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Biomedical subjects

L Chan

Publications and source records attributed to L Chan.

At least 145 records · Page 8Linked to original sources

The generalist role of specialty physicians: is there a hidden system of primary care?

CONTEXT: Despite increased emphasis on primary care in the United States, most care continues to be provided by specialists. The extent to which specialists incorporate elements of primary care in their approach to ambulatory patients is unknown. OBJECTIVES: To examine the extent to which selected medical and surgical subspecialties provide generalist care to Medicare patients, and to compare patterns of care between specialists and generalists. DESIGN: A cross-sectional study of all ambulatory care recorded in Part B of the Washington State Medicare Claims Database in 1994 and 1995. SETTING: Ambulatory practices in Washington State. PATIENTS: Medicare beneficiaries 65 years or older who made office visits to the study physicians. MAIN OUTCOME MEASURES: The extent to which individual specialties accounted for the majority of visits made by patients to physicians (a measure of continuity), provided care outside the traditional domain of their specialty (a measure of comprehensiveness), and provided influenza immunization. RESULTS: A total of 373 505 patients constituted the sample. Patients had an average of 7.48 outpatient visits per year; 9.6% saw only generalists, while 14.7% saw only specialists. The practices of general internists and family physicians differ systematically from the practices of most specialists. Approximately half (49.8%) of all ambulatory visits to general internists and family physicians are made by patients for whom they provide the majority of outpatient care, compared with 21.0% of medical specialist and 11.7% of surgical specialist visits. The rate of influenza immunization was 55.4% for patients who received the majority of their care from generalists, 47.7% from medical specialists, and 39.6% from surgical specialists. Pulmonologists, general surgeons, and gynecologists were more likely than other specialists to provide services outside their specialty. CONCLUSIONS: Most specialists do not assume the principal care responsibility for elderly patients, although a substantial proportion of patients see only specialists for their care. Selected specialties assume the generalist role more often, particularly when they provide the majority of outpatient care for an individual patient.

Aged↗

Is there a limit to massive blood transfusion after severe trauma?

OBJECTIVE: To examine the hypothesis that the futility of short-term care for trauma patients requiring emergency operation can be determined based on the number of units of blood transfused and associated risk factors. DESIGN: A 4-year retrospective review of a cohort of critically injured patients who underwent an emergency operation. SETTING: A large-volume, academic level I, urban trauma center. PATIENTS: One hundred forty-one consecutive patients received massive blood transfusions of 20 U or more of blood during preoperative and intraoperative resuscitation (highest, 68 U). There were 43 survivors (30.5%) and 98 nonsurvivors (69.5%). MAIN OUTCOME MEASURES: Mortality. RESULTS: The number of blood units transfused did not differ between survivors and nonsurvivors (mean +/- SD, 31 +/- 11 vs 32 +/- 10; P = .52). Stepwise multiple regression analysis identified 3 independent variables associated with mortality: need for aortic clamping, intraoperative use of inotropes, and intraoperative time with a systolic blood pressure of 90 mm Hg or less. However, blood usage was not different among the subgroups of patients who had 1 or more of these risk factors. When patients were stratified according to the amount of massive blood transfusion (20-29, 30-39, 40-49, and 50-68 U), the incidence of risk factors was not different across the 4 subgroups. Survival in the presence of risk factors was not affected by the amount of blood transfused. CONCLUSIONS: Although mortality among critically injured patients requiring operation and massive blood transfusion can be correlated with independent risk factors, discontinuation of short-term care cannot be justified based on the need for massive blood transfusion of up to 68 units.

Adult↗

Evolutionary analysis of RNA editing enzymes.

This article focuses on the evolution of apolipoprotein B (apoB) mRNA editing. We review the tools commonly used in homology search and phylogenetic analysis and demonstrate their use in the analysis of RNA-editing enzymes. The ultimate goal is to apply these tools to answer two questions: How did apoB mRNA editing come about? How might it be related to other base substitution editing in the course of evolution.

APOBEC-1 Deaminase↗

Follow-up of colorectal cancer: a meta-analysis.

PURPOSE: The value of intensive follow-up for patients after resection of colorectal cancer remains controversial. This study reviews all randomized and prospective cohort studies to assess the value of aggressive follow-up. METHODS: The literature was searched from the years 1972 to 1996 for studies reporting on the follow-up of patients with colorectal cancer. Randomized and comparative-cohort studies that included history, physical examination, and carcinoembrionic antigen values at least three times a year for at least two years were included in a meta-analysis. Single-cohort studies with intensive follow-up and traditional follow-up were also included in a two-group comparative analysis for each outcome indicator. Outcome indicators were 1) curative resection rates after recurrent cancer, 2) survival rates of curative re-resections, 3) length of survival after recurrence, and 4) cumulative five-year survival. RESULTS: Two randomized and three comparative-cohort studies met these criteria and included 2,005 patients, which were evaluated in the meta-analysis. The cumulative five-year survival was 1.16 times higher in the intensively followed group (P = 0.003). Two and one-half times more curative re-resections were performed for recurrent cancer in those patients undergoing intensive follow-up (P = 0.0001). Those patients in the intensive follow-up group with a recurrence had a 3.62-times higher survival rate than the control (P = 0.0004). Fourteen single-cohort studies were also included in the comparative analysis of 6,641 patients. The findings from these aggregated studies support the results of the meta-analysis. CONCLUSION: Our study concludes that intensive follow-up detects more recurrent cancers at a stage amenable to curative resection, resulting in an improvement in survival of recurrences and an increased overall five-year cumulative rate of survival.

Adult↗

Is adverse pregnancy outcome predictable after blunt abdominal trauma?

OBJECTIVE: The aim of the study was to evaluate the following: (1) pregnancy outcome after blunt abdominal trauma and (2) factors that may predict preterm birth and adverse peripartum outcomes. STUDY DESIGN: All women who had noncatastrophic abdominal trauma and came to the labor and delivery suite July 1994-August 1997 were prospectively evaluated and admitted for continuous uterine and fetal monitoring. A complete blood cell count, coagulation profile, and Kleihauer-Betke stain were performed. Ultrasonographic examination was performed to rule out hematoma. Tocolytic agents were administrated in cases with persistent contractions. Pregnancy outcomes and risk factors were compared between those with preterm birth before 37 weeks' gestation and those who were delivered after 37 weeks' gestation. RESULTS: Delivery information was available for 85 women with blunt abdominal trauma from motor vehicle accident (28), falls (27), and direct assault (30, which included 17 cases of domestic abuse). Four women, 3 of whom were exposed to domestic abuse, were hospitalized twice. Thirteen patients had preterm birth and 72 patients were delivered at term. In all cases the results of Kleihauer-Betke stains, maternal vital signs, blood cell count, coagulation profile, and placental ultrasonographic examinations were normal. The differences between the 2 groups with respect to gestational age at the time of trauma, length of hospital stay, subjective reports of abdominal pain, objective findings of abdominal tenderness, patterns of uterine contractions, interval between trauma and delivery, and Apgar scores were not statistically significant. However, the preterm birth group received magnesium sulfate tocolysis more frequently (31% vs 7%) and had a significantly greater rate of peripartum complications, such as rupture of membranes and abruptio placentae, than the group of patients who delivered at term (46.2% vs 12.5%, P <.05). Women with domestic abuse had increased uterine contractions at the time of abdominal trauma (52.9% vs 19.1%, P =.01) but did not require increased use of tocolysis. Women with domestic abuse had more peripartum complications (41.8% vs 11.8%, P <.01). CONCLUSIONS: Women with noncatastrophic blunt abdominal trauma in pregnancy tend to have favorable neonatal outcomes. Findings or reports of abdominal tenderness and uterine contractions are not predictive of preterm birth. Preterm birth was associated with increased peripartum complications. However, domestic abuse was associated with repeated trauma in the index pregnancy and increased peripartum complications.

Abdominal Injuries↗

Influenza vaccinations of Washington state Medicare beneficiaries seen by physiatrists in the outpatient setting in 1994.

OBJECTIVE: To compare influenza vaccination billing rates for patients seen by physiatrists with those of four other specialties: neurology, rheumatology, family practice, and internal medicine. DESIGN: Retrospective cohort analysis using Medicare billing data. PATIENTS: 234,164 Medicare outpatients seen in Washington state between September 1 and December 31, 1994. RESULTS: Based on Medicare's billing data, only 6 of 99 physiatrists ordered vaccinations, and they immunized only 159 (6%) of the patients seen. An additional 1,109 (42%) patients seen by physiatrists were vaccinated by other physicians. Physiatric patients were less likely to have been vaccinated than those seen by internists, family practitioners, or rheumatologists (p < .002), but equally likely as those seen by neurologists (p = .07). A significantly smaller percentage of physiatrists ordered vaccinations than all other specialties (p < .04). Utilizing pre-existing survey data, the misclassification rate (those immunized but not billed) was estimated at 22% of our original cohort. Thus, approximately 800 patients, one third of those seeing physiatrists, may not have been immunized. We estimated the increase in hospitalization costs to be $117 per nonvaccinated patient (total >$90,000). CONCLUSIONS: Missed opportunities for vaccination by physiatrists appear to be more frequent than in other specialties and have potentially large health and economic costs.

Adult↗

An immunogenic epitope of Chlamydia pneumoniae from a random phage display peptide library is reactive with both monoclonal antibody and patients sera.

Random 15-mer peptides displayed on filamentous phages were screened in binding studies using a Chlamydia pneumoniae-specific monoclonal antibody (RR-402) and affinity-purified, polyclonal sera from patients seropositive for C. pneumoniae infections by the microimmunofluorescence (MIF) test. One 15-mer epitope, epitope Cpnl5A (LASLCNPKPSDAPVT) was identified in both the monoclonal and polyclonal screenings, and showed higher ELISA reactivity with C. pneumoniae MIF-positive sera compared to patients with other chlamydial infections, non-chlamydial respiratory infections and normal healthy sera (MIF-negative). Interestingly, epitope Cpnl5A also showed significant (52%) amino acid sequence homology to the 56 kDa type-specific antigen of Rickettsia tsutsugamushi, a protein implicated in the virulence of this organism.

Amino Acid Sequence↗

Critical pathway for the emergency department management of acute asthma: effect on resource utilization.

STUDY OBJECTIVE: To determine the effect of a critical pathway on resource utilization in asthmatic patients. METHODS: The study combined a prospective analysis of 149 patients with asthma treated by a pathway protocol with a retrospective analysis of 97 patients with asthma treated by conventional means. The setting was a community hospital. RESULTS: Among patients treated by protocol, oxygen use declined by 19% (P = .001), handheld nebulizer treatments by 33% (P = .001), saline locks by 15% (P = .011), and intravenous steroid administration by 13% (P = .034). There was an increase in the use of metered-dose inhalers with spacer by 64% (P = .001) and oral steroids by 18% (P = .027). CONCLUSION: A critical pathway, based primarily on national guidelines, can be an effective means of treating asthma patients in terms of resource utilization.

Acute Disease↗

Acute thrombotic thrombocytopenic purpura presenting as expressive aphasia.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon and potentially fatal disease that is characterized by endothelial cell abnormalities, platelet dysfunction, microangiopathic hemolysis, fever, neurological abnormalities, and renal involvement. Before the introduction of plasmapharesis in the 1970s, TTP was fatal. This case report is presented to illustrate how subtly TTP can present, to discuss the updated criteria for TTP diagnosis, and to emphasize that with effective treatment now available, accurate and early diagnosis is essential to decrease morbidity and mortality.

Acute Disease↗

Sagittal sinus thrombosis after closed head injury.

Superior sagittal sinus thrombosis (SSST) is an unusual disorder, most often attributed to hematological abnormalities, oral contraceptive use, or association with the puerperium. Although SSST secondary to trauma has been reported, it still remains an extremely rare entity. Antemortem diagnosis of SSST is made by findings on computed tomographic scanning, cerebral angiography, or magnetic resonance imaging. Prognosis is variable and spontaneous resolution has been reported. Successful treatment options of spontaneous cases include systemic anticoagulation and thrombolytic therapy along with supportive measures. There are currently no guidelines for the management of SSST associated with traumatic brain injury. This report describes a case of SSST in a man who sustained a closed head injury.

Adult↗

Do patients receive adequate pain control after discharge from the ED?

Studies on the effectiveness of pain management have uniformly concluded that health care providers underestimate or undertreat pain. In the emergency department (ED) in which this study was conducted, physicians receive formal didactic and bedside teaching on pain recognition and management in order to heighten the awareness of patients' need for pain control. The purpose of this study was to determine if this outpatient pain management of patients with acute, painful conditions is better than that reported in the medical literature. In this prospective study, 110 adult patients who had an acute, painful diagnosis were telephoned 48 hours after discharge from the ED and asked if they felt their pain at home was well controlled. Patient satisfaction with pain control was higher (91%) than that reported in the medical literature. Also, pain medication was provided more frequently by this study's ED (95%). Education on pain awareness and treatment is a way to improve pain management.

Adult↗

Epidemiology of major trauma and trauma deaths in Los Angeles County.

BACKGROUND: Our objective was to study population-based trauma-related injuries and deaths in the county of Los Angeles and to identify trends and progress towards meeting the "Year 2000 National Health Objectives." STUDY DESIGN: We did a retrospective study for the year 1996. Data were obtained from the Trauma Registry of the Emergency Medical Services of the Department of Health Services, and the Coroner's Department of the County of Los Angeles. Traumatic injuries and deaths per 100,000 of the population were calculated according to mechanism, race, age, and gender. RESULTS: During 1996, there were 12,136 major trauma admissions in the 13 trauma centers in Los Angeles County. Another 1,929 victims died at the scene or were certified dead at nontrauma centers and were taken to the Coroner's Department (total 14,065 victims). The overall major injury rate was 151.0 per 100,000 population and the death rate was 30.9 per 100,000. The trauma death rate per 100,000 population was 56.4 for African-Americans, 33.5 for Hispanics, 26.3 for Caucasians, and 11.6 for Asians. Homicides were the leading cause of traumatic deaths (45.3%) followed by traffic accidents (31.9% of deaths). Firearms were responsible for 3,899 major injuries or deaths (41.7 per 100,000 population). The overall homicide rate per 100,000 population was 14.0, with a much higher rate for African-Americans (40.4 per 100,000) and Hispanics (18.7 per 100,000) than Caucasians (4.0 per 100,000) or Asians (3.4 per 100,000). African-American males were at very high risk for homicide (73.3 per 100,000), and in the age group 15 to 34 years, this problem reaches epidemic proportions (164.2 per 100,000). Traffic accidents accounted for 69.0 major injuries and 9.6 deaths per 100,000 people. Males were at significantly higher risk of dying in traffic accidents than females. People over 60 years of age were at significantly higher risk of traffic-accident death than younger people, for both passenger and pedestrian groups (p < 0.01). Firearm-related suicides were responsible for 4.6 deaths per 100,000 population. Caucasian males over 65 years were at much higher risk of suicide by penetrating trauma (29.5 per 100,000) than were Hispanics (6.3 per 100,000), Asians (5.4 per 100,000), or African-Americans (no deaths) in the same gender and age group. CONCLUSIONS: Trauma remains a major health problem in the county of Los Angeles. Despite the significant reduction of intentional trauma in 1996, it still exceeds national figures and is much higher than the targeted "Year 2000 National Health Objectives." Aggressive prevention strategies need to focus on the population groups at excessive risks of injury by assault, traffic accidents, and suicides.

Accidents, Traffic↗

Scission of DNA at a preselected sequence using a single-strand-specific chemical nuclease.

BACKGROUND: We were interested in developing a protocol for cleaving large DNAs specifically. Previous attempts to develop such methods have failed to work because of high levels of nonspecific background scission. RESULTS: R-loop formation was chosen for sequence-specific targeting, a method of hybridization whereby an RNA displaces a DNA strand of identical sequence in 70% formamide using Watson-Crick base-pairing, leading to a three-stranded structure. R-loops are stabilized in aqueous solution by modifying the bases with chemical reagents. The R-loop was cleaved using a novel nuclease prepared from the Thr48-->Cys mutant of the single-strand-specific M-13 gene V protein (GVP), which was alkylated with 5-(iodoacetamido-beta-alanyl)1,10-phenanthroline. The cleavage products of the pGEM plasmid were cloned in to the pCR 2.1-TOPO vector. Adenovirus 2 DNA (35.8 kb; tenfold larger than the pGEM plasmid) was also cleaved quantitatively at a preselected sequence. CONCLUSIONS: A new method for cleaving duplex DNA at any preselected sequence was developed. The cleavage method relies on the chemical conversion of M-13 GVP into a nuclease, reflecting GVP's specificity for single-stranded DNA. The GVP chimera is the first example of a semisynthetic secondary structure specific nuclease. The chemical nuclease activity of 1,10-phenanthroline-copper is uniquely suited to this technique because it oxidizes the deoxyribose moiety without generating diffusible intermediates, providing clonable DNA fragments. The protocol could be useful in generating large DNA fragments for mapping the contiguity of probes or defining the exon-intron structure of transcription units.

Adenoviridae↗

Enhanced in vitro and in vivo gene delivery using cationic agent complexed retrovirus vectors.

Retroviruses are, at present, the most efficient integrative vectors available for gene delivery. However, these viruses are still limited by relatively low titres. Although several protocols exist to improve virus titre most of them are time-consuming and unable to provide sufficient virus for in vivo applications. Virus titre can be enhanced by polybrene and other cationic agents. By investigating a broad range of cationic agents for their ability to enhance virus infectivity we found that both ecotropic and amphotropic retrovirus infection could be increased. In particular, the lipopolyamine dioctadecylamidoglycylspermine (DOGS) gave up to one order of magnitude enhancement above polybrene-mediated infection without cytotoxicity. To increase virus infectivity further we combined the enhancing effect of DOGS on virus infectivity with concentration of virus particles by ultrafiltration to reach titres of 1 x 10(9) IU/ml. The in vivo transduction of regenerating rat liver, by an amphotropic retrovirus was increased approximately five-fold by the addition of DOGS compared with virus alone. There was no animal toxicity observed following the administration of DOGS. The improved transduction efficiency seen both in vitro and in vivo following the co-administration of DOGS/virus complexes may be useful for future gene therapy applications.

3T3 Cells↗

Long-term magnesium sulfate tocolysis and maternal osteoporosis in a triplet pregnancy: a case report.

Prolonged infusion of magnesium sulfate has been used for the treatment of refractory preterm labor. Long-term magnesium sulfate tocolytic therapy either alone or in combination with other tocolytic agents has been reported to be safe and effective with minimal maternal side effects. There has been only one previous report of a disturbance in maternal calcium homeostasis, which included decreased distal radius bone density and hypercalciuria as a result of prolonged magnesium sulfate infusion. This article reports the first case of bilateral fracture of the calcanei in the postpartum period secondary to osteoporosis associated with prolonged magnesium sulfate tocolysis and bed rest. A 35-year-old white female with a triplet pregnancy of 25 weeks' gestation was admitted in preterm labor. Bed rest, intravenous magnesium sulfate tocolysis, and intermittent subcutaneous terbutaline were necessary to maintain uterine quiescence for 65 days. The patient received weekly betamethasone for 6 weeks for the acceleration of fetal lung maturation. Daily prenatal multivitamins and low-dose subcutaneous heparin for thromboprophylaxis were given. Efforts at tocolysis were ultimately not successful and the patient underwent a cesarean section delivery at 34 2/7 weeks' gestation. The patient's postoperative course was complicated by osteoporosis and bilateral stress fractures of the calcanei. This case report demonstrates that stress fractures secondary to osteoporosis may be associated with prolonged magnesium sulfate therapy and bed rest in higher order multiple pregnancy. Other possible contributing factors to osteoporosis include heparin thromboprophylaxis and suboptimal calcium supplementation. Therefore, in circumstances of prolonged bed rest and magnesium sulfate tocolysis, additional daily calcium supplementation would be well advised.

Adult↗

One hundred five penetrating cardiac injuries: a 2-year prospective evaluation.

OBJECTIVES: To analyze the parameters measured in the field, during transport, and upon arrival of the physiologic condition of patients sustaining penetrating cardiac injuries, along with the Cardiovascular Respiratory Score (CVRS) component of the Trauma Score, the mechanism and anatomical site of injury, operative characteristics, and cardiac rhythm as predictors of outcome. We also set out to identify a set of patient characteristics that best predict mortality outcome and to correlate cardiac injury grade as determined by the American Association for the Surgery of Trauma-Organ Injury Scale (AAST-OIS) with mortality. METHODS: This report was a prospective study at American College of Surgeons Level I urban trauma center. Interventions included thoracotomy, sternotomy, or both, for resuscitation and definitive repair of cardiac injury. The main outcome measures used were those parameters measuring physiologic condition of patients, CVRS, mechanism and anatomical site of injury, mortality, and grade of injury. RESULTS: A total of 105 patients sustained penetrating cardiac injuries: 68 injuries (65%) were gunshot wounds and 37 injuries (35%) were stab wounds. The mean Injury Severity Score was 36. Of the 105 wounds, 23 wounds (22%) involved multiple-chamber injuries. The overall survival was 35 of 105 patients (33%): survival of gunshot wound victims was 11 of 68 patients (16%); survival of stab wound victims was 24 of 37 patients (65%). Emergency department thoracotomy was performed in 71 of the 105 patients (68%) with 10 survivors (14%). CVRS: 94% mortality (50 of 53) when CVRS = 0, 89% mortality (57 of 64) when CVRS = 0 to 3, and 31% mortality (12 of 39) when CVRS 4 to 11 (p < 0.001). The presence of sinus rhythm when pericardium was opened predicted survival (p < 0.001). Anatomical site of injury (injured chamber) and the presence of tamponade did not predict survival. Stepwise logistic regression analysis identified gunshot wound, exsanguination, and restoration of blood pressure as most predictive variables of mortality. AAST-OIS injury grade and mortality: grade I, 0 of 1 (0%); grade II, 1 of 2 (50%); grade III, 2 of 3 (66%); grade IV, 28 of 50 (56%); grade V, 29 of 38 (76%); grade VI, 10 of 11 (91%). Overall incidence: grades IV-VI, 99 of 105 (94%). CONCLUSIONS: Parameters measuring physiologic condition, CVRS, and mechanism of injury are significant predictors of outcome in penetrating cardiac injuries. AAST-OIS injury grades I-III are rare in penetrating cardiac trauma. AAST-OIS Injury grades IV-VI are common in penetrating cardiac trauma and accurately predict outcome.

Blood Pressure↗

Parental perception of the adequacy of pain control in their child after discharge from the emergency department.

OBJECTIVE: To determine how well the pain of pediatric patients who are discharged from our emergency department (ED) is managed. DESIGN: Prospective, observational case series conducted from 9/21/96 to 3/16/97. SETTING: University tertiary care ED with an annual pediatric census of 11,000, consisting of a diverse racial and socioeconomic population. PATIENTS: Children ages < or = 15 years and discharged from the ED with one of the preselected acute, painful, conditions including fracture, corneal abrasion, ankle sprain with swelling, burn, otitis media with pain at discharge, or exudative pharyngitis. STUDY PROTOCOL: At time of discharge from the ED, data collectors not involved in the patients' care obtained consent from the patient's parent or guardian and completed data collection that included the final diagnosis and any recommended analgesic. Physicians were blinded to patient enrollment. Parents were phoned 48 hours after ED discharge and asked if they believed their child's pain was adequately controlled at home and if they had sought medical care elsewhere. Data were reported as percentages, and confidence intervals (CI) were calculated. RESULTS: From a convenience sample of 75 patients, five could not be contacted, leaving 70 for analysis. The mean age was 5.4+/-4.7 years. Sixty-seven parents (96%; 95% CI, 91-100%) believed their child's pain was well controlled, and 67 patients (96%; 95% CI, 91-100%) received an analgesic prescription. Five parents did not administer the prescribed analgesic because they believed their child's pain was controlled without it. No parent sought further medical care for pain medication for their child. CONCLUSIONS: Our pediatric pain management study showed high analgesic use and high parental satisfaction. Lectures and bedside education may be a way to improve pain management in pediatric patients.

Analgesia↗

Reversal of hypercholesterolemia in apolipoprotein E2 and apolipoprotein E3-Leiden transgenic mice by adenovirus-mediated gene transfer of the VLDL receptor.

We have investigated the interaction of apolipoprotein E2(Arg158-Cys) (apoE2) and apolipoprotein E3-Leiden (apoE3-Leiden) with the very low density lipoprotein (VLDL) receptor in vivo and in vitro to define the possible role of this receptor in lipoprotein metabolism and atherosclerosis. The in vivo binding specificity of the VLDL receptor for apoE2 and apoE3-Leiden was investigated by adenovirus-mediated gene transfer of the VLDL receptor in apoE2 and apoE3-Leiden transgenic mice lacking endogenous mouse apoE (Apoe-/-). Ectopic overexpression of the VLDL receptor gene in the liver resulted in a >50% decrease of plasma cholesterol levels in both apoE2 and apoE3-Leiden transgenic mice compared with liver expression of the beta-galactosidase gene. This reduction in plasma cholesterol was mainly due to a reduction in the VLDL level. Overexpression of the VLDL receptor did not affect the hepatic VLDL triglyceride production, indicating that the hypocholesterolemic effect is due to an increased level of plasma clearance mediated by the VLDL receptor. In vitro binding analysis showed that both apoE2 and apoE3-Leiden VLDL compete efficiently with rabbit beta-VLDL for binding to the VLDL receptor expressed on LDL receptor-deficient Chinese hamster ovary cells. We conclude from these data that both apoE2 and apoE3-Leiden function as proper ligands for the VLDL receptor in vitro and in vivo. This finding substantiates a possible role for the VLDL receptor in atherosclerosis in hyperlipidemic subjects homozygous for apoE2 or carrying apoE3-Leiden and indicates that the VLDL receptor expressed on the liver has therapeutic potential as an alternative route for clearance of binding-defective lipoproteins.

Adenoviridae↗