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Biomedical subjects

J W Mason

Publications and source records attributed to J W Mason.

At least 37 records · Page 2Linked to original sources
PubMed1995

A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators.

BACKGROUND: Myocarditis is a serious disorder, and treatment options are limited. This trial was designed to determine whether immunosuppressive therapy improves left ventricular function in patients with myocarditis and to examine measures of the immune response as predictors of the severity and outcome of disease. METHODS: We randomly assigned 111 patients with a histopathological diagnosis of myocarditis and a left ventricular ejection fraction of less than 0.45 to receive conventional therapy alone or combined with a 24-week regimen of immunosuppressive therapy. Immunosuppressive therapy consisted of prednisone with either cyclosporine or azathioprine. The primary outcome measure was a change in the left ventricular ejection fraction at 28 weeks. RESULTS: In the group as a whole, the mean (+/- SE) left ventricular ejection fraction improved from 0.25 +/- 0.01 at base line to 0.34 +/- 0.02 at 28 weeks (P < 0.001). The mean change in the left ventricular ejection fraction at 28 weeks did not differ significantly between the group of patients who received immunosuppressive therapy (a gain of 0.10; 95 percent confidence interval, 0.07 to 0.12) and the control group (a gain of 0.07; 95 percent confidence interval, 0.03 to 0.12). A higher left ventricular ejection fraction at base line, less intensive conventional drug therapy at base line, and a shorter duration of disease, but not the treatment assignment, were positive independent predictors of the left ventricular ejection fraction at week 28. There was no significant difference in survival between the two groups (P = 0.96). The mortality rate for the entire group was 20 percent at 1 year and 56 percent at 4.3 years. Features suggesting an effective inflammatory response were associated with less severe initial disease. CONCLUSIONS: Our results do not support routine treatment of myocarditis with immunosuppressive drugs. Ventricular function improved regardless of whether patients received immunosuppressive therapy, but long-term mortality was high. Patients with a vigorous inflammatory response had less severe disease.

Adult↗
PubMed1995

Cost of initial therapy in the Electrophysiological Study Versus ECG Monitoring trial (ESVEM).

BACKGROUND: Patients randomized to either serial electrophysiological testing (EPS) or serial Holter monitoring (HM) to guide antiarrhythmic therapy for life-threatening ventricular arrhythmias had equivalent rates of mortality and arrhythmia recurrence in the ESVEM study. This report analyzes the effects of EPS, HM, and clinical factors on the charges for initial evaluation and management of patients with life-threatening ventricular arrhythmias. METHODS AND RESULTS: Ten of 14 clinical centers participating in ESVEM provided bills from the initial hospitalization for randomized patients. Predictors of charges (1991 dollars) were analyzed by linear regression after logarithmic transformation. Initial hospital charge data were obtained for 286 patients randomized in ESVEM (88% of patients eligible for this substudy, 59% of all ESVEM patients). Patients with charge data were somewhat more likely to be older, to be female, and to have failed previous antiarrhythmic drug therapy at study entry and were less likely to have a drug predicted effective after randomization. Mean overall hospital charges were $35,986 (SD, $32,628) with a median of $24,532 (interquartile range, $16,126 to $43,593). Prerandomization patient characteristics generally had insignificant effects on charges, with the exception of presentation with resuscitated sudden death (28% increase in charges, P = .01) and heart failure (26% increase in charges, P = .02). Patients randomized to EPS had higher mean charges for evaluation ($42,002 versus $29,970, P = .0015) as well as more drug trials (3.0 versus 2.1, P = .0001) and a longer hospital stay (19.6 versus 13.9 days, P = .0007). In a multivariate regression model, failure to find an effective drug (P = .0001), the number of drug trials (P = .0001), and resuscitated sudden death as the presenting arrhythmia (P = .0001) were the only independent predictors of higher initial charges. CONCLUSIONS: (1) Initial hospital charges are significantly higher for EPS-guided than HM-guided therapy. (2) The higher charges for EPS-guided therapy were due to a greater number of drug trials and a lower probability of finding an effective drug. (3) Failure to find an effective drug, a larger number of drug trials, and a history of resuscitated sudden death independently predict higher charges.

Aged↗
PubMed1995

Pharmacokinetics and regional electrophysiological effects of intracoronary amiodarone administration.

BACKGROUND: The reason for the delay in onset of the electrophysiological effects and antiarrhythmic efficacy of amiodarone is not clear. The relation between the development of the electrophysiological effects of amiodarone and its myocardial concentration is unknown. We therefore examined the time course of development of electrophysiological effects during intracoronary infusion of amiodarone and related these changes to myocardial concentrations. METHODS AND RESULTS: Amiodarone (0.139 mg/min) or normal saline was infused for 10 hours into the proximal left anterior descending coronary artery of 24 open-chest dogs. Nineteen animals received intracoronary amiodarone and 5 received normal saline (control group). Ten of the 19 that received amiodarone underwent electrophysiological study (amio-EPS group). Sixteen of the 19, including 7 from the amio-EPS group, underwent pharmacological study (PS group). In the amio-EPS group during pacing at a cycle length of 300 ms, changes in conduction velocities in drug-exposed myocardium referenced to nonexposed myocardium at 1 hour of infusion were -3.7% in the longitudinal direction (P = NS) and -7.2% in the transverse direction (P < .05); at 3 hours, -12.9% (P < .05) and -9.1% (P < .05); and at 9 hours, -32.9% (P < .02) and -31.7% (P < .01). These changes were dependent on amiodarone concentration (R2 = .83). There was also an obvious rate-dependent effect that was more pronounced for transverse conduction velocities. This effect was also dependent on amiodarone concentration. In the PS group, amiodarone levels in the drug-exposed myocardium increased from a mean of 5.95 microgram/g at 15 minutes of infusion to 188.88 microgram/g at the 10th hour. This increase was time dependent (R2 = .91). In the nonexposed myocardium, amiodarone levels were always low and increased minimally over time from a mean of 2.68 to 14.45 microgram/g. This increase was also time dependent (R2 = .97). CONCLUSIONS: Selective intracoronary amiodarone infusion resulted in selective drug accumulation and concomitant time-dependent reduction of myocardial conduction velocity. There was a significant correlation between the extent of reduction of conduction velocity and myocardial amiodarone concentration but not coronary arterial or systemic concentration. Repolarization was not significantly altered.

Amiodarone↗
PubMed1995

The Myocarditis Treatment Trial: design, methods and patients enrollment.

The Myocarditis Treatment Trial was a multicentre clinical trial conducted to determine the efficacy of immunosuppressive therapy for treatment of biopsy-documented myocarditis, and to improve understanding of the immunological mechanisms in the development of myocarditis. Thirty-one centres screened 2305 patients with unexplained heart failure, and 2233 patients underwent an endomyocardial biopsy which provided adequate tissue for diagnosis. Those with a positive biopsy and a left ventricular ejection fraction (LVEF) less than 45% were randomly assigned to receive immunosuppressive therapy plus conventional drug therapy for congestive heart failure (66 patients) or conventional therapy only (45 patients) for 24 weeks. For 28 additional weeks all patients received conventional therapy only. In addition to diagnostic and clinical data, serum and myocardial tissue for immunological marker analysis and histopathologic evaluation were collected at baseline and at 12, 28 and 52 weeks after randomization. The primary analysis of efficacy was designed as a comparison of the mean increase in LVEF at week 28 between treatment limbs. Secondary objectives were to evaluate survival differences, and changes in the histopathology of the disease and immunological markers. Randomized patients were relatively young (mean age, 42.0 years +/- 13.8 standard deviation (sd) and entered the Trial with a mean LVEF percent of 24.3 +/- 10.1 sd) and mean exercise treadmill duration of 9.4 (+/- 5.3 sd) minutes. The incidence of biopsy-documented myocarditis was low (9.6%). The analyses of outcome and immunological data are reported elsewhere.

Adolescent↗
PubMed1995

Viability of Vibrio vulnificus in Association with Hemocytes of the American Oyster (Crassostrea virginica).

Certain indigenous estuarine bacteria, such as Vibrio vulnificus, may cause opportunistic human infections after consumption of raw oysters or exposure of tissues to seawater. V. vulnificus is known to be closely associated with oyster (Crassostrea virginica) tissues and is not removed by controlled purification methods, such as UV light-assisted depuration. In fact, when live shellfish are subjected to controlled purification, the number of V. vulnificus cells can markedly increase. A review of previous studies showed that few workers have examined mechanisms in oysters which may influence the persistence of V. vulnificus in shellfish, such as the fate of V. vulnificus following phagocytosis by molluscan hemocytes. The objectives of this study were to define the intracellular viability and extracellular viability of V. vulnificus during the phagocytic process and to study the release of specific lysosomal enzymes. The viability of a virulent estuarine V. vulnificus isolate with opaque morphology was compared with the viability of a translucent, nonvirulent form, the viability of Vibrio cholerae, and the viability of Escherichia coli in phagocytosis experiments. Our results showed that the levels of phagocytosis and bactericidal degradation of the opaque V. vulnificus isolate were less than the levels of phagocytosis and bactericial degradation of the translucent morphotype. These findings indicate that encapsulation may contribute to resistance to ingestion and degradation by hemocytes. The rates of intracellular death of V. cholerae and E. coli exceeded the rate of intracellular death of the opaque V. vulnificus isolate, even though the ingestion or uptake rates did not differ significantly. The levels of lysozyme activity and acid phosphatase activity were not significantly different in hemocyte monolayers inoculated with V. vulnificus.

Journal Article↗
PubMed1995

Low urinary cortisol excretion in Holocaust survivors with posttraumatic stress disorder.

OBJECTIVE: The authors' objective was to compare the urinary cortisol excretion of Holocaust survivors with posttraumatic stress disorder (PTSD) (N = 22) to that of Holocaust survivors without PTSD (N = 25) and comparison subjects not exposed to the Holocaust (N = 15). METHOD: Twenty-four-hour urine samples were collected, and the following day, subjects were evaluated for the presence and severity of past and current PTSD and other psychiatric conditions. RESULTS: Holocaust survivors with PTSD showed significantly lower mean 24-hour urinary cortisol excretion than the two groups of subjects without PTSD. Multiple correlation analysis revealed a significant relationship between cortisol levels and severity of PTSD that was due to a substantial association with scores on the avoidance subscale. CONCLUSIONS: The present findings replicate the authors' previous observation of low urinary cortisol excretion in combat veterans with PTSD and extend these findings to a non-treatment-seeking civilian group. The results also demonstrate that low cortisol levels are associated with PTSD symptoms of a clinically significant nature, rather than occurring as a result of exposure to trauma per se, and that low cortisol levels may persist for decades following exposure to trauma among individuals with chronic PTSD.

Age Factors↗
PubMed1994

Predicting antiarrhythmic drug efficacy.

For years, electrophysiologic testing was regarded as the best way to select effective pharmacologic therapy. But now it appears that Holter monitoring is just as accurate--as well as simpler, safer, and cheaper. Nevertheless, most patients eventually will need an electrophysiologic study because of the high rate of arrhythmia recurrence.

Anti-Arrhythmia Agents↗
PubMed1993

Implications of the ESVEM trial for use of antiarrhythmic drugs that prolong cardiac repolarization.

In both the Cardiac Arrhythmia Suppression Trial (CAST) and the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial, class I antiarrhythmic drugs did not appear to perform well, although in the latter trial the class III agent sotalol performed better than 6 class I agents. The results have led some to conclude that class III drugs are now preferred for treatment of ventricular arrhythmias. However, there are a number of reasons why such a conclusion may not be fully justified on the basis of these 2 trials. The data do suggest a need for a critical appraisal and reorientation of drug therapy of life-threatening ventricular arrhythmias.

Animals↗
PubMed1993

A comparison of electrophysiologic testing with Holter monitoring to predict antiarrhythmic-drug efficacy for ventricular tachyarrhythmias. Electrophysiologic Study versus Electrocardiographic Monitoring Investigators.

BACKGROUND: Invasive electrophysiologic study and noninvasive Holter monitoring (in conjunction with exercise testing) have both been used to evaluate the efficacy of antiarrhythmic drugs in patients with sustained ventricular tachycardia and in survivors of cardiac arrest. We directly compared these two approaches to the prediction of drug efficacy. METHODS: A total of 486 patients who had documented ventricular tachyarrhythmias that were inducible during electrophysiologic study and 10 or more premature ventricular complexes per hour during Holter monitoring were randomly assigned to undergo serial testing of antiarrhythmic-drug efficacy by electrophysiologic study or Holter monitoring. The patients received up to six drugs in random order until one was predicted to be effective either in suppressing inducible arrhythmia (in the electrophysiologic-study group) or in suppressing premature ventricular complexes (in the Holter-monitoring group). The patients were then followed for recurrences of arrhythmia or death. RESULTS: In the electrophysiologic-study group, 108 of 242 patients (45 percent) received a prediction of efficacy, as compared with 188 of 244 patients (77 percent) in the Holter-monitoring group (P < 0.001). Over a six-year follow-up period, there were 150 recurrences of arrhythmia and 46 deaths among the 296 patients receiving drugs predicted to be effective. Thirty-four of the deaths were from arrhythmic causes, and eight were from cardiac causes. There was no significant difference between the two study groups in the actuarial probabilities of these events. The risk of a recurrence of arrhythmia was significantly lower in patients who received sotalol than in those who received other antiarrhythmic drugs, and the risk was lower in those who had not previously failed to respond to antiarrhythmic drugs than in those who had. CONCLUSIONS: Although Holter monitoring led to predictions of antiarrhythmic-drug efficacy more often than did electrophysiologic study in patients with sustained ventricular tachyarrhythmias, there was no significant difference in the success of drug therapy as selected by the two methods.

Actuarial Analysis↗
PubMed1993

A comparison of seven antiarrhythmic drugs in patients with ventricular tachyarrhythmias. Electrophysiologic Study versus Electrocardiographic Monitoring Investigators.

BACKGROUND: The relative efficacies of various antiarrhythmic drugs in the treatment of ventricular tachyarrhythmias are not well known. This study examined the effectiveness of imipramine, mexiletine, pirmenol, procainamide, propafenone, quinidine, and sotalol in patients with ventricular tachyarrhythmias who were enrolled in the Electrophysiologic Study versus Electrocardiographic Monitoring trial. METHODS: Patients were randomly assigned to undergo serial testing of the efficacy of the seven antiarrhythmic drugs by one of two strategies: electrophysiologic study or Holter monitoring together with exercise testing. The seven drugs were then tested for efficacy in random order in patients who were eligible to receive them. The frequencies of predictions of drug efficacy and of adverse drug effects during the initial drug titration were tabulated for all 486 randomized subjects. Patients received long-term treatment with the first antiarrhythmic drug that was predicted to be effective on the basis of drug testing. Recurrences of arrhythmia, deaths, and adverse drug effects during long-term follow-up were recorded for the 296 patients in whom an antiarrhythmic drug was predicted to be effective. RESULTS: In the electrophysiologic-study group, the percentage of patients who had predictions of drug efficacy was higher with sotalol (35 percent) than with the other drugs (16 percent, P < 0.001). There was no significant difference among the drugs in the Holter-monitoring group. The percentage of patients with adverse drug effects was lowest among those receiving sotalol. The actuarial probability of a recurrence of arrhythmia after a prediction of drug efficacy by either strategy was significantly lower for patients treated with sotalol than for patients treated with the other drugs (risk ratio, 0.43; 95 percent confidence interval, 0.29 to 0.62; P < 0.001). With sotalol, as compared with the other drugs combined, there were lower risks of death from any cause (risk ratio, 0.50; 95 percent confidence interval, 0.30 to 0.80; P = 0.004), death from cardiac causes, (0.50; P = 0.02), and death from arrhythmia (0.50; P = 0.04). The cumulative percentage of patients in whom a drug was predicted to be effective and in whom it remained effective and tolerated was higher for sotalol than for the other drugs (P < 0.001). CONCLUSIONS: Sotalol was more effective than the other six antiarrhythmic drugs in preventing death and recurrences of arrhythmia. In patients similar to those in this study, if antiarrhythmic-drug therapy is to be used to prevent recurrences of ventricular tachyarrhythmias, treatment with sotalol and assessment of its potential efficacy by Holter monitoring are a reasonable initial strategy.

Aged↗
PubMed1993

Psychoneuroendocrine assessment of posttraumatic stress disorder: current progress and new directions.

1. Studies in our laboratory have used the psychoendocrine strategy to explore differences in basal hormone levels between patients with posttraumatic stress disorder (PTSD) and other groups. This approach has allowed us to explore the relationship between hormone levels and specific psychological and biological processes which appear to develop following exposure to extreme trauma. 2. The concurrent assessment of several hormonal systems provides an opportunity to explore differences in hormonal patterns in various psychiatric disorders. PTSD appears to be characterized by a specific profile of hormonal changes that is distinct from that of other diagnostic groups and normal controls. These findings raise the possibility that the psychoendocrine approach may be useful in further exploring the pathophysiology and diagnosis of PTSD. 3. This paper reviews psychoendocrine changes in PTSD and describes updated multivariate methods that further elucidate psychological and neurochemical correlates of hormonal alterations in this disorder.

Hormones↗
PubMed1993

Effects of Physicochemical Factors and Bacterial Colony Morphotype on Association of Vibrio vulnificus with Hemocytes of Crassostrea virginica.

Vibrio vulnificus is a naturally occurring marine bacterium that causes invasive disease of immunocompromised humans following the consumption of raw oysters. It is a component of the natural microbiota of Gulf Coast estuaries and has been found to inhabit tissues of oysters, Crassostrea virginica (Gmelin 1791). The interaction of V. vulnificus with oyster host defenses has not been reported in detail. We examined the interaction of V. vulnificus with phagocytic oyster hemocytes as a function of time, temperature, bacterial concentration, pretreatment with hemolymph, and V. vulnificus translucent and opaque colony morphotypes. Within these experimental parameters, the results showed that the association of V. vulnificus with hemocytes increased with time, temperature, and initial V. vulnificus/hemocyte ratio. Pretreatment of V. vulnificus with serum or an increased serum concentration did not enhance V. vulnificus-hemocyte associations, a result suggesting the absence of opsonic activity. More than 50% of hemocytes bound the translucent, avirulent morphotype, whereas 10 to 20% were associated with the opaque, virulent form, a result indicating that the degree of encapsulation was related to resistance to phagocytosis, as previously described for mammalian phagocytes. Understanding these cellular interactions may, in part, explain the persistence of V. vulnificus in oyster tissues and the ecology of V. vulnificus in estuarine environments.

Journal Article↗
PubMed1993

Enhanced suppression of cortisol following dexamethasone administration in posttraumatic stress disorder.

OBJECTIVE: The authors investigated the possibility of enhanced negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis in posttraumatic stress disorder (PTSD) by using a low dose of dexamethasone. METHOD: Baseline blood samples were obtained at 8:00 a.m., and 0.5 mg of dexamethasone was administered to 21 male patients with PTSD and 12 normal age-comparable men at 11:00 p.m. Cortisol and dexamethasone levels were measured 9 and 17 hours after dexamethasone administration. RESULTS: After correction for differences in dexamethasone levels, the PTSD patients showed greater suppression of cortisol in response to dexamethasone than did the normal subjects. This was true even in patients meeting concurrent diagnostic criteria for major depression. CONCLUSIONS: The data support earlier studies showing that HPA abnormalities in PTSD are different from those seen in depression and suggest that the low-dose dexamethasone suppression test may be a potentially useful tool for differentiating the two syndromes and further exploring differences in their pathophysiology.

Adult↗
PubMed1993

Deficits in short-term memory in posttraumatic stress disorder.

OBJECTIVE: The purpose of this study was to compare the memory function of patients with posttraumatic stress disorder (PTSD) to that of matched comparison subjects. METHOD: Vietnam veterans with combat-related PTSD (N = 26) were compared to physically healthy comparison subjects (N = 15) matched for age, race, sex, years of education, handedness, socioeconomic status, and alcohol abuse. Memory and intelligence were assessed with a battery of neuropsychological tests, including the Russell revision of the Wechsler Memory Scale, the Selective Reminding Test, and subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). RESULTS: The PTSD patients scored significantly lower than the comparison subjects on the Wechsler Memory Scale logical memory measures for immediate recall (mean = 11.6, SD = 3.3 versus mean = 20.9, SD = 6.6) and delayed recall (mean = 8.0, SD = 3.3 versus mean = 17.8, SD = 6.4). The PTSD patients also scored significantly lower on the total recall, long-term storage, long-term retrieval, and delayed recall measures for the verbal component of the Selective Reminding Test and on the recall, long-term storage, long-term retrieval, and continuous long-term retrieval measures for the visual component of the Selective Reminding Test. There was no significant difference between the PTSD patients and comparison subjects in prorated full-scale IQ as measured by the WAIS-R. CONCLUSIONS: Patients with PTSD may have deficits in short-term memory. Counseling and rehabilitation that address these deficits may be of value for PTSD patients.

Humans↗
PubMed1993

Effects of acute tryptophan depletion on nocturnal melatonin secretion in humans.

Measurement of melatonin secretion throughout the night provides an index of net noradrenergic activity mediated by postsynaptic beta-adrenergic receptors in the pineal gland. Reduced melatonin secretion in some patients with depression might be related to reduced net noradrenergic function. However, a dysregulation in serotonin function has also been implicated in the pathophysiology of depression. The essential amino acid tryptophan is the precursor for both serotonin and melatonin production. To determine the effects of serotonin function on nocturnal melatonin secretion, eight healthy volunteers underwent active and sham tryptophan depletion in a randomized, double-blind fashion. Blood samples for melatonin and free and total tryptophan were obtained before and after the depletion. Acute tryptophan depletion decreased free and total plasma tryptophan levels to less than 20% of baseline levels. Melatonin secretion, expressed as area under the curve, was decreased in all eight subjects after tryptophan depletion when compared to sham depletion. These results suggest that reduced plasma tryptophan levels, and presumably brain serotonin concentrations, decrease nocturnal melatonin secretion in humans. Additional studies investigating the relationship between serotonin metabolism and pineal function in humans appear warranted.

Adult↗
PubMed1992

Comparison of ST depression recorded by Holter monitors and 12-lead ECGs during coronary angiography and exercise testing.

Data from previous studies are debatable regarding whether Holter monitors are a reliable electrocardiographic indicator of ischemia, for which the 12-lead electrocardiogram (ECG) is the standard. Simultaneous 12-lead and Holter ECGs were performed on 30 patients with typical angina pectoris during coronary angiography or exercise testing. ST depression recorded by both methods was directly compared, using the 12-lead ECG as the reference. The Holter tapes were also scanned by two automated ST analysis programs and the results were compared to 12-lead ECGs. Only 66 of the 178 12-lead ECG ST depression events were also present on the Holter recordings (37.1% Holter sensitivity). ST depression was underestimated by the Holter recordings compared to the 12-lead ECGs (p < 0.0001). The majority (67.0%) of ST depression events identified by one computer program were false positive events. The degree of ST depression was overestimated compared to 12-lead ECGs by the second program (p = 0.0033). Holter-detected ST depression may not be a reliable ECG indicator of myocardial ischemia.

Adult↗