Central Clinical Research Issues in Electrophysiology: Report of the NASPE Committee

DOMANSKI, M.J., et al. : Central Clinical Research Issues in Electrophysiology: Report of the NASPE Committee. This article contains the results of an attempt by appointed members of the North American Society of Pacing and Electrophysiology to define the research frontier in electrophysiology and suggest areas of study as an aid in setting the research agenda.     

Molecular forms of gastrin in peptic ulcer: comparison of serum and tissue concentrations of G17 and G34 in gastric and duodenal ulcer subjects

We have studied the relationships between the main molecular forms of gastrin (G17 and G34) in the serum, antral and duodenal mucosa of duodenal (DU) and gastric (GU) ulcer patients. Fasting serum G17 was similar in both DU and GU (about 6 pmol/l) and in both groups increased about three-fold with feeding. In contrast, basal serum G34 was significantly higher in GU (29 pmol/l) than in DU (12 pmol/l) and the peak post prandial increase over basal of G34 was also higher in GU (57 pmol/l) compared with DU (10 pmol/l). In sharp contrast, in the same groups of DU and GU patients mean total antral gastrin concentrations were similar (about 12 nmol/g), and in both groups 95% of antral gastrin was G17, most of the remainder being G34. In both groups total duodenal gastrin concentrations were about 20% those in antral mucosa and about 70% of duodenal gastrin was attributable to G34. The higher serum G34 in GU could therefore be explained by increased secretion of duodenal gastrin, but further work is needed to examine whether there might also be preferential secretion of antral G34 in GU, or a difference in the metabolism (or volume of distribution) of gastrin variants in GU and DU.     

Subchronic Toxicity of Orally Administered (Gavage and Dosed-Feed) Theophylline in Fischer 344 Rats and B6C3F2 13 Mice

Subchronic Toxicity of Orally Administered (Gavage and Dosed-Feed)Theophylline in Fischer 344 Rats and B6C3F, Mice.COLLINS, J.J., ELWELL, M. R., LAMP, J. C, IV, MANUS, A. C, HEATH, J. E.,and MAKOVEC, G. T. (1988). Fundam Appl Toxicol. 11, 472—484.Theophylline, a methylated xanthine closely resembling caffeineand theobromine, is a widely used pharmaceutical agent for thetreatment of respiratory disorders and certain acute cardiovascularconditions. The National Toxicology Program has conducted 13-weeksubchronic toxicity studies in F344 rats and B6C3F₁ mice (10animals/group) following administration of theophylline viathe diet or by gavage. Administration of theophylline in thefeed (0, 1000, 2000, and 4000 ppm) resulted in no mortalityor body weight effects in F344 rats, but did induce periarteritisof the arteries adjacent to mesenteric lymph nodes and the pancreas,particularly arterioles in the latter. Also observed in ratsdosed with theophylline via the diet was an increased severityof chronic nephropathy in males, especially at the high dose.Administration of theophylline at the same concentrations inthe feed to B6C3Fi 2 mice resulted in no mortality, but terminalbody weights were significantly decreased in all dosed groups.An increased incidence of hepatocellular glycogen depletionwas observed in male and female mice, and this change is believedto represent a physiological alteration exacerbated by the administrationof theophylline. Administration of theophylline by gavage toF344 rats (0, 37.5, 75, and 150 mg/kg) resulted in the earlydeath of one high-dose male and female and significantly decreasedor increased terminal body weights of high-dose males and females,respectively. Similar to the results of the dosed-feed study,male and female rats receiving theophylline by gavage demonstrated a dose-related increase in the incidence and severityof perivascular inflammation of mesen teric arteries. Gavageadministration of theophylline to B6C3F, mice (0, 75, 150, and300 mg/kg) resulted in the early death of all high-dose femalesand 3/10 high-dose males and significant depres sion of terminalbody weights in high- and mid-dose males and low-dose females.As in the dosed feed study, the primary histopathologk changein the mouse subchronic gavage study was hepatocel lular glycogendepletion, although in this case it was seen only in females.In summary, the major target organs for orally administeredtheophylline in 13-week subchronic toxicity studies appear tobe the mesenteric arteries in F344 rats and the liver in B6C3F₁mice. On the basis of organ weight changes and/or minor histopathologiceffects, many other tissues were also affected, particularlythe kidneys in dosed-feed male rats and the uterus in gavage-dosedfemale rats.     

Implantation of a Nonthoracotomy Defibrillator Using a Second Defibrillator Patch in the Abdominal Pocket

Successful implantation of a biphasic nonthoracotomy implantable cardioverter defibrillator may not be achieved with a conventional system. We describe a successful device implantation using a pectoral and abdominal patch electrode system.