Close association between HER-2 amplification and overexpression in human tumors of non-breast origin.

The relationship between HER-2 overexpression and gene amplification is well evaluated in breast cancers but remains unclear or controversial in many other tumor entities. Therefore, we tested the HER-2 status in more than 120 different tumor entities. 5751 tumor samples were analyzed on TMAs by immunohistochemistry (Hercept-Test, DAKO) and fluorescence in situ hybridization (PathVysion, Abbott-Vysis) under highly standardized conditions. HER-2 overexpression (score 2/3+) and amplification occurred most often in breast cancers but was also seen in 18 other tumor entities including cancers of the urinary bladder (amplification in 14.3%, overexpression in 6.7%), stomach (8.3/4.9%), endometrium (6.6/6.8%), lung (2.8/3.1%) and ovary (2.3/1.2%). Remarkably, a strong association between overexpression and amplification was seen in all examined cancer entities. Trastuzumab therapy is highly efficient in HER-2 amplified breast cancer both in metastatic disease and as an adjuvant therapy. A variety of other tumor entities including frequent neoplasms and cancers with often limited therapeutic options have similar patterns of HER-2 alterations as observed in breast cancer (ie high overexpression due to high level gene amplification). Such tumor entities should be carefully evaluated for a possible utility of trastuzumab treatment.     

Radiotherapie des Basalzellkarzinoms im Gesichts‐/Kopfbereich: Bedeutung einer niedrigen Einzeldosis für das Langzeitsergebnis

Hintergrund: Die Radiotherapie spielt eine wichtige Rolle in der Behandlung des Basalzellkarzinoms des Gesichts‐/Kopfbereichs und erreicht Heilungsraten von 92‐96 %. Verschiedene Radiotherapie‐Fraktionierungsschemata sind beschrieben worden. Die vorliegende Arbeit untersucht die Wirksamkeit und (akute und chronische) Nebenwirkungen eines moderat hypofraktionierten Bestrahlungsschemas. Patienten und Methodik: 85 Patienten mit 104 Tumoren erhielten eine Radiotherapie bei einem Basalzellkarzinom des Gesichts‐/Kopfbereiches. In 95 % aller Patienten erfolgte eine Fraktionierung von 5x3 Gray/Woche bis zu einer Gesamtdosis von 57 Gray. Untersucht wurden akute und späte Radiotherapie‐Nebenwirkungen sowie das kosmetische Ergebnis. Ergebnisse: Es wurde kein Lokalrezidiv beobachtet. In 87 % aller Tumoren fanden sich zum Bestrahlungsende nur geringgradige akute Nebenwirkungen. Spätnebenwirkungen waren bei den meisten Patienten ebenfalls geringgradig ausgeprägt. In 94 % aller Tumoren konnte ein “exzellentes” oder “gutes” kosmetisches Ergebnis erreicht werden. Schlussfolgerungen: Das verwendete Bestrahlungsschema erzielt eine sehr hohe lokale Kontrollrate und (“sehr”) “gute” kosmetische (und funktionelle) Ergebnisse. Die verwendete Fraktionierung kann insgesamt als standardisierte Behandlung für ein Basalzellkarzinom des Gesichts‐/Kopfbereiches empfohlen werden.     

Role of the Dorso—Caudal Neostriatum in Filial Imprinting of the Domestic Chick: a Pharmacological and Autoradiographical Approach Focused on the Involvement of NMDA-Receptors

Newly hatched domestic chicks were either acoustically imprinted on 400 Hz tone pulses or visually imprinted on a rotating red light. Compared to naive control animals, both groups of imprinted chicks expressed significantly enhanced stimulus evoked 2-fluoro-2-deoxyglucose (2-FDG) uptake in circumscribed areas of the dorso-caudal neostriatum (Ndc). This enhanced excitability after imprinting seems not to be related to changes of NMDA-receptor densities as measured by quantitative receptor autoradiography. However, pharmacological blockade of NMDA-receptors in the dorso-caudal neostriatum leads to a marked suppression of stimulus-evoked 2-FDG uptake in the dorso-caudal neostriatum and also in the interconnected imprinting relevant forebrain area, medio-rostral neostriatum/hyperstriatum ventrale (MNH). Furthermore, chicks which received bilateral Ndc injections of the competitive NMDA antagonist DL-2-amino-5-phosphono valeric acid (APV) during the imprinting experiments showed a dose-dependent decrease of imprinting success compared to vehicle-injected controls. These results indicate that the dorso-caudal neostriatum may represent a polysensory associative brain region in which visual and acoustic features of imprinting objects may be integrated. The activation in this area evoked by the imprinting stimulus during and after imprinting is critically dependent on NMDA-receptor activation, which appears to be required for this learning process.     

Dietary intakes differ between renal transplant recipients living in patient hotels versus home.

OBJECTIVE: To compare dietary intake and health-related quality of life approximately 6 to 10 weeks after renal transplantation in patients living at home and at a patient hotel, and how the patients were following a heart-healthy diet according to the current American Heart Association guidelines. DESIGN: Cross-sectional observational study. SETTING: Outpatient clinic at Rikshospitalet University Hospital, Norway. PATIENTS: Forty renal transplant patients, 20 patients (14 men and 6 women) in both groups. There were 4 diabetic patients in each group. METHODS: Dietary intake was assessed by 4-day dietary records. Health-related quality of life was investigated by the SF-36 questionnaire. The main outcome variables were daily energy intake and intakes of protein, total fat, saturated fat, cholesterol, fiber, and fruit and vegetables. The variables were tested by 2-sample t-tests, and significance was set at.05. RESULTS: There was no statistically significant difference in daily energy intake between the groups (P =.08), but there were significantly higher daily intakes of protein (P =.003), total fat (P =.03), monounsaturated fat (P =.02), cholesterol (P =.04), fiber (P =.02), calcium (P =.03), and fruit and vegetables (P =.03) in the group living at the patient hotel. The mean intake of saturated fat was 14.5% of total energy in the group living at home and 14.6% in the group living at the patient hotel. There were no significant differences in health-related quality of life between the groups. CONCLUSION: The results suggest that there are differences in dietary intake in renal transplant patients living at home compared with those at a patient hotel. It seems that neither of the groups follows current guidelines for reducing the risk of cardiovascular disease.     

Prognostic Factors for Brain Metastases after Whole Brain Radiotherapy

PURPOSE: Prognostic factors for overall survival of patients treated for brain metastases with whole brain radiotherapy (WBRT) at a single institution were retrospectively evaluated, and the validity of the RTOG recursive partitioning analysis (RPA) for prognostic classes was assessed. PATIENTS AND METHODS: The data of all patients (n = 268) with brain metastases from solid tumors homogeneously treated between 01/1997 and 09/1999 at the University of Heidelberg, Germany, with WBRT without surgery or radiosurgery were reviewed. 13 different patient- and therapy-related variables were evaluated for prognosis. Second, a grouping of the study cohort was performed according to the RTOG RPA prognostic classes. RESULTS: Median survival of the whole population after the start of WBRT was 3.8 months. The 1-year survival rate was 19%. Multivariate analysis revealed that only the Karnofsky performance status, control of the primary and no extracranial disease were independent prognostic factors for overall survival. These are also the main determinants of the RTOG RPA classes. Applying the RTOG RPA classes to the authors' data set revealed three subgroups with significantly different prognosis. CONCLUSION: Based on this analysis, prognostic factors for survival after WBRT in patients with brain metastases could be identified. A total of 19% (n = 44/232) survived > or = 1 year, whereas overall survival was poor. The potential value of the RPA classes in estimating the patient's prognosis could be confirmed.     

Characteristics of users of syringe vending machines in Berlin

Summary Vending machines providing sterile injection equipment are part of the AIDS prevention measures for injecting drug users (IDU) in Berlin. A study was carried out to assess characteristics (history of iv drug use, frequency of use of the machines, contact with counselling units for IDU, attitudes towards the machines, HIV serostatus) in users of syringe vending machines. Of the 313 individuals surveyed 77% reported using the vending machines regularly (more than four times a week). compared to other studies of IDU in Berlin (eg at syringe exchange programmes) the users of the vending machines hat a significantly shorter history of iv drug use. Overall, 72% of the IDU had had contacts at some time with specialised agencies for counselling on drug abuse and AIDS; however, only 33% had such contacts currently. Sixty-five percent of the IDU commented critically on the machines or made suggestions for improvement; 18% had experienced that the machines did not always work well, 14% called for more machines. HIV seroprevalence based on selfreported test results (N=252) was 20%. In multivariate statistical analysis positive HIV serostatus was associated with site of interview, longer history of intravenous drug use, and current contact with counselling agencies. Despite the ready availability of syringes and needles, 25% of the participants reported borrowing injection equipment from other IDU in the previous six months. This proportion was significantly higher in IDU younger than 25 years (39%). In addition to syringe exchange programmes and pharmacies, the syringe vending machines appear to be an important source of sterile injection equipment for IDU in Berlin particularly for those without current contacts to specialised counselling units.

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Charakteristik von Benutzern von Spritzenautomaten in Berlin

Zusammenfassung Automaten zur Abgabe steriler injektionsbestecke sind in Berlin Teil der AIDS-Präventionsmaßnahmen für iv Drogenkonsumenten (IVD). Eine Studie wurde durchgeführt, um Informationen zu bestimmten Charakteristika (Inanspruchnahme der Automaten, Kontakt zu Beratungseinrichtungen für IVD, Kritik/Verbesserungsvorschläge zu den Automaten, HIV-Serostatus) bei den Benutzern der Automaten zu gewinnen Siebenundsiebzig Prozent der 313 Untersuchten benutzten die Automaten regelmäßig (mehr als viermal wöchentlich). Im Vergleich zu einer Studie bei IVD in Spritzentauschprogrammen war die Dauer des iv Drogenkonsums bei den Benutzern der Spritzenautomaten signifikant kürzer. Zwar hatten 72% schon einmal Kontakt zu Beratungseinrichtungen für IVD gehabt, zur Zeit der Untersuchung bestanden solche Kontakte jedoch nur bei 33% Von allen Untersuchten äußerten 65% Kritik oder Verbesserungsvorschläge zu den Automaten bei 18% hatten diese nicht immer funktioniert 14% forderten mehr Automaten. Die HIV-infektionsraten bei denjenigen mit bekanntem Testergebnis (N=252) lag bei 20%. In der multivariaten statistischen Analyse waren, Untersuchungsort, längere Dauer des iv Konsums und aktueller Kontakt zu Beratungseinrichtungen signifikant mit einem positiven HIV-Serostatus assoziiert. Trotz der guten Verfügbarkeit von sterilen injektionsbestecken gaben 25% der Befragten an, in den letzten 6 Monaten gebrauchte Spritzbestecke von anderen IVD benutzt zu haben. Dieser Anteil war bei jüngeren IVD (<25 Jahren) mit 39% signifikant erhöht. Die Spritzenautomaten stellen eine wichtige Ergänzung zur Abgabe von sterilen Spritzen und Kanülen in Spritzentauschprogrammen und Apotheken dar, insbesondere für IVD ohne Kontakt zu spezialisierten Beratungseinrichtungen.

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Caractéristiques des usagers des distributeurs automatiques de seringues à Berlin

Resumé La mise en place de distributeurs automatiques de seringues stériles pour les toxicomanes fait partie des mesures préventives contre le SIDA à Berlin. Une étude a été réalisée pour déterminer les caractéristiques des usagers de distributeurs automatiques (utilisation des distributeurs, contacts avec les services d'aide aux toxicomanes, avis à propos des distributeurs, status sérologique VIH). Parmi les 313 personnes participant à l'étude, 77% ont déclaré utiliser les distributeurs régulièrement (plus de 4 fois par semaine). 72% des participants avaient en des contacts avec des services specialisés d'aide aux toxicomanes mais seulement 33% utilisaient ces services au moment de l'etude. 65% de personnes examinées ont éxprimé leurs critiques ou suggestions pour l'amélioration des distributeurs: 18% ont signalé que les distributeurs ne fonctionnaient pas toujours, 14% demandaient l'installation d'un plus grand nombre de ceux-ci. La prévalence de l'infection à VIH rapportées par les toxicomanes était de 20% (N=252) Une analyse statistique multivariée montre que la séropositivité au VIH est associée avec de lieu de l'examen, la durée de la consommation de drogue par injection et le contact avec des services d'aide. Malgré la disponibilité de seringues stériles; 25% des personnes ont indiqué avoir utilisé du matériel d'injection usagé au cours des 6 derniers mois. Cette proportion était significativement plus élevée parmi les toxicomanes de moins de 25 ans (39%). Les distributeurs automatiques semblent constituer un complément important au programme d'échange de seringues stériles en particulier pour les toxicomanes qui n'ont pas de contact avec les services d'aide aux toxicomanes.

     

Short- and long-term effects of neonatal diazepam exposure on local cerebral glucose utilization in the rat

The short- and long-term consequences of a neonatal exposure to diazepam (DZP) on the postnatal changes in local cerebral metabolic rates for glucose (LCMRglcs) were studied by the quantitative autoradiographic [¹⁴C]2-deoxyglucose method in a total number of 66 brain structures of freely moving rats. Rat pups received a daily subcutaneous injection of 10 mg/kg DZP, of the dissolution vehicle of saline from postnatal day 2 (P2) to 21 (P21). The animals were studied at 4 ages, P10, P14, P21 and P60. DZP induced a decrease in LCMRglcs which was restricted to 13 areas at P10, mainly sensory and limbic regions. At P14, the treatment had significant metabolic effects on 48 structures belonging to all functional systems. By P21, 23 brain areas were still affected by the treatment, mainly sensory, limbic and motor areas. At P60, i.e. at about 40 days after the end of drug exposure, LCMRglcs still decreased in 14 brain regions which were mainly sensory and limbic structures. The structures most sensitive to both short- and long-term consequences of the anticonvulsant treatment are mammillary body, limbic cortices and sensory regions. The dissolution vehicle increased LCMRglcs in a few brain regions at P14 and P60, whereas it decreased metabolic levels in 5 brain regions at P21. The results of the present study show that the brain appears to be particularly vulnerable to the treatment at P14, period of active brain growth, whereas by P21, the drug is more actively metabolized and a tolerance to the treatment may occur. The long-term effects of the treatment are in good accordance with the well-known effects of DZP on anxiety, sedation and memory. The structures most sensitive to early neonatal DZP exposure are the mammillary body, limbic cortices and sensory regions that all contain a high density of benzodiazepine binding sites.