Showing papers by "University of Modena and Reggio Emilia published in 1993"

Complex alteration of thyroid function in healthy centenarians

Abstract: Several changes in thyroid function have been described in the elderly and largely attributed to concomitant nonthyroidal illness. The extent to which aging per se contributes to these changes remains to be elucidated, and scanty data are available in extremely old subjects. The present study was designed to focus on thyroid function during physiological aging, taking advantage of two groups of selected aged individuals: group A of healthy centenarians (n = 41; age range, 100-110 yr) and group B including healthy elderly subjects selected by the criteria of the EURAGE SENIEUR protocol (n = 33; age range, 65-80 yr). Control groups included 98 healthy normal adult subjects (group C; age range, 20-64 yr) and 52 patients with miscellaneous nonthyroidal illness (group D; age range, 28-82 yr). Our previous report of a low prevalence of thyroid autoantibodies in centenarians was confirmed and extended by the finding of a similar low autoantibody prevalence in the highly selected healthy elderly population of group B. Subclinical primary hypothyroidism was found in 3 (7.3%) centenarians, and their data were excluded from further statistical evaluation. No significant difference was found in the median serum free T4 levels of groups A-C. Median (and range) serum free T3 (FT3) was lower in centenarians [3.67 pmol/L (2.3-5.5)] than in group B [5.22 pmol/L (3.4-6.1)] and group C [5.38 pmol/L (2.9-8.4); P < 0.0001 vs. both groups]. Similarly, the median serum TSH level of centenarians [0.97 mU/L (< 0.09 to 2.28)] was lower than those in groups B [1.17 mU/L (0.53-2.74)] and C [1.7 mU/L (0.4-4.8); P < 0.0001 vs. both groups]; moreover, serum TSH was also significantly (P < 0.01) lower in group B than in group C. Both serum FT3 and TSH concentrations showed a significant inverse correlation (r = -0.634; P < 0.0001 and r = -0.377; P < 0.0001, respectively) with age. Median serum FT3 in centenarians was lower than that in group D patients [4.61 pmol/L (2.15-6.6); P < 0.0001]. In contrast, median serum rT3 in centenarians [0.40 nmol/L (0.20-0.77)], although higher than those in groups B [0.24 nmol/L (0.15-0.37); P < 0.0001] and C [0.22 nmol/L (0.05-0.46); P < 0.0001], was significantly lower than that in group D [0.60 nmol/L (0.13-2.08); P < 0.0001]. In conclusion, thyroid function appears to be well preserved until the eighth decade of life if healthy subjects are studied, whereas a reduction of serum FT3 is observed in extreme aging.(ABSTRACT TRUNCATED AT 400 WORDS)

Tumour spectrum in hereditary non-polyposis colorectal cancer (HNPCC) and in families with suspected HNPCC . A population-based study in Northern Italy

Abstract: Hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) is characterized by the early onset of colorectal neoplasms, frequently localized in the right colon, increased occurrence of multiple primaries, vertical transmission and aggregation of tumours in families in accordance to a Mendelian dominant type of inheritance. The syndrome accounts for approximately 5% of all colorectal cancers. The purpose of the present study was to describe the tumour spectrum and the most relevant clinical features of 28 kindreds with HNPCC, classified according to the guidelines of the International Collaborative Study Group, and of 61 "suspected" HNPCC. These families were observed during a 6-year registration of colorectal neoplasms in a health-care district of Northern Italy. Colorectal cancer was by far the most frequent malignancy; gastric cancer was the second. Uterine carcinoma was only slightly more frequent than expected. Lung- and breast-tumour rates were lower than expected. Cancer distribution in the large bowel showed that about two fifths of the tumours developed in the right colon. The occurrence of cancer before the age of 50 to 60 was much more frequent in HNPCC. Multiple tumours developed in 25 patients with HNPCC and in 32 with "suspected" HNPCC. Pancolonoscopy remains the procedure of choice for surveillance; other examinations, such as gastroscopy, gynaecological investigations, urography and cholangiography, are suggested only to selected families. One of the main features of the study was the inclusion of 61 "suspected" HNPCC, a heterogeneous group of families which nonetheless deserves careful follow-up.

P53 gene mutations in medulloblastoma immunohistochemistry gel shift analysis, and sequencing

Abstract: Medulloblastoma (MB), the most common malignant tumor of the CNS in children, bears a loss of the short arm of chromosome 17 in almost half of the cases. The tumor suppressor gene p53 is located on this chromosome and its role in the pathogenesis of this primitive tumor is controversial. Twenty-two

Urinary styrene in the biological monitoring of styrene exposure.

Abstract: The urinary excretion of styrene represents a promising indicator of exposure to this solvent. Nevertheless extensive research under field conditions is scant. In this investigation 214 styrene-exposed workers from 10 fiberglass-reinforced plastics factories were studied. Environmental monitoring was performed by personal passive sampling. Blood styrene and the urinary excretion of styrene and its main metabolites, mandelic acid (MA) and phenylglyoxylic acid (PGA), were measured. The correlation coefficient between the time-weighted average of environmental styrene and the mean urinary excretion of styrene was 0.88 (0.91 after logarithmic transformation), compared with the 0.82 and 0.78 of the end-of-shift MA and PGA values, respectively. A high correlation (0.86) was also found between styrene in the blood and urine. The results, obtained under field conditions with a large group of exposed workers, confirm the usefulness of the urinary excretion of styrene as an exposure index for the biological monitoring of styrene exposure.

Risk of cancer revealed by follow-up of families with hereditary non-polyposis colorectal cancer: a population-based study.

Abstract: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by susceptibility to large-bowel cancer, frequently with early onset and localized in the right colon. Several tumours of other sites may also occur with increased frequency in these families. During the period 1984-1989, 28 families with HNPCC were identified in our Health Care District through a population-based colorectal cancer registry. Moreover, 61 additional families were selected and classified as having "suspected" HNPCC. The objective of the present study is to report the occurrence of new cases of cancer in the 5- to 6-year follow-up of individuals at risk of tumour development in either HNPCC or "suspected" families. There were 374 family members at risk in HNPCC and 468 in "suspected" families, contributing, respectively, 2,377 and 2,712 persons/year at risk. Thirty-four new tumours developed among HNPCC family members vs. 29.3 expected; however, the occurrence of colorectal cancer in this group was significantly higher than expected, and this excess was particularly evident in the age-groups 41-50 and 51-60. In "suspected" HNPCC, 38 new tumours developed vs. 24.5 expected; at variance with the other group, besides colorectal neoplasms, lung, liver and brain tumours also occurred significantly in excess. Moreover, the increased risk was uniformly distributed among different age-groups. In conclusion, HNPCC family members are at increased risk of developing colorectal cancer, with an earlier onset than the general population; in contrast, high-risk individuals in "suspected" HNPCC families seem to be prone to a broader neoplastic spectrum, and risk of tumours does not seem to be limited to any particular age-group.

Disorder of Cerebellar Foliation in Walker's Lissencephaly and Neu-Laxova Syndrome

Abstract: A diffuse disorder of cerebellar foliation was found in eight infants and one fetus with Walker's lissencephaly. The cerebellar cortex consisted of fused and irregularly distorted folia. In the white matter, trilaminated rings of cortex were concentrically arranged around blood vessels and mesenchymal tissue. The normal relative position of the different classes of cortical nerve cells was preserved. Cells of the external granular layer invaded the meninges and migrated along penetrating blood vessels. We believe that this foliation disorder is caused by a defect in the external basal lamina that allows adjacent folia to be fused and sulci obliterated by intrameningeal ectopias of external granule layer cells. Physical forces applied during development probably contribute to the distortion of the gyral pattern. There was a volumetric reduction of the neocerebellum, which might also be a consequence of the basal lamina defect. The cerebellum of a fetus with the Neu-Laxova syndrome showed the same abnormalities as in Walker's lissencephaly. It is postulated that these two conditions belong to a class of prenatal developmental disorders that involves a defect of the extracellular matrix.

Antibody repertoire against the A60 antigen complex during the course of pulmonary tuberculosis

Abstract: The A60 antigen complex is a Mycobacterium bovis (BCG) highly immunodominant antigen containing both B and T-cell epitopes. Clinical-serological studies show that elevated anti-A60 titres are present during tuberculosis. We wished to analyze in detail antibody responses against A60 components during the course of tuberculosis. A mixed longitudinal study was designed including individuals at the onset of tuberculosis, during treatment and after resolution of the disease. The anti-A60 repertoire was analyzed using a western blot assay with A60 as the antigen. While PPD- normals recognized only the 65 kDa heat shock protein (HSP), PPD+ normal individuals displayed low levels of anti-A60 antibodies against dominant antigens. There were immunoglobulin M (IgM) and immunoglobulin G (IgG) consistent with response to a latent infection. Onset tuberculosis was characterized by IgM and IgG antibodies against 52 to 28 kDa antigens; IgM response being limited to earlier phases of the disease. In contrast, IgM antibodies against 25 to 14 kDa antigens appeared only 2-6 months after disease onset. The antibody repertoire of chemotherapy-treated, resolved tuberculosis was exclusively IgG in isotype, as for a memory-type response. Thus, western blot analysis with A60 identifies typical antibody patterns associated with different clinical phases of tuberculosis infection. Such approach may help in identifying new single antigens for serologic diagnosis of active tuberculosis.

Early Abnormalities of the Antibody Response against Mycobacterium tuberculosis in Human Immunodeficiency Virus Infection

Abstract: Among human immunodeficiency virus (HIV)-infected persons, those who react against purified protein derivative (PPD) have higher risk of tuberculosis. Since PPD testing has limited predictive power in HIV-positive populations, new markers of antituberculous immunity were sought by analyzing antibodies to Mycobacterium tuberculosis antigens (PPD and its fraction A60) in 102 HIV-positive subjects, some PPD-positive and some PPD-negative, and in 23 HIV-positive tuberculosis patients. ELISA and Western blotting were used. Forty HIV-negative healthy subjects and 40 HIV-negative tuberculosis patients were evaluated as controls. While all those HIV-negative and PPD-positive had IgG antibodies recognizing the 38-, 28-, and 19-kDa M. tuberculosis antigens, only 26% of those HIV-positive and PPD-positive (all with < 400 CD4+ cells/mm3) and none of the HIV-positive tuberculosis patients recognized them, indicating that the lack of IgG against those antigens, in the presence of a specific IgM response, is a marker of immunodeficiency.

Phosphatidylserine enhances the ability of epidermal Langerhans cells to induce contact hypersensitivity.

Abstract: Phosphatidylserine (PS) modulates several immune functions in vitro, including T cell activation, antibody and cytokine production, and macrophage growth. In the present work we studied the effects of PS on the induction of contact hypersensitivity (CH) in mice. BALB/c mice painted with PS (9.4-75 mg/kg) and with a sensitizing dose of DNFB or oxazolone on the same skin site exhibited a dose-dependent augmentation of CH reactions to either DNFB (> 60%) or oxazolone (> 35%), respectively. Bovine brain PS-enriched phospholipid mixture, lyso-PS, and dipalmitoyl-PS also induced similar enhanced CH responses, whereas phosphatidylglycerols had no effect. Increased CH was observed only when PS was applied from 2 days before to 12 h after DNFB. Immunization of naive syngeneic mice with skin grafts that were treated with PS and DNFB also led to enhanced (> 50%) CH responses. In addition, immunization by iv injection of epidermal cell suspensions enriched for Langerhans cells (LC) or of purified LC that were treated with PS (1-100 microM, 30 min, 37 degrees C), and then modified in vitro with DNBS (1 mg/ml, 30 min, 37 degrees C) led to increased (> 30-75%) CH responses in recipient syngeneic animals. Finally, adoptive transfer of DNFB-immune lymph node cells obtained from mice that were treated with PS induced augmented CH responses in recipient animals. The results suggest that PS is capable of up-regulating the induction of CH in mice by stimulating the APC function of epidermal LC.

Drinking habits and occupational exposure to inhalation anesthetics at low doses

Abstract: The aim of this study was to evaluate certain indicators which are an expression of hepatic (serum aminotransferases activities) and hematologic (erythrocyte mean corpuscular volume) changes among health care personnel exposed to inhalation anaesthetics (nitrous oxide and isoflurane). A total of 172 subjects employed in a single hospital were divided into four groups according to exposure and drinking habits: group (i) non drinkers and unexposed subjects, group (ii) drinkers and unexposed subjects, group (iii) non drinkers and exposed subjects, group (iv) drinkers and exposed subjects. No change in aminotransferases activity or in mean erythrocyte size was detected, which could be regarded as the result of anesthetics exposure. Increased aspartate aminotransferase values among unexposed drinkers were related to alcohol intake. This observation was confirmed by the relationship between AST behaviour and quantitative alcohol intake. Hence, when studying any effect involving functions related to the biotransformation of xenobiotics, in which the liver plays a primary role, the importance of establishing the exact daily amount of ethanol intake is stressed.

[Osteosarcoma: magnetic resonance imaging of the effects of preoperative chemotherapy].

Abstract: The effects of preoperative chemotherapy for osteosarcoma of the extremities were investigated with MR imaging. Forty-six patients affected with high-grade osteosarcomas of the extremities underwent MRI before and after two cycles of preoperative chemotherapy. At the end of treatment all tumors were resected and the rate of tumor necrosis was assessed on histologic sections. The MR images obtained before and after treatment were compared. Decreased tumor size, perilesional intramedullary edema and more marked lesion outline correlated well with positive histologic response to preoperative chemotherapy. Soft tissue edema and joint effusion did not change significantly and no clear correlation with histologic response was observed. Decreased signal intensity on T2-weighted images is likely to indicate response to chemotherapy. Likewise, poor response correlated with unchanged/increased signal intensity. Therefore, MRI appears a useful means to evaluate chemotherapy-induced changes in osteosarcomas of the extremities.