Biomedical subjects

P C Adams

Publications and source records attributed to P C Adams.

At least 109 records · Page 6Linked to original sources

PubMed1992

Intrafamilial variation in hereditary hemochromatosis.

A review of 57 families with hereditary hemochromatosis revealed three pairs of HLA-identical, sex-matched siblings in which the younger sibling demonstrated considerably more iron loading than the older sibling. Liver biopsy, chemical hepatic iron determination, iron absorption studies, and number of venesections required were used to support these observations. Nineteen pairs of HLA identical, sex-matched siblings homozygous for hemochromatosis were found in which the iron loading was more marked in the older sibling. There was no evidence of blood loss, difference in alcohol consumption, or dietary iron loading to explain the increased iron loading in the younger sibling. These three families demonstrate that the rate of iron accumulation may vary within a family and that the extent of iron loading in hereditary hemochromatosis is not solely dependent on the duration of iron accumulation.

Age Factors↗

PubMed1992

Septal rupture after myocardial infarction: is very early surgery really worthwhile?

Despite numerous publications, mostly with small patient populations, the management of post-infarct septal rupture is still not well defined. Although urgent surgery appears to be the therapy of choice it is still unclear whether surgery very early after septal rupture in patients with severe haemodynamic compromise salvages a significant number of patients. In this paper we present the data from a large population of consecutive patients with post-infarct septal rupture from one cardiac centre. From 1980 through 1989, 108 patients with post-infarct septal rupture were seen at this Regional centre of whom 81 had operative repair; 43 (53%) of these survived the early postoperative period. Of 32 patients with cardiogenic shock who had surgery, early operative mortality in those operated on within 48 h of rupture was 90% (18/20) compared with 33% (4/12) in those operated on later (P less than 0.001). All survivors with pre-operative shock had intra-aortic balloon counter-pulsation before operation. Concomitant coronary artery bypass grafting was not associated with improved survival in our patients. Three patients survived long-term without operation. Analysis of population statistics suggest that approximately 270 patients with post-infarction septal rupture were not transferred from peripheral hospitals to the Regional Cardiothoracic Centre for assessment during this decade.

Aged↗

PubMed1992

Liver biopsy under hypnosis.

Two patients underwent outpatient percutaneous liver biopsy under hypnosis without complications. One patient had severe anxiety about the procedure because of a previous adverse experience with liver biopsy and the other had a history of severe allergy to local anesthesia. Both patients had undergone a session of hypnosis at least once prior to the biopsy. One received no local anesthetic and the other received 1% lidocaine as a local anesthetic. Both patients were completely cooperative during the procedure with the required respiratory maneuvers. Both patients stated that they were aware of the procedure under hypnosis but described no pain and would be most willing to have the procedure done under hypnosis in the future. Hypnosis can be a useful method of preparing carefully selected patients for percutaneous liver biopsy.

Adult↗

PubMed1992

The occurrence of early sudden coronary artery occlusion following angioplasty may be predicted from the clinical characteristics of the patients and their coronary lesion morphology.

The aim of this study was to assess whether the incidence of early occlusion following angioplasty was greater among patients with unstable angina and whether the coronary lesions prone to early occlusion could be predicted from their angiographic appearance. Seventy-seven patients who had had a first angioplasty of a native vessel for stable or unstable angina in one twelve month period were included. The angiographic appearances of the angioplastied lesions were classified as either Type 1, which were smooth and unlikely to have thrombus or intimal rupture, or Type 2, which were irregular due to thrombus or intimal rupture. The lesion classification was compared to the patients' clinical features, i.e. stable or unstable angina, and the outcome of the angioplasty. Type 2 lesions occurred in 25% of patients with stable angina but 49% of patients with unstable angina (p less than 0.05). Early sudden occlusion of the angioplastied vessel occurred in 24% of patients with unstable angina but in only 3% of patients with stable angina (p less than 0.05) and in 6% of Type 1 lesions compared with 24% of Type 2 lesions (p less than 0.05). Thus it is possible to identify the clinical characteristics and angiographic appearances of those patients undergoing angioplasty who are most likely to experience early vessel occlusion.

Angina Pectoris↗

PubMed1991

Expression of transferrin receptors on monocytes in hemochromatosis.

To assess whether an abnormality in transferrin receptor expression or regulation could represent an underlying metabolic defect in the reticuloendothelial (RE) system in hemochromatosis, monocytes were analyzed for the expression of the transferrin receptor using a monoclonal antibody (Act II) to the transferrin receptor (CD71) and flow cytometric analysis. Hemochromatosis patients (n = 14), and normal volunteers with no clinical evidence of iron overload (n = 14) were studied. A significant inverse relationship was observed for the relationship between the expression of transferrin receptor on monocytes and log(hepatic iron concentration) in hemochromatosis patients (r = -0.59, P less than .02) and also for the relationship between the expression of transferrin receptor and log(serum ferritin) in normal volunteers (r = -0.90, P less than .001). There was no significant difference in the mean expression of monocyte transferrin receptor between hemochromatosis patients and normal volunteers. However, the expression of the transferrin receptor in hemochromatosis patients was disproportionately higher than would be predicted from the relationship between serum ferritin and transferrin receptor expression in normal volunteers. The inverse relationship of the monocyte transferrin receptor relative to body iron stores in hemochromatosis is consistent with observations in other tissues, and suggests that non-transferrin iron metabolism, including ferritin, requires further investigation in the RE cell in hemochromatosis.

Antibodies↗

PubMed1991

Antithrombotic therapy in the coronary vein graft patient.

Coronary artery bypass grafting is an important therapeutic modality in the treatment of the patient with coronary artery disease; however, long-term results are limited by the development of saphenous vein graft disease early and late after operation. The pathogenesis of early vein graft occlusion is primarily thrombotic, while that occurring later frequently involves thrombosis superimposed on intimal hyperplasia or vein graft atherosclerosis. We describe the role of various platelet inhibitors and anticoagulants in the prevention of saphenous vein graft occlusion following coronary artery bypass grafting.

Coronary Artery Bypass↗

PubMed1991

Long-term survival analysis in hereditary hemochromatosis.

This study investigated the long-term survival rates of 85 patients with hereditary hemochromatosis. Eighty-five patients with documented hereditary hemochromatosis diagnosed between 1958 and 1989 and followed up at the University Hospital (University of Western Ontario) medical center were retrospectively reviewed for this analysis. The current status of the patient was assessed by interview or written questionnaire completed by the patient or the family physician. Estimates of differences in survival rates were obtained using Kaplan-Meier life-table and Cox regression analysis. Liver histology, clinical features of the disease, and number of venesections were analyzed to determine their relationship to survival. In the course of a mean follow-up interval of 8.1 +/- 6.8 years (range, 0-31 years), there were 17 deaths among the 85 hemochromatosis patients. Patients with cirrhosis at the time of diagnosis were 5.5 times more likely to die than noncirrhotic patients. Patients who were noncirrhotic at the time of diagnosis had an estimated survival that was not significantly different from age- and sex-matched members of the normal population. Diabetes did not increase the risk of death after data were controlled for the presence of cirrhosis. Early diagnosis and treatment of hemochromatosis in the precirrhotic stage can lead to long-term survival similar to that in the general population. The presence of cirrhosis significantly increases mortality and is the major clinical factor affecting survival.

Aged↗

PubMed1991

Mucosal iron in the control of iron absorption in a rat intestinal transplant model.

Isogeneic intestinal transplantation of iron-loaded and iron-deficient intestine into iron-deficient rats was performed in 20 Lewis rats to isolate the effect of intestinal mucosal iron on iron absorption. Rats were iron loaded with three weekly IM injections of 50 mg of iron dextran and were rendered iron deficient with an iron-deficient diet for 3 weeks. Iron status was assessed by hepatic and gut mucosal iron determination. Uptake and transfer of 59Fe-ascorbate was measured in an isolated perfused segment of transplanted intestine 48 hours after transplantation. The mean rate of uptake of 59Fe from an iron-loaded intestine (mean mucosal iron concentration, 7.97 +/- 2.02 mumol/g) was 431 +/- 27 nmol/30 min, and from an iron-deficient intestine (mean mucosal iron concentration, 1.35 +/- .84 mumol/g), 743 +/- 222 nmol/30 min (P less than 0.001). The mean transfer of 59Fe from the mucosal cell to the body through an iron-loaded intestine was 63 +/- 22 nmol/30 min, and through an iron-deficient intestine was 86 +/- 32 nmol/30 min (P less than 0.05). These results suggest that the gut mucosal iron concentration regulates the uptake and transfer of iron in the intestine.

Animals↗

PubMed1991

Biochemical liver profile in hemochromatosis. A survey of 100 patients.

To determine the frequency of liver profile abnormalities in hereditary hemochromatosis, we under took a retrospective survey in 100 patients, all of whom had undergone liver biopsy. Liver histology was compared with the biochemical profile, which included aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, bilirubin and albumin determinations. Mild abnormalities in the AST and ALT levels were seen in more than 65% of patients. Patients with cirrhosis had significantly greater elevations in AST, ALT, and alkaline phosphatase, and a significant decrease in albumin (p less than 0.05). Proband cases had more frequent abnormalities than discovered cases within families. Accordingly, we find that mild abnormalities in the biochemical liver profile are common in hemochromatosis and suggest that patients with an unexplained abnormality in the liver profile should be screened for hemochromatosis with a serum ferritin and transferrin saturation.

Adolescent↗

PubMed1991

Complications associated with retained pacemaker leads.

Retention of functionless pacemaker leads may occur following mechanical or infective problems (potentially or definitely infected) or after electrical failure of the lead. One hundred nineteen patients with a pacemaker lead (or leads) retained between 1970 and 1990 were reviewed retrospectively. Lead retention after an intervention dictated by potential or definite infection of the pacing system resulted in complications in 27 of 53 patients (51%), which in 22 patients (42%) were major (septicemia, superior vena cava syndrome, and further surgery under general anesthesia for recurrent "infective" problems) including three deaths. Complications were less likely if lead retention occurred after electrical failure with three minor and two major (surgery under general anesthesia, superior vena cava syndrome) complications in 66 patients (P less than 0.001). Bacteriology of swabs taken at the time of retention in the patients with potential or definite infection was unhelpful in predicting future complications: 8/18 patients (44%) whose swabs were negative had complications of which 5/18 (28%) were major. In our experience retention of functionless pacemaker leads after an intervention dictated by potential or definite infection of the pacing system, is associated with significant morbidity and mortality and should be avoided.

Adolescent↗

PubMed1991

Transplantation of a donor liver with haemochromatosis: evidence against an inherited intrahepatic defect.

An iron loaded liver from a 40 year old man with occult haemochromatosis was transplanted into a 19 year old woman with acute liver failure secondary to a paracetamol overdose. Increased parenchymal hepatic iron was found in a liver specimen at biopsy undertaken because of mild rejection 30 days after transplantation. After transplantation the patient had two episodes of liver rejection confirmed by biopsy. The hepatic iron concentration fell from 161 mumol/g on day 30 after transplant to 26.5 mumol/g (normal less than 40) on day 210. Iron absorption, measured 45 days after transplant, was in the normal range at 12.4%. The rapid fall in hepatic iron and the normal iron absorption study result suggest that the genetic defect of haemochromatosis is not exclusively an intrahepatic defect.

Adult↗

PubMed1991

Monocyte membrane ferritin in hemochromatosis.

To further evaluate a possible abnormality in the reticuloendothelial cells in hemochromatosis, the binding of a monoclonal anti-human liver ferritin antibody to monocytes was studied in 19 patients with hemochromatosis, 8 patients with secondary iron overload, 1 patient with hyperferritinemia without iron overload, and 15 normal volunteers. Binding of the antibody to the monocytes was analyzed using a fluorescence-activated cell sorter (FACS). Binding of the anti-ferritin antibody to monocytes was demonstrated in 34.7 +/- 4.5% (mean +/- standard error) of the monocytes in untreated hemochromatosis patients (mean serum ferritin = 2294 +/- 415 micrograms/L), 6.75 +/- 2.03% in treated hemochromatosis patients (mean serum ferritin = 263 +/- 85 micrograms/L), 12.3 +/- 2.7% of the monocytes in the secondary iron overload patients (mean serum ferritin = 2476 +/- 867 micrograms/L), 4.1% in the patient with hyperferritinemia (serum ferritin = 1192) and 4.1 +/- 0.5% of the monocytes in the normal volunteers (mean serum ferritin = 55.2 +/- 11.9 micrograms/L). % binding of anti-ferritin antibody was significantly greater in hemochromatosis patients compared to patients with secondary iron overload (p less than 0.05) despite a comparable degree of iron overload in the secondary iron overload group. The addition of exogenous human ferritin to samples from treated hemochromatosis patients and normal volunteers did not significantly increase the % of monocytes binding anti-ferritin antibody. These results suggest that monocytes from iron-loaded hemochromatosis patients express increased surface ferritin which may represent release of ferritin and a metabolic defect characteristic of hemochromatosis.

Antibodies, Monoclonal↗

PubMed1991

The effect of human recombinant erythropoietin on iron absorption and hepatic iron in a rat model.

In order to ascertain whether recombinant human erythropoietin (EPO) therapy would result in further intestinal iron absorption in the setting of systemic iron loading, iron absorption was measured in iron-loaded rats receiving EPO therapy and a control group of iron-loaded rats. Parenteral iron dextran (100 mg) resulted in hepatic siderosis with predominantly a reticuloendothelial distribution. EPO was given by intraperitoneal injection (100 U/kg) for 10 days. Radioiron absorption was measured by total body counting. Iron absorption in EPO-treated rats was 4.8 +/- 2.0% (n = 12) and 4.5 +/- 2.2% (n = 10) in the control rats (p greater than 0.05). Mean hemoglobin in the EPO rats was 201 +/- 12.5 g/L and 140 +/- 18.2 g/L in the control rats (p less than 0.001). Mean hepatic iron concentration was 73 +/- 16 mumol/g in the control rats and 34 +/- 9.1 mumol/g in the EPO-treated rats (p less than 0.001). This study suggests that iron-loaded rats do not demonstrate an increase in intestinal iron absorption with EPO therapy despite a significant erythropoiesis. The reduction in hepatic iron concentration suggests that reticuloendothelial iron is accessible and mobilized to produce new red blood cells.

Animals↗

PubMed1991

Enhanced biliary iron excretion with amphiphilic diethylenetriaminepentaacetic acid.

The elimination of toxic metal ions metabolically accumulated by patients remains a difficult clinical problem and a target of drug development. DTPA (diethylenetriaminepentaacetic acid) is a hydrophilic chelating agent with high affinity for divalent and trivalent metal ions including iron but with a limited ability to cross cell membranes for access to iron stores. In this study we have synthesized an amphiphilic form of this chelator-DTPA covalently linked to the phospholipid phosphatidylethanolamine (PE)--to produce a chelator that incorporates completely and stably into liposome membranes for efficient delivery to the liver and reticuloendothelial system. Biliary and urinary excretion of iron were studied in iron-loaded rats (n = 15) in association with a 2-hr intravenous infusion of sonicated liposomes of 1:1 amphiphilic phosphatidylethanolamine-DTPA/egg phosphatidylcholine (L-PE-DTPA) and compared with excretion obtained using equivalent amounts of water-soluble DTPA (alone or mixed with egg phosphatidylcholine liposomes [L-DTPA] as controls). For a 6-hr period, the administration of L-PE-DTPA resulted in approximately a 20-fold increase in biliary iron excretion (480 +/- 160 micrograms/6 hr, mean +/- S.D.) compared with that seen with DTPA (21.2 +/- 4.0 micrograms/6 hr) and L-DTPA (23.1 +/- 5.0 micrograms/6 hr) (p less than 0.05, analysis of variance). Urinary iron excretion was significantly decreased with L-PE-DTPA (41.5 +/- 38 micrograms/6 hr) compared with DTPA (154 +/- 110 micrograms/6 hr) and L-DTPA (86 +/- 17 micrograms/6 hr) (p less than 0.05). Combined biliary and urinary excretion of iron was three to four times greater with L-PE-DTPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1991

Clinical presentation of hemochromatosis: a changing scene.

PURPOSE: To investigate the changing modes of clinical presentation and diagnosis in 93 patients with familial hemochromatosis and to compare the results with other reports from 1935 to the present. PATIENTS AND METHODS: The presenting features and the frequency of signs and symptoms were analyzed in 93 homozygotes from 56 families. RESULTS: Hemochromatosis was detected by chance in 40% of the 56 probands. Abdominal pain (16%), joint pains (11%), and weakness (9%) were prominent features that brought the patient to the physician. Although 38% of the male patients had loss of libido and impotence, these were not identified as presenting features. Features of liver disease (84%), arthritis (11%), and diabetes (2%) led the physician to the diagnosis. Impotence and testicular atrophy were notable, by their absence, in alerting physicians to the presence of hemochromatosis. Screening of family members led to the detection of 37 homozygotes, of whom 46% were asymptomatic. Among this group, arthropathy and gonadal failure were the most common symptoms. The classic triad of hepatomegaly, diabetes, and pigmentation was present in only 8% of patients. Clinical features were rare in patients with less than 5 g of exchangeable body iron and invariably present in those with more than 16 g. CONCLUSION: The presenting clinical features of hemochromatosis have changed since the original description of the disease in 1935. Family studies have led to the earlier discovery of more homozygous women and earlier detection with less iron loading and, as a result, fewer signs and symptoms.

Adolescent↗

PubMed1991

Hepatic zinc in hemochromatosis.

Since an intestinal absorptive interaction between iron and zinc has been described in animals and humans, the possibility of increased accumulation of zinc as well as iron in the liver was studied in patients with hereditary hemochromatosis. Hepatic zinc was determined by atomic absorption spectrophotometry in liver biopsy specimens from 21 homozygotes for hemochromatosis, 21 normal liver samples from autopsies, and 15 cases of cirrhosis unrelated to iron overload. Mean hepatic zinc concentrations in the three groups were compared by one-way analysis of variance. Hemochromatosis patients had hepatic iron determinations by atomic absorption spectrophotometry, and iron absorption studies using 59Fe and total body counting had been previously documented in 18 of the 21 hemochromatosis patients. The mean hepatic zinc was significantly increased at 25.9 +/- 26.7 mumol/g (dry weight) in the hemochromatosis patients, as compared to 4.99 +/- 1.51 mumol/g in the control patients (p less than 0.05), and 2.13 +/- 1.13 mumol/g in the cirrhosis patients without iron overload (p less than 0.05). Hepatic zinc concentration was elevated in hemochromatosis patients who had either normal histology, fibrosis, and cirrhosis. Hepatic zinc concentration was not directly related to patient age, hepatic iron concentration, or iron absorption. In conclusion, hepatic zinc was increased approximately fivefold in patients with hemochromatosis. This finding suggests the concomitant hepatic accumulation of zinc as well as iron in this disorder, possibly by means of increased intestinal absorption of zinc and hepatic sequestration.

Adult↗

PubMed1990

Usefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group).

In a prospective pilot trial of antithrombotic therapy in the acute coronary syndromes (ATACS) of resting and unstable angina pectoris or non-Q-wave myocardial infarction, 3 different antithrombotic regimens in the prevention of recurrent ischemic events were compared for efficacy. Ninety-three patients were randomized to receive aspirin (325 mg/day), or full-dose heparin followed by warfarin, or the combination of aspirin (80 mg/day) plus heparin and then warfarin. Trial antithrombotic therapy was added to standardized antianginal medication and continued for 3 months or until an end point was reached. Analysis, by intention-to-treat, of the 3-month end points, revealed the following: recurrent ischemia occurred in 7 patients (22%) after aspirin, in 6 patients (25%) after heparin and warfarin, and in 16 patients (43%) after aspirin combined with heparin and then warfarin; coronary revascularization occurred in 12 patients (38%) after aspirin, in 12 patients (50%) after heparin and warfarin, and in 22 patients (60%) after aspirin combined with heparin and then warfarin; myocardial infarction occurred in 1 patient (3%) after aspirin, in 3 patients (13%) after heparin and warfarin, and in no patient after aspirin combined with heparin and then warfarin; no deaths occurred after aspirin or after aspirin combined with heparin and then warfarin, but 1 patient (4%) died after warfarin alone; major bleeding occurred in 3 patients (9%) after aspirin, in 2 patients (8%) after heparin and warfarin, and in 3 patients (8%) after aspirin combined with heparin and then warfarin. Recurrent myocardial ischemia occurred at 3 +/- 3 days after randomization.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

PubMed1990

Orthotopic liver transplantation in a patient with combined hemophilia A and B.

A 38-year-old man with severe factor IX and mild factor VIII deficiencies complicated by cirrhosis secondary to chronic non-A non-B hepatitis underwent orthotopic liver transplantation as treatment for both the cirrhosis and his congenital coagulopathy. Intraoperative hemostasis was obtained with factor VII-depleted prothrombin complex concentrate and fresh frozen plasma. Factor VIII and factor IX levels were assayed frequently in the perioperative period, and both returned to normal within 24 hr and remained normal postoperatively. Liver transplantation can be considered as definitive therapy for hemophilia A and/or B with transfusion-related liver disease.

Adolescent↗