Pergolide in the treatment of Parkinson's disease.
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Biomedical subjects
Publications and source records attributed to C Thompson.
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Six patients with myoclonus were given 0.1-0.15 mg lisuride i.v. All patients had stimulus-sensitive myoclonus and an increased size of somatosensory evoked potentials, and in three there was electrophysiological evidence of a cortical event time-locked to the jerks. All subjects showed a considerable diminution of spontaneous, action- and stimulus-evoked jerking. Lisuride has potent central dopaminergic and serotonergic actions. Administration of the dopamine agonists levodopa or apomorphine had no effect on myoclonic jerking in any of the six patients. Detailed pharmacological analysis of the myoclonus in one patient showed that levodopa, apomorphine, and haloperidol had no effect, and that haloperidol did not prevent the therapeutic action of lisuride. 5-Hydroxytryptophan abolished the myoclonus, and methysergide prevented the beneficial effect of lisuride, although it did not alter spontaneous myoclonus. These observations suggest that lisuride improves some types of reflex, stimulus-sensitive cortical myoclonus by a serotonin agonist action.
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The effectiveness of cutaneous electrical stimulation as a muscle-strengthening technique was evaluated by comparison with an isometric regime. Sixteen normal healthy subjects were randomly assigned to either an electrical group or an isometric group. A pretest was given of maximum voluntary force in the quadriceps (extensor) muscles, measured with a cable tensiometer. Subjects then trained (isometrically or by electrical stimulation) four days per week for three weeks. Training by electrical stimulation was via a square-wave pulse (75 Hz and 0.1 ms) with the voltage determined by subject tolerance for ten, 10-sec induced contractions (with 50-sec rest intervals). Isometric training consisted of ten, 10-sec maximal contractions (with 50-sec rest intervals) at each session. Feedback of the generated force was standardised for both groups. Post-training measures were then administered using the same protocol as the pretest. Both groups demonstrated a marked improvement in quadriceps strength of 22 +/- 5.3% for the electrical group and 25 +/- 6.9% increase for the isometric group (p less than 0.02). The change in strength was apparently not dependent on the magnitude of the stimulating voltage (5-10 V) nor on the tension induced. There was no significant difference in the strength gains achieved by the two regimes (p greater than 0.05). No pain, muscle lesions or other ill effects were observed with electrical stimulation. We conclude that cutaneous electrical stimulation is a viable strengthening technique. There are obvious practical applications of this technique to the rehabilitation of patients who are not able to maintain an effective voluntary contraction.
In addition to estrogen receptors, liver contains a second class of estrogen-binding proteins referred to as higher-capacity, lower-affinity (HCLA) binding sites which are distinct from estrogen receptors. HCLA sites comprise two classes of proteins: moderate-affinity (KD = 0.45 microM and 0.24 microM) estrogen-binding sites unique to male cytosol and a low-affinity, nonsaturable estrogen-binding site present in both sexes. The sex differences observed in HCLA sites are apparently a consequence of imprinting by testicular androgen during a critical neonatal period. Neonatal castration causes a reduction in the concentration of HCLA sites in the subsequent adult male. Furthermore, the moderate-affinity sites detected by Scatchard analysis in adult male liver are not observed in neonatal castrates. Cell-free nuclear translocation assays demonstrate that nuclear uptake of cytosolic receptor-ligand complexes is more efficient in females than in males. This sex difference in nuclear uptake can be minimized when the concentration of the ligand is increased to a level necessary to saturate the estrogen receptor in the presence of HCLA sites. Nuclear uptake of receptor-ligand complexes in neonatally castrated males (deficient in HCLA sites) is similar to that seen in adult females. Elevations of serum triglyceride following estradiol exposure have been monitored as an indicator of hepatic responses to estrogen. Our studies have shown that female liver appears more responsive to estrogen exposure than does male liver. While a dose of 20-30 micrograms of estradiol per kilogram of body weight per day was sufficient to produce a 3- to 4-fold increase in the concentration of triglyceride associated with the very low-density lipoprotein fraction in females, a dose of 100 micrograms of estradiol per kilogram of body weight per day was needed to obtain a similar response in males. However, following neonatal castration, estrogen responsiveness in the subsequent adult male rat was similar to that in females, suggesting a role for neonatal androgens in regulating sex differences in the action of hepatic estrogen.
This study examined sucking patterns during breast-feeding in order to investigate the supposed 'nutritive' and 'non-nutritive' sucking dichotomy. The intervals between sucks were determined: they indicated that there is no bimodal distribution corresponding to 'nutritive' and 'non-nutritive' rates of sucking, but rather a complete gradation between the two. In a further experiment in which milk flow was assessed by test-weighing the baby at three-minute intervals during feeding, there was a linear relationship between milk flow and sucking rate: the higher the milk flow, the lower the sucking rate. These results were further substantiated by testing the sucking rate on an empty and full breast, and the sucking pattern of an infant with a non-lactating mother. The study shows that there is no dichotomy between two sucking rates, but rather a continuous variation in response to milk-flow rate.
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Gel-filtration (Sephadex G-75) analysis of hepatic cytosol reveals both qualitative and quantitative sex differences in oestrogen-binding proteins. The elution profile of [(3)H]oestradiol-labelled cytosol shows four species of oestrogen-binding proteins (peaks I, II, IV and V) common to both sexes. The amount of [(3)H]oestradiol binding in peak I is equivalent in both males and females and corresponds quantitatively to the specific oestrogen receptor. The amount of binding in the remaining three peaks is greater in males than females. In addition, an oestrogen-binding protein (peak III) is present that is unique to male cytosol. Proteinase-inhibition studies demonstrate that the observed multiplicity of oestrogen-binding proteins is not an artefact of proteolytic breakdown. Sex differences in oestrogen-binding proteins are absent in immature male and female animals; the oestrogen-binding protein profile in immature rats resembles that of an adult female. Gonadectomy of adult animals does not affect the oestrogen-binding-protein profile. In contrast, neonatal (day 1) castration results in partial feminization of the characteristic oestrogen-binding protein profile seen in the adult male; the appearance of Peak III is suppressed and marked decreases in the amount of oestradiol binding occurs in the remaining peaks. Hypophysectomy of adult animals results in near abolishment of the observed sex differences; the male oestrogen-binding protein profile is partially feminized and the female profile is partially masculinized, as characterized by the appearance of [(3)H]oestradiol binding in the region of peak III and increased amounts of binding in peaks IV and V. The present studies demonstrate a multiplicity of oestrogen-binding proteins in liver cytosol and raise the possibility that the presence of some of these proteins may be imprinted at birth through the hypothalamic-pituitary axis, by a mechanism requiring neonatal androgen exposure.
A study of 196 healthy geriatric females and 26 males confirmed the high prevalence of anemia in this population. Forty-two females (21.4%) had a hematocrit of less than 36% and nine (34%) of the males had a value of less than 40%. A careful evaluation, including a therapeutic trial of oral iron in some subjects, made a diagnosis of iron deficiency anemia in only three and the anemia of chronic disease could be diagnosed in two. No subject had folate or B12 deficiency and hemolytic anemia was not present. Thus, in most of these subjects, the lower hematocrit was not due to commonly recognized causes. Further evaluation revealed a high prevalence of leukopenia in this population; 30% having counts less than 5 X 10(3)/microliter and 10% having values less than 4 X 10(-3)/microliter. Of most importance, leukocyte counts were significantly lower in anemic subjects in whom a high incidence of neutropenia was also demonstrated. This suggests that the mechanisms of the unexplained anemia and neutropenia is an overall reduction in hematopoietic cell numbers. This conclusion is consistent with the observation that many aged subjects have a decreased ability to mount an adequate leukocyte response to infection. These findings suggest that the presence of anemia marks an overall reduction in hematopoietic reserve and provides a clue to those aged subjects of greatest risk of an inadequate response to stress.
For the epidemiological evaluation of iron stores the precision of serum ferritin measurement in the low range are important for the accurate determination of the prevalence of iron deficiency and the detection of subtle changes in serum ferritin levels after food iron manipulation. In addition the recognition of iron overload and the evaluation of its severity are important. In this study samples with low serum ferritin values were repetitively measured in a classic radioimmunoassay (RIA) and in two "2-site" immunoradiometric assays (IRMA), one of which used a polystyrene bead and the other a polystyrene tube fas the solid phase. Variability was significantly less with the IRMA using a bead than that using a tube. Optimum precision was noted when samples were run at the lowest possible dilution (1:10) with relatively long reaction times. The bead IRMA was also more precise that the RIA which had a standard curve with 50% radioactive binding (maximum precision) of 40 ng/ml. Within the normal serum ferritin range (12 to 300 ng/ml) extremely similar results were obtained with an RIA and IRMA. However, when iron overload samples (serum ferritin values greater than 2000 ng/ml) were examined the RIA gave values significantly lower than those obtained by IRMA. The lower values by RIA may be related to the immunological heterogeneity of serum ferritin which is maximized by an assay performed in antigen excess (RIA) and minimized by one performed in antibody excess (IRMA). These observations indicate a need for the development of specific serum ferritin assays for epidemiological studies. By manipulating the components of the standard curve the RIA and IRMA can be optimized to provide maximum precision when low serum ferritin values are being measured. in choosing an assay the ability of the method to determine the severity of iron overload must also be taken into consideration.