Risk factors predicting complications in blood culture-proven typhoid fever in adults

To create a prognostic model for complications of blood culture-proven typhoid fever in adults (> or = 15 y old), a retrospective cohort was assembled though review of the medical records of the hospitalized patients treated for typhoid fever over a 3-y period ending January 1995. Of the 59 patients included, 21 (35.6%) developed various complications of typhoid fever. No patient included died. Four baseline variables (abdominal pain, systolic blood pressure < 100 mmHg, hypoalbuminaemia < 32 g/l and laboratory evidence of disseminated intravascular coagulation) were independently associated with complications and were used to create a prognostic model. The prediction accuracy of the model was determined using the concordance index (c-index). The results (c-index, 0.915 [95%, CI, 89.0-93.0]) showed that the model predicted complications significantly better than chance. The model stratified patients into 3 prognostic stages: low risk for complications (0%; stage I), intermediate risk (42.9%; stage II) and high risk (92.3%; stage III) (p = 0.001). If validated in other settings, it will help clinicians in predicting complications in patients with blood culture-proven typhoid fever on admission.     

Intrathecal chemotherapy with ACNU for meningeal gliomatosis.

ACNU [1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride], one of the chloroethylnitrosoureas (CENUs), is believed to be effective against malignant glioma when intravenously or intrathecally administered. A rat model with meningeal gliomatosis (MG) induced by an intracisternal inoculation of rat C6 or 9L glioma cells was intrathecally and intravenously treated with ACNU in order to test the feasibility of intrathecal chemotherapy with ACNU in the treatment of meningeal gliomatosis. The median survival time (MST) of the animals was significantly prolonged when ACNU was intrathecally administered at dosages of 0.5 to 1.5 mg kg-1 in the early stages of MG, i.e. within 3 days after the tumour inoculation, whereas intravenous therapy with ACNU at a dose of 15 mg kg-1 did not exhibit any efficacy in the rats inoculated with C6 glioma cells (C6-MG). Intrathecal ACNU, however, at dosages of up to 1.5 mg kg-1 failed to demonstrate any therapeutic effect in the late stage of MG, i.e. 5 days after the tumour inoculation, except in the rats inoculated with 9L brain tumour cells (9L-MG). Intravenous chemotherapy with ACNU at a dose of 15 mg kg-1 extended the MST of the 9L-MG rats more significantly in the late stage of MG than in its early stage. This points to the feasibility of intrathecal ACNU in the treatment of meningeal gliomatosis in its early stages, but not in its late stages in which intravenous ACNU might be more effective than intrathecal treatment against MG of which the parenchyma has already been deeply invaded by the tumour.     

Buchbesprechungen

Ohne Zusammenfassung     

199. Die Oberarmschaftfraktur beim Schwerverletzten: Eine Indikation zur Osteosynthese?

Zusammenfassung Die hohe metaphysare Tibiafraktur im Kindesalter ist selten. Bei einem Teil der Frakturen stellt sich trotz nahezu achsengerechter Einstellung ein Valgusfehlwachstum ein. Dies ist mehrfach beschrieben, fiber die Ursache gibt es verschiedene Theorien. Neben anderen wird uber ein 17 Monate altes Mädchen berichtet, bei dem eine Korrekturosteotomie durchgeführt werden mußte. Die Möglichkeiten zur Verhinderung and zur Behandlung werden diskutiert.     

A phenazine analogue of actinomycin D

An analogue of actinomycin D (1), in which the phenoxazone chromophore has been replaced by a phenazine, has been synthesized and characterized. Although this compound (2) lacks the 2-amino group and does not possess the quinoid structure of 1, it does bind to DNA, but less tightly than either 1 or the 2-deamino derivative of 1. NMR and CD spectra indicate that the peptide conformations in 2 are approximately as in 1; there was no apparent asymmetry of the two peptide rings. Compound 2 inhibited nucleic acid synthesis in L1210 cell cultures more effectively than does 2-deaminoactinomycin D, but about one-tenth as well as does actinomycin D.     

Trichostatin A (TSA) sensitizes the human prostatic cancer cell line DU145 to death receptor ligands treatment

The human prostatic carcinoma cell line DU145 has previously been found to be resistant to treatment with TNF-family ligands. However, TRAIL, TNF-alpha and anti-Fas antibodies (Ab) treatment in combination with the histone deacetylase inhibitor Trichostatin A (TSA) converted the phenotype of DU145 from resistant to sensitive. TSA induced 15% cell death but simultaneous treatment with TRAIL, TNF-alpha and anti-Fas Ab resulted in 55%, 70% and 40% cell death, respectively. Simultaneous treatment did not increase the level of TSA-induced histone acetylation, but induced the release of acetylated histones from chromatin into the cytosol. This release was caspase dependent since it was abrogated by Z-VAD-fmk. In addition, treatment with TSA induced caspase-9 activation and resulted in the release of cytochrome c and Smac/DIABLO from mitochondria. To further investigate the role of caspase-9 in TSA-mediated apoptosis we used two different approaches: (1) cells were pretreated with the caspase-9 inhibitor Z-LEHD-fmk, and (2) cells were transfected with a dominant-negative form of caspase-9. Both approaches gave similar results: cells became resistant to treatment with TSA. These data indicate that TSA mediates its effect via the mitochondrial pathway. This was confirmed by examining DU145 overexpressing Bcl-2. These transfectants were resistant to TSA treatment. Taken together, our data shows that only simultaneous treatment with TNF-family ligands and TSA in DU145 resulted in caspase activity sufficient to induce apoptosis. The combination of TSA and TNF-family ligands could potentially be the basis for the treatment of prostate cancer.     

Einfluss von Rettungsmittel und Zielklinik auf die Letalität nach Polytrauma

BACKGROUND: The aim of this study was to document the present knowledge from the medical literature on (1) efficacy of aeromedical evacuation (helicopter emergency medical service, HEMS) and (2) influence of the level of the first receiving hospital on mortality of patients. METHODS: Systematic review of the literature between 1970 and 2003; identification of studies with an evidence level of at least III and included control group; own results. RESULTS: (1) 17 studies concerning the efficacy of HEMS were included into the review. No single study yielded shorter rescue times with the use of HEMS. 11 of 17 studies showed a significantly higher survival rate (8.2 to 52%) with the employment of HEMS especially with mid-degree polytrauma. (2) All 6 relevant studies dealing with hospital level found a considerable lower mortality rate (19 to 42%) for patients treated primarily at a level 1 trauma center or comparable institution. CONCLUSIONS: The analyzed studies showed a trend toward decreased mortality rates with the employment of HEMS. Considering the comparable hospital level and even longer rescue times with HEMS, these differences can be explained with higher quality of initial diagnosis and treatment of the HEMS rescue team. Furthermore, mortality rates can be lowered significantly through primary treatment at a level 1 trauma center. Thus, the more flexible choice of the first receiving hospital represents a specific, clinically relevant advantage of HEMS in emergency medicine.