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Biomedical subjects

R L Collins

Publications and source records attributed to R L Collins.

At least 91 records · Page 5Linked to original sources

Observational learning of a left-right behavioral asymmetry in mice (Mus musculus).

B6D2F1 hybrid mice that were allowed to observe a trained female mouse open a pendulum door to the right (or to the left) to enter a food compartment later solved this problem faster than pupils that had been placed behind a visual barrier. Male pupils that had observed a "left-handed" teacher performed sinistrally; males that had observed a "right-handed" model performed dextrally. Female pupils did not exhibit their demonstrator's laterality. Observational learning may provide a means to maintain certain lateralized behaviors. Such social learning may lead to the emergence of local traditions and to the cultural diffusion of behavioral asymmetries.

Animals↗

The effect of intraperitoneal progesterone on postoperative adhesion formation in rabbits.

The immunosuppressive and anti-inflammatory properties of progesterone (P) have been established. The authors investigated whether the intraperitoneal instillation of P would lessen postoperative adhesion formation in New Zealand white rabbits undergoing pelvic surgical procedures. In phase I, severe, peritoneal lesions were made in the right uterine horn (n = 48). Animals were randomized to receive equal volumes of either (1) Ringer's lactate (RL); (2) 32% dextran 70 (HY; Hyskon Division, Pharmacia, Piscataway, NJ); (3) 500 mg P in oil (PO); or (4) 500 mg aqueous P (PA) at initial laparotomy. In phase II, the distal right uterine horn, including the mesosalpinx, was excised and microsurgical anastomosis was accomplished (n = 45). Aqueous P was not used in phase II; otherwise, the same agents were tested. Six weeks later, the severity of the adhesions formed was graded. The mean adhesion scores for the RL and HY groups were low for the right side in both phases and did not differ (P greater than 0.05). In contrast, higher scores were observed in all the P groups, regardless of the P preparation used or the surgical procedure performed (P less than 0.05).

Animals↗

Evaluation of nabumetone in the treatment of active adult rheumatoid arthritis.

The safety and efficacy of nabumetone and placebo were compared in a three-week, multicenter, double-blind, randomized, parallel evaluation involving patients with class II or III definite or classical rheumatoid arthritis. No patient received concomitant treatment with other nonsteroidal anti-inflammatory agents; however, disease-modifying agents (gold, steroids) were permitted. Of the 139 patients who entered the double-blind phase of the study, all were evaluable for safety, and 113 were evaluable for efficacy. Sixty-one patients received 1,000 mg of nabumetone per day at bedtime, and 50 were given placebo tablets; patients in both groups were permitted up to 3,250 mg of acetaminophen per day as needed for pain. After three weeks, nabumetone-treated patients exhibited a greater degree of improvement from baseline than did the placebo-treated patients, and the degree of improvement was statistically significant for four of seven variables.

Adolescent↗

Six-month multi-center study comparing nabumetone with naproxen in the treatment of osteoarthritis.

This six-month, double-blind, controlled, randomized, parallel study at 13 medical centers compared the safety and efficacy of nabumetone (1,000 mg taken at bedtime) with that of naproxen (250 mg twice daily) in the treatment of osteoarthritis in symptomatic adult outpatients. Five efficacy parameters were measured: patients' assessment of overall osteoarthritis activity and pain, physicians' assessment of overall osteoarthritis activity and pain, and physicians' assessment of pain with respect to a declined activity. All 489 patients who took medication were included in the evaluation of safety, and 455 patients (227 in the nabumetone group and 228 in the naproxen group) were evaluated for efficacy. Significant improvement in all five efficacy parameters occurred in both groups. No significant differences were found between the two groups at the end of the study in any of the five efficacy parameters. Twenty-three percent of nabumetone and 17 percent of naproxen patients withdrew from the study for lack of efficacy. At least one possible or probable treatment-related adverse experience was reported for 45 percent of nabumetone-treated patients and 42 percent of those given naproxen, and in 19 percent of the nabumetone-treated and 18 percent of the naproxen-treated patients these experiences were moderate or severe. However, only 7 percent of patients in each group withdrew from the study due to adverse experiences. Nabumetone and naproxen have comparable safety and efficacy, suggesting that a single, nighttime dose of nabumetone is a convenient, effective, and safe treatment for osteoarthritis.

Adult↗

Relationship between sex-role behaviors and alcohol consumption in undergraduate men and women.

The relationship between sex-typed behaviors and alcohol consumption is examined in a questionnaire study involving male and female undergraduates. A multiple regression analysis indicated that for women, feminine behavior was significantly negatively correlated with total alcohol, beer and distilled spirits consumption. Weight was positively correlated with total alcohol and wine consumption. For men, feminine behavior was negatively correlated with total alcohol, wine and beer consumption. Masculine behavior was positively correlated with total alcohol, wine and beer consumption; weight was negatively correlated with wine consumption. Except in the case of wine, sex-role variables were found to account for more of the variance in alcohol consumption than did biological gender. Feminine behavior was negatively associated with alcohol consumption for both men and women. Masculine behavior was positively associated with alcohol consumption for men.

Adolescent↗

Long-acting gonadotropin hormone-releasing hormone analog used to treat uteri.

Because the size of leiomyomata uteri often decreases significantly after menopause, the authors elected to employ a long-acting gonadotropin hormone-releasing hormone analog (GnRH-alpha) (imbzl-D-His6-Pro9-Net-GnRH) to create a state of pseudomenopause in six patients with leiomyomata uteri diagnosed on the basis of pelvic examination and confirmed by pelvic ultrasonography. Patients received daily, subcutaneous injections of GnRH-alpha (4 micrograms X kg-1 X 24 hour-1) for 6 months. Uterine size (13.8 +/- 4 weeks [mean +/- standard deviation (SD), n = 6]) was determined by pelvic examination and uterine volume (533.9 +/- 394 ml [mean +/- SD, n = 6]) was determined by pelvic ultrasonography before medical therapy was begun. They observed a decrease in uterine size by pelvic examination within 4 weeks of the initiation of therapy, and all patients experienced a decrease in uterine size (9.5 +/- 4 weeks [mean +/- SD, n = 6]) (P less than 0.05) within 8 weeks of initiation of therapy. After 6 months of therapy, uterine size was 229.5 +/- 145 ml (mean +/- SD, n = 6). During treatment, plasma estrogen concentrations were assessed intermittently (every 1 to 4 weeks) and remained less than 4 pg X ml-1 throughout the period of therapy. All six patients have discontinued therapy. There has been no increase in uterine size in these patients for a period from 3 to 7 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Lateralized audiogenic seizure: motor asymmetries exhibited and the effects of interrupted stimulation.

Sensitized SJL/J mice were monaurally tested for susceptibility to sound-induced seizure. The acoustic stimulation was interrupted for 15 s at various points during the biphasic pattern of running which these mice characteristically exhibit before seizing. Asymmetries of run directions and side of fall were noted. In addition, a dramatic reduction in seizure incidence was found when the interruption either extended into the period when the later burst of running would have occurred or began during this running burst. Finally, the results indicate that the latencies to the later running burst and the subsequent seizure are determined at or about the time of the onset of the first burst of running.

Acoustic Stimulation↗

Follicular stimulation versus ovulation induction in juvenile primates: importance of gonadotropin-releasing hormone dose.

We evaluated the dose of GnRH administered by 1-min pulsatile infusion necessary to achieve follicle growth vs. the dose needed for ovulation induction. Doses of 6.0, 0.6, and 0.06 micrograms GnRH were given to juvenile monkeys iv in 1 min once per h for 4 consecutive months. Monkeys receiving hourly 6.0-micrograms doses of GnRH had cyclic elevations of serum estradiol and had menses, but did not ovulate, as evidenced by lack of a corpus luteum at laparoscopy and consistently low progesterone concentrations. These monkeys ovulated only when hCG was administered near midcycle as a surrogate LH surge. In contrast, monkeys receiving 0.6-microgram doses of GnRH frequently had normal ovulatory menstrual cycles and characteristic elevations of progesterone during the luteal phase. Typically, juvenile monkeys receiving hourly 0.06-microgram doses of GnRH initially had development of a dominant follicle contemporaneous with a rise of serum estradiol, but never ovulated or had any subsequent follicular growth or elevated steroidogenic activity. In summary, ovarian follicular development and steroidogenesis in juvenile monkeys can be initiated by doses of GnRH ranging from 0.06-6.0 micrograms/h, although spontaneous ovulation and normal luteal function occurred frequently only with the 0.6 micrograms/h pulses of GnRH. Thus, the dose range of pulsatile GnRH needed for follicle growth is much broader than that required for induction of ovulatory menstrual cycles.

Animals↗

Blockade of the spontaneous midcycle gonadotropin surge in monkeys by RU 486: a progesterone antagonist or agonist?

Preovulatory ovarian secretion of progesterone (P4), several hours before the onset of the typical midcycle gonadotropin surge, occurs in humans and monkeys. We investigated the potentially obligatory role of preovulatory P4 secretion in stimulating the midcycle LH surge by administering a potent P4 antagonist, RU 486(17 beta-hydroxy-11 beta-[4-dimethylaminophenyl-1]17 alpha-[prop-1-ynyl]estra-4,9-dien-3-one), to sexually mature, normally ovulatory cynomolgus monkeys on days 10-12 of the menstrual cycle (n = 18). Monkeys were randomized to receive RU 486 alone (5 mg/day, im; group I); RU 486 plus dexamethasone (1 mg/day, im; group II); dexamethasone alone (group III); or vehicle (ethanol; 0.5 ml; group IV). Before drug treatment, the follicular phases were quite similar among groups. The administration of RU 486 blocked (delayed) the expected gonadotropin surge, despite rising estrogen concentrations (greater than 250 pg/ml). The expected LH surge was delayed by RU 486 (n = 5) or RU 486 with dexamethasone (n = 3) until 36 +/- 7 (+/- SEM) and 27 +/- 8 days in groups I and II, respectively. In contrast, groups III (n = 3) and IV (n = 5) had timely midcycle surges after the administration of dexamethasone or vehicle alone (4 +/- 2 and 6 +/- 2 days, respectively). The intermenstrual interval was lengthened by RU 486 administration in both group I and II animals (61 +/- 6 and 54 +/- 6 days) compared to controls (30 +/- 2; P less than 0.0001). In summary, RU 486 effectively blocked imminent midcycle gonadotropin surges, delayed subsequent folliculogenesis, and significantly extended the menstrual cycle length. If RU 486 acted as a pure P4 antagonist, then P4 is necessary for timely midcycle gonadotropin surges to occur. However, recent evidence showing agonistic properties of RU 486 (in the virtual absence of P4) at both endometrial and pituitary levels may favor a P4-like (agonistic) blockade of the estrogen-induced FSH/LH surges by RU 486.

Animals↗

Prevention of gonadotropin-releasing hormone antagonist induced luteal regression by concurrent exogenous pulsatile gonadotropin administration in monkeys.

We studied the effects of a gonadotropin-releasing hormone (GnRH) antagonist given in midluteal phase. Monkeys received the antagonist (n = 6), [N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10]-GnRH: hydrochloride or vehicle (n = 5). Absent luteinizing hormone (LH) pulsatility, diminished progesterone (P) secretion (P less than 0.01), luteal phase truncation and premature menstruation were observed in all receiving the antagonist. To investigate the site of action, four females received pulsatile exogenous human menopausal gonadotropins (hMG) concurrently, whereby P secretion was sustained and premature menstruation was averted. Equivalent treatment using "pure" FSH, failed to sustain P levels and timely menstruation occurred, confirming the continuing dependence of the corpus luteum on LH. The antagonist acts by central suppression and in turn, diminishes P biosynthesis. LH is luteotropic, since pulsatile LH (hMG), not "pure" FSH, prevented luteolysis.

Animals↗

Brain size and shape in strongly and weakly lateralized mice.

Mice from two selected lines differing markedly in their degree of lateralization, and from a random-bred control line, were studied. The brains of strongly lateralized mice were found to be heavier, and those of weakly lateralized mice to be lighter, than those of control mice of equivalent body weight; the degree of cerebral asymmetry was found to be least in weakly lateralized mice; and the corpora callosa of both selected lines were smaller than those of control mice. These findings are tentatively interpreted in terms of the effects of different behavioral strategies on the development of the central nervous system.

Agenesis of Corpus Callosum↗

Structural asymmetries in brains of mice selected for strong lateralization.

The brains of 18 female mice from two lines selectively bred for lateralization of paw preference were investigated for morphological asymmetries in 5 horizontal sections from mid-dorsoventral planes. Cortical thickness was measured at orbitofrontal, somatosensory and lateral entorhinal regions; volume measures included the hippocampal formation and the striatum. Mice of the strongly lateralized line had stronger asymmetries in 4 of the 5 variables. Discriminant analysis showed that the two mouse lines could be differentiated best by their asymmetries in orbitofrontal cortex and hippocampus (P less than 0.02).

Animals↗

Rheumatoid arthritis and small airways function. Effects of disease activity, smoking, and alpha 1-antitrypsin deficiency.

The sensitive pulmonary function tests of change in maximum expiratory flow (delta Vmax 50) and volume of isoflow were used to determine the effects of rheumatoid arthritis (RA), smoking, and alpha 1-antitrypsin deficiency phenotypes on peripheral airways. Patients were prospectively divided into 4 groups: 14 smokers with RA, 12 nonsmokers with RA, 11 smokers without RA, and 13 nonsmokers without RA. delta Vmax 50 was the most discriminating variable and demonstrated significant small airway obstructive disease in the first 3 groups, with an additive effect in the group of smokers with RA. An increased incidence of the alpha 1-antitrypsin-deficient MS phenotype was seen in the RA smoker group, and this phenotype was associated with severe pulmonary disease.

Arthritis, Rheumatoid↗

Human menopausal gonadotropin/human chorionic gonadotropin-induced ovarian hyperstimulation with transient hyperprolactinemia: steroidogenesis enhanced during bromocriptine therapy in monkeys.

To examine the role of gonadotropin-induced hyperprolactinemia on reproductive function, 17 euprolactinemic ovulatory monkeys were given extended fixed dose regimens of human menopausal gonadotropin (hMG) (12 days), followed by hCG the next day, and some animals then received bromocriptine. All animals were given hMG/hCG from day 3 (D3) until D14, with hCG on D15; those in group I (n = 12) received no further therapy, while those in group II (n = 5) received bromocriptine (0.25 mg/kg X day, im) daily from the day of hCG administration until menses. Ovarian hyperstimulation developed to various degrees in all animals. Based on serum estradiol (E2) levels, 13 were high responders (E2, greater than 1000 pg/ml), 2 were medium responders (E2, 500-1000 pg/ml), and 2 were low responders (E2, 150-500 pg/ml). In group I, transient hyperprolactinemia occurred in the luteal phases in 8 of the 12 animals compared to the follicular phase levels in the same animals (P less than 0.01). In group II, bromocriptine treatment in the luteal phase prevented hyperprolactinemia, but there was no change in the menstrual cycle or luteal phase lengths; however, significant luteal phase increases in progesterone (P less than 0.005) and E2 (P less than 0.02) secretion occurred during bromocriptine therapy. Deliberate hMG/hCG studies in euprolactinemic women seem indicated to learn whether women so treated experience estrogen-progesterone-induced hyperprolactinemia like that in monkeys and, if so, to determine its consequences on the reproductive process.

Animals↗

Endocrine consequences of prolonged ovarian hyperstimulation: hyperprolactinemia, follicular atresia, and premature luteinization.

Eighteen normal ovulatory cynomolgus (Macaca fascicularis) monkeys were given an extended fixed-dose regimen of human menopausal gonadotropin (hMG), which was followed by human chorionic gonadotropin (hCG) administration. Ovarian hyperstimulation developed in responsive subjects to various degrees. Based on their serum estradiol (E2) response, 16 were arbitrarily categorized as high responders (E2 greater than 1000 pg/ml), 3 were medium responders (E2 500 to 1000 pg/ml), and 2 were low responders (E2 150 to 500 pg/ml). Interestingly, one female did not respond to exogenous gonadotropin therapy. The endocrine consequences of prolonged ovarian hyperstimulation include (1) hyperprolactinemia in the luteal phase of 50% of responsive monkeys; (2) frequent atresia of growing follicles, marked by a precipitous decline in serum E2, despite continuous hMG therapy; and (3) seven monkeys with premature serum progesterone elevations up to 1 week before hCG injection, without an overt luteinizing hormone surge. Only 1 of 18 females manifested a typical midcycle luteinizing hormone surge during hMG/hCG treatment. These findings have physiologic implications that are relevant to ovulation induction and in vitro fertilization therapy in infertile women.

Animals↗