Computer-Assisted Reporting System for the Follow-up of Patients with Cardiac Pacemakers

The implantation of large numbers of permanent cardiac pacemakers carries with it the responsibility for continual reassessment of all aspects of patient management. Experience with more than 4,000 pacemaker implants and replacements since 1963 has led to the development of a comprehensive computer-assisted data collection, management, and reporting system for the follow-up of patients with cardiac pacemakers. Over a seven-year period, data forms have been developed for the detailed documentation of pre-operative, intraoperative and follow-up information. These were designed in the form of checklists suitable for direct computer entry using mark-sense document readers. Special emphasis has been placed on pre-operative indications, selection of appropriate pacing systems, reliable follow-up methodology, and monitoring the performance of various pulse-generators. This system makes possible the rapid computer production of hospital records and reports to involved physicians and can be used to schedule follow-up assessments as required. The information also can be used for hospital statistics, billing, research, and pacemaker registration at the provincial, state of federal level. Experience has shown that a computer-assisted methodology is the only practical means of providing adequate follow-up for a large group of patients. In addition, direct access to relevant information helps to create an environment in which essential research can be carried out in the face of demanding clinical practice.     

Circular dichroism and fluorescence spectroscopic analyses of a proline-rich glycoprotein from human parotid saliva

A proline-rich glycoprotein (PRG) was isolated from human parotid saliva and examined by circular dichroism and fluorescence spectroscopy. Addition of guanidine hydrochloride to PRG labeled with an extrinsic dansyl probe had no effect on the fluorescence spectra's 511 nm lambda-max location. Thermodynamic calculations supported the contention that PRG has no significant tertiary structure. Circular dichroism results for PRG were simulated by computer and a secondary structure composed of 70% random coil and 30%β-form conformation was predicted. Circular dichroism of PRG failed to detect either poly-L-proline type I or II structures. Deglycosylation of PRG had no measurable effect on the circular dichroism spectrum, indicating that the carbohydrate side chains had little influence on PRG secondary structure. Based upon mathematical calculations, β-turns were predicted around three glycosylated Asn residues of PRG. These collective data suggest that PRG is composed of a disordered polypeptide chain with at least three of the N-linked Asn residues participating in some type of β-turn.     

Secreted antigens of filarial nematodes: a survey and characterization of in vitro excreted/secreted products of adult Brugia malayi

We report here a broad analysis of the excretory/secretory (E/S) products of adult Brugia malayi, collected by in-vitro cultivation of the parasite. Culture media and conditions were optimized, and non-essential amino acids were found to be crucial for efficient protein synthesis under cell- and serum-free culture conditions. A close correlation was found between total protein secretion, phosphorylcholine-bearing antigen release and lactate production on each day of culture, indicating that E/S molecules are actively secreted. Parasites cultured in vitro take 2-3 days to adjust to the new environment, and show peak levels of secretion at days 3 and 4. The active secretion of phosphorylcholine by the parasite therefore justifies the measurement of this molecule as an indication of active infection, possibly reflecting total worm burdens. By comparing metabolically labelled E/S from male and female worms, several molecules of low mol. wt, namely 10,000, 13,000, 14,000 and 22,000, together with high mol. wt components of above 12,000 were found to be female specific. Tracing the origin of the E/S products, several molecules were also found to be associated with the surface. Among these, there are at least two glycoproteins, 29,000 and 51,000 of which the 29,000 molecule is a major surface protein. The immunogenicity of the E/S was examined and antigenic cross-reactivity was found with sera from most filarial infections but not with non-filarial nematodiases such as hookworm or Trichinella. However, two molecules of low mol. wt, 15,000 and 19,000, were not recognized by anti-Onchocerca sera and appeared to be potential Brugia-specific diagnostic molecules. Possible functional roles of the adult E/S products were examined but we could find no evidence of protease activity in the E/S or glutathione S-transferase activity in either the E/S or in whole somatic extract.     

Prolonged Asymptomatic Torsade de Pointes

Torsade de pointer is often associated with syncope, particularly when prolonged. We report a cane of prolonged asymptomatic torsade de pointes in a 68-year-old woman being treated with quinidine gluconate for paroxysmal atrial fibrillation. Ambulatory monitoring obtained one week after an increase in the daily qninidine dosage demonstrated one minute of polymorphous ventricular tachycardia. The patient remained entirely asymptomatic throughout the time of the arrhythmia. Therefore, a lack of symptoms in patients at risk for torsade de pointes may not exclude the presence of this arrhythmia.     

Control of iron absorption

Intestinal iron absorption plays an essential role in body iron homeostasis, although the mechansim by which iron moves across the cells of the intestinal epithelium and the way in which this process is regulated are poorly understood. Signals to alter iron absorption are received from the body by cells of the intestinal crypt and these signals are translated into an absortion response after the cells have migrated up the villus and differentiated into mature absorptive enterocytes. The intracellular iron concentration of the crypt cell may play an important role in the regulation of this process. Biochemical investigations on the mechanism of iron absorption have met with only limited success and a molecular understanding of this mechanism appears most likely to come from the identification of the genes affected in various inherited disturbances of iron absorption in several mammalian species.     

Improved Efficacy of Mode Switching During Atrial Fibrillation Using Automatic Atrial Sensitivity Adjustment

Automatic mode switching (AMS) during atrial fibrillation (AF) in a dual chamber pacemaker is dependent on the accurate detection of an atrial electrogram. As atrial amplitude is often reduced during AF compared with sinus rhythm, this may result in failure of the AMS and a rapid ventricular response. In addition, undersensing of AF may result in competitive atrial pacing that sustains AF. We hypothesize that the use of automatic atrial sensitivity adjustment (ASA) may enhance AF sensing in a dual chamber pacemaker. We studied the AMS response with and without ASA of the Marathon DDDR (model 294–09, Intermedics, Inc.) pacemaker in 10 patients with paroxysmal AF. Intracardiac atrial electrograms during sinus rhythm and induced AF were recorded onto an analog tape recorder. They were replayed into the pacemaker to assess the AMS response at various starting atrial sensitivities from 3.5 to 0.8 mV with ASA activated and without. Atrial amplitude was reduced during AF. The higher the initial atrial sensitivity, the better is the AMS response and the lower the incidence of AF undersensing. The percentage of AMS before ASA ranged from 2.1% at an atrial sensitivity 3.5 mV to 95.6% at highest sensitivity of 0.5 mV (P < 0.05). After 10 minutes of ASA, the AMS response was improved from 1.7% to 50.6% and from 9.5% to 50.9% at starting atrial sensitivities of 3.5 mV and 2.5 mV, respectively (P < 0.05 in both instances). Undersensing during AF was also significantly reduced after ASA from 70% to 10% at a sensitivity of 3.5 mV and from 33.8% to 10.8% at 2.5 mV. There was no increase in oversensing. In four patients with paroxysmal AF with an implanted pacemaker, ASA improved AMS response in patients with a low implant atrial amplitude. In conclusion, efficacy of mode switching and AF sensing are dependent on the programmed atrial sensitivity, which can be enhanced with the use of ASA, particularly when P wave sensing during AF is borderline.     

Effect of the Implantable Atrial Defibrillator on the Natural History of Atrial Fibrillation

INTRODUCTION: The purpose of our study was to evaluate the effect of repeated cardioversion with an implantable atrial defibrillator on the clinical outcome of patients with atrial fibrillation. METHODS AND RESULTS: The effects of the implantable atrial defibrillator on the total duration of atrial fibrillation, number of atrial fibrillation recurrences, and left atrial size were evaluated prospectively in 16 patients with atrial fibrillation (13 men and 3 women; mean age 58 +/- 11 years). Seven patients had no cardiovascular disease, 5 patients had hypertension, 3 patients had coronary heart disease, and 1 patient had congenital heart disease. Eight patients had paroxysmal atrial fibrillation for a mean duration of 80 +/- 61 months, and eight patients had persistent atrial fibrillation for a mean duration of 68 +/- 119 months. Except for one patient who received digoxin throughout the study, all patients received the same Class I or III antiarrhythmic agent throughout the study. The implantable atrial defibrillator successfully converted 50 (93%) of 54 spontaneous episodes of atrial fibrillation in 12 patients. During the initial 3 months of clinical follow-up, the atrial defibrillator documented 261 +/- 270 hours of atrial fibrillation compared with 126 +/- 172 hours (P = 0.01) during the subsequent 3 months. The left atrial size decreased from 4.4 +/- 0.7 cm at the time of atrial defibrillator implantation to 4.1 +/- 0.6 cm (P = 0.02) 6 months later. The number of atrial fibrillation recurrences did not change. These findings were observed in the absence of changes in drug therapy. No complications were observed. CONCLUSION: Restoration and maintenance of sinus rhythm in patients with atrial fibrillation by repeated cardioversion with an implantable atrial defibrillator was associated with a reduction in the total arrhythmia duration and a reduction in left atrial size. These results suggest that maintenance of sinus rhythm with the atrial defibrillator may reverse the remodeling process associated with atrial fibrillation.     

ACTIVATION OF EXTRACELLULAR SIGNAL-REGULATED KINASE IN HUMAN PROSTATE CANCER

PURPOSE: To investigate the level of expression, activation state, and functional significance of extracellular signal regulated kinase (ERK) in prostate cancer. MATERIALS AND METHODS: Human prostate tissue samples (n = 22) were obtained from patients undergoing radical prostatectomy for localized adenocarcinoma of the prostate (n = 16, age range 44 to 72 years) or normal prostate specimens (n = 6, age ranges 19 to 47 years) obtained from rapid autopsy. Immunoblots, in vitro kinase assays, and immunohistochemistry were used to determine the expression and activation state of ERK in human prostate cancer. RESULTS: Immunoblot and in vitro kinase assays demonstrated a 15-fold increase in ERK activation in prostate cancer specimens compared with normal human prostate tissue; however, ERK expression levels were only 1.3-fold higher in cancer. Immunohistochemical analysis demonstrated similar expression of ERK in cancer and normal tissues; however, phosphorylated ERK demonstrated greater intensity in the cancer specimens. Experiments conducted on a prostate cancer cell line demonstrated that EGF induced activation of ERK and cellular proliferation was partially inhibited by PD98059, a chemical inhibitor of the immediate upstream signaling component responsible of activation of ERK. CONCLUSIONS: Collectively, these data demonstrate a dramatic increase in ERK activation in prostate cancer compared with normal prostate tissue and suggest that inhibitors designed to target this signal transduction cascade might have therapeutic benefit in the treatment of prostate cancer.