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Biomedical subjects

J Theodore

Publications and source records attributed to J Theodore.

At least 91 records · Page 5Linked to original sources
PubMed1987

Primary pulmonary hypertension. Length of survival in patients referred for heart-lung transplantation.

The paucity of data on the natural history of primary pulmonary hypertension (PPH), and the observation that some patients awaiting heart-lung transplantation (HLT) appeared to be living longer than expected, led us to analyze the survival data of patients with PPH who had been referred for consideration of HLT. Ninety patients (female: male = 3.6:1) met clinical and hemodynamic criteria for PPH. Age at diagnosis was 29.8 +/- 7.9 years (mean +/- SD) (range 13-48 years). Symptom duration was 65.9 +/- 47.4 months, while survival from diagnosis was 42.9 +/- 42.6 months, giving a mean lead time of 23 months. Mean pulmonary artery pressure (PAP) at diagnosis was 61.6 +/- 15.0 mm Hg. The incidence of patent foramen ovale (PFO) was 19 percent, postpartum onset 16 percent, family history 6 percent, and cirrhosis 3 percent. The survival of 27 patients who died without operation was 50.3 +/- 52.5 months (median 37 months), with a symptom duration of 68.4 +/- 57.5 months (median 64 months). Both a high mean right atrial pressure (RAP) (p less than 0.025) and high mean PAP (p less than 0.025) correlated inversely with survival. For the whole group, none of the variables, age at diagnosis, sex, mean PAP or mean RAP at diagnosis, symptom duration prior to diagnosis or the presence of a PFO, postpartum onset or positive family history, significantly influenced survival. However, a low cardiac output (p less than 0.05) adversely influenced prognosis. The discrepancy between the mean and median length of survival in our group and previous reports confirms the need for further clarification of natural history and for appropriate clinical trials to assess therapeutic endeavors.

Adolescent↗
PubMed1987

Cardiopulmonary function at maximum tolerable constant work rate exercise following human heart-lung transplantation.

Studies were performed measuring parameters of respiratory and circulatory function at rest and during maximum tolerable constant work rate treadmill exercise in 16 clinically well patients who had undergone heart-lung transplantation for end stage pulmonary hypertension. Ten patients were studied before and within eight weeks following transplantation. Long-term function with exercise was further evaluated with follow up studies at one year (n = 10) and two years (n = 6), posttransplantation. Posttransplant gas exchange and ventilation during exercise are essentially normal with neither being limiting to maximal exercise. Exercise capacity is significantly improved posttransplant, primarily as a result of improvement in the circulation over that found pretransplant in uncorrected pulmonary hypertension. Although improved, circulatory limitations of maximal exercise may still persist. Cardiorespiratory function at maximum tolerable exercise is well maintained following heart-lung transplantation for at least two years, providing no complications occur. This suggests that denervation of the heart and lungs, disruption of the bronchial circulation and pulmonary lymphatics, and the graft ischemia encountered at the time of transplantation impose no serious limitations on long-term cardiopulmonary function. The overall functional capacities of the transplanted heart and lungs are more than adequate for meeting the activities of normal life.

Adult↗
PubMed1987

Lung immunogenicity, rejection, and obliterative bronchiolitis.

Evidence suggests that obliterative bronchiolitis (OB) following human heart-lung transplantation is a form of allograft rejection related to augmented expression of class II major histocompatibility complex antigens (MHCII) on airway epithelium and mediated by activated T cells. Other forms of OB, including those related to viral infection and autoimmune disease, may reflect a similar mechanism.

Bronchitis↗
PubMed1987

Obliterative bronchiolitis after heart-lung transplantation: apparent arrest by augmented immunosuppression.

Obliterative bronchiolitis has been the major complication in long-term survivors of human heart-lung transplantation at our institution. We have assessed the effect of the introduction of a third immunosuppressive agent, azathioprine, on the rate of decline in airflow variables in eight heart-lung transplant recipients with obliterative bronchiolitis, and have compared this rate with that in five patients who did not receive augmented immunosuppressive therapy. Specifically, the rate of decline in forced expiratory flow rate between 25% and 75% of vital capacity improved considerably after institution of this therapy (-5.25 +/- 2.85 compared with -0.27 +/- 0.66 [mean +/- SD]; p less than 0.005), whereas the effect on the ratio of forced expiratory volume in one second to forced vital capacity was more modest (-3.61 +/- 1.52 compared with -0.54 +/- 0.93; p less than 0.005). The rate of decline in airflow variables was similar in both groups before the institution of therapy with azathioprine. These results show that augmented immunosuppressive therapy is capable of slowing the rate of progression of obliterative bronchiolitis in this population; they also suggest that the obliterative bronchiolitis may represent a form of chronic pulmonary allograft rejection.

Adult↗
PubMed1986

Twenty-eight cases of human heart-lung transplantation.

Between March, 1981, and August, 1985, twenty-eight heart-lung transplant operations were done in 27 patients at a single institution. 8 patients died in the perioperative period and adhesions related to previous thoracic surgery proved to be a major risk factor for postoperative haemorrhage. Obliterative bronchiolitis developed in half of the 20 long-term survivors, a mean of 11.2 months (range 2-35 months) after surgery: 4 of these patients died, 3 are functionally limited, 2 were successfully treated with corticosteroids, and the remaining patient was successfully retransplanted. The other 10 long-term survivors returned to a normal life with essentially normal pulmonary function measured at a mean of 22.6 months (range 4-42 months) after transplantation. All the surviving patients have evidence of renal impairment related to cyclosporin nephrotoxicity. The results indicate that, although heart-lung transplantation is compatible with essentially normal long-term pulmonary function, the procedure should not yet be regarded as a routine clinical intervention.

Airway Obstruction↗
PubMed1986

Neurogenic hyperacute ascites in mice.

Four groups of mice were subjected to controlled fatal head trauma and then evaluated for the presence of ascites (neurogenic hyperacute ascites, NHA). The animals died virtually instantaneously and without evidence of maintained pain or suffering. The volume of ascites was determined in one group of animals. Two of the traumatized groups were pretreated, one with the beta-blocker propranolol and the other with the alpha-blocker phentolamine. A fifth, non-traumatized, group which was killed with either inhalation served as a control group. Two more groups of non-traumatized mice were administered either the alpha-adrenergic agonist methoxamine hydrochloride or the beta-agonist isoethrane mesylate before killing by ether inhalation, and then evaluated for ascites. Transudative ascitic fluid was found in 87-100% of untreated traumatized mice and in no control animals. Pretreatment with phentolamine had no effect on the prevalence of ascites. Pretreatment with propranolol produced a significant decrease in the prevalence of ascites compared with trauma alone (P less than 0.001). Isoethrane (beta-agonist) administration caused ascites in 100% of the treated animals. Methoxamine (alpha-agonist) administration did not cause ascites. A previously undescribed consequence of acute brain trauma is described (NHA) which appears to be mediated by beta-sympathetic activity of central origin. NHA is inhibited by beta-blockade and can be simulated with beta-agonist administration.

Acute Disease↗
PubMed1986

Augmented ventilatory response to exercise in pulmonary hypertension.

The ventilatory response to submaximal exercise, defined as the slope of minute ventilation over carbon dioxide production (VE/VCO2), was determined in 12 normal subjects, ten patients with pulmonary hypertension before and after heart-lung transplantation, and eight patients following heart transplantation. Patients with pulmonary hypertension show an augmented ventilatory response compared to normal subjects (pulmonary hypertension [mean, 57.7 +/- 6.8 (SE) ml/ml VCO2; normal subjects, 22.3 +/- 1.4 ml/ml VCO2; p less than 0.001]). Following heart-lung transplantation, VE/VCO2 slope fell to 24.7 +/- 1.6 ml/ml VCO2, a value which is not significantly different than the value in normal subjects. Patients after heart transplantation show a mean slope value of 25.3 +/- 1.3 ml/ml VCO2, which is not significantly different than the normal value or the value found after heart-lung transplantation. The augmented ventilatory response to exercise did not correlate with the usual chemical modulators of ventilation (arterial pH, arterial carbon dioxide tension, or arterial oxygen tension). These results suggest the following: the existence of a neural system in patients with pulmonary hypertension which results in an augmentation of ventilatory drive in response to exercise; the augmented ventilatory response reflects excessive neural activity of pulmonary afferents during exercise; narrow regulation of the ventilatory response to exercise in normal subjects which is preserved in the denervated lung, indicating that pulmonary afferents are not critical to ventilatory control during exercise in the normal subject; and the possible use of measurements of the ventilatory response to exercise as a noninvasive screening test for pulmonary hypertension.

Adult↗
PubMed1986

Steroid-responsive bronchiolitis after human heart-lung transplantation.

This report describes the clinical course of a patient who developed obliterative bronchiolitis after viral infection on three separate occasions. Long-term follow-up is given. It is suggested that the syndrome of late pulmonary deterioration after transplantation may be steroid responsive if treatment is initiated early in the natural history of the syndrome. In addition, it is suggested that increased emphasis should be placed on the documentation of viral infection in transplant recipients to define a possible interaction between infection and rejection.

Adult↗
PubMed1985

Long-term results, hemodynamics, and complications after combined heart and lung transplantation.

During the first 31/2 years of the Stanford heart-lung transplant program, 23 transplants have been carried out in 22 patients with severe pulmonary vascular disease. Actuarial survival curves predict 1 and 2 year survival rates of 71% and 57%, respectively, for all patients. As a result of increasing experience, the early mortality of 26% has been reduced, with only one early death occurring in the last eight patients; prior cardiac surgery was a contributing factor in three of the six patients suffering early deaths. Two late deaths occurred in the series 14 and 15 months after operation. One patient died suddenly as a result of an acute myocardial infarct and the other patient died because of respiratory failure. At autopsy, both patients had severe proliferative coronary atherosclerosis with obliterative bronchiolitis affecting the lungs. An additional patient required a retransplant for obliterative bronchiolitis 37 months after the initial procedure, and he too was found to have severe coronary artery disease. Hemodynamics and left ventricular function were normal in patients studied 1 and 2 years after undergoing the transplantation procedure. Thus, the early mortality and morbidity of combined heart and lung transplantation has been significantly reduced, but the long-term complications, particularly graft atherosclerosis and obliterative bronchiolitis, are yet to be fully controlled.

Actuarial Analysis↗
PubMed1985

Impact of profound reductions of PaO2 on O2 transport and utilization in congenital heart disease.

A group of eight adult patients with congenital cyanotic heart disease (CCHD) with PaO2 values of less than 32 mm Hg at rest and/or exercise were studied. Four of the patients were re-studied after heart-lung transplantation and restoration of PaO2 to normal values. All eight patients showed increased red cell counts (polycythemia), whereas frankly elevated hemoglobin concentrations were found in only one patient. There was no impressive change in the affinity of hemoglobin for O2 as compared to normal subjects. Blood lactate concentrations were normal at rest before transplantation, rose very modestly during moderate exercise, and were normal following transplantation indicating that the concept of anaerobic threshold is not valid in the present group of patients. Cardiac index was not elevated in the pretransplantation period, indicating that an elevated cardiac output is not an essential adaptive mechanism for dealing with hypoxia. In the pre-transplant period, O2 consumption was elevated as compared to normal values and almost doubled during exercise despite a further decline in PaO2 and SaO2; this establishes that the rate of mitochondrial O2 utilization is maintained despite profound reduction in PaO2. These patients are capable of moderate exercise and normal brain function despite severe hypoxia and the absence or attenuation of various adaptive mechanisms for dealing with hypoxia. Further study of the specifics of O2 transport and utilization in similar patients should prove rewarding.

Adult↗
PubMed1984

Coordinate regulation of glycolysis by hypoxia in mammalian cells.

The impact of hypoxic exposure on the activities of all 11 glycolytic enzymes was studied in cell culture into mammalian cells-mouse lung macrophages and L8 rat skeletal muscle cells. During hypoxic exposure, the measured activity of all glycolytic enzymes increased, establishing coordinate regulation. Three nonglycolytic cytoplasmic enzymes showed no change in activity under the same conditions, suggesting a specific mechanism. Hypoxia appears to increase the activities of all glycolytic enzymes whether rate-limiting or not, presumably increasing adenosine triphosphate availability despite decreased O2 supply.

Animals↗
PubMed1984

Heart and lung transplantation for pulmonary hypertension.

Seventeen patients received combined heart and lung transplants at Stanford University between March 1981 and December 1983. All recipients were suffering from end-stage pulmonary hypertension. Five patients died within the first few postoperative weeks, but the remainder were well between 2 and 35 months after operation. Immunosuppression consisted of cyclosporine with an initial course of rabbit antithymocyte globulin, and azathioprine was given for the first 2 postoperative weeks. Maintenance immunosuppression was achieved with cyclosporine and prednisone. Rejection, as diagnosed by cardiac biopsy, was treated with intravenous methylprednisolone. The functional status of the survivors has been good, and upon discharge from the hospital, all returned to normal activity. Our preliminary experience indicates that cardiopulmonary transplantation represents a realistic therapeutic approach for patients with end-stage pulmonary disease.

Adult↗
PubMed1984

Heart-lung transplantation for irreversible pulmonary hypertension.

Combined heart and lung transplantation was carried out in 17 patients at Stanford University between March, 1981, and December, 1983. The recipients were between 22 and 45 years old. All patients had end-stage pulmonary hypertension; 10 had Eisenmenger's syndrome and the remaining 7, primary pulmonary hypertension. Five patients died within the first few postoperative weeks. The remainder are well between four weeks and 33 months from operation. The immunosuppressive protocol has consisted of cyclosporine with an initial course of rabbit antithymocyte globulin. Azathioprine also was given for the first two weeks and then was replaced with prednisone. Rejection, as diagnosed by cardiac biopsy, was treated with high doses of methylprednisolone. Modifications of technique that have developed include the removal of the recipient heart and lungs separately, and preservation of the lungs with a modified Collins' solution instead of a cardioplegic solution. Rejection occurred in 6 of the 12 survivors. Infections developed in 9 patients, but only one resulted in a fatal outcome (Legionella). Thus, the results of clinical heart-lung transplantation have been considerably superior to clinical efforts in lung transplantation. It is suggested that the combined operation is preferable for the following reasons: (1) all diseased tissue is removed, thus eliminating recurrent infection and ventilation/perfusion disparity; (2) transplantation of the entire heart-lung block preserves coronary-bronchial vascular anastomoses and makes airway dehiscence less likely; and (3) to date, diagnosis of rejection by cardiac biopsy has appeared to be a satisfactory method of diagnosing and treating pulmonary rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Clinical heart-lung transplantation.

Combined heart and lung transplantation was carried out in thirteen patients at Stanford University between March 1981 and May 1983. The recipients were between 22 and 45 years old. All patients were suffering from end-stage pulmonary hypertension; nine patients had Eisenmenger's syndrome; the remaining four were transplanted for primary pulmonary hypertension. Three patients died within one month of surgery. The remainder are well at between 22 months and three weeks from operation. The duration of stay in the hospital for the surviving patients ranged from 38 to 85 days. The immunosuppressive protocol has been essentially the same for all recipients, and has consisted of cyclosporine with an initial course of rabbit antithymocyte globulin (RATG) with azathioprine given for the first two weeks, and then replaced with prednisone. Rejection, as diagnosed by cardiac biopsy, was treated with pulses of methylprednisolone. Early complications included bleeding that necessitated reexploration (five patients); damage to the vagus, recurrent laryngeal, or phrenic nerves (three patients); and failure of the donor lungs (one patient). Modifications of technique that have developed include removal of the recipient heart and lungs separately, and preservation of the lungs with a modified Collins' solution instead of a cardioplegic solution. The results of this operation are considerably superior to clinical efforts in lung transplantation. The combined operation may be preferable for the following reasons: All diseased tissue is removed, thus eliminating recurrent infection, and also perfusion/ventilation disparity. Transplantation of the entire heart and lung block preserves coronary-tracheal vascular anastomoses and makes airway dehiscence less likely. Diagnosis of rejection by cardiac biopsy seems to be a satisfactory method of diagnosis and treatment of pulmonary rejection.

Adult↗
PubMed1984

Physiologic aspects of human heart-lung transplantation. Pulmonary function status of the post-transplanted lung.

Pulmonary function measurements were performed before and after heart-lung transplantation in nine patients who had undergone surgery for end-stage pulmonary hypertension. In seven of them, sequential follow-up studies were performed at variable times postoperatively with the longest period 27 months. Pre-transplant studies showed a mild restrictive defect in 33 percent and obstructive disease in 50 percent of the patients, respectively. Arterial hypoxemia was present in all patients. The degree of mechanical changes found did not appear severe enough to account for the marked dyspnea and disability characterizing this group of patients with pulmonary hypertension. Following transplantation, all patients showed striking improvement of symptoms and general physical status. In the early post-transplant period, there was a marked decrease in most lung volumes resulting in a moderately severe restrictive ventilatory defect. Flow parameters that were reduced could be related to decreased volumes and not to intrinsic airway obstruction. Arterial O2 tensions improved dramatically and gas exchange was maintained at essentially normal levels. Lung function tended to improve progressively following transplantation with the passage of time. Heart-lung transplant is consistent with an adequate long-term pulmonary functional state which has the capacity to sustain the normal activities of daily living. From the standpoint of lung function, heart-lung transplantation appears to be acceptable as a form of therapy in selected patients.

Adult↗
PubMed1984

Post-transplant obliterative bronchiolitis and other late lung sequelae in human heart-lung transplantation.

Since March 1981, 19 patients have undergone heart-lung transplantation for end-stage pulmonary vascular disease, with 14 long-term survivors. In five of the survivors, obstructive airway disease has developed with the superimposition of a progressive restrictive ventilatory defect in three of them. None of these five patients showed a tendency for spontaneous improvement of flow rates. Biopsy and postmortem material was available in four of the five patients and showed obliterative bronchiolitis (OB) in three. A fourth patient showed clinical and physiologic data consistent with obliterative bronchitis, but histologic material was not available. Obstructive lung disease without restrictive features developed in a fifth patient, but no histologic evidence of OB was found at transbronchial biopsy. In addition to OB, recurrent lung infections were found in all patients, significant pleural fibrosis in two patients, and bronchiectasis in one patient. Despite these long-term sequelae of human heart-lung transplantation, ten of the 14 surviving patients are leading relatively normal lives.

Adult↗