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PubMed2001

Cerebral effects and blood sparing efficiency of sodium nitroprusside-induced hypotension alone and in combination with acute normovolaemic haemodilution.

The combined reduction of oxygen-carrying capacity and perfusion pressure during the combination of acute normovolaemic haemodilution (ANH) and controlled hypotension (CH) raises concerns of hypoperfusion and ischaemic injury to the brain. Forty-two patients undergoing radical prostatectomy were prospectively allocated to receive CH induced by sodium nitroprusside (mean arterial pressure (MAP) 50 mm Hg), a combination of CH+ANH (post-ANH haematocrit 29%; intraoperative MAP 50 mm Hg), or standard anaesthesia (control). Serum levels of the brain-originated proteins neuron-specific enolase (NSE) and protein S-100, blood loss, transfusion requirements, adverse effects, and postoperative recovery profile were compared among the three groups. Intraoperative blood loss in the CH group (mean (SD)) (788 (193) ml) and CH+ANH group (861 (184) ml) was significantly less than in the control group (1335 (460) ml). Significantly fewer total units of allogeneic packed red blood cells (PRBC) were transfused in the patients receiving hypotensive anaesthesia (CH, 3 units; CH+ANH, 2 units; control, 17 units). There was no difference in immediate postoperative recovery profile among the three groups as determined by the emergence from anaesthesia and time to discharge from the postanaesthesia care unit. Serum S-100 protein concentrations increased significantly in all groups from baseline to peak concentrations 2 h postoperatively (CH 0.25 (0.11) microg litre(-1); CH+ANH 0.31 (0.12) microg litre(-1); control 0.31 (0.10) microg litre(-1)). A return to baseline values was seen within 24 h postoperatively in all patients. No changes in NSE concentrations were seen. Our observations suggest that CH and CH+ANH were effective in reducing blood loss and transfusion requirements in patients undergoing radical prostatectomy. Increased serum S-100 protein concentrations imply a disturbance in astroglial cell membrane integrity and an increased endothelial permeability of the blood-brain barrier. There were no associations between serum S-100 protein or NSE and adverse cognitive effects. Further work needs to be done to determine the prognostic importance of S-100 protein and NSE as surrogate variables of postoperative cerebral complications.

Aged↗
PubMed2003

Markers of the validity of reported energy intake.

Energy intake (EI) is the foundation of the diet, because all other nutrients must be provided within the quantity of food needed to fulfill the energy requirement. Thus if total EI is underestimated, it is probable that the intakes of other nutrients are also underestimated. Under conditions of weight stability, EI equals energy expenditure (EE). Because at the group level weight may be regarded as stable in the timescale of a dietary assessment, the validity of reported EI can be evaluated by comparing it with either measured EE or an estimate of the energy requirement of the population. This paper provides the first comprehensive review of studies in which EI was reported and EE was measured using the doubly labeled water technique. These conclusively demonstrate widespread bias to the underestimation of EI. Because energy requirements of populations or individuals can be conveniently expressed as multiples of the basal metabolic rate (BMR), EE:BMR, reported EI may also be expressed as EI:BMR for comparison. Values of EI:BMR falling below the 95% confidence limit of agreement between these two measures signify the presence of underreporting. A formula for calculating the lower 95% confidence limit was proposed by Goldberg et al. (the Goldberg cutoff). It has been used by numerous authors to identify individual underreporters in different dietary databases to explore the variables associated with underreporting. These studies are also comprehensively reviewed. They explore the characteristics of underreporters and the biases in estimating nutrient intake and in describing meal patterns associated with underreporting. This review also examines some of the problems for the interpretation of data introduced by underreporting and particularly by variable underreporting across subjects. Future directions for research are identified.

Adolescent↗
PubMed2002

Secondary parathyroid hyperplasia in tuberous sclerosis: report of a case with large eosinophilic ganglion-like cells similar to those of subependymal giant cell astrocytoma, tubers, and atypical angiomyolipoma.

We report a case of secondary parathyroid hyperplasia in a 49-year-old man with tuberous sclerosis. Two parathyroid glands had collections of large, eosinophilic ganglion-like endocrine cells that to our knowledge have not been previously described at this site. These cells are morphologically similar to those of subependymal giant cell astrocytoma, tubers, and atypical angiomyolipoma, all of which may arise in the setting of tuberous sclerosis. These large, eosinophilic ganglion-like cells found in different affected organs appear to be distinctive of tuberous sclerosis. We suggest these large eosinophilic cells arise from a common stem cell precursor that acquires variable phenotypes according to alterations in the cellular microenvironment.

Angiomyolipoma↗
PubMed2004

Aberrant Bcl6 protein expression in mantle cell lymphoma.

Mantle cell lymphoma is routinely considered as a Bcl6-negative B-cell lymphoma carrying the translocation t(11;14). Here we describe a series of five Bcl6-positive mantle cell lymphoma cases, including three classic and two blastoid variants. The proliferative index of these cases, measured with the Ki-67 antibody, was slightly higher than in Bcl6-negative mantle cell lymphoma cases (32.2 vs. 23.7%) Bcl6 expression was associated with translocations involving 3q27 in four of the five cases and an extra copy of the BCL6 gene in the fifth. A mutational study of the major mutational cluster in the BCL6 gene revealed no increased mutation rate, except in one case. One of the three cases displayed a high mutational index in the IgVH gene, suggesting exposure to a germinal center microenvironment. Chromosomal alterations involving 3q27 seem to be responsible for this increased Bcl6 expression, which needs to be considered when Bcl6 is used in lymphoma diagnosis.

Aged↗
PubMed1999

Menstrual cycle dependent variability for serum tumor markers CEA, AFP, CA 19-9, CA 125 and CA 15-3 in healthy women.

Information on menstrual cycle dependent variation of tumor markers in healthy women is a subject of diagnostic efficiency and has an impact in elucidating the normal function of these markers. In this study midfollicular and midluteal concentrations of serum CEA, AFP, CA 19-9, CA 125, CA 15-3 and their relations with LH, FSH, prolactin, estradiol and progesterone were evaluated during ovulatory cycles in a group of 23 healthy female individuals. Samples were collected on the 7th and 21st day of the same menstrual cycle. Tumor marker and hormone concentrations were determined with chemiluminescence or electrochemiluminescence EIA methods. A significant phase-dependent difference was observed for CA 15-3, midluteal concentrations (mean +/- SEM; 26.33 +/- 1.56 U/ml) higher than the midfollicular (mean +/- SEM; 19.27 +/- 1.49 U/ml) concentrations (p < 0.001). But an obvious difference for other tumor markers investigated did not exist. Significant correlations of follicular and luteal CA 125 levels with body mass index of the subjects were observed (r:0.52, p < 0.05 and r:0.57, p < 0.005, respectively). CA 15-3 antigen is a product of the MUC-1 gene which is expressed in abundance by endometrial epithelial cells in the secretory phase of the menstrual cycle which may be the potential source of variability. The association of CA 125 levels with obesity suggests a possible role of adipose tissue in CA 125 metabolism. In conclusion our data suggest that in healthy women serum CA 15-3 levels are significantly elevated in the midluteal phase of the menstrual cycle compared to midfollicular phase. Therefore, consideration of menstrual cycle dependent variability for CA 15-3 appears indicated in interpretation of individual results.

Adult↗
PubMed1999

Evaluation of different weight correction methods for antenatal serum screening using data from two multi-centre programmes.

Weight correction of serum markers is widely used when screening for Down's syndrome and open neural tube defects (NTD) because marker concentrations decrease with increasing maternal weight. Log-linear regression is frequently used for determining weight correction factors, but recently reciprocal-linear regression has been suggested to have advantages. We compared both methods of weight correction using data from two screening programmes carried out by this laboratory, one using alpha-fetoprotein (AFP) and total human chorionic gonadotrophin (HCG) (n = 129,143) and the other, AFP and free beta-HCG (n = 39,982). The reciprocal-linear method fitted the data more closely but did not significantly alter the detection rate or screen positive rate (SPR) for Down's syndrome or NTD with either dataset. Without correction, women heavier or lighter than average weight had significantly different SPRs for Down's syndrome and NTD compared with those weighing close to the median weight. Both correction methods smoothed out the variability in the SPR for Down's syndrome to a similar degree, but reciprocal-linear regression was much better at reducing the variability in SPR for NTD and its use is therefore worthwhile.

Biomarkers↗
PubMed1995

Comparison of polysucrose 15000, 51Cr-labelled ethylenediaminetetraacetic acid, and 14C-mannitol as markers of intestinal permeability in man.

BACKGROUND: We recently reported increased intestinal permeability to polysucrose (PS) 15000 in patients with Crohn's disease and in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). We have now compared this new macromolecular marker (14,700 D) with the conventional markers, 51Cr-labelled ethylenediaminetetraacetic acid (EDTA) (342 D) and 14C-mannitol (182 D), in healthy humans. METHODS: Twenty healthy volunteers on four occasions ingested a solution containing PS 15000, 51Cr-EDTA, and 14C-mannitol, the test solution being, respectively, isoosmolar, hyperosmolar, isoosmolar followed by a standard meal, and isoosmolar after 1 week of NSAID treatment. Fractional urinary excretion of the substances was measured over 0-4 h, 4-8 h, and 8-12 h. RESULTS: The excretion of PS 15000 was, like that of 51Cr-EDTA but unlike that of 14C-mannitol, increased by NSAID pretreatment, little affected by hyperosmolar test solution, little correlated to urinary volume, and skew with regard to frequency distribution. Despite being nominally about 40 times lower, the excretion of PS 15000 was highly correlated to that of 51Cr-EDTA but not to that of 14C-mannitol. A standard meal reduced the test variability for all three probes. CONCLUSIONS: PS 15000 may be an alternative to 51Cr-EDTA as a small-intestinal permeability marker. Inclusion of a standard meal reduces test variability.

Adult↗
PubMed1999

Factors that influence the DNA repair capacity of normal and skin cancer-affected individuals.

DNA repair capacity (DRC) was studied in 49 patients affected by basal cell carcinoma (BCC) and 68 cancer-free controls belonging to a larger case-control population enrolled for studying BCC risk factors. DRC was measured in the subjects' peripheral blood lymphocytes by using a host-cell reactivation assay that measures cellular activation of a reporter gene irradiated with UV light. A statistically significant age-related decline in DRC was observed in the controls from 20 to 70 years of age but not in the BCC cases. When the DRC values of the BCC patients and controls were compared by age, young BCC cases (age, < or =40 year) repaired less than the controls, although the difference was not statistically significant. Conversely, older BCC patients (age, >40 years) presented an enhanced repair capacity (P < 0.001) as compared with their controls. The search for possible factors associated with the high repair rate of elderly BCC cases revealed that both target cell physiology and life-style habits may affect host DNA repair. Smoking was the variable that explained most of the increase in DRC among older patients. The understanding of how these factors affect host DRC will be relevant for a correct use of this biomarker.

Adult↗
PubMed2001

[Mechanisms determining the occurrence of microalbuminuria in patients with acute ischemic stroke].

Microalbuminuria is more prevalent in patients with risk factors for cardiovascular diseases and reflects the widespread vascular damage predisposing to atherosclerosis. It is also found in acute clinical conditions, e.g. myocardial infarction, pancreatitis and stroke, and predicts poor outcome. The mechanism leading to increased albuminuria in these conditions is unknown, therefore we designed the study to investigate the relationship between increased urinary albumin excretion in acute stroke and biochemical markers of stress and inflammatory reaction as well as markers of endothelial damage. Sixty patients with first-time ischemic stroke, admitted within 24 hours to the stroke unit took part in the study. We excluded patients with diabetes, infection, nephropathy and abnormal urinalysis. Neurological deficit was assessed on admission and after 24 hours by Scandinavian Stroke Scale. Daily urinary albumin excretion on Day 2 was measured using the immunonephelometric method. The serum cortisol concentration was measured on Day 1 at 6.00 AM, 10.00 AM, 6.00 PM and 10.00 PM. Daily urinary excretion of epinephrine and norepinephrine was measured on Day 1 and on Day 3. We assessed also hematocrit, ESR, serum glucose and fibrinogen, leukocytosis, thrombocytosis and von Willebrand factor activity. Microalbuminuria was found in 46.7% of patients. There was no difference between patients with micro-albuminuria and those without it regarding sex, age and the prevalence of risk factors for stroke. Patients with micro-albuminuria had greater urinary excretion of epinephrine on Day 1. We did not find any differences regarding von Willebrand factor activity, serum cortisol concentration or other assessed variables. In logistic regression analysis the urinary excretion of epinephrine on Day 1 was the only independent variable predicting the occurrence of microalbuminuria in patients with acute ischemic stroke.

Aged↗
PubMed2002

Markers of bone turnover do not predict bone metastases in breast cancer.

Markers of bone turnover are often elevated in patients with prevalent bone metastases (BM). To test whether bone markers may be used as early indicators of developing BM, we prospectively studied 113 women with primary breast cancer. At the time of study inclusion, none of the women had BM, skeletal disease or was on bone active drugs. During follow-up (8-52, median 30 mo.), pt. were seen every 3 mo. and blood/urine specimens were obtained. Eleven patients developed BM (BM+) and each of them was matched to 4 women remaining free of BM (BM-). Markers were serum (s) calcium, sTAP, sBAP, sOC, sPICP, sNTX, sCTX and urinary (u) PYD, uDPD, uNTX, uCTX. All analyses were done in single batches after study end. At any given point in time, marker levels in the BM+ group did not differ from those in the BM- group. Levels at baseline did not predict later BM (OR 0.14-1.01, all ns). 93% of all changes in bone markers were below the least significant change, as defined in an independent group of similar patients. The remaining 7% of values could not be associated in a consistent pattern with the occurrence of BM. We conclude that in patients with primary breast cancer, biochemical markers of bone turnover can not be used to predict or diagnose incident BM. This lack in diagnostic validity is mainly attributable to the high overall and long-term variability of the currently used bone markers.

Adult↗
PubMed1992

An ovarian tumor marker with homology to vaccinia virus contains an IgV-like region and multiple transmembrane domains.

The monoclonal antibody OVTL3 has a highly restricted reactivity with ovarian carcinomas and defines a surface glycoprotein, OA3, which has been used for immunotargeting. To understand why OA3 is found on ovarian tumors we isolated a complementary DNA by expression cloning. The clone encodes a 323-amino acid protein with 5 putative membrane spanning domains, reminiscent of a membrane receptor or channel, but of a new type with little or no sequence similarity with these families of proteins. Interestingly, the OA3 sequence is highly related to a vaccinia virus encoded protein (VA38) and its extracellular domain is a member of the immunoglobulin V region superfamily.

Amino Acid Sequence↗
PubMed2004

Relationship between content and activity of cytochrome P450 and induction of heterocyclic amine DNA adducts in human liver samples in vivo and in vitro.

This study was designed to estimate a correlation between metabolic activation phenotypes and formation of DNA adducts by heterocyclic amines (HCA) in 15 liver samples from healthy donors. The correlation between the amount of endogenous DNA adducts and the content of cytochrome P450 in human liver samples in vivo was statistically significant at r(2) = 0.71 and P < 0.005. Furthermore, the isolated human liver microsomes were treated in vitro with two HCAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-9H-pyrido[2,3-b]indole (A alpha C), which have been recognized to induce two DNA adducts: 3',5'-diphosphate-N-(2'-deoxyguanosin-8-yl)-PhIP (3',5'-pdGp-C8-PhIP) and 3',5'-diphosphate-N-(2'-deoxyguanosin-8-yl)-A alpha C (3',5'-pdGp-C8-A alpha C). The correlations between the amount of DNA adducts induced by both compounds in vitro and the content of cytochrome P450 in human microsomes are statistically significant at r(2) = 0.69 and r(2) = 0.62 (P < 0.001), respectively. Furthermore, the level of DNA adducts after treatment with PhIP and A alpha C correlated with the activities of three isozymes of cytochrome P450: CYP1A1, CYP1A2, and CYP3A4. Therefore, three chemical inhibitors were used in the experiments: ellipticine against CYP1A1, furafylline against CYP1A2, and troleandomycin against CYP3A4. The highest inhibition levels in the formation of 3',5'-pdGp-C8-PhIP and 3',5'-pdGp-C8-A alpha C adducts were estimated to occur in the presence of furafylline at 56% and 69%, respectively. Ellipticine was involved in the inhibition of 40% of 3',5'-pdG-C8-PhIP adducts and in only 18% of the inhibition of 3',5'-pdGp-C8-A alpha C adducts. Troleandomycin did not significantly inhibit the formation of 3',5'-pdGp-C8-PhIP adducts under these conditions, but it inhibited the formation of 31% of the 3',5'-pdGpC8-A alpha C adducts. We conclude that the formation of DNA adducts can be used as a relevant marker of interindividual variability in the metabolic activation of HCAs in humans.

Adult↗
PubMedDate not supplied

Serum tumor markers in monitoring patients: interpretation of results using analytical and biological variation.

During cancer monitoring, data on biological and analytical variation are required in order to define the critical difference which provides an objective means to interpret serial values. We evaluated four tumor markers on serial samples collected from healthy subjects and patients. Analytical coefficients of variation (CV(A)), were obtained from "precision profiles" based on the differences between duplicates cumulated from assay runs in the laboratory. We defined the mean intrasubject biological variation (CV(I)) for CA 19-9 and TPA, separately for healthy people and patients; since the differences between the two groups were not statistically significant, we pooled the results and re-evaluated CV(I) in the combined groups (CA 19-9: CV(I) = 15.9%; TPA: CV(I) = 25.7%). In addition, we evaluated CV(I) for CEA (10.9%) and for TPS (25.9%) in patients. We then evaluated the inter-subject biological variations (CV(G)); the calculated indices of individuality for the four markers were less than 0.6 which shows conventional reference values to be of little utility for interpretation. We finally evaluated the critical differences (p < 0.05) for CA 19-9 (CD = 44.7%), for TPA (CD = 72.5%), CEA (CD = 32.7%) and TPS (CD = 72.5%); these are generally applicable since there was no heterogeneity in intra-subject biological variability.

Adult↗
PubMed1995

[Frequency of HPV infection and level of glutathione in serum of women with cervix dysplasia].

We have investigated the effect of HPV infection on the development of cervix dysplasias and GSH level in the plasma of 312 women, ranging from 18 to 34 years (x = 23.2). HPV-DNA was estimated using the Digene Hybride Capture System and GSH by the high performance liqvid chromatography method (HPLC). HPV infectior can be connected with a risk of cervical pathology and cervical cancer. Besides HPV infection the other risk factor is a low level of one of the most important antioxidant-glutathione (GSH). The level of GSH decreased while the concentration of GSSG increased in the plasma of women with HPV infection, cervix dysplasias and cancer. Simultaneous investigation of biochemical and virologic parameters in conjugation with the known cytopathologic and epidemiologic risk variables can show the factors that may inhibit or promote cervical carcinogenesis.

Adolescent↗
PubMed1993

Identification of an altered immunoglobulin heavy-chain gene rearrangement in the central nervous system in B-precursor acute lymphoblastic leukemia.

In B-precursor acute lymphoblastic leukemia (ALL), the nucleotide sequence of the complementarity determining region III (CDRIII) in the rearranged immunoglobulin heavy chain gene (IgH) has been used as a molecular fingerprint to identify the leukemic cells. In a child with B-precursor ALL without central nervous system (CNS) disease at diagnosis and a subsequent isolated CNS relapse, we examined the stability of the rearranged IgH by comparing the nucleotide sequences of the CDRIII in the leukemic cells from the marrow at diagnosis to the sequences in the leukemic cells from the cerebrospinal fluid at relapse. Whereas two of the three IgH sequences isolated from the leukemic cells at CNS relapse were identical to sequences originally isolated from the marrow lymphoblasts at diagnosis, the third CNS sequence was similar but not identical to the third marrow sequence. The third IgH sequence identified in the CNS differed from the marrow sequence only at the variable gene segment adjoining the CDRIII. Using a detection method based on the polymerase chain reaction, the altered IgH sequence identified in the leukemic cells from the cerebrospinal fluid was noted to be present in the CNS at a higher frequency than the related diagnostic sequence and was not detected in the marrow either at diagnosis or at CNS relapse. These findings indicate that the clonal pattern of leukemia in the CNS may differ from that in the marrow.

Base Sequence↗
PubMed2006

Nitric oxide in breast cancer: induction of vascular endothelial growth factor-C and correlation with metastasis and poor prognosis.

PURPOSE: Metastasis to regional lymph nodes through the lymphatic vessels is a common step in the progression of cancer. Recent evidence suggests that tumor production of vascular endothelial growth factor-C (VEGF-C) promotes lymphagiogenesis, which in turn promotes lymphatic metastasis. Nitric oxide (NO) may also increase metastatic ability in human cancers. EXPERIMENTAL DESIGN: Nitrite/nitrate levels and VEGF-C production were assessed in MDA-MB-231 breast cancer cells after induction and/or inhibition of NO synthesis. Formation of nitrotyrosine, a biomarker for peroxynitrate formation from NO in vivo, was analyzed in primary human breast carcinoma with long-term follow-up. The relationship between nitrotyrosine levels and lymph node status, VEGF-C immunoreactivity, and other established clinicopathologic variables, as well as prognosis, was analyzed. RESULTS: Production of nitrite/nitrate and VEGF-C in MDA-MB-231 cells was increased by treatment with the NO donor DETA NONOate. The NO synthase inhibitor N(G)-nitro-l-arginine methyl ester eliminated this increase. High-grade nitrotyrosine staining was observed in 57.5% (65 of 113) of the invasive breast carcinomas. Nitrotyrosine levels were significantly correlated with VEGF-C immunoreactivity and lymph node metastasis. Survival curves determined by the Kaplan-Meier method showed that high nitrotyrosine levels were associated with reduced disease-free and overall survival. In multivariate analysis, high nitrotyrosine levels emerged as a significant independent predictor for overall survival. CONCLUSIONS: Our data showed a role for NO in stimulating VEGF-C expression in vitro. Formation of its biomarker nitrotyrosine was also correlated with VEGF-C expression and lymph node metastasis. Furthermore, high nitrotyrosine levels may serve as a significant prognostic factor for long-term survival in breast cancer.

Alkenes↗