Comparison of two methods of determining lung de-recruitment, using the forced oscillation technique.

Airway closure has proved to be important in a number of respiratory diseases and may be the primary functional defect in asthma. A surrogate measure of closing volume can be identified using the forced oscillation technique (FOT), by performing a deflation maneuver and examining the resultant reactance (Xrs) lung volume relationship. This study aims to determine if a slow vital capacity maneuver can be used instead of this deflation maneuver and compare it to existing more complex techniques. Three subject groups were included in the study; healthy (n = 29), asthmatic (n = 18), and COPD (n = 10) for a total of 57 subjects. Reactance lung volume curves were generated via FOT recordings during two different breathing manoeuvres (both pre and post bronchodilator). The correlation and agreement between surrogate closing volume (Volcrit) and reactance (Xrscrit) at this volume was analysed. The changes in Volcrit and Xrscrit pre and post bronchodilator were also analysed. Across all three subject groups, the two different measures of Volcrit were shown to be statistically equivalent (p > 0.05) and demonstrated a strong fit to the data (R2 = 0.49, 0.78, 0.59, for asthmatic, COPD and healthy subject groups, respectively). A bias was evident between the two measurements of Xrscrit with statistically different means (p < 0.05). However, the two measurements of Xrscrit displayed the same trends. In conclusion, we have developed an alternative technique for measuring airway closure from FOT recordings. The technique delivers equivalent and possibly more sensitive results to previous methods while being simple and easily performed by the patient.

Gastrointestinal tract development in red deer (Cervus elaphus) calves from 1 to 12 months of age.

This study provides a detailed description of the development of the gastrointestinal tract (GIT) of farmed red deer (Cervus elaphus) calves over the first 12 months of age. GIT development was measured using a combination of computerised tomography (CT) scanning and traditional slaughter plus dissection techniques. Red deer calves of a known birth date were randomly assigned to two treatment groups. A group of five animals were repeatedly CT scanned at 31, 63, 92, 135, 207, 275 and 351 days of age to identify GIT organs and determine their volume. From a group of 20 animals, subsets of four individuals were also scanned at corresponding ages (except 135 days of age). They were immediately euthanised and dissected after CT scanning to compare CT-scanned results with actual anatomical measurements. Individual organ weights were compared with their respective organ volumes determined by CT scanning and were found to have a strong, positive relationship. The combined rumen and reticulum (RR) CT-scanned volume was compared with its volume determined by the water-displacement technique and this also showed good correlation between the two techniques (R = 0.92). The allometric growth rates of organs, relative to animal live weight gains, in descending order, were the rumen, omasum, reticulum, abomasum, caecum blind sac, kidneys, spleen and liver. The red deer GIT was continuing to grow and develop when the last measurement was taken at 351 days of age. The greatest growth of the RR, when expressed in terms of empty weight, was between 31 and 92 days of age. Compared with sheep and cattle, it appears that the red deer have a similar or greater rate of RR development up until approximately 60 to 90 days of age; however, the final increments of GIT maturity in deer may take longer to complete, with the empty weight of the RR gaining 7.5 g/day between 275 and 351 days of age. CT scanning was validated in this study as a viable technique to follow GIT development in the same animals over time, and it provided novel information on allometric organ growth. The success of CT scanning highlights the potential future use of diagnostic imaging for GIT development studies.

Prediction equations for single breath diffusing capacity (Tlco) in a middle aged caucasian population.

BACKGROUND: There are many reference equations for the measurement of single breath carbon monoxide diffusing capacity of the lung (Tlco). However, the testing methodologies vary and there are no well documented studies that have developed reference equations for Tlco and alveolar volume (Va) in middle aged and older populations. AIMS: (1) Develop reference equations for Tlco in a middle aged population using the current American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines; (2) compare the equations with those commonly used in laboratories around the world. METHODS: Healthy subjects (498 male and 474 female) aged 45-71 years were recruited as part of a larger epidemiological study. All participants completed a respiratory questionnaire and had spirometry and single breath Tlco (corrected for haemoglobin) measurements following ATS/ERS guidelines. RESULTS: Mean age was 58 years for males and 57 years for females. For males, factors that predicted Tlco were: height, age, agexheight interaction and being an ex-smoker. For females, factors that predicted Tlco were: height, age, weight and an agexheight interaction. CONCLUSION: We have described new prediction equations for Tlco in a middle aged population that require validation in other populations.

Efficacy, immune responses and side-effects of vaccines against Johne's disease in young red deer (Cervus elaphus) experimentally challenged with Mycobacterium avium subsp paratuberculosis.

AIMS: To test the efficacy of a commercially available and an experimental vaccine against Johne's disease in young red deer (Cervus elaphus), using experimental challenge with live virulent Mycobacterium avium subsp paratuberculosis (M. ptb), measure injection-site reactions, and assess the effects of vaccination and challenge on results of subsequent skin tests and ancillary blood tests for bovine tuberculosis (Tb). METHODS: Ninety 6-8-week-old red deer fawns were randomly allocated to three equal groups of 30, and received either a 1-ml S/C injection of either a commercially available whole-cell killed vaccine with a mineral-oil adjuvant (COM), or a live attenuated M. ptb experimental vaccine with a lipid adjuvant (EXP), or were unvaccinated controls. Ten weeks later (Week 10), all 90 fawns received an oral challenge with approximately 10(8) cfu of a bovine strain of M. ptb daily for 4 days. The fawns were regularly weighed and monitored for clinical signs of Johne's disease, and regularly blood-sampled and tested for antibodies to M. ptb, using the Paralisa test, an IgG1 ELISA, and for antibodies to Mycobacterium bovis, using a similar test. A mid-cervical tuberculin skin test (MCT) was administered at Week 23, and comparative cervical skin tests (CCTs) were administered at Weeks 37 and 57. All animals were electively killed at Week 59, injection sites inspected, gastrointestinal tracts examined for gross lesions, and samples taken for culture and histopathology. RESULTS: There were no clinical cases of Johne's disease but, at slaughter, more gross lesions in intestinal lymph nodes were observed in Control (20%) than COM animals (0%; p<0.05). This latter group also had less severe histopathological lesions in samples of intestines and lymph nodes compared with the Control group (p<0.05), but not deer in the EXP group. Over 89% of deer in all three groups were shown by culture to be infected with M. ptb, while only 21-33% of faecal samples were culture-positive. Time to positive culture was longer for COM vs EXP and Control groups (p<0.01), reflecting fewer M. ptb organisms in samples from the ileocaecal valve (ICV) in that group. Almost all (>or=90%) deer reacted to the MCT at Week 23, and there were no significant differences between groups. One or two deer in each group were classified as Tb reactors to the CCT at Week 37, and none were classified as Tb reactors to the CCT at Week 57. At the time of challenge, over 50% of deer in the COM group were classified as positive (9/28) or suspicious (7/28) for M. ptb antibodies in the Paralisa test, one animal in the EXP group was classified as suspicious, and all the Controls were negative. From Week 23 to the end of the trial, 25/28 (89%) deer in the COM group were Paralisa-positive or -suspicious. The proportion of animals in the EXP and Control groups that were Paralisa-positive peaked at Week 39 (60% and 55%, respectively). The majority of deer in the COM group had significant levels of antibody to M. bovis 10 weeks after vaccination, while the proportion of M. bovis-antibody positive Control deer rose gradually throughout the trial, reaching 23/30 (77%) at slaughter. Injection-site lesions in COM deer ranged from 10-38 mm in diameter 4 weeks after vaccination, and then resolved. Minimal injection-site lesions were observed in EXP deer. At slaughter, 14 months after vaccination, 19/28 deer in the COM group had 5-15-mm nodules that were easily trimmed from the carcass. CONCLUSIONS: The experimental challenge with M. ptb produced subclinical Johne's disease in the majority of deer, but did not cause any clinical disease. The number and severity of gross and microscopic lesions was significantly reduced in the COM compared with Control and EXP groups; vaccination of the EXP group did not appear to give significant protection. Deer vaccinated with the commercial vaccine are likely to give a false-positive reaction to the MCT but should have an avian reaction to the CCT, if it is carried out >12 months after vaccination. Most of the deer vaccinated with the commercial vaccine produced significant levels of antibodies against both M. ptb and M. bovis, which interfered with ancillary Tb tests. If this vaccine or similar oil-based vaccines are used on deer farms in the future, it may be advisable to only vaccinate animals destined for slaughter, that would not need to be Tb-tested, but would be 'works-monitored' for evidence of Tb instead.

The rate of alveolar-capillary uptake of sevoflurane and nitrous oxide following anaesthetic induction.

The rate of anaesthetic gas uptake from the breathing system has been extensively measured, but this does not reflect the true rate of early gas uptake by pulmonary blood, which drives inhalational induction of anaesthesia. In eight patients undergoing coronary bypass surgery, we measured the rate of alveolar-capillary uptake of anaesthetic gases up to 30 min following introduction of 0.5% sevoflurane and 33% nitrous oxide using the reverse Fick method, in which blood partial pressures were measured using a headspace equilibration technique. Simultaneous measurements of gas uptake from the breathing system were made by indirect calorimetry. Measured rates of sevoflurane and nitrous oxide uptake from the breathing system agreed well with previously described formulae when adjusted for inspired concentration. The time course of alveolar-capillary gas uptake followed a characteristic rising curve peaking at 3-4 min and then exponentially declining, and for nitrous oxide was significantly higher than previously estimated.

Intra-uterine transmission of Mycobacterium avium subsp paratuberculosis in subclinically affected red deer (Cervus elaphus).

AIM: To determine the rate of transmission of Mycobacterium avium subsp paratuberculosis (M. ptb) from hind to fetus in utero, and the risk of transmission from dam to fawn via infected colostrum and milk in subclinically affected red deer hinds. METHODS: Hinds were sourced from farms in Otago or Southland and selected for the study if they were positive to the immunoglobulin G1 (IgG1) modified enzyme-linked immunosorbent assay (ELISA) (Paralisa) and exhibited no clinical signs of Johne's disease. The hinds (n=35) were sent to a deer slaughter premises (DSP; n=31) or were killed on-farm (n=4). All post-mortem samples were collected from the fetus first and then from the dam, taking care to avoid cross contamination between samples. Fresh samples (n=185) were collected for culture, and tissue samples (n=72) were collected from 24 hinds and their fetuses for histopathological examination. RESULTS: A total of 24/35 hinds selected were suitable for inclusion in the study. Eighteen of these pregnant hinds were culture-positive for M. ptb, and 14 of these had culture-positive fetuses, representing a transmission rate of 78% (95% confidence interval (CI) =0.58-0.98) from dam to fetus. Of the 16 mammary glands sampled, 11 (69%) were culture-positive for M. ptb while 12/15 (80%) mammary lymph nodes sampled were also culture-positive. CONCLUSIONS: This study demonstrated a high rate of transmission of M. ptb from dam to fetus in red deer, and a potential risk of transmission to fawns suckling from mothers that are subclinically affected with Johne's disease.

Persisting concentrating and second gas effects on oxygenation during N2O anaesthesia.

Theoretical modelling predicts that the concentrating effect of nitrous oxide (N2O) uptake on alveolar oxygenation is a persisting phenomenon at typical levels of ventilation - perfusion (V/Q) inhomogeneity under anaesthesia. We sought clinical confirmation of this in 20 anaesthetised patients. Arterial oxygen pressure (P(aO2)) was measured after a minimum of 30 min of relaxant general anaesthesia with an inspired oxygen (F(I O2)) of 30%. Patients were randomly allocated to two groups. The intervention group had N2O introduced following baseline blood gas measurements, and the control group continued breathing an identical F(I O2) in nitrogen (N2). The primary outcome variable was change in P(aO2). Mean (SD) in P(aO2) was increased by 1.80 (1.80) kPa after receiving a mean of 47.5 min of N2O compared with baseline conditions breathing O2/N2 (p = 0.01). This change was significantly greater (p = 0.03) than that in the control group: + 0.09 (1.37) kPa, p = 0.83 and confirms the presence of significant persisting concentrating and second gas effects.

Prevention of preterm birth: early detection and aggressive treatment with terbutaline.

We evaluated a program for prevention of preterm birth involving early detection and aggressive intervention with subcutaneous terbutaline pump therapy in a high-risk, private patient population. Risk factor screening, frequent cervical examinations, and intensive patient education were used to detect preterm labor before it progressed to an advanced stage. Home terbutaline pump therapy was prescribed for patients with uterine contractions associated with progressive cervical change, after stabilization with IV magnesium sulfate. In this study of 51 patients, home terbutaline pump therapy was successful in 98% of the cases, prolonging pregnancy an average of 6.6 weeks. Mean gestational age at delivery was 37 +/- 1.4 weeks, and infant birth weight averaged 3 kg. Only 22% of infants required admission to the neonatal intensive care unit, with a mean length of stay of 7.25 days. Population factors in this compliant, well-educated patient group may have contributed to the positive outcomes achieved.

Salvage of exposed arteriovenous hemodialysis fistulas.

Arteriovenous fistulas constructed with an interposed segment of expanded polytetrafluoroethylene (PTFE) have been used successfully for long-term hemodialysis, but ultimately these fistulas may fail because of graft thrombosis, infection, or pseudoaneurysm. A PTFE graft may become exposed from skin necrosis at an area of repeated puncture for hemodialysis or from wound breakdown at a site of thrombectomy. Removal of an exposed PTFE graft has heretofore been considered inevitable, especially if a suture line is involved, because of the risk of hemorrhage and infection. We describe coverage of an exposed graft by a simple full-thickness skin flap that is locally rotated and report the successful salvage of five fistulas by this technique. Thus the concept that an exposed graft is infected and must be removed may not always be correct.

Increased C1q binding and arthritis in primary biliary cirrhosis.

Using the C1q binding assay, circulating immune complexes were detected in 31 of 50 (62%) patients with primary biliary cirrhosis and 17 of these had arthritis. This took the form of a seropositive inflammatory polyarthritis in 12 of 18 patients with C1q binding greater than or equal to 20%, whereas a milder seronegative arthritis associated with scleroderma and Raynaud's phenomenon was found in five of 13 patients with C1q binding < 20%. Only two of the 19 patients with normal binding had arthritis and this was of a mild and transient nature. There was a positive correlation between C1q binding and the serum concentrations of IgG and IgM. Results also supported the hypothesis that circulating immune complexes may be involved in the development of arthritis in patients with primary biliary cirrhosis.

IgA and C3 complement in the uninvolved skin in dermatitis herpetiformis after gluten withdrawal.

IgA deposits in the skin in 53 patients with dermatitis herpetiformis (DH) have been studied in relation to treatment. In 19 patients the disorder was controlled by a gluten-freen diet (GFD) alone, in 13 patients by dapsone and GFD and in 18 by dapsone alone. In 3 patients the skin disorder became insignificant and required no treatment. Of the patients taking a GFD alone, six had been clear of skin lesions for 7 years, 5 for 3--5 years, and 8 for periods of 6 months--3 years. IgA deposits were found in all patients in an initial biopsy in a second biopsy after treatment for periods varying from 1 to 7 years. There was no difference in the quantity of IgA, as assessed by the amount of fluorescence, whether patients were controlled with a GFD alone, GFD and dapsone, dapsone alone, or in those in clinical remission. The C3 component of complement was present in the skin in 3 of the 19 patients (16%) controlled by a GFD alone, 6 of the 13 patients (46%) of those controlled by a GFD and dapsone, and in 12 of 18 (66%) of the patients taking dapsone alone, and in one of the patients in clinical remission.

Multiple immune complexes and hypocomplementaemia in dermatitis herpetiformis and coeliac disease.

Circulating immune complexes have been detected in 100% of 59 patients with dermatitis herpetiformis (D.H.), and in 100% of 27 patients with coeliac disease (C.D.). Three methods for detecting immune complexes were employed: radiobioassay, which gave an incidence of 77% in D.H. and 81% in C.D.; C1q binding activity, with which the incidence was 83% and 96%, respectively; and precipitation with 4% polyethylene glycol (69% positivity in D.H., 100% in C.D.). The immune complexes in D.H. and C.D. were compared with those in sera from 23 patients with systemic lupus erythematosus (S.L.E.). Multiple complexes of differing properties were found in D.H. and C.D. but not in S.L.E. The varying nature of the complexes in D.H. and C.D. may account for the damage to different tissues (skin, small intestine, reticuloendothelial system). Low third component of complement was found in 49% and low C4 in 20% of D.H. patients. C3 hypocomplementaemia was found in 26% of patients with C.D.