Synthesis of the protected tridecapeptide (56–68) of the VH domain of mouse myeloma immunoglobulin M603 and its reattachment to resin supports

A protected tridecapeptide, representing a new peptide corresponding to residues 56–68 of the V_H domain in the mouse M603 myeloma protein, has been prepared by solid phase peptide synthesis. The protected tridecapeptide was prepared using the photolabile 4-bromomethyl-(3-nitro)-benzamidomethyl-resin and the multidetachable 2-[4-bromomethyl)phenylacetoxy] propionyl-resin as solid supports. The synthetic protocol and protecting groups were the same for both syntheses. The protected tridecapeptide was removed photolytically from both supports and the sequence integrity was determined by preview analysis using the solid phase Edman degradation procedure. The protected tridecapeptide-OMPA was purified to homogeneity by DMF/H₂O precipitation and LH-60 chromatography. The purity of the protected peptide was further demonstrated by high pressure liquid chromatography on the free peptide after HF deprotection. The protected tridecapeptide was reattached to 4-bromomethyl-(3-nitro)-benzamidomethyl-resin to give the photolabile Boc-(protected) peptidyl-4 - oxymethyl - (3 - nitro) benzamidomethyl - resin in 25% yield. The protected tridecapeptide-oxymethylphenylacetic acid derivative was reattached to aminomethyl-resin to give Boc -(protected)peptidyl-2-[(4-oxymethyl)phenyl]acet-amidomethyl-resin in 45% yield and to 2-bromopropionyl-resin generating the multidetachable Boc - (protected)peptidyl - 2 - [(4 - oxymethyl) phenylacetoxy] propionyl-resin in 80% yield. The reactivity of these reattached peptides was demonstrated by the quantitative coupling of Boc-leucine to the protected peptide-resin. The advantages and disadvantages of the different resins with respect to solid phase fragment synthesis are discussed.     

Eight year experience with the Bjork-Shiley prosthesis in 833 patients

Between December 1970 and June 1978, 833 patients were operatedupon for isolated mitral valve replacement (MVR: 361 patients),isolated aortic valve replacement (AVR: 345 patients) and aorticplus mitral valve replacement (DVR: 127 patients) by use ofthe Björk-Shiley valve. Operative mortality for the entireseries was 15%. The five year survival rate, including operativemortality, calculated by the actuarial method was 81.4% forMVR, 73.1% for AVR and 66.8% for DVR. The five year survivalrate of operative survivors was 94.9% for MVR, 85% for AVR and83.2% for DVR. The five year complication-free survival rate(death/removal/embolus-free survival rate) including operativemortality was 69.7% for MVR, 71.8% for AVR and 62.8% for DVR.The postoperative hemodynamic result was evaluated in 58 consecutivepatients with AVR and DVR. End-diastolic volume fell after operationfrom 161 to 104 ml/m² in AVR and from 156 to 103 ml/m² in DVR.Ejection fraction increased from 54 to 65% in AVR and from 50to 61% in DVR. We conclude: (1) actuarial analysis of prosthesis related deathand complications suggests that the Björk-Shiley valveis an excellent choice when using a mechanical device; (2) asignificant improvement of left ventricular function resultsafter Björk-Shiley valve implantation.     

Rehabilitative Therapies Differentially Alter Proliferation and Survival of Glial Cell Populations in the Perilesional Zone of Cortical Infarcts

卒中后的康复治疗能改善神经环路的重塑,促进功能恢复。但人们对其潜在的细胞分子机制却知之甚少。特别是康复训练对在大脑局部缺血的病理生理过程中扮演着重要角色的胶质细胞的影响,一直不甚明了。现在,作者设计一项实验来检测康复训练对光化学诱导的局灶性脑缺血损伤灶周围(梗死灶位于大鼠前肢感觉运动皮质功能区)的不同胶质细胞种群增殖和存活的影响。造模成功后,标准组小鼠即开始在标准笼中接受每日定期的针对损伤前肢的功能训练,强化组大鼠转移到强化环境中饲养,抓取组大鼠仍然放在标准笼中未给予进一步的治疗。作者通过感觉运动行走测试来评价功能恢复情况,并于梗死后2-6d给予BrdU以标记检测增殖的细胞。分贝在梗死后的第10天和第42天,用免疫细胞化学方法对病灶周围增殖和存活的星形胶质细胞、小胶质细胞/巨噬细胞和成熟或未成熟的少突胶质细胞进行定量检测。结果作者发现,强化环境和抓取训练都能显著提高损伤前肢的功能恢复程度。此外,这些治疗能显著减少梗死灶周围小胶质细胞/巨噬细胞的增殖,其中对损伤前肢的每日训练还能明显提高新生星形胶质细胞的存活率。因此,作者的数据证明,皮质梗死后的康复治疗不仅能促进功能恢复,而且显著影响着病灶周围区胶质细胞的反应。     

Diagnosis of hepatitis C: update 2004

Abstract   Diagnosis of hepatitis C virus infection (HCV) is based on HCV antibody testing by standard serological tests and immunoblot assays for confirmation in special cases. Differentiation of past and ongoing hepatitis C is performed by detection of HCV core antigen and HCV RNA. Ongoing hepatitis C can be assigned to infection with one or multiple HCV sub- and genotypes by characteristic sequence differences. Infection with HCV genotype 2 or 3 is the best pretreatment parameter for prediction of sustained virologic response to interferon-alfa based antiviral therapy. During antiviral therapy, the key to assess virologic treatment response is quantitative measurement of HCV RNA. A decline of HCV RNA concentration from baseline to week 12 of less than 2 log steps or an absolute viral load above 30.000 IU/mL in genotype 1 infected patients is strongly associated with viral non-response. For estimation of early virologic response on the basis of HCV core antigen measurement positive detection of core antigen at week 12 was correlated with virologic non-response. At week 24 of treatment, at the end-of-therapy and during follow-up highly sensitive HCV RNA detection assays are critical for discontinuation of further therapy and correct estimation of virologic response. Mutational analysis of different HCV regions (hypervariable region 1, non-structural protein 5A) may provide additional information about sensitivity/resistance to interferon-based antiviral therapy but have not yet introduced into clinical practice.     

Benefits and Limitations of Rate Adaptive Pacing Under Laboratory and Daily Life Conditions in Patients with Minute Ventilation Single Chamber Pacemakers

Rate adaptive pacing has been shown to improve hemodynamic performance and exercise tolerance during acute testing. However, there remain concerns about its benefit in daily life and possible complications incurred by unnecessary pacing. This double-blind crossover study compared the benefit of rate adaptive (SSIR) versus fixed rate (SSI) pacing under laboratory and daily life conditions in 20 rate incompetent patients with minute ventilation single chamber pacemakers (META II). The heart rate (HR) response during three different exercise tests (treadmill, bicycle ergomctry, walking test) was correlated with the Holler findings during daily life in either pacing mode. The maximal HR was significantly higher in the SSIR-mode compared to the SSI-mode, both during laboratory testing (treadmill: 123 ± 15 vs 93 ± 29 beats/min: ergometry: 118 ± 15 vs 89 ± 27 beats/min; walking test: 127 ± 9 vs 95 ± 26 beats/min, all P values < 0.01) as well as during daily life (Holter: 126 ± 13 vs 103 ± 24 beats/min, P < 0.01). On Holter, the average HR (71 ± 14 vs 71 ± 8 beats/min) and the percentage of paced rhythm (54 % vs 62%, SSI- vs SSIR-mode, P = NS) were not different in either mode. However, despite a 30% rate gain in the SSIR-mode, the exercise capacity remained unchanged, and only 38% of patients preferred the SSIR-mode. Minute ventilation pacemakers provide a physiological rate response to exercise. Irrespective of the protocol used, the findings of laboratory testing are comparable to those during daily life. However, patient selection for rate adaptive single chamber pacing should be made with caution, since the objective benefit of restoring normal chronotropy may subjectively be negligible for most patients.     

Is Antiarrhythmia Device Implantation Safe Under Dual Antiplatelet Therapy?

Background: Device implantations in patients on dual antiplatelet‐therapy (DA‐therapy) continue to rise. The aim of our study was to compile and analyze data on complications of antiarrhythmia device implantation under DA‐therapy. Methods: We prospectively collected data on all device implantations in our department from January 2008 until February 2009. The control group was comprised of patients on acetylsalicylic acid alone or no antiplatelet medication at all (318 subjects). The DA‐therapy group consisted of 109 patients of whom 71 were analyzed retrospectively (implantations from 2002 to 2007). Results: Procedure times were significantly longer in DA‐therapy patients receiving a pacemaker for the first time. In contrast, procedure times did not differ significantly between the two study groups for implantable cardioverter defibrillator (ICD) implantations and for pacemaker replacements. Fluid losses via drainage systems and drainage times were significantly increased in the DA‐therapy group as compared with the control group after pacemaker but not after ICD implantations. Importantly, there were no significant differences in complication rates, particularly the hematoma rate, between the DA‐therapy and the control group. Conclusions: When drainage systems are used, antiarrhythmia device implantation is safe and can be performed without significantly increased risk of clinically relevant hematoma in patients on continued DA‐therapy. (PACE 2010; 394–399)     

Are there physical risk factors for psychogenic non-epileptic seizures in patients with epilepsy?

Patients with epilepsy may have additional psychogenic non-epileptic seizures (PNES). It has been suggested that PNES are more common if patients with epilepsy are female, develop epilepsy later in life and have right-sided brain lesions. We examine whether these or other physical factors affect the risk of PNES in patients with epilepsy in a controlled study. METHODS: Ninety consecutive patients with PNES and concurrent epilepsy (PNES+E group) and 90 consecutive patients with epilepsy alone (epilepsy group) were compared with regard to the variables sex, age at onset of epilepsy, epilepsy type (focal/generalised), location and lateralisation of epileptogenic zone, aetiology of epilepsy, interictal epileptiform potentials, magnetic resonance imaging (MRI) abnormalities, neuropsychological (NPS) deficits and intelligence quotient (IQ). RESULTS: Female sex (P<0.001), abnormal visual memory (P=0.012), global NPS impairment (P=0.029), and low IQ category (P=0.005) were associated with a higher risk of PNES. Other variables did not differ between the groups. CONCLUSIONS: In patients with epilepsy, female sex, poor visual memory or global neuropsychological underperformance and low IQ are associated with an increased risk of PNES. MRI changes, epileptiform EEG abnormalities and location of epileptogenic zone do not show a predilection for one hemisphere.     

Diagnosis and treatment of latent infection with Mycobacterium tuberculosis

In clinical practice, latent infection with Mycobacterium tuberculosis is defined by the presence of an M. tuberculosis‐specific immune response in the absence of active tuberculosis. Targeted testing of individuals from risk groups with the tuberculin skin test or an interferon‐γ release assay is currently the best method to identify those with the highest risk for progression to tuberculosis. Positive predictive values of the immunodiagnostic tests are substantially influenced by the type of test, the age of the person who is tested, the prevalence of tuberculosis in the society and the risk group to which the person belongs. As a general rule, testing should only be offered when preventive chemotherapy will be accepted in the case of a positive test result. Preventive chemotherapy can effectively protect individuals at risk from the development of tuberculosis, although at least 3 months of combination therapy or up to 9 months of monotherapy are required, and overall acceptance rate is low. Improvements of the current generation of immunodiagnostic tests could substantially lower the number of individuals that need to be treated to prevent a case of tuberculosis. If shorter treatment regimens were equally effective than those currently recommended, acceptance of preventive chemotherapy could be much improved.