Programmed Ventricular Stimulation Using Tandem Versus Simple Sequential Protocols

The objective was to determine whether two commonly used ventricular stimulation protocols, one more complex than the other, produced concordant results. If such were the case, the simpler protocol would streamline activities in clinical electrophysiology laboratories. Background: Two programmed ventricular stimulation protocols were compared. (1) With the tandem method, the first extrastimulus (S₂) is moved stepwise to the effective refractory period and then moved out 50 msec; the second extrastimulus (S₃) is then decremented until it fails to capture; S₂ and S₃ are then decremented in a semialternating (tandem) fashion so that both continue to capture. When S₂ reaches the refractory period + 10 msec and S₃ fails to capture, S₃ is then moved out 50 msec, and S₄ is decremented as described for S₃. (2) With the simple sequential method, the first extrastimulus (S₂) is decremented stepwise to the refractory period, and then moved out 10 msec to assure capture; S₃ is then similarly decremented to the refractory period and then moved out 10 msec; and S₄ is then similarly decremented. Methods: This was a prospective, randomized, crossover, consecutive series study. Both protocols were tested in each patient on the same day in randomized order. Results: There were 84 matched studies. Fifty-six patients provided data from baseline electrophysiological studies, and 28 of these provided additional data during drug trials. There was a 93% concordance between the two methods, including tbe primary outcomes of inducibility of clinical arrhythmias, inducibility of nonclinical arrhythmias, and noninducibility (P < 0.001). Discordances were few and evenly distributed between the two protocols (P = NS). Results were similar for baseline studies and drug trials. The simple sequential method required less time to perform (P ≤ 0.01). Conclusions: Tandem and simple sequential protocols provide concordant results. No advantage could be demonstrated for the more complex tandem method.     

Biochemical and Pharmacological Characteristics of 3-Butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline,a New Proton-pump Inhibitor,in Rabbit Gastric Microsomes and in Rats

We have investigated the properties of the newly synthesized proton-pump inhibitor, 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline (YJA20379–6), on gastric mucosal proton-pump (H⁺/K⁺-ATPase) activity, gastric acid secretion and gastroduodenal lesions in experimental rats. YJA20379–6 markedly inhibited H⁺/K⁺-ATPase activity in rabbit isolated gastric mucosal microsomes, confirming its classification as a proton-pump inhibitor. The inhibitory efficacy of YJA20379-6 on the proton pump was approximately 14-times higher than that of omeprazole at pH 7.4. YJA20379–6 given intraduodenally had a potent inhibitory effect on gastric secretion in pylorus-ligated rats (ED50 22.9 mg kg^?1) but was less active than omeprazole. Pretreatment of rats with YJA20379-6 dose-dependently protected the gastric mucosa from damage induced by water-immersion stress, indomethacin and absolute ethanol, and the duodenal mucosa from damage induced by mepirizole. Repeated administration of YJA20379-6 also dose-dependently accelerated the spontaneous healing of acetic acid-induced gastric ulcers. These results suggest that YJA20379-6 has potent anti-secretory and anti-ulcer effects which are exerted by suppression of H⁺/K⁺-ATPase activity in gastric parietal cells. YJA20379–6 might be useful for the clinical treatment of peptic ulcer diseases.     

Squamous cell carcinoma in a frost-bite scar

The development of carcinoma after various forms of scarring injury is well documented in the literature. Such tumours have been recorded in the lung and liver as well as the skin. Only rarely does cold injury lead to subsequent tumour formation. We report a case of squamous cell carcinoma in a frost-bite scar with some comments, especially on scar cancer in other organs, and the possible long-term side-effects of cryosurgery.     

Primary sclerosing cholangitis: An experience from India

Primary sclerosing cholangitis (PSC) is considered to be rare in India. The aim of the present study was to investigate the incidence, clinical profile and outcome of PSC seen in a tertiary care centre. Over a period of 10 years (July, 1984-June, 1994) 18 patients of PSC were diagnosed at cholangiography (14 patients by endoscopic retrograde cholangiopancreatography, two patients by percutaneous transhepatic cholangiography and two patients by both methods). The presence of secondary causes, such as choledocholithiasis, biliary tract surgery, congenital biliary tract anomalies, cholangiocarcinoma and pancreatic diseases, were excluded. These patients were evaluated retrospectively with respect to their clinical presentation, radiological findings, presence of associated idiopathic ulcerative colitis (IUC), treatment instituted and outcome. The mean (±s.d.) age at diagnosis of PSC was 39.0 (±16.1) years with a male: female ratio of 1.57:1. Nine (50%) patients had associated IUC. The diagnosis of IUC preceded that of PSC in all but one case. Fifteen (83.3%) patients had cholestatic jaundice at presentation, while three (16.7%) patients had asymptomatic rise of alkaline phosphatase. Three (16.7%) patients had recurrent cholangitis and five (27.8%) patients developed portal hypertension during the course of the disease. At cholangiography, intrahepatic radicles were involved in all and extrahepatic radicles in 12 (66.6%) cases. Patients were managed with steroids (n= 7), colchicine (n= 3), ursodeoxycholic acid (UDCA; n= 2) and methotrexate (n= 1), along with symptomatic measures. Mean duration of follow up available in 11 (61%) patients was 20.1 months (range: 1 month-8 years). Four (36.4%) patients died. Steroids and colchicine did not have any effect while the one patient on UDCA and one on methotrexate showed improvement. In conclusion, in India PSC does not seem to be a rare entity. Its clinical profile and outcome are somewhat similar to those seen in Western countries.     

Light and transmission-electron microscopy study of enamel organ cells in germectomized human third mandibular molars

Abstract— Using nine serially sectioned germectomized mandibular third molars it was possible to examine light microscopical (LM) and transmission-electron microscopical (TEM) features of maturing human enamel organ cells. The degree of enamel mineralization was estimated by quantitative imbibition studies in polarized light. It was possible to distinguish between three progressive stages of enamel mineralization. The most advanced stage was characterized by external enamel porosity. In the least advanced stages the enamel porosity appeared more extensive beneath a less porous surface layer. Ruffle- and smooth-ended ameloblasts were identified corresponding to the maturing enamel. Smooth-ended ameloblasts were the most frequently observed. However, no preferences for one of the two cell types could be observed in relation to the different stages of enamel mineralization. The maturing human enamel organ cells broadly revealed the same characteristics with respect to morphology features, intracellular organization, and junctional complexes as described in the maturation zone of the rat incisor enamel organ. Our findings therefore add to the view that the basic pattern of amelogenesis is identical in human and rat incisor enamel.     

Application of arylsulphonyl side-chain protected arginines in solid-phase peptide synthesis based on 9- fluorenylmethoxycarbonyl amino protecting strategy

One of the main problems still hampering solid-phase peptide synthesis using orthogonal protection strategies based on the 9-fluorenylmethoxycarbonyl amino protecting group is the difficult removal of currently used arginine arylsulphonyl guanidino protecting groups. Poor acid lability of 4-methoxy-2,3,6-trimethylbenzenesulphonyl-protected arginine has led to the popularity of the newer 2,2,5,7,8-pentamethylchroman-6-sulphonyl guanidino protecting group. This group was initially believed to have lability to trifluoroacetic acid, the reagent commonly used to simultaneously deprotect peptides and detach them from the synthesis resin, comparable to tert.-butyl and trityl type protecting groups used for the protection of other peptide side-chain functionalities. In a comparison of three established cleavage/deprotection mixtures we have shown that this is not always the case, particularly in multiple arginine peptides. We have found that only hard-acid deprotection with trimethylsilyl bromide reliably removed both arylsulphonyl guanidino protecting groups from a variety of arginine-containing peptides.