Effects of blended lithium-zinc heparin on ionized calcium and general clinical chemistry tests.
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Biomedical subjects
Publications and source records attributed to T Thompson.
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Using a two-lever drug discrimination procedure, two groups of four rats each were trained to discriminate the stimulus effects of 1.0 U/kg insulin or 125 mg/kg 2-deoxy-D-glucose (2-DG) from saline. A third group was trained to discriminate food deprivation produced by feeding 23 h prior to sessions from satiation produced by feeding 2 h prior to sessions. Differential responding was a direct function of dose or deprivation level in each group. Rats trained to discriminate insulin responded as if they had received insulin when they received 2-DG and vice versa. Insulin and 2-DG produced deprivation-appropriate responding in two of four rats trained to discriminate food deprivation. Low insulin and 2-DG doses produced drug-appropriate responding in rats deprived 47 h, but not in rats deprived 23 h. Blood glucose level was altered by the training doses of insulin and 2-DG, but not by 23-h deprivation. These results indicate that operations that induce feeding produce discriminable stimuli, and that these effects overlap or interact. Thus, drug discrimination procedures can be useful in the analysis of ingestive behavior.
Seven rats lever pressed under a progressive ratio 3 (PR 3) schedule of food presentation; the number of responses per reinforcer systematically increased during each session. Break point (i.e., the number of responses in the last completed ratio before session termination) was measured under daily methadone (4.5 mg/kg and 3.0 mg/kg) or buprenorphine (0.3 mg/kg) administered prior to experimental sessions. Both drugs initially eliminated rats' food-maintained progressive-ratio responding. Break points during chronic methadone did not return to baseline levels after 80 drug sessions and a dose reduction. In contrast, break points during chronic buprenorphine administration were considerably above baseline control levels for two rats and returned to baseline levels for the third.
Methadone administration is reported to increase food intake in studies examining free feeding and to decrease food reinforced operant responding. In light of this apparent paradox, the present study evaluated methadone's effects on food reinforced operant responding under conditions more typical of free feeding studies than operant studies. The effect of methadone (5 mg/kg) on food intake was examined in rats maintained at 100% of their free feeding weights. Methadone did not increase food intake with food available under a fixed ratio 1 (FR 1) reinforcement schedule. Methadone did not alter response rate when each lever press produced a larger reinforcer (225 mg as opposed to 45 mg), but did increase food intake. When response requirements were changed from lever pressing to interruption of an infrared beam, increases in food intake following methadone administration were observed. Thus, the differences between methadone's effects on free feeding vs. operant chamber food intake may be due to procedural factors such as magnitude of reinforcement and response requirements.
Twelve pigeons key-pecked under a multiple variable interval 15-s, 150-s schedule of food reinforcement. The effects of methadone were studied alone and in combination with chronic daily administration of either imipramine (IMI) or desipramine (DMI). Chronic IMI was also given following reductions in response rates by unsignaled delay-to-reinforcement (UDR). Acute administration of methadone produced dose-dependent reductions in response rates under both schedules of reinforcement. Chronic daily administration of IMI or DMI alone did not result in lasting changes in baseline responding. When administered in combination, chronic daily IMI significantly attenuated the rate-reducing effects of methadone, whereas neither a low nor a high dose of chronic daily DMI was effective. The same dose of chronic daily IMI failed to ameliorate response rate reductions under delayed reinforcement. The behavioral and neurochemical specificity of the antidepressant effect is discussed.
Cocaine can cause myocardial ischemia or infarction. The incidence of these events, and the influence of specific dosing routes or regimens on their occurrence is not established. In the current study, we obtained frequent 12-lead electrocardiograms (ECGs) and continuous 2 or 3 channel ECGs from 20 subjects participating in a behavioral study of smoked cocaine. Subjects received 10 or 11 doses of cocaine 0.4 mg/kg per dose, or 10 doses of 35 mg per dose at 30 min intervals (range 233-408 mg total dose per session). ECGs were also recorded on control days on which subjects received no cocaine. The mean peak plasma cocaine concentration on cocaine days was 640 +/- 262 ng/ml. There were no changes in digitized ST segment amplitude on 12-lead ECGs obtained during cocaine administration (P = 0.098). Of 17 subjects who had technically satisfactory continuous ECGs, four had significant ST segment depression (> 1 mm below the PR segment); two on cocaine days and two on control days (P > 0.5). One subject had frequent premature beats on both cocaine and control days. One subject had an asymptomatic run of 4 ventricular beats 30 s after cocaine administration that could have been due to cocaine. All episodes of ST depression or premature beats were asymptomatic. No evidence of either symptomatic or subclinical cardiac ischemia related to cocaine administration was found. Thus no clinically important adverse events were found as a result of smoked cocaine administered by this dosing regimen to healthy males with a history of heavy cocaine use. Additional study with larger numbers of subjects will be helpful in further assessing the safety of administering smoked cocaine to research subjects.
OBJECTIVE: To study, by direct observation, physically aggressive behavior (PAB) in a cohort of older persons with dementia. DESIGN: Cross-sectional survey. SETTING: A locked special care unit for Alzheimer's Disease and an ordinary skilled unit of two suburban nursing homes. PARTICIPANTS: Twenty men and women with a history of PAB. MEASUREMENTS AND MAIN RESULTS: Portable bar-code-readers and daily diaries were used to determine the frequency of PAB as well as to elucidate the antecedents and consequences of it. PAB was most often directed toward staff (23/28 episodes), usually in the context of personal care (15/23 episodes). In the majority of cases, verbal aggression or non-compliance preceded the PAB. Most often PAB was followed by a rapid return to non-aggressive behavior. CONCLUSIONS: Very little PAB was truly spontaneous, nor was it usually the participant's normal behavior. Most PAB occurred in response to intrusion into the participant's personal space by staff or other residents. The PAB is better understood as a defensive response than an expression of anger.
The management of autoimmune sensorineural hearing loss (SNHL) continues to challenge the otologist. Steroids and cyclophosphamide, the two traditional medications for this malady, are often associated with serious adverse reactions. In an effort to use a less toxic medication, the authors treated five autoimmune SNHL patients with low-dose oral methotrexate. Methotrexate has been found to be very effective in rheumatoid arthritis patients with acceptable adverse reactions. Preliminary results from this study indicate that methotrexate has the potential of being effective for autoimmune SNHL and associated otologic symptoms. Tolerance has been very good and side effects have been minimal.
The opioid antagonist naltrexone was administered to 8 adults with severe or profound mental retardation and extensive histories of self-injurious behavior. Five-minute behavioral samples were observed randomly out of every hour from 8 a.m. through 3 p.m., Monday through Friday, for four 2-week phases (baseline, placebo, 50 mg, and 100 mg). During naltrexone administration, there were fewer days with frequent head-banging and self-biting, whereas there were more days on which blows to the head or self-biting were infrequent. Self-injurious participants slept 1.38 hours less per night during baseline, which was unaffected by naltrexone.
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Rats were trained to discriminate between an intracerebroventricular injection of 1.15 nmol of Neuropeptide Y (NPY) and a sham injection. Rats rapidly learned to press the appropriate lever during training. NPY's discriminative stimulus effects were compared to those of saline, and 1.15-3.45 nmol [Leu31,Pro34]NPY, a Y1 receptor agonist and NPY 20-36, Y2 receptor agonist. [Leu31,Pro34]NPY resulted in NPY-appropriate responding, whereas saline and NPY 20-36 did not. [Leu31,Pro34]NPY also increased food intake, but NPY 20-36 did not. This suggests that NPY's discriminative stimulus and orexigenic effects involve the Y1, but not the Y2, receptor.
BACKGROUND: Etoposide may be schedule dependent in small cell lung cancer (SCLC), and some data suggest a benefit for increased dose intensity in this disease. This study attempted to optimize dose intensity using an outpatient program that included prolonged, oral etoposide administration. METHODS: Cisplatin-etoposide (PE) and cyclophosphamide, doxorubicin, and vincristine (CAV) were alternated at monthly intervals in patients with extensive SCLC. PE was given as cisplatin 50 mg/m2 on days 1 and 8 intravenously (i.v.) and etoposide 50 mg/m2/day for 14 days by mouth. CAV was administered as cyclophosphamide 60 mg/m2/day for 21 days orally, doxorubicin 20 mg/m2/week for three doses, and vincristine 2 mg i.v. on day 1 only. At the end of 4 months, responding patients received an additional course of PE alternating with CAV, and whole-brain irradiation (3000 cGy in 15 fractions) was delivered to clinical complete responders (CR). RESULTS: Among 61 eligible patients, 4 achieved CR, and 11 had a partial remission, by strict Southwest Oncology Group criteria. An additional 20 patients demonstrated greater than 50% tumor shrinkage on one disease assessment but did not have confirming measurements at all sites 4 weeks later. The overall response rate was 57%, including the latter group. The toxicity was primarily hematologic, with three treatment-related deaths from neutropenic infection (5%). Grade 4 neutropenia (< 500/microliters) occurred in nine patients (15%) and Grade 4 thrombocytopenia (< 25,000/microliters), in three (5%). Analysis of the delivered dose intensity (in milligrams per square meter per week) as a function of that which was planned revealed a mean of 93% for all courses. CONCLUSIONS: Although substitution of prolonged oral etoposide in PE and oral cyclophosphamide in CAV proved to be feasible, these results suggest no advantage over those from other reported series using these alternating regimens in which the agents are pulsed. Experience with alternating PE-CAV for extensive SCLC is reviewed.
Subjects performed a timed-response task in which they attempted to synchronize a rapid flexion of the index finger of their preferred hand with the last of a train of four regularly spaced acoustic clicks. The task was used to stabilize the execution time of a simple voluntary response in order to facilitate psychophysical judgments about the subjects' perception of having responded and of having intended to respond. In the first experiment, male subjects (N = 6) adjusted the appearance time of a reference stimulus (a brief percutaneous pulse to the responding finger) until it appeared to be simultaneous with their perception of having made the response. All subjects adjusted the reference stimulus to appear after response onset during the latter half of the force impulse. This finding suggests that the perception of having responded is based on peripheral feedback from the response. In the second experiment, male subjects (N = 6) performed the same motor task, but adjusted the time of the reference stimulus so that it appeared to be simultaneous with their intention to respond. Two subjects were not able to do the task successfully; the remaining four subjects adjusted the reference stimulus to appear from 101 to 145 ms before response onset. This finding suggests that the intention to respond is perceptually separable from the response itself and occurs at a measurable time before response onset.
Two experiments are reported comprising an investigation of individual difference variables associated with self-worth protection. This is a phenomenon whereby students in achievement situations adopt one of a number of strategies, including withdrawing effort, in order to avoid damage to self-esteem which results from attributing failure to inability. Experiment 1 confirmed the adequacy of an operational definition which identified self-worth students on the basis of two criteria. These were deteriorated performance following failure, together with subsequent enhanced performance following a face-saving excuse allowing students to explain failure without implicating low ability. The results of Experiment 2 established that the behaviour of self-worth protective students in achievement situations may be understood in terms of their low academic self-esteem coupled with uncertainty about their level of global self-esteem. Investigation of the manner in which self-worth students explain success and failure outcomes failed to demonstrate a tendency to internalise failure but revealed a propensity on the part of these students to reject due credit for their successes. The implications of these findings in terms of the prevention and modification of self-worth protective reactions in achievement situations are discussed.
Few drug reactions are more life threatening than the sudden development of edema involving the mucosal and submucosal layers of the upper aerodigestive tract. Drug-induced angioedema is a recognized entity of angiotensin-converting enzyme (ACE) inhibitors, and despite reports in medical journals and drug insert warnings, captopril and enalapril continue to be widely prescribed. As these drugs are efficacious and usually well-tolerated in the treatment of mild forms of hypertension, their popularity is rising. From June 1, 1984 to August 1, 1991, 36 patients with angioedema secondary to ACE inhibitors presented at the Medical College of Virginia Hospitals. Thirty were successfully managed with medical therapy. Two were intubated, 1 had placement of a nasal trumpet, and 3 required tracheostomies. Of extreme importance is the recognition that angioedema resulting from ACE inhibitors is probably not immunoglobulin E (IgE) mediated and that antihistaminics and steroids may not alleviate the airway obstruction. The otolaryngologist must be prepared for the need of possible early surgical intervention.
This paper describes the outcome of 15 patients with chlorpromazine (CPZ)-induced abnormal skin pigmentation (ASP) in whom CPZ was replaced with other neuroleptics for three to 13 years. Complete resolution of ASP occurred over a period of six months to five years following substitution with haloperidol (four patients), levomepromazine (three patients), trifluoperazine (one patient), thioproperazine (one patient) as the sole neuroleptic, by a combination of two of the three phenothiazines (four patients) or haloperidol plus pipotiazine (one patient). Resolution was maintained during the remainder of the follow-up period. In one patient, at final follow-up, marked improvement was present three years after CPZ was replaced with levomepromazine. Bilateral lenticular pigmentary deposits persisted in all eight patients examined 3.3 to 13 years after replacing CPZ and less than three months to nine years after resolution of ASP; improvement was noted in only one of these patients. Bilateral endothelial corneal deposits, present in five patients while on CPZ therapy, had disappeared in two patients seven and 13 years, respectively, after replacing CPZ; improvement was noted in two other patients. These findings indicate that: 1. CPZ-induced ASP is completely reversible in most, if not all, patients if CPZ is withdrawn; 2. a variety of neuroleptics including other phenothiazines can be used to replace CPZ without risk of re-emergence of ASP; 3. CPZ-induced lenticular changes persist whereas corneal changes may resolve slowly over a period of many years following replacement of CPZ; 4. ASP and ocular changes induced by CPZ may be subserved by two different pathophysiological mechanisms.
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A variety of opioids and opiates are known to increase short-term food intake. In the present study, we evaluated the effects of methadone on free feeding in satiated rats. We assessed the effect of methadone (0, 1.5, 3.0, 5.0, and 10.0 mg/kg) on food intake 1, 2, 4, and 6 h after injection for 3 consecutive days. Two hours after methadone administration, food intake was inversely related to dose, but after 6 h a direct relationship between dose and feeding was obtained. Food intake increased with repeated methadone administration. In Experiment 2, methadone (5.0 mg/kg) was injected and food was made available 0, 1, 2, or 3 h later. Maximal food intake occurred in the third and fourth hours following methadone administration. As in Experiment 1, food intake increased with repeated methadone administration. Increases in food intake following repeated methadone administration may have been due to the development of tolerance to effects of methadone that may interfere with feeding, such as sedation. In Experiment 3, methadone was administered daily or every fifth day, assuming that spacing injections would retard tolerance development. Repeated daily methadone administration was associated with increased food intake earlier in the session, whereas increases in food intake following spaced methadone administration occurred later in the session. These data indicate that methadone increases short-term feeding in satiated rats. This is in contrast to the reported decrease in food-reinforced behavior noted in operant studies. This contrast may be due to sedating or other disabling effects of methadone.