Bleeding renal angiomyolipomas. CT findings

PURPOSE: To describe our experience in three cases of abdominal haemorrhage caused by bleeding renal angiomyolipomas, which were studied with Computed Tomography (CT). MATERIALS AND METHODS: A retrospective study carried out at our archives identified 3 patients (aged 58.6 on average) with renal angiomyolipomas clinically manifested with acute abdomen and haemorrhage. The patients underwent an emergency CT scan of the abdomen. One patient also under-went a subsequent renal angiography. All patients had surgery and histological characterizations of the renal lesions. RESULTS: The CT study on all three patients allowed detection of a lesion in the kidneys with inhomogeneous density due to haemorrhage. Areas with fat-density values (-60 -80 UH) were always observable within the lesions. The lesions, measuring 5-9 cm, were located in the right kidney in two patients and in the left kidney in one. CONCLUSIONS: In 40% of patients, renal angiomyolipoma may account for a picture of hypovolemic shock, so a correct diagnostic approach is important to guide the surgical approach. CT allows detection of the angiomyolipoma as the cause of the haemorrhage in most cases. The diagnosis is relatively simple when the lesion has typical features such as adipose content, whereas it may be difficult with non-typical aspects. Furthermore the fat content may also be detected in varying quantities in other renal lesions responsible for bleeding.     

Localization of the glutamine transporter SNAT1 in rat cerebral cortex and neighboring structures, with a note on its localization in human cortex

SNAT1 mediates glutamine (Gln) influx into neurons and is believed to replenish the transmitters pools of glutamate (Glu) and gamma-aminobutyric acid (GABA). We investigated its distribution and cellular localization in the cerebral cortex and neighboring regions of rats and humans using light and electron microscopic immunocytochemical methods with specific antibodies. In the first somatic sensory cortex of rats and in areas 9, 10, 21 and 46 of the human cortex, numerous SNAT1-positive (+) cells were present in the cortical parenchyma and in the white matter; >95% of SNAT1+ cells were neurons, but some were astrocytes. Most SNAT1+ cells were pyramidal neurons, but numerous non-pyramidal neurons were also observed: SNAT1/GABA double-labeling studies showed that SNAT1 is expressed in all GABA+ neurons. SNAT1/synaptophysin studies showed that <0.1% of all synaptophysin+ puncta coexpressed SNAT1. SNAT1 immunoreactivity (ir) was also in leptomeninges, ependymal cells and choroid plexus. Electron microscopic studies showed that neuronal SNAT1 ir was almost exclusively observed in perikarya and dendritic profiles. SNAT1 ir was also in distal astrocytic processes, including end feet profiles, and in leptomeninges. These findings suggest that the major function of SNAT1 is not to replenish the transmitter pools of Glu and GABA.     

Left atrial systolic force and cardiac markers of preclinical disease in hypertensive patients: the Hypertension Genetic Epidemiology Network (HyperGEN) Study

BACKGROUND: Left atrial systolic force (LASF) has been recently reported to be associated with prolonged left ventricular (LV) relaxation and concentric LV geometry in a clinical setting. This study analyzes the association of increased LASF to LV geometry and function in hypertensive patients from a population study. METHODS: Doppler echocardiographic findings were examined in 684 subjects with treated hypertension and without prevalent cardiovascular disease from the Hypertension Genetic Epidemiology Network (HyperGEN) Study (426 African American, 448 female, 125 diabetic, 174 obese; age 53.8+/-10.8 years). The LASF was assessed from the mitral orifice area and pulse-wave Doppler peak A flow velocity. The LASF was defined as being high if >14.33 kdynes (90th percentile of the normal distribution in 246 normal adults). RESULTS: The LASF was high in 269 participants (39.3% of study population), who were older and had higher mean body mass index (all P<.01). Participants with high LASF had higher systolic BP and heart rate (both P<.01) but similar diastolic BP. After controlling for covariates, participants with high LASF exhibited higher LV dimensions and mass than those with normal LASF (all P<.01). The prevalence of LV hypertrophy was also higher (P<.001). Participants with high LASF exhibited normal ejection fraction, higher stroke volume, cardiac output, E and A velocities, slower E deceleration, and lower E/A ratio than those with normal LASF (all P<.01). CONCLUSIONS: Enhanced LASF is associated with LV hypertrophy, normal LV chamber function, increased cardiac output, and prolonged relaxation. The LASF is a preload-dependent measure.     

Cocaine-induced Increase in Cortical Acetylcholine Release: Interaction with the Hypothalamo—Pituitary—Adrenal Axis

An influence on drug-taking behaviours of the stress-related hypothalamo-pituitary-adrenal (HPA) axis and its final hormonal mediator, corticosterone, has previously been demonstrated. A role for cortically projecting cholinergic neurons in these behaviours can also be proposed. The experiments presented here examine the effect of the drug of abuse cocaine (15 mg/kg) on the release of acetylcholine (ACh) in the cortex of freely moving rats, using the technique of in vivo microdialysis. To assess a possible modulatory influence of the HPA axis via its final hormonal mediator corticosterone, the cocaine-induced effect on cortical ACh release in intact rats was compared to that in adrenalectomized (ADX) rats, which thus lacked their endogenous source of corticosterone, and in ADX rats in which the cocaine-induced corticosterone peak and/or the basal circadian concentrations of serum corticosterone were simulated by replacement treatments. The results reported here demonstrate that cortical ACh release is greatly increased by cocaine in intact rats; ADX prolongs the return to basal levels of cortical ACh, and the chronic replacement of circadian levels of corticosterone normalizes this effect. In contrast, during the plateau period of cocaine-induced increased cortical ACh release, where no effect of ADX is evident, rats with chronic replacement of corticosterone show an attenuated cocaine-induced cortical ACh release, and the acute replacement of the cocaine-induced corticosterone secretion further attenuates this response. These results demonstrate that cocaine stimulates cortically projecting cholinergic neurons, and that the HPA hormone corticosterone modulates this interaction in a complex manner which merits further investigation.     

Addition of New Androgen Receptor Pathway Inhibitors to Docetaxel and Androgen Deprivation Therapy in Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review and Metanalysis

In recent years, significant changes have occurred in metastatic hormone-sensitive prostate cancer (mHSPC) management, where docetaxel and new androgen receptor pathway inhibitors (ARPI) have been shown to improve overall survival (OS) compared to androgen deprivation therapy (ADT). Recent data could once again radically change mHSPC treatment. PEACE-1 and ARASENS trials demonstrated a survival benefit of the addition of ARPI to docetaxel and ADT combination (triplet therapy), compared to docetaxel and ADT. With multiple options to choose from, it is crucial to identify the patients who would benefit most from triplet therapy. In this meta-analysis, we evaluated the activity of the triplet therapy versus docetaxel plus ADT in mHSPC. A systematic review of PubMed/Medline, Embase, and the proceedings of major international meetings was performed. Five RCTs fulfilled the inclusion criteria. PEACE-1 and ARASENS studies reported disease-free survival (DFS) and OS. Post hoc analysis of three other trials evaluated the combination of ARPI, docetaxel and ADT. Globally, 2538 patients were included (1270 triplet therapy; 1268 docetaxel + ADT). Triplet therapy was associated with improved OS (hazard ratio (HR) 0.74; 95% confidence interval (CI), 0.66–0.83, p < 0.00001). A statistically significant benefit was shown in high-volume mHSPC patients (HR 0.76; 95% CI 0.59–0.97, p = 0.03) and in patients with de novo metastatic disease (HR 0.73; 95% CI, 0.64–0.82, p < 0.00001). The addition of ARPI to standard therapy was associated with DFS improvement (HR 0.41; 95% CI, 0.35–0.49, p < 0.00001). This metanalysis shows a significant OS benefit from concomitant administration of ARPI, docetaxel and ADT in high volume and de novo mHSPC.     

Causes of and prevention strategies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a challenging malignancy of global importance. It is associated with a high rate of mortality and its prevalence in the United States and in Western Europe is increasing. Cirrhosis is the strongest and the most common known risk factor for HCC, usually due to hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. However, different lines of evidence identify in non-alcoholic fatty liver disease (NAFLD) a possible relevant risk factor for occurrence of HCC. Given the continuing increase in the prevalence of obesity and diabetes, the incidence of non-alcoholic steatohepatitis-related HCC may also be expected to increase, and a potential role of behavior treatment and/or insulin-sensitizing drugs can be envisaged. Vaccination against HBV is the most efficient primary prevention measure currently available to reduce the HCC incidence and mortality in high-incidence areas, while data on the role of interferon (IFN) and nucleos(t)ide analogues (NUC) are still controversial. The pooling of data from the literature suggests a slight preventive effect of antiviral therapy on HCC development in patients with HCV-related cirrhosis, but the preventive effect is limited to sustained virological responders.     

Neonatal Monosodium Glutamate Abolishes Corticotropin-Releasing Factor-Induced Epileptogenic Activity in Rats

Intracerebroventricular (i.c.v.) injection of rat corticotropin-releasing factor (rCRF) at doses of 5-20 micrograms in rats induces epileptogenic activity characterized by pacemaker-like spikes localized in the hippocampal leads. Such an effect was still present in rats neonatally treated with saline but was absent in those neonatally treated with monosodium glutamate (MSG), a treatment that caused marked changes in the concentration of several brain neurotransmitters and neuropeptides in hypothalamic nuclei where CRF is highly concentrated and is believed to induce endocrinologic and behavioral effects. The present results suggest the rCRF-induced spiking activity is mediated by activation of neuronal pathways sensitive to MSG neurotoxic effect.