Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hexamethylene bisacetamide (HMBA), a potent differentiating agent, was administered to patients with refractory malignant tumors. Thirteen patients received 30 evaluable courses. HMBA was given by continuous i.v. infusion for 5 days. Therapy was repeated every 28 days, if patients had recovered from toxicity. The starting dose was 24 g/m2/day. Because our previous trial had shown wide interpatient variability in HMBA pharmacokinetics and excess toxicity at HMBA plasma concentrations greater than 2 mM (HMBA doses between 24 and 33.6 g/m2/day), we attempted to individualize each patient's dose based on a dosing scheme using an adaptive (feedback) control algorithm, which assumed linear clearance for HMBA. In all courses, a plasma sample was assayed daily and infusion rates were adjusted to achieve an HMBA plasma concentration of 1.5-2.0 mM (300-400 mg/liter). The patients included 12 men and 1 woman with a median age of 56 years (range, 34-76) and median Karnofsky performance status of 90% (range, 60-100). All patients had received prior chemotherapy and 9 patients had also received radiation therapy. The linear adaptive control algorithm was reasonably precise, with a mean absolute error of 0.28 (SE 0.04) mM. However, adjustments in infusion rate systematically overshot the desired change in steady state concentration, probably due to nonlinear clearance of HMBA. For levels within 24 h of a change in infusion rate, this resulted in significant bias, with a mean error of 0.24 (SE 0.09) mM. The mean absolute error was 0.40 (SE 0.06) mM. A second adaptive control algorithm, using a pharmacokinetic model with parallel first-order (renal) clearance and Michaelis-Menten (nonrenal) clearance and using Bayesian parameter estimation with a priori estimates based on our previous phase I trial, proved to be much more precise than the linear method and was unbiased when applied retrospectively to the same observations, with a mean error (within 24 h of a change in infusion rate) of 0.02 (SE 0.06) mM and a mean absolute error of 0.22 (SE 0.03) mM. Toxicity was reversible in all cases. Neurotoxicity, consisting of hallucinations, agitation, somnolence, or confusion, was seen in 2 patients. Four patients complained of insomnia or anxiety. Mild asymptomatic acidosis was seen in 3 patients. Other toxicity included grade 1-2 nausea and vomiting (10 patients), grade 2 diarrhea (2 patients), grade 3 thrombocytopenia (3 patients), grade 1-3 leukopenia (3 patients), and oral herpes simplex infection (4 patients). Mild reversible renal insufficiency (measured by creatinine clearance) was seen in 8 patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Phase I trial using adaptive control dosing of hexamethylene bisacetamide (NSC 95580). 272 Jun 96

A 65-year-old woman, known to have peptic ulcers, developed nausea and retching. Clinical examination demonstrated pain on pressure in the epigastrium with otherwise normative findings for age. Two gastric ulcers and gastritis with erosions were seen at endoscopy. The patient, who was being treated with digitoxin for heart failure, reported having taken up to four digitoxin tablets (0.07 mg each) daily because she had insomnia. The plasma digitoxin level was between 150 and 160 nmol/l (therapeutic range 17-33 nmol/l), while the ECG showed no signs of digitalis intoxication. Initially the platelet count was 40,000/microliter: there had been no history of thrombocytopenia or symptoms of abnormal haemostasis. Other laboratory tests were within normal limits. After digitoxin had been discontinued, the platelet count rose without further treatment to 373,000/microliter 3 weeks after hospital admission by which time the digitoxin level had fallen to 48.9 nmol/l. The gastrointestinal symptoms regressed completely on treatment with omeprazole (40 mg three times daily for 8 days) and ranitidine (150 mg twice daily).
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PMID:[Reversible thrombocytopenia due to digitoxin overdose]. 800 65

Thirty five patients with imported malaria were hospitalised in a period of 1980-93 in Department of Infectious Diseases of Pomeranian Medical School, Szczecin, Poland. The diagnosis of malaria was established on a base of clinical feature, the presence of Plasmodium in peripharal blood smears and, in some cases, on positive serological tests. Thirty two patients were Polish citizens, and three persons were foreigners. Malaria was caused mostly by invasion of Plasmodium falciparum (62.8), then P. vivax (31, 4), in 1 case--P. ovale and 1 case--mixed invasion occurred (P. falciparum and P. vivax). The majority of cases caused by P. falciparum were imported from Central Africa. Invasions of P. vivax were brought from North Africa, India and Middle East. Malaria in Polish patients was connected with occupational exposure and lack of proper antimalarial prophylaxis was obvious. A clinical course of disease was serious, with one mortal case. Fever, headache, abdominal pain, weakness, jaundice, insomnia were main complaints. Anemia, leucopenia, thrombocytopenia, hyperbilirubinemia, hypertransaminasemia and high serum concentration of urea were observed. A level of parasitemia in peripheral blood varied from minimal to very high (22.5%) in cases of P. falciparum invasions. In treatment chloroquine, fansidar, quinine, primaquine, halfan were used.
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PMID:[Observation of patients with malaria hospitalized during the years 1980-1993 in the Clinic of Infectious Diseases in Szczecin]. 886 94

Adverse events were analyzed in 94 normal donors who underwent PBSC harvest with G-CSF. The median dose of G-CSF was 9.7 microg/kg/day (range, 2.0-16.7), and the duration of administration was 4-6 days. Frequent symptoms were bone pain (71%), general fatigue (33%), headache (28%), insomnia (14%), anorexia (11%), nausea and/or vomiting (11%). One donor (1%) developed grade 3 toxicity bone pain (WHO criteria). WBC counts and ANC increased during G-CSF administration. After leukapheresis, three donors (3%) developed grade 3 toxicity neutropenia. Platelet counts decreased after leukapheresis. Three donors (3%) developed grade 3 thrombocytopenia. The means of both ALP and LDH increased approximately 1.9-fold compared with pretreatment levels. In one pediatric donor (1%), ALP was elevated to the grade 3 toxicity level. From multivariate analysis, the incidence of bone pain increased when G-CSF was given at a dose of 8.8 microg/kg/day or more, headaches were frequent in donors younger than 35 years, and the incidence of nausea and/or vomiting was high in female donors. The peak levels of WBC counts and ANC and post-treatment level of LDH increased in correspondence with the escalation of G-CSF dose. All adverse events normalized on follow-up evaluation. In conclusion, although PBSC harvest for normal donors is acceptable, care must be taken for all donors in terms of their sex and age as well as the G-CSF dose. We recommend less than 8.8 microg/kg/day as the G-CSF dose for PBSC mobilization in normal donors.
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PMID:Peripheral blood stem cell mobilization and apheresis: analysis of adverse events in 94 normal donors. 1057 56

Valganciclovir is a prodrug of ganciclovir which has been developed for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. Oral valganciclovir is rapidly absorbed and hydrolysed to ganciclovir. The oral bioavailability of ganciclovir after oral valganciclovir administration is high. Oral valganciclovir 900 mg provides a daily exposure of ganciclovir comparable to that of intravenous ganciclovir 5 mg/kg. A single, randomised, nonblind study indicated that oral valganciclovir (900mg twice daily for 3 weeks then 900 mg once daily) and intravenous ganciclovir (5 mg/kg twice daily for 3 weeks then 5 mg/kg once daily) were equally effective in the treatment of newly diagnosed CMV retinitis in 160 patients with AIDS. Valganciclovir appears to have a similar tolerability profile to intravenous ganciclovir during induction therapy in patients with AIDS and newly diagnosed CMV retinitis. During maintenance therapy with valganciclovir, the most commonly reported adverse events included neutropenia, anaemia, thrombocytopenia, gastrointestinal (including diarrhoea, nausea, vomiting and abdominal pain), fever, headache, insomnia, peripheral neuropathy, paraesthesia and retinal detachment.
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PMID:Valganciclovir. 1146 75

We examined the use of MGI-114 (6-hydroxymethyacylfulvene) for the treatment of patients with advanced colorectal carcinoma. Twenty-six patients were enrolled, with a median age of 60 years (range 41-75); 64% were male and all patients had a performance status of 0 or 1. We administered a dose of 11 mg/m2/d x 5 days every 4 weeks. With a median of two cycles (range 0-6) administered, no complete responses or partial responses were observed. Four patients had no change in disease (16%); 15 patients (57%) had progressive disease; seven patients were inevaluable (27%). Toxicity was evaluated in 25 of 26 patients. The main toxicities were hematologic, including granulocytopenia and thrombocytopenia. Neuropsychiatric adverse events included hallucination (7.7%), depression/anxiety (15.4%), and/or insomnia (19.2%). Given the lack of antitumor activity, further study of MGI-114 in colorectal cancer does not appear warranted.
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PMID:Phase II study of MGI-114 administered intravenously for 5 days every 28 days to patients with metastatic colorectal cancer. 1271 82

Despite the high objective response rate of advanced ovarian cancer to combination platinum/taxane-based chemotherapy, the majority of patients ultimately experience disease progression. Thus, there is a need to find new management strategies that can improve upon the results of existing therapies. We are currently conducting a phase II trial to explore the toxicity and potential efficacy of a three-drug program, which adds irinotecan (CPT-11, Camptosar) at 100 mg/m2 to carboplatin (Paraplatin) at an area under the concentration-time curve of 5 and paclitaxel at 150 mg/m2 over 3 hours. Treatment was initially given on an every-3-week schedule, but was subsequently changed to an every-4-week schedule due to excessive bone marrow toxicity. The study remains in progress, with 26 patients currently evaluable for toxicity, which has included grade 4 neutropenia (42% incidence), grade 4 thrombocytopenia (12%), and grade 3 emesis (12%), with one patient each experiencing grade 3 diarrhea, hepatic dysfunction, and insomnia. Data regarding response rates are immature. Our preliminary analysis reveals that the combination of carboplatin/paclitaxel/irinotecan can be administered to women with advanced ovarian cancer with significant, but overall acceptable, toxicity. Randomized trials will be required to define a possible role for this three-drug combination chemotherapy regimen in the standard management of advanced ovarian cancer.
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PMID:Toxicity associated with carboplatin/paclitaxel/Irinotecan use in advanced ovarian cancer: preliminary analysis. 1280 Jun 4

Previous studies in Caucasian patients showed treatment of chronic hepatitis C with pegylated interferon/ribavirin was well tolerated, and produced a higher response rate especially in genotype 1 infections. However, it is unknown whether this conclusion can be extrapolated to patients with Chinese ethnic origin. A total of 153 patients with biopsy-proven chronic hepatitis C were randomly assigned to receive either weekly injection of peginterferon alpha-2b 1.5 mcg/kg plus oral ribavirin (1000 or 1200 mg/day, depending on body weight) (PEG group, n = 76) or 3 MU of interferon alpha-2b t.i.w. plus ribavirin (IFN group, n = 77) for 24 weeks. Sustained virological response (SVR) was defined as the sustained disappearance of serum hepatitis C virus (HCV) RNA at 24 weeks after the end of treatment by polymerase chain reaction assay. Baseline demographic, viral and histological characteristics were comparable between the two groups. Using an intent-to-treat analysis, HCV genotype 1 patients showed a significantly higher SVR in patients receiving PEG-IFN rather than IFN (65.8%vs 41.0%, P = 0.019), but no difference was found in genotype non-1 patients (PEG vs IFN: 68.4%vs 86.8%, P = 0.060). Genotype 1 patients (28.6%) in the PEG-IFN group relapsed, as compared with 52.9% in the IFN group (P = 0.040). Multivariate analyses showed early virological response at week 12 of therapy and genotype non-1 were significant predictors to SVR. As compared with the IFN group, patients receiving PEG-IFN had a significantly higher rate of discontinuation, dose reduction, fever, headache, insomnia, leucopenia and thrombocytopenia. In genotype 1 chronic hepatitis C Chinese patient, PEG-IFNalpha2b ribavirin had significantly better SVR and lower relapse rate when compared to IFN/ribavirin. Both regimens can be recommended for genotype non-1 chronic hepatitis C Chinese patients. However, a higher rate of adverse events and discontinuance of therapy were noted in patients treated with PEG-IFNalpha2b ribavirin.
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PMID:Comparison of a 6-month course peginterferon alpha-2b plus ribavirin and interferon alpha-2b plus ribavirin in treating Chinese patients with chronic hepatitis C in Taiwan. 1585 Apr 69

Linezolid is an oxazolidinone, a new class of antibacterial with a unique mechanism of action, namely inhibition of the formation of a functional 70S initiation complex in the 50S bacterial ribosomal subunit. Linezolid is highly active against multidrug-resistant Gram-positive cocci, including meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate and vancomycin-resistant S. aureus, and vancomycin-resistant enterococci; its spectrum of activity also includes some anaerobic bacteria. Linezolid has been studied in several randomized controlled trials for the treatment of patients with community-acquired and nosocomial pneumonia, skin and soft tissue infections (SSTIs), urinary tract infections and bacteraemia. The available evidence suggests that linezolid is at least as effective as vancomycin for patients with nosocomial pneumonia, and there are some retrospective analyses supporting its superiority in comparison with vancomycin for MRSA nosocomial pneumonia, including ventilator-associated pneumonia. Linezolid is more effective than glycopeptides, macrolides and beta-lactams for SSTIs. The limited available data for the treatment of patients with bacteraemia suggest that it may be a better treatment option than vancomycin and beta-lactams for these patients, but questions have arisen regarding patients with catheter-related bacteraemias. Compared with other antibacterials, linezolid is associated with a greater frequency of adverse events, mainly nausea, vomiting, diarrhoea and headaches. Thrombocytopenia also occurs more frequently in patients taking linezolid but there is no increased frequency of anaemia. Other adverse events potentially related to linezolid therapy include fungal infections (moniliasis), hypertension and serotonin-like syndrome, tongue discolouration and taste alterations, dizziness, insomnia, rash and Clostridium difficile-related diarrhoea. The majority of adverse events develop after prolonged administration (i.e. >2 weeks) and subside shortly after discontinuation of linezolid. Peripheral or optic neuropathy, another possible adverse effect, is associated with an even longer duration of treatment (3-6 months). In conclusion, linezolid is an important treatment option for the treatment of patients with multidrug-resistant, Gram-positive bacterial infections. However, in order to reduce the possibility of development of resistance and preserve its activity, the use of linezolid should be restricted to treatment of patients with infections associated with high morbidity and mortality, particularly those caused by multidrug-resistant bacteria.
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PMID:Benefit-risk assessment of linezolid for serious gram-positive bacterial infections. 1870 90

The aim of the study was to monitor the commonest side effects of the treatment of chronic hepatitis with peginterferon alpha-2A (PEG-IFN) and ribaverin (RBV) and the influence of various factors on their development. The work was done in the Department of Infectious Disease, Erevan State Medical University. Monitoring 16 adverse reactions was carried out with the use of special tables within 1, 2, 4 and 6 months after the onset of therapy in patients with genotypes 2 and 3 and in addition after 8, 10 and 12 months in patients with genotype 1. The influence of independent prognostic factors was estimated by logistic regression analysis. The commonest side effects of PEG-IFN plus RBV therapy were leukopenia, thrombocytopenia, weight loss, depression, fatigue, and insomnia that occurred at one time or another in more than half of the patients. Weight loss during therapy amounted to 8.36 kg (95% CI 6.7-10) (maximum 21 kg). Myalgia, anorexia, arthralgia, headache, alopecia, and vomiting were documented in 20-50% of the cases. Anemia, pruritis, eruption, erythema, and hair shedding at injection sites occurred in 1/4 of the patients. It is concluded that logistic regression analysis with matching selected prognostic factors permits to estimate the probability of such side effects as weight loss, flu-like syndrome, and myalgia.
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PMID:[Predicting side effects of the treatment of chronic hepatitis with peginterferon alpha-2A with ribaverin]. 2415 87


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