The Effect of beta-blockade on objectively measured physical fitness in patients with abdominal aortic aneurysms--A blinded interventional study.

BACKGROUND: Perioperative beta-blockade is widely used, especially before vascular surgery; however, its impact on exercise performance assessed using cardiopulmonary exercise testing (CPET) in this group is unknown. We hypothesized that beta-blocker therapy would significantly improve CPET-derived physical fitness in this group. METHODS: We recruited patients with abdominal aortic aneurysms (AAA) of <5.5 cm under surveillance. All patients underwent CPET on and off beta-blockers. Patients routinely prescribed beta-blockers underwent a first CPET on medication. Beta-blockers were stopped for one week before a second CPET. Patients not routinely taking beta-blockers underwent the first CPET off treatment, then performed a second CPET after commencement of bisoprolol for at least 48 h. Oxygen uptake (.VO2) at estimated lactate threshold and .VO2 at peak were primary outcome variables. A linear mixed-effects model was fitted to investigate any difference in adjusted CPET variables on and off beta-blockers. RESULTS: Forty-eight patients completed the study. No difference was observed in .VO2 at estimated lactate threshold and .VO2 at peak; however, a significant decrease in .VE/.VCO2 at estimated lactate threshold and peak, an increase in workload at estimated lactate threshold., O2 pulse and heart rate both at estimated lactate threshold and peak was found with beta-blockers. Patients taking beta-blockers routinely (chronic group) had worse exercise performance (lower .VO2 ). CONCLUSIONS: Beta blockade has a significant impact on CPET-derived exercise performance, albeit without changing .VO2 at estimated lactate threshold and.VO2 at peak. This supports performance of preoperative CPET on or off beta-blockers depending on local perioperative practice. CLINICAL TRIAL REGISTRATION: NCT 02106286.

Effect of bronchodilation on expiratory flow limitation and resting lung mechanics in COPD.

Bronchodilator drugs produce variable improvements in forced expiratory volume in 1 s (FEV(1)), but larger changes in end-expiratory lung volume (EELV) in chronic obstructive pulmonary disease (COPD), which were suggested to be related to the presence of expiratory flow limitation (EFL) at rest. We tested this concept in 42 COPD patients (FEV(1) 42.3+/-13.8% predicted) during spontaneous breathing before and after 5 mg nebulised salbutamol. EFL was detected by within-breath changes in respiratory system reactance measured by a multifrequency forced oscillation method, while changes in EELV were assessed by inspiratory capacity (IC). Bronchodilation (BD) increased IC (from 1.8+/-0.5 to 2.1+/-0.6 L, p<0.001) and reduced inspiration resistance ((insp)) at 5 Hz (from 5.1+/-1.6 to 4.2+/-1.5 cmH(2)OxsxL(-1), p<0.001). (insp) identified BD responders with a discriminative power of 80.1%. In total, 20 patients were flow-limited before BD. They showed worse spirometry and higher residual volume, but significant improvements in IC were seen in all patients irrespective of flow limitation. Changes in (insp) were confined to flow-limited patients, as were reactance changes. BD reduced the degree of heterogeneity in the respiratory system, a change best seen with inspiratory values. BD has complex effects on lung mechanics in COPD, and EFL affects both this and the response of some respiratory variables to treatment. However, changes in EELV are consistently seen, irrespective of the presence of flow limitation at rest.

Septic arthritis in males with haemophilia.

We used data collected as part of the Universal Data Collection (UDC) surveillance project in haemophilia treatment centers (HTC) to study the incidence, risk factors and impact of septic arthritis among males with haemophilia. Patients participating in UDC on two or more occasions were included. Cases were defined as patients with documented joint infection. Characteristics of the cases were compared with those of haemophilia patients without infection. Among the 8026 eligible patients with 36 015 person-years of follow-up, 30 (0.37%) had a documented joint infection (incidence rate 83 per 100 000 person-years). In a logistic regression model, only increasing age (OR = 6.1 for age > or =30), race/ethnicity other than white (OR = 3.9), presence of inhibitor (OR = 3.9), invasive procedure in the past year (OR = 2.7) and presence of one or more target joints (OR = 3.2) remained statistically significant. Central venous access devices use and hepatitis C virus and HIV infection were not associated with septic arthritis risk after adjusting for potential confounders. Study limitations include possible underestimation of septic arthritis rate in this population and its retrospective design. We conclude that septic arthritis is an uncommon complication of haemophilia occurring primarily in joints most affected by bleeding and reparative surgical interventions.

Acute absorption of folic acid from a fortified low-fat spread.

OBJECTIVE: To explore the feasibility of low-fat spreads as vehicles for folic acid (FA) fortification by determining the acute absorption of FA from a fortified spread. DESIGN: Double blind, crossover study to test each of the following treatments administered at 1-weekly intervals: (A) 20 g low-fat (40%) spread fortified with 200 microg FA and a placebo tablet; (B) 20 g low-fat placebo spread and a 200 microg FA tablet; (C) 20 g low-fat placebo spread and a placebo tablet. SUBJECTS: A total of 13 male volunteers, aged 31.8+/-13.2 y. MAIN OUTCOME MEASURES: Plasma total folate concentrations, measured before and up to 10 h after each treatment (n=10 samples per treatment). RESULTS: Plasma folate concentrations were significantly increased compared with baseline values 1 h after administration of the FA tablet, and 1.5 h after the FA spread, and remained significantly higher than the baseline values for up to 7 h after both treatments. The maximum plasma folate response (R(max)), corrected for baseline values and 'placebo response', was established between 1 and 3 h postprandially in response to both FA spread and FA tablet, and no significant difference in R(max) was found between the two treatments (13.4 vs 14.4 nmol/l, P=0.9). The acute absorption of FA from fortified spread relative to that from the tablet, calculated on the basis of area under the plasma folate response curve, was 67% (P=0.04). CONCLUSION: The absorption of FA from fortified low-fat spread, although lower than from a tablet, is effective. These results suggest that low-fat spreads, typically associated with fat-soluble vitamin fortification, may also be considered feasible as vehicles for FA fortification.

Morbillivirus infection in cetaceans of the western Atlantic.

We report serologic evidence of morbillivirus infection in eleven of fifteen species of odontocete cetaceans from the western Atlantic since 1986. Blood samples were obtained both from free-ranging and stranded animals. Virus neutralizing titers were higher against porpoise and dolphin morbilliviruses than against peste des petits ruminants virus, phocine distemper virus or canine distemper virus (CDV). Serum from five species, tested in a heterologous immunoprecipitation assay using radiolabelled CDV, precipitated the nucleocapsid (N) protein. Clinical morbillivirus infection may potentially impact already threatened species such as the harbour porpoise and precipitate mass strandings of socially cohesive odontocetes.

Comparative antibody response in harbour and grey seals naturally infected by a morbillivirus.

The antibody response of free-ranging harbour and grey seals, naturally infected by a morbillivirus, was assessed using a virus neutralizing test and a radio-immunoprecipitation assay. The prevalence of antibody was similar between species, however, grey seals had significantly higher virus neutralizing titers. Serum from clinically healthy grey seals precipitated the nucleocapsid (N) protein along with the hemagglutinin (H) and fusion (F) glycoproteins. By contrast, significantly fewer harbour seal sera precipitated the envelope glycoproteins and responses were weaker than those of grey seals. One harbour seal with acute morbillivirus pneumonia, and two with encephalitis precipitated only the N protein. Serum from four harbour seals with encephalitis weakly recognized the envelope glycoproteins. Thus, the antibody response of grey seals appears more competent than that of harbour seals with respect to morbillivirus antigens. We speculate that this difference between the species may be an important determinant of morbillivirus susceptibility.

A video-based optical system for rapid measurements of chest wall movement.

We tested apparatus developed to measure the movement of the surface of the chest and abdomen, during breathing in the supine subject. A line of light is projected onto the chest wall. The line image from a video camera is analysed to estimate of the height of the surface profile, so that the shape and volume of the object can be derived. The data can provide direct or inferential volume estimates. We compared this system with the widely used inferential system of inductance bands in supine volunteers who breathed using patterns designed to emphasize variability in movements: normal and large breaths, and breathing through an expiratory resistance. We calculated the differences between a spirometer signal and continuous volume estimates using the linear regression method, obtained using signals from the two methods. The volume estimate differences obtained by the optical system and induction bands were not significantly different, but the optical system was more precise. Using the optical device, an acceptable interquartile range of differences from spirometric volume (50 ml) was significantly likely when the optical device was used. During resistive loaded breathing (mean tidal volume 390 ml) direct optical measurements of volume, and inductance band estimates, were compared with tidal volume. The optical system showed distortion of the shape of the abdomen during this breathing pattern. Mean error with the optical system was 64 ml and with the inductance band system was 108 ml (p < 0.05). The optical system gives accurate reproducible results in supine human subjects and additional valuable information on shape changes.

Humoral immune responses in seals infected by phocine distemper virus.

Recently the isolation and characterisation of a morbillivirus which caused high mortality in common seals (Phoca vitulina) in 1988 have been reported. Because of the clinical and pathological similarity of the disease in seals to that of distemper in dogs, the name phocine distemper virus (PDV) has been proposed. There are marked differences in the virus-induced proteins of PDV compared to other morbilliviruses and the humoral immune response of moribund and dead seals to PDV was restricted to some of the internal antigens of PDV, similar to the response described earlier for canine distemper virus infection in dogs.

Epizootiology of morbillivirus infection in harp, hooded, and ringed seals from the Canadian Arctic and western Atlantic.

Using a virus neutralization technique, we found phocine distemper virus (PDV) antibody in 130 (83% of 157) harp seals (Phoca groenlandica) from the western North Atlantic sampled between 1988 and 1993 inclusive. In contrast, only 44 (24% of 185) hooded seals (Cystophora cristata) had antibodies against PDV even though they were sympatric with harp seals and were sampled over a similar period, from 1989 to 1994 inclusive. Antibodies occurred in 106 (41%) of 259 ringed seals (Phoca hispida); this prevalence was higher than expected given the solitary behavior and territoriality characteristic of this species. Seropositive ringed seals were found at each of seven locations across Arctic Canada from Baffin Bay to Amundsen Gulf at which samples were collected between 1992 and 1994. However, the prevalence of infection was highest where ringed seals are sympatric with harp seals in the eastern Canadian Arctic.

Construction and visualisation of three-dimensional facial statistics.

This paper presents a new method for the construction of three-dimensional (3D) probabilistic facial averages and demonstrates the potential for applications in clinical craniofacial research and patient assessment. Averages are constructed from a database of registered laser-range scans and photographic images using feature based image warping. Facial features are extracted using a template of connected contours, adapted to each subject interactively using snakes. Each subject's images are warped to the average template shape and the mean depth, colour and covariance matrix is found at each point. Statistical comparison of individuals with an average or between two averages is visualised by converting the probabilities to a coloured texture map.

Expiratory flow limitation detected by forced oscillation and negative expiratory pressure.

The within-breath change in reactance (Delta(rs)) measured by forced oscillation technique (FOT) at 5 Hz reliably detects expiratory flow limitation in chronic obstructive pulmonary disease (COPD). The present study compared this approach to the standard negative expiratory pressure (NEP) method. In total, 21 COPD patients were studied by applying both techniques to the same breath and in 15 patients the measurements were repeated after bronchodilator. For each patient and condition five NEP tests were performed and independently scored by three operators unaware of the FOT results. In 180 tests, FOT classified 53.3% as flow limited. On average, the operators scored 27.6% of tests flow limited and 47.6% non-flow limited, but could not score 24.8%. The methods disagreed in 7.9% of cases; in 78% of these the NEP scores differed between operators. Bronchodilation reduced NEP and DeltaX(rs) scores, with only the latter achieving significance. Averaging the operators' NEP scores, a threshold between 24.6-30.8% of tidal volume being flow limited by NEP produced 94% agreement between methods. In conclusion, when negative expiratory pressure and forced oscillation technique were both available they showed good agreement. As forced oscillation technique is automatic and can measure multiple breaths over long periods, it is suitable for monitoring expiratory flow limitation continuously and identifying patients' breathing close to the onset of expiratory flow limitation, where intermittent sampling may be unrepresentative.

Intravenous aminophylline in patients admitted to hospital with non-acidotic exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial.

BACKGROUND: Intravenous aminophylline is commonly used in the treatment of exacerbations of chronic obstructive pulmonary disease (COPD), despite limited evidence for its efficacy and known risks of toxicity. We hypothesised that adding intravenous aminophylline to conventional treatment would not produce clinically important changes in the speed of spirometric or symptomatic recovery or shorten hospital stay in patients with exacerbations of COPD. METHODS: Eighty patients admitted to hospital with non-acidotic exacerbations of COPD were recruited at admission to a randomised, double blind, placebo controlled study comparing intravenous aminophylline 0.5 mg/kg/hour after an appropriate loading dose with an equivalent volume of 0.9% saline. The primary outcome was the change in post-bronchodilator forced expiratory volume in 1 second (FEV(1)) over the first 5 days of the admission. Secondary end points were changes in self-reported breathlessness, arterial blood gas tensions, forced vital capacity (FVC), and length of hospital stay. RESULTS: There was no difference in the post-bronchodilator FEV(1) over the first 5 days between the aminophylline and placebo groups. In the aminophylline group, 2 hours of treatment produced a small but significant rise in arterial pH (p = 0.001) and a fall in arterial carbon dioxide tension (p = 0.01) compared with placebo treatment. There were no differences in the severity of breathlessness, post-bronchodilator FVC, or length of hospital stay between the groups. Nausea was a more frequent side effect in the aminophylline group (46% v 22%; p<0.05), but palpitations and headache were noted equally in both groups. CONCLUSIONS: Although intravenous aminophylline produced small improvements in acid-base balance, these did not influence the subsequent clinical course. No evidence was found for any clinically important additional effect of aminophylline treatment when used with high dose nebulised bronchodilators and oral corticosteroids. Given its known toxicity, we cannot therefore recommend the use of intravenous aminophylline in the treatment of non-acidotic COPD exacerbations.

Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2 diabetes.

AIMS: Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important insulinotropic hormones that enhance the insulin secretory response to feeding. Their potential for treating Type 2 diabetes is limited by short biological half-life owing to degradation by dipeptidyl peptidase IV (DPP IV). We investigated the acute effects of metformin on DPP IV activity in Type 2 diabetes to elucidate inhibition of DPP IV as a possible mechanism of action. METHODS: Eight fasting subjects with Type 2 diabetes (5M/3F, age 53.1+/-4.2 years, BMI 36.8+/-1.8 kg/m2, glucose 8.9+/-1.2 mmol/l, HbA1c 7.8+/-0.6%) received placebo or metformin 1 g orally 1 week apart in a random, crossover design. RESULTS: Following metformin, DPP IV activity was suppressed compared with placebo (AUC0-6 h 3230+/-373 vs. 5764+/-504 nmol ml/l, respectively, P=0.001). Circulating glucose, insulin and total GLP-1 were unchanged. Metformin also concentration-dependently inhibited endogenous DPP IV activity in vitro in plasma from Type 2 diabetic subjects. CONCLUSION: Oral metformin effectively inhibits DPP IV activity in Type 2 diabetic patients, suggesting that the drug may have potential for future combination therapy with incretin hormones.

Function of a long-term, GLP-1-treated, insulin-secreting cell line is improved by preventing DPP IV-mediated degradation of GLP-1.

Glucagon-like peptide-1 (GLP-1) is an important insulinotropic hormone with potential in the treatment of type 2 diabetes. However, the short biological half-life of the peptide after cleavage by dipeptidylpeptidase IV (DPP IV) is a major limitation. Inhibition of DPP IV activity and the development of resistant GLP-1 analogues is the subject of ongoing research. In this study, we determined cell growth, insulin content, insulin accumulation and insulin secretory function of a insulin-secreting cell line cultured for 3 days with either GLP-1, GLP-1 plus the DPP IV inhibitor diprotin A (DPA) or stable N-acetyl-GLP-1. Native GLP-1 was rapidly degraded by DPP IV during culture with accumulation of the inactive metabolite GLP-1(9-36)amide. Inclusion of DPA or use of the DPP IV-resistant analogue, N-acetyl-GLP-1, improved cellular function compared to exposure to GLP-1 alone. Most notably, basal and accumulated insulin secretion was enhanced, and glucose responsiveness was improved. However, prolonged GLP-1 treatment resulted in GLP-1 receptor desensitization regardless of DPP IV status. The results indicate that prevention of DPP IV action is necessary for beneficial effects of GLP-1 on pancreatic beta cells and that prolonged exposure to GLP-1(9-36)amide may be detrimental to insulin secretory function. These observations also support the ongoing development of DPP-IV-resistant forms of GLP-1, such as N-acetyl-GLP-1.

A 33-year-old woman with a propranolol and chlorpromazine overdose, with applied nursing diagnoses.

The challenge of emergency nursing comes from opportunities to increase knowledge and integrate it into our clinical practice. We face the challenge of identifying pertinent nursing diagnoses for our patients and linking them with the interventions used in our patients' care. From this information we can verify effectiveness of care and increase nursing's scientific body of knowledge.

Fertility control early in marriage in Ireland a century ago.

PIP: This study sheds light on the beginnings of the fertility decline in Ireland through the analysis of disaggregated data on individual families of couples who married at the beginning of the 20th century. Data on women who had been married nine years or less and before their 35th birthday were extracted from the 1911 Irish manuscript population census (the first to collect information on marital fertility) for 1) a traditional rural area (County Clare), 2) a rural area with large Catholic and non-Catholic populations (Tyrone), and 3) a middle-class suburb of Dublin with a large non-Catholic population (Rathgar). Regression analysis of the variables provided by these data (number of children born, husband's occupation, religion, number of nonsurviving children, age at marriage, and duration of marriage) provided explanations of variations in fertility. As expected, fertility early in marriage was highest in County Clare, with children arriving an average of every two years as compared to every three years in Tyrone and every four years in Rathgar. Thus, for some of these parents, a spacing strategy had been employed by the turn of the century. Catholic marriages in Rathgar were notable more fertile, but religious affiliation had little affect on fertility in Tyrone. The contrast of these findings with those reported earlier may be explained by the focus of the present study on the early years of marriage. The fertility of the rural Catholics in Tyrone was lower than in Clare, perhaps because of the social influence of non-Catholics. Higher socioeconomic status was associated with less fertility in early marriage, and these results support the hypothesis that in urban Ireland, contraception was an innovation which diffused down from the middle classes. In all cases, the older the woman was at marriage, the lower the early marital fertility. Further analysis of these data to determine the extent of child replacement following the death of a child revealed a surprisingly low replacement effect in Tyrone. All regions showed "Malthusian" as well as replacement effects on early marital fertility. This study, while not seeking to overturn the description of the Irish as reluctant participants in the European fertility transition, does point to the practice of family limitation early in marriage.^ieng

Planning nursing education for the 21st century.

In looking towards the 21st century, the faculty at the Presbyterian Hospital School of Nursing, along with the Presbyterian Health Services Corporation and Queen's College, adopted a 1-2-1 programme. The process of developing a new nursing curriculum is presented as the task force proceeded from the philosophy and goals to conceptual framework and curriculum objectives. After discussions with nurse administrators and educators, extensive literature reviews and brainstorming sessions, concepts and subconcepts were chosen to form a philosophy. The metaparadigm of nursing and other related concepts were then organized into a conceptual framework. Ongoing communication and feedback from the faculty ensured group ownership of all documents. The eclectic organizational scheme was a good fit for a large faculty with differing beliefs and values about a nursing curriculum. The process of developing a future orientated nursing curriculum has been exciting, challenging and rewarding. The faculty is committed to the new philosophy, goals and conceptual framework and believe that the 1-2-1 programme will educate future practitioners who are prepared to meet the challenges and changes in health care for the 21st century.