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)

Gated blood pool scanning (GBPS) is an expensive, frequently used test to assess the left ventricular ejection fraction (LVEF). To determine whether a simpler method of evaluating LVEFs was reliable, we compared the LVEFs derived by GBPS with those estimated in a cardiologist's examination in 125 hospitalized patients. Of the physician estimates, 56% were accurate to within 7.5%, while 17% were underestimates and 27% were overestimates. The variables that were most predictive of reduced LVEF included cardiomegaly and pulmonary venous congestion on chest roentgenogram and S3 gallop, hypotension, and sustained left ventricular apex beat on examination. Prior hypertension was correlated with an increased LVEF. Variables associated with physician error in estimating the LVEF included a history of hypertension, bronchodilator therapy, and right bundle-branch block seen on the electrocardiogram. These data suggest that although qualitatively accurate estimates of the LVEF can sometimes be made on the basis of clinical findings, GBPS should be performed when management decisions hinge on a precise knowledge of this value.
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PMID:Left ventricular ejection fraction. Physician estimates compared with gated blood pool scan measurements. 335 8

Prognostic studies hinge on the assembly of a proper inception cohort. The stepwise assembly of a "true" inception cohort of hypertension complicating pregnancy is reported. Standard assembly procedures would have resulted in the preferential reporting of the severest cases of the prognostically worst categories of disease. The less severe cases would have been missed. Prognostic studies should utilize and report a method for assessing potential missed cases, such as a random selection of records for independent review.
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PMID:In search of the true inception cohort. 359 89

The structure of the histidine-binding protein (HBP, M(r) = 26,100), involved solely in active transport, has been determined by the molecular replacement technique and refined to 1.89-A resolution and to an R-factor of 0.199. The structure is that of two protein molecules, each with a bound L-histidine, in the asymmetric unit. Replacement solution was achieved by using a model of the crystal structure of the ligand-free, open-cleft form of the lysine/arginine/ornithine-binding protein which was modified so that the two domains are close to each other by bending the hinge connecting the two domains. The bound histidine is held in place by 10 hydrogen bonds, 2 salt links, and about 60 van der Waals contacts. Elucidation of the HBP structure brings a total of eight different binding proteins structures determined in our laboratory, including those with specificities for monosaccharides, maltodextrins (linear and cyclic), aliphatic amino acids, and inorganic oxyanions. These structures comprise about a third of the entire family of periplasmic binding proteins which act as initial primary high-affinity receptors of active transport in Gram-negative bacteria. Two of the binding proteins with specificities for glucose/galactose and maltodextrins also serve in a similar capacity in chemotaxis. Though these proteins have different molecular weights (ranging from 26,000 to 40,000), amino acid sequences, and ligand specificities, their three-dimensional structures are similar overall. They are elongated (axial ratios of 2:1) and composed of two similar globular domains separated by a deep cleft wherein the ligand-binding site is located. These structures provide understanding of molecular recognition of a variety of ligands at the atomic level and functional roles of the binding proteins.
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PMID:Refined 1.89-A structure of the histidine-binding protein complexed with histidine and its relationship with many other active transport/chemosensory proteins. 816 36

Phenotypic variability in smooth muscle cells accounts, in large part, for the incredible functional diversity required of the involuntary hollow organs of the body (i.e., respiratory passages, blood vessels, gastrointestinal tract, urogenital tract, etc.). In all instances coordination of smooth muscle cell responses, that is, contraction and relaxation, is critical to normal organ function. While numerous biological mechanisms exist for coordinating smooth muscle cell responses, intercellular communication through gap junctions represents a common denominator present in all organ systems. In this report, we review the evidence documenting the presence and functional significance of myocyte gap junctions to physiologically distinct organ systems, and furthermore, provide some examples of their putative roles in organ pathology. Finally, we advance the thesis that despite their ubiquity and heterogeneous expression, gap junctions are nonetheless potentially attractive therapeutic targets for the treatment of certain smooth muscle disorders. Their therapeutic efficacy will necessarily hinge on the existence of connexin isoform-selective junctional effects. The overall rationale for targeting the intercellular pathway is therefore analogous to strategies that target other ubiquitously expressed ion channels, such as calcium or potassium channels. Such strategies have proved efficacious for the treatment of a wide range of human smooth muscle disorders including hypertension, urinary incontinence and sexual function.
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PMID:The physiology, pathophysiology and therapeutic potential of gap junctions in smooth muscle. 1244 95

Human immunoglobulin A is represented by two structurally and functionally distinct subclasses: IgA1 and IgA2. IgA1, which is almost exclusively present in the mesangial deposits in IgA nephropathy patients, contains in its hinge region three to five O-lined carbohydrate chains. A fraction of IgA1 molecules in the circulation of IgA nephropathy patients exhibits aberrant glycosylation. As a result of changes in glycosylation, the neoepitopes represented by glycans are exposed and recognized by naturally occurring antibodies with antiglycan specifciities, and immune complexes are generated. The deposits of these immune complexes in the glomerular mesangia elicit inflammatory response known as IgA nephropathy. Epidemiological studies have shown that dominant hematuria, either isolated or combined with mild proteinuria, is the most frequent urinary syndrome in glomerulonephritis. The morphologic finding of this syndrome is most frequently IgA nephropathy. Originally considered a benign disease, IgA nephropathy is now recognized as a frequent cause of chronic renal failure. The progression is signalized by increasing proteinuria and hypertension. Therefore, a control of blood pressure and lowering of proteinuria remain the corner-stones of the treatment. Angiotensin converting enzyme inhibitors and AT1 blockers may lower both blood pressure and proteinuria and are now increasingly promoted even for treatment of normotensive patients. Steroids are administered to patients with severe proteinuria. High-doses of fish oil seem to slow down the rate of renal failure.
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PMID:[IgA nephropathy. Significance of immunoglobulin A glycosylation in pathogenesis and clinical presentation]. 1265 29

Prevention or retardation of diabetic nephropathy (DN) includes anti-hypertensive treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) on the premises that these drugs have an added protective effect beyond their influence on BP. The present study used a strain of spontaneously hypertensive/NIH-corpulent rats [SHR/NDmc-cp (fat/fat)] as a model of type II DN to unravel the renoprotective effects of anti-hypertensive drugs. Olmesartan (1 or 5 mg/kg per d), an ARB, and hydralazine (5mg/kg per d), an anti-hypertensive drug without effect on the renin-angiotensin system (RAS), were given for 20 wk. BP, renal function, glucose and insulin levels, and proteinuria were monitored. Glomerular lesions and kidney pentosidine content were assessed at the end of the study. Olmesartan (1 and 5 mg) significantly reduced BP and kidney pentosidine content and improved histologic renal damage and proteinuria. The changes were dose-dependent. The effect of hydralazine (5 mg) was similar to that of olmesartan (1 mg) but reached statistical significance only for kidney pentosidine content. The similarity of both drugs' effects on kidney damage and proteinuria suggest that renoprotection does not hinge on manipulation of RAS in these rats. By contrast, the inhibition of renal pentosidine formation assessed both by immunohistochemistry and HPLC suggests a critical role of advanced glycation end product (AGE) formation together with hypertension in the genesis of diabetic nephropathy. This view is supported by the correlation found between renal pentosidine content and proteinuria. The unsuspected AGE-lowering effect of hydralazine was further confirmed in vitro and elucidated; it is due to both reactive carbonyl compounds trapping and modifications of the oxidative metabolism. It is concluded that AGE inhibition should be included in the therapeutic strategy of DN.
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PMID:Anti-hypertensive agents inhibit in vivo the formation of advanced glycation end products and improve renal damage in a type 2 diabetic nephropathy rat model. 1270 91

In IgA nephropathy (IgAN), there is dysregulation of the IgA response to a wide range of antigens. The dysregulation promotes synthesis of polymeric IgA1 (pIgA1) with physicochemical characteristics that favor mesangial deposition, including altered O-glycosylation of the hinge region. This may be the synthesis of IgA in the systemic compartment, which has the phenotype of mucosal IgA. There is not a change in IgA1 structure to an entirely abnormal form; rather, there is a shift that results in a proportional increase in forms of IgA1 also found in healthy individuals. Altered O-glycosylation could favor pIgA1 deposition by promoting formation of macromolecular IgA and immune complexes. Mesangial injury follows through interactions of pIgA1 with the cells and extracellular matrix proteins of the mesangium and the activation of complement. The final clinical expression of IgAN also depends on generic factors, including hypertension and proteinuria, and a fibrotic renal response. No single "IgAN gene" has been identified, and it is likely that multiple interacting genes will eventually prove to underlie susceptibility to IgAN and the risk of progressive renal disease. These new pathogenic insights have not yet led to new therapeutic opportunities.
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PMID:Pathogenesis of IgA nephropathy. 1515 26

Decompressive craniectomy to relieve cerebral edema and intracranial hypertension due to traumatic brain injury is a generally accepted practice; however, the procedure remains controversial because of its uncertain effects on outcome, specific complications such as the syndrome of the sinking skin flap, and the need for subsequent cranioplasty. The authors developed a novel craniotomy technique using titanium bone plates in a hinged fashion, which maintains cerebral protection while reducing postoperative complications and eliminating subsequent cranioplasty procedures. The authors conducted a retrospective review of data obtained in all consecutive patients who had undergone posttraumatic cerebral decompression craniotomy using the hinge technique at a Level I trauma facility between 1990 and 2004. Twenty-five patients, most of whom were male (88%) and Caucasian (88%) with a mean age of 38.2 +/- 16.1 years, underwent the hinge craniotomy. The in-hospital mortality rate was 48%, and good cerebral decompression was achieved. None of the patients required surgery for flap replacement. Long-term follow-up data showed that one patient required subsequent cranioplasty due to infection and one patient presented with cranial deformities. None of the patients presented with bone resorption or sinking flap syndrome. The hinge technique effectively prevents procedure-related morbidity and the need for subsequent surgical bone replacement otherwise introduced by traditional decompressive craniectomy. A randomized controlled trial is required to substantiate these findings.
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PMID:Use of hinge craniotomy for cerebral decompression. Technical note. 1837 72

The need to evaluate potential living kidney donors is more pressing than ever before. Evaluating the potential medical risks to individual donors presents both medical and ethical questions related to quantitative hazards of donor nephrectomy. These include conditions commonly associated with age, such as the decline in glomerular filtration rate, the rise in arterial pressures, and weight gain. The "normal" ranges for many of these characteristics are changing as their importance as predictors of cardiovascular risk is reevaluated and the duration of exposure for a lifetime is considered. Many older donors in good health favor donating a kidney to a spouse, despite the presence of elevated blood pressure or even impaired glucose tolerance. The Mayo Kidney/Pancreas transplant program established an "extended criteria workgroup" to address these issues on an individual basis. Our program now stratifies medical criteria based upon age, allowing more liberal criteria for older donors. As a result, we accept treated hypertension in white donors, emphasizing the importance of informed consent and the need for vigilant follow-up. Our greatest concern relates to the development of obesity, particularly in younger individuals. Many of the long-term results of kidney donation are likely to hinge upon future behavior, including smoking, weight management, and medical follow-up care. Older donors are more likely to have established behavior patterns, an element that makes them better candidates in many respects. Studies to closely track the impact of donor nephrectomy in the current era with changing population demographics and expectations are essential.
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PMID:Expanding criteria for living kidney donors: what are the limits? 1863 76

Rho kinase plays a pivotal role in several cellular processes such as vasoregulation, making it a suitable target for the treatment of hypertension and related disorders. We discovered a new compound class of Rho kinase (ROCK) inhibitors containing a 7-azaindole hinge-binding scaffold tethered to an aminopyrimidine core. Herein we describe the structure-activity relationships elucidated through biochemical and functional assays. The introduction of suitable substituents at the 3-position of the bicyclic moiety led to an increase in activity, which was required to design compounds with favorable pharmacokinetic profile. Azaindole 32 was identified as a highly selective and orally available ROCK inhibitor able to cause a sustained blood pressure reduction in vivo.
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PMID:Design and synthesis of potent and selective azaindole-based Rho kinase (ROCK) inhibitors. 1897 68


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