955 research outputs found
Recommended from our members
A consensus on the diagnosis and treatment of acromegaly complications
In March 2011, the Acromegaly Consensus Group met to revise and update the guidelines on the diagnosis and treatment of acromegaly complications. The meeting was sponsored by the Pituitary Society and the European Neuroendocrinology Association and included experts skilled in the management of acromegaly. Complications considered included cardiovascular, endocrine and metabolic, sleep apnea, bone diseases, and mortality. Outcomes in selected, related clinical conditions were also considered, and included pregnancy, familial acromegaly and invasive macroadenomas. The need for a new disease staging model was considered, and design of such a tool was proposed
In active acromegaly, IGF1 bioactivity is related to soluble Klotho levels and quality of life
The value of measuring IGF1 bioactivity in active acromegaly is unknown. Soluble Klotho (S-Klotho) level is elevated in active acromegaly and it has been suggested that S-Klotho can inhibit activation of the IGF1 receptor (IGF1R). A cross-sectional study was carried out in 15 patients with active acromegaly based on clinical presentation, unsuppressed GH during an oral glucose tolerance test, and elevated total IGF1 levels (>+2 s.d.). Total IGF1 was measured by immunoassay, IGF1 bioactivity by the IGF1R kinase receptor activation assay and S-Klotho by an ELISA. Quality of Life (QoL) was assessed by Acromegaly QoL (AcroQoL) Questionnaire and Short-Form-36 Health Survey Questionnaire (SF-36). Out of 15 patients, nine had IGF1 bioactivity values within the reference range. S-Klotho was higher in active acromegaly compared with controls. Age-adjusted S-Klotho was significantly related to IGF1 bioactivity (r=0.75, P=0.002) and to total IGF1 (r=0.62, P=0.02). IGF1 bioactivity and total IGF1 were inversely related to the physical component summary of the SF-36 (r=−0.78, P=0.002 vs r=−0.60, P=0.03). Moreover, IGF1 bioactivity, but not total IGF1, was significantly inversely related to the physical dimension of the AcroQoL Questionnaire (r=−0.60, P=0.02 vs r=−0.37, P=0.19). In contrast to total IGF1, IGF1 bioactivity was within the reference range in a considerable number of subjects with active acromegaly. Elevated S-Klotho levels may have reduced IGF1 bioactivity. Moreover, IGF1 bioactivity was more strongly related to physical measures of QoL than total IGF1, suggesting that IGF1 bioactivity may better reflect physical limitations perceived in active acromegaly
Feasibility, endocrine and anti-tumour effects of a triple endocrine therapy with tamoxifen, a somatostatin analogue and an antiprolactin in post-menopausal metastatic breast cancer: a randomized study with long-term follow-up.
Suppression of the secretion of prolactin, growth hormone and insulin-like growth factor 1 (IGF-1) might be important in the growth regulation and treatment of breast cancer. Because oestrogens may counteract the anti-tumour effects of such treatment, the combination of an anti-oestrogen (tamoxifen), a somatostatin analogue (octreotide) and a potent anti-prolactin (CV 205-502) might be attractive. In this respect, we performed a first exploratory long-term study on the feasibility of combined treatment and possible clear differences in endocrine and anti-tumour effects during such combined treatment vs standard treatment with tamoxifen alone. Twenty-two post-menopausal patients with metastatic breast cancer (ER and/or PR positive or unknown) were randomized to receive either 40 mg of tamoxifen per day or the combination of 40 mg of tamoxifen plus 75 microg of CV 205-502 orally plus 3 x 0.2 mg of octreotide s.c. as first-line endocrine therapy. An objective response was found in 36% of the patients treated with tamoxifen alone and in 55% of the patients treated with combination therapy. Median time to progression was 33 weeks for patients treated with tamoxifen and 84 weeks for patients treated with combination therapy, but the numbers are too small for hard conclusions. There was no difference in overall post-relapse survival between the two treatment arms. With respect to the endocrine parameters, there was a significant decrease of plasma IGF-1 levels in both treatment arms, whereas during combined treatment plasma growth hormone tended to decrease and plasma prolactin levels were strongly suppressed; in some patients insulin and transforming growth factor alpha (TGF-alpha) decreased during the triple therapy. Although there was no significant difference in mean decrease of plasma IGF-1 levels between the two treatment arms, combined treatment resulted in a more uniform suppression of IGF-1. Therefore, the addition of a somatostatin analogue and an anti-prolactin may potentially enhance the efficacy of anti-oestrogens in the treatment of breast cancer owing to favourable endocrine and possible direct anti-tumour effects. Large phase III trials using depot formulations (to increase the feasibility) of somatostatin analogues are warranted to demonstrate the potential extra beneficial anti-tumour effects of such combination therapy
Visualization of the thymus by substance P receptor scintigraphy in man
Substance P, an 11-amino acid neuropeptide, has an important role in modulating pain transmission through neurokinin 1 and 2 receptors. Substance P and other tachykinins may also play a role in the pathogenesis of inflammatory diseases. In this study we present the results concerning the metabolism of the substance P analogue [111In-DTPA-Arg1]-substance P in man, as well as the visualization of the thymus in patients with immune-mediated diseases. Twelve selected patients were investigated, comprising five with inflammatory bowel disease, one with ophthalmic Graves' disease, one with sclerosing cholangitis, one with Sjogren's syndrome, one with rheumatoid arthritis, one with systemic lupus erythematosus and two with myasthenia gravis. During and after intravenous administration of 150-250 MBq (2.5-5.0 μg) [111In-DTPA-Arg1]-substance P, blood pressure, heart rate and oxygen saturation were monitored. Radioactivity was measured in blood, urine and faeces during the 48 h after injection. Planar and single-photon emission tomographic images were obtained 4 and 24 h after injection. After administration of [111In-DTPA-Arg1]-substance P a transient flush was observed in all patients. Degradation of [111In-DTPA-Arg1] -substance P started in the first minutes after administration, resulting in a half-life of 10 min for the total plasma radioactivity, and of 4 min for the intact radiopharmaceutical, as identified with high-performance liquid chromatography. Urinary excretion accounted for >95% of the radioactivity within 24 h post injection, and up to 0.05% was found in the faeces up to 60 h. In all patients uptake of radioactivity was found in the areolae mammae (in women), liver, spleen, kidneys and urinary bladder. In eight patients a high uptake of [111In-DTPA-Arg1]-substance P was observed in the thymus. We conclude that, despite its short half-life. [111In-DTPA-Arg1]-substance P, a new radiopharmaceutical, can be used to visualize the thymus. This may contribute to the investigation of the role of thymus in immune-mediated diseases. In addition, inflammatory sites in various diseases could be visualized.</p
Visualization of the thymus by substance P receptor scintigraphy in man
Substance P, an 11-amino acid neuropeptide, has an important role in modulating pain transmission through neurokinin 1 and 2 receptors. Substance P and other tachykinins may also play a role in the pathogenesis of inflammatory diseases. In this study we present the results concerning the metabolism of the substance P analogue [111In-DTPA-Arg1]-substance P in man, as well as the visualization of the thymus in patients with immune-mediated diseases. Twelve selected patients were investigated, comprising five with inflammatory bowel disease, one with ophthalmic Graves' disease, one with sclerosing cholangitis, one with Sjogren's syndrome, one with rheumatoid arthritis, one with systemic lupus erythematosus and two with myasthenia gravis. During and after intravenous administration of 150-250 MBq (2.5-5.0 μg) [111In-DTPA-Arg1]-substance P, blood pressure, heart rate and oxygen saturation were monitored. Radioactivity was measured in blood, urine and faeces during the 48 h after injection. Planar and single-photon emission tomographic images were obtained 4 and 24 h after injection. After administration of [111In-DTPA-Arg1]-substance P a transient flush was observed in all patients. Degradation of [111In-DTPA-Arg1] -substance P started in the first minutes after administration, resulting in a half-life of 10 min for the total plasma radioactivity, and of 4 min for the intact radiopharmaceutical, as identified with high-performance liquid chromatography. Urinary excretion accounted for >95% of the radioactivity within 24 h post injection, and up to 0.05% was found in the faeces up to 60 h. In all patients uptake of radioactivity was found in the areolae mammae (in women), liver, spleen, kidneys and urinary bladder. In eight patients a high uptake of [111In-DTPA-Arg1]-substance P was observed in the thymus. We conclude that, despite its short half-life. [111In-DTPA-Arg1]-substance P, a new radiopharmaceutical, can be used to visualize the thymus. This may contribute to the investigation of the role of thymus in immune-mediated diseases. In addition, inflammatory sites in various diseases could be visualized.</p
Somatostatin and dopamine receptors as targets for medical treatment of Cushing's Syndrome
Somatostatin (SS) and dopamine (DA) receptors are widely expressed in neuroendocrine tumours that cause Cushing's Syndrome (CS). Increasing knowledge of specific subtype expression within these tumours and the ability to target these receptor subtypes with high-affinity compounds, has driven the search for new SS- or DA-based medical therapies for the various forms of CS. In Cushing's disease, corticotroph adenomas mainly express dopamine receptor subtype 2 (D2) and somatostatin receptor subtype 5 (sst5), whereas sst2is expressed at lower levels. Activation of these receptors can inhibit ACTH-release in primary cultured corticotroph adenomas and compounds that target either sst5(pasireotide, or SOM230) or D2(cabergoline) have shown significant efficacy in subsets of patients in recent clinical studies. Combination therapy, either by administration of both types of compounds separately or by treatment with novel somatostatin-dopamine chimeric molecules (e.g. BIM-23A760), appears to be a promising approach in this respect. In selected cases of Ectopic ACTH-producing Syndrome (EAS), the sst2-preferring compound octreotide is able to reduce cortisol levels effectively. A recent study showed that D2receptors are also significantly expressed in the majority of EAS and that cabergoline may decrease cortisol levels in subsets of these patients. In both normal adrenal tissue as well as in adrenal adenomas and carcinomas that cause CS, sst and DA receptor expression has been demonstrated. Although selected cases of adrenal CS may benefit from sst or DA-targeted treatment, its total contribution to the treatment of these patients is likely to be low as surgery is effective in most cases
A randomized controlled trial to compare a restrictive strategy to usual care for the effectiveness of cholecystectomy in patients with symptomatic gallstones (SECURE trial protocol)
BACKGROUND: Five to 22 % of the adult Western population has gallstones. Among them, 13 to 22 % become symptomatic during their lifetime. Cholecystectomy is the preferred treatment for symptomatic cholecystolithiasis. Remarkably, cholecystectomy provides symptom relief in only 60-70 % of patients. The objective of this trial is to compare the effectiveness of usual (operative) care with a restrictive strategy using a standardized work-up with stepwise selection for cholecystectomy in patients with gallstones and abdominal complaints. DESIGN AND METHODS: The SECURE-trial is designed as a multicenter, randomized, parallel-arm, non-inferiority trial in patients with abdominal symptoms and ultrasound proven gallstones or sludge. If patients meet the inclusion criteria they will be randomized to either usual care or the restrictive strategy. Patients in the usual care group will be treated according to the physician's knowledge and preference. Patients in the restrictive care group will be treated with interval evaluation and stepwise selection for laparoscopic cholecystectomy. In this stepwise selection, patients strictly meeting the preselected criteria for symptomatic cholecystolithiasis will be offered a cholecystectomy. Patients not meeting these criteria will be assessed for other diagnoses and re-evaluated at 3-monthly intervals. Follow-up consists of web-based questionnaires at 3, 6, 9 and 12 months. The main end point of this trial is defined as the proportion of patients being pain-free at 12 months follow-up. Pain will be assessed with the Izbicki Pain Score and Gallstone Symptom Score. Secondary endpoints will be the proportion of patients with complications due to gallstones or cholecystectomy, the association between the patients' symptoms and treatment and work performance, and ultimately, cost-effectiveness. DISCUSSION: The SECURE trial is the first randomized controlled trial examining the effectiveness of usual care versus restrictive care in patients with symptomatic gallstones. The outcome of this trial will inform clinicians whether a more restrictive strategy can minimize persistent pain in post-operative patients at least as good as usual care does, but at a lower cholecystectomy rate. (The Netherlands National Trial Register NTR4022, 17th December 2012) TRIAL REGISTRATION: The Netherlands National Trial Register NTR4022 http://www.zonmw.nl/nl/projecten/project-detail/scrutinizing-inefficient-use-of-c holecystectomy-a-randomized-trial-concerning-variation-in-practi/samenvatting/
Proton pump inhibitors and risk of gastric cancer: a population-based cohort study
Proton pump inhibitor (PPI) use leads to hypergastrinaemia, which has been associated with gastrointestinal neoplasia. We evaluated the association between PPI use and risk of gastric cancer using population-based health-care registers in North Jutland, Denmark, during 1990–2003. We compared incidence rates among new users of PPI (n=18 790) or histamine-2-antagonists (H2RAs) (n=17 478) and non-users of either drug. Poisson regression analysis was used to estimate incidence rate ratios (IRRs) adjusted for multiple confounders. We incorporated a 1-year lag time to address potential reverse causation. We identified 109 gastric cancer cases among PPI users and 52 cases among H2RA users. After incorporating the 1-year lag time, we observed IRRs for gastric cancer of 1.2 (95% CI: 0.8–2.0) among PPI users and 1.2 (95% CI: 0.8–1.8) among H2RA users compared with non-users. These estimates are in contrast to significant overall IRRs of 9.0 and 2.8, respectively, without the lag time. In lag time analyses, increased IRRs were observed among PPI users with the largest number of prescriptions or the longest follow-up compared with H2RA users or non-users. Although our results point to a major influence of reverse causation and confounding by indication on the association between PPI use and gastric cancer incidence, the finding of increased incidence among PPI users with most prescriptions and longest follow-up warrants further investigation
Increasing incidence of skin disorders in children? A comparison between 1987 and 2001
BACKGROUND: The increasing proportion of skin diseases encountered in general practice represents a substantial part of morbidity in children. Only limited information is available about the frequency of specific skin diseases. We aimed to compare incidence rates of skin diseases in children in general practice between 1987 and 2001. METHODS: We used data on all children aged 0–17 years derived from two consecutive surveys performed in Dutch general practice in 1987 and 2001. Both surveys concerned a longitudinal registration of GP consultations over 12 months. Each disease episode was coded according to the International Classification of Primary Care. Incidence rates of separate skin diseases were calculated by dividing all new episodes for each distinct ICPC code by the average study population at risk. Data were stratified for socio-demographic characteristics. RESULTS: The incidence rate of all skin diseases combined in general practice decreased between 1987 and 2001. Among infants the incidence rate increased. Girls presented more skin diseases to the GP. In the southern part of the Netherlands children consulted their GP more often for skin diseases compared to the northern part. Children of non-Western immigrants presented relatively more skin diseases to the GP. In general practice incidence rates of specific skin diseases such as impetigo, dermatophytosis and atopic dermatitis increased in 2001, whereas warts, contact dermatitis and skin injuries decreased. CONCLUSION: The overall incidence rate of all skin diseases combined in general practice decreased whereas the incidence rates of bacterial, mycotic and atopic skin diseases increased
- …