Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
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To evaluate the nutritional, metabolic and immune effects of dietary arginine, glutamine and omega-3 fatty acids (fish oil) supplementation in immunocompromised patients, we performed a prospective study on the effect of immune formula administered to 11 severe trauma patients (average ISS = 24), 10 burn patients (average % TBSA = 48) and 5 cancer patients. Daily calorie and protein administration were based on the patient's severity (Stress factor with the range of 35-50 kcal/kg/day and 1.5-2.5 g/kg/day, respectively) Starting with half concentration liquid immune formula through nasogastric tube by continuous drip at 30 ml/h and increasing to maximum level within 4 days. The additional energy and protein requirement will be given either by parenteral or oral nutritional support. Various nutritional, metabolic, immunologic and clinical parameters were observed on day 0 (baseline), day 3, 7, and 14. Analysis was performed by paired student-t test. Initial mean serum albumin and transferrin showed mild (trauma) to moderate (burn and cancer) degree of malnutrition. Significant improvement of nutritional parameters was seen at day 7 and 14 in trauma and burn patients. Significant increase of total lymphocyte count (day 7, P < 0.01), CD4 + count (day 7, p < 0.01), CD8 + count (day 7, p < 0.0005 & day 14, p < 0.05), complement C3 (day 7, p < 0.005 day 14, p < 0.01), IgG (day 7, and 14, p < 0.0005), IgA (day 7, p < 0.0005 & day 14, p < 0.05), in all patients. C-reactive protein decreased significantly on day 7 (p < 0.0005) and day 14 (p < 0.005). 3 cases of burn wound infection, one case of UTI and one case of sepsis were observed. Two cases of hyperglycemia in burn, 3 cases of hyperbilirubinemia in trauma, 10 cases of elevated LFT (5 trauma/5 burn), and one case of hyponatremia in cancer patients were observed. Two cases of nausea, 4 cases of vomiting, 5 cases of diarrhea (< 3 times/day), 2 cases of abdominal cramp, 1 case of distension were observed. The feeding of IMMUNE FORMULA was well tolerated and significant improvement was observed in nutritional and immunologic parameters as in other immunoenhancing diets. Further clinical trials of prospective double-blind randomized design are necessary to address the so that the necessity of using immunonutrition in critically ill patients will be clarified.
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PMID:Metabolic and immune effects of dietary arginine, glutamine and omega-3 fatty acids supplementation in immunocompromised patients. 962 33

We have used a relatively new trial methodology, the group sequential design, to prospectively evaluate two dose levels of bolus/infusional 5-fluorouracil (5-FU) and folinic acid in 192 consecutive-patients with advanced colorectal carcinoma. On day 1, all patients received 200 mg m(-2) of folinic acid infusion over 2 h. Cohort A (n = 102 patients) received 500 mg m(-2) 5-FU by i.v. 15-min infusion followed by an infusion of 500 mg m(-2) 5-FU over 22 h. Treatment was repeated on day 2 and further cycles given 2-weekly. After sequential analysis excluded a response rate of over 40%, cohort B (n = 90 patients) received an increased dose of 600 mg m(-2) 5-FU bolus and infusion. Patients had received no prior 5-FU therapy and the two cohorts had similar demographic features. In 179 evaluable patients, the overall response rate was 18% (95% CI 12-24%) with CR of 6% and PR of 12%, with no difference between the two cohorts. Overall median survival was 34 weeks (95% CI 30-39) with no significant difference between cohorts (median survival 32 and 37 weeks in cohort A and B respectively; P = 0.27). On multivariate analysis, poor performance status, elevated initial WBC and alkaline phosphatase and low serum albumin were associated with reduced survival (P < 0.05), and initial raised WBC showed an association with reduced likelihood of response (P = 0.002). Overall toxicity was low with CTC grade 3 mucositis, diarrhoea, nausea or vomiting in < or = 6% of patients and no treatment-related deaths. Significant (grade 3 or above) leucopenia was more common in cohort B than in cohort A (9% and 1% respectively); there were more dose reductions, and the median administered dose intensity was lower in cohort B than in cohort A (89% and 97% respectively; P = 0.006). In this group of relatively unselected patients, we have confirmed a relatively low objective response rate and median survival of 7.8 months with this regimen. There was no significant difference in outcome between the two dose levels but the higher dose of 5-FU was associated with more dose reductions and greater toxicity.
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PMID:Bolus/infusional 5-fluorouracil and folinic acid. A report on two prospective, consecutive phase II studies with 5-fluorouracil dose escalation. 965 65

The seeds of Ricinus communis Linn, RICOM-1013-J, administered as a single oral dose of 2.3-2.5 g once per 12 months protected against pregnancy in 50 women volunteers for a period of one year. The antifertility and contraceptive efficacy of the seed was demonstrated in this study. Clinical observation revealed very minimal side effects. Some of the side effects investigated included headache, nausea, vomiting, weight gain, loss of appetite, raised blood pressure and dysmenorrhoea. Furthermore, both the renal and liver functions were not affected as revealed by urea, electrolyte and creatinine values as well as total bilirubin, conjugated bilirubin, serum albumin, total protein and transaminases values when compared with control values. In addition cholesterol and phospholipids were not significantly altered. When all these results are considered together, it seems unlikely that the antifertility and contraceptive efficacy of RICOM-1013-J is due to hormonal mechanisms alone since side effects, renal and liver function, and cholesterol effects attributable to oestrogen and/or progesterone were minimal in the volunteers.
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PMID:Preliminary clinical investigation of the contraceptive efficacy and chemical pathological effects of RICOM-1013-J of Ricinus communis var minor on women volunteers. 1064 Oct 46

Hemodialysis patients frequently experience such dyspeptic symptoms as nausea, vomiting, abdominal distension, early satiety, and anorexia. Gastroparesis might be a cause of malnutrition, and parameters of gastric emptying are inversely correlated with serum albumin levels. The aim of the present study is to determine whether delayed gastric emptying is related to dyspeptic symptoms. In 54 hemodialysis patients, a standardized history for dyspeptic symptoms was taken. In addition, gastric emptying for solids was measured in 26 patients, using the (13)C-octanoic acid breath test. There was a high prevalence of dysmotility-like dyspepsia in the hemodialyzed population. A significant difference in gastric emptying between dyspeptic hemodialysis patients and healthy volunteers and between dyspeptic and nondyspeptic hemodialysis patients was shown. There was a significant correlation between gastric emptying and dysmotility-like dyspepsia. Serum albumin level inversely correlated with gastric emptying. In conclusion, there is a high prevalence of dysmotility-like dyspepsia in hemodialysis patients. Dyspeptic patients have significantly delayed gastric emptying compared with both healthy volunteers and nondyspeptic patients.
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PMID:Delayed gastric emptying in dyspeptic chronic hemodialysis patients. 1105 52

The treatment of severe lupus nephritis is based on the combination of steroids and cytotoxic drugs. Intravenous cyclophosphamide administered in "pulses" is effective in the induction of remission but other therapeutic alternatives are sought in refractory cases or severely relapsing patients. Mycophenolate mofetil, used in renal transplantation, also can be useful in severe lupus nephritis. We describe the evolution of 6 patients (5 women and 1 man; age 17-45 years) with severe lupus nephropathy who after achieving remission with intravenous cyclophosphamide and steroids (5 cases) or cyclosporin A (1 case) showed relapse of proteinuria and were treated with mycophenolate mofetil (dose 1000-2000 mg/day). Two patients have completed 24 months, 1 patient two cycles of 12 months, 2 patients 18 months and 1 patient 6 months. After this treatment, all patients have achieved remission (3 partial and 3 complete). There was no treatment failure and no one patient discontinued medication; however 1 case relapsed. There were no changes in leucocytes, haemoglobin, serum creatinine and serum albumin. ANA and alpha DNA antibodies decreased. Proteinuria (measured as protein/creatinine urine ratio: initial 3 and final 0.3) and dose of steroids (initial: 17.5 mg/d and final 5 mg/d) decreased significantly (p < 0.05 Wilcoxon t-test). The most common side effects were nausea and abdominal discomfort that improved without discontinuation of treatment. We conclude that mycophenolate mofetil is effective and a safe drug in severe relapsing lupus nephritis.
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PMID:[Mycophenolate mofetil in lupus nephritis]. 1198 81

The authors report on a 44-year-old female hemodialysis (HD) patient who presented with hypercalcemia secondary to isolated adrenocorticotropic hormone (ACTH) deficiency. She had been suffering from nausea and abdominal pain caused by recurrent esophageal ulcer. Blood calcium (Ca) adjusted for serum albumin concentration was increased to 14.9 mg/dL (3.72 mmol/L) concurrently with fever and hypotension. Serum intact parathyroid hormone (PTH)-related peptide was not elevated, but serum intact PTH and 1,25-(OH)2 vitamin D3 were decreased to 31 pg/mL (ng/L) and 8.1 pg/mL (2.6 pmol/L), respectively. Endocrinologic examination found that plasma ACTH was reduced below 5.0 pg/mL (0.22 pmol/L). A single ACTH stimulation normally increased blood cortisol, whereas a single corticotropin-releasing hormone injection failed to increase plasma ACTH and cortisol. Pituitary magnetic resonance imaging disclosed no enlargement of pituitary gland. Circulating bone formation and absorption markers were not elevated. Blood Ca was normalized shortly after pamidronate disodium administration without glucocorticoid supplementation. This case suggested that secondary adrenal insufficiency caused by isolated ACTH deficiency could be an occult cause of severe hypercalcemia in HD subjects.
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PMID:Isolated adrenocorticotropic hormone deficiency presenting with hypercalcemia in a patient on long-term hemodialysis. 1290 Aug 50

Synthetic cannabinoids have a promising future as treatments for nausea, appetite modulation, pain, and many neurological disorders. Transdermal delivery is a convenient and desirable dosage form for these drugs and health conditions. The aim of the present study was to investigate the in vitro transdermal permeation of two synthetic cannabinoids, WIN 55,212-2 and CP 55,940. Transdermal flux, drug content in the skin, and lag times were measured in split-thickness human abdominal skin in flow-through diffusion cells with receiver solutions of 4% bovine serum albumin (BSA) or 0.5% Brij 98. Differential thermal analysis (DSC) was performed in order to determine heats of fusion, melting points, and relative thermodynamic activities. The in vitro diffusion studies in 0.5% Brij 98 indicated that WIN 55,212-2 diffuses across human skin faster than CP 55,940. The WIN 55,212-2 skin disposition concentration levels were also significantly higher than that of CP 55,940. Correspondingly, CP 55,940 was significantly metabolized in the skin. WIN 55,212-2 flux and skin disposition were significantly lower into 4% BSA than into 0.5% Brij 98 receiver solutions. There was no significant difference in the flux, lag time, and drug content in the skin of CP 55,940 in 4% BSA versus 0.5% Brij 98 receiver solutions. The DSC studies showed that CP 55,940 had a significantly lower melting point, smaller heat of fusion, and corresponding higher calculated thermodynamic activity than the more crystalline WIN 55,212-2 mesylate salt. The permeation results indicated that WIN 55,212-2 mesylate, CP 55,940, and other potent synthetic cannabinoids with these physicochemical properties could be ideal candidates for the development of a transdermal therapeutic system.
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PMID:Transdermal permeation of WIN 55,212-2 and CP 55,940 in human skin in vitro. 1515 59

A 58-year-old man with end-stage renal failure secondary to polycystic kidney disease developed a profoundly elevated mycophenolic acid (MPA) free fraction and associated severe toxicity after cadaveric renal transplantation. Initial immunosuppressive therapy was 4 mg/kg body weight bid cyclosporin (Neoral; Novartis Pharmaceutical Co Ltd, Sydney, Australia) given orally with 1 g bid mycophenolate mofetil (MMF) (CellCept; Roche Products Pty Ltd, Sydney, Australia). In the first 5 days posttransplantation, the serum creatinine concentration fell, and the patient developed profound hypoalbuminemia (serum albumin <20 g/L) and hyperbilirubinemia (serum bilirubin >150 micromol/L) that resulted from progressing biliary obstruction. On day 5 posttransplantation, the 2-hour whole-blood cyclosporin concentration and total MPA area under the curve (AUC(0-6)) were low (837 microg/L and 12.6 mg x h/L, respectively), while the total mycophenolic acid glucuronide (MPAG) AUC(0-6) was elevated (1317 mg x h/L). MMF was continued at the same dose, but tacrolimus substituted for cyclosporin. The patient subsequently experienced severe nausea, vomiting, hematemesis, and pancytopenia (nadir white cell count 1.6 x 10(9)/L, platelet count 32 x 10(9)/L, and hemoglobin 73 g/L) that were normalized after cessation of MMF. Retrospective measurement of the free MPA concentration on day 5 showed that free MPA AUC(0-6) was markedly elevated at 2.3 mg x h/L, as was the free fraction, at 18.3%. This case illustrates how altered protein binding can be associated with severe MMF toxicity caused by an increased free MPA concentration despite relatively low total MPA. These data support the monitoring of free MPA concentrations in those patients considered at risk for MMF-related toxicity.
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PMID:Severe toxicity associated with a markedly elevated mycophenolic acid free fraction in a renal transplant recipient. 1525 77

Ascites is the pathological accumulation of fluid within the abdominal cavity. The most common cancers associated with ascites are adenocarcinomas of the ovary, breast, colon, stomach and pancreas. Symptoms include abdominal distension, nausea, vomiting, early satiety, dyspnea, lower extremity edema, weight gain and reduced mobility. There are many potential causes of ascites in cancer patients, including peritoneal carcinomatosis, malignant obstruction of draining lymphatics, portal vein thrombosis, elevated portal venous pressure from cirrhosis, congestive heart failure, constrictive pericarditis, nephrotic syndrome and peritoneal infections. Depending on the clinical presentation and expected survival, a diagnostic evaluation is usually indicated as it will impact both prognosis and the treatment approach. Key tests include serum albumin and protein and a simultaneous diagnostic paracentesis, checking ascitic fluid, WBCs, albumin, protein and cytology. Median survival after diagnosis of malignant ascites is in the range of 1 to 4 months; survival is apt to be longer for ovarian and breast cancers if systemic anti-cancer treatments are available.
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PMID:Management of ascites due to gastrointestinal malignancy. 1970 Aug 95

Patients taking more than 8 courses of S-1 were classified in the continuous group (n=30) and those in whom S-1 was discontinued or reduced due to adverse reactions in the discontinuation/reduction group (n=29). Factors affecting the continuous administration of S-1 as the adjuvant chemotherapy were examined in the two groups. 10 cases in the continuous group and 8 cases in the discontinuation/reduction group began with a stage 1 reduction of the S-1 regimen. Significant factors which affected the reduction or discontinuation of S-1 due to adverse reactions were 1) serum albumin value (Alb) (odds ratio 9.227; 95% confidence interval 1.056-80.603, p=0.0196) and 2) creatinine clearance value (Ccr) (odds ratio 5.850; 95% confidence interval 1. 222-27.995, p=0.0221). Among the reasons for reduction or discontinuation, non-hematotoxicities including malaise, nausea and diarrhea accounted for 24/59 cases (40.7%) and hematotoxicities such as leukopenia for 5/59 cases (8.5%). The present study revealed that most of the reduction or discontinuation of S-1 was due to non-hematotoxicity such as malaise and suggested that these risks increased when Alb decreased to less than 3.5 g/dL and Ccr to less than 80 mL/min. Prognosis is reportedly satisfactory when administration of S-1 is continued for one year even if withdrawal or reduction is necessary during the period. Serious adverse reactions will have ill effects on future compliance with to administration in patients who have experienced them. The above results indicate that the occurrence of non-hematotoxicity should be observed carefully in patients with Alb less than 3.5 g/dL and Ccr less than 80 mL/min at the beginning of S-1 administration, and these patients should receive appropriate guidance. Modification or reduction of S-1 regimen at the beginning may be one way to alleviate hematotoxicity.
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PMID:[Continuous administration and safety of S-1 in adjuvant chemotherapy for gastric cancer]. 2049 11


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