Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of 17 children aged 2-9.5 years with a combination of pivmecillinam and pivampicillin (250-500 mumol 24 h-1) for more than 1 year resulted in a reduction of the free carnitine concentration in serum and muscle to less than 10% of the mean reference value. The decline in serum was slow, with an estimated half-life of about 5 months. Spontaneous replenishment occurred at about the same slow rate. Thus, there is no increase in endogenous carnitine synthesis as a response to increased demand of carnitine for detoxification. Supplementation with carnitine during treatment required at least a four-fold molar excess over pivalic acid to achieve and sustain a normal carnitine concentration. The replenishment of carnitine occurred with a half-life of 1.1-3.0 months. From determination of muscle-carnitine concentration in patients treated with pivaloyl-containing antibiotics and in patients with organic aciduris, we conclude that serum carnitine is a good predictor of carnitine stores in the body. Six non-supplemented patients with a serum free-carnitine concentration of 0.7-2.6 mumol l-1 had an inadequate ketone-body increase during a 24-h fast. Vomiting, nausea and tiredness occurred in three cases following the fasting period. After normalization of the serum-carnitine concentration, a normal response to fasting was observed. Thus, in some organic acidurias, for example medium-chain acyl-CoA dehydrogenase deficiency, a low liver concentration of carnitine may be an important contributing factor to hypoglycaemic and Reye-like attacks. We believe that prodrugs which contain pivalic acid should be avoided if acceptable alternatives exist. If used, supplementation with at least four-fold molar excess of carnitine is advisable.
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PMID:Effects of pivalic acid-containing prodrugs on carnitine homeostasis and on response to fasting in children. 151 15

Thirty-seven patients with advanced malignancies were treated sequentially with recombinant interferon-gamma (rIFN-gamma) and recombinant interleukin-2 (rIL-2) in an outpatient dose escalation clinical trial. rIFN-gamma (0.1 or 0.25 mg/m2/day) was administered by intramuscular injection, days 1-7 and rIL-2 (12, 18, or 24 x 10(6) IU/m2/day) was administered by a 15-min intravenous bolus, days 8-12. Common toxicities encountered included fever, chills, fatigue, neutropenia, and elevations of SGOT, bilirubin, or creatinine. Hypotension and cardiac and pulmonary toxicities were rare. With repeated cycles of therapy, nausea/vomiting and diarrhea associated with the administration of rIL-2 were seen in greater frequency. There were no treatment-related deaths, and no patient required intensive care unit admission for toxicity management. A complete response was observed in one of 11 patients with renal cancer and a partial response was observed in one of seven patients with malignant melanoma. Due to problems with drug supply, further dose escalation could not be continued, and maximum tolerated doses (MTD) were not determined by strict criteria. However, the combination of rIFN-gamma, 0.25 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day, appeared to be beyond the MTD, as three of six patients at this dose level could not complete one cycle of therapy due to toxicity. It is unlikely that higher doses of either agent would be tolerated, and for further study using this schedule, we recommend the doses: rIFN-gamma, 0.1 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day.
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PMID:A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-gamma and recombinant interleukin-2 in patients with cancer. 151 22

This report assesses the validity of subscales from the Quality of Life Index (QLI). Subscale validity is tested across different samples of patients with cancer and other diseases. The results of the factor analyses of different versions of the QLI tested in six studies confirm four important health-related quality of life dimensions. These dimensions are psychological well-being, physical well-being, symptoms/side effects, and nutrition. Psychological well-being is represented by a satisfying life, having a good (general) quality of life, having fun, feeling happy and enjoying life. Physical well-being is defined by tiring easily (fatigue), ability to work/carry out usual tasks, strength, and feeling healthy. The symptoms/side effects dimension is characterized by nausea, vomiting, pain distress, and perhaps, by pain amount and pain frequency. Finally, the nutrition dimension is represented by able to eat/eat sufficiently, eating pleasure/appetite, worry about weight, and possibly also taste changes. Good construct validity can be attributed to these health-related quality of life subscales.
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PMID:Validity of health-related quality of life subscales. 151 79

Cilazapril is a new once-daily angiotensin-converting (ACE) enzyme inhibitor which has been administered to 4,500 patients with mainly mild to moderate essential hypertension in a multinational clinical research program. Sitting diastolic blood pressure was reduced by about 9 mm Hg from baseline (p less than 0.01) after 4 weeks of treatment with cilazapril 1.25-10 mg/day in double-blind placebo-controlled studies. Total responder rates to cilazapril were usually 50-60% compared with 30% to placebo. Adding hydrochlorothiazide 12.5 mg/day to cilazapril 5.0 mg/day increased the total responder rate from 52 to 71%. Double-blind dose titration studies for 8 weeks showed that cilazapril 2.5-5 mg/day possessed equivalent efficacy to usual therapeutic regimens of sustained release propranolol, captopril, hydrochlorothiazide, atenolol and enalapril, Cilazapril did not affect heart rate. During long-term open administration for 52 weeks, or longer, cilazapril, either alone or in combination with hydrochlorothiazide, effectively maintained control of blood pressure. Treatment of patients with severe hypertension with cilazapril plus hydrochlorothiazide achieved a total responder rate of 73%. Adverse events were mostly observed within the first 8-16 weeks of treatment, with headache, dizziness, fatigue, nausea, cough and chest pain being the most frequent. Non-life-threatening angioedema, facial edema and mild hypotension occurred in less than or equal to 0.2% of patients, and orthostatic hypotension was reported in 2%. Abnormal laboratory test values were rarely found with cilazapril treatment. Of the 2.3% of patients with elevated serum creatinine, at any time point during the study and irrespective of outcome on continuation with cilazapril therapy, about two thirds had prior renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cilazapril: an overview of its efficacy and safety in hypertension. 153 34

During the past decade, the development of various gonadotrophin-releasing hormone (Gn-RH) agonists, which induce reversible hypo-oestrogenism has opened a new area in the medical management of endometriosis. In an open, multicentre phase III study, the efficacy, tolerance and safety of the Gn-RH agonist leuprorelin acetate were tested. The preliminary results of 104 women treated in seven German centres are presented. Pelvic endometriosis was diagnosed by laparoscopy and classified according to the American Fertility Society scoring system: 33% of patients had minimal, 22% mild, 28% moderate and 8% severe endometriosis and in 9% no pathological results were obtained. The patients' mean age was 30 +/- 6 years and 66 had infertility problems. Treatment was started within the first 3 days of the menstrual cycle and consisted of a subcutaneous injection of leuprorelin acetate 3.75 mg, repeated once monthly over 24 weeks. A follow-up period of 12 months after the last injection has been completed in 70 patients, including a second laparoscopy. At all visits, symptoms were evaluated, physical examinations performed, and blood samples collected for haematological screening, serum chemistry determinations and measurement of the gonadotrophins oestradiol and progesterone and leuprorelin acetate. The median score at laparoscopy fell from 12 before operation to 8 after operation and 2 after treatment with leuprorelin acetate. Of the total number of patients, 89% had improvements in their endometriosis, 8% a deterioration and 3% no change. Patients reported improvement in the following: dysmenorrhoea 93%, dyspareunia 62% and pelvic pain 70%. However, all women complained of at least one of the following symptoms: hot flushes 86%, sleep disturbance 62%, sweating 61%, headache 41%, nausea 32% and depression 20%. Fifty-five percent of patients reported additional side effects such as vaginal dryness, fatigue and lower abdominal pain. After the third injection, amenorrhoea persisted in 94% of the women. Four weeks after the first leuprorelin acetate injection median concentrations of oestradiol fell from 45 pg/ml to 11 pg/ml, follicle-stimulating hormone from 7 U/L to 3 U/L and luteinising hormone from 5 U/L to 1 U/L and remained almost unchanged over the observation period. During the 6 months' treatment, laboratory parameters showed no significant deviations from normal; only total cholesterol, high-density lipoprotein cholesterol and alkaline phosphatase increased. Treatment results were judged as good and satisfactory in 82% and 11% of cases, respectively. On the basis of this study, it can be concluded that leuprorelin acetate treatment is safe, well tolerated and effective in the medical management of endometriosis and endometriosis-related complaints.
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PMID:Treatment of endometriosis with leuprorelin acetate depot: a German multicentre study. 153 21

Laparoscopic cholecystectomy seems to be the most promising new technique for the treatment of symptomatic gallstone disease. For different reasons, controlled clinical trials comparing comfort and trauma for the patient of conventional versus laparoscopic cholecystectomy are difficult to perform at our institution. We therefore report on the results of our first 400 laparoscopic cholecystectomies using a strict and detailed protocol on technical performance, safety and benefit for the patient. Data was obtained immediately after the operation and after a short-term follow-up. To analyze the technical performance and the safety of the procedure, we developed a new classification system (I-V) of adverse events, including both the patients' and the surgeons' viewpoints. Our results show that in nearly 80% of the cases an optimal result (no adverse events in any respect) was obtained. For different reasons, the surgical procedure had to be changed during the operation in 20 cases (5%). In 3 cases (0.8%), an injury of the common bile duct occurred; 2 patients died (mortality 0.5%). On the first post-operative day, vomiting occurred in only 8% and nausea in 19% of the patients. Pain intensity was always below the level where patients demand analgesic medication and declined near zero the day after the operation. Patients fatigue was measured on a scale from 0-10 and rose from 2.2 preoperatively to 3.3 postoperatively. Only a short hospital stay of 3 days median was required. At short-term follow-up 6 weeks after the operation, pain was only rarely reported, the patients were fit and only 20% avoided some kind of food. We conclude that laparoscopic cholecystectomy is the treatment of choice for this precisely defined patient population with symptomatic gallstone disease.
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PMID:Laparoscopic cholecystectomy: technical performance, safety and patient's benefit. 153 13

We report here the effects of in vivo administration of recombinant interleukin-1 alpha (rIL-1 alpha) to patients with severe, idiopathic aplastic anaemia. Four patients who were refractory to immunosuppressive therapy and were not bone marrow transplantation candidates received daily doses of 0.03 microgram/kg and 0.10 microgram/kg intravenously as 5 d courses. No significant changes in either peripheral blood counts or bone marrow cellularity were observed at either dose during or following therapy. Two patients showed increased numbers of bone marrow progenitor colonies. Lymphocyte phenotyping demonstrated an elevated percentage of CD8+/DR+ activated suppressor T lymphocytes prior to therapy. After rIL-1 alpha administration, the percentage of CD8+/DR+ cells was reduced or returned to normal in all patients. Significant side-effects included fever, rigours, fatigue, headache and nausea. Transient hypotension was observed at both doses in all patients. These results suggest that while rIL-1 alpha can be safely administered, no significant haematologic improvement was observed in patients with severe aplastic anaemia.
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PMID:A trial of recombinant human interleukin-1 in patients with severe refractory aplastic anaemia. 153 97

Nine patients with a recurrent malignant glioma were treated with repeated intracavitary or intracerebroventricular injections of human recombinant interleukin-2 (rIL-2) alone or in combination with systemic interferon-alpha (IFN-alpha). Five patients received only rIL-2 and four were treated with rIL-2 plus subcutaneous injections of IFN-alpha. Therapy was administered on a Monday, Wednesday, Friday schedule for up to 10 weeks, beginning with a dose of 10,000 IU rIL-2/injection. Doses were escalated every two weeks until some toxicity was apparent. The maximum amount of rIL-2 any one patient in this group received was 580,000 IU. Patients on combination immunotherapy were held at an rIL-2 dosage of 10,000 IU while IFN-alpha, which began at 3 million IU, was escalated every other week up to 18 million IU/dose. They were then held at that IFN-alpha dosage and rIL-2 was increased to 50,000 IU. The total amount of rIL-2 and IFN-alpha any one in this group received was 510,000 IU and 417 million IU, respectively. Repeated injections of 10,000 IU rIL-2 were well-tolerated by all nine patients and no change in their functional status was seen. At doses at 50,000 IU rIL-2, increased edema around the tumor cavity was observed by MRI/CT scand in 3/5 patients and clinical side-effects in the form of somnolence and headache along with some morbidity specifically associated with tumor location were also seen. Patients receiving rIL-2+ IFN-alpha showed progressive fatigue, muscle weakness, and occasionally nausea. Two of these patients showed increased peritumoral edema on MRI/CT scan.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of recurrent malignant glioma by repeated intracerebral injections of human recombinant interleukin-2 alone or in combination with systemic interferon-alpha. Results of a phase I clinical trial. 154 81

Based on recent preclinical data suggesting synergism between 5-fluorouracil (5-FU) and interferon alpha (IFN-alpha) and clinical activity of the combination therapy in colon cancer, 14 patients with advanced gastric cancer were treated with combination therapy of 5-FU and recombinant interferon alpha-2b (rIFN alpha-2b) (Intron A, Schering, Kenilworth, NJ, U.S.A.). The maximum tolerated dose was 5-FU 750 mg/m2/day given as a continuous infusion daily for 5 days followed by weekly bolus injection of the same initial daily dose, plus rIFN alpha-2b 5 X 10(6) U given subcutaneously 3 times weekly starting day 1 of 5-FU infusion. The dose-limiting toxicities were fatigue/weakness, diarrhea, and neurologic toxicities such as somnolence and confusion. The other common side effects were nausea, fever, leukocytopenia, thrombocytopenia, and the darkening of the skin. Of 13 evaluable patients, 4 had a partial response (duration 6, 14, 24, and 28 weeks). These data suggest that combination therapy of 5-FU plus rIFN alpha-2b is tolerable and has manageable side effects in patients with advanced gastric cancer. Further Phase II study will be needed to define the antitumor activity of this combination.
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PMID:Combination of 5-fluorouracil and recombinant interferon alpha-2B in advanced gastric cancer. A phase I study. 155 2

We conducted a phase I trial of fluorouracil (5-FU), leucovorin, (LCV), and recombinant interferon-alpha-2b (rIFN-alpha-2b). The doses of each of the three agents were escalated sequentially. 5-FU and LCV were administered by IV bolus, weekly for 6 weeks and rIFN-alpha-2b was administered by subcutaneous injection, three times weekly for 6 weeks. Twenty-nine patients with advanced cancer (75% colon or pancreatic cancer) were treated. Partial remissions were observed in three patients (10%) with previously untreated colon cancer, colon cancer refractory to 5-FU plus LCV and previously untreated pancreatic cancer, respectively. An additional three patients with pancreatic, prostate, and rectal cancer had a 50% reduction in tumor markers but no change in objective tumor measurements. The toxicity of this regimen was tolerable. The most common toxicities were diarrhea, fatigue, flu-like symptoms, nausea/vomiting, and mucositis. However, no fatal or life-threatening toxicities were observed. We conclude that the combination of 5-FU, LCV, and rIFN-alpha-2b can be safely administered and recommend further evaluation of this regimen in patients with tumors of gastrointestinal origin using doses of 5-FU 600 mg/m2, LCV 500 mg/m2, and rIFN-alpha-2b 10 x 10(6) U.
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PMID:A phase I trial of fluorouracil, leucovorin, and recombinant interferon alpha-2b in patients with advanced malignancy. 155 45


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