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Biomedical subjects

M S Cattaruzza

Publications and source records attributed to M S Cattaruzza.

At least 19 recordsLinked to original sources

Long-term clinical outcome of somatostatin analogues for treatment of progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinoma.

BACKGROUND: Knowledge of factors able to predict the clinical outcome of homogenous series of entero-pancreatic endocrine tumours treated with somatostatin analogues is poor. This study was aimed at identifying predictors for efficacy of somatostatin analogues at inhibiting tumour growth and modifying patients' survival during long-term follow-up. PATIENTS AND METHODS: 31 patients with entero-pancreatic well-differentiated endocrine carcinoma received long-acting somatostatin analogues. All had progressive, metastatic disease (87% liver metastases, 38.7% distant extra-hepatic metastases). RESULTS: Response rate after 6 months of treatment was 45.2% (all disease stabilisation: 27.8% of pancreatic vs. 81.8% of intestinal tumours, P = 0.007). The predictors for non-response were: pancreatic tumour (OR 5.8), no previous surgery (OR 6.7), and the presence of distant extra-hepatic metastases, the latter being also confirmed by multivariate analysis (OR 10.0). Responders maintained stabilisation for 26.5 months, and none died during follow-up. Different survival curves were observed for patients, responding at 6 months compared to non-responders (P = 0.004), 3-year survival rate being 100% and 52.3%, respectively. CONCLUSIONS: Distant extra-hepatic metastases are the major predictor of poor efficacy of somatostatin analogues in progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinomas. Patients achieving response after 6 months of treatment, maintain it throughout a long-term follow-up. Non-responders after 6 months of treatment, have a worse survival, and should be considered for alternative treatments.

Adult↗

Long-term follow-up in atrophic body gastritis patients: atrophy and intestinal metaplasia are persistent lesions irrespective of Helicobacter pylori infection.

BACKGROUND: Long-term outcome of atrophic body gastritis has not yet been defined. AIM: To investigate at long-term follow-up the behaviour of atrophy and intestinal metaplasia and the occurrence of neoplastic lesions in atrophic body gastritis patients. METHODS: Overall 106 atrophic body gastritis patients with > or = 4-year follow-up were studied; 38 were Helicobacter pylori-positive at histology + serology and cured of infection (group A), 36 were positive at serology and not treated (group B) and 32 were H. pylori-negative (group C). Patients underwent gastroscopy with antral (n = 3) and body (n = 3) biopsies for histology according to the Sydney System. RESULTS: At 6.7-year follow-up body atrophy and intestinal metaplasia remained unchanged in all 106 patients irrespective of H. pylori status. Antral atrophy was significantly increased at follow-up only in group C, whereas antral intestinal metaplasia was unchanged in all three groups. During follow-up eight (8%) patients developed neoplastic lesions (one adenocarcinoma, one adenoma with low-grade dysplasia and six low-grade dysplasia without endoscopic lesions). Antral atrophic gastritis was present at baseline in all but one (88%) of the eight patients with neoplastic lesions, but only in 15 (15%) of the 98 patients without (P < 0.0001, RR = 26.7). CONCLUSIONS: Atrophy and intestinal metaplasia persist at 6.7-year follow-up and atrophic body gastritis patients with panatrophic gastritis are at increased risk of developing neoplastic lesions.

Adult↗

Does hospital work constitute a risk factor for Helicobacter pylori infection?

The aim of this study was to assess whether clinical work constitutes a risk factor for Helicobacter pylori infection among employees in hospitals. The prevalence of H. pylori infection was analysed in 249 individuals employed in a university teaching hospital according to three categories of hospital workers: (A) personnel from gastrointestinal endoscopy units (N=92); (B) personnel from other hospital units with direct patient contact (N=105); and (C) staff from laboratories and other units with no direct patient contact (N=52). Stool samples from each subject were examined with a validated enzyme-linked immunosorbent assay for the presence of H. pylori antigens. A questionnaire inquiring about sociodemographic and occupational characteristics was completed by each participant. The prevalence of H. pylori infection was 37.0% in group A, 35.2% in group B and 19.2% in group C (P<0.05). Among the different healthcare categories, nurses had a significant higher prevalence of H. pylori infection (P<0.01). No significant association was found between the length of employment or exposure to oral and faecal secretions, and H. pylori infection. Hospital work involving direct patient contact seems to constitute a major risk factor for H. pylori infection compared with hospital work not involving direct patient contact.

Adult↗

A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation.

Knowing the likelihood of failure of noninvasive positive pressure ventilation (NPPV) in patients with exacerbation of chronic obstructive pulmonary disease (COPD) could indicate the best choice between NPPV and endotracheal intubation instituted earlier. For this purpose, two risk charts were designed (at admission and after 2 h of NPPV) that included all relevant measurable clinical prognostic indicators derived from a population representing the patients seen routinely in clinical practice. Risk stratification of NPPV failure was assessed in 1,033 consecutive patients admitted to experienced hospital units, including two intensive care units, six respiratory intermediate care units, and five general wards. NPPV was successful in 797 patients. Patients with a Glasgow Coma Score <11, acute physiology and chronic health evaluation (APACHE) II > or =29, respiratory rate > or =30 breaths x min(-1) and pH at admission <7.25 have a predicted risk of failure >70%. A pH <7.25 after 2 h greatly increases the risk (>90%). The risk charts were validated on an independent group of 145 consecutive COPD patients treated with NPPV due to an acute ventilatory failure episode. To identify patients with a probability of failure >50%, the sensitivity and specificity were 33% and 96.7% on admission and 52.9% and 94.1% after 2 h of NPPV, respectively. The prediction chart, based on data from the current study, can function as a simple tool to predict the risk of failure of noninvasive positive pressure ventilation and thus improve clinical management of patients tailoring medical intervention.

APACHE↗

Expression of the hMSH6 mismatch-repair protein in colon cancer and HeLa cells.

PRINCIPLES: 10 to 15% of human colon cancers are associated with an inherited or somatic defect of the DNA Mismatch Repair (MMR) system, which has evolved to correct biosynthetic errors such as nucleotide mis-incorporations or misalignments arising during DNA replication in the S phase of the cell-cycle. Although expression of the MMR genes was expected to be cell-cycle dependent, we and others observed that the MMR proteins hMSH2 and hMLH1 are expressed constitutively in proliferating cells. METHODS: In this study we extend our observations to another essential MMR protein, hMSH6. We used immunohistochemistry to evaluate the expression pattern of this protein in human colorectal mucosa and tumours, as well as in synchronised HeLa-S3 cells, in which we analysed its steady-state levels during the cell-cycle. RESULTS: We show that the immunohistochemical pattern of expression of hMSH6 in normal colorectal crypts and in colon cancers differs significantly from that of the other MMR proteins, with a much lower percentage of replicating cells being hMSH6-positive. This implies that hMSH6 could be cell-cycle regulated. In order to test this hypothesis in a model system, we synchronised HeLa-S3 cells with mitotic shake-off and found that the hMSH6 protein was detectable throughout the cell-cycle, but that its steady-state level increased when cells progressed from G1 to S-phase. DISCUSSION: The increase of hMSH6 steadystate level when cells enter S-phase was expected, since MMR acts during DNA replication. However, the overall low level of oscillations of hMSH6 during the cell-cycle in this cellular model apparently does not fit the immunohistochemical phenotype. We believe that this discrepancy is due to the fact that human cell lines proliferate at a much higher rate than normal and neoplastic colorectal cells in vivo.

Base Pair Mismatch↗

Sun exposure and sun protection in young European children: an EORTC multicentric study.

Most European children experience exposure to the sun during the summer holidays. The aim of this study was to examine the behaviour of European children when in the sun during their holidays. In 1995-1997, a total of 631 young children were recruited during a multicentric study in Belgium, Germany, France and Italy. For each holiday period from birth, parents gave detailed information on sun exposure and child behaviour. Predictors and trends over time of sun protection were investigated. Forty percent of children were exposed to sunlight in the first and 86% in the sixth year of life. At the same time, the number of children who experienced sunburns rose from 1 to 23%. In the whole period of 6 years, only 8% of children always wore trousers and shirt when in the sun, while 25% children always used a sunscreen. The proportion of sun-exposed children who used sunscreen was stable with age (approximately 50%), while those who always wore trousers and shirts dropped from 46% (1st year) to 19% (6th year). Multinomial logistic regression showed that sunscreen use, but not the wearing of clothes was associated with sun-sensitivity. In summary, sun exposure increases steadily, while sun protection decreases in the first 6 years of life in our cohort of children. In this cohort, use of a sunscreen was much more frequent than the wearing of clothes and a reduction in sun exposure.

Child↗

Tolerance of human MSH2+/- lymphoblastoid cells to the methylating agent temozolomide.

Members of hereditary nonpolyposis colon cancer (HNPCC) families harboring heterozygous germline mutations in the DNA mismatch repair genes hMSH2 or hMLH1 present with tumors generally two to three decades earlier than individuals with nonfamilial sporadic colon cancer. We searched for phenotypic features that might predispose heterozygous cells from HNPCC kindreds to malignant transformation. hMSH2(+/-) lymphoblastoid cell lines were found to be on average about 4-fold more tolerant than wild-type cells to killing by the methylating agent temozolomide, a phenotype that is invariably linked with impairment of the mismatch repair system. This finding was associated with an average 2-fold decrease of the steady-state level of hMSH2 protein in hMSH2(+/-) cell lines. In contrast, hMLH1(+/-) heterozygous cells were indistinguishable from normal controls in these assays. Thus, despite the fact that HNPCC families harboring mutations in hMSH2 or hMLH1 cannot be distinguished clinically, the early stages of the carcinogenic process in hMSH2 and hMLH1 mutation carriers may be different. Should hMSH2(+/-) colonocytes and lymphoblasts harbor a similar phenotype, the increased tolerance of the former to DNA-damaging agents present in the human colon may play a key role in the initiation of the carcinogenic process.

Adaptor Proteins, Signal Transducing↗

Urocanic acid isomers in patients with non-melanoma skin cancer.

BACKGROUND: Cis-urocanic acid (cis-UCA), formed from the naturally occurring trans-isomer in the epidermis on ultraviolet (UV) radiation, initiates some of the changes leading to UV-induced immunosuppression, but its role in cutaneous carcinogenesis has not been fully investigated. OBJECTIVES: To measure the concentration of UCA isomers in the photoexposed and non-photoexposed skin of patients with multiple non-melanoma skin cancer (NMSC), enrolled in different periods of the year, in comparison with control subjects. PATIENTS/METHODS: UCA isomers were determined by high-performance liquid chromatography analysis in samples from the outer arm (photoexposed site) and buttock (non-photoexposed site) obtained from 20 patients and 19 controls during the winter period (October to April), and from five patients and 11 controls during the summer period (June to September). RESULTS: In the winter months, no difference was found between patients and controls in the concentration of UCA or the percentage of cis-UCA in either site. In the summer months, the percentage of cis-UCA in the buttock of patients and controls was similar but it was significantly higher in the arm of the controls (42%) than in the patients (17%). CONCLUSIONS: We conclude that different behaviour regarding sun exposure is the most likely explanation for these results, and that the concentration of UCA and its isomers does not reflect a tendency for individuals to develop NMSC.

Adult↗

Correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi.

BACKGROUND: The validity of clinical and histologic criteria in identifying dysplastic nevi is controversial. Recognition of the dysplastic nevus as a distinct clinicopathologic entity requires demonstration of significant agreement between clinical atypia and histologic dysplasia. OBJECTIVE: We attempted to determine the correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi and to evaluate the sensitivity and specificity of clinical criteria for dysplastic nevi when compared with histopathologic features. METHODS: A total of 940 acquired melanocytic nevi 3 mm in diameter or larger were selected by initially choosing clinically unequivocal dysplastic and nondysplastic nevi and then, from these, histologically unequivocal dysplastic and nondysplastic lesions. The level of concordance between clinical atypia and histologic dysplasia was estimated by kappa statistics. RESULTS: Nevi were classified as clinically dysplastic (n = 499) or nondysplastic (n = 441). On the basis of histologic features, 739 were classified as dysplastic and 201 as nondysplastic. Agreement between clinical atypia and histologic dysplasia was found in 432 nevi, that is, a sensitivity of 58.4% (3-5 mm = 27.2%, >5 mm = 69.8%). Agreement between clinical and histologic criteria on the absence of dysplasia was found in 134 nevi, a specificity of 66.6% (3-5 mm = 92.4%, >5 mm = 47.9%). The kappa value was 0.17 (3-5 mm = 0.14, >5 mm = 0.10). CONCLUSION: The limited sensitivity and specificity together with the negligible kappa value indicate a poor agreement between clinical and histologic diagnoses of dysplastic nevus. The dysplastic nevus cannot be considered a distinct clinicopathologic entity because histologic dysplasia is found in a range of nevi that may or may not show clinical atypia.

Adult↗

The body site distribution of melanocytic naevi in 6-7 year old European children.

The number and size of melanocytic naevi are the main predictors of cutaneous melanoma. Naevus development per unit of skin surface is greatest during childhood. We assessed the body distribution of naevi 2-4.9 mm and > or = 5 mm in 649 European children aged 6-7 years old from Brussels (Belgium), Bochum (Germany), Lyon (France) and Rome (Italy). The numbers of naevi 2-4.9 mm and naevi > or = 5 mm were strongly correlated, especially on the trunk. For naevi 2-4.9 mm, the highest relative densities were found on the face, back, shoulders and the external surface of the arms. The lowest relative densities were found on the hands, legs, feet and abdomen. The relative density of naevi > or = 5 mm was higher on the trunk than on any other body site. Similar body distributions were observed in both sexes and at each centre. The body site distribution of naevi 2-4.9 mm seemed to parallel the usual sun exposure patterns of young European children. It is suggested that the development of naevi > or = 5 mm might be a marker of the vulnerability of melanocytes to the harmful effects of solar radiation. Vulnerability would be maximal on the back, and would decrease from proximal to distal skin areas, with melanocytes of the hands and feet having the lowest vulnerability. The number of naevi acquired on a specific area of skin would result from the combined effects of local vulnerability to solar radiation and local sun exposure history. The origin of acquired body site differences in the susceptibility of melanocytes to ultraviolet radiation is unknown, although it seems to parallel the body site density of sensory innervation.

Belgium↗

Risk of spontaneous abortion in Italy, 1978-1995, and the effect of maternal age, gravidity, marital status, and education.

This paper describes the trend in the risk of spontaneous abortion in Italy from 1974 to 1995. There was a dramatic decline in the risk after the law that legalized induced abortion was passed in 1978, which implies that probably many induced abortions performed before 1978 were registered as spontaneous abortions. Data for 1991 have been extracted from the Italian national registers of births and abortions and analyzed to investigate the effects of maternal age, gravidity, marital status, and education on the risk of spontaneous abortion. In comparison with women under age 20 years, the risk is found to be increased for women aged 35-39 (odds ratio = 1.45) and women over age 40 (odds ratio = 3.10). The odds ratio is almost 2 for women who have been pregnant two or more times previously. Unmarried women have an increased risk (odds ratio = 1.33), but no important effect of education was observed. There is an important interaction between maternal age and gravidity. The risk of spontaneous abortion is excessively high for young women with high gravidity. It is hypothesized that this could be due to the effect of short intervals between pregnancies.

Abortion, Spontaneous↗

Antibodies against human herpesvirus 8 in subjects with non-venereal dermatological conditions.

BACKGROUND: Human herpesvirus 8 (HHV8) is considered as the infectious cofactor involved in the pathogenesis of Kaposi's sarcoma (KS). Its seroprevalence and modes of transmission in the general population are still undetermined. OBJECTIVES: We aimed to estimate the prevalence of HHV8 infection in a population at low risk for sexually transmitted diseases. METHODS: We conducted a seroepidemiological survey on randomly selected individuals attending the dermatology department of a teaching hospital in Rome. Of 257 patients, 248 had their blood analysed for anti-HHV8 antibodies and 201 completed a standardized interview. Serological analysis was performed by an immunofluorescence assay able to detect antilytic antibodies. RESULTS: We found an overall seroprevalence of 15.7% (95% confidence interval, CI 11.4-20.9%), similar in men and women (15.1% vs. 16.3%) and higher at older ages. Seropositivity was not related to sexual habits, while it was significantly associated with a history of hepatitis (seroprevalence 34.6%, adjusted odds ratio, OR 4.08, 95% CI 1.52-11.00) and with a diagnosis of non-melanoma skin cancer (42.9%, OR 4.20, 95% CI 1.26-14.02) or atypical naevi (35.3%, OR 6.21, 95% CI 1.85-20.86). CONCLUSIONS: Our data suggest that a non-sexual mode of transmission of HHV8 infection is plausible in an Italian population at low risk for sexually transmitted diseases and that other factors, besides differences in prevalence of HHV8 infection, may be involved in the epidemiology of classical KS. The unexpectedly high seropositivity rates in subjects with non-melanoma skin cancer and atypical naevi should be viewed with caution and require confirmation.

Adult↗

Sunscreen use, wearing clothes, and number of nevi in 6- to 7-year-old European children. European Organization for Research and Treatment of Cancer Melanoma Cooperative Group.

BACKGROUND: Previous epidemiologic studies have suggested that sunscreen use is associated with an increased risk of melanoma skin cancer. Because high nevi (mole) count in adults is a strong predictor of melanoma, we conducted a study examining the number of nevi in 6- to 7-year-old European children, according to their sunscreen use. METHODS: Whole-body and site-specific counts of nevi 2 mm or larger were performed in 631 children in their first year of primary school in four European cities. Independently, parents were interviewed regarding sun exposure, sunscreen use, and physical sun protection of their child. RESULTS: After adjustment for sun exposure and host characteristics (e.g., skin phototype, eye color), the relative risk for high nevus count on the trunk was 1.68 (95% confidence interval [CI] = 1.09-2.59) for the highest level of sunscreen use and 0.59 (95% CI = 0.36-0.97) for the highest level of wearing of clothes while in the sun. The sun protection factor had no effect on nevus counts despite a high median value of 17.4. Sunburn number was not associated with nevus count. The highest risk associated with sunscreen use was found among children who had never experienced sunburn. CONCLUSIONS: In white, European children, sunscreen use appears to be associated with development of nevi, probably because it allows longer sun exposures. Wearing clothes may be an effective way to prevent proliferation of nevi. Since a high nevus count is a strong predictor of melanoma, sunscreen use may be involved in melanoma occurrence because it may encourage recreational sun exposure.

Child↗

Changes in the medical profession in Great Britain in the xix century.

The nineteenth century was important for medicine in Britain because the foundations of a united medical profession were laid by the Medical Act of 1858. This established the General Medical Council which had the responsibility of maintaining a list of qualified medical practitioners. This not only protected the public from unknowingly using unqualified medical practitioners, but also created a monopoly of medical practice which was protected by law. In the second half of the century, women started to qualify and be registered. The century also saw the development of effective anaesthetics and the idea that the health of the public could be preserved by legislation. The notion of prevention was born, even though after a further one hundred years, the profession is still dominated by the idea that its responsibility is to cure.

Accreditation↗

Melanoma and sunscreen use: need for studies representative of actual behaviours.

Experiments in rodents and humans have shown the ability of sunscreens to prevent UVB-induced skin cancers. Sunscreen use has thus become part of the panoply for melanoma prevention. However, results from epidemiological investigations indicate that sunscreen use could be a risk rather than a protective factor for melanoma. This article discusses possible explanations for discrepancies between experimental and observational results, suggesting that experiments did not reproduce usual human behaviours towards the sunlight. Also, marketing of sunscreens fosters unconsidered exposure to sunlight through associating sunscreen use to the acquisition of a 'safe suntan', or to the possibility to let children go naked into the sunlight without incurring sunburns. It has therefore been hypothesized that, because it prevents sunburn, sunscreen use allows prolonged exposure to sunlight. If this hypothesis holds, modern sunscreens with high protection factor could also represent a threat if their use is motivated by the desire of unrestricted exposure to sunlight. To explore this hypothesis, the design of a retrospective cohort study is presented, including children 5-7 years old, with the total body naevi count as principal endpoint. This study will have the opportunity to examine the qualities of modern sunscreens among young children.

Animals↗

A molecular epidemiological approach to the study of expression of a metastasis marker in primary melanomas and its correlation with individual patient's risk of recurrence or metastasis.

Tumour cells in malignant melanomas express molecules associated with tumour progression; however, up until now, no marker has been able to identify the tumour cells from which metastases are derived. It has recently been shown that in human melanoma cell lines, populations expressing peanut agglutinin (PNA)-binding glycoproteins are able to generate metastases, and that such cells do exist in primary human melanomas, their presence being associated with the degree of local invasion that governs the metastasis risk. To further investigate the correlation between the expression of PNA-binding glycoconjugates by cells from primary melanomas and the patient's individual risk of recurrence or metastasis, a molecular epidemiological approach employing histochemical techniques within a case-control design was developed. The main objective of this study is to determine whether an histochemical staining with the lectin PNA of cells in the primary lesion is associated with an increased risk of local recurrence of metastasis, and with survival, independently of Breslow's tumour thickness. The study comprises the comparison of the PNA labelling index and of the type and intratumour location of the staining as a function of clinical outcome in two matched series of patients with known clinical outcome: patients who had died at 5 years and patients alive at 5 years (to assess association with survival), and patients who experienced a recurrence within the first 5 years and patients alive without recurrence at 5 years (to assess association with risk of recurrence). A matched case-control design was used with a variable number of controls matched to each case. Apart from age (+/-5 years), sex and centre where diagnosis was made, matching was made on histogenetic type and primary tumour thickness (four categories being considered: <0.75, 0.76-1.5, 1.51-3 and >3 mm).

Biomarkers, Tumor↗