Microemulsion formulation increases cyclosporin bioavailability in cystic fibrosis.
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Adult↗
Biomedical subjects
N R Banner
Publications and source records attributed to N R Banner.
Effect of beta blockade on the neurohumoral and cardiopulmonary response to dynamic exercise in cardiac transplant recipients.
OBJECTIVE: To determine the effects of a small dose of beta blocker on neurohumoral and cardiopulmonary responses after cardiac transplantation. BACKGROUND: Cardiac transplant recipients have a reduced exercise capacity and abnormal cardiovascular responses to exercise. The sympathoadrenal response to exercise has been shown to be abnormal with high venous noradrenaline. The effect of beta blockade on these neurohumoral mechanisms has not been defined. METHODS: 10 non-rejecting cardiac transplant recipients were studied. Patients carried out graded exercise to a symptom limited maximum. Blood samples were taken during exercise. Concentrations of noradrenaline, adrenaline, and atrial natriuretic peptide and plasma renin activity were measured. The next day, the exercise and sampling procedure were repeated after an oral dose of propranolol (40 mg). RESULTS: Patients tolerated exercise poorly after beta blockade, which was reflected in the maximum workload reached. Heart rate and blood pressure were significantly higher at rest and during exercise before beta blockade. Although there was no significant difference when resting, mean (SEM) noradrenaline concentrations during peak exercise were higher after beta blockade (16.2 (2) v 23.6 (2.9) nmol/l, p = 0.001). Adrenaline concentrations at peak exercise were also greater after beta blockade (0.89 (0.31) v 1.18 (0.38) nmol/l, p = 0.055). Atrial natriuretic peptide concentrations tended to be higher after beta blockade (118.75 (50.2) v 169.79 (39.3) pmol/l, p = 0.36). There was no significant change in plasma renin activity. CONCLUSIONS: A small oral dose of a competitive beta blocker such as propranolol has an adverse effect on exercise tolerance and cardiovascular response to exercise in cardiac transplant recipients. There are also increased concentrations of circulating noradrenaline and therefore, sympathetic activity during exercise. beta blockers should be used with caution in cardiac transplant recipients.
Administration, Oral↗
Successful double-lung transplantation with direct bronchial artery revascularization.
Double-lung transplantation with tracheal anastomosis has previously resulted in unacceptable ischemic complications of airway healing. Three patients underwent double-lung transplantation at our institution in 1986 and 1987, and 2 of these required later retransplantation because of airway complications. Recently, we began to perform direct revascularization of the bronchial arteries at their origin on the donor descending thoracic aorta, using recipient internal thoracic artery. Eight patients (2 male and 6 female patients; ages, 10-51 years) underwent nine double-lung transplantations with revascularization. The preoperative diagnoses in these patients were cystic fibrosis (2 patients), atrial septal defect and Eisenmenger's syndrome (1 patient), lymphagioleiomyomatosis (1 patient), bronchiectasis (1 patient), alpha 1-antitrypsin deficiency (1 patient), and primary pulmonary hypertension (2 patients); 1 underwent retransplantation because of pulmonary emboli. There have been no significant airway complications in any patient. Two patients died early postoperatively, 1 of early pulmonary dysfunction (at 1 day postoperatively) and 1 of subarachnoid hemorrhage (at 16 days postoperatively; tracheal healing was excellent in this patient). Follow-up in the remaining 6 patients ranged from 5 to 9 months. Internal thoracic artery angiography was performed on seven grafts, which documented patency of the internal thoracic artery in all seven and bronchial artery perfusion in six. Bronchoscopic examinations have demonstrated excellent airway healing in all six of these grafts, with no dehiscence, granulation, or narrowing of the trachea or distal bronchi. Ulceration of the tracheal anastomosis developed anteriorly in the remaining patient, which has resolved. We conclude that double-lung transplantation is an acceptable therapeutic approach when combined with bronchial artery revascularization, and early airway healing has been excellent.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Location, localization and surgical treatment of cardiac pheochromocytoma.
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Adolescent↗
Heterotopic heart transplantation and recipient heart operation in ischemic heart disease.
The role of heterotopic heart transplantation in coronary heart disease has not been defined. Between 1983 and 1988, 28 patients with end-stage ischemic heart disease were managed by heterotopic heart transplantation and adjunctive operation on the recipient heart: coronary artery bypass grafts and aneurysmectomy, 20; coronary artery bypass grafts, 5; and aneurysmectomy, 3. Indications were feasibility of operative procedures to the recipient heart and small donor size (61% of the donors were less than 15 years). The 1-year and 5-year actuarial survival was 79% and 63%. Of the 22 patients who survived to 2-year follow-up, all of whom had been severely limited (New York Heart Association grade III/IV) preoperatively, 20 were in grades I or II at 2-year follow-up (p less than 0.001). In 14 of 22 patients (64%), the recipient heart augmented the donor cardiac output substantially, and in 4 the recipient heart supported the patient when the donor heart failed to eject. In conclusion, this series demonstrates the efficacy of heterotopic transplantation combined with operation to the recipient heart in the management of patients with end-stage ischemic heart disease.
Adult↗
Response to dynamic exercise in cardiac transplant recipients: implications for control of the sodium regulatory hormone atrial natriuretic peptide.
1. To study the importance of cardiac innervation in the regulation of atrial natriuretic peptide, plasma atrial natriuretic peptide levels were measured during symptom-limited, graded exercise on a cycle ergometer in seven male orthotopic cardiac transplant recipients. 2. Resting plasma atrial natriuretic peptide was significantly higher in the transplant recipients than in two control groups, one matched to the transplant recipients (group I) and the other to the age of the donor heart (group II). 3. The response to exercise of the cardiac transplant recipients was compared with the response of control group II. Mean maximal work load achieved with exercise was around 40% lower in the cardiac transplant recipients. During exercise, plasma atrial natriuretic peptide levels increased in both the cardiac transplant recipients and the control subjects. The increase in plasma atrial natriuretic peptide with exercise was greater in absolute, but less in percentage, terms in transplant recipients than in the control subjects. 4. The increase in mean arterial pressure with exercise was similar in patients and in control subjects; however, heart rate increased in the patients by only 33% compared with a rise of 151% in the control group. 5. These results provide insight into the control of the sodium regulatory hormone atrial natriuretic peptide. First, factors other than a change in heart rate appear of importance in the regulation of atrial natriuretic peptide. Secondly, these findings suggest that cardiac innervation is not of dominant importance in the modulation of atrial natriuretic peptide secretion.
Atrial Function↗
Altered cardiovascular and neurohumoral responses to head-up tilt after heart-lung transplantation.
Heart-lung transplantation results in afferent and efferent denervation of the transplanted organs including interruption of the central connections from the low-pressure receptors in the atria and pulmonary veins. We investigated whether the cardiovascular and neurohumoral responses to the postural stimulus of head-up tilt were affected after transplantation. Responses in eight heart-lung transplant recipients were studied and compared with those in eight normal subjects matched for age and sex during passive head-up tilt at 45 degrees for 1 hour. The transplant group had a higher initial heart rate (99 +/- 2 versus 68 +/- 2 beats/min, p less than 0.001) and diastolic blood pressure (88 +/- 5 versus 76 +/- 2 mm Hg, p less than 0.05) than did the control group. The increases in heart rate and diastolic blood pressure during head-up tilt were similar in the two groups. Systolic blood pressure remained unchanged. The decrease in cardiac output (30% versus 18%, p less than 0.05) and the increase in systemic vascular resistance (52% versus 28%, p less than 0.05) were greater in the transplant group. Baseline levels of norepinephrine, epinephrine, vasopressin, and plasma renin activity were similar in the two groups. Atrial natriuretic peptide concentrations were higher in the transplant group (26 +/- 3.8 versus 9.7 +/- 1.6 pmol/l, p less than 0.001). During head-up tilt, plasma norepinephrine levels increased to a greater extent in the transplant group than in the control group (83% versus 53%, p less than 0.01), indicating an increased sympathetic response. In contrast, plasma renin activity increased significantly in the control group but not in the transplant group.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Immunohistochemical demonstration of human cardiac innervation before and after transplantation.
Knowledge about the distribution and origins of peptide-containing nerves in the innervated and transplanted heart is lacking. Immunohistochemical and histochemical techniques were used to visualize human cardiac innervation before and after transplantation. In the recipient heart cardiac nerve fibers and fascicles displayed immunoreactivity for general neural (protein gene product 9.5 and synaptophysin) and Schwann cell markers (S-100). A major proportion of cardiac nerves displayed neuropeptide tyrosine and tyrosine hydroxylase immunofluorescence staining. Subpopulations of nerves contained somatostatin, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P- or neurokinin-like immunoreactivity, and acetylcholinesterase activity. Tissues from cardiac allografts (5 weeks to 63 months after transplantation) contained nerves and ganglion cells that were acetylcholinesterase positive and immunoreactive for the general neural markers. These nerves were less numerous than in recipient hearts and rarely displayed neuropeptide immunostaining. Atrial natriuretic peptide immunoreactivity was localized to myocardial cells in transplanted hearts as well as explanted recipient and postmortem hearts. While most human cardiac allografts remain functionally extrinsically denervated, they appear to contain viable intrinsic nerves, and myocardial cells retain the capacity to produce atrial natriuretic peptide.
Adolescent↗
Persistence of intrinsic neurones and possible phenotypic changes after extrinsic denervation of human respiratory tract by heart-lung transplantation.
Respiratory tract nerves have cell bodies outside (sensory, sympathetic) and inside (parasympathetic) the organ and contain bioactive peptides. These include calcitonin gene-related peptide and tachykinins (sensory nerves), vasoactive intestinal polypeptide (parasympathetic nerves), and neuropeptide with tyrosine (sympathetic nerves). Because transplantation interrupts the extrinsic nerve supply to the tissues, we have examined transplanted human respiratory tracts (n = 11) removed at retransplantation 2 to 42 months after the primary transplant in order to determine whether any nerves and peptide synthesis persist. As controls to establish nerve distribution in human respiratory tract, tissues were obtained from 10 lung resections and five autopsies. Cryostat sections were immunostained to demonstrate the general neural marker PGP 9.5, neuropeptides, and the catecholamine-synthesizing enzyme tyrosine hydroxylase. Nerves immunoreactive for PGP 9.5 were detected in all transplanted tissues. They were fewer in number overall than in control tissue, significantly so in epithelium of trachea and bronchus where they were present sparsely in only three cases. Nerves immunoreactive for tyrosine hydroxylase were significantly fewer in the transplants. Peptide-immunoreactive nerves were also reduced in number in the transplants, except for vasoactive intestinal polypeptide, which was only significantly changed in blood vessels in the lung. Ganglion cells immunoreactive for tyrosine hydroxylase and neuropeptide with tyrosine were seen in the transplanted tissues in five cases, but never in the control tissues. We conclude that whereas some nerves and neuropeptide synthesis persist after extrinsic pulmonary denervation, potentially significant changes also occur, including the appearance in intrinsic parasympathetic neurones of immunoreactivity for a catecholamine-synthesizing enzyme and a peptide normally found in sympathetic nerves.
Adult↗
Physiology of the orthotopic cardiac transplant recipient.
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Atrial Natriuretic Factor↗
Cardiac transplantation in the seventh decade of life.
Twenty-five patients older than 60 years of age underwent cardiac transplantation using an immunosuppression protocol with cyclosporin and azathioprine, but without routine use of oral steroids. There were 24 men and 1 woman (age range 60 to 69 years, mean 63). The etiology of heart disease was coronary artery disease in 21 and idiopathic dilated cardiomyopathy in 4. Six patients had previous coronary artery bypass operations, 1 had undergone repair of an abdominal aneurysm and 1 had pulmonary embolism. Sixteen patients were in New York Heart Association class IV and 9 in class III. Donor mean age was 30 (14 to 46) years. Hospital stay after transplantation was 10 to 90 days (median 11). Four died within 30 days and none from 5 to 59 months (mean 22). The 1-year actuarial survival was 84%. The incidence of rejection was 2.16 episodes per patient. Only 1 patient (4%) had serious infection. Six patients received antihypertensive treatment, 3 had reversible impairment of renal function, 2 had gout and 1 had drop foot. No patient had convulsions, transient ischemic attack or cerebrovascular accident. None had significant psychological problems. The 21 patients currently alive are in New York Heart Association class I. Quality of life, assessed by the Nottingham Health Profile, showed marked improvement. It is concluded that the initial results of cardiac transplantation in the seventh decade of life are encouraging.
Actuarial Analysis↗
Primary cardiac tumours--is there a place for cardiac transplantation?
Between 1979 and 1985, seven patients (five children and two adults) were treated for primary cardiac tumours other than benign atrial myxomas. There were five malignant neoplasms (two non-classifiable sarcomas, one haemangiosarcoma, one histiocytoma and one neurofibrosarcoma) and two benign tumours (fibromas). Echocardiography, cardiac catheterisation, computed tomography and magnetic resonance imaging provided diagnostic confirmation. The two patients with fibroma are alive and well 4 and 5 years after radical resection of the tumours from the interventricular septum. The patient with a neurofibrosarcoma underwent orthotopic cardiac transplantation and is well 5.5 years postoperatively with no evidence of residual disease or recurrence. One patient died awaiting a donor heart for transplantation. Another patient who was a candidate for heart and lung transplantation was found to have an unresectable tumour at the time of operation. One patient with sarcoma who underwent a successful emergency partial resection for relief of cardiac tamponade died 18 months later from widespread metastases. The seventh patient was inoperable due to multiple secondaries. It is concluded that radical resection of large, benign, cardiac tumours can give good results and that early cardiac transplantation probably offers the only hope for patients with malignant tumours of the heart.
Adolescent↗
Altered sympathoadrenal response to dynamic exercise in cardiac transplant recipients.
The cardiac denervation produced by heart transplantation modifies the physiological response to exercise. The cardiorespiratory and sympathoadrenal response of seven "healthy" orthotopic heart transplant recipients was compared to seven age matched normal subjects during progressive dynamic exercise. The initial venous noradrenaline concentration tended to be higher in the transplant group, at 3.6 (SEM 0.6) v 2.9(0.2) nmol-litre-1 (NS). Noradrenaline concentrations were significantly higher in the transplant group during exercise (p less than 0.05, by analysis of variance). The transplant recipients reached a lower maximum workload than the normal subjects, at 102(8) v 170(10) watts (p less than 0.01) and the peak noradrenaline concentrations were similar in the two groups. The fall in noradrenaline concentrations after exercise was similar in the two groups. This showed that noradrenaline clearance was normal in the transplant recipients and the higher noradrenaline level reflected increased sympathetic activity. Despite the normal peak noradrenaline concentration, the transplant recipients achieved lower maximum heart rates than the normal subjects, at 142(3) v 181(5) beats min-1 (p less than 0.01). Adrenaline concentrations were similar in the two groups during submaximal exercise and tended to be lower in the transplant recipients at maximal exercise. The increased sympathetic activity may be a response to altered cardiac performance because of efferent cardiac denervation or to loss of tonic inhibition of sympathetic activity by cardiac receptors due to afferent denervation. Both circulating noradrenaline and adrenaline appear to play a significant role in the heart rate response to exercise after cardiac transplantation.
Adult↗
Cardiopulmonary response to dynamic exercise after heart and combined heart-lung transplantation.
The exercise capacity and cardiopulmonary response to progressive dynamic exercise of eight healthy recipients of heart-lung transplants were compared with those of matched recipients of orthotopic cardiac transplants and normal controls. In both transplant groups the maximum workloads were lower than that in the normal group. The transplant recipients had higher pre-exercise heart rates and lower maximum heart rates than the normal controls. Ventilation during submaximal exercise was similar in the heart transplant group and the controls. The heart-lung group had an increased ventilatory response associated with lower end tidal carbon dioxide concentrations. Exercise capacity after combined heart-lung transplantation is similar to that after cardiac transplantation. Transplant recipients have an abnormal heart rate response during exercise related to cardiac denervation. The altered ventilatory response in heart-lung recipients may be the result of pulmonary denervation.
Adolescent↗
Diastolic function after cardiac and heart-lung transplantation.
The mechanical efficiency of left ventricular contraction and relaxation, the asynchrony of the onset of left ventricular relaxation, the time constant of left ventricular isovolumic pressure decay, and left ventricular chamber and myocardial stiffness were analysed in 32 patients after cardiac (24) and heart-lung transplantation (8). After cardiac transplantation left ventricular myocardial stiffness was increased and a mild degree of incoordinate contraction and relaxation was seen. In contrast, after heart-lung transplantation diastolic function was almost normal. Impairment of passive diastolic properties was significantly related to the ischaemic time of the donor heart and the donor's age. The index of left ventricular asynchrony was related to the ischaemic time and the recipient's age. The interval between transplantation and study did not influence the number of rejection episodes. This study confirms the presence of diastolic dysfunction after cardiac transplantation. Impairment of diastolic function seems to be related to the ischaemic time of the donor heart and to a mismatch between the size of the donor heart and the recipient's needs.
Adolescent↗
End-stage dilated cardiomyopathy. Persistence of enterovirus RNA in myocardium at cardiac transplantation and lack of immune response.
Tissue from the explanted hearts of 21 patients with idiopathic dilated cardiomyopathy or 19 patients with other specific heart muscle diseases were investigated for presence of enterovirus-specific RNA with an enterovirus group-specific cDNA probe. This was complementary to coxsackievirus B2 RNA sequences between nucleotide numbers 6,550 and 7,400, which are highly conserved between enteroviruses. Hearts from six patients with dilated cardiomyopathy and one patient with ischemic heart disease were found to contain virus RNA. Serology revealed that only one patient (dilated cardiomyopathy group) was positive for coxsackievirus B-specific IgM but negative for virus RNA in the myocardium. Quantitation of leukocytes and T-lymphocytes in the myocardium and expression of major histocompatibility locus antigens revealed no significant differences associated with persistence of virus RNA. These data demonstrate that enterovirus RNA persists in myocardium of a significant proportion of patients with end-stage dilated cardiomyopathy in the absence of a continuing cell-mediated or humoral immune response.
Adolescent↗
Combined septal perforation and cardiac rupture after myocardial infarction. Clinical features and surgical considerations of a correctable condition.
The combination of septal perforation and cardiac rupture after myocardial infarction has rarely been reported. This article describes two cases of successful surgical repair of this condition and reviews another three cases previously reported in the literature. The important clinical features were as follows: (1) acute occlusion of a single dominant coronary artery; (2) renewed chest pain before perforation or rupture; (3) electromechanical dissociation at the time of frank rupture; (4) rupture through the left ventricular free wall; (5) in three patients both complications occurred within 3 days of the infarction, and in the other two patients they developed within three weeks. The main surgical considerations are as follows: (1) femoral cannulation to prevent exsanguination before instituting cardiopulmonary bypass; (2) electrically induced fibrillation to avoid systemic embolism; (3) a left ventricular approach to repair the septal perforation followed by infarctectomy; (4) concomitant revascularization was unnecessary. In conclusion, combined septal perforation and cardiac rupture after myocardial infarction is a potentially correctable condition that requires early diagnosis and prompt surgical intervention.
Acute Disease↗
Laser induced intravascular coagulation for the treatment of acute peptic ulcer bleeding.
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Animals↗