Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical pharmacokinetics of trimetrexate were determined in 11 patients during the phase I trial. The plasma drug disappearance curve was triphasic, with a t1/2 alpha of 8 +/- 5 minutes, t1/2 beta of 102 +/- 48 minutes, and t1/2 gamma of 15.2 +/- 5.7 hours. The AUC was 373 +/- 336 (micrograms/ml) hr (normalized to a dose of 200 mg/m2), volume of distribution by the area method (Varea) was 25.2 +/- 16.1 L/m2, total clearance (CL) was 14 +/- 8 ml/min/m2, and renal clearance (CLR) was 8 +/- 6 ml/min/m2. Four patients who received 190 to 200 mg/m2 did not develop severe toxicity. However, three patients who received 120 to 210 mg/m2 developed severe myelosuppression, skin rash, and stomatitis. This latter group had significantly longer terminal half-lives, greater AUCs, smaller Vareas, and lower rates of CL and CLR. One of these patients received an unusually large total amount of trimetrexate (470 mg) because of his obesity. The remaining two patients had renal problems. One developed toxicity despite having received a reduced dose (120 mg/m2) because of impaired renal function. The other patient, with normal renal function, had ascites and had undergone a unilateral nephrectomy for renal carcinoma. These data suggest that prolonged exposure to high trimetrexate levels may lead to increased toxicity. Dosage adjustment may have to be considered for patients who have renal dysfunction.
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PMID:Clinical pharmacology of trimetrexate. 295 40

The purpose of this study was to compare the effect of the Z-track intramuscular injection technique with the effect of the stand and intramuscular injection technique on the severity of discomfort and lesions at the injection site. The subjects of the study were 20 patients with only early tuberculosis excluding another abnormalities (a skin rash, allergy to topical use of alcohol, jaundice, edema, neurosensory abnormality, coagulation defects, obesity and thin). Data collection was done from Feb. 1 to March 15, 1988 by means of Korean Pain Measurement Tool, Visual Analogue Scale, and Objective measures of injection site lesions. The results of this study were as follows: 1) Hypothesis 1; "The severity of subject discomfort is less following administration of the Z-track intramuscular injection technique than following administration injection technique." was not supported. 2) Hypothesis 2; "The degrees of severity subject discomfort is less following administration of the Z-track intramuscular injection technique than following administration of the standard intramuscular injection technique." was not supported. 3) Hypothesis 3; "The severity of injection sites lesions is less following administration of the Z-track intramuscular injection technique than following administration of the standard intramuscular injection techniques." was not supported. 4) The terms that were selected included factor II (mild-moderate pain) of Ratio Scale Measuring Pain using Korean Pain Terms. In conclusion; it was found that there was not a difference from the severity of subject discomfort between two groups, but the degrees of severity of subject discomfort about following administration of the Z-track intramuscular injection was tended to be declined. Therefore further studies suggest that the Z-track intramuscular injection technique can decrease the severity of discomfort in persons receiving frequently intramuscular injections. First of all, it is necessary to be developed an effect tool of dis comfort measurement for the intramuscular injection in Korean.
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PMID:[Comparison of two intramuscular injection technics on the severity of discomfort and lesions at the injection site]. 323 Jul 58

Observations related to the safety of fluoxetine in the treatment of obese patients are reviewed. The adverse event profile in obese patients, though differing slightly from that seen in depressed patients, was similar in that events observed were generally mild and well tolerated. Other than rash, no potentially serious adverse events believed to be related to fluoxetine were observed. Special evaluations of pharmacokinetics, psychomotor impairment, cardiac effects, phospholipidosis and addiction potential have identified no major problems in these areas. It is concluded that fluoxetine use for the treatment of obesity should carry with it minimal risk.
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PMID:Safety of fluoxetine in the treatment of obesity. 350 95

Recent treatment strategies have been directed toward blockade of estrogen action or inhibition of estrogen biosynthesis as a means of inducing regression of hormone-dependent breast cancer. The major source of estrogen in postmenopausal women is the peripheral conversion of androstenedione to estrone through the enzyme aromatase. It is known that aromatase activity increases proportionately with degree of obesity in women. To test the importance of this modulatory factor, we correlated body weight with estrogen excretion in our population of patients with breast cancer and found significant relationships. In situ production of estradiol from plasma precursors within breast cancer tissue may provide another source of estrogen. Major enzymes mediating estrogen biosynthesis were found to be present in tumor biopsy specimens. Aromatase activity was found to be present in 48/61 human tumors, sulfatase in 35/35, and 17 beta -hydroxysteroid dehydrogenase in 41/41. One inhibitor of aromatase, aminoglutethimide, has been extensively studied in patients with breast cancer. The additional effects of this drug on cholesterol side-chain cleavage and on 11-hydroxylase activity require coadministration of replacement glucocorticoid in treatment regimens. In pilot trials, 37% of patients experienced objective tumor regression with a combination of 1000 mg aminoglutethimide and 40 mg hydrocortisone daily. In randomized clinical trials with this regimen, aromatase inhibition with aminoglutethimide produced tumor regression with similar frequency as did surgical hypophysectomy, surgical adrenalectomy, or tamoxifen administration. The side effects of aminoglutethimide, including lethargy, skin rash, and ataxia complicate its use even though these problems are generally transient. Regimens of low-dose aminoglutethimide are being developed to reduce these side effects. Low-dose aminoglutethimide appears to block aromatase effectively and to have limited side effects, and is undergoing extensive clinical trial. A more specific aromatase inhibitor, 4-hydroxyandrostenedione, is now also being tested clinically, whereas MDL 18962, another new selective inhibitor, is undergoing study in animals.
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PMID:Inhibition of aromatase as treatment of breast carcinoma in postmenopausal women. 354 61

Livedo reticularis is a vascular abnormality of the skin resulting in an erythematous reticular rash. The combination of livedo reticularis and stroke-like episodes in adults is known as Sneddon syndrome [Sneddon, IB (1965). Br J Dermatol 77:180-188]. A similar combination of stroke-like episodes and livedo reticularis has been reported to occur in children [Baxter P et al. (1993). Dev Med Child Neuro 35:917-926]. We present here a 7-year-old male with congenital livedo reticularis, obesity, developmental delay, stroke-like episode, hypertension and cystic kidneys. We summarize our patient's findings and family history, and compare his disorder to other possibly related conditions.
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PMID:Livedo reticularis, developmental delay and stroke-like episode in a 7-year-old male. 954 37

A 47-year-old mildly obese female began a weight reduction program that included anorectic therapy with phentermine and phendimetrazine. A normal urinalysis and serum creatinine were documented at the start of therapy. After three weeks of treatment, the patient felt ill and discontinued her treatment. Subsequently she was found to have leukocyturia, a rash on her face and chest, and a rise in her serum creatinine from 0.8 mg/dl to 2.1 mg/dl. A renal biopsy confirmed the diagnosis of acute interstitial nephritis. The patient was treated with corticosteroids and her renal function returned to normal. Despite the recent withdrawal of two anorectic agents due to data linking them to severe cardiac and pulmonary disease, the appetite suppressants phentermine and phendimetrazine remain in widespread usage for the treatment of obesity. This case represents the first report of acute interstitial nephritis associated with phentermine or phendimetrazine.
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PMID:Acute interstitial nephritis following treatment with anorectic agents phentermine and phendimetrazine. 979 71

The paleopathological study of 40 Italian Renaissance mummies has allowed us to perform about 20 diagnoses, of which 5 concern infectious (smallpox, hepatitis, condyloma, syphilis and pneumonia), 4 metabolic (obesity, atherosclerosis, gallstones and uric acid nephrolithiasis), 2 articular (DISH and rheumatoid arthritis) and 2 neoplastic (skin apithelioma and colon adenocarcinoma) diseases. The mummy of an anonymous child, dated back to the 16th century (C14=1569 +/- 60), presented a diffuse vesiculo-pustular exanthema. Macroscopic aspects and regional distribution suggested smallpox, while EM reavealed many egg-shaped, virus-like particles (250 x 50 nm), with a central dense core. Following incubation with anti-smallpox virus antiserum and protein A-gold complex immunostaining, the particles resulted completely covered with protein A-gold. These results clearly show that this Neapolitan child died of a severe form of smallpox some four centuries ago. The mummy of Maria of Aragon, Marquise of Vasto (1503-1568), reavealed on the left arm an oval, cutaneous ulcer (15x10 nm) with linen dressing. Indirect immunofluorescence with anti-treponema pallidum antibody identified a large number of filaments with the morphological characteristics of fluorescent treponemes. EM evidenced typical spirochetes, with axial fibril. These findings clearly demonstrate a treponemal, probably venereal, infection. The mummy of Ferrante I of Aragon, King of Naples (1431-1494), revealed an adenocarcinoma extensively infiltrating the muscles of the small pelvis. A molecular study of the neoplastic tissue evidenced a typical mutation of the K-ras gene codon 12:the normal sequence GGT (glycine) was altered into GAT (aspartic acid). At present this genetic change is the most frequent mutation of the K-ras gene in sporadic colorectal cancer. The alimentary "environment" of the Neapolitan court of the XV century, with its abundance of natural alimentary alkylating agents, well explains this acquired mutation. These and other diseases as, for example, a fatal puerperal complication, a thyroid goiter, a case of Wilson's cirrhosis, some cases of anthracosis and other peculiar traumatic conditions, such as a mortal stab-wound, can elucidate the pathocenosis of the wealthy classes of the Italian Renaissance.
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PMID:Renaissance mummies in Italy. 1162 3

ISIS 104838 is a 20-mer phosphorothioate antisense oligonucleotide (ASO) that binds tumor necrosis factor-alpha (TNF-alpha) mRNA. It carries a 2'-methoxyethyl modification on the five 3' and 5' nucleotide sugars, with 10 central unmodified deoxynucleotides. ISIS 104838 was identified from a 264 ASO screen in phorbol myristate acetate-activated keratinocytes, and the dose response was assessed in lipopolysaccharide (LPS)-activated monocytes. Healthy males received multiple intravenous (i.v.) ISIS 104838 infusions in a placebo-controlled dose escalation trial (0.1-6 mg/kg). Additional volunteers received single or multiple subcutaneous (s.c.) injections. ISIS 104838 suppressed TNF-alpha protein by 85% in stimulated keratinocytes. The IC50 for TNF-alpha mRNA inhibition in stimulated monocytes was <1 microM. For i.v., C(max) occurred at the end of infusion. The effective plasma half-life was 15 to 45 min at 0.1 to 0.5 mg/kg and 1 to 1.8 h for higher doses. The apparent terminal plasma elimination half-life approximated 25 days. Obese subjects had higher plasma levels following equivalent mg/kg doses. For s.c. injections, C(max) occurred at 2 to 4 h and was lower than with equivalent i.v. dosing. Plasma bioavailability compared with i.v. was 82% following a 200 mg/ml s.c. injection. Transient activated partial thromboplastin time prolongation occurred after i.v. infusions and minimally after s.c. injections. Two subjects experienced rash, one a reversible platelet decrease, and mild injection site tenderness was noted. TNF-alpha production by peripheral blood leukocytes, induced ex vivo by LPS, was decreased by ISIS 104838 (p < 0.01). ISIS 104838, a second-generation antisense oligonucleotide, was generally well tolerated intravenously and subcutaneously. The pharmacokinetics support an infrequent dosing interval. Inhibition of TNF-alpha production ex vivo was demonstrated.
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PMID:Phase I trial of ISIS 104838, a 2'-methoxyethyl modified antisense oligonucleotide targeting tumor necrosis factor-alpha. 1243 59

A retrospective review of dengue patients admitted to Queen Sirikit National Institute of Child Health (previously known as Children's Hospital) from 1995 to 1999 revealed 4,532 confirmed cases of dengue infection; 80.9% were dengue hemorrhagic fever (DHF) and 19.1% were dengue fever cases (DF). Among the DHF patients; 30.6% had shock. The majority of them, 66.6%, had a normal nutritional status, while 9.3% were malnourished and 24.2% had obesity as classified by weight for age. Compared with control patients with other diagnoses (excluding HIV/AIDS patients), malnourished children had a lower risk of contracting dengue infection (odds ratio = 0.48, 95% Cl = 0.39-0.60, p = 0.000) while obese children had a greater risk of infection with dengue viruses (odds ratio = 1.96, 95% Cl = 1.55-2.5, p = 0.000). The clinical signs, symptoms and laboratory findings of dengue were almost the same among the 3 groups of malnourished, normal, and obese patients. The minor differences observed were that in obese children liver enlargement was found less often; maculopapular/convalescence rash and elevations of alanine aminotransferase were found more often. Malnourished patients had a higher risk of developing shock (37.8%) than normal (29.9%) and obese patients (30.2%) (p = 0.000). Obese patients had more unusual presentations: encephalopathy (1.3%) and associated infections (4.8%), than normal (0.5% and 2.7%) and malnourished patients (1.2% and 3.1%). Complications of fluid overload were found more in obese patients (6.5%) compared to normal (3.2%) and malnourished patients (2.1%) (p = 0.000). The case-fatality rates (CFR) in malnourished patients and obese patients were 0.5% and 0.4%, respectively, while in normal patients the CFR was 0.07%. Under and over nutrition DHF patients had either a greater risk of shock or unusual presentations and complications, which can lead to severe disease or complications and probably a higher CFR.
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PMID:Is dengue severity related to nutritional status? 1591 44

Intertrigo is inflammation of skinfolds caused by skin-on-skin friction. It is a common skin condition affecting opposing cutaneous or mucocutaneous surfaces. Intertrigo may present as diaper rash in children. The condition appears in natural and obesity-created body folds. The friction in these folds can lead to a variety of complications such as secondary bacterial or fungal infections. The usual approach to managing intertrigo is to minimize moisture and friction with absorptive powders such as cornstarch or with barrier creams. Patients should wear light, nonconstricting, and absorbent clothing and avoid wool and synthetic fibers. Physicians should educate patients about precautions with regard to heat, humidity, and outside activities. Physical exercise usually is desirable, but patients should shower afterward and dry intertriginous areas thoroughly. Wearing open-toed shoes can be beneficial for toe web intertrigo. Secondary bacterial and fungal infections should be treated with antiseptics, antibiotics, or antifungals, depending on the pathogens.
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PMID:Intertrigo and common secondary skin infections. 1615 42


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