Effects of interruption of enterohepatic circulation on biliary lipid secretion in man

To delineate relationships between biliary outputs of bile acids, phospholipids, and cholesterol, studies were carried out in 18 subjects with intact gallbladders and in six with cholecystectomy. Hepatic secretions of three biliary lipids were determined using an intestinal perfusion technique. In studies on subjects with normal gallbladders (study A), continuous infusion of liquid formula was given to stimulate gallbladder contraction, so that gallbladder storage was eliminated and duodenal outputs were equal to hepatic secretion rates. Bile acid pool size and bile lipid outputs were determined under steady-state conditions (intact EHC). Secretion rates of bile acids were then reduced by progressively withdrawing large amounts of bile from the EHC over a 12-hr period, during which biliary lipid secretions were measured continuously. In study B, six subjects without gallbladders ingested three meals of liquid formula during the day and had an overnight fast. Measurements of biliary lipid outputs were made hourly over the 24-hr period. A wide range of bile acid secretion rates occurred under these physiological conditions owing to the lowering of bile acid outputs during fasting. In both studies A and B, bile saturation with cholesterol increased as EHC became interrupted. However, the magnitude of this increase was variable from subject to subject and appeared to depend on two related factors. First, bile saturation was markedly increased in subjects who exhibited a severe reduction of bile acid output on interrupting the EHC. Second, the degree of uncoupling of cholesterol and phospholipid secretion in the lower range of bile acid outputs was also variable. When secretion of cholesterol was well-maintained in the face of decreasing bile acid and phospholipid outputs, bile became supersaturated. Subjects with high biliary cholesterol during intact EHC were especially prone to cholesterol-phospholipid dissociation. However, even at relatively low outputs of cholesterol, interruption of the EHC sometimes caused marked dissociation of secretions of cholesterol and phospholipids causing super-saturated bile at low rates of bile acid flux. Thus, the degree of coupling of cholesterol and phospholipids at low secretion of bile acids was variable from patient to patient and was a major determinant of the extent of increase in bile saturation.     

Mannose-binding lectin and rheumatoid arthritis in southern Chinese

OBJECTIVE: Insufficiency of mannose-binding lectin (MBL) is associated with recurrent infections. Rheumatoid arthritis (RA) may represent an aberrant immune response to infections. This study examined the phenotypic expression and variant alleles of the MBL gene and its etiologic role in Chinese with RA. METHODS: We studied 211 RA patients and 196 healthy subjects. Serum MBL concentrations and codon-54 mutation of the MBL gene and its promoter polymorphisms were analyzed. Clinical characteristics and disease activity were also examined. RESULTS: Patients with RA had significantly lower serum MBL levels and higher frequency of codon-54 mutation of the MBL gene compared with controls. Additionally, there was a significant difference in the distribution of promoter polymorphisms, H/L, between RA patients and controls, although the frequencies of Y/X and those of nonstructural polymorphisms, P/Q, did not differ between the 2 groups. Furthermore, patients with RA had a lower incidence of the highest-producing haplotype HY and a higher incidence of the lowest-producing haplotype LX compared with controls. Serum MBL levels did not correlate with drug treatment or with disease activity. However, patients with erosive and serious extraarticular disease had significantly lower serum MBL levels than those without these disease manifestations at the time of study. Also, significantly more patients with erosive disease had a codon-54 mutation of the MBL gene compared with those with nonerosive disease. CONCLUSION: The codon-54 mutation and low-producing promoter polymorphisms of the MBL gene are associated with RA. A low serum level of MBL predisposes to the development of RA and is a risk factor for severe disease in southern Chinese.     

Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis

There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO _x (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO _x was measured by chemiluminescence. Serum NO _x levels in SSc (n = 43) were significantly higher (72.4 ± 47.8 μM) than age- and sex-matched controls (n = 41; 37.1 ± 13.5 μM; p < 0.001). Serum NO _x were not found to be associated with lung fibrosis defined by lung function parameters or inflammation and fibrosis scores on HRCT. Twenty-two patients were found to have elevated serum NO _x level defined as mean ± 2 SD of normal controls. Logistic regression analysis revealed that age (OR 1.12, p = 0.02) and elevated pulmonary arterial pressure (PAP) (n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO _x . Prednisolone use was associated with lower serum NO _x level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO _x (p = 0.004 by trend). Serum NO _x in SSc patients were elevated compared to healthy controls. Serum NO _x level was determined by multiple factors including age, prednisolone use, and elevated PAP.     

Effectiveness of near-peer simulation for managing the acutely deteriorating patient among residents of an internal medicine junior residency programme

INTRODUCTIONNear-peer teaching is gaining popularity as a teaching modality, as it improves the learner’s understanding, is targeted at an appropriate level and promotes familiarisation. This study was initiated to evaluate the effectiveness of incorporating near-peer instruction into simulation-based training within a junior residency programme.METHODS42 first-year residents from an internal medicine junior residency programme were recruited. Participants underwent a simulation-based training programme conducted over five weeks. Each week involved either an emergency or acute clinical scenario. A structured questionnaire was administered prior to and after the course to compare participants’ perceived knowledge, experience and confidence in managing the clinical scenarios.RESULTSIn our study, 83% of participants agreed/strongly agreed that the scenarios were realistic. There were improvements in perceived knowledge, experience and confidence after the course. The greatest improvement was seen for experience (post-simulation: median 7.00 [interquartile range (IQR) 6.00‒8.00] vs. pre-simulation: median 5.00 [IQR 3.00–6.25]). 65% of participants were keen to help with future training.CONCLUSIONNear-peer simulation training was found to be a viable and valuable method of instruction for first-year residents for increasing experience, instilling confidence and improving perceived knowledge. Integration of such programmes within medical education curricula shows good promise of continuity, with many first-year residents inspired to organise subsequent sessions.     

Comparison of Korean COPD Guideline and GOLD Initiative Report in Term of Acute Exacerbation: A Validation Study for Korean COPD Guideline

The purpose of this study was to compare the Korean COPD guideline to GOLD consensus report in terms of acute exacerbation. A total of 361 patients were enrolled in this study, and 16.9% of them experienced acute exacerbation during the follow-up. A total of 6.3% of patients in GOLD A, 9.5% in GOLD B, 7.7% in GOLD C and 17.0% of GOLD D experienced exacerbation during the first year of follow-up, respectively (P=0.09). There was no one who experienced exacerbation during the first year of follow-up in the Korean group ''ga''. The 12-month exacerbation rates of Korean group ''na'' and ''da'' were 4.5% and 16.0%, respectively (P<0.001). We explore the experience of exacerbation in patients with change of their risk group after applying Korean COPD guideline. A total of 16.0% of the patients who were reclassified from GOLD A to Korean group ''da'' experienced acute exacerbation,and 15.3% from GOLD B to Korean group ''da'' experienced acute exacerbation. In summary, the Korean COPD guideline is useful to differentiate the high risk from low risk for exacerbation in terms of spirometry. This indicates that application of Korean COPD guideline is appropriate to treat Korean COPD patients.     

Association between serum adipocytokine levels and microangiopathies in patients with type 2 diabetes mellitus

Aims/Introduction

It is thought that adipocytokines contribute to the increased risk of vascular complications in type 2 diabetes. However, there is still limited information on the relationship between microangiopathies and adipocytokines, such as adiponectin, leptin and tumor necrosis factor‐α (TNF‐α) in patients with type 2 diabetes.

Materials and Methods

The present study examined the relationship between fasting serum adiponectin, leptin, and TNF‐α levels and microangiopathies in Korean type 2 diabetes. A total of 153 patients were recruited and evaluated for diabetic nephropathy, retinopathy and neuropathy. Serum adiponectin, TNF‐α and leptin levels were measured.

Results

Serum adiponectin levels were significantly lower in patients with nephropathy than in those without nephropathy (P = 0.017), and were significantly higher in patients with retinopathy or neuropathy than those without retinopathy or neuropathy (P = 0.01 and P = 0.002, respectively). The mean levels of leptin were significantly higher in patients with neuropathy than in those without neuropathy (P = 0.002). The mean levels of TNF‐α were not significantly different according to any of the three microangiopathies. Multivariate logistic regression analysis showed that the odds ratio for the presence of neuropathy in the highest tertile of adiponectin was 4.3 (95% confidence interval 1.59–11.62), as compared with the patients in the lowest tertile of adiponectin level.

Conclusions

Levels of adipocytokines were significantly different according to the presence of each microangiopathy. In particular, higher serum adiponectin was independently associated with increased odds for the presence of neuropathy. Future prospective studies with larger numbers of patients are required to establish a direct relationship between plasma adipocytokine concentrations and the development or severity of diabetic microangiopathies.