Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Datelliptium chloride, hydrochloride (SR 95 156B, NSC 626718X, DHE) was studied in a phase I trial of escalating doses given on a single 24-h continuous intravenous infusion schedule. Doses were escalated from 40 to 500 mg/m2 in 19 patients who received a total of 24 courses. Courses were repeated after a minimal interval of 3 weeks. Local venous toxicity occurred at low doses (less than or equal to 100 mg/m2) and was circumvented by the use of a central venous access for higher doses. Other clinical adverse events occurred (greater than or equal to 330 mg/m2), including moderate nausea and vomiting, mild diarrhea, dry mouth, neuropsychiatric manifestations, and fatigue. All of these side effects were reversible and none was dose-limiting. The dose-limiting toxicity was related to hepatic laboratory-test abnormalities in the form of reversible elevations of levels of serum bilirubin and liver enzymes at doses of greater than or equal to 330 mg/m2. The maximum tolerated dose for this schedule is 500 mg/m2. Hematologic toxicity was minimal and non-dose-limiting. Neither drug-related deaths nor objective complete or partial responses were observed. However, a minor response and a long-term disease stabilization were obtained.
 ...
PMID:Phase I study of Datelliptium chloride, hydrochloride given by 24-h continuous intravenous infusion. 162 72

A double-blind comparative study of the nonionic contrast medium iopentol and the ionic contrast medium metrizoate for urography was carried out in 200 adult outpatients. Significantly less discomfort and other side effects were observed following iopentol than following metrizoate. No serious adverse reactions and no clinically significant alterations in heart rate or blood pressure were observed. A questionnaire was used to record delayed symptoms, from 30 min after contrast medium injection and for one week. The response rate was 92% and delayed adverse events were reported by 45%. The incidence of delayed reactions was significantly lower following iopentol than following metrizoate, i.e., delayed arm pain, fatigue, headache, diarrhea, nasal congestion, and rash. Delayed arm pain was probably due to contrast medium induced thrombosis in 1% following iopentol and in 8% following metrizoate. Most other symptoms were probably related to a combination of nocebo effect and coincidentally occurring symptoms. The urograms with both media were of similar high quality. Iopentol was found a suitable contrast medium for urography.
 ...
PMID:Iopentol in urography. A clinical comparison between iopentol and metrizoate including delayed reactions. 163 50

A total of 930 patients have been evaluated for safety in a programme of clinical trials for lisinopril-hydrochlorothiazide combination treatment. Combination therapy with these two agents is generally well tolerated. In clinical trials, adverse experiences in patients treated with a lisinopril-hydrochlorothiazide combination were dizziness (7.5%), headache (5.2%), cough (3.9%), fatigue (3.7%), orthostatic effects (3.2%), diarrhoea (2.5%), nausea (2.2%) and upper respiratory tract infection (2.2%). Withdrawals from treatment have been relatively infrequent comprising dizziness (0.8%), headache (0.3%), cough (0.6%), fatigue (0.4%), diarrhoea (0.2%), orthostatic effects and nausea (0.1% each). The most common laboratory adverse experiences in patients on therapy with the lisinopril-hydrochlorothiazide combination are: increases in serum glucose, triglycerides, uric acid, serum creatinine, blood urea nitrogen and blood urea; and decreases in serum potassium. However, in individual controlled studies, the addition of lisinopril to treatment with hydrochlorothiazide results in attenuation of some of the potentially adverse metabolic affects of the diuretic. Adverse experiences in the patients treated for periods of 50 weeks or more, the elderly and the renally impaired are similar to those seen in the total population. Overall the available data indicate that a fixed dose combination of lisinopril-hydrochlorothiazide is a well-tolerated therapeutic option in patients with mild-to-moderate hypertension.
 ...
PMID:Review of international safety data for lisinopril-hydrochlorothiazide combination treatment. 166 80

Fludarabine phosphate is the 2-fluoro, 5'-monophosphate derivative of vidarabine (ara-A) with the advantages of resistance to deamination by adenosine deaminase (ADA) and improved solubility. The mechanism of cytotoxic action of the compound appears to involve metabolic conversion to the active triphosphate. Fludarabine phosphate has substantial activity against lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL) and low-grade non-Hodgkin's lymphoma (NHL). Its single-agent activity in CLL appears at least comparable to those of other conventional combination regimens. Its activity in Hodgkin's disease, mycosis fungoides, and macroglobulinemia, although suggestive, needs to be further defined and clinical trials are warranted in hairy cell leukemia, prolymphocytic leukemia, and previously untreated myeloma. The compound does not appear active against most common solid tumors. Early clinical trials indicated significant myelosuppression and the potential for severe neurotoxicity. Toxicity on the currently used low-dose schedules includes transient and reversible myelosuppression, nausea and vomiting, diarrhea, somnolence/fatigue, and elevations of liver enzymes and/or serum creatinine. Possible pulmonary toxicity has been suggested in several patients. The currently used low-doses of fludarabine phosphate, even with repeated administration, are well tolerated and appear safe with a negligible risk for severe neurotoxicity. Based on its single-agent activity and tolerability, the Food and Drug Administration recently granted group C designation of the drug for the treatment of patients with refractory CLL outside the clinical trials setting. The use of fludarabine phosphate in combination regimens and its impact on the natural history of the lymphoid malignancies is yet to be determined. Fludarabine phosphate may well occupy a pivotal role in the management of CLL and low-grade NHL.
 ...
PMID:Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies. 170 43

A spherical organism 9-10 microns in diameter, seen in three outbreaks of diarrhea in Southeast Asia and the United States during the past 2 years, bore characteristics of a cyanobacterium when observed in formalin-preserved stool specimens and by electron microscopy. Organisms in freshly passed stool specimens showed an internal morula of lipid-containing globules. In fresh water, the morula divided into two sausage-shaped structures resembling the sporocysts of an isosporid coccidian. After 7 months, the organisms had not developed the crescentic sporozoites seen in the Coccidia but had begun to multiply slowly in culture. It was impossible to stain the internal structures of the organisms because the outer cyst wall ruptured during desiccation, releasing the contents of the cysts. The organisms were readily identified by their intense blue autofluorescence under UV light, but they were also recognizable by bright-field microscopy and by a modified acid-fast stain. Almost all infected persons suffered intermittent diarrhea for 2-3 weeks and many emphasized a feeling of intense fatigue during the course of their illness.
 ...
PMID:Morphologic and staining characteristics of a cyanobacterium-like organism associated with diarrhea. 171 53

Kaposi's sarcoma (KS) is a malignant neoplasm that develops in 20% to 30% of all acquired immunodeficiency syndrome (AIDS) cases. Kaposi's sarcoma primarily involves the skin, but can progress to involve the lungs, gastrointestinal tract, and liver. alpha-Interferon alone or in combination with zivoduvine has activity in acquired immunodeficiency syndrome-related KS, especially in patients with limited disease and CD4 lymphocyte counts over 400/mm3. Patients with progressive or symptomatic visceral disease, however, can be treated more effectively with cytotoxic chemotherapy. We have used a combination of doxorubicin, bleomycin, and vincristine (ABV) and have achieved response rates of over 80%. Discontinuation of therapy, however, is associated with relapse shortly after response (2 to 3 months). Thus, we have begun studies to define a safe and effective maintenance therapy. Such therapies should include antiretroviral agents since most patients succumb to other human immunodeficiency virus complications, and since human immunodeficiency virus directly, through viral proteins, and indirectly, through the induction of cellular genes, induces KS growth. Additionally, agents with antitumor activity and possible antiviral activity, such as alpha-interferon, may be potentially effective in maintenance therapies. We recently studied 21 patients in a phase I study of recombinant interferon alpha-2b (INTRON-A, Schering-Plough Corp, Kenilworth, NJ) alone following ABV chemotherapy. A dose of 10 million units, given in daily subcutaneous injections, was the maximal tolerated dose; higher doses were associated with intolerable fatigue, diarrhea, and fevers. We are currently conducting a phase I/II trial studying the combination of zivoduvine (500 mg/d) and recombinant interferon alpha-2b (5, 10, and 15 million units) as maintenance in patients with advanced or progressive KS.
 ...
PMID:Phase I/II trials of alpha-interferon alone or in combination with zidovudine as maintenance therapy following induction chemotherapy in the treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma. 171 42

Seventeen patients with malignant carcinoid tumour, ten of whom had the malignant carcinoid syndrome, were treated with recombinant alpha-2b interferon by subcutaneous injection (3 MU per dose) three times per week for a median of 12 weeks (range 4-48). No objective tumour responses were observed; however, there was a greater than 50% reduction in 24-hour urinary 5-hydroxyindolacetic acid (5-HIAA) excretion in four of ten patients (40%) with elevated pretreatment levels. Five of ten patients (50%) with flushing, five of seven patients (71%) with diarrhoea and both patients with wheezing experienced relief of symptoms. Three of four patients (75%) with weight loss as their only problem experienced weight gain. Responses occurred within the first eight weeks of treatment, but were generally of short duration. Toxicity occurred in all patients, and consisted mainly of fever, chills, anorexia, fatigue and weight loss. Four patients ceased therapy due to toxic reactions. Although interferon has activity against carcinoid tumours, its benefits are short-lived and toxicity limits its use with increasing dose. Patients with carcinoid syndrome appear to achieve the best therapeutic response, and it is likely that low doses (9-20 million IU weekly) are as effective as higher doses (36-72 million IU weekly).
 ...
PMID:Recombinant alpha-2b interferon in patients with malignant carcinoid tumour. 172 59

A Phase II clinical trial of the combination of 5-fluorouracil (5-FU) and recombinant alpha-2a-interferon (alpha-2a-IFN) was conducted in 44 patients. Patients had not received chemotherapy previously and had measurable metastatic gastric carcinoma. 5-FU was administered as a continuous infusion at a dose of 750 mg/m2/d for 5 consecutive days and as an intravenous bolus at a dose of 750 mg/m2 weekly for 7 weeks beginning on day 12. Recombinant alpha-2a-IFN was administered subcutaneously at a dose of 9 x 10(6) U three times a week during weeks 1 to 8. Patients were examined for response during week 9. Of 44 patients entered, 40 could be examined for response. Nine patients experienced a partial clinical response and one achieved a complete response, for an overall response rate of 25% (95% confidence interval, 13% to 41%). The median duration of response was 13 weeks (range, 9 to 67 weeks) and the median survival time was 29 weeks. Grade 3 to 4 toxicities included granulocytopenia (nine patients), diarrhea (three patients), oral mucositis (seven patients), skin rash (one patient), and fatigue (four patients). One patient died of neutropenic sepsis. This regimen had modest activity with significant toxicity and produced responses of short duration. It did not appear to be superior to existing treatments of metastatic gastric carcinoma.
 ...
PMID:A phase II trial of 5-fluorouracil and recombinant alpha-2a-interferon in previously untreated metastatic gastric carcinoma. 173 78

We evaluated clinical efficacy and tolerability of recombinant alpha 2a interferon (IFN), in a group of 16 patients with AIDS and ARC, including 3 children. All patients were followed up monthly for clinical and immunological studies. The frequency of oportunistic infections (OI) in AIDS, and the following symptoms in all patients were studied: fever, night sweats, fatigue, diarrhoea, weight loss. Immunological parameters (CD3+, CD4+, CD8+ lymphocytes, skin tests to recall antigens, NK activity, lymphoproliferative response to PHA) were also evaluated. Adult patients were treated with 3-6 million IU of r-alpha 2a IFN daily im for 3 months and the 3 times weekly up to 12 months. Pediatric cases were treated with lower doses of 0.5-1.5 million IU using the same time schedule. We observed clinical improvement and reduction of severe infections in 10/15 evaluable patients (4/4 ARC and 6/11 AIDS). Immunological parameters were transiently improved in one third of cases. We observed only mild side effects in r-alpha IFN treatment. We suggest therapy with r-alpha 2a IFN at low dosage should be tried in patients with AIDS for its beneficial effects on OI development.
 ...
PMID:Recombinant alpha-2a interferon treatment in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC): clinical and immunological evaluation. 181 17

A phase I trial of Roussel-Uclaf recombinant human interleukin 2 (IL 2) was performed on 31 cancer bearing patients of the Institut Gustave-Roussy, Villejuif, and the Institut Curie, Paris. This study allowed to define a schedule for administration of IL 2 in continuous infusion over 5 day cycles. This schedule is manageable in patients without major visceral failure. It is reproducibly feasible in conventional medical oncology units, without specialized intensive care facilities. Toxicities, although numerous, are acceptable for IL 2 doses below 24,000,000 IU/m2/day. There is a close relationship between secondary effect severity and IL 2 doses received. Main toxicities were: fever with chills, fatigue and general discomfort in 23 patients, nauseas and vomiting in 12, diarrhea in 10 and cutaneous rashes with erythema and dermal vascularitis in 13. One peculiar feature of this study was the minimal occurrence of manifestation related to leaky capillary syndrome prominant in other studies. Oliguria, functional renal failure and edema were observed in only 4 patients with functionally unique kidney. Five patients had severe anemia, 2 grade III thrombocytopenia, 1 grade IV hepatic cytolysis, 4 severe confusion episodes and 2 hypothyroidism with anti-thyroid microsome auto-antibodies. All these toxicities were reversible after withdrawal of IL 2 treatment. During this phase I trial, 3 therapeutic objective responses were observed, all 3 occurring in patients with metastatic melanoma treated with IL 2 doses equal to, or above 16,000,00 IU/m2/d. Recombinant IL 2 Roussel-Uclaf thus can be administered through a simple, manageable and efficient regimen.
 ...
PMID:[Phase I trial of a recombinant human interleukin 2. Results in patients with disseminated solid tumors]. 182 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>