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Biomedical subjects

M R Johnson

Publications and source records attributed to M R Johnson.

306 records · Page 17Linked to original sources
PubMedDate not supplied

Effect of fluvoxamine, imipramine and placebo on catecholamine function in depressed outpatients.

Many of the specific serotonin reuptake inhibitors appear to have some effect on noradrenergic function. Fluvoxamine is one of the newer agents and its specificity has not been fully assessed. Depressed patients participating in a study comparing the efficacy of fluvoxamine with imipramine and placebo collected 24 hour urine samples (N = 38) and had plasma samples drawn (N = 38) prior to and after 6 weeks of double blind treatment. Urine samples were analyzed for 24 hour output of MHPG, VMA, NMN, MN and HVA. Plasma samples were analyzed for NE levels. Imipramine treatment produced a reduction in urinary MHPG, an increase in the ratio of NMN to MHPG plus VMA, and a trend towards an increase in plasma NE which was significantly different than the effects seen in the fluvoxamine and placebo groups. There was an additional finding in the imipramine group of a significant correlation between percentage change in plasma NE and clinical improvement. Fluvoxamine treatment, on the other hand, produced no clear effect on any measure of noradrenergic function and the antidepressant efficacy of fluvoxamine was unrelated to any noradrenergic variable. These findings lend support to the hypothesis that fluvoxamine does not have significant effects on noradrenergic function.

Adolescent↗
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The metabolic effect of antenatal corticosteroid therapy.

The use of antenatal dexamethasone to mature the fetal lung in pregnancies likely to deliver before 34 weeks is almost universal. It reduces the incidence of respiratory distress syndrome in the newborn and results in an overall improvement in neonatal morbidity and mortality. Although considered to be generally safe, there are concerns about adverse maternal and fetal effects. In a series of studies, we have found that antenatal dexamethasone administration is associated with reduced placental hormone production and maternal bone formation, impaired glucose tolerance and altered function of the hypothalamic-pituitary-adrenal axis. In this article, we have compared our data with other reports in the human and reviewed the relevant animal data. We conclude that further studies on the long-term effects of antenatal dexamethasone therapy in the human are warranted with particular emphasis on the long-term effects on the fetus.

Adrenal Glands↗
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The regulation of the human corpus luteum steroidogenesis: a hypothesis?

The corpus luteum (CL) is an important endocrine organ in the menstrual cycle and in pregnancy. The regulation of its hormonal production has been extensively studied. The steroidogenic abilities of the CL can be rescued by human chorionic gonadotrophin (HCG) but its role in the maintenance of CL function is not clear. We will discuss the hypothesis that there are fetoplacental factors, other than HCG, that modulate CL steroidogenesis.

Animals↗
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Dietary fat saturation and hepatic acylcoenzyme A:cholesterol acyltransferase activity. Effect of n-3 polyunsaturated and long-chain saturated fat.

The acylcoenzyme A:cholesterol acyltransferase (ACAT) activity in liver microsomes from rats fed a diet containing 14% menhaden oil (Mp) for 11 days was 117% higher than that in microsomes from rats fed a corresponding diet containing 14% cocoa butter (Ms). There were no differences in the cholesterol and phospholipid contents of Mp and Ms or in the activities of palmitoyl coenzyme A hydrolase and NADPH cytochrome c reductase. NADPH-dependent lipid peroxidation was higher in Mp, whereas glucose 6-phosphatase activity was higher in Ms. These findings indicate that the ACAT response to differences in dietary fat saturation is not due to a nonspecific effect of these diets on microsomal enzymes. When 1% cholesterol was added to the diets, the cholesterol content and ACAT activity of both microsomal preparations increased, but the ACAT activity of Mp remained 60% higher than that of Ms. Addition of cholesterol by incubation of the microsomes with liposomes also increased ACAT activity. At corresponding cholesterol contents, however, the ACAT activity of Mp remained 50% to 70% above that of Ms. There was no difference in the plasma cholesterol concentration in the two groups of rats, indicating that the ACAT effect probably is not due to a difference in the amount of circulating cholesterol available to the liver. Mp contained 40% more polyunsaturated fatty acids and five times more n-3 polyunsaturates than Ms. These findings suggest that the increase in ACAT activity in Mp is due, at least in part, to the difference in the fatty acid composition of the microsomes.

Acyltransferases↗
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Echocardiographic evaluation of young adults with nonhemorrhagic cerebral infarction.

We reviewed echocardiographic findings in patients aged 15 to 45 years with acute nonhemorrhagic cerebral infarction (NHCI). Among 132 patients with NHCI, 96 (72.7%) had M-mode and two-dimensional echocardiography, including contrast echocardiography with intravenous saline injection when clinically indicated. Echocardiograms were abnormal in 33 patients. Of these, 7 had other conditions that could cause NHCI. Echocardiography corroborated the clinical diagnosis of a cardiogenic source for cerebral infarction in 17 others. The other 9 had no other clues for cardiovascular disease. Potential etiologies of NHCI diagnosed by echocardiography in these 9 cases included: paradoxical embolism, 5 patients; right atrial myxoma, 1; rheumatic mitral valve vegetation, 1; myxomatous mitral valve (marantic endocarditis at postmortem), 1; and left atrial enlargement associated with decreased left ventricular function, 1. Routine echocardiography frequently conveys useful information in patients under age 45 with NHCI. In young patients with cerebral embolism of unknown etiology if routine M-mode and two dimensional echocardiographic studies are normal, contrast echocardiographic studies should be performed to rule out intracardiac shunts and the possibility of paradoxical cerebral embolism.

Adolescent↗
PubMedDate not supplied

Intravenous therapy for chronic heart failure exacerbations.

Chronic heart failure (HF) will be the disease of the new millennium. The last decade has seen major developments in the management of HF, with beta-blockers and ACE inhibitors becoming the cornerstones of therapy by virtue of the reductions in total mortality. However, significant gaps remain. Hospitalization for exacerbations of HF are frequent and account for more than 6 million hospital days from this disease related group. Although a variety of intravenous (IV) agents are available for the management of exacerbations of HF, readmission rates are as high as 20%-47% at 6 months. Acute IV therapy for acute decompensation of chronic HF consists of inotropic agents most of which also have vasodilator properties, vasodilator, and diuretics. In addition, there are newer agents in various developmental stages, especially, calcium sensitizing drugs, vasopressin receptor antagonists, and natriuretic peptides. Despite the multiplicity of agents, there are no well designed, randomized, placebo controlled trials to guide IV inpatient therapy for HF exacerbations. (c)1999 by CHF, Inc.

Journal Article↗
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Cytomegalovirus infections in heart transplant recipients: relationship to immunosuppression.

To determine the relationship of cytomegalovirus infections (CMVI) to immunosuppression in heart transplants, we retrospectively compared demographic and clinical variables in 154 consecutive heart transplant patients. Forty-one CMVI were compared; of these, 30 (73%) were identified in tissue, and nine (22%) were identified by blood or urine culture. Twenty (49%) of the CMVI were self-limited, and 21 (51%) were progressive, requiring treatment. When comparing patients with and without CMVI, demographic variables, mean preexisting heart disease, cyclosporine level, cumulative corticosteroid dose, and the use of anti-T-cell antibodies were examined. Only the use of OKT3 was significantly associated with the subsequent development of CMVI. Although CMVI subsequently developed in 30 of 79 (38%) patients who had received OKT3, CMVI developed in only 11 of 75 (15%) patients who had not received OKT3 (p = 0.01). Furthermore, the incidence of CMVI increased with increasing total OKT3 dose (none, 11 of 64 [17%]; < or = 75 mg, 23 of 66 [35%]; > 75 mg, 6 of 14 [43%]; p = 0.01). Logistic regression showed that the only two variables predictive of CMVI were the use of OKT3 (p = 0.0023) and ischemic rather than idiopathic heart disease before transplantation (p = 0.0098). Rejection rates, incidence of allograft vasculopathy, and 1-year actuarial survival were not influenced by previous CMVI. Pneumocystis carinii pneumonia occurred more frequently in patients with CMVI than in those without (13 of 41 [32%] patients versus 3/113 [3%] patients; p < 0.001). No correlation existed between CMVI and lymphoproliferative disorder (p = 0.84).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
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Transplant coronary disease: nonimmunologic risk factors.

Since the time that coronary artery disease was first described in the transplanted human heart, attempts have been made to define risk factors for its development. Although recent reports have emphasized immunologic and infectious (i.e., cytomegalovirus) mechanisms in the development of transplant coronary disease, the influence of several nonimmunologic risk factors has also been studied. Some of the nonimmunologic risk factors that have been evaluated include recipient characteristics (age, sex, obesity, hyperlipidemia, hypertension, smoking, diabetes mellitus, pretransplantation heart disease), donor characteristics (age, sex), immunosuppressive agents/protocols, and nonimmune mechanisms of endothelial injury (cyclosporine, ischemic time). Studies evaluating the role of these risk factors have produced variable results. One or more studies, however, have suggested an effect of recipient age and sex, donor age and sex, obesity, hyperlipidemia, pretransplantation diagnosis, and ischemic time on the development of transplant coronary disease. The most consistently described relationship has been between hyperlipidemia and transplant coronary disease. Hyperlipidemia is common after heart transplantation, with elevations noted in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. The cause of posttransplantation hyperlipidemia is not well defined, but obesity and the immunosuppressive agents prednisone and cyclosporine play a role. Treatment of posttransplantation hyperlipidemia can be difficult because commonly used lipid-lowering agents have side effects and interactions with immunosuppressive drugs that necessitate caution in their use in the posttransplantation population. Transplant coronary disease almost certainly has a multifactorial cause, with endothelial injury and nonimmunologic risk factors, particularly hyperlipidemia, playing contributory roles. Because hyperlipidemia and the obesity that commonly accompany it are modifiable risk factors, weight loss and treatment of hyperlipidemia are recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
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Oversizing of donor hearts: beneficial or detrimental?

To determine the effects of donor/recipient weight mismatch on allograft function and survival after orthotopic heart transplantation, we retrospectively compared the clinical and the hemodynamic characteristics of recipients weighing more than their donor ("undersized") with those of recipients weighing less than their donor ("oversized"). The median follow-up period was 24 months (range, 0 to 67 months). In 88 patients (59%) donor weight was 1% to 46% less than recipient weight (13.5 +/- 8.9 means +/- SD). In 61 patients (41%) donor weight exceeded recipient weight by 0% to 139% (20% +/- 23%). When recipient ideal body weight was used in the analysis, 75 patients (51%) were undersized by 1% to 59% (13% +/- 10%), and 72 patients (49%) were oversized by 0% to 67% (19% +/- 18%). Preoperative transpulmonary gradient, ventricular function, and exercise tolerance were similar in the two groups. The number and severity of episodes of rejection and infection after transplantation were also similar in the two groups 1, 6, and 12 months after transplantation. When recipient ideal weight was used in the analysis, right ventricular (RV) and left ventricular (LV) ejection fractions (EFs) were within normal limits (RVEF greater than 40%; LVEF greater than or equal to 45%) and similar in the two groups. When recipient actual weight was used in the analysis, the LVEF measured at 12 months after heart transplantation was higher in the oversized than in the undersized group (52 +/- 11 vs 46 +/- 10; p less than 0.05). Postoperative hemodynamic values and exercise tolerance were similar in the two groups regardless of whether recipient weight or ideal body weight were used in the analysis. Forty-six recipients died 0 to 46 months (median, 7 months) after orthotopic heart transplantation. In a Cox regression model, recipients with donor weight greater than recipient ideal weight had a significantly greater risk of death within the follow-up period than did recipients with donor weight less than recipient ideal weight (relative risk = 2.19; p less than 0.05). When percent donor weight/recipient ideal weight mismatch was used as a continuous variable, donor heart oversizing was negatively related to survival, independent of preoperative transpulmonary gradient values (p less than 0.05). In contrast to common belief, oversizing of donor hearts does not improve the outcome of orthotopic heart transplant recipients who have reversible preoperative pulmonary hypertension. Acceptance of undersized donor hearts is not detrimental to allograft function and recipient survival. Use of undersized donor hearts may maximize the use of critically scarce donor organs.

Adult↗
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Prospective randomized trial of OKT3- versus horse antithymocyte globulin-based immunosuppressive prophylaxis in heart transplantation.

To compare monoclonal anti-T3-receptor antibody (OKT3) and horse antithymocyte globulin (HATG) immunoprophylaxis, 23 heart transplant recipients were randomized to OKT3 (N = 12) 5 mg IV x 14 days of HATG (N = 11) 5 mg/kg IV x 10 days and followed up for 216 +/- 137 days receiving triple immunosuppression. Recipient groups were demographically and clinically similar. First rejection occurred later in OKT3 recipients vs HATG recipients (31.7 +/- 18.3 vs 15.1 +/- 2.3 days; p less than 0.01), but the first rejection necessitating intensified immunosuppression occurred at similar times (30.9 +/- 14.6 vs 21.9 +/- 10.2 days; NS). Phenotypic characterization of peripheral blood lymphocytes by flow cytometry revealed that OKT3 and HATG recipients had similar decreases in total T lymphocytes and lymphocyte subpopulations. During the follow-up period rejection rates in the OKT3- and in the HATG-treated patients were 3.4 +/- 2.7 and 5.9 +/- 4.7, respectively (NS). The number of rejection episodes per recipient treated with intensified immunosuppression was 1.4 +/- 1.2 in the OKT3- and 2.0 +/- 3.1 in the HATG-treated patients (NS). Infection rates were 4.9 +/- 5.2 in the OKT3- and 2.7 +/- 1.7 in the HATG-treated patients (NS). The number of infection episodes that necessitated intravenous antimicrobial therapy was 2.7 +/- 2.3 in the OKT3- and 1.6 +/- 1.3 in the HATG-treated recipients (NS). The number and length of hospitalizations were similar in patients given OKT3-based or HATG-based immunoprophylaxis. We conclude that immunosuppressive prophylaxis with OKT3 vs HATG in heart transplant recipients is associated with a slightly lower incidence and severity of rejection and slightly higher infection rates.

Animals↗
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Influence of preoperative transpulmonary gradient on late mortality after orthotopic heart transplantation.

We reviewed the transpulmonary gradient, pulmonary arterial systolic pressure, pulmonary vascular resistance (Wood units), and pulmonary vascular resistance index (Wood units X Body surface area), recorded preoperatively in 109 recipients aged 44.6 +/- 13.5 (mean +/- SD) years who underwent orthotopic heart transplantation between March 1984 and March 1988, to identify which measure of pulmonary hypertension most accurately predicts poor outcome after orthotopic heart transplantation. These recipients were followed up as many as 57 (24.7 +/- 14.5) months after their transplant procedure. Preoperative hemodynamic values were as follows: transpulmonary gradient, 10.4 +/- 4.7 mm Hg; pulmonary artery systolic pressure, 53.6 +/- 14.8 mm Hg; pulmonary vascular resistance, 2.7 +/- 1.8 Wood units; pulmonary vascular resistance index, 4.9 +/- 2.7. Nineteen recipients died within 1 year after orthotopic heart transplantation. Causes of death were acute rejection (8), chronic rejection (1), infection (2), nonspecific orthotopic heart transplant failure (4), bowel ischemia (1), pancreatitis (1), lymphoma (1), and liver failure (1). Preoperative pulmonary arterial systolic pressure, pulmonary vascular resistance, and pulmonary vascular resistance index were not predictive of 1-month, 6-month, or 1-year mortality. One-month mortality rates of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg and of those with transpulmonary gradient less than 12 mm Hg were not significantly different (11% vs 3%; p = 0.12). The 6-month mortality rate of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg, however, was five times greater than that of orthotopic heart transplant recipients with transpulmonary gradient less than 12 mm Hg (24% vs 5%; p = 0.003), and 12-month mortality of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg was increased sevenfold when compared with that of orthotopic heart transplant recipients with transpulmonary gradient less than 12 mm Hg (36% vs 5%; p = 0.0005). These results suggest that presently used measures of pulmonary hypertension do not predict mortality in the first month after orthotopic heart transplantation, but that elevated preoperative transpulmonary gradient is associated with a significant increase in mortality at 6 and 12 months after orthotopic heart transplantation. Prospective randomized trials are needed to determined whether extended preload and afterload reduction before and/or after transplant will favorably influence long-term prognosis of orthotopic heart transplant recipients with elevated preoperative transpulmonary gradient.

Adult↗
PubMedDate not supplied

Heart failure in women: a special approach?

Heart failure causes significant morbidity and mortality in women, especially elderly women. Risk factors for the development of heart failure in women differ from those in men, with hypertension and diabetes playing a greater role in women and ischemic heart disease a greater role in men. However, the risk of developing heart failure after symptomatic myocardial infarction is higher in women than in men. Data from the Studies of Left Ventricular Dysfunction Registry suggest that event rates after the diagnosis of heart failure are greater in women than in men. Only 13% of the patients included in the major heart failure mortality trails were women, and data for the women in these trials have not been reported separately. The survival of women who have undergone heart transplantation is similar to that of men; however, women have more rejection and are more likely to require maintenance corticosteroid therapy. Data are critically needed to determine whether the treatment of heart failure in women, whether medically or by heart transplantation, requires a special approach.

Adult↗
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Circadian rhythm changes in blood pressure and heart rate during the first year after heart transplantation.

Heart transplant recipients (n = 11) were studied before discharge from the hospital and 1, 3, 6, and 12 months after transplantation to (1) examine systolic and diastolic blood pressure and heart rate circadian patterns, (2) detect the presence or absence of nocturnal declines, and (3) describe changes in the mean levels of systolic blood pressure, diastolic blood pressure, and heart rate. An ambulatory blood pressure-monitoring system was used to record blood pressure and heart rate at 1-hour intervals for up to 48 hours. Data were analyzed with descriptive and independent t-test statistics, as well as cosinor analysis for rhythmicity. The majority of the patients had significant (p < 0.05) circadian rhythms for systolic and diastolic blood pressure and heart rate throughout the study, but at times the systolic and diastolic blood pressure acrophases were found to be phase shifted to earlier or later along the time axis (e.g., peak values occurring at 3 AM rather than later in the morning or early afternoon), such that no relationships were found between circadian rhythms and nocturnal declines. More "normal" circadian rhythms were observed for heart rate than for systolic and diastolic blood pressures. The development of hypertension (systolic/diastolic blood pressures > 140/90 mm Hg) was common and by 6 months and 1 year after transplantation 8 of the 10 patients remaining in the study were hypertensive. Increases in mean heart rate of approximately 18% (ranging from 2% to 46%) were also observed during the first postoperative year.

Blood Pressure↗
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Endocardial infiltrates in the transplanted heart: clinical significance emerging from the analysis of 5026 endomyocardial biopsy specimens.

UNLABELLED: To further elucidate the significance of endocardial infiltrates in heart transplant patients, the presence, frequency, and type of endocardial infiltrates were evaluated in 5026 endomyocardial biopsy specimens obtained from 200 heart transplant patients 0 to 75 months after heart transplantation. The relationship of endocardial infiltrates to immunologic, clinical, and demographic variables was then explored. Endocardial infiltrates were detected in 557 endomyocardial biopsy specimens (11%) from 117 heart transplant patients (58%) at 6.3 +/- 9.4 months (mean +/- SD; range, 0 to 49 months) after heart transplantation. Heart transplant patients with endocardial infiltrates were younger (p = 0.03), had a greater incidence of idiopathic dilated cardiomyopathy before heart transplantation (p = 0.05), and included a greater percentage of females (p < 0.05). Both total and treated rejection rates were significantly higher in patients with endocardial infiltrates versus those without endocardial infiltrates (p = 0.0001). Rejection on the subsequent endomyocardial biopsies was more often present in endocardial biopsy specimens with endocardial infiltrates than in those without endocardial infiltrates, both in the presence (37% versus 24%; p < 0.001) and absence (33% versus 19%; p < 0.0001) of concomitant findings of rejection. No association was identified between endocardial infiltrates and posttransplantation lymphoproliferative disorder, cytomegalovirus infection, Epstein-Barr virus infection, or cardiac allograft vasculopathy. Multivariate regression analysis confirmed that the occurrence of endocardial infiltrates is associated with rejection when adjustment is made for patient's age, gender, heart disease before transplantation, follow-up time, and number of endomyocardial biopsies after heart transplantation (p = 0.0001). CONCLUSIONS: (1) Endocardial infiltrates may occur with or without associated endomyocardial biopsy findings of rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
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Heart transplantation as a treatment option for end-stage heart disease in patients older than 65 years of age.

Because of the critical donor organ shortage for heart transplantation, selection of recipients should be based on the potential for maximum benefit. To evaluate the effects of advancing age on outcome after heart transplantation, we compared the clinical variables of 12 recipients aged 65 years or older (66.1 +/- 0.9 years [x +/- standard deviation]; range, 65 to 67 years) with those of 57 patients aged 55 to 64 years (59.3 +/- 2.7 years) at the time of the procedure. The two study groups were similar in sex, race, pretransplantation heart disease, immunocompatibility, maintenance immunosuppression, and length of first hospitalization at the time of the procedure. Groups were also similar regarding the incidence of malignancies, fractures, diabetes, neurologic complications, and renal dysfunction occurring over the follow-up period. Patients 65 years of age or older had a significantly higher number of hospital days (36 +/- 29 versus 15 +/- 18 days; p < 0.02) and increased frequency of infections/month (0.7 +/- 0.3 versus 0.3 +/- 0.4 infections/month; p < 0.03) during the first postoperative year. Older patients had a higher incidence of cytomegalovirus infections (50% versus 19%; p < 0.06), lower rates of rejection at 1 and 6 months after operation (p < 0.03), and more severe functional limitation (p < 0.002) than patients aged 55 to 64 years. One-year actuarial survival was not significantly different in the two groups. The results of our study suggest that, because of lower rejection and higher infection rates, heart transplantation recipients older than 65 years of age should receive less intense immunosuppression.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗