Epidemiologie, Diagnostik und Prävention

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Its diagnosis is based on clinical examination, including ultrasound, laboratory analyses, as well as determination of the tumour marker alpha-fetoprotein (AFP). If evidence for HCC is present, further imaging techniques (CT, MRI), and, if required, histopathological examination are necessary. The most important risk factors are chronic hepatitis B, C, and D, metabolic liver diseases, especially hereditary hemochromatosis, toxins (alcohol, aflatoxin) and states of insulin resistance. This knowledge provides us with strategies for HCC prevention that are of great clinical significance, in particular because, in spite of recent advances, the current therapeutic options for most patients remain very limited.     

A nationwide evaluation of multiple congenital abnormalities in Hungary

A population-based study of 7,049 index patients with multiple congenital abnormalities (MCA) born in Hungary during 1973-1982 was organized by the Hungarian Center for Congenital Anomaly Control. All clinically recognized syndromes and associations which were submitted (2,049) were accepted without any further follow-up. New or supplementary information was requested in the case of unspecified MCA (320). A copy of detailed necropsy records was requested from pathologists in lethal cases (2,022). Following these steps, apparent but not true instances of MCA were excluded (399), and an attempt was made to assign as many of the remainder as possible in 17 well-delineated MCA entities (900). The living index patients with severe MCA were referred where possible to the regional centers for evaluation (864). One hundred and seventy entities were identified, and seven cases were excluded as not representing MCA. In the so-called 3,393 unidentified cases for which no diagnosis was possible, the component abnormalities were tabulated according to their number. The final count was 6,643 cases with MCA, which is equivalent to a birth prevalence of 4.0 per 1,000 total births, and to 10% of recorded cases with congenital anomalies. As a result of this program the proportion of recognized syndromes and associations among children with MCA increased from 29% to 47%. The accuracy of diagnoses has improved, e.g., the occurrence of unspecified cases decreased from 4.5% to 2%. As a result of this study, the number of chromosomal (1,700), Mendelian (557), and teratogenic (104) syndromes and associations (758) was considerably greater than the initial notifications indicated.     

Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET)

NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared ⁷⁶Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [¹¹C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [⁷⁶Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [⁷⁶Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage. Received 19 April and in revised form 10 June 1997     

Cerebral ischemia induces transient intracellular redistribution and intranuclear translocation of the raf proto-oncogene product in hippocampal pyramidal cells

Summary In this report we describe changes in the intracellular redistribution of raf serine/threonine protein kinase (product of the raf proto-oncogene family) in hippocampal neurons following cerebral ischemia in Mongolian gerbils. For immunohistochemical localization studies polyclonal antisera specific for each of the A, B, and Raf-1 isotypes of raf, as well as a pan-raf antisera, were employed. Of these, only sera recognizing B-raf, as well as the general v-raf (raised against the conserved C-terminal region) were positive, indicating that B-raf is the major isotype in this neuronal region. Three different ischemie models were used (repeated 3 times for two min and single 5 or 15 min occlusions, of the common carotid arteries) to demonstrate that ischemie insult causes redistribution of raf protein kinase into the cell nucleus of hippocampal neurons. Increased amounts of raf protein in the nuclei of pyramidal cells following ischemia was confirmed by Western blot analysis of isolated nuclear fractionations. Moreover, an elevation in the level of nuclear raf protein also was detected in the contralateral (i.e. non-occluded hemisphere) neurons of CA1 and CA3 subfields 4 days after the ischemie insult indicating a possible transsynaptic increase in the amount of raf protein along with redistribution. The intranuclear translocation of the immunoreactive material started from the perinucleolar rim and with time extended throughout the nucleus. Enhanced levels and altered redistribution of the raf polypeptide in the nuclei of pyramidal cells of the CA3 subfleld appears to be reversible and returns to the normal level 12 days following the ischemic insult. In addition to triggering the above changes in the intracellular redistribution of raf, ischemie insult also caused an increase in the level of B-raf protein in reactive astrocytes.     

Méthodologie de programmation des investissements biomédicaux

Sur l'initiative de la Direction et de l'ingénieur biomédical, une première évaluation des pratiques de programmation a été conduite au sein du centre hospitalo-universitaire de Nîmes avec l'ensemble des acteurs concernés. L'autoévaluation se poursuit avec l'inclusion de cinq CHU de référence. Les pratiques observées permettent l'élaboration d'un questionnaire. Le questionnaire est structuré selon les phases traditionnelles du processus de programmation : état de connaissance du patrimoine ; recueil des besoins ; analyse ; décision ; réalisation du programme. Par phases, plusieurs questions fermées explorent les variables. Trente établissements sont inclus. Les résultats de l'enquête et les données initialement collectées dressent un panorama des pratiques de programmation des investissements biomédicaux en établissements de soins publics. Le résultat obtenu semble être la première étape de l'élaboration d'un référentiel professionnel. L'ensemble a permis d'étayer une refonte concrète de nos pratiques de programmation.With the initiative of the top management and the biomedical engineer, the first-assessment of the biomedical pratical programmation of the Nîmes University Hospital Center (CHU), has been led by representatives of different departments of the center. The auditing has been done with five members of the Nîmes University Hospital Center (CHU). The practices that observed have helped to create a survey. This survey is structured according to the usual steps of a programmation: statement of properties, collection of needs, analysis, decision, and realisation of the programmation. By groups, several closed questions process the variables. Thirty establishments are taken into account. The results of the study and data initially collected show an array of the practises used for the programming of the biomedical investments into public healthcare establishments. The obtained result seems to be the first stage of the elaboration of a professional reference. The whole has enabled to support a change in the uses of the Nîmes University Hospital Centre (CHU).