Proteomic associations with forced expiratory volume - a Mendelian randomisation study.

A decline in forced expiratory volume (FEV1) is a hallmark of obstructive respiratory diseases, an important cause of morbidity among the elderly. While some data exist on biomarkers that are related to FEV1, we sought to do a systematic analysis of causal relations of biomarkers with FEV1. Data from the general population-based AGES-Reykjavik study were used. Proteomic measurements were done using 4,782 DNA aptamers (SOMAmers). Data from 1,648 participants with spirometric data were used to assess the association of SOMAmer measurements with FEV1 using linear regression. Bi-directional Mendelian randomisation (MR) analyses were done to assess causal relations of observationally associated SOMAmers with FEV1, using genotype and SOMAmer data from 5,368 AGES-Reykjavik participants and genetic associations with FEV1 from a publicly available GWAS (n = 400,102). In observational analyses, 473 SOMAmers were associated with FEV1 after multiple testing adjustment. The most significant were R-Spondin 4, Alkaline Phosphatase, Placental Like 2 and Retinoic Acid Receptor Responder 2. Of the 235 SOMAmers with genetic data, eight were associated with FEV1 in MR analyses. Three were directionally consistent with the observational estimate, Thrombospondin 2 (THBS2), Endoplasmic Reticulum Oxidoreductase 1 Beta and Apolipoprotein M. THBS2 was further supported by a colocalization analysis. Analyses in the reverse direction, testing whether changes in SOMAmer levels were caused by changes in FEV1, were performed but no significant associations were found after multiple testing adjustments. In summary, this large scale proteogenomic analyses of FEV1 reveals protein markers of FEV1, as well as several proteins with potential causality to lung function.

[Spiritual needs of patients in an emergency room]. / Spirituelle Bedürfnisse von Patienten eines Notfallzentrums.

BACKGROUND: Spiritual needs (spN) are important for human beings-independently of religious affiliation. They can be a resource for coping with stressful situations, e.g., those triggered by the acute onset of a disease. Emergency rooms are hospital departments with high medical performance which may cause a particular insecurity among emergency patients. The present study is the first to examine spiritual needs in a sample of patients in the emergency room. METHODS: A total of 383 out of 479 patients were approached and asked to complete the German version of the Spiritual Needs Questionnaire (SpNQ-20). All consented to the collection of demographics and clinical data. The analysis encompassed descriptive statistics, correlations analysis, univariate and multiple variance analysis. RESULTS: The needs for inner peace and generative needs (to pass something on to others, to do something for others) were more important than religious (rN) and existential (eN) needs. We did not find a correlation between spN on the one hand and the reason for consultation, the severity, and the number of comorbidities on the other hand. Age did not play a decisive role, rather, patients' needs, especially rN, were significantly more important among women than among men. CONCLUSION: Even in an emergency situation, people are ready to express their spN. Early assessment of these needs exposes important nonmedical aspects of the sick person and helps to consider the assessed needs. Further studies will show whether this has an impact on the further course of treatment and the well-being of the patients.

They Can Handle the Stress: MPK17 and PMD1 act in a salt-specific pathway.

Arabidopsis MAP KINASE17 (MPK17) was recently identified as a novel regulator of peroxisome division in response to salt stress. Further, the known peroxisome division factor PEROXISOME AND MITOCHONDRIAL DIVISION FACTOR1 (PMD1) genetically acts downstream of MPK17. We previously showed that mutants defective in either MPK17 or PMD1 fail to proliferate peroxisomes in response to NaCl stress. Here, we show that, unlike their abnormal NaCl responses, mpk17 and pmd1 mutants display wild type responses to other stresses known to alter peroxisome proliferation, suggesting that plants distinguish among peroxisome division-inducing stresses and alter the peroxisome division pathway based on the stress applied.

Correlations of Medial Joint Space Width on Fixed-Flexed Standing Computed Tomography and Radiographs With Cartilage and Meniscal Morphology on Magnetic Resonance Imaging.

OBJECTIVE: To assess whether medial tibiofemoral joint space width (JSW) on 3-dimensional (3-D) standing computed tomography (SCT) correlates more closely with magnetic resonance imaging cartilage morphology (CM) and meniscal scores than does radiographic 2-D JSW. METHODS: Participants in the Multicenter Osteoarthritis Study, who had standing fixed-flexion posteroanterior knee radiographs, were recruited. Medial tibiofemoral 3-D JSW on SCT and 2-D JSW on fixed-flexion radiographs were compared with medial tibiofemoral cartilage and meniscal morphology using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Associations between the area of the articular surface with 3-D JSW <2.5 mm on SCT, radiographic minimal 2-D JSW, and the WORMS-CM and meniscal scores were assessed using Spearman's rho. RESULTS: For the 19 participants included (33 knees), mean ± SD age was 66.9 ± 5.4 years, body mass index was 29.5 ± 4.4 kg/m(2) , 42.1% of participants were female, and the Kellgren/Lawrence grades were 0 (21.2%), 1 (36.4%), 2 (18.2%), and 3 (24.2%). The articular surface area with 3-D JSW <2.5 mm on SCT correlated with WORMS-CM scores for the central medial tibia (rs = 0.84, P < 0.001), central medial femur (rs = 0.60, P < 0.007), and posterior medial meniscal tear (rs = 0.39, P < 0.026), as did other cut points for 3-D JSW. Correlations with radiographic minimal 2-D JSW were -0.66, -0.52, and -0.40, respectively, differing from SCT only for tibial cartilage (P = 0.001). CONCLUSION: Greater surface area with a low JSW, measured by SCT, correlates more strongly with the severity of tibial cartilage lesions, while correlating with medial femoral cartilage and meniscal damage to a similar extent as radiographic minimal JSW. SCT may enable valid stratification of participants in clinical trials, through quickly and inexpensively characterizing osteoarthritis features.

Anxiety, depression and quality of life of cancer patients undergoing radiation therapy: a cross-sectional study in a community hospital outpatient centre.

The purpose of the present study is to determine the impact of illness characteristics and psychopathological comorbidity on the quality of life (QoL) of radio-oncological patients in health-related and individual dimensions. Sixty-three of 93 eligible patients (40 women and 23 men) were included in the study during their radiation therapy visit to an outpatient centre annexed to a community hospital in Southern Bavaria, Germany. In a semi-structured interview, we elicited individually relevant life domains rated by the patients according to the 'Schedule for the Evaluation of Individual Quality of Life - Direct Weighting'. In addition, the participants completed the 'European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire Core 30' and the 'Hospital Anxiety and Depression Scale'. We also assessed the demand for psychotherapy and utilization of psycho-oncological services. In total, 9.5% of the examined patients suffer from clinically relevant anxiety and/or depression [total Hospital Anxiety and Depression Scale (HADS) score >19]. There was a weak positive correlation between Karnofsky's Performance Status and QoL. Anxiety and depression were significantly correlated with impaired QoL, especially with impaired individual QoL. There was no association between psychopathological comorbidity and the requirement for psycho-oncological support. Conversely, patients who report difficulties in accepting help had a significantly lower QoL. Psychopathological comorbidity has a considerable influence on QoL of patients undergoing radiotherapy. Measuring the individual QoL appears as an adapted needs assessment and helps the psychotherapist in focusing on the patient's problems and desires. Furthermore, the patient's QoL is a main target in providing or planning mental health care in non-university oncological services.

Patients' health beliefs and coping prior to autologous peripheral stem cell transplantation.

The aim of this study was to determine the associations between health locus of control (LoC), causal attributions and coping in tumour patients prior to autologous peripheral blood stem cell transplantation. Patients completed the Questionnaire of Health Related Control Expectancies, the Questionnaire of Personal Illness Causes (QPIC), and the Freiburg Questionnaire of Coping with Illness. A total of 126 patients (45% women; 54% suffering from a multiple myeloma, 29% from non-Hodgkin lymphomas, and 17% from other malignancies) participated in the study. Cluster analysis yielded four LoC clusters: 'fatalistic external', 'powerful others', 'yeah-sayer' and 'double external'. Self-blaming QPIC items were positively correlated with depressive coping, and 'fate or destiny' attributions with religious coping (P<0.001). The highest scores were found for 'active coping' in the LoC clusters 'powerful others' and 'yeah-sayer'. External LoC and an active coping style prevail before undergoing autologous peripheral blood stem cell transplantation, whereas the depressive coping is less frequent, associated with self-blaming causal attributions. Health beliefs include causal and control attributions, which can improve or impair the patient's adjustment. A mixture between internal and external attributions seems to be most adaptive.

A clinical interview assessing cancer patients' spiritual needs and preferences.

We conducted a phase-I study to test the practicability and usefulness of a short (15-30 min) clinical interview for the assessment of cancer patients' spiritual needs and preferences. Physicians assessed the spirituality of their patients using the semi-structured interview SPIR. The interview focuses on the meaning and effect of spirituality in the patient's life and coping system. Visual Analogue Scales (VAS) and Questionnaires were completed following the interview for rating whether SPIR had been helpful or distressing, and to what extent spirituality seemed important in the patient's life and in coping with cancer disease. Thirty oncological outpatients who all agreed to participate were included. The majority wanted their doctor to be interested in their spiritual orientation. Patients and interviewing physicians evaluated the SPIR interview as helpful (patients mean 6.76 +/- 2.5, physicians 7.31 +/- 1.9, scale from 0 to 10) and non-distressing (patients 1.29 +/- 2.5, physicians 1.15 +/- 1.3, scale from 0 to 10). Following the interview, doctors were able to correctly gauge the importance of spirituality for their patients. Patients who considered the interview as very helpful (VAS > 7) were more often female (P = 0.002). There were no differences between patients who evaluated the SPIR as very helpful and those who did not, as far as diagnosis, educational level or belonging to a religious community were concerned. The present study shows that a short clinical assessment of cancer patients' spirituality is well received by both patients and physicians. The SPIR interview may be a helpful tool for addressing the spiritual domain, planning referrals and ultimately strengthening the patient-physician relationship.

Is perceived social support a predictor of survival for patients undergoing autologous peripheral blood stem cell transplantation?

PURPOSE: Previous research discussed the predictive value of psychosocial variables along with biomedical predictors for survival; such as affective functioning and quality of life. The present study addresses the following research question: does perceived social support prior to PSBCT have an impact on post-transplant survival? SUBJECTS AND METHODS: Ninety-nine patients suffering from Multiple Myeloma (n=55), Non-Hodgkin Lymphoma (n=33), and other malignancies (n=11) completed the Illness Specific Scales of Social Support (ISSS) before undergoing PBSCT. ISSS is comprised of the subscales 'positive social support' and 'problematic social support', e.g. criticising, victimising, or avoiding interactions. RESULTS: The mean score in the subscale 'positive social support' was 3.2 (S.D. 0.54; range 0 until 4), in the subscale 'negative social support' 0.94 (S.D. 0.53). There was no association between positive interactions and survival following PBSCT. Conversely, those patients perceiving problematic social support, showed a correspondence with poor survival following PBSCT (RR=3.649; p=0.015; Cox-regression analysis). The following variables were controlled: Karnofsky Performance Status, interferon treatment, depression and participation in psychotherapy. CONCLUSION: Differentiating between positive and problematic interactions prior to PBSCT helps to recognise detrimental forms of social support. Future research should investigate the clinical implications and help tailor psychotherapeutic intervention.

Individual quality of life of patients undergoing autologous peripheral blood stem cell transplantation.

BACKGROUND: Most quality-of-life (QoL) studies in autologous Peripheral Blood Stem Cell Transplantation (PBSCT) are descriptive and concentrate on symptom severity and functional deficits. The aim of this study is to compare individual QoL (iQoL) with health-related QoL (hrQoL) and functional status of patients before high-dosed therapy/PBSCT. PATIENTS AND METHODS: Multiple Myeloma, non-Hodgkin's Lymphoma and other tumor patients were asked to complete the following measures before high-dosed therapy/PBSCT: the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-life Questionnaire Core 30 (QLQ-C30), and the Schedule for the Evaluation of Individual QoL-Direct Weighting (SEIQoL-DW), a patient-generated instrument which allows the patients to nominate the five most important domains (cues) for their present QoL. The SEIQoL-DW assessment generates: (1) a global QoL score (SEIQoL-INDEX), calculated as Sigma(levelsxweights); (2) the current overall QoL, rated on a visual analogue scale (VAS). Additional measures included demographic data, clinical disease status of remission and Karnofsky's index. RESULTS: Seventy-nine patients completed both types of questionnaires. The QoL domains nominated by the patients were assigned to groups (aggregated cues), the most frequent of which were family (89%), hobbies/pastimes (74%), health (physical, including mobility) (70%), profession/occupation (51%), social life/friends (47%) and marriage/partnership (33%). There was no correlation between the SEIQoL-DW total scores and the EORTC QLQ-C30 scale or the Karnofsky index. CONCLUSION: Individual QoL as assessed by the SEIQoL-DW is unrelated to standard health-status measures such as the EORTC QLQ-C30 or the Karnofsky index. Patient-perceived iQoL in PBSCT seems to depend largely on areas others than health and physical functioning, with the family playing a prominent role.

Prevalence of markers of hepatitis B in the adult German population.

The prevalence of hepatitis B virus markers was investigated in 5305 individuals considered to be representative for the adult German population. After adjustment of the data according to the age and sex distribution in the whole German population an anti-HBc prevalence of 8.71% (95% confidence interval, 7.94-9.48%) and an HBsAg carrier rate of 0.62% (95% confidence interval, 0.40-0.84%) were calculated. Anti-HBc prevalence increased with age from 4.12% in the youngest group to 15.66% in the 61-70-year-old. The percentage of HBsAg carriers showed a maximum of 1.12% in the 41-50-year-old individuals and decreased significantly in the older age groups. 1.40% (95% confidence interval, 1.08-1.72%) of individuals had anti-HBc only. There was a trend to higher rates of this pattern in males than in females; a significantly higher percentage of persons with anti-HBc only was found in anti-HBc-positive individuals below 31 years than in older individuals. Five participants with anti-HBc only (7.7%, or about 0.1% of the whole population) showed HBV-DNA despite the absence of HBsAg. 3.1% of anti-HBc positive individuals where also positive for anti-HCV, that was significantly higher than the percentage of anti-HCV-positives among persons without any HBV marker (0.46%). This study provides a comprehensive picture of the current hepatitis B situation in Germany, showing new data especially on the distribution of HBsAg in the general population and on the subgroup of individuals with anti-HBc only.

Somatostatinoma of the ampulla of vater in celiac sprue.

The increased incidence of gastrointestinal lymphoma and adenocarcinoma in patients with celiac sprue is well recognized, with 10% to 15% developing a gastrointestinal malignancy. Somatostatinomas are rare neuroendocrine tumors that occur most commonly within the pancreatic head or duodenum. Although fewer than 100 cases have been reported, somatostatinomas are often associated with multiple endocrine neoplasia-1 syndrome and von Recklinghausen's disease. The unusual case of a 43-year-old woman with celiac sprue in which a somatostatinoma involving the ampulla of Vater was identified and resected is presented. To our knowledge, somatostatinomas have not been previously reported in patients with celiac sprue.

Rapid effects of lipopolysaccharides on indocyanine green clearance in rat liver.

BACKGROUND: Lipopolysaccharides (LPSs) are thought to be one of the triggers of organ reactions to sepsis, which causes hepatocellular dysfunction. This dysfunction can be demonstrated by a reduction of organic anion transport. The aim of our study was to assess whether the transport of indocyanine green (ICG) is affected by LPS, and whether Kupffer cells are involved. METHODS: Single-pass liver perfusion with ICG at a concentration of 57.8 mg/kg/min was performed for 130 min. pH, oxygen tension and perfusion pressure were continuously measured in influent and effluent. Taurocholate was infused at 48.3 mg/kg/min to achieve a stable bile flow. LPS was added at concentrations of 0.45, 0.9 and 1.44 mg/kg/min for 30 min. ICG was determined photometrically in perfusate and bile. To depress the function of Kupffer cells male Wistar rats were treated with GdCl3 24 h in advance. Primary cultured hepatocytes were used for studying the direct effect of LPS on the uptake rate of ICG. RESULTS: Forty-five minutes after administration of LPS a significant dose-dependent decrease of ICG uptake was seen in animals treated with LPS. Livers of animals pretreated with GdCl3 did not show this decrease. LPS had no direct effect on the uptake of ICG into primary cultured hepatocytes, whereas treatment of these cells with 8-bromo-cGMP resulted in a significant increase of ICG uptake. CONCLUSION: LPS has a rapid dose-dependent effect on the detoxification properties of the liver for ICG. The rapid effect of LPS on ICG uptake in hepatocytes is mediated by Kupffer cells.

Solitary neurofibroma of the anal canal: report of two cases.

Neurofibromas are benign nerve sheath tumors commonly found in patients afflicted with neurofibromatosis-1. In the absence of multiple neurofibromas or a diagnosis of neurofibromatosis-1, neurofibromas are referred to as solitary and have been reported to involve the skin, subcutaneous tissue, deep soft tissue, and viscera of almost all areas of the body. A neurofibroma involving the anal canal is a rare entity, with only one report in the literature. We present two cases in which large masses involving the anal canal of elderly females were locally resected and proved to be neurofibromas by histopathology. Although rare, these tumors should be considered in the differential diagnosis of patients presenting with an anal mass, because resection alone is the treatment of choice.

Schizophrenic psychosis: a contraindication for treatment of hepatitis C with interferon alpha?

Depressive or psychotic symptoms are a well known side-effect of interferon alpha (INF-alpha). Therefore, the questions arises whether a chronic psychosis should be considered a contraindication for the treatment of active hepatitis C with INF-alpha. We report on a 38-year-old woman with a chronic schizophrenic psychosis, who acquired chronic aggressive hepatitis C. Considering the young age of the woman, the potential risk of developing a hepatocellular carcinoma and the result of the liver biopsy, treatment with interferon alpha 2 b (3x5 million IU/week) was started. The patient was seen three times a week, her psychiatric condition was monitored using the positive and negative symptoms score (PANSS). No signs of psychotic or depressive symptoms appeared during INF-alpha therapy. During the first 6 months the liver enzymes dropped slowly but the virus load was increasing. After adding ribavirin to the therapy, the liver enzymes dropped again, and the PCR carried out 9 months after initiation and 6 months after the end of the 12 months INF-alpha treatment did not detect any virus RNA. This positive result should encourage prospective studies including patients with these two diagnoses on whether patients benefit from INF-alpha.

Prevalence of antibodies against hepatitis C virus in the adult German population.

OBJECTIVE: The prevalence of anti-HCV in Germany has been determined for blood donors and certain risk groups, but the burden of disease in the general population remains unknown. The aim of this study was to determine the prevalence of anti-HCV in a study group representing the normal adult German population. DESIGN: A total of 5312 individuals aged 18-70 years were randomly selected from small, middle-sized and big cities in five different German states. Sera were tested for anti-HCV by enzyme immunoassay and immuno dot assay, as well as for anti-HBc and, in the case of a positive result, for anti-HBs and HBsAg. Serological typing was performed in anti-HCV-positive persons. RESULTS: Thirty-nine individuals were anti-HCV positive; indeterminate results (with antibodies against the viral core protein only) were obtained in 20. There was a tendency to higher prevalence rates with increasing age as well as to a higher prevalence in women. Serological typing revealed the presence of genotype 1 in the vast majority of participants (82%); only a minority showed genotype 3 (7.2%) or other genotypes (7.2%). Markers of HBV were seen in 43.6% of the anti-HCV positive individuals, with nearly one third (29.4%) of the double-infected showing anti-HBc as the only marker for HBV. CONCLUSIONS: According to our data, an anti-HCV prevalence of 0.63% (95% confidence interval, CI, 0.42-0.84%) can be assumed in the general adult German population, with higher values in older people and women. Nearly half of the anti-HCV positive individuals also show markers of hepatitis B virus.

Small-bowel and mesentery injuries in blunt trauma.

BACKGROUND: The purpose of this study was to identify factors that would aid in the diagnosis of small-bowel and mesentery injuries (SBMI) in blunt trauma patients. METHODS: Retrospective review of 15,779 blunt trauma patients admitted to a Level I trauma center between January 1991 and December 1996. RESULTS: A total of 5,303 patients sustained abdominal injuries, 70 of whom had more than 111 SBMI. Seventy-nine percent were victims of motor vehicle collisions. Thirty patients had isolated SBMI and 40 had associated intra-abdominal injuries. Twelve patients arrived with systolic blood pressure < 90 mm Hg, eight of whom died. Mean base deficit was -7.3 +/- 6.3 in 52 patients who had arterial blood gases determined. Fifty-three of 60 patients had hematuria. Sixty-seven patients required laparotomy. Delayed exploration occurred in 15 patients who underwent initial computed tomography but had subsequent changes in physical status. Two of 20 patients had negative diagnostic peritoneal lavage on admission and were eventually explored based on abdominal computed tomographic findings and changes in physical examination. There were 15 deaths. Delay in diagnosis (>12 hours after arrival) occurred in nine patients with no deaths or significant morbidities. Mean Injury Severity Score was 29 +/- 16.7: 43 +/- 17 in nonsurvivors and 25 +/- 14.3 in survivors (p < 0.05). CONCLUSION: The diagnosis of SBMI is often made in the presence of associated intra-abdominal injuries. Isolated SBMI are common, however, and special attention to the mechanism of injury, abdominal examination, presence of hematuria, and significant base deficit should raise suspicion to the possibility of SBMI. Findings on abdominal computed tomography that may suggest SBMI and should prompt further evaluation include free fluid, thickened bowel, and extraluminal air. Because delay in diagnosis does not seem to affect morbidity or mortality, dedication to observation and serial physical examinations will aid in the proper identification of elusive SBMI. Mortality, however, does appear to be related to the presence of hypotension on admission and associated injuries.

Outcome of blunt thoracic aortic injury in a level I trauma center: an 8-year review.

BACKGROUND: The purpose of this study was to evaluate our experience with blunt thoracic aortic injury and identify factors predictive of outcome. METHODS: Hospital charts, trauma registry data, and autopsies of 64 patients with blunt thoracic aortic injury from 1988 to 1995 were reviewed. RESULTS: Patients were identified and segregated based on admission physiology. Group 1 patients (n = 19) arrived in arrest. Group 2 patients (n = 10) arrived in shock with systolic BP 90. Group 3 patients (n = 35) arrived with systolic BP>90. All patients in groups 1 and 2 expired. Injury Severity Scores for nonsurvivors in group 3 (n = 12) were significantly higher than survivors. There were no significant differences when comparing time of injury to repair or arrival between groups, or in mortality or paralysis comparing repair techniques or clamp/bypass times. Double lumen endotracheal tubes caused significant operative delays compared to single lumen tubes. CONCLUSIONS: Predictors of survivability were hemodynamic stability on arrival and lower Injury Severity Scores. In thoracic aortic injury patients arriving hemodynamically stable, Injury Severity Score correlated with mortality but not paralysis.

Hepatocyte transport of bile acids and organic anions in endotoxemic rats: impaired uptake and secretion.

BACKGROUND & AIMS: In sepsis, intrahepatic cholestasis occurs frequently, suggesting impaired hepatocyte transport of bile acids and organic anions. The aim of the study was to define the magnitude, time course, and the site of impaired biliary secretion in a rat sepsis model. METHODS: Maximal transport for two bile acids (cholyltaurine and chenodeoxycholyltaurine) and two organic anions (sulfobromophthalein and sulfolithocholyltaurine) was measured in isolated perfused livers at various times after lipopolysaccharide injection. Basolateral and canalicular liver plasma membrane vesicles were used to characterize the impairment in hepatocyte transport. RESULTS: Maximal hepatocyte transport was reduced for all compounds by 60%-81% compared with controls. Bile acid-independent bile flow was reduced by 51%. Impairment was maximal 12 hours after endotoxin injection and recovered thereafter. In basolateral plasma membrane vesicles, sodium-dependent transport for bile acids was reduced by 36%-47%. Sodium-independent transport of organic anions was reduced by 40%-55%. Adenosine triphosphate-stimulated transport was greatly decreased in canalicular vesicles prepared from endotoxemic animals for all four compounds probably because of a reduced number of transport molecules, based on kinetic studies. CONCLUSIONS: Basolateral and canalicular bile acid and organic anion transport are markedly impaired in endotoxemia. These mechanisms may contribute to the cholestasis of sepsis.

Hepatic biotransformation in rodents and physicochemical properties of 23(R)-hydroxychenodeoxycholic acid, a natural alpha-hydroxy bile acid.

The hepatic biotransformation in the rat and hamster of 23(R)-hydroxychenodeoxycholic acid (23(R)OH-CDCA), the alpha-hydroxy derivative of CDCA, was defined; some physiological and physicochemical properties were also assessed. 23(R)OH-CDCA was isolated from duck bile; [24-14C]23(R)OH-CDCA was synthesized. The compound was administered intravenously to anesthetized biliary fistula rats at doses of 1, 3, or 5 mu mol/kg-min and to hamsters at 3 mu mol/min-kg. Biliary bile acids and radioactivity were analyzed by thin-layer chromatography (TLC), high pressure liquid chromatography (HPLC), and gas chromatography-mass spectrometry (GC-MS). Recovery of radioactivity in bile was incomplete (50-70% of infused dose); some was also recovered as breath 14CO2. Radioactivity in bile was present as unchanged compound (25-50%, dose-dependent) and its conjugates (with taurine, with glycine, or with glucuronate). Nor-CDCA (C23) was present in bile (in both unconjugated and conjugated form), indicating that 23(R)OH-CDCA had undergone oxidative decarboxylation (alpha-oxidation) with loss of the C-24 carboxyl group. The alpha-oxidation was 20 +/- 5% (mean +/- SD) of administered dose in the rat and was not dose-dependent; in hamsters, alpha-oxidation was 35 +/- 8%. In rats, the S isomer of 23OH-CDCA also underwent alpha-oxidation (10 +/- 2%). Nor-CDCA also underwent 6beta-hydroxylation to form nor-alpha-muricholic acid, as well as reduction of its C-23 carboxyl group to form the C23 alcohol. The taurine conjugate of 23(R)OH-CDCA [23(R)OH-CDC-tau] was prepared synthetically and characterized by 1H-NMR. By surface tension measurements, it had a critical micellization concentration (CMC) of 3.5 mM (in 0.15 M Na+), as compared to 1.8 mM for CDC-taurine. Aqueous solubility of 23(R)OH-CDCA increased markedly above pH 5, compared to pH 7 for CDCA. When incubated with cholylglycine hydrolase, 23(R)OH-CDC-tau was deconjugated at a rate one-fourth that of CDC-tau. It is concluded that the presence of a 23(R)-hydroxyl group in a 3alpha, 7alpha-dihydroxy bile acid alters its metabolism in the rodent hepatocyte, as evidenced by inefficient conjugation with taurine or glycine, alpha-oxidation to nor (C23) bile acid, and reduction of the nor bile acid to the primary alcohol. The taurine conjugate of 23(R)OH-CDCA, a major biliary bile acid of marine mammals and wading birds, is a biological detergent with properties superior to those of the taurine conjugate of CDCA. Natural C23 nor-bile acids may be formed by alpha-oxidation of alpha-hydroxy C24 bile acids.