Family history as an independent risk factor for ischaemic heart disease in a low incidence area (Galicia, Spain)

It has been suggested that a family history positive for coronaryheart disease (CHD) increases the risk of CHD. We studied thisassociation to determine the degree of risk, the independenceof this association and the presence of interaction of a familyhistory of CHD with the major known risk factors in a law incidencearea. One hundred and six hospital cases (85 males and 21 females)of CHD and 106 hospital controls individually matched with eachcase for sex, age and place of residence (rural–urban)were studied. From every participant, information was collectedon their personal and family history of cardiovascular diseaseand risk factors; height, weight, lipid profile and blood pressurewere measured, and an electrocardiogram was recorded. Conditionallogistic regression was used in the analysis. The observed odds ratio of patients suffering from CHD amongthose with, compared to those without, a positive family historyof CHD was 4.95 (95. confidence interval = 1.27–19.28)after adjusting for the major known risk factors in each individualand their families (no interaction term remained in the model). The results support the hypothesis that a family history ofCHD, acting through mechanisms other than known risk factorsor their familial aggregation, is an independent risk factorfor CHD even in a low incidence area. No interaction effectwas observed between family history and the presence of thethree major risk factors of CHD. This should help to identifyindividuals at greater risk of CHD.     

Insulin-like growth factor (IGF)-I,-II and IGF-binding proteins in the cyst fluid of a patient with astrocytoma

Insulin-like growth factor (IGF)-I,-II and IGF-binding proteins (IGFBPs) were demonstrated in the cyst fluid of a patient with a hypothalamic astrocytoma. The astrocytoma cyst fluid was subjected to gel chromatography at low pH and the IGF-I and IGF-II levels were measured by specific radioimmunoassays. Immunoreactive IGF-I and IGF-II levels were 19 ng/ml and 78 ng/ml respectively. Several-fold higher IGF-II values were obtained when cyst fluid was not extracted or was extracted with acid ethanol before radioimmunoassay analysis. The immunoreactive IGFBP-1 concentration was 26 ng/ml. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and subsequent Western ligand blotting with [¹²⁵I]IGF-II revealed bands at 200, 34.5, 29.5, 24 and 21 kD as visualized by autoradiography. Binding studies demonstrated that these binding proteins bind specifically [¹²⁵I]IGF-I and [¹²⁵I]IGF-II. These observations suggest that IGFs as well as IGF-binding proteins are produced by astrocytoma cells and may act in a paracrine or autocrine fashion capable of modulating the growth of astrocytoma tumours.     

Diffusion of information about genetic risk within families

Recent developments in genetics are likely to exacerbate the ethical issues in clinical practice, especially with regard to privacy and disclosure of genetic information. To evaluate the behaviour of patients with respect to transmitting carrier information, we undertook a survey of 283 families with a balanced chromosomal rearrangement as a model. In these families, 1816 relatives were considered at risk and 806 of them were karyotyped (44.4%). The percentage of karyotypes performed is significantly related to the number of living children of the index couple, the reason for referral, the nature of the anomaly, the training of the counsellor and the age of the index case. This study shows the limits of the screening of at risk individuals within families, based on the willingness of the patients, and addresses practical and ethical issues around family disclosure in medical genetics.     

The geographical distribution of multiple sclerosis,rheumatoid arthritis,rheumatic heart disease and poststreptococcal nephritis in Sardinia: Climatic and socioeconomic factors

Summary The comparative geography of multiple sclerosis (MS) and non-neurological diseases considered to be autoimmune is of great interest. But there are few appropriate investigations. Some have found an increase in the frequency of MS, rheumatoid arthritis and rheumatic heart disease depending on the geographic latitude. Nevertheless, the significance of the latitude effect as an indicator of a possible etiological relationship between MS and these conditions has been questioned. In this paper, the frequency of MS, rheumatoid arthritis, rheumatic heart disease and poststreptococcal nephritis is reported from Sardinia where appreciable differences in climatic and socioeconomic conditions exist. There was a positive correlation of the distribution of MS with the distribution of rheumatic heart disease and poststreptococcal nephritis. On the other hand, no correlation was found with the distribution of rheumatoid arthritis.

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Zusammenfassung Die Ähnlichkeit zwischen Multipler Sklerose (MS) und nicht neurologischen autoimmunen Erkrankungen veranlassen zur Annahme, daß einige gemeinsame ätiologische Mechanismen im Spiele sein könnten. Das Problem der vergleichenden geographischen Verteilung von Multipler Sklerose und autoimmuner Krankheit ist wenig untersucht. Einige Forscher fanden eine ähnliche Zunahme der Häufigkeit der MS, rheumatoider Arthritis und rheumatischer Herzkrankheiten bei zunehmenden Breitengraden. Es besteht allerdings Zweifel, ob tatsächlich dieser latitude effect als ein wirklicher Indikator von ätiologischen Gemeinsamkeiten zwischen den genannten Krankheiten anzusehen ist. Wir berichten in der vorliegenden Arbeit über die Häufigkeit von MS, rheumatoider Arthritis und rheumatischen Herzkrankheiten sowie Nephritis nach Streptokokkeninfektionen in Sardinien, wo nennenswerte Unterschiede in Bezug auf klimatische und sozioökonomische Gegebenheiten bestehen. Die Verteilung der MS zeigte eine positive Korrelation mit der Verteilung rheumatischer Herzkrankheiten und von Nephritis nach Streptokokkeninfektion. Andererseits wurde keine Korrelation mit der Verteilung der Polyarthritis rheumatica festgestellt.

     

Evaluating the mutagenic potential of chemicals the minimal battery and extrapolation problems

During the past ten years growing concern about damage to DNA as an important cause of human ill-health has resulted in an explosive development of the field of genetic toxicology. Adequate regulations to restrict exposure to chemical mutagens require recognition and evaluation of mutagenic activity. For this purpose a qualitative and an extrapolation phase can be distinguished. For the qualitative phase, the minimal battery should consist of at least three tests, that is: (1) tests for gene- or point mutations in bacteria (Salmonella or E. coli) with and without metabolic activation; (2) two tests for point mutations in eukaryotes, or (3) one such test and a test for the detection of chromosome aberrations in mammalian cells in vitro. Depending on experience and facilities, a choice of two can be made out of the following four test systems: (1) Tests for point mutations in mammalian cells in vitro, with and without metabolic activation (deficiency for HGPRT, or TK); (2) the sex-linked recessive lethal test with Drosophila melanogaster; (3) tests with yeast, Saccharomyces cerevisiae, for point mutations, with and without metabolic activation; (4) tests for chromosome aberrations in mammalian cells in vitro, with and without metabolic activation. Two different metabolic activation systems should be employed. For further selection of more sensitive test systems, studies on comparative mutagenesis are considered important. A mammalian test for chromosome aberrations in vivo is not included in this minimal battery. Since under in vivo conditions considerably lower concentrations have to be employed than in vitro, it seems unlikely that positive results will be obtained with an in vivo mammalian cytogenetic assay, following negative results in an in vitro cytogenetic assay or in two different tests for point mutations. The finding that the effective concentration for the production of chromosome breakage events differs from that required to induce point mutations (the two-level effect) will be briefly discussed. When mutagenic compounds are indispensible or, in the case of ubiquitous exposure, a quantification of risks becomes necessary and here one is confronted with many difficulties. Information on damage that is hard to measure directly can be obtained in an indirect way by comparison with end-points that can be determined experimentally, such as alkylation per nucleotide. Names of chemical substances tested: hydroxylamine; diepoxybutane; N-ethyl-N-nitrosourea; methylmethanesulfonate (MMS); DEN; Mitomycin C; Procarbazine; atrazine; benz(a)pyrene; EMS; pyrolitic products; flavonoids; mycotoxins; nitrosamines; TEMGiven at the International Conference Mutagenicity Testing of Pharmaceuticals: Present Status, Paris, 12–14 March, 1980, sponsored by the Fondation de l'Industrie Pharmaceutique pour la Recherche     

Posterior approach in cervical spondylotic myeloradiculopathy

Summary Clinical and radiological data are reported concerning 44 patients suffering from cervical spondylotic myeloradiculopathy, and operated by the posterior approach; late results are evaluated.Type of onset, signs and symptoms are specified. Myeloradicular involvement was present in 52% of cases, medullary in 41%, radicular in 7%. Congenital stenosis was present in 68% of patients.Laminectomy was performed at 2–3 levels in 4 cases, at 4 levels in 10 cases, at 5 levels in 14, and extended to 6 or more levels in 16 patients. Posterior foraminotomy was performed 28 times. At follow-up evaluation (6 months to 8 years) results were excellent good in 46% of cases, fair in 34%, unchanged in 9%, and worse in 11%. First symptoms appeared more than 2 years before surgical treatment in 22 patients, between 2 years and 6 months in 15, and less than 6 months before in 7 patients. In this study a statistically significant inverse relation is demonstrated between: 1. results and duration of the disease, 2. results and gravity of motor deficits.     

Epidemiology and risk factors of pneumonia in critically ill patients

Risk factors for pneumonia were analysed in a large population of critically ill patients, collected in two prospective multicentre pneumonia studies in Italy. Twenty-three intensive care units were involved and the study time was 150 unit months. Only patients without previous pulmonary infection, with intensive care unit stay 48 hours and no rapidly irreversible illness at admission were included. The incidence of pneumonia in the 1475 selected patients was 15% (220 cases). 239 patients died in ICU; the mortality rate was significantly higher in patients developing pneumonia (p<0.0001); pneumonia was found to be an independent highly significant risk factor for death in critically ill patients (OR = 3.88; p<0.0001).Multivariate analysis of seven risk factors for pneumonia showed a significantly higher risk in patients with neuromuscular disease (OR = 3.8, p<0.002), impairment of airway reflexes at admission (OR = 2.93, p<0.0001), and 24h respiratory assistance (OR=3.05, p<0.0001). Impairment of airway reflexes at admission to the emergency room or intensive care unit identifies the population who will experience 3/4 of the overall lower respiratory tract infections.Rapid recognition of at-risk patients seems clinically important and may improve awareness programs and preventive approaches.Intensive Care Unit Group for Infection Control (I.C.U.G.I.C.), a list of participating physician co-authors of the paper is reported at the endCorresponding author.     

Growth factors in melanoma

Human melanoma cells in culture are the source of a wide variety of polypeptide growth factors. Melanoma-derived basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-A and PDGF-B chains, transforming growth factor (TGF)- and TGF-, interleukin (IL)-1 and IL-1, and melanoma growth stimulatory activity (MGSA) have similar biochemical and functional properties when compared to their counterparts produced by untransformed cells. In contrast to melanoma cells, normal melanocytes, even under optimal growth conditions, express only TGF-1 and MGSA at detectable levels suggesting that production of the other growth factors is a tumor-associated phenomenon. Recent evidence suggests that at least two of the growth factors, bFGF and MGSA, contribute to autocrine growth stimulation of melanoma cells. Whether PDGF, TGF-, IL-1, and TGF- act in an autocrine mode is unclear at present. However, these four growth factors are among those secreted by melanoma cells and, therefore, can be expected to interact with normal cells of the tumor stroma in vivo. Such paracrine effects include not only growth modulation in the context of angiogenesis and stroma formation, but also tissue degradation by proteolytic enzymes, the modification of extracellular matrix composition, and expression of adhesion receptors.     

Polyamine involvement in the secretion and action of TGF-α in hormone sensitive human breast cancer cells in culture

These experiments were designed to test polyamine (PA)* involvement in the secretion and action of transforming growth factor (TGF-) in hormone responsive MCF-7 breast cancer cells in liquid culture. At the same time, we evaluated the influence of culture conditions (with serum vs. serum depleted) and subclonality of MCF-7 cells on PA involvement in estrogen (E₂) and TGF- stimulated cell proliferation. Despite inducing a profound suppression of cellular PA levels and inhibiting basal and E₂-stimulated growth, administration of the PA synthesis inhibitor -difluoromethylornithine (DFMO) did not influence either basal or E₂-induced TGF- secretion. In the same experiments, on the other hand, addition of DFMO completely blocked the growth stimulatory effect of exogenous TGF-. However, when the culture conditions were changed to serum-free medium, TGF- and E₂-induced cell proliferation was affected modestly or not at all by DFMO administration, despite similar suppression of cellular ornithine decarboxylase (ODC) activity and PA levels. In addition, different clones of MCF-7 cells differed in their sensitivity to the antiproliferative effect of DFMO as well as in basal levels of ODC activity and PA. We conclude that PAs are not involved in basal or E₂-stimulated TGF- secretion in MCF-7 breast cancer cells. On the other hand, PAs do seem to be important mediators of TGF- and E₂-induced breast cancer cell proliferation, though the degree of such involvement appears to be influenced by serum factors and clonal variability of MCF-7 cells.