| 1. |
- Allen, David B, et al.
(författare)
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GH Safety Workshop Position Paper: a critical appraisal of recombinant human growth hormone therapy in children and adults.
- 2016
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 174:2, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant human growth hormone (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety including; cancer risk, impact on glucose homeostasis and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk and the need for longterm surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.
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| 2. |
- Sarris, Theodoros, et al.
(författare)
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Plasma-neutral interactions in the lower thermosphere-ionosphere : The need for in situ measurements to address focused questions
- 2023
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Ingår i: Frontiers in Astronomy and Space Sciences. - : Frontiers Media SA. - 2296-987X. ; 9
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Forskningsöversikt (refereegranskat)abstract
- The lower thermosphere-ionosphere (LTI) is a key transition region between Earth's atmosphere and space. Interactions between ions and neutrals maximize within the LTI and in particular at altitudes from 100 to 200 km, which is the least visited region of the near-Earth environment. The lack of in situ co-temporal and co-spatial measurements of all relevant parameters and their elusiveness to most remote-sensing methods means that the complex interactions between its neutral and charged constituents remain poorly characterized to this date. This lack of measurements, together with the ambiguity in the quantification of key processes in the 100-200 km altitude range affect current modeling efforts to expand atmospheric models upward to include the LTI and limit current space weather prediction capabilities. We present focused questions in the LTI that are related to the complex interactions between its neutral and charged constituents. These questions concern core physical processes that govern the energetics, dynamics, and chemistry of the LTI and need to be addressed as fundamental and long-standing questions in this critically unexplored boundary region. We also outline the range of in situ measurements that are needed to unambiguously quantify key LTI processes within this region, and present elements of an in situ concept based on past proposed mission concepts.
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| 3. |
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| 4. |
- Chen, Yun
(författare)
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Smooth muscle hypertrophy and the IGF-system
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Insulin-like growth factor-! (IGF-I) has both metabolic and mitogenic effects on smooth muscle cells (SMCs). The effects of IGF-I are modified by a group of binding proteins (IGFBPs). The present study was devoted to smooth muscle hypertrophy and the IGF-system in smooth muscle under different conditions. In urinary bladder, smooth muscle hypertrophy, initiated by partial outletobstruction, was associated with a transient increase in IGF-I mRNA, and pronounced, sustained increases oflGFBP-2 and IGFBP-4 mRNA, as well as increased protein contents of IGF-I and IGFBP-2. Regression of smooth muscle hypertrophy was associated with normalization of levels ofiGF-I, IGFBP-2 and IGFBP-4 mRNA. Expression of the IGF-I receptor did not change significantly. In portal vein, IGF-I mRNA and IGF-1 immunoreactivity were increased inhypertrophy induced by partialligation of the portal vein. Abdominal coarctation caused a rapid hypertensive response accompanied by an increased wet weight of aortic media. This was coincident with a progressive increase in aortic IGFBP-2 mRNA, about 10-fold after 14 days. The levels of IGFBP-4 mRNA in different muscle tissues and liver were decreased by diabetes and fasting, while IGFBP-2 mRNA was regulated in an organspecific 1nanner: with a sustained increase in liver and a decrease in aortic smooth muscle. Smooth muscle hypertrophy also occured in the urinary bladder of diabetic rats. DNA synthesis was increased and peaked at 2 days after induction of diabetes. DNA content per bladder wet weight was decreased by 7 days. Initially there was no changes in IGF-I mRNA, while IGFBP-2 mRNA and protein in the bladders were increased and peaked by 7 days. IGFBP-4 mRNA increased only on day 7. The changes of mRNA in bladder differed from that in liver and aorta, and suggested an early effect of stretching of the bladder due to diuresis, and later a contribution by the diabetic state. In cultured vascular SMCs, mechanical strain stimulated protein synthesis, but had little effect on DNA synthesis. However, mechanical strain potentiated the actions of IG:F'-1 and serum on both protein- and DNA synthesis, and influenced the effects of IGFBP-2. In conclusion, development of smooth muscle hypertrophy is associated with specific changes in IGF-I, IGFBP-2 and IGFBP-4, suggesting that the IGF-system may play a role in this process.
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| 5. |
- Ho, Ken, et al.
(författare)
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Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?
- 2021
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Ingår i: Journal of the Endocrine Society. - : The Endocrine Society. - 2472-1972. ; 5:3
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Forskningsöversikt (refereegranskat)abstract
- The WHO Classification of Endocrine Tumours designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.
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| 6. |
- Jimenez, Camilo, et al.
(författare)
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Follow-up of pituitary tumor volume in patients with acromegaly treated with pegvisomant in clinical trials
- 2008
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 159:5, s. 517-523
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We examined pituitary tumor volumes in patients treated with pegvisomant for 18 months or longer and in whom the tumors were monitored for at least 3 years. We present details on 9 of 304 patients in clinical trials with pegvisomant who experienced tumor growth within the first year of treatment. Method: Magnetic reonance images prior to start of pegvisomant and at last follow-up were examined in 43 patients (14% of participating patients). Twenty-nine had received prior radiation therapy (18% of irradiated patients and all but live received somatostatin analogs between periods of pegvisomant treatment. Results: At follow-up, the received tumor volume was 0.6 cc (range 0.0-19.7 ccl. in comparison with 1.6 cc (0.0-19.7 cc) at baseline (P<0.001). Twenty-five patients, of which 23 received radiation therapy, had tumor volume reduction therapy, had an increase in tumor volume from 1.61 to 1.93 cc. Of the nine patients with tumor growth, six had progressive growth before initiating pegvisomant. Two patients with stable tumors while on octreotide experienced enlargement after octreotide discontinuation but remained stable on long-term pegvisomant therapy. Conclusion: The present data indicate that pegvisomant does not promote tumor growth and suggest that the nine observed cases of tumor progression. which occured within 8 months after commencing pegvisomant, are likely rebound expansions after discontinuation of somatostatin analogs and/or the natural history of aggressively growing pituitary tumors. Continued long-term surveillance of tumor volume, particularly in non-irradiated patients is recommended.
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| 7. |
- van der Lely, Aart Jan, et al.
(författare)
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Development of ACRODAT®, a new software medical device to assess disease activity in patients with acromegaly
- 2017
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 20:6, s. 692-701
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Despite availability of multimodal treatment options for acromegaly, achievement of long-term disease control is suboptimal in a significant number of patients. Furthermore, disease control as defined by biochemical normalization may not always show concordance with disease-related symptoms or patient’s perceived quality of life. We developed and validated a tool to measure disease activity in acromegaly to support decision-making in clinical practice. Methods: An international expert panel (n = 10) convened to define the most critical indicators of disease activity. Patient scenarios were constructed based on these chosen parameters. Subsequently, a panel of 21 renowned endocrinologists at pituitary centers (Europe and Canada) categorized each scenario as stable, mild, or significant disease activity in an online validation study. Results: From expert opinion, five parameters emerged as the best overall indicators to evaluate disease activity: insulin-like growth factor I (IGF-I) level, tumor status, presence of comorbidities (cardiovascular disease, diabetes, sleep apnea), symptoms, and health-related quality of life. In the validation study, IGF-I and tumor status became the predominant parameters selected for classification of patients with moderate or severe disease activity. If IGF-I level was ≤1.2x upper limit of normal and tumor size not significantly increased, the remaining three parameters contributed to the decision in a compensatory manner. Conclusion: The validation study underlined IGF-I and tumor status for routine clinical decision-making, whereas patient-oriented outcome measures received less medical attention. An Acromegaly Disease Activity Tool (ACRODAT) is in development that might assist clinicians towards a more holistic approach to patient management in acromegaly.
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