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Biomedical subjects

M E Billingham

Publications and source records attributed to M E Billingham.

At least 199 records · Page 11Linked to original sources
PubMed1982

Calcification of porcine prosthetic heart valves: a radiographic and light microscopy study.

To determine the incidence and extent of calcification of implanted glutaraldehyde-treated porcine prosthetic heart valves, 82 valves explanted from 73 patients were examined for calcium by radiography and light microscopy. At the time of valve implantation, the patients were 2 1/4-76 years old. The included 15 children (patients younger than 15 years of age, mean age at time of valve implantation 8.7 +/- 4.1 years) and 58 adults (patients older than 15 years, mean age at time of valve implantation 53.5 +/- 15.1 years). Valves explanted from children (average time implanted 4.6 +/- 1.7 years) included four aortic, five mitral, as well as six right ventricle-pulmonary artery conduits and one left ventricle-abdominal aorta conduit. Valves explanted from adults (average time implanted 3.2 +/- 2.5 years) included 32 aortic and 32 mitral, as well as one tricuspid valve and one valve from a right ventricle-pulmonary artery conduit. Calcification of explanted valves was graded from 0 to 4+ based on radiographs. All 16 valves from children were calcified, with grade 3+ or 4+ calcification in each of the aortic and mitral valves. In adult patients, calcification was present in 10 of 33 valves (30%) implanted for less than 3 years (average time implanted 1.0 year), in nine of 11 valves (82%) implanted for 3-5 years (average time implanted 3.7 years) and in 21 of 22 valves (96%) implanted for 5 years or longer (average time implanted 6.2 years). Analysis of variance demonstrated that calcification was strongly related to the duration that valves were implanted (p less than 0.001). Age at the time of valve implantation also had a strong effect (p less than 0.001) on the amount of valvular calcium. Valves from children showed the most calcification, and the amount did not change when valves were implanted in patients 30 years of age or older. Patient sex and valve position had no effect on the amount of calcification. Calcification occurred at each right- and left-heart valve position, most frequently at sites of commissural attachments.

Adolescent↗
PubMed1982

Ultrastructural and functional studies on prolonged myocardial preservation in an experimental heart transplant model.

The effect of ischemia with hypothermic cardioplegic preservation were studied in a heterotopic isograft rat heart transplant model. Hearts with ischemic time periods of 0.5, 4, 8, and 12 hours (n = 5 to 7 transplants per ischemic time period) were analyzed for structural and functional changes 50 days after transplantation. Postoperative recovery was prolonged with increasing duration of preservation times, but all transplants functioned normally 20 minutes and 50 days after transplantation. Function of right ventricular strips from graft and normal hearts were compared in a muscle bath. No differences were observed between baseline or isoproterenol-stimulated myocardium from all grafts or normal hearts. Electron and light microscopy studies of right and left ventricle and ventricular septum samples demonstrated marked fibrosis at 4, 8, and 12 hours of preservation with no differences between the 4, 8 and 12 hour grafts. There were no other differences in other features examined, including necrotic, mitochondrial, I-band, contractility, nuclear, endothelial cell, or intracellular lipid changes. We conclude that (1) except for significant fibrosis, transplants have normal structure and function after 4, 8, and 12 hours of preservation, (2) in assessing the efficacy of hypothermic cardioplegic preservation, chronic structural changes are more sensitive than functional changes, and (3) hypothermic cardioplegic preservation is feasible up to 12 hours but fibrosis may be the ultimate limiting factor in man.

Animals↗
PubMed1982

The durability of porcine xenograft valves and conduits in children.

One hundred four patients younger than 20 years of age underwent intracardiac xenograft valve replacement (n = 41) or extracardiac conduit implantation (n = 63). Long-term follow-up averaged 4.5 and 4.3 years, respectively, and cumulative follow-up totaled 344 patient-years (pt-yr). Thirty patients were followed more than 5 years. Functional results and survival were satisfactory, but valve failure and conduit failure prompted 23 reoperations at linearized rates of 10.1 +/- 2.6% and 4.1 +/- 1.5%/pt-yr, respectively. The rate of valve failure due to leaflet fibrocalcification (primary tissue failure [PTF] was 8.1 +/- 2.4%/pt-yr. Among patients who underwent valve replacement, 52 +/- 13% were free of reoperation at 5 years (59 +/- 13% for PTF only), as were 80 +/- 9% of patients who received an extracardiac conduit. There were no deaths associated with the 22 late reoperations or with the 21 reoperations for PTF. Valve failure was due to PTF in 80% of cases; conversely, isolated valvular PTF was the cause of conduit failure in only one of eight patients. The most common cause of conduit failure was exuberant pseudointimal proliferation in the proximal conduit, which was seen in six of eight patients (75%) with or without other sites of obstruction and responsible for nine of the 15 obstructions (60%). These results underscore the palliative nature of these procedures, militate against indiscriminant use of conduits, prompt consideration of alternative nonconduit techniques where possible, and reemphasize the clinical need for superior valve substitutes and biomaterials for use in the pediatric age group.

Adolescent↗
PubMed1981

Dose-effect and structure-function relationships in doxorubicin cardiomyopathy.

The cardiomyopathy (CM) produced by the anticancer drug doxorubicin (DXR) (Adriamycin) provides a unique opportunity to analyze dose-effect and structure-function relationships during development of myocardial disease. We measured the degree of morphologic damage by ultrastructural examination of endomyocardial biopsy and the degree of performance abnormally by right heart catheterization in patients receiving DXR. Morphologic damage was variable but was proportional to the total cumulative DXR dose between 100 and 600 mg/m2. Performance abnormalities correlated weakly with dose, exhibited a curvilinear relationship, and had a "threshold" for expression. Catheterization abnormalities correlated well with morphologic damage (r = 0.57 to 0.78) in a subgroup of patients in whom exercise hemodynamics were measured, and this relationship also exhibited a curvilinear, threshold configuration. In DXR-CM myocardial damage is proportional to the degree of cytotoxic insult (DXR dose) while myocardial function is preserved until a critical dose or degree of damage is reached, after which myocardial performance deteriorates rapidly.

Biopsy↗
PubMed1981

Myocardial involvement in idiopathic hemochromatosis. Morphologic and clinical improvement following venesection.

We describe a 31 year old male patient who presented with severe cardiomyopathy caused by primary hemochromatosis. After a stormy course, complicated by heart failure and severe ventricular arrythmias, improvement in clinical status and myocardial function occurred. Depletion of myocardial iron was documented by the technique of serial endomyocardial biopsy. Myocardial iron stores were not yet depleted when hypoferremia and iron deficiency anemia occurred. This is the first reported study of myocardial morphology in a successfully treated patient with hemochromatotic cardiomyopathy.

Adult↗
PubMed1981

Pathogenesis and prevention of graft arteriosclerosis in an experimental heart transplant model.

Accelerated graft arteriosclerosis is a major cause of death in human heart transplantation. Despite many investigations, the pathogenesis of this disease remains undetermined and its control inadequate. In this study using a rat heart transplant model and cyclosporin A, a new immunosuppressant, acute rejection was prevented but arteriosclerotic-like vessel disease still developed consistently as early as 20 days postoperatively. The combination of cyclosporin A and dipyridamole prevented the development of this vessel disease in transplanted hearts at 20 and 50 days postoperatively. Sulfinpyrazone and cyclosporin A reduced but did not prevent the disease. These findings suggest that immunologically induced graft arteriosclerosis can be prevented in transplanted rat hearts by the combination of cyclosporin A and dipyridamole.

Animals↗
PubMed1981

Anthracycline-associated cardiac and renal damage in rabbits. Evidence for mediation by vasoactive substances.

We tested the hypothesis that anthracycline-induced cardiac and renal damage is mediated by vasoactive substances. A 1-minute exposure to 5 micrograms per ml. of doxorubicin (DXR, Adriamycin) produced cardiac histamine release in isolated rabbit hearts. Under conditions in which histamine uptake and metabolism were impaired, the administration of DXR, 2 mg. per kg., over 1 minute was associated with elevations in arterial histamine and catecholamines. The chronic weekly administration of DXR produced severe cardiac and renal damage. The administration of combined histaminic and adrenergic blockade with diphenhydramine, cimetidine, phentolamine, and propranolol (DCPP) pre- and immediately post-DXR resulted in near total protection against DXR-mediated cardiac damage and prevented the majority of the renal lesions. The combined administration of diphenhydramine, cimetidine, phentolamine, and propranolol did not appear to be acting by mechanisms other than blockade of vasoactive amine receptors as cardiac uptake of DXR and the DXR antitumor response were not altered by diphenhydramine, cimetidine, phentolamine, and propranolol. This study demonstrates that anthracycline-associated cardiac and renal toxicity may be mediated by vasoactive substances and that anthracycline cardiomyopathy is potentially preventable.

Animals↗
PubMed1980

Biosynthesis of collagen and other matrix proteins by articular cartilage in experimental osteoarthrosis.

Osteoarthrosis was induced in one knee joint of dogs by an established surgical procedure. Changes in the articular cartilage in the biosynthesis of collagen and other proteins were sought by radiochemical labelling in vivo, with the following findings. (1) Collagen synthesis was stimulated in all cartilage surfaces of the experimental joints at 2, 8 and 24 weeks after surgery. Systemic labelling with [3H]proline showed that over 10 times more collagen was being deposited per dry weight of experimental cartilage compared with control cartilage in the unoperated knee. (2) Type-II collagen was the radiolabelled product in all samples of experimental cartilage ranging in quality from undamaged to overtly fibrillated, and was the only collagen detected chemically in the matrix of osteoarthrotic cartilage from either dog or human joints. (3) Hydroxylysine glycosylation was examined in the newly synthesized cartilage collagen by labelling dog joints in vivo with [3H]lysine. In experimental knees the new collagen was less glycosylated than in controls. However, no difference in glycosylation of the total collagen in the tissues was observed by chemical analysis. (4) Over half the protein-bound tritium was extracted by 4 M-guanidinium chloride from control cartilage labelled with [3H]proline, compared with one-quarter or less from experimental cartilage. Two-thirds of the extracted tritium separated in the upper fraction on density-gradient centrifugation in CsCl under associative conditions. Much of this ran with a single protein band on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis under reducing conditions. The identity of this protein was unknown, although it resembled serum albumin in mobility afte disulphide-bond cleavage.

Animals↗
PubMed1980

Rheumatoid arthritis: effects of a new agent (ICI 55 897) on serum acute phase proteins and the erythrocyte sedimentation rate.

Thirty-four patients with rheumatoid arthritis (RA) were treated with a new agent (ICI 55 897) in addition to basic therapy with nonsteroid anti-inflammatory drugs. Five patients had the drug for less than 28 days; the remaining 29 were observed for periods up to a year. At 140 days, when all but 2 patients were in the study, there had been statistically significant improvement in clinical score, serum C-reactive protein, erythrocyte sedimentation rate, and plasma fibrinogen. Thereafter results continued to improve but were biased because some patients had stopped taking the drug. The final conclusion was that 17 patients had improved with 1 late relapse, and 15 had not responded. Adverse effects were trivial except in 2 instances: one patient had a transient unexplained rise in blood urea, another had a haematemesis. Neither effect could be attributed with certainty to the drug. ICI 55 897 has no intrinsic analgesic or anti-inflammatory properties. We suggest the findings of this study indicate that this agent, with low toxicity and the ability to lower acute-phase protein levels, may be an alternative to gold or penicillamine in the treatment of RA.

Adult↗
PubMed1980

Distant heart procurement for human transplantation. Ultrastructural studies.

The paucity of donor hearts for human transplantation can be remedied by distant heart procurement. In the present study, 12 donor hearts obtained at distant locatins were preserved by infusion with 500 ml of cardioplegic solution at 4 degrees C at 150 mm Hg and immersion in 4 degrees C saline for rapid transmural cooling. They were transported in ice-cold saline. Maximal ischemic times were 110-182 minutes. Septal biopsies before coronary reperfusion showed normal mitochondria (11 and 12), normal nuclei (seven of 12), myofibrillar I-bands (six of 12), and capillary endothelial swelling (12 of 12). Septal biopsies 30 minutes after reperfusion showed mitochondrial swelling (six of 10), nuclear damage (10 of 10), myofibrillar contraction (10 of 10), and endothelial swelling (eight of 10). All grafts functioned satisfactorily. Eight of the 12 patients were alive 6-15 months later; four patients died (one of pulmonary hypertension and three of infection). We concluded that (1) human hearts show significant ultrastructural changes after 3 hours of ischemia, but (2) these worsen after reperfusion, and (3) distant heart procurement is feasible for human transplantation.

Cell Nucleus↗
PubMed1979

Infection of glutaraldehyde-preserved porcine valve heterografts.

Gross, histologic and ultrastructural changes associated with bacterial infection are described in four porcine valve heterografts that had been in place in patients for 6 days to 28 months. In one patient, culture of the aortic tissue tag included in the heterograft container grew Mycobacterium chelonei; however, examination of the heterograft, recovered at necropsy 6 days after implantation, revealed small colonies of bacteria that differed morphologically from mycobacteria. A second heterograft was the site of staphylococcal infection associated with extensive destruction of collagen in the leaflets. Similar destruction was observed in a third heterograft, which was found to have organisms on ultrastructural study even though bacterial cultures of the valve were negative. The fourth heterograft, from a patient who died of coronary embolism secondary to dislodgment of vegetative material, contained structures resembling lysed bacteria. Observations in these 4 patients and review of published reports of infection involving 43 other patients with porcine valve heterografts indicates that infection in these valves: (1) develops in the fibrin layer that covers the cusps, (2) can involve the collagen in the leaflets, and (3) is uncommonly (three patients) associated with valve ring abscesses.

Adult↗
PubMed1979

Pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) and various acute phase reactants in rheumatoid arthritis and osteoarthritis.

Pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) concentrations have been measured in matched sera and synovial fluid samples obtained from 36 patients with rheumatoid arthritis and 10 patients with osteoarthritis. Levels of alpha 2-PAG in serum and synovial fluid were significantly higher in rheumatoid arthritis than in osteoarthritis. Calculation of the synovial fluid/serum ratios for alpha 2-PAG gave results which are explicable only if this protein were being synthesised locally. In a longitudinal study of 15 patients with rheumatoid arthritis, concentrations of alpha 2-PAG did not reflect disease activity, unlike those of the classical acute phase reactants, C-reactive protein and caeruloplasmin.

Adult↗