Biomedical subjects

P C Adams

Publications and source records attributed to P C Adams.

At least 91 records · Page 5Linked to original sources

PubMed1995

Iron-responsive element-binding protein in hemochromatosis liver and intestine.

Iron-responsive element-binding protein (IRE-BP) activity was studied in liver and intestinal samples of hemochromatosis and control patients using a short 32P-IRE-RNA probe on "retardation" nondenaturing polyacrylamide gels. IRE-BP activity was assessed in liver biopsy specimens in 36 patients--16 hemochromatosis homozygotes, 4 hemochromatosis heterozygotes, 6 patients with secondary iron overload, and 10 control patients with normal hepatic iron concentrations. Intestinal IRE-BP activity was assessed in 14 hemochromatosis homozygotes and 16 normal subjects. Endogenous IRE-BP activity was determined from 32P retarded on the gel, and total IRE-BP activity was assessed after reducing tissue samples with 2-mercaptoethanol. Hepatic endogenous IRE-BP activity was inversely related to hepatic iron concentration (r = .59, P < .0002). Mean hepatic endogenous IRE-BP activity in the hemochromatosis homozygotes, 0.25 +/- 0.04 pmol/mg protein, was significantly decreased compared with values in the normal controls, 0.45 +/- 0.06 pmol/mg protein, P < .05. Hepatic total IRE-BP was also significantly decreased in the hemochromatosis patients by gel retardation assay and Western blotting with anti-IRE-BP antibody. Intestinal endogenous IRE-BP activity, total IRE-BP activity, and iron concentration did not significantly differ between hemochromatosis patients and normal control subjects. This suggests that both endogenous IRE-BP activity and the total amount of the protein are downregulated in the liver by tissue iron. Intestinal IRE-BP activity that regulates intestinal transferrin receptor expression is normal in hemochromatosis and appropriate for the intracellular iron concentration.

Adult↗

PubMed1995

Metabolism of [14C]1,3-dinitrobenzene by rat small intestinal mucosa in vitro.

The small intestine can metabolize a variety of substances and can play a role in the presystemic clearance of ingested compounds. Relatively little is known about the ability of small intestine to catalyze the presystemic reductive metabolism of xenobiotics. 1,3-Dinitrobenzene (1,3-DNB), which is known to undergo reductive biotransformation in an intact, oxygenated isolated perfused intestinal preparation, was used as a model substrate for reductive enzymes of the small intestine of the rat. Subcellular fractions from duodenal, jejunal, and ileal regions of rat small intestinal mucosa were used to characterize the enzyme source(s) of those reductive reactions of 1,3-DNB that are relevant in the oxygenated intestinal tissue. 1,3-DNB was reduced to 3-nitroaniline (3-NA) by cytosol from duodenum and jejunum. The rate of reduction was 2 times faster when incubations contained duodenal rather than jejunal cytosol. Jejunal cytosol-catalyzed reduction of 1,3-DNB was supported by hypoxanthine, NADPH, or NADH. Duodenal microsomes catalyzed the reduction of 1,3-DNB to 3-NA in the presence of supplemental NADPH or NADH; however, the reaction was very slow. Jejunal microsomes, ileal microsomes, and ileal cytosol failed to catalyze the reduction of 1,3-DNB. Studies with chemical inhibitors suggested possible roles for DT diaphorase, glutathione reductase, or xanthine oxidase in the jejunal cytosol-catalyzed reaction. Purified, commercially available xanthine oxidase (from buttermilk) catalyzed the reduction of 1,3-DNB to 3-NA when supplemented with NADH or hypoxanthine.

Animals↗

PubMed1994

Prevalence of abnormal iron studies in heterozygotes for hereditary hemochromatosis: an analysis of 255 heterozygotes.

Iron studies were compared in 434 patients from 80 hemochromatosis families classified as putative homozygotes, heterozygotes, and normal by HLA typing. There were 28 of 255 (11%) heterozygotes with an elevated serum ferritin and 22 of 255 (8.6%) with an elevated transferrin saturation. Serum ferritin (140 +/- 10.2 micrograms/liter; mean +/- standard error) was greater in heterozygotes than in normal subjects (87 +/- 8.5 micrograms/liter; P < .05, Mann Whitney test). Transferrin saturation was greater in heterozygotes (38% +/- 0.88%) than in normal patients (29% +/- 1.1%; P < .0001). Mean hepatic iron concentration was 54 +/- 6 mumol/g (n = 17), and the hepatic iron index was < 2 in these patients. Most heterozygotes for hemochromatosis have a normal serum ferritin and transferrin saturation. Heterozygotes with minor elevations in serum ferritin or transferrin saturation do not have significant iron overload as assessed by hepatic iron concentration.

Female↗

PubMed1994

Hereditary hemochromatosis and red cell aplasia.

A 63-year-old white man with myasthenia gravis and red cell aplasia was found to have hepatic iron overload. The differential diagnosis included hereditary hemochromatosis and secondary iron overload related to red cell aplasia. Family studies of siblings, including HLA typing, initially suggested a diagnosis of secondary iron overload. The investigation of a remote sibling led to the final diagnosis of hereditary hemochromatosis. The case illustrates the importance of complete family investigations in the differentiation between hereditary hemochromatosis and secondary iron overload and the potential hazard of using HLA typing as an indirect genetic test for hereditary hemochromatosis.

Diagnosis, Differential↗

PubMed1994

Vascular alpha-adrenergic responsiveness is reduced in cirrhosis.

Cirrhosis of the liver is associated with altered cardiovascular regulation. Patients with cirrhosis often have decreased total peripheral vascular resistance despite increased sympathetic activity. To determine whether this reduction in effective sympathetic activity may be caused by an alteration in vascular adrenergic responsiveness, we studied nine patients with biopsy-proven cirrhosis and 12 age-matched control subjects. To assess human vascular adrenergic responsiveness, we used dorsal hand vein linear variable differential transformer techniques. Sensitivity for phenylephrine-mediated vasoconstriction was significantly reduced in patients with cirrhosis (median effective dose [ED50] for phenylephrine: cirrhosis, 1514 ng/min; control subjects, 282 ng/min; p = 0.026). In contrast, the effect of isoproterenol did not differ (cirrhosis: 89% +/- 15% of maximal nitroglycerin effect; control subjects 79% +/- 6%; ED50 for isoproterenol: cirrhosis, 38 ng/min; control subjects, 20 ng/min). These studies indicate that vascular alpha-adrenergic responsiveness in patients with cirrhosis is decreased, whereas beta-adrenergic responsiveness remains intact. A selective decrease in vascular alpha-adrenergic responsiveness may contribute to the decreased peripheral vascular resistance in cirrhosis.

Adult↗

PubMed1994

Multiple arteriovenous malformations in a man with a connective tissue disorder.

Multiple arteriovenous malformations in patients with connective tissue disorders are not reported. We describe a man with cutaneous, ligament/articular and vascular features suggestive of a connective tissue disorder and who also has multiple arteriovenous malformations resulting in a high output circulatory state. Chest pain due to arteriovenous malformations originating from subclavian vessels has caused considerable morbidity.

Adult↗

PubMed1994

Prospective evaluation of a prostacyclin-sparing aspirin formulation and heparin/warfarin in aspirin users with unstable angina or non-Q wave myocardial infarction at rest. The Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

The aim of this trial was to compare the efficacy of combination antithrombotic therapy with a prostacyclin-sparing aspirin plus anticoagulation versus conventional aspirin plus anticoagulation, when added to antianginal therapy, in patients with unstable angina or non-Q wave myocardial infarction already being treated with aspirin. In a double-blind (for the aspirin) study, 144 prior aspirin users were randomized; 72 patients received controlled-release, prostacyclin-sparing aspirin 75 mg daily plus anticoagulation (intravenous heparin followed by warfarin to maintain the international normalized ratio at 2-3), and 72 patients received conventional aspirin 75 mg daily plus the same anticoagulation. Controlled-release aspirin was formulated to preserve endothelial cell prostacyclin synthesis. Trial therapy was begun by 13.2 +/- 12.3 h of qualifying pain, and continued for 12 weeks. The frequency of recurrent angina with electrocardiographic changes, myocardial infarction, or death, was analysed by intention to treat. At 12 weeks, events were: [table: see text] Twenty-six of the 42 (62%) recurrent ischaemic events occurred within 7 days of presentation. Four of the 144 patients (3%) experienced a major bleeding complication. It is concluded that in spite of maximal antithrombotic therapy, there is a significant failure rate of medical therapy in aspirin users presenting with unstable angina or non-Q wave myocardial infarction while at rest. Prostacyclin-sparing aspirin offers no clinical benefit over conventional aspirin.

Adult↗

PubMed1994

Coronary artery disease is associated with increased lipoprotein(a) concentrations independent of the size of circulating apolipoprotein(a) isoforms.

Lipoprotein(a) [Lp(a)] concentration and apolipoprotein(a) [apo(a)] isoforms (identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE] and Western blotting) were determined in a group of 508 asymptomatic Caucasian members of the community and in 318 Caucasian patients with angiographically defined coronary artery disease (CAD). Conventional risk factors for CAD were also measured. Lp(a) concentration was almost twice as high in subjects with CAD (geometric mean, 152 mg/L [geometric SD, 10 to 1398 mg/L]) as in asymptomatic control subjects (geometric mean, 84 mg/L [geometric SD, 21 to 334 mg/L]). Asymptomatic women had higher concentrations of Lp(a) than asymptomatic men. Patients with CAD were older and were more likely to have smoked and to have a first-degree relative with premature CAD (< 55 years of age), and a higher proportion were male. Patients with CAD had higher concentrations of Lp(a) independently of the number of isoform bands expressed. When apo(a) isoforms were allocated to 1 of 10 classes on the basis of their molecular size (Rf versus apoB in SDS-PAGE), patients with CAD did not express an excess of low-molecular-mass (higher concentration) isoforms but did express a higher proportion of double-band phenotypes with fewer "null" phenotypes. The relationship between the two isoform bands in a double-band phenotype was the same in both populations. Isoform mobility was defined as a continuous variable equal to the mobility of a single isoform band (single-band phenotypes) or the mean of the two isoforms in a double-band phenotype. Two variables, isoform mobility and the number of isoform bands expressed, were used to summarize the large range of isoform patterns (at least 45) that could be identified. Isoform mobility, the number of isoform bands expressed, and the presence of CAD were the three most important independent predictors of Lp(a) concentration (descending order). Only sex and LDL cholesterol were additional independent predictors of Lp(a) concentration in step-wise regression models including a wide range of demographic factors and lipid and glycemic risk factors. We conclude that Lp(a) concentration is associated with CAD independently of the isoform pattern expressed. The apo(a) gene locus exerts a strong control over circulating Lp(a) concentration, and a better understanding of the control of expression of the apo(a) gene will be essential to understand the relationship between Lp(a) and CAD.

Apolipoproteins A↗

PubMed1994

Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

BACKGROUND: The purpose of this study was to compare combination antithrombotic therapy with aspirin plus anticoagulation versus aspirin alone, when added to conventional antianginal therapy in patients with unstable rest angina or non-Q-wave myocardial infarction who were nonprior aspirin users. METHODS AND RESULTS: Two hundred fourteen patients were randomized; 109 were randomized to receive aspirin alone (162.5 mg daily) and 105 to receive a combination of aspirin plus anticoagulation, ie, aspirin 162.5 mg daily plus heparin (activated partial thromboplastin time, two times control) followed by aspirin 162.5 mg daily plus warfarin (international normalized ratio, 2 to 3). Trial therapy was begun by 9.5 +/- 8.8 hours of qualifying pain and was continued for 12 weeks. Primary end points were recurrent angina with ECG changes, myocardial infarction, and/or death. Analysis by intention to treat of primary events at 12 weeks was performed. At 14 days, there was a significant reduction in total ischemic events in the combination group versus aspirin alone (10.5% versus 27%, P = .004). An efficacy analysis of primary events at 12 weeks also revealed a large reduction in total ischemic events in the combination group versus aspirin alone (13% versus 25%, P = .06). Bleeding complications were slightly more common with combination therapy. CONCLUSIONS: In nonprior aspirin users, combination antithrombotic therapy with aspirin plus anticoagulation significantly reduces recurrent ischemic events in the early phase of unstable angina.

Angina, Unstable↗

PubMed1994

Hepatic iron and zinc concentrations after portacaval shunting for nonalcoholic cirrhosis.

Hepatic iron and zinc concentrations were determined in 26 consecutive nonalcoholic cirrhotic patients who had previously undergone portacaval shunting and then liver transplantation and 37 control patients. Stainable iron was graded on a scale of 0 to 4; 11 shunt patients and 3 control patients had grade 2 to 4 iron staining. Mean hepatic iron concentration was significantly increased (20.1 +/- 4.1 mumol/gm) in the shunt group compared with the control group (9.1 +/- 2.3 mumol/gm) (normal value, < 35 mumol/gm) (p = .015, Student's t test). Mean hepatic iron index (hepatic iron/age) was 0.5 +/- 0.10 in the shunt group and 0.19 +/- 0.04 in the control group (p = 0.002). One shunt patient had a hepatic iron index of greater than 2. Hepatic zinc was not significantly different between the shunt group (2.42 +/- 0.18 mumol/gm) and the control group (2.56 +/- 0.14 mumol/gm). Serial biopsy specimens were analyzed in 17 cases (6 shunt, 11 controls), and the mean annual rate of iron accumulation was significantly greater in shunt patients (4.75 mumol/gm/yr) than in control cases (0.93 mumol/gm/yr, p = 0.037). Although increased stainable iron was common after portacaval shunting, quantitative iron analysis demonstrated increased hepatic iron concentrations in only 6 of 26 shunt patients and 3 of 37 control patients (p = 0.14, chi 2 test). Quantitative hepatic iron analysis demonstrated in this study that portacaval shunt patients have far less accumulated iron than hemochromatosis patients and are unlikely to have tissue injury resulting from iron overload.

Adult↗

PubMed1993

Prospective comparison of unstable angina versus non-Q wave myocardial infarction during antithrombotic therapy. Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

OBJECTIVES: This study was designed to compare the response of unstable angina and non-Q wave myocardial infarction during treatment with antithrombotic therapy. BACKGROUND: Antithrombotic therapy is beneficial in patients with these two coronary syndromes. METHODS: In a multicenter trial of antithrombotic therapy in unstable angina or non-Q wave myocardial infarction, 358 patients admitted within 48 h of chest pain were randomized to antithrombotic therapy with either 1) aspirin alone, or 2) aspirin plus heparin followed by aspirin plus warfarin, and were prospectively followed up for 12 weeks. Admission cardiac enzyme analyses revealed unstable angina in 268 patients and non-Q wave myocardial infarction in 62. Given an event rate of about 25%, this study has a power of 80% to detect a 50% difference between the two groups. RESULTS: Patients with unstable angina and non-Q wave myocardial infarction were similar with regard to age, gender, coronary risk factors and prior antianginal medication. Primary end points at 12 weeks were recurrent ischemia, infarction and death. [table: see text] In the non-Q wave group, all infarctions and death occurred within the 1st week. CONCLUSIONS: Patients with unstable angina or non-Q wave myocardial infarction on antithrombotic therapy have a similar total number of ischemic events by 12 weeks. However, despite maximal medical therapy with antianginal and antithrombotic medication, patients with non-Q wave infarction have a significantly higher rate of reinfarction and death.

Adrenergic beta-Antagonists↗

PubMed1993

Association between impaired glucose tolerance and circulating concentration of Lp(a) lipoprotein in relation to coronary heart disease.

OBJECTIVE: To examine whether impaired glucose tolerance and raised Lp(a) lipoprotein concentrations are associated in subjects with coronary artery disease. DESIGN: Study of two subject populations, one with and one without symptomatic coronary artery disease. Case-control analysis of patients with impaired glucose tolerance and normal glucose tolerance performed in each subject population independently. SETTING: A general practice and a hospital ward in Newcastle upon Tyne. SUBJECTS: 517 apparently healthy subjects, 13 with impaired glucose tolerance, and 245 patients who had undergone coronary artery bypass graft surgery 12 months before, 51 with impaired glucose tolerance. MAIN OUTCOME MEASURES: Serum Lp(a) lipoprotein concentration, plasma glucose concentration before and after oral challenge with 75 g glucose monohydrate, and Lp(a) lipoprotein isoforms. RESULTS: In both the asymptomatic subjects and the subjects with coronary artery disease there was no significant difference between subjects with impaired glucose tolerance and subjects with normal and body mass index in serum Lp(a) lipoprotein concentrations (geometric mean 61 (geometric SD 4) mg/l v 83 (5) mg/l for asymptomatic subjects, 175 (3) v 197 (2) for subjects with heart disease), nor was there any difference in the proportion of subjects who had Lp(a) lipoprotein concentrations > 300 mg/l (31% v 23% for asymptomatic subjects, 37% v 37% for subjects with heart disease). For both subject groups there was no significant correlation between Lp(a) lipoprotein concentration and plasma glucose concentration after a glucose tolerance test, nor did Lp(a) lipoprotein concentration vary by quintile of glucose concentration after the test. Examination of Lp(a) lipoprotein isoforms in the subjects with coronary artery disease revealed an inverse relation between isoform size and plasma Lp(a) lipoprotein concentration, but there was no evidence that impaired glucose tolerance was associated with particular Lp(a) lipoprotein isoforms. CONCLUSION: Raised Lp(a) lipoprotein concentrations are not responsible for the association between impaired glucose tolerance and coronary artery disease.

Blood Glucose↗

PubMed1993

Rate of iron reaccumulation following iron depletion in hereditary hemochromatosis. Implications for venesection therapy.

Although venesection therapy is well established for the initial depletion of iron stores in hereditary hemochromatosis, the frequency of subsequent therapy has not been clearly defined. In this study, 21 homozygotes (16 male, five female; mean age of 58, with a range of 26 to 77 years) who had completed initial venesection therapy were followed without further venesections for a mean of 4.0 years (range of 1 to 10.4 years) with iron reaccumulation assessed by annual serum ferritin concentration. Over the follow-up period, the mean rise in serum ferritin was 99 (micrograms/l)/year (range of 1.2 to 241 micrograms/l). The mean interval for the ferritin to become elevated above the normal range in 10 patients was 3.8 years. Eleven of 21 patients required no further venesection therapy over the follow-up interval. There was no significant correlation between the annual rate of ferritin increase and the age or amount of iron removed by prior venesections. These data demonstrate that monitoring body iron stores annually and the selective use of venesections if iron stores reaccumulate is a safe alternative to lifelong venesections every 2-4 months. Many homozygotes will not require reinitiation of venesection therapy for > 4 years. Annual monitoring of body iron stores with reinstitution of weekly venesection when the serum ferritin exceeds the upper limit of normal was a safe alternative to long-term maintenance venesection.

Adult↗

PubMed1993

Plasma potassium, serum magnesium and ventricular fibrillation: a prospective study.

Low plasma potassium and magnesium concentrations have been advanced as risk factors for ventricular fibrillation (VF). For potassium, this assertion is based almost exclusively on retrospective data; for magnesium the evidence shows an association with ventricular arrhythmias but no direct association with VF. We studied the relationship between these electrolytes and VF prospectively. Plasma potassium and serum magnesium concentrations were measured on admission to our coronary care unit. Drug therapy, time from onset of symptoms, ECG, enzyme changes and clinical status were all recorded. VF was confirmed by analysis of 24 h monitoring tapes. Mean plasma potassium in the 21 patients with VF who had measurements prior to their arrhythmia was 3.49 +/- 0.54 mmol/l, lower than that of the 1165 patients without VF (mean K 3.88 +/- 0.57 mmol/l, p < 0.05). Plasma potassium concentrations in the 17 patients with myocardial infarction and VF were lower (mean 3.58 +/- 0.41 mmol/l) than in those without VF (n = 417, mean 3.89 +/- 0.61 mmol/l) (p < 0.05). Mean serum magnesium in the 12 patients with VF, measured prior to their arrhythmia (all with myocardial infarction) was 0.80 +/- 0.07 mmol/l, which was not different from the mean for patients without VF (n = 781, 0.82 +/- 0.09 mmol/l) or from the mean of 0.81 +/- 0.08 mmol/l for those with infarction but not VF (n = 331). Low plasma potassium concentrations are associated with increased risk of ventricular fibrillation, but low serum magnesium concentrations are not.

Female↗

PubMed1993

Delays to thrombolysis in the treatment of myocardial infarction.

In-hospital delays to thrombolysis were significantly shorter when thrombolysis was available on admission to the accident and emergency department than after transfer to the coronary care unit (median 60 min v 84 min, p < 0.0001). With direct admission by general practitioners to a coronary care unit the subsequent in-hospital delay was shorter (median 39 min p = 0.0004), but overall delay to thrombolysis longer (median 220 v 170 min, p = 0.0019) because of longer pre-hospital delays. Overall delay was shortest with emergency ambulance referral and thrombolysis being administered in the accident and emergency department.

Aged↗

PubMed1993

Uptake of ferritin by isolated rat hepatocytes. Effect of metabolic inhibitors and iron.

To further characterize the hepatic endocytic pathway of ferritin, the effects of inhibitors of intracellular dissociation of ligands (monensin 15 microM, chloroquine 400 microM), intracellular proteolysis (leupeptin 100 microM) and iron loading on the endocytosis of 125I-rat liver ferritin were studied in isolated rat hepatocytes. Cell associated radioactivity at 37 degrees C was decreased by 27% with chloroquine and 18% with monensin after 4 h. Cell associated radioactivity increased by 38% with leupeptin at 37 degrees C. Acid soluble radioactivity in the extracellular medium was significantly decreased at 4 h in the leupeptin group, which suggests that leupeptin inhibited the lysosomal degradation of the 125I-ferritin resulting in intracellular accumulation of ligand rather than increased uptake of ferritin. Iron loading of cells (5.4-fold increase in intracellular iron) did not significantly alter the binding or accumulation of 125I-ferritin. The characteristics of the endocytic pathway for ferritin are more similar to the asialoglycoprotein receptor than the transferrin receptor, and the hepatic uptake of ferritin is unaffected in this study by increasing the intracellular iron concentration.

Animals↗

PubMed1992

A simple, sensitive technique for classification of apolipoprotein(a) isoforms by sodium dodecyl sulphate-polyacrylamide gel electrophoresis.

Lipoprotein(a) (Lp(a)) is a lipoprotein containing a unique glycoprotein, apolipoprotein(a) (apo(a)), which shows considerable heterogeneity of apparent molecular mass on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). A unifying classification of isoform has been lacking. A simple sensitive procedure for classifying apo(a) isoforms was developed in which the relative mobility of apo(a) on SDS-PAGE was related to that of apolipoprotein (apo) B-100 (Rf vs B). After Western blotting apo(a) bands were visualised by a sensitive double antibody technique employing commercial polyclonal antibodies (sheep antihuman Lp(a) antibody, alkaline phosphatase-linked donkey antisheep antibody). The technique was sensitive (lower limit of detection 0.02 micrograms apo(a)) and had good reproducibility (coefficient of variation 0.9-6.4%). Ten isoform mobilities are described (less than 0.35, 0.40, 0.50, 0.60, 0.70, 0.80, 1.0, 1.10, greater than 1.15). Individuals may have single or double band phenotypes. This classification is compatible with those previously described and the method is suitable for many laboratories, as it employs standard equipment and commercially available materials.

Apolipoproteins A↗

PubMed1992

Human leukocyte antigen typing of siblings in hereditary hemochromatosis: a cost approach.

To assess the clinical value of human leukocyte antigen typing in the diagnosis and management of hereditary hemochromatosis, 105 siblings of 35 proband cases of hemochromatosis were retrospectively analyzed to study whether the exclusion of human leukocyte antigen typing would have adversely affected management. All siblings and probands had already been tested for human leukocyte antigen-A and human leukocyte antigen-B typing, serum ferritin and transferrin saturation. The median age of siblings was 55 yr (range = 11 to 82). Siblings were categorized according to putative genotype (homozygote, heterozygote and normal) using human leukocyte antigen typing. Phenotypic expression of hemochromatosis was considered to be iron overload as indicated by an elevated ferritin (male = greater than 350 micrograms/L, female = greater than 200 micrograms/L) and/or transferrin saturation (greater than 55%). Six of 37 homozygotes had a normal ferritin and transferrin saturation, with five of these patients under 32 yr old. No putative heterozygotes with both an abnormal ferritin and transferrin saturation were seen, although 12 of 48 (25%) heterozygotes had either an elevated ferritin or transferrin saturation. Twenty of 20 normal siblings had a normal ferritin and transferrin saturation. To assess the cost of screening with and without human leukocyte antigen typing, a cost model simulation was used that compared the costs of both methods in a hypothetical family (proband, homozygote, heterozygote and normal sibling).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗