Blood glucose response after oral lactulose intake in type 2 diabetic individuals

BACKGROUNDLactulose is approved for the symptomatic treatment of constipation, a gastrointestinal (GI) complication common in individuals with diabetes. Lactulose products contain carbohydrate impurities (e.g., lactose, fructose, galactose), which occur during the lactulose manufacturing process. These impurities may affect the blood glucose levels of individuals with type 2 diabetes mellitus (T2DM) using lactulose for the treatment of mild constipation. A previous study in healthy subjects revealed no increase in blood glucose levels after oral lactulose intake. However, it is still unclear whether the intake of lactulose increases blood glucose levels in individuals with diabetes.AIMTo evaluate the blood glucose profile after oral lactulose intake in mildly constipated, non-insulin-dependent subjects with T2DM in an outpatient setting.METHODSThis prospective, double-blind, randomized, controlled, single-center trial was conducted at the Clinical Research Center at the Medical University of Graz, Austria, in 24 adult Caucasian mildly constipated, non-insulin-dependent subjects with T2DM. Eligible subjects were randomized and assigned to one of six treatment sequences, each consisting of four treatments stratified by sex using an incomplete block design. Subjects received a single dose of 20 g or 30 g lactulose (crystal and liquid formulation), water as negative control or 30 g glucose as positive control. Capillary blood glucose concentrations were measured over a period of 180 min post dose. The primary endpoint was the baseline-corrected area under the curve of blood glucose concentrations over the complete assessment period [AUC_{baseline_c (0-180 min)}]. Quantitative comparisons were performed for both lactulose doses and formulations vs water for the equal lactulose dose vs glucose, as well as for liquid lactulose vs crystal lactulose. Safety parameters included GI tolerability, which was assessed at 180 min and 24 h post dose, and adverse events occurring up to 24 h post dose.RESULTSIn 24 randomized and analyzed subjects blood glucose concentration-time curves after intake of 20 g and 30 g lactulose were almost identical to those after water intake for both lactulose formulations despite the different amounts of carbohydrate impurities (≤ 3.0% for crystals and approx. 30% for liquid). The primary endpoint [AUC_{baseline_c (0-180 min)}] was not significantly different between lactulose and water regardless of lactulose dose and formulation. Also with regard to all secondary endpoints lactulose formulations showed comparable results to water with one exception concerning maximum glucose level. A minor increase in maximum blood glucose was observed after the 30 g dose, liquid lactulose, in comparison to water with a mean treatment difference of 0.63 mmol/L (95% confidence intervals: 0.19, 1.07). Intake of 30 g glucose significantly increased all blood glucose endpoints vs 30 g liquid and crystal lactulose, respectively (all P < 0.0001). No differences in blood glucose response were observed between the different lactulose formulations. As expected, lactulose increased the number of bowel movements and was generally well tolerated. Subjects experienced only mild to moderate GI symptoms due to the laxative action of lactulose.CONCLUSIONBlood glucose AUC_{baseline_c (0-180 min)} levels in mildly constipated, non-insulin dependent subjects with T2DM are not affected by the carbohydrate impurities contained in 20 g and 30 g crystal or liquid lactulose formulations.     

Die Furchung der Gro?hirnrinde bei einer 18j?hrigen Tigerin

Ohne ZusammenfassungMit 8 Textabbildungen.     

Serum β2-Microglobulin and Serum Thymidine Kinase are Independent Predictors of Progression-Free Survival in Chronic Lymphocytic Leukemia and Immunocytoma

Chronic lymphocytic leukemia (CLL) and immunocytoma (IC) are remarkably heterogeneous with regard to their clinical course. The current staging systems can distinguish prognostic subgroups, but do not seem to predict the risk of disease progression of an individual patient with sufficient accuracy. Given the increase of treatment options for CLL and IC, additional parameters are needed to decide which patients may benefit from early or intensified treatment. It has been shown that two biochemical markers, serum β₂microglobulin (s-β₂) and serum thymidine kinase (s-TK), might identify CLL and IC patients at high risk of disease progression. Therefore, the prognostic value of these two serum parameters was compared with a panel of several established prognostic factors in a prospective clinical trial. 113 patients with CLL and 41 patients with IC (mean age ± SD 63.9 ± 10.7 years) were included. The following parameters were determined: histopathological diagnosis (IC vs. CLL), age, sex, performance status (Karnofsky index), B symptoms, peripheral blood lymphocyte count, platelet count, blood hemoglobin, serum lactate dehydrogenase (s-LDH), S-β₂M, s-TK, serum creatinine, number of lymph node areas involved, prior therapy, and the time from diagnosis to inclusion in the study. Univariate analyses showed that nine parameters (Karnofsky index, peripheral blood lymphocytosis, platelet count, blood hemoglobin, lymph node areas involved, pretreatment, s-LDH, s-β₂M, and s-TK) significantly predicted progression-free survival. In a Cox regression model, only four of these parameters provided independent prognostic information on progression-free survival: 1. S-β₂M, 2. Karnofsky index, 3. platelet count, and 4. s-TK. The results show that s-β₂M and s-TK independently predict progression-free survival in patients with CLL and IC, and suggest that these prognostic factors may allow an improved prediction of progression-free survival, particularly in early disease stages.     

Multicenter P300 brain mapping of impaired attention to cues in hyperkinetic children

OBJECTIVE: To measure specific neurophysiological attention deficits in children with hyperkinetic disorders (HD; the ICD-10 diagnosis for severe and pervasive attention-deficit/hyperactivity disorder [ADHD]). METHOD: In a multicenter sample of 148 children with HD and control children aged 8 to 14 years, event-related potential maps were recorded during a cued continuous performance test (A-X/O-X). Maps to cues (requiring attention but no response) and distractors and performance were tested for differences between age- and sex-matched HD and control groups (n = 57 each), as well as between clinics (n = 5). RESULTS: The N1, P3a, and P3b maps revealed reliable attention effects, with larger amplitudes after cues than after distractors, and only minor differences across clinics. Children with HD missed more targets, made more false alarms, and had larger N1 followed by smaller P3b amplitudes after cues than did controls. Cue-P3b amplitude correlated with detecting subsequent targets. Cue-P3b tomography indicated posterior sources that were attenuated in children with HD. CONCLUSIONS: Brain mapping indicates that children with HD attend to cues (preceding potential targets) with increased initial orienting (N1) followed by insufficient resource allocation (P3b). These multiple, condition-specific attention deficits in HD within 300 msec extend previous results on ADHD and underline the importance of high temporal resolution in mapping severe attention deficits.     

Acute effects of N-acetylcysteine on skeletal muscle microcirculation following closed soft tissue trauma in rats.

Trauma-induced microcirculatory dysfunction, formation of free radicals and decreased endothelial release of nitric oxide (NO) contribute to evolving tissue damage following skeletal muscle injury. Administration of N-acetylcysteine (NAC) known to scavenge free radicals and generate NO is considered a valuable therapeutic approach. Thus, the objective of this study was to quantitatively analyze the acute effects of NAC on skeletal muscle microcirculation and leukocyte-endothelial cell interaction following severe standardized closed soft tissue injury (CSTI). Severe CSTI was induced in the hindlimbs of 14 male anesthetized Sprague-Dawley rats using the controlled impact injury technique. Rats were randomly assigned (n = 7) to high-dose intravenous infusion of NAC (400 mg/kg body weight) or isovolemic normal saline (NS). Non-injured, sham-operated animals (n = 7) were subjected to the same surgical procedures but did not receive any additional fluid. Creatin kinase (CK) activity was assessed at baseline, 1 h before and 2 h following posttraumatic NAC or NS infusion. Microcirculation of the extensor digitorum longus (EDL) muscle was analyzed using intravital microscopy and Laser-Doppler flowmetry (LDF). Edema index (EI) was calculated by measuring the EDL wet-to-dry weight ratio (EI=injured/contralateral limb). EDL-muscles were analyzed for desmin immunoreactivity and granulocyte infiltration. Microvascular deteriorations observed following NS-infusion were effectively reversed by NAC: Functional capillary density was restored to levels found in sham-operated animals and leukocyte adherence was significantly (p < 0.05) reduced compared to the NS group. NAC significantly (p < 0.05) increased erythrocyte flux determined by Laser-Doppler flowmetry. Posttraumatic serum CK levels and EI were significantly (p < 0.05) decreased by NAC. During the posttraumatic acute phase, single infusion of NAC markedly reduced posttraumatic microvascular dysfunction, attenuated both leukocyte adherence and tissue infiltration. NAC also decreased CSTI-induced edema formation and myonecrosis as reflected by attenuated serum CK levels and attenuated loss of desmin immunoreactivity. NAC may serve as an effective therapeutic strategy by supporting microvascular blood supply and tissue viability in the early posttraumatic period. Additional studies aimed at long-term analysis and investigation of injury severity--or dosage dependency are needed.     

Dilemmas of focus group recruitment and implementation: a pilot perspective

In this paper, Isis Lioba Howatson-Jones reviews some of the dilemmas experienced in arranging focus groups, particularly for the novice researcher and draws upon a pilot research project on qualified nurses' learning as illustration. The paper explores ways of overcoming recruitment and method issues during the pilot phase of a study, and presents a number of recommendations for the practice and conduct of focus groups.     

Cost‐effectiveness of psoriasis therapy with etanercept in Germany

Background: We estimated the cost‐effectiveness of intermittent therapy with etanercept in patients with moderate‐to‐severe plaque‐type psoriasis in comparison to non‐systemic therapy in Germany. Patients and Methods: We performed a cost‐utility analysis using the endpoint costs per quality‐adjusted life year gained (costs/QALY). For this purpose, we adapted a UK‐based Markov model by means of resource use data that we derived from a German cost study. Efficacy data, information on frequency of adverse events and changes in quality of life were derived from three pooled clinical trials. We extrapolated the further course of the disease and its treatment over a 10 year course. Results: For patients with an initial Psoriasis Area and Severity Index (PASI) > 10 and a Dermatology Life Quality Index (DLQI) > 10 the incremental cost‐effectiveness ratio (ICER) for etanercept compared to non‐systemic therapy was 45,491 €/QALY. For patients with PASI and DLQI > 15 costs/QALY were 32,058 € and among patients with severe plaque psoriasis (DLQI and PASI > 20) 18,154 € . Conclusions: According to internationally accepted levels of cost‐effectiveness thresholds, the intermittent treatment of (moderate to) severe plaque‐type psoriasis with etanercept is a cost‐effective measure within the German healthcare system.     

Blood glucose response after oral intake of lactulose in healthy volunteers: A randomized,controlled, cross-over study

AIM To investigate possible changes of blood glucose levels after oral intake of lactulose in healthy subjects.METHODS The study was performed as prospective, randomized, two-part study with 4-way cross-over design with n = 12 in each study arm. Capillary blood glucose levels were determined over a time period of 180 min after intake of a single dose of 10 g or 20 g lactulose provided as crystal or liquid formulation. During the manufacturing process of lactulose, impurities with sugars(e.g., lactose, fructose, galactose) occur. Water and 20 g glucose were used as control and reference. Because lactulose is used as a functional food ingredient, it may also be consumed by people with impaired glucose tolerance, including diabetics. Therefore, it is of interest to determine whether the described carbohydrate impurities may increase blood glucose levels after ingestion. RESULTS The blood glucose concentration-time curves after intake of 10 g lactulose, 20 g lactulose, and water were almost identical. None of the three applications showed any changes in blood glucose levels. After intake of 20 g glucose, blood glucose concentration increased by approximately 3 mmol/L(mean Cmax = 8.3 mmol/L), reaching maximum levels after approximately 30 min and returning to baseline within approximately 90 min, which was significantly different to the corresponding 20 g lactulose formulations(P 0.0001). Comparing the two lactulose formulations, crystals and liquid, in the dosage of 10 g and 20 g, there was no difference in the blood glucose profile and calculated pharmacokinetic parameters despite the different amounts of carbohydrate impurities(1.5% for crystals and 26.45% for liquid). Anyhow, the absolute amount of single sugars was low with 0.3 g in crystals and 5.29 g in liquid formulation in the 20 g dosages. Lactulose was well tolerated by most volunteers, and only some reported mild to moderate mainly gastrointestinal side effects. CONCLUSION The unchanged blood glucose levels after lactulose intake in healthy subjects suggest its safe use in subjects with impaired glucose tolerance.