Iatrogenic bile duct injury – a cost analysis

Introduction. Iatrogenic bile duct lesions following cholecystectomy represent a feared complication occurring in up to 0.9%. The aim of the present study was to estimate the total cost associated with both minor and major bile duct injuries. Material and methods. Detailed information on 24 consecutive patients, out of which 14 were considered to have minor and 10 patients considered as having major bile duct injury, provided the underlying information that rendered calculations on average individual costs for both groups of injuries. Results and discussion. Calculating individual costs for minor and major bile duct injuries with actual incidences of cholecystectomies performed and the incidence of iatrogenic bile duct injury demonstrated that the total costs, including in-hospital cost, sick leave and loss of production, were substantial. For the management of minor bile duct injuries costs were within the range of 136,787–159,585 EUR and for the management of major bile duct injuries from 336,903–449,204 EUR per million inhabitants and year. The total costs for the management of all types of bile duct injuries were thus within the range of 473,690–608,789 EUR per million inhabitants annually for the society.     

Antibodies against lysophosphatidylcholine and oxidized LDL in patients with SLE

Lysophosphatidylcholine (LPC) is present in oxidized low density lipoprotein (oxLDL), which is implicated in atherosclerosis. Antibodies to cardiolipin (aCL) and oxLDL (aoxLDL) have been shown to crossreact. LPC is formed by hydrolysis of phosphatidylcholine (PC) in LDL and cell membranes, induced by phospholipase A2 or by oxidation. We here demonstrate the presence of enhanced antibody levels to LPC in 184 patients with SLE as compared to 85 healthy, age-matched controls. The antibody reactivity to LPC was not specifically related to oxidation of the fatty acid moiety in LPC, since LPC containing only the saturated fatty acid palmitic acid showed equivalent antibody levels as LPC containing unsaturated fatty acids. aPC were significantly lower as compared to aLPC, indicating that hydrolysis of PC at the sn-2 position increases the antigenic potential of the molecule. Beta-glycoprotein 1 was a cofactor for aCL, but not for aoxLDL or aLPC, and the antigenicity of these compounds is therefore not directly related to beta2GP1. There was a close correlation between aoxLDL, aCL and aLPC and both LPC and oxLDL competitively inhibited aCL-binding to CL. LPC, oxLDL and CL thus display a common antigenic site, which could be formed by removal of a fatty acid at the sn-2 position, possibly due to the activity to phospholipase A2 and/or oxidation. This study indicates the potential role of LDL-oxidation and phospholipase A2 in SLE.     

Increased exercise ejection fraction and reversed remodeling after long-term treatment with metoprolol in congestive heart failure: a randomized, stratified, double-blind, placebo-controlled trial in mild to moderate heart failure due to ischemic or idiopathic dilated cardiomyopathy

BACKGROUND: the effects of long-term administration of beta-blockers on left ventricular (LV) function during exercise in patients with ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (DCM) are controversial. PATIENTS AND METHODS: patients with stable congestive heart failure (CHF) (New York heart association [NYHA] class II and III) and ejection fraction (EF) < or =0.40 were randomized to metoprolol, 50 mg t.i.d. or placebo for 6 months. Patients were divided into two groups: ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (DCM). The mean EF was 0.29 in both groups and 92% were taking angiotensin-converting enzyme (ACE) inhibitors. In the IHD group, 84% had suffered a myocardial infarction (MI) and 64% had undergone revascularization at least 6 months before the study. LV volumes were measured by equilibrium radionuclide angiography. Mitral regurgitation was assessed by Doppler echocardiography. All values are changes for metoprolol subtracted by changes for placebo. RESULTS: metoprolol improved LV function markedly both at rest and during sub-maximal exercise in both groups. The mean increase in EF was 0.069 at rest (P<0.001) and 0.078 during submaximal exercise (P<0.001). LV end-diastolic volume decreased by 22 ml at rest (P=0.006) and by 15 ml during exercise (P=0.006). LV end-systolic volume decreased by 23 ml both at rest (P=0.001) and during exercise (P=0.004). Exercise time increased by 39 s (P=0.08). In the metoprolol group, mitral regurgitation decreased (P=0.0026) and only one patient developed atrial fibrillation vs. eight in the placebo group (P=0.01). CONCLUSION: metoprolol improves EF both at rest and during submaximal exercise and prevents LV dilatation in mild to moderate CHF due to IHD or DCM.     

Viridans streptococcal septicaemia in neutropenic patients: role of proinflammatory cytokines

The immunostimulatory activity of viridans streptococcal strains isolated from neutropenic patients with severe sepsis (n=9) or uncomplicated bacteraemia (n=10) was compared. Peripheral blood mononuclear cells from healthy individuals were stimulated with heat-killed bacteria or culture supernatants, and cytokine production assessed. All strains were potent inducers of IL1beta, IL8, and TNFalpha production. Heat-killed bacteria induced consistently higher IL1beta and TNFalpha production than did the cell-free bacterial supernatants (P<0.01). The strains did not induce any proliferative response, nor any significant TNFbeta or IFNgamma production. No difference in cytokine-inducing capacity could be detected between the cohorts of severe and nonsevere isolates. Comparison of strains causing severe and nonsevere episodes in the same patient (n=2) revealed a significantly higher induction of IL1beta by the severe episodes associated isolates as compared to the nonsevere (P<0.04). The study underscores the importance of the host-pathogen interplay in determining the level of inflammation, and hence the severity of disease.     

Treatment of abdominally obese men with a serotonin reuptake inhibitor: a pilot study

OBJECTIVE: To investigate the effects of a selective serotonin reuptake inhibitor (SSRI) on the neuroendocrine and autonomic nervous system perturbations found in abdominal obesity. DESIGN: Treatment for 6 months with citalopram and for 6 months with placebo using a double-blind, cross-over design, with a 2-month wash-out period between treatment periods. SUBJECTS: Sixteen healthy men, 45-60 years, moderately obese and with an abdominal fat distribution. MEASUREMENTS: Anthropometry, three different depression rating scales, serum lipids, testosterone, IGF-I, oral glucose tolerance test (OGTT), pituitary stimulation with corticotropin releasing hormone (CRH), arithmetic stress test, and excretion of cortisol and metoxycatecholamines in urine, collected during 24 h. RESULTS: Cortisol concentrations in the morning were low before treatment, indicating a perturbed function of the hypothalamic-pituitary-adrenal (HPA) axis. After treatment with citalopram morning cortisol concentrations rose to normal. Cortisol concentrations after stimulation with CRH or stress were elevated by citalopram treatment, but urinary cortisol excretion was unchanged. The glucose concentrations after OGTT (120 min) tended to be reduced, with unchanged insulin concentrations, whilst other metabolic values did not change during treatment. Heart rate after administration of CRH, and during laboratory stress test, decreased by treatment with citalopram. Diurnal urinary excretion of metoxycatecholamines tended to decrease. Neither body mass index nor waist/hip circumference ratio decreased. Depression scores were within normal limits before treatment and did not change. CONCLUSION: The results of this pilot study indicate improvements in the regulation of neuroendocrine-autonomic systems as well as metabolism in abdominal obesity during treatment with an SSRI.     

Surgery for Crohn colitis over a twenty-eight-year period: fewer stomas and the replacement of total colectomy by segmental resection

BACKGROUND: This study describes how surgery for Crohn colitis developed between 1970 and 1997, towards the end of which period limited resection and medical maintenance treatment was introduced. METHODS: A cohort of 211 patients with Crohn colitis (115 population-based), of which 84 had a primary colonic resection (42 population-based), was investigated regarding indication for surgery, the time from diagnosis to operation, type of primary colonic resection, risk for permanent stoma and medication over four 7-year periods. RESULTS: Comparison of the periods 1970-90 and 1991-97 revealed that active disease as an indication for surgery decreased from 64% to 25% (P<0.01) while stricture as an indication increased from 9% to 50% (P < 0.001). Median time from diagnosis to operation increased from 3.5 to 11.5 years (P < 0.01). Proctocolectomy or colectomy fell from 68.8% to 10% of the primary resections, whereas segmental resection increased from 31.2% to 90%. At the end of the first 7-year period, 26% had medical maintenance treatment, steroids or azathioprine taken by 7%. Corresponding figures for the last period were 70% and 49%. Patients diagnosed during the last two time-periods had less risk for surgery (P = 0.017), permanent stoma (P < 0.01) and total colectomy (P < 0.01). Findings were similar in the population-based cohort. CONCLUSIONS: Current management of Crohn colitis implies a longer period between diagnosis and surgery, a reduced risk for surgery and permanent stoma, and the replacement of total colectomy by segmental resection.     

Expression of the signal transduction molecule zeta in peripheral and tumour-associated lymphocytes in Hodgkin's disease in relation to the Epstein-Barr virus status of the tumour cells

We investigated whether the described immune evasion of Epstein-Barr virus (EBV)-infected malignant Hodgkin and Reed-Sternberg (HRS) cells in Hodgkin's disease (HD) is paralleled by a disturbed expression of the signal transduction molecule zeta associated with CD3 and CD16 in tumour-associated T lymphocytes (TAL). Flow cytometric analysis revealed a significantly lower zeta expression in CD3+/4+, CD3+/8+ and CD16+ patient peripheral blood lymphocytes (PBL; n = 10) compared with normal donor PBLs (n = 11). When patient PBLs were compared with the corresponding TAL, the latter showed a significantly higher (CD3+/4+) or equal (CD3+/8+) zeta expression. The EBV status of the tumours did not correlate with zeta expression in the TAL. Immunohistochemical staining revealed zeta-positive lymphocytes among the adjacent bystander cells of the HRS cells in all analysed tumours (n = 8), irrespective of tumour EBV status. In conclusion, these results do not support downregulation of zeta in TAL as a critical mechanism contributing specifically to the immune escape of EBV+ HRS cells.     

Serum inhibin B,FSH, LH and testosterone levels before and after human chorionic gonadotropin stimulation in prepubertal boys with cryptorchidism

BACKGROUND: Several studies have indicated that cryptorchidism is associated with degenerative changes in both Sertoli cells and germ cells. The gonadal peptide hormone inhibin B reflects Sertoli cell function. Low inhibin B levels are found in a large portion of formerly cryptorchid men who show compromised seminiferous tubule function. It is not known if inhibin B can be used to demonstrate early damage of seminiferous tubules in prepubertal boys with cryptorchidism. METHODS: We investigated the relationship between serum levels of inhibin B, testosterone, FSH and LH in 62 prepubertal boys with uni- and bilateral cryptorchidism. Furthermore, we investigated the changes in serum levels of inhibin B and the corresponding changes in serum levels of FSH, LH and testosterone during a short course (3 weeks) of human chorionic gonadotropin (hCG) injections in 18 of these cryptorchid boys. RESULTS: In the 62 prepubertal boys with uni- or bilateral cryptorchidism there were no significant differences in baseline levels (median and range) of inhibin B (88 (20-195) pg/ml vs 78 (35-182) pg/ml; not significant), LH (0.08 (<0.05-0.99) IU/l vs 0.06 (<0.05-1.61) IU/l; not significant) and FSH (0.60 (0.08-3.73) IU/l vs 0.85 (0.25-2.55); not significant) compared with 156 healthy prepubertal boys, and there were no differences in hormonal levels between boys with uni- or bilateral cryptorchidism. There was no correlation between baseline levels of inhibin B and FSH. In boys younger than 9 years, we found no correlation between baseline levels of inhibin B and LH whereas, in boys older than 9 years, baseline levels of inhibin B were positively correlated to baseline LH (Spearman rank correlation coefficient ((R(s))=0.58, P=0.03). Treatment with hCG (1500 IU intramuscularly twice weekly for 3 weeks) resulted in descensus of testes in 9 out of 18 patients. In all boys but one, irrespective of age, hCG induced a marked increase in testosterone into the adult range (from undetectable to 21.8 (7.0-35.4) nmol/l; P<0.001) and completely suppressed FSH and LH levels. Serum levels of inhibin B increased significantly from 116 (50-195) pg/ml to 147 (94-248) pg/ml (P<0.05), but not uniformly. The increase in serum levels of inhibin B was inversely correlated to baseline inhibin B (Rs=-0.52, P=0.03) and baseline FSH (R(s)=-0.59, P<0.01). CONCLUSIONS: We therefore suggest that, in the prepubertal testes, inhibin B is secreted from the prepubertal Sertoli cells following hCG, whereas early pubertal testes with more differentiated Sertoli cells are not able to secrete inhibin B in response to hCG stimulation, perhaps due to lack of germ cell-derived betaB-subunits. We found (a) normal inhibin B levels in prepubertal boys with uni- or bilateral cryptorchidism, (b) that hCG stimulated testosterone markedly and suppressed FSH and LH levels and (c) that hCG treatment stimulated inhibin B levels in the youngest cryptorchid boys. In the oldest prepubertal boys no hCG-induced changes in inhibin B were shown.