Gastric motility: Measurement, symptoms and therapy

Gastric motility disorders, including delayed gastric emptying (gastroparesis), impaired postprandial fundic relaxation, and gastric myoelectrical disorders, can occur in type 1 diabetes, chronic renal failure, and functional dyspepsia (FD). Symptoms like upper abdominal pain, early satiation, bloating, nausea and vomiting may be related to gastroparesis. Diabetic gastroparesis is related to autonomic neuropathy. Scintigraphy is the gold standard in measuring gastric emptying, but it is expensive, requires specific equipment, and exposes patients to radiation. It also gives information about the intragastric distribution of the test meal. The 13C-octanoic acid breath test (OBT) is an alternative, indirect method of measuring gastric emptying with a stable isotope. Electrogastrography (EGG) registers the slow wave originating in the pacemaker area of the stomach and regulating the peristaltic contractions of the antrum. This study compares these three methods of measuring gastric motility in patients with type 1 diabetes, functional dyspepsia, and chronic renal failure. Currently no effective drugs for treating gastric motility disorders are available. We studied the effect of nizatidine on gastric emptying, because in preliminary studies this drug has proven to have a prokinetic effect due to its cholinergic properties. Of the type 1 patients, 26% had delayed gastric emptying of solids as measured by scintigraphy. Abnormal intragastric distribution of the test meal occurred in 37% of the patients, indicating impaired fundic relaxation. The autonomic neuropathy score correlated positively with the gastric emptying rate of solids (P = 0.006), but HbA1C, plasma glucose levels, or abdominal symptoms were unrelated to gastric emptying or intragastric distribution of the test meal. Gastric emptying of both solids and liquids was normal in all FD patients but abnormal intragastric distribution occurred in 38% of the patients. Nizatidine improved symptom scores and quality of life in FD patients, but not significantly. Instead of enhancing, nizatidine slowed gastric emptying in FD patients (P < 0.05). No significant difference appeared in the frequency of the gastric slow waves measured by EGG in the patients and controls. The correlation between gastric half-emptying times of solids measured by scintigraphy and OBT was poor both in type 1 diabetes and FD patients. According to this study, dynamic dual-tracer scintigraphy is more accurate than OBT or EGG in measuring gastric emptying of solids. Additionally it provides information about gastric emptying of liquids and the intragastric distribution of the ingested test meal.

A Nationwide Study on Breast Cancer Risk in Postmenopausal Women Using Hormone Therapy in Finland

Since national differences exist in genes, environment, diet and life habits and also in the use of postmenopausal hormone therapy (HT), the associations between different hormone therapies and the risk for breast cancer were studied among Finnish postmenopausal women. All Finnish women over 50 years of age who used HT were identified from the national medical reimbursement register, established in 1994, and followed up for breast cancer incidence (n= 8,382 cases) until 2005 with the aid of the Finnish Cancer Registry. The risk for breast cancer in HT users was compared to that in the general female population of the same age. Among women using oral or transdermal estradiol alone (ET) (n = 110,984) during the study period 1994-2002 the standardized incidence ratio (SIR) for breast cancer in users for < 5 years was 0.93 (95% confidence interval (CI) 0.80–1.04), and in users for ≥ 5 years 1.44 (1.29–1.59). This therapy was associated with similar rises in ductal and lobular types of breast cancer. Both localized stage (1.45; 1.26–1.66) and cancers spread to regional nodes (1.35; 1.09–1.65) were associated with the use of systemic ET. Oral estriol or vaginal estrogens were not accompanied with a risk for breast cancer. The use of estrogen-progestagen therapy (EPT) in the study period 1994-2005 (n= 221,551) was accompanied with an increased incidence of breast cancer (1.31;1.20-1.42) among women using oral or transdermal EPT for 3-5 years, and the incidence increased along with the increasing duration of exposure (≥10 years, 2.07;1.84-2.30). Continuous EPT entailed a significantly higher (2.44; 2.17-2.72) breast cancer incidence compared to sequential EPT (1.78; 1.64-1.90) after 5 years of use. The use of norethisterone acetate (NETA) as a supplement to estradiol was accompanied with a higher incidence of breast cancer after 5 years of use (2.03; 1.88-2.18) than that of medroxyprogesterone acetate (MPA) (1.64; 1.49-1.79). The SIR for the lobular type of breast cancer was increased within 3 years of EPT exposure (1.35; 1.18-1.53), and the incidence of the lobular type of breast cancer (2.93; 2.33-3.64) was significantly higher than that of the ductal type (1.92; 1.67-2.18) after 10 years of exposure. To control for some confounding factors, two case control studies were performed. All Finnish women between the ages of 50-62 in 1995-2007 and diagnosed with a first invasive breast cancer (n= 9,956) were identified from the Finnish Cancer Registry, and 3 controls of similar age (n=29,868) without breast cancer were retrieved from the Finnish national population registry. Subjects were linked to the medical reimbursement register for defining the HT use. The use of ET was not associated with an increased risk for breast cancer (1.00; 0.92-1.08). Neither was progestagen-only therapy used less than 3 years. However, the use of tibolone was associated with an elevated risk for breast cancer (1.39; 1.07-1.81). The case-control study confirmed the results of EPT regarding sequential vs. continuous use of progestagen, including progestagen released continuously by an intrauterine device; the increased risk was seen already within 3 years of use (1.65;1.32-2.07). The dose of NETA was not a determinant as regards the breast cancer risk. Both systemic ET, and EPT are associated with an elevation in the risk for breast cancer. These risks resemble to a large extent those seen in several other countries. The use of an intrauterine system alone or as a complement to systemic estradiol is also associated with a breast cancer risk. These data emphasize the need for detailed information to women who are considering starting the use of HT.

Synthesis, structure and magnetic behavior of a new three-dimensional Manganese phosphite-oxalate: [C2N2H10][Mn-2(II)(OH2)(2)(HPO3)(2)(C2O4)]

A novel manganese phosphite-oxalate, [C2N2H10][Mn-2(II)(OH2)(2)(HPO3)(2)(C2O4)] has been hydothermally synthesized and its structure determined by single-crystal X-ray diffraction. The structure consists of neutral manganese phosphite layers, [Mn(HPO3)](infinity), formed by MnO6 octahedra and HPO3 units, cross-linked by the oxalate moieties. The organic cations occupy the middle of the 8-membered one dimensional channels. Magnetic studies indicate weak antiferromagnetic interactions between the Mn2+ ions. (C) 2009 Elsevier Inc. All rights reserved.

Circulating Glucocorticoid Bioactivity and Serum Glucocorticoid-Responsive Biomarkers during Steroid Therapy in Children and Adolescents with Inflammatory Bowel Disease

Objective: Glucocorticoid therapy is used worldwide to treat various inflammatory and immune conditions, including inflammatory bowel disease (IBD). In IBD, 80% of the patients obtain a positive response to the therapy; however the development of glucocorticoid-related side-effects is common. Our aim was therefore to study the possibility of optimizing glucocorticoid therapy in children and adolescents with IBD by measuring circulating glucocorticoid bioactivity (GBA) and serum glucocorticoid-responsive biomarkers in patients receiving steroid treatment for active disease. Methods: A total of sixty-nine paediatric IBD patients from the Paediatric Outpatient Clinics of the University Hospitals of Helsinki and Tampere participated in the studies. Control patients included 101 non-IBD patients and 41 disease controls in remission. In patients with active disease, blood samples were withdrawn before the glucocorticoid therapy was started, at 2-4 weeks after the initiation of the steroid and at 1-month intervals thereafter. Clinical response to glucocorticoid treatment and the development of steroid adverse events was carefully registered. GBA was analyzed with a COS-1 cell bioassay. The measured glucocorticoid therapy-responsive biomarkers included adipocyte-derived adiponectin and leptin, bone turnover-related collagen markers amino-terminal type I procollagen propeptide (PINP) and carboxyterminal telopeptide of type I collagen (ICTP) as well as insulin-like growth factor 1 (IGF-1) and sex hormone-binding globulin (SHBG), and inflammatory marker high-sensitivity C-reactive protein (hs-CRP). Results: The most promising marker for glucocorticoid sensitivity was serum adiponectin that associated with steroid therapy–related adverse events. Serum leptin indicated a similar trend. In contrast, circulating GBA rose in all subjects receiving glucocorticoid treatment but did not associate with the clinical response to steroids or with glucocorticoid therapy-related side-effects. Of notice, young patients (<10 years) showed similar GBA levels than older patients, despite receiving higher weight-adjusted doses of glucocorticoid. Markers of bone formation were lower in children with active IBD than in the control patients, probably reflecting the suppressive effect of the active inflammation. The onset of the glucocorticoid therapy further suppressed bone turnover. Inflammatory marker hs-CRP decreased readily after the initiation of the steroid, however the decrease did not associate with the clinical response to glucocorticoids. Conclusions: This is the first study to show that adipocyte-derived adiponectin associates with steroid therapy-induced side-effects. Further studies are needed, but it is possible that the adiponectin measurement could aid the recognition of glucocorticoid-sensitive patients in the future. GBA and the other markers reflecting glucocorticoid activity in different tissues changed during the treatment, however their change did not correlate with the therapeutic response to steroids or with the development of glucocorticoid-related side effects and therefore cannot guide the therapy in these patients. Studies such as as the present one that combine clinical data with newly developed biomolecular technology are needed to step-by-step build a general picture of the glucocorticoid actions in different tissues.

On the mechanical behavior of compacted pack ice : A theoretical and numerical investigation

Pack ice is an aggregate of ice floes drifting on the sea surface. The forces controlling the motion and deformation of pack ice are air and water drag forces, sea surface tilt, Coriolis force and the internal force due to the interaction between ice floes. In this thesis, the mechanical behavior of compacted pack ice is investigated using theoretical and numerical methods, focusing on the three basic material properties: compressive strength, yield curve and flow rule. A high-resolution three-category sea ice model is applied to investigate the sea ice dynamics in two small basins, the whole Gulf Riga and the inside Pärnu Bay, focusing on the calibration of the compressive strength for thin ice. These two basins are on the scales of 100 km and 20 km, respectively, with typical ice thickness of 10-30 cm. The model is found capable of capturing the main characteristics of the ice dynamics. The compressive strength is calibrated to be about 30 kPa, consistent with the values from most large-scale sea ice dynamic studies. In addition, the numerical study in Pärnu Bay suggests that the shear strength drops significantly when the ice-floe size markedly decreases. A characteristic inversion method is developed to probe the yield curve of compacted pack ice. The basis of this method is the relationship between the intersection angle of linear kinematic features (LKFs) in sea ice and the slope of the yield curve. A summary of the observed LKFs shows that they can be basically divided into three groups: intersecting leads, uniaxial opening leads and uniaxial pressure ridges. Based on the available observed angles, the yield curve is determined to be a curved diamond. Comparisons of this yield curve with those from other methods show that it possesses almost all the advantages identified by the other methods. A new constitutive law is proposed, where the yield curve is a diamond and the flow rule is a combination of the normal and co-axial flow rule. The non-normal co-axial flow rule is necessary for the Coulombic yield constraint. This constitutive law not only captures the main features of forming LKFs but also takes the advantage of avoiding overestimating divergence during shear deformation. Moreover, this study provides a method for observing the flow rule for pack ice during deformation.

Finnish Dosimetric Practice for Epithermal Neutron Beam Dosimetry in Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) is a form of chemically targeted radiotherapy that utilises the high neutron capture cross-section of boron-10 isotope to achieve a preferential dose increase in the tumour. The BNCT dosimetry poses a special challenge as the radiation dose absorbed by the irradiated tissues consists of several dose different components. Dosimetry is important as the effect of the radiation on the tissue is correlated with the radiation dose. Consistent and reliable radiation dose delivery and dosimetry are thus basic requirements for radiotherapy. The international recommendations for are not directly applicable to BNCT dosimetry. The existing dosimetry guidance for BNCT provides recommendations but also calls for investigating for complementary methods for comparison and improved accuracy. In this thesis the quality assurance and stability measurements of the neutron beam monitors used in dose delivery are presented. The beam monitors were found not to be affected by the presence of a phantom in the beam and that the effect of the reactor core power distribution was less than 1%. The weekly stability test with activation detectors has been generally reproducible within the recommended tolerance value of 2%. An established toolkit for epithermal neutron beams for determination of the dose components is presented and applied in an international dosimetric intercomparison. The measured quantities (neutron flux, fast neutron and photon dose) by the groups in the intercomparison were generally in agreement within the stated uncertainties. However, the uncertainties were large, ranging from 3-30% (1 standard deviation), emphasising the importance of dosimetric intercomparisons if clinical data is to be compared between different centers. Measurements with the Exradin type 2M ionisation chamber have been repeated in the epithermal neutron beam in the same measurement configuration over the course of 10 years. The presented results exclude severe sensitivity changes to thermal neutrons that have been reported for this type of chamber. Microdosimetry and polymer gel dosimetry as complementary methods for epithermal neutron beam dosimetry are studied. For microdosimetry the comparison of results with ionisation chambers and computer simulation showed that the photon dose measured with microdosimetry was lower than with the two other methods. The disagreement was within the uncertainties. For neutron dose the simulation and microdosimetry results agreed within 10% while the ionisation chamber technique gave 10-30% lower neutron dose rates than the two other methods. The response of the BANG-3 gel was found to be linear for both photon and epithermal neutron beam irradiation. The dose distribution normalised to dose maximum measured by MAGIC polymer gel was found to agree well with the simulated result near the dose maximum while the spatial difference between measured and simulated 30% isodose line was more than 1 cm. In both the BANG-3 and MAGIC gel studies, the interpretation of the results was complicated by the presence of high-LET radiation.

Electrical switching behavior of bulk Si15Te85-xSbx chalcogenide glasses - A study of compositional dependence

Studies on the electrical switching behavior of melt quenched bulk Si15Te85-xSbx glasses have been undertaken in the composition range (1 <= x <= 10), in order to understand the effect of Sb addition on the electrical switching behavior of Si15Te85-x base glass. It has been observed that all the Si15Te85-xSbx glasses studied exhibit a smooth memory type switching. Further, the switching voltages are found to decrease almost linearly with Sb content, which indicates that the metallicity of the dopant plays a dominant role in this system compared to network connectivity/rigidity. The thickness dependence of switching voltage (V-th) indicates a clear thermal origin for the switching mechanism. The temperature variation of switching voltages reveals that the Si15Te85-xSbx glasses studied have a moderate thermal stability. (C) 2009 Elsevier B.V. All rights reserved.

Surface spin glass behavior in sol–gel derived La0.7Ca0.3MnO3 nanotubes

We report the fabrication of La0.7Ca0.3MnO3 nanotubes (LCMONTs) with a diameter of about 200 nm, by a modified sol-gel method utilizing nanochannel alumina templates. High resolution transmission electron microscopy confirmed that the obtained LCMONTs are made up of nanoparticles (8-12 nm), which are randomly aligned in the wall of the nanotubes. The strong irreversibility between zero field cooling (ZFC) and field cooling (FC) magnetization curves as well as a cusplike peak in the ZFC curve gives strong support for surface spin glass behavior.

Proton magnetic resonance spectroscopy of a boron neutron capture therapy 10B-carrier, L-p-boronophenylalanine-fructose complex

Boron neutron capture therapy (BNCT) is a radiotherapy that has mainly been used to treat malignant brain tumours, melanomas, and head and neck cancer. In BNCT, the patient receives an intravenous infusion of a 10B-carrier, which accumulates in the tumour area. The tumour is irradiated with epithermal or thermal neutrons, which result in a boron neutron capture reaction that generates heavy particles to damage tumour cells. In Finland, boronophenylalanine fructose (BPA-F) is used as the 10B-carrier. Currently, the drifting of boron from blood to tumour as well as the spatial and temporal accumulation of boron in the brain, are not precisely known. Proton magnetic resonance spectroscopy (1H MRS) could be used for selective BPA-F detection and quantification as aromatic protons of BPA resonate in the spectrum region, which is clear of brain metabolite signals. This study, which included both phantom and in vivo studies, examined the validity of 1H MRS as a tool for BPA detection. In the phantom study, BPA quantification was studied at 1.5 and 3.0 T with single voxel 1H MRS, and at 1.5 T with magnetic resonance imaging (MRSI). The detection limit of BPA was determined in phantom conditions at 1.5 T and 3.0 T using single voxel 1H MRS, and at 1.5 T using MRSI. In phantom conditions, BPA quantification accuracy of ± 5% and ± 15% were achieved with single voxel MRS using external or internal (internal water signal) concentration references, respectively. For MRSI, a quantification accuracy of <5% was obtained using an internal concentration reference (creatine). The detection limits of BPA in phantom conditions for the PRESS sequence were 0.7 (3.0 T) and 1.4 mM (1.5 T) mM with 20 × 20 × 20 mm3 single voxel MRS, and 1.0 mM with acquisition-weighted MRSI (nominal voxel volume 10(RL) × 10(AP) × 7.5(SI) mm3), respectively. In the in vivo study, an MRSI or single voxel MRS or both was performed for ten patients (patients 1-10) on the day of BNCT. Three patients had glioblastoma multiforme (GBM), and five patients had a recurrent or progressing GBM or anaplastic astrocytoma gradus III, and two patients had head and neck cancer. For nine patients (patients 1-9), MRS/MRSI was performed 70-140 min after the second irradiation field, and for one patient (patient 10), the MRSI study began 11 min before the end of the BPA-F infusion and ended 6 min after the end of the infusion. In comparison, single voxel MRS was performed before BNCT, for two patients (patients 3 and 9), and for one patient (patient 9), MRSI was performed one month after treatment. For one patient (patient 10), MRSI was performed four days before infusion. Signals from the tumour spectrum aromatic region were detected on the day of BNCT in three patients, indicating that in favourable cases, it is possible to detect BPA in vivo in the patient’s brain after BNCT treatment or at the end of BPA-F infusion. However, because the shape and position of the detected signals did not exactly match the BPA spectrum detected in the in vitro conditions, assignment of BPA is difficult. The opportunity to perform MRS immediately after the end of BPA-F infusion for more patients is necessary to evaluate the suitability of 1H MRS for BPA detection or quantification for treatment planning purposes. However, it could be possible to use MRSI as criteria in selecting patients for BNCT.

Overview No.144 - Mechanical behavior of amorphous alloys

The mechanical properties of amorphous alloys have proven both scientifically unique and of potential practical interest, although the underlying deformation physics of these materials remain less firmly established as compared with crystalline alloys. In this article, we review recent advances in understanding the mechanical behavior of metallic glasses, with particular emphasis on the deformation and fracture mechanisms. Atomistic as well as continuum modeling and experimental work on elasticity, plastic flow and localization, fracture and fatigue are all discussed, and theoretical developments are connected, where possible, with macroscopic experimental responses. The role of glass structure on mechanical properties, and conversely, the effect of deformation upon glass structure, are also described. The mechanical properties of metallic glass-derivative materials – including in situ and ex situ composites, foams and nanocrystal-reinforced glasses – are reviewed as well. Finally, we identify a number of important unresolved issues for the field.