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PubMed1998

Longitudinal changes in inflammatory markers in nasal lavage of cotton workers. Relation to endotoxin exposure and lung function changes.

OBJECTIVES: The aim of this study was to evaluate time-related changes in inflammatory markers in nasal lavage (NAL) in relation to endotoxin exposure and lung function changes. METHODS: Endotoxin in cotton dust is well known to elicit proinflammatory mediators involved in acute or chronic respiratory inflammation due to cotton dust. We applied nasal lavage as well as lung function and exposure measurements in a small group (n = 11) of cotton workers during 6 weeks of observation (after 2 weeks free of exposure). Several inflammatory markers in NAL, such as interleukin 8 (IL-8), IL-6, and down-stream mediators, including soluble tumor necrosis factor receptor 75 (sTNF-R75) and soluble intercellular adhesion molecule 1 (ICAM-1), cell counts, marker of epithelial response (uric acid), and marker of plasma exudation (albumin) were measured. RESULTS: At the exposure levels examined in this study [cotton dust, geometric mean (GM) = 1.10 mg/m3; endotoxin, GM = 2,869 EU/m3], several inflammatory markers in NAL such as IL-8, sTNF-R75, and albumin tended to increase through the measurement period with increasing airborne endotoxin concentration (in six workers who had paired measurements in weeks 1 and 6). Although no statistical significance was reached, airborne endotoxin exposure and all inflammatory markers in NAL were relatively higher in cotton workers with a 6-week lung function decrease. CONCLUSION: The data suggest that inflammatory markers in NAL are associated with repeated airborne endotoxin exposure.

Adult↗
PubMed1992

Longitudinal changes in lateral ventricular volume in patients with dementia of the Alzheimer type.

We determined the rates of lateral ventricular enlargement and decline in cognitive performance for 11 men and nine women with dementia of the Alzheimer type (DAT), and compared these rates with the same measures obtained for age-matched healthy controls (nine men and eight women). DAT patients, as a group, had only mild cognitive impairment at initial evaluation, and each patient was followed from 9 months to over 7 years with yearly evaluations. Six DAT patients had isolated memory impairment as their only cognitive deficit early in the course of the disease. The rate of total lateral ventricle enlargement (cm3/yr) was significantly different between DAT and healthy controls, and was more specific and sensitive to the diagnosis of DAT than comparison of cross-sectional volumes at final evaluation. The rate of total lateral ventricular enlargement did not differ significantly by patient sex, ventricular size at initial evaluation, age, or degree of cognitive impairment as measured by Mini Mental State Examination scores. However, in the six DAT patients initially found to have isolated memory impairment, the rate of ventricular enlargement during the period of isolated memory impairment was significantly less than the rate of ventricular enlargement after the onset of nonmemory cognitive impairment. The diagnostic power of total lateral ventricular measures made from two CTs separated by 1 year and obtained early in the course of the illness, however, was only 0.33. We conclude that the total lateral ventricular enlargement accompanying DAT is due to continuous, pathologic cell loss, significantly greater than cell loss due to the healthy aging process.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2001

Longitudinal changes in bone lead concentration: implications for modelling of human bone lead metabolism.

In this study, 539 occupationally exposed subjects received in vivo bone lead measurements using 109Cd excited K X-ray fluorescence (109Cd K XRF). Of these subjects, 327 had previously been measured five years earlier. Measurements were made from both tibia and calcaneus samples, taken to reflect cortical and trabecular bone, respectively. Changes in tibia lead concentration related negatively to initial tibia lead concentration and positively to both lead exposure between the measurement dates and initial calcaneus lead concentration. This finding confirmed and strengthened the interpretation of an earlier study involving fewer subjects. With the larger data set it was possible to examine subgroups of subjects. This showed that people aged less than 40 years had a shorter half-life for the release of lead from the tibia (4.9, 95% CI 3.6-7.8 years) than did those older than 40 (13.8, 95% CI 9.7-23.8 years). Similarly, less intensely exposed subjects (lifetime average blood lead < or = 25 micrograms dL-1) had a shorter tibia lead half-life (6.2, 95% CI 4.7-9.0 years) than those with a lifetime average blood lead > 25 micrograms dL-1 (14.7, 95% CI 9.7-29.9 years). Age and measures of lead exposure were strongly correlated; nevertheless, age matched subgroups with high and low intensity exposures showed clearance rates that were significantly different at the 10% level, with the lower exposure intensity again being associated with the faster clearance. These findings imply that current models of human lead metabolism should be examined with a view to adjusting them to account for kinetic rates varying with age and probably also with exposure level.

Adult↗
PubMed1994

The oral gram-negative anaerobic microflora in young children: longitudinal changes from edentulous to dentate mouth.

Eruption of primary teeth has a great influence on the oral environment by providing suitable niches for bacterial colonization. The composition of oral gram-negative anaerobic microflora was investigated in 21 young children (mean age 32 months) with primary dentition. The bacterial findings of samples were compared with those of the same children collected at their edentulous infant period (mean age 3 months). During the primary period, 2 samples were collected from each child: a sample with dental floss from gingival margin of 2 teeth and stimulated saliva pooled with a mucosal swab sample. Both samples were cultured aerobically and anaerobically using nonselective and selective media. Prevotella melaninogenica, nonpigmented Prevotella spp., Fusobacterium nucleatum group and Capnocytophaga spp. were found in all children at the older age, whereas they occurred in edentulous mouth in 76%, 62%, 67% and 19%, respectively. The occurrence of Prevotella loescheii increased from 14% to 90%, Prevotella intermedia from 10% to 67%, Leptotrichia spp. from 24 to 71%, Campylobacter (Wolinella) spp. from 5 to 43% and Eikenella corrodens from 5 to 57%. Only the occurrence of Bacteroides gracilis and Veillonella spp. remained at about the same level. Species not isolated from the edentulous mouth, such as Prevotella denticola, Fusobacterium spp. other than the F. nucleatum group and Selenomonas spp. were now detected in 71%, 71% and 43% of the children. The stability of the colonizing P. melaninogenica strain(s) in the oral cavity was determined by using ribotyping; 1-2 isolates per child from the edentulous infant period of 9 children and 3-15 isolates per child from their primary dentition period were analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Typing Techniques↗
PubMed1997

Antiresorptive therapy in hyperthyroid patients: longitudinal changes in bone and mineral metabolism.

The effect of antiresorptive therapy with nasal calcitonin (CT) in recently diagnosed hyperthyroid patients on conventional medical therapy as well as the evolution of bone metabolism were assessed. Forty-five patients with recent-onset hyperthyroidism (<12 weeks) were sex and menopause stratified and randomly allocated to treatment with carbimazole (Neotomizol), carbimazole plus low dose CT (Calsynar; 100 IU/day, 2 days/week), or carbimazole plus high dose CT (Calsynar; 100 IU/day, 14 days/month). Bone mineral density was measured by dual x-ray absorptiometry in lumbar spine, femoral neck, and Ward's triangle at 0, 9, and 18 months of treatment. We also determined free T4, free T3, TSH, osteocalcin, total and bone alkaline phosphatases, tartrate-resistant acid phosphatase, type I collagen C telopeptide, and urinary hydroxyproline every 3 months of follow-up. No significant difference was observed among treatments. A euthyroid state was attained at 3 months. Bone mass increased significantly at the 9 month evaluation (P < 0.05), with a 5-10% net gain during follow-up. Nevertheless, final bone mass was 4-8% smaller than expected. Bone formation markers were increased at 0 and 3 months, with reductions at 6-9 months; resorption bone markers showed a significant reduction at the 3 month evaluation. These results indicate that the euthyroid state partially reduces hyperthyroidism-associated osteopenia, with a bone mass recovery period during the 6-9 early months of effective treatment. This recovery phase is characterized by raised bone formation markers and reduced bone resorption markers. The treatment with nasal CT at the doses assayed has no additional effect over that of attainment of the euthyroid state.

Absorptiometry, Photon↗
PubMed2002

Longitudinal changes in brain magnetic resonance imaging findings in children with sickle cell disease.

Children with sickle cell anemia (HbSS) are at high risk for neurologically overt cerebral infarcts associated with stroke and neurologically silent cerebral infarcts correlated with neuropsychometric deficit. We used complete magnetic resonance imaging (MRI) histories from 266 HbSS children, aged 6 through 19 years, who were enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD) to examine silent infarct prevalence, localization, recurrence, and progression. We report a baseline prevalence of 21.8%, marginally higher than previously reported due to improved imaging technologies. Although we observed no overall sex difference in prevalence, most lesions in girls occurred before age 6, whereas boys remained at risk until age 10. Silent infarcts were significantly smaller and less likely to be found in the frontal or parietal cortex than were infarcts associated with stroke. Children with silent infarct had an increased incidence of new stroke (1.03/100 patient-years) and new or more extensive silent infarct (7.06/100 patient-years) relative to stroke incidence among all children in our cohort (0.54/100 patient-years). Both events were substantially less frequent than the risk of stroke recurrence among children not provided chronic transfusion therapy. Although chronic transfusion is known to decrease occurrence of new silent infarcts and strokes in children with elevated cerebral arterial blood flow velocity, further study is required to determine its risk-benefit ratio in children with silent infarct and normal velocities. Until safe and effective preventive strategies against infarct recurrence are discovered, MRI studies are best reserved for children with neurologic symptoms, neuropsychometric deficits, or elevated cerebral artery velocities.

Adolescent↗
PubMed2002

Longitudinal changes in ferritin during chronic transfusion: a report from the Stroke Prevention Trial in Sickle Cell Anemia (STOP).

PURPOSE: Chronic red cell transfusion has been used for prevention of recurrent stroke in patients with sickle cell disease for three decades, and its effectiveness in primary prevention was recently shown. Iron overload, the inevitable result of chronic transfusion, is commonly monitored with serum ferritin concentration. PATIENTS AND METHODS: Sixty-one patients at high risk for stroke received chronic transfusion in a clinical trial of stroke prevention. A serum ferritin level of less than 500 ng/mL was required for study entry. Ferritin levels were obtained quarterly. Fifty patients who had four or more ferritin measurements were included in this analysis. Transfusions were administered as exchange or simple, with washed, reconstituted, or packed red blood cells, at the discretion of the site investigator. RESULTS: Serum ferritin levels increased linearly with cumulative transfusion volume during the first four ferritin measurements, but the rate of increase varied widely among patients. Rates of increase varied similarly among 23 patients who received exclusively simple transfusion with packed red cells and in five patients who received exchange transfusions. Thirty-two patients received a total transfusion volume of more than 250 mL/kg. Ferritin continued to increase linearly after the first four measurements in 14, but the remaining 18 experienced a plateau before the level reached 3,000 ng/mL. Six of those with a linear increase never reached a ferritin level of 3,000 ng/dL. CONCLUSIONS: There was strong intrapatient correlation between serum ferritin levels and volume transfused but wide interpatient variability early during chronic transfusion therapy. Intrapatient correlation declined at transfusion volumes of more than 250 mL/kg. Direct iron store assessment is needed to determine the clinical significance of serum ferritin variability.

Adolescent↗
PubMedDate not supplied

Quantitative electroencephalography in mild cognitive impairment: longitudinal changes and possible prediction of Alzheimer's disease.

The present study evaluated the clinical course of patients with mild cognitive impairment (MCI), the pattern of electroencephalography (EEG) changes following cognitive deterioration, as well as the potential of neurophysiological measures in predicting dementia. Twenty-seven subjects with MCI were followed for a mean follow up period of 21 months. Fourteen subjects (52%) progressed (P MCI) to clinically manifest Alzheimer's disease (AD), and 13 (48%) remained stable (S MCI). The two MCI subgroups did not differ in baseline EEG measures between each other and the healthy controls (n = 16), but had significantly lower theta relative power at left temporal, temporo-occipital, centro-parietal, and right temporo-occipital derivation when compared to the reference AD group (n = 15). The P MCI baseline alpha band temporo-parietal coherence, alpha relative power values at left temporal and temporo-occipital derivations, theta relative power values at frontal derivations, and the mean frequency at centro-parietal and temporo-occipital derivations overlapped with those for AD and control groups. After the follow-up, the P MCI patients had significantly higher theta relative power and lower beta relative power and mean frequency at the temporal and temporo-occipital derivations. A logistic regression model of baseline EEG values adjusted for baseline Mini-Mental Test Examination showed that the important predictors were alpha and theta relative power and mean frequency from left temporo-occipital derivation (T5-O1), which classified 85% of MCI subjects correctly.

Adult↗
PubMed1998

Longitudinal changes in pancreatic beta-cell function and metabolic clearance rate of insulin in pregnant women with normal and abnormal glucose tolerance.

OBJECTIVE: To evaluate basal pancreatic beta-cell secretion and suppression during infused insulin and the metabolic clearance rate of insulin in women with normal and abnormal glucose tolerance prior to conception and during pregnancy. RESEARCH DESIGN AND METHODS: Seven women with normal glucose tolerance and nine women with abnormal glucose tolerance during gestation were evaluated prior to conception, in early (12-14 weeks) and late (34-36 weeks) gestation. Basal insulin and C-peptide were measured after an 11-h fast and during the last 40 min of a 2-h hyperinsulinemic-euglycemic clamp at 40 mU.m-2.m-1. Suppression of basal C-peptide was calculated as the steady-state C-peptide/basal C-peptide. The metabolic clearance rate of insulin was calculated by dividing the insulin infusion rate by the steady-state insulin concentration, which was corrected for residual beta-cell secretion. RESULTS: No significant differences were noted in the following parameters between women with normal and abnormal glucose tolerance with advancing gestation: increase in basal insulin (P = 0.20) and C-peptide (P = 0.12), ability of infused insulin to decrease basal C-peptide concentration (P = 0.22), and metabolic clearance rate of insulin (P = 0.76). There was a significant 65% increase in both basal insulin (P = 0.0005) and C-peptide (P = 0.0002) concentrations in all subjects with advancing gestation. There was a significant (P = 0.0001) decrease in the ability of the infused insulin to decrease basal C-peptide concentration. C-peptide as a percentage of the basal was 64% before conception, 74% in early pregnancy, and 108% in late pregnancy. The metabolic clearance rate of insulin significantly (P = 0.0005) increased with advancing gestation: pregravid 442 ml.m-2.min-1, early pregnancy 514 ml.m-2. min-1, and 526 ml.m-2.min-1 in late pregnancy. CONCLUSIONS: Pregnancy is accompanied by progressive alterations in insulin kinetics, which are partly responsible for the hyperinsulinemia of this condition. These alterations are more likely a homeostatic response to the increased physiological insulin resistance of pregnancy.

Adult↗
PubMed2005

Longitudinal changes in insulin sensitivity and secretion from birth to age three years in small- and appropriate-for-gestational-age children.

AIMS/HYPOTHESIS: Insulin resistance and type 2 diabetes risk in human subjects who were small-for-gestational-age (SGA) at birth may be a consequence of rapid early postnatal weight gain. MATERIALS AND METHODS: We prospectively studied early changes in fasting insulin sensitivity and insulin secretion, assessed by a short intravenous glucose tolerance test that was conducted several times from birth to 3 years of age in 55 SGA (birthweight below fifth percentile) newborns and in 13 newborns with a birthweight appropriate for gestational age (AGA). RESULTS: Most SGA infants showed postnatal upward weight centile crossing and by 3 years were similar in size to AGA infants. SGA infants had lower pre-feed insulin levels at postnatal age 48 h than AGA infants (median 34.4 vs 59.7 pmol/l, p<0.05), but by the age of 3 years they had higher fasting insulin levels (median 38.9 vs 23.8 pmol/l, p<0.005), which were related to rate of weight gain between 0 and 3 years (r=0.47, p=0.0003). First-phase insulin secretion did not differ between SGA and AGA infants, but SGA infants had a lower glucose disposition index (beta cell compensation) (median 235 vs 501 min mmol(-1) l(-1), p=0.02), which persisted after allowing for postnatal weight gain (p=0.009). CONCLUSIONS/INTERPRETATION: SGA infants showed a marked transition from lower pre-feed insulin and increased insulin sensitivity at birth to insulin resistance over the first 3 years of life. This transition was related to rapid postnatal weight gain, which could indicate a propensity to central fat deposition. The additional observation of reduced compensatory beta cell secretion underlines the need for long-term surveillance of glucose homeostasis in all SGA subjects, whether or not they show postnatal catch-up growth.

Birth Weight↗
PubMed1994

Using cost-effectiveness analysis for formulary decision making: from theory into practice.

The growth of expenditures on healthcare and pharmaceutical products is a concern to third-party payers because of the absence of market discipline (price signals that consumers face). Cost-effectiveness analysis is a method that allows third-party payers to systematically make judgements about the 'value for money' of these products. It moves beyond simple unit price comparisons of alternate interventions/products to consider the full stream of relevant cost and benefits. As formulary committees begin to adopt the systematic use of cost-effectiveness analyses to inform the debate, the exercise will move from an academic to a more practical application. This transition will require several important changes including defining the purpose of cost-effectiveness analysis, measurement of outcomes and data, format of reports, and contractual arrangements between the pharmaceutical industry and analysts. As more 'real world' experience is gained in the practical application of cost-effectiveness analysis, the quality of data will improve as will its value as an aid to decision making.

Cost-Benefit Analysis↗
PubMed1994

Longitudinal changes in myocardial basic fibroblast growth factor (FGF-2) activity following coronary artery ligation in the dog.

Although fibroblast growth factor has been identified in normal and ischemic myocardium, temporal changes in mitogenic activity due to fibroblast growth factors in ischemic tissue have not been well established, nor has correlation been made with the known early increases in coronary collateral flow. This study sought to measure fibroblast growth factor activity in myocardium after coronary ligation. Accordingly the left anterior descending coronary artery of dogs was ligated and coronary collateral flow measured with radioactive microspheres. The heart was arrested after 2 h (four dogs), 1 week (four dogs), 2 weeks (three dogs), or 8 weeks (four dogs). Just before arrest collateral flow was again measured with radioactive microspheres, and the perfusion territory of the ligated vessel was demarcated with an intracoronary injection of Evans blue. The stained ischemic region was separated into central and peripheral portions. A transmural sample was removed from each portion for quantitation of tissue radioactivity and the rest was used for isolation of fibroblast growth factor and the measurement of mitogenic activity with vascular endothelial cells. To determine which fibroblast growth factor (FGF-1 or FGF-2) was being produced by the myocardium, aliquots of the isolated protein were first treated with specific antibodies to FGF-1 or FGF-2 before being assayed for mitogenicity. Coronary collateral flow did not change between 5 min and 2 h following coronary ligation, but was significantly increased at later time points. The ischemic/normal myocardial basic fibroblast growth factor mitogenic activity ratio in the peripheral ischemic tissue was increased after 2 h of ischemia (1.41 +/- 0.34), but the increase was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Longitudinal changes in lung function and respiratory symptoms in progressive systemic sclerosis. Prospective study.

Most patients with progressive systemic sclerosis (PSS) exhibit lung involvement. However, the natural history of lung disease in PSS remains poorly defined. To evaluate lung function over time in PSS, a battery of lung function tests were prospectively performed serially between 1973 and 1982 in 61 patients with PSS. Functional indexes of restriction (vital capacity and total lung capacity) and diffusion impairment (diffusing capacity) showed greater-than-expected annual rates of change. Male subjects showed a trend toward faster declines in forced vital capacity, forced expired volume in one second, total lung capacity, and functional residual capacity and a more rapid increase in static recoil pressure at 90 percent of total lung capacity than did female subjects. Nonsmokers had greater rates of decline in total lung capacity and static lung compliance (but not in forced vital capacity or diffusing capacity) and a greater rate of increase in static recoil pressure than did current and former smokers. Level of lung function at initial study visit, age, race, and chlorambucil therapy had no significant effect on the annual rates of change in lung function, whereas longer duration of disease prior to study entry was associated with a slower annual decrease in lung volumes. Between the first and last visits (mean interval 3.1 years, maximum nine years), the frequency of abnormality in pulmonary function test results showed significant change only in the diffusing capacity (60 percent increasing to 82 percent) and static lung compliance (40 percent increasing to 54 percent), whereas the frequency of respiratory symptoms showed little change. These findings indicate an overall indolent progression of PSS-related lung disease, with substantial individual variability.

Adult↗
PubMed1977

Longitudinal changes of brain amino acid content occurring before, during and after epileptic activity.

In cats affected with cortical epileptogenic foci induced by penicillin application to and cobalt implantation into the pericruciate area, the brain amino acids contents were determined in the focus as well as in extrafocal areas. In different groups of animals, brain removal for biochemical determinations was performed at different times before, during and after epilepsy and the values compared to controls. The only amino acid to show a significant change before appearance of spikes in both types of epilepsy was taurine, which decreased. Cobalt epilepsy was accompanied by changes in a larger number of amino acids than penicillin epilepsy: in the former the brain content of taurine, GABA, aspartate, glutamate, serine, threonine, glycine and alanine was altered. The changes were proportional to the severity of epilepsy and more prominent in the focus area. After disappearance of spikes the levels of most amino acids returned to normal except for some amino acids, previously unaffected by penicillin epilepsy, which were decreased. It is proposed that the decrease in brain taurine, occurring before the appearance of penicillin and cobalt epilepsy, could increase the excitability of a certain neuronal population and thus, by potentiating the effects on neurons of penicillin and cobalt, contribute to the initiation of epilepsy.

Amino Acids↗
PubMed1987

Longitudinal changes in sweet preferences in humans.

Preferences for the taste of sucrose were measured in 44 humans when they were 11-15 years of age and again in the same individuals 9-10 years later when they were 19-25 years of age. Preferred level of sweet decreased over the intervening years. This suggests that in humans, as in rats, heightened preferences for sweet observed in the young decline with age.

Adolescent↗
PubMed1985

Longitudinal changes in left ventricular diastolic function in hypertrophic cardiomyopathy.

Digitised M-mode echocardiography was used to study the changes in left ventricular diastolic function over a 3-year period in 11 patients with hypertrophic cardiomyopathy an 14 normals. Compared to normal, in hypertrophic cardiomyopathy, isovolumic relaxation was prolonged (P less than 0.001) and mitral valve opening delayed relative to minimum dimension (P less than 0.001). There was a wide range of values for the peak rates of dimension increase and wall thinning, and although the means were normal, 6 and 8 patients respectively were outside the normal range. There were no significant mean changes in function during the 3.4 +/- 0.3 years of follow-up, but, in 3 patients, marked alterations in relaxation were observed. They showed a gross reduction in the delay in mitral valve opening (125 to 55 125 to 35 and 110 to 75 msec). There was little overall change in isovolumic relaxation in two, but in one patient it reduced from 95 to 50 msec. In most patients with hypertrophic cardiomyopathy, relaxation and diastolic function appear to remain stable over a period of 3 years, and none had an apparent deterioration. Some patients may have an apparently spontaneous "improvement" in function similar in extent to that described due to the therapeutic action of calcium antagonists.

Adult↗