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Biomedical subjects

L Watkins

Publications and source records attributed to L Watkins.

At least 55 records · Page 3Linked to original sources

Distribution of a monoclonal antibody-recognized protective protein immunogen on the outer membranes of Pasteurella multocida rabbit isolates.

The distribution of a monoclonal antibody (MAb)-recognized protective protein immunogen on the outer membrane of 153 Pasteurella multocida rabbit isolates was determined by dot blot (DB) analysis. MAb 1608 reacted with 36 (24%) of the 153 clinical isolates. The DB-positive clinical isolates expressed capsular antigens A, D, and nontypable and somatic antigens 2, 3, 10, 12, 15, and nontypable. Western blot (immunoblot) analysis with adsorbed and eluted MAb 1608 confirmed that the antigenic determinant identified was located on the cell surface. With MAb 1608 as a probe for antibody-accessible radioimmunoassay, 31 of 36 DB-positive P. multocida rabbit isolates were shown to have surface-exposed and antibody-accessible antigenic determinants, while 44 of 44 DB-negative isolates were negative by antibody-accessible radioimmunoassay. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed DB-negative P. multocida isolates both with (6 of 13, 46%) and without (7 of 13, 54%) the 37.5-kilodalton protein. This study establishes that the protective antigenic determinant of the 37.5-kilodalton outer membrane protein is present in 24% of rabbit clinical isolates tested and is detectable in P. multocida strains distributed among the major somatic types (3, 10, 12, and 15) and the capsular types (A and D) commonly isolated from rabbits in North America.

Animals↗

Predictors of perioperative mortality in patients with unstable postinfarction angina.

Factors associated with increased operative mortality in patients with postinfarction angina have not been defined. Two hundred twenty-five patients underwent urgent coronary artery bypass grafting from 1982 through 1986. One hundred sixty-two men and 63 women averaged 62 years of age (range, 35-87 years). Operative mortality was 5.3%. To assess the predictors of perioperative mortality, 16 variables were evaluated by univariate and multivariate analyses. Significant independent predictors of perioperative mortality were the presence of a transmural anterior myocardial infarction (p less than 0.0005) and the need for preoperative intra-aortic balloon pumping for angina or congestive heart failure (p = 0.009). All perioperative mortalities (12 patients) occurred in this subset (anterior myocardial infarction, intra-aortic balloon pumping, or both) that included 101 patients. The mean follow-up period was 27.8 months (range, 1-69 months). There were 11 late deaths, resulting in an actuarial survival of 92 +/- 2%, 91 +/- 2%, 88 +/- 2.6%, and 88 +/- 4% at 1,2,3, and 4 years, respectively. Ninety-six percent of survivors were assigned to New York Heart Association Class I or II for congestive heart failure, and 96% were assigned to Class I or II for angina. Urgent coronary artery bypass grafting can be performed in patients with unstable postinfarction angina with acceptable mortality, although a significant increase in risk exists for patients with preoperative transmural anterior myocardial infarction, intra-aortic balloon pumping, or both.

Adult↗

Success of chronic defibrillation and the role of antiarrhythmic drugs with the automatic implantable cardioverter/defibrillator.

Because the automatic internal cardioverter defibrillator's long-term ability to reduce arrhythmic mortality in patients with ventricular tachycardia/fibrillation is unknown, it is important to determine whether the threshold for defibrillation changes over time. Serial defibrillation thresholds were measured in 23 patients over a mean replacement time of 24.8 +/- 7.5 months. In all cases the lead system was a superior vena cava coil to a left ventricular epicardial patch. The defibrillation threshold for the entire group increased from 12.3 +/- 4.7 J to 16.9 +/- 5.9 J (p less than 0.05). Striking increases in the defibrillation threshold were seen in the subgroup of patients taking amiodarone (from 10.9 +/- 4.3 J at implantation to 20.0 +/- 4.7 J at replacement, p less than 0.05). Defibrillation threshold decreased in patients taking no antiarrhythmic drugs or taking class I agents. Thus, the increase in mean defibrillation threshold was the result of an increase in the patients taking amiodarone. These data suggest that at initial implantation lead systems associated with the lowest defibrillation threshold should be used and the defibrillation threshold should be measured at generator change to guarantee an adequate margin of safety.

Aged↗

Ten-year analysis of the Björk-Shiley standard aortic valve.

Long-term performance characteristics of the Björk-Shiley standard aortic valve were determined by analyzing the follow-up of 514 patients undergoing operation between 1971 and 1981. Cumulative follow-up was 2,601 patient-years (average, 5.3 +/- 3.8 years); 53% (238/452) of hospital survivors have been followed more than 5 years. Valve-related complications expressed as both actuarial event-free percents (+/- standard error at 10 years) and first-event linearized determinations (percent per patient-year) occurred at the following rates: thromboembolism, 82 +/- 3 and 2.3 +/- 0.3, respectively; anticoagulant-related hemorrhage, 60 +/- 4 and 5.6 +/- 0.5; prosthetic valve endocarditis, 94 +/- 2 and 0.8 +/- 0.2; valve thrombosis, 97 +/- 1 and 0.4 +/- 0.1; reoperation, 94 +/- 2 and 0.6 +/- 0.2; valve failure, 82 +/- 4 and 1.6 +/- 0.2; and composite valve-related morbidity and mortality, 46 +/- 4 and 8.8 +/- 0.2. Overall survival was 72 +/- 2% at 5 years and 55 +/- 3% at 10 years; valve-related complications accounted for 22% of the late deaths. Although no instance of structural valve failure could be identified, 25% of valve-related complications resulted from valve failure, of which 67% were fatal. By 10 years, 54% of patients had experienced at least one form of major valve-related complication, 16% of which proved fatal. The Björk-Shiley standard aortic valve has late valve-related complications similar to other existing mechanical prostheses that have been subjected to long-term analysis.

Adult↗

Pathologic findings related to the lead system and repeated defibrillations in patients with the automatic implantable cardioverter-defibrillator.

The purpose of the present study was to examine at autopsy the effect of multiple defibrillations on the myocardium and the pathologic consequences of short- and long-term placement of the intravascular and interpericardial leads of the automatic implantable cardioverter-defibrillator. Twenty-five patients were examined at autopsy; 8 of them underwent lead implantation only and 17 received both leads and the automatic implantable cardioverter-defibrillator. Twelve patients (48%) died of ventricular tachycardia or ventricular fibrillation; seven (28%) died of other causes. Acute pericarditis occurred in all patients, resulting in a localized, progressive fibrosis around the apical patch lead without giving rise to pericardial restriction. Thrombus formation was associated with the superior vena cava spring electrode in four patients (17%) and the right ventricular rate-sensing electrode in one patient (4%). Asymptomatic pulmonary emboli occurred in two patients (8%). In one patient who underwent defibrillation 59 times, superior vena cava changes consisted of vein wall destruction, fibrosis and thrombus formation. Pathologic changes under the apical patch related to defibrillation were observed in seven patients; two of these had fewer than 5 defibrillations, one had 8 defibrillations and four had 21 to 74 defibrillations. These changes consisted of contraction band necrosis in four patients, vacuolar cytoplasmic clearing and loss of myocytes confined to the myocardium under the patch electrode in five patients who had multiple defibrillations. The observed pathologic changes were estimated to affect less than 2% of the total myocardial mass. Thus, the automatic implantable cardioverter-defibrillator lead system and multiple defibrillations result in localized myocardial injury confined to the tissue under the patch electrode.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Automatic implantable cardioverter defibrillator/permanent pacemaker interaction: loss of pacemaker capture following AICD discharge.

A 78-year-old man treated with amiodarone for recurrent ventricular tachycardia, had sequential placement of a bipolar VVI pacemaker and an automatic implantable cardioverter defibrillator (AICD). During defibrillation threshold testing, there was failure to capture of the pacer in the post-shock period. The time of failure to capture appeared energy-related: the greater the energy delivered, the longer the failure to capture. Careful attention will be necessary in constructing combined AICD/pacemaker units.

Aged↗

Prostaglandin involvement in the responses of the rabbit eye to water-soluble marihuana-derived material.

Both anticoagulants (heparin and streptokinase) and non-steroidal anti-inflammatory compounds (aspirin and indomethacin) were used against a water-soluble derivative of marihuana, MDM. While the anticoagulants had no effect on the ocular effects of MDM, both aspirin and indomethacin altered the time course and effected the MDM-induced reduction of intraocular pressure. The usual initial hypertensive effect of intravenous MDM was eliminated and the later intraocular pressure fall occurred earlier as well as being inhibited by about 35 to 50%. Assay for prostaglandins revealed that intravenous MDM (3.86 micrograms) caused a marked rise in PGE2 concentration of the aqueous humor and iris-ciliary body during the first hour or two after administration of MDM, but normal values occurred at 4, 6, and 8 hours when the intraocular pressure is reduced by up to 60%. Following intravitreal MDM (0.002 microgram), however, the PGE2 levels remained unchanged over 24 hours, despite the induction of a fall in intraocular pressure between 14 and 18 hours which lasts for many hours. Prostaglandin appears to be involved in the hypertensive phase of intraocular pressure change after intravenous MDM injection; and, while the fall in intraocular pressure may contain a component partially mediated by prostaglandins, there is no evidence that intravitreal MDM induces any effect on prostaglandin levels. The involvement of prostaglandins, therefore, in the mediation of MDM-induced ocular hypotensive effects is apparently small.

Animals↗

The effects of age on outcome after coronary bypass surgery.

To study the effects of increasing age on outcome after coronary artery bypass grafting (CABG), 684 patients who underwent CABG from 1980 to 1985 were entered into a noncurrent prospective study. Patients were matched by date of operation and placed into three groups according to age: (1) 70 and older, (2) 55 to 69, or (3) less than 55. In addition to intraoperative and postoperative data collected on all patients, follow-up was obtained on 97% of the patients at a mean of 30 +/- 16 months. Older patients were more often female (p less than .002), and white (p less than .001) and had more preexisting cerebrovascular disease (p less than .0001), peripheral vascular disease (p less than .001), unstable angina (p less than .0001), and longer mean bypass pump times (p less than .001). Older patients had a higher hospital mortality (9.3% vs 2.2%), suffered more complications, including stroke, wound infection, reoperation for bleeding, need for intropic drug support, and prolonged ventilation, and had longer mean postoperative hospital stays (14 vs 9 days, p less than .0001). After discharge, mortality rates were similar in all groups, as was recurrence of symptoms and degree of rehabilitation. While patient age at operation significantly influenced hospital mortality and morbidity, this appeared to be a consequence of the greater frequency of risk factors in patients over 70 years of age. In addition, late follow-up failed to demonstrate any significant differences based on age alone in survival or functional status among patients undergoing CABG.

Activities of Daily Living↗

Comparative analysis of mechanical and bioprosthetic valves after aortic valve replacement.

Comparative long-term performance characteristics of Björk-Shiley mechanical and bioprosthetic valves were analyzed for patients undergoing aortic valve replacement between 1976 and 1981. A total of 419 patients received either a standard Björk-Shiley (n = 266) or bioprosthetic (porcine, n = 126, or pericardial, n = 27) aortic valve. Cumulative patient follow-up was 1,705 patient-years; the average patient follow-up was 4.1 +/- 2.7 years. Survival data were obtained for all but 11 patients (97% complete follow-up) up to 9 years after operation. Survival at 5 years was 81% +/- 4% (+/- standard error) for Björk-Shiley and for bioprosthetic valve recipients. Valve failure in the Björk-Shiley group was predominantly due to valve-related mortality and did not result from structural failure. Patients with bioprosthetic valves experienced valve failure as a result of prosthetic valve endocarditis and intrinsic valve degeneration. Although patients with bioprostheses experienced a lower incidence of valve-related morbidity than Björk-Shiley valve recipients (p less than 0.03), no difference could be demonstrated in the incidence of valve-related mortality or valve failure at 5 years between bioprosthetic and Björk-Shiley valves. Mortality rate from valve failure was higher for Björk-Shiley (86%, 12/14) than bioprosthetic valves (36%, 5/14) (p less than 0.01).

Actuarial Analysis↗

Treatment of malignant ventricular arrhythmias with endocardial resection and implantation of the automatic cardioverter-defibrillator.

Although ventricular resection guided by endocardial mapping has been a successful treatment for drug-refractory ventricular arrhythmias, 20 to 30 percent of patients still have postoperative sustained ventricular tachycardia or sudden death. To improve the outcome of the procedure, we implanted an automatic cardioverter-defibrillator in conjunction with endocardial resection in 28 patients, all of whom had had previous myocardial infarctions and between one and five cardiac arrests. There were three perioperative deaths. During follow-up of 8 to 51 months (mean, 25), 4 of the 25 survivors had recurrences of hypotensive ventricular tachycardia, which in all instances were automatically terminated by the implanted device. One patient, whose automatic cardioverter-defibrillator was not functional, died suddenly. We conclude that patients undergoing mapping-directed endocardial resection can be provided with additional protection against recurrent ventricular tachyarrhythmias or sudden death by implantation of an automatic cardioverter-defibrillator.

Adult↗

Management of the prolonged QT syndrome and recurrent ventricular fibrillation with an implantable automatic cardioverter-defibrillator.

Two patients with the prolonged QT syndrome and recurrent ventricular tachyarrhythmias are presented, one of them refractory to combination antiarrhythmic drug therapy and bilateral stellate ganglion blockade. We implanted and tested in vivo an automatic cardioverter-defibrillator to provide a cardiac monitoring system with the capability of delivering a 25 J electrical discharge to the heart if rapid ventricular tachycardia or ventricular fibrillation is detected. Arrhythmia induction in the electrophysiology laboratory confirmed the appropriate recognition of the arrhythmias in each patient, with prompt discharge of the device and resultant termination of the tachycardias. We suggest that implantation of such a device may provide an effective adjunct to antiarrhythmic drug therapy in the management of infrequent, but potentially lethal, ventricular arrhythmias occurring in patients with the prolonged QT syndrome.

Adult↗

Failure of 2-deoxy-D-glucose to stimulate feeding in deermice.

Deermice (Peromyscus maniculatus) did not increase their food intake above baseline following treatment with 2-deoxy-D-glucose (2DG, 500 or 1000 mg/kg). They did eat more following food deprivation or treatment with insulin at a high dose (100 U/kg). House mice (Mus musculus) showed hyperphagia to 2DG, low dose of insulin (5 U/kg) and deprivation.

Animals↗

Stroke following coronary artery bypass grafting: a ten-year study.

To identify possible risk factors for the occurrence of stroke during coronary artery bypass grafting (CABG), the cases of 3,279 consecutive patients having isolated CABG from 1974 to 1983 were reviewed. During this period, the risk of death fell from 3.9% to 2.6%. The stroke rate, however, fell initially but then rose from 0.57% in 1979 to 2.4% in 1983. Adjustment of these data for age clearly demonstrated that the risk of stroke has increased largely because of an increase in the mean age of patients undergoing CABG procedures. A case-control study involving all 56 stroke victims and 112 control patients was used to identify those risk factors significantly associated with the development of stroke in univariate analysis: increased age (63 versus 57 years in stroke patients and controls, respectively; p less than 0.0001); preexisting cerebrovascular disease (20% versus 8%; p less than 0.03); severe atherosclerosis of the ascending aorta (14% versus 3%; p less than 0.005); protracted cardiopulmonary bypass time (122 minutes versus 105 minutes; p less than 0.005); and severe perioperative hypotension (23% versus 4%; p less than 0.0001). Other variables not found to correlate with postoperative stroke included previous myocardial infarction, hypertension, diabetes mellitus, lower extremity vascular disease, preoperative left ventricular function, and intraoperative perfusion techniques. Elderly patients who have preexisting cerebrovascular disease or severe atherosclerosis of the ascending aorta or who require extensive revascularization procedures have a significantly increased risk of postoperative stroke.

Age Factors↗

Coronary artery bypass grafting in women. A ten-year perspective.

Between January 1974 and December 1983, 3279 patients have undergone isolated coronary artery bypass (CAB) grafting at the Johns Hopkins Hospital. There were 639 women in this group. Women represented 18 to 22% of the patients having isolated CAB grafting throughout the 10-year period, except in 1976 when only 13% of the CAB patients were women. Mean age-at-operation for women has increased from 53.9 to 61.1 years since 1974, and was higher than the mean operative age of men during each of the 10 years. Although the oldest woman undergoing CAB grafting in 1974 was 64 years old, the eldest in 1983 was 84 years old. Except for an older mean age-at-operation for women and a higher incidence of unstable angina prior to surgery, the only other significant difference in the clinical status of female versus male CAB patients, detected by a case control analysis, was the smaller body surface area of women compared to men. Although operative mortality was significantly greater for women during most of this review period, mortality was similar during 1983 (2.6% for men versus 2.4% for women), in spite of a significantly higher incidence of unstable angina in the female group (54% for women versus 35% for men). The improved survival noted following coronary bypass grafting in women, which occurred in spite of the advancing age of the female group, supports an aggressive approach to surgical intervention in women with severe coronary artery disease.

Age Factors↗

Clinical experience with the automatic implantable defibrillator.

Since February 1980, worldwide, over 400 survivors of sudden arrhythmic death have been treated with the automatic implantable defibrillator. Recently, the device has been further improved; it is now a cardioverter-defibrillator (AICD), able to treat ventricular tachycardias as well as ventricular fibrillation. There are two defibrillating electrodes which are used also for waveform analysis; one is located in the superior vena cava, the other is placed over the cardia apex. A third bipolar right ventricular electrode serves for rate counting and R-wave synchronization. When ventricular fibrillation occurs, a 25-joule pulse is delivered; when ventricular tachycardia faster than a preset rate is detected, the discharge is R-wave synchronized. Special batteries can deliver over 100 shocks or provide a three-year monitoring life. Implantation of the device can be achieved through a thoracotomy or by a subxiphoid or a subcostal approach. Thus far, the longest follow-up period has been 58 months. Actuarial analysis shows the one-year mortality attributed to arrhythmias reduced to less than 2%. Thus, the automatic cardioverter-defibrillator can reliably identify and correct potentially lethal ventricular tachyarrhythmias, leading to a substantial increase in survival in properly selected high-risk patients.

Death, Sudden↗

Enhancement of deoxyguanosine kinase activity in human lung fibroblast cells infected with human cytomegalovirus.

Studies were conducted to establish the relationship between deoxyguanosine kinase activity and human cytomegalovirus (HCMV) infection. Using both PAGE and isoelectric focusing techniques, extracts from untreated and infected cells were examined for deoxyguanosine kinase activity. The analyses resulted in identical migration rates for deoxyguanosine kinase activity in both infected and uninfected extracts. These data and kinetic studies based on apparent Km values suggest that HCMV enhanced a cellular kinase activity rather than coded for a virus specific enzyme. Furthermore, our results indicated that infected cells, like normal fibroblasts, contain two deoxyguanosine kinase activities, one of mitochondrial and another of cytosolic origin. Of particular interest was the observation that HCMV infection caused an enhancement of the mitochondrial enzymatic activity while the cytosolic activity showed no change. Deoxycytidine kinase activity which is associated with cytosolic deoxyguanosine kinase was unaffected by HCMV infection.

Cells, Cultured↗

The treatment of malignant ventricular arrhythmias with combined endocardial resection and implantation of the automatic defibrillator: preliminary report.

Fourteen patients with refractory ventricular tachyarrhythmias were treated with combined endocardial resection and implantation of the automatic defibrillator. There were 11 men and 3 women with a mean age of 53 years (range, 41 to 58 years). All patients had coronary artery disease; the mean ejection fraction was 26%, and the mean number of cardiac arrests was 2.6. Programmed electrical stimulation induced sustained ventricular tachycardia in 13 patients and nonsustained ventricular tachycardia in 1. Operative endocardial mapping in the 13 patients with sustained ventricular tachycardia demonstrated a septal focus of early activation in 9 patients and a nonseptal site in 4. Following resection, sustained ventricular tachycardia could not be reinduced. There was 1 operative death. Programmed electrical stimulation performed one month after operation induced ventricular tachycardia in 5 patients, but tachycardia could not be induced in the other 8 survivors. The longest follow-up was 32 months; the average was 17 months. There were 2 late deaths. One patient died of myocardial infarction and 1 of pulmonary edema following a routine cholecystectomy. In another patient, late ventricular tachycardia developed but was automatically terminated by the implanted defibrillator. These results suggest that endocardial resection combined with implantation of the automatic defibrillator may offer the greatest protection yet available to patients with malignant ventricular tachyarrhythmias.

Adult↗