Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin.

PURPOSE: Polymorphic epithelial mucin (PEM or MUC1) is being studied as a vaccine substrate for the immunotherapy of patients with adenocarcinoma. The present study analyzes the incidence of naturally occurring MUC1 antibodies in early breast cancer patients and relates the presence of these antibodies in pretreatment serum to outcome of disease. MATERIALS AND METHODS: We measured immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to MUC1 with an enzyme-linked immunoassay (PEM.CIg), which uses a MUC1 triple-tandem repeat peptide conjugated to bovine serum albumin, in pretreatment serum samples obtained from 154 breast cancer patients (52 with stage I disease and 102 with stage II) and 302 controls. The median disease-specific survival time of breast cancer patients was 74 months (range, 15 to 118 months). A positive test result was defined as MUC1 IgG or IgM antibody levels equal to or greater than the corresponding rounded-up median results obtained in the total breast cancer population. RESULTS: A positive test result for both MUC1 IgG and IgM antibodies in pretreatment serum was associated with a significant benefit in disease-specific survival in stage I and II (P =.0116) breast cancer patients. Positive IgG and IgM MUC1 antibody levels had significant additional prognostic value to stage (P =.0437) in multivariate analysis. Disease-free survival probability did not differ significantly. However, stage II patients who tested positive for MUC1 IgG and IgM antibody and who relapsed had predominantly local recurrences or contralateral disease, as opposed to recurrences at distant sites in the patients with a negative humoral response (P =.026). CONCLUSION: Early breast cancer patients with a natural humoral response to MUC1 have a higher probability of freedom from distant failure and a better disease-specific survival. MUC1 antibodies may control hematogenic tumor dissemination and outgrowth by aiding the destruction of circulating or seeded MUC1-expressing tumor cells. Vaccination of breast cancer patients with MUC1-derived (glyco)peptides in an adjuvant setting may favorably influence the outcome of disease.

Oral 17 beta-estradiol continuously combined with dydrogesterone lowers serum lipoprotein(a) concentrations in healthy postmenopausal women.

Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis. Serum Lp(a) concentrations increase after menopause, and postmenopausal estrogen replacement appears to decrease Lp(a) levels. In a randomized, double blind study, we examined the effects of 6-month treatment with daily 17 beta-estradiol (E2; 2 mg, orally) continuously combined with one of four dosages [2.5 mg (n = 41), 5 mg (n = 38), 10 mg (n = 38), and 15 mg (n = 20)] of dydrogesterone on fasting serum Lp(a) concentrations in 137 healthy postmenopausal women. At baseline, no significant differences were noted among the four treatment groups. During the study period of 6 months the median serum Lp(a) concentration decreased significantly from 128 mg/L (range, 5-1660) to 110 mg/L (range, 1-1530) in the total population, corresponding to a reduction of 13% (P < 0.001). The percent changes in serum Lp(a) correlated positively with the percent changes in serum E2 at 3 as well as 6 months of therapy (r = 0.38; P < 0.001 and r = 0.35; P < 0.001, respectively). A dose response of dydrogesterone on serum Lp(a) was not found. In addition, serum lipids and (apo)lipoproteins improved significantly in all four treatment groups. In conclusion, oral E2 continuously combined with dydrogesterone has beneficial effects on the lipid and lipoprotein profile and is effective in lowering Lp(a) concentrations in postmenopausal women.

Memory complaints and APOE-epsilon4 accelerate cognitive decline in cognitively normal elderly.

OBJECTIVE: To investigate to what extent subjective memory complaints and APOE-epsilon4 allele carriage predict future cognitive decline in cognitively intact elderly persons, by evaluating both their separate and combined effects. METHODS: We selected 1,168 subjects from the population-based Longitudinal Aging Study Amsterdam who were 62 to 85 years of age and had no obvious cognitive impairment at baseline (Mini-Mental State Examination [MMSE] score, > or =27). Memory complaints and APOE phenotypes were assessed at baseline. MMSE, the Auditory Verbal Learning Test (memory: immediate recall and delayed recall), and the Alphabet Coding Task-15 (information processing speed) were used to study cognitive decline. Follow-up data were collected after 3 and 6 years. Data were analyzed with generalized estimating equations, adjusted for age, sex, education, and depression. RESULTS: Baseline memory complaints were reported by 25.5% of the cognitively intact elderly persons. Overall, 25.3% of the subjects were carriers of at least one APOE-epsilon4 allele. Memory complaints were associated with a greater rate of decline in all cognitive measures, except immediate recall. In addition, APOE-epsilon4 allele carriers had a greater rate of cognitive decline shown by MMSE scores and slower information processing speeds after 6 years. The effects of both memory complaints and APOE-epsilon4 allele carriage were additive: subjects with both factors had a two times higher cognitive decline than did subjects without both factors. CONCLUSIONS: Both memory complaints and APOE-epsilon4 allele carriage predict cognitive decline at an early stage. This finding highlights the importance of subjective memory complaints, which are important even at an early stage when objective tests are still unable to detect cognitive deficits and are especially important for elderly carriers of the APOE-epsilon4 allele because they have an additional risk.

APOE-epsilon4 is associated with memory decline in cognitively impaired elderly.

OBJECTIVE: To investigate whether the association between APOE-epsilon4 and memory decline is modified by baseline cognition and age in a population-based elderly sample. METHODS: The study sample consisted of 1,243 subjects, 62 to 85 years old, with a Mini-Mental State Examination (MMSE) score between 21 and 30 and known APOE phenotypes. Memory performance was measured with an abbreviated Auditory Verbal Learning Test (AVLT) at baseline and repeated after 3 years (n = 854). Memory decline was defined as a decrease of at least 1 SD from the mean change score on immediate recall (IR), delayed recall (DR), and retention, based on the AVLT. RESULTS: Multivariate logistic regression analyses showed that APOE-epsilon4 is associated with memory decline in cognitively impaired subjects (MMSE score, 21 to 26) (OR for decline on IR adjusted for age, sex, education, and baseline recall score, 3.8; 95% CI, 1.4 to 10.0; adjusted OR for decline on DR, 2.9; 95% CI, 1.2 to 7.0; adjusted OR for decline on retention, 3.3; 95% CI, 1.1 to 10. 1), but not in cognitively normal subjects (MMSE score, 27 to 30) (adjusted OR for decline on IR, 1.1; 95% CI, 0.6 to 2.0; adjusted OR for decline on DR, 1.0; 95% CI, 0.6 to 1.8; adjusted OR for decline on retention, 1.5; 95% CI, 0.7 to 3.0). In particular, cognitively impaired epsilon4 carriers older than 75 years were at high risk of memory decline (adjusted OR for decline on IR, 4.5; 95% CI, 1.4 to 13.8; adjusted OR for decline on DR, 3.6; 95% CI, 1.2 to 10.8; adjusted OR for decline on retention, 6.6; 95% CI, 1.5 to 29.7). CONCLUSIONS: APOE-epsilon4 was associated with memory decline in subjects with cognitive impairment, but not in normally functioning subjects. Contrary to AD studies, our study suggests that the risk of APOE-epsilon4 on memory decline does not decrease at higher ages.

Humoral immune response to polymorphic epithelial mucin (MUC-1) in patients with benign and malignant breast tumours.

To investigate the clinical significance of an immune response to the MUC-1 encoded polymorphic epithelial mucin (PEM) breast cancer, circulating immune complexes containing PEM (PEM.CIC) were measured in sera from 96 healthy women, in pretreatment serum samples from 40 patients with benign breast tumours and from 140 patients with breast cancer and in serum samples from 61 breast cancer patients with recurrent or progressive disease. PEM.CIC were measured using a sandwich enzyme-linked immunoassay, and PEM serum levels were measured with CA 15.3 IRMA (Centocor Inc., Malvern, Pennsylvania, U.S.A.). Cut-off levels used for PEM.CIC and CA 15.3 were 120 Optical Density Units (O.D.) x 10(3) and 30 U/ml, respectively. In benign tumours, positivity for PEM.CIC was 37.5% (15/40). 36 of the 140 patients (25.7%) in the breast cancer pretreatment group had elevated PEM.CIC values. In patients with advanced metastatic disease, positivity for PEM.CIC was 18% (11/61). PEM.CIC was elevated in 32% (24/74) of node-negative patients, but only in 20% (12/59) of node-positive patients and absolute values were higher in node-negative patients (Mann-Whitney U test, two-tailed P = 0.0168). There was an inverse correlation between positivity for PEM.CIC and extent of disease: while 3 of the 6 patients with a carcinoma in situ were positive, only 1 of the 15 patients with more than five nodes involved had elevated levels of PEM.CIC. All 7 patients with distant metastases at first diagnosis were PEM.CIC negative. 28 out of 133 patients had a recurrence during the observation period (median 55 months, range 27-84 months). 23 of these 28 patients (82%) were PEM.CIC negative at the moment of first diagnosis. None of the patients with pretreatment elevation of both PEM.CIC and CA 15.3 (n = 13) relapsed. Our preliminary clinical results suggest that a humoral immune response to PEM protects against disease progression, and further support the idea of using synthetic peptides or glycopeptides containing the immunogenic core of the mucin as cancer vaccines.

CA 125 serum levels in the early post-operative period do not reflect tumour reduction obtained by cytoreductive surgery.

In order to assess whether CA 125 serum levels reflect the outcome of cytoreductive surgery, CA 125 antigen levels were determined prior to and after debulking surgery in 50 ovarian cancer patients and compared to CA 125 serum levels before and after surgery in a control group of 140 patients undergoing laparotomy for various malignant or benign diseases. A significant CA 125 decrease in the first post-operative week was seen in 56% of ovarian cancer patients whereas 26% remained stable and 18% showed a significant increase after surgery. Although removal of tumour had been complete in all 14 stage I-II ovarian carcinomas, only 2 of these patients showed a subsequent significant CA 125 decrease after cytoreductive surgery, while 4 patients showed a significant increase. Such increases of CA 125 following surgery were also seen in uterine carcinomas (30%), in gastrointestinal carcinomas (75%) and in patients after laparotomy for benign gynaecological diseases (23%). CA 125 pre-treatment levels were significantly lower in patients with post-operative increases than in patients with stable or decreasing CA 125 patterns. Patients with stable CA 125 levels also had lower CA 125 pretreatment levels compared to patients with a post-operative CA 125 decrease. Post-operative increases were observed for at least 2 weeks after debulking in the case of ovarian cancer. Pre-operative levels of these patients were either within the normal range or moderately elevated. Serial measurements during surgery in partial debulking showed a rapid CA 125 decline within 24 h followed by increasing CA 125 values thereafter. Our data indicate that CA 125 serum levels in the direct post-operative period do not always reflect the outcome of cytoreductive surgery. There appears to be an effect on CA 125 levels caused by the abdominal surgical procedure itself. Consequently, CA 125 levels after abdominal surgery should be interpreted with caution.

IgA contamination of IgG prepared on a protein A column.

When protein A is used for the isolation of IgG from pooled human serum further purification steps may be necessary since the IgG is contaminated with approximately 30% of the IgA originally present in the starting material. No preference for binding of an IgA subclass to protein A was found. In addition part of the IgG3 subclass binds to protein A.

Phase I therapy study of 186Re-labeled chimeric monoclonal antibody U36 in patients with squamous cell carcinoma of the head and neck.

UNLABELLED: A phase I therapy study was conducted to determine the safety, maximum tolerated dose (MTD), pharmacokinetics, dosimetry, immunogenicity, and therapeutic potential of 186Re-labeled anti-CD44v6 chimeric monoclonal antibody (cMAb) U36 in patients with squamous cell carcinoma of the head and neck (HNSCC). The potential of a diagnostic study with 99mTc-cMAb U36 to predict the biodistribution of 186Re-cMAb U36 was evaluated. METHODS: Thirteen patients with recurrent or metastatic HNSCC were given 750 MBq 99mTc-cMAb U36 (2 mg) followed 1 wk later by a single dose of 186Re-cMAb U36 (12 or 52 mg) in radiation dose-escalating steps of 0.4, 1.0, and 1.5 GBq/m2. After each administration, planar and SPECT images were obtained, and the pharmacokinetics and development of human antimurine as well as anti-cMAb responses were determined. Radiation absorbed doses to tumor, red marrow, and organs were calculated. RESULTS: Administration was well tolerated, and excellent targeting of tumor lesions was seen in all patients. Dose-limiting myelotoxicity (thrombocytopenia being most prominent) was the only toxicity observed, resulting in grade 4 myelotoxicity in 2 patients treated with 1.5 GBq/m2. The MTD was established at 1.0 GBq/m2, at which a transient grade 3 thrombocytopenia was seen in 1 patient. One patient showed stable disease for 6 mo after treatment at the MTD. The 2 patients with dose-limiting myelotoxicity showed a marked reduction in tumor size. The reduction was of short duration and, therefore, not considered an objective response. Tumor absorbed doses at MTD ranged from 3.0 to 18.1 Gy. Red marrow doses ranged from 20 to 112 cGy (mean, 51 +/- 16 cGy/GBq) and correlated with platelet nadir (r = 0.8; P < 0.01). Pharmacokinetics varied between patients treated at the same dose level and were accurately predicted by the diagnostic procedure. Five patients experienced a human anti-cMAb response, 1 of which was a human antimouse antibody response. CONCLUSION: This study shows that 186Re-cMAb U36 can be safely administered, with dose-limiting myelotoxicity at 41 mCi/m2. The use of cMAb U36 instead of its murine counterpart did not decrease the induction of human antibody responses. The availability of a 99mTc-labeled diagnostic study that can predict the pharmacokinetics of 186Re-cMAb U36 offers the possibility of using such a study for selection of a safe radioimmunotherapy dose.

The effects of sex steroids on plasma levels of marker proteins of endothelial cell functioning.

We studied thirteen male-to-female (M-->F) and ten female-to-male (F-->M) transsexuals who, for four months, received cross-sex treatment with, respectively, ethinylestradiol and cyproterone acetate, and with testosterone esters. We assessed the effects of treatment on plasma levels of tissue-type plasminogen activator (tPA), von Willebrand factor (vWF), vWF-propeptide (vWF:AgII) and big-endothelin-1 (big-ET-1), four proteins that are markers of endothelial cell functioning. We also measured urokinase-type PA (uPA) and plasminogen activator inhibitor-type 1 (PAI-1), which may not be endothelium-derived but share major clearance pathways with tPA. In M-->F transsexuals, mean plasma levels of tPA (minus 4.4 ng/ml), big-ET-1 (minus 0.8 pg/ml), uPA (minus 0.5 ng/ml) and PAI-1 (minus 26 ng/ml) decreased (all Ps < or =0.02). The level of vWF increased (plus 24%; P = 0.005), while vWF: AgII did not change (P = 0.49). In F-->M transsexuals, levels of big-ET-1 increased (plus 0.4 pg/ml; P = 0.02), while tPA, uPA and PAI-1 did not change (all Ps >0.25). In this group vWF decreased (minus 14%; P = 0.06), but vWF:AgII did not change (P = 0.38). Estrogens and androgens have clear effects on plasma levels of endothelial marker proteins. The mechanisms behind these effects are complex and appear to involve both altered secretion (big-ET-1) and processing and/or clearance (vWF and possibly tPA). Therefore, effects of hormones on the levels of endothelial marker proteins do not necessarily reflect changes in endothelial cell functioning, at least with regard to changes in vWF level associated with the oral administration of high doses of ethinylestradiol and cyproterone acetate to healthy men and the parenteral administration of testosterone to healthy women.

Modulation of plasma endothelin levels by the menstrual cycle.

Blood pressure varies during the menstrual cycle, but the reason for this is unclear. Administration of (synthetic) sex hormones can influence the level of vasoactive substances such as endothelin (ET). However, it is not known whether short-term variations in sex hormone levels in physiological situations affect ET levels. We assessed the effects of the menstrual cycle on plasma ET-1 in 8 healthy premenopausal women not using oral contraceptives (OCs) and 8 premenopausal women using OCs. ET-1 levels were measured in all subjects on days 1 to 3 (menstrual phase), 9 to 12 (follicular phase), and 20 to 23 (luteal phase) of the menstrual cycle. ET-1 levels remained constant in OC users (2.4 +/- 0.4, 2.6 +/- 0.4, and 2.4 +/- 0.4 pg/mL on days 1 to 3, 9 to 12, and 20 to 23 of the pill cycle). In contrast, ET-1 levels in non-OC users decreased in all women during the follicular and luteal phase of the menstrual cycle compared with the menstrual (low-estrogenic) phase (3.6 +/- 0.5, 2.8 +/- 0.5, and 2.9 +/- 0.3 pg/mL for the menstrual, follicular, and luteal phase, respectively, P < .01 for menstrual vfollicular and P < .01 for menstrual v luteal). The differences between OC users and nonusers were significant in the menstrual phase of the cycle (P < .01). We conclude that ET levels fluctuate during the menstrual cycle. Previously reported effects of the menstrual cycle on blood pressure may be partly explained by the effects of sex hormones on the level of vasoactive mediators. This fluctuation is not present in OC users. Studies on hemodynamic parameters in premenopausal women should account for hormonal variations in the various phases of the menstrual cycle.

Total plasma fibronectin as a marker of pregnancy-induced hypertensive disorders: a longitudinal study.

OBJECTIVE: To determine normal values of total plasma fibronectin in all three gestational trimesters and to examine 1) whether total plasma fibronectin levels differ between normotensive, hypertensive, and preeclamptic women; and 2) whether total plasma fibronectin may serve as an early marker of pregnancy-induced hypertensive disorders. METHODS: Total plasma fibronectin was measured in 376 nulliparous women once in each trimester of pregnancy. Normotensive controls (n = 222) and subjects with pregnancy-induced hypertensive disorders (n = 154) were identified after delivery. The group with pregnancy-induced hypertensive disorders was subdivided into a gestational hypertensive group (n = 125) and a preeclamptic group (n = 29). A complete total plasma fibronectin data set was obtained from 347 subjects. Trends in total plasma fibronectin values were compared for the different groups and relative risks (RRs) were calculated after optimal cutoff levels had been determined by receiver operating characteristic curves. RESULTS: Total plasma fibronectin values (+/- standard error of the mean) were 227 +/- 3 mg/L in the first, 219 +/- 3 mg/L in the second, and 260 +/- 5 mg/L in the third trimesters in normotensive pregnancies. In the first trimester and persisting throughout pregnancy, total plasma fibronectin levels were significantly higher in patients with pregnancy-induced hypertensive disorders than in controls and showed a sharper increase throughout pregnancy. Increased first-trimester total plasma fibronectin levels result in an RR of 1.4 (95% confidence interval [CI] 1.1, 1.8) of developing a pregnancy-induced hypertensive disorder in general. The RR for the development of preeclampsia was 1.7 (95% CI 0.9, 3.4), which was not significant, when the first-trimester total plasma fibronectin level was above the cutoff level of 240 mg/L. The RR for developing preeclampsia was 3.8 (95% CI 1.8, 8.0) when the second-trimester total plasma fibronectin level increased above 230 mg/L. CONCLUSION: The findings of the present study confirm those of previous studies that have found increased total plasma fibronectin levels in pregnancy-induced hypertensive disorders. This study discovered that in these women, total plasma fibronectin levels are elevated in the first trimester. Total plasma fibronectin appears to be a poor predictor of preeclampsia when measured in a general pregnant population. Therefore, total plasma fibronectin should not be used as a routine screening test in a low-risk population. However, obstetricians may use total plasma fibronectin values to help determine the relative risk of developing pregnancy-induced hypertensive disorders.

Circulating endothelin in cardiac operations: influence of blood pressure and endotoxin.

BACKGROUND: Endothelin is involved in the control of cardiovascular and renal functions and acts as a neuromodulator. METHODS: In a prospective study among 15 male patients who underwent coronary artery bypass grafting, we investigated the release pattern and possible stimuli of circulating endothelin. RESULTS: We detected a steep increase in endothelin concentrations after the onset of cardiopulmonary bypass (CPB), and a second minor increase during CPB. The steep increase in endothelin concentrations correlated with the change in arterial pressures at the onset of CPB (r = -0.57; p < 0.03). The slow increase in endothelin concentrations during CPB, however, correlated with mean endotoxin levels during and after CPB (r = 0.60; p < 0.02). CONCLUSIONS: The change in arterial pressure at the onset of CPB seems to induce a steep and fast increase in circulating endothelin level, which is probably mediated through the baroreceptors. The slow increase in endothelin level during CPB is associated with increased circulating endotoxin concentration. It may be that either endothelin-mediated vasoconstriction induces endotoxin transmigration from the intestine or endotoxin stimulates secretion from endothelial cells.

Microtiter enzyme-linked immunosorbent assay using recombinant derived antigens versus western blot in the confirmation of presence of antibodies against the human immunodeficiency virus type 1.

A microtiter enzyme-linked immunosorbent assay using recombinant derived antigens was compared with the Western blot (Dupont) in the confirmation of the presence of antibodies against the human immunodeficiency virus type 1 (HIV-1). Of 104 sera (104 individuals) that were negative by a screening ELISA, 91 were also negative by both confirmation assays. In three sera only the microtiter assay was found to be indeterminate, and in nine other sera only Western blot. The only microtiter assay positive serum was from a male patient at risk for infection with HIV. 279 sera from 83 patients were found positive by screening. Of these, 223 sera were positive in both confirmation assays, and no serum was negative. Only one serum was indeterminate by the microtiter ELISA in contrast to 55 sera, including follow-up samples from 25 patients, most of whom had AIDS, by Western blot (Dupont criteria). However, the number of Western blot indeterminate sera decreased substantially applying less stringent criteria for interpretation. In conclusion, the microtiter ELISA performed well as a confirmation test for the presence of antibodies against HIV-1. In addition, the results demonstrate that in the microtiter assay the envelope peptide kp41 is highly discriminative in detecting anti-HIV-1 negative and anti-HIV-1 positive sera.

CSF-IgM measurement in neurovenereological disease.

An immune response within the central nervous system (CNS) is reflected by an increase of immunoglobulin concentrations in the cerebrospinal fluid. IgM is considered the first class of immunoglobulins to be increased after infection. Calculation of the IgM and IgG-index reflects immunological activity within the CNS. Insight in this activity is essential in the diagnosis of several neurological diseases, especially neurosyphilis. A new fast solid phase, double sandwich enzyme-immuno assay for the measurement of IgM in the CSF is described and applied in 71 neurovenereological patients.

Changed transferrin sialylation in Parkinson's disease.

Variation in the sialylation pattern of transferrin was studied in serum and cerebrospinal fluid (CSF) of 90 patients with Parkinson's disease (PD), dementing and non-dementing, de novo and treated, and was compared with the variation observed in a group of 21 age-matched healthy controls. In serum and CSF of PD patients the proportional contribution of the different sialo-transferrins was independent of sex or dementia. However, a significant shift was found towards the more sialylated fractions for serum transferrin in both de novo and treated PD patients. This shift was not observed for CSF transferrin. The contribution of the tau-transferrin fraction, reduced in de novo PD patients, returns on treatment to the level observed for healthy controls. These observations may be important, as the degree of sialylation of transferrin in serum and CSF plays a role in the homeostasis of iron, and suggest that alterations in transferrin sialylation may play a role in the pathophysiology of PD.

The use of biliary CEA measurements in the diagnosis of recurrent colorectal cancer.

To assess the usefulness of biliary CEA determinations in the diagnosis of recurrent tumour, gallbladder bile was sampled in patients who underwent laparotomy for proven or suspected recurrent colorectal cancer and in control patients. Biliary CEA concentrations in controls were < 5 ng/ml, whereas significantly elevated CEA concentrations were found in the bile of all patients with tumour recurrence. Serum concentrations in these patients were elevated in 77% only. In a series of 12 patients with (a) suspicious lesion(s) on liver imaging but normal serum CEA concentration during follow-up, biliary CEA determination differentiated clearly between metastases and benign lesions. Biliary CEA determination seems to aid detection of tumour recurrence at an early stage and may preclude unnecessary surgery in patients with undefined liver lesions.

The beta-core fragment of human chorionic gonadotropin: biochemical background and clinical application.

In this review an overview is given of the possible applications and usefulness of the beta-core fragment of hCG (beta cf-hCG) as an urinary tumor marker. Expression of human Chorionic Gonadotropin (hCG) is an important indicator of malignant transformation. The biochemical background of this glycoprotein hormone and the degradation pathway towards beta cf-hCG is described. There are two main pathways: peripheral degradation in the serum and the renal parenchymal degradation. HCG and its subunits show immunoreactivity and cross-reactivity with other glycoprotein hormones and their subunits. The different "in house" methods to determine beta cf-hCG developed and used by various research institutes are described. In various types of cancer, concentrations of hCG as well as its beta-subunit may be elevated, allowing the clinical use of these substances as a tumor marker. The relation between laboratory outcome and clinical status is assessed, with emphasis on the beta cf-hCG in gynecological malignancies. The limitations of the use of beta cf-hCG as a tumor marker are discussed. The stability of beta cf-hCG may allow distant follow-up in samples sent to the laboratory by mail.

Urinary gonadotropin peptide (UGP) and serum CA 125 in gynaecologic practice, a clinical prospective study.

BACKGROUND: Beta human chorionic gonadotropin (beta-hCG) is expressed in human fetal tissue and cancer cells of various histologic types. It is degraded to the beta-core fragment (beta cf-hCG) which is concentrated in urine, and is known as urinary gonadotropin peptide (UGP). The objective of this study was to assess 1) the value of urinary gonadotropin peptide (UGP) as a single test and the combination of UGP with CA 125 as a diagnostic test in predicting the benign or malignant origin of gynecologic disease, 2) the influence of surgical removal of the tumor on the levels of UGP and CA 125, 3) the influence of the urinary concentration on the UGP levels in relation to the test results. PATIENTS, MATERIALS, METHODS AND STATISTICS: Serum and urine were collected from 31 gynecological patients with malignant and non-malignant disease, preoperatively, and 1 week and 6 weeks after surgery. Optimal cut-off levels were determined by Receiver Operating Characteristic-curves (ROC). Sensitivity (SENS), specificity (SPEC), positive (PPV) and negative predictive value (NPV) and overall test accuracy (ACC) for their ability to discriminate benign from malignant masses were calculated. Logistic regression analysis was performed to calculate the contribution of CA 125, UGP and UGP/creatinine (UGP/creat) to a model predicting malignancy. RESULTS: The optimal cut-off level for UGP was found 1 fmol/l, for UGP/creat 1.33 fmol/mg creatinine and for CA 125 100 kU/L. The distribution of the urinary creatinine values varied considerably (median = 8.3 mmol/l, range 0.6-25.8 mmol/l). The correlation coefficient (r) between log UGP and log CA 125 was 0.44 (p = 0.001) and between log UGP/creat and log CA 125 0.53 (p < 0.0001). CONCLUSIONS: UGP may be used as a tumor maker in gynecological disease. However, CA 125 as single test discriminates malignant from benign disease better than UGP or UGP/creat. In a logistic model the combination of CA 125 with UGP and UGP/creat predicts the benign or malignant character in 89% of the study population. Significant changes in UGP and UGP/creat levels were seen after removal of benign tumors, however, this was not found in ovarian cancer patients. Correction of the UGP values for the urinary concentration improved the results slightly.

A rapid and sensitive immunosorbent assay for urinary albumin.

We describe a fast, simple and sensitive microtiter scale competitive ELISA for the determination of urinary albumin. All reagents are commercially available. In the standard procedure, a minimum concentration of 0.8 mg albumin/L can be measured, although, applying another dilution, 0.04 mg/L can be detected. Within-batch coefficient of variation was 6.9% and 5.6% (at 1:20 and 1:50 dilution, respectively); between-batch variation was 8.6% and 5.6% respectively. The influence of urine pH and other urine components is minimised in the assay diluting with a casein-containing buffer.

Nasal secretions from patients with polyps and healthy individuals, collected with a new aspiration system: evaluation of total protein and immunoglobulin concentrations.

This study was designed, first, to test a new system for aspiration of human nasal secretions and, secondly, to evaluate protein and immunoglobulin concentrations in these secretions at different levels of secretory activity. The direct aspiration system combines the advantages of minimal irritation of the nasal mucosa with the facility to determine concentrations per gram of secretion. The total protein and immunoglobulin concentrations were inversely related to the amount of secretion obtained. Variations in fluid secretion throughout the day may be responsible for this relationship. The inverse relationship was much more significant in patients with nasal polyps, in which much higher concentrations were found, than in healthy subjects. Ratios of immunoglobulin to total protein were independent of the amount of secretion obtained. Compared to the controls, the ratios of IgM and IgG to protein in the secretions of the patients were significantly increased. The secretory immunoglobulin A to total protein ratios were only slightly higher in the patients' secretions.