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1.
Radiologie (Heidelb) ; 62(10): 835-843, 2022 Oct.
Article in German | MEDLINE | ID: mdl-35771235

ABSTRACT

BACKGROUND: Imaging of the postoperative shoulder joint includes complex, diagnostically challenging changes regarding the anatomical structures. OBJECTIVES: Case-based presentation of common surgical procedures, expected postoperative findings, and typical complications. MATERIALS AND METHODS: Interdisciplinary evaluation of (didactically instructive) cases and discussion of pertinent literature and expert opinions. RESULTS: Presentation of normal postoperative findings and complications after subacromial decompression, surgical treatment of rotator cuff lesions, SLAP (superior labral anterior to posterior) lesions/lesions of the long biceps tendon, Bankart lesions as well as instability-related procedures and after shoulder arthroplasty. Discussion of the appropriate use of imaging methods with a focus on magnetic resonance imaging (MRI), which are supplemented by computed tomography (CT), and conventional x­ray images. CONCLUSION: The broad spectrum of complex findings as well as the evermore developing and thereby changing surgical procedures result in significant challenges in the radiological evaluation of the postoperative shoulder joint. To differentiate physiological reactions from pathological changes it is necessary to have general knowledge of the common surgical procedures, expected postoperative findings and possible complications. A variety imaging modalities can be used to further advance diagnostic precision.


Subject(s)
Rotator Cuff Injuries , Shoulder Injuries , Shoulder Joint , Shoulder , Tomography, X-Ray Computed , Humans , Postoperative Period , Rotator Cuff/surgery , Rotator Cuff Injuries/diagnostic imaging , Shoulder/diagnostic imaging , Shoulder Injuries/diagnostic imaging , Shoulder Joint/diagnostic imaging
2.
Int J Obstet Anesth ; 46: 102974, 2021 05.
Article in English | MEDLINE | ID: mdl-33780714

ABSTRACT

BACKGROUND: Recent warnings postulate a possible damaging effect of volatile anesthetics on the fetus. In our archive of fetal surgeries, we found wide variation in dosing of volatile anesthetics during spina bifida surgeries. We hypothesized that there was an association between volatile anesthetic exposure and uterine activity. METHODS: Sixty anesthesia records from spina bifida operations were assessed. We analyzed the course of the administered volatile anesthetic during surgery and calculated from each patient's anesthesia record the volatile anesthetic exposure expressed in vol%h. We divided the records into two post hoc groups of the 20 lowest exposure (Group L) versus the 20 highest exposure (Group H), and compared them for uterine activity and fetal heart rate. RESULTS: The number of contractions per hour was significantly greater in Group H (mean 1.3, SD ±â€¯1.2) compared with Group L (mean 0.5, SD ±â€¯0.6, P=0.049). There was no difference between the groups for the administration of the tocolytic drug atosiban (P=0.29). The course of the mean arterial pressure did not significantly differ but group H needed significantly more vasoactive medication (P <0.05). CONCLUSIONS: We found that a lower intra-operative volatile anesthetic exposure than recommended in the MOMS-trial (i.e. <2.0 minimum alveolar concentration [MAC]) was not associated with an increase in intra-operative uterine activity. This is an indication that during spina bifida surgery, 2.0 MAC may not be necessary to avoid potentially harmful uterine activity.


Subject(s)
Anesthetics , Spinal Dysraphism , Female , Fetus , Humans , Pregnancy , Prenatal Care , Retrospective Studies
3.
Lupus ; 27(11): 1759-1768, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29996703

ABSTRACT

Background This review summarizes current knowledge about cardiovascular reflex tests (CVRTs) and other selected autonomic nervous system (ANS) assessment tests in systemic lupus erythematosus (SLE) patients and assesses their clinical utility in this group of patients. Methods The PubMed database was searched for terms associated with CVRTs and SLE. Only papers available in full text and published in English were considered. Ultimately, 13 were selected and analyzed. Results In most of the studies CVRTs results were reported more likely to be abnormal in patients with SLE when compared with controls. The reported prevalence of ANS dysfunction in SLE, diagnosed using CVRTs, ranged from 23.5% to 82.7% of patients, likely because of different definitions of ANS dysfunction, variability in methods of performing CVRTs, and potential confounding factors. In general CVRTs results did not correlate with SLE activity or disease duration, but some CVRTs results correlated with some peptides associated with ANS function, including neuropeptide Y and vasoactive intestinal peptide. Conclusion Patients with SLE generally have abnormal or borderline results of CVRTs, which indicate prevalent abnormalities of the ANS in SLE. Performance of CVRTs requires good standardization of test conditions and familiarity with the proper administration and interpretation of these tests.


Subject(s)
Autonomic Nervous System Diseases/diagnosis , Autonomic Nervous System Diseases/etiology , Heart Rate/physiology , Lupus Erythematosus, Systemic/complications , Reflex/physiology , Blood Pressure , Humans
4.
Lupus ; 27(8): 1225-1239, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29697012

ABSTRACT

Aim The aim of this review was to summarize current knowledge about the scientific findings and potential clinical utility of heart rate variability measures in patients with systemic lupus erythematosus. Methods PubMed, Embase and Scopus databases were searched for the terms associated with systemic lupus erythematosus and heart rate variability, including controlled vocabulary, when appropriate. Articles published in English and available in full text were considered. Finally, 11 publications were selected, according to the systematic review protocol and were analyzed. Results In general, heart rate variability, measured in the time and frequency domains, was reported to be decreased in patients with systemic lupus erythematosus compared with controls. In some systemic lupus erythematosus studies, heart rate variability was found to correlate with inflammatory markers and albumin levels. A novel heart rate variability measure, heart rate turbulence onset, was shown to be increased, while heart rate turbulence slope was decreased in systemic lupus erythematosus patients. Reports of associations of changes in heart rate variability parameters with increasing systemic lupus erythematosus activity were inconsistent, showing decreasing heart rate variability or no relationship. However, the low/high frequency ratio was, in some studies, reported to increase with increasing disease activity or to be inversely correlated with albumin levels. Conclusions Patients with systemic lupus erythematosus have abnormal heart rate variability, which reflects cardiac autonomic dysfunction and may be related to inflammatory cytokines but not necessarily to disease activity. Thus measurement of heart rate variability could be a useful clinical tool for monitoring autonomic dysfunction in systemic lupus erythematosus, and may potentially provide prognostic information.


Subject(s)
Autonomic Nervous System/physiopathology , Cytokines/metabolism , Heart Rate , Lupus Erythematosus, Systemic/complications , Biomarkers , Humans
5.
Anaesthesia ; 73(6): 719-729, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29411358

ABSTRACT

Tranexamic acid is used both pre-hospital and in-hospital as an antifibrinolytic drug to treat or prevent hyperfibrinolysis in trauma patients; dosing, however, remains empirical. We aimed to measure plasma levels of tranexamic acid in patients receiving pre-hospital anti-hyperfibrinolytic therapy and to build a population pharmacokinetic model to propose an optimised dosing regimen. Seventy-three trauma patients were enrolled and each received tranexamic acid 1 g intravenously pre-hospital. A blood sample was drawn after arrival in the emergency department, and we measured the plasma tranexamic acid concentration using liquid chromatography-mass spectrometry, and modelled the data using non-linear mixed effect modelling. Tranexamic acid was administered at a median (IQR [range]) time of 43 (30-55 [5-135]) min after trauma. Plasma tranexamic acid levels were determined on arrival at hospital, 57 (43-70 [20-148]) min after pre-hospital administration of the drug. The measured concentration was 28.7 (21.5-38.5 [8.7-89.0]) µg.ml-1 . Our subjects had sustained severe trauma; injury severity score 20 (16-29 [5-75]), including penetrating injury in 2.8% and isolated traumatic brain injury in 19.7%. The pharmacokinetics were ascribed a two-compartment open model with body-weight as the main covariate. As tranexamic acid concentrations may fall below therapeutic levels during initial hospital treatment, we propose additional dosing schemes to maintain a specific target blood concentration for as long as required. This is the first study to investigate plasma level and pharmacokinetics of tranexamic acid after pre-hospital administration in trauma patients. Our proposed dosing regimen could be used in subsequent clinical trials to better study efficacy and tolerance profiles with controlled blood concentrations.


Subject(s)
Antifibrinolytic Agents/administration & dosage , Antifibrinolytic Agents/pharmacokinetics , Tranexamic Acid/administration & dosage , Tranexamic Acid/pharmacokinetics , Wounds and Injuries/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antifibrinolytic Agents/adverse effects , Brain Injuries, Traumatic/drug therapy , Drug Administration Schedule , Emergency Medical Services , Female , Humans , Injury Severity Score , Male , Middle Aged , Prospective Studies , Tranexamic Acid/adverse effects , Young Adult
6.
Anaesthesia ; 72(11): 1317-1326, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28542848

ABSTRACT

Trauma promotes trauma-induced coagulopathy, which requires urgent treatment with fixed-ratio transfusions of red blood cells, fresh frozen plasma and platelet concentrates, or goal-directed administration of coagulation factors based on viscoelastic testing. This retrospective observational study compared two time periods before (2005-2007) and after (2012-2014) the implementation of changes in trauma management protocols which included: use of goal-directed coagulation management; admission of patients to designated trauma centres; whole-body computed tomography scanning on admission; damage control surgery; permissive hypotension; restrictive fluid resuscitation; and administration of tranexamic acid. The incidence of massive transfusion (≥ 10 units of red blood cells from emergency department arrival until intensive care unit admission) was compared with the predicted incidence according to the trauma associated severe haemorrhage score. All adult (≥ 16 years) trauma patients primarily admitted to the University Hospital Zürich with an injury severity score ≥ 16 were included. In 2005-2007, the observed and trauma associated severe haemorrhage score that predicted the incidence of massive transfusion were identical, whereas in 2012-2014 the observed incidence was less than half that predicted (3.7% vs. 7.5%). Compared to 2005-2007, the proportion of patients transfused with red blood cells and fresh frozen plasma was significantly lower in 2012-2014 in both the emergency department (43% vs. 17%; 31% vs. 6%, respectively), and after 24 h (53% vs. 27%; 37% vs. 16%, respectively). The use of tranexamic acid and coagulation factor XIII also increased significantly in the 2012-2014 time period. Implementation of a revised trauma management strategy, which included goal-directed coagulation management, was associated with a reduced incidence of massive transfusion and a reduction in the transfusion of red blood cells and fresh frozen plasma.


Subject(s)
Blood Transfusion/standards , Wounds and Injuries/therapy , Adult , Aged , Anticoagulants/therapeutic use , Clinical Protocols , Cohort Studies , Erythrocyte Transfusion , Female , Goals , Hemorrhage/blood , Hemorrhage/drug therapy , Humans , Incidence , Injury Severity Score , Length of Stay , Male , Middle Aged , Plasma , Retrospective Studies , Treatment Outcome , Wounds and Injuries/blood , Wounds and Injuries/mortality
8.
Cell Death Differ ; 21(12): 1950-60, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25146928

ABSTRACT

Bromodomain-containing protein 4 (BRD4) is an important epigenetic reader implicated in the pathogenesis of a number of different cancers and other diseases. Brd4-null mouse embryos die shortly after implantation and are compromised in their ability to maintain the inner cell mass, which gives rise to embryonic stem cells (ESCs). Here we report that BRD4 regulates expression of the pluripotency factor Nanog in mouse ESCs and preimplantation embryos, as well as in human ESCs and embryonic cancer stem cells. Inhibition of BRD4 function using a chemical inhibitor, small interfering RNAs, or a dominant-negative approach suppresses Nanog expression, and abolishes the self-renewal ability of ESCs. We also find that BRD4 associates with BRG1 (brahma-related gene 1, aka Smarca4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4)), a key regulator of ESC self-renewal and pluripotency, in the Nanog regulatory regions to regulate Nanog expression. Our study identifies Nanog as a novel BRD4 target gene, providing new insights for the biological function of BRD4 in stem cells and mouse embryos. Knowledge gained from these non-cancerous systems will facilitate future investigations of how Brd4 dysfunction leads to cancers.


Subject(s)
Blastocyst/metabolism , Embryonic Stem Cells/metabolism , Homeodomain Proteins/metabolism , Nuclear Proteins/physiology , Transcription Factors/physiology , Animals , Blastocyst/cytology , Cell Differentiation , DNA Helicases/metabolism , Female , Gene Expression , Gene Expression Regulation, Developmental , HEK293 Cells , Homeodomain Proteins/genetics , Humans , Male , Mice, Inbred C57BL , Nanog Homeobox Protein , Nuclear Proteins/metabolism , Promoter Regions, Genetic , Transcription Factors/metabolism
9.
Magn Reson Imaging ; 32(10): 1418-27, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25131625

ABSTRACT

Nondestructive studies of physiological processes in agronomic products require increasingly higher spatial and temporal resolutions. Nuclear Magnetic Resonance (NMR) imaging is a non-invasive technique providing physiological and morphological information on biological tissues. The aim of this study was to design a robust and accurate quantitative measurement method based on NMR imaging combined with contrast agent (CA) for mapping and quantifying water transport in growing cherry tomato fruits. A multiple flip-angle Spoiled Gradient Echo (SGE) imaging sequence was used to evaluate the intrinsic parameters maps M0 and T1 of the fruit tissues. Water transport and paths flow were monitored using Gd(3+)/[Fe(CN)6](3-)/D-mannitol nanoparticles as a tracer. This dynamic study was carried out using a compartmental modeling. The CA was preferentially accumulated in the surrounding tissues of columella and in the seed envelopes. The total quantities and the average volume flow of water estimated are: 198 mg, 1.76 mm(3)/h for the columella and 326 mg, 2.91 mm(3)/h for the seed envelopes. We demonstrate in this paper that the NMR imaging technique coupled with efficient and biocompatible CA in physiological medium has the potential to become a major tool in plant physiology research.


Subject(s)
Fruit/physiology , Image Processing, Computer-Assisted/methods , Magnetic Resonance Spectroscopy/methods , Solanum lycopersicum/physiology , Algorithms , Biocompatible Materials/chemistry , Computer Simulation , Contrast Media , Gadolinium/chemistry , Mannitol/chemistry , Nanoparticles/chemistry , Phantoms, Imaging , Reproducibility of Results , Seeds , Water/chemistry
10.
Acta Anaesthesiol Scand ; 58(5): 630-7, 2014 May.
Article in English | MEDLINE | ID: mdl-24601892

ABSTRACT

BACKGROUND: Novel oral anticoagulants are now encountered in patients needing emergency surgery. Knowledge and treatment options are limited. METHODS AND RESULT: We present the case of a 76-year-old patient who suffered from an acute Stanford type A aortic dissection, needing emergency surgical aortic repair. He was anticoagulated with dabigatran due to past atrial fibrillation. Despite haemodiafiltration, surgical revision and massive transfusion of packed red blood cells, fresh frozen plasma, platelets, coagulation factors, and recombinant factor VIIa, the patient died from intractable bleeding with sustained therapeutic levels of dabigatran. CONCLUSION: After reviewing the literature, we summarize the limited treatment options and show possible approaches for patients treated with dabigatran needing emergency surgery.


Subject(s)
Anticoagulants/adverse effects , Aortic Aneurysm, Thoracic/complications , Aortic Dissection/complications , Benzimidazoles/adverse effects , Pyridines/adverse effects , Shock, Hemorrhagic/etiology , Aged , Aortic Dissection/surgery , Aortic Dissection/therapy , Anticoagulants/blood , Anticoagulants/therapeutic use , Aortic Aneurysm, Thoracic/surgery , Aortic Aneurysm, Thoracic/therapy , Aortic Valve Insufficiency/complications , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Benzimidazoles/blood , Benzimidazoles/therapeutic use , Blood Coagulation Factors/therapeutic use , Blood Coagulation Tests , Blood Component Transfusion , Cardiac Tamponade/etiology , Cardiac Tamponade/surgery , Cardiopulmonary Bypass , Dabigatran , Emergencies , Fatal Outcome , Heart Valve Prosthesis Implantation , Hemodiafiltration , Heparin/therapeutic use , Humans , Hypertension/complications , Hypertrophy, Left Ventricular/complications , Male , Pyridines/blood , Pyridines/therapeutic use , Shock, Hemorrhagic/chemically induced , Shock, Hemorrhagic/drug therapy , Thrombelastography , Tranexamic Acid/therapeutic use
11.
Diabetes Obes Metab ; 16(5): 467-77, 2014 May.
Article in English | MEDLINE | ID: mdl-24528605

ABSTRACT

AIM: The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and pioglitazone. METHODS: In this randomized, double-blind, phase 3 study, patients (N = 342) received canagliflozin 100 or 300 mg during a 26-week, placebo-controlled, core period and a 26-week, active-controlled extension in which placebo-treated patients were switched to sitagliptin 100 mg. Efficacy comparisons for canagliflozin versus placebo at week 26 are reported, with no comparisons versus sitagliptin at week 52 (sitagliptin used to maintain double-blind and control for safety). Safety data are reported for canagliflozin and placebo/sitagliptin. RESULTS: Canagliflozin 100 and 300 mg significantly lowered haemoglobin A1c (HbA1c) compared with placebo at week 26 (-0.89%, -1.03% and -0.26%; p < 0.001); reductions with canagliflozin 100 and 300 mg were maintained at week 52 (-0.92% and -1.03%). Relative to placebo, both canagliflozin doses significantly reduced body weight (-2.5 and -3.5 kg), fasting plasma glucose and systolic blood pressure (BP) at week 26 (p < 0.05 for all), with reductions maintained at week 52. Overall adverse event (AE) incidence over 52 weeks was 69.9, 76.3 and 76.5% with canagliflozin 100 and 300 mg and placebo/sitagliptin; AE-related discontinuation and serious AE rates were low. Incidences of genital mycotic infections and AEs related to osmotic diuresis and volume depletion were higher with canagliflozin than placebo/sitagliptin. CONCLUSION: Canagliflozin improved glycaemic control, reduced body weight and systolic BP, and was generally well tolerated in patients with T2DM on metformin and pioglitazone over 52 weeks.


Subject(s)
Blood Glucose/drug effects , Diabetes Mellitus, Type 2/drug therapy , Glucosides/therapeutic use , Hypoglycemic Agents/therapeutic use , Metformin/administration & dosage , Thiazolidinediones/administration & dosage , Thiophenes/therapeutic use , Blood Glucose/metabolism , Blood Pressure/drug effects , Canagliflozin , Candidiasis/chemically induced , Diabetes Mellitus, Type 2/blood , Diuretics, Osmotic/adverse effects , Double-Blind Method , Drug Therapy, Combination , Female , Genital Diseases, Female/chemically induced , Genital Diseases, Male/chemically induced , Glucosides/administration & dosage , Glucosides/adverse effects , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Lipids , Male , Middle Aged , Pioglitazone , Pyrazines/administration & dosage , Sitagliptin Phosphate , Thiophenes/administration & dosage , Thiophenes/adverse effects , Treatment Outcome , Triazoles/administration & dosage , Weight Loss
12.
Thromb Haemost ; 109(5): 897-900, 2013 May.
Article in English | MEDLINE | ID: mdl-23467701

ABSTRACT

In view of the high case fatality rates of patients with chronic obstructive pulmonary disease (COPD) who have pulmonary embolism (PE) we speculated that such patients might benefit from vena cava filters. To test this hypothesis we assessed the database of the Nationwide Inpatient Sample. From 1998-2009, 440,370 patients were hospitalised with PE and COPD who were not in shock or ventilator-dependent and did not receive thrombolytic therapy or pulmonary embolectomy. In-hospital all-cause case fatality rate among those with filters was 5,890 of 68,800 (8.6%) (95% confidence interval [CI] = 8.4-8.8) compared with 38,960 of 371,570 (10.5%) (95% CI = 10.4-10.6) (p<0.0001) who did not receive filters. Case fatality rate was age-dependent. Only those who were older than aged 50 years had a lower in-hospital all-cause case fatality rate with filters. Among such patients, absolute risk reduction was 2.1% (95% CI = 1.9-2.3). The greatest reduction of case fatality rate with vena cava filters was shown in patients >aged 80 years, 11,720 of 81,600 (14.4%) compared with 1,570 of 17,220 (9.1%) (p<0.0001). In conclusion, a somewhat lower in-hospital all-cause case fatality rate was shown with vena filters in stable patients with PE >aged 50 years who also had COPD. The benefit was greatest in elderly patients. The benefit in terms of a decreased case fatality rate would seem to outweigh the risks of vena cava filters in such patients.


Subject(s)
Hospital Mortality , Hospitalization , Pulmonary Disease, Chronic Obstructive/mortality , Pulmonary Embolism/mortality , Pulmonary Embolism/therapy , Vena Cava Filters , Adult , Age Factors , Aged , Aged, 80 and over , Chi-Square Distribution , Female , Humans , Linear Models , Male , Middle Aged , Patient Selection , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Embolism/complications , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , United States , Vena Cava Filters/adverse effects , Young Adult
13.
Nervenarzt ; 84(1): 14-9, 2013 Jan.
Article in German | MEDLINE | ID: mdl-22318360

ABSTRACT

Hormonal fluctuations during the perimenopausal transition lead to physical discomfort but are also frequently accompanied by mood swings, depressive symptoms, anxiety and sleeping disorders. The important role of the neurotransmitter serotonin in the pathogenesis of anxiety disorders and major depression is unquestioned, but only little is known about the influence of sex hormones on the serotonergic system. This review provides an overview of potential risk factors for the occurrence of affective disorders in the menopausal transition and discusses possible therapeutic options. Current research findings from longitudinal studies testing the efficacy of hormone replacement therapy and antidepressants with effects on the serotonergic neurotransmission on physical and mental discomforts during menopause are presented. Furthermore, studies using positron emission tomography and genetic methods that explore the effects of sex steroids on different components of the serotonergic system are shown. The interactions between estrogen, progesterone and the serotonergic system are described, and possible neurobiological and endocrinological mechanisms underlying depressive symptoms in the perimenopause are elucidated.


Subject(s)
Anxiety Disorders/drug therapy , Brain/drug effects , Climacteric/drug effects , Climacteric/psychology , Depressive Disorder/drug therapy , Estrogen Replacement Therapy , Serotonergic Neurons/drug effects , Serotonin/metabolism , Antidepressive Agents/therapeutic use , Anxiety Disorders/psychology , Austria , Depressive Disorder/psychology , Drug Therapy, Combination , Female , Humans , Longitudinal Studies , Receptor, Serotonin, 5-HT1A/drug effects , Selective Serotonin Reuptake Inhibitors/therapeutic use , Treatment Outcome
15.
Mol Psychiatry ; 18(1): 93-100, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22751491

ABSTRACT

Electroconvulsive therapy (ECT) is a potent therapy in severe treatment-refractory depression. Although commonly applied in psychiatric clinical routine since decades, the exact neurobiological mechanism regarding its efficacy remains unclear. Results from preclinical and clinical studies emphasize a crucial involvement of the serotonin-1A receptor (5-HT(1A)) in the mode of action of antidepressant treatment. This includes associations between treatment response and changes in 5-HT(1A) function and density by antidepressants. Further, alterations of the 5-HT(1A) receptor are consistently reported in depression. To elucidate the effect of ECT on 5-HT(1A) receptor binding, 12 subjects with severe treatment-resistant major depression underwent three positron emission tomography (PET) measurements using the highly selective radioligand [carbonyl-(11)C]WAY100635, twice before (test-retest variability) and once after 10.08±2.35 ECT sessions. Ten patients (~83%) were responders to ECT. The voxel-wise comparison of the 5-HT(1A) receptor binding (BP(ND)) before and after ECT revealed a widespread reduction in cortical and subcortical regions (P<0.05 corrected), except for the occipital cortex and the cerebellum. Strongest reductions were found in regions consistently reported to be altered in major depression and involved in emotion regulation, such as the subgenual part of the anterior cingulate cortex (-27.5%), the orbitofrontal cortex (-30.1%), the amygdala (-31.8%), the hippocampus (-30.6%) and the insula (-28.9%). No significant change was found in the raphe nuclei. There was no significant difference in receptor binding in any region comparing the first two PET scans conducted before ECT. This PET study proposes a global involvement of the postsynaptic 5-HT(1A) receptor binding in the effect of ECT.


Subject(s)
Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/therapy , Electroconvulsive Therapy/methods , Receptor, Serotonin, 5-HT1A/metabolism , Adult , Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use , Brain Mapping , Carbon Isotopes/pharmacokinetics , Female , Humans , Male , Middle Aged , Piperazines/pharmacokinetics , Positron-Emission Tomography/methods , Protein Binding/drug effects , Protein Binding/physiology , Pyridines/pharmacokinetics , Serotonin Antagonists/pharmacokinetics , Young Adult
16.
Clin Med (Lond) ; 12(3): 293-4, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22783787

ABSTRACT

Acute neurovisceral attacks of porphyria can be life threatening. They are rare and notoriously difficult to diagnose clinically, but should be considered, particularly in female patients with unexplained abdominal pain, and associated neurological or psychiatric features or hyponatraemia. The diagnosis might be suggested by altered urine colour and can be confirmed by finding an elevated porphobilinogen concentration in fresh urine protected from light. Severe attacks require treatment with intravenous haem arginate and supportive management with safe drugs, including adequate analgesia. Intravenous glucose in water solutions are contraindicated as they aggravate hyponatraemia, which can prove fatal.


Subject(s)
Abdominal Pain/etiology , Hallucinations/etiology , Hyponatremia/etiology , Porphyria, Acute Intermittent , Adolescent , Analgesics/therapeutic use , Arginine/therapeutic use , Disease Management , Fatal Outcome , Female , Heme/therapeutic use , Humans , Monitoring, Physiologic , Porphobilinogen/urine , Porphyria, Acute Intermittent/complications , Porphyria, Acute Intermittent/metabolism , Porphyria, Acute Intermittent/physiopathology , Porphyria, Acute Intermittent/therapy , Water-Electrolyte Balance
17.
Vet Parasitol ; 188(1-2): 190-3, 2012 Aug 13.
Article in English | MEDLINE | ID: mdl-22459111

ABSTRACT

Anthelmintic resistance by gastrointestinal nematodes of sheep continues to be an issue of global interest. While the recent introduction in some countries of one or two new anthelmintic classes (amino-acetonitrile derivatives [AAD] and spiroindoles [SI]) has been welcomed, it is important that there is no relaxation in parasite control and the management of drug resistance. Monepantel (an AAD) was the first new anthelmintic to be approved for use (New Zealand, 2009) and was followed a year later in the same country by a combination of derquantel (a SI) and abamectin. The present study determined the efficacy of the new anthelmintic products and abamectin against fourth-stage larvae of macrocyclic lactone-resistant Teladorsagia spp. in lambs. Efficacies were calculated by comparing post-mortem nematode burdens of treated animals with those of untreated control sheep, and were 98.5, 86.3 and 34.0% for monepantel, abamectin/derquantel and abamectin, respectively. The nematode burdens of monepantel- and abamectin/derquantel-treated sheep were significantly lower than those sheep treated with abamectin and the untreated controls. Similarly, the burden of the monepantel group was significantly lower than that of the abamectin/derquantel group. These findings provide an opportunity to reinforce the recommendation that farmers and animal health advisors need to know the resistance status of nematode populations on subject farms to ensure effective control programs are designed and implemented. Such control programs should include an appropriate choice of anthelmintic(s), monitoring parasite burdens for correct timing of treatments, and pasture management to reduce larval challenge balanced with the maintenance of drug-susceptible populations in refugia.


Subject(s)
Aminoacetonitrile/analogs & derivatives , Indoles/therapeutic use , Ivermectin/analogs & derivatives , Nematode Infections/veterinary , Oxepins/therapeutic use , Sheep Diseases/drug therapy , Aminoacetonitrile/administration & dosage , Aminoacetonitrile/therapeutic use , Animals , Anthelmintics/administration & dosage , Anthelmintics/therapeutic use , Drug Combinations , Indoles/administration & dosage , Ivermectin/administration & dosage , Ivermectin/therapeutic use , Larva/drug effects , Nematoda/drug effects , Nematode Infections/drug therapy , Oxepins/administration & dosage , Sheep , Sheep Diseases/parasitology
18.
Diabetes Obes Metab ; 14(8): 709-16, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22340428

ABSTRACT

AIM: G-protein coupled receptor agonists are currently under investigation for their potential utility in patients with type 2 diabetes mellitus (T2DM). The objective was to determine the pharmacokinetics, pharmacodynamics, safety and tolerability of GPR119 agonist, JNJ-38431055 in T2DM subjects. METHODS: This was a randomized, double-blind, placebo- and positive-controled, single-dose cross-over study and a randomized, double-blind, placebo-controled multiple-dose parallel design study. The study was conducted at 4 US research centres. Two different experiments involving 25 and 32 different subjects were performed in male and female subjects, aged 25-60 years, mean body mass index between 22 and 39.9 kg/m2 who had T2DM diagnosed 6 months to 10 years before screening. JNJ-38431055 (100 and 500 mg) or sitagliptin (100 mg) as a single-dose or JNJ-38431055 (500 mg) once daily for 14 consecutive days were tested. Effects on stimulated plasma glucose, insulin, C-peptide and incretin concentrations were pre-specified outcomes. RESULTS: JNJ-38431055 was well tolerated and not associated with hypoglycaemia. Plasma systemic exposure of JNJ-38431055 increased as the dose increased, was approximately two-fold greater after multiple-dose administration, and attained steady-state after approximately 8 days. Compared with placebo, single-dose administration of oral JNJ-38431055 decreased glucose excursion during an oral glucose tolerance test, but multiple-dose administration did not alter 24-h weighted mean glucose. Multiple dosing of JNJ-38431055 increased post-meal total glucagon-like peptide 1 and gastric insulinotropic peptide concentrations compared to baseline. CONCLUSIONS: These studies provide evidence of limited glucose lowering and incretin activity for JNJ-38431055 in subjects with T2DM.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Glucagon-Like Peptide 1/blood , Incretins/blood , Pyrazines/pharmacology , Receptors, G-Protein-Coupled/agonists , Triazoles/pharmacology , Administration, Oral , Adult , Blood Glucose/drug effects , Cross-Over Studies , Diabetes Mellitus, Type 2/blood , Dipeptidyl-Peptidase IV Inhibitors/administration & dosage , Double-Blind Method , Female , Glucagon-Like Peptide 1/drug effects , Glucose Tolerance Test , Humans , Male , Middle Aged , Pyrazines/administration & dosage , Sitagliptin Phosphate , Treatment Outcome , Triazoles/administration & dosage
19.
Vet Parasitol ; 186(3-4): 513-7, 2012 May 25.
Article in English | MEDLINE | ID: mdl-22169404

ABSTRACT

Three experiments defined the resistance profile of a population of Haemonchus contortus, which was shown to express multiple resistances to the benzimidazole, levamisole, macrocyclic lactone and salicylanilide anthelmintic classes when given as a registered combination. Study 1 was a faecal egg count reduction (FECR) test and the efficacies for the anthelmintics were monepantel, 100%; abamectin+levamisole+oxfendazole, 40.0%; and abamectin+levamisole+oxfendazole+naphthalophos, 100%. No larvae were recovered from the post-treatment cultures for monepantel or the 4-way treatment, and for the 3-way treatment the culture was 100% Haemonchus spp. Efficacies in Study 2 were calculated from mean post-mortem nematode burdens of H. contortus and were levamisole+oxfendazole, 3.1%; abamectin+levamisole+oxfendazole, 5.0%; ivermectin, 0.4%; moxidectin, 28.4% and closantel, 70.2%. Study 3 was also a FECR test that resulted in efficacies of 100% for monepantel and 83.0% for a formulated 4-way combination of abamectin+levamisole+albendazole+closantel. Larvae recovered from the post-treatment culture for the combination-treated sheep were all Haemonchus spp. Multi-resistant parasites such as examined in these studies are a continuing challenge to be managed by farmers and their advisors. Control programs must be planned and well-managed, and should include on-farm testing for anthelmintic resistance, monitoring of nematode burdens (by FEC and larval culture) to determine appropriate treatment times and the management of pastures to reduce the overall parasite challenge. This should be in balance with the generation, use and maintenance of drug-susceptible nematode populations in refugia.


Subject(s)
Aminoacetonitrile/analogs & derivatives , Anthelmintics/therapeutic use , Haemonchiasis/veterinary , Sheep Diseases/drug therapy , Aminoacetonitrile/administration & dosage , Aminoacetonitrile/therapeutic use , Animals , Anthelmintics/administration & dosage , Drug Therapy, Combination , Female , Haemonchiasis/drug therapy , Haemonchus , Male , Sheep
20.
Eur Surg Res ; 48(1): 16-25, 2012.
Article in English | MEDLINE | ID: mdl-22189343

ABSTRACT

BACKGROUND: The patient's individual anemia tolerance is pivotal when blood transfusions become necessary, but are not feasible for some reason. To date, the effects of neuromuscular blockade (NMB) on anemia tolerance have not been investigated. METHODS: 14 anesthetized and mechanically ventilated pigs were randomly assigned to the Roc group (3.78 mg/kg rocuronium bromide followed by continuous infusion of 1 mg/kg/min, n = 7) or to the Sal group (administration of the corresponding volume of normal saline, n = 7). Subsequently, acute normovolemic anemia was induced by simultaneous exchange of whole blood for a 6% hydroxyethyl starch solution (130/0.4) until a sudden decrease of total body O(2) consumption (VO(2)) indicated a critical limitation of O(2) transport capacity. The Hb concentration quantified at this time point (Hb(crit)) was the primary endpoint of the protocol. Secondary endpoints were parameters of hemodynamics, O(2) transport and tissue oxygenation. RESULTS: Hb(crit) was significantly lower in the Roc group (2.4 ± 0.5 vs. 3.2 ± 0.7 g/dl) reflecting increased anemia tolerance. NMB with rocuronium bromide reduced skeletal muscular VO(2) and total body O(2) extraction rate. As the cardiac index increased simultaneously, total body VO(2) only decreased marginally in the Roc group (change of VO(2) relative to baseline -1.7 ± 0.8 vs. 3.2 ± 1.9% in the Sal group, p < 0.05). CONCLUSION: Deep NMB with rocuronium bromide increases the tolerance of acute normovolemic anemia. The underlying mechanism most likely involves a reduction of skeletal muscular VO(2). During acellular treatment of an acute blood loss, NMB might play an adjuvant role in situations where profound stages of normovolemic anemia have to be tolerated (e.g. bridging an unexpected blood loss until blood products become available for transfusion).


Subject(s)
Androstanols/pharmacology , Anemia/physiopathology , Energy Metabolism/drug effects , Neuromuscular Nondepolarizing Agents/pharmacology , Oxygen Consumption/drug effects , Anemia/drug therapy , Anesthesia , Animals , Female , Hemodilution , Male , Models, Animal , Rocuronium , Swine
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