Intramyocardial blood volume,perfusion and transit time in response to embolization of different sized microvessels

OBJECTIVE: To study the role of the coronary microcirculation in response to different-sized microemboli, we measured changes in intramyocardial microvascular blood volume (Bv), perfusion (F) and transit time (TT) and also microvascular patterns of injury. METHODS: Bv, F and TT were quantitated in 24 pigs at baseline and again 2 min after repeat injections of 10- or 100-microm microspheres at rest or during intracoronary adenosine infusion. The association of Bv and TT was assessed in the microsphere pigs and in nine control pigs. Microvascular injury was studied on gross-pathologic and histologic samples. RESULTS: At rest, initial injection of 10-microm microspheres led to increases in Bv and F, but progressively decreased with additional injections. In contrast, even small numbers of 100-microm microspheres always led to decreases in Bv and F. Injection of microspheres during adenosine-induced vasodilation always resulted in decreases in peak Bv and F irrespective of their diameters, but microvascular TTs remained unaltered. In control pigs, however, TTs were inversely related to adenosine-induced changes in Bv. Histologically, 100-microm microspheres resulted in patchy distribution of microcirculatory plugging, while 10-microm microspheres induced contiguous hemorrhagic myocardial injury. CONCLUSION: Microsphere-induced changes in intramyocardial Bv and F and the associated pattern of myocardial injury are related to the size of embolized microvessels and the initial perfusion state. Microvascular functional volume reserve mechanisms appear to play a key role accompanying flow- and TT-preservation.     

Radiologische Diagnostik beim akuten Schädel-Hirn-Trauma

Purpose. Head injury alone or in combination with multiple trauma is the main cause of death and severe disability in individuals under 45 years old. This review is intended to describe the relevant imaging modalities, to analyze their specific value and limitations and to illustrate the most important radiologic findings. The indications for diagnostic imaging within the context of an interdisciplinary linkage of diagnostic and therapeutic measures are discussed. Material and methods. Recent publications are analyzed and compared to the experiences of our own hospital. In terms of a critical synoptic assessment the currently best standard of care is described in consideration of an interdisciplinary care concept. Results. Radiologic imaging modalities crucially contribute to the complete injury assessment and provide an indispensable basis for any therapeutic decision. Comprehensive neuromonitoring and reliable demonstration of delayed or secondary brain damage is impossible without modern imaging technology. Computed tomography (CT) further continues to be the most important imaging modality, while magnetic resonance imaging despite it's partly superior diagnostic informations remains reserved to particular diagnostic problems. Conclusions. Suitable constructive prerequisites, an interdisciplinary care concept and integration of the radiologist in hospital-adapted diagnostic and therapeutic algorithms significantly improves the outcome of patients with acute head injury. Beside the correct diagnosis itself the time to establish a diagnosis above all has a crucial impact on successful management and good outcome of these patients.     

Tobacco smoke carcinogens,DNA damage and p53 mutations in smoking-associated cancers

It is estimated that cigarette smoking kills over 1 000 000 people each year by causing lung cancer as well as many other neoplasmas. p53 mutations are frequent in tobacco-related cancers and the mutation load is often higher in cancers from smokers than from nonsmokers. In lung cancers, the p53 mutational patterns are different between smokers and nonsmokers with an excess of G to T transversions in smoking-associated cancers. The prevalence of G to T transversions is 30% in smokers' lung cancer but only 12% in lung cancers of nonsmokers. A similar trend exists, albeit less marked, in laryngeal cancers and in head and neck cancers. This type of mutation is infrequent in most other tumors aside from hepatocellular carcinoma. At several p53 mutational hotspots common to all cancers, such as codons 248 and 273, a large fraction of the mutations are G to T events in lung cancers but are almost exclusively G to A transitions in non-tobacco-related cancers. Two important classes of tobacco smoke carcinogens are the polycyclic aromatic hydrocarbons (PAH) and the nicotine-derived nitrosamines. Recent studies have indicated that there is a strong coincidence of G to T transversion hotspots in lung cancers and sites of preferential formation of PAH adducts along the p53 gene. Endogenously methylated CpG dinucleotides are the preferred sites for G to T transversions, accounting for more than 50% of such mutations in lung tumors. The same dinucleotide, when present within CpG-methylated mutational reporter genes, is the target of G to T transversion hotspots in cells exposed to the model PAH compound benzo[a]pyrene-7,8-diol-9,10-epoxide. As summarized here, a number of other tobacco smoke carcinogens also can cause G to T transversion mutations. The available data suggest that p53 mutations in lung cancers can be attributed to direct DNA damage from cigarette smoke carcinogens rather than to selection of pre-existing endogenous mutations.     

The kinetics of deregulation of expression by de novo methylation of the h19 imprinting control region in cancer cells

Epigenetic lesions are common in neoplasia and range from hypermethylation of subsets of CpG islands to loss of imprinting. By exploiting an episomal model system and the strong de novo methylation capacity of a human cancer cell line, we show that an H19 minigene rapidly becomes methylated and silenced, mimicking the inactivation of the maternal H19 allele in a range of cancers. Although the H19 imprinting control region (ICR) initially displayed methylation protection, it eventually succumbed to the pressure mounted by the de novo methylation machinery of the JEG-3 cells. Importantly, we were able to visualize the kinetics of the loss of the H19 ICR chromatin insulator function in association with chromatin compaction. Our results document that a strong de novo methylation machinery leads to loss of methylation privilege states of H19 ICR to functionally manifest loss of insulator function in a matter of only a few days in human cancer cells.     

Whole-body computed tomography in polytrauma: techniques and management

An interdisciplinary team should be involved in the diagnosis and management of severely injured patients. The adoption of criteria for starting treatment for multiple trauma avoids underestimation of seriousness of injury. These criteria are established by the circumstances of the accident, the patterns of trauma, and the vital findings. Basic diagnosis comprises a limited number of plain films in the trauma room, including supine chest, lateral cervical spine, and pelvis, and ultrasound of abdomen, pleura, and pericardium. Organ diagnosis using CT is complementary and depends on the clinical findings and findings from the basic investigations. We recommend spiral CT (skull base 2/2/4 mm, cerebrum 8/8/8 mm native) and after intravenous contrast medium thoracic (5/7.5/5 mm) and abdominal CT (8/12/8 mm). Image reconstruction of bony structures can be added. The CT and the trauma center should be in close proximity; time-consuming transfers must be avoided. If this is not possible, a CT can be integrated in the trauma room. Our hospital trauma registry contains over 2200 entries. A quality committee has been established and external quality control is implemented.     

Sonographischer Zufallsbefund einer unklaren intraperitonealen Raumforderung

Ohne Zusammenfassung     

Angiotropic large-cell lymphoma presenting as pulmonary small vessel occlusive disease

Angiotropic lymphoma (AL) is an unusual variant of extranodal lymphoma, characterized by massive proliferation of neoplastic lymphoid cells almost exclusively within blood vessels. Whereas the lymphoid origin of this disease is widely accepted it still remains unclear whether AL is a distinct entity that originates in the blood vessels or whether it represents a form of secondary intravascular dissemination of a primary solid lymphoma. The present case is unusual because death by right heart failure owing to extensive intravascular proliferation of neoplastic cells and subsequent occlusion of pulmonary blood vessels has not been described so far. In addition, the patient had suffered from a solid deposit of a large-cell B-lymphoma months before the angiotropic manifestation, suggesting that AL might develop out of more common types of non-Hodgkin's lymphomas.     

Decreased cortisol secretion by adrenal glands perfused with the P-glycoprotein inhibitor valspodar and mitotane or doxorubicin

The aim of this study was to investigate the role of P-glycoprotein (P-gp) in the adrenal gland. It has been presumed that P-gp, rather than being involved in physiological cortisol secretion, plays a role in protecting the adrenacortical cells from xenobiotics. To explore this a study was performed on perfused bovine adrenal glands. Individual experimental groups were perfused with either a selective P-gp blocker (valspodar) alone, with a xenobiotic (mitotane or doxorubicin) alone or with both valspodar and a xenobiotic. The cumulative amounts of cortisol secreted in each individual group were calculated and the two-sample t-test was used to compare the mean values of cumulative amounts. The mean value of cortisol secreted from the group of adrenals perfused with the P-gp blocker was not significantly different from that of the control group. Treatment with either mitotane or doxorubicin decreased the amount of cortisol secreted but not significantly when compared to the amount of cortisol secreted in basal conditions. However, treatment with the P-gp blocker valspodar in addition to either mitotane or doxorubicin significantly decreased cortisol secreted compared to the amount of cortisol secreted by the glands treated with either mitotane (p=0.009) or doxorubicin (p=0.017) alone. The regressive changes discovered in all experimental groups were most prominent when valspodar was used with either mitotane or doxorubicin. We found that P-gp blockade increases by xenobiotic (mitotane and doxorubicin)-induced damage of adrenocortical cells, which points to a role of P-gp in the protection of adrenal gland from xenobiotics.