Doppler echocardiographic patterns in patients with acromegaly.

Cardiovascular problems have long been recognized as responsible for an increased morbidity and mortality in patients with acromegaly. The aim of the present study was to evaluate echocardiographically the prevalence of cardiomyopathy in a cohort of acromegalic patients and to analyze the results in relation to demographic, clinical and hormonal data. This study, a retrospective controlled clinical trial, was performed in 25 acromegalic patients, 12 men and 13 women aged 26-66 years (mean: 52.6). Fifteen patients had an active disease, 10 were cured by previous pituitary surgery. The same echocardiographic parameters were analyzed in 50 healthy subjects aged 30-70 years (mean: 51.4). Serum GH was determined on at least 4 samples drawn over 24 hours and plasma IGF-I on a single point. Standardized parameters of diastolic and systolic function were evaluated by real-time Doppler echocardiography. Twelve patients with active acromegaly underwent also 48-hour ECG registering. Left ventricular (LV) hypertrophy was found in 14/25 patients (56%). No difference was found between patients with active disease (53%) and patients with cured acromegaly (60%). LV mass index was significantly increased in acromegalics in comparison with healthy subjects (137 +/- 43 g/m2 vs 96 +/- 16 g/m2, p < 0.01) and also the indices of LV diastolic function were significantly impaired. Asymmetric septal hypertrophy was found only in one patient. Hypertension was detected in 9/25 patients (36%) without difference between patients with active or cured disease (40% vs 30%, NS). No significant correlation was found between hormonal or clinical data and echocardiographic findings. During Holter monitoring, heart rate of acromegalics was not significantly different from that of controls (78 +/- 12 bpm vs 72 +/- 10 bpm, NS) and only isolated supraventricular or ventricular premature complexes (Lown class 1) were detected. In conclusion, this study provides evidence of subclinical LV dysfunction in acromegaly in the absence of other known causes of heart disease and no significant difference in echocardiographic pattern was apparent between active or cured acromegalics.

Clinical utility of tissue polypeptide antigen determination in lung cancer management.

In view of the fact that pulmonary malignancies still represent an important cause of tumor death and that the high rate of unsuccessful treatment may be partly due to the late clinical presentation, efforts should be spent not only to develop new and effective treatments but also to improve early diagnosis and to identify prognostic factors and parameters useful for the monitoring of the treatment. Tumor markers, if used properly, can provide a useful support for the management of patients suffering from various malignancies, including lung cancer patients. The clinical significance of one of the most widely used tumor markers, Tissue Polypeptide Antigen (TPA), has been reviewed and showed this marker to be useful to the clinician for the management of patients with pulmonary malignancy, as a complementary tool for diagnosing and staging the tumor as well as for monitoring treatment response or relapse occurrence.

[Measurement of skeletal alkaline phosphatase in prostatic carcinoma. Preliminary report]. / Il dosaggio della fosfatasi alcalina scheletrica nel carcinoma prostatico. Rapporto preliminare.

Bone metastases frequently occur in prostate carcinoma. Total body radionuclide scan with diphosphonate methylene labelled with 99Tc is commonly used to diagnose such metastases. However this technique is aspecific and frequently unreliable. In recent years several biological markers dealing with bone metabolism were studied. Serum determination of skeletal alkaline phosphatase (ALP) and moreover of its bone isoenzyme (BAP) could be considered a reliable index of osteoblastic activity. In this preliminary report we analyzed a group of 43 patients affected by prostate carcinoma with or without bone metastases. The American Urological Association (AUA) staging system was adopted. Sixteen patients were D2, bone metastases had been suspected by means of radionuclide bone scan and confirmed by Computerized Tomography and/or aimed X-rays. Tandem R-Ostase by Hybritech was used to measure BAP, normal value is set to 20 micrograms/L. All D2 tumours had pathological BAP values (mean value 87.50 micrograms/l); 1/3 stage A, 5/13 stage B, 5/9 stage C and 0/2 stage D1 patients had pathological findings. One of this patients, stage C, revealed a bone metastase at a later bone scan.

CYFRA 21-1 as a tumour marker for bronchogenic carcinoma.

Despite extensive research, the role of the commonly employed tumour markers in the diagnosis of lung carcinoma is yet to be clarified. The utility of a new marker, CYFRA 21-1, in the preoperative evaluation of patients with bronchogenic carcinoma was investigated. CYFRA 21-1 was determined with a radiometric assay in serum of 280 patients with lung cancer and 208 patients with various nonmalignant lung diseases. The levels of the marker were significantly higher in lung cancer patients. Among benign lung diseases, elevated CYFRA 21-1 levels were found in pulmonary fibrosis. Using a cut-off of 3.2 ng.ml-1 (95th percentile of levels obtained in benign lung disease), the total sensitivity of the marker was 48%. The best sensitivity was obtained in squamous cell lung cancer (60%). The highest values of CYFRA 21-1 were found in metastatic lung cancer, and the marker sensitivity was more elevated in stage IIIb and IV. On the other hand, 40% of patients with surgically resectable lung cancer had CYFRA 21-1 levels above the cut-off. We conclude that CYFRA 21-1 may be satisfactorily employed in the differential diagnosis between malignant and benign lung diseases in association with other clinical and radiological data.

Intramuscular calcitriol for uraemic children with severe hyperparathyroidism and hypercalcaemia.

The effect of intramuscular calcitriol was evaluated in five children (aged 1-16 years) with severe chronic renal failure and hyperparathyroidism [range of intact parathyroid hormone (PTH) 400-1,200 pg/ml]. All five children had been on oral calcitriol or 1 alpha-hydroxyvitamin D3 treatment (5-20 ng/kg per day), but an adequate, efficacious dosage could not be achieved since any attempt of increasing the dosage resulted in severe hypercalcaemia (> 2.9 mmol/l). Intramuscular calcitriol was given three times weekly for 5 months at an initial dosage of 65-70 ng/kg to all but one patient who received 100 ng/kg. In the first three patients, treatment resulted in an 86%-98% fall in serum PTH compared with baseline levels and serum calcium never exceeded 2.65 mmol/l, except for one episode of hypercalcaemia in one patient. In the last two patients, serum calcium rose above normal limits, thus calcitriol had to be discontinued several times and then restarted at a lower dosage (40 ng/kg); PTH fell by 61% and 73%, respectively, compared with basal values. All patients had very low pre-treatment levels of serum 1,25-dihydroxyvitamin D3 (5-15 pg/ml) which were normalized (35-56 pg/ml) by the intramuscular calcitriol-treatment. Serum phosphorus and magnesium did not vary in any of the five patients. No side effects were observed at the injection site. Intramuscular calcitriol seems a useful therapeutic option for patients with severe hyperparathyroidism associated with a high serum calcium level when treated with conventional oral calcitriol.

Disappearance curves of tumor markers after radical surgery.

CEA serum levels were sampled from 15 patients with lung carcinoma, 12 patients with colon carcinoma, and 5 patients with gastric carcinoma before and after radical excision of the malignancy. In addition, TPA serum levels were measured in 7 patients with lung carcinoma and CA 19.9 serum levels in 9 patients with colon carcinoma, before and after curative surgery. Irrespective of the primary malignancy, a CEA half-life of approximately 3 days was calculated. The normalization time was related to the preoperative level of the marker, being longer when the preoperative CEA level was > 20 ng/ml. The TPA half-life was slightly longer than 1 day, ranging from less than 1 day to more than 3 days, with a normalization time of about 20 days. The CA 19.9 half-life was slightly longer than 1 day with variations from less than 1 day to about 3 days. Many factors, especially associated inflammatory processes and hepatic clearance imbalances, may influence marker kinetics in the postoperative period. A correct evaluation of the clinical significance of tumor marker half-life after radical surgery will require a larger number of patients as well as careful and prolonged follow-up.

Mitral annulus size in isolated mitral stenosis.

M-mode and two-dimensional echocardiographic images were obtained using the planimeter method in the short axis view and calculated by Doppler-derived pressure half-time in 24 patients with mitral stenosis before and after surgical commissurotomy and posterior annuloplasty. The diameter of the mitral valve annulus was measured in the standard long axis view and in the apical four-chamber view using two-dimensional echocardiography. Preoperatively, the mitral annulus was dilated in all patients as a consequence of left atrial dilation. This could be one of the factors causing residual regurgitation after surgical mitral commissurotomy. However, more data are needed to demonstrate that annuloplasty can prevent the development of mitral regurgitation after surgery.

Immunohistochemical detection of carcinoembryonic antigen (CEA) in non-neoplastic lung disease.

Carcinoembryonic antigen (CEA), though typically associated with malignant epithelial neoplasms, is known to be present at elevated levels even in the serum of normal individuals and of patients suffering from interstitial diseases of the lung. Few reports have addressed the question of the possible source of CEA immunoreactivity within the lung parenchyma. Two patients with elevated CEA serum levels were studied by immunohistochemistry on open lung biopsy specimens. Two different antibodies (one absorbed with non-specific cross-reacting antigen, NCA) were used. The results show that bronchiolar cells and type II pneumocytes are focally positive with both antibodies; the immunoreaction is preserved even after absorption with NCA. In agreement with experimental data on CEA synthesis in fetal bronchial cell lines, these findings indicate that interstitial lung disorders may induce abnormal CEA-like substance expression. In these cases, where no epithelial neoplasms subsequently develop, the cutoff level for CEA in serum should be raised. Bronchiolar and alveolar cells appear primarily responsible for CEA-like substance production.

[A cancer marker study in patients with neoplastic pathology of the neck and head area]. / Studio di markers oncologici in pazienti con patologia neoplastica del distretto cervico-cefalico.

Specific markers able to detect either the presence of tumours or to identify the histological type of tumour are not currently available. Previous work yields an inconsistent picture of actual effectiveness of oncological markers, we therefore carried out a study on the cancer patients in our clinic. The present paper considered five markers (CEA, SCC, ca 19-9, TPA and Ferritin) and tested their effectiveness in diagnosing and following patients with head and neck neoplasias. The study was carried out on 102 patients, divided into three groups: 59 had been histologically diagnosed cancer but had not received any treatment (first group), the remaining 43 who had been treated (second group). We have also monitored the first group of no treated patients six months after therapy (third group). Our results suggest that while no significant conclusions may be drawn from SCC and CA 19-9, we found interesting results concerning Ferritin. Indeed Ferritin values increased by 22% in the first group, by 26% in the second one and by 19% in the third one. CEA and TPA values increased in non treated patients only by 22% and 12% respectively while they did not alter in the treated ones and they altered by 10.5% and by 10% respectively six months after therapy. Although our data are still preliminary and speculative and further evidence is needed, we can infer that the stage of the cancer and the positive markers appear to be concluded. The correlation is even stronger when all the cases are considered, without introducing the statistical and epidemiological variables.

Atrial natriuretic peptide and bronchial hyperresponsiveness in patients with mitral stenosis.

Atrial natriuretic peptide (ANP) has been reported to have protective effects against methacholine-induced bronchoconstriction in asthmatics. The aim of the study was to evaluate the relationship between plasma ANP levels and bronchial responsiveness to methacholine in patients with mitral stenosis. In 12 patients with moderate mitral stenosis, age 35-58 years, 9 female, 8 in NYHA class 2, 4 in NYHA class 3 for symptoms, plasma ANP and bronchial threshold to methacholine (PD20FEV1) were determined. The same measurements were performed in 10 asthmatic patients, hyperresponsive to methacholine, and in 10 normal subjects, nonresponsive to methacholine. Mean +/- SE plasma ANP levels were significantly higher in patients with mitral stenosis in comparison with asthmatics and normals (159 +/- 41.8, 7.3 +/- 0.98, 7.6 +/- 1.3, respectively, p < 0.01). In patients with mitral stenosis there was a significant relationship between plasma ANP and PD20FEV1 (r = 0.81, p < 0.01). No relationship was found between ANP and PD20FEV1 in asthmatics. In conclusion, in patients with mitral stenosis ANP seems to play a protective role against bronchial hyperresponsiveness to methacholine.

Effect of testosterone on bone in hypogonadal males.

Bone mineral content (BMC) and testosterone levels were evaluated and compared in 10 hypogonadal males and 10 normal, age-matched controls. In 6 of the subjects an investigation was also carried out into the effects of testosterone administration on lumbar BMC, calcitonin (CT) response to hypercalcaemia, osteocalcin (BGP) and the fasting urinary calcium/creatinine and hydroxyproline/creatinine ratios. Our results confirm that male hypogonadism is characterized by a low BMC and that testosterone administration is able to improve this parameter and to increase both basal BGP and CT response to hypercalcaemia. Testosterone therefore probably acts on bone tissue through both a direct action on osteoblast cells and an improvement in CT secretion.

Clinical significance of tumor necrosis factor in patients with bronchogenic carcinoma and benign lung diseases: a comparative study.

Tumor Necrosis Factor (TNF) was determined in the serum of 72 lung carcinoma patients. Twenty-four healthy subjects younger than 50 years and 10 healthy subjects older than 70 years were considered as control group. TNF was also measured in 20 patients with stage I sarcoidosis and in 15 patients with pulmonary fibrosis. The marker was detected in 32% of cases in the neoplastic group, in 37.5% of disease confined to the chest and in 25% of advanced disease cases. A large proportion of TNF-positive samples was found in sarcoidosis (30%), and even larger in pulmonary fibrosis (66.6%). TNF was also present in healthy subjects older than 70 (40%). We conclude that TNF is not specific of malignancy, being demonstrable in other benign pulmonary diseases and even in the course of physiological aging.

Value of exercise stress test, radionuclide angiography and coronary angiography in predicting new coronary events in asymptomatic patients after a first episode of myocardial infarction.

One-hundred-and-fifty-five consecutive symptom-free patients underwent maximal treadmill exercise testing, rest and stress radionuclide angiography at least two months after an uncomplicated acute myocardial infarction; of these, 90 underwent coronary angiography. All patients were followed-up for a mean of 32 +/- 13 months regarding the prediction of hard (death and reinfarction) and soft (angina and coronary surgery) coronary events. The specificity, sensitivity, positive and negative predictive value of exercise stress test were 47%, 76% and 41% for any coronary events; none of the patients who incurred a hard coronary event showed ischemia during electrocardiographic exercise tests. Sensitivity, specificity and positive predictive value for failure to increase the ejection fraction of at least 5% were 60%, 45% and 30% for any coronary event and 25%, 49% and 2% for any hard coronary event. The presence of multivessel disease at coronary angiography showed a sensitivity of 62% for any coronary event and of 67% for hard coronary events; specificities were 66% and 57%, and predictive values were 52% and 10%, respectively. It is concluded that electrocardiographic exercise testing, radionuclide angiography and coronary angiography are not helpful two months after an episode of uncomplicated myocardial infarction in order to identify patients who will suffer a new coronary event.

TAF test in primary esophageal carcinoma: comparison with other tumor markers.

An ELISA method for the determination of circulating specific HSV-TAA antibodies has recently become available (TAF test). The presence of TAF was tested in serum of 154 patients with primary esophageal carcinoma, collected in three institutions. The overall TAF-test positivity rate was 57.1%, being significantly lower in stage IV than in stage III patients. The concordance rate between TAF and CEA, ferritin, TPA, SCC and TATI was low, suggesting that TAF is probably independent of the other tumor markers evaluated. The clinical role of TAF-test determination in patients with esophageal carcinoma is currently under evaluation.

[Immunological variations after thymic stimulation with special reference to IL2-RS in patients operated for neoplasms]. / Variazioni immunologiche dopo stimolazione timica con particolare riguardo all'IL2-RS, nel paziente operato per neoplasia.

The paper reports a study which was carried out to assess immunological function by assaying IL2 in cancer-operated patients treated with thymostimulin. The results of the study show that, used in normally fed, immunodepressed patients, this immunomodulator is able to normalise levels of lymphocyte subpopulations and to bring serum concentrations of IL2-RS to the levels of normoergic patients.

Tumor-associated trypsin inhibitor (TATI) in pleural effusions.

The purpose of this study was to evaluate the usefulness of tumor-associated trypsin inhibitor (TATI) determination in serum and pleural fluid for differential diagnosis of relapsing pleural effusions. The concentrations of TATI were determined in samples of serum and pleural fluid from 51 patients with pleural effusions comprising 20 benign exudates, 5 transudates and 26 malignant effusions. TATI levels overlapped in benign and malignant fluids. This precludes the use of this marker for diagnosis of pleural effusions. For this purpose CEA seems to be the best tumor marker with a sensitivity frequently higher than that of cytology.

Tumor-associated trypsin inhibitor (TATI) in the diagnosis of lung cancer.

To evaluate the usefulness of tumor-associated trypsin inhibitor (TATI) as a marker for the diagnosis of lung cancer we determined serum levels of this peptide in 255 patients with lung cancer and in 74 patients with chronic obstructive lung disease. A reference population consisting of 151 healthy volunteers was also studied. TATI concentrations were measured by radioimmunoassay. As a cut-off point we used the 99th percentile of the TATI concentrations in a reference population, which was 32 micrograms/l. TATI does not appear to be a good tumor marker in lung cancer. Its sensitivity is poor in comparison with CEA and TPA. The correlation between TATI levels and stage of the disease and histological type was weak.