Synthesis of the very acid-sensitive Fmoc-Cys(Mmt)-OH and its application in solid-phase peptide synthesis

S-4-methoxytrityl cysteine was synthesized and converted into the corresponding Fmoc-Cys(Mmt)-OH by its reaction with Fmoc-OSu. As compared to the corresponding Fmoc-Cys(Trt)-OH, the S-Mmt-function was found to be considerably more acid labile. Quantitative S-Mmt-removal occurs selectively in the presence of groups of the tert butyl type and S-Trt by treatment with 0.5–1.0% TFA. The new derivative was successfully utilized in the SPPS of Tyr¹-somatostatin on 2-chlorotrityl resin. In this synthesis groups of the Trt-type were exclusively used for amino acid side-chain protection. Quantitative cleavage from the resin and complete deprotection was performed by treatment with 3% TFA in DCM–TES (95:5) for 30 min at RT. We observed no reduction of tryptophan under these conditions. © Munksgaard 1996.     

Radiofrequency Ablation of Symptomatic but Benign Ventricular Arrhythmias

Two cases are presented where ablation of severely symptomatic ventricular arrhythmias not responding to medical therapy was accomplished with radiofrequency current application. After a routine programmed stimulation protocol, a quadripolar ablation catheter with a 4-mm tip was advanced percutaneously into the left ventricle in one case and into the right ventricle in the second case; and after precise pace mapping, the arrhythmogenic focus was successfully ablated using radiofrequency current. The postablation ambulatory recording revealed virtual eradication of ventricular ectopy in both cases. In conclusion, in severely symptomatic cases of "benign" ventricular arrhythmias, radiofrequency ablation offers an effective therapeutic alternative.     

Occupational transmission of HIV in health care workers: A review

Health care workers have a small but real risk of acquiringHIV infection as a result of occupational exposure. In thispaper, we review all reports in the scientific literature from1984 through to December 1993 of confirmed and probable casesof HIV seroconversion after a specific occupational exposure.A total of 64 confirmed cases have been reported, 24 in Europe,36 in the USA and 4 in other countries. Most seroconversionshave resulted from percutaneous exposure (91%) to AIDS patients(62%), usually caused by hollow bore needlestick injuries inflictedduring blood drawing procedures. Almost all seroconversionshave been detected within 6 months of exposure (94%) and haveusually been preceded by an episode of acute illness (73%).Ten seroconversions have occurred in spite of partial or completecourses of zidovudine prophylaxis. An additional 113 probablecases have been reported, 75 in the USA, 35 in Europe and 3in other countries. Aggregating the results of the prospectivestudies carried out, it is calculated that the risk of seroconversionfollowing percutaneous exposure is 0.33% or 3 in 1000 exposures(95% Cl: 0.21–0.52%), while the risk following mucocutaneousexposure is much lower (0.04%, 95% Cl: 0.006–0.31%). Thedocumented failure of zidovudine prophylaxis following occupationalexposure in a number of instances indicate its effect is, atbest, only partial; furthermore, exposure to source patientswho have been receiving the drug may lead to transmission ofzidovudine-resistant strains of HIV. Risk factors for occupationalexposure to HIV and for transmission, given that an exposurehas occurred, are discussed.     

Abnormal Automaticity as Mechanism of Atrial Tachycardia in the Human Heart—Electrophysiologic and Histologic Correlation:

Abnormal Automaticity in Human Atrium, introduction: A 32-year-old woman was operated upon because of drug refractory atrial tachycardia.
Methods and Results: Electrophysiologic study was performed prior to operation. During surgery, epicardial mapping of the electrical activity of the left atrium was performed. The left atrial appendage was resected and studied in a tissue bath. Thereafter, histologic examination was performed. Polarity of the P wave in the surface ECG suggested that the tachycardia originated high in the left atrium. Epicardial mapping disclosed earliest activation in the apex of the left atrial appendage. Intracellular recordings from surgical specimen made at the site of origin, which was marked during surgery, revealed cells with phase 4 depolarization at cycle lengths ranging from 360 to 540 msec. Exit block prevented spread of activation from the spontaneously firing cells to surrounding tissue. Histology showed that spontaneous activity arose in an area with abnormal cells-characterized by an amorphous, pale eosinophilic staining cytoplasm and absence of nuclei-surrounded by normal myocytes.
Conclusion: The observations indicate that the mechanism of the atrial tachycardia was based on abnormal automaticity in an area consisting of a conglomeration of normal and abnormal myocytes.     

2-Chlorotrityl chloride resin

The esterification of 2-chlorotrityl chloride resin with Fmoc-amino acids in the presence of DIEA is studied under various conditions. High esterification yields are obtained using 0.6 equiv. Fmoc-amino acid/mmol resin in DCM or DCE, in 25 min, at room temperature. The reaction proceeds without by product formation even in the case of Fmoc-Asn and Fmoc-Gln. The quantitative and easy cleavage of amino acids and peptides from 2-chlorotrityl resin, by using AcOH/TFE/DCM mixtures, is accomplished within 15-60 min at room temperature, while t-butyl type protecting groups remain unaffected. Under these exceptionally mild conditions 2-chlorotrityl cations generated during the cleavage of amino acids and peptides from resin do not attack the nucleophilic side chains of Trp. Met, and Tyr.     

In Vivo Ventricular Lesion Growth in Radiofrequency Catheter Ablation

While radiofrequency catheter ablation has proved highly effective in the treafment of various supravenfricular tQchyarrhythmias, resulls in the trentment of ventricular tachycardia invite improvement. Knowledge of lesion growth in vivo might improve understanding of this discrepancy. So far only information from in vitro and in vivo studies using a small 2 mm tip eiectrode is available. Growlh of ventricular radiofrequency lesions created with a 4 mm ahlalion electrode was studied in 11 closed-chest dogs. Endocardia] ablations were performed at 31 left and 35 right ventricuiar sites at a power setting of 25 Watts and 5, 10, 20, 30 or 60 seconds pulse duration. Macroscopic and histopathologic lesion examination were performed after one week survival. Mean lesion volume increased from 52 mm³ after 5 seconds pulse duration to a maximum 388 mm³ and approximately 7 mm depth after 30 seconds. Lesions were prolate spheroid in form, with a sparing of subendocardial myocardium and maximum lesion diameter at some millimeters depth. Results indicate that catheter positioning at no more tlian 7 mm from the target is required for successful ablation. Due to lesion geometry, subendocardial targets demand even more exact catheter positioning, while subepicardial substrates may not be ammenable to ablation if ventricular wall thickness exceeds 7 mm at the ablation site. Repeated pulses at adjacent sites may be required for ablation of extended arrhytbmogenic areas. Volume at 5 seconds was only approximately 15% of mature lesions. Therefore, the use of a short'test pulse after careful mapping may be useful to pinpoint the most appropriate site for ablation in discrete pathways.     

Differential Effect of Biventricular and Right Ventricular DDD Pacing on Coronary Flow Reserve in Patients With Ischemic Cardiomyopathy

CRT and Coronary Flow Reserve. Background: Cardiac resynchronization therapy (CRT) has become a mainstay in heart failure management. There are also indications that upgrading of existing pacemakers to CRT systems may be of benefit. The aim of this study was to assess the effect of biventricular (BiV), compared with right ventricular (RV), pacing, on coronary flow reserve (CFR), in patients with ischemic cardiomyopathy. Methods and Results: From our database of heart failure patients implanted with BiV pacemakers, 20 patients (10 responders and 10 non‐responders to CRT) were randomly selected. Left anterior descending artery coronary flow reserve was measured invasively, under BiV and RV pacing, using intracoronary adenosine to induce hyperemia. In all the 20 patients, there was a significant difference in the pairwise comparison between CFR recorded during BiV and RV pacing (mean difference 0.15, 95% confidence interval 0.07–0.23, P = 0.001). When comparing responders to non‐responders, there was a significant difference as to the effect of BiV, compared with RV, pacing on CFR: mean difference (BiV minus RV CFR) was 0.26 ± 0.06 (95% confidence interval 0.13–0.39; P = 0.002), while in non‐responders the difference was 0.04 ± 0.03 (95% confidence interval ?0.02 to 0.10; P = 0.168). Conclusion: BiV pacing is overall associated to higher CFR, compared with RV DDD pacing. This difference is almost exclusively attributable to the beneficial effect of CRT on coronary flow reserve in CRT‐responders. This effect may contribute to the beneficial action of resynchronization in the failing heart and can be viewed in the context of reports of the usefulness of upgrading RV pacemakers to CRT systems. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1233‐1239, November 2010)     

Successful use of infliximab in a patient with neuro‐Behçet’s disease

Behçet′s disease (BD) is a systemic vasculitic disorder of unknown aetiology characterised by recurrent oral and often genital ulcers, which may be associated with ocular, cutaneous, articular, neurological or vascular involvement. We report a 52‐year‐old woman diagnosed of neuro‐BD who was treated with infliximab with a dramatic response to this treatment.