Mass campaigns and general health services: conclusions. 1965.
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Communicable Disease Control↗
Biomedical subjects
C L Gonzalez
Publications and source records attributed to C L Gonzalez.
Chronic prenatal exposure to phenobarbital and long-term behavior effects on mice offspring.
OBJECTIVE: To assess the impact of chronic prenatal exposure to phenobarbital on long-term behavior in mice offspring. METHODS: Twenty-eight C3H/He mice were randomized to receive diet chow containing either a daily therapeutic dose of phenobarbital (2.5 mg in 10-g chow) or a placebo for 1 week before mating and throughout gestation. Offspring from eight litters of each treatment group were evaluated using motor function, arousal/motivation, anxiety-provoking and cognition tasks. RESULTS: No significant differences between groups were found in duration of gestation, litter size and birth weights. Fewer counts in a locomotor chamber were observed in phenobarbital-exposed offspring (524 +/- 31 vs. 688 +/- 54 for 60 min, p < 0.02; 4174 +/- 229 vs. 5230 +/- 406 for 22 h, p < 0.05). Initial reactions to a startle were more apparent among phenobarbital-exposed offspring (p < 0.03). Impaired co-ordination of hindlimbs was observed in the phenobarbital-exposed offspring during the wire maneuver (p < 0.001). Fewer entries into the mirrored chamber were observed after phenobarbital exposure (2.1 vs. 4.5; p < 0.05). Exposure to phenobarbital was not found to affect responses to learning and memory tasks (homing, tube runway, water runway, Morris maze). CONCLUSION: Although cognition was unaffected by prenatal exposure to phenobarbital, subtle effects on locomotor activity, hindlimb co-ordination and responses to anxiety-provoking conditions require human correlation.
Animals↗
Nicotine improvement of Morris water task performance after fimbria-fornix lesion is blocked by mecamylamine.
The focus of this study was to analyze the effects of nicotine on behavioural compensation after fimbria-fornix (FF) lesions in rats tested on the Morris water task (MWT). Nicotine (0.3 mg/kg) was injected subcutaneously for 11 consecutive days before, for 11 consecutive days after, or for 11 consecutive days before and after a FF lesion. Additionally, a lesion group was included that was given mecamylamine (1.0 mg/kg), a nicotine antagonist, 10 min before nicotine administration as well as mecamylamine-only, no treatment lesion, and sham groups. All drug administration ceased 24 h before three consecutive days of behavioural testing on the MWT. Results showed that the sham group and animals receiving both a pre- and post-lesion treatment of nicotine performed significantly better than all other groups, and the pre- and post-lesion nicotine group performed equivalent to sham controls on both acquisition and a probe trial. The compensatory effect of nicotine was blocked by mecamylamine. This study demonstrates that nicotine stimulates recovery from brain damage and the results are discussed in relation to neural mechanisms and potential applications.
Animals↗
Deficits in allothetic and idiothetic spatial behavior in rats with posterior cingulate cortex lesions.
The cingulate cortex plays a central role in bridging neocortical and limbic structures involved in allothetic navigation, a form of navigation requiring the use of external cues. Animals can also navigate using idiothetic cues, which are cues generated by self-movement, but there have been no definitive tests of whether cingulate cortex also plays a role in idiothetic navigation. Rats with anterior cingulate (medial frontal) and posterior cingulate cortex (retrosplenial) suction ablations were trained to search for large food pellets on an open table, and the accuracy with which they returned home with the food was measured. In the idiothetic task they searched for food from a novel starting location under infrared light, and with surface olfactory cues displaced. The rats also received two tests of allothetic navigation. They were tested on a matching-to-place task in which they foraged for food from a number of successively presented new locations under normal room light, and they were trained to locate a hidden platform in a swimming pool (Morris place task). The group with posterior cingulate cortex lesions was severely impaired on all of the navigation tasks whereas the group with anterior cingulate cortex lesions displayed no deficit on the idiothetic task and only moderate deficits on the other tasks. The results demonstrate a role for posterior cingulate region in idiothetic navigation.
Animals↗
Effect of prenatally administered hypericum (St John's wort) on growth and physical maturation of mouse offspring.
OBJECTIVE: Our purpose was to determine whether prenatal exposure to the herb hypericum (St John's wort) affects long-term growth and physical maturation of mouse offspring. STUDY DESIGN: Forty CD-1 mice were randomly assigned to receive daily doses of either 180 mg/kg per day hypericum (n = 20) or a placebo (n = 20) for 2 weeks before conception and throughout gestation. Perinatal outcomes, growth, and physical milestones of the offspring were compared in a blinded manner. Variables were compared by analysis of variance or by chi2 testing. RESULTS: The gestational ages at delivery and litter sizes did not differ between the hypericum-exposed and the placebo-exposed offspring. The body weight, body length, and head circumference measurements from postnatal day 3 through adulthood increased in a manner that was indistinguishable between the two groups of offspring, regardless of gender. No differences in reaching physical milestones (teeth eruptions, eye opening, external genitalia) were noted between the 2 groups. The reproductive capability, perinatal outcomes, and growth and development of the second-generation offspring were unaffected by hypericum exposure. CONCLUSION: Maternal administration of hypericum before and throughout gestation did not affect long-term growth and physical maturation of exposed mouse offspring.
Animals↗
Multiple courses of antenatal betamethasone and cognitive development of mice offspring.
OBJECTIVE: To measure the effect of multiple courses of antenatal betamethasone, used for lung maturation, on long-term cognition of mice offspring. METHODS: Forty gravid CD-1 mice were randomly assigned to receive one of four treatments (n = 10 per group): 0.1 mg betamethasone or saline placebo, given subcutaneously either once daily on gestational days 13-16 or twice daily on days 14 and 15. This dose of betamethasone given on gestational day 14 causes fetal lung maturation in mice. Three offspring per gender in each litter underwent standard cognitive tasks as juveniles and as adults. Analysis of variance or Kruskal-Wallis testing was used to compare data. RESULTS: Learning acquisition and memory were indistinguishable between the betamethasone-exposed and the corresponding placebo-exposed offspring when performing the following tasks: juvenile runway with adult memory, adult water runway and Morris spatial maze. This lack of difference in task performance between treatment groups persisted after controlling for gender and for each multiple-course regimen. CONCLUSION: Multiple courses of antenatal corticosteroids did not impact the mouse offsprings' long-term learning and memory.
Animals↗
Placebo-controlled, blinded comparison of antenatal betamethasone on mouse liver development.
The objective of this investigation was to evaluate, in a placebo-controlled manner, the developing mouse liver after antenatal exposure either to a single dose or to a multidose of betamethasone. Ninety gravid CD-1 mice were randomly divided into three groups (n = 30/group) to receive either saline (0.25 mL s.c.) or betamethasone (0.10 mg s.c.) as a single dose on gestational day (GD) 14 of a 19-day gestation or as a 0.10 mg dose given twice daily on GD 14 and on GD 15 (4 doses). GD 0 is defined by the presence of a copulatory plug. These exposures of betamethasone cause fetal mouse lung maturation as would be observed in premature humans at 24-34 weeks of gestation. The livers were removed either from the fetuses on GD 16.5 or from the offspring on postnatal day 1, 3, 5, and 120. Special stains were used to evaluate hepatocyte architecture, glycoprotein and glycogen content, extramedullary hematopoiesis and iron storage. Hepatocyte intranuclear DNA content, cell size, and cell shape were measured by image analysis (CAS 200). At GD 16.5, betamethasone produced a significant decrease in the liver/body weight ratio that, when compared with the placebo group, was greater with the multidose (p < 0.01) than with the single dose (p < 0.05). 16.5 GD single dose hepatocytes were smaller in size as compared to placebo without impact on intranuclear DNA (p < 0.01). Single dose PND 1 hepatocytes demonstrated an increase in intranuclear DNA as compared to placebo but without change in cell size (p < 0.001). The prenatal reduced liver weight recovered in the newborn period. No difference in microscopic architecture of the hepatocytes or histologic differences between either of the three treatment groups was found in glycogen deposition, extramedullary hematopoiesis or iron metabolism at GD 16.5 and postnatally. It was concluded antenatal betamethasone can cause a decrease in the liver/body weight ratio in the fetal mouse that recovers eventually without any functional impact as assessed histologically.
Animals↗
Nicotine improves Morris water task performance in rats given medial frontal cortex lesions.
The object of this study was to investigate whether nicotine would improve cognitive impairments produced by medial frontal cortex lesions in rats behaviorally tested on the Morris water task (MWT). Rats were assigned to either a lesion or sham group. In the lesion group, animals were given vehicle (peanut oil) treatment or treatment with nicotine for 11 consecutive days before, after, or before and after a medial frontal cortex lesion. Additionally, a sham group was included that was given vehicle both before and after the lesion. Results showed that lesioned rats receiving pre- or post-operative nicotine treatment demonstrated improved Morris task acquisition performance relative to the lesioned group given the vehicle, although a deficit was shown relative to shams. On the probe trial, rats that received a pre- and post-treatment of nicotine demonstrated performance equivalent to shams and had significantly better performance than rats that received nicotine treatment before the lesion and lesioned animals treated with the vehicle. These results demonstrate that nicotine has therapeutic effects in rats that have received cortical injury.
Animals↗
A cautionary note regarding drug and brain lesion studies that use swimming pool tasks: partial reinforcement impairs acquisition of place learning in a swimming pool but not on dry land.
Spatial tasks are used widely in neurobiological studies because it is thought that they provide an unbiased assessment of the integrity of neural structures that mediate spatial learning. For example, in the Morris swimming pool place task, animals are required to locate a hidden platform in a swimming pool in relation to environmental cues. Treatments that result in an animal's failure to find the platform are assumed to reflect defects in the function of neural systems involved in spatial learning. The present study demonstrates, however, that an animal's reinforcement history can contribute to its spatial performance. Animals were trained in the Morris place task with the platform present on 100, 75 or 50% of trials. Relative to the 100% group, the 75% group was impaired in place acquisition, and the 50% group failed to learn. Even placing the 50% group animals onto the platform at the completion of an unsuccessful trial failed to improve acquisition. Animals trained to search for food on an identical dry maze problem were not affected by similar reinforcement schedules. The present findings demonstrate that the Morris swimming pool place task does not provide an unbiased assessment of spatial learning: A treatment effect may be confounded with reinforcement history. The results are discussed in relation to widespread applications of the Morris place task to neurobiological problems.
Analysis of Variance↗
Effect of antenatal exposure to Saint John's wort (Hypericum) on neurobehavior of developing mice.
OBJECTIVE: We conducted, in a randomized, placebo-controlled manner, behavioral testing on mice offspring exposed antenatally to the herbal antidepressant Saint John's wort (Hypericum ). STUDY DESIGN: A daily dose of Saint John's wort (0.75 mg/g of food consumed), equivalent to that in human beings according to body surface, was chosen because it has been shown to cause an antidepressant effect in adult mice. CD-1 mice were randomly assigned to consume either Saint John's wort (n = 45) or a placebo (n = 45) for 2 weeks before conception and throughout gestation. Behavioral testing consisted of early developmental tasks of geotaxis, separation vocalization, and homing, followed by motor, anxiety, and depression assessments into adulthood. RESULTS: Birth weights of male offspring were less in the Saint John's wort group than in the placebo group (1.68 vs. 1.75 g; P<.01). Offspring in both treatment groups showed no long-term statistical differences in early developmental tasks, locomotor activity, and exploratory behavior throughout development. Performances on a depression task (forced swim) and on anxiety tasks (elevated plus maze as juveniles and adults) revealed no differences between treatment groups. CONCLUSION: Antenatal exposure to a therapeutic dose of Saint John's wort showed no long-term deficits on selected behavioral tasks by developing mice offspring.
Animals↗
Impact of antenatal exposure of mice to fenfluramine on cardiac development and long-term growth of the offspring.
The objective of this investigation was to determine, in a placebo-controlled manner, whether antenatal exposure to formulations of fenfluramine and dexfenfluramine impacted cardiac development and long-term growth of exposed mice offspring. One hundred forty-four CD-1 mice were randomized to six treatment groups (n=23 or 25) to obtain, per group, 5 gravids for killing on gestational day (GD) 15 and < or =10 deliveries for assessing growth of the offspring. Either fenfluramine preparation was administered in feed bars in two doses: 1 and 3.2 times the equivalent human daily dosage according to body surface area. The drugs were given from 2 weeks before mating until GD 15. The mice ingested each drug at target values, averaging 10.5+/-0.3 and 31.8+/-1.9 mg/kg/d for fenfluramine and 5.0+/-0.2 and 16.2+/-0.4 mg/kg/d for dexfenfluramine. The drug concentration was about 36% in the fetal brain compared with the adult brain. The maternal and the offspring hearts, including mitral and aortic valves, of fenfluramine-exposed mice were indistinguishable from the placebo-exposed mice. The duration of gestation and the litter size were the same between the treatment groups. The mean body weights, body lengths, and head circumferences and early functional testing did not differ significantly between the fenfluramine or dexfenfluramine-exposed offspring and the placebo-exposed offspring. There were no significant treatment differences in growth measured as body weights to PND 120. Neither fenfluramine formulation, given before conception and during gestation, impacted cardiac development and long-term growth of the mice offspring.
Abnormalities, Drug-Induced↗
Behavioral changes in developing mice after prenatal exposure to paroxetine (Paxil)
OBJECTIVE: The aim of this study was to conduct in a randomized, placebo-controlled manner behavioral testing on mice offspring exposed prenatally to the selective serotonin reuptake inhibitor paroxetine. STUDY DESIGN: Forty-one CD-1 mice consumed paroxetine (Paxil, n = 21) or a placebo (n = 20) for 2 weeks before conception and throughout gestation. The daily dose of paroxetine used, 30 mg x kg(-1) x d(-1), is known to achieve concentrations in the rat serum equivalent to the upper therapeutic level in human beings and to achieve concentrations in the fetal rat brain equivalent to those in the adult mouse. Behavioral testing consisted of multiple tasks during early development, followed by motor, anxiety, reproduction, and depression tasks in the juvenile and adult periods. RESULTS: Offspring in the 2 treatment groups showed no statistical differences in many early development tasks (geotaxis, homing, social play) or in locomotor and exploratory activities throughout development. Performances during a depression task (forced swim), anxiety tasks (elevated plus maze as juveniles and adults), and reproduction revealed no treatment differences. Offspring exposed prenatally to paroxetine had a 15% to 25% increase in separation vocalization (P <.04) and a significant increase in male aggression during cage changing (P <.03). CONCLUSION: Prenatal exposure to a clinically relevant dose of paroxetine in mice produced no major behavioral alterations but did heighten performance on select anxiety testing in infant offspring and on aggressive behavior in adult males.
Aggression↗
Placebo-controlled comparison between a single dose and a multidose of betamethasone in accelerating lung maturation of mice offspring.
OBJECTIVE: Our purpose was to determine, in a placebo-controlled manner with a mouse model, whether a multidose of betamethasone is more beneficial than a single dose in accelerating fetal lung maturation. STUDY DESIGN: Ninety gravid CD-1 mice were randomly assigned to 1 of 3 groups (n = 30) to receive either a placebo (0.25 mL subcutaneously) or betamethasone (0.1 mg subcutaneously) as a single dose on gestational day 14 or as a multidose twice daily on gestational day 14 and 15. Ten pregnancies in each group were terminated at gestational day 16.5 to observe the neonatal breathing pattern (scale 0 to 5; 5 is unlabored breathing) and the lung histologic findings (scale 0 to 5; 5 is alveolar budding). The lungs of the offspring belonging to the remaining 20 pregnancies in each group were removed and weighed at postnatal day 1, 3, 5, or 120. RESULTS: Fetuses exposed to a multidose of betamethasone displayed a higher breathing score at gestational day 16.5 than either to a single dose or to the placebo (mean score 4.6 vs 3.8 or 1.3; P <. 001). Alveolar development was greater after exposure to a multidose of betamethasone than after a single dose or after a placebo (mean score 4.4 vs 3.5 or 1.6; P <.001). The lung weights at gestational day 16.5 were less after a multidose of betamethasone than after a single dose of either betamethasone or a placebo (18.3 +/- 1.0 g vs 21.4 +/- 1.3 g or 23.3 +/- 1.3 g; P <.02). The lung/body weight ratio was similarly affected. This reduced weight of the lungs persisted postnatally into adulthood. CONCLUSIONS: With a CD-1 mouse model, a multidose of antenatal betamethasone accelerated fetal lung maturation more than after a single dose but was accompanied with a decrease in lung weight that persisted into adulthood.
Animals↗
Impact of multiple antenatal doses of betamethasone on growth and development of mice offspring.
OBJECTIVE: Our purpose was to determine in a randomized, placebo-controlled manner whether multiple antenatal doses of betamethasone affect long-term growth and development of exposed mouse offspring. STUDY DESIGN: Sixty pregnant CD-1 mice received either two, four, or eight antepartum doses of 0.1 mg betamethasone or placebo. Perinatal outcomes, growth, and development of the offspring were compared in a blinded manner. Variables were compared by analysis of variance or chi 2 testing. RESULTS: Betamethasone-exposed subjects gained less weight during pregnancy and were delivered of fewer live pups, with fewer male survivors and lower birth weights. These trends were dose related. Growth measurements were similar after the neonatal period. No differences in functional development and physical maturation in the offspring were noted. The reproductive capability, perinatal outcomes, and growth and development of the second-generation offspring were unaffected by betamethasone exposure. CONCLUSION: Multiple antenatal dosings of betamethasone, reaching toxic levels, did not have an impact on the long-term growth and development of the surviving mouse offspring.
Animals↗
A placebo-controlled comparison between betamethasone and dexamethasone for fetal maturation: differences in neurobehavioral development of mice offspring.
OBJECTIVE: Our purpose was to determine whether antenatal betamethasone or dexamethasone is the preferred drug by use of neurobehavioral development assessment of exposed mice offspring. STUDY DESIGN: Thirty adult CD-1 mice were randomly assigned to one of three groups (n = 10) to be administered a single subcutaneous dose of either a placebo (0.9% sodium chloride), betamethasone (0.10 mg), or dexamethasone (0.10 mg) on day 14 (74%) of gestation. The offspring then performed a battery of sensory, motor, motivational-anxiety, cognitive, and social tasks. Data were compared with use of analysis of variance, Kruskal-Wallis, or chi2 testing where appropriate. RESULTS: The offspring from the three treatment groups were indistinguishable at birth. Dexamethasone exposure induced a brief developmental delay. Separation anxiety was increased in the dexamethasone-exposed group in the perinatal period, whereas exposure to both corticosteroids decreased anxiety in the juvenile period, continuing into adulthood among male betamethasone-exposed mice. Selective enhancement of a memory process occurred in betamethasone-exposed mice, whereas dexamethasone exposure resulted in a decrement. Socialization as to place preference while awake and asleep varied among the three treatment groups. Corticosteroid treatment did not induce significant changes in sensory, motor, motivation, and learning performances or in reproductive capability and progeny development. CONCLUSION: Subtle differences in offspring performances of neurobehavioral development tasks favored antenatal betamethasone rather than dexamethasone. This finding, along with the knowledge that dexamethasone is less potent in accelerating lung maturity in the fetal mouse, suggests that betamethasone may be the preferred corticosteroid to use when human preterm delivery is imminent.
Animals↗
Hodgkin's disease following non-Hodgkin's lymphoma.
The risk of Hodgkin's disease following non-Hodgkin's lymphoma (NHL) was estimated using information collected by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Histopathologic material representing both diagnoses was reviewed for 11 patients in whom Hodgkin's disease was reported after NHL. Diagnoses of both diseases were confirmed in nine patients. Comparisons with population rates indicated that patients with NHL are at an almost threefold risk of subsequently having Hodgkin's disease. Survival in this series was poor; seven of the nine patients died within 16 months after the diagnosis of Hodgkin's disease.
Adult↗
Delta-positive T-cell lymphoma that produces interferon gamma.
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Histiocytosis, Non-Langerhans-Cell↗
My4 antibody staining of non-Hodgkin's lymphomas.
The My4 antibody, one of a number of monoclonal antibodies that react with the CD14 antigen, was originally reported to weakly stain monocytes, macrophages, and granulocytes. However, recent studies have shown that the My4 antibody also stains normal peripheral blood B lymphocytes and some subtypes of B-cell non-Hodgkin's lymphoma. Thus, the authors have studied a large series of non-Hodgkin's lymphomas stained with the My4 antibody. In frozen sections of reactive lymph node biopsy specimens, the My4 antibody strongly stained mantle zone B lymphocytes and weakly reacted with dendritic reticulum cells and histiocytes. In a series of 245 non-Hodgkin's lymphomas, the My4 antibody stained 111 (45%) cases: 108 of 189 (57%) B-cell lymphomas, 3 of 50 (6%) T-cell lymphomas, and 0 of 6 null cell lymphomas. My4-positive B-cell lymphomas occurred in all histologic subtypes with the exception of small noncleaved cell lymphomas. Follicular lymphomas were most often My4 positive (82%). My4 antibody staining showed no correlation with Working Formulation grade. All three My4-positive T-cell lymphomas had a mature T-cell phenotype. Seventy-six of the 111 (68%) My4-positive lymphomas were also analyzed with at least one other anti-CD14 antibody, either Mo2 and/or Leu-M3. In all cases the antigens that react with Mo2 and Leu-M3 were not expressed. Thus, the staining of reactive and neoplastic B cells by My4 appears to be unique to this antibody and is not a feature of all anti-CD14 antibodies.
Antibodies, Monoclonal↗