Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome

Purpose

In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m²) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.

Angiotensin and mineralocorticoid receptor antagonism attenuates cardiac oxidative stress in angiotensin II‐infused rats

Angiotensin II (Ang II) and aldosterone contribute to hypertension, oxidative stress and cardiovascular damage, but the contributions of aldosterone during Ang II‐dependent hypertension are not well defined because of the difficulty to assess each independently. To test the hypothesis that during Ang II infusion, oxidative and nitrosative damage is mediated through both the mineralocorticoid receptor (MR) and angiotensin type 1 receptor (AT1), five groups of Sprague–Dawley rats were studied: (i) control; (ii) Ang II infused (80 ng/min × 28 days); (iii) Ang II + AT1 receptor blocker (ARB; 10 mg losartan/kg per day × 21 days); (iv) Ang II + mineralocorticoid receptor (MR) antagonist (Epl; 100 mg eplerenone/day × 21 days); and (v) Ang II + ARB + Epl (Combo; × 21 days). Both ARB and combination treatments completely alleviated the Ang II‐induced hypertension, whereas eplerenone treatment only prolonged the onset of the hypertension. Eplerenone treatment exacerbated the Ang II‐mediated increase in plasma and heart aldosterone 2.3‐ and 1.8‐fold, respectively, while ARB treatment reduced both. Chronic MR blockade was sufficient to ameliorate the AT1‐mediated increase in oxidative damage. All treatments normalized protein oxidation (nitrotyrosine) levels; however, only ARB and Combo treatments completely reduced lipid peroxidation (4‐hydroxynonenal) to control levels. Collectively, these data suggest that receptor signalling, and not the elevated arterial blood pressure, is the principal culprit in the oxidative stress‐associated cardiovascular damage in Ang II‐dependent hypertension.     

Subclinical coronary atherosclerosis is more pronounced in men and women with lower socio-economic status: associations in a population-based study. Coronary atherosclerosis and social status.

BACKGROUND: Social inequalities of manifest coronary heart diseases are well documented in modern societies. Less evidence is available on subclinical atherosclerotic disease despite the opportunity to investigate processes underlying this association. Therefore, we examined the relationship between coronary artery calcification as a sign of subclinical coronary atherosclerosis, socio-economic status and established cardiovascular risk factors in a healthy population. DESIGN: Cross-sectional. METHODS: In a population-based sample of 4487 men and women coronary artery calcification was assessed by electron beam computed tomography quantified by the Agatston score. Socio-economic status was assessed by two indicators, education and income. First, we investigated associations between the social measures and calcification. Second, we assessed the influence of cardiovascular risk factors on this association. RESULTS: After adjustment for age, men with 10 and less years of formal education had a 70% increase in calcification score compared with men with high education. The respective increase for women was 80%. For income the association was weaker (among men 20% higher for the lowest compared with the highest quartile; and among women 50% higher, respectively). Consecutive adjustment for cardiovascular risk factors significantly attenuated the observed association of socio-economic status with calcification. CONCLUSIONS: Social inequalities in coronary heart diseases seem to influence signs of subclinical coronary atherosclerosis as measured by coronary artery calcification. Importantly, cumulation of major cardiovascular risk factors in lower socio-economic groups accounted for a substantial part of this association.     

Kingella kingae: from medical rarity to an emerging paediatric pathogen

In recent years, Kingella kingae has emerged as an important cause of invasive infections in young children, especially septic arthritis, osteomyelitis, spondylodiscitis, bacteraemia, and endocarditis, and less frequently lower respiratory tract infections and meningitis. The organism is part of the pharyngeal flora of young children and is transmitted from child-to-child. The clinical presentation of invasive K kingae disease is often subtle and laboratory tests are frequently normal. A substantial fraction of children with invasive K kingae infections have a recent history of stomatitis or symptoms of upper-respiratory-tract infection. The organism is susceptible to a wide array of antibiotics that are usually given empirically to young children including beta lactams, and with the exception of cases of endocarditis, the disease runs a benign clinical course. Although isolation and recognition of the organism is not difficult, clinicians and microbiologists should be aware of its fastidious nature. To optimise the recovery of K kingae, inoculation of synovial fluid specimens into blood culture vials is strongly recommended.     

Aeroportia and acute abdominal pain: ischemic bowel necrosis

Pneumatosis intestinalis and aeroportia are typical findings of mesenteric ischemia. The second carries a worse prognosis than the former. We report the case of a patient presenting with acute abdominal pain and acidosis after admission to the coronary unit for myocardial infarction. An emergent abdominal CT scan showed aeroportia. Laparotomy confirmed extended bowel necrosis. Aeroportia is a typical feature of ischemic bowel necrosis, often associated with advanced disease and bad prognosis. In the presence of acute abdominal pain, aeroportia should be considered as a sign of ischemic bowel necrosis. Emergent laparotomy is warranted.     

Gastric antral vascular ectasia:clinical presentation and therapeutic management

The gastric antral vascular ectasia (GAVE) or watermelon stomach is an increasingly recognized cause of persistent upper gastrointestinal bleeding, which has typical endoscopic and histological findings. This disease is most frequent in elderly women, and several associated conditions have been well established. Some patients with severe portal hypertensive gastropathy may have a GAVE like appearence. Nevertheless, a correct diagnosis is relevant in order to choose an appropiate treatment. The objective of the current study is to analyze the clinical features and treatment of a group of patients with GAVE evaluated at our Institution. A review of the current literature was also performed. Six women and three men with GAVE were admitted at the Buenos Aires British Hospital between November 1998 and January 2004. Endoscopic biopsy was performed in eight patients and was consistent with GAVE in all cases. Four patients with chronic anaemia as unique manifestation were successfully treated with iron supplements. Endoscopic treatment was performed in 4 patients, 3 of them were treated with bipolar electrocautery and 1 with argon plasma coagulation. An antrectomy was carried out in the ninth patient. The resolution of the bleeding was observed in all cases with the different therapeutics options used.     

Immunological changes after highly active antiretroviral therapy with lopinavir-ritonavir in heavily pretreated HIV-infected children

We evaluated the effect of salvage antiretroviral therapy with lopinavir/ritonavir (LPV/r) on the immune system of heavily antiretroviral pretreated HIV-infected children. We carried out a longitudinal study in 20 antiretroviral experienced HIV-infected children to determine the changes in several immunological parameters (T cell subsets, thymic function) every 3 months during 18 months of follow-up on salvage therapy with LPV/r. Statistical analyses were performed with the Wilcoxon test, taking as a reference the basal value at the entry in the study. HIV-infected children showed an increase of CD4+ T cells, a decrease in CD8+ T cells, and an increase in T cell rearrangement excision circle (TRECs) levels. The percentage of HIV children with undetectable viral load (VL < or = 400 copies/ml) increased significantly (p = 0.007) and the percentage with SI viral phenotype decreased significantly (p = 0.002) at the end of the study. Thus, the viral phenotype changed to NSI/R5 after salvage therapy with LPV/r. Interestingly, we observed a significant decrease of memory (CD4+ CD45RO+) and a moderate decrease of activated (CD4+ HLA-DR+, CD4+ HLA-DR+CD38, CD4+, CD45RO+HLA-DR+) CD4+ T cells during the follow-up. On the other hand, memory (CD8+ CD45RO+ and CD8+ CD45RO+CD38+), activated (CD8+ HLA-DR+CD38+, CD8+ HLA-DR+, CD8+ CD38+), and effector (CD8+ CD57+, CD8+ CD28(-)CD57+) CD8+ T cells had a very significant decrease during follow-up. Our data indicate an immune system reconstitution in heavily pretreated HIV-infected children in response to salvage therapy with LPV/r as a consequence of a decrease in immune system activation and an increase in thymic function.