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.     

Optimized Pulse Durations Minimize the Effect of Polarity Reversal on Defibrillation Efficacy with Biphasic Shocks

There are conflicting results on the effect of polarity change on the defibrillation efficacy of biphasic shocks possibly caused by different shock durations. The goal of the present study was to investigate the influence of polarity reversal on defibrillation efficacy for different biphasic shock durations in a porcine animal model. In eight anesthesized pigs using a transvenous/submuscular lead system DFTs for 4 phase 1 durations were determined: 8.1 ms, 6 ms, 3.8 ms and 1.7 ms. The phase 1/phase 2 ratio was constant at 60%/40%. For cathodal shocks, the defibrillation coil in the right ventricular apex was the cathode during phase 1 and for anodal shocks it was the anode. For both polarities, the strength-duration curve revealed a DFT minimum at 3.8 ms (cathodal shocks: 21.3 +/- 6.4 J, P < 0.001; anodal shocks: 21.9 +/- 8 J, P = 0.05). For anodal shocks and phase 1 durations of 1.7, 3.8, and 6 ms there was no significant difference of the stored energy at the DFT compared to cathodal shocks. In contrast, significantly lower DFTs were observed for anodal shocks with a phase 1 duration of 8.1 ms (28.8 +/- 6.4 J compared to 33.1 +/- 5.9 J for cathodal shocks, P = 0.006). The effect of lower defibrillation energy requirements with polarity reversal depends on the total biphasic shock duration; for the pulse duration with the lowest DFT, polarity reversal does not increase defibrillation efficacy of biphasic shocks.     

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.     

Influence of Renal Sympathetic Denervation on Quality of Life

Background

Therapy‐resistant arterial hypertension causing psychosocial stress and is associated with cardiovascular morbidity and mortality. The aim of the study was to evaluate the effect on quality of life (QoL) in patients with resistant hypertension undergoing renal sympathetic denervation (RSD).

Methods and Results

We analyzed responses to the SF‐36 Quality of Life Questionnaire provided by patients with resistant arterial hypertension after RSD. Thirty consecutive patients from 2 centers were included in this study, from October 2011 until February 2012. The phone interview was performed after the 3‐month follow‐up. A significant reduction (26 ± 13.5 mmHg) in systolic blood pressure (BP) was detected at the 3‐month follow‐up (142.0 ± 15.1 mmHg vs 168.0 ± 13.7 mmHg; P < 0.001). Seventy‐five percent of the patients indicated that their health situation was a lot better (better, 21%; equal to, 4%) 3 months after RSD compared to the time before the therapeutic procedure. Furthermore, the majority of patients felt full of pep (always, 29%; mostly, 58%; quite often, 8%; sometimes, 4%), and full of energy (always, 25%; mostly, 54%; quite often, 16.7%; sometimes, 4.2%) after the procedure. Recipients of RSD indicated that they felt more light and healthy, and nearly all recipients (93%) described a loss of anxiety and indisposition.

Conclusions

This investigation revealed that sufficient BP reduction by RSD and time following therapeutic success lead to significant improvements in patient QoL. (J Interven Cardiol 2013;26:536‐541)

     

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.     

Risk of Ventricular Arrhythmias in Survivors of Myocardial Infarction

The most recent studies have made it clear that the prognosis of asymptomatic post-MI patients has significantly improved in the last two decades. Holter monitoring as well as a low LyEF still is an important method for the risk stratification in the thrombolytic era of patients with post-MI. Patients with normal noninvasive tests do have a good prognosis. The electrophysiological stimulation seems to be the clinically most valuable single method to predict arrhythmic events. However, as an invasive procedure it is not suitable as a screening test for a large cohort. The stepwise risk stratification technique using first noninvasive followed by invasive procedures seem to be most suitable and effective for identifying asymptomatic infarct survivors which incidence of arrhythmic events is as high as the recurrence rate of patients who had been resuscitated from ventricular fibrillation. Consequently, prophylactic implantation of a defibrillator in asymptomatic MI patients, whose positive predictive value is around 30% becomes more and more interesting.