurium that promote survival and that may be important for the success of this bacterium as a pathogen.

The value of risks scores for predicting postoperative nausea and vomiting when used to compare patient group in a randomised controlled trial.

Whilst conducting a randomised controlled trial into the effects of combination anti-emetics, we endeavoured to confirm that our patient groups were matched using the predictive scoring systems for postoperative nausea and vomiting (PONV) and postoperative vomiting (POV) reported in the literature. One hundred and seventy-seven female patients attending for day case gynaecological surgery were studied and their individual risks of PONV and POV were calculated using four predictive models for PONV and two predictive models for POV. The scoring systems were then evaluated to see if agreement existed between them using the method described by Bland and Altman. Bias and 95% limits of agreement were calculated for each combination. Agreement between scoring systems was poor. As the scoring systems gave widely divergent predictions, we concluded that the predictive risk for PONV or POV would be dependent upon the scoring system chosen, thus limiting their usefulness in this role.

Copper/zinc superoxide dismutase is phosphorylated and modulated specifically by granulocyte-colony stimulating factor in myeloid cells.

Using two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2-D SDS-PAGE) of 32P-labeled cytosolic and membrane extracts, we identified a 21.5 kDa phosphoprotein with an isoelectric point of 6.0 in NFS-60 cells that was phosphorylated maximally at 15 min by treatment with granulocyte-colony stimulating factor (G-CSF) but not with interlevkin-3 (IL-3) or colony-stimulating factor-1 (macrophage-colony stimulating factor (CSF-1 (M-CSF)). The phosphorylation of this protein, designated 21.5/6.0, was unaffected by a series of antiproliferative agents [32]. These findings suggested that the 21.5/6.0 phosphoprotein may be involved in specific G-CSF-mediated biological responses such as activation and/or differentiation. We sought to characterize this 21.5/6.0 by a novel combination of 2-D SDS-PAGE and hydroxyapatite (HTP)-chromatography. Amino acid sequence determination of 21.5/6.0 revealed it to share a high level of homology with copper/zinc superoxide dismutase (Cu/Zn-SOD), indicating that a Cu/Zn-SOD is phosphorylated following treatment with G-CSF. This is the first report of the phosphorylation and possible involvement of Cu/Zn-SOD protein in granulocyte activation/differentiation events. In addition, Cu/Zn-SOD levels and activity were diminished by G-CSF but not IL-3 treatment. This new protocol combining 2-D SDS-PAGE and HTP-chromatography allows the characterization of low abundance phosphoproteins involved in the cellular responses to G-CSF and presumably to other cytokines/growth factors.

An unusual atrial mass.

Giant coronary artery aneurysm is a rare manifestation of coronary artery disease. This patient presented at echocardiography and was successfully managed by surgical resection.

Mechanisms of genome maintenance and rearrangement: current research and recent advances in DNA repair and recombination.

The topics of the talks at the annual DNA Repair Network Meeting at City University, London were as usual wide-ranging and provided an absorbing programme. Covered in the 17 talks were the autoproteolysis of O(6)-methylguanine DNA alkyltransferase in Escherichia coli; identification of new intermediates in meiotic recombination in Saccharomyces cerevisiae; the SMC (structural maintenance of chromosomes) family of proteins in Schizosaccharomyces pombe; transposition and V(D)J recombination; mammalian Rad51 foci formation in Rad54, Rad52, XRCC2 and XRCC3 mutants; biochemical analysis of DNA-PK, ATM (ataxia telangiectasia mutated) and ATR (AT related); other human DNA repair deficiencies and their incidence, including xeroderma pigmentosum and a new DNA ligase IV-deficient patient, and back, once again, to alkyltransferase, this time in humans and its manipulation for engineering drug resistance in bone marrow for cancer treatment.