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)

In preparing a decision about the legal status of khat in the Netherlands, the Dutch Minister of Health requested CAM (Coordination point Assessment and Monitoring new drugs) to assess the overall risk of khat in the Netherlands. The present paper is a redraft of a report which formed the scientific basis of the risk evaluation procedure (October 2007). This report reviews the scientific data about khat available in the international literature. In addition, the report contains some information specific for the Netherlands (prevalence, availability of khat and public order aspects). The main psychoactive compounds in khat leaves are cathine and cathinone, which are some 2- to 10-fold less active than amphetamine. Acute health problems are rarely seen, and are usually related with malnutrition, social and financial problems. Khat has a low addictive potential. Chronic toxicity of khat is modest when used in low amounts, whereas at high levels, khat use is associated with adverse effects, like hypertension, heart rhythm disorders, insomnia and loss of appetite. In addition, khat users show a higher prevalence of cancers in the digestive tract. At population level, khat does not lead to specific health risks in the Netherlands, as its use is confined to East-African immigrants. A relationship between khat use and psychiatric disorders has been suggested, but the reports are contradictory, and such studies are presumably heavily confounded by posttraumatic and social stress. In the Netherlands (and other countries), khat use occasionally leads to minor disturbance of civil order in the public domain (loud talking, spitting), but is not related to criminal activities. Following the assessment, CAM estimated the overall risk potential of khat use in the Netherlands as very low. A similar conclusion may be drawn for countries with a comparable prevalence of khat use and khat related public order disturbance.
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PMID:Risk assessment of khat use in the Netherlands: a review based on adverse health effects, prevalence, criminal involvement and public order. 1878 27

A 72-year-old woman was admitted to our hospital because of massive proteinuria of 2.2 g/day. She had seen a general practitioner for management of Basedow disease, diabetes mellitus and hypertension for 24 years. On admission, she complained of anorexia and nausea. Laboratory data showed serum creatinine of 3.62 mg/dL and MPO-ANCA of 68 EU. Renal biopsy revealed crescentic glomerulonephritis complicated with membranous nephropathy. Thiamazole (MMI), which was being given for Basedow disease for years, was withdrawn on the suspicion as a cause of MPO-ANCA. Three years after the withdrawal of MMI, renal failure slowly progressed to the end-stage, while MPO-ANCA was negative. She was introduced onto hemodialysis. At that time, MPO-ANCA became positive again, the titer being 12.9 EU. Therefore, we suspected a relapse of ANCA-related vasculitis and performed steroid pulse therapy on the patient with methylprednisolone at 0.5 g/day for 3 days. On hospital day 14, MPO-ANCA became negative. On day 25, however, severe acute pancreatitis developed and a pancreatic tumor lesion was found on CT. In spite of amelioration of the pancreatitis by medical treatment, the pancreatic tumor lesion did not show any significant change. On day 48, she died of multiple organ failure. Autopsy showed a mucinous cyst adenoma of pancreas and necrotizing pancreatitis. We suspected steroid therapy as the cause of the pancreatic lesions.
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PMID:[MPO-ANCA related vasculitis complicating mucinous cystadenoma of the pancreas and severe acute pancreatitis after steroid pulse therapy: a case report]. 1906 54

White coat hypertension (WCH) is most likely a disorder associated with metabolic syndrome. The study was performed at the Internal Medicine Polyclinic of Dumlupinar University on routine check-up patients. WCH cases who were overweight or obese and desiring weight loss were divided into two subgroups according to whether they preferred to achieve weight loss by medication or diet therapy. The study included 324 cases (204 females) with WCH, 45 of whom were in normal weight range. Therefore, 86.1% (279) of cases with WCH were either overweight or obese, and 41.3% (134) of all WCH cases had dyslipidemia. Twenty-five cases (14.7%) stopped metformin therapy due to excessive anorexia. At the end of a 6-month period, there were highly significant differences between the two groups with respect to the prevalences of resolved WCH, hyperbetalipoproteinemia, hypertriglyceridemia, dyslipidemia, overweight and obesity, and decreased fasting plasma glucose below 110 mg/dL (P < 0.001 for all). Due to gradually increased prevalences of impaired glucose tolerance, type 2 diabetes mellitus, dyslipidemia, excess body weight, and obesity-like disorders from sustained normotension towards WCH and hypertension (HT) cases, and very high prevalences of excess weight and dyslipidemia in the WCH group, WCH may be an associated disorder of metabolic syndrome rather than just being a predisposing factor of atherosclerosis or HT alone. Thus, the management of WCH should not focus solely on the regulation of blood pressure with antihypertensive medications, but rather on the prevention of future excess weight and various associated disorders, and metformin alone is an effective therapeutic option, most likely due to its powerful inhibitory effect on appetite.
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PMID:Treatment of white coat hypertension with metformin. 1907 83

Sorafenib (Nexavar) is an orally active multikinase inhibitor that is approved in the EU for the treatment of hepatocellular carcinoma. Monotherapy with sorafenib prolongs overall survival and delays the time to progression in patients with advanced hepatocellular carcinoma who are not candidates for potentially curative treatment or transarterial chemoembolization. Sorafenib is generally well tolerated in patients with advanced hepatocellular carcinoma. Thus, sorafenib represents an important advance in the treatment of advanced hepatocellular carcinoma and is the new standard of care for this condition. The bi-aryl urea sorafenib is an oral multikinase inhibitor that inhibits cell surface tyrosine kinase receptors (e.g. vascular endothelial growth factor receptors and platelet-derived growth factor receptor-beta) and downstream intracellular serine/threonine kinases (e.g. Raf-1, wild-type B-Raf and mutant B-Raf); these kinases are involved in tumour cell proliferation and tumour angiogenesis. In vitro, dose-dependent inhibition of cell proliferation and induction of apoptosis was seen with sorafenib in human hepatocellular carcinoma cells lines. Sorafenib demonstrated dose-dependent antitumour activity in a murine xenograft model of human hepatocellular carcinoma. Steady-state plasma concentrations were reached within 7 days in patients with advanced, refractory solid tumours who received twice-daily oral sorafenib. Metabolism of sorafenib occurs primarily in the liver and is mediated via cytochrome P450 (CYP) 3A4 and uridine diphosphate glucuronosyltransferase 1A9. In advanced hepatocellular carcinoma, differences in sorafenib pharmacokinetics between Child-Pugh A and B patients were not considered clinically significant. Sorafenib may be associated with drug interactions. For example, sorafenib exposure was reduced by an average 37% with concomitant administration of the CYP3A4 inducer rifampicin (rifampin); sorafenib concentrations may also be decreased by other CYP3A4 inducers. Monotherapy with oral sorafenib 400 mg twice daily prolonged median overall survival and delayed the median time to progression in patients with advanced hepatocellular carcinoma, according to the results of two randomized, double-blind, placebo-controlled, multicentre, phase III trials (the SHARP trial and the Asia-Pacific trial). There was no significant difference between sorafenib and placebo recipients in the median time to symptomatic progression in either trial. The vast majority of patients included in these trials were Child-Pugh A. Combination therapy with sorafenib plus doxorubicin did not delay the median time to progression to a significant extent compared with doxorubicin alone in patients with advanced hepatocellular carcinoma, according to the results of a randomized, double-blind, phase II trial. However, the median durations of overall survival and progression-free survival were significantly longer in patients receiving sorafenib plus doxorubicin than in those receiving doxorubicin alone. Combination therapy with sorafenib plus tegafur/uracil or mitomycin also showed potential in advanced hepatocellular carcinoma, according to the results of noncomparative trials. Monotherapy with oral sorafenib was generally well tolerated in patients with advanced hepatocellular carcinoma, with a manageable adverse effect profile; diarrhoea and hand-foot skin reaction were consistently the most commonly occurring drug-related adverse events in clinical trials. In the SHARP trial, drug-related adverse events of any grade occurring in significantly more sorafenib than placebo recipients included diarrhoea, hand-foot skin reaction, anorexia, alopecia, weight loss, dry skin, abdominal pain, voice changes and 'other' dermatological events. A similar tolerability profile was seen in the Asia-Pacific trial. As expected given the addition of a chemotherapy agent, the adverse event profile in patients with advanced hepatocellular carcinoma who received combination therapy with sorafenib plus doxorubicin differed somewhat to that seen with sorafenib monotherapy in the SHARP trial. In patients receiving sorafenib plus doxorubicin, the most commonly occurring all-cause adverse events (all grades) included fatigue, neutropenia, diarrhoea, elevated bilirubin levels, abdominal pain, hand-foot skin reaction, left ventricular dysfunction, hypertension and febrile neutropenia.
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PMID:Sorafenib: a review of its use in advanced hepatocellular carcinoma. 1922 77

Over the last 30 years, several questionnaires have been developed and validated in order to assess many aspects of the motivation to eat that might be susceptible to impair adequate food intake and body weight control. A few of such questionnaires are described here, in particular, the "Three Factor Eating Questionnaire" also called the "Eating Inventory", and the "Dutch Eating Behavior Questionnaire". Critical aspects of the motivation to eat assessed by these tools are presented, such as dietary restraint, disinhibition, hunger, vulnerability to eat in response to external cues or emotional states, etc. These questionnaires were developed for use in the general population with the aim to identify critical aspects of the motivation to eat that might predispose to weight gain. They have been widely used in many countries and have allowed an improved understanding of the individual characteristics that predispose to body weight gain or resistance to weight loss. Originally, poor body weight control was attributed to a high level of dietary "restraint", or in other words, the tendency to deliberately restrict one's food intake for body weight control purposes. Such dietary restraint was suspected to lead to a number of physical and psychological difficulties, among which poor self-esteem and a paradoxical tendency to gain weight, resulting from the incapacity to maintain strict restraint over time. More recent studies have established that a motivational trait called "Disinhibition" is a strong predictor of body weight gain over time and of poor outcome of dieting. "Disinhibition" corresponds to a tendency to lose control over one's eating behavior and ingest excessively large quantities of food substances, in response to a variety of cues and circumstances. In addition to its untoward effect on weight, disinhibition also predicts various risk factors and pathologies, such as hypertension and diabetes. Other potentially critical dimensions for adequate body weight control are "emotional eating" and "externality", which represent an individual's vulnerability to eat in response to emotional states or external cues, respectively. These questionnaires have been translated into French and validated for the French population. Average data are available for normal weight and obese French men and women. A gender difference is often reported: women, and even young girls, tend to have higher scores than males for most dimensions. These questionnaires have been extensively used in populations without psychiatric disorders, with the only exception of diagnosed eating disorders such as anorexia and bulimia nervosa. The questionnaires have not been used until now in populations with other types of psychiatric disorders, such as schizophrenia or bipolar disease. Their relevance for such populations is now an important question, since last generation pharmaceutical treatments of such psychiatric disorders seem to adversely affect body weight control. It then becomes critical to know whether the psychological dimensions assessed by such questionnaires reflect the action of pharmacological agents that induce weight gain. A research project is now in progress at Sainte-Anne Hospital to investigate many dimensions of the motivation to eat, as assessed by the questionnaires, in psychiatric patients receiving various types of antipsychotic agents. The results of this original study might provide hints about the mechanisms that lead to body weight gain in patients receiving certain types of antipsychotic pharmacological agents and potentially help in preventing or reversing the weight gain associated with such treatments.
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PMID:[Assessing various aspects of the motivation to eat that can affect food intake and body weight control]. 1939 89

Medical statements from previous epidemiologic studies consider temporal arteritis as extremely rare or absent in Hispanic patients. A probable genetic protective condition was proposed as an explanation for this. We performed a descriptive observational, retrospective, comparable and not randomized study in the southern region of Puerto Rico (Ponce Area). The period for recollection of data was July/2002 to March/2004. We reviewed all the information of the clinical charts of patients diagnosed with temporal arteritis who were seen in the medical offices of one internist and two rheumatologists of the teaching staff of Damas Hospital. The subjects of our study consisted of 11 patients (8 female and 3 male), between the ages of 70 to 90, all of Hispanic origin, with a diagnosis of temporal arteritis. Frequencies and percentages were used to describe the data of the study. Headache was the most common symptom. Other symptoms included the presence of fatigue, malaise, anorexia, scalp tenderness, amaurosis fugax and decreased vision. Laboratory results showed the presence of a mild leukocytosis and anemia in most of the patients. Renal and liver functions were observed to be well-preserved, and serum electrolyte levels were within normal limits. The increase of the ESR and C Reactive Protein values and positive unilateral and bilateral biopsy studies were statistically significant. All of the above characterization of Hispanic population with temporal arteritis cited in our study correlates well with the classic description of the disease in previous epidemiological studies conducted on non-Hispanic subjects. Our study confirmed the presence of temporal arteritis in a Hispanic population. The disease was more prevalent in women than men, with a female to male ratio of 2:6, which is the lowest ratio found for this disease compared to previous epidemiological studies. In our study group, the disease was found in patients over 70 years of age, with a mean age of 75.7. Arterial hypertension was the most commonly associated condition in our patients, probably due to its high prevalence in our community. The clinical characteristics of our patients correlate closely with the previous data from other ethnic groups.
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PMID:Temporal arteritis in Puerto Rico Hispanics. 1961 May 72

Sunitinib is a novel, oral, multi-targeted tyrosine kinase inhibitor with antiproliferative effects against cancer cells and antiangiogenic properties. Sunitinib was recently approved for the first-line treatment of patients with advanced renal cell carcinoma (RCC) and for the treatment of patients with gastrointestinal stromal tumours (GIST) after disease progression or intolerance to imatinib therapy. The main purpose of this benefit-risk assessment is to review data on sunitinib efficacy along with its toxicity in patients with GIST and RCC. Sunitinib demonstrates a high level of efficacy with acceptable tolerability using either the 50 mg daily oral dosing for 4 weeks every 6 weeks or a continuous daily administration schedule at a lower dose. Hypertension and asthenia appear to be the most common adverse effects with sunitinib. Diarrhoea, anorexia, disgeusia, stomatitis and skin toxicity are other clinically relevant toxicities. Fatigue may, at least in part, be related to the development of hypothyroidism during sunitinib therapy. Skin toxicity consists of bullous lesion in the soles and palms that may require treatment discontinuation for a few days and/or dose reduction. Thyroid hormone levels should be monitored during treatment with sunitinib, with the occurrence of clinical signs of hypothyroidism needing treatment with levothyroxine sodium. Hypertension usually requires standard antihypertensive therapy and treatment discontinuation is less frequently necessary. Mild neutropenia and thrombocytopenia usually require no intervention. A decrease in left ventricular ejection fraction is a rare but potentially life-threatening complication. Although usually well tolerated, sunitinib needs to be administered cautiously with medical follow-up in patients with cancer to prevent, avoid and treat adverse effects in order to improve patient compliance. Its established antitumor activity requires attempting to maintain the highest tolerable dose in individual patients. Current oral formulations allow physicians to modulate dosages (between 25 and 50 mg/day) and/or schedules (4 weeks on, 2 weeks off or continuous administration) to optimize the benefit-risk profile of sunitinib in individual patients.
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PMID:Benefit-risk assessment of sunitinib in gastrointestinal stromal tumours and renal cancer. 1967 Sep 13

A 64-year-old woman with hypertension and hyperlipidemia was admitted to our hospital for the investigation and management of general fatigue, anorexia, a 5-kg weight loss, and a 4-week history of high-grade fever. She had no symptoms of headache, myalgia, or arthralgia, and the physical examination was unremarkable. The laboratory tests revealed renal dysfunction with urine abnormalities that had not been observed 1 year earlier. A renal biopsy showed granulomatous small arteritis without necrotic lesions or glomerular pathology. An immunohistochemical study of the infiltrating leukocytes showed a predominance of CD4+ T cells followed by CD8+ T cells, and only a few macrophages. The condition drastically improved after treatment with 30 mg/day of oral prednisolone. The granulomatous renal arteritis was considered a variant of giant cell arteritis, because it showed the peculiar finding of a few macrophages in the granulomatous lesions.
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PMID:Isolated granulomatous renal arteritis: a variant form of giant cell arteritis with few macrophages. 2007 89

The nociceptin opioid (NOP) receptor is the most recently discovered member of the family of the opioid receptors; its endogenous agonist is the peptide nociceptin. Due to the subsequent elucidation of its physiological role in both central and peripheral nervous system and in some non-neural tissues, there is a rapidly growing interest in the pharmacological application of substances active on this receptor. Despite the current clinical use of a morphinane-based NOP/MOP mixed ligand (buprenorphine) as an analgesic and in the treatment of drug addictions, so far just a few clinical trials have been made with selective NOP ligands. However, the perspective of their utilization is rapidly growing. Agonists can find applications in the treatment of neuropathic pain, anxiety, cough, drug addition, urinary incontinence, anorexia, congestive heart failure, hypertension; and antagonists for pain, depression, Parkinson's disease, obesity, and as memory enhancers. Besides peptide ligands, which are still subjected to many pharmacological investigations, many different chemical classes of NOP ligands have been discovered: piperidines, nortropanes, spiropiperidines, 4-amino-quinolines and quinazolines, and others. The new advances in establishing structure-activity relationships, also with the help of modeling studies, can permit the development of more active and selective molecules.
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PMID:Development of nociceptin receptor (NOP) agonists and antagonists. 2009 19

PURPOSE Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit. This randomized, double-blind, placebo-controlled phase III study evaluated efficacy and safety of pazopanib monotherapy in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS Adult patients with measurable, locally advanced, and/or metastatic RCC were randomly assigned 2:1 to receive oral pazopanib or placebo. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response rate (Response Evaluation Criteria in Solid Tumors), and safety. Radiographic assessments of tumors were independently reviewed. Results Of 435 patients enrolled, 233 were treatment naive (54%) and 202 were cytokine pretreated (46%). PFS was significantly prolonged with pazopanib compared with placebo in the overall study population (median, PFS 9.2 v 4.2 months; hazard ratio [HR], 0.46; 95% CI, 0.34 to 0.62; P < .0001), the treatment-naive subpopulation (median PFS 11.1 v 2.8 months; HR, 0.40; 95% CI, 0.27 to 0.60; P < .0001), and the cytokine-pretreated subpopulation (median PFS, 7.4 v 4.2 months; HR, 0.54; 95% CI, 0.35 to 0.84; P < .001). The objective response rate was 30% with pazopanib compared with 3% with placebo (P < .001). The median duration of response was longer than 1 year. The most common adverse events were diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. There was no evidence of clinically important differences in quality of life for pazopanib versus placebo. CONCLUSION Pazopanib demonstrated significant improvement in PFS and tumor response compared with placebo in treatment-naive and cytokine-pretreated patients with advanced and/or metastatic RCC.
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PMID:Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. 2081 65


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