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Biomedical subjects

S Mariotti

Publications and source records attributed to S Mariotti.

At least 73 records · Page 4Linked to original sources

[The general practitioner faced with the choice of hospitalization: an analysis of the data from the Follow-Up System computerized network].

The Project "Informatization of the General Practitioner" aimed at networking the work stations of a randomized set of 150 general practitioners equipped with the "Follow-Up System" software, for the collection of information related to the activity carried out, to be electronically transferred to a central unit was developed in the frame of the finalized Project of the National Research Council: "Prevention and Control of the Disease Factors". During the project activity, a study on prescribed hospitalizations was carried out. The contents of items regarding hospitalization diagnosis show that diagnoses concerning diseases included in chapter ICD-9: "Symptoms, signs and morbid conditions not well defined" represent 30.3% of the total; most of these undefined syndromes can be identified under the item "abdominal pain" with 18.2% of cases. Obviously in the case of appendicitis (12.1% of hospitalizations) the hospitalization carried out by the physician resulted to be necessary, in the case of biliary lithiasis (8 cases, 7.4%), the physician could have treated the patient without hospitalization. The interest of such data is to induce a sort of provocation in order to observe, within 8% of hospitalizations following abdominal pain, what rate of hospitalization could be avoided, giving the adequate support to the general practitioner in order to decide the behaviour to have.

Adolescent↗

The "Sardinia-IDDM study": an attempt to unravel the cause of insulin-dependent diabetes mellitus in one of the countries with the highest incidence of the disease in the world.

Sardinia and Finland have the highest incidence of IDDM in the world. Thus, both regions represent ideal observatories for investigating the environmental, genetic and immunological factors, which have led to this dramatic increase. We have concentrated our efforts in Sardinia. Among several projects, there is the mapping of the Island for hot and cold spots for overt IDDM. In order to map the Island for pre-IDDM, we have collected and bled around 10,000 school children (age 6-14 years) and we are now in the process to enroll around 30,000 newborn. We report here our initial results, which show that progression to IDDM is accompanied in both cohorts by the presence of a combination of ICA with either GAD and IA-2 antibodies or both. This approach should lead to design reliable models of IDDM prediction in the general population, which will benefit an early insulin treatment and, hopefully, an effective prevention of the disease.

Adolescent↗

Sources of uncertainty in estimating HIV infection rates by back-calculation: an application to Italian data.

The effects on back-calculated HIV diffusion estimates of the uncertainties in a number of factors that may potentially influence the estimation process are examined and compared. More specifically, the effect on HIV infection estimates of uncertainties in: (i) the sequence of periodical AIDS incidence cases; (ii) the estimation of the AIDS incubation period, including the influence of therapeutic treatment on the same; and (iii) the choice of a particular back-calculation method, including the stochastic uncertainty associated with each method, are examined. The choice of one particular back-calculation model over another, among three different methods considered, seems to be a minor component of the uncertainty, when compared to the uncertainty, due to all other sources. HIV incidence and prevalence in Italy for different risk categories are estimated.

Algorithms↗

Successful immunosenescence and the remodelling of immune responses with ageing.

In recent decades, major theoretical and technological advances have been achieved in the field of immunology. These have allowed the scientific community to analyse the immune system in a much more sophisticated manner than was possible even 20 years ago. Moreover, great theoretical changes have also occurred in gerontology-in particular, the hypothesis has been put forward that ageing and diseases are two different phenomena, and that successful ageing, i.e. ageing in good psychophysical conditions, is really possible for most humans and animals. Immunosenescence was then carefully investigated, either in selected healthy people of advanced age or in the oldest old people, such as healthy centenarians. The main results showed that most immune parameters are indeed well preserved even at this far advanced age. This paper deals with some of the most important theoretical problems of immunosenescence. An immunological tenet was that the most important phenomenon of immunosenescence is the involution of the thymus. In most textbooks and papers it is taken for granted that the thymus starts its involution immediately after puberty. When people aged 60-65 were considered old, it was not difficult to think that they could live for the rest of their life with a fully involuted thymus. The findings on centenarians challenge this tenet, as they have only a small reduction of T lymphocytes, and a relatively normal number of virgin and memory T cells, together with a functional T cell repertoire. Other observations reported here on centenarians, concerning the activity of B lymphocytes and the cytokine network, as well as those on the well-preserved innate immunity and the cells' capability of undergoing proliferation after appropriate stimuli, suggest that complex immune changes occur with age, but also indicate that we have to modify our attitude, to grasp the new scenario which is emerging. Immunosenescence can no longer be considered as a unidirectional deterioration, and this complex phenomenon is much better described by terms such as 'remodelling', 'reshaping' or 'retuning'.

Aging↗

Age-related modifications in the regulation of the hypothalamic-pituitary-thyroid axis.

We studied the hypothalamic-pituitary-thyroid function in two groups of healthy elderly subjects: group A (n = 23, age range 65-80 years), and group B (n = 11, age range 81-92 years), and in 32 controls, aged 20-60. A TRH test for TSH and prolactin was performed in all subjects, while the TSH circadian modulation was evaluated in elderly subjects only. Group B showed significantly lower fT3 and TSH, and higher fT4 levels with respect to controls (fT3: 4.4 +/- 0.2 vs. 5.2 +/- 0.2 pmol/l, p < 0.05; fT4: 13.1 +/- 0.9 vs. 11.4 +/- 0.4 pmol/l, p < 0.05; TSH: 1.07 +/- 0.21 vs. 1.46 +/- 0.13 mIU/l, p < 0.05). Morning TSH showed an inverse correlation with age (r = -0.42; p < 0.02) among the 34 elderly subjects, but not among controls. Evidence for TSH circadian modulation was found only in group A (nighttime TSH: 1.60 +/- 0.17, vs. daytime: 1.25 +/- 0.13 mIU/l, p < 0.001). The TRH-stimulated TSH peak was reduced among all elderly subjects with respect to controls (A: 6.26 +/- 0.64 mIU/l, p = 0.01; B: 5.02 +/- 0.58 mIU/l, p < 0.01). The maximal PRL response was also blunted (A: 25.7 +/- 2.6 micrograms/l, B: 27.7 +/- 5.2 micrograms/l, p < 0.0005). In conclusion, a resetting of the pituitary threshold of the TSH feedback suppression, along with complex alterations in peripheral thyroid hormone levels, may progressively develop in older people, becoming apparent only with extreme senescence. Moreover, the TSH nocturnal surge may be lost with increasing age, thus providing evidence also for hypothalamic dysfunction.

Adult↗

Double phase parathyroid technetium-99m-MIBI scintigraphy to identify functional autonomy in secondary hyperparathyroidism.

UNLABELLED: Double-phase 99mTc-methoxyisobutylisonitrile (MIBI) parathyroid scintigraphy has been proposed to detect hyperplastic parathyroid tissue, but the clinical usefulness of this technique in secondary hyperparathyroidism is still debated. METHODS: Technetium-99m-MIBI parathyroid scintigraphy associated with parathyroid echography and [99mTc]pertechnetate thyroid scans were performed on 38 patients with chronic renal failure (CRF) and secondary hyperparathyroidism. In all patients, serum calcium, phosphorus, FT3, FT4, TSH, calcitonin and intact PTH (iPTH) were determined. Nine patients eventually underwent neck exploration and 28 parathyroid glands were removed. RESULTS: Thyroid diseases were excluded in all patients. Echography revealed parathyroid enlargement in 22/38 (58%) patients, while MIBI scintigraphy was positive in 28/38 (74%), including 5 ectopic glands. Mean serum iPTH concentration was significantly higher in MIBI-positive glands compared to MIBI-negative glands, but several discrepancies were observed in single patients. A significant positive correlation between serum iPTH and gland size was observed when MIBI-positive, but not MIBI-negative, parathyroids were considered. A paradoxical positive correlation between serum calcium and iPTH concentrations was found in MIBI-positive patients. CONCLUSION: Double-phase 99mTc-MIBI scintigraphy is positive in the majority of patients with uremic hyperparathyroidism. Comparison of scintigraphic data with morphological and functional data strongly suggests that 99mTc-MIBI scans do not reveal simple parathyroid enlargement but rather, identify the presence of hyperfunctioning (autonomous) parathyroid tissue suggestive of tertiary hyperparathyroidism.

Adult↗

Lipoprotein(a) plasma concentrations, apolipoprotein (a) polymorphism and family history of coronary heart disease in patients with essential hypertension.

AIM: The purpose of the study was to investigate lipoprotein (a) (Lp(a)) levels and apolipoprotein (a) (apo(a)) phenotypes, and their relationship with a family history of coronary heart disease (CHD) in patients with essential hypertension (EH). METHODS: One hundred and eight newly diagnosed patients with mild to moderate EH and 159 controls were studied. Lp(a) levels were determined with an ELISA method. Apo(a) isoforms were identified by a capillary immunoblotting technique. RESULTS: Lp(a) levels and frequency distribution of apo(a) isoforms did not show significant differences between patients and controls. Lp(a) levels in hypertensives with a family history of CHD were significantly higher than in those without a family history of CHD (P < 0.01). Hypertensives with a family history of CHD showed significantly different frequencies of apo(a) isoforms to those without a family history of CHD (P < 0.05). In EH patients with a family history of CHD, apo(a) isoforms of low molecular weight (MW) had a higher prevalence (62.6%), while in hypertensives without a family history of CHD, apo(a) isoforms of high MW were prevalent (81.6%); the difference between the two subgroups was significant (P < 0.001). Multivariate analysis showed that both Lp(a) levels and apo(a) isoforms of low MW are significant variables in distinguishing between the subgroups. CONCLUSIONS: Lp(a) levels and apo(a) phenotypes do not differ between hypertensives and controls. High Lp(a) levels and apo(a) isoforms of low MW are strongly associated with a family history of CHD in hypertensives. The quantification of Lp(a) levels and the characterization of apo(a) phenotypes may be used for assessment of familial predisposition to CHD in hypertensives.

Apolipoproteins↗

Cancer mortality in migrant populations within Italy.

METHODS. Mortality rates for four types of cancer (stomach, colorectal, lung, and breast cancer) in migrant populations were compared to those of individuals who still resided in the political region in which they were born. The effects on mortality rates of place of birth and of place of residence were studied, comparing different regression models. RESULTS. Overall, people who were born in the South and who later migrated had significantly higher mortality rates than the southern population, but lower than the population in the area of residence, for most cancers. Place of birth and place of residence showed different power in explaining the observed mortality rates for different cancer sites: place of birth was a stronger predictor for stomach and breast cancers, while residence was a stronger predictor for lung and colorectal cancers. The status of 'migrant' was found to be an overall risk factor. The compatibility of the results obtained with different aetiological hypotheses is discussed.

Adult↗

Effect of sex, age and transmission category on the progression to AIDS and survival of zidovudine-treated symptomatic patients.

OBJECTIVE: To evaluate the effect of transmission category and demographic, clinical and immunological characteristics on the progression to AIDS and survival of zidovudine-treated patients. DESIGN: Prospective multicentre cohort study of symptomatic non-AIDS patients. SETTING: Eighty-three clinical centres reporting data to the National Zidovudine Registry. PATIENTS: A total of 1468 patients enrolled between July 1987 and January 1991 were analysed. MAIN OUTCOME MEASURES: Three-year AIDS-free survival probability estimates since therapy start. Cox proportional hazards regression analysis was used to identify independent predictors of progression to AIDS and survival. RESULTS: Faster progression was associated with increasing age (8% risk increase for a 5-year increase), low baseline CD4+ count (39% risk increase for 100 x 10(6)/l cells decrease), and zidovudine > 1000 mg/day (20% risk increase compared with < or = 1000 mg/day). Homosexual men had a 33% risk increase compared with other risk groups. The presence of fever and oral candidiasis at enrolment were also independently associated with a higher risk of progression. Differences in the risk of progression were not significant between men and women. Older age, baseline CD4+ count, homosexual behaviour, fever and oral candidiasis were independently associated with a shorter survival. CONCLUSIONS: Our results confirm that age and baseline CD4+ count are independent predictors of progression, but do not provide evidence for differences in clinical outcome between the sexes. The higher risk of progression to AIDS and shorter survival for homosexual men appears to be correlated with the higher risk of developing Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

Thyroid autoimmunity and ageing.

Ageing is associated with the appearance of several serum autoantibodies, including thyroid autoantibodies. The biological and clinical significance of this phenomenon is still unknown, since, with the exception of primary myxedema, the prevalence of clinically overt thyroid autoimmune diseases is not increased in the elderly. The peculiar link between autoimmune thyroid failure and ageing is also underscored by the high prevalence of subclinical hypothyroidism in elderly subjects with positive serum thyroid autoantibodies, and could be the consequence of preferential age-dependent expression of destructive effector mechanisms and/or increased target gland susceptibility. Thyroid autoimmunity and subclinical hypothyroidism have also been implicated in the pathogenesis of other age-associated disorders, in particular coronary heart disease. Interestingly, recent data from our laboratories showed that thyroid autoantibodies are rare in healthy centenarians and in other highly selected aged populations, while they are frequently observed in unselected or hospitalized elderly. Taken together, these data suggest that thyroid autoimmune phenomena are not the consequence of the ageing process itself, but rather might be related to age-associated disease.

Aging↗

Assay of thyroglobulin in serum with thyroglobulin autoantibodies: an unobtainable goal?

Measurement of thyroglobulin (Tg) in serum with anti-Tg autoantibodies (TgAb) represents a difficult challenge. Immunoradiometric assays (IRMA) employing monoclonal anti-Tg antibodies not cross-reacting with endogenous TgAb have recently been developed and proposed for Tg assays in TgAb-positive sera. The aim of the present investigation was to assess the clinical reliability of this approach. Assays of serum Tg in patients with and without TgAb using one such monoclonal antibody IRMA (Thyroglobulin IRMA-Pasteur; IRMA-1) were compared with those obtained by a conventional IRMA employing polyclonal anti-Tg antibodies (HTGK-Sorin; IRMA-2). Preliminary studies for assessment of the interference of TgAb showed that the recovery of added Tg was significantly higher (P < 0.01) when determined by IRMA-1 (64.6 +/- 23%) than by IRMA-2 (49.5 +/- 20%). Study groups included 79 patients with differentiated thyroid carcinoma (DTC) treated by total thyroidectomy and radioiodine ablation; 24 had no metastases or residual thyroid tissue, 31 had a thyroid residue, and 24 had metastatic disease. Seventy-five patients with autoimmune thyroid disease (47 with Graves' and 28 with Hashimoto's disease) were also included. In TgAb-negative sera from DTC patients, similar Tg concentrations were found by both IRMA, i.e. undetectable in most patients with no residual thyroid or neoplastic tissue, low to moderately elevated in the majority of those with residual thyroid tissue, and markedly elevated in all patients with metastatic disease. Serum Tg was undetectable by both assays in several TgAb-positive sera from DTC patients with residual thyroid tissue or metastatic disease, respectively, in whom a detectable or even high serum Tg concentration was expected. Despite the lower in vitro interference of TgAb in IRMA-1, there was no difference between the two assays. In the group of patients with thyroid autoimmune disease, serum Tg concentrations were found to be high in TgAb-negative sera and much lower in TgAb-positive sera by both IRMAs. In conclusion, the present study demonstrates that the use of a monoclonal antibody IRMA for serum Tg, although less susceptible to in vitro TgAb interference, does not necessarily provide any substantial advantage with respect to a conventional polyclonal IRMA in detecting Tg in TgAb-positive sera. The finding of undetectable or lower than expected serum Tg by either method in TgAb-positive serum may well reflect a truly reduced serum Tg concentration. This might be due to an accelerated Tg metabolic clearance in the presence of TgAb.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Identification of the thyroid Na+/I- cotransporter as a potential autoantigen in thyroid autoimmune disease.

The thyroid gland is the target of several autoimmune diseases. Specific thyroid proteins have been identified as autoantigens associated with these diseases (e.g. thyroperoxidase, thyroglobulin and the thyrotrophin (TSH) receptor). In this paper, we report that the serum of a patient suffering from Hashimoto's thyroiditis, autoimmune gastritis and rheumatoid arthritis was able to inhibit the chronic TSH-induced I- uptake of dog thyrocytes in culture, even at a 1:1000-fold dilution, without affecting their 86Rb+ uptake. This blocking activity is rare as 147 sera (from patients positive for antibodies to the thyroid microsomes and the gastric parietal cell antigen, patients with Sjögren's syndrome, patients with a high titre of microsomal antibodies and low or negative for antibodies to thyroperoxidase, and patients with a high titre of microsomal antibodies and frank hypothyroidism) were negative when tested for their ability to inhibit I- uptake. Subsequently we tested 20 murine monoclonal antibodies previously obtained by immunizing mice with a crude human thyroid membrane preparation, which were all negative when tested against thyroglobulin and thyroperoxidase. One of the monoclonal antibodies displayed a 50% inhibition of the chronic TSH-induced 125I- uptake of dog thyrocytes without affecting the 86Rb+ uptake of the cells. Immunoglobulins purified from the ascite fluid by affinity chromatography on a protein A cellulose column had the same characteristics. Taken together, the data suggest that thyroidal 125I- uptake can be inhibited by antibodies, that autoantibodies in the patient's serum are most probably responsible for the observed inhibition and therefore that the Na+/I- cotransporter is probably an autoantigen.

Animals↗

Relationship between eating patterns meeting recommendations and subsequent mortality in 20 years.

OBJECTIVE: Study of the relationships of conformity to dietary recommendations and subsequent rates of total mortality and mortality from specific causes. DESIGN: Prospective investigation of risk factors related to cardiovascular disease. SETTING: Two Italian rural cohorts of the Seven Countries Study. SUBJECTS: The study populations are defined samples from two villages, Crevalcore in Northern Italy and Montegiorgio in Central Italy. The examination in 1965, which included an individual dietary survey, involved 1538 men aged 45-64 years. The 20-year follow-up system was able to track every participant. RESULTS: Conformity to recommended levels of intake of carbohydrates (55-75% of calories) is associated to the relative risks: 0.84 (0.68-1.03) for total mortality, 0.73 (0.50-1.07) for cancer mortality, 1.34 (0.90-1.99) for coronary heart disease mortality. Relative risks for other nutrients are reported. CONCLUSIONS: Overall, recommended levels of intake of macronutrients are associated with lower total mortality, but are not equally appropriate for specific causes of death, cancer and coronary heart disease. Diet-associated differences in mortality persisted after adjustment for confounding by age, smoking habit and physical activity. In this population, intakes meeting the principal recommendations (total carbohydrate and total fat) seem to involve automatically meeting the other recommendations. SPONSORSHIP: Research partly supported by the project 'ACRO-clinical uses of Oncological Research' (contract 93.02289.PF39) and by the project 'FATMA-Risk Factors and Disease Control' (contract 93.00773.PF41) of the Italian National Research Council, CNR.

Adult↗

An experimental network of general practitioners for purposes of epidemiological surveillance in Italy.

A Computer Network of General Practitioners (GPs) has been established, connecting 150 general practitioners representing a statistically selected national sample, homogeneously distributed all over Italy. The purpose of the network is to increase the epidemiological surveillance on the health status of the Italian community, to collect useful data on the routine activity of the GPs, to promote computer use among them, and to organize some "ad hoc" investigations on specific subjects (case-control studies). To this purpose, a specific software was developed, both to meet the requirements of epidemiological research and to manage general practitioners' clinical files. A working prototype of a health card using micro-computer technology will also be experimented with a subset of the GPs.

Computer Communication Networks↗