Computed tomography and tumor markers as diagnostic alternatives to second-look surgery in the treatment of malignant ovarian tumors]

Advanced malignant ovarian cancers are treated, after initial surgery, with first-choice mono/polychemotherapy, the response to which is evaluated by means of second-look laparotomy. The poor prognostic value of second-look results, the incidence of false negatives, the lack of valuable second-choice therapies, and the high incidence of complications after repeated interventions, lead to the testing of diagnostic imaging modalities--especially CT and tumor markers (Ca 125 and Ca 15-3). To define their actual clinical value, CT and serum assays of Ca 125 and Ca 15-3 have been performed on 32 treated patients affected with ovarian cancers (stages II-IV), who were clinically free of disease. The results have been compared with second-look pathology, but especially with patient follow-up (min. 24 months). Second-look laparotomy yielded a high number of false negatives (9/22 = 41%); moreover, many important/severe complications were observed. Thus, its value appears to be questionable. CT exhibited high positive predictive value (76.9% over the 24-month follow-up); high for both Ca 125 and Ca 15-3 (100% respectively, at 24-month follow-up) thus, few false positives were observed. Moreover CT, having higher sensitivity (55.5%) than Ca 125 (11.5%) and Ca 15-3 (27.7%), has greater diagnostic capabilities, especially when the lesion is in extraperitoneal location.     

ROMEO: rethink organization to improve education and outcomes.

AIMS: Scarcity of resources, expertise and evidence-based models have so far limited delivery of patient-centred diabetes education. We have developed and validated a group care approach that is applicable to everyday clinical practice and cost-effective in improving metabolic control, knowledge of diabetes, health behaviours, and quality of life in Type 2 diabetes. A clinical trial (ROMEO) was planned to evaluate applicability and reproducibility of group care in other outpatients facilities and assess its impact on a larger patient population. METHODS: Multicentre, randomized, controlled clinical trial of group vs. individual care in the routine management of Type 2 diabetes. Nine hundred patient aged < 80, with diabetes of > or =1 year known duration, treated by either diet alone or diet and oral agents, will be recruited in 15 centres and followed for 4 years. Training of physicians, nurses and dietitians included preparation of operating manual and videos, interactive sessions, and evaluation of local facilities and resources. RESULTS: Primary measurements: 3-monthly HbA1c, fasting blood glucose, body weight, waist-hip ratio, yearly blood lipids, and bi-yearly assessment of knowledge of diabetes, health behaviours and quality of life. Secondary outcomes: systolic and diastolic blood pressure, evaluation of ECG for ischaemia and QT interval, hypoglycaemic and anti-hypertensive medication and cardiovascular events. Analysis will be by intention-to-treat. DISCUSSION: If ROMEO confirms that group care can be successfully implemented in different clinics, a novel clinico-pedagogic tool will have been acquired to support patient-centred education, improve lifestyle and outcomes, support team work, enhance providers' attitudes and competencies and ameliorate diabetes care organization.     

Spatial and temporal pattern of purkinje cell degeneration in shaker mutant rats with hereditary cerebellar ataxia

Temporal-spatial patterns of surviving Purkinje cells were studied quantitatively in a rat mutant (shaker) with differential hereditary cerebellar ataxia and Purkinje cell degeneration. Shaker rat mutants are characterized behaviorally as mild if they are ataxic or as strong if they have ataxia and tremor. Purkinje cells degenerate in both mild and strong shaker mutants, but the temporal and spatial patterns of cell death are strikingly different. In mild shaker mutants, Purkinje cell death is temporally restricted, with 31-46% of the Purkinje cells in lobules I-IX dying by 3 months of age. Very few Purkinje cells degenerate after this age. Purkinje cell death is spatially random. In lobules I-IX, every second, third, or fourth Purkinje cell degenerates. Purkinje cells in lobule X do not degenerate. In strong shaker mutants, Purkinje cell degeneration is temporally protracted and spatially restricted. By 3 months of age, most Purkinje cells in lobules I-VIa, -b, and -d, and -d have degenerated. Numerous Purkinje cells in the paravermis of lobules VIIb-VIII have also degenerated. Surviving Purkinje cells in the vermis and lateral hemisphere of lobules VIIb-VIII are aligned in parasagittally oriented stripes or transversely oriented bands. Purkinje cells continue to degenerate in localized areas of the posterior lobe such that, by 18 months of age, surviving Purkinje cells are limited primarily to lobules VIc, VIIa, IXd, and X. Quantitative analysis indicates that none of the Purkinje cells in these lobules degenerate.     

QSAR in a series of muscarinic agents. Note VI. Five-membered cyclic ligands

Proceeding in our study on the muscarinic receptor site, a refinement of its topology by means of Quantitative Structure-Activity Relationships has been carried out. Specific key structures have been selected considering not only muscarine and the corresponding desether derivative, but also a set of cyclopentenyltrimethylammoniummethyl salts. These derivatives, considered in a correlation equation extended to all of the five-membered cyclic structures previously examined, significantly improve understanding of contributions of critical ligand substructures to the overall interaction. The results obtained reinforce the reliability of correlation equations in structure-activity studies.     

Transglutaminase in cell proliferation and transformation

Transglutaminase (TGase) activity was reduced in intact mitogen-stimulated human peripheral blood lymphocytes (PBL) when compared to intact resting PBL. Moreover, a treatment of the same quiescent immunocompetent cells with purified liver TGase and Ca²⁺ completely suppressed the mitogen-induced blast transformation. A decrease in TGase activity in neoplastically transformed seminal vesicle epithelial cells with respect to their normal parent counterpart was also observed. Our data support the notion of a possible implication of TGase in cell proliferation and transformation.     

The application of trend surface models to the analysis of time factors in Swiss cancer mortality

To study different temporal components on cancer mortality (age, period and cohort) methods of graphic representation were applied to Swiss mortality data from 1950 to 1984. Maps using continuous slopes ("contour maps") and based on eight tones of grey according to the absolute distribution of rates were used to represent the surfaces defined by the matrix of various age-specific rates. Further, progressively more complex regression surface equations were defined, on the basis of two independent variables (age/cohort) and a dependent one (each age-specific mortality rate). General patterns of trends in cancer mortality were thus identified, permitting definition of important cohort (e.g., upwards for lung and other tobacco-related neoplasms, or downwards for stomach) or period (e.g., downwards for intestines or thyroid cancers) effects, besides the major underlying age component. For most cancer sites, even the lower order (1st to 3rd) models utilised provided excellent fitting, allowing immediate identification of the residuals (e.g., high or low mortality points) as well as estimates of first-order interactions between the three factors, although the parameters of the main effects remained still undetermined. Thus, the method should be essentially used as summary guide to illustrate and understand the general patterns of age, period and cohort effects in (cancer) mortality, although they cannot conceptually solve the inherent problem of identifiability of the three components.     

First-year results of a community-based study of stroke incidence in Umbria, Italy

The SEPIVAC study (Italian initials for "epidemiologic study of incidence of acute cerebrovascular disease") is a community-based epidemiologic survey of incidence and outcome of cerebrovascular disease in the territory of the 6th Local Health Unit, Umbria, Italy, where 49,101 people live. All cases were registered with the study either by notification from general practitioners or by check of hospital admission within the study area and in the two hospitals of Perugia. Death certificates were looked at as well. Patients were registered with the study when the clinical picture fulfilled the definition of stroke and transient ischemic attack (TIA) adopted for this study. Patients were followed up at approximately 30 days and 6 months. During the first year of the study (September 1, 1986 to August 31, 1987), 189 cases were registered: 108 suffered a "first ever in a lifetime" stroke, 30 a recurrent stroke, and 51 a "first ever in a lifetime" transient ischemic attack. Sixty-one percent of patients (71% of first strokes) had a computed tomography scan. For our study, the crude annual incidence rate of first stroke was 2.2 per 1,000 (confidence intervals 1.81-2.66); the standardized rate to the European population was 1.36 (confidence intervals 1.06-1.74). At least 83% of first strokes were due to cerebral ischemia; in 26 cases a clinical diagnosis of lacunar ischemia was made. The 30-day case fatality rate was 21%; 25% of our patients had recovered completely or almost completely after 1 month.     

Reproductive factors and breast cancer: An overview

Summary Despite extensive research, there is still uncertainty on the separate effects of parity and age at first birth on breast cancer risk. Thus, information on these variables from formal epidemiological articles published in English since 1970 is reviewed in the present article. Among 26 studies considered, one found no significant association with either variable, seven showed an association between age at first birth but not parity and breast cancer risk, six an association with parity but not age at first birth, and in twelve studies both variables appeared to be independently related with breast cancer risk. Various reasons for these apparent differences can be considered, including heterogeneity between various populations (for instance, the proportion of multiparous women in studies showing no association with parity tended to be higher than in studies finding an inverse relation with parity), criteria for selection of cases and controls, influence of age and other covariates (among which the interval between pregnancies is of particular interest) and, of course, the role of chance. The data reviewed suggest, from an aetiological viewpoint, that both parity and age at first birth have some independent effect on breast carcinogenesis. From a public health viewpoint, however, it appears that the importance of age at first birth is greater, since the trend is linear across subsequent age levels, while the protection of parity seems to be quantitatively relevant only for women with four or five births or more.

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Fortpflanzungsfaktoren und Brustkrebs: eine Übersicht

Zusammenfassung Trotz intensiver Forschung bestehen immer noch Zweifel über die einzelnen Auswirkungen von Parität und Alter bei der Erstgeburt auf das Brustkrebsrisiko. Deshalb werden in diesem Artikel die Arbeiten, welche seit 1970 in Englisch veröffentlicht worden sind, analysiert. Von den 26 berücksichtigten Studien fand eine keine eindeutige Beziehung zu diesen beiden Variablen. Sieben wiesen eine Beziehung mit dem Alter bei der Erstgeburt nach, jedoch nicht mit der Parität. Sechs fanden einen Zusammenhang mit der Parität, aber nicht mit Alter bei Erstgeburt und aus 12 Studien ging hervor, dass beide Faktoren unabhängig voneinander mit dem Brustkrebsrisiko verbunden sind. Es gibt verschiedene Hypothesen, diese Diskrepanzen zu erklären, darunter auch die Verschiedenartigkeit in den untersuchten Bevölkerungen (so lag z.B. die Proportion der Frauen mit mehreren Geburten in jenen Studien, die nicht mit Parität verbunden sind höher, als in jenen, welche eine Verbindung zur Parität fanden), die Auswahlkriterien für Fälle und Kontrollen, der Einfluss des Alters und von anderen Variablen (wobei der Zeitabstand zwischen den Schwangerschaften besonders interessant ist) und natürlich die Rolle des Zufalls. Die gesichteten Resultate deuten vom ätiologischen Sichtpunkt darauf hin, dass Parität und Alter bei der Erstgeburt unabhängig voneinander das Brustkrebsrisiko beeinflussen. Die Beziehung zwischen dem Alter bei der Erstgeburt und der Brustkrebshäufigkeit scheint, vom Standpunkt der Sozialmedizin aus, jedoch von grösserer Bedeutung zu sein, da das Risiko in jeder Altersklasse linear ansteigt. Der Schutzeffekt der Parität hingegen ist erst von der vierten oder fünften Geburt an nachzuweisen.

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Les facteurs reproductifs et le cancer du sein: un résumé

Résumé Malgré des recherches approfondies, des doutes subsistent quant aux effets de parité et d'âge à la première naissance sur le risque du cancer du sein. Différents travaux parus en anglais depuis 1970 sont analysés dans cet article. Des 26 études analysées, une seule ne démontrait pas d'association. Sept ont montré une association avec l'âge à la première naissance mais pas avec la parité. Six ont démontré une association avec la parité mais non avec l'âge à la première naissance et 12 études ont montré une influence indépendante de ces deux facteurs sur le risque de cancer du sein. Différentes hypothèses peuvent être considérées pour ces différences apparentes, y compris l'hétérogénéité entre les populations étudiées (par exemple la proportion de femmes multipares est plus élevée dans les études démontrant une association avec la parité que dans celles avec une relation inverse), la sélection des cas et des témoins, la structure de l'âge, ainsi que d'autres facteurs comme par exemple l'intervalle entre les grossesses et bien sûr le hasard. Ces données laissent apparaître que la parité, ainsi que l'âge à la première naissance, peuvent influencer d'une manière indépendante le risque du cancer du sein. La corrélation entre l'âge à la première naissance et le cancer du sein est très importante pour la santé publique, étant donné que le risque augmente avec chaque classe d'âge, tandis que la parité n'a un effet protecteur qu'à partir de la quatrième ou de la cinquième naissance.

     

Onco-suppressor genes in human cancer

The analysis of the molecular mechanisms governing multistep carcinogenesis became experimentally approachable since the identification and characterization in tumor cells of altered or activated versions of cellular genes (oncogenes) that normally control cell growth and differentiation. The activating mutations confer new properties to the oncogene products and should therefore be considered as gain of function mutations. In addition, the oncogenes appear to act as dominant genetic traits since they act also in the presence of the homologous wild-type allele. However, the concept of a dominance of the transformed phenotype has been challenged by early experiments with somatic cell hybrids which showed that the fusion of normal and malignant cells may suppress the tumorigenic phenotype. The suppression or reversion of the malignant phenotype by the introduction of a normal chromosome into a tumor cell line has lent support to the idea that a family of cellular genes are coding for factors capable to interact with the cell-growth control machinery. These genes seem to reconstitute the normal control of cell growth even in the presence of an activated oncogene. In addition, a two-mutation model has been proposed to explain the epidemiological and clinical features of childhood cancers. According to the model, the development of these malignancies can be caused by the loss or inactivation of both alleles of cellular genes, as suggested by the somatic cell hybrid experiments where the function of the inactivated genes is restored by the contribution of those derived from the normal parental cells. This family of genes is designated as onco-suppressor genes since their product is necessary for the normal regulated cell growth and is lacking or inactivated in malignant cells. At gene level they should be considered as recessive genetic traits, since the tumor phenotype appears when both alleles of an onco-suppressor gene are inactivated. The mutations affecting their normal functions belong to the type "loss of function". The molecular analysis of retinoblastoma has led to the cloning and sequencing of the related onco-suppressor gene (RB gene) whose product displays the features of a gene-regulatory protein. In addition, a binding between the RB product and various viral onco-proteins (E1A, large T, E7) has been demonstrated, thus suggesting a mechanism of RB inactivation by which some DNA viruses can transform the host cell.(ABSTRACT TRUNCATED AT 400 WORDS)     

The wheat variety used in the diet of laying hens influences colonization with the intestinal spirochaete Brachyspira intermedia.

This study investigated whether feeding different wheat varieties to laying hens could influence colonization with the intestinal spirochaete Brachyspira intermedia. Fifty ISA-Brown laying hens were divided into two groups. One group were fed a laying-hen diet formulated with wheat variety Westonia, and one were fed the diet incorporating variety Stilleto. Each group was divided into 15 hens experimentally infected with B. intermedia and 10 uninfected controls. The 30 infected hens were housed in individual cages in one room, and the controls were similarly housed in another room. Following administration of cultures of B. intermedia strain HB60 by crop-tube over 3 days, cloacal swabs were taken for spirochaete culture every 3 to 4 days. The water content of caecal faeces, and egg production and body weight were measured weekly. The hens were killed after 4 weeks, the caeca cultured for spirochaetes and the viscosity of the ileal contents measured. A total of 48/120 (40%) of the excreta samples from infected hens fed Westonia contained B. intermedia, compared with 21/120 (17.5%) for Stiletto (P = 0.0002). The ileal viscosity of hens fed Westonia also was higher (P = 0.048), but viscosity was not clearly related to the non-starch polysaccharide (NSP) content of the wheats. Westonia had a slightly higher total NSP content than Stiletto, but the ratio of soluble to insoluble NSP was lower. Infected hens developed wetter excreta, but neither infection nor diet altered egg production. In conclusion, the wheat variety can influence colonization with B. intermedia, apparently through diet-related alterations in the intestinal microenvironment.