Management und Kontrolle einer Influenzapandemie Konzeptionelle Überlegungen für einen deutschen Influenzapandemieplan

The World Health Organization (WHO) and the majority of the influenza experts assume that an influenza pandemic might reemerge again at any time. Therefore WHO has called upon all member states to set up a national pandemic preparedness plan. For Germany such a plan is long overdue. In order to gain as much time as possible early identification of the pandemic virus is of highest priority. Furthermore progression of a pandemic is influenced by the time needed to develop a subtype specific vaccine as well as by the vaccines availability. However, in case of a pandemic a shortage of vaccines and prophylactic pharmaceuticals cannot be avoided. Therefore, decisions have to be made in order to establish priorities concerning the vaccination and the prophylactic and/or therapeutic antimicrobial treatment of selected sub-populations. There is also a need to lay down measures ensuring the distribution of vaccines and antiviral drugs, adequate health care and ambulance service, and the organization of dignified funerals of the deceased. It is also necessary to enter into an early agreement with vaccine manufacturers on a guaranteed supply of respective batches of vaccine doses. In addition procedures should be established to allow an increase in vaccine production in case of a pandemic. There is also a need for early agreements with the manufacturers of antiviral agents and for a decision concerning the establishment of a national stockpile to guarantee an adequate supply. Some measures must already be taken in the inter-pandemic period. Those are: enhancement of surveillance and research, development of new vaccines and new methods of vaccine production, licensing of new vaccines in case of a pandemic and establishment of a national influenza committee. Problems like the effectiveness of antiepidemic measures, such as immigration control and the closing of schools, must be solved in advance of a pandemic.     

Perforated colorectal neoplasms: correlation of clinical, contrast enema, and CT examinations

Results of clinical, contrast enema (CE), and computed tomographic (CT) examinations in 39 patients with perforated colorectal neoplasms were retrospectively reviewed. Twenty patients were toxemic at initial presentation, but in only four patients was the diagnosis of perforated colorectal neoplasm initially suspected clinically. CE study was performed in 22 patients and enabled the diagnosis of perforated neoplasm in 11 cases, neoplasm alone in eight, and neither neoplasm nor perforation in three. CT was performed in 38 patients and enabled the diagnosis of perforated neoplasm in 36; pericolic phlegmon but no mass lesion was evident in two. In 16 patients, CT also demonstrated metastatic disease. Because of its reliability in establishing the diagnosis and staging the extent of the inflammatory and neoplastic disease, CT is indicated in cases of suspected or proved perforated colorectal neoplasm and in cases in which CE study findings are indeterminate or suggestive of perforated neoplasm.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Effects of rifampicin on the peripheral turnover kinetics of thyroid hormones in mice and in men

The induction of mixed function hepatic oxygenases by rifampicin is known to increase the metabolic clearance rate (MCR) of T4. By performing T3 and rT3 kinetics we have shown that rifampicin also increases the MCR of T3 and rT3. Using the fall of serum T4 during TSH suppression as an indirect marker of the production rate (PR) of T4, we have demonstrated that there was no major change in monodeiodination nor any shift to either 5'- or 5-monodeiodination. Rifampicin stimulates in mice the mixed function hepatic oxygenases. However, we were unable to increase hepatic deiodinase activity (deiodinase type I) in this species. It is therefore possible that the increased MCR of T4 in man is not mediated by an increased conversion rate either. As mixed function hepatic oxygenases are known to increase hepatic conjugation it is suggested that rifampicin increases the biliary excretion of iodothyronine conjugates.