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Biomedical subjects

J Seggie

Publications and source records attributed to J Seggie.

At least 19 recordsLinked to original sources
PubMed1992

Glycine toxicokinetics: vitreous fluid concentration and visual impairment.

We report the results of kinetic experiments in sheep. Following systemic loading with 45 g glycine, plasma, cerebral spinal fluid (CSF), and vitreous fluid from the vitreous body of the eye were assayed for glycine concentrations. Mean baseline plasma, CSF, and vitreous glycine concentrations were 730, 46, and 191 mumol/L respectively. One hour after loading, values were 21292, 1103, and 1150 mumol/L respectively. During the succeeding 7 h plasma and CSF concentrations fell in parallel but remained above normal. In contrast the vitreous concentrations remained high and did not change significantly during the 7 h post-infusion period. Retinal glycine receptors may be particularly vulnerable to neurotoxic effects of glycine because of these pharmacokinetic properties.

Animals↗
PubMed1991

Retinal pigment epithelium response and the use of the EOG and Arden Ratio in depression.

Supersensitivity to light in depression has been observed with both neuroendocrine and ophthalmological assessment methods. The biological defect underlying this abnormality may be localized in either the photoreceptors, the retinal pigmented epithelium, or some interaction of the two. The present study assessed responses of the retinal pigmented epithelium (RPE). All subjects underwent thorough ophthalmological and mood assessments. The electrooculogram (EOG) was used to measure standing potentials of the RPE in response to light and dark in 20 normal controls and 20 unmedicated depressed patients. Both groups were matched for age, sex, time of day for the procedure, and prior lighting history. Reproducibility of the EOG measure on two independent occasions for 13 control subjects had an intrasubject reliability coefficient of 0.70. The mean +/- SD Arden Ratio (light peak/dark trough) of the control group (2.13 +/- 0.42) compared to the depressed group (2.28 +/- 0.72) showed no statistical difference. There was, however, a significant difference between groups in response to darkness; depressed patients had a lower standing potential in the dark compared to controls, suggesting supersensitivity to light. No difference between groups was detected in standing potentials at baseline or in response to light. Supersensitivity to light in depression may be related to abnormal function of the RPE, but the inherent reliability of the EOG precludes the use of this instrument in pursuing this hypothesis.

Adult↗
PubMed1989

The effect of lithium on pupillary response to pulses of light in sheep.

Administration of lithium carbonate to sheep in the dose range of 600-1800 mg/day resulted in a linearly described rise in lithium levels in plasma and red blood cells. In contrast to the rodent model but in agreement with the human condition, plasma lithium levels exceeded those of red blood cells. Polydipsia and body weight changes were not evident. At plasma levels of 0.70-0.8 mM/l, lithium attenuated the ability of the pupil to constrict in response to 30-sec pulses of light in the 25-150 microW/cm2 intensity range but not the ability to dilate in the dark. Thus, similar to observations in normal human volunteers and bipolar patients, lithium reduces sensitivity to light. The sheep is proposed as a useful model for studying the actions of lithium.

Animals↗
PubMed1989

Antidepressant medication reverses increased sensitivity to light in depression: preliminary report.

1. Sensitivity to blue light was quantified using a Friedman Central Field Analyzer and the Dark Adaptation Threshold procedure. 2. Patients diagnosed as having a major depressive disorder using research diagnostic criteria had dark adaptation thresholds quantified after a 10 day drug wash out and again after antidepressant drug therapy. 3. Prior to drug treatment patients were significantly more sensitive to light than controls as measured by cone but not rod thresholds. 4. Following drug treatment both cone and rod thresholds were reduced in patients. In comparison to controls, drug treatment normalized cone threshold and reduced rod threshold in patients. 5. These data provide ophthalmological evidence for increased sensitivity to light in non medicated depressive disorder and a reduction in sensitivity following antidepressant drug therapy. 6. The possibility of altered retinal function and consequently the ability to perceive and use light for entrainment of circadian rhythm in affective disorder deserves further study.

Adaptation, Ocular↗
PubMed1989

Effect of chronic lithium on sensitivity to light in male and female bipolar patients.

1. Sensitivity to white light was quantified in euthymic bipolar male and female patients maintained on long term lithium therapy and age and sex matched unmedicated controls. 2. The Dark Adaptation Threshold procedure was used to assess sensitivity of both the cone and rod photoreceptors to short pulses of light. 3. Male and female controls did not differ in sensitivity to light. 4. Male patients in comparison to both controls and female patients evidenced reduced sensitivity to light during the cone and rod portion of the dark adaptation procedure. 5. Female patients did not differ from controls on sensitivity to light. 6. Using these and other published data the results were interpreted as suggesting that lithium reduces sensitivity to light during adaptation to dark.

Adaptation, Ocular↗
PubMed1989

Glycine inhibition of pupillary responses to pulses of light in conscious sheep.

The use of a 1.5% glycine solution as a bladder irrigant during surgical removal of the prostate has been associated with transient visual impairment. Glycine is thought to be an inhibitory retinal transmitter. Adult female sheep were infused with a 1.5% glycine solution to provide a dose of 0, 7.5, 15, 30, or 60 g of glycine. The volume control was a solution of dextrose and saline. The degree of constriction of the pupil in response to 30 seconds of bright light following dilation in the dark was used as an index of visual response. Observations were made before and 2, 4, 6, 12, 24, 48, 96, and 192 hours after a single infusion. Significant inhibition of pupil response to light but not to the dark was apparent following systemically administered glycine resulting in plasma levels over 5000 mumol/L. Inhibition of pupil response was paralleled by behavioral indices of visual impairment but not by changes in plasma sodium, potassium, chloride or osmolality. The duration of the effect was dose dependent with visual impairment following a single high dose of glycine being detectable five days later and long after glycine levels had returned to normal. However, the relationship between dose, time, and effect appears to be complex. It is important to note that the present observations occurred at plasma glycine levels frequently experienced in routine surgical practice. The finding that significant long term detrimental effects of glycine could be detected should evoke a re-evaluation of the use of glycine as an irrigating solution for surgical procedures and stimulate further investigation of the effects of glycine on retinal function and the ability to perceive light.

Animals↗
PubMed1987

Lithium and rhythms of beta-adrenergic ([3H]CGP-12177) binding in intact rat retina, pineal gland, and hypothalamus.

A new assay technique for the determination of neurotransmitter binding in retinal fragments has been used to characterize and quantify beta-adrenergic receptors with the ligand [3H]CGP-12177. This assay allowed us to quantify beta-adrenergic receptors in the retina, pineal gland, and hypothalamus obtained from individual rats during a 10-hr period around the switch from light to dark under a 12-hr light/12-hr dark lighting cycle. A significant rhythm of beta-adrenergic binding was observed in the retina and pineal gland. These rhythms were abolished by chronic lithium treatment. In contrast to previous observations in whole brain preparations, lithium did not affect beta-adrenergic binding in brain tissue (hypothalamus) using this assay. Our data suggest that lithium may attenuate beta-adrenergic receptor down-regulation in pineal and retinal tissue. To the extent that this mechanism is important for the coding of information about light and dark in the environment, these observations might assist in our understanding of the clinical chronopharmacological properties reported for lithium.

Animals↗
PubMed1987

Dysregulation of neuroendocrine crossroads: depression, circadian rhythms and the retina--a hypothesis.

The pathophysiology of depression and the mechanism of action of lithium and other antidepressant drugs involve alterations in circadian rhythms. These include changes in both the intrinsic rhythm of circadian oscillators and in the sensitivity of the retina to LIGHT. The retina in humans is the only photoreceptor for circadian entrainment. The retinal-hypothalamic-pineal axis is the essential pathway for neuronal entrainment of rhythms which use light as a phase cue. A common substance throughout this axis in many species is MELATONIN. Retinal melatonin has been implicated in regulation of the sensitivity of the retina to light. The hypothalamus, at THE NEUROENDOCRINE CROSSROADS, has a central role in the integration of neurotransmitters and hormones in circadian rhythms. DYSREGULATION of the hypothalamic-pituitary-adrenal, as well as -gonadal, axes has been documented in depressed patients. Abnormalities in circulating melatonin have also been found in patients with affective disorders. It is speculated that the availability of melatonin along the retinal-hypothalamic-pineal axis may have important implications in the genesis of affective disorders. More specifically--is there a latent biochemical defect which causes a phase shift and change in circadian rhythms of melatonin and/or other neurotransmitters in the retina which then alters the sensitivity of the retina to light (for the visible spectrum) which in turn desynchronizes all other biological rhythms thus disrupting mental well-being? We suggest that variations of retinal photosensitivity in humans can be measured by using a visual testing system, and that depressed patients might show changes in photosensitivity which could be corrected when treated with lithium and/or antidepressants. It is our working hypothesis that the primary defect in depression may be a change in retinal function, and that behavioural and neuroendocrine concomitants of this disorder are secondary events.

Circadian Rhythm↗
PubMed1987

Lithium and circadian patterns of melatonin in the retina, hypothalamus, pineal and serum.

Lithium, a widely used substance for treatment of manic-depressive illness has been reported to alter the phase relationship of a variety of circadian rhythms which have been implicated in the aetiology of depression and manic-depressive disorder. Although its mechanism of action is not understood, the theraputic action of lithium has been related to its ability to alter circadian rhythms. Chronic lithium administration to rats resulted in lithium levels comparable to the human theraputic range. These lithium levels affected a broad range of biological variables by significantly modifying their circadian pattern of variation, notably during the dark period of an alternating 12h light/12h dark schedule. These included water intake, body weight, retina weight and pineal, serum, retina and hypothalamic melatonin measures. Retinal lithium levels were significantly higher than serum lithium levels and retinal melatonin levels were reduced by lithium. The data are interpreted as suggesting that lithium may exert its theraputic effects by influencing melatonin levels at several locations along the retinal-hypothalamic-pineal pathway, resulting in a modulation of the potential cue value of this physiological stimulus for synchronization of circadian rhythms. Such an effect of lithium could have important chronobiological implications for circadian rhythms which use light and dark as a phase cue.

Animals↗
PubMed1987

Effects of fornix transection and pituitary-adrenal modulation on extinction behavior.

We examined whether the absence of a dynamic pituitary-adrenal response contributes to the behavioral deficit seen in hippocampally damaged rats following the transition to extinction of a learned behavior. In the first experiment, total lever presses and detailed behaviors of rats with fornix transection and replacement ACTH4-10 or ACTH were compared with the behavior of fornix-transected and sham-transection groups during acquisition and extinction of lever pressing. Fornix-transected rats showed increased resistance to extinction and an altered pattern or mode of extinction responding. ACTH4-10 or ACTH acted similarly in reducing extinction lever presses in fornix-transected rats without altering the mode of extinction responding. In the second experiment the extinction behaviors of rats with fornix transection were compared with those of normal, sham-transection adrenalectomized, or dexamethasone-treated rats. Fornix-transected rats again showed increased resistance to extinction and a different mode of responding during extinction. Adrenalectomized rats showed an extinction deficit but differed from fornix-transected rats. The behavior of dexamethasone-treated rats was similar to that of controls. The results are interpreted to mean that ACTH and corticosterone both affect extinction behavior (in opposite ways) but do not account for the extinction deficit seen in hippocampally damaged rats.

Adrenocorticotropic Hormone↗
PubMed1979

Patterns of hepatic injury induced by methyldopa.

Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.

Adult↗
PubMed1979

Differential effects of basolateral amygdala lesions on behavior, corticosterone, and prolactin responses.

The present experiment examines hormone-behavior relationships following manipulation of the amygdala. Affective behavior and levels of corticosterone and prolactin were compared in rats with lesions of the basolateral amygdala and in nonlesioned and sham-operated controls. Animals with lesions of the basolateral amygdala were found to be hyperreactive and to have normal resting levels of corticosterone and prolactin but potentiated corticosterone responses to stress. Normal prolactin stress responses were unaltered by the lesion. The results are discussed in relation to behavioral and endocrine changes seen following other limbic system lesions.

Amygdala↗
PubMed1977

Cirrhosis of the liver in Rhodesian Blacks.

Thirty-five Black patients with cirrhosis of the liver were admitted to the professorial unit over a 1-year period and were included in a carefully planned prospective study. Men predominated over women in a ratio of 3:1. Alcohol consumption in the form of African beer was significantly higher in cirrhotic patients than in a control population. The clinical picture was neither predominantly that of alcoholic nor of cryptogenic cirrhosis. Hepatomegaly, porphyria cutanea tarda, ascites, splenomegaly and oesophageal varices were common. There was a complete absence of gynaecomastia, spider naevi and liver palms. Histologically, the majority of patients had macronodular cirrhosis, and only 1 patient had micronodular cirrhosis and minimal fatty change. Hepatitis B surface antigen (HbsAg) was not detected in any patient, despite a positive HbAg rate of 4% in Black African blood donors, determined by means of the same laboratory technique.

Adult↗
PubMed1977

Hepatocellular carcinoma in the Rhodesian African.

We have carried out a prospective survey of 28 primary liver carcinomas over one year. Hepatocellular carcinoma is the commonest malignancy seen in Rhodesian blacks, which results in a high index of suspicion and accounts for the 96.4% positive diagnosis before death in this study. The age distribution was evenly spread through adult life with no definite peak incidence. Some were young and without evidence of chronic liver disease, but many had the stigmata of established hepatic disease. This contrasts with the common assertion that in areas of high incidence for primary liver cancer those affected are mainly young and lack signs of chronic liver disease. The commonest presenting symptoms were abdominal pain and swelling and weight loss. Hepatomegaly, often tender and nodular, was present in all but one. The incidence of alpha-feto protein, 46.5%, is low compared with other countries where primary liver cancer is common. Hepatitis B antigen was absent in all 28, suggesting that there is no association between the persistence of the antigen and hepatocellular carcinoma in Rhodesia. Liver function tests, although abnormal, were never diagnostic of primary liver cancer. We have confirmed the association of high alcohol consumption and cirrhosis with hepatocellular carcinoma.

Adult↗
PubMed1977

Effect of psychosocial stimuli and limbic lesions on prolactin at rest and following stress.

Many of the factors altering corticosterone in the rat have similar effects on prolactin. Resting prolactin, like corticosterone, is higher in animals housed singly than in those multiply housed. Unlike corticosterone, gentling did not lower prolactin. An exquisite sensitivity to environmental stimuli which results in rapid elevations in prolactin levels has been indentified in the rat which is considerably greater than that for corticosterone. Like corticosterone, the pattern of prolactin stress responses varies according to time of day. This differential sensitivity may well account for the diurnal variation in prolactin reported by some investigators. The limbic system has an important influence on prolactin. Lesions of the septal region do not modify resting levels but alter the pattern of prolactin stress responses in ways which are only partly similar to the effects of such lesions on corticosterone. In rhesus monkeys, individual variation in resting prolactin levels was observed, similar to that seen in the human. Levels are stable over periods of up to 50 days and are characteristic of the individual animal. In response to the stress of electric shock or shaping to a bar press response, prolactin elevation occurs only in animals with high resting levels, suggesting that a common mechanism is responsible for controlling both resting levels and magnitude of stress responses.

Animals↗