HCV genotypes in patients with liver disease of different stages and severity

AIMS/MATERIAL: Hepatitis C virus (HCV) genotyping was performed in 213 anti-HCV-positive patients with chronic liver disease ranging from minimal histological changes to hepatocellular carcinoma. One hundred and twenty-two patients had non-cirrhotic chronic active or persistent hepatitis (including 29 who were asymptomatic with persistently normal ALT levels) (chronic liver disease group). The other 91 had hepatocellular carcinoma and, in all but three cases, cirrhosis (hepatocellular carcinoma group). RESULTS: The overall prevalence of HCV variants was: 54.9% type 1b, 37.8% type 2, 2.5% type 1a, 2.0% type 3a, 2.0% type 4a. The genotype distribution showed no relation to the stage (chronic liver disease vs. hepatocellular carcinoma) or severity (chronic active vs. chronic persistent hepatitis) of the liver disease, or to the duration of the disease (<10 years vs. >10 years). Within the hepatocellular carcinoma group, the duration of type-1b disease was similar to that of type-2 infections. Ages at the time of infection and genotype were both independently associated with progression to cirrhosis and hepatocellular carcinoma, but multivariate analysis revealed that the effect of age was much stronger than that of genotype 1b. CONCLUSIONS: The predominance of HCV type 1b in this study reflects the higher frequency of this variant in our area. Our findings indicate that infections caused by each HCV genotype are capable of progressing to hepatocellular carcinoma.     

Decreased baroreflex sensitivity in patients with stable coronary artery disease is correlated with the severity of coronary narrowing

Although studies have shown that arterial baroreflex sensitivity (BRS) is decreased in patients with acute myocardial infarction, BRS changes in patients with stable coronary artery disease (CAD) have not been studied extensively. We assessed BRS by the phenylephrine method in 55 normotensive and nondiabetic patients with chronic effort angina, old myocardial infarction, or both. The control group consisted of 24 age-matched patients without coronary lesions. To identify factors that determine BRS in stable CAD, we performed multivariate analysis using age, sex, left ventricular ejection fraction, pulmonary artery wedge pressure, resting systolic blood pressure, resting heart rate, the number of stenotic coronary arteries, history of myocardial infarction, and the presence or absence of angina pectoris as variables. BRS was significantly lower in patients with CAD than in control subjects (5.9 +/- 2.9 vs 6.9 +/- 2.4 ms/mm Hg, p < 0.05). In patients with CAD, BRS was inversely correlated with age, the resting heart rate, and the number of stenotic coronary vessels (p < 0.001, p < 0.005, and p < 0.005, respectively), but was independent of other clinical parameters, including the history of myocardial infarction. In control subjects, BRS was significantly correlated only with age. These results indicate that BRS is decreased in patients with stable CAD, and this decrease is correlated with the extent and severity of coronary narrowing.     

Prevalence of coronary artery disease and peripheral artery disease in patients with different types of primary hyperlipidemia

The prevalence of coronary artery disease (CAD) and peripheral artery disease (PAD) was studied in 280 (203 males, 77 females) patients with different types of primary hyperlipoproteinemia. In primary hyperbetalipoproteinemia the prevalence of CAD (45% for Type IIa and 47% for Type IIb) is significatly higher than that in the other types of hyperlipoproteinemia (38% for Type IV and 17% for Type V). On the other hand, PAD prevalence is much higher in hypertriglyceridemia (21% in Type IIb and 20% in Type V) than in hypercholesterolemia alone (9% in Type IIa). These results suggest ths atherosclerotic complications are concerned. Moreover, the high frequency of PAD found in hypertriglyceridemia can be related to the high occurrence of diabetes in these patients. The effects of other major risk factors of atherosclerosis (smoking and hypertension) were also evaluated. Our results indicate that the association of hypercholestolemia and hypertension is more dangerous than the co-occurence of hypercholesterolemia and smoking.     

Investigation of coronary artery disease in diabetes: is screening of asymptomatic patients necessary?

A common missense mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, a C to T substitution at nucleotide 677, is responsible for reduced MTHFR activity and associated with modestly increased plasma homocysteine concentrations. Since underlying maternal vascular disease increases the risk of pre-eclampsia, we had the working hypothesis that pre-eclampsia patients would have an increased T677 allele frequency compared with controls. The MTHFR genotypes were determined in 67 pre-eclampsia patients, 98 normal pregnant women, and 260 healthy adults by the PCR/RFLP method. The T677 allele and the genotype homozygous for the T677 allele were significantly increased in the pre-eclamptic group compared with the controls (p < 0.02 and p < 0.004, respectively). The data indicate that the T677 variant of the MTHFR gene is one of the genetic risk factors for pre-eclampsia.     

Relation among stenosis severity, myocardial blood flow, and flow reserve in patients with coronary artery disease

BACKGROUND: Coronary arteriography is considered the "gold standard" for evaluating the severity of a coronary stenosis. Because the resistance to blood flow through a stenotic lesion depends on a number of lesion characteristics, the physiological significance of coronary lesions of intermediate severity is often difficult to determine from angiography alone. This study of patients with coronary artery disease seeks to determine the relation between myocardial blood flow and flow reserve measured by positron emission tomography (PET) and the percent area stenosis on quantitative coronary arteriography. METHODS AND RESULTS: We studied 28 subjects: 18 patients with coronary artery disease (66 +/- 8 years) and 10 age-matched healthy volunteers (64 +/- 13 years) with dynamic N-13 ammonia PET imaging at rest and after dipyridamole (0.56 mg/kg). The percent cross-sectional area stenosis was quantified on the coronary arteriograms as described by Brown et al. In the 18 patients, a total of 41 non-infarct-related coronary vessels were analyzed. Myocardial blood flows in normal regions of patients with coronary artery disease were not different than those in healthy volunteers, both at rest and after dipyridamole. As a result, the myocardial flow reserve was also similar in both groups (2.4 +/- 0.4 versus 2.6 +/- 0.7, respectively; P = NS). Quantitative PET estimates of hyperemic blood flow (r = .81, P < .00001), flow reserve (r = .78, P < .00001), and an index of the "minimal coronary resistance" (r = .78, P < .00001) were inversely and nonlinearly correlated with the percent area stenosis on angiography. Of note, PET estimates of myocardial flow reserve successfully differentiated coronary lesions of intermediate severity (50% to 70% and 70% to 90%; 2.4 +/- 0.4 versus 1.8 +/- 0.5, respectively; P = .04). CONCLUSIONS: In patients with coronary artery disease, non-invasive measurements of myocardial blood flow and flow reserve by PET are inversely and nonlinearly related to stenosis severity as defined by quantitative angiography. Importantly, coronary lesions of intermediate severity have a differential flow reserve that decreases as stenosis increases that can be detected noninvasively by PET, thus allowing better definition of the functional importance of known coronary stenosis.     

Bone mineral affection in asymptomatic adult patients with celiac disease

OBJECTIVES: Osteopenia is a well-known complication of overt celiac disease, but whether such defective bone mineralization is present among asymptomatic or silent patients is not known. Our objectives were: 1) to examine bone mineralization of a group of asymptomatic celiac patients; 2) to compare these results with those of symptomatic patients. METHODS: Bone mineral density of the spine and total skeleton by dual energy x-ray absorptiometry and serum parameters of mineral metabolism of eight recently diagnosed asymptomatic patients with celiac disease were studied. Results were compared with those obtained in 20 untreated symptomatic celiacs, 14 patients treated with gluten-free diet for a mean time of 15 yr, and 153 healthy adult subjects, matched by sex and age. RESULTS: Four and five out of eight asymptomatic patients presented with reduced mineralization of the spine and the total skeleton, respectively (> 1 SD below normal values for sex and age). Two patients presented with severe osteopenia of the spine, and the other three presented with severe osteopenia of the whole skeleton (> 2 SD below mean normal values). Osteopenia at plane bone level (total skeleton) was significantly lower when compared to healthy controls (p < 0.02). Symptomatic untreated patients had significantly more severe deterioration of bone mineralization than did asymptomatics (p < 0.05) and treated patients (p < 0.05). No difference in bone mineral density was observed between treated patients and asymptomatic celiacs. Serum levels of calcium, alkaline phosphatase, 25-OH vitamin D, and parathormone did not show conclusive abnormalities. CONCLUSIONS: Our findings provide direct evidence that reduced bone mineralization occurs in asymptomatic celiac patients before any other symptom becomes evident. Only early diagnosis and treatment of celiac disease can avoid the deterioration of the bone structure observed in all clinical status of celiac disease.     

Frequency and causes of shunt revisions in different cerebrospinal fluid shunt types

Shunt complications and revisions are common in hydrocephalic patients treated with a ventriculo-atrial or a ventriculo-peritoneal shunt. The reported revision rate differs very much but the rate of revision is close to 50% in many papers. Data from 884 hydrocephalic patients treated with various shunt types in the period 1958-1989 were recorded retrospectively in order to evaluate the frequency of revision for various shunt types and secondly to analyse the specific reasons for the shunt revisions. The rate of shunt revision was 45%. The Pudenz shunt was revised more often (62%) than the remaining shunt types. The Hakim and the Orbis-Sigma shunts had fewer revisions (35% and 27%, respectively) than the other observed shunt types. A defect of or an obstruction in the ventricular catheters was a frequent cause of revision followed by a defect or an obstruction of the distal catheter, a displacement of the distal catheter and an acute infection. Because of the higher rate of revision for the Pudenz shunt the rate of the above mentioned specific complications is also higher in most of the subgroups for that specific shunt type. Driven by these experiences it is reasonable to seek to develop and introduce new shunt types in an attempt to reduce the complication rate.     

Hyperinsulinism in patients with coronary artery disease

AIM: To assess the clinical impact of hyperinsulinism and major coronary risk factors in patients with angiographically documented or excluded coronary artery disease (CAD), a clinical study was carried out in 268 men admitted for left heart catheterization. METHODS: Fasting immunoreactive insulin (IRI) levels were correlated to all major cardiovascular risk factors and to the presence and degree of CAD. RESULTS: IRI levels were correlated significantly with the degree of CAD (one-vessel disease: mean IRI 9.45 microU/ml +/- 0.43 SEM; two-vessel disease: mean IRI 10.4 microU/ml +/- 0.71 SEM; three-vessel disease: mean IRI 11.88 microU/ml +/- 0.98 SEM) and inversely to the high-density lipoprotein level (P < 0.05). In patients with arterial hypertension, IRI levels were elevated, without a significant difference between those with and those without CAD, whereas the IRI levels of non-hypertensive men with CAD (n = 81; mean IRI 9.85 microU/ml +/- 0.51 SEM) differed significantly (P < 0.05) from those of non-hypertensive men without CAD (n = 59; mean IRI 7.76 microU/ml +/- 0.43 SEM). IRI levels were significantly higher (P < 0.05) in obese patients (n = 65; mean IRI 11.68 microU/ml +/- 0.70 SEM versus n = 203; mean IRI 9.32 microU/ml +/- 0.34 SEM), in patients with elevated triglycerides (n = 58 mean IRI 11.59 microU/ml +/- 0.81 SEM versus n = 210; mean IRI 9.42 microU/ml +/- 0.33 SEM), and in patients with lowered HDL cholesterol (n = 178; mean IRI 11.06 microU/ml +/- 0.63 SEM versus n = 90; mean IRI 9.29 microU/ml +/- 0.34 SEM). Diabetic patients on angiotensin converting enzyme inhibitor therapy (n = 11; mean IRI 7.91 microU/ml +/- 0.91 SEM) had significantly (P < 0.05) lower IRI levels than those not treated with ACE inhibitors (n = 25; mean IRI 12.96 microU/ml +/- 1.47 SEM). IRI levels exceeding 8 microU/ml were associated with a 1.98-fold risk for CAD compared with IRI levels below 8 microU/ml. Stepwise logistic regression showed that insulin was an independent determinant of CAD. CONCLUSION: Knowledge of the fasting insulin level is an important contribution to the identification of patients with, or at risk of, CAD.     

Should there be systematic screening of coronary heart disease in asymptomatic patients with risk factors alone? A decision analysis approach

The problem of choosing between detection of asymptomatic coronary heart disease (CHD) in patients at risk and primary prevention was assessed in a decision analysis model. Most of the relevant data were derived from the WOSCOP study, which evaluated the effects of statins in asymptomatic hypercholesterolaemic subjects. This study is considered to be a model of primary prevention measurement. Over a 5-year period, 10% of control subjects had events related to CHD, with a 20% mortality rate which was reduced by 33% under statin administration. A decision tree was used to compare these two sets of data (controls and treated patients) with those of a third option in which an exercise test, 201Tl scintigraphy and, in certain cases, coronary arteriography were used to detect and treat CHD at an asymptomatic stage. The test characteristics and outcomes correspond as closely as possible to previously reported data, concerning what can be expected in this particular situation. Over a wide range of CHD probabilities, screening appeared to be better than primary prevention. This result is robust since it was not modified by sensitivity analysis for most of the data. A sharp decrease in the sensitivity of the first two tests and a marked increase in the effectiveness of primary prevention would alter the decision in favour of primary prevention, whereas an increased death rate from CHD and higher CHD probability would favour the utility of screening. As the cost-effectiveness of screening compares favourably with that of primary prevention, it may be useful to assess the validity of this model in a prospective controlled study.     

Adult height, stroke, and coronary heart disease

Trace toxic metals in municipal solid waste may escape from the incineration process in flue gas, in dry collected ash, in wet scrubbed ash, or as a suspended aerosol. Therefore, understanding the behavior of heavy metals in the flue gas and the best controls in the air pollution control equipment are important and necessary. The control conditions of water cooling and spray dryer systems during incineration processes significantly influence the formation of heavy metal compounds. The formation of chromium (Cr), lead (Pb), and cadmium (Cd) species under various control conditions (water cooling tower and spray dryer reactor) was investigated in this study. The object of the experiment is to understand the effects of water cooling and spray dryer systems individually on the formation of heavy metal species. The operating parameters that are evaluated include different control systems, control temperatures, and chlorine content. A thermodynamic equilibrium model was also used to evaluate experimental data. In order to match real incineration conditions, a two-stage simulation was performed in this experiment. The results showed that the relationship of speciation between the simulation prediction and X-ray diffraction (XRD) analysis is consistent for Cr compounds; both indicated that Cr2O3 is the major species. The relationship is almost the same for Cd compounds, but not for Pb compounds.     

Odor identification in Huntington's disease patients and asymptomatic gene carriers

Odor identification was assessed in 20 Huntington's disease (HD) patients, 20 normal adults with the genetic mutation that causes HD, and 20 mutation-negative adults. The University of Pennsylvania Smell Identification Test (UPSIT) revealed substantial odor identification deficits only in HD patients.     

Efficacy and pharmacokinetics of gallopamil in patients with coronary artery disease

We prospectively studied 10 patients with stable exertional ischaemia, selected from a larger group of patients referred for suspected coronary artery disease or to detect residual ischaemia after myocardial infarction, to evaluate pharmacokinetic changes during chronic treatment with gallopamil and its correlation with clinical efficacy in patients with coronary artery disease. Our study consisted of a 1-week run-in single-blind placebo treatment and a 4-week single-blind gallopamil treatment. At the end of the run-in period patients underwent two different exercise tests, the first 2 hours and the second 7 hours after placebo administration. During active treatment all patients underwent two different exercise tests, the first 2 hours and the second 7 hours after gallopamil (50 mg) administration on the 1st and 28th days of gallopamil therapy. On the same days in eight of the patients we evaluated gallopamil pharmacokinetic changes. Our data revealed a rapid increase of unchanged gallopamil and its metabolite (norgallopamil) in the plasma, and a peak concentration of these substances about 2 hour after oral administration on both the 1st and 28th day of observation. Moreover, our results demonstrated an increase between the first and 28th day of treatment in peak concentration of unchanged gallopamil in the plasma, and of AUC 0-infinity and AUC o-c values during chronic treatment with gallopamil. Our clinical data showed an improvement in exercise results during gallopamil therapy related to increased concentration of the drug.     

Angiographically documented coronary artery disease in asymptomatic middle aged men suspected of silent ischaemic heart disease

One hundred and fourteen asymptomatic middle aged men, with a positive stress test, underwent coronary angiography at Armed Forces Institute of Cardiology/National Institute of Heart Diseases (AFIC/NIHD), Rawalpindi. Of these, 66 (58%) were found to have significant disease (> 50% luminal narrowing in at least one of the major epicardial arteries) while 48 (42%) had normal coronary arteries. Of the former, 27 (41%) had 1-vessel CAD, 18 (27%) had 2-vessel CAD and 21 (32%) had 3-vessel CAD. There were significantly more hypertensives, hyperlipidaemics and diabetics in CAD group, while other risk factors were the same. The overall risk factor prevalence was low. The major reasons for performing coronary angiography were a positive stress test done as part of routine annual medical checkup and resting ECG changes of enough significance to warrant further investigations. It is concluded that the presence of significant coronary artery disease can be silent in a large number of asymptomatic middle aged men, especially those who have conventional risk factors.     

Obstructive sleep apnea in patients with coronary heart disease

Patients with obstructive sleep apnea have an increased cardiovascular morbidity and mortality, those with co-existent coronary artery disease being particularly at risk. The object of our study was to evaluate the prevalence of obstructive sleep apnea in patients with coronary artery disease. 153 patients (117 men, 36 women) with verified coronary artery disease were given a highly sensitive standardized questionnaire. The 59 patients with pathological results were then checked with a 6-channel non-laboratory monitoring system. 22.2% of all patients had a respiratory disturbance index (RDI) above 5/h. and 14.4% above 10/h. 13.3% had a pathological RDI and additionally suffered from excessive daytime sleepiness. Patients with coronary artery disease have a high prevalence of obstructive sleep apnea and should consequently be screened for this sleep-related breathing disorder.     

Frequency of silent ischemic heart disease in patients with diabetes mellitus

Early detection of silent ischaemia plays an important role in prevention of sudden cardiac death and acute myocardial infarction. More frequent occurrence of silent ischaemia in patients with diabetes mellitus and manifestations of ischaemic heart disease has been relayed in several studies. No studies aimed at frequency of occurrence of silent ischaemia in diabetic patients without clinical symptoms of ischaemic heart disease have been performed yet. Objectives of this study were the examination of the latter case. This study involved 67 patients with diabetes mellitus without clinical symptoms of ischaemic heart disease. The average duration time of diabetes mellitus was 11 years. The patients were divided in two groups. The first group included 26 patients with insulin dependent diabetes mellitus. The second group included 41 patients with non insulin dependent diabetes mellitus. The first control group consisted of 35 non diabetic patients with ischaemic heart disease, and the second control group consisted of 22 healthy volunteers. 24-hours ambulatory Holter monitoring and ECG exercise test were performed in all subjects. The diagnosis of silent ischaemia was established in patients with positive results of both examinations in ECG-records without any following pain. In case of only one positive results the dipyridamole stress echocardiography test with ECG was carried out to prove the diagnosis. It was proved, that silent ischaemia occurs in 19.2% of patients with insulin dependent diabetes mellitus and in 22% non insulin diabetic patients. No statistic differences between frequency of silent ischaemia occurrence in both groups were revealed. The application of 24-hours Holter monitoring combined with ECG-exercise stress test seems to be the best method in early recognition of silent ischaemia in diabetic patients.     

Effect of social deprivation on disease severity and outcome in patients with rheumatoid arthritis

OBJECTIVE: Social deprivation is now recognised to have an important impact on morbidity and mortality. This study sought to ascertain the effect of deprivation, if any, on disease severity, functional disability, and outcome in rheumatoid patients in Glasgow. METHODS: 814 patients with rheumatoid arthritis (RA) were assessed for clinical, functional, and laboratory indices of disease activity. Deprivation categories for individual patients were determined using the Carstairs index. Five year follow up is available for 440 patients. RESULTS: The study population of RA patients live largely in the most deprived areas. Patients from deprived areas have significantly poorer function at outset and at five years as defined by the Health Assessment Questionnaire (HAQ) score. This is not attributable to differences in disease duration in patients from the most deprived regions or compliance with treatment. Furthermore, these patients do not achieve over five years the initial functional level of those living in the most advantaged localities. CONCLUSION: RA patients from deprived areas have poorer function, which is associated with greater need--medical, social, and paramedical. Strategies and resources for healthcare need to be adjusted according to this variation.