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Biomedical subjects

J F Douglas

Publications and source records attributed to J F Douglas.

At least 37 records · Page 2Linked to original sources

Evaluation of 13-week inhalation toxicity study on methyl t-butyl ether (MTBE) in Fischer 344 rats.

Methyl-t-butyl ether (MTBE) is widely used as an octane enhancing agent in gasoline. A 13-week inhalation study was conducted in Fischer 344 rats to provide information on potential target organs and toxicity of MTBE, and to ascertain a no-observed-adverse-effect level (NOAEL) for MTBE. Male and female Fischer 344 rats were exposed to target doses of MTBE vapor of 0, 800, 4000 and 8000 ppm for 6 h a day, 5 days per week for 13 weeks: MTBE produced no mortalities. At 8000 ppm, males and females showed a decrease in body weights compared to controls. The only notable effect on clinical observation was ataxia at 8000 ppm, which was apparent during the first 4 weeks of treatment. Mild hematological and clinical chemistry changes were observed in the 8000 ppm group. At 8000 ppm, animals showed increased serum levels of corticosteroids, which suggest some stress-like effect. At necropsy, there were no treatment-related gross lesions. Absolute and relative organ weights (liver, adrenals and kidneys) were increased in both sexes at 4000 and 8000 ppm, but there were no microscopic lesions in these tissues with the exception of the kidney. Microscopic examination of other tissues revealed no effects with the exception that at 8000 ppm, male rats showed: mild increased size of hyaline droplets within the kidney, mild increase in hemosiderosis in the spleen and higher incidence of hyperplasia in the lymph nodes. The highest NOAEL was judged at 800 ppm.

Administration, Inhalation↗

Long-term survivors of pediatric heart transplantation: a multicenter report of sixty-eight children who have survived longer than five years.

OBJECTIVE: Short-term survival after pediatric heart transplantation is now excellent, but ultimately the efficacy of this procedure will depend on duration and quality of survival. We sought to evaluate the clinical course of long-term survivors of heart transplantation in childhood. METHODS: Patients who had undergone heart transplantation at the university hospitals of Stanford, Columbia, and Pittsburgh between 1975 and 1989 and survived longer than 5 years from transplantation were identified and their clinical courses retrospectively reviewed. RESULTS: Sixty eight children have survived more than 5 years from transplantation, and 60 (88%) are currently alive with a median follow-up of 6.8 years (5 to 17.9 years). Thirteen have survived more than 10 years from transplantation. Renal dysfunction caused by immunosuppressive agents was common, and two patients required late renal transplantation. Lymphoproliferative disease or other neoplasm occurred in 12 patients, but none resulted in death. Coronary artery disease was diagnosed in 13 patients (19%), leading to retransplantation in eight. Death after 5 years was related to acute or chronic rejection in 5 of 8 cases. Two of the deaths were directly related to noncompliance with immunosuppressive medication. All survivors are in New York Heart Association class 1. CONCLUSIONS: Long-term survival with good quality of life can be achieved after heart transplantation in childhood, though complications of immunosuppression remain common. Posttransplantation coronary artery disease is emerging as the main factor limiting long term graft and patient survival.

Adolescent↗

Autonomic neuropathy predisposing to arrhythmias in hemodialysis patients.

Arrhythmias are frequent among the dialysis population and can cause symptoms of palpitations or dizziness. Since autonomic disturbances are known to cause an increased arrhythmogenic stimulus, we questioned whether the presence of central autonomic neuropathy increased the frequency of arrhythmias as identified by 24-hour electrocardiographic monitoring in dialysis patients. Seventy-one patients were randomly chosen from patients established on dialysis in two centers. The mean age of the patients was 71.3 years (median age, 67 years) and median duration on dialysis was 17.0 months (range, 1 to 175 months). Four patients had diabetes. Each patient was tested for autonomic control of blood pressure and heart rate, and underwent Holter electrocardiographic monitoring, commencing 30 minutes before dialysis, for a 24-hour period. The tapes were then analyzed for ventricular and atrial rhythm changes. There was a significantly increased incidence of arrhythmias in individuals with abnormal blood pressure responses (P = 0.005), heart rate responses (P = 0.01), and combined blood pressure and heart rate responses (P = 0.004). We conclude that patients with autonomic dysfunction had an increased frequency of arrhythmias during dialysis.

Adult↗

Prognostic markers in older patients starting renal replacement therapy.

AIMS: We assessed all patients starting renal replacement therapy during a 1-year period to identify factors influencing 1-year survival in older and younger dialysis patients. METHODS: Data was collected from 113 patients. Twenty-four possible prognostic factors were introduced into a multivariate, time-based analysis. RESULTS: Hazard ratios, and hence risk of mortality, were increased with increasing alcohol consumption, cardiac dyskinesis, age at onset of dialysis, serum phosphate, number of comorbid illnesses, and Karnofsky score (listed in decreasing order of risk). Risk of death within 1 year was reduced in patients with normal serum albumin and higher Barthel scores at the time of commencing dialysis. No age interactions were found. In the elderly age group the risk of death was also increased if left ventricular dilatation was present. Comorbidity and the age of onset were not independent risk factors in patients aged over 65 years at the time of starting dialysis. CONCLUSIONS: All factors listed above increase the 1-year mortality of elderly patients. Factors known to increase medium-term morbidity in dialysis patients including diabetes mellitus, ischaemic heart disease, and hypertension do not appear to be important in the short-term survival of older patient on dialysis.

Adult↗

Heart transplantation in children with congenital heart disease.

OBJECTIVES: The aim of this study was to describe heart transplantation in children with congenital heart disease and to compare the results with those in children undergoing transplantation for other cardiac diseases. BACKGROUND: Reports describe decreased survival after heart transplantation in children with congenital heart disease compared with those with cardiomyopathy. However, transplantation is increasingly being considered in the surgical management of children with complex congenital heart disease. Present-day results from this group require reassessment. METHODS: The diagnoses, previous operations and indications for transplantation were characterized in children with congenital heart disease. Pretransplant course, graft ischemia time, post-transplant survival and outcome (rejection frequency, infection rate, length of hospital stay) were compared with those in children undergoing transplantation for other reasons (n = 47). RESULTS: Thirty-seven children (mean [+/- SD] age 9 +/- 6 years) with congenital heart disease underwent transplantation; 86% had undergone one or more previous operations. Repair of extracardiac defects at transplantation was necessary in 23 patients. Causes of death after transplantation were donor failure in two patients, surgical bleeding in two, pulmonary hemorrhage in one, infection in four, rejection in three and graft atherosclerosis in one. No difference in 1- and 5-year survival rates (70% vs. 77% and 64% vs. 65%, respectively), rejection frequency or length of hospital stay was seen between children with and without congenital heart disease. Cardiopulmonary bypass and donor ischemia time were significantly longer in patients with congenital heart disease. Serious infections were more common in children with than without congenital heart disease (13 of 37 vs. 6 of 47, respectively, p = 0.01). CONCLUSIONS: Despite the more complex cardiac surgery required at implantation and longer donor ischemic time, heart transplantation can be performed in children with complex congenital heart disease with success similar to that in patients with other cardiac diseases.

Adolescent↗

Increased renal allograft thrombosis in CAPD patients.

In a retrospective analysis of 202 renal transplant procedures in the years 1989-1992 we identified an excess of grafts lost from primary renovascular thrombosis in patients receiving continuous ambulatory peritoneal dialysis (CAPD) compared to haemodialysis (HD) patients (9 CAPD versus 0 HD, Chi-squared = 9.63; P < 0.01). All graft losses from thrombosis occurred within 16 days of surgery. Possible predisposing causes were identified in three patients. Donor age was greater in CAPD patients losing their kidneys from thrombosis compared to the overall CAPD group [mean (SD) years, 43.0(12.9) versus 29.1(15.8); P = 0.01] whereas no significant difference in haematocrit, platelet count, antibody status, cyclosporin use, peroperative hypotension, primary diagnosis, smoking, or diabetes mellitus was found. Data from the EDTA registry for 1990-91 show that graft loss from primary renovascular thrombosis in UK-treated patients was reported in 7.1% of CAPD recipients compared with 1.8% in haemodialysis. We suggest that CAPD patients are at greater risk of graft loss from renovascular thrombosis than HD patients and may require more intensive fluid and anticoagulant treatment in the perioperative period.

Adolescent↗

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Adolescent↗

Decreasing incidence of coronary disease in pediatric cardiac transplant recipients using increased immunosuppression.

BACKGROUND: Coronary artery disease (CAD) is a limiting factor to long-term survival in cardiac transplant recipients, affecting from 30% to 50% of patients by 4 years after surgery. Can the incidence of CAD be lowered with augmentation of immunosuppression? METHODS AND RESULTS: We compared the incidence of CAD in our pediatric transplant population with nine potential risk factors, including immunosuppressive regimen. The study group consisted of 55 patients who survived more than 1 year (or to first angiogram) or had autopsies. Coronary angiograms were performed yearly and compared sequentially. The mean follow-up of 55 patients was 36 months. Mean age was 10.3 +/- 6 years (range, 4 months to 18 years). Thirteen patients received double immunosuppression with cyclosporine and prednisone, and 42 received triple therapy with cyclosporine, prednisone, and azathioprine. Significant CAD occurred in 10 grafts (6 deaths and 3 retransplants). Cause for graft loss in 6 patients with CAD was acute rejection. CAD was detected by angiogram in only 2 patients. Nine of 10 patients received double therapy (P < .001). There was no difference in mean follow-up between immunosuppression groups. There was a higher rejection frequency for double therapy (0.19 +/- 0.16 rejections per patient month) compared with triple therapy (0.07 +/- 0.11). Ten patients were rejection free in the triple therapy group. CONCLUSIONS: We experienced a significant decrease in the incidence of CAD in our pediatric cardiac transplant recipients using increased immunosuppressive therapy. Type of immunosuppressive regimen (double) and rejection frequency were independent predictors for CAD by multivariate analysis.

Azathioprine↗

Accelerated retinopathy and nephropathy in diabetic pregnancy.

We report a case of severe deterioration in sight despite good metabolic control in a pregnant diabetic patient which has not recovered at two years post-delivery. This was accompanied by a deterioration in renal function which similarly has not improved.

Adult↗

Live donor renal transplantation--the experience of the Belfast Renal Unit.

Live donor renal transplants are often preferred to cadaver grafts because of better graft survival. In a retrospective study of 41 live donor transplants performed in the Belfast Renal Unit from 1971 until November 1988, actual graft survival at 2 and 5 years was 84% and 69% respectively. Corresponding patient survival rates were 87% and 81%. These results are no better than those of cadaver grafts. A subdivision of patients considered to be relatively poor risk for transplantation showed less favourable results than those who were good risk. 15% of the donors suffered post-operative complications, which occurred more often in older donors. Live donor transplantation is not necessarily preferable to cadaver organ graft, and is not recommended for poor risk recipients or donors aged over 50 years.

Graft Survival↗

Ten-year results of renal transplantation using only azathioprine and low-dose prednisolone as immunosuppression.

This paper describes the results of renal transplants carried out in a single center more than 10 years ago. One hundred fifty-five recipients received 170 grafts; 164 from cadavers and 6 from living-related donors. All patients received the same immunosuppressive therapy with azathioprine and low-dose steroid. 1. The total actual patient survival was 67.1% at 10 years; 104 patients survived and 51 died. 2. The actual first cadaver graft survival was 54.7% at 10 years; 82 grafts survived and 68 were lost. Death with a functioning graft was the commonest cause of graft loss. 3. Ninety-seven patients and 70 first cadaver grafts survived in the 12th year. Two patients survived with first cadaver grafts into the 21st year. 4. Tissue match grade was not related to cadaver graft survival at 10 years. 5. Five of the 6 recipients of living-related donor kidneys survived but only 3 of their grafts were functioning after 10 years.

Adolescent↗

Ten-year results of renal transplantation with azathioprine and prednisolone as only immunosuppression.

93 patients received 102 renal transplants between 1968 and 1977. 99 grafts were from cadavers and 3 were from live donors; 93 were first grafts, 7 were second, and 2 were third. At 10 years total actual patient survival was 66.6%. 50 (55.5%) of 90 first cadaver grafts, and 52.2% of all cadaver grafts, survived at 10 years. Cardiovascular disease was the commonest cause of death, being responsible for 18 of 31 deaths (58%).

Adolescent↗

Visual recovery in orbital vasculitis.

A 46-year-old woman with polyarteritis nodosa and chronic renal failure developed sudden loss of vision which was associated with orbital vasculitis. Treatment with cyclophosphamide produced rapid improvement in vision, which has been preserved with maintenance doses of cyclophosphamide and prednisolone.

Blindness↗

Renal replacement treatment for diabetic nephropathy in Northern Ireland 1979-1987.

Twenty-three patients with end-stage renal failure due to diabetic nephropathy received renal replacement treatment. All patients had insulin-dependent diabetes mellitus. Nineteen transplants were performed in seventeen patients. Two-year graft survival for all transplants was 74% with a two-year patient survival post-transplantation of 81%. Overall two-year patient survival was 73%, compared with 82% in non-diabetic patients receiving renal replacement treatment. In diabetic patients accepted for treatment there was a high incidence of non-renal complications, particularly vascular disease. An aggressive approach to the treatment of vascular disease in these patients may improve overall survival rates.

Adult↗