(1/723) Extinction of responding maintained by timeout from avoidance.
The resistance to extinction of lever pressing maintained by timeout from avoidance was examined. Rats were trained under a concurrent schedule in which responses on one lever postponed shock on a free-operant avoidance (Sidman) schedule (response-shock interval = 30 s) and responses on another lever produced 2 min of signaled timeout from avoidance on a variable-ratio 15 schedule. Following extended training (106 to 363 2-hr sessions), two experiments were conducted. In Experiment 1 two different methods of extinction were compared. In one session, all shocks were omitted, and there was some weakening of avoidance but little change in timeout responding. In another session, responding on the timeout lever was ineffective, and under these conditions timeout responding showed rapid extinction. The within-session patterns produced by extinction manipulations were different than the effects of drugs such as morphine, which also reduces timeout responding. In Experiment 2 shock was omitted for many consecutive sessions. Response rates on the avoidance lever declined relatively rapidly, with noticeable reductions within 5 to 10 sessions. Extinction of the timeout lever response was much slower than extinction of avoidance in all 4 rats, and 2 rats continued responding at baseline levels for more than 20 extinction sessions. These results show that lever pressing maintained by negative reinforcement can be highly resistant to extinction. The persistence of responding on the timeout lever after avoidance extinction is not readily explained by current theories. (+info)
(2/723) Antiemetic efficacy of granisetron plus dexamethasone in bone marrow transplant patients receiving chemotherapy and total body irradiation.
Few trials exist regarding the antiemetic efficacy of granisetron in bone marrow transplant (BMT) recipients conditioned with high-dose chemotherapy and total body irradiation (TBI). In this single-center, open-label, prospective, trial, the antiemetic efficacy and safety of granisetron plus dexamethasone were evaluated in 26 patients conditioned with cyclophosphamide-containing regimens (the majority receiving 60 mg/kg per day on 2 consecutive days), and TBI (12 Gy divided over 4 days). Daily intravenous doses of granisetron 1 mg plus dexamethasone 10 mg were given 30 min prior to chemotherapy or radiation, and continued for 24 h after the last conditioning treatment for a median of 6 days (range 3-9). Emetic control was defined by the number of emetic episodes occurring within a 24 h period, or the requirement for rescue medication for nausea or vomiting. A total of 25 patients completed 186 evaluable treatment days. Response (emetic control by treatment days) was complete in 50% of patients, major in 48%, minor in 2%, and there were no failures. Adverse effects were minor, with diarrhea (15%), headache (14%), and constipation (11%) reported most often. Based on these results, the antiemetic regimen of granisetron plus dexamethasone appears effective and well tolerated during BMT conditioning with high-dose cyclophosphamide and TBI. (+info)
(3/723) Is the development of myocardial tolerance to repeated ischemia in humans due to preconditioning or to collateral recruitment?
OBJECTIVES: The purpose of this study in patients with quantitatively determined, poorly developed coronary collaterals was to assess the contribution of ischemic as well as adenosine-induced preconditioning and of collateral recruitment to the development of tolerance against repetitive myocardial ischemia. BACKGROUND: The development of myocardial tolerance to repeated ischemia is nowadays interpreted to be due to biochemical adaptation (i.e., ischemic preconditioning). METHODS: In 30 patients undergoing percutaneous transluminal coronary angioplasty, myocardial adaptation to ischemia was measured using intracoronary (i.c.) electrocardiographic (ECG) ST segment elevation changes obtained from a 0.014-in. (0.036 cm) pressure guidewire positioned distal to the stenosis during three subsequent 2-min balloon occlusions. Simultaneously, an i.c. pressure-derived collateral flow index (CFI, no unit) was determined as the ratio between distal occlusive minus central venous pressure divided by the mean aortic minus central venous pressure. The study patients were divided into two groups according to the pretreatment with i.c. adenosine (2.4 mg/min for 10 min starting 20 min before the first occlusion, n = 15) or with normal saline (control group, n = 15). RESULTS: Collateral flow index at the first occlusion was not different between the groups (0.15 +/- 0.10 in the adenosine group and 0.13 +/- 0.11 in the control group, p = NS), and it increased significantly and similarly to 0.20 +/- 0.14 and to 0.19 +/- 0.10, respectively (p < 0.01) during the third occlusion. The i.c. ECG ST elevation (normalized for the QRS amplitude) was not different between the two groups at the first occlusion (0.25 +/- 0.13 in the adenosine group, 0.25 +/- 0.19 in the control group). It decreased significantly during subsequent coronary occlusions to 0.20 +/- 0.15 and to 0.17 +/- 0.13, respectively. There was a correlation between the change in CFI (first to third occlusion; deltaCFI) and the respective ST elevation shift (deltaST): deltaST = -0.02 to 0.78 x deltaCFI; r = 0.54, p = 0.02. CONCLUSIONS: Even in patients with few coronary collaterals, the myocardial adaptation to repetitive ischemia is closely related to collateral recruitment. Pharmacologic preconditioning using a treatment with i.c. adenosine before angioplasty does not occur. The variable responses of ECG signs of ischemic adaptation to collateral channel opening suggest that ischemic preconditioning is a relevant factor in the development of ischemic tolerance. (+info)
(4/723) Intravenous administration of diazepam in patients with chronic liver disease.
The EEG response and drug kinetics after intravenous infusion of diazepam at 1-0 mg/min until nystagmus, dysarthria, and moderate sedation developed, has been investigated in five normal subjects and 17 patients with chronic liver disease. Diazepam induced adequate premedication with a similar clinical response in all subjects with no adverse reactions. Maximal response was during or within five minutes of infusion. The dose of diazepam required in liver chronic disease was 17-9 +/- 1-4 mg (M +/- SEM) compared with 27 +/- 5-4 mg in controls (p less than 0-01). Dose correlated significantly with serum albumin (p less than 0-05). Baseline mean dominant frequency (MDF) and slow wave index (SWI) significantly correlated with albumin (p less than 0-01). After diazepam, the MDF decreased and SWI increased. The change was greatest at the time of maximal clinical response. It was greater in liverdisease and was greatest in patients with previous hepaticencephalopathy. In spite of reduced dose requirements in liver disease, there was no significant difference in plasma concentration at the end of drug infusion... (+info)
(5/723) Balanced pre-emptive analgesia: does it work? A double-blind, controlled study in bilaterally symmetrical oral surgery.
We studied 32 patients undergoing bilateral symmetrical lower third molar surgery under general anaesthesia to determine if the combined effects of pre-emptive local anaesthetic block using 0.5% bupivacaine, together with i.v. tenoxicam and alfentanil had any benefits over postoperative administration. Patients acted as their own controls and were allocated randomly to have surgery start on one side, the second side always being the pre-emptive side. Difference in pain intensity between the two sides was determined using visual analogue scales completed by each individual at 6 h, and at 1, 3 and 6 days after operation. A long-form McGill pain questionnaire was also used to assess difference in pain intensity between the two sides on the morning after surgery. There was no significant difference in pain intensity at any time after surgery. Our findings indicate that the combined use of pre-emptive analgesia from 0.5% bupivacaine, tenoxicam and alfentanil did not reduce postoperative pain intensity in patients undergoing molar exodontia. (+info)
(6/723) Effectiveness of preoperative analgesics on postoperative dental pain: a study.
Patients undergoing extractions of third molar teeth under general anesthesia were given a placebo, diclofenac (a nonsteroidal anti-inflammatory drug) 100 mg, or methadone (an opiate) 10 mg 60 to 90 min prior to surgery, and their pain scores and postoperative medication requirements were measured for 3 days. All patients received local anesthetic blocks and analgesic drugs during the perioperative period. There were no significant differences between the three groups in the pain scores and medication requirements during the period of study. It was concluded that preoperative use of nonsteroidal anti-inflammatory drugs and opiates may not offer a preemptive analgesic effect in patients who have had adequate analgesia during the surgery. Continued use of analgesic drugs during the postoperative period is perhaps more useful for this purpose. There appears to be a higher incidence of vomiting following opiates (methadone), precluding its clinical use in day-care patients. (+info)
(7/723) A pilot study of the efficacy of oral midazolam for sedation in pediatric dental patients.
Oral midazolam is being used for conscious sedation in dentistry with little documentation assessing its efficacy. In order to accumulate preliminary data, a randomized, double-blind, controlled, crossover, multi-site pilot study was conducted. The objective was to determine if 0.6 mg/kg of oral midazolam was an equally effective or superior means of achieving conscious sedation in the uncooperative pediatric dental patient, compared with a commonly used agent, 50 mg/kg of oral chloral hydrate. Twenty-three children in three clinics who required dentistry with local anesthetic and were determined to exhibit behavior rated as "negative" or "definitely negative" based on the Frankl scale were assessed. They were evaluated with respect to acceptance of medication; initial level of anxiety at each appointment; level of sedation prior to and acceptance of local anesthetic; movement and crying during the procedure; and overall behavior. The results showed that the group randomly assigned to receive midazolam had a significantly greater initial level of anxiety for that appointment (P < 0.02), a finding that could clearly confound further determination of the efficacy of these drugs. Patients given oral midazolam had an increased level of sedation prior to the administration of local anesthetic compared with those given chloral hydrate (P < 0.015). No statistically significant differences were noted in any of the other parameters. The age of the patient was found to have no correlation with the difference in overall behavior (r = -0.09). These preliminary data warrant further clinical trials. (+info)
(8/723) Intranasal midazolam plasma concentration profile and its effect on anxiety associated with dental procedures.
The objectives of this study were to describe the serum concentration time profile for midazolam following intranasal administration to adult dental surgery patients and to ascertain the effect of midazolam on anxiety. Six female patients received a single 20 mg (0.32 to 0.53 mg/kg) dose of midazolam. Blood samples were collected at 5, 10, 20, 30, 45, and 60 min following dose administration. Midazolam plasma concentrations were determined by gas chromatography. Anxiety was evaluated using a 100-mm visual analogue scale. The maximum concentration of midazolam was reached 25.8 min (range 18 to 35 min) following dose administration. Maximum concentrations were variable. However, there was no relationship between the weight-adjusted dose and maximal concentration. Patients experiencing baseline anxiety exhibited a trend toward reduction in their measured anxiety score (P = 0.06). Plasma concentrations above the hypothesized minimum effective concentration for sedative effects were attained when midazolam was administered intranasally to adult dental patients. (+info)