Molecular detection of cytokeratin-19-positive cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic significance.

PURPOSE: To evaluate the prognostic significance of molecular detection of cytokeratin 19 (CK-19) mRNA-positive cells by nested reverse transcriptase polymerase chain reaction (RT-PCR) in the peripheral blood of women with stages I and II breast cancer before adjuvant chemotherapy. PATIENTS AND METHODS: The sensitivity and specificity of CK-19 mRNA detection by nested RT-PCR were investigated using MCF-7 and ARH-77 cells and blood from healthy women and patients with hematologic malignancies, metastatic colorectal cancer, and early and metastatic breast cancer. Peripheral blood from 148 patients with operable breast cancer, obtained before initiation of any adjuvant therapy, was tested for the presence of CK-19 mRNA-positive cells. RESULTS: The nested RT-PCR assay for CK-19 mRNA detected one MCF-7 tumor cell in 10(6) normal peripheral blood mononuclear cells in four of five experiments; no signal was detected with the CK-19-negative ARH-77 cells. CK-19 mRNA was detected in the peripheral blood of 3.7% of healthy blood donors, 14.3% of patients with hematologic malignancies, and 3.2% of patients with metastatic colorectal cancer. Detection rates for CK-19 mRNA-positive cells in the bone marrow/blood of patients with early or metastatic breast cancer were 63%/30% and 74%/52%, respectively. For stages I and II breast cancer, detection of CK-19-positive cells in the peripheral blood before adjuvant therapy was associated with reduced disease-free interval (P =.0007) and overall survival (P =.01). In multivariate analysis, detection of peripheral-blood CK-19-positive cells was an independent prognostic factor for disease relapse and death. CONCLUSION: Molecular detection of CK-19 mRNA-positive cells by RT-PCR in the peripheral blood of patients with stages I and II breast cancer before initiation of adjuvant therapy has independent prognostic value as a marker of poor clinical outcome.

Nutrition during pregnancy: the effects of an educational intervention program in Greece.

An intervention program was undertaken to assess dietary habits and the impact of nutrition education among pregnant women in the rural county of Florina, northern Greece. Analysis of dietary habits, nutrient intake, hemoglobin, and serum vitamin concentrations in an intervention and control group indicated that the population was adequately nourished although nutrient intake was below recommended levels for pregnant women. Nutrition counseling was associated with improvements in dietary intake and significantly greater maternal weight gain (p less than 0.05). Mean birth weight was slightly higher in the intervention group but so was the incidence of low birth weight (4.5% vs 3.9%). The prematurity rate was marginally lower in the intervention group (p less than 0.04), as was the number of perinatal deaths (9 vs 11). The results indicate that nutrition counseling during pregnancy can improve dietary intake and maternal weight gain but the mediating influence on low frequency pregnancy outcomes is indeterminate in a population that is not nutritionally at risk.

Coronary-heart-disease risk-factor status of the Cretan urban population in the 1980s.

The traditional Cretan diet has been associated with low coronary-heart-disease (CHD) mortality rates. This study reports on the prevalence of CHD risk factors among 387 Cretan bank employees. Mean cholesterol concentration has risen by 36% over 26-y; dietary intake has changed: consumption of meat, fish, and cheese has increased and consumption of bread, fruit, and potatoes has decreased. Although the percentage contribution of fat to total energy intake has decreased from 40% to 36%, there has been a reduction in monounsaturated fatty acid consumption and an increase in the consumption of saturated fatty acids whereas the consumption of polyunsaturates has not been altered. Exception for diminished physical activity, the prevalence of other risk factors (smoking, blood pressure, and body mass index) remained relatively stable over this period. These changes in the CHD risk-factor status of the Cretan urban population occurred over a period in which CHD mortality rates are reported to have increased.

Incidence of breast cancer on Crete, 1994-1995.

The aim of this study was to present epidemiological results relating to malignant neoplasms of breast using primary data from the island of Crete, Greece, 1994-1995. The patients were all female residents of Crete with breast cancer first diagnosed during 1994 and 1995, 208 and 207 new incident cases, respectively. The data were collected and analysed by the Cancer Registry of Crete (CRC). Direct age-standardised rates (ASR) for incidence and cumulative risk (to age 75 years) were calculated for Crete as a whole. Standardised incidence ratios (SIR) were calculated for the 20 provinces (administrative regions); these were also smoothed using Bayesian methods. The ASR for incidence per 100000 person-years was 70.6. The truncated rate (age 40 years and above) was 153.7. The SIR for the 20 provinces showed no marked variations, with three exceptions, two of which had ratios higher than 1 and one lower. Bayesian smoothing of provincial incidence rates showed that throughout Crete, the risk of breast cancer shows considerable uniformity. The incidence rate of breast cancer on Crete is higher than that of Greece overall, and is comparable with other southern European countries. A possible explanation is that the published incidence for Greece may be an underestimation of the true rate. The small variability in breast cancer incidence within Crete probably reflects the homogeneity of the population and environmental and social conditions.

Mammographic findings and occupational exposure to pesticides currently in use on Crete.

This is a preliminary report of an outreach mammographic-screening programme on Crete. The screening is part of a study to test if occupational exposure to pesticides in greenhouses (mainly organophosphates and organocarbamates), may increase the risk of malignant or premalignant findings in mammographic examination. A total of 1062 women (aged 40--75 years) were recruited between 1988 and 1993 and followed-up until 1998: 522 worked for at least 10 years in greenhouses for more than 4 h daily (exposed), and 540 never worked in agriculture (non-exposed). Statistics include detection rates and relative risks of mammographic findings. 'Exposed' women had a significantly (P<0.05) higher risk than 'non-exposed' for fibroadenoma, ductal hyperplasia, sclerotic adenosis, fibrohyperplastic disease, cystic disease and inflammatory mastitis. There were no significant differences in the detection rates of fibrocystic changes, lipoma and malignant changes or malignant tumours. Compared with older women (aged 50--75 years), younger women (aged 40--49 years), particularly in the 'exposed' group, had a higher detection rate of malignant tumours. These preliminary results indicate that 'exposed' women may have higher risks of incidence for a number of lesions, which are risk markers for subsequent invasive breast cancers. They confirm also that early screening for breast cancer is effective and provides an opportunity for a reduction in breast cancer mortality.

The inflammatory bowel disease questionnaire: a review of its national validation studies.

Health-related quality of life (HRQoL) is an important measure of illness perception on the part of the patient. The Inflammatory Bowel Disease Questionnaire (IBDQ) is a widely used questionnaire for HRQoL assessment in patients with inflammatory bowel diseases (IBDs). This questionnaire has been adapted and validated into several languages and cultural milieus. The aim of this study is to review the methods used by several adaptation studies for assessing the validity and reliability of the adapted IBDQ. A search was made of the Medline database for relevant articles since 1989. Standard validation criteria were used for including studies for further evaluation. The following aspects of the validation procedure were examined: translation, construct validity, reliability, sensitivity to change, and used statistical methods. Nine validation studies of the IBDQ, in England and in non English-speaking countries (Holland, Spain, Korea, Sweden, Greece, and China) were selected. All studies concluded that the adapted instrument was valid and reliable. Only few modifications were proposed. Two studies recommended the split of the four dimensions of the original questionnaire in five. Assessing HRQoL in patients with IBD is an ever-increasing practice, especially in clinical trials. IBDQ was proven to be valid and reliable in several cultural and linguistic milieus when appropriate validation procedures were applied.

ZD1839, a novel, oral epidermal growth factor receptor-tyrosine kinase inhibitor, as salvage treatment in patients with advanced non-small cell lung cancer. Experience from a single center participating in a compassionate use program.

OBJECTIVE: We evaluated the efficacy and tolerability of the orally active, selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) ZD1839 in patients with pretreated advanced non-small cell lung cancer (NSCLC) participating in a compassionate use program. PATIENTS AND METHODS: Thirty-one patients with advanced, unresectable and progressive NSCLC, previously treated with one or two chemotherapy regimens, received ZD1839 250 mg orally once daily. Patients who had received only one prior chemotherapy regimen had to be considered unsuitable for second-line chemotherapy. RESULTS: The disease control rate was 32% (95% CI: 15.8-48.7) (1/31 patients had a partial response and 9/31 patients had stable disease) and the median overall survival 23 weeks (range 4-40). Symptom improvement was reported by 39% of patients overall and by 83% of patients who achieved disease control. The median time to symptom improvement was 3 weeks (range 2-4). Adverse events were generally mild (grade I or II) and reversible and consisted mostly of skin rash, diarrhea and fatigue. CONCLUSIONS: ZD1839 demonstrated clinically meaningful antitumor activity with significant improvement in symptoms in this heavily pretreated group of patients with advanced NSCLC. Furthermore, ZD1839 showed a favorable toxicity profile, with the majority of adverse events being mild and reversible.

Correlation between age-related macular degeneration and pseudoexfoliation syndrome in the population of Crete (Greece).

OBJECTIVE: To evaluate the epidemiological correlation between age-related macular degeneration and pseudoexfoliation syndrome in the inhabitants of the island of Crete (Greece). SUBJECTS AND METHODS: A total of 777 persons (315 men and 462 women, aged 40-99 years), representing a randomized sample (1.43%) of the Cretan population, underwent slitlamp and fundus examinations according to protocol. The results were statistically analyzed. RESULTS: The prevalence of pseudoexfoliation was 16.1% (21.3% in men and 12.6% in women) and that of maculopathy, 7.9% (11.7% in men and 5.2% in women). The conditions were significantly correlated with each other (P = .002). Also, both displayed a significant direct correlation with age and altitude (for pseudoexfoliation, P<.001 and P = .002 for age and altitude, respectively; for age-related macular degeneration, P<.001 for age and for altitude) and an increase in bilateral incidence with progressing age. CONCLUSIONS: The observed prevalences of pseudoexfoliation and maculopathy were lower than those reported in the mainland of Greece and other Mediterranean regions. The correlation between age-related macular degeneration and pseudoexfoliation syndrome may be explained by the relationship of each disease with age and altitude.

Association of specific HLA phenotypes with left ventricular mass and carotid intima-media thickness in hypertensives.

The aim of this study was to investigate the hypothesis that the expression of certain HLA antigens may constitute a risk marker for cardiovascular hypertrophy in subjects with arterial hypertension. We examined 158 subjects with newly diagnosed arterial hypertension. HLA class I (-A, -B, -Cw) and class II (-DR, -DQ) antigens were studied by two-step microlymphocytotoxic technique in peripheral T and B lymphocytes. Carotid intima-media thickness (IMT) was determined noninvasively by ultrasonography. The left ventricular mass was calculated according to the formula of Devereux and was normalized by the individual's height (LVM/h). The individuals with DR13 and DR17 were characterized by higher values of IMT compared to those without these HLA (0.096+/-0.018 cm v 0.085+/-0.021 cm, P = .011, 0.100+/-0.019 cm v 0.084+/-0.021 cm, P = .012, respectively). The presence of HLA DQ7 was characterized by markedly higher values of IMT that just failed to reach statistical significance (0.091+/-0.019 cm v 0.084+/-0.022 cm, P = .045). Furthermore, subjects with HLA DQ7 and DR11 exhibited higher values of LVM/h in comparison to those without these HLA (191.3+/-36.2 g/m v 166.9+/-41.0 g/m, P = .029 and 194.6+/-34.3 g/m v 166.6+/-40.9 g/m, P = .034, respectively). Hypertensive subjects with HLA B51 tended to have lower LVM/h (166.6+/-39.0 g/m with v 176.0+/-41.7 g/m without HLA B51, P = .045). In conclusion, it can be postulated that certain HLA phenotypes exhibit an association with increased carotid IMT and left ventricular mass in hypertensive subjects. The determination of these antigens may help to identify subjects at high risk for cardiovascular events.

Serum levels of tumor necrosis factor and soluble interleukin 2 receptor as markers of disease activity and prognosis in childhood leukemia and lymphoma.

The serum levels of soluble interleukin 2 receptor (SIL-2R) and tumor necrosis factor (TNF) were assessed in 69 children from 6 months to 14 years old who suffered from acute lymphoblastic leukemia (39), Hodgkin's disease (15), non-Hodgkin's lymphoma (15) and in 54 normal age-matched controls prior to any therapy and at remission. Both SIL-2R and TNF levels were significantly higher at diagnosis compared with normal controls (P < 0.001), but decreased significantly at remission. The SIL-2R and TNF levels were significantly higher in an advanced stage of lymphoma than in an early stage. In the patients with acute lymphoblastic leukemia (ALL) and lymphoma, higher levels of SIL-2R (> 1030 units/ml) and TNF (> 30 pg/ml) were associated with a poorer treatment outcome (P < 0.01). Our findings indicate that elevated TNF serum secretion together with SIL-2R are useful markers in childhood ALL and lymphoma and can be used to assess both disease activity and prognosis in this group of malignancies.

Regular firing patterns of suprachiasmatic neurons maintained in vitro.

Cells of the suprachiasmatic nucleus (SCN) recorded in vitro display a characteristic firing pattern. Unlike many other central neurons, they have the ability to fire at a constant low rate with fixed interspike interval. This regularity is most pronounced at firing rates above 3-5 spikes/s. Spontaneous firing below 3 spikes/s was less regular but became increasingly regular as the firing rate was increased. Similarly, regular discharges became irregular when the firing rate was reduced below 3-5 spikes/s. The mean spontaneous firing rate was 5.6 +/- 1.6, range less than 1 to 12 spikes/s and cells were resistant to attempts to increase their rate of firing beyond 15-20 spikes/s. Statistical analysis showed that the firing patterns of all the cells studied formed a single continuous population in terms of their interspike interval distributions, and that these distributions were a function of the firing rate. Addition of either of two commonly used anesthetics, urethane or sodium pentabarbitone, disrupted previously stable, regular activity.

Prognostic value of ploidy of primary tumour and nodal secondaries in colorectal cancers.

Tumour ploidy is of prognostic value in colorectal cancer, DNA aneuploid tumours having a worse outlook. Nearly all studies have concentrated on the DNA content of the primary tumour. We have examined the ploidy of the primary tumour and its lymph node metastases in 71 cases of Dukes' stage C disease, to see whether this provides greater prognostic information than the primary alone. Analysis was performed using formalin-fixed, paraffin-embedded tumour sections. Ploidy of primary and metastases was different in 20 cases (28%), aneuploid nodes being seen with diploid primaries and vice versa. Ploidy of both the primary (chi 2 = 4.86, P = 0.03) and secondary (chi 2 = 4.86, P = 0.03) tumours predicted survival in univariate analysis. Combining the ploidy of primary and nodes, three prognostic groups could be defined--diploid primaries with diploid metastases (hazard relative to both aneuploid, 0.36) had significantly better survival than cases where the ploidy of the primary and nodes were mixed (relative hazard 0.47-0.56), which did better than cases with aneuploid primary and nodes. This study demonstrates that ploidy variation between primary and secondary tumours is common, and better prognostic information may be gained by studying both.

Management by nurses of primary headache: a pilot study.

Primary headache is a very common condition and one that nurses encounter in many different care settings. Yet there is a lack of evidence as to whether advice given to sufferers is effective and what improvements may be expected in the condition. The aim of this study was to evaluate the advice given by a nurse to primary headache sufferers. The design was quasi-experimental. An experimental group (n = 19) and a control group (n = 25) of primary headache sufferers had their headache parameters of frequency, severity duration and disability (Migraine Disability Assessment) over the previous six months assessed. The experimental group then received advice in the form of health education from a nurse. Both groups kept a headache diary for six months. After six months both groups had their headache parameters assessed again. Compared to the control group, there was a significant reduction in the severity of headaches experienced by the experimental group (p = 0.006). Although there were reductions in frequency and duration of headaches experienced by the experimental group compared to the control group, these were not significant (p = 0.664 and p = 0.235, respectively). The Migraine Disability Assessment showed a trend towards reduced scores in the experimental group compared to controls which were not significant (p = 0.535). This pilot study suggests that health education can be effective in reducing the severity of headaches. However, a larger study over a longer period is needed to evaluate improvements in headache parameters.

HLA phenotypes as promoters of cardiovascular remodelling in subjects with arterial hypertension.

The objective of this study was to investigate the association between human leukocyte antigens (HLA) phenotypes and cardiovascular remodelling, as expressed by left ventricular mass (LVM) and carotid intima-media thickness (IMT), in hypertensives. We examined 153 subjects with arterial hypertension and 61 normotensive controls living in the greater Athens area. The population was classified into three groups and specifically group I (normotensives), group II with Grade 1 hypertension and group III with Grade 2 or 3 hypertension. HLA class I and class II antigens were studied by microlymphocytotoxic technique. Carotid IMT and LVM were determined by ultrasonography. The prevalence of HLA DQ7 in the hypertensive cohort was 27.4% that was significantly smaller than the 52.5% among the controls (P = 0.002). The HLA DR11 was found in 24.0% of the hypertensives and in 52.5% of the controls (P < 0.001). Group III hypertensives with HLA DR11 exhibited significantly higher LVM/h in comparison to the hypertensives without this HLA (199.0 +/- 28.8 vs 171.2+44.1g/m, P = 0.009). This association was not present in groups I and II. Similarly, group III hypertensives with HLA DQ7 were characterized by higher IMT in comparison to those without this HLA (0.94 +/- 0.19 vs 0.83 +/- 0.23 mm, P = 0.048). HLA DR17 was associated with higher IMT in both groups II and III (1.00 +/- 0.19 vs 0.82 +/- 0.19 mm, P = 0.046 and 1.01 +/- 0.23 vs 0.84 +/- 0.22 mm, P = 0.049, respectively) but not in group I. In conclusion, certain HLA phenotypes may be related to the levels of arterial blood pressure. Moreover, it seems that these HLA phenotypes may identify subjects with arterial hypertension that are more prone to develop cardiovascular hypertrophy.

Molecular detection of cancer cells in the peripheral blood of patients with breast cancer: comparison of CK-19, CEA and maspin as detection markers.

PURPOSE: To investigate and compare the diagnostic value of the detection of cytokeratin 19 (CK-19), carcinoembryonic antigen (CEA) and maspin mRNA by nested RT-PCR in the peripheral blood of women with breast cancer. MATERIALS AND METHODS: The tumor cell lines MCF-7 and LOVO were used in an experimental tumor cell dilution model to determine the sensitivity of the nested RT-PCR for the 3 detection markers. RT-PCR analysis was performed in the peripheral blood of 54 healthy female blood donors, 28 patients with hematological malignancies, 31 with metastatic colorectal cancer, 75 with operable and 50 with metastatic breast cancer before receiving any cytotoxic chemotherapy, as well as in the bone marrow aspirates of 61 breast cancer patients. RESULTS: Nested RT-PCR for CK-19 mRNA presented the highest sensitivity by detecting 1 tumor cell amongst 10(6) PBMC in 4 out of 5 experiments. CK-19 mRNA was detected in the peripheral blood of 3.7% of female blood donors, 14.3% of hematological malignancies, 32% of operable and 42% of metastatic breast cancer patients. CEA mRNA was undetectable in the blood of female blood donors but was detected in blood samples of 3.5% of hematological malignancies, 19.3% of colorectal cancer and 10% of breast cancer patients. Maspin mRNA was undetectable in the blood of female blood donors, patients with hematological malignancies and colorectal cancer but was detected in 9.3% of operable and 14% of metastatic breast cancer patients. Maspin mRNA positivity correlated with tumor size in patients with early stage breast cancer (p = 0.057). The detection rates of CK-19 and maspin mRNA in bone marrow aspirates were 33% and 11% for operable and 62% and 9% for metastatic breast cancer, respectively. During follow-up, 27.4% of blood samples were positive for CK-19 mRNA versus 10.7% for maspin mRNA in patients with operable breast cancer with a concordance rate of only 12.7% for positives and 86% for negatives. CONCLUSION: RT-PCR positivity for CK-19 mRNA is the most sensitive detection marker for occult tumor cells in operable and metastatic breast cancer, although nested RT-PCR for maspin mRNA appears to be more specific.

Ulcerative colitis is as common in Crete as in northern Europe: a 5-year prospective study.

OBJECTIVE: To study the incidence of ulcerative colitis and to analyse the pattern of the disease in the prefecture of Heraklion, Crete. PARTICIPANTS: The population at risk comprised 263,670 inhabitants in the prefecture of Heraklion (2641 km2). The two regional hospitals, five health centres, 109 private family doctors and 145 specialists participated in the study. METHODS: A prospective and population-based epidemiological study of ulcerative colitis over five years from 1990 to the end of 1994. RESULTS: Overall, 117 patients with ulcerative colitis (75 males and 42 females) were newly diagnosed during the study period. The mean annual incidence of the disease for the years 1990-1994 was 8.9 per 10(5) inhabitants (95% CI 7.2-10.4). The male to female ratio was 1.8:1. There were no significant difference between the age-specific incidences of the age groups. The majority (51.3%) of the patients were exsmokers and one-third had never smoked. A family history of first-degree relatives positive for inflammatory bowel disease was obtained in 9.6% of our patients. CONCLUSION: Ulcerative colitis is common in Crete; its incidence is as high as in Northern Europe.

Cadaveric donotransplantation: nurses' attitudes, knowledge and behaviour.

Human organ transplantation is an important treatment for certain medical conditions, and for irreversible organ failure. There is a shortfall in the number of organs required for transplantation. The close and continuous proximity of nurses to potential donors and their families make them critical links in the organ donation process. Therefore, success in organ procurement may depend on nurses' awareness and integration of knowledge about donotransplantation (the process of organ/tissue donation and transplantation). Postal questionnaires were distributed throughout the United Kingdom (UK) to 2465 registered nurses, to assess their personal attitudes, knowledge and behaviour regarding cadaveric donotransplantation. One thousand, three hundred and thirty-three questionnaires were returned, a response rate of 54%. Overall, nurses held positive attitudes to donotransplantation, with 78% agreeing with organ donation and only 10% clearly being opposed. However, nurses were found to share ambivalent attitudes of altruism and fear which appear to surround decisions about donation. Factor analysis was used to further explore nurses' attitude structure. Six factors were confirmed providing a non-significant likelihood ratio fit (P = 0.468) and a well reproduced correlation matrix. The factors related to: (1) the value and contribution made by donotransplantation; (2) the unique idea of having another's tissue in one's own body; (3) the importance of organ donation; (4) the individual's moral, and nurses' professional rejection of the responsibility for organ/tissue donation; (5) the post-mortem mutilation of the body; and, (6) the potential distress donation may cause a bereaved family. Comparisons were made between certain of nurses' specialist groups and significant differences were found. Comparisons of factor scores between certain specialist groups or other strata were assessed by analysis of variance. Nurses working in renal units were significantly more in favour of donotransplantation than any other group of nurses.

Design, methods and participation. Euronut SENECA investigators.

At the initiative of EC/Euronut a European Community project (SENECA) began in 1988, with 19 research groups working on the major nutritional issues affecting the growing number of elderly people in Europe. Some 2600 people born between 1913 and 1918 were studied, using strictly standardized methodology. Data have been collected on the dietary intake of these people, their nutritional status, physical activity, life-style, health and performance. It is envisaged that the SENECA project will be continued according to a mixed longitudinal design. The mean response rate in a group of 18 communities in which a non-participation study was conducted was 51%, while 60% of the non-responders were prepared to complete a non-responders' questionnaire. On the basis of the data collected from both responders and non-responders, it was found that males, non-smokers, healthy and better educated persons participated better in the SENECA study than females, smokers, persons who judged their health to be poor, and persons with comparatively poor education, respectively. Housing (having a garden), age, and marital state (single) were only of minor importance for the participation. Persons who did not eat a cooked meal daily, generally participated less, but this differed between towns. It is demonstrated how stratum-specific weighting factors can be calculated to partially remove bias due to selectivity in participation.

Improved statistical classification methods in computerized psychiatric diagnosis.

BACKGROUND: Mainstream psychiatric diagnosis involves mainly sequential, expert-system-derived, logical decision rules. Among the few statistical classification methods that have been sporadically evaluated are Bayes, k-nearest neighbor, and discriminant analysis classifiers. METHODS: A statistical classification method based on artificial neural networks (ANN) with task-specific constrained architectures was applied to a sample of 796 clinical interviews, where the symptom evaluation and the diagnostic judgments were made using the Psychiatric State Examination (PSE) system. The proposed constrained ANN (CANN) method was compared with other statistical classification methods. RESULTS: CANN was found to be superior to all other considered methods, having an overall "correct" classification rate of 80% when applied to test data. Similarly, the concordance coefficients of agreement with the PSE diagnostic categories were all very high. Among the other used methods, discriminant analysis had slightly inferior performance but better generalization capability. CONCLUSIONS: The proposed CANN method has a definite utility in psychiatric diagnosis and requires further evaluation, perhaps alongside other standard classification systems and/or with larger samples.

Assaying of tumor necrosis factor alpha, complement factors, and alpha-1-antitrypsin in the diagnosis of malignant serous effusions.

The objective of this study was to measure the concentrations of tumor necrosis factor-alpha (TNFalpha) in pleural and peritoneal effusions of different causes and to verify whether TNFalpha, alpha-1-antitrypsin (alpha1AT), and complement factors C3 and C4 can be used in the differential diagnosis of serous effusion. One hundred forty-five serous effusions of various origins were analyzed. TNFalpha, alpha1AT, and complement factors C3 and C4 concentrations were measured simultaneously in blood and serous effusion using commercially available methods. Serous effusions were classified as follows: 102 exudates and 43 transudates. All variables were found to have good diagnostic value in the differential diagnosis of serous effusion. In the stepwise discriminant analysis, four variables were selected, producing a significant discriminant function (p < 0.001). Their order of selection was alpha1AT effusion, C4 serum, TNFalpha-effusion, and C3 effusion. Combined use of these variables increased remarkably the diagnostic value (in diagnosing exudates versus transudates) giving sensitivity = 93.14%; specificity = 90.70%; positive predictive value = 95.96%; negative predictive value = 84.78%. Determination of TNFalpha, complement factors C3 and C4, and alpha1AT may be a significant parameter in the differential diagnosis of serous effusions, particularly in those patients with malignant disease. Moreover, the combination of them significantly increased their diagnostic power.