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Open access

Ulla Schmidt, Birte Nygaard, Ebbe Winther Jensen, Jan Kvetny, Anne Jarløv, and Jens Faber

Background

A recent randomized controlled trial suggests that hypothyroid subjects may find levothyroxine (l-T4) and levotriiodothyronine combination therapy to be superior to l-T4 monotherapy in terms of quality of life, suggesting that the brain registered increased T3 availability during the combination therapy.

Hypothesis

Peripheral tissue might also be stimulated during T4/T3 combination therapy compared with T4 monotherapy.

Methods

Serum levels of sex hormone-binding globulin (SHBG), pro-collagen-1-N-terminal peptide (PINP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (representing hepatocyte, osteoblast, and cardiomyocyte stimulation respectively) were measured in 26 hypothyroid subjects in a double-blind, randomized, crossover trial, which compared the replacement therapy with T4/T3 in combination (50 μg T4 was substituted with 20 μg T3) to T4 alone (once daily regimens). This was performed to obtain unaltered serum TSH levels during the trial and between the two treatment groups. Blood sampling was performed 24 h after the last intake of thyroid hormone medication.

Results

TSH remained unaltered between the groups ((median) 0.83 vs 1.18 mU/l in T4/T3 combination and T4 monotherapy respectively; P=0.534). SHBG increased from (median) 75 nmol/l at baseline to 83 nmol/l in the T4/T3 group (P=0.015) but remained unaltered in the T4 group (67 nmol/l); thus, it was higher in the T4/T3 vs T4 group (P=0.041). PINP levels were higher in the T4/T3 therapy (48 vs 40 μg/l (P<0.001)). NT-proBNP did not differ between the groups.

Conclusions

T4/T3 combination therapy in hypothyroidism seems to have more metabolic effects than the T4 monotherapy.

Open access

Thomas Reinehr, Alberto Sánchez-Guijo, Nina Lass, and Stefan A Wudy

Objective

Little information is available on the steroid sulfates profile in obese children. Therefore, we examined whether sulfated steroids are linked with weight status and associated comorbidities in obese children.

Methods

We analyzed 66 obese children (mean age 10.5 ± 2.5 years, 57.6% female, 53.9% prepubertal, mean BMI 27.0 ± 4.6 kg/m2, 50% with BMI-SDS reduction >0.5, 50% without BMI-SDS reduction) who participated in an outpatient 1-year intervention program based on exercise, behavior and nutrition therapy. We measured intact sulfated steroids (cholesterol sulfate (CS), pregnenolone sulfate (PregS), 17αOH pregnenolone sulfate (17OH-PregS), 16αOH dehydroepiandrosterone sulfate (16OH-DHEAS), DHEAS, androstenediol-3-sulfate, androsterone sulfate and epiandrosterone sulfate) by LC–MS/MS, and insulin resistance index HOMA, lipids, blood pressure at baseline and 1 year later.

Results

All sulfated steroids except 17OH-PregS, 16OH-DHEAS, androsterone sulfate and epiandrosterone sulfate were higher in boys compared to girls. Concentrations of CS before intervention were higher in children who lost weight. After 1 year of treatment, both groups showed increased levels of DHEAS, 16OH-DHEAS and androstenediol-3-sulfate, but PregS was only increased in children with weight loss. None of the steroid sulfates was significantly related to cardiovascular risk factors or HOMA except 17OH-PregS, which was associated with systolic blood pressure both in cross-sectional (β-coefficient: 0.09 ± 0.07, P = 0.020) and longitudinal analyses (β-coefficient: 0.06 ± 0.04, P = 0.013) in multiple linear regression analyses.

Conclusions

Since higher steroid sulfation capacity was associated with successful weight intervention in children disruption of sulfation may be associated with difficulties to lose weight. Future studies are necessary to prove this hypothesis.

Open access

Aldo Bonaventura, Fabrizio Montecucco, and Franco Dallegri

The prevalence of type 2 diabetes mellitus (T2DM) is increasing all over the world. Targeting good glycemic control is fundamental to avoid the complications of diabetes linked to hyperglycemia. This narrative review is based on material searched for and obtained via PubMed up to April 2015. The search terms we used were: ‘hypoglycemia, diabetes, complications’ in combination with ‘iatrogenic, treatment, symptoms.’ Serious complications might occur from an inappropriate treatment of hyperglycemia. The most frequent complication is iatrogenic hypoglycemia that is often associated with autonomic and neuroglycopenic symptoms. Furthermore, hypoglycemia causes acute cardiovascular effects, which may explain some of the typical symptoms: ischemia, QT prolongation, and arrhythmia. With regards to the latter, the night represents a dangerous period because of the major increase in arrhythmias and the prolonged period of hypoglycemia; indeed, sleep has been shown to blunt the sympatho-adrenal response to hypoglycemia. Two main strategies have been implemented to reduce these effects: monitoring blood glucose values and individualized HbA1c goals. Several drugs for the treatment of T2DM are currently available and different combinations have been recommended to achieve individualized glycemic targets, considering age, comorbidities, disease duration, and life expectancy. In conclusion, according to international guidelines, hypoglycemia-avoiding therapy must reach an individualized glycemic goal, which is the lowest HbA1c not causing severe hypoglycemia and preserving awareness of hypoglycemia.

Open access

Kaisu Luiro, Kristiina Aittomäki, Pekka Jousilahti, and Juha S Tapanainen

Objective

To study the use of hormone therapy (HT), morbidity and reproductive outcomes of women with primary ovarian insufficiency (POI) due to FSH-resistant ovaries (FSHRO).

Design

A prospective follow-up study in a university-based tertiary clinic setting.

Methods

Twenty-six women with an inactivating A189V FSH receptor mutation were investigated by means of a health questionnaire and clinical examination. Twenty-two returned the health questionnaire and 14 were clinically examined. Main outcome measures in the health questionnaire were reported as HT, morbidity, medication and infertility treatment outcomes. In the clinical study, risk factors for cardiovascular disease (CVD) and metabolic syndrome (MetS) were compared to age-matched controls from a national population survey (FINRISK). Average number of controls was 326 per FSHRO subject (range 178–430). Bone mineral density and whole-body composition were analyzed with DXA. Psychological and sexual well-being was assessed with Beck Depression Inventory (BDI21), Generalized Anxiety Disorder 7 (GAD-7) and Female Sexual Function Index (FSFI) questionnaires.

Results

HT was initiated late (median 18 years of age) compared with normal puberty and the median time of use was shorter (20–22 years) than the normal fertile period. Osteopenia was detected in 9/14 of the FSHRO women despite HT. No major risk factors for CVD or diabetes were found.

Conclusions

HT of 20 years seems to be associated with a similar cardiovascular and metabolic risk factor profile as in the population control group. However, optimal bone health may require an early-onset and longer period of HT, which would better correspond to the natural fertile period.

Open access

Jan Calissendorff and Henrik Falhammar

Background

Graves’ disease is a common cause of hyperthyroidism. Three therapies have been used for decades: pharmacologic therapy, surgery and radioiodine. In case of adverse events, especially agranulocytosis or hepatotoxicity, pre-treatment with Lugol’s solution containing iodine/potassium iodide to induce euthyroidism before surgery could be advocated, but this has rarely been reported.

Methods

All patients hospitalised due to uncontrolled hyperthyroidism at the Karolinska University Hospital 2005–2015 and treated with Lugol’s solution were included. All electronic files were carefully reviewed manually, with focus on the cause of treatment and admission, demographic data, and effects of iodine on thyroid hormone levels and pulse frequency.

Results

Twenty-seven patients were included. Lugol’s solution had been chosen due to agranulocytosis in 9 (33%), hepatotoxicity in 2 (7%), other side effects in 11 (41%) and poor adherence to medication in 5 (19%). Levels of free T4, free T3 and heart rate decreased significantly after 5–9 days of iodine therapy (free T4 53–20 pmol/L, P = 0.0002; free T3 20–6.5 pmol/L, P = 0.04; heart rate 87–76 beats/min P = 0.0007), whereas TSH remained unchanged. Side effects were noted in 4 (15%) (rash n = 2, rash and vomiting n = 1, swelling of fingers n = 1). Thyroidectomy was performed in 26 patients (96%) and one was treated with radioiodine; all treatments were without serious complications.

Conclusion

Treatment of uncontrolled hyperthyroidism with Lugol’s solution before definitive treatment is safe and it decreases thyroid hormone levels and heart rate. Side effects were limited. Lugol’s solution could be recommended pre-operatively in Graves’ disease with failed medical treatment, especially if side effects to anti-thyroid drugs have occurred.

Open access

Alexander Tacey, Lewan Parker, Bu B Yeap, John Joseph, Ee M Lim, Andrew Garnham, David L Hare, Tara Brennan-Speranza, and Itamar Levinger

The aim of this study was to investigate the effect of a single dose of prednisolone on (A) high-intensity interval cycling performance and (B) post-exercise metabolic, hormonal and haematological responses. Nine young men participated in this double-blind, randomised, cross-over study. The participants completed exercise sessions (4 × 4 min cycling bouts at 90–95% of peak heart rate), 12 h after ingesting prednisolone (20 mg) or placebo. Work load was adjusted to maintain the same relative heart rate between the sessions. Exercise performance was measured as total work performed. Blood samples were taken at rest, immediately post exercise and up to 3 h post exercise. Prednisolone ingestion decreased total work performed by 5% (P < 0.05). Baseline blood glucose was elevated following prednisolone compared to placebo (P < 0.001). Three hours post exercise, blood glucose in the prednisolone trial was reduced to a level equivalent to the baseline concentration in the placebo trial (P > 0.05). Prednisolone suppressed the increase in blood lactate immediately post exercise (P < 0.05). Total white blood cell count was elevated at all time-points with prednisolone (P < 0.01). Androgens and sex hormone-binding globulin were elevated immediately after exercise, irrespective of prednisolone or placebo. In contrast, prednisolone significantly reduced the ratio of testosterone/luteinizing hormone (P < 0.01). Acute prednisolone treatment impairs high-intensity interval cycling performance and alters metabolic and haematological parameters in healthy young men. Exercise may be an effective tool to minimise the effect of prednisolone on blood glucose levels.

Open access

Richard P Steeds, Vandana Sagar, Shishir Shetty, Tessa Oelofse, Harjot Singh, Raheel Ahmad, Elizabeth Bradley, Rachel Moore, Suzanne Vickrage, Stacey Smith, Ivan Yim, Yasir S Elhassan, Hema Venkataraman, John Ayuk, Stephen Rooney, and Tahir Shah

Carcinoid heart disease (CHD) is a consequence of valvular fibrosis triggered by vasoactive substances released from neuroendocrine tumours, classically in those with metastatic disease and resulting in tricuspid and pulmonary valve failure. CHD affects one in five patients who have carcinoid syndrome (CS). Valve leaflets become thickened, retracted and immobile, resulting most often in regurgitation that causes right ventricular dilatation and ultimately, right heart failure. The development of CHD heralds a significantly worse prognosis than those patients with CS who do not develop valvular disease. Diagnosis requires a low threshold of suspicion in all patients with CS, since symptoms occur late in the disease process and clinical signs are difficult to elicit. As a result, routine screening is recommended using the biomarker, N-terminal pro-natriuretic peptide, and regular echocardiography is then required for diagnosis and follow-up. There is no direct medical therapy for CHD, but the focus of non-surgical care is to control CS symptoms, reduce tumour load and decrease hormone levels. Valve surgery improves long-term outcome for those with severe disease compared to medical management, although peri-operative mortality remains at between 10 and 20% in experienced centres. Therefore, care needs to be multidisciplinary at all stages, with clear discussion with the patient and between teams to ensure optimum outcome for these often-complex patients.

Open access

Willem de Ronde and Diederik L Smit

This review summarizes 10 years experience with male abusers of anabolic androgenic steroids (AAS). The typical user of AAS is male, aged between 20 and 40 and lifting weights. Illegal AAS are cheap and easily obtained via internet or local suppliers. AAS are mostly used in cycles with a duration between 6 and 18 weeks. Most AAS cycles contain multiple agents, used simultaneously in a dose vastly exceeding a substitution dose. A variety of other performance and image-enhancing drugs are commonly used, including human growth hormone, thyroid hormone, tamoxifen, clomiphene citrate and human chorionic gonadotrophin. Short-term clinical and biochemical side effects are well established. Long-term side effects are uncertain, but may include heart failure, mood-and anxiety disorders, hypogonadism and subfertility. We share our views on the management of common health problems associated with AAS abuse.

Open access

Ashley N Reeb, Andrea Ziegler, and Reigh-Yi Lin

Follicular thyroid cancer (FTC) is the second most common type of thyroid cancers. In order to develop more effective personalized therapies, it is necessary to thoroughly evaluate patient-derived cell lines in in vivo preclinical models before using them to test new, targeted therapies. This study evaluates the tumorigenic and metastatic potential of a panel of three human FTC cell lines (WRO, FTC-238, and TT1609-CO2) with defined genetic mutations in two in vivo murine models: an orthotopic thyroid cancer model to study tumor progression and a tail vein injection model to study metastasis. All cell lines developed tumors in the orthotopic model, with take rates of 100%. Notably, WRO-derived tumors grew two to four times faster than tumors arising from the FTC-238 and TT2609-CO2 cell lines. These results mirrored those of a tail vein injection model for lung metastasis: one hundred percent of mice injected with WRO cells in the tail vein exhibited aggressive growth of bilateral lung metastases within 35 days. In contrast, tail vein injection of FTC-238 or TT2609-CO2 cells did not result in lung metastasis. Together, our work demonstrates that these human FTC cell lines display highly varied tumorigenic and metastatic potential in vivo with WRO being the most aggressive cell line in both orthotopic and lung metastasis models. This information will be valuable when selecting cell lines for preclinical drug testing.

Open access

H A Booij, W D C Gaykema, K A J Kuijpers, M J M Pouwels, and H M den Hertog

Background

Poststroke fatigue (PSF) is a highly prevalent and debilitating condition. However, the etiology remains incompletely understood. Literature suggests the co-prevalence of pituitary dysfunction (PD) with stroke, and the question raises whether this could be a contributing factor to the development of PSF. This study reviews the prevalence of PD after stroke and other acquired brain injuries and its association with fatigue.

Summary

We performed a bibliographic literature search of MEDLINE and EMBASE databases for English language studies on PD in adult patients with stroke, traumatic brain injury (TBI) or aneurysmatic subarachnoid hemorrhage (aSAH). Forty-two articles were selected for review. Up to 82% of patients were found to have any degree of PD after stroke. Growth hormone deficiency was most commonly found. In aSAH and TBI, prevalences up to 49.3% were reported. However, data differed widely between studies, mostly due to methodological differences including the diagnostic methods used to define PD and the focus on the acute or chronic phase. Data on PD and outcome after stroke, aSAH and TBI are conflicting. No studies were found investigating the association between PD and PSF. Data on the association between PD and fatigue after aSAH and TBI were scarce and conflicting, and fatigue is rarely been investigated as a primary end point.

Key messages

Data according to the prevalence of PD after stroke and other acquired brain injury suggest a high prevalence of PD after these conditions. However, the clinical relevance and especially the association with fatigue need to be established.