Biomedical subjects

J B Young

Publications and source records attributed to J B Young.

At least 19 recordsLinked to original sources

PubMed1992

Cardiac allograft arteriopathy: an ischemic burden of a different sort.

As heart transplant recipients live longer, an accelerated and distinct form of coronary artery disease develops that adversely affects survival. Indeed, cardiac allograft arteriopathy may be detected in as many as 90% of heart transplant recipients after 5 years. The precise incidence is not easily determined because the disease can be difficult to recognize when noninvasive tests are used; even angiography has substantive limitations. The distinct characteristics of this type of coronary artery disease result in a different form of chronic ischemic syndrome. The angiographic hallmark of allograft arteriopathy is an extensive, diffuse, obliterative process that primarily involves distal, small, subendocardial arteries. Endothelial injury seems to trigger the disease process. The arteriopathy is likely immunologically mediated and promoted or exacerbated by traditional atherosclerotic disease risk factors. Viral infection may be involved as well. To gain a better understanding of allograft arteriopathy, it is worthwhile to review its incidence, pathophysiology, prognosis, prevention, and treatment.

Coronary Disease↗

PubMed1992

The Bradford community stroke trial: results at six months.

OBJECTIVE: Comparison of day hospital attendance and home physiotherapy for stroke patients leaving hospital to determine which service produces greater functional and social improvement for the patient, reduces emotional stress for the care giver, and lessens the need for community support. DESIGN: Stratified, randomised trial of stroke patients attending day hospital two days a week or receiving home treatment from a community physiotherapist. The six month assessment results are reported in this paper. SUBJECTS: Patients over 60 years old resident within the Bradford metropolitan district discharged home after a new stroke with residual disability. SETTING: Four day hospitals in two health authorities and domiciliary work undertaken by experienced community physiotherapists. MAIN OUTCOME MEASURES: Barthel index, functional ambulatory categories, Motor Club assessment, Frenchay activities index, and Nottingham health profile were used. Carers' stress was indicated by the general health questionnaire. Treatment given and community care provided were recorded. RESULTS: Of 124 patients recruited, 108 were available for reassessment at six months. Both treatment groups had significantly improved in functional abilities between discharge and six months. The improvements were significantly greater for patients treated at home (Mann-Whitney test; Barthel index, median difference 2 (95% confidence interval 0 to 3) p = 0.01; Motor Club assessment, median difference 2 (1 to 5), p = 0.01). The home treated patients received less treatment (median difference 16 (11 to 21) treatments, p less than 0.001). More than a third of patients in both groups showed depressed mood, and a quarter of care givers were emotionally distressed. CONCLUSIONS: Home physiotherapy seems to be slightly more effective and more resource efficient than day hospital attendance and should be the preferred rehabilitation method for aftercare of stroke patients. New strategies are needed to address psychosocial function for both patients and care givers.

Activities of Daily Living↗

PubMed1992

The myocardial renin-angiotensin system: existence, importance, and clinical implications.

Major components of the renin-angiotensin system have been localized to cardiac tissue. Cardiac-derived angiotensin II may benefit myocardial contractility but may promote detrimental myocardial hypertrophy, coronary vasoconstriction, and arrhythmias. The benefits of ACE inhibition probably extend beyond the classic circulating RAS to include the heart directly.

Angiotensin I↗

PubMed1992

Attenuation of waiting time mortality with heterotopic heart transplantation.

As the number of heart transplants and the number of transplant programs has increased, so has the waiting time for a suitable organ. To more accurately assess the magnitude of this increase and the influence of recipient size, we reviewed waiting times for large (body surface area greater than or equal to 1.95 m2) and small (body surface area less than 1.95 m2) patients with respect to era of transplantation. Patients who underwent transplantation early (1984 to December 31, 1986) waited 35 +/- 47 days (mean +/- standard deviation), whereas patients who underwent transplantation in the late era (1987 to September 30, 1989) waited 83 +/- 102 days (p = 0.001). Large patients waited longer (130 +/- 142 days) in the late era than did small patients (60 +/- 67 days; p = 0.008). During the heterotopic era (October 1, 1989 to June 30, 1990), waiting times for large patients who received a heterotopic transplant (67 +/- 46 days) were significantly shorter than those for patients who received an orthotopic transplant (166 +/- 157 days; p = 0.05). Waiting times for small patients remained unchanged. In addition, waiting time mortality decreased from 24% to 9% (p less than 0.05). Comparison of orthotopic and heterotopic procedures performed during the same era revealed no significant differences in recipient age, preoperative status, graft ischemic time, donor age, early and midterm survival, or early postoperative functional status. Heterotopic heart transplantation may effectively increase the size of the donor pool, decrease the waiting time, and decrease waiting time mortality without increasing the morbidity of the procedure.

Body Surface Area↗

PubMed1992

Hyperlipidemia after heart transplantation: report of a 6-year experience, with treatment recommendations.

Mean plasma lipid values in 100 patients who survived greater than 3 months after heart transplantation increased significantly at 3 months over pretransplantation values: total cholesterol from 168 +/- 7 to 234 +/- 7 mg/dl, low density lipoprotein (LDL) cholesterol from 111 +/- 6 to 148 +/- 6 mg/dl, high density lipoprotein (HDL) cholesterol from 34 +/- 1 to 47 +/- 1 mg/dl and triglycerides from 107 +/- 6 to 195 +/- 10 mg/dl. There were no significant increases after this time. The LDL cholesterol values reamined greater than or equal to 130 mg/dl in 64% of patients and triglyceride values remained greater than or equal to 200 mg/dl in 41% of patients 6 months after postoperative dietary instructions. Beginning in 1985, select patients whose total cholesterol values remained greater than 300 mg/dl despite 6 months of dietary intervention were treated with lovastatin given alone in a high dose (40 to 80 mg/day) or in combination with another hypolipidemic agent. Four of the five patients so treated developed rhabdomyolysis; two of the four had acute renal failure. Beginning in 1988, a second protocol--lovastatin at 20 mg/day as monotherapy--was used in patients who despite dietary intervention had total cholesterol greater than 240 mg/dl (mean follow-up 13 months). In the 15 patients so treated, mean total cholesterol decreased from 299 +/- 10 mg/dl before treatment with lovastatin to 235 +/- 9 mg/dl during treatment (21% reduction, p less than 0.001) and mean LDL cholesterol was reduced from a baseline value of 190 +/- 10 to 132 +/- 12 mg/dl during treatment (31% reduction, p less than 0.001). In this study, lovastatin at a dose of less than or equal to 20 mg/day as monotherapy was a well tolerated, effective treatment for hyperlipidemia after heart transplantation. It did not result in rhabdomyolysis and required no alteration in immunosuppressive therapy. However, the dose should not exceed 20 mg/day and combination therapy with either gemfibrozil or nicotinic acid should be avoided, even if the target LDL cholesterol value is not reached.

Analysis of Variance↗

PubMed1992

Relationship of catecholamine excretion to body size, obesity, and nutrient intake in middle-aged and elderly men.

Catecholamine release from sympathetic nerves and the adrenal medulla is influenced by diet under controlled research conditions. To test whether diet affects catecholamine excretion in free-living men, the urinary content of dopamine (DA), epinephrine (Epi), or norepinephrine (NE) was measured in 24-h collections provided by 572 participants of the Normative Aging Study of the Veterans Administration. Average daily intakes of energy and macronutrients were assessed by means of a semiquantitative food frequency questionnaire and sodium intake by quantitation of sodium excretion. Catecholamine excretion was also examined in relation to anthropometric variables. Because DA and Epi excretion were inversely related to age, all subsequent analyses included adjustments for age. Although DA and NE were positively related to measures of body size and fatness, Epi was negatively related to body fatness. Excretion rates of all three catecholamines were directly related to total energy intake and inversely related to energy-adjusted CHO consumption.

Adult↗

PubMed1992

Effect of cold exposure and nutrient intake on sympathetic nervous system activity in rat kidney.

Renal sympathetic nervous system (SNS) responses to environmental temperature and diet were evaluated using [3H]norepinephrine ([3H]NE) turnover as the index of sympathetic activity. Pharmacological studies first demonstrated that renal NE was localized principally within storage granules of renal sympathetic nerves and regulated by central sympathetic outflow. Acute exposure to cold (4 degrees C), which increased cardiac SNS activity (P < 0.00005), had no effect on renal SNS. A 48-h fast suppressed renal [3H]NE turnover by 37% (P = 0.00024) and cardiac [3H]NE turnover by 48% (P = 0.00608). Dietary supplementation with sucrose did not affect [3H]NE turnover in kidney in either of two separate experiments, although it increased cardiac NE turnover in both. On the other hand, lard feeding significantly increased [3H]NE turnover in both kidney and heart, whereas dietary protein supplementation exerted no effect on either renal or cardiac [3H]NE turnover. These studies demonstrate a unique pattern of sympathetic regulation in kidney, one which is highly responsive to fasting and dietary fat, but not to cold exposure or dietary sucrose.

Animals↗

PubMed1992

Coronary angioplasty in cardiac transplant patients. Results of a multicenter study.

BACKGROUND: Accelerated allograft atherosclerosis is the main cause of death of cardiac transplant recipients after the first year after transplantation. Because no medical therapy is known to prevent or retard graft atherosclerosis and transplantation is associated with a shortened allograft survival, alternative, palliative therapy with percutaneous transluminal coronary angioplasty (PTCA) has been attempted. Because no single medical center has performed angioplasty in a large number of cardiac transplant recipients, representatives of 11 medical centers retrospectively analyzed their complete experience of coronary angioplasty in cardiac transplant patients to determine the safety, efficacy, limitations, and long-term outcome of angioplasty in allograft coronary vascular disease. METHODS AND RESULTS: Thirty-five patients underwent 51 angioplasty procedures for 95 lesions 46 +/- 5 months (mean +/- SEM) after transplantation. The primary indications for angioplasty included angiographic coronary disease in 22 cases (43%) and noninvasive evidence of ischemia in 18 procedures (35%). Angiographic success, defined as less than or equal to 50% post-PTCA stenosis, occurred in 88 of 95 lesions (93%). Mean pre-PTCA stenosis was 83 +/- 1.1%; mean post-PTCA stenosis was 29 +/- 2.1% (p less than 0.0001). Periprocedural complications included myocardial infarction and late in-hospital death in one patient and three groin hematomas. Twenty-three of the 35 patients (66%) had no major adverse outcome such as death, retransplantation, or myocardial infarction at 13 +/- 3 months after angioplasty. Four patients died less than 6 months after angioplasty, and four died more than 6 months after angioplasty (range, 6-23 months). Two patients had retransplantation 2 months after PTCA, and one patients had retransplantation 18 months after angioplasty. CONCLUSIONS: Coronary angioplasty may be applied in selected cardiac transplant recipients with comparable success and complication rates to routine angioplasty. Whether angioplasty prolongs allografts survival remains to be determined by a prospective, controlled trial.

Angioplasty, Balloon, Coronary↗

PubMed1992

Altered dopaminergic responses in hypertension.

Biogenic amine metabolism may be altered in hypertension and thus contribute to its pathophysiology. This report describes an abnormality in dopamine excretion in hypertensive subjects in the postabsorptive state that persists despite an increase in dietary precursors for dopamine supplied by a protein meal. We studied seven normotensive and six nonmedicated hypertensive men after two different meals: 60 g protein and a noncaloric electrolyte-equivalent broth. Overall mean sodium excretion was 56% higher in the hypertensive group throughout both meal studies (p less than 0.01), implying higher chronic dietary sodium intake. Despite this, overall urinary excretion of dopamine tended to be lower in hypertensive than in normotensive subjects (p = 0.06). Hypertensive also differed from normotensive subjects in their response to protein feeding. In the normotensive subjects there was a 23% increase in urinary dopamine excretion (p less than 0.05), which was not seen after the noncaloric meal. In the hypertensive subjects, there was no change in urinary dopamine after the protein meal. In the normotensive subjects there was a 74% increase in sodium excretion (p less than 0.01) after the protein meal, but no significant change was seen in the hypertensive subjects. There were no differences in baseline renal plasma flow or glomerular filtration rate between the groups and no statistically significant differences between the groups in their renal hemodynamic responses to the meals. In summary, hypertensive subjects have less renal dopamine production for the amount of sodium ingested and a decreased renal dopamine production in response to a protein load as compared with normotensive subjects, consistent with a renal defect in conversion of DOPA to dopamine.

Aged↗

PubMed1992

Relationship of urinary serotonin excretion to cigarette smoking and respiratory symptoms. The Normative Aging Study.

The relationship of 2-h urinary excretion of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) to cigarette smoking and respiratory symptoms was examined among 631 male participants in the Normative Aging Study (age range, 44 to 85 years). The amount of serotonin excreted in urine was inversely related to age (p less than 0.001). Mean 2-h excretion of serotonin varied from 8.01 micrograms for men 40 to 49 years of age to 5.84 micrograms for those 70 years of age or over. No clear relationship was evident between the amount of 5-HIAA excreted in urine and age. After adjustment for age, current smokers were found to excrete more serotonin (p less than 0.001) and 5-HIAA (p = 0.001) than never smokers. Former smokers did not differ significantly from never smokers in these respects. After adjustment for age and smoking status in a multivariate model, chronic cough was a significant predictor of serotonin excretion (p = 0.005); chronic cough was less predictive of 5-HIAA excretion (p = 0.07). Other respiratory symptoms were unrelated to urinary excretion of serotonin and 5-HIAA. The mechanisms underlying the observed relationships of urinary serotonin and 5-HIAA excretion to smoking and to chronic cough and their potential relevance to chronic bronchitis remain to be determined.

Age Factors↗

PubMed1992

Sympathoadrenal activity in human obesity: heterogeneity of findings since 1980.

Alterations in sympathetic nervous system (SNS) activity are widely believed to contribute to the pathophysiology of the obese state. Disagreement, however, exists as to whether the predominant sympathetic abnormality is a decrease in neuronal activity (leading to diminished sympathetically-mediated energy expenditure and weight gain) or an increase (leading to hypertension). Findings summarized from over 40 separate studies support both hypotheses as well as the alternative thesis that SNS activity does not differ in obese humans compared to lean controls. Another abnormality being noted with increasing frequency in human obesity is reduced adrenaline (Ad) levels in plasma, both at rest or in response to a stimulus such as physical activity. Whether diminished adrenal medullary function is a cause or consequence of the obese state and whether the adrenal medulla plays any role in the regulation of energy metabolism on a daily basis are not known at the present time. Thus, while depressed SNS activity may be a sufficient explanation for the development of obesity, it is not a necessary condition. Suppressed adrenal medullary function may also contribute to this disorder.

Epinephrine↗

PubMed1992

Diminished epinephrine excretion in genetically obese (ob/ob) mice and monosodium glutamate-treated rats.

While numerous studies have examined sympathetic nervous system activity in experimental obesity, adrenal medullary function in this condition has received less attention. The experiments described herein evaluated adrenal medullary secretion by measurement of urinary epinephrine (Epi) excretion in genetically obese (ob/ob) mice and monosodium glutamate (MSG)-treated rats. In both male and female ob/ob mice Epi excretion was reduced 42% (P less than 0.015) and 47% (P less than 0.025), respectively, despite higher rates of urine output and excretion for other amines in obese compared to lean animals. In a similar fashion, urinary Epi was also lower in MSG-treated adult rats than in untreated controls; this reduction was out of proportion to group differences in body weight or excretion of other catecholamines. Administration of D,L-fenfluramine to mice, or dietary protein supplementation in rats, increased Epi excretion to the same extent in obese and lean animals. These findings indicate that secretion of Epi by the adrenal medulla is diminished, but is normally responsive to stimulation in these two models of animals obesity, and are thus consistent with accumulating evidence of a functional impairment in adrenal medullary secretion in animal and human obesity.

Adrenal Medulla↗

PubMed1992

Central 5-hydroxytryptamine2 receptors are involved in the adrenal catecholamine-releasing and hyperglycemic effects of the 5-hydroxytryptamine indirect agonist d-fenfluramine in the conscious rat.

Stimulation of either the 5-hydroxytryptamine (5-HT)1A, the 5-HT1C or the 5-HT2 receptor subtype triggers adrenal catecholamine release and hyperglycemia. Nonetheless, the identity of the serotonergic receptors that mediate the effects of 5-HT release upon the sympathoadrenal system (and on plasma glucose) is still unknown. Thus, we have examined the effects of the 5-HT uptake inhibitor and releaser d-fenfluramine (d-Fen) on plasma epinephrine (EPI), norepinephrine (NE) and glucose levels in conscious rats. Acute administration of d-Fen (1-8 mg/kg i.v.) promoted early increases in plasma EPI and glucose levels, whereas increases in plasma NE levels were less marked. The effects of a 4-mg/kg dose of d-Fen were then evaluated. Prior adrenalectomy prevented d-Fen-induced hyperglycemia but not d-Fen-induced increases in plasma NE levels. Pretreatment (15 min beforehand) with either the 5-HT1C/5-HT2 receptor antagonist LY 53857 (0.3 mg/kg i.v.) or the 5-HT2 receptor/alpha-1 adrenoceptor antagonist ketanserin (0.3 mg/kg i.v.) markedly diminished the EPI-releasing effect of d-Fen. Pretreatment with the 5-HT1C receptor agonist/5-HT2 receptor antagonist m-chlorophenylpiperazine (1 mg/kg i.v.) tended to decrease the EPI-releasing effect of d-Fen, whereas that with the peripheral 5-HT1C/5-HT2 receptor antagonist BW 501C67 (0.5 mg/kg i.v.) did not alter the EPI-releasing effect of d-Fen. In addition, pretreatment with either LY 53857 or ketanserin prevented the hyperglycemic effect of d-Fen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1991

Insensitivity of noninvasive tests to detect coronary artery vasculopathy after heart transplant.

Obstructive coronary artery vasculopathy can be a major problem after cardiac transplant. The use of noninvasive tests to detect coronary artery vasculopathy was studied in 73 consecutive patients after heart transplant. Angiographically or autopsy-proved coronary artery disease was noted in 19 consecutive patients (26%) followed prospectively for 2.5 +/- 1.3 years (mean +/- standard deviation). Patients underwent yearly surveillance echocardiographic, rest/exercise-gated wall motion, oral dipyridamole thallium, ambulatory electrocardiographic monitor and angiographic studies. Positive test results were defined by decrease in ejection fraction, wall motion abnormality, failure to increase ejection fraction, lack of systolic blood pressure increase, and ischemic ST changes at maximal exercise (or on ambulatory monitor). Wall motion abnormalities and depressed ejection fraction on echocardiography were also abnormal studies as were fixed or reversible perfusion defects on thallium scan. Angiograms were considered positive when 50% luminal narrowing was observed and autopsy coronary artery vasculopathy was defined as cross-sectional coronary obstruction greater than or equal to 70%. No procedure that was examined proved to be a sensitive noninvasive detector of heart transplant coronary artery vasculopathy. All except ambulatory electrocardiographic monitoring had positive predictive values less than 50%. Interestingly, of the techniques evaluated, echocardiography was most sensitive (53%). The poor predictive ability of noninvasive testing in this population may be due to the fact that these tests are designed to detect effects of ischemia rather than coronary obstruction alone. Use of these particular noninvasive modalities routinely after heart transplant to detect coronary artery vasculopathy should be reconsidered because of their low sensitivity and predictive value when used as a surveillance screen.

Adult↗

PubMed1991

Biliary surgery after cardiac transplantation.

Many patients have undergone successful cardiac transplantation. These patients are at risk of developing the same surgical diseases as the general population. The side effects of immunotherapy may mandate intervention at a different point in the natural history of these processes. From February 1984 through December 1989, 24 patients underwent an operative biliary tract procedure following cardiac transplantation. Seventeen patients underwent elective cholecystectomy with intraoperative cholangiography. The mean hospital stay was 5.4 days, and there was no morbidity or mortality. Seven patients underwent urgent procedures; four of them developed severe complications and three died as a result of their biliary tract disease. Two patients in the urgent group had previously exhibited symptoms of biliary tract disease, and five were previously asymptomatic. There was no significant difference in time from transplantation to biliary procedure between the elective group (mean, 17 months; range, 3 weeks to 47 months) and the urgent group (mean, 18 months; range, 3 weeks to 44 months). Patients who undergo cardiac transplantation should be screened for cholelithiasis. The presence of symptoms should not be required before recommending operative intervention.

Adult↗

PubMed1991

Heterotopic heart transplantation and native heart ventricular arrhythmias.

Heterotopic heart transplantation has been said to be contraindicated in patients with serious native heart arrhythmias that produce hemodynamic instability. Placement of heterotopic allografts, however, can theoretically act as a biological biventricular assist device to provide hemodynamic support during these unstable rhythms. Further, this operation might beneficially alter the hemodynamic milieu of heart failure such that the arrhythmias are ameliorated. Described is our experience with 4 patients with heart failure receiving heterotopic cardiac allografts, documenting changes in native heart arrhythmia that occurred. These cases demonstrate that heterotopic grafts can adequately sustain hemodynamics during malignant native heart dysrhythmia. We believe native heart ventricular arrhythmias are not a contraindication to heterotopic heart transplantation.

Arrhythmias, Cardiac↗

PubMed1991

Effects of monosodium glutamate and gold thioglucose on dietary regulation of sympathetic nervous system activity in rodents.

Neonatal administration of monosodium glutamate (MSG) disrupts hypothalamic regulation of a number of neuroendocrine systems. Studies described in this report using techniques of norepinephrine (NE) turnover examined sympathetic nervous system (SNS) activity in heart and interscapular brown adipose tissue (IBAT) of animals given MSG as neonates. Although in every experiment overall rates of NE turnover were lower in MSG-treated mice and rats, the differences were due exclusively to diminished tissue NE content, especially in IBAT. Fractional rates of NE turnover did not differ between groups. In contrast to animals with lesions in the ventromedial hypothalamus produced by gold thioglucose (AuTG) or electric current, MSG-treated mice and rats varied SNS activity in heart and IBAT in accord with changes in nutrient intake. Thus, SNS activity, both at baseline and in response to dietary manipulation, is probably not affected by neonatal MSG administration.

Adipose Tissue, Brown↗

PubMed1991

Changes in urinary catecholamine excretion after smoking cessation.

Excretion levels of norepinephrine, epinephrine, and dopamine were assessed in 17 habitual cigarette smokers while smoking and periodically during 30 days of abstinence to determine whether a pattern of transient change existed, suggestive of sympathetic nervous system (SNS) involvement in tobacco withdrawal. Excretion of all three catecholamines declined 1 day after abstinence but did not return to precessation levels during the rest of the follow-up period. The results suggest that postcessation declines in excretion may be permanent changes caused by loss of tobacco's agonist effects, rather than transient withdrawal phenomena resulting from SNS adaptation to the stimulatory effects of tobacco.

Adult↗