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Sökning: WFRF:(Edén Engström Britt)

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1.
  • Nilsson, Anna G, et al. (författare)
  • Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency.
  • 2014
  • Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 171:3, s. 369-77
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency. Design: Randomized, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. Methods: Sixty-four adults with primary AI started stage 1 and an additional 16 entered stage 3. Patients received DR-HC 20-40 mg once daily and hydrocortisone 20-40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness). Results: In stage 1, patients had a median 1.5 (range 1-9) intercurrent illness events with DR-HC and 1.0 (1-8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1-3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure. Conclusions: This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI, and has demonstrated that such treatment is well tolerated during 24 consecutive months of therapy.
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2.
  • Bäcklund, Nils, et al. (författare)
  • Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing's syndrome
  • 2020
  • Ingår i: European journal of endocrinology. - Society of the European Journal of Endocrinology. - 1479-683X. ; 182:6, s. 569-582
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The challenge of diagnosing Cushing's syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST). Design and methods: Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves. Results: The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70-99%) and specificity of 96% (91-98%) for cortisol, and a 100% (84-100%) sensitivity and 95% (90-98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75-100%) sensitivity and 96% (92-99%) specificity with cortisol, and 100% (83-100%) sensitivity and 94% (89-97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h. Conclusion: Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better.
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3.
  • Holmer, Helene, et al. (författare)
  • Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone
  • 2007
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - Oxford University Press. - 1945-7197. ; 92:9, s. 3560-3567
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown. Objective: The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus ( T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls. Design and Participants: The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively. Results: Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication. Conclusions: The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity.
4.
  • Ragnarsson, Oskar, 1971-, et al. (författare)
  • Overall and disease-specific mortality in patients with Cushing's disease: a Swedish nationwide study.
  • 2019
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197. ; 104:6
  • Tidskriftsartikel (refereegranskat)abstract
    • It is still a matter of debate whether patients with Cushing's disease (CD) in remission have increased mortality.To study overall and disease-specific mortality, and predictive factors, in an unselected nationwide cohort of patients with CD.A retrospective study on patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardised mortality ratios (SMRs) with 95% confidence intervals (CI) were calculated and Cox regression models were used to identify predictors of mortality.Five-hundred-and-two patients [387 women (77%)] with CD were identified, of whom 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 years (SD 16) and median follow-up time was 13 years (IQR 6-23). The observed number of deaths was 133 versus 54 expected, resulting in an overall SMR of 2.5 (95% CI 2.1-2.9). The commonest cause of death was cardiovascular diseases [SMR 3.3 (95% CI 2.6 -4.3)]. Excess mortality was also found due to infections and suicides. SMR in patients in remission was 1.9 (95% CI 1.5-2.3), where bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality whereas growth hormone replacement was associated with improved outcome.This large nationwide study shows that patients with CD have an excess mortality. The findings illustrate the importance of obtaining remission and continued active surveillance, along with adequate hormone replacement, and evaluation of cardiovascular risk and mental health.
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5.
  • Zetterling, Maria, 1966-, et al. (författare)
  • Cortisol and ACTH dynamics in the acute phase of subarachnoid haemorrhage
  • ????
  • Ingår i: British Journal of Neurosurgery. - 0268-8697 .- 1360-046X.
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Objective: </strong>An adequate response of hypothalamic-pituitary-adrenal (HPA) axis is important for survival and recovery after a severe disease. The hypothalamus and the pituitary glands are at risk of damage after subarachnoid haemorrhage (SAH). A better understanding of the hormonal changes would be valuable for optimizing care in the acute phase of SAH.</p> <p><strong>Patients:</strong> 55 patients with spontaneous SAH were evaluated regarding morning levels of S-Cortisol and P-ACTH seven days after the bleeding. In a subgroup of 20 patients the diurnal changes of S-Cortisol and P-ACTH levels were studied and U-Cortisol measured. The relations of hormone levels to clinical and radiological parameters and to outcome were assessed.</p> <p><strong>Results: </strong>S-Cortisol and P-ACTH were elevated the day of SAH. S-Cortisol levels below reference range were uncommon. Early global cerebral oedema was associated with higher S-Cortisol concentrations at admission and a worse WFNS and RLS85 grade. Patients in better WFNS grade had higher U-Cortisol levels. All patients showed diurnal variations of S-Cortisol and P-ACTH. A reversed diurnal variation of S-Cortisol was more frequently seen in mechanically ventilated patients. Periods of suppressed P-ACTH associated with S-Cortisol peaks occurred especially in periods of secondary brain ischemia.</p> <p><strong>Conclusion: </strong>There is a HPA response<strong> </strong>acutely<strong> </strong>after<strong> </strong>SAH with an increase of P-ACTH and S-Cortisol levels. Higher U-Cortisol levels in patients in a better clinical grade may indicate a more robust response of the HPA system. Global cerebral oedema was associated with higher S-Cortisol levels at admission and may be the result of the stress response initiated by the brain injury. Periods of suppressed P-ACTH occurred particularly in periods of brain ischemia, indicating a possibly connection between brain ischemia and ACTH suppression. These two novel findings should be evaluated in further studies.</p>
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6.
  • Zetterling, Maria, et al. (författare)
  • Cortisol and adrenocorticotropic hormone dynamics in the acute phase of subarachnoid haemorrhage
  • 2011
  • Ingår i: British Journal of Neurosurgery. - 0268-8697 .- 1360-046X. ; 25:6, s. 684-692
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Objective. An adequate response of hypothalamic-pituitary-adrenal (HPA) axis is important for survival and recovery after a severe disease. The hypothalamus and the pituitary glands are at risk of damage after subarachnoid haemorrhage (SAH). A better understanding of the hormonal changes would be valuable for optimising care in the acute phase of SAH. Patients. Fifty-five patients with spontaneous SAH were evaluated regarding morning concentrations of serum (S)-cortisol and P-adrenocorticotropic hormone (ACTH) 7 days after the bleeding. In a subgroup of 20 patients, the diurnal changes of S-cortisol and P-ACTH were studied and urine (U)-cortisol was measured. The relationships of hormone concentrations to clinical and radiological parameters and to outcome were assessed. Results. S-cortisol and P-ACTH were elevated the day of SAH. S-cortisol concentrations below reference range were uncommon. Early global cerebral oedema was associated with higher S-cortisol concentrations at admission and a worse World Federation of Neurological Surgeons (WFNS) and Reaction Level Scale 85 grade. Global cerebral oedema was shown to be a predictor of S-cortisol at admittance. Patients in better WFNS grade displayed higher U-cortisol. All patients showed diurnal variations of S-cortisol and P-ACTH. A reversed diurnal variation of S-cortisol was more frequently found in mechanically ventilated patients. Periods of suppressed P-ACTH associated with S-cortisol peaks occurred especially in periods of secondary brain ischaemia. Conclusion. There was an HPA response acutely after SAH with an increase in P-ACTH and S-cortisol. Higher U-cortisol in patients in a better clinical grade may indicate a more robust response of the HPA system. Global cerebral oedema was associated with higher S-cortisol at admission and was a predictor of S-cortisol concentrations. Global cerebral oedema may be the result of the stress response initiated by the brain injury. Periods of suppressed P-ACTH occurred particularly in periods of brain ischaemia, indicating a possible connection between brain ischaemia and ACTH suppression.</p>
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7.
  • Zetterling, Maria, et al. (författare)
  • Somatotropic and thyroid hormones in the acute phase of subarachnoid haemorrhage
  • 2013
  • Ingår i: Acta Neurochirurgica. - 0001-6268 .- 0942-0940. ; 155:11, s. 2053-2062
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Somatotropic and thyroid hormones are probably important for the recovery after acute brain injury. Still, the dynamics of these hormones after spontaneous subarachnoid haemorrhage (SAH) is not well described. The purpose of this study was to investigate the relation between somatotropic and thyroid hormones and clinical factors after SAH. Twenty patients with spontaneous SAH were included prospectively. Serum concentrations of TSH, fT4, T3, IGF-1 and GH were measured once a day for 7 days after SAH. Hormone patterns and serum concentrations were compared to the severity of SAH, neurological condition at admission, clinical course and outcome of the patients. During the first week after SAH, all patients showed increased GH and IGF-1 concentrations. In the whole group, concentrations of TSH increased, whereas T3 and fT4 decreased. There were no relations of serum concentrations of IGF-1 or GH to clinical condition at admission, clinical course or outcome of the patients. Half of the patients showed low T3 serum concentrations. A complicated course was associated with a deeper fall in TSH and T3 concentrations. There were negative correlations for mean concentrations of TSH and T3 versus WFNS grade and a positive correlation for T3 versus GOS after 6 months, indicating that low concentrations of TSH and T3 were connected to worse SAH grade and poor outcome. All patients showed increased GH and IGF-1 concentrations irrespective of the grade of SAH or clinical course. Patients with a complicated clinical course showed a more pronounced fall in TSH and T3 concentrations and low serum T3 concentrations were related to a more serious SAH and poor patient outcome. These results need to be studied further and they may contribute to the accumulated knowledge needed to understand the complex mechanisms influencing the unpredictable clinical course after SAH.</p>
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8.
  • Abrahamsson, Niclas, et al. (författare)
  • Gastric Bypass Surgery Elevates NT-ProBNP Levels
  • 2013
  • Ingår i: Obesity Surgery. - 0960-8923 .- 1708-0428. ; 23:9, s. 1421-1426
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>Background</strong></p><p>Brain natriuretic peptide (BNP) is produced in the heart in response to stretching of the myocardium. BNP levels are negatively correlated to obesity, and in obese subjects, a reduced BNP responsiveness has been described. Diet-induced weight loss has been found to lower or to have no effect on BNP levels, whereas gastric banding and gastric bypass have reported divergent results. We studied obese patients undergoing gastric bypass (GBP) surgery during follow-up of 1 year.</p><p><strong>Methods</strong></p><p>Twenty patients, 18 women, mean 41 (SD 9.5) years old, with a mean preoperative BMI of 44.6 (SD 5.5) kg/m<sup>2</sup> were examined. N-terminal pro-brain natriuretic peptide (NT-ProBNP), glucose and insulin were measured preoperatively, at day 6 and months 1, 6 and 12. In 14 of the patients, samples were also taken at days 1, 2 and 4.</p><p><strong>Results</strong></p><p>The NT-ProBNP levels showed a marked increase during the postoperative week (from 54 pg/mL preop to 359 pg/mL on day 2 and fell to 155 on day 6). At 1 year, NT-ProBNP was 122 pg/mL (125 % increase, <em>p</em> = 0.01). Glucose, insulin and HOMA indices decreased shortly after surgery without correlation to NT-ProBNP change. Mean BMI was reduced from 44.6 to 30.5 kg/m<sup>2</sup> at 1 year and was not related to NT-ProBNP change.</p><p><strong>Conclusions</strong></p><p>The data indicate that GBP surgery rapidly alters the tone of BNP release, by a mechanism not related to weight loss or to changes in glucometabolic parameters. The GBP-induced conversion of obese subjects, from low to high NT-ProBNP responders, is likely to influence the evaluation of cardiac function in GBP operated individuals.</p>
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9.
  • Abrahamsson, Niclas, et al. (författare)
  • GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery : a potential new indication?
  • 2013
  • Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 169:6, s. 885-889
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Objective: The number of morbidly obese subjects submitted to bariatric surgery is rising worldwide. In a fraction of patients undergoing gastric bypass (GBP), episodes with late postprandial hypoglycemia (PPHG) develop 1-3 years after surgery. The pathogenesis of this phenomenon is not fully understood; meal-induced rapid and exaggerated increases of circulating incretins and insulin appear to be at least partially responsible. Current treatments include low-carbohydrate diets, inhibition of glucose intestinal uptake, reduction of insulin secretion with calcium channel blockers, somatostatin analogs, or diazoxide, a KATP channel opener. Even partial pancreatectomy has been advocated. In type 2 diabetes, GLP1 analogs have a well-documented effect of stabilizing glucose levels without causing hypoglycemia. Design: We explored GLP1 analogs as open treatment in five consecutive GBP cases seeking medical attention because of late postprandial hypoglycemic symptoms. Results: Glucose measured in connection with the episodes in four of the cases had been 2.7, 2.5, 1.8, and 1.6 mmol/l respectively. The patients consistently described that the analogs eliminated their symptoms, which relapsed in four of the five patients when treatment was reduced/discontinued. The drug effect was further documented in one case by repeated 24-h continuous glucose measurements. Conclusion: These open, uncontrolled observations suggest that GLP1 analogs might provide a new treatment option in patients with problems of late PPHG.</p>
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10.
  • Abrahamsson, Niclas, et al. (författare)
  • Hypoglycemia in everyday life after gastric bypass and duodenal switch
  • 2015
  • Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 173:1, s. 91-100
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Design: Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life. Methods: Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study. Results: The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (&lt; 3.3 mmol/l, or 60 mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol, P &lt; 0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period. Conclusion: Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.</p>
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