The impact of endovascular repair of ruptured abdominal aortic aneurysm on the gastrointestinal and renal function.

Introduction. Systemic effects of ruptured abdominal aortic aneurysm (rAAA) may be altered by the mode of surgery. This study aimed to determine systemic effects of endovascular aneurysm repair (EVAR) compared to open repair (OR). Patients and Methods. Consecutive patients with rAAA were repaired by OR or EVAR according to computerised tomographic (CT) findings. Renal function was monitored by estimated glomerular filtration rate (eGFR), serum urea and creatinine, and urinary albumin creatinine ratio (ACR). Hepatic function was assessed postoperatively for 5 days. Intestinal function was determined by the paracetamol absorption test. Intestinal permeability was assessed by urinary lactulose/mannitol ratio. Results. 30 rAAA patients were included. Fourteen had eEVAR and sixteen eOR. Serum urea were higher in eOR, while creatinine was similar between groups. Hepatic function showed no intergroup difference. Paracetamol absorption was increased in eEVAR group at day 3 compared to day 1 (P = 0.03), with no similar result in eOR (P = 0.24). Peak lactulose/mannitol ratio was higher in eOR (P = 0.03), with higher urinary L/M ratio in eOR at day 3 (P = 0.02). Clinical intestinal function returned quicker in eEVAR (P = 0.02). Conclusion. EVAR attenuated the organ dysfunction compared to open repair. However, a larger comparative trial would be required to validate this. The clinical trial is registered with reference number EUDRACT: 2013-003373-12.

The inflammatory response to ruptured abdominal aortic aneurysm is altered by endovascular repair.

Introduction. Ruptured abdominal aortic aneurysm (rAAA) causes a significant inflammatory response. The study aims to investigate this response following endovascular and open repair of ruptured AAA. Patients and Methods. Consecutive rAAA patients had either endovascular aneurysm repair (EVAR) or open repair (OR). Blood samples were taken for cytokines, lipid hydroperoxides (LOOH), antioxidants, and neutrophil elastase/ α 1-anti-trypsin complexes (NE/AAT) before surgery, 6 hours after clamp release and 1, 3, 5 days postoperatively. Results. 30 patients were included in the study, with 14 undergoing eEVAR and 16 eOR, with comparable baseline comorbidities, age, and parameters. IL-6 peaked higher in eOR patients (P = 0.04), while p75TNFr was similar between groups except at day 5 (P = 0.04). The NE/AAT concentrations were higher in eOR patients (P = 0.01), particularly in the first postoperative day, and correlated with blood (r = 0.398, P = 0.029) and platelet (r = 0.424, P = 0.020) volume transfused. C-reactive protein rose and lipid hydroperoxide fell in both groups without significant intergroup difference. Vitamins C and E, lycopene, and ß -carotene levels were similar between groups. Conclusion. EVAR is associated with lower systemic inflammatory response compared to OR. Its increased future use may thereby improve outcomes for patients.

Recurrent bilateral varicose veins secondary to tricuspid regurgitation.

BACKGROUND: Varicose veins are a common condition. We present a case of recurrent veins due to tricuspid regurgitation. CASE HISTORY: A 55-year-old female presented with large bilateral varicosities. On examination these were extensive and pulsatile in nature over both legs. Three and 5 years previously she presented with similar signs and had undergone bilateral venous surgery including Trendelenburg procedure. Past medical history included successful atrial septal defect repair in 1995. Severe tricuspid regurgitation and right heart failure was diagnosed in 2000, followed by annuloplasty 2 years later. Prior to attempting venous surgery the third time an echocardiogram was performed. This demonstrated severe tricuspid regurgitation again and therefore surgery was not undertaken at this time. DISCUSSION: Concurrent valvular disease should be fully investigated and optimised before consideration is given to surgery, with a multidisciplinary approach being essential in its management.

Successful delayed secondary open conversion after endovascular repair using partial explantation technique: a single-center experience.

BACKGROUND: Endovascular aneurysm repair (EVAR) reduces the morbidity and mortality associated with abdominal aortic aneurysm repair, but in some patients endoleak or aneurysm expansion may necessitate secondary open conversion (SOC). We reviewed the outcomes after delayed SOC following EVAR in consecutive patients at a single center. METHODS: We retrospectively reviewed all patients undergoing EVAR to identify a cohort undergoing delayed SOC in a single center between 1998 and 2008. We analyzed delayed SOC patients for operative indications, technique, and early outcomes. We made specific comment on the surgical techniques used, with respect to partial or total endograft explantation. RESULTS: Delayed SOC was carried out in 10/285 (3.5%) consecutive patients implanted with the Zenith endograft; during this period, two further patients had SOC after initial EVAR in another center. Graft types were Zenith (n = 10), Talent (n = 1), and AneuRx (n = 1). Indications for open conversion were infected graft (n = 3), sac expansion (n = 3), type 1 endoleak (n = 2), type 2 endoleak (n = 2), juxtarenal aneurysm (n = 1), and rupture (n = 1). Explantation techniques were partial explantation with in situ replacement (n = 7), full explantation with axillobifemoral bypass (n = 3), in situ replacement (n = 1), and suturing (n = 1)Complete stent explantation was required in 4 patients with axillo-bifemoral bypass in three of them. 7 patients had partial stent explantation and one patient stent was left insitu. Postoperative morbidities included myocardial infarction (n = 1), renal dialysis (n = 1), and chest infection (n = 3). No 30-day mortality was noted, and all patients were discharged from hospital and remain well with median follow-up of 5 months (interquartile range 1.7-26.7). CONCLUSION: SOC after EVAR is feasible in selected patients with low morbidity and mortality. Partial explantation with in situ replacement, in the absence of sepsis, may be the preferred revascularization option but may require long-term follow-up.

A prospective randomized single blind trial of Fleet phosphate enema versus glycerin suppositories as preparation for flexible sigmoidoscopy.

AIM: This study compared the efficacy and patient acceptability of two methods of bowel preparation for flexible sigmoidoscopy. METHODS: Patients attending for outpatient flexible sigmoidoscopy were prospectively randomized to receive one Fleet ready-to-use enema or 2 x 4 g glycerin suppositories, 2 h preprocedure. Patient and endoscopist questionnaires were used to compare the outcomes. RESULTS: From November 2000 to August 2001, 203 (male = 95; female = 108) patients were randomized. Patient data available for 163 patients (enema = 93; suppository = 70) revealed: ease of use (enema = 52; suppository = 25; P < 0.02, Fisher's exact); assistance required (enema = 19; suppository = 3; P < 0.005, Fisher's exact); grade of effectiveness (enema = 83; suppository = 44; P < 0.0001, Fisher's exact), and whether patients wished to try another preparation in future (enema = 16; suppository = 24; P = 0.016, Fisher's exact). Endoscopist data available for 151 patients (enema = 76; suppository = 75) revealed: average depth of insertion (enema = 53.6 +/- 11.6 cm; suppository 46.3 +/- 13.7 cm; P < 0.001, Student's t test); acceptable (excellent + good) quality of preparation [enema = 60 (78.9%); suppository = 34 (45.3%); P < 0.0001, Fisher's exact]. CONCLUSION: Bowel preparation for flexible sigmoidoscopy using a single Fleet enema is acceptable to patients and more effective than glycerin suppositories.

The effects of cilostazol on exercise-induced ischaemia-reperfusion injury in patients with peripheral arterial disease.

OBJECTIVES: Cilostazol improves walking distance in peripheral arterial disease (PAD) patients. The study objectives were to assess the effects of cilostazol on walking distance, followed by the additional assessment of cilostazol on exercise-induced ischaemia-reperfusion injury in such patients. METHODS: PAD patients were prospectively recruited to a double-blinded, placebo-controlled trial. Patients were randomised to receive either cilostazol 100mg or placebo twice a day. The primary end-point was an improvement in walking distance. Secondary end-points included the assessment of oxygen-derived free-radical generation, antioxidant consumption and other markers of the inflammatory cascade. Initial and absolute claudication distances (ICDs and ACDs, respectively) were measured on a treadmill. Inflammatory response was assessed before and 30 min post-exercise by measuring lipid hydroperoxide, ascorbate, alpha-tocopherol, beta-carotene, P-selectin, intracellular and vascular cell-adhesion molecules (I-CAM and V-CAM), thromboxane B(2) (TXB(2)), interleukin-6, interleukin-10, high-sensitive C-reactive protein (hsCRP), albumin-creatinine ratio (ACR) and urinary levels of p75TNF receptor. All tests were performed at baseline and 6 and 24 weeks. RESULTS: One hundred and six PAD patients (of whom 73 were males) were recruited and successfully randomised from December 2004 to January 2006. Patients who received cilostazol demonstrated a more significant improvement in the mean percentage change from baseline in ACD (77.2% vs. 26.6% at 6 weeks, p=0.026 and 161.7% vs. 79.0% at 24 weeks, p=0.048) as compared to the placebo. Cilostazol reduced lipid hydroperoxide levels compared to a placebo-related increase before and after exercise (6 weeks: pre-exercise: -11.8% vs. +5.8%, p=0.003 and post-exercise: -12.3% vs. +13.9%, p=0.007 and 24 weeks: pre-exercise -15.5% vs. +12.0%, p=0.025 and post-exercise: -9.2% vs. +1.9%, p=0.028). beta-Carotene levels were significantly increased in the cilostazol group, compared to placebo, before exercise at 6 and 24 weeks (6 weeks: 34.5% vs. -7.4%, p=0.028; 24 weeks: 34.3% vs. 17.7%, p=0.048). Cilostazol also significantly reduced P-selectin, I-CAM and V-CAM levels at 24 weeks as compared to baseline (p<0.05). There was no difference between treatment groups for ascorbate, alpha-tocopherol, interleukin-6 and -10, hsCRP and p75TNF receptor levels. CONCLUSIONS: Cilostazol significantly improves ACD, in addition to attenuating exercise-induced ischaemia-reperfusion injury, in PAD patients.

A prospective randomized single-blind comparison of three methods of bowel preparation for outpatient flexible sigmoidoscopy.

BACKGROUND: Preparation for outpatient flexible sigmoidoscopy using a self-administered phosphate enema is the standard practice in our unit, but it provides acceptable bowel preparation in only 80% of patients. This study compared two methods of bowel preparation with the current standard in an attempt to improve efficacy and acceptability. METHODS: From January to September 2003, patients scheduled for out-patient flexible sigmoidoscopy were prospectively randomized to 3 groups: group 1: one Fleet enema 2 h pre-procedure; group 2: two Fleet enemas, one on the evening prior to sigmoidoscopy and one 2 h pre-procedure; group 3: lactulose 30 ml orally 48 and 24 h prior to sigmoidoscopy, plus a single Fleet enema 2 h pre-procedure. A patient questionnaire was used to assess side effects and tolerance. The endoscopists questionnaire assessed the indication for the procedure, quality of preparation, depth of insertion, and pathological findings identified. Power calculations were based on the 80% acceptable preparation rate obtained using a single enema. RESULTS: For this study, 305 patients were randomized to the three groups. Patient data were available for 261 patients (group 1 = 105; group 2 = 81; group 3 = 75), and endoscopist data were available for 251 patients (group 1 = 97; group 2 = 79; group 3 = 75). No difference was noted between the groups with regard to age, gender, procedure indication, grade of endoscopist, or patient acceptability variables (ease of use: p = 0.09; assistance required: p = 0.11; cramps experienced: p = 0.84; alternative method: p = 0.25). There was no significant difference between the groups in terms of depth of insertion (p = 0.42-chi-squared test) or abnormalities noted (p = 0.34-chi-squared test). Nor was there any difference in the quality of preparation of patients in group 1 versus group 2 (p = 0.39-Fishers exact test) or group 1 versus group 3 (p = 0.13-Fishers exact). However, lactulose + Fleet resulted in significantly fewer patients with acceptable preparation compared with those who administered two Fleet enemas (p = 0.02- Fishers exact test). CONCLUSIONS: The addition of a Fleet enema or oral lactulose over and above a single Fleet enema gives no significant improvement in the acceptability or efficacy of bowel preparation.

Epstein-Barr virus expression in Hodgkin's lymphoma in Kuwait.

The epidemiology of Hodgkin's lymphoma (HL) shows wide geographic variation in histological subtypes and in its association with the Epstein-Barr virus (EBV). The proportion of EBV positive HL is low in industrialized countries, high in non-industrialized countries and intermediate in early-industrialized countries. Reports from the Persian Gulf and Middle East are very limited. The aim of this study was to determine the epidemiology of HL in Kuwait, an early-industrialized country in the Persian Gulf, and to delineate the extent of its association with EBV. We reviewed 134 cases of HL for histological classification and demographic data. 107 cases were examined for the presence of EBV using immunohistochemistry (IHC) for the latent membrane protein I (LMPI) and in-situ hybridization (ISH) for EBVencoded RNA (EBER). 70.4% of the patients were males and 29.6% were females. The male: female ratio was 2.4:1. The mean age was 30.6 years (range, 4-71 years). Mixed cellularity HL (MCHL) was the most common subtype (45.5%), followed by nodular sclerosis (37.3%), nodular lymphocyte predominant (6.7%), lymphocyte rich (3%) and lymphocyte depletion (3%). 4.5% of cases were unclassifiable. EBV expression was seen in 56%, was significantly higher in MCHL, in children, and in males. Our findings suggest that the frequency of EBV expression in HL in Kuwait is similar to other early-industrialized countries. Further research from other countries in the Persian Gulf and the Middle East should shed more light on the epidemiology of HL and its relation to EBV in this region.

Seminal vesicle masses detected incidentally during transrectal sonographic examination of the prostate.

PURPOSE: The aim of this study was to review the incidence and type of seminal vesicle (SV) masses discovered during transrectal sonography (TRUS) of the prostate. METHODS: Patients were a consecutive series of men referred for TRUS of the prostate because of lower urinary tract symptoms or elevated prostate-specific antigen levels, who were found on TRUS to have SV masses. Patients with prostate cancer involving the SVs were excluded. Cystic lesions were sampled by fine-needle aspiration and solid lesions by core biopsy, all under sonographic guidance. RESULTS: Of the 450 patients who underwent TRUS between January 1997 and December 2001, 10 (2%) were found to have SV masses; 5 masses were cystic and 5 were solid. Cytologic evaluation of aspirated specimens revealed benign findings in all 5 cysts. Four of the 5 patients with solid SV masses had chronic schistosomiasis, and the mass in the fifth patient was a metastatic deposit from a renal cell carcinoma. CONCLUSIONS: SV masses may be responsible for lower urinary tract symptoms in a small fraction of cases. A cystic mass is presumptively benign, whereas a solid lesion has a small probability of being malignant, especially if the patient has a primary neoplasm elsewhere. Schistosomiasis should always be considered when making a differential diagnosis in patients who live in areas where infestation is endemic.

Expression of E-cadherin in human colorectal cancer.

AIM: To investigate the expression of E-cadherin, a calcium-dependent cell-cell adhesion molecule in colorectal carcinoma. Antibodies to E-Cadherin were used to establish the association of their expression with the clinicopathological characteristics of this disease using immunohistochemical methods. METHODS: Immunohistochemical analysis for E-cadherin was carried out in formalin-fixed, paraffin-embedded sections of neoplastic colorectal tissues and non-neoplastic ones adjacent to the lesion from 49 patients who underwent surgery, by the standard peroxidase-antiperoxidase method. Expression of this antigen in normal and malignant epithelium and stromal cells was compared. RESULTS: Both neoplastic and normal tissues showed expression of E-cadherin. There was, however, higher expression of E-cadherin in epithelial cells in both tumour and normal tissues than stromal cells. The percentage of expression in epithelial cells of well-differentiated tumours was significantly higher than moderately differentiated tumours. Loss of normal membranous expression and the presence of cytoplasmic and mixed staining were found frequently in tumour tissues (p = 0.004). This loss of membranous expression, however, did not correlate with Duke's staging, tumour grade, sex, size or site of the tumour. CONCLUSION: This study suggests that the lower expression of E-cadherin in less differentiated tumours may explain their aggressive nature, although loss of membranous expression was not significantly correlated to Duke's staging, tumour grade, sex, size and site of tumour.

Leiomyosarcoma complicating chronic inflammation of the testis.

OBJECTIVE: To report on a case of leiomyosarcoma of the testis that appeared to have arisen from a background of chronic testicular inflammation. CLINICAL PRESENTATION: A 65-year-old man with a 15-year history of diabetes mellitus and low-grade discomfort and swelling in the right testis presented as an emergency with exacerbation of the pain and swelling of the testis. Repeated ultrasound examination of the testis in the past 5 years had suggested a chronic testicular inflammatory disorder. Ultrasound during the current emergency case admission revealed a normal left testis, but a large heterogeneous solid mass with a moderate intratesticular calcification in the right testis and the presence of a moderate hydrocele. Serum alpha-fetoprotein and beta-human chorionic gonadotropin were normal. A right radical orchidectomy was performed. Histopathology and immunohistochemistry revealed primary leiomyosarcoma of the right testis. There was no spermatic cord or venous involvement. One year after orchidectomy there was no sign of metastasis. CONCLUSION: Radical orchidectomy followed by surveillance appears to be the treatment of choice for this testicular leiomyosarcoma, which seemed to have run an indolent course compared to other testicular tumours.

Gastrointestinal stromal tumors: clinicopathological and immunohistochemical features.

OBJECTIVES: To study the clinicopathological and immunohistochemical features of gastrointestinal stromal tumors (GISTs) in Kuwait. MATERIALS AND METHODS: Hematoxylin- and eosin-stained sections of primary gastrointestinal mesenchymal tumors were reviewed. Immunohistochemical staining was performed using a panel of antibodies to determine muscle and neural differentiation, the incidence of CD117 and CD34 expression, as well as bcl-2 and cytokeratin expression. Each stain was interpreted as negative or positive. The staining intensity of positive cases was graded as weak, moderate or strong. RESULTS: The age range was 25-80 with an average age of 54 and a male:female ratio of 3:2. The stomach was the most common site for these tumors, followed by the small intestine. Histologically, 46% were classified as malignant and 54% were benign. Most of the malignant tumors occurred in males, particularly in the stomach or small intestine. There was no significant difference in patient age between malignant and benign tumors. The most sensitive markers were muscle-specific actin for muscle differentiation and glial fibrillary acidic protein for neural differentiation. CD117 expression was seen in 81% and CD34 in 54% of all tumors. CONCLUSIONS: The results of this study show that the stomach is the most common site for these tumors, that malignant tumors are more likely to occur in the small intestine than in the stomach, and that there is no difference between benign and malignant tumors with regard to age. Our findings are comparable to those of other workers, although our male:female ratio was slightly higher.

Expression of CD44s in human colorectal cancer.

CD44s is a cell adhesion molecule, which belongs to the family of hyaluronan binding proteins. Anti-body to CD44s is used to establish the association of its expression with the clinicopathological characteristics of colorectal cancer using immunohistochemical methods. The aim of this study is to investigate the expression of the standard form of CD44 (CD44s) in colorectal cancer tissues as compared to adjacent normal colonic tissues. Furthermore, the level of expression of CD44s in colorectal cancer tissues was correlated with the degree of histological differentiation, Duke s classification, sex, size and site of the tumor. Immunohistochemical analysis for CD44s was carried out in 49 paraffin-fixed sections of neoplastic colorectal tissues and non-neoplastic ones adjacent to the lesion, by the standard peroxidase-antiperoxidase method. Expression of these antigens were compared in normal and malignant epithelium and stromal cells. The results show that the level of CD44s in the epithelial and stromal cells was significantly higher in the colorectal cancer tissues than the normal ones. However, there was no association between the percentages of expressions of CD44s and the degree of histological differentiation, Duke s classification, sex or size of the tumor. There was however, a significantly higher expression of CD44s in the epithelium of rectal cancer than that of colonic cancer. This study indicates that the expression of CD44s is significantly higher in colorectal cancer tissues. However, further studies are required to understand its role in tumor progression and metastasis of this disease.

Basidiobolus ranarum as an etiologic agent of gastrointestinal zygomycosis.

Basidiobolus ranarum is a known cause of subcutaneous zygomycosis. Recently, its etiologic role in gastrointestinal infections has been increasingly recognized. While the clinical presentation of the subcutaneous disease is quite characteristic and the disease is easy to diagnose, gastrointestinal basidiobolomycosis poses diagnostic difficulties; its clinical presentation is nonspecific, there are no identifiable risk factors, and all age groups are susceptible. The case of gastrointestinal basidiobolomycosis described in the present report occurred in a 41-year-old Indian male who had a history of repair of a left inguinal hernia 2 years earlier and who is native to the southern part of India, where the subcutaneous form of the disease is indigenous. Diagnosis is based on the isolation of B. ranarum from cultures of urine and demonstration of broad, sparsely septate hyphal elements in histopathologic sections of the colon, with characteristic eosinophilic infiltration and the Splendore-Hoeppli phenomenon. The titers of both immunoglobulin G (IgG) and IgM antibodies to locally produced antigen of the fungus were elevated. The patient failed to respond to 8 weeks of amphotericin B therapy, and the isolate was later found to be resistant to amphotericin B, itraconazole, fluconazole, and flucytosine but susceptible to ketoconazole and miconazole. One other noteworthy feature of the fungus was that the patient's serum showed raised levels of Th2-type cytokines (interleukins 4 and 10) and tumor necrosis factor alpha. The present report underscores the need to consider gastrointestinal basidiobolomycosis in the differential diagnosis of inflammatory bowel diseases and suggests that, perhaps, more time should be invested in developing standardized serologic reagents that can be used as part of a less invasive means of diagnosis of the disease.

Multiple mechanisms, independent of sterol regulatory element binding proteins, regulate low density lipoprotein gene transcription.

Transcription of the LDL receptor gene is markedly enhanced in the Jurkat T cell line by stimulation with the combination of the phorbol ester phorbol 12-myristate 13-acetate (PMA) and the protein synthesis inhibitor cycloheximide (CHX). The DNA sequences necessary for this response were identified by analysis of Jurkat T cells permanently transfected with reporter gene expression vectors containing fragments of the LDL receptor promoter extending from 68 bp to 1472 bp 5' of the major transcription start site. The magnitude of the response of this array of promoter fragments to stimulation with PMA and CHX was similar to that previously observed with a approximately 6.5 kb promoter fragment. However, the various promoter fragments differed with regard to the role of the sterol regulatory element-1 (SRE-1) sequence. Thus, whereas a 142 bp promoter mediated transcription stimulated by PMA and CHX independently of SRE-1, a shorter 115 bp promoter was absolutely dependent on SRE-1. Furthermore, internal deletion of promoter sequences from -142 bp to -113 bp from longer promoter constructs in which the SRE-1 was mutated prevented the induction of transcription by PMA and CHX. Electrophoretic mobility shift assays (EMSAs) demonstrated sequence-specific, stimulus-independent binding by Jurkat nuclear proteins to the novel response element mapped between -142 and -115. Even though the minimal 115 bp or 68 bp promoter fragment required an intact SRE-1 to respond to PMA and CHX, transcriptional induction persisted when nuclear levels of sterol regulatory element binding proteins (SREBPs) were made undetectable by culture in suppressive sterols. Taken together, these data indicate that non-sterol stimuli such as the combination of PMA and CHX induce LDL receptor gene transcription through at least two distinct promoter elements, neither of which requires the presence of SREBPs. However, the element proximal to the transcription start site is dependent on the SRE-1.

Sterol-independent, sterol response element-dependent, regulation of low density lipoprotein receptor gene expression.

Stimulation with phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore ionomycin increased native low density lipoprotein (LDL) receptor gene expression in the human leukemic T cell line Jurkat when cells were cultured in the absence of sterols and also increased nuclear accumulation of sterol regulatory element binding protein (SREBP)-1. PMA and ionomycin likewise increased LDL receptor mRNA levels when cells were cultured in the presence of suppressive concentrations of sterols, when neither SREBP-1 nor SREBP-2 was detectable in the nucleus. These findings indicated that mitogen-induced up-regulation of the LDL receptor gene could be independent of sterol-regulated transcription factors. The involvement of sterol regulatory element (SRE)-1 was analyzed by transfection of LDL receptor promoter constructs. Promoter fragments of either the 5' 1472 or 142 base pairs induced reporter gene expression after mitogenic stimulation when cells were cultured in the absence or presence of sterols. Mutation of the SRE-1 sequence in either construct abolished sterol-mediated regulation of transcription. However, mutation of the SRE-1 sequence in the 1472 base pair promoter fragment did not alter mitogenic induction of transcription, whereas mutation of SRE-1 in the 142 base pair promoter fragment completely prevented up-regulation of transcription. Taken together, these results demonstrate that the LDL receptor promoter contains at least one 5' SRE-independent as well as an SRE-dependent response element. Furthermore, the data suggest that the SRE-dependent response may not involve the action of either SREBP-1 or -2. Thus, mitogen-induced transcription of the LDL receptor promoter is regulated by diverse sterol-independent mechanisms.