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Results for “Biomarker variability”

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PubMed2003

Predictive value of serum thymidine kinase level for Ig-V mutational status in B-CLL.

In B-CLL IgV(H) genes mutational status is a major prognostic factor. Since sequencing of IgV(H) genes is not available in most laboratories, an easily performed surrogate assay is desirable. To identify the best surrogate assay, and to better discriminate prognostic subgroups we analyzed clinical and biological data from 58 typical CLL cases. A higher serum thymidine kinase level (>15 U/l) proved to be a strong predictor of mutational status, and the only independent one among the studied parameters. To further identify prognostic subgroups, cluster analysis was employed on 38 cases on which all data were available, which segregated two groups including 25 and 13 patients, respectively. These two clusters differed by their proliferative potential and appeared to discriminate patients with very different clinical course and outcome. s-TK was strikingly different among these two clusters, suggesting that s-TK level could be used routinely to identify patients at risk of progression.

Aged↗

PubMed2000

Markers of hypercoagulation and von Willebrand factor in postmenopausal women with unstable coronary artery disease. Discriminatory ability regarding unstable coronary artery disease and coronary atherosclerosis using receiver operating characteristics.

OBJECTIVES: Many women with typical anginal chest pain have normal coronary angiograms. The pathogenetic mechanisms behind the chest pain in these patients are unknown but may be due to increased thrombogenicity. We evaluated markers of hypercoagulation and thrombosis in women with clinical signs of unstable coronary artery disease (CAD). METHODS AND RESULTS: A total of 158 patients with unstable CAD and 101 controls were examined: 16% of the patients had normal vessels and 84% had coronary atherosclerosis at coronary angiography. Mean plasma concentrations of von Willebrand factor antigen, soluble fibrin (SF), thrombin-antithrombin complex and D-dimer were significantly higher, whereas there was no difference regarding prothrombin fragment 1+2 between patients and controls. Patients with coronary atherosclerosis had higher mean plasma levels for most variables compared with those with normal coronary vessels, although only significantly higher for SF. D-Dimer was significantly higher in patients with normal coronary vessels compared with the control group. Although multivariate analyses showed strong significant correlations of the haemostatic variables to the diagnosis of unstable CAD, receiver operating characteristics (ROC) revealed that none of the variables represented high diagnostic accuracy in separating patients with unstable CAD. Likewise, none of the variables was particularly good at identifying coronary atherosclerosis. CONCLUSION: Our results are in favour of a hypercoagulable state in postmenopausal women with unstable CAD and coronary atherosclerosis, whereas this does not seem to be the case in patients with normal vessels. ROC revealed no variable to be particularly clinically useful in separating patients from controls or patients from those without coronary atherosclerosis.

Aged↗

PubMed2002

A non-invasively determined surrogate of cardiac power ('circulatory power') at peak exercise is a powerful prognostic factor in chronic heart failure.

OBJECTIVES: This study was designed to assess the prognostic value of a new variable derived from a cardiopulmonary exercise test, the circulatory power, a surrogate of cardiac power, at peak exercise, in patients with chronic heart failure. BACKGROUND: Peak exercise cardiac power and stroke work are invasive parameters with recently proven prognostic value. It is unclear whether these variables have better prognostic value than peak oxygen uptake (VO(2)). METHODS: The study population comprised 175 patients with chronic heart failure (ejection fraction <45%) who underwent a cardiopulmonary exercise test. Circulatory power and circulatory stroke work were defined as the product of systolic arterial pressure and VO(2) and oxygen pulse, respectively. Prognostic value was assessed by survival curves (Kaplan-Meier method) and uni- and multivariate Cox analyses. RESULTS: With a mean follow-up of 25+/-10 months, ejection fraction, heart rate, systolic arterial pressure, peak VO(2), VCO(2), the anaerobic threshold, minute ventilation, the ventilatory equivalents of oxygen and carbon dioxide, the half times of VO(2) and VCO(2) recoveries, and the circulatory stroke work and power predicted outcome. Multivariate analysis demonstrated that the peak circulatory power (chi-square=19.9, P<0.001) (but not peak circulatory stroke work) was the only variable predictive of prognosis. CONCLUSION: The prognostic value of cardiopulmonary exercise tests in heart failure patients can be improved by assessing a new variable, the circulatory power - a surrogate of cardiac power - at peak exercise.

Adult↗

PubMed2001

B cells in epithelial and perivascular compartments of human adult thymus.

The thymus is the site of T-cell differentiation. However, the relatively recent observation that B cells are also present in the human thymus has prompted studies to determine the origin and function of these B cells. Our studies show that phenotypically distinguishable B cell populations are located within both the thymic medulla and the thymic perivascular space and that cellular trafficking occurs between these compartments, including B cells trafficking from the periphery. The numbers of thymic B cells increase with age, correlating with increases in lymphocyte-rich regions of thymic perivascular space that are prominent between ages 10 and 50 years. B cells within both thymic epithelial and perivascular compartments contain mutated immunoglobulin VH sequences characteristic of post-germinal center B cells, suggesting that the B cells that most often give rise to thymic B-cell lymphomas may originate from either the thymic medulla or perivascular space.

Adolescent↗

PubMed2005

Proliferating cell nuclear antigen--a marker for ovarian follicle counts.

Enumerating ovarian follicles is an effective way to estimate the extent of ovarian toxicity in female rodents exposed to xenobiotics. Differential follicle counts are useful in safety assessment bioassays and in interspecies extrapolation of ovarian toxicity. Counting the follicles in H&E-stained sections is labor intensive, tedious, and costly. In the present study we demonstrated that in rat formalin-fixed, paraffin-embedded ovary sections follicles of all degrees of maturity can be visualized by the use of antibody directed against proliferating cell nuclear antigen (PCNA). Follicles are easily distinguished from ovarian background with the ability to detect and identify primordial follicles being enhanced. This translates into a significant decrease in variability of follicle counts, labor, and cost. Specifically, variability dropped from 11% to 0.2%, the counting time was reduced by 46%, and the cost by 48%.

Animals↗

PubMed2001

Longitudinal study of urinary 8-hydroxy-2'-deoxyguanosine excretion in healthy adults.

Numerous studies have investigated the urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a biomarker for the assessment of oxidative DNA damage in humans. In this study, we performed six consecutive series of measurement of urinary levels of 8-OHdG in 68 healthy probands, in order to provide information on the intra- and inter-individual variability of 8-OHdG and to estimate the influence of smoking, age, sex, body weight and body mass index (BMI) on the excretion of 8-OHdG. The intra-individual coefficient of variation (CV) of urinary 8-OHdG/24 h ranged from 0.18 to 1.06 (mean CV = 0.48). Women excreted significantly lower amounts of 8-OHdG/24 h than men, but the difference lost its significance when the body weight or urinary creatinine were used as covariates. By multiple linear regression analysis significant correlations between the mean individual levels of 8-OHdG/24 h excretion and urinary creatinine (rp = 0.61), and cotinine (rp = 0.27) have been observed, whereas no statistically significant effect of age, body weight and BMI was found. The 8-OHdG/creatinine ratio was found to be significantly increased in 23 smokers (1.95 +/- 0.40 mumol/mol) opposed to 45 non-smoking probands (1.62 +/- 0.50 mumol/mol), which is in good agreement with previously published data. No effect of passive smoking on the excretion of 8-OHdG was found. From our data we conclude that the intra-individual variability of urinary 8-OHdG excretion has been underestimated so far, indicating that values of 8-OHdG measured by single spot monitoring are not representative for individual base levels.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1995

Passive and active maternal smoking during pregnancy, as measured by serum cotinine, and postnatal smoke exposure. II. Effects on neurodevelopment at age 5 years.

The authors sought to determine the neurobehavioral effects of prenatal exposure to maternal active smoking and environmental tobacco smoke (ETS), assessed by maternal serum cotinine level, and of postnatal exposure to smoke based on maternal report. Five-year-old children (n = 2,124) who were participants in the Child Health and Development Studies in Oakland, California, between 1964 and 1967 were evaluated with the use of the Peabody Picture Vocabulary Test (PPVT) and the Raven Coloured Progressive Matrices Test, and also assessed on a behavioral rating scale completed by the mother that included questions on activity level. Children of ETS-exposed women did not differ from children of other nonsmokers on neurobehavioral assessment. Children whose mothers smoked during pregnancy had somewhat higher adjusted Raven (p = 0.10) and PPVT scores (p = 0.06) than children of nonsmokers, although they did not differ in their activity level (p = 0.32). However, children smoke-exposed during childhood did have lower adjusted Raven (p = 0.01) and PPVT scores (p = 0.16), and were rated more active by their mothers (p = 0.04). These differences may be attributed to uncontrolled confounding of sociobehavioral variables. However, the authors cannot rule out the possibility that ETS exposure during childhood may be more hazardous to neurodevelopment than prenatal exposure.

Biomarkers↗

PubMed1997

Oncogene and cytokine expression of human colorectal tumors responding to immunotherapy.

Tumor samples from five patients with metastatic colorectal cancer who demonstrated tumor regressions in clinical trials of interleukin (IL)-1 beta, IL-2, and adoptive cellular therapy were analyzed for oncogene and cytokine mRNA expression. Tumors from eight nonresponding patients were also studied. Mutations of the ras protooncogene and overexpression of c-myc protooncogene were observed in both responding and nonresponding tumors. In contrast, none of the responding tumors expressed transforming growth factor (TGF)-beta 1 mRNA, whereas nonresponding tumors did. The expression of IL-1, IL-6, IL-8, IL-10, tumor necrosis factor-alpha, granulocyte macrophage-colony-stimulating factor, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, macrophage chemotactic protein, and RANTES was variable between responding and nonresponding patients. Although we cannot conclude that a pattern of oncogene and/or cytokine mRNA expression specifically characterizes sensitive colorectal cancers, these analyses-the assessment of TGF-beta 1 mRNA in particular-merit further evaluation as biomarkers prognostic of immunotherapy response.

Colorectal Neoplasms↗

PubMed1991

Severity of illness correlates with alterations in energy metabolism in the pediatric intensive care unit.

OBJECTIVE: To evaluate the correlations between severity of illness scoring systems and biochemical markers of physiologic stress. SETTING: Tertiary care pediatric ICU in a university hospital. DESIGN: A prospective, clinical study. PATIENTS: Twelve patients aged 2 to 120 months (four patients aged less than 12 months) with varying diagnoses including sepsis, cardiovascular surgery, respiratory failure. INTERVENTIONS: Oxygen consumption (VO2), daily total urinary nitrogen, and the branch chain to aromatic amino acid ratio were correlated with the Physiologic Stability Index, Pediatric Risk of Mortality score, and Therapeutic Intervention Scoring System. Linear regression analysis and multivariate stepwise regression analysis were used to analyze the data. MEASUREMENTS AND MAIN RESULTS: Pediatric Risk of Mortality score and Physiologic Stability Index correlated with VO2 (r2 = .69, p less than .001 and r2 = .52, p less than .01, respectively) and with daily total urinary nitrogen excretion (r2 = .66, p less than .001 and r2 = .62, p less than .01, respectively). The Therapeutic Intervention Scoring System correlated with the total urinary nitrogen excretion (r2 = .69, p less than .001) and branch chain to aromatic amino acid ratio (r2 = .49, p less than .01). Correlations existed between Pediatric Risk of Mortality score and Physiologic Stability Index (r2 = .88, p less than .001) and Pediatric Risk of Mortality score and Therapeutic Intervention Scoring System (r2 = .48, p less than .01). CONCLUSIONS: The correlations were independent of diagnostic category, suggesting that the alterations in biochemical variables were most directly related to the overall severity of illness as measured by the scoring system.

Amino Acids, Branched-Chain↗

PubMedDate not supplied

Psychosocial modulation of antibody to Epstein-Barr viral capsid antigen and human herpesvirus type-6 in HIV-1-infected and at-risk gay men.

We investigated the effects of two behavioral interventions--aerobic exercise and cognitive behavioral stress management (CBSM)--on Epstein-Barr virus viral capsid antigen (EBV-VCA) and human herpesvirus type-6 (HHV-6) antibody modulation in 65 asymptomatic gay men measured at several time points in the 5 weeks preceding and following notification of their human immunodeficiency virus-type 1 (HIV-1) serostatus. After accounting for potential immunomodulatory confounds, we found that HIV-1 seropositive men had higher EBV-VCA antibody titers than those diagnosed as seronegative at every time point during the study; however, no significant differences were found with respect to HHV-6. Among HIV-1 seropositive and seronegative subjects, respectively, those randomized to either behavioral intervention had significant decreases in both EBV-VCA and HHV-6 antibody titers over the course of the intervention as compared with assessment-only controls (of HIV-1 seropositive and seronegative status) whose antibody titers did not significantly change and which remained consistently higher than either serostatus-matched intervention group over subsequent time points, independent of total immunoglobulin G levels and degree of polyclonal B cell activation. In attempting to explain serostatus differences in EBV and HHV-6 values, it was found that HIV-1 seropositive men had significantly lower CD4 cells, CD4:CD8 ratio, and blastogenic response to phytohemagglutinin (PHA), as well as significantly higher CD8 cells at baseline. No significant differences were found between the HIV-1 seropositive and seronegative men with respect to anxiety and depression at baseline. Since the greatest changes in EBV and HHV-6 occurred between baseline and week 10, we correlated changes in immune (CD4, CD8, CD4:CD8 ratio, PHA stimulation) and distress-related markers (state depression and anxiety) with EBV and HHV-6 change scores over this time period. No significant correlations were found between any of these immune- or distress-related variable and the antibody change scores suggesting that the mechanisms by which EBV and HHV-6 antibodies are being modulated by these interventions possibly involve other, yet to be determined, immune, neuroendocrine, and/or psychologic variables.

Acquired Immunodeficiency Syndrome↗

PubMed2006

The immunohistochemical profile of malignant mesotheliomas of the tunica vaginalis: a study of 20 cases.

Malignant mesotheliomas of the testis arise from the tunica vaginalis, formed from the evagination of the abdominal peritoneum into the scrotum. The immunohistochemical profile of the tunica vaginalis and associated neoplasms is often extrapolated from thoracic studies. Testicular series are uncommon, usually derived from previous case studies and literature reviews. The immunohistochemical findings in 20 cases originally diagnosed as malignant mesotheliomas are presented. Archival testicular malignant mesothelioma specimens from 1959 to 2004 were collected from hospitals throughout the United Kingdom and from the authors' own archives. Hematoxylin and eosin-stained sections were reviewed, and selected sections from each case were then examined using an immunohistochemical panel of eight antibodies: calretinin (Zymed, 1:200), epithelial membrane antigen (EMA) (DAKO, 1:50), thrombomodulin (DAKO 1:5), CK7 (DAKO, 1:100), CK5-CK6 (DAKO, 1:10), BerEp4 (DAKO, 1:25), carcinoembryonic antigen (CEA) (DAKO, 1:10), and CK20 (DAKO, 1:100). The EnVision technique was used for all antibodies. Sections were reviewed independently by three pathologists. Electron microscopy was performed on selected cases. In all cases, the morphologic light microscopy criteria for a diagnosis of malignant mesothelioma were present. However, two tumors were later excluded from the study because of diffuse strong positive immunostaining with CK20 and BerEp4 and an ultrastructural appearance of adenocarcinoma. Of the remaining cases, 15 of 18 (83%) were purely epithelioid in type, showing a mixture of papillary, tubular, and solid patterns, and 3 of 18 (17%) showed a mixed sarcomatoid/epithelioid pattern. All cases were positive for calretinin and EMA (100%), 16 of 18 (89%) were positive for thrombomodulin, and 15 of 18 (83%) were positive for CK7. CK5-CK6 positivity was present in 13 of 18 (72%) but varied in strength and distribution; 2 of 18 (11%) were positive for BerEp4. All the cases were negative for CK20 and CEA. Four of the 18 cases were examined by electron microscopy, which revealed long thin microvilli supporting a diagnosis of malignant mesothelioma. This study has shown that the immunocytochemical profile of testicular malignant mesotheliomas is similar to those arising in the pleura, with diffuse positivity for calretinin, EMA, thrombomodulin, and CK7, and negative for CK20 and CEA. Focal weak positivity may be encountered with BerEp4. However, histopathologists should be aware of the variability in CK5-6 staining in testicular specimens when compared with pleural mesotheliomas.

Aged↗

PubMed2002

Automated analysis of brachial ultrasound image sequences: early detection of cardiovascular disease via surrogates of endothelial function.

Early detection of cardiovascular disease would allow timely institution of preventive measures. Arterial endothelium play a primary role in processes leading to the development of atherosclerotic plaque and cardiovascular disease in general. Determination of flow-mediated dilatation (FMD) of brachial arteries from B-mode ultrasound image sequences offers a noninvasive surrogate index of endothelial function. A highly automated method for analysis of brachial ultrasound image sequences is reported and its performance assessed. The method overcomes the variability of brachial ultrasound images across subjects by incorporating machine learning and quality control steps. The automated method outperformed conventional manual analysis by providing a decreased analysis bias, increased reproducibility, and improved measurement accuracy. Consequently, it decreases inter- and intraobserver as well interinstitution variability. The method has been employed in a number of population studies with thousands of subjects analyzed.

Arterial Occlusive Diseases↗

PubMed2004

Laboratory tests in adults with monoarticular arthritis: can they rule out a septic joint?

UNLABELLED: It is difficult to differentiate septic arthritis from other causes of monoarticular arthritis solely with a history and physical examination. The clinician must rely on ancillary tests to make a diagnosis, such as the white blood cell count of peripheral blood (WBC), the erythrocyte sedimentation rate (ESR), and the white blood cell count of the joint fluid (jWBC) obtained from arthrocentesis. Although it is known that septic arthritis is associated with abnormalities in these tests, the majority of the data are based on studies in the pediatric population. In addition, although several emergency medicine texts indicate that a jWBC greater than 50,000 cells/mm(3) is "positive," it is known that septic arthritis can occur in patients with low jWBCs. OBJECTIVES: To determine whether specific ancillary tests have sufficiently high sensitivities to rule out septic arthritis in adults. METHODS: This was a retrospective consecutive case series of patients from an urban emergency department (ED). Patients at least 18 years old who had septic arthritis confirmed by positive arthrocentesis culture or operative findings were included in the study. WBC greater than 11,000 cells/mm(3), ESR greater than 30 mm/hr, and jWBC greater than 50,000 cells/mm(3) were considered elevated. RESULTS: Seventy-three patients met the inclusion criteria. The sensitivities of an elevated WBC, ESR, or jWBC in adults who had septic arthritis were 48%, 96%, and 64%, respectively. There were broad ranges of WBC, ESR, or jWBC among the patients. More than one third of adult patients with septic arthritis had jWBCs less than 50,000 cells/mm(3). All patients had an abnormality in at least one of these tests. CONCLUSIONS: The WBC, ESR, and jWBC are extremely variable in adults with septic arthritis. Laboratory tests do not rule out septic arthritis with accuracy.

Arthritis, Infectious↗

PubMed1998

Relationship between didanosine exposure and surrogate marker response in human immunodeficiency virus-infected outpatients.

We used information available from routine clinic visits to characterize the pharmacokinetics of didanosine in 82 human immunodeficiency virus-infected patients. A total of 271 blood samples were collected for the measurement of didanosine concentrations in plasma (mean +/- standard deviation [SD], 3.30 +/- 2.21 samples/patient). Bayesian estimates of didanosine oral clearance (CL[oral]) were obtained for these patients by the POSTHOC option within the NONMEM software package. Population priors from a previous NONMEM analysis of didanosine pharmacokinetics were used. The mean +/- SD CL(oral) was 132 +/- 27.7 liters/h, which agrees reasonably well with estimates obtained from previous pharmacokinetic studies of didanosine. Estimates of individual didanosine exposure were then used to consider potential relationships between drug exposure and surrogate marker response over a 6-month period. No correlations were found between the didanosine area under the concentration-time curve from 0 to 6 months and the absolute CD4 cell count (r = 0.305; 0.1 < P < 0.2), weight response (r = 0.0857; P > 0.4), or percentage of CD4 lymphocytes (r = 0.0559; P > 0.4). Future efforts to characterize didanosine exposure in outpatients by random sampling methods should involve more directed efforts to limit residual variability in the data.

Adult↗

PubMedDate not supplied

Nutrition support in acute pancreatitis: a systematic review of the literature.

BACKGROUND: Failure to use the gastrointestinal (GI) tract in patients with acute pancreatitis may exacerbate the stress response and disease severity, leading to greater incidence of complications and prolonged hospitalization. The objectives of this study were to determine the optimum route for nutrition support, whether nutrition therapy is better than no artificial nutrition support, whether specific additives to enteral or parenteral therapy can further enhance their efficacy, and whether methodologic differences in delivery of enteral nutrition (EN) influence tolerance. METHODS: A computerized search was performed of MEDLINE, Cochrane database, EMBASE, and reference lists of pertinent review articles for prospective randomized trials in adult patients with acute pancreatitis that evaluated interventions with nutrition therapy. Primary outcome data and surrogate endpoint parameters (for nutrition indices, stress markers, and measures of the inflammatory/immune response) were extracted in duplicate independently. Where appropriate, meta-analysis was performed by random-effects model. RESULTS: From 119 articles screened, 27 randomized controlled trials were included and analyzed. In patients admitted for acute pancreatitis, meta-analysis of 7 trials showed that use of EN was associated with a significant reduction in infectious morbidity (risk ratio [RR] = 0.46; 95% confidence interval [CI], 0.29 - 0.74; p = .001) and hospital length of stay (LOS; weighted mean difference [WMD] = -3.94; 95% CI, -5.86 to -2.02; p < .0001), a trend toward reduced organ failure (RR = 0.59; 95% CI, 0.28-1.27; p = .18), with no effect on mortality (RR = 0.88; 95% CI, 0.43-1.79; p = .72) when compared with use of parenteral nutrition (PN). Results from individual studies suggest that EN in comparison to PN reduces oxidative stress, hastens resolution of the disease process, and costs less. Insufficient data exist to determine whether EN improves outcome over standard therapy (no artificial nutrition support) in patients admitted for acute pancreatitis. However, in those patients requiring surgery for complications of acute pancreatitis, meta-analysis of 2 trials indicates that provision of EN postoperatively may reduce mortality (RR = 0.26; 95% CI, 0.06 - 1.09; p = .06) compared with standard therapy. PN provided early within 24 hours of admission was shown to worsen outcome, whereas PN provided later after full-volume resuscitation appeared to improve outcome when compared with standard therapy. In early individual studies, specific supplements added to EN, such as arginine, glutamine, omega-3 polyunsaturated fatty acids, and probiotics, may be associated with a positive impact on patient outcome in acute pancreatitis, compared with EN alone without the supplements, but studies are too few to make strong treatment recommendations. Supplementation of PN with parenteral glutamine was shown to reduce oxidative stress and improve patient outcome (reduced duration of nutrition therapy and decreased hospital LOS) compared with PN alone in patients with acute pancreatis. A wide range of tolerance to EN exists, irrespective of known influences such as mode (continuous vs bolus) and level of infusion within the GI tract (gastric vs postpyloric). CONCLUSIONS: Patients with acute severe pancreatitis should begin EN early because such therapy modulates the stress response, promotes more rapid resolution of the disease process, and results in better outcome. In this sense, EN is the preferred route and has eclipsed PN as the new "gold standard" of nutrition therapy. When PN is used, it should be initiated after 5 days. The favorable effect of both EN and PN on patient outcome may be further enhanced by supplementation with modulators of inflammation and systemic immunity. Individual variability allows for a wide range of tolerance to EN, even in severe pancreatitis.

Acute Disease↗

PubMed2006

Assessing stability of gene selection in microarray data analysis.

BACKGROUND: The number of genes declared differentially expressed is a random variable and its variability can be assessed by resampling techniques. Another important stability indicator is the frequency with which a given gene is selected across subsamples. We have conducted studies to assess stability and some other properties of several gene selection procedures with biological and simulated data. RESULTS: Using resampling techniques we have found that some genes are selected much less frequently (across sub-samples) than other genes with the same adjusted p-values. The extent to which this type of instability manifests itself can be assessed by a method introduced in this paper. The effect of correlation between gene expression levels on the performance of multiple testing procedures is studied by computer simulations. CONCLUSION: Resampling represents a tool for reducing the set of initially selected genes to those with a sufficiently high selection frequency. Using resampling techniques it is also possible to assess variability of different performance indicators. Stability properties of several multiple testing procedures are described at length in the present paper.

Biomarkers, Tumor↗

PubMed1996

Oral contraceptives alter circadian rhythm parameters of cortisol, melatonin, blood pressure, heart rate, skin blood flow, transepidermal water loss, and skin amino acids of healthy young women.

Sixteen healthy women users and nonusers of oral contraceptives (OC) volunteered to document a set of circadian rhythms. Nine were taking OC providing ethynyl estradiol (0.03-0.05 mg/24h, 21 days/month) combined with DL- or L-norgestrel or norethisterone. There was no group difference (p > 0.05) in median age (22 years), weight (57 kg), and height (162) cm). Data were obtained at fixed hours, 5 times/24h, during a 48-h span, in November. (Day activity from approximately 08:00 to approximately 23:00 h and night rest). Environmental conditions were controlled, using air-conditioned rooms of constant temperature (26 degrees +/- 0.5) and relative humidity 45% +/- 1. Both cosinor and ANOVA were used for statistical analyses. All circadian rhythms were validated with one exception: that of salivary melatonin was not detected in OC users. The 24h mean (M) exhibited group differences for certain variables: M was greater in OC than non-OC users for systolic blood pressure (p < 0.0001), heart rate (p < 0.01), skin blood flow (p < 0.04), and transepidermal water loss (p < 0.02). M was lower in OC than non-OC users in salivary cortisol (p < 0.04) and skin amino acids (p < 0.003). No group difference was detected in any other documented rhythms: diastolic blood pressure, grip strength of both hands, oral temperature, self-rated fatigue, and the skin variables of urea, lactate, triglycerides, and acid phosphatase activity.

Adult↗

PubMed1991

Prognostic value of serum beta-2 microglobulin in low-grade lymphoma.

OBJECTIVE: To evaluate serum beta-2 microglobulin (beta-2M) and other prognostic indicators in previously untreated low-grade lymphoma. DESIGN: Cohort study of 80 patients with uniformly treated low-grade lymphoma, followed for a median of 21 months. These 80 patients, all of whom had serum beta-2M drawn within 2 weeks before starting therapy, were derived from a cohort of 119 previously untreated patients entered into one of three clinical trials. SETTING: Tertiary referral cancer center. PATIENTS: Eighty previously untreated stage I to IV patients (mean age, 55 years). INTERVENTION: Treatment was given according to Ann Arbor stage: Patients in stage IV were treated with CHOP-bleomycin and maintained on interferon therapy; those in stage III received CHOP-bleomycin and radiotherapy; and those in stages I and II received COP-bleomycin and radiotherapy. MEASUREMENTS: Outcome was determined by assessing complete remission rate and time to treatment failure. Univariate and multivariate analyses were used. RESULTS: The complete remission rate for patients with a beta-2M level of 3.0 mg/L or greater was 36% compared with 71% for those with a level of less than 3.0 mg/L. Using multivariate analysis that tested beta-2M as a continuous variable, it was selected as the most significant factor for complete response. The adjusted odds ratio was 0.285 (95% CI, 0.101 to 0.809). The Ann Arbor stage had marginal significance (adjusted odds ratio, 0.435; CI, 0.150 to 1.263). For time to treatment failure, beta-2M was the only variable retained in the multivariate model. At 42 months, no patient with a beta-2M level of 3.0 mg/L or greater was projected to be in remission as compared with 85% of patients with a beta-2M level of less than 3.0 mg/L. CONCLUSIONS: The serum beta-2M level is a good predictor of complete response and time to treatment failure. A larger number of patients should be studied to clarify the role of other potentially independent variables such as stage and age.

Adult↗