Ursodeoxycholate has no beneficial effect on liver function or histology in biliary cirrhosis in the rat

In different cholestatic conditions, the beneficial effects of the tertiary bile acid, ursodeoxycholate, have been described. It is unclear, however, whether ursodeoxycholate also affects the functional and structural alterations induced by chronic biliary obstruction. Therefore, we studied the effect of ursodeoxycholate (100 mg/kg/day) on microsomal function as assessed in vivo by the aminopyrine breath test, on portal hypertension and on the structural composition of the liver in rats with chronic (3-week) biliary obstruction. Hepatic composition was assessed stereologically. Ursodeoxycholate had no effect on any of the parameters measured. We conclude that this form of treatment does not affect advanced liver disease due to common bile duct obstruction. This finding supports one of the proposed mechanisms of action of ursodeoxycholate, namely that it interferes with the ileal absorption of more toxic endogenous bile salts.     

Interleukin-6 has no effect on surfactant or lung function in different lung insults

The current study determined if interleukin-6 (IL-6) had a causative role in the lung dysfunction and/or surfactant alterations associated with three different lung insults. IL-6 (or saline) was instilled into rats followed by mechanical ventilation in vivo for 4 hours. Also, IL-6 (-/-) and wild-type mice were subjected to 3 insults: ex vivo injurious mechanical ventilation; cecal ligation and perforation; and hyperoxia exposure. In all experiments, the presence or absence of IL-6 did not significantly influence gas exchange, lung compliance, or various surfactant measurements. These results suggest that IL-6 may have a limited role in the surfactant alterations observed in acute lung injury.     

Thrombopoietin has a differentiative effect on late-stage human erythropoiesis

To further explore the mechanism of the effect of thrombopoietin (TPO) on erythropoiesis, we used a two-phase culture system to investigate the effect of TPO on late-stage human erythroid lineage differentiation. In serum-free suspension and semisolid cultures of human peripheral blood derived erythroid progenitors, TPO alone did not produce benzidine-positive cells. However, in serum-containing culture, TPO alone stimulated erythroid cell proliferation and differentiation, demonstrated by erythroid colony formation, production of benzidine-positive cells and haemoglobin (Hb) synthesis. Monoclonal anti-human erythropoietin antibody and anti-human erythropoietin receptor antibody completely abrogated the erythroid differentiative ability of TPO in the serum-containing systems. This implied that binding of EPO and EPO-R was essential for erythropoiesis and the resultant signal transduction may be augmented by the signals emanating from TPO-c-Mpl interaction. Experiment of withdrawal of TPO further demonstrated the involvement of TPO in late-stage erythropoiesis. RT-PCR results showed that there was EPO-R but not c-Mpl expression on developing erythroblasts induced by TPO in serum-containing system. Our results establish that TPO affects not only the proliferation of erythroid progenitors but also the differentiation of erythroid progenitors to mature erythroid cells.     

Spontaneous bacterial peritonitis has no effect on the long-term prognosis of cirrhosis patients with ascites

Introduction and objectivesSpontaneous bacterial peritonitis (SBP) is a frequent complication to cirrhosis with an unclear long-term prognosis. We aimed to examine its effect on mortality in two independent patient cohorts.Patients and methodsWe used Danish healthcare data on cirrhosis patients with a first-time paracentesis in 2000–2014 and data from three randomized controlled trials on satavaptan treatment of ascites conducted in 2006–2008. We used the Kaplan-Meier method to estimate cumulative mortality, and Cox regression to compare the confounder-adjusted mortality hazard for patients with vs. without SBP.ResultsIn the Danish Healthcare Cohort, we included 1.282 patients of whom 133 (10.4%) had SBP. The SBP patients’ cumulative 4-month mortality was 51.2% (95% CI: 43.0–59.9%) vs. 34.7% (95% CI: 32.0–37.6) in those without SBP. The SBP patients’ confounder-adjusted mortality hazard was 1.54-fold higher (95% CI: 1.18–2.00) in the four months after paracentesis, but was not increased thereafter (confounder-adjusted mortality hazard 1.02, 95% 0.72–1.46). In the satavaptan trial data of 1,198 cirrhosis patients with ascites, the 93 patients with SBP had a cumulative 4-month mortality of 38.6% (95% CI: 29.3–49.7) compared with 11.4% (95% CI: 8.5–15.2) in those without. The SBP patients’ confounder-adjusted mortality hazard ratio was 3.86 (95% CI: 2.44–6.12) during the first four months, and was 1.23 (95% CI: 0.54–2.83) thereafter.ConclusionsIn both cohorts of patients with cirrhosis, an SBP episode had a high short-term mortality compared to patients without SBP, and had no lasting effect on the long-term mortality.     

Smokeless tobacco or nicotine replacement therapy has no effect on serum immunoglobulin levels

BACKGROUND: Tobacco smokers have lower serum levels of immunoglobulin (Ig)G, mainly due to lower levels of IgG2, than non-smokers. The component(s) in tobacco smoke responsible for this effect is unknown, but animal studies have implicated nicotine as a major contributor to the immunologic effects of smoking. Does nicotine exposure due to use of smokeless tobacco (oral moist snuff) or nicotine replacement therapy influence serum Ig levels in humans? METHODS: Serum content of Ig classes and IgG subclasses was analysed in 77 non-smoking nicotine consumers, including 48 users of oral moist snuff (smokeless tobacco users) and 29 ex-smokers on nicotine replacement therapy, and compared with 44 healthy controls. Former smokers in any group had quit smoking at least 6 months prior to study entry. Ig class and IgG subclass levels were determined by radial immunodiffusion. Systemic nicotine exposure was excluded and confirmed by measuring urine content of cotinine using a quantitative radioimmunoassay. RESULTS: Ig class and IgG subclass levels did not differ significantly between the groups, with the sole exception of IgG4, which was significantly lower in nicotine consumers than in healthy subjects (0.4 +/- 0.3 vs. 0.6 +/- 0.4 g/l, mean +/- SD, 95% confidence interval [-0.3;-0.05]). There was no correlation between any Ig variable and cotinine concentration. CONCLUSIONS: The decreased levels of IgG and IgG2 seen in tobacco smokers do not seem to be an effect of systemic exposure to nicotine.     

Recombinant human interleukin-11 improves thrombocytopenia in patients with cirrhosis

To elucidate the hematopoietic activity of recombinant human interleukin-11 (rhIL-11, [Neumega, Cambridge, MA]) in patients with cirrhosis and thrombocytopenia, we administered rhIL-11 at 50 microg/kg/d subcutaneously to 10 patients for 10 days with a 30-day follow-up period. All treated patients (n = 9) experienced a gradual, yet significant increase in their platelet count above the baseline value (P < or =.01) reaching the peak value (median, 93,000/microL; range, 60,000-206,000/microL) at a median of 13 days (range, 6-23 days). Eight patients (89%) had a significant increase of > or =50% over the baseline value (P <.05). Moreover, further increases to > or =60,000/microL, > or =80,000/microL, and > or =100,000/microL were observed in 100%, 78%, and 33% of the patients, respectively. A subsequent decline in platelet count was observed at a median of 19 days (range, 7-26 days) after the occurrence of peak concentration. A significant increase in neutrophil count was also demonstrated starting on the third day of treatment (P < or =.01). Concurrent with an increase in the serum level of fibrinogen, transaminase levels declined significantly during treatment period, while bilirubin levels continued to drop for up to 20 days after the initiation of treatment (P <.05). The most frequent effects were due to plasma volume expansion, including conjunctival redness and edema. In conclusion, rhIL-11 can improve platelet counts in patients with early cirrhosis and these patients could benefit from rhIL-11 treatment. However, given the high frequency of regimen-related toxicity, the use of rhIL-11 in patients with cirrhosis should be administered with caution.     

Intravenous insulin has no effect on myocardial contractility or heart rate in healthy subjects

Summary To evaluate the acute effects of intravenous insulin on myocardial contractility and heart rate, echocardiography was performed in 12 healthy subjects and continuous heart rate recording in 11 healthy subjects before and during eugly-caemic insulin and glucose infusion. The rate of insulin infusion was 0.5–1.0 mU·kg^–1·min^–1. Serum insulin concentration was increased from 14.1±5.5 (mean±SD) to a plateau level of 91.3±22.8 mU/l. Left ventricular end-diastolic diameter, ejection phase indices and the heart rate remained at basal levels during the intervention. Thus moderate hyperinsulinaemia, induced by euglycaemic insulin and glucose infusion, has no inotropic or chronotropic effects in healthy supine subjects.     

Ultrasound has no anti-inflammatory effect.

The use of therapeutic ultrasound within the Health Service is widespread and growing. The most common indication is to reduce inflammation. We have tested the influence of ultrasound on a model of acute inflammation in the rat, and we have found a complete absence of any anti-inflammatory action.     

Naproxen has greater antipyretic effect on Hodgkin's disease-related fever than no other tumours or infection

In 28 febrile patients with malignant lymphoma or leukaemia, the hourly temperatures were recorded following an oral dose of 125 mg naproxen (50% of normal single adult analgesic dose). 15 patients had clinical infection, and 13 had fever secondary to their malignant disease. Compared to controls, there was no significant antipyretic effect of 125 mg naproxen in infected patients, whereas this small dose in patients without infection had a significant effect. In the uninfected patients, the antipyretic effect was significantly more marked in fever related to Hodgkin's disease than to non-Hodgkin lymphoma or leukaemia. This selective antipyretic effect of a prostaglandin-synthesis inhibitor in tumour-related fever, especially in Hodgkin's disease, is unexplained but may be useful in the palliative treatment of patients with advanced disease.     

Thrombopoietin concentrations are low in patients with cirrhosis and thrombocytopenia and are restored after orthotopic liver transplantation

BACKGROUND: Thrombocytopenia in cirrhotic patients may be due to deficient production of thrombopoietin. AIMS: To determine the relation between thrombopoietin and thrombocytopenia in cirrhotic patients before and after orthotopic liver transplantation. METHODS: Thrombopoietin concentrations and platelet counts were measured in 43 cirrhotic patients and 21 normal controls and serially for 14 days after transplantation in 23/43 patients. RESULTS: 27 of the 43 patients had thrombocytopenia (platelet count less than 120 x 10(9)/l; group 1) whereas 16 patients had normal platelet count (group 2). Thrombopoietin concentrations were lower in group 1 than in group 2 (92.5 (20.3-286.3) v 226.6 (30.1-848.3) pg/ml, p=0.003) and normal controls (92.5 (20.3-286.3) v 158.3 (22.5-232.9) pg/ml, p=0.028). Post-transplantation thrombopoietin concentrations increased with a peak at day 5. The rise was significant in patients with low pretransplantation platelet count (89.1 (21.29-247.6) to 545.1 (66.2-2569) pg/ml; n=16, p=0.001) but not in those with normal platelet count (262.8 (30.1-848.3) to 315.1 (114-954.6) pg/ml; n=7, p=0.47). No correlation was found pretransplantation between spleen volume and platelet count (r=-0.11, p=0.6) or thrombopoietin concentrations (r=-0.04, p=0.8). However, pretransplantation thrombopoietin concentrations correlated with platelet count (r=0.47, p=0.0015), whereas an inverse correlation was found between peak thrombopoietin concentrations and nadir platelet count (r=-0.41 p=0. 049) post-transplantation. CONCLUSIONS: Inadequate thrombopoietin production may contribute to cirrhotic thrombocytopenia. Thrombopoietin production is restored after liver transplantation leading to the resolution of thrombocytopenia.     

Serum interleukin-6 has no discriminatory role in paraproteinaemia nor a prognostic role in multiple myeloma.

We determined interleukin-6 (IL-6) levels in the serum of 212 well-defined patients with newly diagnosed paraproteinaemia and evaluated its discriminatory value and prognostic role in multiple myeloma (MM). Results were compared with serum neural cell adhesion molecule and beta-2-microglobulin, both established prognostic MM markers. Paraproteinaemia-related diagnoses were: MM (60), other haematological diseases (46), solid tumours (35), autoimmune diseases (17) and monoclonal gammopathy of unknown significance (MGUS) (54). The range of IL-6 levels in all diagnostic groups overlapped widely and did not serve as a discriminatory marker in newly diagnosed paraproteinaemia even when patients with infection or fever (42) were excluded. In MM high IL-6 levels (>/= 50 pg/ml) were not associated with a shorter survival (P = 0.24). We compared our results with 20 published studies on serum IL-6 in paraproteinaemia and/or MM. IL-6 data have to be related to the assay used (bio- or immunoassay) and to the status of MM (newly diagnosed, during therapy, progressive disease). We conclude that serum IL-6 is not specific for paraproteinaemia-related diseases and will not serve as a reliable discriminatory or prognostic marker in paraproteinaemia and MM.     

Helicobacter pylori has no effect on plasma ghrelin levels

OBJECTIVE: Helicobacter pylori is the major etiologic agent for chronic active gastritis, and it also plays a crucial role in gastric and duodenal ulcer disease, as well as in gastric carcinoma. H. pylori infection has been shown to decrease plasma somatostatin (SST) and increase plasma gastrin concentrations. Ghrelin is a recently discovered peptide produced mostly in the stomach of rodents and humans and is secreted into the bloodstream. There is no data in the literature about the relationship between H. pylori and ghrelin. DESIGN: Thirty-nine age- and BMI-matched H. pylori infection positive and negative women, from whom biopsy specimens were taken during gastric endoscopy, were included in the study. METHODS: Total ghrelin was measured by enzyme immunoassay (EIA) in Medistek. All samples were measured in duplicate and averaged; results differing by more than 20% were re-assayed. Two biopsy specimens from antrum, corpus and fundus were obtained. RESULTS: Fifteen of the subjects were H. pylori negative and 24 were H. pylori positive. Age, BMI, lipid profile and insulin sensitivity indices of the groups were similar. Plasma ghrelin levels (375.92+/-7.10 vs 370.00+/-4.14 pmol/l; P>0.05) of H. pylori negative and positive groups did not differ significantly. CONCLUSION: H. pylori has no effect on plasma ghrelin concentration.     

Short-term hypothyroidism has no effect on serum leptin concentrations

The aim of the study is to determine the effect of short-term hypothyroidism on serum leptin levels. For this purpose 30 patients with past medical history of thyroidectomy for differentiated thyroid carcinoma were included. Serum leptin concentrations were similar when patients were on thyrotrophin-suppressive thyroxine therapy than when were admitted 4 weeks after stopping thyroxine treatment to perform a routine 131I scan in hypothyroid status (17.0 +/- s.e.m. 2.14 vs. 17.6 +/- s.e.m. 2.41 ng/ml; p = n.s.). Moreover, no differences were obtained when the analysis was performed separately in men and in women. We conclude that short-term hypothyroidism does not alter serum leptin concentrations. Furthermore, our results suggest that thyroid hormones do not operate through changes in serum leptin levels to regulate energy expenditure.     

Screening for autoantibodies in chronic hepatitis C patients has no effect on treatment initiation or outcome

Autoantibodies in hepatitis C virus–infected patients may indicate autoimmune hepatitis or other immune‐mediated diseases. This may impact safety and efficacy of interferon‐based therapy of chronic hepatitis C. We investigated the association between a positive test result for a variety of autoantibodies and the initiation and efficacy of therapy for chronic hepatitis C. We analysed an observational cohort of 24 306 patients for an association between autoantibodies and treatment outcome. 8241 patients were tested simultaneously for antinuclear antibodies (ANA), liver kidney microsomal antibodies (LKM), smooth muscle antibodies (SMA) and antimitochondrial antibodies (AMA). Matched‐pair analysis was performed matching one autoantibody‐positive patient to three controls. Control patients had negative tests for all four antibodies. Analyses were performed for patients with a single positive autoantibody test and for patients with multiple positive autoantibody tests. A positive test result for ANA, LKM, SMA or AMA did not affect the physician's decision to initiate therapy with pegylated interferon and ribavirin. In addition, a positive test for one or multiple autoantibodies did not adversely affect sustained virologic response. There was no difference in fibrosis stage or alanine transaminase at baseline or during therapy irrespective of antibody status. Thyroid dysfunction was more frequent in patients with positive LKM antibodies (P = 0.004). Initiation of therapy for chronic hepatitis C and outcome were not affected by the presence of ANA, LKM, SMA or AMA. Routine testing of these autoantibodies seems not warranted. Determination of autoantibodies should be guided by individualized clinical decisions.     

Substituting enzymatically interesterified butter for native butter has no effect on lipemia or lipoproteinemia in Man

The aim of this study was to determine whether substituting enzymatically interesterified butter for native butter in the usual diet affects lipid and lipoprotein levels in man. Parameters studied were serum total cholesterol, LDL-cholesterol, HDL-cholesterol, free cholesterol, phospholipids, triglycerides, apoA1 and apoB and the fatty acid composition of serum triglycerides, free fatty acids, phospholipids and cholesterol esters. Subjects were healthy volunteers and a controlled design was used. The only mathematically significant difference found when interesterified butter was substituted for butter was an about 7% lower fraction of oleic acid in the serum cholesterol esters (p = 0.005). In contrast to an earlier study where chemically interesterified butter fat was substituted for native butter, no indications are found in this study that replacing native butter by enzymatically interesterified butter, in amounts normally consumed, may have any beneficial effect on health.     

Famotidine has no significant effect on gonadal function in man

The effect of a single bedtime dose of famotidine 40 mg on gonadal function was studied in 8 male duodenal ulcer patients. The drug was orally administered for 4 weeks. Our results show that this new H2 blocker influences basal and stimulated serum levels of neither testosterone nor gonadotrophins (LH, FSH). Besides, no significant variations were observed before and after famotidine treatment in seminal fluid characteristics evaluated in 5 out of 8 cases. It can be concluded that famotidine appears to leave gonadal function unaffected in man.     

Anemia in early rheumatoid arthritis is associated with interleukin 6-mediated bone marrow suppression, but has no effect on disease course or mortality

OBJECTIVE: Anemia of chronic disease (ACD) is the most common extraarticular manifestation of rheumatoid arthritis (RA), but there is limited information on the cause and consequences of ACD. We investigated the prevalence, relation with proinflammatory cytokines, and effect on disease outcome of ACD in patients with RA. METHODS: The presence of anemia was analyzed in a cohort of 111 consecutive patients with early RA. Anemia was related to markers of erythropoiesis and inflammation [clinically and by levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum interleukin 1beta (IL-1beta), IL-2, IL-6, IL-8, and tumor necrosis factor-alpha]. The frequency of various disease outcomes during the mean followup of 74 months was compared between ACD and nonanemic patients. RESULTS: ACD was present in 25% during the first year of disease. ACD was associated with higher CRP (45 vs 22 g/l; p = 0.04) and ESR levels (54 vs 33 mm/h; p = 0.002). Hemoglobin levels were inversely correlated with serum erythropoietin (p = 0.003) in univariate analysis, but in multivariate analysis only ESR (p = 0.005) and IL-6 (p = 0.056) remained as independent predictors of hemoglobin levels. Presence of ACD was not associated with later development of disease manifestations or mortality. CONCLUSION: While ACD affected 25% of patients with RA early in the disease course, this had no influence on disease outcome including mortality during the following 6 years. The association between IL-6 and ACD suggests that IL-6-mediated bone marrow suppression is the main mechanism for development of ACD in RA.