Biomedical subjects

C W Ko

Publications and source records attributed to C W Ko.

At least 19 recordsLinked to original sources

PubMed2001

Light-emitting carbazole derivatives: potential electroluminescent materials.

Stable carbazole derivatives that contain peripheral diarylamines at the 3- and 6-positions and an ethyl or aryl substituent at the 9-position of the carbazole moiety have been synthesized via palladium-catalyzed C-N bond formation. These new carbazole compounds (carbs) are amorphous with high glass transition temperatures (T(g), 120-194 degrees C) and high thermal decomposition temperatures (T(d) > 450 degrees C). The compounds are weakly to moderately luminescent in nature. The emission wavelength ranges from green to blue and is dependent on the substituent at the peripheral nitrogen atoms. Two types of light-emitting diodes were constructed from carb: (I) ITO/carb/TPBI/Mg:Ag and (II) ITO/carb/Alq(3)/Mg:Ag, where TPBI and Alq(3) are 1,3,5-tris(N-phenylbenzimidazol-2-yl)benzene and tris(8-hydroxyquinoline) aluminum, respectively. In type I devices, the carb functions as the hole-transporting as well as emitting material. In type II devices, either carb, or Alq(3) is the light-emitting material. Several green light-emitting devices exhibit exceptional maximum brightness, and the physical performance appears to be better than those of typical green light-emitting devices of the structure ITO/diamine/Alq(3)/Mg:Ag. The relation between the LUMO of the carb and the performance of the light-emitting diode is discussed.

Journal Article↗

PubMed2001

Hospitalizations for fractures after renal transplantation in the United States.

PURPOSE: To investigate the incidence, risk factors, and associated mortality of fractures in renal transplant recipients. METHODS: Retrospective registry study of 33,479 patients in the United States Renal Data System (USRDS) who received kidney transplants between 1 July 1994 and 30 June 1997. Associations with hospitalizations for a primary discharge diagnosis of fractures (all causes) were assessed. RESULTS: Renal transplant recipients had an adjusted incidence ratio for fractures of 4.59 (95% confidence interval 3.29 to 6.31). In multivariate analysis, recipients with prevalent fractures, as well as recipients who were Caucasian, women, in the lower quartiles of recipient weight (<95.9 kg), had end stage renal disease caused by diabetes, and had prolonged pretransplant dialysis were at increased risk for hospitalization because of fractures after transplantation. Recipients hospitalized for hip fractures had decreased all-cause survival (hazard ratio for mortality 1.60, 95% CI 1.13 to 2.26) in Cox Regression analysis. CONCLUSIONS: In the early post-transplant course (<3 years), renal transplant recipients had a greater incidence of fractures than the general population, which were associated with decreased patient survival. Preventive efforts should focus on recipients with the risk factors identified in this analysis, most of which can be easily obtained through history and physical examination.

Female↗

PubMed2001

Graft loss due to recurrent focal segmental glomerulosclerosis in renal transplant recipients in the United States.

Rates of and risk factors for graft loss and graft loss resulting from recurrent focal segmental glomerulosclerosis (FSGS) have not been studied in a national population. A retrospective analysis was performed on a national registry (1999 United States Renal Data System) of 101,808 renal transplant recipients (October 1, 1987, to December 31, 1996). Of these, 3,861 recipients of solitary renal transplants who had end-stage renal disease resulting from FSGS met inclusion criteria. Outcomes were graft loss and graft loss resulting from recurrent FSGS. As a percentage of all graft loss, recurrent FSGS accounted for 18.7% in living donor recipients and 7.8% in cadaveric recipients. In white recipients, the corresponding figures were 27% and 13%. In multivariate analysis, factors associated with graft loss resulting from recurrent FSGS were white recipient, donor African-American kidney in white recipient, younger recipient age, and treatment for rejection. African-American recipients had higher rates of graft loss overall. A living donor was associated with superior overall graft survival. Among renal transplant recipients with FSGS, white recipients had a higher risk of graft loss resulting from recurrent FSGS, disproportionately seen in recipients of African-American kidneys. The role of donor/recipient race pairing on graft loss resulting from recurrent FSGS should be validated. Living donor had no association with graft loss from recurrent FSGS after correction for other factors. African-American recipients with FSGS may have the most to gain from a living donor, given their improved graft survival and decreased risk of graft loss resulting from recurrent FSGS. This is a US government work. There are no restrictions on its use.

Analysis of Variance↗

PubMed2001

The correlation of depression and gastric dysrhythmia in functional dyspepsia.

Psychologic factors in functional dyspepsia have been discussed in many previous articles. However, the relationship between depression and functional dyspepsia is still obscure. We investigated the impact of depression on clinical symptoms and gastric dysrhythmia in functional dyspepsia. Thirty-nine patients with functional dyspepsia and 18 healthy subjects were included. Patients were investigated with clinical symptoms assessment, Zung's self-rating depression scale, and electrogastrography. Patients with functional dyspepsia were divided into two groups: 21 patients with depression and 18 patients without depression. The depressed patients had similar total gastrointestinal symptom severity scores compared with the nondepressed patients, but with higher total symptom frequency scores (p < 0.05). With regards to symptoms, the depressed patients had higher abdominal fullness severity and frequency scores and nausea frequency scores. The patients with functional dyspepsia had a lower percentage of normal slow wave in both the fasting and fed states and a higher percentage of bradygastria in the fasting state and tachygastria in the postprandial state (p < 0.05). There was no significant difference in the percentage of bradygastria or tachygastria between the depressed and nondepressed patients. There was no correlation between the specific type of electrogastrographic abnormality and the presence or absence of depression in functional dyspepsia patients.

Adult↗

PubMed2001

Severe gastrointestinal bleeding after hematopoietic cell transplantation, 1987-1997: incidence, causes, and outcome.

OBJECTIVE: Severe GI bleeding after hematopoietic cell transplantation is commonly due to lesions that are unusual in nontransplant patients. The frequency of GI bleeding appears to have decreased over the last decade, but the reasons have not been readily apparent. We sought to determine the incidence of severe bleeding during two time periods, to describe the causes and outcomes of bleeding, and to analyze the reasons behind an apparent decline in severe bleeding over the decade covered. METHODS: During 1986-1987 and 1996-1997, we followed all patients with and without severe bleeding at our institution, a marrow transplant center. RESULTS: Over this decade, the incidence of severe bleeding declined from 50/467 (10.7%) to 15/635 (2.4%) (p < 0.0001). Overall mortality from intestinal bleeding declined from 3.6% to 0.9% (p = 0.002), but mortality in those with bleeding remained high (34% vs 40%). The onset (day 42 vs 47) and platelet counts (35,994 vs 37,600/microl) were similar, but the sites and causes of bleeding were different. During 1986-1987, 27/50 patients bled from multiple GI sites, viral and fungal ulcers, or graft-versus-host disease (GVHD). Over the decade, bleeding from GVHD had decreased 80% (p < 0.0001), and bleeding from viral (p < 0.0001) and fungal (p = 0.023) ulcers almost disappeared. CONCLUSIONS: The incidence of severe GI bleeding has declined significantly over the last decade because of prevention of viral and fungal infections and severe acute GVHD. However, severe bleeding after transplant remains a highly morbid event, particularly among patients with GVHD.

Adult↗

PubMed2000

Factors associated with caregivers' choice of infant sleep position, 1994-1998: the National Infant Sleep Position Study.

CONTEXT: The success and simplicity of the 1994 national "Back to Sleep" campaign to reduce sudden infant death syndrome provides an opportunity to study which elements determine whether a behavior will change in the desired direction in response to a public health intervention. OBJECTIVE: To examine sociodemographic characteristics, motivation, and message exposure to ascertain which factors influenced a caregiver's choice of infant sleep position after implementation of the campaign. DESIGN: Annual nationally representative telephone surveys conducted between 1994 and 1998. SETTING: The 48 contiguous United States. PARTICIPANTS: Nighttime caregivers of infants born within the 7 months prior to interview between 1994 and 1998. Approximately 1000 interviews were conducted each year. MAIN OUTCOME MEASURES: The position the infant was usually placed in for sleep, sleep position recommendations received from specific sources, and reasons reported for position choice. RESULTS: Between 1994 and 1998, prone placement declined from 44% to 17% among white infants and from 53% to 32% among black infants. Supine placement increased from 27% to 58% among white infants and from 17% to 31% among black infants. During this period, reports of supine recommendations from at least 1 source doubled from 38% to 79%. From 1995 to 1998, 86% of caregivers who placed the infant prone reported receiving only nonprone recommendations. Infant comfort was given as a reason for prone placement by 82% of these caregivers. In multivariate analysis, physician recommendation of "supine not prone" had the strongest influence and was associated with decreased prone placement (odds ratio [OR], 0.25 [95% confidence interval [CI], 0.16-0.39]) and increased supine placement (OR, 3.37 [95% CI, 2.38-4.76]). Recommendations from all 4 sources (the physician, neonatal nurse, reading materials, and radio/television) further increased the probability of supine placement (OR, 6.01 [95% CI, 4.57-7.90]). Other factors independently associated with increased prone and decreased supine placement included maternal black race, parity of more than 1, and living in a southern or mid-Atlantic state. CONCLUSIONS: According to our study, as of 1998, approximately one fifth of infants were still placed prone, and only half were placed supine. Recommendations of supine placement during infancy by physicians at well-baby checks and by neonatal nursery staff and print and broadcast media have increased the proportion of infants placed supine. Caregiver beliefs regarding perceived advantages of prone sleeping should be addressed to attain further reduction in prone placement.

Choice Behavior↗

PubMed2000

Apolipoprotein E genotype and the risk of gallbladder disease in pregnancy.

The E4 allele of apolipoprotein E (apoE4) has previously been associated with symptomatic gallstone disease. The aim of this study was to determine if apoE4 is associated with the development of gallbladder sludge and/or stones during pregnancy. We conducted a nested case-control study based on an ongoing cohort study of gallbladder disease in pregnancy. Women in this study receive gallbladder ultrasounds in each trimester of pregnancy. Cases (n = 52) were defined as women with incident gallbladder sludge or stones diagnosed at the third trimester ultrasound. Controls (n = 104) were defined as women without gallbladder sludge or stones on any of 3 study ultrasounds. ApoE genotyping was performed from stored white blood cell pellets. Data were analyzed by stratified analysis and multivariate logistic regression. Cases and controls were similar in baseline characteristics. Forty-two women had sludge, 6 had gallstones, and 4 had both sludge and stones. After adjusting for risk factors such as age, parity, and body mass index, the odds ratio (OR) for the association between heterozygosity or homozygosity for the apoE4 allele and incident gallbladder sludge or stones was 0.91 (95% confidence interval [CI], 0.41-2.02). Further adjustment for family medical history and serum lipid levels did not substantially change these results (OR, 0.73; 95% CI, 0.29-1.82). In conclusion, apoE4 appears to have little or no overall association with the development of new gallbladder sludge or stones in pregnancy. However, an effect could not be ruled out in certain subgroups, such as blacks or women who are homozygous for apoE4.

Apolipoprotein E4↗

PubMed2000

Telomere length and telomerase catalytic subunit expression in non-astrocytic gliomas.

Telomerase activation has been implicated as a major factor in the development of cancer. In our previous study we reported on the telomerase activity of a variety of gliomas. To further investigate the role of telomere and telomerase regulation in the pathogenesis of non-astrocytic gliomas, we examined the telomere length and the mRNA expression of telomerase reverse transcriptase gene (hTERT) and telomerase-associated protein (hTEP) in a series of 27 oligodendroglial and 18 ependymal tumors in this study. No statistical difference was found between the mean telomere length in telomerase-positive and telomerase-negative tumors (11.5 kb vs 13.1 kb; p = 0.424), although a slightly shorter length was observed in telomerase-positive oligodendroglial tumors. mRNA expression of hTERT was highly correlated with the telomerase activity status. hTERT was expressed in 8/8 (100%) and 2/2 (100%) telomerase-positive oligodendroglial and ependymal tumors, respectively, whereas 3/6 (50%) telomerase-negative oligodendroglial tumors and no telomerase-negative ependymal tumors showed expression. In contrast, hTEP1 mRNA was widely expressed in both telomerase-positive and telomerase-negative oligodendroglial and ependymal tumors. Our data support the notion that hTERT plays a critical role in determining the enzymatic activity of human telomerase. It has recently been proposed that both p16(INK4)/Rb pathway inactivation and telomerase activity were required for immortalization of epithelial cells. Although lack of p(16INK4a) expression was detected in a substantial proportion of tumors, no correlation between the p16(INK4a) or pRb protein expression and telomerase activity was observed in our series of non-astrocytic tumors.

Adolescent↗

PubMed2000

Automatic spike detection via an artificial neural network using raw EEG data: effects of data preparation and implications in the limitations of online recognition.

OBJECTIVE: Automatic detection of epileptic EEG spikes via an artificial neural network has been reported to be feasible using raw EEG data as input. This study re-investigated its suitability by further exploring the effects of data preparation on classification performance testing. METHODS: Six hundred EEG files (300 spikes and 300 non-spikes) taken from 20 patients were included in this study. Raw EEG data were sent to the neural network using the architecture reported to give best performance (30 input-layer and 6 hidden-layer neurons). RESULTS: Significantly larger weighting of the 10th input-layer neuron was found after training with prepared raw EEG data. The classification process was thus dominated by the peak location. Subsequent analysis showed that online spike detection with an erroneously trained network yielded an area less than 0.5 under the receiver-operating-characteristic curve, and hence performed inferiorly to random assignments. Networks trained and tested using the same unprepared EEG data achieved no better than about 87% true classification rate at equal sensitivity and specificity. CONCLUSIONS: The high true classification rate reported previously is believed to be an artifact arising from erroneous data preparation and off-line validation. Spike detection using raw EEG data as input is unlikely to be feasible under current computer technology.

Brain↗

PubMed2000

Nasogastric lansoprazole is effective in suppressing gastric acid secretion in critically ill patients.

AIM: To evaluate the effect of nasogastric lansoprazole on acid suppression in critically ill patients. METHODS: Patients were eligible for the study if they had a nasogastric tube in place and had not received acid-suppressive agents for 3 days prior to enrolment into the study. Patients with active gastrointestinal bleeding or a baseline gastric pH > 4.0 were excluded. Patients served as their own controls during a 24 h lead-in period. Lansoprazole 30 mg was administered once daily with water through a nasogastric tube for 2 days. Intragastric pH was measured by continuous 24 h pH-metry for 3 days. RESULTS: Fifteen patients were enrolled into the study. The baseline median 24 h intragastric pH was 2.25 +/- 1.01, and increased to 6.70 +/- 0.82 (P= 0.001) after 2 days of lansoprazole. Mean percentage of time intragastric pH was > or = 4.0 was 25 +/- 13% at baseline, and increased to 84 +/- 14% (P=0. 001) after 2 days of lansoprazole. CONCLUSIONS: Nasogastric lansoprazole 30 mg daily is effective in suppressing gastric acid secretion in critically ill patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2000

Cost-effectiveness of strategies for primary prevention of nonsteroidal anti-inflammatory drug-induced peptic ulcer disease.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of peptic ulcer disease by 5- to 7-fold in the first 3 months of treatment. This study examined the relative cost-effectiveness of different strategies for the primary prevention of NSAID-induced ulcers in patients that are starting NSAID treatment. MEASUREMENTS AND MAIN RESULTS: A decision analysis model was developed to compare the cost-effectiveness of 6 prophylactic strategies relative to no prophylaxis for patients 65 years of age starting a 3-month course of NSAIDs: (1) testing for Helicobacter pylori infection and treating those with positive tests; (2) empiric treatment of all patients for Helicobacter pylori; (3) conventional-dose histamine2 receptor antagonists; (4) high-dose histamine2 receptor antagonists; (5) misoprostol; and (6) omeprazole. Costs were estimated from 1997 Medicare reimbursement schedules and the Drug Topics Red Book. Empiric treatment of Helicobacter pylori with bismuth, metronidazole, and tetracycline was cost-saving in the baseline analysis. Selective treatment of Helicobacter pylori, misoprostol, omeprazole, and conventional-dose or high-dose histamine2 receptor antagonists cost $23,800, $46,100, $34,400, and $15,600 or $21,500 per year of life saved, respectively, relative to prophylaxis. The results were sensitive to the probability of an ulcer, the probability and mortality of ulcer complications, and the cost of, efficacy of, and compliance with prophylaxis. The cost-effectiveness estimates did not change substantially when costs associated with antibiotic resistance of Helicobacter pylori were incorporated. CONCLUSIONS: Several strategies for primary prevention of NSAID-induced ulcers in patients starting NSAIDs were estimated to have acceptable cost-effectiveness relative to prophylaxis. Empirically treating all patients for Helicobacter pylori with bismuth, metronidazole, and tetracycline was projected to be cost-saving in older patients.

Adult↗

PubMed1999

Nasopharyngeal carcinoma cell line (C666-1) consistently harbouring Epstein-Barr virus.

We have established a cell line (C666-1) from undifferentiated nasopharyngeal carcinoma (NPC). This cell line consistently carries the Epstein-Barr virus (EBV) in long-term cultures. C666-1 is a subclone of its parental cell line, C666, derived from an NPC xenograft of southern Chinese origin. It grows as an adherent culture and lacks contact inhibition. In addition, it is tumorigenic in athymic nude mice. The cells consistently express EBV-encoded RNAs and are positively stained for cytokeratin, an epithelial marker. In addition, they express EBNA1 protein, LMP1 and LMP2 transcripts and thus resemble the EBV latency II pattern. The virus genotype is EBV-1 with the latent membrane protein 1 gene showing a 30-bp deletion at the carboxyl terminus, both consistent with findings in southern Chinese NPC tumours. Cytogenetic analysis revealed a sub-diploid status with a chromosomal modal number of 45. C666-1 is unique among NPC cell lines in that it carries EBV. These cells may serve as a good investigative tool as the viral latency pattern and genotype are observed in the majority of primary NPC biopsies from Chinese patients.

Animals↗

PubMed1999

Biliary sludge.

Biliary sludge was first described with the advent of ultrasonography in the 1970s. It is defined as a mixture of particulate matter and bile that occurs when solutes in bile precipitate. Its composition varies, but cholesterol monohydrate crystals, calcium bilirubinate, and other calcium salts are the most common components. The clinical course of biliary sludge varies, and complete resolution, a waxing and waning course, and progression to gallstones are all possible outcomes. Biliary sludge may cause complications, including biliary colic, acute pancreatitis, and acute cholecystitis. Clinical conditions and events associated with the formation of biliary sludge include rapid weight loss, pregnancy, ceftriaxone therapy, octreotide therapy, and bone marrow or solid organ transplantation. Sludge may be diagnosed on ultrasonography or bile microscopy, and the optimal diagnostic method depends on the clinical setting. This paper proposes a protocol for the microscopic diagnosis of sludge. There are no proven methods for the prevention of sludge formation, even in high-risk patients, and patients should not be routinely monitored for the development of sludge. Asymptomatic patients with sludge can be managed expectantly. If patients with sludge develop symptoms or complications, cholecystectomy should be considered as the definitive therapy. Further studies of the pathogenesis, natural history, and clinical associations of biliary sludge will be essential to our understanding of gallstones and other biliary tract abnormalities.

Acute Disease↗

PubMed1999

Detection of chromosomal imbalances in growth hormone-secreting pituitary tumors by comparative genomic hybridization.

Although recent molecular investigations have identified a number of genetic alterations that are associated with the development of pituitary adenomas, the exact pathogenesis mechanism of these tumors remains largely unknown. In this study, we used a genome-wide survey to detect specific genetic changes within the genome of pituitary adenomas. A series of 10 growth hormone-secreting adenomas were analyzed for their genetic imbalances on all 22 autosomes by comparative genomic hybridization (CGH). Chromosomal imbalances were detected in 8 GH-secreting adenomas, whereas 2 tumors had no detectable genetic abnormalities. Chromosome gains were more frequent than losses. Overrepresentation of whole or parts of chromosomes were detected in 5/10 (50%) in 19, 3/10 (30%) in each of 5, 9, and 22q, 2/10 (20%) in 17p12-q21, whereas DNA loss were 3/10 (30%) in 13q and 2/10 (20%) in 18. No detectable gain or loss of genetic material was observed in chromosomes 7, 8, 10, 12, 15, and 20. The findings of overrepresentation of chromosomes 5q, 9p, 17q and DNA loss of chromosome 18 were consistent with those detected in nonfunctioning adenomas (Daniely M, Aviram A, Adams EF, et al:J Clin Endocrinol Metab 83:1801-1805, 1998) suggesting that the development of pituitary tumors, at least in somatotroph and nonfunctioning adenomas, may share common pathway. Frequent amplifications in chromosomes 19 and 22q imply that candidate genes residing in these chromosomal regions may be involved in the pathogenesis of GH-secreting adenomas.

Adenoma↗

PubMed1999

Recombinant human growth hormone and Gitelman's syndrome.

Gitelman's syndrome is a primary renal tubular disorder with hypokalemic metabolic alkalosis, hypocalciuria, and magnesium deficiency. Short stature is one of clinical manifestations in children. The pathogenesis of short stature in Gitelman's syndrome is not known. To evaluate whether growth hormone (GH) is deficient and whether recombinant human GH (rhGH) improves growth rate, rhGH therapy was tried in a child with Gitelman's syndrome. Both height and body weight were less than the third percentile. Laboratory and radiologic findings suggested GH deficiency. During the first 6 months, rhGH therapy with potassium supplement markedly elevated growth rate from 3.8 cm/yr to 12.0 cm/yr. After cessation of rhGH, height increment markedly decreased to the pretreatment level of 3.6 cm/yr during the second 6 months. Additionally, hypomagnesemia was corrected after rhGH therapy. Accordingly, GH deficiency may contribute to short stature in children with Gitelman's syndrome, and rhGH therapy would be an excellent adjunctive treatment for short children with Gitelman's syndrome whose condition is resistant to conventional therapies in terms of growth.

Bartter Syndrome↗

PubMed1999

Gallstone formation. Local factors.

Bile supersaturation is necessary for cholesterol gallstones to form. Not all people with supersaturated bile form gallstones, however, and additional factors must be present. The role of pronucleating substances has been extensively studied. Of these, proteins, especially mucin, are best understood. Mucin is secreted by the gallbladder epithelium and may act as a nidus for crystal nucleation. Other proteins that may act as pronucleators include alpha 1-acid glycoprotein, alpha 1-antichymotrypsin, phospholipase C, and a small calcium binding protein. The role of antinucleating factors is less well understood. Certain drugs, including octreotide and ceftriaxone, may also predispose to stone formation. Another local factor is gallbladder stasis, a well-known risk factor for pigment stone formation. More recent research has focused on the role of bacterial infection, which has long been believed to be a factor in pigment gallstone formation. Newer data also support a role for infection in cholesterol gallstone pathogenesis. Additionally, genetic factors that may predispose a patient to cholesterol gallstones have been identified in mice and in humans.

Animals↗

PubMed1999

Regulation of renal laminin in mice with type II diabetes.

This study examines the regulation of renal laminin in the db/db mouse, a model of type II diabetes characterized by extensive remodeling of extracellular matrix. Immunohistochemistry demonstrated an increase in the contents of laminin chains including beta1 chain in the mesangium and tubular basement membranes at 1, 2, 3, and 4 mo of diabetes. Immunofluorescence with an antibody against the recently discovered laminin alpha5 chain showed that in the normal mouse, the protein had a restricted distribution to the glomerular and tubular basement membranes with scant expression in the mesangium of older mice. In the diabetic mouse, the laminin alpha5 chain content of the glomerular and tubular basement membranes was increased, with marked expression in the mesangium. Northern analysis revealed a significant decrease in the renal cortical contents of alpha5, beta1, and gamma1 chain mRNA in the diabetic mice compared to control, at each of the time points. In situ hybridization showed decreased abundance of alpha5 transcripts in the glomeruli of diabetic mice compared to nondiabetic controls. Analysis of mRNA changes by Northern and in situ hybridization studies demonstrated that the reduction in laminin transcripts involved both glomerular and tubular elements. These observations demonstrate that laminin accumulation in the db/db mice with type II diabetes is due to nontranscriptional mechanisms. Because previous investigations in rodents with type I diabetes have shown that the increase in renal laminin content was associated with a corresponding increment in laminin chain transcript levels, it appears that the mechanisms underlying augmentation in renal matrix laminin content may be distinct in the two types of diabetes.

Animals↗

PubMed1998

Biliary lipid composition after liver transplantation: effect of allograft function and cyclosporine.

Biliary lipid composition and bile flow are altered after orthotopic liver transplantation. Cyclosporine may have additional effects on biliary lipid composition and secretion. We studied the effects of liver transplantation, allograft function, and cyclosporine on biliary lipids in humans. Changes in lipid composition and secretion were correlated with serum cyclosporine levels, clinical events, and allograft function. Bile samples were withdrawn via a T-tube at interval time points in 17 patients during the first 3 months posttransplantation. Total and individual bile acid, cholesterol, and phospholipid were determined using high-performance liquid chromatography. Biliary lipid profiles were then correlated with clinical events, serum cyclosporine levels, and other clinical laboratory values. Biliary lipid concentrations decreased in 3 patients during periods of graft dysfunction (acute cellular rejection, drug-induced hepatitis, and inferior vena caval thrombosis) and increased with resolution of the graft injury. Serum cyclosporine levels were positively correlated with total bile acid, cholesterol, and phospholipid concentrations in bile. There was no relationship between the composition of secreted bile acids and serum cyclosporine levels. Bile acid, cholesterol, and phospholipid secretion were not uncoupled in the presence of cyclosporine. We concluded that (1) a decrease in biliary lipid concentrations may be an indicator of worsened graft function in some allografts; (2) biliary lipid concentrations are correlated with increasing cyclosporine levels; and (3) bile acid composition is unchanged, and uncoupling of secretion of other biliary lipids is not observed in the presence of cyclosporine.

Adolescent↗