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Biomedical subjects

P C Adams

Publications and source records attributed to P C Adams.

At least 127 records · Page 7Linked to original sources
PubMed1990

Hepatic ferritin uptake and hepatic iron.

The effect of hepatic iron on the uptake of ferritin was studied by perfusing livers from normal, iron-deficient and iron-loaded rats with 125I-labeled ferritin. Unlabeled ferritin with tracer doses of labeled ferritin in concentrations of 0.02 to 2,700 nmol/L were studied. Rats were made iron deficient by feeding an established iron-deficient diet for 3 wk. Rats were iron loaded by injection of iron dextran (50 mg/wk) for 3 wk. The mean percentage of uptake of ferritin was similar for doses ranging from 0.22 to 22.2 nmol/L of 125I-labeled ferritin. Uptake of ferritin in the normal animal was saturable, with an apparent maximal velocity of uptake of approximately 9.1 pmol/gm/min and a Michaelis-Menten constant of approximately 5 nmol/L at 37 degrees C. Uptake was minimal at 4 degrees C. The mean uptake of ferritin was 78% +/- 10% in the iron-deficient rats (mean hepatic iron = 1.5 mumol/gm), 79% +/- 10% in the normal animals (mean hepatic iron = 9.2 mumol/gm) and 78% +/- 8% in the iron-loaded animals (mean hepatic iron = 192 mumol/gm). In this experimental system, modulation of hepatic iron did not affect uptake of ferritin, suggesting that regulation of the hepatic ferritin receptor may not depend on hepatic iron content. The rapid uptake of ferritin by the liver despite iron overload is consistent with other observations of the nonregulation of non-transferrin-bound iron by hepatic iron and may play a role in the progressive iron overload seen in hemochromatosis.

Animals↗
PubMed1990

Hepatic iron in hemochromatosis.

Ninety-two families with familial hemochromatosis were reviewed and analyzed in regard to hepatic iron and the value of the hepatic iron index (hepatic iron/age). Hepatic iron was measured in 29 hemochromatosis homozygotes, in 10 hemochromatosis heterozygotes, and in 30 control patients with other liver diseases. Hepatic iron content increased with age in homozygotes. Hepatic iron index differentiated homozygotes from heterozygotes (P less than 0.05) and heterozygotes from controls (P less than 0.05). The hepatic iron index is a useful measurement in the diagnosis and management of patients with familial hemochromatosis.

Aging↗
PubMed1990

Hepatic drug clearance: the effect of age using indocyanine green as a model compound.

The hepatic extraction ratio and clearance of indocyanine green (ICG) were determined and used to derive apparent liver blood flow in nine subjects between the ages of 22 and 83 years. There was no correlation between the hepatic extraction ratio of ICG and age (rs = -0.435, NS). There was a significant negative correlation between both ICG clearance and age (rs = -0.710, P less than 0.05) and apparent liver blood flow and age (rs = -0.750, P less than 0.05). These results validate the comparison of liver blood flow values derived from ICG clearance in humans over a wide age range and confirm that liver blood flow does fall with age.

Adult↗
PubMed1990

Familial iron overload with possible autosomal dominant inheritance.

A 96 member Melanesian kindred with 31 cases of iron overload is reported. Liver biopsies from 19 of these patients showed features similar to those of genetic haemochromatosis in Caucasians, but in contrast to the previous reported HLA-linked autosomal recessive pattern of inheritance for haemochromatosis, this family shows a pattern that is most consistent with autosomal dominant inheritance. This is suggested by involvement of three and possibly four consecutive generations, with a high frequency of transmission from parents to children and equal gender distribution. Linkage and segregation analysis supported dominant inheritance, with no demonstrable HLA linkage.

Female↗
PubMed1990

Hepatic iron and iron absorption in hemochromatosis.

The relationship between iron absorption and hepatic iron was studied in 21 patients with hemochromatosis. Iron absorption was studied using 59Fe and total body counting and hepatic iron was measured by atomic absorption spectrophotometry. Iron absorption was inversely related to hepatic iron concentration (r = -0.51, p = 0.009) in this patient population. This observation suggests that iron absorption is regulated by body iron stores even in hemochromatosis, and does not support the hypothesis that the primary metabolic defect in hemochromatosis is a deregulation of iron absorption in relation to iron stores.

Absorption↗
PubMed1989

Hepatic iron in the control of iron absorption in a rat liver transplantation model.

Rat liver transplantation was utilized to study the effect of hepatic iron on the control of iron absorption. Six iron-loaded and six normal livers were transplanted into normal or iron-loaded animals. Iron absorption was measured pretransplant and 10 days posttransplant by total-body counting (59Fe). The animals were loaded with oral carbonyl iron to produce a predominantly parenchymal hepatic iron distribution and with parenteral iron dextran to produce a predominantly reticuloendothelial iron distribution. The carbonyl iron-loaded livers contained 175 +/- 6.6, the iron dextran livers 180 +/- 41, and the normal livers 6.6 +/- 2.8 mumol FE/g dry wt. Iron absorption was unchanged by the insertion of normal livers into normal animals. The transplantation of carbonyl iron-loaded livers into normal animals caused a marked decrease in iron absorption posttransplant from 7.2 +/- 0.9% to 0.3 +/- 0.4% (P less than .001) posttransplant. Neither the transplantation of iron dextran-loaded livers into normal animals nor the transplantation of normal livers into iron-loaded animals significantly altered iron absorption at 10 days posttransplant. These results are consistent with the hypothesis that hepatocyte iron stores are a major determining factor controlling iron absorption.

Absorption↗
PubMed1989

Pacemaker-induced superior vena cava syndrome: report of four cases and review of the literature.

Superior vena cava syndrome due to transvenous pacing leads is a rare event. We describe four cases. One occurred among 3,100 primary pacemaker insertions performed at our institution. In the other three cases the primary insertion had been performed elsewhere. Over 30 cases have been reported previously. Local infection, which preceded the development of superior vena cava syndrome in each of our four cases, and the presence of a severed retained lead, as in three of our cases, are important predisposing factors. There is no strong evidence that multiple lead insertion, if each lead remains intact, significantly increases the risk. The pathology at the site of obstruction includes thrombosis and in some cases fibrotic narrowing. Venous angiography is useful to show the site of obstruction, the extent of collateral circulation and to assess the response to treatment. Treatment should include removal of any infected pacemaker apparatus, anticoagulation and, if symptoms are of recent onset, thrombolytic therapy. Most patients improve but in those who do not angioplasty or surgical relief of the obstruction may be helpful.

Aged↗
PubMed1988

Solid phase immunoradiometric assay for porcine serum ferritin.

1. A solid phase immunoradiometric assay using anti-serum coated polystyrene tubes, is described for the assay of porcine serum ferritin. 2. The mean concentration of ferritin in the serum of both male and female pigs (Sus scrofa) was 12.1 micrograms/l +/- 8.7 micrograms (range less than 1-35 micrograms/l) and no sex differences were observed in 40 pigs from 1 day to 4 years old. 3. Serum ferritin increased with increasing body iron stores in iron loaded pigs as assessed by hepatic iron concentration. 4. The assay is sensitive (detecting less than 1 microgram/l), reproducible, specific and it does not cross-react with human or rat ferritin.

Animals↗
PubMed1988

Isolation of a porcine hepatic ferritin receptor.

1. A ferritin receptor has been isolated from porcine liver and has been partially purified using affinity chromatography. 2. A binding assay has been developed which utilizes a hepatic ferritin receptor coupled to a microparticulate support which facilitates the separation of bound and free ligand. 3. An affinity constant of 2.9 x 10(9) mol-1 litre was determined for the purified hepatic ferritin receptor. 4. The molecular weight of the receptor was estimated to be approximately 53,000 by gel electrophoresis. 5. Binding of ferritin to the insolubilized receptor was unaffected by a 100-fold excess of bovine albumin, porcine and human transferrin, and human asialo-orosomucoid. 6. Binding was specific for porcine ferritin with no demonstrable binding of rat or human ferritin.

Animals↗
PubMed1988

Neonatal hemochromatosis: a case and review of the literature.

Hemochromatosis is a disease in which the inappropriate absorption of iron over 30-40 yr results in tissue iron overload and the development of cirrhosis of the liver, diabetes, hypogonadism, arthropathy, and skin pigmentation. We present an infant who died at 2 days of age, and who was found to have massive iron overload in the liver. This case is consistent with a rare condition that has been called neonatal hemochromatosis. This disease is discussed in the context of an overview of iron metabolism and adult hemochromatosis.

Hemochromatosis↗
PubMed1987

Platelet/vessel wall interactions, rheologic factors and thrombogenic substrate in acute coronary syndromes: preventive strategies.

Thrombosis is an important pathogenetic factor in acute coronary syndromes, including unstable angina, myocardial infarction and sudden death. In all of these conditions, atherosclerotic plaque fissuring is a key inciting event. Minor injury to the vessel wall brings into play interactions between platelets and the wall. Platelet adhesion and aggregation ensue, modulated by a number of factors and substances. More severe injury to the vessel wall exposes the blood to other thrombogenic substances. Platelet deposition is also affected by rheologic (blood flow) factors at the site of injury, depending on the degree of stenosis and the resulting shear rates. The mechanism of unstable angina appears to be related to these factors in the following sequence: mild stenosis and minor injury with plaque fissuring, platelet responses, labile thrombosis, intermittent ischemia and pain at rest. Vasoconstriction may contribute to the symptoms. Although developing from the same origin, infarction may stem from a greater degree of vessel wall damage resulting in more permanent thrombus. Such considerations provide a focus for preventive strategies, including the optimal use of current inhibitors of platelet adhesion and aggregation and the application of peptide receptor blockers and monoclonal antibodies. Also important is control of rheologic factors by preventing stenosis or correcting it with angioplasty and thrombolytic therapy. Further elucidation of the critical role of thrombosis in coronary syndromes will facilitate progress toward the ultimate goal of primary prevention.

Blood Flow Velocity↗
PubMed1987

The effect of thrombolytic therapy with anisoylated plasminogen streptokinase activator complex on the indicators of myocardial salvage.

The role of anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction, in effecting thrombolysis, in limiting infarct size and in preserving myocardial function, was assessed by comparing APSAC and placebo in a double-blind, randomised trial. Between October 1984 and April 1985, 43 patients (mean age 57.3 years) with evolving infarctions (19 anterior/24 inferior) were randomised. All patients received treatment within 3 hours of the onset of pain. Patients over 70 years of age or with contraindications to thrombolytic therapy were excluded. Response to therapy was assessed by comparing reductions in summated ECG R wave amplitude and changes in QRS score at 24 hours and 7 days in the leads with ST abnormalities on admission. Radionuclide ejection fractions (EF) were performed 2 to 6 months after infarction. Evidence of successful reperfusion was based on non-invasive parameters. Mean time to peak cardiac enzyme release was shorter in the active treatment group, indicating effective thrombolysis (11.5 hours vs 17.6 hours; p less than 0.01). No differences were found in R wave reduction or QRS score at either 24 hours or 7 days, between active and placebo groups in total or when divided by infarct site. No difference was seen between the EFs of the groups in total or between inferior infarct groups. The mean EF of the treated anterior group was higher than that of the untreated group (p less than 0.05). Successful thrombolysis was seen in the actively treated group. Evidence of myocardial salvage and preservation was seen among treated patients with anterior infarcts only.

Adult↗
PubMed1987

Role of platelets in atherogenesis: relevance to coronary arterial restenosis after angioplasty.

There is now considerable evidence to suggest that some aspects of early lesion formation and later lesion growth are a reaction to injury. Hemodynamic factors are important in determining the site of injury and may produce injury directly. Injury can lead to atherogenesis in animal models as well as in humans. Superficial injury exposes the subendothelium, allowing platelet adhesion, which at high shear rates is dependent on vWF. Platelet adhesion and degranulation release PDGF, which stimulates smooth muscle cell proliferation, synthetic functions, and vasoconstriction. LDL stimulates smooth muscle cell growth as well as damages endothelium in some experimental systems. Thus, a link is provided between platelet and lipid involvement in atherosclerosis. Direct evidence for a role of platelets in atherogenesis comes from studies in which animals were treated to reduce platelet number or function or in which platelet function is genetically impaired (pigs with von Willebrand's disease). In these models, reduced platelet function is associated with less atherosclerosis. Deeper injury exposes collagen, with subsequent platelet aggregation, thrombin and fibrin generation. The role of reduced production of PGI2 and fibrinolytic agents following severe damage is unknown. Deep injury to the vessel occurs during plaque fissuring, the pathologic process underlying most cases of myocardial infarction, unstable angina, and some cases of sudden death. Angioplasty produces amelioration of many patients' symptoms and is safe. However, acute occlusion occurs occasionally, and restenosis in the first year occurs in some 30 percent of patients treated. Angioplasty damages the arterial wall, with endothelial denudation and intimal and medial splitting. Why does this, and plaque injury, by stimulating platelet deposition, not produce more restenosis? Changes in arterial anatomy are likely to be important: the increase in vessel diameter and in blood flow produce conditions less favorable for thrombotic or arteriosclerotic restenosis.

Angioplasty, Balloon↗