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Results for “Biomarker variability”

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PubMed2007

Biomarker versus environmental factors: seasonal variations and modelling multixenobiotic defence (MXD) transport activity in transplanted zebra mussels.

The occurrence of biomarker temporal variations linked to environmental factors makes it difficult to distinguish the specific effect of pollution. The present work aims to investigate the seasonal variations of the transport activity of the multixenobiotic defence (MXD), which is used as a biological tool for the monitoring of pollution in aquatic ecosystems. The MXD transport activity was monitored monthly from August 2001 to October 2002 in zebra mussels (Dreissena polymorpha) transplanted to three sites in the Moselle River. The 'efflux method' was used to evaluate functional activity of MXD by assessing rhodamine B efflux with or without an inhibitor (verapamil). Environmental parameters were provided by a French regulatory agency (Water Agency) that monitors river water quality. The results of a principal components analysis describe the seasonal cycle of water characteristics and demonstrate that MXD activity is subjected to significant temporal variations. These data were described with a generalised linear model that enables it to link MXD variability to the seasonal variations of environmental parameters such as temperature or levels of organic contamination. This work proposes a modelling approach and highlights that the occurrence of seasonal variations in MXD response has to be taken into account in the interpretation of in situ monitoring studies.

Animals↗

PubMed2004

Early detection of prostate cancer in African-American men through use of multiple biomarkers: human kallikrein 2 (hK2), prostate-specific antigen (PSA), and free PSA (fPSA).

Recent studies have reported enhanced prostate cancer detection in Caucasians with serum human glandular kallikrein 2 (hK2) in combination with total- (tPSA) and free-prostate-specific antigen (fPSA). The purpose of this study is to validate these findings in an African-American patient cohort. A total of 137 African-American men were found by routine screening to have tPSA levels above 2.5 ng/ml or an abnormal digital rectal examination. Sera were drawn prior to biopsy of the prostate and Hybritech PSA, FPSA and hK2 (for research use only, not for use in diagnostic procedures) concentrations were determined on Beckman Coulter's Access immunoanalyzer. These independent variables and the ratios of percent fPSA (%fPSA), hK2/tPSA, hK2/fPSA, and hK2*tPSA/fPSA were compared between cancer and non-cancer groups. In all, 49 of 137 men had prostate cancer. hK2 and its calculated ratios outperformed tPSA on receiver operator characteristic (ROC) analysis, but %fPSA had statistically the highest area under the curve (AUC) at 0.801. When restricting the analysis to only the tPSA range of 4.0-10 ng/ml, hK2/fPSA yielded the highest AUC (0.721). The ratio of hK2/fPSA was also found to increase the positive predictive value (PPV) of the %fPSA ranges less than 10 and 10-25%. %fPSA offered the best performance and highest specificity in prostate cancer detection in African-American males over the entire range of tPSA. hK2/fPSA may offer modest improvement in the tPSA range of 4.0-10 ng/ml. Furthermore, hK2/fPSA can enhance the PPV of low %fPSA values. Therefore, the use of multiple biomarkers may ultimately increase the specificity of prostate cancer screening in African-American men.

Black or African American↗

PubMed1998

Biomarkers of immunotoxicity in fish and other non-mammalian sentinel species: predictive value for mammals?

Through the efforts of different laboratories, a battery of immunological assays is available to predict the immunotoxicity of xenobiotics. These assays, originally developed in rodents, have been adapted for use in a variety of animal species and are now used routinely in these models to assess the immunotoxicity of different chemical classes. For example, our laboratory has employed assays that measure antibody-forming cell response to T-dependent antigens, T- and B-cell lymphoproliferation, macrophage function, and host resistance against infectious bacteria to assess metal-induced immunotoxicity in laboratory-reared Japanese medaka (Oryzias latipes); immunologically-related assays measuring antioxidant activity have also been used in this capacity. Results of the aforementioned investigations have shown the usefulness of these endpoints to reliably demonstrate chemical-mediated immunotoxicity in teleost systems. Many of these same endpoints have also proved successful for predicting the immunotoxic effects of contaminated aquatic environments in feral fish populations. For example, smallmouth bass collected from a chlorinated hydrocarbon-contaminated site demonstrated significant changes in blood cell profiles and kidney phagocyte function compared to fish collected from a 'clean water' reference site. Some of these same immune parameters have also been used successfully to predict the immunotoxicity of polluted aquatic environments in feral populations of fish-eating birds and harbor seals. While interspecies extrapolation is difficult and should be approached with caution due to variables such as metabolism and pharmacokinetics, results from these studies demonstrate the usefulness of these immune assays to predict the immunomodulating effects of xenobiotics in fish and other wildlife species, as well as the applicability of fish to serve as additional/alternate animal models for mammalian species in immunotoxicological studies.

Animals↗

PubMed1990

Fingernail growth rate as a biomarker of aging in the pigtailed macaque (Macaca nemestrina).

Rate of fingernail growth (FNG) of the middle digit of the right hand was assessed in 46 healthy pigtailed macaques at approximately 6-month intervals for 4 to 6 years. Mean FNG for 24 females, ranging in mean age at measurement from 7 to 24 years, was 104 mu/day; the mean for 22 males, ranging from 7 to 20 years, was 111 mu/day. Longitudinal analysis showed that FNG declined in animals of both sexes and that the rate of decline (-4.8 mu/day/year) did not differ between them, i.e., the mean regression coefficients (beta) of the two sexes were significantly different from zero and not significantly different from each other. Results of cross-sectional analysis differed from those of longitudinal analysis in that the mean FNG appeared to be more rapid in males than in females, particularly in the older animals. Inter- and intra-individual variability in FNG did not increase with age. FNG appears to be an excellent functional marker of the rate of aging because the direction of change is essentially decremental, a significant degree of change can be detected in a few years, and the rate of change is relatively constant across the adult lifespan. In addition, measurement of FNG is innocuous, quantitative, inexpensive, and simple.

Aging↗

PubMedDate not supplied

Evaluation of 8-hydroxydeoxyguanosine in human oral cells: the importance of tobacco smoke and urban environment.

The DNA adduct 8-hydroxydeoxyguanosine (8-OHdG) has been widely used as a sensitive biomarker for oxidative damage. To investigate the role of environmental factors on oxidative DNA damage formation, the level of 8-OHdG was determined in oral cells from 109 healthy volunteers by an immunohistochemical method. A statistically significantly higher content of 8-OHdG was detected in oral cells from smokers (111 +/- 55, n = 38) compared with non smokers (78 +/- 48, n = 71), (p < 0.01). Moreover, subjects living in an urban area showed a higher level of oxidative damage with respect to those living in a countryside-suburban area (99 +/- 53, n = 58 vs. 78 +/- 51, n = 51), (p = 0.03). No significant association was detected between 8-OHdG in oral cells and other variables such as passive smoke, oral infections, alcohol or vitamin intake and grilled food consumption. This work suggests that tobacco smoke and environmental exposure to pollutants lead to a measurable increase of oxidative damage in oral cells and confirms that the immunoperoxidase method is an appropriate approach for epidemiological analyses.

8-Hydroxy-2'-Deoxyguanosine↗

PubMedDate not supplied

Measuring lysosomal stability as an effective tool for marine coastal environmental monitoring.

The use of lysosomal stability in the mussel, Mytilus galloprovincialis, as a potential biomarker of environmental contamination has been evaluated along the Portuguese coast. To this end, the neutral red retention (NRR) time was measured in mussel haemocytes gathered from nine different locations reflecting different degrees of anthropogenic contamination. Mussels collected in the vicinity of industrial and urban areas showed the lowest lysosomal stability. Additionally, no significant seasonal variability (winter-spring/summer) for NRR time was observed. In order to further support the usefulness of this method as an integrated tool for monitoring marine coastal environments, we compared the levels of xenobiotics in mussel tissues with the obtained NRR values. The results highlighted a consistent pattern, with the lowest lysosomal stability intimately correlated with the higher contaminant concentrations. In summary, this integrated approach further demonstrated that the NRR assay can provide useful and objective indications of the real health status of organisms subjected to different stress agents, being a valid option for environmental monitoring.

Animals↗

PubMed2005

The fundamental flaw in obesity research.

The basic problem with comparative diet trials is our inability to measure what people eat. All conventional instruments depend on subjects' reports. Most trials lack independent biochemical, physiological or genetic measures of intake. So, we do not know if subjects actually follow the diets being tested and compared. We can assess weight gain/loss, but we fail in a fundamental scientific requirement, accurately measuring the independent variable in a causal experiment. Worse, we know most subjects under-report their energy intake and its components, the obese especially. The problem is compounded by attempts to show diets' effects on other risk factors, like triglycerides. Researchers seek to correlate two variables, without having accurately measured one of them, producing misleading associations. The consequence is we do not know if the results of any current diet trials are valid or reliable. Developing rigorous measures of food intake is the highest priority in obesity research. That involves improvements in technology as well as science. We need: (1) biomarkers of intake for energy, macro- and micro-nutrients and other food components relevant to weight gain/loss; (2) field measuring instruments that are cheap, rapid, painless, non-intrusive and self-administerable; and (3) electronic data transmission systems that preclude subjects' ability to misreport.

Biomedical Research↗

PubMed2005

Dietary protein type and cardiovascular disease risk factors.

Observational studies suggested a negative association between vegetable protein and cardiovascular disease risk, whereas intervention studies have been less consistent. The majority of interventional studies that have evaluated the effects of soy protein compared to animal protein have used casein. Relative to casein, the effect of soy protein on lipids and lipoprotein appears to be variable and less dramatic than originally reported. When compared to animal proteins other than casein, relatively large intakes of soy protein (>/=25 g/d) appear to have a consistent, albeit small ( asymptotically equal to 5%), hypocholesterolemic effect. When assessed, no consistent additional benefit of soy protein on other cardiovascular disease risk factors; Lp(a), inflammatory markers, biomarkers of oxidative stress and endothelial function, has been reported. The data available on the effect of dietary protein on plasma lipids, lipoprotein levels, and cardiovascular disease risk factors is difficult to interpret and insufficient to account for the discrepancy between the observational and interventional studies.

Animals↗

PubMed2006

Noninvasive markers of fibrosis for longitudinal assessment of fibrosis in chronic liver disease: are they ready for prime time?

Over the past decade, there has been a renewed enthusiasm to develop noninvasive serum markers or tests to assess the presence and severity of fibrosis in chronic liver disease. Although a single marker or test has lacked the necessary accuracy to predict fibrosis, different combinations of these markers or tests have shown encouraging results. However, inter-laboratory variability and inconsistent results with liver diseases of varying etiologies have made it difficult to assess the reliability of these markers in clinical practice. In this issue of the journal, Poynard et al. describe the "histological" response to lamivudine in patients with chronic Hepatitis B Virus (HBV) over a 24-month period using surrogate serum biomarkers (Fibrotest-Actitest, FT-AT) without corroborating histological data. Investigators found improvement in fibrosis and inflammation in 85% and 91%, respectively, despite the emergence of YMDD mutation in 41.5% of patients. The higher improvement rates reported in this study should be interpreted with caution for a number of reasons including the absence of data on virological response rates, corroboratory histological data, and data on the validity of FT to evaluate fibrosis in a longitudinal manner. Although FT has been studied extensively by the authors of the current study, to date there are only few independent studies. In addition to significant inter-laboratory variations, these studies have shown that significant fibrosis could be missed, or conversely significant fibrosis diagnosed in the absence of minimal or no fibrosis in about 15% to 20% of patients. We may be approaching a time when serum biomarkers may become an integral part of the assessment of patients with chronic liver disease, but published evidence suggests that these markers are not yet ready for prime time.

Biomarkers↗

PubMed2001

Expression of the translation initiation factor eIF4E in the polyp-cancer sequence in the colon.

The eukaryotic translation initiation factor 4E (eIF4E) has been shown to play a key role in cell growth, and several studies have documented an increased expression of eIF4E in a number of solid tumors, including breast, bladder, cervical, and head and neck cancers. This study was done to evaluate the potential role of eIF4E in the polyp-cancer sequence in the colorectum. Eighty-seven cases with lesions in the colorectum with a variety of histopathological diagnoses were randomly selected from the archives of the Pathology Department at Louisiana State University Health Sciences Center-Shreveport. Appropriate sections were selected for immunostaining with eIF4E. The medical records of the patients were reviewed, and demographic information was collected. All statistical analyses were performed using SAS software. A statistically significant relationship was found between the level of eIF4E expression and histological type of lesion: the lowest level of eIF4E expression was found in normal colon tissue, whereas the highest level of eIF4E expression was found in colorectal adenocarcinomas. Carcinomatous lesions were found to have a 43 times higher chance of having a high level of eIF4E expression compared with normal tissue (95% confidence interval, 8.0-213.6, P < 0.0001). In a multivariate analysis, histological type was the only variable that showed a significant relationship with eIF4E expression; no effect was found due to age, gender, race, history of polyps, and family history. The results from this study are consistent with other data from the literature and support the suggestion that eIF4E is strongly involved in colon tumorigenesis. eIF4E might be a useful intermediate biomarker for use in chemoprevention intervention studies in patients with colorectal polyps.

Adenocarcinoma↗

PubMed2004

Pharmacogenomics in breast cancer: current trends and future directions.

Pharmacogenomics is the study of genetic variations between individuals to predict the risk of toxic side effects and the probability that a patient will respond to single- or multidrug chemotherapy. Breast cancer remains one of the most common cancers among women worldwide and is second only to lung cancer in cancer-related death. A better understanding of the mechanisms of initiation and progression of breast cancer is needed for early diagnosis and development of better therapeutic methodologies. Differences in cancer patients' responses to chemotherapy have often been attributed to pathogenesis and severity of the disease, drug interactions, patient's age, gender, nutritional status, organ functions and tumor biology. It is now well recognized that genetic variations in drug target genes, disease pathway genes and drug metabolizing enzymes can have greater influence on drug efficacy and toxicity. In addition, germline variants can be used to study breast cancer susceptibility, as well as the variable response to both drug and radiation therapy used in the treatment of breast cancer. This review discusses clinically relevant individual gene variations that influence breast cancer susceptibility and cancer therapy, as well as the microarray-based expression profiling studies that have great potential in cancer pharmacogenomics in terms of tumor classification, drug and biomarker discovery and drug efficacy testing.

Age Factors↗

PubMed2026

Proteomic profiling of bone for the estimation of post-mortem interval and post-mortem submersion interval: a systematic review.

Accurate estimation of the Post-Mortem Interval (PMI) and Post-Mortem Submersion Interval (PMSI) remains a persistent challenge in forensic science, especially when traditional morphological and entomological methods fail due to advanced decomposition or in aquatic environments. Proteomic profiling of bone tissues has recently emerged as a promising approach, leveraging the predictable degradation patterns of bone proteins to estimate time since death more reliably. This systematic review, conducted in accordance with PRISMA guidelines, analyzed 24 peer-reviewed studies focusing on the application of proteomic techniques to bone tissue for PMI and PMSI estimation. The included studies were evaluated based on sample type, analytical techniques used, identified biomarkers, environmental conditions assessed, and the overall reliability and reproducibility of the findings. The review found that specific bone proteins, particularly collagen, osteocalcin, fetuin-A, etc. exhibited consistent degradation patterns that correlated strongly with elapsed post-mortem time. Cortical bone was identified as a more stable and informative matrix compared to trabecular bone. Mass spectrometry, especially LC-MS/MS, emerged as the predominant analytical technique due to its high sensitivity and accuracy in detecting low-abundance proteins over extended PMIs and PMSIs. However, protein degradation rates were significantly influenced by environmental variables such as temperature, humidity, soil pH, and microbial activity. This review also emphasizes the transformative role of bone proteomics in advancing forensic science while identifying key gaps that must be addressed to achieve global standardization and practical implementation in diverse forensic contexts. The integration of proteomics with other emerging technologies, such as machine learning algorithms and computational modeling, may further enhance the precision of PMI and PMSI estimation in future applications.

Postmortem Changes↗

PubMed2007

Expression of p53 in colorectal carcinoma: correlation with clinicopathologic features.

BACKGROUND: The p53 gene mutation is closely related to carcinogenesis in most malignant diseases. The main function of wild p53 protein is to maintain the integrity of genes by detecting mutations and preventing the division of cells with damaged DNA. The mutated form of p53 protein is overexpressed due to an extended half-life and can be easily detected by immunohistochemistry. OBJECTIVE: To estimate the frequency of p53 protein overexpression in colorectal carcinoma and its correlation with some clinicopathologic variables. METHODS: One hundred paraffin-preserved colorectal carcinoma samples were collected randomly from patients undergoing tumor resection from April 1995 through April 2001 in Omid Hospital, affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. The overexpression of p53 protein was studied using a monoclonal antibody (clone DO-7; Dako). The number of cells stained were classified semiquantitatively as (-): <5% positive cells, (+): 5 - 25% positive cells, (++): 25 - 75% positive cells, and (+++): >75% positive cells. Clinicopathologic data including gender, age, tumor location, histologic type, and stage (Astler-Coller) were collected from the files maintained at the Department of Pathology. The correlation between p53 protein overexpression and each variable was evaluated using Chi-square analysis. RESULTS: p53 staining was positive in 59 of 100 specimens. Out of these 100 specimens, 16 were weekly (+), 16 moderately (++), and 27 intensely (+++) positive for p53 protein over-expression. There was no significant correlation between p53 staining and gender (P = 0.34), age (< 40 vs. > or = 40 yr; P = 0.74), site of tumor (right vs. left colon and rectum; P = 0.26), pathologic type (mucinous vs. nonmucinous; P = 0.63), and stage of the disease (P = 0.12). CONCLUSION: Considering the p53 protein overexpression in a relatively high percentage of patients, it seems that p53 mutation plays an important role in development of colorectal carcinoma. There was no significant association between p53 protein expression and some common clinicopathologic variables such as age, gender, site of tumor, pathologic type, and stage of the disease.

Adult↗

PubMed2001

Tumor growth pattern and thymidine phosphorylase expression are related with the risk of hematogenous metastasis in patients with Astler Coller B1/B2 colorectal carcinoma.

BACKGROUND: The benefit of adjuvant chemotherapy appears to be limited for patients with Astler Coller B1/B2 colorectal carcinoma but may be better in a subgroup of patients with a high recurrence risk. In the current case-control analysis, the authors evaluated whether patients with a high risk of hematogenous metastasis could be identified by means of a thorough histologic and immunohistochemical examination of the resection specimens. METHODS: A database was built for all patients treated in a general teaching hospital for colorectal carcinoma between 1985 and 1995. From this database, all patients with an Astler Coller B1 or B2 tumor who subsequently had developed hematogenous metastases were taken as cases. For each case, three matched controls (age, Astler Coller, year of diagnosis) without metachronous metastases were selected. The resection specimens of cases and controls were blindly examined by two observers for the following: World Health Organization (WHO) classification; differentiation grade; growth pattern; lymphocytic, fibroblastic, and eosinophilic reaction; angioinvasion; number of lymph nodes examined; expression of E-cadherin, vascular endothelial growth factor and thymidine phosphorylase (TP); P53; microvessel density. RESULTS: Twenty-two cases and 65 controls were included in the analysis. Tumor growth pattern and tumor TP expression both independently contributed to recurrence risk. With these 2 variables, 4 subgroups could be identified with a recurrence risk ranging from 0% to 42%. CONCLUSIONS: Tumor growth pattern and degree of TP expression both appear to be related to the recurrence risk. Prospective trials should point out whether these variables can be implemented in the decision making concerning adjuvant chemotherapy.

Biomarkers, Tumor↗

PubMed1995

Identification of novel genes from stomach cancer cell lines by differential display.

Gastric cancer is a leading cause of cancer death in many parts of the world. None of the tumor markers available to date provide for a reliable screening/diagnostic test. By using differential display technology on gastric cancer nonmetastatic (RF1) and metastatic (RF48) cell lines, we have isolated six novel cDNA clones. Five of them have not been previously identified. However, one of them appears to be the human homolog of the bovine oligomycin sensitivity conferral protein (oscp). Northern blot analysis showed that this clone is expressed at a much higher level in the metastatic (RF48) than the nonmetastatic (RF1) cancer cell line from the same patient. High level expression of the same gene is also observed in the breast cancer cell lines BT20 and T47D. The other five novel clones isolated showed either low or no expression in the RF1 and RF48 gastric cell lines, but variable levels of expression were detectable in breast cancers cell lines and normal tissues.

Adenosine Triphosphatases↗

PubMed2006

Ascites is the primary cause of cancer antigen-125 (CA-125) elevation in systemic lupus erythematosus (SLE) patients with nephrotic syndrome.

Tumor markers or tumor antigens are used for the monitoring of the response to treatment, follow-up, and potentially for diagnosis and screening. However, use of CA-125 serum assay as a single diagnostic tool is restricted by the fact that it is also produced by normal epithelia, not only by the ovarian cancer cells. Systemic lupus eryhtematosus (SLE) and related systemic autoimmune syndromes are associated with elevation of CA-125. In this group of patients antigen elevation had been tried to be linked with SLE disease activity. Although not found to be related with the disease activity, CA-125 serum levels were found to be related with the presence of nephrotic syndrome in the English literature. Although particularly important, the presence of ascites was not taken into consideration during the statistical analysis of the relationship between CA-125 elevation and nephrotic syndrome in SLE patients. However most of the SLE patients with nephrotic syndrome would have had accompanying ascites secondary to protein loss. Ascites itself could induce elevation in CA-125 serum levels. With this in mind we can hypothesize that the development of ascites was the primary cause for the elevation of CA-125 in SLE patients with nephrotic syndrome rather than the nephrotic syndrome itself. Probably the presence of ascites was the cause of observed relationship. Most likely ascites was a confounding variable biasing the results and statistical analysis. Failure to control for the presence of confounding variables such as ascites might lead to bias in all clinical trials. Otherwise a causative role for nephrotic syndrome in the elevation of serum CA-125 level seems somewhat inconsequential.

Animals↗

PubMed1998

Atherogenic, hemostatic, and other potential risk markers in subjects with previous isolated myocardial infarction compared with long-standing uncomplicated stable angina.

BACKGROUND: Several atherogenic, hemostatic, inflammatory, and genetic parameters and markers have been implicated as risk factors in coronary artery disease, although whether they are risk factors for acute as opposed to chronic coronary disease is unclear. METHODS AND RESULTS: Fifty subjects with an isolated myocardial infarction >3 months previously were compared with 50 subjects with a minimum 3-year history of stable angina, documented coronary artery disease, normal electrocardiogram and normal ventricular wall motion, and no episode suggesting infarction or unstable angina. Biologic variables analyzed included apolipoprotein B (apo B), lipoprotein (a), C-reactive protein (CRP), fibrinogen, factor VII, tissue plasminogen activator (TPA) and inhibitor (PAI-1), thrombin-antithrombin (TAT), fragment 1+2 (F1+2), von Willebrand factor (vWF), activated protein C resistance, homocyst(e)ine, anticardiolipin antibodies, blood group, and the angiotensin-converting enzyme insertion/deletion (I/D) and angiotensin II receptor gene polymorphisms. There were no significant differences between the 2 groups for any of the variables studied, although fibrinogen and F 1+2 tended to be slightly higher in the angina group (P = .09 for each). These significant correlations were present: age with fibrinogen, homocyst(e)ine, and vWF; factor VII with apo B, homocyst(e)ine, and TPA; apo B with TPA and CRP; CRP with fibrinogen, TPA, PAI-1, and factor VII; fibrinogen with vWF. CONCLUSIONS: Examination of atherogenic, hemostatic, inflammation, and genetic variables in the clinically quiescent state permitted no distinction between subjects with a previous isolated myocardial infarction in contrast to those with long-standing uncomplicated stable angina, favoring the notion that acute coronary events occur at random on a varying background of atherosclerosis. The multiple correlations found among these variables also underscore their complex interaction in the atherosclerotic process.

Adult↗

PubMed2004

Initial healing rates of venous ulcers: are they useful as predictors of healing?

Clinical trials that follow venous ulcers to complete healing can be costly because of the prolonged healing time involved. Initial healing rates in venous ulcers are calculated by 2 methods, which are based on a metric using wound area and perimeter. It has been proposed that these rates allow the prediction of complete healing and that they may be useful as surrogate end points for clinical trials. The objective of this study was to compare the 2 proposed methods for calculating initial healing rates and determine their usefulness in predicting the healing of venous ulcers. Venous leg ulcers from patients enrolled in a randomized, double-blind, placebo-controlled study were measured weekly for up to 12 weeks. Their healing status was determined for up to 24 weeks. Initial healing rates were calculated using the 2 proposed methods. The ability of these rates to predict time to complete healing was assessed. Information from 17 patients was available. The initial healing rates, calculated by either method, were quite similar; both methods produced the same median value of 0.046 cm/week in our patients. Five of the patients had negative initial healing rates, which do not allow any prediction of a healing time. Three of 7 patients predicted to heal within 24 weeks failed to do so. One of the 5 patients was predicted to heal at some time after 24 weeks but actually healed within 24 weeks. None of the 5 patients with negative initial healing rates healed within 24 weeks. Initial healing rates, as calculated by either method, have limited utility in describing healing curves and predicting a healing time. This poor predictive ability argues against using these initial healing rates as surrogate end points for clinical trials. The great variability observed in venous ulcer healing curves may limit the development of useful predictive models in this patient population.

Aged↗