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At least 595 records · Page 33Linked to original sources
PubMed2000

Serial assessment of left ventricular diastolic function after Fontan procedure.

OBJECTIVE: To assess longitudinal changes in systemic ventricular diastolic function late after the Fontan procedure. DESIGN AND PATIENTS: Prospective study of 13 patients at 2.8 (2.0) years (early) and again at 11.4 (2.0) years (late) after the Fontan procedure by Doppler echocardiography with simultaneous ECG, phonocardiogram, and respirometer. SETTING: Tertiary paediatric cardiac centre. RESULTS: The isovolumic relaxation time (IVRT) was significantly longer, and E wave deceleration time, E and A wave velocities, and E:A velocity ratio were reduced compared to normal both early and late after the procedure. The mean (SD) z score of IVRT decreased significantly from +2.50 (1.00) to +1.24 (0.80) (p = 0.002), and the z score of the E wave deceleration time decreased from -1.69 (1.31) to -2.40 (1.47) (p = 0.03) during follow up. The A wave deceleration time also tended to decrease (early 80 (12) ms v late 73 (11) ms, p = 0.13) with increased follow up. There were no changes of the E and A wave velocities and E:A velocity ratio. The E wave velocity was inversely related to IVRT both early (r = -0.82, p = 0.001) and late (r = -0.59, p = 0.034) after the operation. The prevalence of diastolic flow during isovolumic relaxation decreased from 85% (11/13) to 38% (5/13) (p = 0.04), while that of mid diastolic flow increased from 23% (3/13) to 77% (10/13) (p = 0.02) between the two assessments. CONCLUSIONS: Left ventricular diastolic function remains highly abnormal late after the Fontan procedure. The longitudinal changes demonstrated on follow up are compatible with reduction of left ventricular compliance in addition to persisting abnormalities of relaxation.

Blood Flow Velocity↗
PubMed2001

Cigarette smoking and asthma.

Cigarette smoking is a well-know health hazard, probably not least for patients suffering from asthma. This review gives a short overview concerning the effects of passive and active smoking on the inception and outcome with regard to longitudinal changes in lung function and mortality for patients with asthma. Substantial evidence suggests that smoking affects asthma adversely. Exposure to environmental tobacco smoke in children, especially maternal smoking, may be a significant risk factor for asthma. Environmental tobacco exposure in patients with established asthma is not only associated with more severe symptoms, but also with lower quality of life, reduced lung function, and increased health care utilisation for asthma, including hospital admissions. Active smoking appears not to be a significant risk factor for asthma, but it is associated with worse outcome with regard to both longitudinal changes in lung function and asthma-related mortality. Based on the current knowledge, it therefore seems of utmost importance to encourage patients with asthma not to smoke. In line with this, patients with asthma should be given full support in their right to a smoke-free environment.

Adult↗
PubMed2006

The natural course of beta-cell function in nondiabetic and diabetic individuals: the Insulin Resistance Atherosclerosis Study.

Data from the UKPDS (U.K. Prospective Diabetes Study) indicate a continuous decline in beta-cell function in patients with type 2 diabetes. We studied longitudinal changes in beta-cell function (follow-up of 5.2 years) in subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes, using acute insulin response (AIR) and insulin sensitivity index (S(i)) from a frequently sampled intravenous glucose tolerance test among African-American, Hispanic, and non-Hispanic white subjects aged 40-69 years. At baseline, decreasing levels of both S(i) and AIR (either unadjusted or adjusted for S(i)) mirrored deteriorating glucose tolerance status at baseline and at follow-up. A different pattern was found with respect to longitudinal changes; S(i) declined in each glucose tolerance category, ranging from -0.81 x10(-4) min(-1) x muU(-1) x ml(-1) in NGT at baseline and NGT at follow-up (NGT/NGT) to -1.06 x10(-4) in NGT/diabetes, whereas the directional change in AIR principally determined the glucose tolerance status at follow-up. In NGT/NGT S(i) decreased by 35% and AIR increased by 34%. Results were similar in each of the three ethnic groups. These data shed light on the natural course of beta-cell function; over 5.2 years, mean insulin sensitivity declined in each glucose tolerance category. The change in AIR, however, principally determined glucose tolerance status at follow-up; NGT was maintained by a compensatory increase in insulin secretion. Failure to increase insulin secretion led to IGT, and a decrease in insulin secretion led to overt diabetes. This data may have important implications for the prevention and treatment of type 2 diabetes.

Atherosclerosis↗
PubMed2026

Metabolomic Signatures of Inflammation in Chronic Kidney Disease.

RATIONALE & OBJECTIVE: Inflammation is associated with adverse kidney, cardiovascular, and mortality outcomes. Investigation of the metabolic milieu as it relates to inflammation may provide important insights into these disease processes. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: African American Study of Kidney Disease and Hypertension (AASK), Atherosclerosis Risk in Communities (ARIC) study, and Boston Kidney Biopsy Cohort (BKBC) participants with available metabolomics and inflammatory protein data. PREDICTORS: Baseline blood levels of 718 metabolites. OUTCOMES: Baseline and longitudinal changes in blood levels of tumor necrosis factor receptors 1 and 2 (TNFR1, TNFR2), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukins 6, 8, and 10 (IL-6, IL-8, IL-10), uromodulin (UMOD), and epidermal growth factor (EGF). ANALYTICAL APPROACH: Multivariable linear regression and linear mixed-effects models. RESULTS: Among 491 AASK participants (mean age 54 years; 37% women; mean glomerular filtration rate, 45 mL/min/1.73 m2), 367 cross-sectional associations between metabolites and inflammatory proteins were significant after correction for multiple comparisons. The direction of association was mostly positive for TNFR1 (97%), TNFR2 (97%), IL-8 (77%), and IL-10 (100%); negative for UMOD (80%) and EGF (97%); and variable for TNF-⍺, IFN-γ, and IL-6. Pathways were distinct for several inflammatory proteins (eg, tryptophan metabolism for TNFR2). Forty-five associations between metabolites and longitudinal change in inflammatory proteins were identified. Notable metabolites included tigylcarnitine and N 2,N 5-diacetylornithine, which were associated with 2-year increases in TNFR1 and/or TNFR2, and 1,5-anhydroglucitol, where lower levels were associated with decreases in UMOD. In ARIC (n = 3,773) and BKBC (n = 413), replication of cross-sectional associations was excellent for TNFR1 (ARIC 83%; BKBC 85%) and TNFR2 (ARIC 64%; BKBC 79%) but poor for IL-8 (ARIC 3%; BKBC 3%). LIMITATIONS: Metabolite data limited to baseline visit; potential for residual confounding. CONCLUSIONS: Using an untargeted approach, multiple metabolites were cross-sectionally and longitudinally associated with inflammatory proteins in persons with chronic kidney disease.

Chronic kidney disease↗
PubMed2000

The course of cognitive impairment in preclinical Alzheimer disease: three- and 6-year follow-up of a population-based sample.

OBJECTIVES: To examine the ability of the total score and individual items from the Mini-Mental State Examination in predicting the development of Alzheimer disease (AD) across a 3- and 6-year period in a population-based sample, and to describe the longitudinal changes in these measures across the same follow-up periods. DESIGN: Prospective follow-up of a community-based cohort, with 3 times of testing across a 6-year period. At each time of measurement, participants were clinically examined by physicians to identify demented and nondemented participants according to Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria. PARTICIPANTS: The study population consisted of all participants who were nondemented at the first follow-up and participated in the second follow-up examination. Among those, 459 remained nondemented and 73 developed AD during the second follow-up period. RESULTS: Baseline differences in the total Mini-Mental State Examination score and the delayed memory item were seen 6 years before eventual dementia diagnosis (P<.01). Analysis of the longitudinal changes showed no differences in the rate of decline for the incident AD or nondemented group between time 1 and time 2 (P>.10). However, the incident AD group exhibited precipitous declines in 8 of the 10 subscales between time 2 and time 3, the point at which they were clinically diagnosed (P<.01). Logistic regression analyses showed that only the delayed memory item was a significant predictor of who would develop AD, independent of age, sex, and years of education, at both of the first 2 times of measurement (P<.001). CONCLUSIONS: The diagnosis of AD is preceded by a long preclinical phase in which deficits in memory performance are most common. These deficits remain relatively stable up until the time that a dementia diagnosis can be rendered. Arch Neurol. 2000.

Aged↗
PubMed1994

Longitudinal estimates of pulmonary function decline in grain workers.

We conducted a cohort analysis of longitudinal changes in pulmonary function test values in male grain elevator workers in five regions of Canada over a 6-yr period involving three observations. Pulmonary function tests were obtained approximately each 3 yr during an observation interval called a "cycle". The periods of the cycles were 1978-81 (Cycle I), 1981-84 (Cycle II), and 1984-87 (Cycle III), respectively. Data on respiratory symptoms and pulmonary function tests were collected on the same 881 workers in Cycles I and II (mean ages +/- SE: 37.0 +/- 0.48 yr at Cycle I), on the same 1,294 workers in Cycles I, II, and III (34.6 +/- 0.34 yr at Cycle I), and on the same 1,021 workers in Cycles II and III (33.9 +/- 0.38 yr at Cycle II) for a total of 3,196 workers with two or more observations over the 6-yr period. The proportion of current smokers decreased from Cycle I to Cycle III. Autoregression analysis of longitudinal changes in lung function data showed that predictors of FEV1 were height, years in the industry, smoking status, and geographic region. The mean annual losses in FEV1 (FVC) were 28.7 ml (26.4 ml), 38.4 ml (41.9 ml), and 41.7 ml (32.3 ml) for nonsmokers, ex-smokers, and current smokers, respectively. The annual loss of FEV1 (FVC) was 9.2 ml (21.1 ml) for those who were in the grain industry for less than 5 yr and 52.6 ml (60.8 ml) for those who were exposed for 20 yr or more.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

Impaired cardiovascular recovery following stress predicts 3-year increases in blood pressure.

OBJECTIVE: To assess whether variation in the rate of cardiovascular recovery following exposure to acute psychological stress predicts changes in blood pressure longitudinally, independently of blood pressure at baseline and other covariates. DESIGN: A 3-year longitudinal study. PARTICIPANTS: A total of 209 men and women aged 45-59 years at baseline, with no history of cardiovascular disease including hypertension. METHOD: Measurement of blood pressure, heart rate, heart rate variability, cardiac index and total peripheral resistance at rest, during two moderately stressful behavioural tasks and up to 45 min post-stress. Stress reactivity was defined as the difference in values between tasks and baseline, and post-stress recovery as the difference between recovery levels and baseline. OUTCOME MEASURES: Resting blood pressure measured at baseline and 3 years later. Seven individuals had been prescribed hypertensive medication on follow-up. RESULTS: Increases in systolic blood pressure (SBP) were predicted by impaired post-stress recovery of SBP (P < 0.001), diastolic blood pressure (DBP) (P < 0.001) and total peripheral resistance (P = 0.003), independently of baseline blood pressure, age, gender, socio-economic status, hypertensive medication, body mass and smoking. The adjusted odds of an increase in SBP > or = 5 mmHg were 3.50 [95% confidence interval (CI) 1.19 to 10.8] for individuals with poor compared with effective post-stress recovery of SBP. Three-year increases in diastolic pressure were predicted by impaired recovery of SBP (P < 0.001) and DBP (P = 0.009) pressure and by heart rate variability during tasks (P = 0.002), independently of covariates. CONCLUSIONS: Impaired post-stress recovery and less consistently heightened acute stress reactivity may index disturbances in the regulation of cardiovascular stress responses that contribute to longitudinal changes in blood pressure in middle-aged men and women.

Acute Disease↗
PubMed2000

Longitudinal threshold changes in older men with audiometric notches.

Age-related hearing loss (presbycusis) is a multifactorial process that results chiefly from the accumulating effects of noise damage and aging on the cochlea. Noise damage is typically evidenced clinically by a discrete elevation (notch) of the auditory thresholds in the 3-6 kHz region of the audiogram whereas aging affects the highest frequencies first. To determine whether the presence of such high-frequency notches influences auditory aging, we examined the 15 year change in audiometric thresholds in 203 men from the Framingham Heart Study cohort. The mean age at the first hearing test was 64 years (range 58-80). Occupational and recreational noise exposure over the 15 years was assumed to be minimal due to the age of the subjects. The presence or absence of a notch was determined using a piecewise linear/parabolic curve fitting strategy. A discrete elevation of the pure-tone thresholds of 15-34 dB in the 3-6 kHz region was deemed a small notch (N1), and elevations of 35 dB or greater were deemed large notches (N2). Absence of a notch (N0) was encoded those ears with <15 dB elevation in the 3-6 kHz region. The presence and absence of notches correlated with the subjects' history of noise exposure. The 15 year pattern of change in age-adjusted pure-tone thresholds varied significantly by notch category. There was less change over time in the notch frequencies (3-6 kHz) and significantly greater change in the adjacent frequency of 2 kHz in the N2 group as compared to the N0 and N1 groups. The adjacent frequency of 8 kHz showed a significant, but smaller, change in the N1 group as compared to the N0 and N2 groups. The change at 2 kHz was independent of the starting hearing level at E15, whereas the changes at 4-8 kHz were influenced by the hearing level at E15. These data suggest that the noise-damaged ear does not 'age' at the same rate as the non-noise damaged ear. The finding of increased loss at 2 kHz suggests that the effects of noise damage may continue long after the noise exposure has stopped. The mechanism for this finding is unknown but presumably results from prior noise-induced damage to the cochlea.

Aged↗
PubMed2005

Measurement and analysis of access resistance and polarization impedance in cochlear implant recipients.

BACKGROUND: Impedance measurements are commonly performed at the end of cochlear implant surgery, not only to confirm that all electrodes are working but also to monitor the impedances of the newly implanted electrodes. The current method of testing allows the determination of only the overall electrode impedance but not its components, access resistance and polarization impedance. To determine whether any longitudinal change in the electrode impedance is caused by a change in the endocochlear environment or rather caused by a change in the surface quality of the electrode, it is necessary to extract access resistance and polarization impedance. METHODS: We applied an impedance model that enabled us to calculate access resistance and polarization impedance after measurement of electrode impedance at three points along the voltage waveform. RESULTS: The results show that the value of the components of electrode impedance varied with time after surgery: access resistance increased slowly over time, whereas polarization impedance increased up to Week 2 but decreased after commencement of electrical stimulation at that stage. These results are consistent with the hypothesis that a layer of fibrous tissue forms around the electrode within the cochlear canal, resulting in a slow increase of access resistance, whereas a layer of proteins forms on the surface of the electrode in the early phase after implantation. Electrical stimulation appears to disperse this surface layer, thereby reducing both the polarization impedance and electrode impedance. CONCLUSION: The method presented enables the extraction of more detailed information about the longitudinal changes in the intracochlear environment after cochlear implantation.

Acoustic Impedance Tests↗
PubMed1999

Longitudinal occlusal changes from primary to permanent dentition in children with normal primary occlusion.

This purpose of this research was to examine the stability of normal occlusion during the transition from primary to permanent dentition. The sample consisted of 128 children (83 boys and 45 girls) 4.5 to 5.5 years old with normal occlusion in the primary dentition. The subjects were reexamined at 12.5 to 13.5 years. None had received orthodontic treatment. Although all the subjects had normal occlusion in the primary dentition, 72.7% (73.5% boys and 71.1% girls) had developed anomalies following eruption of the permanent teeth. These anomalies included crowding, Class II Division 1 or Class II Division 2 malocclusion, mesial occlusion complex, lateral crossbite, anterior crossbite, premature tooth loss, openbite or other anomalies.

Adolescent↗
PubMed1990

[Experimental study on the plastic deformation of underlying mucosa in lower posterior denture caused by occlusal stress after denture wearing].

In the treatment of removable dentures including mucosa born, it is essential to secure the occlusion based on adequate consideration of deformation of mucous membrane. This means that it is necessary to clarify the plastic deformation of underlying soft tissues after denture insertion. With the objective of assessing the influence of the difference in the supporting pressure of the underlying soft tissues, the longitudinal changes of the tissue surface after insertion of denture were observed. The non-pressure areas with special conditions were established between the basal surface of the dentures and the surface of the underlying soft tissues. Removable free end dentures with cylindrical non-pressure cavity (3 mm in diameter and 2 mm in depth) in the basal surface were prepared for 20 subjects having a missing of lower posterior region. Such three non-pressure cavities were positioned in the following locations: in a mesio-distal location corresponding to the distal region of the first molar, at the alveolar crest, at a location halfway between the alveolar crest and the buccal denture border, and a location halfway between the alveolar crest and the lingual denture border. Impressions were taken from the subjects' jaws after the fixed numbers of days following initiation of denture wearing. Contours of the non-pressure areas were measured in 100 jaw models. Results. 1. Swelling of the mucous membrane of the non-pressure area 1) Subjects are classified into the following 5 types on the bases of longitudinal changes in the swelling height of the mucous membrane in the non-pressure area. Type S-1: Marked increase in swelling height observed within the first 3 days after insertion of dentures, but practically no change in swelling height until the 30th post installation day. Type S-2: Marked increase in swelling height observed within the first 3 days after insertion of dentures, and swelling height increased continuously until the 30th post installation day. Type S-3: Marked increase in swelling height observed within the first 3 days after insertion of dentures, but swelling height decreased continuously until the 30th post-installation day. Type G: Increase in swelling height comparatively small within the first 3 days after insertion of dentures, but swelling height increased until the 30th post-installation day. Type N: No increase in swelling height observed until the 30th post-installation day. 2) Swelling height and frequency in each location according to type.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2003

Is knee radiography useful for studying the efficacy of a disease-modifying osteoarthritis drug in humans?

Recent research on the radiographic imaging of knee OA has helped clarify the features of imaging protocols that contribute to accurate representation of disease severity--specifically, the thickness of articular cartilage--and to sensitive detection of disease progression. The absence of standards for reproducible positioning of the knee in the conventional standing AP view obscures the true rate and variability of JSN in knee OA. Moreover, the standing AP view is susceptible to systematic bias insofar as longitudinal changes in knee pain might lead to over- or underestimation of radiographic JSW depending on the direction of change in pain. More recent protocols for standardized knee radiography have been designed to achieve reproducible alignment of the medical tibial plateau and x-ray beam. As a group these protocols permit measurement of tibiofemoral JSW with remarkable precision--the sine qua non of sensitivity to change--however, only limited longitudinal data is available to permit a direct evaluation of the suitability of these protocols for use in clinical DMOAD trials. Longitudinal studies published to date suggest that fluoroscopic positioning methods are superior to nonfluoroscopic methods with respect to reproducing the position of the knee in serial examinations performed several years apart. Fluoroscopic methods also appear to be superior with respect to achieving parallel alignment of the medial tibial plateau and x-ray beam in serial radiographs, a positioning marker strongly associated with sensitive detection of JSN in knee OA. It is important to note that while the various standardization protocols described in this article perform with great success in short-term demonstrations of the reproducibility of positioning and radiographic JSW, differences clearly exist between protocols in the quality of performance over intervals relevant to clinical DMOAD trials. Over intervals of 2 to 3 years, changes in patient characteristics (e.g., severity of knee pain, body weight, load bearing, varus--valgus deformity) and uncontrollable events related to radiography (e.g., technologist turnover, equipment upgrades) have ample opportunity to affect the technical quality of a radiological knee examination. It is difficult, therefore, to conclude whether or not an apparent difference with respect to sensitivity to OA progression between specific radiographic protocols, implemented in separate locations with different cohorts, reflects a robust difference in technical quality or uncontrollable patient variables and events. The most informative recent studies have provided the results of head-to-head longitudinal comparisons of alternative standardization protocols or conventional examination methods performed concurrently in the same subjects [20,22]. Additional comparative studies of this nature are needed, however, to fully characterize the strengths and weaknesses of currently available alternatives in a way that will permit generalizable conclusions regarding the best radiographic methods for multicenter DMOAD trials.

Biomechanical Phenomena↗
PubMed2002

Long-term effects of partial unilateral ureteral obstruction on renal hemodynamics and morphology in newborn rats: a magnetic resonance imaging study.

We assessed the longitudinal changes in renal vein blood flow (RVBF) and kidney volume in response to neonatally induced partial unilateral ureteral obstruction (PUUO) in rats with a magnetic resonance imaging (MRI) technique. During anesthesia, either the upper third or two thirds of the left ureter was embedded into the psoas muscle in newborn rats, creating either a mild (n=20) or a severe (n=9) partial obstruction. Control groups consisted of sham-operated (n=12) and non-operated (n=15) rats. During the following 24 weeks, RVBF and kidney volume were measured sequentially every 2-6 weeks with MRI, beginning 9 days after the operation. Both mild and severe obstruction caused a time-dependent decrease in RVBF. At week 24, the mean RVBF had decreased to 79% of the controls in the mildly obstructed kidneys (mean+/-SE: 1.45+/-0.14 vs 1.84+/-0.08 ml/min/100 g body weight, P<0.05) and to 57% of controls in the severely obstructed kidneys (1.05+/-0.10 vs 1.84+/-0.08 ml/min/100 g body weight, P<0.05). The renal pelvis volume increased and the renal parenchymal volume decreased significantly in the severely obstructed kidneys compared to the mildly obstructed kidneys. A good correlation was found between kidney volume measured in vivo using MRI and that measured in vitro (r>0.8, P<0.05), and between RVBF and renal parenchymal volume (r=0.758, P<0.01). In conclusion, the degree of reduction in RVBF depends on the severity and the duration of the PUUO. MRI can safely and reliably be used to monitor the longitudinal changes in RVBF and kidney volume in rats from early life.

Animals↗
PubMed2004

Oropharyngeal scintigraphy: a reliable technique for the quantitative evaluation of oral-pharyngeal swallowing.

A valid and reliable technique to quantify the efficiency of the oral-pharyngeal phase of swallowing is needed to measure objectively the severity of dysphagia and longitudinal changes in swallowing in response to intervention. The objective of this study was to develop and validate a scintigraphic technique to quantify the efficiency of bolus clearance during the oral-pharyngeal swallow and assess its diagnostic accuracy. To accomplish this, postswallow oral and pharyngeal counts of residual for technetium-labeled 5- and 10-ml water boluses and regional transit times were measured in 3 separate healthy control groups and in a group of patients with proven oral-pharyngeal dysphagia. Repeat measures were obtained in one group of aged (> 55yr) controls to establish test-retest reliability. Scintigraphic transit measures were validated by comparison with radiographic temporal measures. Scintigraphic measures in those with proven dysphagia were compared with radiographic classification of oral vs. pharyngeal dysfunction to establish their diagnostic accuracy. We found that oral ( p = 0.04), but not pharyngeal, isotope clearance is swallowed bolus-dependently. Scintigraphic transit times do not differ from times derived radiographically. All scintigraphic measures have extremely good test-retest reliability. The mean difference between test and retest for oral residual was -1% (95% CI -3%-1%) and for pharyngeal residual it was -2% (95% CI -5%-1%). Scintigraphic transit times have very poor diagnostic accuracy for regional dysfunction. Abnormal oral and pharyngeal residuals have positive predictive values of 100% and 92%, respectively, for regional dysfunction. We conclude that oral-pharyngeal scintigraphic clearance is highly reliable, bolus volume-dependent, and has a high predictive value for regional dysfunction. It may prove useful in assessment of dysphagia severity and longitudinal change.

Adolescent↗
PubMed2001

Effect of alignment of the medial tibial plateau and x-ray beam on apparent progression of osteoarthritis in the standing anteroposterior knee radiograph.

OBJECTIVE: Previous studies of knee osteoarthritis (OA) have yielded variable estimates of the rate of joint space narrowing (JSN) in the standing anteroposterior (AP) radiograph, due largely to longitudinal changes in the alignment of the medial tibial plateau (MTP) and x-ray beam. To characterize this bias, we examined serial radiographs of subjects with knee OA in population-based and clinical OA cohorts from 3 locations in the United States and the United Kingdom. METHODS: Radiographic features of knee OA (e.g., osteophytosis, JSN) and MTP alignment in 428 OA knees were evaluated by consensus of 2 readers. Alignment was considered satisfactory if the anterior and posterior margins of the MTP were superimposed within 1 mm. Readers were blinded to subject identity, and films were read in random order. The minimum medial joint space width was also measured manually (standard error of repeated measurements 0.20 mm) in serial knee images. RESULTS: Only 14% of serial radiographs exhibited alignment of the MTP in both images. In OA knees with satisfactory alignment in both images, the mean rate of JSN over 2-3 years (0.26 mm/year) was significantly larger (P = 0.004) than that in OA knees with misalignment in 1 or both radiographs and was 86% more rapid than the mean JSN in all OA knees. Moreover, the within-group standard deviation of JSN was significantly smaller among knees with reproduced alignment of the MTP than in knees in which misalignment occurred in 1 or both images (P = 0.006). CONCLUSION: Poor standardization of knee positioning in serial standing AP radiographs in previous studies of OA progression has obscured the rate and variability of articular cartilage loss in subjects with knee OA. True JSN (i.e., JSN that is not attributable to longitudinal changes in the alignment of the MTP with the x-ray beam in serial radiographic examinations) may occur more rapidly, and with less between-subject variability, than that previously thought to be characteristic of knee OA.

Aged↗
PubMed1994

Effects of therapy with interferon-alpha on peripheral blood lymphocyte subsets and NK activity in patients with chronic hepatitis C.

Longitudinal changes in lymphocyte subpopulations, including total and activated T cells, B cells, and NK cells as well as NK activity and 2',5'-oligoadenylate synthetase (2'5' AS) levels were determined in peripheral blood before, during, and after therapy with human recombinant interferon-alpha (HurIFN-alpha) in 39 patients with serologically and biopsy-confirmed chronic hepatitis C. Immunologic data obtained at baseline and during IFN-alpha administration were correlated with the clinical response to IFN-alpha therapy defined as a normalization of the serum alanine aminotransferase level. There were 23 responders (R) and 13 nonresponders (NR) to IFN-alpha and 3 patients were not evaluable. Prior to the use of IFN-alpha, the patients tended to have higher numbers of activated (DR+) T and NK cells but a lower number of CD3+CD25+ T cells than normal controls. During IFN-alpha therapy, highly significant induction of 2'5'AS was observed. The numbers of circulating WBC, total lymphocytes, and T and B cells were reduced during IFN-alpha therapy. In contrast, both the absolute number and percentage of activated CD3+CD25+ and CD4+DR+ T cells increased in response to the IFN-alpha therapy. The percentage of activated CD56+DR+ NK cells was also significantly elevated over the pretreatment baseline. IFN-alpha therapy had no effect on NK activity in peripheral blood mononuclear cells. No differences in the immunologic profile of R vs NR were noted, except that the number of IL2R+ T cells was increased transiently early during IFN-alpha therapy but only in the NR group. It was not possible to reliably discriminate between R vs NR to IFN-alpha therapy on the basis of longitudinal changes in the phenotype or function of immune effector cells.

2',5'-Oligoadenylate Synthetase↗
PubMed2003

Polymorphisms in the CYP19 and AR genes--relation to bone mass and longitudinal bone changes in postmenopausal women with or without hormone replacement therapy: The Danish Osteoporosis Prevention Study.

Polymorphisms in the androgen receptor ( AR) gene and genes encoding enzymes involved in synthesis of sex steroids (e.g., the CYP19 gene encoding aromatase) have recently received attention in osteoporosis research. In the Danish Osteoporosis Prevention Study, recent postmenopausal women were allocated to either hormone replacement therapy (HRT) or no treatment. We genotyped 1792 women for the CYP19 (TTTA)(n) repeat [short (TTTA)(n 7)] the CYP19 C(1558)-T, and the AR (CAG)(n) repeat polymorphism [short (CAG)(n < 22), long (CAG)(n >or= 22)], and investigated associations with bone mineral density (BMD) and 5-year change in BMD. The CYP19 polymorphisms were in strong linkage disequilibrium. Perimenopausal bone mass or bone loss in untreated women was not associated with the CYP19 polymorphisms. In hormone-treated women, BMD increase in the femoral neck was highest (+0.3%/year) for long CYP19 alleles, lowest (-0.09%/year) for short alleles, and intermediate (-0.002%/year) in heterozygous women, P = 0.015. Differences were also significant in the lumbar spine, total hip, and ultradistal forearm. The C(1558)-T T-allele was associated with a more pronounced response to HRT ( P = 0.04, total hip). AR genotype was not related to BMD, but a modifying effect of sex hormone-binding globulin (SHBG) was present. In the highest SHBG quartile (SHBG > 95 nmol/1, n = 222), AR genotype was associated with baseline BMD (femoral neck: P < 0.001, total hip: P = 0.008), but without a clear gene dosage effect. We have demonstrated that polymorphisms in the CYP19 gene are associated with the magnitude of bone gain in response to HRT and that the (CAG)(n) repeat polymorphism in the AR gene is associated with bone mass in women with high levels of SHBG. These findings emphasize the complexity of the genetics of bone mass and bone loss.

Alleles↗
PubMed2004

Two single nucleotide polymorphisms in the CYP17 and COMT Genes--relation to bone mass and longitudinal bone changes in postmenopausal women with or without hormone replacement therapy. The Danish Osteoporosis Prevention Study.

Sex steroids are important physiologic regulators of bone mass, and genes regulating sex steroid production and metabolism are obvious as candidate genes for osteoporosis susceptibility. We present data from a study of 1795 recent postmenopausal women, assigned to either hormone replacement therapy (HRT) or no treatment and followed for 5 years. The association between bone mass measurements and two single nucleotide polymorphisms, a T (A1) to C (A2) transition in the 5'-UTR of the cytochrome P450c17alpha (CYP17) gene and a G (Val) to A (Met) transition in exon 4 of the catechol- O-methyltransferase (COMT) gene, was evaluated. Association with CYP17 genotype was modified by body mass index (BMI). In lean women, individuals homozygous for the CYP17 A2 allele were 1 cm shorter and had lower baseline BMD (bone mineral density), BMC, and CSA (cross sectional area) in the spine and femoral neck than did other women (BMD spine A2A2: 0.975 g/cm2 versus 1.011 g/cm2 in A1A1 + A1A2, P = 0.002). Conversely, an adverse association with A2A2 and bone loss over 5 years seemed present only in overweight women, but differences were small. Response to HRT was not dependent on CYP17 genotype. COMT genotype was not associated with bone mass at baseline, bone loss in untreated women, or response to HRT. In conclusion, the A2 allele of the CYP17 T(27)-C polymorphism is associated with reduced bone mass and bone size in lean perimenopausal women, whereas high BMI protects against this negative association. The COMT G(1947)-A polymorphism is not associated with bone parameters in this study.

5' Untranslated Regions↗