Organization and expression of genes involved in the biosynthesis of K99 fimbriae.

Escherichia coli K-12 minicells were used to study the expression of plasmid pFK99 encoding for the production of K99 fimbriae. Plasmid pFK99 is composed of a 6.7-kilobase pair DNA fragment derived from the wild-type K99 plasmid and the vector pBR322. The cloned K99 DNA expressed seven polypeptides with apparent masses of 18.2, 19.0, 21.0, 21.5, 26.5, 33.5, and 76.0 kilodaltons (kd). The 18.2-kd polypeptide was identified as the K99 fimbrial subunit by reaction with specific anti-K99 antibodies. The fimbrial subunit and the 19.0-, 26.5-, 33.5-, and 76.0-kd polypeptides appeared to be synthesized in a precursor form which was ca. 2 kd larger than the mature polypeptide. The location of the structural genes encoding the seven polypeptides on the physical map of pFK99 was established by analyzing a set of deletion derivatives of pFK99. The gene encoding the fimbrial subunit was located at the promoter proximal end of the K99 operon. Only mutants with a deletion in the gene encoding the 33.5- or the 19.0-kd polypeptide or both showed a weak expression of the K99 antigen and a comparably weak agglutination of horse or sheep erythrocytes. None of the deletion mutants was able to adhere to calf intestinal epithelial cells.     

First report of a vincristine dose-related Raynaud's phenomenon in an adolescent with malignant brain tumor

The authors report a case of a vincristine-induced, reproducible dose-related Raynaud's phenomenon. It occurred in a 14-year-old boy with a malignant brain tumor who received repeated vincristine injections. The authors describe how they handled this severe secondary Raynaud's phenomenon with acral cutaneous tissue necrosis. Reducing the dose of the vinca-alkaloid injections, together with an additional medication with a calcium-channel blocking agent, was a successful strategy in this patient. There are few case reports of secondary Raynaud's phenomenon in adult oncologic patients receiving certain anticancer drugs (including vincristine, bleomycin, and cisplatin), and to the authors' knowledge this kind of vincristine toxicity has not previously been described in either adults or children.     

CD38 low IgG-secreting cells are precursors of various CD38 high-expressing plasma cell populations

Despite the important role immunoglobulin G (IgG)-secreting plasma cells play in memory immune responses, the differentiation and homeostasis of these cells are not completely understood. Here, we studied the differentiation of human IgG-secreting cells ex vivo and in vitro, identifying these cells by the cellular affinity matrix technology. Several subpopulations of IgG-secreting cells were identified among the cells isolated from tonsils and bone marrow, particularly differing in the expression levels of CD9, CD19, and CD38. CD38 low IgG-secreting cells were present exclusively in the tonsils. A major fraction of these cells appeared to be early plasma cell precursors, as upon activation of B cells in vitro, IgG secretion preceded up-regulation of CD38, and on tonsillar sections, IgG-containing, CD38 low cells with a plasmacytoid phenotype were found in follicles, where plasma cell differentiation starts. A unitary phenotype of migratory peripheral blood IgG-secreting cells suggests that all bone marrow plasma cell populations share a common precursor cell. These data are compatible with a multistep model for plasma cell differentiation and imply that a common CD38 low IgG-secreting precursor gives rise to a diverse plasma cell compartment.     

Elective endovascular stent-graft repair of atherosclerotic thoracic aortic aneurysms: clinical results and midterm follow-up

OBJECTIVE: The purpose of this study was to evaluate the clinical and midterm results after endovascular treatment of atherosclerotic thoracic aortic aneurysms. MATERIALS AND METHODS: Twenty-eight consecutive patients who were 53-82 years old (mean age, 71.6 years) were treated with a commercially available endoprosthesis. Subclavian transposition or bypass surgery was performed before the procedure in eight patients. Size dynamics of the aneurysms were analyzed on the basis of diameter and thrombus volume measurements obtained on three-dimensional CT reconstructions before hospital discharge (n = 22) and at the 1-year (n = 22), 2-year (n = 12), and 3-year (n = 5) follow-ups. RESULTS: The technical success rate was 100%. There was no 30-day mortality. None of the patients had symptoms due to spinal cord ischemia. The survival rate at 1, 2, and 3 years was 96.1%, 90.9%, and 80.2%, respectively. During the perioperative period, patients presented with leukocytosis (37%), fever (36%), elevated C-reactive protein value (92%), pleural effusion (50%), and periaortic atelectasis (41%). Three early type I endoleaks sealed spontaneously. Three early type II endoleaks persisted over time, and one late type II endoleak was detected. In patients with type II endoleaks, thrombus volume of the aneurysms was constant (n = 2) or increased (n = 2). In patients without endoleaks, mean thrombus volume decreased (-53.2 +/- 56.8 mL, -40%) significantly (p = 0.001) during the first year. There was no significant interval decrease between the 1- and 2-year follow-ups (mean, -2.4 mL, p = 0.92) and between the 2- and 3-year follow-ups (mean, -0.4 mL, p = 0.68). CONCLUSION: Endovascular treatment of atherosclerotic thoracic aortic aneurysms may result in a substantial reduction of the aneurysm sac in patients without endoleaks.     

Increasing the injection volume by dilution improves the onset of motor blockade,but not sensory blockade of ropivacaine for brachial plexus block

BACKGROUND AND OBJECTIVE: Ropivacaine used for axillary plexus block provides effective motor and sensory blockade. Varying clinical dosage recommendations exist. Increasing the dosage by increasing the concentration showed no improvement in onset. We compared the behaviour of a constant dose of ropivacaine 150 mg diluted in a 30, 40 or 60 mL injection volume for axillary (brachial) plexus block. METHODS: A prospective, randomized, observer-blinded study on patients undergoing elective hand surgery was conducted in a community hospital. Three groups of patients with a constant dose of ropivacaine 150 mg, diluted in 30,40 or 60 mL NaCl 0.9%, for axillary plexus blockade were compared for onset times of motor and sensory block onset by assessing muscle strength, two-point discrimination and constant-touch sensation. RESULTS: Increasing the injection volume of ropivacaine 150 mg to 60 mL led to a faster onset of motor block, but not of sensory block, in axillary plexus block, compared with 30 or 40 mL volumes of injection. CONCLUSIONS: The data show that the onset of motor, but not of sensory block, is accelerated by increasing the injection volume to 60 mL using ropivacaine 150 mg for axillary plexus block. This may be useful for a more rapid determination of whether the brachial plexus block is effective. However, when performing surgery in the area of the block, sensory block onset seems more important.     

Recurrent gastric adenocarcinoma with unusual metastatic localization and excellent response to docetaxel and 5-FU continuous infusion

BACKGROUND: Metastatic gastric cancer is usually treated with cisplatin- and 5-FU-based chemotherapy regimens. There are good data for the combination regimen ECF (epirubicin, cisplatin and 5-FU), which is therefore often regarded as a reference treatment. Docetaxel shows promising activity against gastric cancer as single agent and in combinations. To develop a well-tolerable combination chemotherapy for an ambulant setting we initiated a randomized phase II study, comparing docetaxel and 5-FU continuous infusion (DF) with ECF. CASE REPORT: A 66-year-old patient with the history of a curatively resected gastric cancer 2 years previously presented with abdominal masses and lesions in his spleen. Histology proved metastases of gastric adenocarcinoma. The patient was treated with docetaxel (75 mg/m2, d1) and 5-FU continuous infusion (200 mg/m2/d, d1-21, q3w) within our study. Already after 2 cycles of chemotherapy he showed symptomatic improvement and partial remission of his tumor, which was confirmed after the 3rd cycle. In our ongoing study so far 50 patients are evaluable for response. Objective tumor response (CR + PR) could be documented in 44% of patients in the DF arm as well as in the ECF arm. CONCLUSION: Docetaxel and 5-FU continuous infusion is an active regimen which could possibly be used as an alternative to established treatment protocols.     

Growth inhibitors in the treatment of malignant neoplasms

Growth inhibitors are an integral part of the regulatory mechanisms involved in the growth and differentiation of cells and tissues. Aberration in the response to growth inhibitors leads to the escape of the cell from the cell cycle control mechanisms and may lead to the development of malignancies. The inactivation of tumor suppressor genes, activation of oncogenes leads to the acquisition of an invasive and increasingly malignant immunophenotype and secretory profile by transformed cells. The commencement of the complex process of carcinogenesis, and subsequent, rapid tumor growth and progression of mammalian neoplasms depends upon the continuous de novo formation of capillaries (angiogenesis). The generation of a malignant, invasive cellular immunophenotype (CIP) and distant metastases, as aspects of tumor progression, are also NRA-dependent processes. Specific molecules with cytostatic/cytotoxic growth inhibitory effects represent a very diverse group of factors. Growth inhibitors may regulate the cell cycle at various levels, and growth inhibitors comprise a heterogeneous group of agents including cytokines, growth factors, steroid hormones, etc. The phenomenon of multidrug resistance to a wide spectrum of cytostatic/cytotoxic agents has posed a major difficulty in the effective chemotherapeutical treatment of cancer patients. The development of novel therapeutic regimens should be based on the observations of the growth inhibitory profile of the particular malignancy, in addition to its immunophenotype and genotype, and the devisement of 'individualized' combinations of factors, including gene and immuno-therapeutical options, targeting different aspects of the malignant disease.