Paraneoplastic hypoglycaemia secondary to IGF-2 secretion from a metastatic gastrointestinal stromal tumour

We report the case of a 79-year-old male with previous history of non-Hodgkin's lymphoma in remission, who presented acutely to the Accident and Emergency department with recurrent episodes of hypoglycaemia. At the time of presentation, a random glucose was low at 1.4 mmol/l, which upon correction resolved his symptoms. In hindsight, the patient recalled having had similar episodes periodically over the past 2 months to which he did not give much notice. While hospitalized, he continued having episodes of symptomatic hypoglycaemia, requiring treatment with intravenous dextrose and per os steroids. Once stable, he was discharged on oral prednisolone and dietary advice. A computed tomography scan performed during inpatient stay showed multiple deposits in the abdomen. An ultrasound guided biopsy of one of the liver deposits was performed. Immunohistochemistry supported the diagnosis of a gastrointestinal stromal tumour (GIST) positive for CD34 and CD117. The diagnosis of non-islet cell tumour hypoglycaemia (NICTH) secondary to an IGF2 secreting GIST was confirmed with further biochemical investigations (IGF2=105.9 nmol/l; IGF2:IGF1 ratio 23, Upper Level of Normal (ULN) <10). Targeted cytoreductive treatment with Imatinib mesylate following assessment of the tumour's mutational status was successful in preventing hypoglycaemia over a 21-month follow-up observation period

Orexin-A exerts equivocal role in atherosclerosis process depending on the duration of exposure : in vitro study

Orexin-A is a peptide hormone that plays a crucial role in feeding regulation and energy homeostasis. Diurnal intermittent fasting (DIF) has been found to increase orexin-A plasma levels during fasting hours, while Ramadan fasting which resembles DIF, has led to beneficial effects on endothelial function. Herein, we aimed to investigate the effects of orexin-A on the expression of molecules involved in the atherogenesis process: Monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase-1 and 2 (TIMP-1 and TIMP-2), in human aortic endothelial cells (HAECs). HAECs were incubated with orexin-A at concentrations of 40 ng/mL, 200 ng/mL and 400 ng/mL for 6, 12 and 24 h. The mRNA levels of MCP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 and orexin-1 receptor were measured by real-time qPCR. We also evaluated the MMP-2, p38, phospho-p38, NF-κΒ/p65 as well as TIMP-1 protein levels by Western blot and ELISA, respectively. MMP-2 activity was measured by gelatin zymography. Short-term 6-h incubation of HAECs with orexin-A at a high concentration (400 ng/mL) decreased MCP-1, MMP-2 expression, MMP-2/TIMP-1 ratio (p < 0.05), and MMP-2 activity, while incubation for 24 h increased MCP-1, MMP-2 expression (p < 0.05), MMP-2/TIMP-1 and MMP-2/TIMP-2 ratio (p < 0.01 and p < 0.05, respectively) as well as MMP-2 activity. The dual effects of orexin-A are mediated, at least in part, via regulation of p38 and NF-κΒ pathway. Orexin-A may have an equivocal role in atherosclerosis process with its effects depending on the duration of exposure

Synergistic Gravity and the Role of Resonances in GRS-Inspired Braneworlds

We consider 5D braneworld models of quasi-localized gravity in which 4D gravity is reproduced at intermediate scales while the extra dimension opens up at both the very short and the very long distances, where the geometry is flat. Our main interest is the interplay between the zero mode of these models, whenever a normalizable zero mode exists, and the effects of zero energy graviton resonant modes coming from the contributions of massive KK modes. We first consider a compactified version of the GRS model and find that quasi-localized gravity is characterized by a scale for which both the resonance and the zero mode have significant contribution to 4D gravity. Above this scale, gravity is primarily mediated by the zero mode, while the resonance gives only minor corrections. Next, we consider an asymmetric version of the standard non-compact GRS model, characterized by different cosmological constants on each AdS side. We show that a resonance is present but the asymmetry, through the form of the localizing potential, can weaken it, resulting in a shorter lifetime and, thus, in a shorter distance scale for 4D gravity. As a third model exhibiting quasi-localization, we consider a version of the GRS model in which the central positive tension brane has been replaced by a configuration of a scalar field propagating in the bulk.Comment: 18 pages, 3 figures, added 1 figure, revised version as published in Class. Quant. Gra

Using late-time optical and near-infrared spectra to constrain Type Ia supernova explosion properties

The late-time spectra of Type Ia supernovae (SNe Ia) are powerful probes of the underlying physics of their explosions. We investigate the late-time optical and near-infrared spectra of seven SNe Ia obtained at the VLT with XShooter at $>$200 d after explosion. At these epochs, the inner Fe-rich ejecta can be studied. We use a line-fitting analysis to determine the relative line fluxes, velocity shifts, and line widths of prominent features contributing to the spectra ([Fe II], [Ni II], and [Co III]). By focussing on [Fe II] and [Ni II] emission lines in the ~7000-7500 \AA\ region of the spectrum, we find that the ratio of stable [Ni II] to mainly radioactively-produced [Fe II] for most SNe Ia in the sample is consistent with Chandrasekhar-mass delayed-detonation explosion models, as well as sub-Chandrasekhar mass explosions that have metallicity values above solar. The mean measured Ni/Fe abundance of our sample is consistent with the solar value. The more highly ionised [Co III] emission lines are found to be more centrally located in the ejecta and have broader lines than the [Fe II] and [Ni II] features. Our analysis also strengthens previous results that SNe Ia with higher Si II velocities at maximum light preferentially display blueshifted [Fe II] 7155 \AA\ lines at late times. Our combined results lead us to speculate that the majority of normal SN Ia explosions produce ejecta distributions that deviate significantly from spherical symmetry.Comment: 17 pages, 12 figure, accepted for publication in MNRA

Severe paraneoplastic hypoglycemia secondary to a gastrointestinal stromal tumour masquerading as a stroke

We report the case of a 70-year-old previously healthy female who presented acutely to the Accident and Emergency department with left-sided vasomotor symptoms including reduced muscle tone, weakness upon walking and slurred speech. Physical examination confirmed hemiparesis with VIIth nerve palsy and profound hepatomegaly. A random glucose was low at 1.7 mmol/l, which upon correction resolved her symptoms. In hindsight, the patient recalled having had similar episodes periodically over the past 3 months to which she did not give much attention. While hospitalized, she continued having episodes of symptomatic hypoglycaemia during most nights, requiring treatment with i.v. dextrose and/or glucagon. Blood tests including insulin and C-peptide were invariably suppressed, in correlation with low glucose. A Synacthen stimulation test was normal (Cort (0′) 390 nmol/l, Cort (30′) 773 nmol/l). A computed tomography scan showed multiple lobulated masses in the abdomen, liver and pelvis. An ultrasound guided biopsy of one of the pelvic masses was performed. Immunohistochemistry supported the diagnosis of a gastrointestinal stromal tumour (GIST) positive for CD34 and CD117. A diagnosis of a non islet cell tumour hypoglycaemia (NICTH) secondary to an IGF2 secreting GIST was confirmed with further biochemical investigations (IGF2=96.5 nmol/l; IGF2:IGF1 ratio 18.9, ULN <10). Treatment with growth hormone resolved the patient's hypoglycaemic symptoms and subsequent targeted therapy with Imatinib was successful in controlling disease progression over an 8-year observation period

The value of PRL in predicting prolactinοma in hyperprolactinemic PCOS

Background To identify a serum prolactin (PRL) cut‐off value indicative of a PRL‐producing adenoma in women with Polycystic Ovarian Syndrome (PCOS) and hyperprolactinemia and characterize such patients. Materials and methods In the present retrospective case‐control study the medical records of 528 PCOS women were reviewed. Pituitary magnetic resonance imaging (MRI) was performed in PCOS patients with PRL levels ≥94.0 ng/mL and/or symptoms suspicious of a pituitary adenoma (PA). Prolactinoma diagnosis was made in the presence of an MRI‐identifiable PA with biochemical and radiological response to dopamine agonists. Receiver operating characteristic (ROC) curve analysis was performed to determine a serum PRL threshold that could identify hyperprolactinemic PCOS subjects with prolactinomas. Clinical, metabolic and endocrine parameters were also analysed. Results Among 528 patients with PCOS, 60 (11.4%) had elevated PRL levels. Of 44 (73.3%) patients who had pituitary imaging, 19 had PAs, 18 normal MRI and 7 other abnormalities. Patients harboring prolactinomas had significantly higher PRL levels compared to patients without adenomas (median PRL 95.4 vs. 49.2 ng/mL, p<0.0001). A PRL threshold of 85.2 ng/mL could distinguish patients with prolactinomas with 77% sensitivity and 100% specificity [Area Under the curve (AUC) (95%) 0.91(0.8‐1.018), p=0.0001]. PCOS women with prolactinomas were younger and had lower LH levels compared to women without prolactinomas. Conclusions In women with PCOS, PRL levels exceeding 85.2 ng/mL are highly suggestive of a prolactinoma warranting pituitary imaging. Pituitary MRI could also be considered in young PCOS patients with milder PRL elevation and low LH levels

DGP Cosmology with a Non-Minimally Coupled Scalar Field on the Brane

We construct a DGP inspired braneworld scenario where a scalar field non-minimally coupled to the induced Ricci curvature is present on the brane. First we investigate the status of gravitational potential with non-minimal coupling and observational constraints on this non-minimal model. Then we further deepen the idea of embedding of FRW cosmology in this non-minimal setup. Cosmological implications of this scenario are examined with details and the quintessence and late-time expansion of the universe within this framework are examined. Some observational constraints imposed on this non-minimal scenario are studied and relation of this model with dark radiation formalism is determined with details.Comment: 26 pages, 3 eps figure

Laparoscopic adjustable gastric banding – should a second chance be given?

Background: Obesity is a chronic relapsing-remitting disease and a global pandemic, being associated with multiple comorbidities. Laparoscopic adjustable gastric banding (LAGB) is one of the safest surgical procedures used for the treatment of obesity, and even though its popularity has been decreasing over time, it still remains an option for a certain group of patients, producing considerable weight loss and improvement in obesity-associated comorbidities. Methods: The aim of this study was to evaluate the impact of weight loss following LAGB on obesity-associated comorbidities, and to identify factors that could predict better response to surgery, and patient sub-groups exhibiting greatest benefit. A total of 99 severely obese patients (81.2% women, mean age 44.19 ± 10.94 years, mean body mass index (BMI) 51.84 ± 8.77 kg/m2) underwent LAGB in a single institution. Results obtained 1, 2, and 5 years postoperatively were compared with the pre-operative values using SPPS software version 20. Results: A significant drop in BMI was recorded throughout the follow-up period, as well as in A1c and triglycerides, with greatest improvement seen 2 years after surgery (51.8 ± 8.7 kg/m2 vs 42.3 ± 9.2 kg/m2, p < 0.05, 55.5 ± 19.1 mmol/mol vs 45.8 ± 13.7 mmol/mol, p < 0.05, and 2.2 ± 1.7 mmol/l vs 1.5 ± 0.6 mmol/l). Better outcomes were seen in younger patients, with lower duration of diabetes before surgery, and lower pre-operative systolic blood pressure. Conclusions: Younger age, lower degree of obesity, and lower severity of comorbidities at the time of surgery can be important predictors of successful weight loss, making this group of patients the ideal candidates for LAGB