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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted a phase I study of CI-898 (trimetrexate), a new diaminoquinazoline antifolate in 22 patients with solid cancer in a multicenter collaborative study. The dosage schedule was single-dose intravenous administration (single treatment), followed by one or two courses of 5-day intravenous administration (5-day treatment) at 3-week intervals. Starting at 2 mg/m2 (1 n), the dose was increased up to 15 mg/m2 (7.5 n) for single treatment and 12 mg/m2 (6 n) for 5-day treatment. Evaluable cases numbered 18 for single treatment and 17 for 5-day treatment. In single treatment, the highest dose of 15 mg/m2 caused no serious side effect and did not reach the maximum tolerated dose (MTD). In 5-day treatment, leukocytopenia and thrombocytopenia were found dose dependently, the dose-limiting factor was bone marrow depression, and MTD was 10 mg/m2/day. The leukocyte and platelet counts reached the nadir in 1-3 weeks after initiation of 5-day treatment. The recovery from the nadir required about one week. Subjective side effects included mucitis (mouth, anus), malaise and gastro-intestinal symptoms (nausea, anorexia, diarrhea). None of alopecia, cardiotoxicity and nephrotoxicity were found. In the present phase I study, a tendency of tumor reduction was found in one case each of breast cancer (adenoma) and lung cancer (squamous cell carcinoma). The plasma concentration of the unchanged compound after single treatment showed a biphasic elimination pattern (t1/2 alpha 0.8-1.4 hr, t1/2 beta 9.4-13.0hr). The urinary excretion of the unchanged compound was 14.7-23.5% of the administered dose. In 5-day treatment, no accumulation was found. From the results of the present study, the recommended dosage of CI-898 in the early phase II study was considered to be 8 mg/m2/day intravenously for 5 days (every 3-4 weeks).
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PMID:[Phase I study of CI-898. CI-898 Study Group]. 183 40

A retrospective analysis of 133 patients who received continuous epidural fentanyl for postoperative analgesia is presented. Using a concentration of 5 micrograms/mL of fentanyl, patients received continuous epidural infusions for 24 to 72 hours postoperatively. The average rate of infusion was 60 micrograms/h. A total of 59.3% of the patients received no additional narcotics; 26.3% required supplemental narcotics during the first 24 hours only. Three percent had the infusion discontinued because it provided poor pain control. Side effects were less than, or comparable to, those of epidural morphine. Respiratory depression, defined as a respiratory rate of less than 8, or apnea did not occur. Urinary retention occurred in one patient. Pruritus occurred in 4% (6 patients). Nausea occurred in 25.5%, a rate comparable to that which occurred with epidural morphine. No side effects occurred in 70.6% of the patients reviewed. These data show that epidural fentanyl provides good to excellent pain relief with minimal side effects.
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PMID:Postoperative analgesia with epidural fentanyl. 183 46

To determine the lowest effective dose of epidural sufentanil given for analgesia, 41 patients undergoing elective abdominal gynecologic surgery during continuous epidural anesthesia (lidocaine 2%) were randomly assigned to one of four postoperative treatment groups. Patients received an epidural bolus of either 25 (group A), 40 (group B), 55 (group C), or 70 micrograms (group D) sufentanil in 10 mL of saline. They were evaluated for the next 8 h using a 10-cm visual analogue scale. Except for two individuals in group A, all patients achieved a visual analogue scale score of 1 cm or less during the study interval. The onset of analgesia was most rapid in the two higher dose groups (A vs C and D; P less than 0.05). Pairwise comparison between groups showed a significant difference in the time needed to achieve maximum pain relief between the lowest and highest treatment groups (A vs D; P less than 0.05). Duration of analgesia was also significantly longer in groups C and D than in group A (208.0 +/- 21.1 and 224.0 +/- 14.7 vs 140.0 +/- 10.7 min; P less than 0.05). There were no differences among groups with regard to mean respiratory rate, level of sedation, 24-h narcotic requirements, or incidence of nausea, vomiting, and pruritus (P = NS). A single patient in group D suffered profound respiratory depression within seconds of administration. We conclude that, in patients recovering from lower abdominal surgery, a single 40-55-micrograms epidural bolus of sufentanil provides 3-3.5 h of effective analgesia, and that larger doses are not warranted.
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PMID:Epidural sufentanil for postoperative analgesia: dose-response in patients recovering from major gynecologic surgery. 183 24

This paper will review experimental and clinical studies investigating analgesic effects of opioids outside the central nervous system. The experimental data indicate that 1) opioids can produce antinociceptive effects in the periphery mediated by local opioid receptors, 2) three different receptor types (mu, delta, kappa) can become active in peripheral tissue, 3) inflammatory hyperalgesic conditions are especially amenable to peripheral opioid actions and 4) the activation of opioid receptors located on primary afferent neurons is the most likely mechanism of action. The evidence from clinical studies is equivocal so far, partly because of methodological shortcomings. More extensive controlled studies investigating the effects of local application of opioids in the vicinity of peripheral nerve terminals or of compounds unable to cross the blood-brain barrier are warranted in view of the potential avoidance of central side effects such as respiratory depression, dependence, nausea or sedation.
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PMID:Peripheral analgesic actions of opioids. 184 45

The efficacy and safety of bepridil hydrochloride (200 to 400 mg/day) were evaluated in patients with chronic stable angina refractory to maximal tolerated doses of diltiazem (median 360 mg/day) in a randomized, multicenter, double-blind, parallel study. Baseline diltiazem data were obtained during a 2-week period, after which 86 patients were randomized to bepridil (n = 46) or diltiazem (n = 40). Angina frequency, nitroglycerin consumption and ischemic manifestations induced by exercise treadmill testing were evaluated over 8 weeks. Bepridil significantly (p less than 0.05) increased time to angina onset, time to 1 and 2 mm of ST-segment depression, total exercise time and total work over baseline values. Changes in time to angina onset and time to 1 mm of ST-segment depression were significantly (p less than 0.05) greater for bepridil than for diltiazem. Angina frequency and nitroglycerin consumption did not differ significantly between groups. Compared with baseline, bepridil significantly (p less than 0.001) decreased heart rate (mean 4 beats/min) and prolonged QTc (mean 35 ms). The most frequent adverse effects in both groups were nausea, asthenia, dizziness, headache and diarrhea. Four patients taking bepridil and 1 taking diltiazem withdrew from the study because of adverse reactions. No sudden deaths, myocardial infarctions or instances of sustained ventricular tachycardia or torsades de pointes occurred in either group. The data indicate that bepridil provided safe and effective antianginal and antiischemic therapy in patients with chronic stable angina who exhibited less than optimal response to maximal tolerated doses of diltiazem.
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PMID:Comparative efficacy and safety of bepridil and diltiazem in chronic stable angina pectoris refractory to diltiazem. The Bepridil Collaborative Study Group. 185 72

In an effort to determine the incidence of respiratory depression and other side effects of subarachnoid morphine, we conducted the following prospective study in a large number (856) of young female patients undergoing cesarean delivery in one hospital. During the period from July 1987 to January 1989, patients receiving subarachnoid hyperbaric bupivacaine combined with 0.2 mg preservative-free morphine were included. They were continuously monitored for 24 hours using a pulse oximeter. For 24 hours, the vital signs, including respiratory rate every hour, and the side effects, including pruritus, nausea, and vomiting, were recorded. The need for analgesia and the total dose of opioids during the first 24 hours were documented. Our results showed that respiratory depression (SaO2 less than or equal to 85% and/or respiratory rate ten breaths per minute or less) occurred in eight patients, all of whom were markedly obese. Fifty-eight percent of the patients did not require analgesics for 24 hours. In those requiring an added opioid, the dose was (9.1 +/- 0.5 mg morphine, mean +/- SEM). Eighty-five percent of the patients were satisfied with the postoperative analgesia. Six percent were dissatisfied due to the side effects, i.e., pruritus, nausea and/or vomiting. Nine percent were dissatisfied with the pulse oximeter because it caused false alarms and limited their mobility.
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PMID:The addition of 0.2 mg subarachnoid morphine to hyperbaric bupivacaine for cesarean delivery: a prospective study of 856 cases. 188 70

The present study sought to relate the well-being of night workers to that of the working population in general. One hundred and ninety-seven male permanent night security guards were interviewed with regard to the occurrence of various symptoms during the previous 12-month period. The results were compared with the results from similar interviews with a representative national sample of males (n = 1769) in the Swedish workforce. An age standardized morbidity ratio was computed with control for various background variables. The results showed that the security guards had a 2-3 times higher occurrence of sleep disturbances and fatigue than the national sample. Among the variables not differing from the national sample were gastrointestinal problems, headache, nervous problems, depression, nausea, diarrhoea, and haemorrhoids. It was concluded that sleep/wake disturbances are considerably more usual in permanent night security guards than in the working population as a whole.
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PMID:Self-reported health and well-being amongst night security guards: a comparison with the working population. 188 8

The use of epidural morphine for postoperative analgesia outside of intensive care units remains controversial. In this report our anesthesiology-based acute pain service documents experience with 1,106 consecutive postoperative patients treated with epidural morphine on regular surgical wards. This experience involved 4,343 total patient days of care and 11,089 individual epidural morphine injections. On a 0-10 verbal analog scale, patient-reported median pain scores at rest and with coughing or ambulation were 1 (inter-quartile range 3) and 4 (interquartile range 4), respectively. The incidence of side effects requiring medication were as follows: pruritus 24%, nausea 29%, and respiratory depression 0.2%. There were no deaths, neurologic injuries, or infections associated with the technique. Migration of epidural catheters into the subarachnoid space and into epidural veins each occurred twice. Overall, 1,051 of the 1,106 patients (95%) experienced none of the following problems: catheter obstruction, premature dislodgement, painful injections, catheter migration, infection, or respiratory depression. We conclude that postoperative pain can be safely and effectively treated with epidural morphine on surgical wards.
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PMID:Postoperative epidural morphine is safe on surgical wards. 172 29

In a six-week double-blind randomized trial, preceded by a one-week period of single-blind placebo treatment, the efficacy and the side-effects of fluvoxamine (100-300 mg/d) (n = 24) and maprotiline (50-150 mg/d) (n = 24) were compared in moderately depressed outpatients with DSM-III Major Depression (n = 22) or Dysthymic Disorder (n = 26). Efficacy was measured by means of the Hamilton Depression Rating Scale, the Zung Depression Selfrating Scale, and a Clinical Global Impression of Severity Scale. Side-effects were evaluated by an Adverse Event Inventory and a Psychosomatic Symptom Scale. A statistically significant improvement was achieved in both treatment groups but success rates were modest: in both groups, 29% of the patients achieved a clinically significant improvement after six weeks of treatment. After six weeks of treatment, no difference in efficacy was found between fluvoxamine and maprotiline. Nausea was the most common complaint in the fluvoxamine group, while in the maprotiline group, it was dry mouth and constipation. One maprotiline-treated patient developed a convulsive attack.
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PMID:Randomized double-blind study of fluvoxamine and maprotiline in treatment of depression. 190 18

Results are presented of the first double-blind, placebo-controlled trial of a novel antidepressant venlafaxine, which preclinically has demonstrated serotonin, norepinephrine, and dopamine reuptake inhibiting effects. Sixty outpatients meeting DSM-III-R criteria for major depression were randomized to receive 6 weeks of treatment with one of three fixed doses of venlafaxine--25 mg three times a day, 75 mg three times a day, or 125 mg three times a day--or placebo. Significant improvement was observed in depression scores at all doses, with the high dose resulting in earlier improvement, by week 2. For the combined venlafaxine treatment groups, 68% achieved a moderate or marked improvement on the Clinical Global Impression scale, compared with only 31% for the placebo group. Venlafaxine was well tolerated, and nervousness, sweating, and nausea were the only adverse effects observed more frequently with drug compared with placebo.
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PMID:Placebo-controlled trial of venlafaxine for the treatment of major depression. 191 21


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