Biomedical subjects

R L Cooper

Publications and source records attributed to R L Cooper.

At least 127 records · Page 7Linked to original sources

PubMed1989

Effect of lindane on hormonal control of reproductive function in the female rat.

The effect of the gamma isomer of 1,2,3,4,5,6-hexachlorocyclohexane, lindane, on reproductive function in the female rat was examined in two experiments. In the first experiment, chronic treatment with 0, 5, 10, 20, and 40 mg/kg lindane delayed vaginal opening and disrupted ovarian cyclicity until approximately 110 days of age. Thereafter, regular ovarian cycles were present in the majority of females in all dose groups. When killed on the day of vaginal proestrus, the females receiving the two higher doses of lindane had smaller pituitary and uterine weights, lower serum and pituitary luteinizing hormone (LH) and prolactin, and higher pituitary follicle stimulating hormone (FSH) concentrations than the oil-treated control females. Serum estrogen concentrations were not different from controls in the 5 and 20 mg/kg groups, significantly greater than the controls in the 10 mg/kg group, and significantly less than the controls in the group receiving 40 mg/kg. In a second experiment, the uterine weight and pituitary hormone response of 28-day-old, lindane-treated females to a 10-micrograms injection of estradiol benzoate (EB) were investigated. The uteri of the lindane-treated prepubertal females were smaller than controls at 30 hr after EB injection. Furthermore, the EB-induced increase in serum luteinizing hormone, observed at 30 hr after EB injection, was lower in the lindane-treated animals. Similarly, the reduction in pituitary LH, FSH, and prolactin induced by EB was not as great in the lindane-treated animals as in the controls. Serum estrogen concentrations in the lindane-treated animals were not different from controls. These data indicate that lindane may effectively block the response of estrogen-dependent tissues to this ovarian steroid hormone and that this apparent antiestrogenic effect of lindane is responsible for the disturbances observed in the neuroendocrine control of ovarian function in the rat.

Animals↗

PubMed1989

Serum and testicular testosterone and androgen binding protein profiles following subchronic treatment with carbendazim.

While the general toxicity of the benzimidazole pesticides for mammals is low, one of these compounds, carbendazim (MBC), causes degeneration of testicular tissue and decreases spermatogenic activity at doses well below the LD50 value. A study conducted by S. D. Carter, R. A. Hess, and J. W. Laskey (1987, Biol. Reprod. 37, 709-717) showed that treatment with 400 mg/kg/day MBC resulted in severe seminiferous tubular atrophy and infertility. Since spermatogenesis is an androgen-dependent process, we characterized the effects of MBC (0-400 mg/kg/day) on the endocrine function of the rat testes. Following subchronic (85 day) exposure, serum hormones (TSH, LH, FSH, and Prl) were measured as were androgen binding protein (ABP) and testosterone in testicular fluids (interstitial fluid and seminiferous tubule fluid). In addition, the functional capacity of the Leydig cell to secrete testosterone was assessed in vitro following an hCG challenge. Subchronic treatment with MBC at doses of 50-100 mg/kg/day had no effect on pituitary or testicular hormone concentrations: 200 mg/kg/day elevated the testosterone concentration in the seminiferous tubule fluid and the ABP concentration in both the interstitial fluid and the seminiferous tubule fluid without affecting serum testosterone or ABP concentrations. The 400 mg/kg/day dose resulted in increased concentration of both testosterone and ABP in the interstitial fluid and seminiferous tubule fluid and elevated serum ABP, with no change in serum testosterone. This endocrine profile is consistent with the testicular atrophy and "Sertoli cell-only" syndrome seen in these animals as reported by Gray et al. (1987, Toxicologist 7, 717). We conclude that seminiferous tubule fluid testosterone may be a result of two factors: (1) increased interstitial fluid testosterone concentrations and (2) decreased testosterone outflow from the testis to the general circulation. Also, increased ABP in the interstitial fluid may reflect a change in the relative secretion of ABP into the interstitial fluid and the seminiferous tubules.

Androgen-Binding Protein↗

PubMed1989

A new method for continuous intraocular drug delivery.

A novel device for the continuous intraocular delivery of drugs is described. The active intraocular component of the device is made from hollow haemodialysis fibres. During operation, the drug to be administered diffuses from a small extraocular reservoir to the intraocular fibres, where it passes through the semipermeable walls and into the vitreous body. The delivery of gentamicin by the device into the vitreous body of the cat is compared with direct intraocular injection techniques. Characteristics of the process of drug delivery were influenced by the geometry and design of the device. A reservoir concentration of 10 g/L gentamicin sulphate in a device with four fibres, each 5 mm long, resulted in stable vitreal gentamicin levels of 104 to 128 mg/L at 10 hours. Intravitreal injection of 0.1 ml of a 10 g/L solution of gentamicin caused localised peaks of intravitreal gentamicin concentration in the range 1180 to 3296 mg/L, before falling to 356 to 665 mg/L at 10 hours. The device provides the opportunity of a more controlled and continuous drug delivery, thus avoiding the high localised concentrations that may occur with direct injection techniques in which the required dose is delivered as a bolus. Refinement of a device of this type may result in a clinically useful method of intraocular drug delivery for drugs which present a risk of localised retinal toxicity or require repetitive administration with conventional intraocular injection techniques.

Animals↗

PubMed1989

'Hot' corneal grafts--a long-term study.

A six-year follow-up of nine of 13 eyes treated by therapeutic keratoplasty for suppurative keratitis is described. One of the thirteen cases died three years after surgery and three were lost to follow-up. Two of the nine refused reoperation after early graft failure. Of the remaining seven, three had retained good functional visual acuity. Three of the penetrating keratoplasties required regrafting two to four years later, when conditions were less critical. Long-term results indicate that therapeutic keratoplasty may be an alternative modality for the management of suppurative keratitis with satisfactory long-term optical results.

Adult↗

PubMed1989

Fourier analysis of the nerve fiber layer by digital imaging techniques.

We introduce a new method to examine the retinal nerve fiber layer (RNFL) that may detect early changes in its structure due to glaucoma. Viewed in the conventional manner, in a plane perpendicular to the retina, we get an estimation of the structural integrity of the RNFL. Viewed from a plane parallel to the retina, the RNFL forms a contour surface of hills and valleys. In our method red free fundus slides are digitally acquired. A waveform, representing a topographic profile cut through the resulting representation of the RNFL contour surface, was analyzed using Fourier's transform. Three cycles/mm in the Fourier power spectrum was used as an arbitrary cutoff to discriminate normal from glaucomatous RNFL. The Fourier power spectrum from normal RNFL was shifted to higher spatial frequencies, while the power spectrum from glaucomatous RNFL was shifted to lower spatial frequencies. Thus, Fourier Analysis can reveal information about such a wave form which is not obvious by visual inspection or by densitometric techniques. This method may allow for an even earlier diagnosis of injury to the optic nerve due to glaucoma.

Fourier Analysis↗

PubMed1989

Pharmacokinetics of intravitreal injection. Assessment of a gentamicin model by ocular dialysis.

Intravitreal drug administration is the treatment of choice for bacterial endophtalmitis, but improved knowledge of vitreal pharmacokinetics is essential for the development of optimal antibiotic regimes. We used our recently developed sampling device to estimate vitreal gentamicin concentrations for up to 30 hr after an intravitreal bolus injection of gentamicin. The device is based on the principle of dialysis, whereby a constant flow rate of dialysate through a loop of dialysis fiber in the vitreous attains a gentamicin concentration proportional to the intravitreal gentamicin level around the fiber. The dialysate is continuously recovered and the collected samples then assayed for gentamicin. Normal cat eyes and those with induced bacterial endophthalmitis formed the two groups tested. Concentration-time data fitted well to an open single compartment pharmacokinetic model that incorporated the processes of transfer of drug from the injection site to the sampling site (a function of diffusion within the vitreous), and the elimination from the sampling site (a function of elimination from the vitreous). The initial phase of transfer between the injection and sampling site was rapid and rates were comparable in the two groups. Elimination rate constants were uniformly greater in infected eyes than in controls (0.107 hr-1 compared to 0.055 hr-1). Aqueous humor gentamicin concentrations in control eyes varied between 3 and 6 times those found in fellow infected eyes at the end of each experiment. Accelerated elimination of gentamicin from the vitreous body of eyes with endophthalmitis may be explained by increased permeability of the blood-retinal barrier.

Animals↗

PubMed1988

Changes in testicular and serum hormone concentrations in the male rat following treatment with m-dinitrobenzene.

m-Dinitrobenzene (m-DNB)-induced testicular atrophy has been attributed to a direct effect upon the germinal epithelium. However, such degenerative changes in the germinal epithelium should induce shifts in the testicular hormonal milieu, which would in turn alter the hypothalamic-pituitary gonadal axis in general. This study evaluated the endocrine status of male rats (killed 3 hr, 24 hr, 1 week, and 2 weeks) following a single oral dose of m-DNB (32 mg m-DNB/kg). Serum and pituitary leuteinizing hormone, follicle-stimulating hormone (FSH), and protactin and hypothalamic gonadotropin-releasing hormone (GnRH) concentrations were determined. Testosterone and androgen-binding protein concentrations in serum, interstitial fluid, seminiferous tubule fluid, and caput epididymis were also determined. In vitro basal and hCG-stimulated testosterone release was determined in the decapsulated testis. Results of the present study indicate that pituitary hormone concentrations and hypothalamic GnRH were unaffected after a single oral dose of m-DNB. Serum FSH was elevated at 2 weeks. There was a transient decrease in serum testosterone at 24 hr, which returned to control values at 1 and 2 weeks. Interstitial fluid, seminiferous tubule fluid, and caput epididymal testosterone concentrations were increased at 1 and 2 weeks. Basal testosterone release in vitro was increased at 2 weeks, while hCG-stimulated testosterone release was increased at 1 and 2 weeks. Androgen-binding protein concentrations in serum and interstitial fluid were increased at 1 and 2 weeks. Androgen-binding protein was increased at 24 hr and 1 week in seminiferous tubule fluid, but returned to control concentrations by 2 weeks. However, the total tubular content of androgen-binding protein was dramatically decreased at 2 weeks. Androgen-binding protein in the caput epididymis was unaltered following m-DNB treatment. These data demonstrate that m-DNB exerts a direct effect on the testes and not through alterations in hypothalamic and pituitary control of gonadal function.

Animals↗

PubMed1988

Age-related changes in the regional distribution of hormones in the male rat anterior pituitary.

Some heterogeneity in the localization of hormone-containing cells has been reported in the mammalian anterior pituitary. Since age-related changes are present in pituitary hormone concentrations, the present study was designed to explore if such changes in the male rat are regionally consistent. The results show clear geographic patterns in the presence of immunoreactive LH, FSH, prolactin and TSH. In the two year-old male, specific regional declines in hormone concentrations were present. With one regional exception, such was not the case when values were expressed in total hormonal content. A fall in gonadotropins still appeared in the medial area of the most caudal strip. The results suggest that with age, there is a displacement of hormone-containing cells in the pituitary and that for the gonadotropes this effect appears to be more prominent within the medio-caudal area.

Aging↗

PubMed1988

Ocular dialysis. A new technique for in vivo intraocular pharmacokinetic measurements.

A new technique, using the principle of dialysis, enables continuous determination of the concentration of compounds within the vitreous humor of the eye. A semipermeable catheter inserted into the cat vitreous cavity was continuously perfused with a normal saline solution. Gentamicin concentration in the dialysate, after subconjunctival or intravitreal injection, was used to calculate gentamicin concentration in the vitreous from the catheter's recovery ratio, as calibrated in vitro. After subconjunctival injection, no gentamicin was detected in the vitreous for up to eight hours. From four to eight hours after intravitreal injection of approximately 100 micrograms of gentamicin sulfate, its vitreal concentration ranged from 30 to 80 mg/L and from nine to 16 hours it fell from 26 to 22 mg/L. This method may prove useful for the study of the pharmacokinetics of many drugs and metabolites in the eye.

Animals↗

PubMed1988

Possible antiestrogenic activity of lindane in female rats.

During chronic peroral (PO) treatment of weanling, female Fischer 344 rats with daily injections (0.069 mmol/kg) of either 1,1'-(2,2,2-trichloroethylidene) bis [4-chlorobenzene] (p,p'-DDT), 2,4-dichlorophenoxy acetic acid (2,4-D), or gamma-hexachlorocyclohexane (lindane), the lindane treatment induced a significant 20% increase in body weight after 110 days. Further investigation with 0, 5, 10, 20, and 40 mg/kg lindane confirmed a significant increase in average body weight gain at the two highest doses after ten weeks of treatment. Significantly greater food consumption was observed, and the Lee index indicated that lindane treatment induced obesity. In addition to obesity, lindane caused a delay in vaginal opening, disrupted estrous cycling, reduced pituitary and uterine weight, and elevated food consumption during proestrus (when appetite is normally suppressed by estradiol). These responses suggest that, by inducing alterations in the reproductive function of the female rat and by interfering with hormonal regulation of energy balance, lindane may be antiestrogenic rather than estrogenic as previously proposed.

Animals↗

PubMed1988

Computerised densitometry of red-free retinal photographs correlated with automatic perimetry.

An image analyser installed in a 16 bit personal computer was used to measure grey levels in red free photographs of normal and glaucomatous eyes. Regional photographic image intensity and density were correlated with Humphrey Field Analyser results for corresponding areas of visual field. Two methods for standardising photographic exposure by histogram equalisation and slide were compared in two groups of eyes from 13 subjects. For histogram equalisation, r2 varied from 0.16 to 0.29 for linear fits in temporal retinal quadrants. For the histogram slide, r2 varied between 0.19 to 0.45 for linear fits. Similar results were found for mean histogram equalised image intensity versus Humphrey Field Analyser global indices: Mean Deviation, (r2 = 0.27) and Pattern Standard Deviation, (r2 = 0.37). For histogram equalised image data, resistant line analysis showed a linear goodness of fit of 0.92 and for histogram slide goodness of fit was 0.97 for upper and 0.87 for lower temporal quadrants.

Color↗

PubMed1988

Rat brain catecholamine release at 1, 10, 20, and 100 ATA heliox, nitrox, and trimix.

The pattern of neurotransmitter release in the rat caudate and hypothalamus was studied following exposure to pressure in combination with various gas mixtures. The caudate was selected for its control of extrapyramidal motor output. The hypothalamus was studied because of its involvement in autonomic responses. The neurotransmitters chosen for study were norepinephrine (NE) and dopamine (DA). Change of neurotransmitter concentration from control values and neurotransmitter turnover rate were chosen as measures of neuronal activity in the selected brain regions. Exposure to 100 ATA heliox resulted in a significant (P less than 0.05) increase in hypothalamic DA concentrations; however, NE concentrations remained relatively unchanged. One hundred ATA heliox produced the opposite effect on caudate DA concentrations; these values dropped to 1% of chamber control values. High partial pressures of nitrogen as seen with 100 ATA trimix and 20 ATA nitrox resulted in significant decreases in both DA and NE concentrations (both P less than 0.05) in the hypothalamus. These same exposures also produced significant decreases in DA concentrations in the caudate (P less than 0.05). Regional (caudate vs. hypothalamus) changes in neurotransmitter release in response to different pressures and/or gas mixtures may offer explanations for the physiologic and neurologic changes observed during nitrogen narcosis and high pressure nervous syndrome.

Animals↗

PubMed1987

Age-related alterations in the stimulated release in vitro of catecholamines and luteinizing hormone-releasing hormone from the male rat hypothalamus.

Using an in vitro perifusion system, the present study investigated the possibility that alterations in catecholamine and luteinizing hormone-releasing hormone (LHRH) secretion from the male rat mediobasal hypothalamus are present during the period of middle-age. The results indicate that, while tissue concentrations and baseline secretion of norepinephrine, dopamine and LHRH were similar between age groups, the patterns of dopamine and LHRH release in response to a series of depolarizing stimuli was different in the older animals. After all challenges, dopamine concentrations in the perifusate declined much more sharply for the middle-aged group, a finding that may be associated with a decrease with age in the pool of transmitter available for ready release. Also, tissue fragments from young adult rats were able to maintain the release of LHRH to a greater extent than tissue from the middle-aged animals, but only for the initial challenge period. The typical episodic pattern of LHRH release appeared to be disrupted in the older group following a second stimulus. It is possible that these age-related changes are early components of a disruption in the hypothalamic mechanisms governing gonadotropin secretion.

Aging↗

PubMed1987

Molteno tube implants: long-term results.

The Molteno implant is a well recognised method of treating end-stage secondary glaucoma. Several variations of the technique have been described in the literature, but few reports of long-term studies have been published. This paper reports the results of a series of patients followed for two to six years. Indications for the procedure and results are put forward.

Adolescent↗

PubMed1987

Laser iridotomy.

The outcome of 64 consecutive argon laser iridotomies was examined retrospectively. The patients were followed for a mean of 18 months. Argon laser iridotomy was shown to be effective in treating chronic angle-closure glaucoma, those patients without field loss faring better than those with field loss: 34% of the latter group eventually required a trabeculectomy. It is suggested that patients be carefully followed-up after iridotomy, particularly those with loss of visual field.

Adult↗

PubMed1987

Pharmacodynamics and pharmacokinetics of ethanol, diazepam and pentobarbital in young and aged rats.

Sleeping time was measured in groups of old and young rats following the intraperitoneal injection of pentobarbital (39.5 mg.kg-1), diazepam (30 mg.kg-1) and ethanol (3 g.kg-1). Concentrations of pentobarbital, and unbound and total diazepam in serum, and ethanol in breath were quantified; as well as whole brain concentrations of diazepam and N-demethyldiazepam. Healthy old rats slept significantly longer than young rats after receiving diazepam and ethanol but not pentobarbital. There were no significant differences in serum or whole brain concentrations of diazepam or N-demethyldiazepam between healthy young and old rats. There were also no changes in the serum pentobarbital or breath ethanol concentrations between the young and old rats. Increases in pharmacologic effect that occur with aging may be caused by alterations in pharmacokinetic parameters or changes at the site of drug action. The cause of an increased pharmacodynamic effect depends upon the specific drug, possibly because these compounds affect the same receptorionophore complex at different sites.

Aging↗

PubMed1986

Effects of low subchronic doses of methoxychlor on the rat hypothalamic-pituitary reproductive axis.

The pesticide methoxychlor (MXC) is known to possess a weak estrogenic action and has been found to have a number of toxic effects on the rodent reproductive system, primarily at the gonadal level. The purpose of this study was to explore the influence of MXC on the pituitary and hypothalamic components of the male reproductive system at dose levels that were without detectable testicular effects. At 21 days, male Long-Evans rats were gavaged daily with 25 or 50 mg/kg MXC in corn oil. Controls received vehicle only. After 8 weeks of dosing, no significant changes were seen in serum LH, FSH, or prolactin, nor in the pituitary concentrations of LH or FSH. Pituitary prolactin was elevated for both doses, and pituitary fragments perifused in vitro released more prolactin than did controls. The concentration of gonadotropin-releasing hormone (GnRH) was higher in the mediobasal hypothalamus, but only for the 50-mg/kg group. At this dose, there was a corresponding increase in the KCl-stimulated release of GnRH. The data suggest that previously reported reproductive effects of MXC may be mediated, at least in part, through an elevation in prolactin concentration and release, which in turn is able to influence hypothalamic levels of GnRH. This prolactinemic effect may well represent an early component of the adverse action of MXC on the reproductive system.

Administration, Oral↗

PubMed1986

Mass screening of the optic disc for glaucoma: a follow-up study.

Because of the high false positive and negative rates for detection of suspects when screening for glaucoma by tonometry, we screened 12 156 subjects over the age of 40 years or with a stated family history of glaucoma by examining the optic discs. This was followed by Schiotz tonometry. Eight hundred and twelve (6.7%) suspects were referred to their primary physician for investigation by an ophthalmologists. A database program was used to send out follow-up letters to both suspects and ophthalmologists. Three hundred and seventy-nine replies were received from ophthalmologists: 100 (26.4%) of these suspects had ocular hypertension and 68 (17.9%) had glaucoma. Of these 68, 60 (15.8%) had chronic simple glaucoma, five (1.3%) had secondary open-angle glaucoma, and three (0.79%) had primary closed-angle glaucoma. The prevalence of all types of glaucoma in this group for which follow-up was obtained was at least 0.56% of the total number screened. Assuming that the prevalence was similar for the group for whom no replies were obtained, the prevalence of glaucoma in this population is approximately 1.19%. Screening by optic disc examination is therefore likely to detect most cases of glaucoma.

Aged↗