Haloperidol serum levels were determined by the recently developed radioimmunoassay technique to elucidate the relationship between serum levels and clinical effects and that between serum levels and adverse effects. The serum levels of haloperidol in divided daily doses schedule reached to the steady state more rapidly (within 7 days) than in single dose schedule. The single daily dose schedule showed significantly wider diurnal variation than the divided daily doses schedule. No remarkable differences in serum concentration was noted between different types of oral haloperidol preparation (liquid, granule, tablet). No definite relationship was established between the serum concentration of haloperidol and incidence of tardive dyskinesia. No definite positive relationship between clinical effects and serum concentration of haloperidol could obtained.

Administration, Oral↗

PubMed1984

The relationship between haloperidol blood levels and clinical responses.

Haloperidol blood levels in patients were determined to elucidate the relationship between blood levels and clinical effects. Determinations of haloperidol serum were performed by radioimmunoassay and the clinical status was estimated using BPRS. The relationship between haloperidol serum levels and BPRS total score was studied in 20 chronic schizophrenics currently receiving haloperidol treatment. The results did not show positive relationship between these two. Another 11 schizophrenic patients were treated with daily doses of average 6 mg of haloperidol. The patients were classified into improved and unchanged group according to the changes of BPRS total score. All 7 cases classified into the improved group had short duration of the illness less than one year. In this group, the levels were lower initially but gradually rised in paralled with the increase of extent of recovery on BPRS. Furthermore, improvement of psychopathology by means of decrease of BPRS total score was still found after haloperidol serum levels reached a plateau. The results did not support the view that high blood concentration of haloperidol might contribute to the clinical effects, but still suggested utility of measuring blood levels in acute or subacute patients being treated with haloperidol medications.

Adult↗

PubMed1984

Meningoencephalitis due to serratia marcescens infection in neonates.

Six autopsy cases of Serratia meningoencephalitis were reported. The symptoms of this infection become apparent at an early stage in neonates; the meningoencephalitis in these six cases was severe, with or without inflammatory lesions in other organs. Serratia marcescens was originally described as a nonpathogenic organism; however, it is believed that after entering the blood stream of neonates, it becomes pathogenic, especially to the central nervous system. Meningoencephalitis due to Serratia marcescens is very severe and takes a rapid and progressive course against which no antibiotics have been found effective. Prevention of this infection is therefore considered of crucial importance.

Cerebrospinal Fluid↗

PubMed1984

Thyrotropin-induced acceleration of calcium efflux from mouse thyroid: evidence for inhibition by excess iodide.

We investigated the effect of TSH on calcium transport in mouse thyroid, as well as the influence of iodide thereupon. Thyroid lobes were incubated in Krebs-Ringer bicarbonate buffer containing [45Ca2+] and the time-dependent uptake of [45Ca2+] by the lobes was observed. In the presence of 0.5 mU/ml TSH, the uptake of [45Ca2+] was significantly depressed at early phases of incubation (from 20 to 40 min). Similarly, (Bu)2cAMP (DBC) depressed the [45Ca2+] uptake. The efflux of calcium was also studied by using thyroid lobes preloaded with [45Ca2+]. In the presence of 0.5 mU/ml TSH, [45Ca2+] release from the lobes was doubled in comparison with the control lobes incubated without TSH. DBC similarly accelerated [45Ca2+] release from the lobes. The acute administration of excess iodide to mice fed a low iodine diet inhibits the TSH-induced adenylate cyclase activation in thyroids. The acceleration of calcium efflux induced by TSH was completely abolished by the acute administration of excess iodide in thyroids obtained from animals fed a low iodine diet. Similarly, DBC-induced acceleration of calcium efflux was inhibited by pretreatment with excess iodide. However, the inhibitory effect of iodide on TSH- or DBC-induced acceleration of calcium efflux was not observed in thyroids obtained from mice fed a regular diet. Inhibition of TSH-induced acceleration of calcium efflux by iodide was diminished by treatment of mice with methimazole before iodide. These results suggest that 1) TSH accelerates calcium efflux from the thyroid as a result of accumulation of cAMP in the thyroid, and that 2) iodide inhibits calcium efflux by inhibition of TSH-induced adenylate cyclase activation and by inhibition of the mechanism(s) which is (are) activated by cAMP.

Animals↗

PubMed1984

The effect of thyroid hormone on the high affinity Ca2+-ATPase in rat liver plasma membrane.

The effect of thyroid hormone on the high affinity Ca2+-ATPase activity in rat liver plasma membrane was studied. The high affinity Ca2+-ATPase activity in plasma membrane was activated by 10(-7)-10(-5) M of Ca2+ and was inhibited by 70 microM trifluoperazine. Thyroidectomy of rats was associated with an increase in the activity of high affinity Ca2+-ATPase. The increased enzyme activity was normalized by T4 administration to the animals. On the other hand, Na+-K+-ATPase activity in the membrane was decreased by thyroidectomy and the decreased enzyme activity was normalized by T4 administration. The results suggest that thyroid hormone inhibits the Ca2+ extrusion system by inhibiting calmodulin-independent high affinity Ca2+-ATPase in liver plasma membrane.

Animals↗

PubMed1984

Effect of calcium ion on triiodothyronine binding to kidney outer mitochondrial membrane in vitro.

The effect of calcium ion on 3,5,3'-triiodothyronine (T3) binding to rat kidney outer mitochondrial membranes was examined in vitro. The outer mitochondrial membranes were prepared by using a discontinuous sucrose density gradient centrifugation. The membrane fraction, which is enriched with monoamine oxidase activity, contained specific binding sites for T3. Scatchard analysis of T3 binding to outer mitochondrial membranes gave an association constant (Ka) of 0.53 X 10(10)M-1. The binding of [125I]-T3 to the membranes was inhibited by the addition of CaCl2(0.25 X 10(-4)--2.5 X 10(-3)M). 50% inhibition was obtained by 0.75 X 10(-4)M CaCl2 in the presence of 0.1 mM EGTA. When outer mitochondrial membranes were solubilized with Triton X-100, four main T3 binding activities were isolated by a gel filtration study. On the other hand, the binding of [125I]-T3 to the solubilized T3 receptors derived from outer mitochondrial membranes was not strongly inhibited by calcium. When outer mitochondrial membranes were preincubated in the presence of 1 mM calcium, the number of T3 binding sites in the membranes was decreased, and this was associated with an increase in the number of T3 binding sites in the supernatants of the incubation mixture. Scatchard analysis showed that the number of T3 binding sites in the membranes is decreased by calcium ion without any change in the association constant. In studies with gel filtration of receptors which are released by Ca2+ from outer mitochondrial membranes, three main T3 binding activities were isolated. Mg2+, Mn2+, Zn2+ and Cu2+ did not affect T3 binding to outer mitochondrial membranes. The results indicate that calcium ion regulates T3 binding to the outer mitochondrial membrane through the release of T3 receptors from the membranes.

Animals↗

PubMed1984

Effects of long-term treatment with thyroxine on pituitary TSH secretion and heart action in patients with hypothyroidism.

The effects of thyroxine (T4) treatment on pituitary thyrotroph cells and on the heart were studied in 68 female patients with hypothyroidism. During the initial 12 months of T4 treatment, relatively small doses of T4 (1.3 micrograms/kg) normalized serum T4, triiodothyronine (T3), TSH and lipid concentrations in mild hypothyroidism, while moderate doses of T4 (1.7-2.0 micrograms/kg) normalized serum T4, T3 and lipid concentrations but not serum TSH levels or the volume of sella turcica in moderate and severe hypothyroidism; however, serum TSH levels and the volume of sella turcica returned to normal with continuation of these doses of T4. Systolic time intervals (ET/PEP) can discriminate between euthyroid and hyperthyroid states and agree well with serum TSH levels. However, ET/PEP was unequivocally elevated in about 40% of treated hypothyroid patients with normal serum T3, T4 and TSH levels which had been maintained over 48-54 months. Since the reciprocal relationship between free T4 and TSH levels was maintained in all treated patients, elevated ET/PEP with normal TSH levels indicates that the heart is more sensitive to thyroid hormones than the pituitary thyrotroph in 40% of treated hypothyroid patients. During T4 treatment in patients with hypothyroidism, ET/PEP should be followed and T4 doses adjusted to maintain normal ET/PEP rather than normal serum TSH levels, especially in older patients in whom T4 may aggravate angina pectoris or provoke myocardial infarction.

Female↗

PubMed1984

Age-related alterations of pituitary-thyroid function in normal female subjects and in female patients with simple goitre.

Age-related alterations in pituitary-thyroid function were studied in 173 female patients with simple goitre and in 70 normal female subjects. They were divided into 4 groups according to age: A group, less than 19 years; B group, 20 to 29 years; C group, 30 to 39 years; D group, 40 to 59 years. Serum triiodothyronine (T3) concentrations decreased progressively but insignificantly with age in female patients with simple goitre and in normal female subjects, whereas serum thyroxine (T4) concentrations remained constant throughout the studied age range. Only in female patients with simple goitre, did basal serum TSH concentrations show a tendency to increase with age. However, thyrotrophin-releasing hormone (TRH)-stimulated increase of serum TSH was progressively augmented with age both in female patients with simple goitre and in normal female subjects; the magnitude of change was greater in the former group. As reflected by acute increases of serum T3 and T4 concentrations, thyroidal responsiveness to endogenous TSH was progressively depressed with age in female patients with simple goitre and in normal female subjects. This age-related thyroidal refractoriness to TSH was more apparent when the changes were expressed as delta T3 (stimulated T3 - basal T3)/delta TSH (maximum TSH after TRH - basal TSH), and delta T4 (stimulated T4 - basal T4)/delta TSH. Delta T4/delta TSH was lower in female patients with simple goitre than in normal female subjects in all age groups. However, the difference was significant only for delta T4/delta TSH in group A. Thyroidal responsiveness to exogenous TSH also gradually declined with age in female patients with simple goitre.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1984