Obésité, hypertension artérielle,hypercholestérolémie et diabète non traités chez les adultes infectés ou pas par le VIH à Mbuji-Mayi (République démocratique du Congo)

Little is known about the major cardiovascular risk factors in HIV-infected as compared to the HIV-uninfected patients in the Democratic Republic of Congo (DR Congo). We determined the prevalence of hypertension, obesity (BMI ≥ 30 kg/m²), total cholesterol > 200 mg/dl, HDLcholesterol &≤ 40 mg/dl, and glycemia > 126 mg/dl. We also calculated the average and/or median of total cholesterol, HDL-cholesterol, and glycemia among HIV-infected and HIV-uninfected patients.We conducted a cross-sectional study that enrolled 592 HIV-uninfected and 445 HIV-infected patients of whom 425 (95.5%) were on first-line antiretroviral therapy based on stavudine–lamivudine–nevirapine. Clinical and laboratory data of the patients were collected. The results were analyzed by chi-square, t-student, and Wilcoxon rank sum tests. 11.5% of HIV-infected patients had an average blood pressure suggesting hypertension versus 10.6% of HIV-uninfected (P = 0.751). But in absolute value, HIVinfected patients had a median of diastolic blood pressure of 90 mmHg versus 85 mmHg of HIV-uninfected (P < 0.001). 4.04% of HIV-infected patients had a BMI suggesting obesity versus 6.08% of HIV-uninfected patients (P = 0.187). For fasting glucose: 2.50% of HIV-infected patients versus 4.20% of HIV-uninfected patients had a serum fasting glucose suggesting diabetes (P<0.176). 11.9% of HIV-infected patients had a total cholesterol greater than 200 mg/dl versus 7.4% of HIVuninfected patients (P=0.019). For HDL-cholesterol: 36.40% of HIV-infected patients had a serum fasting ≤ 40 mg/dl versus 15.70% of HIV-uninfected patients (P < 0.001). HIV-infected patients had a median fasting total cholesterol higher (140 mg/ dl) thanHIV-uninfected patients (133mg/dl) [P=0.015].HIVuninfected patients had a median fasting HDL-cholesterol higher (58.5 mg/dl) than HIV-infected patients (49 mg/dl) [P < 0.001]. HIV-infected women were more likely to have a higher mean of total cholesterol: 147.70 #x00B1; 52.09 mg/dl versus 135.72 &#x00B1; 48.23 mg/dl for the HIV-infected men (P = 0.014) and of HDL-cholesterol: 55.80 ± 30.77 mg/dl versus 48.24 ± 28.57mg/dl for the HIV-infected men (P = 0.008). In this study population, prevalence of hypertension was elevated in HIVinfected versus HIV-uninfected patients. Being HIV positive on first-line antiretroviral therapy based on stavudine–lamivudine–nevirapine was associated with high prevalence of total cholesterol > 200 mg/dl and HDL-cholesterol ≤ 40 mg/dl. Proactive screening and prompt management of dyslipidemia and hypertension in this population should be a priority.     

Serum-cholesterol-lowering effect of metronidazole and possible mechanisms of action

Summary In five patients with Crohn's disease long-term therapy with metronidazole (400 mg b.i.d.) was followed by a significant reduction of total serum cholesterol from 179 mg/dl to 156 mg/dl, 134 mg/dl, and 143 mg/dl, after 2–4 months, 6 months, and 9–12 months, respectively. Lipoprotein analysis before and after 3 weeks of administration of metronidazol (400 mg/day) to five normolipemic volunteers revealed that LDL-cholesterol was reduced by 21% (P<0.05), whereas HDL-cholesterol remained unchanged. Biliary secretion of cholesterol and bile acids were reduced by 13% and 20% (P<0.05), respectively, which might suggest a decreased sterol synthesis. The amount and percentage of intestinal cholesterol absorption were decreased by 33% and 22% (P<0.05). Thus, a possible decrease in sterol synthesis and a reduction of cholesterol absorption might be responsible for the serum-cholesterol-lowering effect of metronidazole. However, caution should be taken when considering metronidazole for long-term treatment of patients with hypercholesterolemia due to possible side effects.This project was supported by a grant from Sandoz Stiftung für therapeutische Forschung.The authors thank Mrs. P. Pitters, G. Westphal, H., Ahten und Mr. S. Weiner for their technical assistance     

The prognostic significance of hypocholesterolemia in hospitalized patients

Summary Hypocholesterolemia (<120 mg/dl) was found in 200 out of 3,700 patients admitted consecutively to a University Department of Internal Medicine. In 91, hypocholesterolemia as defined above could be confirmed in a second serum sample on the following day. Mortality during hospitalization in this group was 32%. When diagnoses were grouped into 5 categories, prognosis was particularly poor in heart (36%) and liver disease (31%) and in malignancies (33%), while patients with malabsorption syndromes had a considerably better prognosis (10% mortality). Hypocholesterolemia was associated with a low cholesterol/phospholipid ratio and may be among the first signs of further deterioration of disease.     

Treatment of coronary heart disease by diet and exercise: Fasting and diurnal lipoproteins

Summary The effects of a combined exercise and low-fat dientary regimen were studied in 11 patients with angiographically documented coronary heart disease (cholesterol 233 mg/dl, triglycerides 158 mg/dl) and 13 comparable patients (cholesterol 224 mg/dl, triglycerides 174 mg/dl) on usual care. During one year, fasting serum lipoproteins were lowered to ideal levels in the intervention group (cholesterol 191 mg/dl, triglycerides 100 mg/dl, LDL-cholesterol 121 mg/dl). There was no change of triglycerides and cholesterol on usual care while LDL-cholesterol rose significantly. Neither regimen had any effect on HDL-cholesterol. Diurnal triglycerides as a presumptive measure of IDL in the intervention group were diminished by 39%. The study demonstrates the feasibility of a diet and exercise regimen to normalize midly elevated plasma lipid levels and thus to possibly affect the course of coronary heart disease without drugs.Abbreviations Chol cholesterol - TG triglycerides - HDL high density lipoproteins - LDL low density lipoproteins - LP(a) lipoprotein (a) - P/S polyunsaturated to saturated fatty acid ratio - Int. Intervention group - C Control group Supported by Bundesministerium für Forschung und Technologie     

Lipid lowering treatment with bezafibrate in patients on chronic haemodialysis: Pharmacokinetics and effects

Summary Hyperlipidaemia may contribute to the high rate of cardiovascular complications in patients on chronic haemodialysis (CHD). However, possibilities of lipid lowering therapy in CHD are still limited. The applicability of bezafibrate (BF), a recently developed clofibrate analogue, was investigated in patients on CHD with triglyceride and/or total cholesterol levels above 300 mg/dl.The lipid lowering effect was studied in a placebo-controlled trial over 6 months in 19 patients. Long-term effect was followed in six patients over a mean period of 29 months.Elimination half-life and mean therapeutic serum concentration were calculated by 72-h BF serum profiles, obtained after the first drug administration of a single 200-mg dose and during steady state after 12 weeks of treatment. Elimination half-lives were 17 h at start and 22 h after 12 weeks compared with 2 h in subjects with normal renal function. Dose reduction to 200 mg every 3rd day was necessary and resulted in a mean therapeutic serum concentration of 3.4 mg/l, which was similar to 3.0 mg/l of normal subjects, who received the dose optimal for lowering of lipids (200 mg 3 × /day). The protein-bound serum fraction of BF was decreased to 8% in CHD patients, compared with 95% found in normal subjects.BF therapy resulted in a marked reduction of serum triglycerides from 478 mg/dl by 31% and total cholesterol levels from 311 mg/dl by 19% as well as -Lp-cholesterol from 178 mg/dl by 17%, whereas the initially low -Lp-cholesterol increased significantly from 18,3 mg/dl by 58%. Under long-term therapy not only continuously low triglyceride and cholesterol levels could be maintained, moreover a further decline (–20% and –7%) could be achieved.Safety laboratory controls, comprising haemoglobin, bilirubin, liver enzymes, CK and albumin, showed no significant changes apart from a slight reversible increase in CK and a decrease in gamma-GT and alkaline phosphatase. Subjective side effects were not reported. Under this dosage schedule, BF therapy was thus effective and safe, improving potentially atherogenic disturbances of lipid metabolism.Abbreviations BF bezafibrate - CHD chronic haemodialysis - HDL high density lipoproteins - IDL intermediate density lipoproteins - LDL low density lipoproteins - VLDL very low density lipoproteins     

The effect of the apolipoprotein E polymorphism on lipid levels in patients with familial defective apolipoprotein B-100

Summary Serum lipid concentrations of patients with familial defective apolipoprotein B-100 (FDB) show a high interindividual variability although the underlying defect is caused by a single point mutation. On the other hand, several genetic factors modulating serum cholesterol levels are known, such as DNA polymorphisms of the apopolipoprotein B or the apolipoprotein E (apo E) gene. To assess the effect of the apo E polymorphism on serum cholesterol, lipid levels of FDB patients (n=36) were compared with those of a normolipidemic control group (n=272) according to their apo E genotype. For the FDB group mean values of low-density lipoprotein (LDL) cholesterol (mg/dl) were 225.7 ± 53.7 for E3/2 genotype (n = 3), 234.2±48.3 for E3/3 genotype (n=20), and 252.4±73.8 for E4/3 genotype (n=13). Means of triglycerides (mg/dl) were 121.0±21.2, 114.8± 60.7, and 110.0 ± 62.8 for the respective apo E genotypes. The calculated average effect of the apo E alleles on LDL cholesterol levels was –6.0% for allele e2 and +3.7% for e4 relative to the whole FDB group. The effect on triglyceride levels was +7.5% for e2 and –3.6% for e4. The control group showed a similar variation in LDL cholesterol depending on the different apo E genotypes. About 6% of the total variation in LDL cholesterol can be accounted for by the apo E locus in normolipidemic and hypercholesterolemic individuals alike.Abbreviations FDB familial defective apolipoprotein B-100 - apo apolipoprotein - LDL low-density lipoprotein - VLDL very low density lipoprotein - HDL high-density lipoprotein - PCR polymerase chain reaction Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

Reduced cholesterol levels in African-American adults with sickle cell disease

In a recent study of boys and girls with sickle cell disease (SCD) in Nigeria, a common finding with this genetic hematologic disorder was a marked reduction in total cholesterol. Epidemiologic studies have identified a relation between low serum levels of total cholesterol (< 130 mg/dL) and increased mortality from all causes. We were interested in knowing if hypocholesterolemia was present in African-American adults with SCD. We therefore compared the plasma lipid profiles of the 16 men and 20 women with SCD who received care at the University of Texas Medical Branch at Galveston between 1996 and 2001 with those of 2,415 gender-matched African Americans who were seen at the same hospital but who did not have SCD. The age-adjusted mean total cholesterol concentrations of the SCD males and females were 147 +/- 42 mg/dL and 179 +/- 36 mg/dL, compared to male and female control values of 200 +/- 75 mg/dL and 216 +/- 61 mg/dL, respectively. These differences between SCD subjects and controls were statistically significant (p < 0.001). The LDL-cholesterol levels of the men and women with SCD (68 +/- 28 mg/dl and 95 +/- 33 mg/dl, respectively) were also significantly reduced relative to the controls (121 +/- 58 mg/dl and 128 +/- 54 mg/dl, respectively, p = 0.001). The triglyceride levels of the men with SCD were much reduced relative to the male controls (102 +/- 34 mg/dL versus 194 +/- 215 mg/dL, p = 0.02), but were not different between the SCD females and their control group. The HDL-cholesterol levels of the SCD subjects and the controls were not different. These results indicate that total cholesterol and LDL-cholesterol concentrations are significantly reduced in adult men and women with SCD in the United States, and should heighten interest in the implication that low levels of cholesterol might exacerbate the medical problems inherent in this genetic disease.     

Lipoprotein lipase activity in patients with combined hyperlipidaemia

The aetiology of familial combined hyperlipidaemia remains obscure, with both genetic and environmental factors contributing to the phenotype, which is frequently associated with premature coronary heart disease. We have studied lipoprotein lipase (LPL) activity and hepatic lipase (HL) activity in patients with coronary heart disease to determine whether variation in lipase activities contributes to this phenotype. Forty-one patients (mean age 50 years; 30 male) were selected on the basis of cholesterol levels above 6.5 mmol/l and triglyceride levels above 2.2 mmol/1, with apoprotein B values over the 90th percentile. There was a family history of premature coronary heart disease in 78% and a personal history in 64%, at mean age 44, the patient group therefore predominantly corresponded to the common definition of familial combined hyperlipidaemia, appropriate in the absence of molecular markers. None of the patients was diabetic; hypertension and smoking were not over represented. Blood samples were taken following intravenous administration of heparin (100IU/kg body wt), and LPL and HL activities were measured. Mean post-heparin LPL was significantly lower in patients than controls 10 min after heparin administration (2.98 ± 1.04 and 3.86 ± 0.93 mol ml^-1 h^-1, respectively, P = 0.001), and 37% patients had values below the 10th percentile of controls. Both male and female patients had significantly higher HL activities than their respective controls at 5, 10, 20 and 30 minutes postheparin. As expected, both female patients and controls had lower HL activities than males, although this sex difference did not reach statistical significance in the patient group. Mean lipid and lipoprotein results were: cholesterol 8.2 mmol/1; triglycerides 4.2 mmol/l; high-density lipoprotein cholesterol 0.90 mmol/1; apoprotein Al 122 mg/dl; apoprotein B 171 mg/dl; lipoprotein (a) 23 mg/dl (median 10 mg/dl). High-density lipoprotein cholesterol and triglycerides were negatively correlated (r = -0.26, P = 0.05). HL was significantly related to body mass index at all time points whereas the negative correlation between post-heparin LPL and body mass index was significant only 30 min after heparin administration. Post-heparin LPL was only weakly correlated with triglycerides 10 and 20 min after heparin administration. These lipid and lipoprotein results are clearly potentially atherogenic as indicated by the extent of premature coronary heart disease in the group described. A decrease in LPL activity may contribute to this pattern.Abbreviations FCHL familial combined hyperlipidaemia - CHD coronary heart disease - LPL lipoprotein lipase - HL hepatic lipase - HDL high-density lipoprotein - VLDL very low density lipoprotein; - apo apoprotein - TG triglyceride - BMI body mass index Correspondence to: M. Seed     

Parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentration in elderly patients

Summary In 50 patients of a geriatric hospital (33 women, aged 65–96 years, mean age 80 years, and 17 men, aged 68–91, mean age 78.3 years) calcium, albumin, phosphate, urea, creatinine, parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were determined. Forty patients with serum creatinine levels up to 1.4 mg/dl (124 mol/l) and 10 patients with creatinine concentrations 1.5 mg/dl (132mol/l) were evaluated. In patients with normal creatinine, a positive correlation was found between parathyroid hormone and age (r=0.41;P<0.01). In patients with elevated creatinine, negative correlations were found in 1,25-dihydroxyvitamin D and calcium (r=–0.724;P<0.05), 1,25dihydroxyvitamin D and creatinine (r=–0.79;P<0.01) and 1,25-dihydroxyvitamin D and phosphate (r=–0.87;P< 0.002). The best correlation was observed in patients with elevated serum creatinine for 1,25-dihydroxyvitamin D and phosphate (r=–0.91;P< 0.001). The results suggest that low levels of calcium and phosphate stimulate the 1-hydroxylation of 25-hydroxyvitamin D even in advanced age and that the calcium metabolism of these patients is frequently disturbed. Nineteen patients had low levels of 25-hydroxyvitamin D, indicating an insufficient supply of vitamin D or rare exposure to sunlight. In 49 of 50 patients, one ore more of the parameters of calcium metabolism were outside the normal range.Abbreviations 25-OH-D 25-hydroxyvitamin D - 1,25(OH)₂D 1,25-dihydroxyvitamin D - PTH parathyroid hormone Supported by the Deutsche Forschungsgemeinschaft (Schm 405–407)     

Prognostic factors of mid-term clinical outcome in congestive heart failure patients discharged after acute decompensation

Introduction

Risk stratification in congestive heart failure (CHF) patients is based on a variety of clinical and laboratory variables. We analysed renal function, BNP, water composition, echocardiographic and functional determinations in predicting mid-term outcome in CHF patients discharged after decompensation.

Material and methods

All subjects with NYHA class II-IV were enrolled at hospital discharge. NYHA class, BNP, water body composition, non-invasive cardiac output and echocardiogram were analysed. Death, cardiac transplantation and hospital readmission for CHF were scheduled.

Results

Two-hundred and thirty-seven (64.5% males, age 71.1±10.1) patients were discharged after obtaining normal hydration; left ventricular ejection fraction (LVEF) was 43.2±16.2%, cardiac output was 3.8±1.1 l/min and BNP at discharge resulted 401.3±501.7 pg/ml. During the 14-month follow-up 15 patients (6.3%) died, 1 (0.4%) underwent cardiac transplantation and 18 (7.6%) were readmitted for CHF (event group); in 203 (85.6%) no events were observed (no-event group). Higher NYHA class (2.1±0.7 vs. 1.9±0.4, p=0.01), BNP at discharge (750.2±527.3 pg/ml vs. 340.7±474.3 pg/ml, p=0.002) and impaired LVEF (33.7±15.7% vs. 44.5±15.8%, p=0.0001) and creatinine (1.7±0.6 vs. 1.2±0.8 mg/dl, p=0.004) were noticed in the event group. At multivariate Cox analysis LVEF (p=0.0009), plasma creatinine (p=0.006) and BNP at discharge (p=0.001) were associated with adverse mid-term outcome. Kaplan-Meier survival curves demonstrated that adding cut-off points for creatinine 1.5 mg/dl and discharged BNP of 250 pg/ml discriminated significantly prognosis (p=0.0001; log rank 21.09).

Conclusions

In predicting mid-term clinical prognosis in CHF patients discharged after acute decompensation, BNP at discharge ≥ 250 pg/ml added with plasma creatinine > 1.5 mg/dl are strong adverse predictors.     

Haemostasis and antithrombin III in the full-term newborn foal

Thirty-three Standardbred foals received a physical examination and had blood drawn for anti-thrombin III (AT III), immunoglobulin G (IgG), and haemostasis evaluation between 24 and 72 h of age. Based on physical examination, a normal haemogram within reference intervals and serum IgG concentration >600 mg/dl, 19 foals remained in the study. AT III values for protein concentration (mg/dl) and activity (mg/dl and percentage thrombin inhibition) were determined by rocket immunoelectrophoresis and chromogenic substrate assay, respectively, and compared to the reference intervals for adults. In 19 healthy, full-term foals, the mean plasma AT III activity for percentage thrombin inhibition (75.9%), mean amount of active AT III (19.2 mg/dl) and the mean plasma AT III concentration (28.7 mg/dl) were significantly (P<0.05) lower than the reference interval of adult values. The mean active AT III concentration for both foals (19.2 mg/dl) and adults (24.6 mg/dl) was significantly (P<0.05) less than their AT III concentration, 28.7 and 44.3 mg/dl, respectively. Fibrinogen degradation products (FDPs) were increased in 100% of the foals, with 12 of 19 (63%) having FDPs >10 <40 g/dl). Platelet count, prothrombin time, activated partial thromboplastin time and fibrinogen did not differ significantly from those of adult values.These findings support the view that haemostasis in the full term foal is characterised as a hypercoagulable state by the significant decrease in plasma AT III activity and concentration and increase in split products of fibrin and fibrinogen.     

Prognostic factors in multiple myeloma: role of β2-microglobulin and thymidine kinase

Summary Serum ₂- microglobulin, serum thymidine kinase, and commonly used prognostic parameters were investigated for their prognostic value in a well-defined group of patients with multiple myeloma (n = 207). Multivariate analysis showed hemoglobin to be the parameter of strongest prognostic value. Only albumin, serum ₂-microglobulin and serum thymidine kinase added further prognostic information. When tested for efficiency in recognizing patients with poor (average survival time < 1 year) and good (average survival time > 5 years) prognosis, serum ₂-microglobulin was best (80%), followed by total urinary protein (78%), hemoglobin (76%), and albumin (75%).     

Severe dyslipidemia and immune activation in HIV patients with dysglycemia

Background and Objective: Diabetes mellitus (DM) is common in human immunodeficiency virus (HIV)-infected patients. However, the relationship between dysglycemia, lipid metabolism, and immune activation in HIV patients is poorly understood.

Methods: We retrospectively analyzed the clinical data of 180 HIV patients, including 153 patients undergoing highly active antiretroviral therapy (HAART) and 27 HAART-naive patients. DM was defined as fasting serum glucose levels ≥126 mg/dl, and impaired fasting glucose (IFG) was defined as serum glucose levels of 101–125 mg/dl at two different time points. Lipid metabolic indexes were measured. CD4+, CD8+, and CD8+ HLA-DR+ T cells were determined by flow cytometry.

Results: IFM and DM percentages were higher in the HAART group than in the HAART-naive group (59.5% vs. 48.1% and 21.6% vs. 7.4%, respectively; p < 0.01). Additionally, DM percentage was high in patients receiving HAART containing protease inhibitors. Serum levels of triglycerides and very low-density lipoprotein cholesterol were higher in IFG and DM HAART patients than in euglycemic HAART patients (p < 0.05). Serum triglyceride levels were higher in HAART-naive DM patients than in other patients (p < 0.05). CD8+ and CD8+ HLA-DR+ cell counts were higher in IFG and DM HAART patients than in euglycemic HAART patients (p < 0.05). Ordinal logistic regression analysis suggested that TRIG, VLDL, CD8, and HAART were predictors of glucose metabolic disorders.

Conclusion: HIV patients with hyperglycemia have severe dyslipidemia and immune activation, and HAART is an important impact factor of glucose and lipid metabolic disorders.     

Clinical and immunologic analyses of 103 patients with common variable immunodeficiency

Common variable immunodeficiency (CVI) or hypogammaglobulinemia is a heterogeneous primary immunodeficiency disease in which B cells produce little or no antibody. Since the disease is relatively rare and the spectrum of associated illnesses is broad, patients are given care by a variety of specialists. Thus it has been difficult to determine the incidence of specific complications. In these studies we analyzed 103 consecutively referred CVI patients of age range 3–71 years (average, 29 years) who were followed for a period of 1–13 years (total of 750 patient years). The average serum IgG was 174.4 mg/dl for untreated patients and 301 mg/dl for patients treated with intramuscular immunoglobulin at the time of the first visit. The average IgA was 14.5, and the average IgM was 80.7, with no difference between or after immunoglobulin treatment. About one-half of the patients had T-cell dysfunction, but lymphocyte stimulation responses were inversely related to age, which implies worsened T-cell immunity with age. Serum IgG and IgA levels were found to be statistically associated (P=0.008), and serum IgG was related to lymphocyte stimulation with concanavalin A (P=0.01). By 1986, 79 patients were alive, 23 had died, and 1 could not be located. Recurrent bacterial illnesses were common to all patients, and 22% had developed chronic lung disease, 22% autoimmune disease, 15% cancer, 13% hepatitis, and 9% malabsorption. Autoimmune disease was more common in females, and cancer was more likely to develop in the fifth and sixth decades. In 11% of the group, other family members were found to be immunodeficient (hypogammaglobulinemic or IgA deficient). Nine patients died of respiratory insufficiency (with or without other complications), and seven patients died of cancer. These data provide valuable information about the immunologic abnormalities and the spectrum and frequency of illnesses associated with hypogammaglobulinemia.     

Plasma lipids and lipoproteins response to a dietary challenge: analysis of four candidate genes

The possible role of four candidate genes in lipid and lipoprotein response to diet was examined in 63 male students. Four site polymorphisms (signal peptide insertion/deletion, Xba I, Msp I and Eco RT) of the apo B gene, three RFLPs ( Ava II, Stu I, and Hinc II) of the LDL receptor gene, two SSCPs of the cholesterol 7α-hydroxylase gene and the common apo E genotypes were determined. The average reductions induced by diet in participants homozygous for the absence of the Xba I restriction site (X—X—) of the apo B gene compared to those harboring this site (X+) were: 14.5 mg/dl and 9.4 mg/dl for total cholesterol (TC) ( p <0.09) and 15.5 mg/dl and 7.9 mg/dl for LDL-C ( p <0.003), respectively. Differences in dietary responsiveness among the apo E, LDL receptor and the cholesterol 7α-hydroxylase genotypes were largely insignificant. Using the four apo B polymorphic sites, six unambiguous haplotypes were constructed and a model for their possible evolutionary relationship is presented. Genetic variation in the apo B gene region, as defined by haplotypes, accounted for 8.7% and 24.3% of the phenotypic variance in TC and LDL-C response to diet, respectively. Sequence analysis of a candidate locus, the putative LDL receptor binding region of apo B and its flanking sequences, was performed in two individuals, one homozygous for an apo B "hyper-responding" and another for the "lower-responding" haplotype, and no differences were found. In conclusion, haplotypes at the apo B gene locus are associated with dietary response of TC and LDL-C in young males. Yet, the sequence variation responsible for these differences is possibly located outside the putative LDL receptor binding domain.     

Effects of recombinant leukocyte interferon on serum immunoglobulin concentrations and lymphocyte subpopulations in chronic hepatitis B

To investigate immune effects of interferon (IFN) therapy in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, serum immunoglobulin concentrations and peripheral lymphocyte subpopulations were sequentially studied before, during, and after therapy in nine patients who were treated with recombinant human -IFN in doses ranging from 3 to 10 million units per day for 28 days. Serum immunoglobulin A levels decreased significantly, from 414±23 mg/dl (mean ± SE) to 379±28 mg/dl (P<0.05), after the first week of therapy and to a bottom value of 323±20 mg/dl (P<0.001) at the fourth week. Immunoglobulin G levels decreased significantly, from 2603±175 to 2328±169 mg/dl (P<0.005), after the first week of therapy and to a bottom value of 2005±199 mg/dl (P<0.001) at the fourth week. Immunoglobulin M levels were also reduced significantly after 3 weeks of therapy (from 229±23 to 188±15 mg/dl;P<0.01). These reductions in immunoglobulins A, G, and M returned to pretreatment levels by 4 months after the end of the therapy. In lymphocyte subpopulations, significant depressions were found in CD3-, CD4-, CD8-, and B1-positive cells in peripheral blood after the first week of therapy (CD3, from 1700±114 to 1234±114/mm³,P<0.005; CD4, from 1036±88 to 780±64/mm³,P<0.005; CD8, from 620±57 to 426±60/mm³,P<0.05; and B1, from 519±84 to 276±48/mm³,P<0.01) followed during therapy, while Leul la-positive cells did not change significantly. During the 6-month follow-up period, three patients had a sustained clinical remission in which HBeAg disappeared from serum. Disappearance of HBeAg was unassociated with initial levels or percentage changes of serum immunoglobulins and peripheral lymphocytes expressing each of the test markers in these patients. These findings suggest that immune effects of IFN therapy are independent from its antiviral effects.     

The interleukin 28B rs12979860 C/T polymorphism and serum cholesterol as predictors of fibrosis progression in patients with chronic hepatitis C and persistently normal transaminases

The interleukin 28B (IL‐28B) rs12979860 C/T polymorphism is a predictor of spontaneous and treatment‐induced hepatitis C virus (HCV) clearance. The C/C genotype is associated with higher serum cholesterol, predictor of a favorable outcome in chronic hepatitis C. Whether IL‐28B polymorphism and serum cholesterol play a role in modulating the history of mild hepatitis C is unknown. To clarify this issue, 93 untreated patients infected with HCV with normal or near‐normal transaminases and an initial Ishak staging score ≤1 were investigated retrospectively in the longitudinal study (median histological follow‐up of 10 years). An additional confirmatory cohort of 143 patients with chronic HCV infection and abnormal levels of transaminases was evaluated in the cross‐sectional study. In the longitudinal study, at the end of follow‐up, Ishak staging scores progressed more frequently among carriers of a T/* allele who had a baseline serum cholesterol ≤175 mg/dl than in remaining patients: 6/36 (change ≤0), 15/45 (change 1–2), 6/12 (change ≥3), improvement chi‐square P < 0.02, OR 3.1, 95% C.I. 1.3–7.7. In the cross‐sectional study, the frequency of patients carrying the T/T genotype or serum cholesterol values ≤175 mg/dl increased starting from those with a staging score ≤2 (36/76, 47.4%), to those with a staging score of 3–4 (26/41, 63.4%) and to those with a staging score of 5–6 (20/26, 76.9%, P < 0.01 for linear trend). In conclusion, the interaction between IL‐28B rs12979860 T/T genotype and low serum cholesterol concentration is an independent predictor of a worse disease course among patients infected with HCV with normal or near‐normal transaminases. J. Med. Virol. 84:747–755, 2012. © 2012 Wiley Periodicals, Inc.     

Comparative effects of two HMG-CoA reductase inhibitors (lovastatin and pravastatin) on serum lipids and lipoproteins

The effects of the HMG-CoA reductase inhibitors lovastatin and pravastatin were studied over 4 months on serum lipids and lipoproteins in 35 patients with severe primary hypercholesterolaemia. In 17 patients 20 mg of lovastatin/day lowered the total cholesterol level by 18% (baseline 373 mg/dl) and LDL cholesterol by 20% (baseline 300 mg/dl). The corresponding data for 40 and 80 mg of lovastatin/day were respectively -23% and -29% for total cholesterol, and -30% and -36% for LDL cholesterol. Pravastatin at 20 mg/day lowered the total cholesterol in 18 patients by 20% (baseline 373 mg/dl) and LDL cholesterol by 24% (baseline 307 mg/dl). The corresponding data for 40 mg of pravastatin per day were 24% for total cholesterol and 30% for LDL cholesterol. So the effects of both HMG-CoA reductase inhibitors on total and LDL cholesterol are comparable. HDL (high-density lipoprotein) cholesterol was increased by lovastatin, whereas pravastatin showed no influence on HDL cholesterol. The reduction of serum triglycerides, VLDL triglycerides and VLDL cholesterol was more pronounced under treatment with lovastatin than under pravastatin.     

Comparative primate atherosclerosis: I. Tissue Cholesterol Concentration and Pathologic Anatomy

Stump-tailed macaques (Macaca arctoides), African green monkeys (Cercopithecus aethiops), squirrel monkeys (Saimiri sciureus), and woolly monkeys (Lagothrix lagothricha) were fed control, solid atherogenic (1 mg cholesterol/cal) or liquid diets containing 0, 0.5, or 1 mg cholesterol/cal.Stump-tailed macaques fed the solid atherogenic diet had the highest tissue and serum cholesterol concentration (about 700 mg/dl) and the most extensive atherosclerosis. These monkeys appeared to respond differently to diets containing 1 mg cholesterol/cal. Those animals fed the liquid diet had higher liver cholesterol concentration but lower serum cholesterol concentration than animals fed the solid diet. African green monkeys fed the solid atherogenic diet had serum cholesterol concentrations of about 450 mg/dl. A greater percentage of the abdominal aorta was covered by plaque than the thoracic aorta. Coronary artery atherosclerosis was focal with the largest plaques being found in the left main coronary artery. The microscopic appearance of these plaques was similar to that of plaques from people.Squirrel monkeys fed the atherogenic diet were the most variable group. The average serum cholesterol concentration averaged about 450 mg/dl (range: 291 to 716). The percentage of aorta covered by plaque ranged from 0 to 55% with more thoracic than abdominal aortic atherosclerosis. There were findings consistent with hemorrhage in plaques from two animals. These monkeys, like stump-tailed macaques but unlike African green monkeys had relatively high liver cholesterol concentrations.Woolly monkeys appeared to develop atherosclerosis when fed 1 mg cholesterol/cal but did not have greatly elevated serum cholesterol concentrations.