The role of 21-hydroxylase in the pathogenesis of adrenal masses: review of the literature and focus on our own experience.

An exaggerated response of 17- hydroxyprogesterone (17-OHP) to exogenous ACTH stimulation has been found in 30 to 70% of patients with incidentally discovered adrenal tumors, supporting the concept that congenital 21- hydroxylase deficiency may be a predisposing factor for adrenocortical tumorigenesis. Decreased expression of 21-hydroxylase gene has been observed in sporadic non-functioning adrenocortical adenomas and adrenocortical carcinomas, in agreement with the reduced steroidogenic activity found in these types of tumors. Screening studies for the presence of mutations in CYP21A2 gene, encoding 21-hydroxylase, in patients with sporadic adrenocortical tumors yielded discordant results. Overall, a higher frequency of germline 21-hydroxylase mutation carriers has been found among patients with adrenal tumors, including incidentalomas, than in the general population. However, the presence of mutations did not correlate with endocrine test results and tumor mass features, suggesting that 21-hydroxylase deficiency does not represent a relevant mechanism in adrenal tumorigenesis. Mechanisms leading to reduced 21-hydroxylase expression and activity are still unknown.

Pulmonary dirofilariasis in man: a new Italian case. Review of the European literature.

In June 1991 a 62-year-old retired man, from Udine (northern Italy), was suddenly affected by dyspnoea. X-ray and CT control detected a coin lesion in the lung, in May 1992 this lesion was removed surgically. Histological examination revealed the presence of a nematode inside an arteriole which had provoked a small infarct in the pulmonary tissue. The parasite presented marked regressive phenomena that made an accurate morphological analysis impossible. However, in the light of certain details of the cuticle, and by analogy with four similar cases occurring in northern Italy, as well as 10 others (nine subcutaneous and one submucosa) reported in man from the same region (Venetia) over the last 15 years, the aetiologic agent was thought to be Dirofilaria (N.) repens. Over all 10 cases of human pulmonary dirofilariasis were reported in Europe: five in Italy, probably by D (N.) repens, two in Germany, in patients coming from Corsica and two in Spain (only by serology), attributed to D. immitis. In addition one case was reported in U.S.A. in a man who previously visited Italy.

Epidermal growth factor receptor in lung malignancies. Comparison between cancer and normal tissue.

Epidermal growth factor receptors (EGFr) were measured using a radioligand binding assay, in membrane preparations from 51 human non-small cell lung cancers and in normal tissue of the same patients. The binding characteristics of EGFr were similar in tumour and normal lung membranes (range of dissociation constant of high affinity sites: 0.1-0.6 nM). However, the concentrations in tumours (median, 16.4 fmol mg-1 of protein; range, 1.5-176) were significantly higher than in normal tissues (median, 7.4 fmol mg-1 of protein; range, 1.9-13.4). The receptor levels in normal tissue were normally distributed. It was therefore possible to define a normal/pathologic cut-off level (12.9 fmol mg-1 of protein). In 57% of cases EGFr in cancer was higher than the cut-off. No relationships were found between receptor concentrations and positivity rates of EGFr and histology, stage, lymph node positivity and pT. A trend for a direct relation between receptor positivity and grading was found.

[Atrial fibrillation in a cohort of the elderly: etiopathogenic role of occult hyperthyroidism and diagnostic and therapeutic considerations. Results of the CASTEL (CArdiovascular STudy in the ELderly)]. / Fibrillazione atriale in una coorte di anziani: ruolo eziopatogenetico dell'ipertiroidismo occulto e considerazioni diagnostiche e terapeutiche. Risultati dello studio epidemiologico CASTEL (CArdiovascular STudy in the ELderly).

This work was performed in order to evaluate the weight of hyperthyroidism on the genesis of atrial fibrillation in elderly subjects. The data are from the CASTEL (CArdiovascular STudy in the ELderly), an epidemiologic study performed in a town of northern Italy (Castelfranco Veneto), whose 3088 elderly subjects were called and 2254 enrolled for a 7-year intervention trial. From 2224 elderly persons examined in the present study, 90 had atrial fibrillation (AF) as determined by the presence of Minnesota Code 8-3; the other 2134 were used as control population. In the 90 with AF and in the randomly chosen controls, the thyroid function was studied by means of the TRH-test. Taking into consideration an increase of TSH greater than 0.5 or greater than or greater than 1 muUI/ml over the basal value after TRH administration, 5.5% of subjects with atrial fibrillation had a suppressed response (i.e. hyperthyroidism); taking into consideration a peak value of TSH greater than or equal to 2.3 muUI/ml irrespective to the basal value, the prevalence of hyperthyroidism was higher (17.8%), but not different than in control subjects. In conclusion, hyperthyroidism is frequent in elderly subjects but it does not play a role in the pathophysiology of AF. On the contrary, AF may be explained in the majority of cases by concomitant cardiovascular disease, i.e. left atrial enlargement, arterial hypertension, myocardial ischemia, and heart failure.

The CASTEL project (CArdiovascular STudy in the ELderly): protocol, study design, and preliminary results of the initial survey.

The CASTEL (CArdiovascular STudy in the ELderly) has been performed in order to evaluate the prevalence of hypertension of people aged 65 years or more, to evaluate the cardiovascular risk of elderly subjects from a general population, to verify the feasibility and effectiveness of a systematic continuous community-based hypertension control program in the elderly, and finally to evaluate whether a population-based therapeutic intervention was able to extend to a great number of elderly hypertensive patients the benefits of a better control of hypertension. Only the preliminary results of the initial survey are described in this paper, since the final data collection will be available at the end of 1991. The prevalence of hypertension in elderly subjects of the CASTEL was 51.2% (44.6% for males, 52.2% for females), that of isolated systolic hypertension was 8.8% among the whole population sample (2254 subjects) and 23.4% among the subgroup of 850 hypertensives screened following the WHO criteria; 8 visits were performed during the initial screening and prevalence of hypertension regularly decreased from the first visit to the last one. Taking into consideration the mean of the last 2 blood pressure measurements performed during visit 8, average systolic blood pressure was 175.5 +/- 25.9 mmHg and diastolic 93.5 +/- 13.0 mmHg. Some correlations between blood pressure and other biological parameters are also discussed.

[Human pulmonary dirofilariasis. A third case in Italy]. / Dirofilariasi polmonare nell'uomo. Un terzo caso in Italia.

A new case of Human Pulmonary Dirofilariasis, the third in Italy, is described. It occurred in August 1990 in a 66 years old man, living in San Donà di Piave (province of Venice). The pulmonary infarctual lesion caused few symptoms and was discovered by chance during a chest X-ray examination as a coin lesion and suspected to be of a neoplastic origin. The histological findings allowed the exact diagnosis, identifying the causal agent as Dirofilaria probably repens, a nematode common parasite of dogs in the Old World and recognised agent of over 90 human cases of Subcutaneous Dirofilariasis reported in Italy. The parasite was an immature male in advanced regressive conditions. It was inside the lumen of a small artery, surrounded by necrotic-phlogistic tissue with granulomatous giantcellular aspects of the foreign body type. Some questions are raised by the authors in relation to the presence of human cases by D. repens and not by D. immitis (dog heartworm) in areas of Italy where this last species is much more prevalent than the former in canine populations; to the fact that the 3 Italian pulmonary cases (which are the only ones reported in Europe) happened in the same restricted geographic area (Veneto and Emilia-Romagna regions); and finally to the fact that all the 3 cases occurred in elderly people.

[Cardiovascular effects of coffee consumption in the aged: the CASTEL epidemiologic study]. / Effetti cardiovascolari del consumo di caffè nell'anziano: lo studio epidemiologico CASTEL.

The data obtained from 2240 subjects aged 65 years or more from the general population of Castelfranco Veneto (Italy) included in the CASTEL (CArdiovascular STudy in the ELderly) epidemiological Italian project were analyzed in relation to coffee consumption. Subjects were divided into 3 classes: class 1 (N = 109): non coffee drinkers; class 2 (N = 1554): 1 to 2 cups of coffee per day; class 3 (N = 577): 3 or more cups per day. The results were described by ANOVA, Tukey post hoc test and Pearson correlation coefficient with Bonferroni's conservative correction. In classes 2 and 3 total cholesterol, apolipoprotein B100 and calculated LDL-cholesterol were higher than in class 1. The number of cups of coffee per day directly correlated to both the number of cigarettes per day and the number of drinks per week. Although these data seem to indicate a convergence of risk factors (cholesterol, smoking, alcohol) in coffee drinkers, no increase in the prevalence of cardiovascular events was found in coffee drinkers in comparison with non drinkers. This could be attributed to the fact that prevalence of hypertension and diabetes did not increase with increasing coffee consumption; on the contrary, they were lower in classes 2 and 3 than in class 1.

Carcinoembryonic antigen, ferritin, tissue polypeptide antigen, and CA15/3 in breast cancer: relationship between carcinoma and normal breast tissue.

The study of tumor markers in breast cancer tissue may supply information on the tumor's biological features and its clinical behaviour. Forty-nine primary breast cancer patients are evaluable to date. CEA, ferritin, TPA and CA15/3 were measured with radioimmunometric methods in the cytosol of carcinoma and normal tissue from the same breast. The concentrations of the four markers were higher in the tumor than in normal tissue in 42/49 cases for CEA, 47/49 for ferritin, 42/49 for TPA and in 24/29 for CA15/3. However, an overlap was found between carcinoma and normal tissue levels, particularly for CEA and TPA. We can conclude that the four substances studied may be markers of malignancy in breast carcinoma when non-malignant breast tissue from the same patient is determined at the same time, whereas assays within a single, unknown breast tissue sample may be useful only in the case of ferritin and, partly, CA15/3.

Estrogen and progesterone receptors in breast carcinoma and in nonmalignant breast tissue.

Since 1983 we have studied the relationship, in the same patient, between receptor status in breast carcinoma and in nonmalignant breast tissue. Fifty patients have been evaluated to date. The total unoccupied cytosol estrogen and progesterone receptors were determined by a dextran-coated charcoal method. In nonmalignant breast tissue we found a measurable receptor concentration above the sensitivity of the method in 62% of cases for estrogen receptors and in 44% of cases for progesterone receptors. No relationships were found between the receptor level of each tumor and that of the corresponding benign tissue. The data suggest that the levels of the receptors in the tumor and in the nonmalignant tissue are totally independent.