The relationship between meal composition and long-term diet choice.

When animals are offered a choice of feeds that are nutritionally complementary, they are able to select a consistent combination of these feeds over long periods of time. Analysis of how such consistent diet choice is achieved, in terms of short-term feeding behavior, may further our knowledge of how animals regulate nutrient intake. Previous work, on meal pattern analysis and on nutrient synchronization, led us to hypothesize that animals may select a consistent diet within a meal. In three experiments cows were offered a choice between high- (H) and low- (L) protein feeds and short-term feeding behavior data were collected using computerized feeders. Feeding behavior was first analyzed in terms of visit characteristics. A greater average daily intake of H, relative to L, was more closely related to the ratio of H visits to L visits than to differences in the intake per visit to feeders supplying H or L. Individual meal criteria were estimated using a mixed-distribution model, and visits were clustered into meals. Cows typically had approximately six meals per day. The observed frequency distribution of meal composition, in terms of the proportion of visits to H feeders, was determined. Subsequently, the observed visits were randomly reclustered into bouts consisting of the same number of visits as were observed in meals, and the frequency distribution of random bout composition was calculated. If frequency distributions of meals and random bouts coincide, then this is evidence that cows do not regulate diet choice within a meal. Comparison of the frequency distributions of meals and random bouts provided no evidence that cows attempted to achieve their long-term average diet composition within a meal. We also investigated whether cows tried to achieve a consistent diet choice within a meal by adjusting their intake per visit, depending on the feed type visited and the proportion of visits to H feeders in a meal. There was no evidence that this occurred. In conclusion, our analyses have shown that cows did not attempt to select within a meal a consistent diet in terms of protein to energy ratio. Indeed, our data and the literature suggest that the timeframe over which the intake of energy and protein is regulated must be greater than a meal in a number of animal species.

The use of mixed distribution models to determine bout criteria for analysis of animal behaviour.

Feeding behaviour consists of feeding events, separated by non-feeding intervals. Feeding events are often clustered into bouts, which may be called meals. Grouping feeding events into meals requires the determination of a bout or meal criterion, that is, the longest interval accepted as part of a meal. Tolkamp & Kyriazakis (1999a) proposed a three-Gaussian model to estimate meal criteria. The three Gaussians each described the frequency distribution of the log(e)-transformed lengths of a population of intervals. These populations were thought to be: (1) short intervals within meals; (2) intervals within meals during which animals drink; (3) intervals between meals. This model predicted that the probability of an animal starting a meal would first increase, and then decrease with time since the last meal. This contrasts with expectations based on the satiety concept, which predicts that the probability of an animal starting a meal will increase with time since the last meal. This discrepancy is related to the symmetrical nature of the Gaussian distribution. Alternatively, the two-parameter Weibull distribution can take a skewed form and perhaps is more suitable to describe the different populations of intervals. In this study, models consisting of combinations of Gaussian and Weibull distributions were examined for their suitability to describe the observed feeding behaviour of cows. Weibulls did not improve the description of the populations of within-meal intervals, compared to Gaussians. However, the Weibull distribution was found to describe the between-meal population of intervals statistically better than the Gaussian. Additionally, this inclusion of a Weibull, as opposed to a Gaussian, resulted in predictions that were in better agreement with the satiety concept over the entire range of interval lengths observed. A model based on Gaussians to describe the within-meal populations of intervals and a Weibull to describe the population of between-meal intervals is, therefore, proposed. This model leads to biologically more satisfactory estimates of bout criteria than previous models and is likely to be applicable both across species and behaviours.

Changes in epithelial lining fluid albumin associated with smoking and interstitial lung disease.

Albumin is an important plasma protein which is useful in the assessment of in vivo membrane permeability in the lung. In subjects with interstitial lung disease (ILD) the relationship between albumin recovered from bronchoalveolar lavage (BAL) and other markers of inflammatory activity may provide useful information of the pathogenesis of the disease process. Unfortunately, its measurement is hampered by the variable dilution in BAL fluid. In this study, urea was used as a marker of epithelial lining fluid (ELF) dilution allowing the calculation of an apparent epithelial lining fluid volume and adjusted albumin content. We examined the relationship between ELF albumin content and BAL cell counts, immunoglobulin content, respiratory function tests and gallium lung scans in both smokers and nonsmokers with and without interstitial lung disease. Forty seven subjects with connective tissue disease and interstitial lung disease and 51 subjects with either connective tissue disease but no pulmonary involvement or non pulmonary malignancy (18 current smokers) underwent BAL, gallium lung scans and respiratory function tests. The subjects with ILD were further subdivided into those with active ILD or bronchiolitis using cluster analysis. In smokers without ILD an increased ELF volume and a decrease in ELF albumin were found. Increased ELF albumin was related to increased age. In subjects with ILD, increased albumin was strongly correlated with increased BAL lymphocyte absolute and differential counts, which overwhelmed any age or smoking effect. These findings suggest a possible causal relationship between lung vascular permeability and lymphocyte numbers in subjects with interstitial lung disease and reinforce the need to consider smoking and age as confounding factors in BAL analysis.

Unilateral carotid stenosis and impaired cerebral hemispheric vascular reserve.

Single photon emission computed tomography (SPECT) scanning with 99TcHMPAO (Ceretec) was used to demonstrate regional cerebral blood flow (rCBF) in sixteen patients with hemodynamically significant unilateral carotid stenosis. All patients were demonstrated by cerebral computed tomography to be without cerebral infarction. When dysautoregulation was induced by intravenous acetazolamide, eight patients demonstrated a perfusion defect ipsilateral to carotid stenosis. Repeat SPECT scanning with dysautoregulation following carotid endarterectomy showed improved or normal cerebral perfusion in seven of these patients. The results suggest that a hemodynamic mechanism for cerebral ischemic events, including transient ischemic attacks (TIA) may be more common than previously suspected. Carotid disobliteration usually improves ipsilateral cerebrovascular reserve in patients with a preoperative perfusion defect.

Smoking-induced changes in epithelial lining fluid volume, cell density and protein.

Bronchoalveolar lavage has proved a useful research technique for recovering cellular and molecular contents of the lower respiratory tract. Because the recovered fluid is variably diluted, an accurate estimation of molecular and cellular concentrations can only be made if the epithelial lining fluid volume recovered is also known. It has been suggested that smoking may alter epithelial lining fluid volume by reducing clearance or by stimulating production and, thus, affect the interpretation of bronchoalveolar lavage studies. In this study, urea was used as an endogenous marker of epithelial lining fluid volume in a comparison of 26 smokers and 31 nonsmokers. The mean epithelial lining fluid volume recovered from smokers was significantly greater than that of nonsmokers (2.4 +/- 1.40 ml vs 1.2 +/- 0.75 ml, p less than 0.005). The total cellular concentration in the bronchoalveolar lavage fluid in smokers was also greater (94.2 +/- 46 x 10(6) vs 33.9 +/- 21.5 x 10(6) cells per 300 ml lavage), even when corrected for bronchoalveolar lavage volume recovered (63.1 +/- 32.5 x 10(6) vs 24.9 +/- 13.3 x 10(6) cells per 100 ml recovered lavage fluid). This was true for macrophage, lymphocyte and neutrophil cell numbers. However, when corrected for the apparent epithelial lining fluid volume, only the macrophage count remained significantly higher in the smokers compared with nonsmokers (30.66 +/- 20.7 x 10(6) vs 18.21 +/- 8.6 x 10(6) macrophages.ml-1 ELF). In addition, concentrations of albumin and immunoglobulin M (IgM) were significantly lower in smokers after correction for epithelial lining fluid volume. These results highlight smoking as a confounding factor in the interpretation of bronchoalveolar lavage data.(ABSTRACT TRUNCATED AT 250 WORDS)

The differing patterns of interstitial lung involvement in connective tissue diseases.

Connective tissue disorders (CTD) have a relatively high incidence of pulmonary complications but their delineation has been hampered by difficulties inherent in the diagnostic techniques. One fresh approach to this problem is based on a clustering method that uses data from 8 separate investigations to cluster the patients into 4 distinctly separate categories representing normal nonsmoker, normal smokers, those with active interstitial lung disease and those with bronchiolitis. Using this method, a large group of patients with CTD have been examined to assess the nature and extent of their pulmonary complications. Subjects in the first cluster had a normal test profile across all variables, and included no current active smokers. The normal smoking cluster contained only smokers who had a high total lavage cell number with a relative increase in macrophages and a decrease in lymphocytes. In this group, all respiratory variables were normal with the exception of a mildly depressed DLCO, also known to be associated with smoking. The general characteristics of the active interstitial lung disease cluster was a markedly depressed DLCO indicating impaired gas exchange, and elevated gallium index, bronchoalveolar lavage (BAL) cell number and neutrophil and lymphocyte percentages, all indicating an active inflammatory process. However more careful analysis of this group suggested the presence of 2 subgroups, one with a lymphocytic alveolitis, and another with a neutrophilic alveolitis. The bronchiolitis cluster characteristics were a markedly depressed maximal mid expiratory flow rate and raised BAL lymphocyte percentage and gallium index. The distribution of patients within the cluster groupings suggested that Sjögren's syndrome, often an accompaniment of other CTD, is most frequently associated with pulmonary disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative pulmonary gallium scanning in interstitial lung disease.

The mechanisms responsible for gallium uptake in chronic, non-infective, diffuse lung disease are not completely understood. This study attempted to clarify some of them. A lung/liver gallium index was calculated in 113 subjects, some normal and some with various interstitial lung diseases, predominantly those associated with connective tissue disease. The mean gallium index was significantly higher in the groups with active interstitial lung disease (5.7) and non-infective bronchiolitis (4.1) compared with non-smoking normals (3.0; P less than 0.05). To investigate the mechanisms responsible for gallium uptake, the gallium index was correlated with bronchoalveolar lavage findings, respiratory function tests and clinical features. Significant correlations (P less than 0.05) were found with age in non-smoking normals; lavage macrophages in smoking normals; age but no other parameter in bronchiolitis; lavage lymphocytes, lavage albumin and improvement in diffusion capacity for carbon monoxide in those with active interstitial lung disease. It is concluded that in normal smokers gallium uptake may be due to a macrophage-mediated process. Gallium uptake in active interstitial lung disease associated with connective tissue disease appears to be an immunological process in which transport and retention of gallium is associated with that of albumin.

Use of technetium-HMPAO to demonstrate changes in cerebral blood flow reserve following carotid endarterectomy.

Cerebral perfusion through stenosed internal carotid arteries is usually maintained by autoregulation. However, flow reserve may be reduced, suggesting hemodynamically significant stenosis, and such reduction should be improved by carotid endarterectomy. This concept was studied in 20 subjects with unilateral internal carotid artery stenosis (major stenosis greater than or equal to 70%, minor stenosis less than or equal to 50%). Thirteen had experienced recent transient ischemic attacks and seven had no definite focal symptoms. Subjects underwent Tc-HMPAO cerebral SPECT during acetazolamide dysautoregulation before and after internal carotid endarterectomy. Nine (45%) had perfusion defects that improved after surgery, suggesting surgery had improved cerebral flow reserve. Seven had defects that did not improve after surgery. Four had worsened or new defects after surgery, suggesting perioperative infarcts. The relatively large proportion of patients with improved cerebral blood flow reserve after surgery suggests that this technique may have a significant role to play in assessing which patients might benefit from carotid endarterectomy.

Interstitial lung disease associated with connective tissue diseases. The use of statistical structure analysis in model development.

Interstitial lung disorders associated with the connective tissue diseases are thought to be quite common, but their precise analysis is fraught with difficulty because of the absence of a Gold Standard that, short of open lung biopsy, is not available. Analysis is hampered by the biologic variability in test results, large overlap between the normal and the disease population for individual tests, the confounding effect of smoking, and the complexities of viewing multidimensional data. In order to better define the pattern of the lung involvement, an entirely different approach has been adopted that is based on the use of graphic and clustering techniques to define the multivariate structure inherent in the data, then discriminant analysis to assign patients into distinct clusters. Using this approach it has been possible to group patients into four distinct clusters based on the result of respiratory function studies, gallium lung scan, bronchoalveolar lavage, and smoking status. These clusters are a normal smoking cluster and a normal nonsmoking cluster, a cluster of patients with active ILD, and a cluster with bronchiolitis. The validity of this method has been verified, and an algorithm has been developed that allows the assignment of any new patient entering the study into one of these clusters. This type of analysis offers a valuable new approach to the categorization of patients into distinct groups based on the results of multiple investigations.

Bone scanning in the early assessment of nasal bone graft viability.

This study examined the role of radionuclide bone scanning in the early assessment of free autologous cancellous bone grafts in augmentation rhinoplasty and compared the failure rates of grafts taken from the calvaria and ilium. Twenty patients had three-phase bone scanning of the facial regions performed between 2 and 15 wk after rhinoplasty, and a comparison was made with the results of clinical assessment and X-ray findings 3 mo after surgery. Eleven patients had grafts taken from the calvaria and nine had iliac grafts. On lateral views, bone graft uptake of isotope, which was less than or equal to the adjacent soft tissue, was found in 2 out of 20 patients and this finding predicted subsequent graft failure as measured by clinical assessment and X-ray evidence of bone resorption. Both failures had grafts taken from the calvaria while none from the ilium failed. These failure rates, however, were not significantly different.

Corticosteroid effects on proximal femur bone loss.

Prolonged high-dose corticosteroid therapy is known to result in an increased risk of osteoporotic fracture. Reductions in bone density have been demonstrated at the distal radius and lumbar spine in patients receiving corticosteroids; however there have been few studies of bone density in the hip (the most important site of osteoporotic fracture) in this context. To examine the effect of corticosteroids on the hip we measured bone mineral density (BMD) by dual-photon absorptiometry at three sites in the proximal femur as well as the lumbar spine in 32 patients aged 18-77 years who had been treated with corticosteroids (mean daily prednisone dose 12.7 mg) for up to 23 years. BMD was compared with the expected values using age regressions in normal subjects. BMD was significantly reduced in the femoral neck, Ward's triangle, and the trochanteric region (p less than 0.001 all sites). In the lumbar spine BMD was also significantly reduced (p less than 0.001). We also measured BMD serially in 29 patients receiving corticosteroids. BMD measurements were made in 12 patients who had already been treated with long-term corticosteroids at the time of first BMD measurement (chronic group) and from the commencement of corticosteroid therapy in 17 patients (acute group). The mean (+/- SEM) change in BMD (g/cm2 per year) in the lumbar spine and femoral neck were 0.006 +/- 0.006 and -0.021 +/- 0.007, respectively, for the chronic group and -0.02 +/- 0.005 and -0.039 +/- 0.006 for the acute group.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone density of élite female athletes with stress fractures.

To investigate whether stress fractures occurring in élite female athletes are related to reductions in bone mineral density (BMD), we measured BMD in nine athletes with such fractures and nine athletes without fractures who were matched for age, weight, height and sport. BMD was measured in three regions: upper limbs (distal radius), axial skeleton (lumbar spine) and lower limbs (femoral neck) by photon absorptiometry. The number of menses per year was significantly less (P less than 0.04) and the age of menarche was significantly delayed (mean +/- SD; 16.1 +/- 0.4 v. 14.4 +/- 1.5 years, P less than 0.02) in the fracture group compared with the non-fracture group. There was no significant difference in BMD between the two groups at any of the measurement sites. Moreover although the fractures occurred mainly in lower limb bones, at sites characterised by predominantly cortical bone, all athletes had femoral neck BMD values within the 95% confidence limits for normal non-athletic women. We conclude that stress fractures in élite female athletes are largely independent of BMD.

Reproducibility of radionuclide left ventricular ejection fraction in patients awaiting cardiac transplantation.

Radionuclide-derived left ventricular ejection fraction (LVEF) is used to assess LV systolic function, to follow trends in the natural history of dilated cardiomyopathy, and to prioritize patients waiting for cardiac transplantation. Reproducibility of LVEF at extremely low levels has not, however, been reported. To assess the reproducibility of radionuclide LVEF at levels below 0.30 EF U, 17 highly symptomatic patients (NYHA Class III/IV) with dilated cardiomyopathy were studied on two occasions, 72 hours apart. Sequential scans were analyzed by two independent observers. Mean LVEF was 0.18 +/- 0.06 U (scan 1) and 0.17 +/- 0.06 U (scan 2). Interoperator reproducibility (SD) was 0.03 U (R = 0.76), interscan reproducibility (SD) was 0.03 U (R = 0.62), and overall reproducibility (SD) was 0.04 U (R = 0.50). The interobserver variation of 0.03 (actually 0.027) was just over one half that seen in normal volunteers (variation 0.05, n = 29) studied previously in this department. A change of greater than or equal to 0.08 U (2SD) in either direction is highly likely to represent a real change in LV function in those with LVEF less than or equal to 0.30 units, compared with the change of at least 0.10 units required in those with normal LV function. Lower interobserver and interscan reproducibility should be taken into account when interpreting sequential scans in patients with severe LV dysfunction.

The presence of Sjögren's syndrome is a major determinant of the pattern of interstitial lung disease in scleroderma and other connective tissue diseases.

A number of patients with scleroderma, Sjögren's syndrome and other connective tissue diseases (CTD) were assessed to ascertain the prevalence of respiratory abnormalities as defined by bronchoalveolar lavage (BAL), standard respiratory function studies and gallium scan of the lung, and the relationship of these abnormalities to the presence or absence of dyspnea. These results suggest that respiratory symptoms are very common in CTD and in scleroderma, particularly if Sjögren's syndrome is also present. Our findings also suggest the presence of 2 patterns of interstitial lung involvement in scleroderma. In scleroderma alone this appears to be characterized by the presence of increased neutrophil proportions in the BAL, decreased DLCO, and no increase in gallium uptake within the lung. Where scleroderma is associated with Sjögren's syndrome, there is an increase in the proportion of lymphocytes in the BAL and respiratory symptoms are very prominent, the latter associated with an increase in gallium uptake within the lung. This suggests that Sjögren's is a major determinant of the pattern of interstitial lung disease seen in CTD.

Effects of low dose corticosteroids on bone mass in rheumatoid arthritis: a longitudinal study.

Low dose corticosteroids are effective in suppressing synovitis in rheumatoid arthritis (RA), but there remains concern about their side effects, particularly osteoporosis. To examine the effects of low dose corticosteroids on bone loss in RA bone mineral density (BMD) was measured in the lumbar spine and hip for up to two years in 15 patients treated with these agents (mean dose prednis(ol)one 6.6 mg/day). 15 patients not receiving them, and 15 age matched controls. The initial BMD at both skeletal sites was significantly reduced in both patient groups compared with controls. The mean change in bone density was 0.2, 0.1, and -0.1% a year in the spine and -2.0, -1.9, and -1.0% a year in the hip respectively for the three groups. These rates of bone loss were not significantly different between groups at either site. These findings suggest that low dose corticosteroid treatment in RA is not associated with an increased risk of osteoporosis.

Muscle strength, physical fitness, and weight but not age predict femoral neck bone mass.

Hip fractures are the most serious complication of osteoporosis. Although low proximal femoral bone mineral density (BMD) does not cause hip fractures directly, it is clearly a prerequisite for the increased risk associated with aging. To investigate the mechanism of the age-related decline in proximal femoral bone mineral density, we have examined the relative importance of muscle strength, physical fitness, and body mass index (BMI) in addition to age in the determination of proximal femoral BMD in 73 healthy female volunteers age 20-75 years. Muscle strength was an independent predictor of BMD at all three sites in the proximal femur as well as in the lumbar spine and forearm; proximal femur BMD was also predicted by physical fitness. BMI was a positive predictor of bone mass at all sites. In the proximal femur, age was not an independent predictor of BMD at any site. In postmenopausal women muscle strength was a significant predictor of bone mass in the femur and forearm, but not in the spine. However, BMI remained predictive of bone mineral at all sites. Muscle strength, physical fitness, and weight appear to exert independent effects upon bone mass. Age effects may be mediated indirectly through associated changes in these factors. The integrated physical load on the skeleton may be a final common pathway.

Effects of tobacco use on axial and appendicular bone mineral density.

Tobacco use has been identified as being a risk factor for the development of osteoporosis. While some data have suggested an effect on peripheral bone mass there are little previous data examining the role of tobacco use in axial skeletal bone loss. We examined tobacco use in relation to lumbar spine and proximal femur bone mineral density and forearm bone mineral content in 203 women. Data from identical twin pairs, comprising a subgroup of the larger group as well as a small number of male twin pairs, was also analyzed. The data show a difference in lumbar and proximal femur BMD of 0.03 and 0.06 g/cm2 respectively between smoking and nonsmoking identical twins. There was however no difference in the cross-sectional studies and no significant deleterious effect detected of tobacco use on forearm bone mineral content. The effect of smoking on lumbar and proximal femur bone mineral density, in identical twins discordant for tobacco use, was equivalent on average to 3 to 4 years of normal postmenopausal bone loss.

Noninvasive predictors of cardiac events after myocardial infarction. Complementary value of exercise testing and signal-averaged electrocardiography.

Signal-averaged electrocardiography, resting radionuclide ventriculography and Holter monitoring were performed prior to hospital discharge, to assess their value in predicting recurrent cardiac events in 210 survivors of acute myocardial infarction. In addition, 153 of these patients also underwent exercise radionuclide ventriculographic assessment. During median follow-up of 14 months (6-24 months), there were 16 cardiac deaths, 15 patients had recurrent infarction and 7 patients represented with symptomatic ventricular tachycardia. Cox regression analysis identified independent predictors of 'ischemic events' (death or re-infarction) as a previous history of infarction (p = 0.01), Killip class III-IV (p = 0.03) and an abnormal exercise radionuclide study (p = 0.04); and predictors of 'arrhythmic events' (sustained ventricular tachycardia or sudden death) as an abnormal signal-averaged electrocardiograph (p = 0.01) and left ventricular ejection fraction less than 40% (p = 0.03). Patients with an abnormal signal-averaged electrocardiograph and reduced left ventricular ejection fraction had a 34% incidence of arrhythmic events during the first 6 months compared with a 4% incidence among patients without late potentials. In those patients who underwent exercise testing and signal averaging, 85% of total cardiac events and all cardiac deaths were predicted by an abnormality of either noninvasive test. In addition, exercise testing and signal-averaged ECG were independent predictors of outcome. Hence, using a combination of noninvasive tests, patients can be stratified according to the risk of recurrent life-threatening cardiac events after myocardial infarction; such patients may be suitable for intensive investigation and considered for trials involving active intervention.

Bone mineral density in Australia compared with the United States.

Bone density measurements are currently being performed throughout the world in the diagnosis and management of osteoporosis as well as in research into this major health problem. However, it is not clear to what extent bone mineral density (BMD) values determined by dual-photon absorptiometry at one center can be applied to another. This is particularly relevant for the quantitative comparison of results from studies carried out in different laboratories. Furthermore, many centers now acquiring densitometers may not have the resources to determine their own normal range, relying instead on a "normal" range provided by the manufacturer. The question of the comparability of BMD data obtained in different centers was examined by comparing the normal range for the lumbar spine and proximal femur in 203 normal white Australian women and 892 normal white U.S. women, obtained using the same model densitometer. The two populations were compared according to decade. From superimposition of the Australian individual values on the North American normal ranges, only minor differences between the two populations were seen at any of the sites measured at any decade. None of these minor differences were statistically significant. This study shows a close similarity between BMD values in both the proximal femur and lumbar spine in normal white women in Australia and North America, provided the same model densitometer is used. Thus data obtained from different centers in populations with similar ethnic composition may be compared directly. These findings provide for the first time a sound basis for the quantitative comparison of the at times conflicting studies carried out in widely differing settings around the world.

Cerebral perfusion defects, dysautoregulation and carotid stenosis.

Single Photon Emission Computed Tomography (SPECT), imaging of cerebral blood flow was carried out in ten patients with haemodynamically significant carotid stenosis. Before and after carotid endarterectomy each patient was investigated by 3--dimensional SPECT brain scanning using technetium--hexamethyl propyleneamine oxine (99 mTcHMPAO, ceretec). Brain blood flow was normal before and after operation in 3 patients whose autoregulation was kept intact. Seven patients received acetazolamide to limit cerebral vascular reactivity and in four of these, preoperative perfusion defects were visible. After carotid endarterectomy the ipsilateral perfusion defects were abolished and it is concluded that carotid stenosis can reduce perfusion in the dysautoregulation brain and that carotid reconstruction can restore normal flow.