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.     

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.     

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)     

Centrofacial lentiginosis

Forty patients with centrofacial lentiginosis have been studied. A greater than normal number of bone abnormalities, malformations due to dysraphia, endocrine dysfunctions, and neurological diseases, but not psychiatric impairment, were found.     

AMERICAN CUTANEOUS LEISHMANIASIS: INTERMEDIATE FORM

A man of Portuguese nationality presented with increased volume of the forehead and multiple pustules, which subsequently ulcerated. The pustules appeared progressively on the rest of the face and in the right scapular region during a period of 2 years.
Physical examination revealed multiple rounded ulcers of different sizes with erythematous and infiltrated borders covered by serosanguineous scabs on the face and right scapular region (Figs. 1 and 2).
The otorhinolaryngologic examination showed an infiltrate of granulomatous aspect in the anterior third of the septum. Posterior rhinoscopy was normal.
When the patient was first seen, complete hematology and hepatic and renal tests were normal. Additional tests included: HIV, nonreactive; venereal disease reference laboratory test, nonreactive; chest x-ray, normal; Montenegro skin test, 14 mm; purified protein derivative, 0 mm.
The skin biopsy revealed a granulomatous infiltrate with a dense infiltrate composed principally of plasmocytes, with few lymphocytes (Fig. 3).
A skin smear stained with Giemsa and culture of biopsy material in blood agar were positive for the presence of Leishmania. Antibodies against Leishmania measured in an ELISA test were strongly positive, titer 1:6400. Typing of the isolate using absorbed polyclonal antisera revealed Leishmania braziiiensis .
During hospitalization, the patient received systemic immunotherapy with a combined vaccine containing heat-killed Leishmania mexicana promastigotes and bcg ,^1,2 as well as chemotherapy with meglumine antimoniate in a dose of 50 mg/kg/day IM, two cycles of 20 days with an in-terval of 7 days of rest.
The patient presented clinical healing of his lesions without relapse during a 2 year follow up after completion of therapy.     

POSTOPERATIVE ANALGESIA WITH EXTRADURAL CLONIDINE

The analgesic effect of extradural clonidine was evaluated ina double-blind study. In the recovery room, following orthopaedicor perineal surgery 20 ASA I and II patients were allocatedrandomly to two groups. The extradural clonidine (EC) groupreceived clonidine 2 µg kg^–1 in isotonic salinesolution 15 µg ml^–1. The extradural saline (ES)group received the equivalent volume of plain isotonic salinesolution. Pain was evaluated by a visual analogue scale (VAS)at 15-min intervals for the first 2 h and subsequently at 30-minintervals for the following 4 h. Morphine 5 mg was given s.c.when patients complained of pain after extradural saline orclonidine. In the EC group, the mean (SD) maximum pain reliefwas 68.2 (24.1)% of the initial VAS score, but it was only 14.7(25.2)% in the ES group. The mean duration of analgesia, beforeinjection of morphine, was significantly longer in the EC group(210 (87) min) compared with the ES group (45 (27) min) (P <0.001). Drowsiness and moderate hypotension were observed inthe EC group.     

Increased hepatic microsomal activity after halothane anaesthesia in children

The effect of anaesthesia and surgery on microsomal enzyme activity was studied in 19 children aged 4-9 years, scheduled for tonsillectomy. The children were randomly allocated to either halothane or ketamine anaesthesia. Antipyrine clearance was measured before and 4 days after surgery by a salivary one-sample technique. Statistically significant (p less than 0.001) increases in antipyrine clearance was found in children who received halothane anaesthesia. The antipyrine clearance was increased by a mean of 26% 4 days after surgery, compared with a pre-operative control measurement. No significant change in antipyrine clearance was observed in children who received ketamine anaesthesia. There was also a significant difference in antipyrine clearance changes after surgery between the two groups (p less than 0.05). Halothane has enzyme-inducing properties after a single exposure in children, while a single dose of ketamine does not.