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Biomedical subjects

B Massie

Publications and source records attributed to B Massie.

At least 109 records · Page 6Linked to original sources
PubMed1989

Chronic aortic insufficiency: factors associated with progression to aortic valve replacement.

STUDY OBJECTIVE: To determine whether the initial measurement of clinical variables in patients with chronic stable aortic insufficiency is helpful in identifying patients at risk for earlier progression to aortic valve replacement. DESIGN: Prospective analysis of a cohort of patients for a median follow-up time of 44 months (range, 8 to 57). SETTING: Referral-based cardiology clinics at two university hospitals and their affiliated Veterans Administration medical centers. PATIENTS: Cohort of 50 asymptomatic or minimally symptomatic patients with chronic aortic insufficiency and left ventricular enlargement. Patients had preserved left ventricular ejection fraction at rest and no evidence of coronary artery disease or significant noncardiac illness. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Baseline evaluation included a history and physical examination, chest roentgenogram. M-mode echocardiogram, treadmill test, and radionuclide angiogram done at rest and during supine bicycle exercise. Ten patients progressed to surgery because of the onset of limiting symptoms or objective evidence of left ventricular dysfunction, or both; the overall rate was 4% +/- 3% per year. The Breslow and Mantel-Cox statistics were used to compute survival (surgery-free) dichotomized by prognostic variables. The progression to surgery was earlier in patients with left ventricular end-diastolic volume indices of 150 cc/m2 or more, end-systolic volume indices of 60 cc/m2 or more, a left ventricular ejection fraction at maximal exercise of less than 0.50, or an end-systolic wall stress of 86 dynes/cm2 or more. CONCLUSIONS: Patients at higher and lower risk for early progression to aortic valve replacement can be identified through the measurement of left ventricular size and function. This information can be used to decide the frequency and intensity of follow-up evaluation in these patients.

Actuarial Analysis↗
PubMed1989

Clinical magnetic resonance spectroscopy of brain, heart, liver, kidney, and cancer. A quantitative approach.

Clinical studies using 31P and 1H MRS with a whole body 2.0 T MRI/MRS system are described. In most cases, techniques to quantitate absolute molar concentrations of metabolites in various organs were used. In the brain, AIDS, chronic stroke, and white matter lesions were associated with alterations of brain 31P metabolites. Epilepsy was associated with increased pH in the seizure focus. In the heart, dilated cardiomyopathy was associated with increased PDE/ATP while PCr/ATP was unchanged. In the liver, alcoholic hepatitis and cirrhosis were associated with diminished hepatic ATP while alcoholic hepatitis had increased pH and cirrhosis had decreased pH. This allowed differentiation of normal liver, alcoholic hepatitis, and alcoholic cirrhosis without biopsy. In the prostate, malignancy was associated with increased PME/ATP and decreased PCr/ATP. The PME/PCr was greatly increased in malignant prostate with no overlap in normals. Other cancers outside the brain had increased PME and effective treatment was often associated with diminished PME. 1H MRS of the brain was performed using ISIS and outer volume suppression pulses for volume localization. Excellent high resolution 1H water-suppressed spectra were obtained at echo times as short as 30 ms, showing well resolved peaks for lactate, N-acetylaspartate, glutamate, choline, creatinine, and inositol. 1H MRS demonstrated that the uptake of ethanol by the brain was slower than the rise of ethanol in blood. 31P spectroscopic imaging of the brain with resolution of 2.25 x 2.25 x 2.5 cm produced metabolic images and high resolution spectra from desired regions of interest.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1989

Predictors of total mortality and sudden death in mild to moderate heart failure. Captopril-Digoxin Study Group.

The relation between baseline clinical variables and subsequent mortality was examined in 295 patients with mild to moderate heart failure who participated in a multicenter trial comparing the effect on treadmill exercise tolerance of captopril, digoxin and placebo given in addition to a diuretic drug. At baseline study, all patients had a left ventricular ejection fraction less than or equal to 40%; 81% were in New York Heart Association functional class II. The etiology of heart failure was ischemic in 62% and nonischemic in 38%. During an average follow-up period of 16 months, 47 patients (16%) died and 24 deaths were classified as sudden. By univariate analysis, left ventricular ejection fraction, ventricular premature beat frequency, couplet frequency, ventricular tachycardia frequency, functional class, treadmill exercise time and nonischemic heart disease were statistically associated with mortality. With multiple logistic regression analysis, left ventricular ejection fraction was identified as the variable most closely associated with total mortality (p = 0.006). Twenty-seven percent of patients with an ejection fraction less than or equal to 20% died compared with 7% with an ejection fraction greater than or equal to 30%. Ventricular tachycardia frequency on Holter monitoring was independently associated with both total mortality (p = 0.008) and sudden death (p = 0.003). Patients with a ventricular tachycardia frequency of greater than 0.088 events/h had a mortality rate of 34% compared with 12% in those without ventricular tachycardia. In the multivariate model, functional class (p = 0.02) and etiology of nonischemic heart disease (p = 0.04) remained as independent predictors of mortality, whereas treadmill exercise duration did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output, Low↗
PubMed1989

Response of myocardial metabolites to graded regional ischemia: 31P NMR spectroscopy of porcine myocardium in vivo.

The changes in myocardial high energy phosphates and pH during regional ischemia, and their potential role in mediating functional abnormalities, is unclear. To determine the degree of regional blood flow reduction required to induce changes in high energy phosphates and pH, and to correlate these metabolic changes with alterations in blood flow, 31P nuclear magnetic resonance spectroscopy was employed in an in vivo porcine model of graded coronary stenosis. Simultaneous measurements of regional blood flow and phosphate compounds were made during various steady-state degrees of regional ischemia in which subendocardial blood flow was reduced by as much as 80%. ATP did not fall over the total range of graded ischemia, while phosphocreatine (PCr), inorganic phosphate (Pi), and pH all changed progressively after blood flow was reduced below 50% of normal. The ratio of PCr/Pi (a measure of the energy reserve of the myocardium) was strongly correlated to subendocardial blood flow (r = 0.94) and declined by 25% when blood flow was reduced by only 21% below normal. These findings indicate that PCr/Pi is a sensitive marker of ischemia and support the hypothesis that the in vivo energy status of the myocardium is closely coupled to myocardial blood flow.

Adenosine Triphosphate↗
PubMed1989

Magnetic resonance spectroscopy of the heart.

MRS has clearly established itself as an important investigative tool for the study of cardiac metabolism and energetics. In animal models, it can provide insight into basic metabolic processes in both health and disease. Its nondestructive nature and capacity for serial measurements in the same system have given scientists the ability to monitor changes in biologic systems over time, while its ability to measure different nuclei, and hence different metabolic processes, gives it immense flexibility. In relative contrast to animal studies, human cardiac MRS is in its infancy. To date, cardiac 31P spectroscopy has been successfully implemented in only a few centers. These studies have primarily examined normal subjects to establish the feasibility of such examinations with a variety of techniques. The few reports of metabolic abnormalities detected by 31P NMR have been limited by problems of accurate spatial localization and large sample volumes. The ultimate utility of human spectroscopy, with phosphorus or any other nucleus, will depend on the success of efforts to increase the sensitivity and spatial selectivity of the NMR experiment. These efforts include utilizing systems of higher field strength and homogeneity, as well as improving pulse sequences and radio frequency coil designs. In addition, demonstration of some degree of sensitivity and specificity of metabolic abnormalities in disease states will be necessary before clinical use is indicated. If these requirements are met, human cardiac spectroscopy may provide useful information about cardiac metabolic processes and, combined with proton NMR imaging, may enable complete noninvasive evaluation with one technology. The rapid advances over the past few years attest to the feasibility of this goal.

Animals↗
PubMed1989

Magnetic resonance spectroscopy. Evaluation of ischemic heart disease.

Magnetic resonance spectroscopy (MRS) is a valuable tool for the study of myocardial ischemia. Phosphorus (31P) MRS can detect changes in high-energy phosphates resulting from ischemia and has been used to determine the sensitivity of metabolic changes to ischemia as well as to investigate the metabolic factors important for myocardial dysfunction. The mechanisms mediating postischemic dysfunction have been investigated using 31P MRS, as have interventions to limit metabolic and functional damage from ischemia. These investigations have laid the groundwork for human cardiac studies. While abnormalities following myocardial infarction have been shown in man, further work must be performed to reliably acquire localized spectra under conditions of ischemia.

Adenosine Triphosphate↗
PubMed1988

Alterations of skeletal muscle metabolism in humans studied by phosphorus 31 magnetic resonance spectroscopy in congestive heart failure.

Muscle metabolism of the finger flexor muscle of the dominant arm was examined in patients with congestive heart failure and age-related controls. Phosphocreatine utilization and decrease in pH during exercise was significantly greater in patients than in controls. Recovery rates were slow in some of these patients. Measurements of forearm blood flow at rest or during exercise were not significantly reduced in patients compared with controls. The inorganic phosphate peak was split during exercise in some of the patients, suggesting the presence of more glycolytic fibers in their muscles. These observations suggest that metabolic abnormalities may be present in the skeletal muscles of patients with heart failure that are not due to reduced nutritive blood flow. This may, in part, explain the lack of correlation between measurements of cardiac function and exercise tolerance in these patients.

Adenosine Triphosphate↗
PubMed1988

Nuclear magnetic resonance imaging-guided phosphorus-31 spectroscopy of the human heart.

Phosphorus-31 nuclear magnetic resonance spectroscopy can determine the status of high energy phosphates in vivo. However, its application to human cardiac studies requires precise spatial localization without significant contamination from other tissues. Using image-selected in-vivo spectroscopy (ISIS), a technique that allows three-dimensional localization of the volume of interest, 12 subjects were studied to determine the feasibility and reproducibility of phosphorus-31 spectroscopy of the human heart. Nuclear magnetic resonance imaging was performed using a commercial 1.5 tesla system to define the volume of interest. Phosphorus-31 spectra were obtained from the septum and anteroapical region of the left ventricle in 10 studies. Relative peak heights and areas were determined for high energy phosphates. The mean phosphocreatine to adenosine triphosphate ratio was 1.33 +/- 0.19 by height analysis and 1.23 +/- 0.27 by area analysis. Duplicate measurements in four subjects showed a reproducibility of less than or equal to 10% in three of the subjects. All spectra showed significant signal contribution from the 2,3 diphosphoglycerate in chamber red cells without evidence of skeletal muscle contamination. These results demonstrate the feasibility of image-guided phosphorus-31 spectroscopy for human cardiac studies and indicate the potential of this technique to study metabolic disturbances in human myocardial disease.

Adenosine Triphosphate↗
PubMed1988

Expression of bicistronic measles virus P/C mRNA by using hybrid adenoviruses: levels of C protein synthesized in vivo are unaffected by the presence or absence of the upstream P initiator codon.

The measles virus (MV) P/C mRNA is functionally bicistronic. Translation is presumed to initiate at both the first and second 5'-proximal AUG codons, leading, respectively, to synthesis of the P and C polypeptides from different overlapping reading frames. To study the function and differential expression of these polypeptides, we have constructed hybrid human adenoviruses capable of expressing high levels of P and C together or of C alone. Cloned cDNA corresponding to the MV P/C gene was coupled to the adenovirus type 2 (Ad2) major late promoter, most of the Ad2 tripartite leader sequence, and the simian virus 40 3'-end processing signal and then used to replace most of the E1a-E1b region of the Ad5 genome in two hybrid adenoviruses: one (Ad5MV/PC13) which contained both 5'-proximal AUG codons of the P/C mRNA and another (Ad5MV/C3) which retained only the second. The sequence context for the P protein initiator AUG codon in Ad5MV/PC13 was made more favorable (GAGAUGG) than the relatively unfavorable context (CCGAUGG) seen in the native MV P/C mRNA. After infection of 293 cells (which provide complementary E1a-E1b functions), both viruses directed equal amounts of P/C-specific mRNA transcription. Ad5MV/PC13 directed the synthesis of both P and C proteins, while Ad5MV/C3 directed the synthesis of C protein alone. Ad5-expressed P protein was phosphorylated, while C was not. C protein had a similar diffuse cytoplasmic localization in both MV and Ad5-infected cells. Ad5MV/C3 and Ad5MV/PC13 directed equal amounts of C protein expression in 293 cells at a level approximately 15 times greater than that seen in MV-infected cells. Thus the level of C protein expression was unaffected by the presence or absence of an out-of-frame upstream AUG codon in a favorable sequence context. This observation cannot be explained by the scanning model for ribosomal initiation and suggests that ribosomes may be binding directly at an internal mRNA site at or near the initiator AUG codon for the C protein.

Adenoviridae↗
PubMed1988

Long-term vasodilator therapy of chronic aortic insufficiency. A randomized double-blinded, placebo-controlled clinical trial.

Although vasodilator drugs acutely reduce regurgitation and improve cardiac performance in aortic insufficiency, their long-term effects on left ventricular size and function are uncertain. Consequently, we performed a double-blinded, placebo-controlled trial using hydralazine in 80 minimally symptomatic patients who had clinically stable, moderate-to-severe aortic insufficiency. Patients randomized to hydralazine displayed a progressive reduction in left ventricular end-diastolic volume index (LVEDVI) measured by radionuclide angiography, the predetermined end point of the study. At 24 months, mean LVEDVI had been reduced by 30 +/- 38 ml/m2, an 18% reduction from baseline. In contrast, LVEDVI changed minimally in patients randomized to placebo, and the intergroup differences over time were statistically significant (p less than 0.03). The hydralazine group also experienced reductions in left ventricular end-systolic volume index and increases in ejection fraction that were significantly different (both p less than 0.01) from changes in placebo-treated patients. These findings show that long-term treatment with hydralazine reduces the volume overload in aortic insufficiency and suggest that such therapy may have a beneficial effect on the natural history of the disease.

Administration, Oral↗
PubMed1987

Skeletal muscle metabolism in patients with congestive heart failure: relation to clinical severity and blood flow.

We and others have previously demonstrated excessive phosphocreatine (PCr) depletion and acidosis in skeletal muscle during exercise in patients with congestive heart failure (CHF). In the present study, we performed serial measurements of PCr and pH during gradually incremental flexor digitorum superficialis exercise in 22 patients with CHF and 11 age-matched controls to determine: (1) whether abnormalities were present at the same relative workloads (a comparison that would at least partially compensate for differences in muscle mass), (2) the temporable course of the metabolic changes, (3) the relationship of the metabolic findings to clinical variables, and (4) the relationship of the metabolic abnormalities to forearm blood flow. The patients with CHF had significantly lower [PCr] and pH at all submaximal levels of exercise, and these abnormalities were apparent from the onset of low-level exercise. There was considerable heterogeneity among the patients with CHF with respect to the metabolic findings, with 14 of 22 exhibiting either PCr or pH values more than 2 SDs below normal. Patients whose capacity was more limited during the protocol had lower [PCr], and especially pH, at low loads than did other patients with CHF or the control subjects. The more symptomatic patients and those with more limited bicycle exercise tolerance also had lower pH values. In contrast, there were no significant differences in forearm blood flow between the patients and controls and no relationship between forearm blood and either clinical variables or the metabolic findings. These results indicate that skeletal muscle metabolic abnormalities are present in many patients with CHF and that they are not primarily due to either muscle atrophy or impaired blood flow. These changes may explain in part the marked heterogeneity of symptom status and exercise capacity of patients with similar degrees of cardiac dysfunction.

Blood Flow Velocity↗
PubMed1987

Diltiazem and propranolol in mild to moderate essential hypertension as monotherapy or with hydrochlorothiazide.

We compared the safety and efficacy of diltiazem and propranolol, and examined demographic factors influencing responses to these agents. One hundred ninety-six patients with supine diastolic blood pressures of 95 to 114 mm Hg were treated with propranolol (80 to 240 mg twice a day) or a sustained-release preparation of diltiazem (60 to 180 mg twice a day) in a double-blind, randomized, parallel group protocol for 6 months. Hydrochlorothiazide was added for patients not achieving the treatment goal. Both agents produced nearly identical and highly significant (p less than 0.001) reductions in supine blood pressure. There were no significant differences at the end of the optional combination therapy phase, although additional reduction with hydrochlorothiazide was slightly greater in the propranolol group. Blood pressure responses in relation to age, gender, race, and smoking history showed that diltiazem produced greater changes in older subjects and women, whereas propranolol was less effective in blacks. However, these differences were not critical.

Adult↗
PubMed1986

Construction of a helper-free recombinant adenovirus that expresses polyomavirus large T antigen.

Adenovirus-polyomavirus recombinant viruses were constructed in vitro by inserting a hybrid transcription unit composed of the adenovirus type 2 major late promoter and the early coding region of polyomavirus into the adenovirus type 5 vector Ad5 delta E1/dl309. The vector lacks the E1a and E1b transcription units and contains a unique restriction endonuclease cleavage site in their place. The polyomavirus genomic insert contained a small deletion which precluded the synthesis of functional small and middle T antigen but allowed for the synthesis of large T antigen. One recombinant virus, Ad5PyR39, which contained the hybrid transcription unit in the opposite transcriptional orientation from the overall direction of late-gene transcription, was studied in detail. Ad5PyR39 replicated efficiently without a helper virus in human 293 cells and expressed hybrid mRNAs of the expected size and composition that were translated to yield large T antigen. The large T antigen synthesized in 293 cells was the same size as that produced in mouse 3T6 cells lytically infected with polyomavirus, and this protein bound efficiently and specifically to the large-T-antigen-binding sites in polyomavirus DNA. Moreover, the large T antigen encoded by the recombinant virus proved capable of catalyzing the replication in mouse 3T6 cells of a plasmid containing the polyomavirus origin for DNA replication. Comparison of the amount of large T antigen produced in 3T6 cells infected with polyomavirus with that in 293 cells infected with Ad5PyR39, under optimal conditions for each system, revealed at least a fivefold greater yield of the protein on a per cell basis in the latter system compared with the former. Ad5PyR39 should prove to be useful to isolate large quantities of functional polyomavirus large T antigen for structural and biochemical studies.

Adenoviridae↗
PubMed1986

Updated diagnosis and management of congestive heart failure.

It is not uncommon to see elderly patients with a few nonspecific complaints who, on examination and workup, have findings of advanced congestive heart failure. Because of the potential for misdiagnosis and misclassification of the underlying pathophysiology, most patients should undergo a noninvasive measurement of left-ventricular function, such as echocardiography or radionuclide angiography.

Aged↗
PubMed1985

Association between the exercise ejection fraction response and systolic wall stress in patients with chronic aortic insufficiency.

We studied the exercise ejection fraction response in 56 patients with chronic aortic insufficiency. All had left ventricular dilatation but preserved resting ejection fraction and minimal or no symptoms. The exercise ejection fraction increased by 0.05 units or greater in 18 (32%) patients (group I), remained within 0.05 units of the resting value in 18 (32%) patients (group II), and fell by 0.05 units or greater in 20 (36%) patients (group III). There were no significant differences among the groups in left ventricular end-diastolic dimension, end-systolic dimension, or fractional shortening by echocardiography or in resting left ventricular volumes and ejection fraction by radionuclide angiography. Left ventricular end-systolic wall stress was significantly higher in group III than in either group I or group II (89 +/- 20 vs 70 +/- 18 and 69 +/- 17 X 10(3) dyne/cm2; p less than .005). At peak exercise there were no differences among groups in systolic blood pressure. However, end-systolic volume increased from 65 +/- 28 to 77 +/- 36 ml/m2 in group III and fell from 50 +/- 21 to 28 +/- 18 ml/m2 in group I during exercise. Thus, at peak exercise end-systolic volume was nearly three times greater in group III than in group I. Although stress could not be determined directly during exercise, the directional changes in its determinants suggest that it also would have been higher in group III patients. A highly significant inverse correlation was present between the ejection fraction response and the change in end-systolic volume (r = -.87, p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗