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PubMed2001

Genetic variation and obesity in Australian women: a prospective study.

OBJECTIVE: A number of candidate genes have been implicated in the pathogenesis of obesity in humans. This study examines associations between longitudinal changes in body mass and composition and the presence of polymorphisms in the beta-3 adrenergic receptor, tumor necrosis factor-alpha, leptin, and leptin receptor (Lepr) in a cohort of Australian women. RESEARCH METHODS AND PROCEDURES: Healthy white Australian women (n = 335) were randomly selected from the Barwon region of Victoria and underwent baseline anthropometry and double-energy X-ray absorptiometry for assessment of body mass and adiposity. These measurements were repeated again at 2-year follow-up. Genomic DNA was extracted and used for polymerase chain reaction-based genotyping of all polymorphisms. RESULTS: The Pro1019Pro Lepr polymorphism was associated with longitudinal increases in body weight (p = 0.02), fat mass (p = 0.05), and body mass index (p = 0.01) in this study, and individuals homozygous for the A allele at this locus had a greater propensity to gain body fat over time. The largest effects on body composition seemed to be in individuals already obese at baseline. Changes in body weight, fat mass, percent body fat, and body mass index over a 2-year period were not associated with genetic variation in the beta-3 adrenergic receptor (Trp64Arg), tumor necrosis factor-alpha promoter, or leptin genes in non-obese or obese women. DISCUSSION: These results suggest that a Lepr polymorphism is involved in the regulation of body mass and adiposity in obese Australian white women, which may have implications for the treatment of obesity in this population.

Absorptiometry, Photon↗

PubMed2005

A longitudinal 3-dimensional size and shape comparison of untreated Class I and Class II subjects.

BACKGROUND: The invention of the Broadbent-Bolton cephalometer in 1925 made possible the collection of 3-dimensional data from biorthogonal plain film head radiographs. The objective of this study was to compare longitudinal changes in the shape and size of craniofacial structures between 16 untreated Class II Division 1 girls and 16 untreated Class I Bolton girls. METHODS: Procrustes analyses were used to compare differences in 30 cephalometric landmarks that were 3-dimensional. The same methods were also used to analyze changes of 4 subsets of landmarks (maxilla, mandible, midface, and cranial vault). Comparisons included shape and size differences between adjacent age groups at ages 6, 11, and 15 in the Class II sample as well as between the Class I and Class II samples at each age. RESULTS: Overall, the craniofacial complex underwent continuous shape change from ages 6 to 15 in both samples. In the Class II sample, the smallest contribution to craniofacial shape change was seen for the mandibular landmarks between ages 6 and 11. Compared with the Class I sample, the Class II sample had (1) a longer facial pattern, (2) the smallest mandibular shape difference at age 6 and the largest at age 15, and (3) more protrusive maxillary landmarks at all ages compared with the Class I sample. The Class II sample also had the largest change in size from ages 11 to 15 (6.5%), whereas the Class I sample showed the greatest size change (10.5%) from ages 6 to 11. CONCLUSIONS: Clinically significant size and shape differences were observed during growth and development between Class II and Class I subjects in this sample.

Adolescent↗

PubMed2004

[Effects of smoking habits on pulmonary function. Cross-sectional and longitudinal studies in male subjects on medical check-up].

Cross-sectional and longitudinal studies were done to evaluate effects of cigarette smoking and smoking cessation on age-related pulmonary function decline. Data on pulmonary function from 11,875 healthy asymptomatic men between the ages of 35 and 74 years were analyzed on the basis of smoking habits in each age group. Longitudinal changes in pulmonary function during a 5-yr period were also assessed in relation to smoking habits in 1888 healthy men. Cross-sectional studies showed that the difference of FEV1 between man current smokers and men who had never smoked is small at younger ages but increases with increases in age. A beneficial effect on FEV1 decline was observed in former smokers, even in less than 1 year after smoking cessation. Longitudinally, current smokers showed a more rapid decline in FEV1 in 5 years than nonsmokers. The men who quitted smoking had lower rates of decline in FEV1 than those who continued to smoke. These results indicate that cigarette smoking is associated with reduced pulmonary function and that smoking cessation may have a beneficial effect on FEV1 decline. Provision of a smoking cessation program for all smokers, especially those with a rapid decline of FEV1, should be considered a very important strategy to prevent progression of COPD.

Adult↗

PubMed1998

Isometric muscle strength is an indicator of self-reported physical functional disability in patients with rheumatoid arthritis.

The objective of our study was to examine (1) whether isometric muscle strength contributes to the explanation of the physical functional disability of a rheumatoid arthritis (RA) patient population after accounting for other disease parameters and demographic variables and (2) whether change in isometric muscle strength is an indicator of change in physical functional disability. Sixty-five consecutive patients fulfilling the American Rheumatism Association 1987 revised criteria for RA were included in the study. Isometric muscle strength was measured with a validated Muscle Strength Index (MSI) calculated as the mean score of standardized isometric extension and flexion strength of the knee and elbow joints. Physical functional disability was measured with the physical dimension of the Health Assessment Questionnaire (HAQ). For 56 patients, we could obtain 1 yr follow-up data. Cross-sectionally, there was a significant correlation (r = -0.51, P < 0.01) between the MSI and the HAQ. Muscle strength remained a significant determinant of the HAQ in multivariate analysis accounting for disease and demographic variables. Longitudinally, change in MSI explained additional variance of change in HAQ after accounting for change in pain, the most important correlate of change in HAQ.

Adult↗

PubMed2000

Growth, dietary intake, and trace element status in pubescent athletes and schoolchildren.

PURPOSE: To examine interactions between club-level sports training, dietary intake, and nutritional status during puberty. METHODS: A 2-yr prospective study was undertaken with 64 boys (40 ice hockey players, 24 controls) and 71 girls (28 gymnasts, figure skaters, and runners, 43 controls). The boys' age in the beginning of the study was 12-13 yr, whereas the girls were 11-12 yr. The following variables were measured in the beginning, and after 1 and 2 yr: physical activity level (record), dietary intake (record), blood hemoglobin concentration, serum ferritin, zinc and copper concentration, anthropometric indices (height, weight, skinfolds, upper arm muscle girth), and biological maturation (self-report). RESULTS AND CONCLUSIONS: The changes in the anthropometric variables throughout the study period were not different between the athletes and controls (P = 0.09). The athlete boys had higher mean energy, iron and zinc intakes, and higher mean serum zinc concentration than the controls (P < or = 0.003). The athlete and control girls' dietary intakes and biochemical indices of trace element status were not different from each other (P < or = 0.13). Moreover, sports participation was not associated with the longitudinal changes in trace element status (P > or = 0.08). These data suggest that club-level sports training does not affect growth, maturation or nutritional status during puberty.

Adolescent↗

PubMed2000

Longitudinal relationship among growth, nutritional status, and pulmonary function in children with cystic fibrosis: analysis of the Cystic Fibrosis Foundation National CF Patient Registry.

OBJECTIVE: To determine prospectively the relationship among growth, nutritional status, and pulmonary function over a 4-year period in a large cohort of children with cystic fibrosis (CF). STUDY DESIGN: CF Foundation National CF Patient Registry data collected from 1991 to 1995 for 968 children (507 male) aged 5 to 8 years with pancreatic insufficiency and forced expiratory volume in 1 second within 60% to 140% of predicted values (FEV(1)%) were analyzed longitudinally. Variables hypothesized to affect FEV(1)% included age, sex, z scores for height, weight, percent of height-appropriate body weight, and annual number of days hospitalized. RESULTS: The significant decline in FEV(1)% was curvilinear and dependent on baseline FEV(1)%; children with initial FEV(1)% > or = 90 declined 2.6 U/y more than those with initial FEV(1)% <90. Boys gained but girls declined in z scores for height. Girls decreased in z scores for weight at a greater rate than boys. The z scores for weight and percent of height-appropriate body weight were significantly associated with longitudinal changes in FEV(1)%, after adjustment was done for hospitalizations. CONCLUSIONS: Growth, nutritional status, and pulmonary function are not stable in prepubertal children with CF and pancreatic insufficiency. Important sex-related differences in growth occur before puberty. Growth and nutritional status are associated with changes in FEV(1)%, suggesting that nutritional intervention may slow the decline in pulmonary function in children with CF.

Body Height↗

PubMed2006

Long-term effect of bezafibrate on pancreatic beta-cell function and insulin resistance in patients with diabetes.

OBJECTIVE: Development of insulin resistance (IR) and the progressive failure of the pancreatic beta-cell function (BCF) may be important in the pathogenesis of type 2 diabetes. Influence of peroxisome proliferator-activated receptors ligand bezafibrate on BCF and IR in patients with diabetes is unknown. The present study was aimed to investigate the long-term effect of bezafibrate on these parameters in diabetic patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study. METHODS: Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained from 351 diabetic patients (168 treated by bezafibrate and 183 by placebo) who completed a 2-year of randomized, double-blind, placebo-controlled study period. The homeostatic indexes of BCF (HOMA-BCF) and IR (HOMA-IR) were calculated according to the homeostasis model of assessment. RESULTS: Both groups displayed similar baseline characteristics. During follow-up, in the placebo group there was 28% rise of HOMA-IR (p<0.001). In contrast, HOMA-IR in patients in the bezafibrate group did not change (p=0.99). The intergroup differences in HOMA-IR percentage changes were in favor of bezafibrate (p=0.01). HOMA-BCF values have significantly decreased by 13.9% (p=0.04) in patients of placebo group, whereas in patients of bezafibrate group HOMA-BCF was stable during follow-up and its alterations (-2.9%) were non-significant (p=0.59). CONCLUSIONS: Diabetic patients from the placebo group demonstrated a progressive declining of BCF and an increasing of IR over 2 years of follow-up. These longitudinal changes were attenuated when patients used bezafibrate.

Aged↗

PubMed1999

Bridging activity as a mode of stress testing for persons with hemiplegia.

OBJECTIVE: To establish a stress testing protocol for hemiplegic persons using graded bridging activity at the rates of 3 to 24 repetitions per minute. DESIGN: Paired comparisons of exercise parameters and admission and discharge data between hemiplegic and control groups. SETTING: Inpatient rehabilitation program of a tertiary rehabilitation center in Japan. PATIENTS: (1) Preliminary study: five hemiplegic patients. (2) Comparison with normal subjects: 39 hemiplegic patients and 10 age-matched controls. (3) Study of reproducibility: five hemiplegic patients and five controls. (4) Longitudinal changes: 30 hemiplegic patients. MAIN OUTCOME MEASURES: Oxygen consumption (VO2), heart rate (HR), and HR oxygen coefficient (regression coefficient between HR and VO2). RESULTS: The testing protocol was applicable to 88.6% of hemiplegic patients. The relationship between HR and VO2 was linear, and HR oxygen coefficient was significantly lower in hemiplegic patients than the controls. The intraclass correlation coefficients were greater than 0.7 for VO2, HR, and HR oxygen coefficient, indicating satisfactory reproducibility. HR decreased longitudinally for the same stress levels and the HR oxygen coefficient increased, indicating improved fitness level. CONCLUSIONS: The bridging activity protocol is a useful mode for stress-testing hemiplegic persons. The linearity between HR and VO2 with this protocol allows us to use the indices of fitness obtainable from this relationship.

Activities of Daily Living↗

PubMedDate not supplied

Postural hypotension and EEG variables predict cognitive decline: results from a 5-year follow-up of healthy elderly women.

Quantified electroencephalographic activity (EEG) has been used to study normal ageing and dementia. Few studies have described longitudinal changes in the very old. A cognitive decline has been described in subjects with white-matter lesions and hypertension but the association with hypotension is unclear. Our aim was to study the predictive value of quantified EEG for the development of cognitive decline and associations with postural hypotension. Participants. Thirty-three healthy women aged 75-95 years, with no signs of cerebrovascular disease, dementia or acute illness at baseline examination took part in a longitudinal 5-year follow-up study. The women were recruited from a random selection using the Municipal Registry. Quantified EEG was assessed twice and recorded on a Siemens-Elema connected to a Biological Banker. The medical and neuropsychological examination was conducted twice. Dementia was classified according to DSM criteria. The assessment included Mini-Mental Scale Examination (MMSE), spatial and vocabulary tests. Blood pressure was measured in supine position and an orthostatic test was performed with continuous ECG recording. Seven women (cases) developed cognitive decline at the 5-year follow-up, defined as newly developed MMSE < 27 and dementia symptoms. Low beta activity at baseline predicted development of cognitive decline. The women who remained healthy at follow-up showed an increase of alpha and theta activity. The cases had a higher orthostatic blood pressure fall during tilting at baseline (16 mm Hg) than the controls (1 mm Hg, p < 0.01). The orthostatic reaction was correlated with increased levels of theta and alpha activity at follow-up (r = -0.47 to -0.52; p < 0.01). Low beta activity predicts for cognitive decline in the elderly and an orthostatic blood pressure reaction is a risk factor for cognitive decline.

Aged↗

PubMedDate not supplied

Effect of hyperopic photorefractive keratectomy on corneal sensitivity: a longitudinal study.

PURPOSE: To investigate corneal sensitivity after photorefractive keratectomy (PRK) for low hyperopia, as measured with a non-invasive stimulus. METHODS: Two experimental groups were recruited: a control group of 17 patients (mean age 61.65 years) who underwent no treatment, and a PRK group of 11 patients (mean age 58.64 years) who underwent one of three attempted hyperopic corrections: +2.00 D (two patients), +3.00 D (four patients), +4.00 D (five patients). Corneal sensitivity was assessed centrally and peripherally, at temporal, medial, and inferior locations, approximately 1 mm from the limbus, using the Non-Contact Corneal Aesthesiometer (NCCA). Measurements were taken at each location for the control group and at preoperative, and postoperative weeks 1 and 2, 1, 3, and 6 months for the PRK group. RESULTS: Comparison of control and PRK groups (preoperative sensation threshold) (t-test): central P=.715, temporal P=.719, medial P=.943, inferior P= .920. Comparison of longitudinal changes in PRK group (one-way ANOVA): central P=.612, temporal P=.997, medial P=.981, inferior P=.993. CONCLUSIONS: Using the Non-Contact Corneal Aesthesiometer, no significant difference was found between the control and PRK groups for preoperative sensation thresholds, and no significant change in corneal sensitivity was found between any of the test time periods at any of the four corneal test locations for the PRK group.

Adult↗

PubMed2026

Longitudinal surveillance of antibiotic resistance and virulence evolution in Clostridioides difficile: a 4-year retrospective study of hospitalized patients in a tertiary hospital in China.

UNLABELLED: Clostridioides difficile (C. difficile) is the primary pathogen responsible for nosocomial infectious diarrhea and pseudomembranous colitis. In China, metronidazole and vancomycin are the preferred treatments for C. difficile infection (CDI). This study aimed to investigate the evolution of vancomycin (VA) and metronidazole (MTZ) resistance, as well as the longitudinal changes in virulence over time, using next-generation sequencing, drug susceptibility tests, and analysis of resistance and virulence genes. Additionally, we monitored the emergence of the highly virulent C. difficile strain RT027 and the spread and potential outbreak of C. difficile in the hospital setting. A random stratified sampling method was used to select 114 fecal samples from inpatients at Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, between 2021 and 2024. Clinical data from the enrolled patients were also collected. We conducted antigen and toxin protein detection for C. difficile, strain isolation and identification, drug sensitivity tests, whole genome sequencing, and bioinformatics analysis. This included comparisons of drug resistance genes, detection of toxin genes, and the construction of phylogenetic trees based on pan-genome analysis to investigate the resistance and toxin gene variations in C. difficile. Among the 114 samples collected from Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, no vancomycin- or metronidazole-resistant strains were identified. However, the average minimum inhibitory concentration (MIC) of C. difficile to vancomycin increased annually (H = 33.208, P < 0.05). The average MIC of C. difficile to metronidazole was highest in 2022 but decreased in 2023 and 2024 (H = 41.990, P < 0.05). Notably, in 2024, one C. difficile strain exhibited an MIC for metronidazole at the resistance threshold (2.00 μg/mL). Further Spearman correlation analysis of the strain years with drug sensitivity results revealed a positive correlation between strain years and the MIC levels of vancomycin and metronidazole (r = 0.528, P < 0.05; r = 0.377, P < 0.05). The proportion of toxin-producing strains increased annually, with 100% of strains in 2024 producing toxins, representing the highest proportion compared to the previous three years (X² =11.75, P < 0.05). Both vancomycin and metronidazole remain effective for the treatment of CDI in clinical practice. However, the sensitivity of C. difficile to these two drugs is gradually decreasing, and the rate of toxin gene carriage is also rising in clinical cases. No hospital outbreaks of C. difficile infections were identified in this study. IMPORTANCE: Clostridioides difficile has developed resistance to multiple antibiotics, including cephalosporins, clindamycin, and fluoroquinolones. This has exacerbated the global antibiotic resistance crisis. In China, according to current treatment guidelines, vancomycin and metronidazole are the preferred first-line drugs for treating C. difficile infections. However, there are reports indicating the emergence of new resistance to both vancomycin and metronidazole. Although there is extensive research on the long-term antibiotic resistance of C. difficile abroad, research on the continuous monitoring of antibiotic resistance and potential outbreaks of C. difficile in China is relatively limited. To fill this gap, we studied positive C. difficile strains from a tertiary general hospital in China. Through Next-Generation Sequencing (NGS), drug sensitivity testing, and analysis of drug resistance and virulence genes, we revealed the evolution of C. difficile's resistance to vancomycin and metronidazole, as well as changes in virulence, and monitored the spread within the hospital and potential outbreaks of C. difficile.

Humans↗

PubMed2002

Bone metabolism during the perimenopausal transition: a prospective study.

OBJECTIVE: Changes in biochemical markers of bone formation and resorption were followed over the course of 1 year in premenopausal, perimenopausal and early postmenopausal women. METHODS: Sixty-four subjects were analyzed, grouped according to their menstrual pattern, menopausal complaints and endocrinological parameters to be premenopausal (n=20), perimenopausal (n=24) or early postmenopausal (n=20). The parameters studied at four visits during the 12-month study period were the urinary pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD), and N-terminal telopeptide (NTX) as bone resorption markers, as well as osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) in serum, representing bone formation. The longitudinal changes over time as well as intergroup differences were analyzed using generalized estimating equations (GEE) in connection with Wald statistics. RESULTS: Over the course of 1 year BAP levels decreased in the late premenopausal group (P<0.05). The perimenopausal group exhibited significant changes of PYD, DPD and OC (P<0.01), NTX levels were higher than in premenopause. Postmenopausal subjects had elevated NTX values, while PYD and DPD levels remained close to the perimenopausal range. Only for OC a time effect was seen during postmenopause. CONCLUSIONS: Changes in bone turnover already begin in late premenopause, when decreased bone formation may precede increased bone resorption. The rise of NTX from late premenopause through early postmenopause indicates diagnostic sensitivity of this parameter to changes in bone metabolism induced by estrogen withdrawal. PYD and DPD do not follow this pattern, but change significantly with time during perimenopause to then remain largely unchanged in early postmenopause.

Adult↗

PubMed2005

Imaging the developing epileptic brain.

Accurate identification of cortical malformations in children with epilepsy can be crucial for successful clinical management. Although standard head-coil magnetic resonance imaging (MRI) at 1.5 tesla (T) can be used to view the macrostructure of the brain, phased array technology at both 1.5 and 3T significantly improves signal-to-noise ratio (SNR). As a result, spatial resolution and contrast can be optimized to increase visual detection of subtle macrostructural changes that occur with small epileptogenic lesions. In addition, these improvements in SNR allow more accurate quantitative analysis of brain macrostructure and more accurate assessment of brain microstructure using newer sophisticated imaging techniques. For example, phased array imaging enables more accurate diffusion tensor imaging (DTI), and 3T imaging, when combined with phased array technology, enables more informative diffusion spectroscopic imaging (DSI). Recent technological improvements therefore result in improved lesion detection and enable assessment of cerebral growth trajectories and associated longitudinal changes in tissue microstructural organization that occur in association with various types of epilepsy. This article presents a brief comparison of imaging techniques currently in use, both clinically and experimentally, to diagnose, treat, and increase our understanding of the neuropathology of epilepsy in the developing brain.

Adult↗

PubMed1998

Left ventricular structure and function in children infected with human immunodeficiency virus: the prospective P2C2 HIV Multicenter Study. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) Study Group.

BACKGROUND: The frequency of, course of, and factors associated with cardiovascular abnormalities in pediatric HIV are incompletely understood. METHODS AND RESULTS: A baseline echocardiogram (median age, 2.1 years) and 2 years of follow-up every 4 months were obtained as part of a prospective study on 196 vertically HIV-infected children. Age- or body surface area-adjusted z scores were calculated by use of data from normal control subjects. Although 88% had symptomatic HIV infection, only 2 had CHF at enrollment, with a 2-year cumulative incidence of 4.7% (95% CI, 1.5% to 7.9%). All mean cardiac measurements were abnormal at baseline (decreased left ventricular fractional shortening [LV FS] and contractility and increased heart rate and LV dimension, mass, and wall stresses). Most of the abnormal baseline cardiac measurements correlated with depressed CD4 cell count z scores and the presence of HIV encephalopathy. Heart rate and LV mass showed significantly progressive abnormalities, whereas FS and contractility tended to decline. No association was seen between longitudinal changes in FS and CD4 cell count z score. Children who developed encephalopathy during follow-up had depressed initial FS, and FS continued to decline during follow-up. CONCLUSIONS: Subclinical cardiac abnormalities in HIV-infected children are common, persistent, and often progressive. Dilated cardiomyopathy (depressed contractility and dilatation) and inappropriate LV hypertrophy (elevated LV mass in the setting of decreased height and weight) were noted. Depressed LV function correlated with immune dysfunction at baseline but not longitudinally, suggesting that the CD4 cell count may not be a useful surrogate marker of HIV-associated LV dysfunction. However, the development of encephalopathy may signal a decline in FS.

AIDS Dementia Complex↗

PubMed2005

Is there cognitive decline 1 year after CABG? Comparison with surgical and nonsurgical controls.

BACKGROUND: It is widely assumed that decline in cognition after coronary artery bypass grafting (CABG) is related to use of the cardiopulmonary bypass pump. Because most studies have not included comparable control groups, it remains unclear whether postoperative cognitive changes are specific to cardiopulmonary bypass, general aspects of surgery, or vascular pathologies of the aging brain. METHODS: This nonrandomized study included four groups: CABG patients (n = 140); off-pump coronary surgery (n = 72); nonsurgical cardiac controls (NSCC) with diagnosed coronary artery disease but no surgery (n = 99); and heart healthy controls (HHC) with no cardiac risk factors (n = 69). Subjects were evaluated at baseline (preoperatively), 3 months, and 12 months. Eight cognitive domains and a global cognitive score, as well as depressive and subjective symptoms were analyzed. RESULTS: At baseline, patients with coronary artery disease (CABG, off-pump, and NSCC) had lower performance than the HHC group in several cognitive domains. By 3 months, all groups had improved. From 3 to 12 months, there were minimal intrasubject changes for all groups. No consistent differences between the CABG and off-pump patients were observed. CONCLUSIONS: Compared with heart healthy controls (HHC), the groups with coronary artery disease had lower cognitive test scores at baseline. There was no evidence that the cognitive test performance of coronary artery bypass grafting (CABG) patients differed from that of control groups with coronary artery disease over a 1-year period. This study emphasizes the need for appropriate control groups for interpreting longitudinal changes in cognitive performance after CABG.

Aged↗

PubMed2000

Hemodynamic changes and systemic activation of coagulation and fibrinolysis during controlled endotoxemia in pigs.

In this study, we have established a pig model that can combine extensive hemodynamic monitoring with simultaneous repetitive (serial) blood sampling for the study of multiple variables related to the hemostatic system. Sixteen healthy young pigs were studied to evaluate the influence of continuous endotoxin infusion on hemodynamic patterns and activation of coagulation and fibrinolysis. The chief aim of the study was to investigate the applicability of analytical methods primarily developed for use with human plasma samples in quantification of factors and reaction products of the porcine coagulation and fibrinolytic systems, and further, to use these methods to study the longitudinal changes in the plasma levels of these hemostatic variables as a consequence of endotoxin infusion. We found that acute, controlled endotoxemia induced a hemodynamic state of shock and reduced pulmonary gas exchange. Simultaneously, a gradual increase in peripheral blood mononuclear cell tissue factor activity was demonstrated, and increased maximally 5.5-fold 4 hours after onset of endotoxin infusion. Thrombin-antithrombin complexes increased in plasma to maximum levels after 3 hours, accompanied by an ethanol gelation test that was regularly positive after 1 to 2 hours, and fibrin monomer levels that gradually increased maximally 3.8-fold after 6 hours. These changes were followed by gradual decreases of both fibrinogen and factor VII levels, mainly due to consumption. Plasma levels of tissue type plasminogen activator activity peaked at 1.5 hours (11.3-fold increase), whereas the peak of plasminogen activator inhibitor-1 activity (14-fold increase at 4.5 hours) was delayed compared to tissue plasminogen activator and completely extinguished plasma tissue plasminogen activator activity. The sequential activation of coagulation and fibrinolysis established a procoagulant state favoring disseminated intravascular coagulation and microthrombus formation, potentially leading to multiple organ dysfunction.

Animals↗

PubMed2005

A longitudinal study of brain morphometrics using serial magnetic resonance imaging analysis in a canine model of aging.

Longitudinal changes in cortical atrophy, ventricular enlargement, and lesion development in serial MRI scans collected from 47 healthy dogs from 1999 (8-11 years old) to 2002 (11-14 years old) were studied. The first method involved manual region of interest volumetric analysis to examine changes in cerebral and ventricular volume during the three years. No change in cerebral volume was detected but ventricular volume increased significantly each year in 2000, 2001, and 2002. Increased ventricular volume parallels early studies of age-dependent ventricular enlargement in the brain of aging beagle dogs. The second method involved a visual analysis of co-registered serial MRIs for each subject. Consistent with the volumetric results, there was no visible change in cortical thickness indicating no cerebral atrophy, but a significant increase in ventricular size was noted. Visual examination also revealed a significant increase in number of dogs who developed aging lesions over the last 2 years in 2001 and 2002. Additionally, a disproportionate number of lesions were recorded in the frontal cortex and caudate nucleus compared to other brain regions. These lesion findings are consistent with other studies in the aging dog that suggest that the frontal lobes may be particularly vulnerable to age-related changes.

Aging↗

PubMed2006

Concentrations of plasminogen activators and their inhibitors in blood preconceptionally, during and after pregnancy.

BACKGROUND: Haemostasis is a complex balance of activating and inhibitory pathways resulting in coagulation and lysis. Normal pregnancy is associated with hypercoagulation that is even more profound in complicated pregnancies. OBJECTIVE: To study the role of the plasminogen-activator system in complicated pregnancy with regard to haemostasis, it is essential to have reference values of components of this system during uneventful pregnancy. In this study we investigated the concentrations of six different components of the plasminogen-activator system preconceptionally, during and after uncomplicated pregnancies. MATERIAL AND METHODS: Tissue-type and urokinase-type plasminogen activator (tPA and uPA), plasminogen inhibitor type-1 and -2 (PAI-1 and-2), and the complexes between tPA and PAI-1, and between uPA and PAI-1 (tPA-PAI-1, uPA-PAI-1) were measured by ELISAs in blood obtained preconceptionally, at 6, 10, 20, 32 weeks of gestation, and 6 weeks after delivery in uncomplicated pregnancies (n=41; all six parameters n=22). RESULTS: tPA and uPA concentrations decreased in the first 10 weeks of pregnancy and subsequently increased in the third trimester. PAI-1 concentrations increased in the third trimester and PAI-2 concentrations increased throughout pregnancy (preconception versus 32 weeks of gestation; 38.73 versus 102.23ng/ml, and 0.024 versus 151.06ng/ml, respectively). tPA-PAI-1 and uPA-PAI-1 complex concentrations decreased in the first trimester, followed by an increase in the third trimester. The concentrations of all components returned to the preconception values 6 weeks after delivery. CONCLUSION: This study provides longitudinal data on activating and inhibitory components of the plasminogen-activator system during pregnancy. Insight in the longitudinal changes in these concentrations may be of help in the understanding of the thrombotic tendency in pregnancy complications such as preeclampsia.

Adult↗