Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Positron emission tomography (PET) is perfectly suited for quantitative imaging of the kidneys, and the recent improvements in detector technology, computer hardware, and image processing software add to its appeal. Multiple positron emitting radioisotopes can be used for renal imaging. Some, including carbon-11, nitrogen-13, and oxygen-15, can be used at institutions with an on-site cyclotron. Other radioisotopes that may be even more useful in a clinical setting are those that either can be obtained from radionuclide generators (rubidium-82, copper-62) or have a sufficiently long half-life for transportation (fluorine-18). The clinical use of functional renal PET studies (blood flow, glomerular filtration rate) has been slow, in part because of the success of concurrent technologies, including single-photon emission computed tomography (SPECT) and planar gamma camera imaging. Renal blood flow studies can be performed with O-15-labeled water, N-13-labeled ammonia, rubidium-82, and copper-labeled PTSM. With these tracers, renal blood flow can be quantified using a modified microsphere kinetic model. Glomerular filtration can be imaged and quantified with gallium-68 EDTA or cobalt-55 EDTA. Measurements of renal blood flow with PET have potential applications in renovascular disease, in transplant rejection or acute tubular necrosis, in drug-induced nephropathies, ureteral obstruction, before and after revascularization, and before and after the placement of ureteral stents. The most important clinical application for imaging glomerular function with PET would be renovascular hypertension. Molecular imaging of the kidneys with PET is rather limited. At present, research is focused on the investigation of metabolism (acetate), membrane transporters (organic cation and anion transporters, pepT1 and pepT2, GLUT, SGLT), enzymes (ACE), and receptors (AT1R). Because many nephrological and urological disorders are initiated at the molecular and organelle levels and may remain localized at their origin for an extended period of time, new disease-specific molecular probes for PET studies of the kidneys need to be developed. Future applications of molecular renal imaging are likely to involve studies of tissue hypoxia and apoptosis in renovascular renal disease, renal cancer, and obstructive nephropathy, monitoring the molecular signatures of atherosclerotic plaques, measuring endothelial dysfunction and response to balloon revascularization and restenosis, molecular assessment of the nephrotoxic effects of cyclosporine, anticancer drugs, and radiation therapy. New radioligands will enhance the staging and follow-up of renal and prostate cancer. Methods will be developed for investigation of the kinetics of drug-delivery systems and delivery and deposition of prodrugs, reporter gene technology, delivery of gene therapy (nuclear and mitochondrial), assessment of the delivery of cellular, viral, and nonviral vectors (liposomes, polycations, fusion proteins, electroporation, hematopoietic stems cells). Of particular importance will be investigations of stem cell kinetics, including local presence, bloodborne migration, activation, seeding, and its role in renal remodeling (psychological, pathological, and therapy induced). Methods also could be established for investigating the role of receptors and oncoproteins in cellular proliferation, apoptosis, tubular atrophy, and interstitial fibrosis; monitoring ras gene targeting in kidney diseases, assessing cell therapy devices (bioartificial filters, renal tubule assist devices, and bioarticial kidneys), and targeting of signal transduction moleculas with growth factors and cytokines. These potential new approaches are, at best, in an experimental stage, and more research will be needed for their implementation.
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PMID:Future direction of renal positron emission tomography. 1635 95

Myocardial perfusion (MP) may differ in physiologic and pathologic left ventricular hypertrophy (LVH). We compared MP in LVH in elite athletes and patients with hypertension with healthy, age-matched subjects. We included 12 rowers with LVH, 19 patients with hypertension with LVH, and 2 age-matched groups of healthy subjects (n = 11 and n = 12). The left ventricular mass index was determined echocardiographically. MP was measured by N-13 ammonia positron emission tomography. The maximal perfusion and perfusion reserve were studied using dipyridamole, and endothelial function was assessed by a cold pressor test. The degree of LVH was similar in athletes and those with hypertension. Compared with controls, athletes had 20% lower baseline MP (p <0.05), a similar response to the cold pressor test, and a higher perfusion reserve (31%, p <0.05). The patients with hypertension had a 25% higher baseline MP (p <0.05), a reduced increase during the cold pressor test (12% vs 25% in controls, p <0.05), and a reduced perfusion reserve (27% lower, p <0.001). The peak global perfusion (MP x left ventricular mass index) was 62% higher in athletes (p <0.05) than in controls, but the peak global perfusion in patients with hypertension did not differ from that of controls. In conclusion, physiologic LVH in athletes is suited for a high peak workload at the cost of only a small increase in basal myocardial oxygen consumption. In contrast, LVH in the presence of hypertension is a good adaptation to the increased baseline workload with maintained maximal cardiac performance. Endothelial dysfunction may contribute to the reduced perfusion reserve seen in hypertensive LVH.
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PMID:Positron emission tomographic evaluation of regulation of myocardial perfusion in physiological (elite athletes) and pathological (systemic hypertension) left ventricular hypertrophy. 1636 Mar 59

Stimulation of the nasal passages with ammonia vapors can initiate a nasopharyngeal response that resembles the diving response. This response consists of a sympathetically mediated increase in peripheral vascular resistance, parasympathetically mediated bradycardia and an apnea. The current study investigated the role of the anterior ethmoidal nerve (AEN) in the nasopharyngeal response in the rat, as it is thought that the AEN provides the main sensory innervation of the nasal passages. When both AENs were intact, nasal stimulation caused significant bradycardia, hypertension, and apnea and produced Fos label ventrally within the ipsilateral medullary dorsal horn (MDH) and paratrigeminal nucleus just caudal to the obex. This labeling presumably represents activation of second-order trigeminal neurons. When only one AEN was intact, the nasopharyngeal response was slightly attenuated, and a similar pattern of Fos labeling was only seen in the trigeminal nucleus ipsilateral to the intact AEN. The trigeminal labeling contralateral to the intact AEN was significantly reduced. When both AENs were cut, the nasopharyngeal response to nasal stimulation consisted of only a slight apnea and an increase in arterial pressure; the resultant Fos labeling within the trigeminal nucleus was significantly reduced. Cutting both AENs but not stimulating the nasal passages also produced some Fos labeling within the trigeminal nucleus. These findings suggest that a single AEN can provide sufficient afferent input to initiate the cardiorespiratory changes consistent with the nasopharyngeal response. We conclude that the AEN provides a unique afferent contribution that is capable of producing the diving response.
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PMID:The anterior ethmoidal nerve is necessary for the initiation of the nasopharyngeal response in the rat. 1646 47

The management of children with end-stage chronic liver disease and acute liver failure mandates a multidisciplinary approach and intense monitoring. In recent years, considerable progress has been made in developing specific and supportive medical measures, but studies and publications have mainly concerned adult patients. Therapeutic approaches to complications of end-stage chronic liver disease and acute liver failure (e.g. refractory ascites, hepatorenal syndrome, encephalopathy, and cerebral edema) that may be applied to children are reviewed in this article.Mild-to-moderate ascites should be managed by modest salt restriction and oral diuretic therapy in the first instance. Large volume paracentesis associated with colloid volume expansion and diuretic therapy may be effective for acute relief. Treatment of hepatorenal syndrome type 1 with vasopressin analogs (terlipressin) is recommended prior to liver transplantation in order to improve renal function. Prevention and treatment of chronic hepatic encephalopathy are directed primarily at controlling the events that may precipitate hepatic encephalopathy and at reducing ammonia generation and increasing its detoxification or removal. In addition to reduction of gut ammonia production using non-absorbable disaccharides such as lactulose and/or antibacterials such as neomycin, sodium benzoate may be used on a long-term basis to prevent, stabilize, or improve hepatic encephalopathy. The management of hepatic encephalopathy in acute liver failure is considerably more unsatisfactory; treatment is aimed at preventing brain edema and intracranial hypertension. Extracorporeal liver support devices are now used commonly in critically ill children with acute renal failure, advanced hepatic encephalopathy, cerebral edema, intracranial hypertension, and severe coagulopathy. Continuous renal replacement therapy could potentially help support patients until liver transplantation is performed or liver regeneration occurs. The Molecular Adsorbent Recirculating System (MARS or albumin dialysis) is the liver support system most frequently used worldwide in adults and appears to offer distinct advantages over hepatocyte-based systems. There are no specific medical therapies or devices that can correct all of the functions of the liver. Apart from a few metabolic diseases presenting with severe liver dysfunction for which specific medical therapies may preclude the need for liver transplantation, liver transplantation still remains the only definitive therapy in most instances of end-stage chronic liver disease and acute liver failure. Future research should focus on gaining a better understanding of the mechanisms responsible for liver cell death and liver regeneration, as well as developments in hepatocyte transplantation and liver-directed gene therapy.
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PMID:New management options for end-stage chronic liver disease and acute liver failure: potential for pediatric patients. 1649 8

Severe intracranial hypertension (IH) in the setting of fulminant hepatic failure (FHF) carries a high mortality and is a challenging disease for the critical care provider. Despite considerable improvements in the understanding of the pathophysiology of cerebral edema during liver failure, therapeutic maneuvers that are currently available to treat this disease are limited. Orthotopic liver transplantation is currently the only definitive therapeutic strategy that improves outcomes in patients with FHF. However, many patients die prior to the availability of donor organs, often because of cerebral herniation. Currently, two important theories prevail in the understanding of the pathophysiology of IH during FHF. Ammonia and glutamine causes cytotoxic cerebral injury while cerebral vasodilation caused by loss of autoregulation increases intracranial pressure (ICP) and predisposes to herniation. Although ammonia-reducing strategies are limited in humans, modulation of cerebral blood flow seems promising, at least during the early stages of hepatic encephalopathy. ICP monitoring, transcranial Doppler, and jugular venous oximetry offer valuable information regarding intracranial dynamics. Induced hypothermia, hypertonic saline, propofol sedation, and indomethacin are some of the newer therapies that have been shown to improve survival in patients with severe IH. In this article, we review the pathophysiology of IH in patients with FHF and outline various therapeutic strategies currently available in managing these patients in the critical care setting.
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PMID:Therapy of intracranial hypertension in patients with fulminant hepatic failure. 1662 10

Fulminant hepatic failure (FHF) is often complicated with cerebral edema, intracranial hypertension, and coma. Cytotoxic and vasogenic factors have been recognized in the etiology of cerebral edema. One of the main causes seems to be the accumulation of glutamine in astrocytes, which is produced from ammonia and the excitatory neurotransmitter glutamate. Ammonia is detoxified within the brain in astrocytes, where it increases the osmotic pressure for water. Ammonia-induced astrocytic water accumulation seems to act as an integrative trigger for the development of intracranial hypertension. While cerebral blood flow is sometimes reduced in the first stage of FHF, as compensatory cerebral vasoconstriction to reduce mean arterial pressure, it later increases as hyperammonemia decreases cerebral arteriolar tone. Despite vasodilation in the systemic and splanchnic beds at early stages of the disease, cerebral vessel resistance may increase, so that cerebral perfusion pressure may be preserved. When cerebral vascular tone is no longer effective in the course of illness, vasodilation gradually develops and rapidly becomes poorly responsive to carbon dioxide stimulation, which signifies loss of autoregulatory tone and cerebral hyperemia develops. Prolonged excessive flow may lead to brain swelling, vasogenic edema, and intracerebral hemorrhage. Brain edema further aggravates the critically reduced cerebral perfusion and is responsible for the high mortality.
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PMID:Cerebral blood flow in fulminant hepatitis. 1664 70

Liver failure results in significant alterations of the brain glutamate system. Ammonia and the astrocyte play major roles in such alterations, which affect several components of the brain glutamate system, namely its synthesis, intercellular transport (uptake and release), and function. In addition to the neurological symptoms of hepatic encephalopathy, modified glutamatergic regulation may contribute to other cerebral complications of liver failure, such as brain edema, intracranial hypertension and changes in cerebral blood flow. A better understanding of the cause and precise nature of the alterations of the brain glutamate system in liver failure could lead to new therapeutic avenues for the cerebral complications of liver disease.
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PMID:The brain glutamate system in liver failure. 1677 37

Patients with FHF have a high risk of cerebral edema and intracranial hypertension. The pathophysiological background for this phenomenon is not completely settled, but alteration in CBF as well as cerebral metabolism seems to be of importance. Mechanical hyperventilation has a prompt effect on intracranial pressure. This effect is assumed to be caused by the hypocapnia induced alkalosis which produces vasoconstriction and thereby a decrease in CBF and cerebral blood volume. It has been stated that hyperventilation may be harmful to patients with FHF, but only few studies have addressed the effect of hyperventilation upon cerebral metabolism. In the present clinical studies we evaluated the effect of short-term mechanical hyperventilation upon cerebral circulation and metabolism in patients with FHF. Although global CBF was reduced in patients with FHF it tightly matched the cerebral oxidative requirements. Already in the early phase of FHF there was a prominent cerebral efflux of glutamine that could not be accounted for by cerebral ammonia uptake. Moderate hyperventilation reduced global CBF without compromising cerebral oxidative metabolism. In addition, moderate hyperventilation restored cerebral autoregulation in most patients with FHF, and normalised the cerebral nitrogen balance during short-term interventions. Studies of global and regional cerebral carbon dioxide reactivity showed normal global as well as regional cerebral carbon dioxide reactivity in almost all patients with FHF. However, cerebral perfusion in frontal brain regions as well as basal ganglia is low in FHF as compared to healthy subjects, which may make these regions at risk of hypoperfusion during pronounced hyperventilation. It is concluded that moderate short-term hyperventilation does not compromise cerebral oxidative metabolism. Recommendation of its prolonged use in FHF awaits further studies. Furthermore, the data of this thesis demonstrates that alterations in cerebral glutamine and ammonia metabolism precedes increases of CBF, which seems to be a phenomenon that takes place later during the disease course, i.e., immediately before intracranial pressure is rising.
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PMID:The effect of hyperventilation upon cerebral blood flow and metabolism in patients with fulminant hepatic failure. 1752 26

Patients experiencing acute elevations of ammonia present to the ICU with encephalopathy, which may progress quickly to cerebral herniation. Patient survival requires immediate treatment of intracerebral hypertension and the reduction of ammonia levels. When hyperammonemia is not thought to be the result of liver failure, treatment for an occult disorder of metabolism must begin prior to the confirmation of an etiology. This article reviews ammonia metabolism, the effects of ammonia on the brain, the causes of hyperammonemia, and the diagnosis of inborn errors of metabolism in adult patients.
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PMID:Hyperammonemia in the ICU. 1793 24

Patients with acute liver failure (ALF) display impairment of cerebral blood flow (CBF) autoregulation, which may contribute to the development of fatal intracranial hypertension, but the pathophysiological mechanism remains unclear. In this study, we examined whether loss of liver mass causes impairment of CBF autoregulation. Four rat models were chosen, each representing different aspects of ALF: galactosamine (GlN) intoxication represented liver necrosis, 90% hepatectomy (PHx90) represented reduction in liver mass, portacaval anastomosis (PCA) represented shunting of blood/toxins into the systemic circulation thus mimicking intrahepatic shunting in ALF, PCA+NH(3) provided information about the additional effects of hyperammonemia Rats were intubated and sedated with pentobarbital. We measured CBF with laser Doppler, intracranial pressure (ICP) was measured in the fossa posterior and registered with a pressure transducer, brain water was measured using the wet-to-dry method, and cerebral glutamine/glutamate was measured enzymatically. The CBF autoregulatory index in both the GlN and PHx90 groups differed significantly from the control group. Conversely, CBF autoregulation was intact in the PCA and PCA+NH(3) groups despite high arterial ammonia, high cerebral glutamine concentration, and increased CBF and ICP. Increased water content of the brainstem or cerebellum was not associated with defective CBF autoregulation. In conclusion, impairment of CBF autoregulation is not caused by brain edema/high ICP. Nor does portacaval shunting or hyperammonemia impair autoregulation. Rather, massive liver necrosis and reduced liver mass are associated with loss of CBF autoregulation.
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PMID:Cerebral blood flow autoregulation in experimental liver failure. 1805 32


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