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Left ventricular mass in the elderly. The Cardiovascular Health Study.

Left ventricular (LV) mass, as estimated from M-mode echocardiography (echo), has previously been shown to be an independent predictor of incident cardiovascular disease morbidity and mortality. We evaluated the relationship at baseline of echo LV mass to relevant cardiovascular disease risk factors and other potential covariates in the Cardiovascular Health Study, multicenter study sponsored by the National Heart, Lung, and Blood Institute of 5201 men and women aged 65 years or older (mean, 73). Two-dimensionally directed M-mode echo LV mass measurements could be obtained in 1357 men and 2053 women (66% of this elderly cohort). Stepwise linear regression analyses of the relationship of echo LV mass to demographic and risk factor, physical activity, electrocardiographic, and prevalent disease variables resulted in a model that explained 37% of the variance for the entire cohort. In order of decreasing importance, factors positively associated with echo LV mass were body weight, male sex, systolic pressure, presence of congestive heart failure, present smoking, major and minor electrocardiographic abnormalities, treatment for hypertension, valvular heart disease, aortic regurgitation by color Doppler, and mitral regurgitation by color Doppler (in men) whereas diastolic pressure, bioresistance (a measure of adiposity), and high-density lipoprotein cholesterol were inversely related to echo LV mass. Although height and weight were both related to LV mass, height added nothing once weight was entered in multiple linear regression analyses. Furthermore, in the multiple regression models, diastolic pressure was inversely and systolic BP positively related to LV mass, with similar magnitudes for their coefficients. In consonance with these findings, pulse pressure was positively related to LV mass in bivariate analyses. Multiple linear regression analyses explained less of the variance for ventricular septal thickness (R2 = .13) and LV posterior wall thickness (R2 = .14) than for LV mass (R2 = .37) and LV diastolic dimension (R2 = .27). Intriguing findings in the elderly Cardiovascular Health Study cohort included the presence of pulse pressure as a positive correlate, and high-density lipoprotein cholesterol as an inverse correlate, of LV mass. Longitudinal studies in the Cardiovascular Health Study cohort will help to clarify the importance of demographic, risk factor, and other variables, and changes in these variables, in predicting changes in echo LV mass and its components as well as the prognostic significance of LV mass in the elderly.

Aged↗

Spatial and temporal processing of threshold data for detection of progressive glaucomatous visual field loss.

OBJECTIVE: To evaluate the effect of spatial and temporal filtering of threshold visual field data on the ability of pointwise linear regression (PLR) to detect progressive glaucomatous visual field loss. METHODS: Longitudinal visual field data (Full-Threshold Program 30-2 test point pattern) were simulated using a computer model of glaucomatous visual field progression. This approach permitted construction of a "gold standard" because matching visual field data without variability could be generated and analyzed. Four clustered progressive defects were produced, consisting of 2, 3, 9, and 18 locations, respectively, each with progression rates of -1 and -2.5 dB/y. Pointwise linear regression was used to identify progressive test locations (criterion for progression of statistically significant slope of < or =-1 dB/y, P<.05). Each visual field series was analyzed after the following 3 procedures: (1) no filtering (unprocessed data), (2) Gaussian spatial possessing (3 x 3 grid), and (3) temporal processing (2 field moving average). The effect of spatial and temporal processing on PLR discriminatory power for progression detection was quantified by comparison with the gold standard. RESULTS: Spatial processing reduced PLR sensitivity to levels below that achieved for analysis of unprocessed data for small progressive defects (< or =9 locations) or at the low true progression rate (-1 dB/y). Under these conditions, spatial processing caused small PLR specificity improvement. Spatial processing only improved PLR sensitivity above unprocessed levels when progressive defects were large and changing rapidly (progression rate of -2.5 dB/y). Temporal processing gave consistent PLR improvement in sensitivity for all defect sizes and true progression rates. Pointwise linear regression sensitivity gain provided by temporal processing allowed progression to be detected 2 to 3 visual fields earlier than for analysis of raw data. Specificity dropped slightly as a result of temporal processing but remained at 89% or above for all conditions studied. CONCLUSIONS: Gaussian spatial processing reduces PLR discriminatory power with low true progression rates or small progressive defect sizes and, therefore, is of limited use for detection of progressive visual field loss. Temporal processing improves the sensitivity of PLR and reduces the number of tests required to detect progressive loss with minimal loss of specificity. CLINICAL RELEVANCE: Image processing techniques can be applied to threshold visual field data to enhance sensitivity or specificity of PLR for the determination of progressive change. This investigation demonstrates that temporal processing may assist with the detection of significant progressive visual field loss with fewer test results than unprocessed data.

Computer Simulation↗

Different relations between infarct size and occluded bed size in barbiturate-anesthetized versus conscious dogs.

The relation between infarct size and occluded bed size in barbiturate-anesthetized (n = 32) and conscious (n = 34) dogs was compared using models of the left anterior descending (n = 43) and circumflex (n = 23) coronary arteries with 2 day old infarcts. Infarct and occluded bed (postmortem coronary arteriography) masses were measured by computerized planimetry of weighed left ventricular rings. For either type of occlusion, infarcts were larger in anesthetized than in conscious dogs (56 versus 33% occluded bed, p less than 0.001), with greater slopes of the linear regressions between infarct size and occluded bed size (p less than 0.001) and less epicardial sparing (p less than 0.05) on topographic mapping. Although arterial and left atrial pressures were similar in the two groups, heart rates were higher in the anesthetized dogs, both before (127 versus 88 beats/min, p less than 0.001) and after (151 versus 109 beats/min, p less than 0.001) occlusion. Myocardial blood flow distribution (radioactive microspheres, n = 33) favored the epicardium in anesthetized dogs, with lower endocardial-epicardial flow ratios pre- and postocclusion. Also, the level of total plasma catecholamines (radioenzymatic assay) was higher in barbiturate-anesthetized (n = 5) than in conscious (n = 5) dogs. Increasing the heart rate in conscious dogs (n = 18) to that of the anesthetized group (139 beats/min) by pacing produced larger infarcts and greater linear regression slopes, as seen in anesthetized dogs. Decreasing the heart rate in anesthetized dogs (n = 7) to that of the conscious group (98 beats/min) by sinoatrial node destruction and pacing resulted in smaller infarcts and lower linear regression slope, as seen in conscious dogs. Thus, the larger infarcts in barbiturate-anesthetized dogs appeared to be related mainly to the tachycardia, although transmural maldistribution of flow and increased circulating catecholamines might have contributed.

Analysis of Variance↗

Transdermal delivery of drugs with differing lipophilicities using azone analogs as dermal penetration enhancers.

Six model drugs were selected for this study based on their degree of lipophilicity as represented by their log P values (range = -0.95 to 3.51). They included 2,4-dihydroxy-5-fluoropyrimidine (5-fluorouracil); 1,3,7-trimethylxanthine (caffeine); [(2-hydroxybenzoyl)amino]-acetic acid (salicyluric acid); 2-hydroxybenzoic acid (salicylic acid); 9 alpha-fluoro-16 alpha-hydroxyprednisolone 16 alpha, 17 alpha-acetonide (triamcinolone acetonide); and alpha-methyl-4-[2-methylpropyl]benzeneacetic acid (ibuprofen). Six dermal penetration enhancers [Azone or 1-dodecylhexahydro-2H-azepin-2-one (1), N-dodecyl-2-pyrrolidinone (2), N-dodecyl-2-piperidinone (3), N-dodecyl-N-(2-methoxyethyl)acetamide (4), N-(2,2-dihydroxyethyl)dodecylamine (5), and 2-(1-nonyl)-1,3-dioxolane (6)] were tested in vitro across full-thickness hairless mouse skin with each of the drugs. The relationship between lipophilicity (log P) and efficacy (represented by the enhancement ratio of flux) of the drugs when coadministered with the enhancers was examined using linear regression. The three cyclic enhancers (1-3) exhibited linear relationships, indicating that they were more effective at enhancing the penetration of hydrophilic drugs R2 = 0.8997 for 1, 0.8801 for 2, and 0.804 for 3) when evaluating all the model drugs except triamcinolone acetonide (TA). The two acyclic enhancers (4 and 5) showed a similar relationship, but their correlation coefficients were lower at 0.6463 for 4 and 0.6213 for 5. Studies with the dioxolane (6) yielded no relationship between the lipophilicity of the drug and the efficacy of the enhancer, with an R2 of 0.002. Overall, 6 was the least effective enhancer studied. The steroid TA was not included in the linear regression analysis. Of the six model drugs studied, TA exhibited the largest increase in transdermal delivery when enhancers 1-6 were used.

Animals↗

Effects of age on hormonal and ultrasound markers of ovarian reserve in Chinese women with proven fertility.

BACKGROUND: A woman's fertility is remarkably reduced with increasing age. Reproductive age can be assessed by a number of ovarian reserve tests. There are very few studies addressing the effects of age on these markers in fertile women, especially in Asia. METHODS: On the second to fourth day of the menstrual period, fertile Chinese women with regular monthly cycles and no history of ovarian surgery underwent a transvaginal scan with colour Doppler to determine ovarian volume, total antral follicle count (AFC) and mean peak systolic velocity (PSV) of ovarian stromal blood flow, and their serum FSH and inhibin B levels were checked. RESULTS: Out of 145 women scanned, 119 were included in the final analysis. AFC is the only ovarian reserve marker that was significantly different among four age groups (</=20, 21-30, 31-40 and >40 years). AFC had the best correlation with the age of the women, followed by FSH level and ovarian volume. The decline of AFC with age was 3.8% per year (95% confidence interval 2.7-4.9%) in the conventional linear regression model, which was not improved by the biphasic linear regression model. CONCLUSION: Of the parameters tested, AFC showed the best correlation with women's age and declined linearly at a rate of 3.8% per year.

Adolescent↗

Oxygen consumption and pressure-volume area of abnormal contractions in canine heart.

Oxygen consumption rates (VO2) of isovolumic and normally ejecting contractions are closely correlated with their systolic pressure-volume areas (PVA) in a stable canine left ventricle. PVA is the area in the pressure-volume (PV) diagram that is circumscribed by the end-systolic and end-diastolic PV relation curves and the systolic segment of the PV loop trajectory. We studied whether VO2s of abnormally loaded ejecting contractions were similarly correlated with their PVAs. Various abnormally ejecting contractions were produced in the left ventricle of the cross-circulated canine heart. VO2 and PVA data of the various abnormal contractions and the isovolumic and normally ejecting contractions were pooled together, to which the correlation and regression analyses were applied. They could be fitted by a linear regression analyses were applied. They could be fitted by a linear regression line with a high correlation coefficient and a slight scatter in each heart. We therefore conclude that PVA is the primary correlate of VO2, not only in the isovolumic and normally ejecting contractions but also in various abnormally loaded contractions in a given canine left ventricle with a stable contractile state.

Animals↗

Fentanyl pretreatment modifies anaesthetic induction with etomidate.

Haemodynamic changes and side-effects of induction of anaesthesia with etomidate were evaluated in 60 ASA Class I or II patients. The objective was to find an optimal pre-induction dose of fentanyl which eliminated haemodynamic changes and side-effects during induction and intubation without introducing other problems. Patients were randomly assigned to four groups according to the pretreatment dose of fentanyl (Group I = 2 ml normal saline; Group II = 100 micrograms of fentanyl; Group III = 250 micrograms of fentanyl; Group IV = 500 micrograms of fentanyl) administered intravenously five minutes prior to induction of anaesthesia with etomidate, 0.3 mg/kg. There was an increasing incidence of apnoea (53, 87, 87 and 100% in Groups I-IV respectively) and a decreasing incidence of myoclonus (60, 33, 13 and 0% in Groups I-IV respectively) and injection pain (53, 13, 7 and 0% in Groups I-IV respectively), P less than 0.002 chi-square test for linear trends, with increasing fentanyl dosage. The incidences of postoperative nausea and vomiting were similar in the four groups. There were also significant linear regression relationships (P less than 0.01 ANOVA for linear regression) between increasing doses of fentanyl administered before etomidate and the prevention of increases in systolic blood pressure and heart rate during the induction-intubation sequence. The data demonstrate that increasing pre-induction doses of fentanyl are more effective at minimising side-effects and preventing increases in systolic arterial blood pressure and heart rate but also increase the incidence of apnoea during induction. The results suggest that 500 micrograms of fentanyl is an ideal pretreatment dose in fit patients prior to anaesthetic induction with etomidate.

Adult↗

Uric Acid Levels Are Associated with Bone Mineral Density in Mexican Populations: A Longitudinal Study.

Background: Inconsistent epidemiological evidence between uric acid (UA) and bone mineral density (BMD) has been observed. Therefore, we evaluated the association between UA and BMD in Mexican adults. Methods: This analysis was conducted on 1423 participants from the Health Workers Cohort Study. We explored cross-sectional associations using linear regression and longitudinal associations using fixed-effects linear regression by sex and age groups (<45 and &#x2265;45 years). Results: In females <45 years old, the cross-sectional analysis showed that UA levels were positively associated with total hip BMD. However, in the longitudinal analysis, we observed a negative association with the femoral neck and lumbar spine BMD. In contrast, in males <45 years old, we found an increase in total hip and femoral neck BMD in the groups with high levels of UA in the longitudinal association. On the other hand, in females &#x2265;45 years old, we observed a longitudinal association between UA and loss of BMD at different sites. We did not observe an association between UA levels and BMD in males &#x2265;45 years old. Conclusions: Our results suggest higher serum UA levels are associated with low BMD at different skeletal sites in Mexican females. Further studies are needed to delineate the underlying mechanisms behind this observation.

Male↗

CD4 lymphocyte enumeration in patients with human immunodeficiency virus infection using three-colour and four-colour dual-platform flow cytometry: an inter-laboratory comparative evaluation.

INTRODUCTION: This study aims to evaluate the correlation and agreement between 2 methodologies of CD4 lymphocyte enumeration. MATERIALS AND METHODS: Fifty-two blood samples from patients with human immunodeficiency virus (HIV) infection were sent for CD4 lymphocyte enumeration at 2 major hospitals using dual-platform flow cytometry where the absolute lymphocyte counts were determined on separate haematology analyzers. CD4 cell enumeration was accomplished using 3-colour flow cytometry on the FACSCalibur cytometer (Becton Dickinson) in Hospital A and 4-colour flow cytometry on the Coulter Epic XL cytometer (Beckman Coulter) in Hospital B. The percentages and absolute counts of CD4 lymphocytes obtained were analysed using both linear regression and Bland-Altman plots. RESULTS: On linear regression plots, the total white cell counts, absolute lymphocyte counts, CD4 lymphocyte percentages and absolute CD4 counts from the 2 hospitals correlated well with correlation coefficients, r > 0.95. On the Bland-Altman plots, there was a mean difference of 0.13 x 10(9)/L and 0.06 x 10(9)/L in the total white cell and absolute lymphocyte counts from the 2 hospitals respectively. The CD4 lymphocyte percentages revealed a mean difference of only 0.05% (95% limits of agreement, -3.6 to 3.7%) but there was a mean difference of 14/uL in the absolute CD4 lymphocyte counts (95% limits of agreement, -113 to 142/uL). CONCLUSIONS: The CD4 lymphocyte percentages obtained using the 3-colour and 4-colour flow cytometry correlated and agreed well. However, the absolute CD4 lymphocyte counts obtained using the dual-platform technique in both the hospitals did not agree well. Hence, absolute CD4 lymphocyte counts from the 2 hospitals cannot be used interchangeably in clinical practice due to poor inter-laboratory comparability.

CD4 Lymphocyte Count↗

The use of evoked potentials for clinical correlation and surgical outcome in cervical spondylotic myelopathy with intramedullary high signal intensity on MRI.

OBJECTIVE: To investigate the use of motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) for clinical significance and surgical outcome in patients with cervical spondylotic myelopathy (CSM) with intramedullary high signal intensity on T2 weighted MRI. METHODS: Forty nine patients were scored according to the modified Japanese Orthopaedic Association (JOA) score for cervical myelopathy. MEP and SEP studies were performed and the results were categorised as normal or abnormal. Thirty nine patients who had received surgical decompression were re-evaluated after 6 months. Surgical outcome was represented by the recovery ratio of the JOA score. RESULTS: Abnormal MEPs were observed in 44 patients (arm: 43; leg: 30). Abnormal SEPs were found in 32 patients: (median: 24; tibial: 23). Patients with abnormal SEPs had a worse JOA score than those with normal SEPs. Thirty nine patients received surgical treatment. Patients younger than 55 had better recovery ratios than those who were 55 or older (p = 0.005, two sample Student's t test). Patients with normal median SEPs also had better recovery ratios than those with abnormal median SEPs (p = 0.007, two sample Student's t test). Among median SEP variables, only N9-20 was significantly associated with recovery ratio (p = 0.016, stepwise linear regression), with age factor controlled (p = 0.025, stepwise linear regression). CONCLUSION: Arm MEP was the most sensitive EP test for detecting myelopathy in patients with chronic CSM. Median and tibial SEPs correlated well with the severity of myelopathy while normal median SEPs correlated with good surgical outcome. Among median SEP variables, only N9-20 correlated with surgical outcome.

Adult↗

Values for the free to total prostate-specific antigen ratio as a function of age: necessity of reference range validation.

OBJECTIVE: To measure the levels of free prostate-specific antigen (PSA), total PSA, and free to total PSA ratio in a population of men with no known prostate pathology aged from 20 to 70 years. PATIENTS AND METHODS: Serum total PSA and free PSA values were determined in 1,502 patients due for a systematic health examination. The digital rectal examination was only proposed for those over 50 years of age. The assays were determined on the AsXYM apparatus, from Abbott laboratories, by MEIA technology with monoclonal antibodies. RESULTS: 1,274 men were available for study. The mean age was 43.6 +/- 11 years (range 20-69 years). The total PSA level was stable up to 40 years. Beyond that, it increased with age. There was a linear regression between the age and the logarithm of the total PSA rate (r = 0.26, p < 0.0001) from 40 to 70 years. The upper limit of the normal value (95th percentile) increased from 1.07 for the 20- to 30-year age range to 2.82 for the 60- to 70-year range. The free PSA level was stable up to 50 years of age. It then significantly increased. The upper limit of the normal value was measured as 0.42 in the range of 20-30 years and as 0.53 in the range of 60-70 years with an annual average increase rate of roughly 0.5%. Overall there was a linear regression between age and the free PSA rate (r = 0.12, p < 0.0001). The upper limit of the free to total PSA ratio, measured as being 0.68 in the range of 20-29 years, dropped towards 60-69 years with an upper limit of the normal of 0.48. The average annual reduction rate was around 0.70%. There was a linear regression between the age and the free to total PSA ratio (r = 0.17, p < 0.0001). CONCLUSION: These total PSA levels are lower than the ones measured in other studies with other assay methods. These variations stress the importance of validating reference values of total PSA and free PSA as a function of the assay method and the population to which they are applied before using them as an aid in the diagnosis of prostate cancer.

Adult↗

Evaluation of predictive ability of APACHE II system and hospital outcome in Canadian intensive care unit patients.

OBJECTIVES: To evaluate the ability of the acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system to predict patient outcome in two Canadian intensive care units (ICUs). To compare the severity of illness and outcome of Canadian ICU patients with existing United States data. DESIGN: Prospective data collection on 1,724 Canadian ICU patients for validation of the APACHE II system. Comparison of the outcome of Canadian ICU patients to retrospective United States data on 4,087 patients from the 1985 APACHE II multicenter study. SETTING: Canadian data from two university teaching hospital ICUs. United States data from 13 ICUs, ten of which were in university teaching hospitals. PATIENTS: Consecutive patients admitted to adult medical/surgical ICUs. Coronary care unit, neurosurgical and cardiac surgery patients were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For each patient, demographic data, diagnosis, APACHE II score and hospital survival data were collected. The predicted risk of death was calculated for each patient using the APACHE II risk of death equation. The accuracy in outcome prediction of the APACHE II system was assessed by means of the receiver operating characteristic curve, 2 x 2 decision matrices and linear regression analysis. The severity of illness and hospital mortality for the Canadian patients was compared with that of United States patients from the 1985 APACHE II multicenter study. In 1,724 Canadian ICU patients, the mean +/- SEM APACHE II score was 16.5 +/- 0.2. The predicted death rate was 24.7% and the observed death rate was 24.8%. Using receiver operating curve analysis, good correlation was found between predicted outcome and observed outcome. The area under the curve was 0.86. From the 2 x 2 decision matrix constructed for a predicted risk of death of 0.5, 83% of patients were correctly classified. The sensitivity was 50.9% and the specificity was 93.6%. When observed death rate was plotted against predicted death rate, linear regression analysis gave an r2 of .99. Canadian patients had a higher death rate and APACHE II score than the United States patients. After controlling for severity of illness using the APACHE II score, the Canadian and United States death rates were similar. CONCLUSIONS: The ability of the APACHE II system in predicting group outcome is validated in this Canadian ICU population by receiver operating characteristic curve, 2 x 2 decision matrices and linear regression analysis. The Canadian patients had a higher overall hospital death rate than the United States patients. After controlling for severity of illness using APACHE II scores, the hospital death rate was comparable between the Canadian and United States patients.

APACHE↗

Low-frequency vs. high-frequency respiratory mechanics after methacholine challenge in artificially ventilated rabbits.

Respiratory system resistance (Rrs) and elastance (Ers) were estimated by two methods, before and after methacholine in six anesthetized, paralyzed, and artificially ventilated rabbits. Rrs and Ers were obtained (1) by multiple linear regression analysis of the relationship between tracheal pressure and tidal volume and flow [Rrs(mlr)], Ers(mlr), and (2) by analysis of the Fourier transforms of tracheal pressure and flow resulting from 4 to 30 Hz pseudorandom pressure oscillations delivered by an Infant Star respirator [Rrs(os), Ers(os)]. Rrs(os) was significantly lower than Rrs(mlr). For instance, Rrs(os) at 20 Hz [Rrs(os)20] was (mean +/- SD) 17.3 +/- 3.5 vs 21.4 +/- 3.6 cm H2O x L-1 x s (P < 0.01) for Rrs(mlr). Ers(os) was significantly higher than the respective value obtained by multiple linear regression (718.2 +/- 81.0 vs 403.7 +/- 43.0 cm H2O L-1; P < 0.01). After methacholine, the changes of respiratory mechanics were similar with both methods. Rrs(mlr) and Rrs(os)20 increased respectively by 131 +/- 45 and 134 +/- 76%, and Ers(mlr) and Ers(os) increased respectively by 63 +/- 7 and 54 +/- 13%. A significant correlation was observed between Rrs(mlr) and Rrs(os)20 (r = 0.97) and between Ers(mlr) and Ers(os) (r = 0.96). We conclude that positive response to methacholine may be detected by forced oscillation as well as by multiple linear regression. However, the identified physiological components of the lung response (alteration in lung viscoelastic properties, increased lung inhomogeneity or increased intrathoracic airway shunt) are likely to be different with each method.

Airway Resistance↗

Linking gene expression data with patient survival times using partial least squares.

There is an increasing need to link the large amount of genotypic data, gathered using microarrays for example, with various phenotypic data from patients. The classification problem in which gene expression data serve as predictors and a class label phenotype as the binary outcome variable has been examined extensively, but there has been less emphasis in dealing with other types of phenotypic data. In particular, patient survival times with censoring are often not used directly as a response variable due to the complications that arise from censoring. We show that the issues involving censored data can be circumvented by reformulating the problem as a standard Poisson regression problem. The procedure for solving the transformed problem is a combination of two approaches: partial least squares, a regression technique that is especially effective when there is severe collinearity due to a large number of predictors, and generalized linear regression, which extends standard linear regression to deal with various types of response variables. The linear combinations of the original variables identified by the method are highly correlated with the patient survival times and at the same time account for the variability in the covariates. The algorithm is fast, as it does not involve any matrix decompositions in the iterations. We apply our method to data sets from lung carcinoma and diffuse large B-cell lymphoma studies to verify its effectiveness.

Algorithms↗

Comparison of three nonlinear and spline regression models for describing chicken growth curves.

This study compared three non-linear growth models (Richards, Gompertz, and logistic) and the spline linear regression model using BW measurements from an unselected, randombred chicken population. Based on the goodness of fit criteria, the nonlinear models (NLM) fitted the data better than the spline regression model. The four-parameter Richards model was expected to have the best overall fit; however, because the shape parameter predicted was close to 1.0, which corresponded with the Gompertz curve, there were no differences between the Richards and Gompertz models for the data used. The growth parameters predicted with the logistic model were different from those predicted by the Richards and Gompertz models. It was concluded that growth parameters predicted with different models with fixed inflection points are not directly comparable. The spline linear regression model is a compound function consisting of a series of linear models. It can be used to compartmentalize growth into segments and also substitute as an alternative to asymptotic models when the data are truncated before the asymptote is attained. The relationship between the growth trajectory (m) and carcass composition measurements were also investigated. Carcass yields among the different growth trajectories (m) were similar within sexes. However, the proportions of the major breast muscle and abdominal fat differed according to the m a bird followed.

Abdomen↗

Glucosamine sulfate and cartilage type II collagen degradation in patients with knee osteoarthritis: randomized discontinuation trial results employing biomarkers.

OBJECTIVE: To determine whether glucosamine sulfate has an effect on cartilage type II collagen degradation in patients with knee osteoarthritis (OA). METHODS: A randomized, double blind, placebo controlled glucosamine discontinuation trial was conducted in 137 subjects with knee OA, who had had at least moderate relief of knee pain after starting glucosamine. Subjects were randomized to glucosamine at prestudy dose or placebo at an equivalent dose. Treatment was continued to Week 24 or disease flare, whichever occurred first. Serum and urine samples were collected at Weeks 0, 4, 12, and 24 or flare visit. Samples were analyzed in triplicate for 2 type II collagen degradation biomarkers: C2C epitope (COL2-3/4C(long)) and C1,2C epitope (COL2-3/4C(short)). The primary outcome was the mean change in serum and urine C1,2C/C2C ratio in the glucosamine and placebo groups from baseline to final (flare or Week 24) visit. Linear regression analyses were conducted to adjust for potential confounders. Due to non-normal distributions, the data were log-transformed (lnC1,2C/C2C). Secondary outcomes included comparison of mean change scores at final visit compared to baseline for serum and urine C1,2C and C2C in the 2 treatment groups and in Flare versus No-Flare groups. RESULTS: Baseline and final visit samples were available in 130 subjects for serum analysis and 126 subjects for urinalysis. No significant difference was seen between placebo and glucosamine groups in the serum C1,2C/C2C ratio, with a mean (SD) change from baseline to final visit of 0.8 (27.8) and -0.1 (1.8), respectively (mean difference 0.9; 95% CI -6.0, 7.7, p = 0.80). Similarly, no differences between treatment groups were seen for mean change in urine C1,2C/C2C (p = 0.82), or for mean change in C2C or C1,2C. In linear regression analysis, after adjustment for sex, radiographic severity, baseline lnC1,2C/C2C ratio, WOMAC function, and flare status, treatment was not a significant predictor of final serum or urine lnC1,2C/C2C ratio. When those who experienced flare were contrasted with those without flare, there was a nonsignificant trend toward a difference in mean baseline to final visit change score for serum C1,2C/C2C ratio (p = 0.12). In addition, in the multivariable linear regression analysis, flare status showed a borderline association with final visit serum lnC1,2C/C2C ratio (p = 0.16). CONCLUSION: No statistically significant effect of glucosamine sulfate on type II collagen fragment levels in serum or urine was observed for knee OA over 6 months. Further research is necessary to elucidate which biopathologic systems, if any, are affected by glucosamine treatment. While collagen degradation products may be of value in predicting progression, at least as defined by clinical flare, a larger dataset would be needed to prove this.

Biomarkers↗

The effect of punctal occlusion on tear production, tear clearance, and ocular surface sensation in normal subjects.

PURPOSE: To evaluate the effect of temporary punctal occlusion on tear production, tear clearance, and ocular surface sensation in normal subjects. METHODS: Noncomparative interventional case series. Punctal occlusion with silicone punctal plugs was performed on nine normal subjects without complaints of ocular irritation and no known history of ocular surface disease. The lower punctum of both eyes was occluded in five subjects. The upper and lower puncta of only one eye were occluded in four subjects. Corneal and conjunctival sensations were measured with the Cochet-Bonnet anesthesiometer. Tear fluorescein clearance was evaluated with a CytoFluor II fluorophotometer by measuring the fluorescein concentration in minimally stimulated tear samples collected from the inferior tear meniscus 15 minutes after instillation of fluorescein. Schirmer test was performed without anesthesia. The tests were performed at days 0, 1, 3, 7, and 14 to 17 after punctal occlusion. Relationships were analyzed with linear regressions, and a quadratic term was used to model a return to preocclusion levels. Paired t test was used to study the change in tear fluorescein concentration. RESULTS: In subjects who had the lower puncta of both eyes occluded, conjunctival sensation decreased in both eyes (right eye, P =.008; left eye, P =.003), but there was no change in corneal sensation. Their tear fluorescein clearance did not show a significant change from baseline (P =.90). However, a decrease in Schirmer test scores approached statistical significance (P =.056). In subjects with both puncta of only one eye occluded, we noted a decrease in corneal sensation (occluded eye, P =.042; nonoccluded eye, P =.036), conjunctival sensation (occluded, P =.001; nonoccluded, P =.060), and Schirmer scores (occluded, P =.022; nonoccluded, P =.011). Linear regression did not show a significant change in tear fluorescein clearance for either eye (occluded, P =.28; nonoccluded, P =.44). However, paired t test showed a significant worsening of tear clearance in the occluded eye from day 0 to day 3 (P =.001) followed by a subsequent improvement in tear clearance from day 3 to the end of the study period (P =.045). Paired t test did not reveal any significant changes in tear clearance in the nonoccluded eye. The quadratic term of the linear regression model demonstrated an increase toward preocclusion levels that approached statistical significance for corneal sensation (occluded, P =.053; nonoccluded, P =.099). It was statistically significant for conjunctival sensation (occluded, P =.001; nonoccluded, P =.045) and Schirmer scores (occluded, P =.047; nonoccluded, P =.044). CONCLUSIONS: Temporary punctal occlusion in normal subjects decreases tear production and ocular surface sensation. Our findings suggest that in addition to blocking tear drainage, punctal occlusion may affect the ocular surface/lacrimal gland interaction. These effects were more pronounced in subjects with both upper and lower puncta occluded. In normal subjects, there appears to be an autoregulatory mechanism to return tear production, tear clearance, and ocular surface sensation to preocclusion levels 14 to 17 days after punctal occlusion.

Conjunctiva↗

Influence of pregnancy and breast-feeding on quantitative ultrasonometry of bone in postmenopausal women.

OBJECTIVE: Reproductive factors such as parity and breast-feeding may be associated with low bone mass and osteoporotic fractures in later years. In this study, os calcis quantitative ultrasonometry was used to elucidate the relationship between parity, lactation and bone mass in postmenopausal women. DESIGN: This was a comparison study using subsequent matched pairs analysis as well as multiple linear regression analysis. The study was carried out at five centers in Germany. The study included 2,080 postmenopausal women (age (mean +/- SD) 58.8 +/- 8.2 years), who were attending for routine check-up and in whom diseases and drug treatments known to affect bone metabolism had been excluded. METHODS AND OUTCOME MEASURES: Women underwent quantitative ultrasonometry (QUS) measurement at the heel. Values of the ultrasonometry variables -speed of sound, broadband ultrasound attenuation and stiffness index -were calculated and compared for nulliparous and parous women and for women who had and had not breast-fed. Because of some significant intergroup differences, and to determine any effect of the number of live births and the duration of breast-feeding on ultrasonometry results, second analyses were undertaken using equally sized samples, matched for possible confounding variables such as age and body mass index (matched pairs). In these analyses, nulliparous women were compared with parous women, grouped according to number of live births, and women who had never breast-fed were compared with women who had breast-fed, grouped according to duration of breast-feeding. Furthermore, a multiple linear regression analysis was performed to examine the combined effects of reproductive factors on QUS variables. RESULTS: No statistically significant associations were found between ultrasonometry variables and parity or breast-feeding, even after controlling for confounding variables in matched-pairs analysis or in a multiple linear regression analysis.

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