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Background: Decreased amyloid beta (1-42) (Abeta42) and increased (phosphorylated) tau in cerebrospinal fluid (CSF) are considered to be a reflection of plaques, tangles, and neuronal degeneration in Alzheimer's disease (AD). Atrophy of the medial temporal lobe (MTA) on magnetic resonance imaging (MRI) reflects neuronal loss in this area., Objective: To compare diagnostic accuracy of CSF biomarkers and MTA in AD versus controls., Methods: Abeta42, tau and tau phosphorylated at threonine 181 (Ptau-181) were measured in CSF from 61 AD patients and 32 controls by sandwich enzyme-linked immunosorbent assay. A CSF biomarker profile for AD was constructed. MTA was rated visually on MRI., Results: When AD patients and controls were evaluated separately, no correlations were present between the CSF markers and MTA score. Both MTA and CSF biomarker profile were independently associated with the diagnosis AD (MTA: OR (95% CI)=28 (3-239); CSF biomarker profile: OR (95% CI)=57 (13-262)). Among individuals younger than 65 years old and without MTA 60% suffered AD, and the finding of an abnormal CSF biomarker profile was limited to AD patients only., Conclusions: MTA and CSF biomarkers seem to be of incremental value for the diagnosis AD. CSF analysis is most sensitive in the absence of MTA, and especially among early-onset AD patients.

Objective: The purpose of this study was to assess the differential diagnostic potential of a combination of CA 125, CA 15-3, and CA 72-4 antigens in the definition of malignant disease, especially ovarian carcinoma in patients with a pelvic mass., Study Design: A total of 412 patients were evaluated in a multicenter, retrospective study., Results: Two hundred twenty-six malignant, 171 benign pelvic tumors (of which 129 were benign ovarian tumors), and 15 borderline tumors were evaluated. One hundred thirty-three patients had ovarian carcinoma. In 76 cases (55%), the International Federation of Gynecology and Obstetrics stage was III or IV. Borderline tumors (n = 15) were excluded from the statistical calculations. CA 125 antigen was the most sensitive marker for ovarian carcinoma (81%). The highest specificity and positive predictive value was obtained with CA 15-3 antigen (95% and 92%, respectively). Considering a concomitant elevation of all 3 markers as positive, a positive predictive value of 97% was found. However, only 28% of the patients in the total group and 41% of the patients with ovarian carcinoma had a concomitant elevation of all 3 markers. The combination of all 3 markers with levels below the cut-off resulted in a (false-positive) positive predictive value for malignancy between 12% and 36%. With the use of logistic regression analysis, we found a correct prediction in 73% of the cases. CA 15-3 antigen makes the most significant (P <.0001) contribution to the logistic model in the prediction of malignancy in the total group, with all pelvic masses with an odds ratio of 3.86., Conclusion: The combination of a simultaneous elevated level of CA 125, CA 15-3, and CA 72-4 antigens was predictive for malignant disease in almost all cases. However, such concomitant elevation was found in few of the malignant masses. Logistic regression analysis revealed that CA 15-3 antigen makes the most significant contribution to a model for the prediction of malignancy in the total group. The logistic model gave a correct prediction in 73% to 83%. The present tumor marker panel seems inferior to combinations with other test modalities, which include ultrasonography and/or physical examination and/or menopausal status or age.

Objective: The objective of this study was to evaluate the extent to which endothelin and the eicosanoids prostacyclin and thromboxane A2 are involved in the pathophysiology of gestational hypertension and preeclampsia., Study Design: In a longitudinal design, venous blood samples and 24-hour urine specimens were collected from 396 women in each trimester of pregnancy. After delivery of all patients, venous plasma endothelin was assessed in 20 subjects with identified preeclampsia, 48 subjects with gestational hypertension, and 59 normotensive subjects. Urinary excretions of the thromboxane A2 and of the prostacyclin metabolites thromboxane B2 and 6-keto-prostaglandin F1 alpha were assessed in 16 subjects with preeclampsia, 35 subjects with gestational hypertension, and 31 normotensive subjects., Results: Endothelin levels showed a second-trimester drop in all groups. In all 3 gestational trimesters a high correlation was found between the excretion of thromboxane B2 and that of 6-keto-prostaglandin F1 alpha (P <.001). The overall thromboxane B2 and 6-keto-prostaglandin F1 alpha urinary excretions increased throughout pregnancy and the overall thromboxane B2 /6-keto-prostaglandin F1 alpha ratio decreased. No significant differences in endothelin, thromboxane B2, and 6-keto-prostaglandin F1 alpha excretion levels or in thromboxane B2 /6-keto-prostaglandin F1 alpha ratios were found between women with preeclampsia, gestational hypertension, and normotension. Only in a small group of patients with severe preeclampsia (n = 2) and severe gestational hypertension (n = 2) were increased second-trimester endothelin values and increased thromboxane B2 /6-keto-prostaglandin F1 alpha ratios found., Conclusion: In this longitudinal study we found no evidence for prostacyclin deficiency or increased endothelin levels in preeclampsia. Only women with severe preeclampsia and severe gestational hypertension expressed increased endothelin levels and thromboxane dominance over prostacyclin.

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.

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.

Objective: Our purpose was to establish reference values for six monoclonal antibody-based serum immunoassays applied in patients with carcinoma of the female genital tract., Study Design: Sera from 938 healthy women (median age 48.0 years, range 37 to 76 years) were assayed for levels of CA 125, CA 15.3 (two methods), CA M29, CA M26, and mucin-like cancer antigen (MCA)., Results: Reference values, defined as those including 95% of healthy controls, were in women with unknown menopausal status as follows: CA 125, 37 U/ml; CA 15.3 (Centocor), 33 U/ml; CA 15.3 (Boehringer Mannheim), 28 U/ml; CA M26, 83 U/ml; CA M29, 13 U/ml; and MCA, 19 U/ml. Postmenopausal values were significantly lower for CA 125 and CA M26 and significantly higher for CA M29 and CA 15.3 (both methods). MCA serum levels were age independent., Conclusion: Reference values found were not in accord with those generally applied in gynecologic oncology. In addition, serum levels were influenced significantly by menopausal status (except with MCA).

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.

Objective: In recent years an increasing amount of evidence supports the concept that preeclampsia is an endothelial disease. The purpose of our study was to evaluate the extent to which endothelial cell dysfunction is involved in pathophysiology of preeclampsia., Study Design: We studied the urinary excretion of thromboxane B2 and 6-keto-prostaglandin F1 alpha and the venous plasma endothelin levels in 23 preeclamptic patients and in control subjects. In six of these patients and in six controls arterial plasma endothelin levels were also measured. In addition, plasma levels of calcitonin gene-related peptide and plasma fibronectin levels were measured. Results were analyzed by Wilcoxon's rank-sum test or signed-rank test., Results: In preeclampsia the urinary thromboxane B2/6-keto-prostaglandin F1 alpha ratio (p < 0.001), venous plasma endothelin levels (p < 0.001), and plasma fibronectin levels (p < 0.001) were significantly elevated compared with normotensive pregnancy. Arterial plasma endothelin levels were significantly higher than venous plasma endothelin levels in normotensive and hypertensive patients (p < 0.05). Calcitonin gene-related peptide levels showed a wide range in normotensive pregnancy and in preeclampsia, but the difference was not significant., Conclusions: These results confirm the extensive involvement of the endothelium in the pathophysiology of preeclampsia. Preeclamptic vasoconstriction seems to be mediated by an increase in the vasoconstrictor autocoids thromboxane A2 and endothelin. Production of prostacyclin by the vessel wall and endovascular trophoblast might be just a pivotal escape mechanism of the uteroplacental circulation. Calcitonin gene-related peptide appears not to be involved in the pathophysiology of preeclampsia.

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.

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.