Squamous cell carcinoma-related antigen (SCCr-Ag), sICAM-1 and beta 2-microglobulin are useful markers of disease activity in psoriasis.

Several published studies suggest the involvement of immune and inflammatory factors in psoriasis. We recently demonstrated that the number of circulating ICAM-1 + lymphocytes and the levels beta 2-microglobulin are useful parameters in monitoring the activity of the disease. In this study we investigated serum levels of SCCr-Ag in 24 patients with psoriasis in order to determine whether this antigen is a marker of disease activity. Our results demonstrated high serum levels of SCCr-Ag, IL-2, sIL-2R, sCD4, sCD8, sICAM-1 and beta 2-microglobulin in the acute phase of psoriasis. Furthermore, we found a positive correlation of SCC with TBSA, PASI score, sICAM-1 and beta 2-microglobulin. These data demonstrate that serum levels of SCCr-Ag depend on the severity of the disease and correlate with both immunological and inflammatory markers of disease activity. We suggest that expression of SCCr-Ag may be induced by cytokines in the microenvironment of psoriatic lesions, suggesting that SCC-Ag may play a role in the inflammatory process.

The role of serum and gastric juice levels of carcinoembryonic antigen, CA19.9 and CA72.4 in patients with gastric cancer.

PURPOSE: The aim of the present study was to investigate carcinoembryonic antigen (CEA), CA19.9, and CA72.4 in the serum and gastric juice of patients with gastric cancer. METHODS: Serum and gastric juice tumor markers CEA, CA19.9, and CA72.4 were measured in 59 patients who had gastric adenocarcinomas and were undergoing curative gastrectomy. The same markers were measured in 47 patients with benign gastric disorders and in 40 healthy subjects. The correlation between the serum and gastric juice levels of tumor markers and several clinicopathological factors were evaluated by univariate analysis. The significance of the tumor markers as prognostic factors was assessed both by univariate and multivariate analysis. RESULTS: The positivity rates of serum CEA, CA19.9, and CA72.4 were 57.6%, 38.9%, and 18.6% respectively. The positivity rates of gastric juice CEA, CA19.9, and CA72.4 were 62.7%, 30.5%, and 23.7% respectively. The combination of serum and gastric juice markers gave a positivity of 81.3%. There was no correlation between serum and gastric juice level of each tumor marker. Positivity of gastric juice markers did not correlate with prognosis. A significant difference in prognosis was observed between patients positive and negative for serum CEA and CA19.9. Multivariate analysis also revealed that serum CEA and CA19.9 levels were independent prognostic factors. CONCLUSIONS: Levels of both serum and gastric juice tumor markers continue to have only limited diagnostic usefulness in gastric cancer patients. CEA and CA19.9 in the preoperative sera are good prognostic factors, whereas the presence of tumor markers in the gastric juice does not play any prognostic role.

[Comparison of free/total PSA (F/T PSA) ratio and PSA density (PSAD) in the early diagnosis of cancer of the prostate]. / Confronto tra il rapporto PSA libero/totale (F/T PSA) e la densità di PSA (PSAD) nella diagnosi precoce del cancro della prostata.

The identification of the immuno reactive molecular forms of PSA has permitted the identification of a correlation between Free PSA and Total PSA as the most important factor in the early diagnosis of prostate cancer. Cut-off of 0.15 ng/ml seems to be the most appropriate. The Authors consider that the use of this limit is important in the decision to carry out a prostate biopsy on the patients with PSA in the range of 4-10 ng/ml who have neither any clinical symptoms nor an abnormal transrectal ultrasound. In particular the sensitivity and the specificity of F/T PSA and the density of PSA (PSAD) have been compared at his limit of 0.15. In our study of 60 patients (of whom 22 were affected by cancer and 38 by BPH) we have noticed that 27/60 patients had a value of PSA between 4 and 10 ng/ml and negative DRE and TRUS. On the whole the F/T PSA report showed a slightly higher specificity than PSAD; in contrast PSAD showed a slightly higher sensitivity. In conclusion, to identify the early detection of this cancer both tests are required as well as a biopsy.

[Urinary PSA (uPSA) in the monitoring of local recurrence following radical prostatectomy]. / I1 PSA urinario (PSAu) nel monitoraggio della recidiva locale dopo prostatectomia radicale.

The level of urinary PSA (PSAu) was measured for use as a marker in some clinical situations involving prostate cancer patients. Limits of physiological and pathological values, a quantity of which comes from the urethral glands and the umbilical median ligament (urachus), are still unknown. To establish the quantity of PSA secretion in the urethra, female PSAu was measured and found to be significantly low (< 0.1 ng/ml). The Authors report on 25 PR patients with negative margins and who had not received hormonal therapy for 30 months. The PSAu and the PSAs were measured on the 30th and the 60th day, and every 3 months thereafter in the first year and every 6 months in the second year. In 5 cases we observed an increase of PSAu between the 5th and 18th months. In 3 cases the PSAs increased 2 to 6 months later compared to the PSAu. In these 3 cases the biopsy indicated the presence of a localized relapse. Therefore the Authors recommend measuring the PSAu (cut-off 0.1 ng/ml) in the follow-up of the PR patients because the measurement may both identify a localized relapse earlier than the PSAs and indicate the localized response to hormonal or radiotherapy.

Preliminary results of clinical evaluation of the free/total prostate-specific antigen ratio in a multicentric study.

AIMS AND BACKGROUND: The free/total (F/T) prostate-specific antigen (PSA) ratio is probably the most promising tool proposed to increase the specificity of PSA in the diagnosis of prostate cancer. The aim of the present study was to evaluate the clinical value of the F/T ratio in 138 patients with benign hyperplasia, 101 with untreated prostate cancer, and 176 apparently healthy men. METHODS: We used a new immunometric assay of free PSA (FPSA-RIACT, CIS Diagnostici, Italy) which has shown good analytical performance; sample handling and storage under routine conditions did not affect the antigen stability. RESULTS: The diagnostic efficiency of the F/T ratio was significantly better than that of total PSA. In patients with total PSA ranging from 4 to 10 ng/ml, at a specificity level of 95% total PSA showed a sensitivity of 7%, whereas the sensitivity of F/T increased to 70%. Using the F/T ratio as a decision tool in association with total PSA and considering all cases candidate to biopsy (total PSA greater than 3.79 ng/ml corresponding to the 95% level), we demonstrated a 35% reduction of total biopsies that would have been required on the basis of total PSA alone. CONCLUSIONS: The determination of the percentage of F/T serum PSA significantly improves the specificity of the marker, particularly in the 4-10 ng/ml dose range where unnecessary prostate biopsies can be reduced.

Atrial natriuretic peptide in normotensive and hypertensive heart transplanted patients.

AIM OF THE STUDY: The present study is aimed to investigate the 24-hour pattern of Atrial Natriuretic Peptide (ANP) plasma concentration in normotensive (N) and hypertensive (H) heart transplanted patients (HTP) in order to detect the pathophysiological role of blood pressure regimen for ANP increase in HTP. METHODS: Eight NHTP and five HHTP have been investigated, all being hemodynamically compensated, without histological evidence of rejection and treated by Cyclosporine, Azathioprine and Prednisone. The control group was constituted by 10 clinically healthy subjects (CHS). ANP was assayed six times over the 24 h span. The contrasts between groups were statistically analyzed by means of Student's t-test for the 24 h mean values. RESULTS: The t-test found a statistically significant difference between the ANP 24 h mean levels either of CHS and HTP or NHTP and HHTP. The ANP 24 h mean plasma levels are increased of 190.4% in HHTP and of 44.3% in NHTP in comparison with CHS. DISCUSSION: The findings suggest that the further elevation of ANP in HHTP is a compensatory mechanism to antagonize high blood pressure. Moreover, being the ANP percent increase in HHTP three times more.

Comparison of immunoassays for tumor markers CA 19-9, CA 15-3 and CA 125: data from an international quality assessment scheme.

Data collected in the 1993 and 1994 cycles of an international external quality assessment (EQA) program and in a national multicenter collaborative study were cumulatively analyzed to evaluate the standardization of the methods currently in use for the assay of mucinous tumor markers CA 19-9, CA 15-3 and CA 125. On average the between-laboratory variability was 15.2 and 16.0 CV% for CA 15-3 and CA 125 respectively; the between-laboratory variability found for CA 19-9 was markedly worse (mean 28.3 CV%). The variability component attributable to systematic differences between different methods/kits was relatively small for CA 15-3 and CA 125 (18% and 24% of the total variability) but markedly larger for CA 19-9 (48% of the total variability). The agreement of CA 19-9 results worsened in the last few years when new nonisotopic techniques became available. The precision of the methods/kits most used in the survey ranged from 9.9 to 13.3 CV% for CA 125 and from 11.6 to 13.9 CV% for CA 15-3. For these two tumor markers the precision of the traditional IRMAs does not appear different from that of the new fully automated nonisotopic techniques. The precision of CA 19-9 methods was on average worse (from 11.7 to 19.6 CV%) although two automated systems exhibited a precision better than that of IRMAs. In conclusion, the results of this study indicate that CA 15-3 and CA 125 are satisfactorily assayed whereas CA 19-9 assay appears affected by larger differences between methods and by poorer precision of laboratories and kits.

Evaluation of cytokeratin 19 serum fragments (CYFRA 21-1) in patients with lung cancer: results of a multicenter trial.

Recently, a new immunometric assay (Cyfra 21-1) was developed to measure serum concentrations of a soluble fragment of cytokeratin subunit 19. With this method, supplied by Boehringer Mannheim (EIA Test Cyfra 21-1), an Italian multicenter trial was performed in patients with lung cancer. Cyfra 21-1 serum levels were determined in 568 normal subjects (blood donors), 607 patients with non-malignant diseases (491 respiratory diseases) and 730 patients with malignancies. In the latter group 584 had lung cancer. All these 584 patients had pathologically confirmed disease; 314 were epidermoid tumors, 166 adenocarcinomas, 88 small cell cancers and 16 large cell cancers. In the 568 healthy blood donors the mean Cyfra 21-1 value was 0.91 ng/ml (SD 0.47 ng/ml; range 0.05-2.90 ng/ml). A threshold of 1.9 ng/ml was chosen as the upper limit of normality. High levels of Cyfra 21-1 were observed in patients with chronic hepatitis (positivity rate: 17/51-33.3%) and with pancreatitis (positivity rate 5/16-31.3%). In 114 out of 491 (23.2%) patients with respiratory diseases Cyfra 21-1 showed values greater than 1.9 ng/ml. The overall sensitivity (all stages) of Cyfra 21-1 in lung cancer was 65.6% (383/584). When the histology was considered the highest positivity rates were found in patients with squamous cell tumors (226/314; 72%) followed by adenocarcinomas (105/166; 63%). In patients with SCLC the global sensitivity was 52.3% (46/88). Higher sensitivity of Cyfra 21-1 was observed from stage I to stage IV (53.9% vs 85.7%; Chi square: p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-four-hour pattern of atrial natriuretic peptide in heart transplantation: evidence for lack of circadian rhythm. Temporal inter-relationships with plasma renin activity, aldosterone and cortisol.

We have investigated the circadian rhythm of plasma atrial natriuretic peptide in 13 stable output heart transplanted patients, all without evidence of histological rejection and cardiac impairment, following antirejection therapy with Cyclosporine, Azathioprine and Prednisone. The 24-h pattern of plasma renin activity, plasma aldosterone and plasma cortisol has been studied as well. All the investigated variables were assayed six times over the 24-h span. The circadian time-qualified data were analyzed by ANOVA and Cosinor method. The 24-h mean levels of atrial natriuretic peptide, plasma renin activity and plasma aldosterone are significantly increased, while the concentrations of plasma cortisol are reduced in the heart transplanted recipients. ANOVA detected a significant within-day variability of all these humoral variables only in healthy subjects. A statistically significant circadian rhythm was validated by Cosinor procedure for all the investigated molecules in healthy subjects but not in heart transplanted patients. In our opinion, the increase of atrial natriuretic peptide is a counterregulatory mechanism aimed to compensate the cyclosporine-mediated activation of the renin-angiotensin-aldosterone system. The disappearance of the plasma renin activity, aldosterone and atrial natriuretic peptide circadian rhythm can be ascribed to the constant activation of the renin-angiotensin-aldosterone system. The hypocortisolism is due, in our opinion, both to glucocorticoid therapy and increase of plasma ANP concentration.

Lack of circadian rhythm of plasma concentrations of vasoactive intestinal peptide in patients with orthotopic heart transplants.

OBJECTIVE: To study the circadian pattern of plasma concentrations of vasoactive intestinal peptide (VIP) in patients with orthotopic heart transplants. Circulating VIP is known to have neural and immunological sources. PATIENTS AND METHODS: 13 patients with orthotopic heart transplants were studied 12-53 months (mean 31.8 months) after operation. All were haemodynamically compensated and had no histological evidence of rejection. They were being treated with cyclosporin, azathioprine, and prednisone. Ten healthy individuals were studied as controls. Circulating VIP was assayed six times within a 24h period. Time qualified data were analysed by ANOVA and the cosinor method. Student's t test for unpaired data and Bingham's test for cosinor-derived parameters were used for statistical comparisons. RESULTS: Plasma concentrations of VIP were lower in the patients with orthotopic heart transplants than in the controls (p < 0.001). ANOVA and the cosinor method respectively showed a statistically significant within-day variability and circadian rhythm in the controls but not in the patients with heart transplants. DISCUSSION: The low plasma concentrations of VIP in the patients with heart transplants could be the result of the lack of contribution by the cardiac VIPergic fibres, a reduction of VIP release by the pharmacologically suppressed immune system, the inhibitory effects of cyclosporin on neural function and humoral secretions, and the effects of negative feedback on VIP release of high concentrations of atrial natriuretic peptide. The lack of the circadian rhythm suggests a structural disorder, which should be further investigated.

Effect of aging on circadian rhythm of atrial natriuretic peptide, plasma renin activity, and plasma aldosterone.

Atrial natriuretic peptide (ANP) shows a nychtohemeral fluctuation and an age-related trend. The aim of this study was to explore the circadian rhythm of ANP as a function of age. Circadian rhythms of plasma renin activity (PRA), aldosterone (PA), and cortisol (PC) were explored as well. Twenty clinically healthy subjects, 10 young (20-25 yrs) and 10 elderly (65-75 yrs), were investigated, while recumbent, after synchronization to light-dark regimen and meal timing. Blood samples for RIA tests were collected six times during the 24-hr span. The chronobiologic analysis in young subjects demonstrated a significant circadian rhythm for all the investigated variables with an acrophase-timing located at 16.48 for ANP, 4.44 for PRA, 5.32 for PA, and 7.12 for PC. In elderly subjects we documented an important increase of 24-hr mean plasma levels but not a statistically significant circadian rhythm for ANP, and a decrease in mean value of PRA which maintained, however, a significant periodic 24-hr oscillation in parallel with PA and PC. The results in young subjects reinforce the concept that ANP plays physiologically an inhibitory role on the phasic secretion of renin. The lack of the circadian rhythm for ANP along with the divergent changes in ANP and PRA 24-hr mean concentration of elderly subjects both suggest that ANP exerts with advancing age only a counterregulatory role on the tonic rather than the phasic release of renin.

[The circadian rhythm of plasma vasoactive intestinal peptide, atrial natriuretic peptide, renin activity, aldosterone and cortisol in heart transplantation. The effects of immunosuppressive therapy]. / Ritmo circadiano di peptide vasoattivo intestinale, peptide natriuretico atriale, attività reninica, aldosterone e cortisolo plasmatici nel trapianto di cuore. Effetti della terapia immunosopressiva.

Vasoactive intestinal peptide (VIP) is released both by neural endings and lymphocytes. Aim of our investigation was to study the effects of immunosuppressive therapy on VIP plasma concentrations. The research has been performed on 10 heart transplanted patients assuming cyclosporine (CYCL) and prednisone (PRED). The circulating T lymphocyte subsets, atrial natriuretic peptide (ANP), plasma renin activity (PRA), plasma aldosterone (PA) and plasma cortisol (PC) have been also assayed. Blood pressure (BP) and heart rate (HR) have been monitored over a 24-hour period to detect whether circulating VIP in heart transplanted patients is influenced by pharmacologically-induced interactions. Seriate samplings along the 24-hour span have been performed. Mean values of ANP, PRA and PA were increased, while VIP, PC and T lymphocyte subsets were decreased in heart transplanted patients as compared to clinically healthy subjects. ANOVA and Cosinor analysis showed, respectively, a statistically significant 24-hour variability and circadian rhythm for all the investigated variables only in normal subjects. BP and HR circadian rhythm in heart transplanted patients suggest that the adrenergic activity regulating the cardiovascular system is restored. This finding argues that the reduction in VIP plasma concentrations is likely due to the decreased lymphocyte production secondary to immunosuppressive therapy, or can also be ascribed to the inhibiting action of high circulating levels of ANP.

The circadian rhythm of atrial natriuretic peptide, vasoactive intestinal peptide, beta-endorphin and cortisol in healthy young and elderly subjects.

Atrial natriuretic peptide, vasoactive intestinal peptide, beta-endorphin and cortisol are humoral variables characterized by a 24-h periodicity. We evaluated the circadian rhythm of these peptides and hormones in healthy subjects who were young (between 20-25 years) or elderly (between 65-75 years). All were on controlled diets. Blood samples were collected six times during a 24-h period (at 06.00, 08.00, 12.00, 18.00, 20.00 and 24.00 h) beginning 8-h after start of recumbency. The time-related data were analysed by the Cosinor method in order to validate the circadian rhythm and to quantify rhythmometric parameters which included the midline estimate of rhythm (mesor). In contrast to the young subjects, Cosinor analysis failed to reveal a significant circadian rhythm in elderly subjects, for plasma cortisol. In elderly subjects oscillation (mesor) of atrial nutriuretic peptide was higher, while that of vasoactive intestinal peptide and beta-endorphins was lower. The results suggest changes in the physiological secretion of these three peptides in healthy elderly subjects.

Vasoactive intestinal peptide fluctuates in human blood with a circadian rhythm.

The vasoactive intestinal peptide (VIP) may be radioimmunoassayed in systemic venous blood. The plasma concentrations of VIP were investigated in human blood according to a chronobiological design. The study documented a circadian rhythmicity in time-qualified concentrations of VIP. Accordingly, VIP may be ascribed to biological variables characterized by periodicity in their physiological attributes. The rhythmic physiology of VIP is, however, highly disturbed in its tonic and phasic properties during senescence.

Temporal interrelationships between circadian rhythms of vasoactive intestinal peptide and T lymphocyte subpopulations.

Recent investigations documented an immunosuppressive action of VIP. Previous studies demonstrated that T lymphocytes exhibit a circadian rhythm (CR). This investigation was, thus, performed with the aim of detecting the relationships intercurrent between the 24-h patterns of VIP and T lymphocyte subsets. The hypothesis was formulated that circulating VIP may play a role in controlling the CR of T cells. The research was carried out on 10 clinically healthy subjects, tested six times during the 24-h span by assaying circulating levels of VIP and total T (OKT3), T helper (OKT4), and T suppressor/cytotoxic (OKT8) lymphocytes. Time data series were analyzed by Cosinor method. All investigated variables were seen to be characterized by a statistically significant CR. While the acrophase of VIP CR was found to be located at 18.20, the crest of OKT3, OKT4, OKT8 CR was seen to occur at 03.04, 02.16 and 02.56, respectively. The phase shift was found to be significant, suggesting that VIP and T lymphocytes physiologically fluctuate with a phase angle during their nyctohemeral cyclicity. The finding can be regarded as an indirect evidence of a negative VIPergic chronoregulation of CR of T lymphocytes.

Day-time changes for pituitary-thyroid hormones denote a rhythmic structure not detectable in elderly subjects.

The day-time concentrations of TSH, T3, T4, FT3 and FT4 were investigated in clinically healthy volunteers, 20 young individuals, aged from 20 to 27 years, and 12 elderly subjects, aged from 70 to 81 years. Nocturnal sampling was purposely avoided in order to eliminate the interindividual differences in sleep patterns. The day-time series were analysed by means of cosinor analysis to interpolate the best-fitting sinusoidal wave that covers the day-night period. The reconstruction of the circadian sinusoidal wave was validated for TSH, T3, T4, FT3 and FT4 in young subjects, and, with limitation, for T4 in elderly individuals. The findings suggest that the day time patterns of TSH, T3, FT4 and FT3 in elderly subjects are characterized by a dyschronism that is not detectable in young subjects. The investigation of the day-time concentrations is suggested as a cost-effective tool for exploring the circadian cycle of the pituitary-thyroid hormones in aged people.