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PubMed2026

Mechanism-Driven Diagnostic Development: A Specimen-Aware Framework Illustrated by Colorectal Cancer and Solid Tumours.

Translational oncology has moved rapidly from histopathology and single-analyte biomarkers toward multi-dimensional molecular profiling. Yet many clinically deployed tests still use reductionist biomarker strategies that under-represent cancer complexity. This review examines whether a mechanistic, multi-layered, and specimen-aware approach can improve cancer detection, classification, prognosis, minimal residual disease (MRD) assessment, and therapeutic selection. Evidence across solid tumours shows that genomic alterations alone incompletely explain tumour state, metastatic behaviour, immune evasion, or therapeutic vulnerability. Integrated genome and transcriptome analyses, proteogenomics, single-cell atlases, fragmentomic, methylation based cell-free DNA assays, metabolomics and microbiome assessments reveal clinically relevant biology that single modality tests cannot determine. Minimally invasive collected specimens can extend access to screening, diagnosis and longitudinal monitoring, but the choice of specimen should be matched to disease biology and analytes that represent mechanisms of oncogenesis. However, translation remains constrained by pre-analytical variability, contamination, differences in tumour shedding behaviour, clonal haematopoiesis, translation of generated models, incomplete external validation and uncertain downstream clinical utility for emerging platforms. This review provides a commentary on the future of cancer diagnostics, the considerations and barriers to clinical translation, the relationship between utility and dimensionality of biomarkers assessed and the emerging rationale towards mechanistically grounded integrated models.

biomarkers↗
PubMedDate not supplied

Immunofluorometric quantification of human kallikrein 5 expression in ovarian cancer cytosols and its association with unfavorable patient prognosis.

Human kallikrein 5 (hK5; encoded by the KLK5 gene) is a secreted serine protease expressed in hormonally regulated tissues, including the breast and ovary. We have previously reported regulation of the KLK5 gene by estrogens and progestins and its clinical value as a marker of poor prognosis in breast and ovarian cancers. We thus hypothesized that hK5 may represent a potential biomarker for ovarian carcinomas, at the protein level. Using a newly developed ELISA, hK5 levels were quantified (nanograms per milligram of total protein) in 22 low malignant potential (LMP) and 132 epithelial ovarian tumors and correlated with various clinicopathological variables and outcome [progression-free survival (PFS), overall survival (OS)]. hK5 concentration in LMP tumors ranged from 0 to 2.3 ng/mg (mean = 0.24) and from 0 to 220 ng/mg (mean = 3.35) in ovarian tumor cytosols (p = 0.002). Using a cutoff value of 0.15 ng/mg, 60% of ovarian tumors were categorized as hK5 positive. We found a strong correlation between patients with hK5-positive tumors and disease stages III/IV and grade 3 tumors (all p < 0.05). Univariate survival analysis revealed that hK5-positive patients had a significantly shorter PFS and OS (p < 0.05). Kaplan-Meier survival curves further confirmed an increased risk of relapse and death in women with hK5-positive tumors (p = 0.015 and p = 0.019, respectively). Multivariate analysis indicated that the prognostic value of hK5 was not independent from other parameters in the entire group of patients. When stratified by tumor grade (G1/2 vs. G3) and debulking success (optimal vs. suboptimal), univariate and multivariate analyses demonstrated that hK5 was an independent indicator of poor prognosis for patients with grade 3 tumors and with optimal debulking (p < 0.05). In patients with disease stage I/II versus III/IV, hK5 positivity was independently associated with a shorter PFS (p = 0.046) and marginally decreased OS (p = 0.08), in multivariate analysis. Lastly, we observed a fairly weak, positive, but statistically significant correlation between the expression levels of tissue hK5 and tissue CA125 (r(s) = 0.297; p < 0.001). Our findings provide evidence for an association between hK5 and more aggressive forms of epithelial ovarian cancer.

Adult↗
PubMed2003

Genomic EcoRI polymorphism and cosmid sequencing reveal an insertion/deletion and a new IGLV5 allele in the human immunoglobulin lambda variable locus (22q11.2/IGLV).

The human immunoglobulin lambda locus ( IGL) is mapped at Chromosome 22q11.2, spanning about 1 Mb of DNA, and directs the synthesis of lambda-type immunoglobulin light chains. The positions of about 73-74 germline V-lambda genes, depending on the haplotypes, are known, with 29-33 of them being functional IGLV genes. These genes were divided into 11 subgroups ( IGLV1 to IGLV11) distributed into three gene clusters ( VA, VB, and VC). We constructed a high-resolution restriction map of a 37-kb cosmid clone (cosmid 8.3) harboring genes of the IGLV1, IGLV7, and IGLV5 families and the non-coding sequences IGLV(I)-42 and IGLV(VII)-41-1, located at cluster VB of the IGL locus. These IGLV genes were associated with unique EcoRI fragments detectable in Southern blots of genomic DNA. Population RFLP has revealed new IGLV alleles and haplotypes. We used the restriction map of cosmid 8.3 and the IMGT database as a reference for RFLP studies. EcoRI Southern blot hybridizations with subgroup-specific probes of the functional and open reading frame sequences present in cosmid 8.3 revealed different frequencies of IGLV gene fragments, as well as deletions of IGLV1-50 and IGLV5-39 genes and RFLP involving IGLV5-45 and IGLV5-48 genes. All members of the IGLV7 subgroup were monomorphic. Sequencing of the genes present in cosmid 8.3 revealed a new allelic variant of the IGLV5 subgroup. These data contribute to a better understanding of the contribution of the germline IGLV genes to the human genetic background and polymorphism.

Alleles↗
PubMed2004

Dietary amelioration of Helicobacter pylori infection: design criteria for a clinical trial.

The longitudinal stability of the urea breath test (UBT), which measures urease as a biomarker for infection with Helicobacter pylori (a major risk factor for gastric cancer), was evaluated in the environs of Tsukuba, Japan. 13C-UBT measurements were monitored at four time points in 46 free-living, H. pylori-infected, asymptomatic volunteers over a period of 7 weeks. Subjects were asked to refrain from eating cruciferous vegetables, which might confound interpretation of results. Their compliance was monitored using both dietary records and direct biochemical testing of overnight urine. There was large between-subject UBT variation in this population (logUBT mean, 3.34; SD, 0.67). Within-subject (longitudinal) UBT values were remarkably stable in about one-quarter of the subjects (coefficients of variations for these individuals were <21%), whereas coefficients of variations in the highest quartile of variability ranged from 40% to 80%. About half of the sequential UBTs (63 of 138 such measurement pairs) changed >10 per thousand "delta over baseline" between measurements. This study provides the elements to optimize the design of a clinical trial in this population to examine the efficacy of a dietary intervention to reduce H. pylori infection. The number of subjects required to detect a 30% difference in average UBT value is highly dependent on the baseline stability of UBT measurements. For the least variable quartile, as few as 12 subjects would be needed; for the most variable quartile, at least 147 subjects would be required in each arm.

Adult↗
PubMed1996

Measurement of the urinary benzene metabolite trans,trans-muconic acid from benzene exposure in humans.

The concentration of the urinary benzene metabolite trans, trans-muconic acid was measured after exposure to benzene contained in environmental tobacco smoke (ETS). Volunteers were exposed to environmental tobacco smoke at different exposure levels and for different exposure durations. Urine samples were collected preexposure and postexposure for 24 h on exposure days. To determine background levels, urine samples were also collected on three individual days when no exposure to ETS occurred. Urinary muconic acid was elevated following benzene exposure in ETS compared to an individual's background level and can be a useful biomarker in control, characterized studies of sub-parts-per-million (sub-ppm) benzene exposures. However, the use of muconic acid as a bio-marker of benzene exposure at sub-ppm levels in the general population is problematic because of variability in the time between exposure and excretion and in an individual's background excretion rate. Urinary muconic acid associated with benzene in ETS exposure was excreted within 12 h of the exposure. A higher proportion of the benzene dose following environmental exposure in the sub-ppm range was excreted as urinary muconic acid (mean of 25%, range 7.2-58%) than found in either animal or occupational studies at higher benzene doses. The higher proportion of benzene excretion as urinary muconic acid at low benzene exposure indicates that the relationship between exposure and metabolism by the ring opening pathway is nonlinear in humans, and extrapolation from high doses to environmental benzene exposure potentially underestimates health risks mediated by the ring opening metabolic pathway that produces muconic acid, as has been suggested by previous animal data.

Adult↗
PubMed2004

A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry.

CONTEXT: Accurate estimation of risk for untoward outcomes after patients have been hospitalized for an acute coronary syndrome (ACS) may help clinicians guide the type and intensity of therapy. OBJECTIVE: To develop a simple decision tool for bedside risk estimation of 6-month mortality in patients surviving admission for an ACS. DESIGN, SETTING, AND PATIENTS: A multinational registry, involving 94 hospitals in 14 countries, that used data from the Global Registry of Acute Coronary Events (GRACE) to develop and validate a multivariable stepwise regression model for death during 6 months postdischarge. From 17,142 patients presenting with an ACS from April 1, 1999, to March 31, 2002, and discharged alive, 15,007 (87.5%) had complete 6-month follow-up and represented the development cohort for a model that was subsequently tested on a validation cohort of 7638 patients admitted from April 1, 2002, to December 31, 2003. MAIN OUTCOME MEASURE: All-cause mortality during 6 months postdischarge after admission for an ACS. RESULTS: The 6-month mortality rates were similar in the development (n = 717; 4.8%) and validation cohorts (n = 331; 4.7%). The risk-prediction tool for all forms of ACS identified 9 variables predictive of 6-month mortality: older age, history of myocardial infarction, history of heart failure, increased pulse rate at presentation, lower systolic blood pressure at presentation, elevated initial serum creatinine level, elevated initial serum cardiac biomarker levels, ST-segment depression on presenting electrocardiogram, and not having a percutaneous coronary intervention performed in hospital. The c statistics for the development and validation cohorts were 0.81 and 0.75, respectively. CONCLUSIONS: The GRACE 6-month postdischarge prediction model is a simple, robust tool for predicting mortality in patients with ACS. Clinicians may find it simple to use and applicable to clinical practice.

Aged↗
PubMedDate not supplied

The H-ras oncogene product p21 and prognosis in human breast cancer.

The protein product of the H-ras oncogene, p21, has been measured semiquantitatively in solubilized particulate fractions of 160 primary tumours from patients presenting without evidence of distant metastatic breast cancer. Levels of p21 have then been related to factors of established prognostic significance, and to clinical outcome after primary treatment in terms of disease-free interval and survival times. p21 was detected by Western blotting in all tumour fractions, but amounts varied markedly between different tumours. There was no significant relationship between levels of p21 and the menopausal status of the patient, tumour oestrogen receptors, grade, and clinical stage. However, there was a significant trend for tumours to be associated with lymph node involvement as p21 was increasingly expressed. Elevated levels of p21 were also significantly related to early disease recurrence and death from cancer. Multivariate stepwise analysis showed that both p21 and lymph node status were independent statistically significant factors for disease recurrence and survival, and that no other parameter was significant for clinical outcome after adjustment for p21 and lymph node status. These results indicate that tumour levels of p21 are an important prognostic variable in patients with early breast cancer.

Biomarkers, Tumor↗
PubMed1992

Transcriptionally active non-ligand binding oestrogen receptors in breast cancer.

Data were obtained on soluble oestrogen (ER) and progesterone (PR) receptors from 273 primary breast tumours, using an enzyme immunoassay (EIA) and ligand binding assay with dextran-coated charcoal (DCC) or isoelectric focussing separations. The p29 and total cathepsin D content was also assayed in the same samples. Tumours expressing ER (by either steroid binding assay or EIA) had higher levels of p29 than those which did not express the receptor (P < 0.0001). Moreover, tumours co-expressing ER, PR and p29 appeared to have higher levels of cathepsin D than those which were negative for at least one protein (P < 0.0001). Twenty out of the 273 human breast cancer samples, containing a level of ER positive by EIA, which did not bind labelled oestradiol, were identified; isoelectric focussing showed that such a receptor was also unable to bind hydroxytamoxifen. These tumours did not significantly differ from those in the whole population in their capacity to express ER (positive by EIA), PR, p29 and cathepsin D. It was concluded that the EIA can detect both a ligand binding ER and a receptor which is able to initiate PR transcription but does not bind radio-labelled ligands in vitro; such a receptor could have a bearing on the variability of tumour response to endocrine therapy.

Biomarkers, Tumor↗
PubMed2004

Interventions with antioxidants and nutrients in relation to oxidative DNA damage and repair.

Cells are constantly exposed to oxidants from metabolic and other biochemical reactions as well as external factors, suggesting that DNA repair systems and nutritional antioxidants are important determinants for low levels of DNA damage and cancer risk. The effects of single antioxidants, as well as various vegetables, fruits and carotenoid- and polyphenolic-rich products, have been assessed with biomarkers, mainly including DNA damage in white blood cells (WBC), urinary excretion of oxidized bases and nucleosides and DNA repair capacity. The basal levels of oxidative DNA damage, and effects of the interventions have been rather variable, possibly reflecting differences in the populations, regimens, and the type of assays. In general, single dose antioxidant interventions have shown protective effects with respect to WBC DNA oxidation. Studies with continuous ingestion of antioxidants show mixed results with respect to effects on oxidative DNA damage in WBC, possibly due to various problems with design, statistical power and period effects. Studies with only male subjects appear to show consistent antioxidant effects in terms of reduced levels of oxidized pyrimidines. Investigations of oxidatively stressed subjects, e.g. HIV-infected patients or diabetics, suggest beneficial outcomes in populations with high initial levels of oxidative DNA damage. Recent research on the effect of antioxidants on DNA repair enzymes suggest effects in terms of increased removal of oxidized purines, whereas mRNA levels of the relevant DNA repair genes appears to be unaffected by an antioxidant-rich diet. In the future, care should be taken with respect to design of intervention studies and considerations of gender effect, genotypes of defence enzymes as well as DNA repair capacity.

Antioxidants↗
PubMed2006

New American Joint Commission on Cancer staging system for melanoma: prognostic impact and future directions.

Accurate melanoma staging is critical in establishing management strategies and estimating disease relapse. Combined with assessment of comorbidities and understanding treatment toxicities, risk assessment is central to offering appropriate surgical or systemic therapies. The American Joint Commission on Cancer (AJCC) melanoma staging system provides survival estimates within anatomically defined disease categories. Newer prognostic factors and methods of prognostic analyses can augment predictions for the presence of micro-metastatic disease and further define the risk for relapse. This article highlights relevant changes, evidence supporting future incorporation of more recently defined prognostic variables, novel approaches used as adjuncts to the current staging system, and future directions of the AJCC staging committee.

Advisory Committees↗
PubMed1996

Early detection in lung cancer. Case finding and screening.

There is general agreement that the most effective approach to lung cancer is primary prevention--stop smoking. Richards has proposed the MVROCST--the Monosyllabic Verbal Response Office Cancer Screening Test: "Do you smoke?" If "yes," intervene. If "no," move on. Ample evidence exists that a clear message from a physician to a patient about the importance of stopping smoking makes a difference. In contrast to the maze of arguments and data on early detection, this is something that each physician clearly can and should do. A reduced risk for lung cancer may begin as early as 5 years after cessation of cigarette use. Huuskonen has proposed conceptualizing screening as a coordinated intervention with the goal of identifying populations at risk and working to modify that risk. Primary prevention should be central to any efforts to reduce mortality from lung cancer, and attention to this area needs to increase despite the difficulties and frustration. Despite declining percentages of smokers in the population as a whole, it is estimated that more than 3000 teenagers become regular smokers each day in the United States. In this environment, the question of whether to recommend a CXR or sputum for early detection is not going to disappear in the near future. The NCI has recognized the persistent and important nature of this debate and is currently funding the Prostate, Lung, Colon and Ovary Cancer Screening Trial. This is a large and powerful randomized study of men and women aged 60 to 74. The lung cancer arm is designed to look at the usefulness of a yearly CXR intervention in reducing cancer-specific mortality. The overall power of the study (based on national mortality data) is 0.99 for a 15% reduction in lung cancer mortality and 0.89 for a 10% reduction, with differentially better sensitivity in men than women. The study is currently in progress at multiple sites and will be completed over the next 12 to 14 years. In the meantime, what is the right approach? It is useful in considering this question to return to the concepts of early detection, screening, and case finding. 1. Early detection in lung cancer remains a concept of uncertain applicability because of the unknowns and variability in the natural history of the disease. The available, accessible, and acceptable detection tools appear to be inadequate by current evidence. This is not a static field, however, and new work in the area of biomarkers carries promise for significantly more sensitive and specific techniques. Tockman and colleagues conclude that early detection is conceptually sound, although not currently practical, and further research may expand the role of intervention. In the end, a judgement on early detection in lung cancer must be linked to the proposed setting--screening or case finding. 2. Screening, defined as the application of a test to the general population to define disease risk further with the implied benefit of improved treatment and outcome, cannot be recommended for lung cancer. This is the perspective of the major organizations cited previously, and it is based on admittedly imperfect but nonetheless convincing data. 3. Case finding, the situation of the patient who seeks care and is available for informed discussion and negotiation on possible testing, is a potentially different situation.(ABSTRACT TRUNCATED)

Decision Trees↗
PubMed2002

A light microscopic and immunohistochemical evaluation of scars.

BACKGROUND: Scars are commonly encountered by dermatopathologists and usually do not present a diagnostic challenge. However, in some cases, the pathologist may need to consider a broad differential diagnosis including fibrohistiocytic tumors, smooth muscle tumors, myofibroblastic proliferations and desmoplastic malignant melanoma. Although specific histologic aspects of scars have been well studied, a complete histochemical profile of scars, especially at various stages of evolution, has not been described. METHODS: Twenty-five cases of scars including 8 normal scars, 5 hypertrophic scars and 12 keloids were studied. Sections were examined with Verhoeff van Giesson, colloidal iron, Giemsa, smooth muscle actin (SMA), CD34, Factor XIIIa and S-100. RESULTS: All scars were negative for CD34 expression. Factor XIIIa immunostaining identified only rare dermal dendrocytes. S-100 was absent in 23 of 25 cases and stained scattered cells (less than 10%) in the other 2 cases. SMA was positive in 14 of 25 cases with 6 of these showing staining of up to 50% of spindled cells. Elastic fibers were markedly reduced or absent in all cases, mucin showed moderate or marked staining in three-fourths of the cases and dermal mast cells showed a moderate increase in 5 cases. CONCLUSIONS: These findings confirm prior reports that negative staining with CD34, Factor XIIIa and S-100 can help differentiate scars from dermatofibrosarcoma protuberans, dermatofibroma and desmoplastic malignant melanoma, respectively. SMA staining is much more variable and requires careful interpretation.

Actins↗
PubMed2001

Association between serum triiodothyronine (t3) level and risk of disease recurrence in men with localized prostate cancer.

We assessed the relationship of serum triiodothyronine (t3) level and risk of disease recurrence in men treated for localized prostate cancer. Participants in our study were found through urology and radiation oncology clinics, and all eligible patients were asked to take part. All patients had been initially diagnosed on the basis of rising prostate specific antigen (PSA) or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Serum (t3) level was determined by chemoluminescent assay with a standard, commercially available instrument (Immulite Diagnostic Products Corporation, Los Angeles, California). Sixty-eight men with prostate cancer were studied. In our treatment protocol, patients are divided into three risk groups: low risk: serum PSA</=10, stage</=T2a, or Gleason grade</=6. These patients are treated with a radioactive implant; moderate risk: serum PSA 10-15 or Gleason 7 or stage</=T2b. These patients are treated with 3 months of combined hormonal therapy followed by an implant; high risk: Gleason >7, tumor in seminal vesicle biopsy, serum PSA >15 or stage T2c or T3. These patients are treated with 3 months combined hormonal therapy, an implant, and after 2 months break 6000 rad external beam radiotherapy. There was a significant increase in serum t3 with risk category (P=0.011). Tukey's multiple range B-test showed a significant difference between the t3 levels of the high risk patients, when compared to the t3 levels of the moderate (P=0.013) and low risk patients (P=0.041). The range test showed no significant difference between the t3 levels of the moderate and low risk patients (P=0.897). Because t3 levels may be affected by age, we performed multivariate linear regression, with t3 as the dependent variable. There was a statistically significant (P=0.035) association of t3 level with risk group, but there was no significant association of t3 with age (P=0.803). Multivariate linear regression, with t3 as dependent variable, PSA, Gleason score, and stage as independent variables showed a significant overall association of the three independent variables with t3 (P=0.042), though individually the relationships were not significant. None of the men had a t3 level that was above the normal range for our laboratory (137 ng/dl). Urologists are actively seeking additional biomarkers of prostate cancer aggressiveness. Many prostate cancers are quite indolent and may never cause a problem, but it is impossible to identify such tumors with certainty. Further studies of serum t3 level as a biomarker in prostate cancer might therefore be worthwhile. With more and better biomarkers, many older men might be spared the rigors of radiation therapy and/or surgery and the complications. Also, new prostate cancer therapies might be directed toward inhibiting the mitogenic effects of t3.Prostate Cancer and Prostatic Diseases (2001) 4, 232-234.

Journal Article↗
PubMed2000

Adequacy in hemodialysis: new concepts derived from online urea monitoring.

BACKGROUND: The estimation of urea kinetic parameters [urea generation rate (Gu), normalized protein catabolic rate (NPCR), and dialysis dose (Kt/V)] is routinely performed during a single hemodialysis session as a representative sample of a stable series. To ascertain whether the stability assumption is tenable and to estimate the variability of urea kinetic parameters, a number of stable patients on regular dialysis treatment in their usual clinical setting were followed. METHODS: Thirteen stable patients on regular hemodialysis aged 61 +/- 11 were monitored from 5 to 24 weeks (median, 10 weeks) with the urea biosensor system in double-chamber hemodiafiltration. Body weight did not change appreciably. Residual renal function was negligible or absent. Weekly averaged urea concentration (TACw), Gu, NPCR, and Kt/Veq were calculated, and their serial patterns and interrelationships were evaluated through graphical analysis and linear regression. RESULTS: In six patients, the urea pool was substantially unchanged, but variability of Gu and Kt/V was comparable to that of the other groups. In three patients, body urea pool increased. Gu went from 4. 78 +/- 0.44 to 5.40 +/- 0.65 mg/min, and Kt/V went from 1.25 +/- 0. 25 to 1.34 +/- 0.31. In four patients, body urea pool decreased; Gu went from to 6.55 +/- 1.91 to 5.85 +/- 2.26 mg/min, and Kt/V did not change appreciably. Parameters might change in a nearly linear trend or occasionally as abrupt or oscillating phases. Gu was the main factor involved, and the only one affecting four of the seven unstable patients. Kt/V was never solely involved. CONCLUSIONS: Our data indicate that the estimation of urea kinetic parameters is often affected by a non-negligible degree of variability, which can be ascribed to the variability of the dialytic dose delivered and, above all, to the daily changes of diet protein assumption.

Aged↗
PubMed1997

Desmoplastic melanoma of the vulva.

The clinical and pathological features of a nonulcerated desmoplastic melanoma in the vulva of a 52-year-old woman are presented. Pleomorphic neoplastic spindle cells, fibroblasts and collagen formed a poorly demarcated 18 mm dermal mass. No adjacent intraepidermal component was seen. Immunoreactivity was demonstrated for S100 protein, vimentin, neuron-specific enolase and actin, but not for HMB-45, CAM 5.2, cytokeratin, epithelial membrane antigen, desmin or CD34. Electron microscopic examination was noncontributory. Treatment included a left hemivulvectomy with ipsilateral groin node dissection followed by radiotherapy. The tumor recurred six weeks later and was unresectable. The patient is alive with symptoms nine months after presentation. This is the first case report of a vulvar desmoplastic melanoma without neural involvement or an intraepidermal component. The variable tumor cytomorphology, nonspecific immunohistochemical and ultrastructural features render a diagnosis more difficult than with other primary cutaneous melanomas.

Biomarkers↗
PubMed2003

Lifestyle changes after a health dialogue. Results from the Live for Life health promotion programme.

OBJECTIVE: To evaluate the effect of a health dialogue on lifestyle habits, and to relate the lifestyle changes to changes of biological risk markers for ischaemic heart disease. DESIGN: Cross-sectional study, intervention and follow-up. SETTING: The community of Habo, population 9500, located in Skaraborg, Sweden. PATIENTS: All 35-year-old inhabitants in Habo were invited to a health examination during a study period between 1989 and 1992. A community intervention programme was combined with a health examination consisting of a health dialogue with a specially trained nurse and use of a "health curve" as an educational tool. The effect of the health examination was examined by comparing baseline characteristics of participants in 1989-1992 with their follow-up data in 1993. RESULTS: Participants in the health dialogue who were re-examined reported lifestyle improvements including less smoking, decreased dietary fat intake and increased physical activity. Those who reported improved dietary intake and increased physical activity improved their biological risk markers correspondingly (body mass index, waist to hip ratio, serum cholesterol concentration). CONCLUSIONS: The combination of a community and an individually based health programme can be effective with respect to lifestyle variables and, in those improving their lifestyle, in biological risk markers.

Adult↗
PubMed2001

Serum concentration of hepatocyte growth factor predicts perioperative surgical stress in children.

OBJECTIVE: To find out whether preoperative serum concentrations of hepatocyte growth factor (HGF) can indicate the general condition of sick children and can predict their postoperative inflammatory response. DESIGN: Non-randomised study. SETTING: University hospital, Japan. SUBJECTS: 41 children who required operation and 41 healthy controls. INTERVENTIONS: Samples of peripheral venous blood were obtained during the operation. MAIN OUTCOME MEASURES: Circulating concentrations of HGF, interleukin-6 (IL-6), and C-reactive protein (CRP); neutrophil counts; and nutritional variables including serum cholinesterase, albumin, and body weight: ideal body weight ratio. RESULTS: The mean serum concentration of HGF in the patients was significantly higher than in the normal controls. Preoperative HGF was related to the preoperative nutritional state, the postoperative IL-6 response, and the development of infective complications. CONCLUSIONS: The serum HGF concentration may be a useful variable for evaluating general condition and predicting perioperative surgical stress in sick children.

Adolescent↗