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Biomedical subjects

C L Mitchell

Publications and source records attributed to C L Mitchell.

11 recordsLinked to original sources
PubMed1979

Screening for neurobehavioral toxicity: the need for and examples of validation of testing procedures.

The need for a sensitive and reliable screen to assess environmental agents for potential behavioral and neurological toxicity is discussed. Factors involving strategy, choice of animals and doses, route of administration, duration of study and requirements for the selection of neurobehavioral tests are also evaluated. The primary emphasis concerns the need for standardization and validation of neurobehavioral tests to be used in neurotoxicology. It is suggested that test validation be accomplished by comparing the observed results of known neurotoxicants in animal models which are chosen to predict effects based on reported human symptomatology. As a means of demonstrating how test validation is used in our laboratory, data from a number of experiments concerning the effects of a variety of chemical agents on three measures of motor functioning were discussed. The neurobehavioral effects of acrylamide, and agent known to produce "dying-back" axonopathies, were assessed using separate techniques presumed to measure hindlimb and forelimb functioning and general motor activity. The prediction that acrylamide will first decrease hindlimb functioning, while decreasing forelimb grip strength and motor activity at higher doses, was confirmed. The validity of the hindlimb measurement was supported using a neurotoxicant, carbon disulfide, known to affect motor functioning in a manner similar to acrylamide. The validity of the forelimb technique was shown indirectly using normative data collected from rats of both sexes tested at various ages, i.e., males were stronger than females and grip scores changed as a function of age. The relative sensitivities of the fore- and hindlimb measurements were found to be approximately the same when used to assess the effects of known muscle relaxants, such as phenobarbital and chlordiazepoxide. Finally, it was predicted and confirmed that an environmental agent believed to affect behavior secondarily to effects on other organ systems would affect all measures of motor functioning at approximately the same dose.

Animals↗
PubMed1978

Behavioral and neurological toxicity of polybrominated biphenyls in rats and mice.

Male, albino rats of the F-344/N strain and mice of the B6C3F1 strain were dosed by gavage, 5 days per week for a toal of 22 doses with 0.03--30 mg/kg of FireMaster FF-1, 0.168-16.8 Mg/kg of 2,4,5,2',4',5'-hexabromobiphenyl (HBB), or corn oil vehicle. A battery of tests was administered at the end of repeated dosing (30 day examination) and 30 days after dosing ceased (60 day test). FF-1 and, to a much lesser extent, HBB decreased body weight and performance on a variety of tests designed to detect neuromuscular dysfunction. Included in these tests were activity in the open field, forelimb grip strength, and muscular reflexes. Visual placement responses were also decreased in some animals, while hypothermia was observed in others. Emotionally, as measured by the number of defecations and urinations in the open field, was not affected by exposure to either compound. At the end of 30 day test, mice were less affected by exposure to these polybrominated biphenyls (PBBs) than rats; rats tended to worsen during the 30 days of no dosing, while mice tended to improve. These experiments indicate that oral dosing with levels of PBBs below those required to produce signs of acute toxicity produced behavioral or neurological toxicity when given repeatedly.

Animals↗
PubMed1978

The reinforcing properties of procaine and d-amphetamine compared in rhesus monkeys.

Twelve rhesus monkeys were studied under a fixed-ratio (FR) schedule of intravenous procaine or d-amphetamine injection from 8 A.M. to 4 P.M. daily. Under the FR schedule, every nth lever press produced an injection. The FR value (n) and the dose per injection of procaine and d-amphetamine were varied systematically. At a FR value of 10, responding was maintained by doses of procaine ranging from 0.125 to 12 mg/kg/injection and by doses of d-amphetamine ranging from 0.01 to 0.1 mg/kg/injection. At doses of 1 mg/kg/injection of procaine and 0.1 mg/kg/injection of d-amphetamine, responding was maintained at FR values up to 100 by procaine and d-amphetamine but not by saline. Responding and drug intake were relatively constant throughout each 8-hour session with procaine, but responding tended to decrease and was more variable over the session with d-amphetamine. No toxic effects were observed in doses up to 6 mg/kg/injection with procaine. At this dose, eating and drinking ceased during the period of access to the drug. One of the four monkeys died at 8 mg/kg/injection of procaine. At 12 mg/kg/injection all three monkeys tested showed signs of toxicity.

Animals↗
PubMed1977

The surgical technique for hindquarter amputation. A report of 19 cases.

The surgical technique for hindquarter amputation is described in a step-by-step manner. Since 1955 we have performed 19 such operations for eradication of malignant bone and soft tissue tumors in the pelvic, hip and upper thigh regions. Three hindquarter amputations were performed for local recurrence following initial wide excision. The overall 5-year survival rate for our 19 patients was 42.1 per cent. Malignant soft tissue tumors appear to have a much better 5-year survival rate than malignant bone tumors (60 per cent vs. 22.2 percent). We feel that surgery is still the treatment of choice. However, in the presence of proper indications, chemotherapy and radiotherapy should be added to surgery in order to prolong survival time and save lives.

Adolescent↗
PubMed1977

Analgesic studies with nefopam hydrochloride.

Nefopam hydrochloride[3] is a novel analgesic agent possessing an activity profile distinct from that of narcotic, narcotic agonist-antagonist and analgesic antiinflammatory agents. Analgesic activity is demonstrated in a variety of laboratory procedures with rodents, cats and monkeys. The analgesic potency of nefopam hydrochloride is generally similar to that of codeine phosphate. The compound lacks potential for tolerance development and does not exhibit cross-tolerance with morphine sulfate.

Animals↗
PubMed1976

The design and analysis of experiments for the assessment of drug interactions.

It was pointed out that all fields of biological research have one feature common: inherent variability. Since this is the case and since it is not feasible to examine the entire population one is interested in, the experimenter is forced to give probability statements concerning any treatment differences observed. In order to do this, it is necessary for the experiment to be designed in such a way that a statistical analysis of the data will yield a valid answer to the question, "What is the probability that the differences observed could have occurred by chance?" The importance of randomization in the selection of the samples was emphasized. The problem of determining the sample size was discussed in relation to Type I (rejecting the null hypothesis when it is true) and Type II (accepting the null hypothesis when it is false) errors. It was suggested that too little attention is given to the possibility of Type II errors in biological research. It was emphasized that the specific question, or questions, one is asking should be precisely formulated prior to the design of the experiment, since hazily formulated ideas are difficult to discuss and virtually impossible to test for correctness. Once the experiment has been designed, both the questions and the design should be critically and logically evaluated for any fallacies. If the investigator has any doubts about the design or the manner in which the data will be analyzed, a statistician should be consulted before the experiment is conducted. A statistician cannot extract meaningful results from data collected with a faulty design. It was emphasized that it is important to know both the dose effect and time effect of each substance on the responses to be measured, in order to provide a rationale for the doses used in the interaction studies and the time after dosing at which the effect is to be measured. The design of drug interaction experiments is based, in part, on whether or not both substances when given alone affect the response. If both substances are active, one determines the potency of one substance relative to the other in affecting the response. This can be done for either quantitative or quantal data. Once the relative potency has been determined, subsequent studies involve combining fractional doses of the substances and comparing the results against those obtained using standard doses of the substances individually. Doses of the combination and the single substances are picked such that equivalent responses should be obtained if the effect of the two together is additive. The null hypothesis is that the two compounds behave as though they were different forms of the same substance, one of which is possibly (depending on the potency ratio) diluted with an inert substance. Equivalence of response can be tested using such parametric tests as Student's t or analysis of variance (or their nonparametric equivalents) for quantitative data. Additivity is inferred if the null hypothesis is accepted...

Animals↗
PubMed1975

Alteration in escape responding in the cat. A lesion and degeneration and comparison following stimulation studies.

15 cats were trained to cross a hurdle in a shuttle box when stimulated through a single bipolar electrode chronically implanted in the subthalamic, mesencephalic and most rostral pontine tegmentum. A lesion was then made through one or both electrode poles. Upon recovery, three patterns of response emerged: (1) crossing with higher threshold or longer latencies; (2) no crossing, or (3) no change in crossing. The response pattern correlated with the anatomic findings. The nine animals that crossed before but not after the lesion, showed either lesions or heavy axonal and terminal degeneration in the H2 field.

Animals↗
PubMedDate not supplied

Temporary occlusion of the common iliac artery during hemipelvectomy.

The surgical technique for temporarily occluding the common iliac artery during hemipelvectomy has been described. Not only can this technique significantly reduce the blood loss and operative time, but it may also minimize postoperative complications and increase the chances of a complete eradication of the primary malignant disease.

Amputation, Surgical↗