Biomedical subjects
Publications and source records attributed to R Ohman.
A medium frequency flicker stimulus of 10 Hz is evaluated in routine clinical ERG recording in detecting cone disorders. Tested on a number of normal eyes and on eyes with confirmed or suspected retinal disease it appears to be very useful as a complement to the standard program with the Krakau-Ohman apparatus. It yields an easily recordable and quantified response.
Twenty-one serum samples from 11 schizophrenic patients receiving long-term haloperidol therapy were analyzed for haloperidol concentrations by two different radioimmunoassays (RIAs) and gas chromatography (GC). There was a good correspondence between the RIA and GC values over a wide range of drug concentrations. However, compared with the specific GC technique, both RIA methods overestimated haloperidol concentrations, reflecting differences in the specificities of the two RIA antibodies. One of the RIA methods had the requisite specificity for application to patients treated with long-term haloperidol therapy, although further methodological refinement will be required for its general clinical application. Haloperidol values determined by GC and RIA analyses correlated highly with prolactin concentrations in the same samples, suggesting that the usefulness of prolactin measurement as an "in vivo bioassay" for circulating levels of haloperidol should be further explored.
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Gas chromatographic, mass fragmentographic and liquid chromatographic techniques for the determinations of bromocriptine (2-bromo-alpha-ergocriptine; Parlodel) in human plasma are described. These methods were found to be suitable for determining concentrations of bromocriptine down to 0.5, 1.0 and 10.0 microgram/l, respectively. Accuracy, specificity and analytical capacity were satisfactory for all three methods. Gas chromatography was compared with liquid chromatography, and the two methods were demonstrated to give identical results in patients treated with bromocriptine for Parkinson's disease. Gas chromatography was also compared with mass fragmentography, and the results from these two assays were also in agreement.
Plasma levels of prolactin, FSH, LH, progesterone and 17-beta-oestradiol in twenty women with premenstrual tension were compared with those in twenty controls. The former group was studied also during treatment with bromocriptine. The mean prolactin level in the PMT group was lower in the follicular phase than in the luteal phase (P less than 0.01), but there was no difference between the PMT and control group in the luteal phase. No differences were found between the controls and the PMT group in FSH,LH, 17-beta-oestradiol and progesterone levels in the luteal phase. Bromocriptine suppressed prolactin concentrations (P less than 0.01), but had no effect on the FSH, LH, 17-B-oestradiol or progesterone levels.
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A method has been developed for the quantitative determination of haloperidol in brain and other tissues. Such determinations have been made after acute and chronic administration of haloperidol to Sprague-Dawley rats. Different regions of the brain including the striatum, the limbic forebrain and the cerebellum have been analyzed separately. The haloperidol effects on Dopa formation have been studied in the same tissue samples. The stimulation of prolactin secretion via blockade of hypothalamic dopaminergic mechanisms and behavioural effects of the drug have been evaluated in parallel experiments. The elimination of haloperidol from brain tissue is a multiphasic process. The fourth phase of elimination is the slowest with a half life of 4 days. No strict correlation was found between serum and brain concentrations of haloperidol. Both after acute and chronic administration there exists apparently a saturating dose above which the brain concentration of the drug increases very little. The dose seems to coincide with that beyond which little increase in Dopa formation is observed. A pharmacokinetic analysis suggests an element of saturable binding or transfer of haloperidol to brain tissue. This mechanism is not preferentially localized to areas of brain rich in dopaminergic synapses. A good correlation was found between the haloperidol concentration in the brain on the one hand and its effects on behaviour, on serum prolactin values and on Dopa formation on the other.
An apparatus for ERG recording in clinical practice using light-emitting diodes as stimulation light is described and evaluated. By introducing special electronic devices, slow potentials (c-wave) can be recorded and there is no need for a shielded cage. The function of the set-up is trouble-free and the reproducibility is very satisfying.
Fifty-three psychiatric patients who had been receiving treatment with lithium continuously for more than two years were examined to estimate the prevalence of lithium-induced hypothyroidism. It was found to be 20 per cent among women. No men were affected among these patients. In order to study the characteristics of the disorder further cases were drawn from another population. One third of the patients developed hypothyroidism during their first year of treatment, others not until after 9 years. About two thirds of the female patients with hypothyroidism had thyroid antibodies. All cases with lithium-induced hypothyroidism showed elevated levels of serum thyrotropin, which in our experience is the laboratory examination of choice in these as well as other cases of "primary" hypothyroidism. Since the probability of detecting these cases at a given control visit was found to be low, we feel that such visits need not include extensive laboratory investigations. Hypothyroid patients responding well to lithium treatment should continue their medication combined with appropriate thyroxine substitution.
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Prolactin response to electroconvulsive therapy (E.C.T.)was investigated in nine patients with endogenous depression. Four patients undergoing minor gynaecological surgery who had had the same type of intravenous anaesthesia as the E.C.T. group were studied as controls. 15 minutes after E.C.T. there was a 10 to 50 fold increase in serum-prolactin in eight of the patients. The effects of anaesthesia and surgery on serum-prolactin in the controls were negligible.
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The aqueous flare (AF) of an intact rabbit eye was measured by a photoelectric instrument. Local application of prostaglandin E2 (PGE2) and its precursor arachidonic acid (AA) gave an almost identical increase of the AF. The response to AA but not to PGE2 was inhibited by pretreating the eye locally with a solution of indomethacin. The ability of indomethacin to inhibit the aqueous flare response (AFR) to an agent is assumed to indicate that a kind of prostaglandin is the effector of the AF. Indomethacin blocked the AFR to infrared irradiation of the iris and to intravenous administration of endotoxin but not to subcutaneous administration of alpha-melanocyte-stimulating hormone (alpha-MSH).
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