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Biomedical subjects

M Bergomi

Publications and source records attributed to M Bergomi.

At least 19 recordsLinked to original sources

Risk of sporadic amyotrophic lateral sclerosis associated with seropositivity for herpesviruses and echovirus-7.

We examined the association between risk of sporadic amyotrophic lateral sclerosis (ALS) and seroprevalence of antibodies to echovirus-7 (echo-7) and herpesviruses 6, 7, and 8 through a population-based case-control study. We enrolled in a northern Italy area 20 newly diagnosed ALS cases and 20 referents. Risk of ALS was higher in subjects seropositive for echo-7 when we used the immunofluorescent assay, while little increase was noted with the neutralization test. Considering the different characteristics of these two serological assays, these results suggest an association between disease risk and infection with enterovirus (EV) family members (not specifically echo-7). ALS risk was slightly associated with seropositivity of human herpesvirus-6 (odds ratio: 3.2; p = 0.102) and more strongly with human herpesvirus-8 seropositivity (odds ratio: 8.4; p = 0.064), though these point estimates were statistically unstable due to the limited number of observed cases. The findings of this study warrant further investigation in larger studies of the possible etiologic role of EV or herpesvirus infection in sporadic ALS.

Amyotrophic Lateral Sclerosis↗

Risk of birth defects in a population exposed to environmental lead pollution.

To investigate the relation between environmental lead and risk of birth defects in humans, we examined the prevalence at birth of congenital anomalies in an industrial area of northern Italy heavily polluted with lead. Through a population-based registry of birth defects, we identified anomalies diagnosed during three consecutive periods characterized by decreasing environmental lead exposure, 1982-1986, 1987-1990 and 1991-1995. In the lead-polluted area, we observed an excess risk of cardiovascular defects which decreased from 2.59 [95% confidence interval (CI) 1.68-3.82] in the first period to 1.18 (95% CI 0.62-2.06) and 0.97 (95% CI 0.57-1.54) in the subsequent periods. We also found an excess risk of oral clefts and musculoskeletal anomalies, with decreasing trends over time. We could not identify homogeneous patterns of temporal variation for other congenital anomalies, neither did we detect cases of neural tube defects. These results appear to support an association between severe parental lead exposure and specific birth defects.

Congenital Abnormalities↗

Reproductive outcomes in a population exposed long-term to inorganic selenium via drinking water.

Despite being an essential element in mammals and lower animals at very low doses, selenium is recognized as a teratogen and a growth-inhibiting substance in several animal species. Some inorganic selenium compounds have also been shown to be mutagenic and pro-oxidant: however, very little is known about their effects on human reproduction. Between 1972 and 1988, a few thousand residents in the municipality of Reggio Emilia, northern Italy, were accidentally exposed to drinking water with unusually high levels of inorganic selenium (selenate), range 7-9 microg/l, through a local public water supply system. We found no deleterious effect on overall body weight and length of newborns and stillborns delivered by 18 women previously exposed to high-selenium tapwater. Rates of spontaneous abortions, however, were increased slightly (RR = 1.73; 95% CI = 0.62-4.80), compared with rates among unexposed women from the same municipality. From 1980 through 1988 the prevalence of congenital malformations at birth among the exposed population was similar to that expected, but estimates were imprecise owing to small numbers. Results do not suggest marked effects on human reproduction from chronic exposure to selenate in drinking water at < 10 microg/l.

Abortion, Spontaneous↗

Mortality in a population with long-term exposure to inorganic selenium via drinking water.

We analyzed the 1986-1997 mortality in a cohort of 2065 residents of an Italian municipality which had been exposed to drinking water with a high content of inorganic selenium over a long period of time, and compared it with mortality in the remainder of the municipal population. Mortality from malignant neoplasms increased [standardized mortality ratio (SMR) 1.17, 95% confidence interval (CI) 0.96-1.42], mainly due to an excess mortality from melanoma and colorectal cancer in both sexes, kidney cancer in men, and lymphoid malignancies in women. Overall cardiovascular mortality changed little (SMR 1.05, 95% CI 0.89-1.23), despite the higher cerebrovascular mortality (SMR 1.43, 95% CI 1.03-1.93). Coronary disease mortality slightly decreased (SMR 0.87, 95% CI 0.63-1.16), due to a low mortality among women. We also noted an excess mortality from Parkinson's disease in men and from motor neuron disease in women. Evaluation of these findings is, however, hampered by the lack of information about potential lifestyle confounders, the fact that the exposure could only be characterized by a simple dichotomization, and the inconsistencies of most estimates between the two sexes.

Adult↗

Rising melanoma incidence in an Italian community from 1986 to 1997.

We examined the incidence of primary invasive melanoma in the municipality of Reggio Emilia, northern Italy, in the period from 1986 to 1997. We identified 169 cases, five of which were intraocular. After adjustment for confounders, the risk of having a thick melanoma (Breslow > or = 1 mm) did not decrease over time, except in older females. The age-standardized incidence of cutaneous melanoma during the entire study period was 7.57 in males and 11 in females; from 1986-1991 to 1992-1997, it rose from 5.04 to 10.04 cases/100,000 person-years in males and from 8.96 to 13.09 cases/100,000 person-years in females. In males, the increase in incidence was almost entirely confined to subjects aged 30 or more, suggesting a possible cohort effect. We noted rising age-standardized incidences over time both in males with thin tumours (Breslow < 1 mm) (from 2.05 to 4.38 cases/100,000 person-years) and thick tumours (from 2.73 to 5.51 cases/100,000 person-years), while in females the increase was limited to thin melanomas (from 3.14 to 6.93 cases/100,000 person-years), mainly due to an increase in the older age groups (50 69 years and > or =70 years). The increase in thick melanomas among males and the expected cohort effects suggests antecedent exposure to environmental risk factors.

Adolescent↗

Excess melanoma incidence in a cohort exposed to high levels of environmental selenium.

Epidemiological studies on the relation between selenium and human cancer have yielded strongly conflicting results. Prompted by the observation of a positive association between selenium intake and site-specific cancers, including melanoma, in a large cohort of nurses, we studied the 11-year melanoma incidence in an Italian cohort that consumed unusually high levels of inorganic selenium in tap water from 1975 to 1985. The setting was Reggio Emilia, an Italian municipality that provided a natural experiment relating to intake of high levels of inorganic selenium. We identified 2,065 individuals with high selenium exposure, who contributed a total of 20,179 person-years of follow-up, and we compared their experience with the 1,384,386 person-years of follow-up in the remaining population of Reggio Emilia. We included all cases of pathologically confirmed malignant melanoma, including intraocular melanoma, identified from the Reggio Emilia Hospital, the Bologna regional registry of hospital discharges, and the Milan National Cancer Institute. Eight cases of malignant melanoma occurred in the exposed cohort during the follow-up. Melanoma incidence was 3.9 times greater in the exposed than in the unexposed cohort (95% exact confidence limits, 1.8-7.4).

Adolescent↗

Lead, cadmium, and selenium in the blood of patients with sporadic amyotrophic lateral sclerosis.

We determined whole blood lead and cadmium levels, and serum selenium levels in patients with sporadic amyotrophic lateral sclerosis and age- and sex-matched controls. Disability due to the disease directly correlated with lead levels, and there was a strong inverse correlation with selenium concentrations. Lead and selenium concentrations tended to be similar in the cases and controls, both in the study population as a whole and after the removal from the analysis of the patients with the highest degree of disability. In the patients with limited disability, cadmium concentrations were higher than in the controls. Our findings lend limited support to a possible involvement of cadmium, but not lead, in the etiology of sporadic amyotrophic lateral sclerosis, and strongly suggest that short-term indicators of exposure are inadequate to investigate the relationship between selenium and the disease.

Aged↗

Zinc and copper status and blood pressure.

In order to elucidate the relationships between Zn and Cu and blood pressure, the present case-control study was carried out. Zn and Cu status was evaluated in 60 subjects, pharmacologically untreated, affected by mild stable hypertension and in 60 normotensives matched for sex, age and smoking habits. Different markers of Zn and Cu status, including serum, erythrocyte and urine levels of the two trace elements and activities of some Zn- or Cu-dependent enzymes (alkaline phosphatase, lactic dehydrogenase, superoxide dismutase and lysyl oxidase) were evaluated. No significant difference between hypertensives and normotensives was observed in the mean levels of Zn and Cu as well as in Zn- or Cu-dependent enzymes, though higher levels of serum copper were associated with increased risk of hypertension. Interesting relationships between the biological parameters investigated were observed in the hypertensive subjects. Inverse correlations between blood pressures and serum Zn were observed. Furthermore, blood pressure was inversely related to lysyl oxidase activity. These findings give further support to the hypothesis that an imbalance of Zn and Cu bioavailability may be associated to hypertensive condition.

Alkaline Phosphatase↗

Amyotrophic lateral sclerosis after long-term exposure to drinking water with high selenium content.

We examined 9 years' incidence of amyotrophic lateral sclerosis, a disease previously associated with a high-selenium environment, in a cohort of 5,182 residents of Reggio Emilia, Italy. This cohort had accidentally been exposed to drinking water with high selenium content. Four cases were diagnosed during the follow-up. Using the remainder of the municipal population as the reference group, the standardized incidence ratio was 4.22 (95% confidence interval = 1.15-10.80). The standardized incidence ratio was higher after limiting the analysis to the subcohort with the longest ascertainable exposure period. The findings appear to confirm a causal association between overexposure to environmental selenium and amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis↗

Cancer mortality in a residential cohort exposed to environmental selenium through drinking water.

Cancer mortality from 1986 to 1992 was examined in a cohort of 4419 individuals who had been residing in an area of the municipality of Reggio Emilia, northern Italy, where tap water with unusually high selenium content was accidentally supplied. Mortality for all cancers was not significantly different, both in males and in females, from that expected using death rates in the remaining municipal population as standard rates. No significant difference in mortality for site-specific cancers was observed in males, while in females a higher mortality for malignancies of the lymphatic-hematopoietic tissue overall considered and for non-Hodgkin's lymphoma was detected. Even if evaluation of the results is hampered by the low number of cancer deaths on which the analysis is based, findings of the study do not support the hypothesis of a strong inverse independent relationship between dietary intake of selenium and cancer mortality in humans.

Adult↗

Synthesis and antitumor activity of a new class of pyrazolo[4,3-e]pyrrolo[1,2-a][1,4]diazepinone analogues of pyrrolo[1,4][2,1-c]benzodiazepines.

A new class of pyrrolo[1,4]benzodiazepine (PBD) analogues featuring a pyrazolo[4,3-e]pyrrolo[1,2-a][1,4]diazepinone ring system has been designed and synthesized. These compounds, 2a-o, are characterized by the substitution of the aromatic A ring, characteristic of the PBDs, with a disubstituted pyrazole ring bearing alkyl and benzyl substituents at N6 or N7 and alkyl or carbomethoxy substituents at C8. Biological evaluation revealed an appreciable in vitro cytotoxic activity for compounds 2a,b,f-i.

Animals↗

Changes in drinking water selenium and mortality for coronary disease in a residential cohort.

In a part of the municipal territory of Reggio Emilia, northern Italy, selenium in drinking water decreased from 7 micrograms/L to less than 1 micrograms/L. In a cohort of 4419 individuals, previously exposed for at least 5 yr to the drinking water with higher selenium content, the 7-yr temporal distribution of deaths for coronary disease and for stroke was analyzed to examine a possible relationship with changes in drinking water selenium. From January 1986 until August 1988, when tap water selenium was 7 micrograms/L, deaths for coronary disease were one in males and two in females. After the decrease in drinking water selenium, 21 and 10 coronary deaths were observed, respectively, in males and in females from September 1988 to December 1992. No significant difference in the temporal distribution of stroke deaths was observed both in males and in females. Even if an effect of chance and aging in the temporal distribution of coronary deaths may not be excluded, findings of the study seem to be consistent with the hypothesis of a beneficial effect of selenium on coronary disease mortality.

Adolescent↗

Biochemical and haemodynamic indicators of stress in truck drivers.

In order to investigate the extent of stress reaction during driving, this study was carried out on truck drivers engaged in long distance work. For each driver, epinephrine, norepinephrine, and cortisol were measured in urine, and dynamic ECG and blood pressure were monitored. The excretion rates of catecholamines showed great individual differences in the size of variations related to driving conditions. Epinephrine excretion rates were particularly high when weather and traffic conditions were more stressful. A relationship was found between epinephrine urinary levels and state-anxiety scores. Urinary excretion of norepinephrine was generally increased at the end of the working day and while driving in fog. The pattern of cortisol was not affected by the stress related to driving. The highest mean heart rates were monitored during difficult traffic and bad weather conditions.

Adult↗

Relationship between low lead exposure and somatic growth in adolescents.

The possible effects of moderate lead exposure on human growth and development are not well defined. This study was carried out in order to evaluate the relationship between somatic growth and lead exposure. 418 subjects (202 males and 216 females) aged 11-13 years in good health and living in an area of the northern region of Italy were submitted to the following determinations: blood lead levels (PbB), serum concentrations of gonadotropins (LH, FSH) and sex-steroid hormones (DHA-S, T, E2) and anthropometric measurements (stature and weight). The mean blood levels were 85.39 and 70.08 micrograms/1, respectively, for males and females. Significant and negative relationships were found between blood lead levels and stature in 13 years old males and 12 years old females (p = 0.009 and p = 0.006, respectively). Negative relationships between lead in blood and LH and FSH were found only in males with lead levels higher than 90 micrograms/1. Our findings seem to suggest that even for low lead exposure this metal may affect stature growth and gonadotropins levels.

Adolescent↗

Involvement of somatically acquired ecotropic viruses in the immunogenicity of nude-transplanted NIH/3T3 transformed cell lines.

Immunogenic tumor variants were previously derived after transplantation in vivo into nude mice of NIH/3T3-transformed cell lines. Nude-passaged cell lines were rejected by immunocompetent H-2q NIH mice, were recognized by specific CTL clones, and expressed new retroviral Ag. The aim of the present work was to investigate whether somatically acquired proviral sequences were present in the genome of nude-passaged cells and to test directly for a causative relationship between murine leukemia virus (MuLV) expression and immunogenicity. Southern blot analysis of PstI-digested DNA indicated that in contrast to the parental NIH/3T3 transformed cell lines (pT, T12N/5a, NS-1) all the nude-passaged immunogenic variants (pT-nude, T12N/5a-nude, NS-1-nude) contained newly acquired ecotropic-related proviruses. Immediately after in vitro establishment, these tumors displayed multiple integration sites as assessed by analysis of 3' proviral-cellular junctions. Long term in vitro culture of one of the cell lines (pT-nude) resulted in a cell line (pT-nude/vitro) that was clonal or oligo-clonal with respect to viral integration. Northern blot analysis established that the new proviruses were actively transcribed in all the immunogenic variants. To assess whether the somatically acquired ecotropic proviral sequences encode for target structures recognized by specific CTL, obtained after immunization of NIH mice with pT-nude, the parental cell line pT was transfected with plasmids containing the entire AKV MuLV genome, the cloned AKV gag or env genes. Screening of transfectants for their ability to stimulate the production of TNF by anti-pT-nude effectors indicated that cells transfected with the entire ecotropic virus or with MuLV-env gene products could be recognized by an NIH anti-pT-nude CTL line and NIH anti-pT-nude Kq-restricted CTL clones as well as the immunizing target pT-nude.

3T3 Cells↗

Hypertension in newly diagnosed non-insulin-dependent diabetic subjects.

Medical records of newly diagnosed non-insulin-dependent diabetic patients attending a Diabetic Centre in Modena, northern Italy, during the period 1985-88 were reviewed to analyze the prevalence of hypertension at age of diagnosis of diabetes and its association with selected risk factors. The prevalence of hypertension was also determined in a representative sample of control subjects. In the multivariate analysis, greater body mass index and older age, but not smoking, were strongly associated with increased rates of hypertension both in control and in diabetic subjects. In diabetic patients, family history of diabetes, defined as presence of diabetes in close relatives, was not significantly associated with hypertension, while rates of hypertension were significantly lower in patients who reported at least one parent affected by diabetes. After adjustment for age and body mass index, newly diagnosed non-insulin-dependent diabetes was not an independent risk factor for hypertension. These findings seem to be consistent with the hypothesis that diabetes and hypertension are not linked by a common genetic background.

Adult↗

[Heart insufficiency treated with beta-blocking agents. Comparison of responders and non-responders].

In the last few years several Authors reported positive results using beta-blocking therapy in chronic heart failure. They also observed a group of patients who did not improve after this treatment. The aim of our study was comparing hemodynamic, neurohumoral and heart rate responses to beta-blockers in 2 groups of patients: Group A, patients who improved and Group B, patients who did not improve their clinical conditions after beta-blockade. We studied 26 patients with chronic heart failure of different origin: coronary artery disease and idiopathic dilative cardiomyopathy. They were treated with atenolol 50 mg/die for at least 1 year. Patients were divided into 2 groups: Group A including patients who increased the exercise time and the peak VO2 (> or = 2 ml/min/kg) and Group B, patients who did not increase exercise time and peak VO2 during beta-blockers. In Group A patients we observed a correlation between heart rate and end-diastolic volume by scintigraphy. We did not observe this correlation in Group B patients. The ejection fraction, evaluated by scintigraphy, significantly increased in Group A, while in Group B did not change. In both groups of patients we observed that plasmatic norepinephrine decreased significantly. In our opinion, this reduction is not due to an amelioration of organ clearance, because it was observed even in patients who did not show an increase of cardiac index and of ejection fraction. We suggest that the decrease of plasmatic norepinephrine might be the effect of beta-blockade and that it is not related to clinical response after treatment.

Adrenergic beta-Antagonists↗

Eradication of a disseminated mouse lymphoma by 1,3-bis(2-chloroethyl)-1-nitrosourea is immunologically mediated and accompanied by de novo generation of anti-tumor cytotoxicity.

The anti-tumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was examined in BALB/c mice bearing increasing burdens of a syngeneic lymphoma (YC8). A single i.p. injection of the drug resulted in over 75% of cures when given at day 3, 5, 7 or 10 after an i.v. inoculum of 10(4) YC8 cells. The efficacy of BCNU on mice bearing large tumor burdens (from day 5 on) was not only due to its tumoricidal activity, but was immunologically mediated. Residual tumorigenic cells could be recovered in the livers of 5-day tumor bearers (TB) up to 2 weeks after BCNU treatment and only a low percentage of cures could be achieved when BCNU was administered to nude mice. In addition, BCNU-cured mice specifically rejected a lethal YC8 challenge and their splenocytes developed anti-tumor cytotoxicity in response to in vitro stimulation with YC8 cells. During kinetic experiments a 2-week period elapsed after BCNU injection before an anti-tumor cytotoxic T-lymphocyte (CTL) response could be generated by spleen cells of BCNU-treated 5-day TB. This period was characterized by immunosuppression as evaluated from impairment in the generation of lymphokine-activated killer (LAK) cells or of allospecific primary CTL responses by spleen cells from BCNU-treated 5-day TB and BCNU-treated normal mice. LAK cells first recovered and could be generated 7 days later, whereas primary allospecific CTL responses could only be detected by day 14, concomitantly with the generation of anti-tumor cytotoxicity by 5-day TB. The development of secondary in vitro CTL responses, however, was permanently abrogated. Spleen cells from BALB/c mice immunized either with YC8 or with DBA/2 minor histocompatibility antigens and treated with BCNU 1 week after the last immunization failed to mount an in vitro CTL response to their immunizing antigen, even when the cultures were supplemented with recombinant interleukin-2.

Animals↗