Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 177
Filter
1.
J Eur Acad Dermatol Venereol ; 38(7): 1251-1280, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38456584

ABSTRACT

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes.


Subject(s)
Consensus , Scleroderma, Localized , Scleroderma, Systemic , Humans , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/therapy , Scleroderma, Localized/diagnosis , Scleroderma, Localized/therapy , Diagnosis, Differential
2.
Waste Manag ; 145: 92-101, 2022 May 15.
Article in English | MEDLINE | ID: mdl-35525002

ABSTRACT

A biocover system was established at Klintholm landfill in Denmark in 2009 to mitigate methane emissions, and the system exhibited high mitigation efficiency during the first year after implementation. The biocover system was revisited in 2016/2017, and a series of field and laboratory tests were carried out to evaluate functionality about six years after establishment. Three field campaigns were executed in three different barometric pressure conditions, namely increasing, stable and decreasing. Local surface flux measurements and gas concentration profiles in the methane oxidation layer showed that barometric pressure changes had a significant effect on gas emission and methane oxidation. Elevated concentrations of oxygen were observed in the gas distribution layer, and field data showed that significant methane oxidation took place in this location. This finding was verified in laboratory-based methane oxidation incubation tests. Temperatures higher than ambient temperature were observed throughout the methane oxidation layer, with average temperatures ranging between 13 and 27 °C, even in the coldest month of the year. Field measurements showed that total methane emissions from the whole landfill cell were at the same level or lower than measurements performed in 2009/2010 after implementation of the biocover system, and laboratory tests showed methane oxidation potential approximately equal to former tests. In spite of an inhomogeneous distribution of landfill gas load to the methane oxidation layer, the performance of the biocover system had not declined over the 6-7 years since its establishment, even though no maintenance had been carried out in the intervening years.


Subject(s)
Air Pollutants , Refuse Disposal , Air Pollutants/analysis , Methane/analysis , Oxidation-Reduction , Temperature , Waste Disposal Facilities
3.
Br J Dermatol ; 185(6): 1169-1175, 2021 12.
Article in English | MEDLINE | ID: mdl-33969479

ABSTRACT

BACKGROUND: Pyoderma gangrenosum (PG) is an ulcerative skin disease associated with comorbidities and increased mortality; however, the literature on this topic is scarce. OBJECTIVES: To investigate the mortality, prevalence and risk of comorbidities in patients with PG. METHODS: This nationwide registry nested case-control study included all inpatients and outpatients diagnosed with PG in tertiary dermatology centres in Denmark between 1 January 1994 and 31 December 2016. Each case was matched on date of birth and sex with 10 unique controls. The Danish National Patient Registry was used to identify all patients and to gather information on comorbidity. Information on age, sex, vital status and emigration was obtained from the Danish Civil Registration System. The outcomes were 19 different comorbidities and all-cause mortality. Prevalence was assessed from odds ratios (ORs) for specific comorbidities at the time of PG diagnosis. The risk of developing specific comorbidities and death was assessed using hazard ratios (HRs) obtained using the Cox proportional-hazards model. RESULTS: A total of 1604 patients with PG were matched with 16 039 controls. Some associations were known, e.g. inflammatory bowel disease [OR 19·15 (15·27-24·02), HR 6·51 (4·24-10·01)], while others have not been described previously, e.g. osteoporosis [OR 1·57 (1·22-2·02), HR 2·59 (2·08-3·22)]. Mortality was significantly increased among patients with PG [HR 2·79 (2·57-3·03)]. CONCLUSIONS: Patients with PG have increased mortality and an increased prevalence and risk of both previously reported and novel comorbidities that may have severe consequences if left undiagnosed. Our findings are mainly related to moderate and severe PG.


Subject(s)
Pyoderma Gangrenosum , Case-Control Studies , Comorbidity , Denmark/epidemiology , Humans , Pyoderma Gangrenosum/epidemiology , Registries , Risk Factors
4.
Int J Clin Pharm ; 43(2): 351-357, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32430881

ABSTRACT

Background Transdermal opioids are widely used among elderly adults with chronic pain. However, transdermal patches may be involved in a significant proportion of opioid-related patient safety incidents, as the application process includes several subprocesses, each associated with an individual risk of error. Objective The aim was to obtain specific knowledge on patient safety incidents related to transdermal opioid treatment within both the primary care sector and the hospital sector in Denmark. Setting The study is descriptive with data provided by the Danish Patient Safety Database. Methods We manually retrieved all patient safety incidents concerning transdermal opioids reported for 2018 from (1) the hospital sector and (2) the primary care sector. Study data were collected and managed using REDCap electronic data capture tools. Main outcome measure The available information for each incident was sorted into the following categories: location, medication process, type of problem, outcome at time of reporting, and outcome classification. Results A total of 866 patient safety incidents involving transdermal opioids were reported to the Danish Patient Safety Database in 2018. No fatal incidents were present in the database. In 386 cases, the incidents were reported as harmful, and these 386 cases were analysed. Most reports came from the primary care sector (nursing home, home care or social housing). The majority of incidents were related to the administration of the patch in the medication process, and the most prevalent problem was the omission of doses. Conclusion This study has demonstrated that the administration of transdermal opioids is challenging and may cause harm, particularly in the primary care sector. To improve patient safety, optimized systems, including guidelines on drug management and the continuing education of healthcare personnel in transdermal opioid management, are necessary. These guidelines should preferably incorporate reminders and checklists, since the omission of doses was the most reported problem.


Subject(s)
Analgesics, Opioid , Patient Safety , Adult , Aged , Analgesics, Opioid/adverse effects , Databases, Factual , Denmark/epidemiology , Hospitals , Humans
5.
J Environ Manage ; 274: 111181, 2020 Nov 15.
Article in English | MEDLINE | ID: mdl-32810679

ABSTRACT

Aquatic macrophytes grow abundantly in many lowland streams and play a key role in ecosystem functioning, such as nutrient retention. In this study, we performed a microcosm experiment to quantify and compare the contribution of two freshwater macrophyte growth forms to nutrient cycling. We measured and compared inorganic nitrogen (NH4-N and NO3-N) and phosphorus (PO4-P) uptake kinetic parameters (Vmax and Cmin) in 12 submerged and seven amphibious plant species. We tested whether relative growth rate (RGR) was related to high Vmax and low Cmin, and quantified changes in nutrient uptake kinetic in a subset of six out of 19 plants species during the growth season. Uptake rates of NH4-N were higher in submerged compared to amphibious plants, whereas uptake rates of NO3-N were significantly higher in amphibious species; PO4-P uptake kinetics were not significantly different between the two growth forms. There were also significant seasonal differences in Vmax NH4-N rate among both submerged and amphibious species and in Vmax NO3-N among amphibious species. Highest uptake rates were observed in summer for both submerged and amphibious species. Overall, we found that nutrient uptake kinetics differed between the two growth forms within and between seasons. Consequently, the presence of both growth forms should extend the period of nutrient uptake across the year and enhance nutrient uptake within seasons. We conclude that higher functional diversity enhances annual nutrient uptake in streams and that stream restoration efforts should consider increasing the niche space available for both submerged and amphibious species.


Subject(s)
Ecosystem , Phosphorus , Nitrogen , Nutrients , Rivers
6.
Clin Nutr ESPEN ; 35: 141-145, 2020 02.
Article in English | MEDLINE | ID: mdl-31987108

ABSTRACT

BACKGROUND: Liver fibrosis is a well-known complication of long-term use of parenteral nutrition in patients with intestinal failure associated to the nutrient composition in parenteral nutrition. This study investigates the prevalence of significant liver fibrosis and identifies risk factors for liver fibrosis. METHODS: This was a retrospective study of 35 parenteral nutrition-dependent patients with intestinal failure and 54 patients with intestinal insufficiency and oral nutrition only with a valid liver stiffness measurement obtained with transient elastography from November 2016 to August 2018. Clinical and demographic parameters including age, fat mass index and fat-free mass index, intact colon or colectomy, and nutritional management were analyzed for their association with liver stiffness. RESULTS: A prevalence for liver fibrosis (liver stiffness >7.0 kPa) was established at 37.1% in parenteral nutrition-dependent patients and at 22.2% in patients on oral nutrition. Several factors were significantly and independently associated with liver fibrosis including lipids in home parenteral nutrition (OR 10.66, p = 0.010) and colectomies (OR 3.24, p = 0.036). CONCLUSION: More than a third of patients receiving home parenteral nutrition have liver fibrosis. Several risk factors were demonstrated such as the amount of lipids and performed colectomies despite current international guidelines for lipids are followed. Our findings emphasize suggest a new perspective to prevent significant hepatic complications: colectomies.


Subject(s)
Liver Cirrhosis , Malnutrition , Parenteral Nutrition, Home/adverse effects , Adult , Aged , Colon , Female , Humans , Intestinal Diseases , Intestines , Liver , Liver Cirrhosis/epidemiology , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Parenteral Nutrition, Total , Prevalence , Retrospective Studies , Risk Factors
7.
Sci Rep ; 9(1): 12069, 2019 08 19.
Article in English | MEDLINE | ID: mdl-31427677

ABSTRACT

Visceral adipose tissue is an immunogenic tissue, which turns detrimental during obesity by activation of proinflammatory macrophages. During aging, chronic inflammation increases proportional to visceral adipose tissue (VAT) mass and associates with escalating morbidity and mortality. Here, we utilize a mouse model to investigate the inflammatory status of visceral adipose tissue in lean aging mice and assess the effects of exercise training interventions. We randomized adult (11 months; n = 21) and old (23 months; n = 27) mice to resistance training (RT) or endurance training (ET), or to a sedentary control group (S). Strikingly, we observed an anti-inflammatory phenotype in the old mice, consisting of higher accumulation of M2 macrophages and IL-10 expression, compared to the adult mice. In concordance, old mice also had less VAT mass and smaller adipocytes compared to adult mice. In both age groups, exercise training enhanced the anti-inflammatory phenotype and increased PGC1-α mRNA expression. Intriguingly, the brown adipose tissue marker UCP1 was modestly higher in old mice, while remained unchanged by the intervention. In conclusion, in the absence of obesity, visceral adipose tissue possesses a pronounced anti-inflammatory phenotype during aging which is further enhanced by exercise.


Subject(s)
Aging/physiology , Intra-Abdominal Fat/physiology , Obesity/physiopathology , Physical Conditioning, Animal , Adipocytes/metabolism , Adipocytes/physiology , Animals , Humans , Inflammation/metabolism , Inflammation/prevention & control , Intra-Abdominal Fat/metabolism , Macrophages/metabolism , Macrophages/physiology , Mice , Obesity/metabolism , Phenotype , Resistance Training
8.
Sci Rep ; 8(1): 16785, 2018 Nov 14.
Article in English | MEDLINE | ID: mdl-30429526

ABSTRACT

Melting at the base of the Antarctic Ice Sheet influences ice dynamics and our ability to recover ancient climatic records from deep ice cores. Basal melt rates are affected by geothermal flux, one of the least constrained properties of the Antarctic continent. Estimates of Antarctic geothermal flux are typically regional in nature, derived from geological, magnetic or seismic data, or from sparse point measurements at ice core sites. We analyse ice-penetrating radar data upstream of South Pole revealing a ~100 km long and 50 km wide area where internal ice sheet layers converge with the bed. Ice sheet modelling shows that this englacial layer configuration requires basal melting of up to 6 ± 1 mm a-1 and a geothermal flux of 120 ± 20 mW m-2, more than double the values expected for this cratonic sector of East Antarctica. We suggest high heat producing Precambrian basement rocks and hydrothermal circulation along a major fault system cause this anomaly. We conclude that local geothermal flux anomalies could be more widespread in East Antarctica. Assessing their influence on subglacial hydrology and ice sheet dynamics requires new detailed geophysical observations, especially in candidate areas for deep ice core drilling and at the onset of major ice streams.

9.
Transbound Emerg Dis ; 65(4): 1024-1032, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29457702

ABSTRACT

Since the introduction of African swine fever virus (ASFV) into the Baltic states and Poland in 2014, the disease has continued to spread within these regions. In 2017, the virus spread further west and the first cases of disease were reported in the Czech Republic and Romania, in wild boar and domestic pigs, respectively. To control further spread, knowledge of different modes of transmission, including indirect transmission via a contaminated environment, is crucial. Up until now, such an indirect mode of transmission has not been demonstrated. In this study, transmission via an environment contaminated with excretions from ASFV-infected pigs was investigated. Following euthanasia of pigs that were infected with an isolate of ASFV from Poland (POL/2015/Podlaskie/Lindholm), healthy pigs were introduced into the pens, in which the ASFV-infected pigs had been housed. Introduction was performed at 1, 3, 5 or 7 days, following euthanasia of the infected pig groups. Pigs, that were introduced into the contaminated environment after 1 day, developed clinical disease within 1 week, and both ASFV DNA and infectious virus were isolated from their blood. However, pigs introduced into the contaminated pens after 3, 5 or 7 days did not develop any signs of ASFV infection and no viral DNA was detected in blood samples obtained from these pigs within the following 3 weeks. Thus, it was shown that exposure of pigs to an environment contaminated with ASFV can result in infection. However, the time window for transmissibility of ASFV seems very limited, and, within our experimental system, there appears to be a rapid decrease in the infectivity of ASFV in the environment.


Subject(s)
African Swine Fever Virus/physiology , African Swine Fever/transmission , Environmental Monitoring , Swine Diseases/transmission , African Swine Fever/virology , African Swine Fever Virus/isolation & purification , Animals , Antibodies, Viral/blood , DNA, Viral/genetics , Enzyme-Linked Immunosorbent Assay/veterinary , Poland/epidemiology , Real-Time Polymerase Chain Reaction/veterinary , Sus scrofa/virology , Swine , Swine Diseases/virology , Time Factors
10.
Allergy ; 73(2): 498-504, 2018 02.
Article in English | MEDLINE | ID: mdl-28929567

ABSTRACT

BACKGROUND: Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. METHODS: The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational age <32 weeks, birth weight <1000 g, known immunodeficiency or no Danish-speaking parent. Data were collected through telephone interviews and clinical examinations until 13 months. RESULTS: Clinical atopic dermatitis was diagnosed in 466/2,052 (22.7%) children in the BCG group and 495/1,952 (25.4%) children in the control group (RR = 0.90 [95% confidence intervals 0.80-1.00]). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition (RR 0.84 (0.74-0.95)) and children without atopic predisposition (RR 1.09 [0.88-1.37]) (test of no interaction, P = .04). CONCLUSION: Among children with atopic predisposition, the number-needed-to-treat with BCG to prevent one case of atopic dermatitis was 21 (12-76).


Subject(s)
BCG Vaccine/therapeutic use , Dermatitis, Atopic/prevention & control , Dermatitis, Atopic/epidemiology , Female , Humans , Infant , Infant, Newborn , Male , Netherlands/epidemiology
11.
Biol Lett ; 14(12): 20180635, 2018 12 21.
Article in English | MEDLINE | ID: mdl-30958246

ABSTRACT

It is a generally accepted theory that ecological functions are enhanced with increased diversity in plant communities due to species complementarity effects. We tested this theory in a mesocosm study using freshwater submerged plant beds to determine if increasing species number caused overyielding and species complementarity. We applied a maximum of four species in the plant beds corresponding to the typical species number in natural freshwater plant beds. We found no clear effects of species number (1-4) on biomass production and thus no conclusive overyielding and complementarity effect. This may be explained by low species differentiation among the four species in plant traits relevant for resource acquisition in freshwater, or that other species interactions, e.g. allelopathy, were inhibiting overyielding. The existing knowledge on species complementarity in aquatic plant communities is sparse and inconclusive and calls for more research.


Subject(s)
Ecosystem , Wetlands , Biomass , Fresh Water , Hydrocharitaceae/growth & development , Potamogetonaceae/growth & development , Ranunculus/growth & development
12.
J Eur Acad Dermatol Venereol ; 31(10): 1581-1594, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28786499

ABSTRACT

The term 'sclerosing diseases of the skin' comprises specific dermatological entities which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this guideline provides clinicians with an overview of the diagnosis and treatment of scleromyxedema, scleredema (of Buschke) and nephrogenic systemic sclerosis (nephrogenic fibrosing dermopathy).


Subject(s)
Nephrogenic Fibrosing Dermopathy/diagnosis , Nephrogenic Fibrosing Dermopathy/therapy , Scleredema Adultorum/diagnosis , Scleredema Adultorum/therapy , Scleromyxedema/diagnosis , Scleromyxedema/therapy , Diagnosis, Differential , Humans , Nephrogenic Fibrosing Dermopathy/pathology , Scleredema Adultorum/pathology , Scleromyxedema/pathology
13.
J Eur Acad Dermatol Venereol ; 31(9): 1401-1424, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28792092

ABSTRACT

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this guideline provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes of systemic sclerosis with diseases of the rheumatological spectrum.


Subject(s)
Scleroderma, Localized , Scleroderma, Systemic , Undifferentiated Connective Tissue Diseases , Humans , Diagnosis, Differential , Europe , Physical Examination , Prognosis , Scleroderma, Localized/diagnosis , Scleroderma, Localized/pathology , Scleroderma, Localized/therapy , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/pathology , Scleroderma, Systemic/therapy , Undifferentiated Connective Tissue Diseases/diagnosis , Undifferentiated Connective Tissue Diseases/pathology , Undifferentiated Connective Tissue Diseases/therapy
14.
Br J Dermatol ; 176(6): 1486-1491, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28235244

ABSTRACT

BACKGROUND: Bullous pemphigoid (BP) is a disease of the elderly and may be associated with neurological and cardiovascular diseases and diabetes. Mortality rates strongly exceed those of the background population. OBJECTIVES: To investigate the frequency of comorbidities and their temporal relation to BP. METHODS: A register-based matched-cohort study on all Danish patients with a hospital-based diagnosis of BP (n = 3281). The main outcomes were multiple sclerosis (MS), Parkinson disease (PD), Alzheimer disease (AD), stroke, diabetes types 1 and 2, malignancies, ischaemic heart disease (IHD), hypertension and eventually death. RESULTS: At baseline, patients with BP had increased prevalences of MS [odds ratio (OR) 9·7, 95% confidence interval (CI) 6·0-15·6], PD (OR 4·2, 95% CI 3·1-5·8), AD (OR 2·6, 95% CI 1·8-3·5) and stroke (OR 2·7, 95% CI 2·4-2·9). Furthermore, malignancies, cardiovascular disease and diabetes were over-represented among patients with BP: type 1 diabetes (OR 3·1, 95% CI 2·5-3·8), type 2 diabetes (OR 2·3, 95% CI 2·0-2·6), malignancies (OR 1·3, 95% CI 1·1-1·4), IHD (OR 1·7, 95% CI 1·5-1·9) and hypertension (OR 2·0, 95% CI 1·8-2·2). During follow-up, the risk of MS was significantly higher among patients with BP [hazard ratio (HR) 9·4, 95% CI 4·9-18·0], even if events during the first year after diagnosis of BP were excluded (HR 5·1, 95% CI 2·3-11·3). Patients with BP had an average increased mortality rate of 2·04 (95% CI 1·96-2·13). CONCLUSIONS: We discovered a significantly increased frequency of MS among patients with BP. At the time of diagnosis, patients with BP had an excessive number of comorbidities and an increased mortality rate over the following years.


Subject(s)
Multiple Chronic Conditions/mortality , Multiple Sclerosis/complications , Pemphigoid, Bullous/complications , Adult , Age of Onset , Aged , Aged, 80 and over , Denmark/epidemiology , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multiple Sclerosis/mortality , Pemphigoid, Bullous/mortality , Registries
15.
Article in English | MEDLINE | ID: mdl-28086261

ABSTRACT

BACKGROUND: Gastrointestinal symptoms are common in the general population and may originate from disturbances in gut motility. However, fundamental mechanistic understanding of motility remains inadequate, especially of the less accessible regions of the small bowel and colon. Hence, refinement and validation of objective methods to evaluate motility of the whole gut is important. Such techniques may be applied in clinical settings as diagnostic tools, in research to elucidate underlying mechanisms of diseases, and to evaluate how the gut responds to various drugs. A wide array of such methods exists; however, a limited number are used universally due to drawbacks like radiation exposure, lack of standardization, and difficulties interpreting data. In recent years, several new methods such as the 3D-Transit system and magnetic resonance imaging assessments on small bowel and colonic motility have emerged, with the advantages that they are less invasive, use no radiation, and provide much more detailed information. PURPOSE: This review outlines well-established and emerging methods to evaluate small bowel and colonic motility in clinical settings and in research. The latter include the 3D-Transit system, magnetic resonance imaging assessments, and high-resolution manometry. Procedures, indications, and the relative strengths and weaknesses of each method are summarized.


Subject(s)
Gastrointestinal Motility/physiology , Intestine, Large/diagnostic imaging , Intestine, Large/physiology , Intestine, Small/diagnostic imaging , Intestine, Small/physiology , Manometry/methods , Breath Tests/methods , Gastrointestinal Diseases/diagnostic imaging , Gastrointestinal Diseases/physiopathology , Gastrointestinal Transit/physiology , Humans , Magnetic Resonance Imaging/methods , Radionuclide Imaging/methods
16.
Eur J Pharm Sci ; 99: 337-342, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-28063968

ABSTRACT

AIM: A high inter-individual variation in the pharmacokinetics and pharmacodynamics of morphine has been observed. Genetic polymorphisms in genes encoding the organic cation transporter isoform 1 (OCT1), the efflux transporter p-glycoprotein (ABCB1), and the UDP-glucuronosyltransferase-2B7 (UGT2B7) may influence morphine pharmacokinetics and thus, also pharmacodynamics. The aim of this study was to evaluate the association between OCT1, ABCB1, and UGT2B7 variants, and morphine pharmacokinetics and -dynamics in healthy volunteers. METHODS: Pharmacokinetic and pharmacodynamic data were collected from a double-blinded, randomized, crossover trial in 37 healthy subjects. Pharmacokinetic data were analyzed in NONMEM®, and the time-concentration relationship of morphine, morphine-3-glucuronide, and morphine-6-glucuronide was parameterized as the transit compartment rate constant (ktr), clearance (CL), and volume of distribution (VD). The area under the plasma concentration-time curve (AUC0-150min) and the maximum plasma concentration (Cmax) were also calculated. Pharmacodynamic data were measured as pain tolerance thresholds to mechanical stimulation of the rectum and muscle, as well as tonic cold pain stimulation ("the cold pressor test" where hand was immersed in cold water). Six different single nucleotide polymorphisms in three different genes (OCT1 (n=22), ABCB1 (n=37), and UGT2B (n=22)) were examined. RESULTS: Neither AUC0-150min, ktr, CL, nor VD were associated with genetic variants in OCT1, ABCB1, and UGT2B7 (all P>0.05). Similarly, the antinociceptive effects of morphine on rectal, muscle, and cold pressor tests were not associated with these genetic variants (all P>0.05). CONCLUSIONS: In this experimental study in healthy volunteers, we found no association between different genotypes of OCT1, ABCB1, and UGT2B7, and morphine pharmacokinetics and pharmacodynamics. Nonetheless, due to methodological limitations we cannot exclude that associations exist.


Subject(s)
Glucuronosyltransferase/genetics , Morphine/pharmacokinetics , Octamer Transcription Factor-1/genetics , Polymorphism, Single Nucleotide/genetics , ATP Binding Cassette Transporter, Subfamily B/genetics , Adult , Cross-Over Studies , Double-Blind Method , Female , Genotype , Humans , Male , Randomized Controlled Trials as Topic , Young Adult
17.
Article in English | MEDLINE | ID: mdl-27989852

ABSTRACT

BACKGROUND: Standardized objective methods to assess the analgesic effects of opioids, enable identification of underlying mechanisms of drug actions in the central nervous system. Opioids may exert their effect on both cortical and spinal levels. In this study actions of morphine at both levels were investigated, followed by analysis of a possible correlation between the cortical processing and spinal transmission. METHODS: The study was conducted after a double-blinded, two-way crossover design in thirty-nine healthy participants. Each participant received 30mg morphine or placebo as oral solution in randomized order. The electroencephalogram (EEG) was recorded during rest and during immersion of the hand into ice-water. Electrical stimulation of the sole of the foot was used to elicit the nociceptive withdrawal reflex and the reflex amplitude was recorded. RESULTS: Data from thirty subjects was included in the data analysis. There was no change in the activity in resting EEG (P>0.05) after morphine administration as compared to placebo. During cold pressor stimulation, morphine significantly lowered the relative activity in the delta (1-4Hz) band (P=0.03) and increased the activity in the alpha (8-12Hz) band (P=0.001) as compared to placebo. The reflex amplitudes significantly decreased after morphine administration (P=0.047) as compared to placebo. There was no correlation between individual EEG changes during cold pressor stimulation and the decrease in the reflex amplitude after morphine administration (P>0.05). CONCLUSIONS: Cold pressor EEG and the nociceptive reflex were more sensitive to morphine analgesia than resting EEG and can be used as standardized objective methods to assess opioid effects. However, no correlation between the analgesic effect of morphine on the spinal and cortical assessments could be demonstrated.


Subject(s)
Cerebral Cortex/physiology , Cold Temperature/adverse effects , Electroencephalography/methods , Pain Measurement/methods , Reflex/physiology , Spinal Cord/physiology , Adult , Analgesics, Opioid/pharmacology , Cerebral Cortex/drug effects , Cross-Over Studies , Double-Blind Method , Electric Stimulation/adverse effects , Electroencephalography/drug effects , Female , Humans , Male , Morphine/pharmacology , Pain Measurement/drug effects , Reflex/drug effects , Spinal Cord/drug effects , Young Adult
18.
Eur J Neurosci ; 44(11): 2966-2974, 2016 12.
Article in English | MEDLINE | ID: mdl-27748551

ABSTRACT

Severe pain is often treated with opioids. Antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) have also shown a pain relieving effect, but for both SNRI and opioids, the specific mode of action in humans remains vague. This study investigated how oxycodone and venlafaxine affect spinal and supraspinal pain processing. Twenty volunteers were included in this randomized cross-over study comparing 5-day treatment with venlafaxine, oxycodone and placebo. As a proxy of the spinal pain transmission, the nociceptive withdrawal reflex (NWR) to electrical stimulation on the sole of the foot was recorded at the tibialis anterior muscle before and after 5 days of treatment. For the supraspinal activity, 61-channel electroencephalogram evoked potentials (EPs) to the electrical stimulations were simultaneously recorded. Areas under curve (AUCs) of the EMG signals were analyzed. Latencies and AUCs were computed for the major EP peaks and brain source analysis was done. The NWR was decreased in venlafaxine arm (P = 0.02), but the EP parameters did not change. Oxycodone increased the AUC of the EP response (P = 0.04). Oxycodone also shifted the cingulate activity anteriorly in the mid-cingulate-operculum network (P < 0.01), and the cingulate activity was increased while the operculum activity was decreased (P = 0.02). Venlafaxine exerts its effects on the modulation of spinal nociceptive transmission, which may reflect changes in balance between descending inhibition and descending facilitation. Oxycodone, on the other hand, exerts its effects at the cortical level. This study sheds light on how opioids and SNRI drugs modify the human central nervous system and where their effects dominate.


Subject(s)
Analgesics, Opioid/pharmacology , Nociception/drug effects , Nociceptive Pain/drug therapy , Oxycodone/pharmacology , Serotonin and Noradrenaline Reuptake Inhibitors/pharmacology , Venlafaxine Hydrochloride/pharmacology , Adult , Analgesics, Opioid/therapeutic use , Case-Control Studies , Evoked Potentials, Motor , Evoked Potentials, Somatosensory , Humans , Male , Neural Inhibition , Oxycodone/therapeutic use , Pain Threshold , Reaction Time , Serotonin and Noradrenaline Reuptake Inhibitors/therapeutic use , Spinal Cord/physiology , Spinal Cord/physiopathology , Venlafaxine Hydrochloride/therapeutic use
19.
J Bioeth Inq ; 13(3): 419-29, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27365102

ABSTRACT

Pre-Implantation Genetic Diagnosis (PGD) represents the first fusion of genomics and assisted reproduction and the first reproductive technology that allows prospective parents to screen and select the genetic characteristics of their potential offspring. However, for some, the idea that we can intervene in the mechanisms of human existence at such a fundamental level can be, at a minimum, worrying and, at most, repugnant. Religious doctrines particularly are likely to collide with the rapidly advancing capability for science to make such interventions. This paper focuses on opinions and arguments of selected religious scholars regarding ethical issues pertaining to PGD. In-depth interviews were conducted with religious scholars from three different religious organizations in the Klang Valley, Malaysia. Findings showed that Christian scholars are very sceptical of the long-term use of PGD because of its possible effect on the value of humanity and the parent-children relationship. This differs from Islamic scholars, who view PGD as God-given knowledge in medical science to further help humans understand medical genetics. For Buddhist scholars, PGD is considered to be new medical technology that can be used to save lives, avoid suffering, and bring happiness to those who need it. Our results suggest that it is important to include the opinions and views of religious scholars when it comes to new medical technologies such as PGD, as their opinions will have a significant impact on people from various faiths, particularly in a multi-religious country like Malaysia where society places high value on marital relationships and on the traditional concepts of family.


Subject(s)
Attitude , Ethics , Genetic Testing/ethics , Prenatal Diagnosis/ethics , Religion and Medicine , Reproductive Techniques, Assisted/ethics , Technology/ethics , Buddhism , Choice Behavior/ethics , Christianity , Genomics , Humans , Islam , Malaysia , Parents
20.
Eur J Pain ; 20(8): 1214-22, 2016 09.
Article in English | MEDLINE | ID: mdl-26919233

ABSTRACT

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a major health problem that is frequently accompanied by debilitating oesophageal pain symptoms. OBJECTIVES: The first objective of the study was to examine the association between catastrophizing and oesophageal pain sensitivity. The second objective was to examine whether catastrophizing was associated with the magnitude of acid-induced oesophageal sensitization. METHODS: Twenty-five healthy volunteers (median age: 24.0 years; range: 22-31) were recruited and were asked to complete the Pain Catastrophizing Scale (PCS). During two subsequent study visits, mechanical, thermal, and electrical pain sensitivity in the oesophagus was assessed before and after inducing oesophageal sensitization using a 30-min intraluminal oesophageal acid perfusion procedure. RESULTS: Analyses were conducted based on data averaged across the two study visits. At baseline, catastrophizing was significantly associated with mechanical (r = -0.42, p < 0.05) and electrical (r = -0.60, p < 0.01) pain thresholds. After acid perfusion, catastrophizing was also significantly associated with mechanical (r = -0.58, p < 0.01) and electrical (r = -0.50, p < 0.05) pain thresholds. Catastrophizing was not significantly associated with thermal pain thresholds. Subsequent analyses revealed that catastrophizing was not significantly associated with the magnitude of acid-induced oesophageal sensitization. CONCLUSION: Taken together, findings from the present study suggest that catastrophic thinking exerts an influence on oesophageal pain sensitivity, but not necessarily on the magnitude of acid-induced oesophageal sensitization. WHAT DOES THIS STUDY ADD?: Catastrophizing is associated with heightened pain sensitivity in the oesophagus. This was substantiated by assessing responses to noxious stimulation of the oesophagus using an experimental paradigm mimicking features and symptoms experienced by patients with gastro-oesophageal reflux disease (GORD).


Subject(s)
Catastrophization/psychology , Gastroesophageal Reflux/psychology , Pain/psychology , Adult , Cross-Over Studies , Double-Blind Method , Female , Gastroesophageal Reflux/drug therapy , Humans , Male , Pain/diagnosis , Pain/etiology , Pain Perception , Pain Threshold , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...