Protection of pigs against challenge with virulent <i>Streptococcus suis</i> serotype 2 strains by a muramidase-released protein and extracellular factor vaccine

The efficacy of a muramidase-released protein (MRP) and extracellular factor (EF) vaccine in preventing infection and disease in pigs challenged either with a homologous or a heterologous Streptococcus suis serotype 2 strain (MRP EF ) was compared with the efficacy of a vaccine containing formalin-killed bacterin of S suis serotype 2 (MRP EF ). The enhancement of the immune response by different adjuvants (a water-in-oil emulsion [wo] and an aluminium hydroxide-based adjuvant [AH]) and their side effects were also studied. The MRP and EF were purified by affinity chromatography. Pigs were vaccinated twice at three weeks and six weeks of age and challenged intravenously with virulent S suis serotype 2 strains (MRP EF ) at eight weeks of age. At challenge, the pigs vaccinated with MRP EF/WO had high anti-MRP and anti-EF titres and were protected as effectively as pigs vaccinated with wo-formulated vaccines with bacterin. Eight of the nine pigs survived the challenge and almost no clinical signs of disease were observed. The titres obtained with the MRP EF/AH vaccine were low and only two of the five pigs were protected. Pigs vaccinated with either MRP or EF were less well protected; three of the four pigs died after challenge but the clinical signs of disease were significantly less severe than those observed in the placebo-vaccinated pigs. The protective capacity of the bacterin/AH vaccine was very low, and the mortality among these pigs was as high as in the placebo-vaccinated pigs (80 per cent). Postmortem histological examination revealed meningitis, polyserositis and arthritis in the clinically affected pigs. The results demonstrate that a subunit vaccine containing both MRP and EF, formulated with the wo adjuvant, protected pigs against challenge with virulent S suis type 2 strains

The pleomorphic xanthoastrocytoma and its differential diagnosis: A study of five cases

__Abstract__ Five brain tumors with the histopathologic features of pleomorphic xanthoastrocytomas (PXAs) are presented. Computed tomography scans showed a remarkable homology. Two cases had atypical localizations for a PXA, while one 46-year-old patient did not conform to the normal age distribution of this tumor. Nevertheless, in these cases, the histopathology was always characteristic for PXA, a remarkable pleomorphism, in addition to simultaneous expression of glial fibrillary acidic protein and histiocytic markers in the various tumor cells. In one of the presented tumors, however, clusters of neoplastic neuronal cells were also found. In this particular case, differential diagnostic criteria to distinguish between a PXA and a desmoplastic infantile ganglioglioma are lacking

Asymmetrische elektrophile alpha-Amidoalkylierung, 8. Mitt.: Gewinnung optisch aktiver alpha-Phenacylpyrrolidinamide und erste asymmetrische Totalsynthese des Norruspolins

Durch Reaktion des duralen nicht-racemischen α-Methoxyamids 1 mit den Silylenolethern 2a-d werden stereoselektiv die a-Phenacylpyrrolidinamide (R)4J{SyS*-* synthetisiert Die geminalen Bisamide (/?)-H/(S)-13 werden durch Umsetzung von 1 mit dem Bistrimethylsilylimidat 11 erhalten. (/?)-4d wird für die Gewinnung des optisch aktiven Norruspolins (R)-16 (ee £ 84%) eingesetz

Calcium and magnesium in human toenails do not reflect bone mineral density

Nail mineral composition is influenced by several physiological and pathological processes. Potentially, nails could be used to monitor alterations in the level of incorporation of specific elements produced by nutritional abnormalities, disease states or chronic exposure to toxic agents. The purpose of this study was to investigate whether the calcium and magnesium content in nail clippings, as measured by instrumental neutron activation analysis (INAA), correlates with bone mineral density (BMD), as measured by quantitative microdensitometry (QMD), and therefore could be interesting as a screening instrument for osteoporosis. The study involved 220 women, who participated in a breast cancer screening project (the DOM-project) in Utrecht, the Netherlands. The correlations found between Ca and Mg measurements and bone mineral densities were very low (correlation coefficients ranging from 0.03 to 0.18). It is concluded that Ca and Mg measurements in nail clippings by INAA cannot be used for screening purposes in the prevention of osteoporosis

Surgeons produce innovative ideas which are frequently lost in the labyrinth of patents

Thoracic and cardiovascular surgery are innovative specialties that regularly recruit the latest technological developments into their armoury of devices and equipment. The introduction of new technology is dependant on patents; an important but single component of intellectual property. Patents enable the attribution of rights to concepts, ideas and inventions and this facilitates ownership, subsequent licensing and overall management of innovation and its outcome. It is not just thoracic and cardiovascular surgery, but the healthcare world in general that experiences ongoing technological evolution; so to remain contemporary, it is important that those in positions of responsibility are familiar with the relevant processes. This requires basic medico-legal knowledge and may be entwined with significant financial responsibility. Penetrating clinical, academic and industrial environments, informed awareness of patents also contributes to important leadership skills, encouraging the incorporation of innovation into the professional milieu. We aim to present through this manuscript an overview of these issues in order to promote awareness of patents within thoracic and cardiovascular surgery using a descriptive and practical approac

Role of glucose and CcpA in capsule expression and virulence of Streptococcus suis

Streptococcus suis is one of the most important pathogens in pigs and is also an emerging zoonotic agent. After crossing the epithelial barrier, S. suis causes bacteraemia, resulting in meningitis, endocarditis and bronchopneumonia. Since the host environment seems to be an important regulatory component for virulence, we related expression of virulence determinants of S. suis to glucose availability during growth and to the sugar metabolism regulator catabolite control protein A (CcpA). We found that expression of the virulence-associated genes arcB, representing arcABC operon expression, cps2A, representing capsular locus expression, as well as sly, ofs, sao and epf, differed significantly between exponential and early stationary growth of a highly virulent serotype 2 strain. Deletion of ccpA altered the expression of the surface-associated virulence factors arcB, sao and eno, as well as the two currently proven virulence factors in pigs, ofs and cps2A, in early exponential growth. Global expression analysis using a cDNA expression array revealed 259 differentially expressed genes in early exponential growth, of which 141 were more highly expressed in the CcpA mutant strain 10¿ccpA and 118 were expressed to a lower extent. Interestingly, among the latter genes, 18 could be related to capsule and cell wall synthesis. Correspondingly, electron microscopy characterization of strain 10¿ccpA revealed a markedly reduced thickness of the capsule. This phenotype correlated with enhanced binding to porcine plasma proteins and a reduced resistance to killing by porcine neutrophils. Taken together, our data demonstrate that CcpA has a significant effect on the capsule synthesis and virulence properties of S. suis

Translation to success of surgical innovation

Contemporary thoracic and cardiovascular surgery uses extensive equipment and devices to enable its performance. As the specialties develop and new frontiers are crossed, the technology needs to advance in a parallel fashion. Strokes of genius or problem-solving brain-storming may generate great ideas, but the metamorphosis of an idea into a physical functioning tool requires a lot more than just a thinking process. A modern surgical device is the end-point of a sophisticated, complicated and potentially treacherous route, which incorporates new skills and knowledge acquisition. Processes including technology transfer, commercialisation, corporate and product development, intellectual property and regulatory routes all play pivotal roles in this voyage. Many good ideas may fall by the wayside for a multitude of reasons as they may not be marketable or may be badly marketed. In this article, we attempt to illuminate the components required in the process of surgical innovation, which we believe must remain in the remit of the modern-day thoracic and cardiovascular surgeo

How to manage the left subclavian artery during endovascular stenting of the thoracic aorta

We performed a systematic review of the literature to establish whether revascularisation of the left subclavian territory is necessary when this artery is covered by a stent. We retrieved data from 99 studies incorporating 4906 patients. Incidences of left-arm ischaemia (0.0% vs 9.2%, p=0.002) and stroke (4.7% vs 7.2%, p≪0.001) were significantly less following revascularisation, although mortality (10.5% vs 3.4%, p=0.032) and endoleak incidence (25.8% vs 12.6%, p=0.008) were increased. No significant differences in spinal-cord ischaemia were seen. Revascularisation may reduce downstream ischaemic complications but can cause significant risk. Indications must be carefully considered on an individual patient basi

The course of neuropathy after cessation of cisplatin treatment, combined with Org 2766 or placebo

Peripheral neuropathy is an important and disabling side-effect of cisplatin treatment. A new drug, Org 2766, has been found to prevent this neuropathy up to 1 month after treatment. A group of 18 patients with ovarian cancer, who participated in an earlier randomized study with placebo or Org 2766, together with cisplatin and cyclophophamide, were thereafter prospectively followed up to 2 years after discontinuation of treatment to monitor the development of neurological signs and symptoms and vibration perception threshold (VPT). Exploratory, descriptive data analysis shows that between 1 and 4 months after the last cycle the average sum score for neurological signs and symptoms and VPT had deteriorated compared with 1 month after treatment. Thereafter a gradual but incomplete improvement was seen between 4-12 and 12-24 months after treatment. These changes were seen in all patients regardless of previous treatment with Org 2766 or placebo, but deterioration was less pronounced in patients previously treated with Org 2766. These results suggests that treatment with Org 2766 to prevent a cisplatin-induced neuropathy should possibly be continued up to 4 months after the last cycle of cisplatin

Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972

BACKGROUND: Oligodendroglial tumors are chemosensitive, with two-thirds of patients responding to PCV combination chemotherapy with procarbazine, lomustine (CCNU) and vincristine. Temozolomide (TMZ), a new alkylating and methylating agent has shown high response rates in recurrent anaplastic astrocytoma. We investigated this drug in recurrent oligodendroglial tumors (OD) and mixed oligoastrocytomas (OA) after prior PCV chemotherapy and radiation therapy. PATIENTS AND METHODS: In a prospective non-randomized multicenter phase II trial patients were treated with TMZ 150 mg/m(2) on days 1-5 in cycles of 28 days for 12 cycles. Eligible patients had a recurrence after prior PCV chemotherapy, with measurable and enhancing disease as shown by magnetic resonance imaging. Pathology and all responses were centrally reviewed. RESULTS: Thirty-two eligible patients were included. In four patients the pathology review did not confirm the presence of an OD or OA. Twelve of 24 patients [50%, 95% confidence interval (CI) 29% to 71%] evaluable for response to first-line PCV chemotherapy had responded to PCV. Temozolomide was in general well tolerated; the most frequent side-effects were hematological. One patient discontinued treatment due to toxicity. In seven of 28 patients (25%, 95% CI 11% to 45%) with histologically confirmed OD an objective response to TMZ was observed. Median time to progression for responding patients was 8.0 months. After 6 and 12 months from the start of treatment, 29% and 11% of patients, respectively, were still free from progression. CONCLUSIONS: TMZ may be regarded as the preferred second-line treatment in OD after failure of PCV chemotherapy. Further studies on TMZ in OD are indicated