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Biomedical subjects

P C Adams

Publications and source records attributed to P C Adams.

At least 55 records · Page 3Linked to original sources
PubMed1998

Acute coronary syndromes in the United States and United Kingdom: a comparison of approaches. The Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

BACKGROUND: Patients with coronary artery disease are managed differently in different countries. HYPOTHESIS: These variations in patient management may affect clinical outcome, a possibility that should be taken into consideration in multicenter studies. METHODS: In a binational, 3 months study of antithrombotic treatment of patients with unstable angina and non-Q-wave infarction (ATACS), we compared the experience in the four enrollment centers in the United States (US) with the three centers in the United Kingdom (UK). The 59 US patients and the 299 UK patients were similar with regard to age, rates of prior revascularization, prior positive exercise tests, medication use, and aspirin use. RESULTS: US patients were more commonly women (45 vs. 28%), diabetic (30 vs. 4%), or hypertensive (52 vs. 31%), and had a prior coronary angiogram (30 vs. 18%). After enrollment, coronary angiography was performed more frequently in the US than in the UK (61 vs. 22%). Although the distribution of coronary disease was similar, revascularization without recurrent angina (19 vs. 4%, p < 0.001), or following recurrent angina (8 vs. 3%), was significantly more frequent in the US. Combined primary end points (recurrent angina, myocardial infarction, or death) did not differ between US (29%) and UK (25%) patients. CONCLUSION: Therefore, international studies of acute coronary disease need to account for different treatments in different countries. These differences, in the small ATACS study, did not have a major impact on the composite primary outcome variables.

Adult↗
PubMed1998

Genotypic/phenotypic correlations in genetic hemochromatosis: evolution of diagnostic criteria.

BACKGROUND & AIMS: The identification of a candidate gene for hereditary hemochromatosis in 69%-100% of patients with hemochromatosis has resulted in a diagnostic genotypic test (C282Y). The aim of this study was to reassess the phenotypic diagnostic criteria for hemochromatosis in patients homozygous for the C282Y mutation of the HFE gene. METHODS: Transferrin saturation, ferritin, hepatic iron index, and iron removed by venesection were studied in C282Y++ homozygotes and C282Y-- putative homozygotes. RESULTS: Patients were homozygous for the C282Y mutation in 122 of 128 cases (95%). In C282Y homozygotes, the results were as follows: hepatic iron index, >1.9 in 91.3%; transferrin saturation, >55% in 90%; serum ferritin, >300 microg/L in 96% of men and >200 microg/L in 97% of women; and iron removed, >5 g in 70% of men and 73% of women. There were four homozygotes for C282Y with no biochemical evidence of iron overload. CONCLUSIONS: The sensitivity of the phenotypic tests in decreasing order was as follows: serum ferritin, hepatic iron index, transferrin saturation, and iron removed by venesection. Although the genetic test is useful in the diagnostic algorithm, this study has shown both iron-loaded patients without the mutation and homozygous patients without iron overload.

Adult↗
PubMed1998

Implications of genotyping of spouses to limit investigation of children in genetic hemochromatosis.

BACKGROUND: A genetic test for hemochromatosis has allowed for the first time, genotypic identification of heterozygotes. The purpose of this study is to determine whether genotyping of spouses of homozygotes results in fewer investigations of children and subsequent cost savings. METHODS: Two hundred and ninety one children of homozygotes were studied using HLA typing, transferrin saturation and serum ferritin. Ninety six percent of the probands were homozygous for the C282Y mutation of the HFE gene. Pedigrees were reviewed to determine cost savings incurred if the spouse had been genotyped to guide follow-up studies in the children. Paternity was confirmed by HLA studies. RESULTS: There were 13 homozygotes identified. All homozygous children tested (10/10) were homozygous for the C282Y mutation. There were no iron loaded children identified in homozygotes negative for the C282Y mutation. Genotyping of the spouse eliminated the need for the investigation of 269 children. The cost savings of this strategy were modeled using the cost of the family studies (consultation, iron studies) minus the cost of spouse assessment (consultation, genotyping) plus the cost of assessment of children in families in which the spouse was a heterozygote. The spousal genotyping strategy resulted in a cost savings of 39%. CONCLUSION: Genotying the spouse of a homozygote is the best cost-efficient strategy in pedigree studies because it leads to more selective investigation of children for the hemochromatosis gene.

Base Sequence↗
PubMed1998

Atrial flutter with 1:1 atrioventricular conduction caused by propafenone.

We describe a case of 1:1 atrial flutter in a patient with coronary disease taking propafenone. In atrial flutter, the atrial rate is usually about 300 beats/min with 2:1 AV conduction and a ventricular rate of 150 beats/min. Class IA antiarrhythmic drugs, especially quinidine and disopyramide, may cause 1:1 AV response because they reduce atrial rate and are vagolytic. However, propafenone is a Class IC agent and has no anticholinergic properties, and the occurrence of 1:1 AV conduction at a rate of about 250 beats/min is an important side effect that, although uncommon, should be recognized.

Anti-Arrhythmia Agents↗
PubMed1997

Clinical features of genetic hemochromatosis in women compared with men.

BACKGROUND: The clinical expression of hemochromatosis is presumed to be less frequent and less severe in women than in men because of the iron loss associated with menses and pregnancy, but this hypothesis has not been validated. OBJECTIVE: To compare the clinical features of women who have genetic hemochromatosis with those of men who have the disease. DESIGN: Cross-sectional study. SETTING: Tertiary referral centers for hemochromatosis in France and Canada. PATIENTS: 176 women and 176 men with hemochromatosis, matched for year of birth. MEASUREMENTS: Age at presentation, clinical symptoms, transferrin saturation, serum ferritin level, hepatic iron concentration, and hepatic iron index. RESULTS: Hepatic iron concentration and hepatic iron index were similar in men and women. Women had lower serum ferritin levels than men did (911 micrograms/L compared with 1911 micrograms/L; mean difference, 1000 micrograms/L [95% CI, 669 micrograms/L to 1331 micrograms/L]) and less iron removed by venesections (5.5 g and 8.6 g; mean difference, 3.1 g [CI, 1.5 g to 4.8 g]). Compared with women, men had a higher incidence of cirrhosis (25.6% and 13.8%; mean difference, 11.8 percentage points [CI, 3.2 to 20.4 percentage points]) and diabetes (15.9% and 7.4%; mean difference, 8.5 percentage points [CI, 1.9 to 5.2 percentage points]). Compared with men, women had a higher incidence of fatigue (64.8% and 42%; mean difference, -22.8 percentage points [CI, -32.9 to -12.5 percentage points]) and pigmentation (48% and 44.9%; mean difference, -13.1 percentage points [CI, -23.4 to 2.7 percentage points]). Hepatic iron concentration and hepatic iron index were greater in women in whom menstruation had stopped before 50 years of age. Serum ferritin levels and transferrin saturation were normal in 6.2% of women and 0% of men. CONCLUSIONS: Women with genetic hemochromatosis can have full phenotypic expression of the disease, including cirrhosis. Recognizing the nonspecific nature of presenting symptoms in women is essential for early diagnosis and treatment.

Age Factors↗
PubMed1997

The relationship between iron overload, clinical symptoms, and age in 410 patients with genetic hemochromatosis.

The aim of this study was to investigate the relationship between iron overload, age, and clinical symptoms in genetic hemochromatosis. The relationship was studied between clinical symptoms and liver iron concentration, serum ferritin, and iron removed in a retrospective study of 410 homozygotes diagnosed using strict criteria. No significant relationship was found between liver iron concentration, iron removed by venesection, and serum ferritin level with age. The prevalence of cirrhosis, diabetes, cardiac disease, pigmentation, and fatigue increased as liver iron concentration increased. The most common presentations at diagnosis were fatigue or as an incidental finding in all age groups. Twenty-seven percent of patients (110 of 410) had no clinical symptoms of hemochromatosis. Iron accumulation is highly variable in patients with genetic hemochromatosis. The significant relationship between liver iron concentration and cirrhosis, diabetes, cardiac disease, pigmentation, and fatigue confirms the importance of iron toxicity in the pathogenesis of hepatic and extrahepatic disease. The nonspecific nature of the presenting features in patients and the presence of significant clinical symptoms in patients discovered through family investigations underscore the importance of family and population screening for hemochromatosis.

Adolescent↗
PubMed1997

Clinical and family studies in genetic hemochromatosis: microsatellite and HFE studies in five atypical families.

A candidate gene (HFE) has been described for hereditary hemochromatosis on chromosome 6. The study of well-defined atypical hemochromatosis families using genetic markers may increase our understanding of the sensitivity and the specificity of genotyping in hemochromatosis. One hundred and thirteen Canadian families with genetic hemochromatosis were surveyed to find atypical families as possible examples of people with genetic recombinations. All families underwent clinical investigations including iron studies and HLA typing. Each individual was typed at three polymorphic microsatellite loci (D6S105, D6S1260, and D6S299) on chromosome 6. Sixteen subjects were studied for the two missense mutations described for the candidate gene for hemochromatosis (C282Y, H63D). There were eight HLA-identical siblings found in four different families (five men, three women; age range 30-72) with normal transferrin saturation and ferritin levels. There were two patients identified who were homozygous for the C282Y mutation without biochemical evidence of iron overload, and two patients with no evidence of the mutation with significant iron overload. Our conclusions are as follows: 1) finding HLA-identical siblings without iron overload does not confirm a genetic recombination, 2) difficulties in phenotypic definition of disease and the description of new iron overload syndromes that may differ from classical genetic HC cause complicated genetic studies, and 3) finding iron-loaded patients without a C282Y mutation and patients that are homozygous for the C282Y mutation without evidence of iron overload may limit the use of genotyping in population screening for hemochromatosis.

Adult↗
PubMed1997

Evaluation of the hepatic iron index as a diagnostic criterion for genetic hemochromatosis.

The hepatic iron index was originally described as a useful test to discriminate genetic hemochromatosis from alcoholic siderosis. To evaluate the hepatic iron index as a diagnostic criterion, it is essential to evaluate a cohort of hemochromatosis patients in whom the diagnosis has been established with great certainty. The presence of a sibling with identical human leukocyte antigen (HLA) and with iron overload was considered to be the gold standard for the diagnosis. Hepatic iron index was reviewed retrospectively in 55 homozygotes and in 189 patients who did not have hemochromatosis and were referred for hepatic iron analysis. Four of 55 homozygotes (7%) had a hepatic iron index of < or = 1.9. Hepatic iron concentration was increased in all 4 patients, ranging from 36 to 100 micromol/gm dry weight, (normal value <35.5 micromol/gm). Twelve of 189 (6%) patients without hemochromatosis had hepatic iron indexes > 1.9. The positive likelihood ratio for a hepatic iron index of 1.9 was 12.4. Area under the receiver operating characteristic curve was 0.94 (0.9 to 0.99, 95% confidence interval). The hepatic iron index remains a useful tool in the diagnosis of genetic hemochromatosis. However, it should not be an absolute criterion for the diagnosis and should be interpreted in combination with clinical assessment and genetic studies.

Adult↗
PubMed1997

Predictive value of family history in diagnosis of hereditary hemochromatosis.

Our objective was to study the predictive value of the family history in the initial diagnosis of hereditary hemochromatosis. Sixty five hemochromatosis proband patients and 66 control patients with chronic liver disease were assessed for a family history of hemochromatosis, cirrhosis, diabetes, and arthritis. There were no significant differences in the frequency of cirrhosis, diabetes, and arthritis between hemochromatosis patients and control patients. A family history of hemochromatosis was present in 3.6% of hemochromatosis patients and none of the control patients. Multivariate discriminative analysis demonstrated that the combination of cirrhosis, diabetes, and arthritis could only predict the diagnosis of hemochromatosis in 48% of cases. We conclude that a family history of cirrhosis, arthritis, and diabetes is not more common in hemochromatosis patients compared to control patients with chronic liver disease.

Arthritis↗
PubMed1997

Outcome after coronary artery surgery in women and men in the north of England.

We prospectively studied, for 1 year initially, 353 consecutive patients (297 male 56 female, 57.2 +/- 7.32 years) with chronic stable angina admitted for coronary artery bypass graft (CABG) surgery in the North East of England. Patients generally had severe anginal symptoms (median 36 months duration) despite anti-anginal therapy (90% taking two or more anti-anginal drugs). Women were more severely symptomatic than men prior to surgery, despite a similar severity of angiographically-defined coronary artery disease, suggesting possible referral bias. Women were given fewer grafts than men in operations carrying similar risks. After surgery, clinical outcome was generally good but women had a higher mortality (12-month mortality 14% in women vs. 6% in men), and higher morbidity in terms of readmissions, angina symptoms, antianginal drug use and effort tolerance. This series describes clinical practice in an area of high coronary disease morbidity and mortality. It identifies the real risks for women with severe symptomatic disease undergoing coronary artery surgery. We believe it highlights the need for improved risk stratification in the treatment of women with angina, and a consideration of alternative treatment strategies for those women destined to have a poor outcome from CABG.

Angina Pectoris↗
PubMed1997

Serum Lp(a) lipoprotein concentration is not associated with clinical and angiographic outcome five years after coronary artery bypass graft surgery.

OBJECTIVE: To examine the association between serum Lp(a) lipoprotein concentration and clinical and angiographic outcomes five years after coronary artery bypass graft (CABG) surgery. SETTING: A regional cardiothoracic centre, Freeman Hospital, and the University Clinical Investigation Unit, Royal Victoria Infirmary, Newcastle upon Tyne. PATIENTS AND DESIGN: 353 consecutive patients (56 female, 297 male, mean age 57-2 years) undergoing first time CABG surgery for stable angina were studied prospectively. MAIN OUTCOME MEASURES: Late cardiac death (beyond 30 days) and non-fatal myocardial infarction; prevalence of angina five years after surgery in 291 (94%) survivors and vein graft patency (evaluated by patient) in 118 survivors five years after surgery. Serum Lp(a) concentration and lipid profiles were measured before operation, and 3, 6, 12, and 60 months after surgery. Lipid profiles were also measured 24 months after surgery. RESULTS: Weighted Lp(a) concentration (by tertile) was not associated with late cardiac death or with the combination of late cardiac death and non-fatal myocardial infarction, with the presence of angina, or with vein graft occlusion. The association remained non-significant if analysis was restricted to the upper tertile of LDL cholesterol (> 4.1 mmol/l) or to patients under the age of 55 years at the time of surgery. CONCLUSIONS: Serum Lp(a) concentration did not predict late cardiac death, the combination of late cardiac death and non-fatal myocardial infarction, or the prevalence of angina or vein graft occlusion five years after CABG surgery.

Angina Pectoris↗
PubMed1997

Factors affecting glucose tolerance in hereditary hemochromatosis.

OBJECTIVE: To determine insulin action and insulin secretory function in patients with hemochromatosis, and to find evidence for or against hypothesized pathogenetic mechanisms for the abnormal glucose metabolism associated with hemochromatosis. These mechanisms include decreased beta-cell secretion of insulin due to iron overload, insulin resistance and genetic factors. DESIGN: Prospective in vivo study. PARTICIPANTS: Seventeen subjects with hemochromatosis, of whom 4 had cirrhosis but not diabetes mellitus, 6 had diabetes mellitus and 7 had neither; 10 controls. INTERVENTIONS: Insulin sensitivity and insulin secretion were determined during an intravenous glucose tolerance test. Insulin secretion was measured as the acute insulin response to glucose (AIRg). Insulin sensitivity (Si) was quantified with the minimal-model method. Of the patients with hemochromatosis, 14 agreed to undergo a second metabolic study after treatment with venous phlebotomy. RESULTS: All subjects with hereditary hemochromatosis had impaired glucose tolerance as measured by K(g) (rate of glucose disappearance). Subjects who were free of both diabetes mellitus and liver cirrhosis had a normal S1 and a decreased AIRg. In these subjects, phlebotomy treatment normalized serum ferritin levels, increased AIRg by 35% and normalized glucose tolerance (K(g)). Subjects with hemochromatosis and cirrhosis had a reduced Si and maintained a normal insulin secretion. Phlebotomy treatment did not change these parameters. Subjects with hemochromatosis and diabetes mellitus had both a reduced Si and AIRg, and these parameters were unaffected by phlebotomy treatment. CONCLUSIONS: These results suggest that iron overload can impair insulin secretion and glucose tolerance early in hereditary hemochromatosis, before cirrhosis occurs. Phlebotomy treatment can reverse these defects. Impaired glucose tolerance resulting from insulin resistance in subjects with cirrhosis or diabetes mellitus is not affected by phlebotomy treatment.

Adult↗
PubMed1996

The absorption and first-pass metabolism of [14C]-1,3-dinitrobenzene in the isolated vascularly perfused rat small intestine.

We tested the hypothesis that the small intestine is capable of the first-pass, reductive metabolism of xenobiotics. A simplified version of the isolated vascularly perfused rat small intestine was developed to test this hypothesis with 1,3-dinitrobenzene (1,3-DNB) as a model xenobiotic. Both 3-nitroaniline (3-NA) and 3-nitroacetanilide (3-NAA) were formed and absorbed following intralumenal doses of 1,3-DNB (1.8 or 4.2 mumol) to isolated vascularly perfused rat small intestine. Dose, fasting, or antibiotic pretreatment had no effect on the absorption and metabolism of 1,3-DNB in this model system. The failure of antibiotic pretreatment to alter the metabolism of 1,3-DNA indicated that 1,3-DNB metabolism was mammalian rather than microfloral in origin. All data from experiments initiated with lumenal 1,3-DNB were fit to a pharmacokinetic model (model A). ANOVA analysis revealed that dose, fasting, or antibiotic pretreatment had no statistically significant effect on the model-dependent parameters. 3-NA (1.5 mumol) was administered to the lumen of isolated vascularly perfused rat small intestine to evaluate model A predictions for the absorption and metabolism of this metabolite. All data from experiments initiated with 3-NA were fit to a pharmacokinetic model (model B). Comparison of corresponding model-dependent pharmacokinetic parameters (i.e. those parameters which describe the same processes in models A and B) revealed quantitative differences. Evidence for significant quantitative differences in the pharmacokinetics or metabolism of formed versus preformed 3-NA in rat small intestine may require better definition of the rate constants used to describe tissue and lumenal processes or identification and incorporation of the remaining unidentified metabolites into the models.

Acetanilides↗