Effect of liraglutide on anthropometric measurements, sagittal abdominal diameter and adiponectin levels in people with type 2 diabetes treated with multiple daily insulin injections: evaluations from a randomized trial (MDI-liraglutide study 5).

AIM: Use of the glucagon-like peptide 1 receptor agonist liraglutide has been shown to reduce weight. Different types of anthropometric measurements can be used to measure adiposity. This study evaluated the effect of liraglutide on sagittal abdominal diameter, waist circumference, waist-to-hip ratio and adiponectin levels in people with type 2 diabetes (T2D) treated with multiple daily insulin injections (MDI). MATERIALS AND METHODS: In the multicentre, double-blind, placebo-controlled MDI-liraglutide trial, 124 individuals with T2D treated with MDI were randomized to either liraglutide or placebo. Basal values of weight, waist circumference, waist-to-hip ratio, sagittal abdominal diameter and adiponectin were compared with measurements at 12 and 24 weeks after randomization. RESULTS: Baseline-adjusted mean weight loss was 3.8 ± 2.9 kg greater in liraglutide than placebo-treated individuals (p < 0.0001). Waist circumference was reduced by 2.9 ± 4.3 cm and 0.2 ± 3.6 cm in the liraglutide and placebo groups, respectively, after 24 weeks (baseline-adjusted mean difference: 2.6 ± 4.0 cm, p = 0.0005). Corresponding reductions in sagittal abdominal diameter were 1.1 ± 1.7 cm and 0.0 ± 1.8 cm (baseline-adjusted mean difference: 1.1 ± 1.7 cm, p = 0.0008). Hip circumference was reduced in patients randomized to liraglutide (baseline-adjusted mean difference between treatment groups: 2.8 ± 3.8 cm, p = 0.0001), but there was no significant difference between the groups in either waist-to-hip ratio (baseline-adjusted mean difference: 0.0 ± 0.04 cm, p = 0.51) or adiponectin levels (baseline-adjusted mean difference: 0.8 ± 3.3 mg L-1, p = 0.17). Lower HbA1c and mean glucose levels measured by masked continuous glucose monitoring at baseline were associated with greater effects of liraglutide on reductions in waist circumference and sagittal abdominal diameter. CONCLUSIONS: In patients with T2D, adding liraglutide to MDI may reduce abdominal and hip obesity to a similar extent, suggesting an effect on both visceral and subcutaneous fat. Liraglutide had greater effects on reducing abdominal obesity in patients with less pronounced long-term hyperglycaemia but did not affect adiponectin levels.

First-Time Fathers' Experience of Support from Midwives in Maternity Clinics: An Interview Study.

BACKGROUND: Research shows that first-time fathers want to take part in preparation for birth and parenthood but they describe being excluded by health professionals. AIM: The aim of this study was to illustrate first-time fathers' experiences of support from midwives in maternity clinics as a step in the validation of "The Father Perceived-Professional-Support" (The FaPPS) scale. METHODS: A qualitative content analysis with an inductive and deductive approach was used; seven first-time fathers were strategically selected and interviewed. In the inductive part the following open question was asked: "How did you perceive the support from the antenatal midwife/midwives?" In the deductive part, the fathers were asked to respond to the FaPPS scale, in order to receive their thoughts and understanding of the scale, inspired by the "Think-aloud" method. FINDINGS: The inductive results showed two main categories: Experience of not knowing what support they needed and Experience of being excluded. The fathers found support from other fathers in parental education classes, but they lack time to discuss. Overall it seems as if the fathers answered both from their own perspective and from the mothers' perspective. This was not evident in the deductive results. The FaPPs scale should therefore include professionals' ability to strengthen social support from other first-time fathers and professionals' ability to offer support to the mother. Conclusion and Clinical Implications. The fathers experienced exclusion both by themselves and also by midwives. Midwives should offer both parents the opportunity to pose questions. It is important for expectant fathers that time for discussion is planned in parental education classes. The FaPPS scale is useful but needs further development. Parts of our result are in line with earlier research, for decades; therefore it is necessary to focus more on support for fathers.

Protonation of different goethite surfaces--Unified models for NaNO3 and NaCl media.

Acid-base titration data for two goethites samples in sodium nitrate and sodium chloride media are discussed. The data are modeled based on various surface complexation models in the framework of the multi site complexation (MUSIC) model. Various assumptions with respect to the goethite morphology are considered in determining the site density of the surface functional groups. The results from the various model applications are not statistically significant in terms of goodness of fit. More importantly, various published assumptions with respect to the goethite morphology (i.e., the contributions of different crystal planes and their repercussions on the "overall" site densities of the various surface functional groups) do not significantly affect the final model parameters within simple 1-pK approximations. The simultaneous fit of the chloride and nitrate data results in electrolyte binding constants, which are applicable over a wide range of electrolyte concentrations including mixtures of chloride and nitrate. Model parameters for the goethite sample with 90 m2/g specific surface area are in excellent agreement with parameters that were independently obtained by another group on different goethite titration data sets.

The bone morphogenetic protein type Ib receptor is a major mediator of glial differentiation and cell survival in adult hippocampal progenitor cell culture.

Bone morphogenetic proteins (BMPs) act as growth regulators and inducers of differentiation. They transduce their signal via three different type I receptors, termed activin receptor-like kinase 2 (Alk2), Alk3, or bone morphogenetic protein receptor Ia (BMPRIa) and Alk6 or BMPRIb. Little is known about functional differences between the three type I receptors. Here, we have investigated consequences of constitutively active (ca) and dominant negative (dn) type I receptor overexpression in adult-derived hippocampal progenitor cells (AHPs). The dn receptors have a nonfunctional intracellular but functional extracellular domain. They thus trap BMPs that are endogenously produced by AHPs. We found that effects obtained by overexpression of dnAlk2 and dnAlk6 were similar, suggesting similar ligand binding patterns for these receptors. Thus, cell survival was decreased, glial fibrillary acidic protein (GFAP) expression was reduced, whereas the number of oligodendrocytes increased. No effect on neuronal differentiation was seen. Whereas the expression of Alk2 and Alk3 mRNA remained unchanged, the Alk6 mRNA was induced after impaired BMP signaling. After dnAlk3 overexpression, cell survival and astroglial differentiation increased in parallel to augmented Alk6 receptor signaling. We conclude that endogenous BMPs mediate cell survival, astroglial differentiation and the suppression of oligodendrocytic cell fate mainly via the Alk6 receptor in AHP culture.

Peripheral arterial disease. Contrast-enhanced 3D MR angiography of the lower leg and foot compared with conventional angiography.

PURPOSE: To determine whether contrast-enhanced 3D MR angiography (CE MRA) could replace digital subtraction angiography (DSA) for the evaluation of atherosclerotic peripheral vascular disease of the lower leg and foot. MATERIAL AND METHODS: Thirty-five patients with symptoms of atherosclerotic disease of the leg were examined prospectively with CE MRA of the foot and the lower legs as well as with DSA from the aorta to the pedal arches. The MRA technique was focused on optimal imaging of the arteries of the foot. RESULTS: The agreement between CE MRA and DSA for grading of stenosis was moderate to good (weighted kappa-values 0.48-0.80). The sensitivity of CE MRA for detection of significant stenosis (> or = 50%) was 92% and the specificity was 64% with DSA as gold standard. CONCLUSION: CE MRA is a fairly accurate method for the demonstration of atherosclerotic disease below the knee including the pedal arches. It can replace DSA for the assessment of distal arteries in patients with impaired renal function. However, image quality and resolution still needs to be improved before CE MRA can become the method of choice in all patients.

Residual insulin secretion is not coupled to a maintained glucagon response to hypoglycaemia in long-term type 1 diabetes.

OBJECTIVES: To evaluate the influence of residual beta-cell function on glucagon secretion and glucose counter-regulation following hypoglycaemia in type 1 diabetes. DESIGN AND SUBJECTS: The hormonal counter-regulatory responses to standardized insulin-induced hypoglycaemia were investigated, 18 patients with type 1 diabetes of long duration and 12 healthy subjects were investigated. Nine of the diabetic patients (diabetes duration 17 +/- 1 years) had residual insulin secretion, as reflected by persistent urinary C-peptide excretion. The other nine diabetic patients (diabetes duration 21 +/- 1 years) were C-peptide negative. RESULTS: Similar hypoglycaemic nadirs were found in all groups (2.1-2.3 mmol L-1), whereas the recovery of plasma glucose levels was delayed similarly in the diabetic groups. In the control subjects, plasma glucagon increased ( approximately 50%). No significant glucagon response was registered in either of the two diabetic groups. The maximum plasma adrenaline and pancreatic polypeptides (PP) responses to hypoglycaemia were comparable in the two diabetic patient groups; the peak values being lower (P < 0.05) than in the controls. Plasma noradrenaline, growth hormone and cortisol responses to hypoglycaemia were similar in all three groups. CONCLUSION: Residual beta-cell function in patients with long-term type 1 diabetes is not accompanied by preservation of the glucagon response to hypoglycaemia. As the two markers of autonomic function (adrenaline and PP) were similarly reduced in the two diabetic groups, the findings instead favour the concept that the defective glucagon secretory response to hypoglycaemia is because of autonomic nervous dysfunction.

Frequent use of the hospital emergency department is indicative of high use of other health care services.

STUDY OBJECTIVE: We sought to determine the proportion of emergency department patients who frequently use the ED and to compare their frequency of use of other health care services at non-ED sites. METHODS: A computerized patient database covering all ambulatory visits and hospital admissions at all care facilities in the county of Stockholm, Sweden, was used. Frequent ED patients were defined as those making 4 or more visits in a 12-month period. RESULTS: Frequent users comprised 4% of total ED patients, accounting for 18% of the ED visits. The ED was the only source of ambulatory care for 13% of frequent versus 27% of rare ED users (1 ED visit). Primary care visits were made by 72% of frequent ED users versus 57% by rare ED visitors. The corresponding figures for hospital admission were 80% and 36%, respectively. Frequent ED visitors were also more likely to use other care facilities repeatedly: their odds ratio (adjusted for age and sex) was 3.43 (95% confidence interval [CI] 3.10 to 3.78) for 5 or more primary care visits and 29.98 (95% CI 26.33 to 34.15) for 5 or more hospital admissions. In addition, heavy users had an elevated mortality (standardized mortality ratio 1.55; 95% CI 1.26 to 1.90). CONCLUSION: High ED use patients are also high users of other health care services, presumably because they are sicker than average. A further indication of serious ill health is their higher than expected mortality. This knowledge might be helpful for care providers in their endeavors to find appropriate ways of meeting the needs of this vulnerable patient category.

Depressive symptoms in hypothyroid disorder with some observations on biochemical correlates.

Lumbar punctures and ratings of depressive symptoms were done in hypothyroid patients before and during L-thyroxine therapy. Before treatment, the most prominent symptoms were concentration difficulties, lassitude, and reduced sexual interest. All patients suffered from sleep disturbances. Suicidal thoughts did not occur at all. Inner tension was negatively correlated with the anxiogenic cholecystokinin tetrapeptide (CCK-4) in the cerebrospinal fluid (CSF), while reduced sexual interest was negatively correlated with CSF tryptophan. Furthermore, failing memory correlated negatively with T3 as well as T4 in serum. A positive correlation was found between failing memory and serum TSH. All patients improved significantly during treatment. No biochemical correlates were found. In conclusion, hypothyroidism is associated with major depressive symptoms. CSF CCK-4 and tryptophan, as well as serum thyroid hormones, may constitute biochemical correlates for some of these symptoms.

CSF collection time at lumbar puncture is influenced by plasma cholesterol and triglycerides.

It is a fairly well-known fact that the CSF collection time (tapping time) at lumbar puncture may influence CSF levels of monoamine compounds (e.g. the serotonin metabolite 5-hydroxyindoleacetic acid, 5-HIAA) and some neuropeptides. Since serum levels of cholesterol and triglycerides and low CSF levels of 5-HIAA have been linked to violent behaviour and impulsivity, we investigated retrospectively whether serum cholesterol and triglycerides affect CSF collection time. The series consists of 14 healthy males lumbar punctured at the L(4-5) level. We found that both serum cholesterol and serum triglycerides influenced the CSF collection time for 12 ml of CSF (R = 0.77; p = 0.0067). There was no correlation between cholesterol in serum and CSF, nor between cholesterol in the CSF and collection time. However, we accidentally found a correlation between cholesterol in the CSF and age. The proposed hypothesis tries to explain why cholesterol- and triglyceride-rich lipoprotein particles modify the CSF collection time and influence endothelial function with a subsequent effect on CSF production and/or intraspinal pressure. Thus, it may be of interest to pay attention to serum cholesterol and triglycerides, their effect on CSF collection time and, in the next step, their putative impact on levels of various compounds in the CSF.

MR imaging following herniography in patients with unclear groin pain.

The aims of the present study were to assess if MRI gives the same diagnostic information as herniography concerning the presence of hernias and reveals other causes of groin pain. The prospective study enrolled 20 patients referred for herniography, 6 women and 14 men, mean age 48 years. After herniography the patients underwent MRI using T1-weighted, fat-suppressed inversion recovery (STIR), and magnetic resonance cholangiopancreaticography (MRCP) pulse sequences. No contrast medium was administered at MRI. Herniography revealed 11 hernias and MRI depicted 8 of these. Magnetic resonance imaging depicted well the anatomy in the groins. In 3 patients where hernias were not revealed, MRI revealed inflammatory changes in the symphysis region as a possible cause of groin pain. The primary diagnostic tool for diagnosing hernias is herniography. If the herniogram is normal, MRI may reveal other causes of groin pain and may also better visualize related structures in the groin.

Pyrocatechol Violet Complexation at the Boehmite-Water Interface.

Acid/base reactions and pyrocatechol violet complexation at the boehmite-solution interface have been investigated in 0.10 M K(Cl) solution at 298.2 K in the range 5.0

Metal Ion Coordination at the Water-Manganite (gamma-MnOOH) Interface.

The local structure of Cd(II) surface complexes adsorbed onto manganite (gamma-MnOOH) has been investigated by extended X-ray absorption fine structure (EXAFS) spectroscopy. Adsorption experiments were carried out within the pH range 7.4-9.8 and with surface coverage from 2.2 to 8.9 µmol/m(2). Quantitative analysis of the EXAFS spectra shows little difference in the local coordination environment of Cd regardless of the coverage. Analysis of the first shell required a third cumulant in an asymmetric distribution model (i.e., non-Gaussian distribution), indicating distorted CdO(6) octahedra with an average Cd-O distance of 2.31 Å. A single second shell of Mn neighbors at a constant distance of 3.33 Å was detected. This comparatively short distance shows that inner-sphere complexes are formed. No Cd neighbor was found which means that cadmium hydroxide precipitation or cluster formation does not occur at the surface at the experimental conditions probed in this study. We assign the Cd-Mn distance to edge sharing between CdO(6) and MnO(6) octahedra, with a geometry similar to that in the mixed solid Cd(2)Mn(3)O(8). This adsorption mode is possible on the {110} and {010} cleavage planes of manganite. Copyright 2000 Academic Press.

Benzenecarboxylate Surface Complexation at the Goethite (alpha-FeOOH)/Water Interface.

A surface complexation model describing the adsorption of three benzenecarboxylates (phthalate, trimellitate, and pyromellitate) on goethite (alpha-FeOOH) was calibrated on data using goethite particles of 37 and 43 m(2)/g surface area. The models predict potentiometric titration and batch adsorption data with the multisite complexation model coupled with the three-plane model to account for surface electrostatics. The modeling parameters were found to be similar to those calibrated on benzenecarboxylate adsorption data on goethite particles of 90 m(2)/g (Boily et al. Geochim. Cosmochim. Acta, in press). The significance of the benzenecarboxylate-dependent values of the modeling parameters is also discussed. The values of the capacitances of the inner- and outer-Helmholtz planes were shown to be important modeling parameters to model the benzenecarboxylate-dependent slopes of the adsorption edges. It was shown that the larger the charge of the ligand, the larger the capacitance of the outer-Helmholtz plane. Copyright 2000 Academic Press.

CT and MR imaging of the liver. Clinical importance of nutritional status.

PURPOSE: In an experimental study in rats a correlation between nutritional status and hepatic attenuation in CT and signal intensities in MR imaging was shown. Is physiological nutritional status of importance in clinical CT and MR imaging? MATERIAL AND METHODS: In a cross-over study including 12 healthy volunteers (6 women and 6 men, mean age 34 years), CT and MR imaging of the liver were performed with nutritional status at three different levels, i.e., normal, fasting and after glycogen-rich meals. CT and MR were performed on clinical imaging systems and hepatic attenuation and signal intensity, respectively, were assessed. In MR, T1-weighted, proton density-weighted and T2-weighted pulse-sequences were used. RESULTS: In CT there were significantly (p<0.01) higher liver attenuations in normal nutritional status and after glycogen rich-meals compared to the fasting condition. The difference between fasting and glycogen-rich meals were 10.5 HU for men, 7.4 for women and mean 8.8 HU for all 12 volunteers. In MR imaging the differences were small and non-significant. The results of this study are in accordance with an earlier experimental study in rats. CONCLUSION: In CT it may be of importance not to have patients in a fasting condition as it lowers the attenuation in normal liver tissue. The findings are important for planning of clinical studies where hepatic attenuation will be assessed and may be of some importance in clinical CT. In MR imaging the results indicate that the nutritional status is of less importance.

The influence of lipophilicity on binding of boronated DNA-intercalating compounds in human glioma spheroids.

Five boronated DNA-intercalating compounds [5-ortho-carboranyl phenanthridinium (5-o-CP), 5-para-carboranyl phenanthridinium (5-p-CP), 6-para-carboranyl phenanthridinium, water-soluble boronated phenanthridinium and water-soluble boronated acridine (WSA1)], primarily developed for boron neutron capture therapy (BNCT), were analysed regarding their binding in cultured human malignant glioma spheroids. Comparisons were made with the corresponding DNA intercalators ethidium bromide and acridine orange. Octanol/phosphate buffered saline-water coefficients were determined for all compounds, and it was found that the most lipophilic (5-o-CP and 5-p-CP) were most toxic and accumulated high amounts of boron in monolayer cells. These compounds bound primarily in the outermost part of spheroids with poor penetration into the inner region, even after 2 days of continuous exposure. On the other hand, the most hydrophilic compound (WSA1) showed lower toxicity and lower boron accumulation in monolayer cells, and rapid binding in the inner region of spheroids. A reasonable explanation for this observation is that the lipophilic compounds interact mainly with lipophilic parts of the cells, like cellular membranes, and therefore rapidly binds to cells, preventing penetration and binding to cells in the deeper region of the spheroids. The possibility of using these compounds for BNCT are discussed.

Competitive Metal Ion Adsorption in Goethite Systems Using In Situ Voltammetric Methods and Potentiometry.

Competitive complexation with respect to the binary-metal ion combinations Cu(II)-Zn(II), Cu(II)-Pb(II), and Pb(II)-Zn(II) were studied at the goethite (alpha-FeOOH)-water interface (25 degrees C, I = 0.1 M NaNO(3)). In addition to potentiometric titrations and batch adsorption experiments, an in situ voltammetric technique was utilized. Sorption studies were performed within the ranges 3.5

Cholecystokinin peptides in cerebrospinal fluid: a study in healthy male subjects lumbar-punctured without preceding strict bed-rest.

In a recent study we analysed the concentrations of two forms of cholecystokinin (CCK), CCK-8S (sulphated) and CCK-4 in cerebrospinal fluid (CSF) obtained from 14 healthy male volunteers lumbar-punctured after a minimum of eight hours of strict bed-rest. We have now lumbar-punctured another group of 14 healthy males, using the same procedure except for the requirement of strict bed-rest prior to puncture. In contrast to our previous study, the concentration of CCK-4 (but not CCK-8S) was significantly higher in the second CSF fraction (7-12 ml) than in the first one (0-6 ml). On using the concentration ratio between the second and first fraction, CCK-8S (but not CCK-4) correlated positively with the atmospheric pressure, which is in contrast to our previous study in which a significant negative correlation was found. When the lumbar CSF concentrations were expressed as the concentration per minute of tapping-time (an estimate of the mass flow), atmospheric pressure, age and the neuraxis distance in the lying position made significant contributions to the variance in CCK-8S. A significant positive correlation with atmospheric pressure was found for CCK-4. In conclusion, the results indicate that the question of strict bed-rest or not prior to lumbar puncture may have to be considered when interpreting data on lumbar CSF concentrations of CCK. A controlled study is warranted.