Radiotherapy in acromegaly: the argument against

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73294/1/j.1365-2265.2003.01704.x.pd

Gene Expression Signature in Adipose Tissue of Acromegaly Patients.

To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly

Acromegaly

In the majority of cases, acromegaly is due to GH hypersecretion by a somatotroph pituitary tumor. The etiology of acromegaly is not known, and may be related to GHRH hypersecretion, intrinsic pituitary defect, or a combination thereof. Recent physiologic data and molecular biology techniques provide insights into the pathophysiology of this condition. Treatment options include surgery, radiation, and judicious administration of pharmacologic compounds inhibiting GH secretion and tumor growth.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29921/1/0000278.pd

Nowhere to Run; Nowhere to Hide: The Reality of Being a Law Library Director in Times of Great Opportunity and Significant Challenges

This is an edited version of remarks presented at \u27Nowhere to Run, Nowhere to Hide\u27: The Reality of Being a Law Library Director in Times of Great Opportunity and Significant Challenges, January 5, 2015, at the Association of American Law Schools Annual Meeting, Washington, D.C

Wind-induced ground motion: dynamic model and non-uniform structure for ground

Wind-induced ground vibrations are a source of noise in seismic surveys. In a previous study, a wind-ground coupling theory was developed to predict the power spectral density (PSD) of ground motions caused by wind perturbations on the ground surface. The prediction was developed using a superposition of the point source response of an elastic isotropic homogeneous medium deforming quasi-statically with the statistical description of the wind-induced pressure fluctuations on the ground. Model predictions and field measurements were in agreement for the normal component of the displacement but under predicted the horizontal component. In this paper, two generalizations are investigated to see if they lead to increased horizontal displacement predictions: 1. First, the dynamic point source response is calculated and incorporated in the ground displacement calculation. Measured ground responses are used to incorporate losses into the dynamic calculation. 2. The quasi-static response function for three different types of non-uniform grounds are calculated and used in the seismic wind noise superposition. The dynamic point source response and the three more realistic ground models result in larger horizontal displacements for the point source at distances on the order of 1 m or greater from the source. However, the superposition to predict the seismic wind noise is dominated by the displacements very close to the point source where the prediction is unchanged. This research indicates that the modeling of the wind-induced pressure source distribution must be improved to predict the observed equivalency of the vertical and horizontal displacements

Medical Management of Growth Hormone-Secreting Pituitary Adenomas

The primary treatment of acromegaly remains transsphenoidal adenomectomy, yet the tissue overgrowth of acromegaly often progresses following surgery, and responds to radiotherapy only after significant delay. Persistently elevated serum growth hormone (GH) and insulin-like growth factor-I (IGF-I) concentrations can be normalized in about half of post-surgery acromegalics using the pharmacologic alternatives presently available, the dopamine agonists (DA) and somatostatin (SST) analogs. Cabergoline, the most efficacious DA, normalizes IGF-I in approximately 37% of patients, whereas the long-acting SST analogs, Octreotide LAR and Lanreotide SR, do so in 66%. Significant tumor shrinkage may be attained with SST analogs in particular, and when necessary, the primary medical treatment of acromegaly may be successfully addressed with this class of drugs. Greatly enhanced efficacy is expected from the GH receptor antagonist pegvisomant, which is nearing market availability and will enable the normalization of serum IGF-I in virtually all patients treated. We review here the pharmacologic treatments of excessive GH secretion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47513/1/11102_2004_Article_5115783.pd