Contribution of myocardium responsible for ventricular tachycardia to abnormalities detected by analysis of signal-averaged ECGs.

BACKGROUND: Current methods of signal-averaged ECG analysis interrogate the terminal 40 msec of the QRS complex and/or the ST segment and have a low positive-predictive accuracy for detecting vulnerability to sustained ventricular tachycardia (VT). The extent to which abnormalities detected during these ECG intervals are generated by myocardial tissue responsible for VT has not been well defined. The purpose of this study was to determine when, during sinus rhythm, myocardium responsible for VT is activated. METHODS AND RESULTS: Three-dimensional ventricular activation maps were analyzed during sinus rhythm and during 10 VTs in eight patients with healed myocardial infarctions undergoing arrhythmia surgery for sustained monomorphic VT. The mechanism of VT was focal in five instances and macroreentrant in five. During sinus beats, myocardium responsible for all focal VTs activated 43 +/- 38 msec before the onset of the terminal 40-msec interval of the QRS complex. During sinus rhythm, activation of the myocardium critical to macroreentrant VT began 72 +/- 13 msec before the onset of the terminal QRS interval and in only three instances extended 2-25 msec into the terminal 40 msec of the QRS complex. Electrograms recorded during the ST segment represented late activation of epicardial sites overlying zones of infarction that were temporally and spatially remote from tissue critical to VT. CONCLUSIONS: Current methods of signal-averaged ECG analysis limiting interrogation to the terminal QRS/ST segment exclude detection of > 95% of the signals generated by myocardium responsible for sustained VT. These results establish a pathophysiological basis for expanding signal-averaged ECG analysis to include more of the cardiac cycle.

Improved detection of accessory pathways that bridge posterior septal and left posterior regions in the Wolff-Parkinson-White syndrome.

To improve the detection of accessory pathways that bridge the posterior septum and left posterior free wall, catheter maps of the coronary sinus from 21 patients (group I) who needed dissection of both these anatomic regions were compared with data from 23 (group II) with pathways confined to the posterior septum and from 9 (group III) with left posterior pathways. A decapolar catheter was used to map the coronary sinus in 0.5 to 1 cm steps. Intraoperative mapping was performed with a 16-electrode band. Catheter maps during atrial pacing and orthodromic supraventricular tachycardia were analyzed for the site of earliest activation and for differences in a new directional measure of conduction time between adjacent mapping sites. The site of earliest activation alone did not distinguish accessory pathways that bridged both anatomic regions, because 14 of 21 patients (66%) in group I would have been misclassified to either group II or III. In contrast, anterograde and retrograde directional conduction times distinguished patients in group I from those in groups II (p less than 0.01 to less than 0.0003) and III (p less than 0.04 to less than 0.0001). A multivariate model that incorporated the observed differences in directional interelectrode conduction times improved the identification of group I patients, with a sensitivity of 87% and a specificity of 90%. The results define new features in activation patterns measurable during catheter mapping that identify accessory pathways that bridge the posterior septum and left posterior free wall.

Adenosine versus verapamil in the treatment of supraventricular tachycardia: a randomized double-crossover trial.

The safety and efficacy of verapamil and adenosine in the acute termination of supraventricular tachycardia were compared in a randomized double-crossover trial. Of 32 eligible patients with either spontaneous or induced narrow complex tachycardia, seven (22%) patients experienced conversion to sinus rhythm with carotid sinus massage. The other 25 patients were randomly assigned to receive either adenosine (n = 14) or verapamil (n = 11). Relative drug efficacies were 100% for adenosine versus 73% for verapamil, p = NS. Adenosine given at less than or equal to 120 micrograms/kg caused conversion in 12 (86%) of 14 patients. The other two patients required 20 mg adenosine for conversion. After conversion the systolic blood pressure increased significantly in the adenosine group but not in the verapamil group. Reinitiation of tachycardia occurred in two (14%) of 14 patients randomized to the adenosine group. Serious adverse hemodynamic effects were observed in one (9%) of 11 patients randomized to verapamil. The incidence of conversion arrhythmias was similar in both treatment groups (adenosine 57%, verapamil 50%, p = NS).

Surgical correction of the Wolff-Parkinson-White syndrome.

The results of corrective surgery in 75 consecutive patients with Wolff-Parkinson-White (WPW) syndrome are reported. There were 47 male and 28 female patients with a median age of 27 years. Intraoperative mapping disclosed 88 accessory pathways, of which 83 were successfully divided at the primary operation without mortality. Two patients underwent successful reoperation at three days and two years respectively. Patient success rates were 93% and 96% for first and total operations. Complications, usually minor, occurred in 20 patients, including permanent pacemaker implantation in two. Surgical correction of WPW syndrome is recommended as a safe alternative to lifelong medical treatment.

Operations for Wolff-Parkinson-White syndrome.

Forty-six patients with symptomatic tachycardia underwent operations to divide 55 atrioventricular accessory pathways. Mean age was 29 years (range 11 to 63). Ten patients (22%) had associated cardiac disease, including two with a congenital diverticulum of the coronary sinus and six (13%) who had concomitant surgical procedures. A bipolar hand-held electrode was used in 22 operations, and simultaneous multisite mapping in the last 24 operations. Ten patients (22%) had multiple accessory pathways. A modified endocardial approach was used. The overall patient success rate was 93% with 91% to 93% of accessory pathways successfully divided. The perioperative morbidity was 17%. There were two reoperations. There were no early or late deaths. Patients have been followed up for a mean of 16 months. There were five recurrences of preexcitation (two early, three late). Two of these patients (both with a congenital diverticulum of the coronary sinus) had reoperation. One patient had late recurrence of atrial fibrillation. Operation for the Wolff-Parkinson-White syndrome has a high probability of success with a low operative risk.

Fludarabine: a review.

The new fluorinated adenine analog, fludarabine, has been tested for efficacy in many tumor types over the past ten years. Two other similar nucleoside analogs are currently available for commercial use. Cytarabine is used principally as an antileukemic agent, and vidarabine as an antiviral. Unlike vidarabine, fludarabine is resistant to deactivation by adenosine deaminase. Data from Phase I and II trials suggest that fludarabine is potentially effective in a number of leukemias, including acute lymphocytic leukemia, acute nonlymphocytic leukemia, and chronic lymphocytic leukemia (CLL). Unfortunately, the doses required to achieve adequate response in the acute leukemias (greater than 75 mg/m2) were above the maximum tolerated dose, resulting in intolerable granulocytopenia, thrombocytopenia, and a life-threatening neurotoxic syndrome. In CLL: however, the dose required to achieve a satisfactory response is well within tolerated limits. Long-term survival statistics are not yet available, but historical perspective strongly correlates response to other agents with increased survival times. Toxicities seen at dose regimens of 15-40 mg/m2/d for five consecutive days include somnolence, metabolic acidosis, confusion, fatigue, nausea, vomiting, increase in serum creatinine and aminotransferase concentrations, and pulmonary and hepatic abnormalities. Mild to severe hematologic toxicity has been observed at all dose levels.

Catheter ablation of the atrioventricular junction in patients with refractory atrial arrhythmias.

Twelve patients with refractory symptomatic atrial arrhythmias were evaluated for closed chest ablation and permanent pacemaker implantation. This was successful in nine of the 11 patients in whom ablation was attempted. Two of these nine patients required two separate ablative procedures. Three patients underwent open surgical ablation. Electrical ablation had failed in two of these patients and had not been undertaken in the remaining patient (inadequate His recording). The mean His amplitude and delivered energy levels were not significantly different between the two groups. Complications occurred in three patients and were minor. Because ventricular arrhythmias and late sudden death are recognised complications in a minority of patients undergoing closed chest ablation of the A-V junction it should be restricted to patients with symptomatic atrial arrhythmias who have failed maximal medical treatment.

Distribution of ultramicrobacteria in a gulf coast estuary and induction of ultramicrobacteria.

The abundance of ultramicrobacteria (i.e., bacteria that pass through a 0.2µm filter) in a subtropical Alabama estuary was determined during a 1-year period. Although phenotypic and molecular characterization indicated that the population of ultramicrobacteria was dominated byVibrio species, species ofListonella andPseudomonas were also abundant. Vibrios occurred with the greatest frequency in waters whose salinities were less than 14‰, and were the most abundant species of the total ultramicrobacterial population year-round, whilePseudomonas species were absent or considerably reduced during the winter months. The total number of ultramicrobacteria showed an inverse relationship to total heterotrophic bacteria as measured by colony-forming units (CFU)/ml and to water quality as measured by several parameters. Analysis by generic composition indicated that both salinity and temperature significantly affected the distribution of these organisms. Laboratory studies revealed that strains of vibrios under starvation in both static and continuous-flow microcosms could be induced to form cells that passed through 0.2 and/or 0.4µm filters. Cells exposed to low nutrients became very small; some grew on both oligotrophic (5.5 mg carbon/liter) and eutrophic (5.5 g carbon/liter) media; and some few cells grew only on oligotrophic media. By passing selected vibrio strains on progressively diluted nutrient media, cells were also obtained that were small, that passed through 0.4µm filters, and that could grow in oligotrophic media. These results suggest that ultramicrobacteria in estuaries (at least some portion of the population) may be nutrientstarved or low nutrient-induced forms of certain heterotrophic, eutrophic, autochthonous, estuarine bacteria.

Effect of nutrient deprivation on lipid, carbohydrate, DNA, RNA, and protein levels in Vibrio cholerae.

The response of Vibrio cholerae to low nutrient levels was determined by measuring the concentrations of lipids, carbohydrates, DNA, RNA, and proteins over a 30-day starvation period. Ultrastructural integrity was observed by transmission electron microscopy. Total lipids and carbohydrates declined rapidly within the first 7 days, while DNA and protein exhibited a more constant decline over the 30 days of starvation. In contrast, RNA showed little decrease upon starvation. Although neutral lipids were lost, the percentage of neutral lipids did not decline as rapidly as the phospholipids. Detectable levels of poly-beta-hydroxybutyrate disappeared completely by 7 days. Carbohydrate profiles revealed the relative loss of the five-carbon sugar ribose and N-acetylglucosamine and a relative increase in the total six-carbon sugars, especially glucose. Morphologically, ribosomes appeared to exhibit no structural change, while inclusion bodies and mesosomelike structures disappeared completely, and cell wall and membrane integrity was lost. The data suggest that V. cholerae differs somewhat from other marine vibrios in its response to low nutrients but shares some characteristics in common with them. The data also suggest that certain lipids and carbohydrates may provide the endogenous energy sources needed for dormancy preparation and cell maintenance under nutrient starvation.

Phospholipid ester-linked fatty acid profile changes during nutrient deprivation of Vibrio cholerae: increases in the trans/cis ratio and proportions of cyclopropyl fatty acids.

The phospholipid ester-linked fatty acids of 0-day-, 7-day-, and 30-day-starved cultures of Vibrio cholerae were compared. Statistically significant trends were noted in the fatty acid profiles as the cells starved. The amount of the cis-monoenoic fatty acids declined (e.g., 16:1 omega 7c: 0 day, 39%; 7 day, 18%; 30 day, 11%). In contrast, the saturated fatty acids, the cyclopropyl derivatives of the cis-monoenoic fatty acids, and trans-monoenoic fatty acids increased during starvation. For instance, the amounts of 16:1 omega 7t were: 0 day, 1%; 7 day, 13%; 30 day, 17%; which increased the trans/cis ratio for 16:1 omega 7 from 0.02 (0 day) to 0.70 (7 day) to 1.56 (30 day). This may be due to the reported high turnover rates of cis-monoenoic fatty acids of membrane phospholipids and the availability of enzymes for the metabolism of these isomers. During starvation-induced phospholipid loss, the cis-monoenoic fatty acids would, therefore, be preferentially utilized. The ability to either synthesize trans-monoenoic acids (which are not easily metabolized by bacteria) or modify the more volatile cis-monoenoic acids to their cyclopropyl derivatives may be a survival mechanism which helps maintain a functional (although structurally altered) membrane during starvation-induced lipid utilization. In addition, a trans/cis fatty acid ratio significantly greater than that reported for most bacterial cultures and environmental samples (less than 0.1) may be used as a starvation or stress lipid index. Such a ratio could help determine the nutritional status of ultramicrobacteria and other reported dormant cells in natural aquatic environments.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug precipitation within i.v. tubing: a potential hazard of chemotherapy administration.

Because relatively undiluted concentrations of drugs are maintained for prolonged periods in the Y-side arm of rapidly flowing iv infusions, we visually determined compatibilities of ten commonly used cancer chemotherapy drugs and four adjunctive drugs including droperidol, metoclopramide, furosemide, and heparin. Droperidol was found to be incompatible with furosemide, methotrexate, leucovorin, heparin, and 5-FU. Furosemide was incompatible with metoclopramide, doxorubicin, vincristine, and vinblastine in addition to droperidol. Doxorubicin was incompatible with heparin. If these drugs were administered sequentially into the Y-side arm of an iv infusion, precipitation would be expected with drug inactivation and possible drug embolization to the pulmonary circulation. Flushing the Y-side arm with a compatible solution after drug administration will prevent this problem.

Isolation and characterization of a new Cytophaga species implicated in a work-related lung disease.

A yellow-pigmented, gram-negative, gliding bacterium isolated from an industrial water spray air humidification system was implicated as a causative agent in several occurrences of lung disease with hypersensitivity pneumonitis-like symptoms. The bacterium, designated WF-164, lacked microcysts or fruiting bodies and had a DNA base composition of 34.8 mol% of guanine plus cytosine. Gliding, flexing, nonflagellated cells measuring 0.3 by 3.5 to 8.9 micron were observed by using light and electron microscopy. Tests to determine utilization of selected carbohydrates revealed an amylolitic, chitinoclastic, noncellulytic bacterium. A number of additional biochemical and physiological tests were performed. DNA homology studies detected a 77.8% similarity to Cytophaga aquatilis (ATCC 29551). Comparisons of cellular fatty acid and carbohydrate contents of isolate WF-164 with a Flexibacter sp., several Cytophaga spp., and Flavobacterium reference strains revealed similar patterns to that of C. aquatilis. On the basis of these characteristics, isolate WF-164 was identified as a new Cytophaga sp.

A Cytophaga species endotoxin as a putative agent of occupation-related lung disease.

A previous study suggested that a biologically active bacterial endotoxin was a putative agent of lung disease in a textile-producing facility. The endotoxin was isolated from the biomass growing in a chilled-water spray air humidification system. The bacterial flora of the air humidification system were isolated and taxonomically identified to the genus level. By using indirect immunofluorescence assays, a serologically reactive Cytophaga species was identified. A serologically reactive, biologically active (Limulus assay) endotoxin was purified from phenol extracts of the Cytophaga species. The endotoxin contained sugars, hexosamines, and lipids identical to those found in the humidifier biomass endotoxin. All subjects with biopsy-proven and suspected lung disease had antibodies directed toward the purified Cytophaga endotoxin. The data suggest that the Cytophaga endotoxin is the putative agent of lung disease in the textile facility.

Effect of Processing and Storing Oyster Meats on Concentrations of Indicator Bacteria, Vibrios and Aeromonas hydrophila.

Oyster meats were examined from three commercial processing plants at different stages of processing and storage for four standard indicator bacterial groups, five species of vibrios reported to be associated with shellfish associated gastroenteritis, and Aeromonas hydrophila . Processing reduced the overall microbial load, but the individual bacterial groups examined remained statistically the same throughout processing. Upon storage, the concentration of Vibrio parahaemolyticus significantly declined with a concomitant increase in levels of A. hydrophila , and the levels of all other Vibrio spp. remained statistically the same. The findings suggest that, while processing results in a cleaner appearing product, processing does not eliminate potentially pathogenic vibrios. However, processing and subsequent storage of oyster meats do not appear to increase the levels of vibrios.

Effects of nutrient deprivation on Vibrio cholerae.

Environmental and clinical strains of Vibrio cholerae were exposed to nutrient-free artificial seawater and filtered natural seawater microcosms for selected time intervals and examined for changes in cell morphology and number. Cells observed by transmission electron and epifluorescence microscopy were found to undergo gross alterations in cell morphology with time of exposure. The vibroid cells decreased in volume by 85% and developed into small coccoid forms surrounded by remnant cell walls. The initial number of cells inoculated into nutrient-free microcosms (culturable count and direct viable count) increased 2.5 log10 within 3 days, and even after 75 days the number of viable cells was still 1 to 2 log10 higher than the initial inoculum size. Nutrient-depleted coccoid-shaped cells were restored to normal size and assumed a bacillary shape within 3 h and began to divide within 5 h after nutrient supplementation. The increase in cell number and decrease in cell volume under nutrient-depleted conditions, as well as the rapid growth response after nutrient supplementation, may describe some of the survival mechanisms of V. cholerae in the aquatic environment.

Effects of storage on microbial loads of two commercially important shellfish species, Crassostrea virginica and Mercenaria campechiensis.

The effects of storage on the microbial load in two commercially important species of shellfish were examined. Oysters (Crassostrea virginica) were stored as shellstock, shucked meats, and fully processed meats at four temperatures for up to 21 days, and clams (Mercenaria campechiensis) were stored only as shellstock. The concentrations of most microbiological groups of organisms increased with the duration and temperature of storage in both shellfish species, although the increases were significantly lower in claims. Concentrations of Vibrio cholerae rose by approximately 1 log in oysters stored as shellstock after 7 days at 2 degrees C, and Lac+ vibrios increased 2 logs at 8 degrees C. Total counts of bacteria, fungi, coliforms, fecal streptococci, Aeromonas hydrophila, and clostridia were significantly higher in shucked oysters than in those stored as shellstock. Fecal coliforms were statistically the same, but V. cholerae, Vibrio parahaemolyticus, and the Lac+ vibrios were higher in oysters stored as shellstock. The concentrations of all microbial groups were higher in fully processed oysters than in shucked meats, with the exception of the vibrios, which showed no significant difference among the treatments. The results showed that although traditional methods of storing shellfish resulted in an overall increase in the microbial load, vibrio levels increased only in oysters stored as shellstock. Although fecal coliform and total bacterial counts did not correlate with those for vibrios in fresh oysters, strong correlations were observed in oysters stored for 7 days, suggesting that these indicators may be useful in monitoring oyster quality when meats are stored for a limited time as shellstock.

Relationship among fecal coliforms, Escherichia coli, and Salmonella spp. in shellfish.

The relationship of fecal coliforms, Escherichia coli, and Salmonella spp. was examined in freshly harvested and stored shellfish. In 16 of 40 freshly collected oyster samples, fecal coliform levels were above the recommended wholesale level suggested by the National Shellfish Sanitation Program (less than or equal to 230/100 g), and Salmonella spp. were present in three of these samples. Salmonella spp. were not, however, present in any sample containing less than 230 fecal coliforms per 100 g. Analysis of the data suggests that low fecal coliform levels in both fresh and stored oysters are good indicators of the absence of Salmonella spp., but that high levels of fecal coliforms are somewhat limited in predicting the presence of Salmonella spp. E. coli levels correlated very strongly with fecal coliform levels in both fresh and stored oysters and clams, suggesting that there is no advantage in replacing fecal coliforms with E. coli as an indicator of shellfish quality.