[Analysis on migration of HIV/AIDS cases and related factors in Liangshan Yi Autonomous Prefecture in Sichuan province, 2020].

Objective: To analyze the migration of the HIV/AIDS cases and related factors in Liangshan Yi autonomous prefecture (Liangshan). Methods: According to HIV/AIDS Comprehensive Response Information Management System of China Information System for Disease Control and Prevention, a total of 28 772 HIV/AIDS cases who had follow-up records in Liangshan in 2020 were included in the survey. The migration of the HIV/AIDS cases was described and the related factors were analyzed using multiple logistic regression models, and the migration destinations of the HIV/AIDS cases were mapped. Results: Among the 28 772 HIV/AIDS cases, 20.89% (6 010/28 772) had migration in 2020. Multivariate logistic regression analysis showed that among the HIV/AIDS cases, the migration related factors included being aged 15-24 years (compared with being aged 0-14 years, OR=2.74, 95%CI:2.04-3.69) and ethnic group (compared with Han ethnic group, OR=2.44, 95%CI:2.19-2.72), having education level of junior high school (compared with having education level of primary school or below, OR=1.25, 95%CI:1.14-1.38), being unmarried (compared with being married, OR=1.29, 95%CI:1.20-1.39), being engaged in business services (compared with being engaged in farming, OR=1.96, 95%CI:1.31-2.92), receiving antiviral treatment <1 year (compared with receiving antiviral treatment >3 years, OR=1.42, 95%CI:1.26-1.61), having recent CD4+T lymphocytes (CD4) counts >500 cells/µl (compared with having recent CD4 counts <200 cells/µl, OR=1.15, 95%CI:1.03-1.29). The geographical distribution maps showed that among all cities in Sichuan, Xichang (13.26%, 797/6 010) and Chengdu (10.12%,608/6 010) were the main migration destinations of the HIV/AIDS cases, and the provinces outside Sichuan where the HIV/AIDS cases would like to migrate to were mainly Guangdong (18.19%, 1 093/6 010) and Zhejiang provinces (7.67%, 461/6 010) in 2020. The HIV/AIDS cases who migrated where Liangshan, within Sichuan province, and to other provinces accounted for 27.67% (1 663/6 010), 15.34% (922/6 010) and 56.99% (3 425/6 010), respectively. Conclusions: More attention should be paid to the mobility characteristics and the classification management of HIV/AIDS cases according to their characteristics in Liangshan. Timely access to information on changes in the place of work and residence of HIV/AIDS cases should be warranted when they have migration. Good referrals and management for mobility of HIV/AIDS cases in different places should be made to reduce loss to follow-up and improving interventions.

An unblinded, randomised phase II study of platinum-based chemotherapy with vitamin B12 and folic acid supplementation in the treatment of lung cancer with plasma homocysteine blood levels as a biomarker of severe neutropenic toxicity.

BACKGROUND: Vitamin B12 and folic acid (referred to as vitamin supplementation) improves the toxicity profile of pemetrexed containing regimens. Low baseline vitamin B12 and folate levels are reflected in a raised total homocysteine level (HC). Studies have suggested that pretreatment HC levels predict neutropenia toxicity. We have tested supplementation with vitamin B12 and folate in non-pemetrexed platinum-based regimens to decrease treatment-related toxicity and looked for a correlation between toxicity and change in homocysteine levels. PATIENT AND METHOD: Eighty-three patients with advanced lung cancer and malignant mesothelioma were randomly assigned to receive platinum-based chemotherapy with (arm A) or without (arm B) vitamin B12 and folic acid supplementation. The primary end point was grade 3/4 neutropenia and death within 30 days of treatment. Secondary end points included quality of life, overall survival (OS) and the relationship between baseline and post supplementation HC levels and toxicity. RESULTS: In the intention-to-treat population, no significant difference was seen between the two groups with respect to chemotherapy-induced grade 3/4 neutropenia and death within 30 days of chemotherapy (36% vs 37%; p=0.966, emesis (2% vs 6%; p=0.9) or OS (12.3 months vs 7 months; p=0.41). There was no significant difference in survival rates by baseline HC level (p=0.9). Decrease in HC with vitamin supplementation was less frequent than expected. High baseline HC levels decreased with vitamin supplementation in only 9/36 (25%) patients (successful supplementation). Post hoc analysis showed that patients in arm A who were successfully supplemented (9/36=25%) had less neutropenic toxicity (0% vs 69%; p=0.02) compared to unsupplemented patients. CONCLUSIONS: The addition of vitamin B12 and folic acid to platinum-containing regimens did not overall improve the toxicity, quality of life or OS. Rates of grade 3/4 neutropenia at 36/37% was as predicted. Further studies to increase the rate of successful supplementation and to further test the biomarker potential of post supplementation HC levels in predicting chemotherapy-induced neutropenia in platinum-based chemotherapy are warranted. TRIAL REGISTRATION NUMBER: EudracCT 2005-002736-10 ISRCTN8734355.

Late presentation of simple virilising 21-hydroxylase deficiency in a Chinese woman with Turner's syndrome.

Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a well-known disorder of sexual development (previously known as ambiguous genitalia) in genotypic female neonates. We report on a 66-year-old Chinese, brought up as male, with a simple virilising form of congenital adrenal hyperplasia associated with Turner's syndrome (karyotype 45,X/47,XXX/46,XX). His late presentation was recognised due to his exceptionally short stature and persistent sexual ambiguity. His condition was only brought to medical attention as he developed a huge abdominal mass, which later turned out to be a benign ovarian mucinous cyst. It is therefore important to look out for co-existing congenital adrenal hyperplasia in patients with Turner's syndrome and virilisation, after the presence of Y chromosome material has been excluded.

Rainwater harvesting in schools in Taiwan: system characteristics and water quality.

In order to understand the current status of rainwater harvesting (RWH) practices in Taiwan's schools, a study was carried out to examine the RWH system performance, water usage, and water quality in these sites. A total of 29 schools in various regions were selected for this investigation, including 7 in the northern, 7 in the central, 8 in the southern, and 7 in the eastern regions of Taiwan. Water quality indicators tested were: pH, temperature, conductivity, oxidation-reduction potential, suspended solid, total organic carbon, fecal coliform, and total coliform. From this study, it was found that RWH systems in these sites generally had two different designs: one that collected rainwater only, and one that collected both rainwater and grey water. From statistical analysis, it was found that water quality indicators such as suspended solids, total organic carbon, and fecal coliform were significantly affected by the water source and site location. Fecal coliforms in most of the sites we studied were high and not qualified for toilet flushing. The average water retention time of 2.4 months was long and considered to be the main reason to cause high fecal coliform counts. Finally, the benefit analysis was conducted to evaluate economic feasibility of rainwater harvesting for these schools. It turned out that 20% of them were able to gain economic benefits from using rainwater.

Cell cycle stage analysis of rabbit foetal fibroblasts and cumulus cells.

Synchronization of the cell cycle stages in G0/G1 phase is one of the key factors determining the success of nuclear transplantation. Serum deprivation, contact inhibition and chemical inhibitors are widely used methods for this purpose. In this study, cell cycle stages of foetal fibroblasts and cumulus cells were determined using flow cytometry [fluorescence-activated cell scan (FACS)]. Foetal fibroblasts (in vitro cultured for 72-120 h) and fresh cumulus cells were analysed in Experiment 1. Fifty to 55% proliferating fibroblasts remained in G0/G1 phase compared with 78% in confluent culture (p <0.05). In contrast to foetal fibroblasts, fresh cumulus cells maintained 90% of the population in the G0/G1 stage. When serum was retrieved from the proliferating fibroblasts from day 1 to day 5 (Experiment 2), proportions of G0/G1 cells increased from the initial ratio of 53 to 87% at day 4 of starvation, which was significantly higher than the non-starved proliferating cells (p <0.05). In Experiment 3, fibroblasts were treated with aphidicolin (0.1 microg/ml, 6 h), demicolcine (0.5 microg/ml, 10 h), or a combination of these two chemicals to synchronize the cell cycle stages. Surprisingly, no differences or significantly lower in the proportions of G0/G1)phase cells were detected (25-50%) compared with the uncontrolled growing cells (53%). These results suggested that fresh cumulus cells rest their cell cycle in G0/G1 stage. Serum deprivation became effective in the first 24 h and reached the highest proportions during days 4-5 after deprivation. Chemical synchronization of the cell cycle stage of rabbit foetal fibroblasts to G0/G1 phase appeared less effective compared to serum deprivation.

Correlations of extractable heavy metals with organic matters in contaminated river sediments.

In southern Taiwan, almost all the main rivers have been contaminated by anthropogenic heavy metals and organic matters. The main pollution sources include agricultural, industrial, and domestic activities. River sediments potentially have large capacities to accumulate heavy metals and organic matters when the river water flows through it. The sediments sampled from high contaminated river (the Yenshui River) and moderately contaminated rivers (the Tsengwen, Chishui, Potzu, and Peikang Rivers) were used to realize correlations between each kind of aqua regia extractable heavy metals (Co, Cr, Cu, Zn, Ni, Pb, Mn, and Fe) and organic matters in vertical sediment cores. Organic matters and aqua regia extractable heavy metal concentrations, analyzed by strong acid-digested extraction, were determined in vertical profile segments from downstream sediments of the five rivers. Sum of six aqua regia extractable heavy metals (Co, Cr, Cu, Zn, Ni, and Pb) were below 3,000 mg/kg in sediments of the Yenshui River, and below 500 mg/kg in the other four rivers' sediments. Strongly positive correlations (r = 0.83-0.95) between each kind of aqua regia extractable heavy metals and organic matters (concentration range between 0.6 to 3.8%) were observed in sediments of the Yenshui River. The slopes of the linear regressive lines approximated the average metal complexation ratios with organic matters in the sediments. In sediments of the other four rivers, smaller positive correlation coefficients between aqua regia extractable heavy metals and organic matters (below 2.6%) were observed. The complexation ratios derived from the four moderately polluted river sediments were smaller than those derived from the highly contaminated river sediments, indicating that the importance of organic matters in the accumulation of heavy metals in river sediments.

CO(2) laser treatment in 244 patients with respiratory papillomas.

OBJECTIVE: Respiratory papillomas (RP) tend to recur and the difficulty in eradicating the disease makes their treatment frustrating. Meticulous CO(2) laser excisions every 2 months has been the most effective treatment to date. This article analyzes the results of this plan in 244 patients with RP in the nose, nasopharynx, pharynx, hypopharynx, larynx, trachea, lung parenchyma, and skin. METHODS: Two hundred forty-four patients with recurrent RP were treated by the senior author with CO(2) laser excisions and, in some cases, podophyllum and alpha interferon. Demographics, initial distribution of papillomas, number of operations performed on each patient, and current results were evaluated. RESULTS: Careful laser excisions of RPs every 2 months achieved "remission" of disease (no visible RP on indirect or often direct laryngoscopy 2 mo after last removal) in 37% of patients, "clearance" of the disease process (no RP clinically apparent for 3 y after last removal) in 6%, and "cure" (no clinical recurrence for 5 y after last removal) in 17%. Juvenile-onset RP tends to follow a more aggressive course than adult-onset RP. Four patients (1.6%) developed malignant transformation of their papillomas. Except for ones in lung parenchyma, RP in areas other than the true vocal cords tend to be cleared faster because aggressive removal does not cause hoarseness. Lung parenchyma RPs are eventually fatal because of pulmonary failure from abscesses and cysts resulting from a lack of effective treatment. CONCLUSION: Frequent and meticulously performed CO(2) laser excisions can achieve significant voice and airway improvement, and some clinical "cures." However, effective antiviral medicines and/or immunologic agents are needed to achieve true cures with elimination of all human papilloma virus 6 and 11 viruses.

Conservative management of infections in cochlear implant recipients.

OBJECTIVE: The goal of this study was to evaluate a conservative management strategy of postoperative infection after cochlear implantation. METHODS: A retrospective review of the medical records of 108 cochlear implant patients operated on at the University of California, San Francisco between 1991 and 2000 and 133 cochlear implant patients from the University of Iowa between 1997 and 2000 showed 4 patients with evidence of postoperative infections. The clinical presentation, intervention, laboratory results, and outcome are analyzed in each case. RESULTS: Minimal surgical intervention with limited incision and drainage with prolonged postoperative antibiotics was effective in treating postoperative cochlear implant infections without the need for device removal. Implant function remained unaffected after surgery. CONCLUSION: Postoperative cochlear implant infections can be effectively controlled with limited surgical and prolonged medical management. Chronic implant infections may be explained by a primary immunodeficiency. With appropriate treatment leading to infection control, a conservative management strategy is advocated before consideration of device explantation.

Correlation analyses on binding behavior of heavy metals with sediment matrices.

This article presents the amounts of heavy metals bound to the sediment matrices (carbonates, Fe-oxides, Mn-oxides, and organic matter), the correlations between any two heavy-metal binding fractions, and the correlations between sediment matrices and their heavy-metal binding fractions. Data consisted of 313 sets obtained from five main rivers (located in southern Taiwan) were analyzed by statistical methods. Among six heavy metals analyzed (Zn, Cu. Pb, Ni, Cr, and Co), the statistical results show that Zn is primarily bound to organic matter, and Cr is primarily bound to Fe-oxides. Principal component analysis (PCA) and correlation analysis (CA) result in significant correlations between carbonates bound Ni and carbonates bound Cr, Fe-oxides bound Ni and Fe-oxides bound Cr, and Mn-oxides bound Cu and Mn-oxides bound Cr. From linear regression results, the levels of the six heavy metals bound to either organic matter or Fe-oxides is moderately dependent on the contents of organic matter or Fe-oxides, especially true for Cr and Pb. According to slope values of linear regression, Cu and Cr have the highest specific binding amounts (SBA) to organic matter and Fe-oxides, respectively. A significant correlation between organic matter and organically bound heavy metals implied that organic matter contained in the sediments of the Potzu river and the Yenshui river can be adequately used as a normalizing agent. However, the six heavy metals bound to either carbonates or Mn-oxides do not correlate with carbonates or Mn-oxides. The obtained results also imply that competitions of various sediment phases in association with heavy metals occur, and organic matter and Fe-oxides are more accessible to heavy metals than other sediment phases.

LDL receptor-related protein mediates cell-surface clustering and hepatic sequestration of chylomicron remnants in LDLR-deficient mice.

It has been proposed that in the liver, chylomicron remnants (lipoproteins carrying dietary lipid) may be sequestered before being internalized by hepatocytes. To study this, chylomicron remnants labeled with a fluorescent dye were perfused into isolated livers of LDL receptor-deficient (LDLR-deficient) mice (Ldlr(-/-)) and examined by confocal microscopy. In contrast to livers from normal mice, there was clustering of the chylomicron remnants on the cell surface in the space of DISSE: These remnant clusters colocalized with clusters of LDLR-related protein (LRP) and could be eliminated by low concentrations of receptor-associated protein, an inhibitor of LRP. When competed with ligands of heparan sulfate proteoglycans (HSPGs), the remnant clusters still appeared but were fewer in number, although syndecans (membrane HSPGs) colocalized with the remnant clusters. This suggests that the clustering of remnants is not dependent on syndecans but that the syndecans may modify the binding of remnants. These results establish that sequestration is a novel process, the clustering of remnants in the space of DISSE: The clustering involves remnants binding to the LRP, and this may be stabilized by binding with syndecans, eventually followed by endocytosis.

Multivariate correlations of geochemical binding phases of heavy metals in contaminated river sediment.

Distributions of geochemical binding phases of seven heavy metals (Cr, Cu, Co, Zn, Ni, Pb, and Cd) in sediment cores taken from six heavily polluted sites of the Ell-Ren River in Southern Taiwan were studied. Sequential extraction procedures (SEP) were used to determine the variations of heavy metal binding phases (exchangeable, bound to carbonates, bound to manganese-oxides, bound to iron-oxides, and bound to organic matter) in different sediment depths. Multivariate analyses were used to explore the correlations among these geochemical binding phases of heavy metals. Results showed that the total amounts of various binding phases of heavy metals significantly varied with sediment depth, but their binding behaviors in various phases did not significantly change with depth. The organic matter content in the sediments increased with increasing Fe-oxide content. In addition, the binding affinities of carbonates with Zn, Pb, and Ni were higher than the affinities of carbonates with the other heavy metals. The binding affinity of Fe-oxides with Cr was higher than the affinities of Fe-oxides with the other heavy metals. Both correlation matrixes and principal component analyses demonstrated that distributions of Cu, Zn, Ni, and Cd had significant correlations with each other in both different depth horizons and various geochemical binding phases. The results indicate that these heavy metals might be discharged from the same pollution sources in the past, and also showed stable geochemical binding behaviors with the high silt sediment. However, Co had a poor correlation with the other six heavy metals in various binding phases, except with organic matter. Binding behaviors of Pb in the phases of bound to carbonates and exchangeable were different from the other six heavy metals. Cu was inversly correlated with the other six heavy metals in its binding behavior with reducible phases (Fe-/Mn-oxides).

Postprandial lipoproteins and atherosclerosis.

During the postprandial state, dietary lipid is transported from the intestine to peripheral tissues by plasma lipoproteins called chylomicrons. In the capillary beds of peripheral tissues, chylomicron triglycerides are lipolyzed by the enzyme, lipoprotein lipase, allowing the delivery of free fatty acids to the cells. As a result, this produces a new particle of smaller size and enriched with cholesteryl ester referred to as chylomicron remnants. These particles are rapidly removed from the blood primarily by the liver. The liver has a complex chylomicron remnant removal system which is comprised of a combination of different mechanisms that include the low-density-lipoprotein receptor (LDLR) and the LDLR-related-protein (LRP). Furthermore, it has been suggested that there is a sequestration component whereby chylomicron remnants bind to heparan sulfate proteoglycans (HSPG) and/or hepatic lipase; this is then followed by transport to one or both of the above receptors for hepatic uptake. Over the years, a major concern has arisen about the association of chylomicron remnants and coronary heart disease (CHD) in man. Slow removal of chylomicron remnants, as reflected by a prolonged postprandial state, is now commonly observed in patients with CHD and those that have abnormal lipid disorders such as hypertriglyceridemia, familial hypercholesterolemia, familial combined hyperlipidemia and non-insulin-dependent-diabetes-mellitus. The present review will focus on (a) the details of the metabolic pathway (exogenous pathway) that describes the two-step processing of postprandial lipoproteins, (b) the role of the liver, the receptors, and the importance of efficient removal of chylomicron remnants from the blood circulation, and (c) the potential atherogenic effects of chylomicron remnants on the arterial wall.

Chemical binding of heavy metals in anoxic river sediments.

Acid volatile sulfides (AVS) in sediments are available for binding with divalent cationic metals through the formation of insoluble metal-sulfide complexes, thereby controlling the metal bioavailability and subsequent toxicity to benthic biocommunities. However, when the molar concentrations of simultaneously extracted metals (SEM) were greater than AVS, the unexpectedly low or nondetectable levels of metal in pore water could also be found. Thus, except AVS, additional binding phases in sediments were supposed to provide the binding sites for SEM. The aims of this study are to realize the spatial distribution of AVS, SEM, and other binding phases of heavy metals in anoxic sediments of the Ell-Ren river and to elucidate what may be the main additional binding phases except AVS in the anoxic river sediments. By comparing the spatial distributions of SEM/ AVS ratio with various binding phases in extremely anoxic sediments (redox potential was between -115 and -208 mV), both organic matter and carbonates could be considered to be the main additional binding phases of SEM other than AVS. In addition, AVS appeared to have the priority to bind with SEM. By comparing the binding phases of heavy metals before and after AVS extraction, it could be found that Fe-oxides could also be considered to be the main additional binding phase associated with Zn in slightly anoxic sediments (redox potential was between -50 and -130mV), while organic matter with Cu being the next.

Rapid initial removal of chylomicron remnants by the mouse liver does not require hepatically localized apolipoprotein E.

Apolipoprotein E (apoE) is a ligand for the low density lipoprotein receptor (LDLR) and the low density lipoprotein receptor-related protein (LRP). The aim of the present study was to clarify the role of hepatically localized apoE in the rapid initial removal of chylomicron remnants by using the isolated perfused liver. Radiolabeled chylomicron remnants were perfused in a single nonrecirculating pass into the livers of C57BL/6J (wild-type) mice, apoE-knockout mice, and apoE/LDLR-knockout mice for a period of 20 min. Aliquots of the perfusate leaving the liver were collected at regular intervals and the rate of removal of radioactivity was determined. At a trace concentration of chylomicron remnants (0.05 microgram of protein per ml), wild-type mouse livers removed at a steady state of 50-55% of total chylomicron remnants perfused per pass; livers from apoE-knockout mice had the same capacity as wild-type mouse livers. When the concentration of remnants was increased to 12 microgram of protein per ml, a level at which it has been shown that LDL receptor and LRP are near saturation, the capacity of the wild-type mouse livers to remove chylomicron remnants was decreased to 10-25% per pass, confirming that the removal mechanisms were nearing saturation. However, instead of finding a greater reduction in the removal rates or impairment in chylomicron remnant removal, livers from apoE-knockout mice were just as efficient as those from wild-type mice in removing remnants. Livers of mice that lacked both apoE and the LDLR also had a similar rate of removal at relatively low remnant concentrations (0.05-0.5 microgram/ml), but had reduced capacity in removing remnants at a relatively high concentration (4-12 microgram/ml) of chylomicron remnants ( approximately 20% per pass). The rate of removal at these concentrations, however, was similar to that attributed to the LRP in previous studies. Chylomicron remnants, whose apolipoproteins were disrupted by trypsinization, were removed at a normal rate by wild-type mouse livers but there was almost no removal by apoE-knockout mouse livers. At higher concentrations, however, the removal of apolipoprotein-disrupted chylomicron remnants was decreased. Our present findings do not support the hypothesis that hepatically localized apoE is a critical factor in the rapid initial removal of chylomicron remnants by either of the major pathways but do suggest that hepatically localized apoE can be added to lipoproteins to accelerate their uptake, although this process may have a limited capacity to compensate for apoE deficiency on lipoproteins.

Chylomicron-remnant-induced foam cell formation and cytotoxicity: a possible mechanism of cell death in atherosclerosis.

The effects of chylomicron remnants on cytoplasmic lipid loading and cell viability were assessed in cultures of human monocyte-derived macrophages and rabbit arterial smooth muscle cells. At a cholesterol concentration of 150 microg/ml, chylomicron remnants induced substantial cytoplasmic lipid loading of macrophages, but not of smooth muscle cells, within 6 h of exposure. Chylomicron remnants were found to be cytotoxic to macrophages and smooth muscle cells, although the latter were generally more resistant. Chylomicron remnants contained no detectable oxysterols (>1 ng) and contained less non-esterified ('free') fatty acids than non-lipolysed nascent chylomicrons. Chylomicron-remnant-induced cytotoxicity appeared to be time- and dose-dependent. Macrophage and smooth muscle cell viability were inversely related to the production of superoxide free radicals and were significantly improved in the combined presence of superoxide dismutase and catalase. Collectively, our data suggest that, in macrophages, cell viability is compromised as a consequence of superoxide free radical production following uptake of chylomicron remnants. We would suggest that, in arterial smooth muscle cells, chylomicron-remnant-induced cell death also occurs as a consequence of superoxide free radical production. Our observations in the present study suggest that macrophage foam cells in atherosclerotic plaques might be derived from the cellular uptake of chylomicron remnants. Furthermore, arterial accumulation of chylomicron remnants might contribute to plaque destabilization as a consequence of cell death following superoxide free radical production by macrophages and smooth muscle cells.

Inner ear malformations and hearing loss in linear nevus sebaceous syndrome.

OBJECTIVE: Linear nevus sebaceous syndrome (LNSS) is a rare disorder comprising of nevus sebaceous, seizures, and mental retardation. While extensive literature describe the dermatologic, neurologic, as well as ophthalmologic manifestations of this LNSS, otologic problems have not been previously described. The objective of this report is to describe the otologic manifestation of a patient with LNSS. METHODS: A child with LNSS was referred to the Otologic clinic for evaluation of hearing loss. Pertinent findings on history, physical findings, audiometric testing, and imaging studies are discussed. RESULTS: Audiometric testing showed bilateral conductive hearing loss. Computerized tomography of the temporal bone demonstrated widened internal auditory canals and dysplastic lateral semicircular canals. CONCLUSION: LNSS can be associated with hearing impairment and inner ear malformations. The evaluation of a child with LNSS should include otologic and audiologic testing.

Evaluation of the components of the chylomicron remnant removal mechanism by use of the isolated perfused mouse liver.

The isolated perfused mouse liver was utilized to evaluate the relative contribution of various molecules believed to participate in the removal of chylomicron remnants by the liver. Sixty percent of asialofetuin was removed from the perfusate per pass; bovine serum albumin was not removed. Normal mouse livers removed chylomicron remnants more efficiently (40-50%/pass) than nascent chylomicrons (10-20%/pass). The fractional removal rate of remnants decreased as their concentration in the perfusate increased demonstrating saturability. Remnant removal by livers of low density lipoprotein receptor-deficient (LDLRD) mice paralleled that of normal mice at low remnant concentrations (0.05, 0.2 microg protein/ml); as concentration increased (4-16 microg protein/ml), removal by LDLRD livers was reduced. About 50% of the capacity to remove remnants was due to the LDL receptor. The role of the LDLR-related protein (LRP) was estimated using the receptor-associated protein (RAP). Four microg/ml of RAP inhibited only LRP; it reduced the removal of remnants by 30-40% in normal livers. When RAP was included in the perfusate of LDLRD livers, remnant removal persisted but was diminished, particularly late in the perfusion; the capacity was approximately 30% of controls. The present study has established that there is more than one mechanism operating for the removal of chylomicron remnants by the liver, provides estimates of the concentration of each to the removal of remnants, and indicates a method for further studies. It is concluded that in normal livers, the LDL receptor has the greatest capacity for removing chylomicron remnants. The LRP contributes to the process as well and a third component, perhaps "sequestration," accounts for up to 30% of the capacity for the initial removal of chylomicron remnants.

Accumulation of chylomicron remnants in homozygous subjects with familial hypercholesterolaemia.

BACKGROUND: Post-prandial lipoprotein kinetics were investigated in subjects who lack functioning low-density lipoprotein (LDL) receptors [homozygous familial hypercholesterolaemia (FH)]. METHODS: An oral fat load was given, and chylomicron plasma kinetics was determined by monitoring the clearance of triglyceride, retinyl palmitate and apolipoprotein B48, calculated as the area under the curve, for 7.5 h. In addition, the binding and uptake of chylomicron remnants by fibroblasts of FH and control subjects were assessed in vitro. RESULTS: Based on the plasma kinetics of chylomicron triglyceride, retinyl palmitate and apolipoprotein B48 after a lipid meal, chylomicron clearance was found to be substantially delayed compared with normolipidaemic control subjects. Consistent with involvement of the LDL receptor in chylomicron clearance, binding and uptake of chylomicron remnants by fibroblasts of FH subjects was found to be substantially less than in cells from control subjects. CONCLUSION: This study shows that, in addition to LDL, chylomicron metabolism is severely impaired in FH and that the LDL receptor is significantly involved in the clearance of post-prandial lipoproteins. Moreover, this study raises the possibility that in FH, and in other disorders in which LDL receptor expression is reduced, atherogenesis might be a post-prandial disease.

Cerebellopontine angle tumor outcomes in patients with hazardous occupations.

Cerebellopontine angle (CPA) tumor surgery can produce a spectrum of sensory and motor deficits that can alter a patient's lifestyle and occupation. An important consideration is whether patients can return to full occupational status especially when hazardous duties are involved. Outcome data in CPA tumor surgery usually report that most patients are able to return to preoperative function; however, whether these patients can return to hazardous duties is not specified. A retrospective study of 380 consecutive, operated CPA tumor patients was performed and 37 were identified who engaged in hazardous occupations including active military service, working at dangerous heights, piloting jet aircraft, aircraft navigating, and factory work with high-impact machinery. Overall, patients were able to resume full-time work in their previous occupations and 86% of patients reported that they were able to resume hazardous duties. CPA tumor surgery is compatible with continued full occupational duties after surgery, even for patients employed in hazardous situations.

Binding and uptake of chylomicron remnants by cultured arterial smooth muscle cells from normal and Watanabe-heritable-hyperlipidemic rabbits.

Chylomicron remnants (RM's) may be involved in atherogenesis because they can be delivered to the subendothelial space of arterial vessels and serve as substrate for arterial cells. A number of proteins may bind RM's, however, the quantitative significance of these is not established. The aim of this study was to identify the primary RM binding site of arterial smooth muscle cells (SMC's). At 4 degrees C, SMC's displayed saturable high affinity binding of RM's. In receptor competition studies, LDL inhibited binding of RM's by almost 60% suggesting involvement of the apolipoprotein B100/E receptor. Unlabeled RM's were more effective with an EC50 significantly less than for unlabeled LDL. Furthermore, at 37 degrees C RM uptake was three times greater than LDL, consistent with greater affinity of the apolipoprotein B100/E receptor for lipoproteins containing apolipoprotein E. In SMC's from homozygote Watanabe heritable hyperlipidemic (WHHL) rabbits, the binding and degradation of chylomicron remnants was severely impaired. SMC's from cross-bred WHHL rabbits exhibited levels of binding and degradation intermediate between homozygote WHHL rabbits and controls. We confirmed that the apolipoprotein B100/E receptor is the primary mechanism by which arterial smooth muscle cells bind and degrade RM's using a polyclonal antibody which specifically recognises the receptor. In the presence of the antibody, RM binding and degradation were inhibited by 90%.