Congenital venous anomalies associated with retrocaval ureter: evaluation using computed tomography.

BACKGROUND: Retrocaval ureter is a rare congenital anomaly resulting from anomalous development of inferior vena cava (IVC) and not from anomalous of the ureter. The anomaly always occurs on the right side due to regression of right supracardinal vein and persistence of right posterior cardinal vein. Retrocaval ureter tends to be associated with various vena cava anomalies because of the embryogenesis. We aimed to identify the prevalence of associated congenital venous anomalies (CVA) resulting from cardinal vein development in adults with retrocaval ureter using computed tomography (CT) images. MATERIALS AND METHODS: The study included 22 adults with retrocaval ureter. We evaluated CT findings and determined the incidence of associated CVA using thin slice data sets from CT scanner with 64 or more detectors. We compared the prevalence of CVA in the retrocaval ureter group (mean age: 57 ± 19 years) and in the control group of 6189 adults with normal ureter (mean age: 66 ± 14 years). RESULTS: In the retrocaval ureter group, 4 (18.2%) adults had CVA including double IVC, right double IVC, preisthmic IVC with horseshoe kidney, and preaortic iliac confluence. One of 2 adults with preaortic iliac confluence had right double right IVC. In the control group, 49 (0.79%) adults had CVA including 37 double IVC, 11 left IVC, and 1 IVC interruption azygos continuation. Fifteen horseshow kidneys were found. The prevalence of associated CVA in the retrocaval ureter group was higher than that in the control group (p < 0.001). CONCLUSIONS: Retrocaval ureter is frequently associated with CVA. Various CVA with retrocaval ureter could happen because of abnormal development of not only the right posterior or supra cardinal vein but also other cardinal veins.

Hybrid surgical and endovascular therapy in multifocal peripheral TASC D lesions: up to three-year follow-up.

AIM: The authors described their three-year experience with hybrid surgical and endovascular therapy for multifocal peripheral TASC D lesions, involving both the aortoiliac and/or superficial femoral and common femoral arteries. METHODS: From February 2005 to March 2008, 21 lower limbs in 20 patients with multifocal peripheral artery disease, involving the aortoiliac and/or superficial femoral as well as common femoral arteries, were treated by hybrid surgical and endovascular therapy, such as aortoiliac and/or superficial femoral artery stenting as an adjunct to common femoral artery endarterectomy. Technical and hemodynamic success as well as primary and primary assisted patency and limb salvage rates were determined in concordance with the Society for Vascular Surgery guidelines. RESULTS: All lower limbs successfully underwent successful hybrid surgical and endovascular therapy. The average ABPI before and after hybrid therapy significantly increased from 0.50 +/- 0.32 to 0.79 +/- 0.24 (P = 0.0022). The mean duration of follow-up was 357 days (range, 4 to 1400 days). Over all, the primary patency rates were 94%, 70% and 70% at 6, 12, and 24 months, respectively, and the primary assisted patency rates were 94% at 24 months. The limb salvage rate was 100% at 24 months. The survival rates were 95%, 88%, and 88% at 6, 12, and 24 months, respectively. The primary patency rate for intermittent claudication was significantly higher that that for critical limb ischemia, while no significant difference was found in the assisted primary patency and survival rates between intermittent claudication and critical limb ischemia. CONCLUSION: Hybrid surgical and endovascular therapy, such as aortoiliac and/or superficial femoral artery stenting as an adjunct to common femoral artery endarterectomy, can provide a less invasive yet effective and durable option to patients with multifocal peripheral artery disease.

Stent placement in the superficial femoral artery for patients on chronic hemodialysis with peripheral artery disease.

AIM: Chronic hemodialysis is associated with a high prevalence of peripheral artery disease (PAD), and patients on chronic hemodialysis with PAD have an increased risk of critical limb ischemia. The present study assessed the hemodynamic and clinical outcomes of stent placement in the superficial femoral artery (SFA) for patients on chronic hemodialysis. METHODS: Between February 2005 to August 2008, 43 consecutive lower limbs in 42 patients with SFA lesions that were successfully treated by primary stent placement were included in this study. Those were divided into a dialysis group (18 limbs) and a nondialysis group (25 limbs). Outcome measures included primary patency, assisted primary patency, limb salvage, and survival. RESULTS: Patients were significantly younger and presented with significantly more symptomatic limb ischemia in the dialysis group compared to the nondialysis group, despite comparable TransAtlantic Inter-Society Consensus (TASC) classification scores of SFA lesions between the two groups. The primary patency, primary assisted patency, limb salvage, and survival rates of the dialysis group were similar to those of the nondialysis group. CONCLUSIONS: Stent placement in the SFA is a feasible, safe, and effective procedure in patients on chronic hemodialysis with PAD, and may be offered as a first-choice therapeutic option for these patients.

Effects of ML-236b (compactin) on sterol synthesis and low density lipoprotein receptor activities in fibroblasts of patients with homozygous familial hypercholesterolemia.

We studied biochemical genetics of low density lipoprotein (LDL) receptor mutations in fibroblasts from six homozygous and five heterozygous patients with familial hypercholesterolemia (FH). Three of six homozygotes are receptor-negative type and the other three homozygotes are receptor-defective type. In the cells from three receptor-negative homozygotes, the receptor binding, internalization, and degradation of (125)I-LDL were 0.5+/-0.3 ng/mg protein (mean+/-SEM), 14+/-8 and 8+/-6 ng/mg protein per 6 h (four normal cells; 44+/-3, 386+/-32, and 1,335+/-214 ng/mg protein per 6 h), respectively. In the cells from three receptor-defective homozygotes, the receptor binding, internalization, and degradation of (125)I-LDL were 6+/-2, 29+/-8, and 90+/-32 ng/mg protein per 6 h, respectively. In these six homozygotes, two pairs of siblings are included. Two siblings in the same family were classified as receptor-negative and two siblings in another family were classified as receptor-defective. The receptor-negative phenotypes and the receptor-defective phenotypes bred true in individual families. The cells from five heterozygotes showed approximately 46% of the normal activities of receptor.ML-236B, competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), completely inhibited the incorporation of [(14)C]acetate into digitonin-precipitable sterols in fibroblasts from normal subjects and heterozygous and homozygous patients with FH with the concentration of 0.5 mug/ml. However, at 0.05 mug/ml of ML-236B sterol synthesis in fibroblasts from homozygotes was not completely suppressed in contrast to normal and heterozygous cells. Moreover, after preincubation with 0.05 mug/ml of ML-236B for 24 h in medium containing lipoproteins, sterol synthesis in the cells from receptor-negative homozygote showed 75% of the initial activity compared with that of 25% without preincubation. In the cells from a normal subject and a heterozygote, sterol synthesis was inhibited even after preincubation. These results suggest that (a) the inhibitory effect of ML-236B is overcome in homozygote cells by their high intracellular levels of HMG-CoA reductase and (b) that a higher dose of ML-236B may be required to lower serum cholesterol levels in FH homozygotes than in heterozygotes.

Genetic cholesteryl ester transfer protein deficiency caused by two prevalent mutations as a major determinant of increased levels of high density lipoprotein cholesterol.

Genetic determinants of HDL cholesterol (HDL-C) levels in the general population are poorly understood. We previously described plasma cholesteryl ester transfer protein (CETP) deficiency due to an intron 14 G(+1)-to-A mutation(Int14 A) in several families with very high HDL-C levels in Japan. Subjects with HDL-C > or = 100 mg/dl (n = 130) were screened by PCR single strand conformational polymorphism analysis of the CETP gene. Two other mutations were identified by DNA sequencing or primer-mediated restriction map modification of PCR products: a novel intron 14 splice donor site mutation caused by a T insertion at position +3 from the exon14/intron14 boundary (Int14 T) and a missense mutation (Asp442 to Gly) within exon 15 (D442G). The Int14 T mutation was only found in one family. However, the D442G and Int14 A mutations were highly prevalent in subjects with HDL-C > or = 60 mg/dl, with combined allele frequencies of 9%, 12%, 21% and 43% for HDL-C 60-79, 80-99, 100-119, and > or = 120 mg/dl, respectively. Furthermore, prevalences of the D442G and Int14 A mutations were extremely high in a general sample of Japanese men (n = 236), with heterozygote frequencies of 7% and 2%, respectively. These two mutations accounted for about 10% of the total variance of HDL-C in this population. The phenotype in a genetic compound heterozygote (Int14 T and Int14 A) was similar to that of Int14 A homozygotes (no detectable CETP and markedly increased HDL-C), indicating that the Int14 T produces a null allele. In four D442G homozygotes, mean HDL-C levels (86 +/- 26 mg/dl) were lower than in Int14 A homozygotes (158 +/- 35 mg/dl), reflecting residual CETP activity in plasma. In 47 D442G heterozygotes, mean HDL-C levels were 91 +/- 23 mg/dl, similar to the level in D442G homozygotes, and significantly greater than mean HDL-C levels in Int14 A heterozygotes (69 +/- 15 mg/dl). Thus, the D442G mutation acts differently to the null mutations with weaker effects on HDL in the homozygous state and stronger effects in the heterozygotes, suggesting dominant expression of a partially defective allele. CETP deficiency, reflecting two prevalent mutations (D442G and Int14 A), is the first example of a genetic deficiency state which is sufficiently common to explain a significant fraction of the variation in HDL-C in the general population.

Intermediate-term results of angioscopy-assisted anterior valve sinus plication for primary deep venous insufficiency.

AIM: The intermediate-term efficacy of angioscopy-assisted anterior valve sinus plication for primary deep venous insufficiency was evaluated. METHODS: Twelve limbs in 11 patients had class 4 or higher disease on the SVS/ISCVS classification. Descending venography revealed grade-3 or 4-reflux in all limbs. The limbs were treated with angioscopy-assisted anterior valve sinus plication of the highest valve of the superficial femoral vein. Clinical evaluation and air plethysmography were performed at the final follow-up. RESULTS: The mean follow-up was 38.4 months with a range of 24 to 48 months. Postoperative descending venography revealed significant improvement of the reflux of the superficial femoral vein. At the final follow-up, all patients reported relief of subjective symptoms. The ulcers healed and did not recur in the single limb with class-6 disease, the ulcers did not recur in four class-5 limbs, and there was a distinct clinical improvement with resolution of skin changes in the seven class-4 limbs. The venous filling index measured by air plethysmography was in a normal range in 8 of the 12 limbs. CONCLUSIONS: Angioscopy-assisted anterior valve sinus plication may be a surgical technique that results in intermediate-term clinical and hemodynamic improvement in patients with primary deep venous insufficiency.

Magnetic resonance venography of the lower limb.

Prior to surgery or endovascular therapy for the lower extremity varicose veins or deep venous thrombosis (DVT), ultrasonography provides useful information. But it depends on the operator's technique, each image is limited to a small field of view and interpretation may be subjective. On the other hand, magnetic resonance (MR) imaging is now available with several postprocessing techniques using workstations to demonstrate the gross and objective morphology of these lesions less invasively than the conventional ascending venography. As non-contrast MR venography, fat suppressed three-dimensional (3D) coronal balanced turbo field echo (bTFE) is mainly applied in the semisupine position. The varicose veins on the muscle fascia are easily recognized on volume rendering and the perforating veins can be identified on maximum intensity projection (MIP) and axial multiplanar reconstructions. Gadolinium-enhanced fluid attenuated inversion recovery-bTFE is added when coexisting joint effusion or edema masks the veins. For DVT, direct thrombus imaging (DTI) using fat suppressed 3D coronal inversion recovery-prepared blood suppressed gradient echo sequence is applied. However, the signal intensity of DVT depends on the clot's age on DTI and is sometimes confusing on bTFE. After gadolinium administration, blood shows higher signal intensity than clots regardless of the age and DVT can be easily depicted as filling defects on the axial reformations and summarized on the soap bubble-MIP.

Real-time coverage monitoring of initial oxidation processes on Si(001) by means of surface differential reflectance.

Initial oxidation processes on Si(001) have been studied by means of surface differential reflectance (SDR). The time courses of the SDR spectra measured during thermal oxidation at 820 and 920 K allowed two different growth modes, Langmuir-type adsorption and two-dimensional island growth, to be distinguished. No photon energy dependence was observed in the time course of the SDR intensity at either temperature. On the other hand, different uptake curves were observed at different photon energies for oxidation at 300 K. The difference between the oxidation mechanisms at 300 K and at high temperatures was qualitatively apparent from SDR results, because significant photon energy dependence was observed only at 300 K. Possible assignments of the spectral components in the SDR spectra are discussed.

Effects of long-term anticonvulsant therapy on copper, zinc, and magnesium in hair and serum of epileptics.

The effects of long-term anticonvulsant therapy on copper (Cu), zinc (Zn), and magnesium (Mg) in the serum and hair were investigated in epileptics. Hair concentrations of Cu in both male and female epileptics, Zn in male epileptics, and Mg in female epileptics were significantly decreased when compared with those of age-matched and gender-matched controls. Hair Cu concentrations were significantly decreased in male epileptics; a significant decrease in hair Mg concentration was observed in female epileptics when compared with schizophrenics. An increased serum Cu concentration was found in female epileptics and a decreased Zn concentration was found in male epileptics. These findings suggest that long-term anticonvulsant therapy could induce alterations in both the metabolism and distribution of Cu, Zn, and Mg.

Autoradiographic localization of CCK-8 binding sites in the rat brain: effects of chronic methamphetamine administration on these sites.

The effects of chronic methamphetamine (MAP) administration (at a dose of 4 mg/kg for 14 days) on [3H]pCCK-8 binding sites in the rat brain were investigated by an in vitro quantitative receptor autoradiographic technique. The number of [3H]pCCK-8 binding sites was significantly reduced in layers III and IV of the medial frontal, anterior, and posterior cingulate cortices, in layers II-IV of the retrosplenial cortex, in layers III-VI of the dorsal insular cortex, and in the reticular nucleus of the thalamus, compared to these numbers in a control group of rats that received physiologic saline. Further, chronic methamphetamine administration led to a significant increase in the number of these binding sites in layer I of the entorhinal cortex. These findings indicate the CCK peptides in the limbic lobe may be closely related to the development of the behavioral changes associated with methamphetamine sensitization. In addition, these results provide supporting evidence for the involvement of the limbic system in the pathophysiology of schizophrenia.

Removal of apolipoprotein E-enriched high density lipoprotein by LDL-apheresis in familial hypercholesterolaemia: a possible activation of the reverse cholesterol transport system.

The presence of apo E-containing HDL in familial hypercholesterolaemia was investigated and its removal by LDL-apheresis using a dextran sulphate cellulose column was demonstrated by measurement of the apo E/apo A-I molar ratio of serum and by nondenaturing polyacrylamide gel electrophoresis followed by immunoblotting. The molar ratios of apo E/apo A-I in the density greater than 1.063 kg/l fraction of serum obtained from two homozygous patients with familial hypercholesterolaemia were higher (0.021 and 0.030) than that from normal subjects (mean +/- SE 0.011 +/- 0.002) (P less than 0.05). Polyacrylamide gel electrophoresis and immunoblotting showed an increase in apo E-containing HDL similar to HDL2, in the plasma obtained from the homozygous patient with familial hypercholesterolaemia. The increased amounts of apo E-enriched HDL were removed from plasma by adsorption with a dextran-sulphate cellulose column. These results suggested that LDL-apheresis using the dextran-sulphate cellulose column, may cause an increase in the turnover rate of the apo E-containing HDL and thus facilitate cholesterol removal from the peripheral tissues.

A new low density lipoprotein apheresis system using two dextran sulfate cellulose columns in an automated column regenerating unit (LDL continuous apheresis).

We describe a new low density lipoprotein (LDL) apheresis system using dextran sulfate cellulose column in an automated column regenerating unit (LDL continuous apheresis). Two columns containing 150 ml of dextran sulfate cellulose were used, and the whole extracorporeal circulation was about 400 ml in volume. After 600 ml of plasma was adsorbed into the first column, the second column was used as an adsorbent and meanwhile the first column was regenerated. Thus, the 2 columns were used alternately without losing the potency of the columns. As the apparatus was automatically controlled by a computerized unit, no extra manipulation is necessary compared with the conventional single-column method. By treating 4-5 liters of plasma, non-high density lipoprotein (HDL)-cholesterol levels decreased by 63-71%, and HDL-cholesterol levels remained unchanged. Thus, this new method of LDL apheresis can safely reduce LDL-cholesterol to any desired level and will be applicable for the treatment of child and adult family hypercholesterolemic patients with severe coronary heart disease.

Long-term probucol treatment results in regression of xanthomas, but in progression of coronary atherosclerosis in a heterozygous patient with familial hypercholesterolemia.

A 66-year-old male heterozygous familial hypercholesterolemia (FH) patient with significant coronary atherosclerosis has been treated by us with probucol (1000 mg daily) for eight years. This treatment has produced significant reductions in the cholesterol levels of his serum, low density lipoprotein (LDL), and high density lipoprotein (HDL) from 237 +/- 20 mg/dl (mean +/- S.D.) to 156 +/- 15, from 175 +/- 8 to 111 +/- 16 mg/dl, and from 23 +/- 4 to 19 +/- 2 mg/dl, respectively. These reductions have been maintained for eight years. Serum triglyceride levels also decreased, from 220 +/- 54 to 146 +/- 36 md/dl. During this period, marked regression of xanthomas on the eyelids and finger extensor tendons was observed, while thickness of the Achilles tendons was reduced from 21.0 mm to 13.0 mm. On other hand, effort-induced anginal symptoms requiring additional antianginal medication have been noticed, and angiographically-demonstrated coronary atherosclerosis has progressed significantly during these eight years. These observations lead us to suggest that maintaining low levels of HDL cholesterol with probucol, even though resulting in satisfactory reduction of LDL cholesterol and marked regression of xanthomas, appears to be associated with the progression of atherosclerosis in the coronary arteries.

Clinical characteristics of double heterozygotes with familial hypercholesterolemia and cholesteryl ester transfer protein deficiency.

Coronary heart disease (CHD) in familial hypercholesterolemia (FH) may be modified by genetic and/or environmental factors. We described the effect of the cholesteryl ester transfer protein (CETP) gene on CHD in heterozygous FH caused by low density lipoprotein receptor (LDL-R) gene mutation. In 288 unrelated Japanese subjects with heterozygous FH, the allele frequency of an intron 14 G(+1)-to-A mutation (Int14 A) and a missense mutation in exon 15 (Asp442 to Gly, D442G) was 0.3 and 3.0%, respectively. HDL-C levels (1.55 +/- 0.08 mmol/l) in FH patients with heterozygous CETP deficiency were higher than those (1.19 +/- 0.08 mmol/l) in FH without CETP deficiency (P < 0.03), while LDL-C levels in FH with CETP deficiency were moderately reduced. However, two FH patients with CETP deficiency suffered myocardial infarction, and six patients had effort angina pectoris and/or coronary atherosclerosis. No difference in the score of coronary stenosis index (CSI) was found in FH with/without CETP deficiency, although CSI was inversely correlated with HDL-C levels (P < 0.05). Thus, the effect of increased HDL-C levels caused by partial deficiency of CETP is insufficient to prevent CHD in FH.

Opposite effects on serum cholesteryl ester transfer protein levels between long-term treatments with pravastatin and probucol in patients with primary hypercholesterolemia and xanthoma.

Long-term effects of pravastatin and probucol on serum cholesteryl ester transfer protein (CETP) and xanthoma/xanthelasma size were compared. Twenty-three patients with primary hypercholesterolemia and xanthoma/xanthelasma, including 11 patients with heterozygous familial hypercholesterolemia, were treated with pravastatin (20 mg/day) or probucol (1000 mg/day) for 24 months. Serum CETP levels were measured by sandwich ELISA. In 11 patients (six men and five women, 55 +/- 2 [SE] yr) treated with pravastatin, serum cholesterol levels decreased from 262 +/- 13 to 229 +/- 13 mg/dl during the 24-month treatment period (P = 0.05). Serum HDL cholesterol levels were not changed. Serum CETP levels decreased from 2.5 +/- 0.2 to 2.0 +/- 0.2 microg/ml (-21%, P = 0.002). By contrast, in 12 patients (four men and eight women, 57 +/- 4 year) treated with probucol, serum cholesterol levels did not significantly decrease from 236 +/- 11 to 207 +/- 13 mg/dl. Serum HDL cholesterol levels decreased from 44 +/- 2 to 30 +/- 2 mg/dl (P = 0.009). Serum CETP levels increased from 2.3 +/- 0.1 to 2.8 +/- 0.2 microg/ml (+23%, P = 0.02). Xanthelasma regression was found in two of four patients (50%) each treated with pravastatin and probucol, respectively. In contrast, Achilles' tendon xanthoma regressed in four of five patients (80%) treated with pravastatin, but only in two of five patients (40%) treated with probucol. Patients with xanthoma/xanthelasma regression after 2 years treatment had higher baseline levels of serum CETP than those without regression (2.7 +/- 0.2 microg/ml [n = 9] versus 2.1 +/- 0.2 microg/ml [n = 7], P = 0.05). Serial changes in serum CETP levels during treatment with pravastatin and probucol were discordant, but not related to the degree of xanthoma regression. However, higher level of serum HDL3 cholesterol was an independent factor in the smaller size of Achilles' tendon xanthoma at baseline. In addition, higher levels of serum HDL3 triglyceride on lipid-lowering therapy (6 months) appear to be a common predictor of regression of Achilles' tendon xanthoma in the treatment with either pravastatin or probucol.

Effects of CS-514 (eptastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on serum lipid and apolipoprotein levels in heterozygous familial hypercholesterolemic patients treated by low density lipoprotein (LDL)-apheresis.

Nine heterozygous patients with familial hypercholesterolemia (FH) were treated by low density lipoprotein (LDL)-apheresis using dextran sulfate cellulose columns. After more than 3 procedures of LDL-apheresis without drug therapy, combination therapy with LDL-apheresis and CS-514 (eptastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase, at a dose of 10 mg twice daily was started. Pre- and post-apheresis serum cholesterol levels were decreased significantly by CS-514, from 289 +/- 24 mg/dl (mean +/- SEM) to 247 +/- 25 mg/dl and from 118 +/- 7 mg/dl to 106 +/- 9 mg/dl, respectively. Pre- and post-apheresis apolipoprotein B levels decreased significantly on CS-514 from 160 +/- 9 mg/dl to 138 +/- 8 mg/dl and from 58 +/- 6 mg/dl to 45 +/- 6 mg/dl, respectively. No adverse effects were observed during the combination therapy. Thus, the addition of an inhibitor of HMG-CoA reductase to LDL-apheresis is a useful method for further reducing serum cholesterol and apolipoprotein B levels in FH heterozygotes.

Coronary angiographic characteristics in Japanese patients with heterozygous familial hypercholesterolemia.

Coronary angiographic findings were analyzed in 51 consecutive patients (36 males and 15 females) with heterozygous familial hypercholesterolemia (FH) and 279 consecutive patients (216 males and 63 females) without FH (non-FH). The coronary stenosis index and over 75% stenosis vessel subset were almost three times as high in the FH group. The incidence of myocardial infarction was almost twice as high in the FH group. Levels of total cholesterol and its lipoprotein fractions, except HDL-cholesterol, were almost twice as high in the FH group. In the FH group aged under 50 years, the two parameters of coronary angiogram and the incidence of myocardial infarction were significantly higher in males than in females. However, in the group aged over 50 years, all three parameters were not significantly different between those in males and females. The level of HDL-cholesterol was significantly lower in males than in females. A significantly higher incidence (18%) of coronary ectasia was observed in the FH group compared with the incidence (2%) in non-FH. All patients with coronary ectasia were males, except one female with FH. On comparison of the males among the FH patients with those among the non-FH patients matched for total cholesterol, age and other risk factors, the FH patients were associated with a significantly higher degree of coronary atherosclerosis and lower level of HDL-cholesterol. Seven FH patients with a normal coronary angiogram were observed. However, any factors as regards age, total cholesterol, HDL-cholesterol and Achilles tendon thickness failed to distinguish between the FH patients with a normal coronary angiogram and those without.(ABSTRACT TRUNCATED AT 250 WORDS)

Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia.

Lipoprotein patterns and cholesteryl ester transfer activity (CETA) were examined in 2 patients with familial hyperalphalipoproteinaemia (FHALP). The proband was a healthy 58-year-old Japanese male who had an HDL cholesterol of 7.83 mmol/l (301 mg/dl). His sister's HDL cholesterol was 4.52 mmol/l (174 mg/dl), which suggested that both were homozygous carriers of FHALP. In both subjects HDL showed a high cholesterol/apo A-I ratio and appeared to be a larger-sized particle than normal HDL on agarose gel chromatography. Two of the proband's children showed higher HDL cholesterol levels (1.74 mmol/l, 2.16 mmol/l) than normal, but another 2 children showed normal levels (1.48 mmol/l, 1.40 mmol/l). However, the ratios of HDL cholesterol to total cholesterol and to apo A-I in all children were higher than normal. These data suggest, but do not prove, that all his children were heterozygotes. Apo B levels in all of the family members studied were lower than normal (47-80 mg/dl). Deceased members of the same family had not died from cardiovascular disease. Cholesteryl-ester transfer activity was studied in both patients. When serum or lipoprotein deficient serum (d greater than 1.21) and [3H]cholesteryl ester labelled HDL3 were incubated in the presence of an LCAT inhibitor, there was no evidence of cholesteryl ester transfer from HDL to VLDL and/or LDL, unlike normal subjects. The deficiency of CETA in these patients with FHALP presumably accounted for the increase in particle size and cholesterol enrichment of HDL.

Serum lipoprotein lipid concentration and composition in homozygous and heterozygous patients with cholesteryl ester transfer protein deficiency.

Six homozygous, 10 heterozygous and 8 unaffected subjects in a CETP deficient family confirmed by CETP gene analysis were studied to characterize serum lipoproteins separated by ultracentrifugation, and to examine the relations between CETP levels and lipoprotein lipid concentration and composition. The serum CETP levels were measured by radioimmunoassay using 125I-labeled monoclonal antibodies (TP2). The serum CETP levels in the homozygotes were undetectable and those in the heterozygotes were significantly lower than those in the unaffected subjects (1.5 +/- 0.1 vs. 2.2 +/- 0.5 microgram/ml, P less than 0.01). In the HDL fraction, esterified cholesterol (EC) levels in the homozygotes were significantly increased (P less than 0.01), and those in the heterozygotes were slightly increased (n.s.), in comparison with those in the unaffected and the normolipidemic controls. The EC levels in the IDL fractions were lower in the homozygotes than in the normolipidemic controls. The EC/triglyceride (TG) molar ratios in IDL, the fraction obtained from the homo- and heterozygotes, were lower than those from the unaffected subjects (P less than 0.01 and less than 0.01, respectively), and the EC/TG ratios in the HDL fraction obtained from the homo- and heterozygotes were higher than those from the unaffected subjects (P less than 0.01 and n.s., respectively). Linear regression analysis showed that positive correlates of the serum CETP levels in all subjects were: IDL-EC (r = 0.463), HDL-TG (r = 0.603) and VLDL- and IDL-EC/TG ratio (r = 0.698 and 0.843).(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of lipoprotein(a) by LDL-apheresis using a dextran sulfate cellulose column in patients with familial hypercholesterolemia.

Lipoprotein(a) (Lp(a)) was eliminated by LDL-apheresis using a dextran sulfate cellulose column in 3 homozygous and 10 heterozygous familial hypercholesterolemic patients. Immediately after LDL-apheresis by the LA-15 system (continuous LDL apheresis), there were significant reductions in Lp(a) concentrations (28.6 +/- 11.8 mg/dl (mean +/- S.E.) to 9.6 +/- 5.6 mg/dl (P < 0.01)), and in LDL-cholesterol concentrations (156 +/- 32 mg/dl to 48 +/- 18 mg/dl (P < 0.01)). Immediately following LDL-apheresis, Lp(a) and LDL-cholesterol were reduced by 67.4% +/- 11.6% and 68.3% +/- 11.8%, respectively. The removal of Lp(a) paralleled that of LDL-cholesterol. The reduced levels of Lp(a) nearly returned to baseline within 7 days. In 6 of the heterozygous FH patients the rates of recovery of LDL cholesterol and Lp(a) were calculated, according to Apstein's equation after discontinuing lipid altering drug treatment for 4 weeks. Mean constant k values of LDL cholesterol and Lp(a) were 0.354 (range: 0.136-0.752) and 0.427 (range 0.112-0.933), respectively. The average concentration during the 7 days following LDL-apheresis was calculated. Average reductions were 28% in LDL cholesterol and 18% in Lp(a). Pravastatin treatment, which continued for 4 weeks, significantly decreased LDL cholesterol (P < 0.01); however, before LDL-apheresis pravastatin treatment significantly increased Lp(a) levels (P < 0.05) in a small number (n = 6) of the FH patients, who had been regularly treated with LDL-apheresis. These results suggest that LDL-apheresis using the dextran sulfate cellulose column is an effective treatment to reduce levels of serum Lp(a) and LDL proportionally. This therapy may be of value in the prevention and regression of coronary artery disease in FH patients.