Acute Effects of Ocrelizumab Infusion in Multiple Sclerosis Patients

B cell-depleting therapies such as ocrelizumab (OCR) are highly effective in people with multiple sclerosis (MS). Especially at treatment start and initial infusion, infusion-related reactions (IRR) are a common adverse event. The relevance of acute changes of cell-depleting therapies on peripheral immune compartments and routine lab testing is important for clinical practice. We systematically analyzed routine blood parameters, detailed blood immunophenotyping and serum cytokine profiles in 45 MS patients starting on OCR. Blood samples were collected before and after corticosteroid premedication and directly after each OCR infusion of the first three ocrelizumab infusions. Blood B cells were rapidly depleted and accompanied only by a mild cytokine release at the first OCR infusion. Cytokine release was not significantly detectable from a third application in line with decreasing IRRs. B cell depletion was accompanied by short-lived changes in other immune cell populations in number, activation and cytokine secretion after each OCR infusion. Standard lab parameters did not show any clinically relevant changes. Our data demonstrate only mild changes during the first OCR infusion, which are not present any more during long-term treatment.     

Cerebral metabolic effects of sequential periods of hypothermic circulatory arrest

During repair of congenital heart defects, extended periods of hypothermic circulatory arrest (CA) have been shown to cause short-term cerebral metabolic and flow abnormalities as well as long-term neuropsychologic dysfunction. Occasionally, a second period of CA is required during the same operative setting to revise a complicated repair. However, the metabolic effects of two consecutive periods of CA on the brain are unclear. In this study, we compared the recovery of cerebral metabolism after 60 minutes of CA with that after two sequential 30-minute periods of CA separated by a brief period of rewarming (30'SEQ). Fifteen neonatal piglets (2 to 3 kg) were placed on cardiopulmonary bypass at 100 mL.kg-1 x min-1 and cooled to 18 degrees C. Each animal then underwent either 60 minutes of uninterrupted cardiopulmonary bypass at 18 degrees C, 60 minutes of CA, or two 30-minute periods of CA separated by a brief period of rewarming. After these experimental periods, animals were rewarmed to 37 degrees C and weaned from cardiopulmonary bypass. Data were obtained before cardiopulmonary bypass and after cardiopulmonary bypass at 37 degrees C and included measurements of cerebral blood flow by xenon 133 clearance, arterial and sagittal sinus blood gases, and cerebral metabolism (mL O2.100 g-1 x min-1). Our results demonstrated that acute recovery of cerebral metabolism was significantly impaired after 60 minutes of CA and that recovery of cerebral metabolism after two sequential 30-minute periods of CA was significantly better than after 60 minutes of continuous CA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thermally Activated Martensitic Transformations in Mg-PSZ

The thermally activated, stress-assisted martensitic tetragonal → monoclinic ( t → m ) and tetragonal → orthorhombic ( t → o ) transformations in a high-toughness Mg-PSZ were investigated by monitoring the phase assemblage with Raman spectroscopy after a variety of heat treatments and loading conditions. After a short anneal at 1000°C, which transforms m - and o -ZrO₂ to the t polymorph, isothermal t → m and t → o transformations occur at room temperature during the months following the anneal. The transformation rates in the annealed samples are greatly enhanced under external stress. Alternatively, samples containing regions of significant residual stress, introduced by indentation for example, and then annealed at relatively low temperatures, underwent additional thermally activated transformation in the stressed regions. The thermodynamics and kinetics of this complex transformation "plasticity," and its effect on mechanical properties, are discussed.     

Ex vivo gene therapy prevents chronic graft vascular disease in cardiac allografts

There continues to be considerable effort towards the construction of compound libraries targeted for the inhibition of protease enzymes. New tag-encoding methods for library deconvolution have been applied to this problem and there has been particular interest in novel solid-phase linkers for the introduction of key pharmacophore groups required for protease inhibition. Recent reports have tended to focus on nonpeptidic libraries, and, notably, structure-based design methods are now being applied to direct library design.     

Low-frequency vibrations in the treatment of patients with acute maxillary sinusitis and ethmoiditis. Non-specific resistance and immunity

Effect of sodium hypochlorite disinfection of impressions on the size and quality of plaster models is studied. Twenty-minute submerging of silicone impressions in 0.5% sodium hypochlorite solution did not change their size and did not deteriorate the quality of surface and hardness of plaster models. Stomalgin impressions cannot be disinfected by sodium hypochlorite solution because of expressed destructive effect of this disinfectant on the impressions.     

Age-associated alterations in calcium current and its modulation in cardiac myocytes

Stimulatory effects of several types of adjuvants on secondary antibody response to inactivated Newcastle disease virus (iNDV) were examined in chickens. For this purpose, animals were primed with iNDV without adjuvant resulting in a low but significant antibody response, boosted with iNDV plus adjuvant 3 weeks later, and analysed for specific antibody titres in serum 3 weeks after the booster. Water-in-mineral oil emulsion (W/O) caused significant increase in antibody titres measured in an indirect enzyme-linked immunosorbent (ELISA), haemagglutination inhibition (HI), and virus neutralisation (VN) assay. The adjuvants tested included three oil-in-water emulsions (i.e. mineral oil-in-water, sulpholipo(SL)-Ficoll400/squalane-in-water and sulpholipo-cyclodextrin/squalane-in-water), three negatively-charged polymers with high molecular weight (i.e. polyacrylate, polystyrenesulphonate and sulpho(S)-Ficoll400) and two surface-active agents (i.e. dimethyldioctadecylammonium bromide (DDA) and Quil A). These adjuvants enhanced significantly the secondary immune response but none reached the titre obtained with W/O. Combinations of adjuvants with distinct physicochemical properties, i.e. polyacrylate and DDA revealed only slight, beneficial effects. We concluded that the various types of adjuvants tested can stimulate secondary immune responses in primed animals but that W/O is superior.     

Multicenter prospective study of the current status of treatment for bleeding ulcer in Germany

The current state of ulcer treatment in Germany was analysed in a prospective multi-centre study. It was based on 1139 consecutive patients admitted to the participating hospitals because of upper gastrointestinal bleeding. The source of the bleeding was identified by diagnostic endoscopy in 1075 patients (94%), from a gastric and/or duodenal ulcer in 546 of them (mean age 62 +/- 18 years). Using Forrest's classification, 4% of patients were in bleeding stage Ia, 17% in stage Ib, 16% stage IIa, 30% stage IIb and 33% stage III. An attempt to arrest bleeding through the endoscope was made in 233 patients (43%): more often with tissue-preserving substances (epinephrine +/- NaCl in 36%, fibrin glue +/- epinephrine in 24%) than with tissue-damaging procedures (epinephrine + polidocanol +/- NaCl in 26%, epinephrine + thermocoagulation in 7%). Primary haemostasis was achieved in 219 patients (94%). There was a total of 66 recurrences of bleeding (12%), but the rate was 18% after endoscopic haemostasis. 64 patients (12%) required operative intervention, including initial emergency operations. Severe complications (infections, organic failure) occurred in 82 patients (16%). 114 of the 546 patients were in the high risk group (older than 60 years; high amount of bleeding). Their bleeding recurrence and mortality rates (27 and 22%, respectively) were significantly higher (P < 0.01) than those of the total group. Overall mortality rate was 11% (58 patients). The mortality rate depended on the severity of initial bleeding (26% for Forrest group Ia). After recurrent bleeding the mortality rate was 34% with conservative and 33% with operative treatment. 7% of all deaths were the direct result of bleeding. The following factors prognostically closely correlated with mortality rate: age of patient (P < 0.01); haemoglobin < 8 g/dl on admission (P < 0.05); initial severity of bleeding (Forrest group I; P < 0.05); and recurrence of bleeding (P < 0.001).