Expression analysis of the genes involved in estradiol and progesterone action in human ovarian endometriosis.

Endometriosis is defined as the presence of endometrial glands and stroma within extrauterine sites, and it is well known that endometriosis is an estrogen-dependent disease. The defective formation and metabolism of steroid hormones is responsible for the promotion and development of endometriosis. In the present study we examined the mRNA levels of six enzymes that are involved in the metabolism of estrogen and progesterone--aromatase, 17beta-hydroxysteroid dehydrogenase (17beta-HSD) types 1, 2 and 7, sulfatase and sulfotransferase--and of the steroid receptors--estrogen receptors alpha and beta (ERalpha, ERbeta) and progesterone receptors A and B (PRAB)--implicated in human ovarian endometriosis. We analyzed 16 samples of ovarian endometriosis and 9 of normal endometrium. The real-time polymerase chain reaction analyses revealed that six of the nine genes investigated are differentially regulated. Aromatase, 17beta-HSD types 1 and 7, sulfatase and ERbeta were statistically significantly upregulated, while ERalpha was significantly downregulated, in the endometriosis group compared with the control group. There were no significant differences in 17beta-HSD type 2, sulfotransferase and PRAB gene expression. Our results indicate that, in addition to the previously reported upregulation of aromatase, upregulation of 17beta-HSD types 1 and 7 and sulfatase can also increase the local estradiol concentration. This could thus be responsible for the estrogen-dependent growth of endometriotic tissue. Surprisingly ERalpha was downregulated.     

Fronto-temporal disconnectivity in schizotypal personality disorder: a diffusion tensor imaging study.

BACKGROUND: Using diffusion tensor imaging (DTI), we previously reported abnormalities in two critical white matter tracts in schizophrenia, the uncinate fasciculus (UF) and the cingulum bundle (CB), both related to fronto-temporal connectivity. Here, we investigate these two bundles in unmedicated subjects with schizotypal personality disorder (SPD). METHODS: Fifteen male SPD subjects and 15 male control subjects were scanned with line-scan DTI. Fractional anisotropy (FA) and mean diffusivity (D(m)) were used to quantify water diffusion, and cross-sectional area was defined with a directional threshold method. Exploratory correlation analyses were evaluated with Spearman's rho, followed by post hoc hierarchical regression analyses. RESULTS: We found bilaterally reduced FA in the UF of SPD subjects. For CB, there was no significant group difference for FA or D(m) measures. Additionally, in SPD, reduced FA in the right UF was correlated with clinical symptoms, including ideas of reference, suspiciousness, restricted affect, and social anxiety. In contrast, left UF area was correlated with measures of cognitive function, including general intelligence, verbal and visual memory, and executive performance. CONCLUSIONS: These findings in SPD suggest altered fronto-temporal connectivity through the UF, similar to findings in schizophrenia, and intact neocortical-limbic connectivity through the CB, in marked contrast with what has been reported in schizophrenia.     

Male breast cancer: Austrian experience

Data were collected on 169 men treated for breast cancer at 36 surgical departments in Austria between 1970 and 1991. We report here several of their clinical features and assess the importance of established prognostic factors. After a median observation period of 51 months 60 patients (35%) suffered a recurrence. The estimated 5-year recurrence-free survival for the entire group was 55%, and the estimated 5-year overall survival was 62%. Although stage-adjusted data are comparable to those for female breast cancer, the outcome in this series may be attributed to a relatively high frequency of advanced tumor stages. Tumor size (recurrence-free survival p=0.00001; overall survival p=0.03) and axillary lymph node status (recurrence-free survival p=0.0001; overall survival p=0.0001) proved to have a prognostic impact. Using a multivariate analysis, axillary lymph node status (recurrence-free survival p=0.001; overall survival p=0.01) still had prognostic influence. The various procedures used had no effect on local recurrence.

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Resumen Se recolectaron datos en 169 hombres tratados por cáncer mamario en 16 departamentos quirúrgicos de Austria en el período 1970 a 1991. En el presente estudio reportamos diferentes características clínicas y tratamos de definir la importancia de factores establecidos de pronóstico. Luego de un período promedio de observación de 51 meses, se observó recurrencia en 60 pacientes (35%). La tasa estimada de sobrevida libre de enfermedad recurrente para la totalidad del grupo fue 55% y la tasa estimada de sobrevida global a 5 años fue 62%. En tanto que la estadificación de los datos es comparable a la de las mujeres con cáncer mamario, el resultado final en esta serie puede ser atribuido a una frecuencia relativamente alta de tumor en estados avanzados. El tamaño del tumor (sobrevida libre de recurrencia p=0.0001; sobrevida global p=0.03) y estado de los ganglios axilares (sobrevida libre de recurrencia p=0.00001; sobrevida global p=0.0001) demostró tener impacto en cuanto al pronós neo. En el análisis multivariable, el estado de los ganglios linfáticos axilares (sobrevida libre de recurrencia p=0.0001; sobrevida global p=0.01) retuvo su influencia pronóstica. Los diferentes procedimientos operatorios de tratamiento local no demostraron efecto en cuanto a la recurrencia local.

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Résumé On a analysé les dossiers de 169 hommes traités pour un cancer du sein dans 36 centres chirurgicaux en Autriche entre 1970 et 1991. Les données cliniques ont été analysés et des facteurs pronostiques établis. Après une période d'observation médiane de 51 mois, 60 patients (35%) avaient une récidive. La survie à 5 ans sans maladie a été évaluée à 55% pour le groupe entier, alors que la survie à 5 ans globale a été de 62%. Lorsqu'on a comparé ces cas à des cancers de sein chez la femme, on s'est rendu compte que l'évolution dans cette série était peut-être en rapport avec un nombre plus important de stades avancés de patients avec cancer. On a démontré que la taille de la tumeur (survie sans récidive; p =0.0001; survie globale p=0.03) et l'état des ganglions axillaires (survie sans récidive p=0,00001, survie globale p=0,0001) avaient une valeur pronostique. En analyse multifactorielle, l'état ganglionnaire axillaire était toujours considéré comme facteur pronostique (survie sans récidive p=0.0001; survie globale p=0.01). Les interventions locales n'avaient aucune influence pronostique sur les récidives locales.

     

Familial recurrence of congenital heart disease in patients with ostium secundum atrial septal defect.

AIMS: Ostium secundum atrial septal defect (osASD) is one of the most common cardiac malformations. Few data are available on the familial recurrence of congenital heart disease (CHD), in particular, in a large group of patients with isolated osASD. The aim is to investigate the familial recurrence of CHD in up to third-degree relatives from a large sample of consecutively enrolled patients with osASD, taking into account the influence of degree of relatedness (as number of relatives). METHODS AND RESULTS: From January 1998 to December 2002, we enrolled 583 patients with osASD and 408 healthy subjects, referred to our tertiary centre. We hypothesized that a positive family history required at least one relative with CHD to constitute a risk factor. In this model of analysis, the null hypothesis is a similar familial history between cases and controls. Among 583 patients with osASD, 109 (19%) had at least one relative with CHD. Among the 408 healthy subjects studied, only 23 (6%) had a family history of CHD. A familial recurrence of CHD was demonstrated in 72 of 312 (23%) patients with isolated osASD and in 37 of 271 (13.6%) patients with non-isolated osASD. Familial recurrence of isolated osASD was demonstrated in 22 of 312 patients (7%) with an isolated osASD and only in six of 271 patients (2.2%) with non-isolated osASD. The familial recurrence risk of isolated osASD in patients with isolated osASD was higher in sibs, especially in sisters (33.3%). CONCLUSION: This study underscores the role of genetic factors in the determination of CHD, particularly osASD. Our results could represent the basis for further studies to calculate a 'value of family history' to adapt the familial recurrence to the real size of each family group. In this way, we could select families with a 'tendency' to develop CHD, particularly osASD. In these families, we could analyse the genetic pattern to establish abnormalities and the bases of CHD.     

PUVA-Bad-Photochemotherapie bei Acrodermatitis continua suppurativa Hallopeau

Zusammenfassung Ein 73j?hriger Patient mit seit 8 Jahren bestehender, therapieresistenter, chronisch rezidivierender Acrodermatitis continua suppurativa Hallopeau wurde mit einer selektiven PUVA-Bad-Photochemotherapie der H?nde über 10 Wochen behandelt. Die 8-Methoxypsoralenkonzentration des Badewassers betrug 1,0 mg/l; 20 min nach dem Handbad erfolgte die UVA-Bestrahlung. Die kumulative UVA-Dosis bei 32 Bestrahlungen betrug 54,6 J/cm² an den Palmae und 26,8 J/cm² an den Handrücken, wobei die UVA-Einzeldosen von 0,5 bis 2,5 J/cm² an den Handinnenfl?chen und von 0,2 bis 1,4 J/cm² an den Handrücken reichten. Bereits nach 16 Behandlungen kam es zu einer deutlichen Befundbesserung und nach 8 weiteren Bestrahlungen zu einer vollst?ndigen Abheilung der Acrodermatitis continua. Die folgenden 4 Wochen wurde mit einer Erhaltungtherapie von 2 Bestrahlungen pro Woche behandelt. W?hrend der 4monatigen Nachbeobachtungszeit kam es zu keinem Rezidiv. Aufgrund ihrer guten klinischen Wirksamkeit bei fehlenden systemischen Nebenwirkungen kann die PUVA-Bad-Photochemotherapie der H?nde eine effektive therapeutische Alternative in der Behandlung der Acrodermatitis continua suppurativa Hallopeau darstellen, deren Vorteile insbesondere in der M?glichkeit einer selektiven Photosensibilisierung umschriebener Hautareale zu sehen ist. Eingegangen am 1. Oktober 1996 Angenommen am 22. Januar 1997     

Ovarielle Suppression in der adjuvanten Therapie des Mammakarzinoms: GnRH-Analoga, Ovarektomie oder Radiomenolyse - "Stein der Weisen" statt "Kammer des Schreckens"?

Hintergrund: Bei prämenopausalen Patientinnen mit rezeptorpositiven Mammakarzinomen stellt die ovarielle Suppression einen wichtigen Schritt in der adjuvanten Therapie dar. Neben der GnRH-Analoga kommen hierfür die Ovarektomie oder die Radiomenolyse infrage. Patienten und Methode: Die vorliegende Arbeit stellt die Vorteile der einzelnen Therapieoptionen den therapiebedingten Nebenwirkungen gegenüber und vergleicht die Methoden untereinander. Ergebnisse: Wegen der Reversibilität und der Patientenakzeptanz sollten GnRH-Analoga besonders bei jüngeren prämenopausalen Patientinnen angewendet werden. In der Differentialtherapie von Patientinnen, bei denen die Langzeitnebenwirkungen einer iatrogen induzierten Menopause weniger zu befürchten sind, kommen auch die anderen Verfahren in Betracht. Hierbei stehen Radiomenolyse und Ovarektomie gleichwertig nebeneinander. Schlussfolgerung: Die differentialtherapeutische Entscheidung zu einer der Methoden sollte individualisiert werden. Auch bei zunehmendem Gebrauch der GnRH-Analoga stellt die Radiomenolyse eine zeitgemäße und kostengünstige Therapiemodalität besonders bei peri- oder prämenopausalen Patientinnen über 45 Jahren dar. Background: Ovarian suppression in the adjuvant treatment of perimenopausal women with breast cancer is an important option. The therapeutic goal can be accomplished by administration of GnRH-analogues, ovarectomy or radiocastration. Patients and Methods: We describe the advantages and the therapy related side effects and compare the different treatment modalities with each other. Results: Because of its reversibility and patients' compliance GnRH-analogues seem to be advantageous especially in younger premenopausal women. When longer term side effects of artificially induced menopause are less important, therapeutic alternatives such as radiocastration or ovarectomy are effective without obvious superiority between these options. Conclusion: Even in the background of the increasing use of GnRH-analogues radiocastration remains still a therapeutic alternative because of its cost-effectiveness and feasibility. This accounts especially for peri- or premenopausal women above the age of 45.