Special education and research: a recent survey.
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Biomedical subjects
Publications and source records attributed to J Roberts.
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The overwhelming majority of girls presenting with primary amenorrhoea have aetiologies with their roots in disturbances of embryogenesis and/or the endocrinology of sexual differentiation. This review will deal with the fundamentals of embryology and endocrinology relevant to the subject and then discuss the findings in a group of one hundred and forty patients with primary amenorrhoea as they relate to these disturbances.
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We treated 13 adult patients with acute leukemia or chronic myelocytic leukemia (CML) in blast phase using succinylated Acinetobacter glutaminase-asparaginase (SAGA) administered on a daily dose schedule. SAGA reduced the peripheral blast count in two patients with acute lymphoblastic leukemia and two with blastic CML; however, no patient achieved either complete or partial remission. Marked central nervous system toxic effects (encephalopathy and coma) were observed, limiting treatment in patients whose disease appeared responsive; this effect finally prompted early discontinuance of the trial. Other toxic effects observed included nausea, hyperglycemia, and respiratory alkalosis. Hypersensitivity reactions to the enzyme were not seen. Pharmacologic analyses showed that prolonged blood glutamine depletion was achieved only by daily enzyme administration; however, we noted the importance of performing amino acid analysis on blood which was deproteinized immediately following phlebotomy. Our results demonstrate excessive central nervous system toxicity when glutaminase-asparaginase is administered on a daily schedule. Because of this effect, we propose that future trials of similar enzymes be limited to short courses of enzyme therapy, possibly with the addition of antimetabolites or amino acid analogs, which could enhance the antitumor effect without increasing toxicity.
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This study determined whether the protective effect of reserpine against ouabain-induced ventricular arrhythmias in the cat is due to an action of the drug on the adrenergic nerve terminal. Reserpine (5 mg/kg i.p.) administered 24 h prior to ouabain (2 micrograms/kg per min i.v., until death) increased the dose of ouabain to produce premature ventricular contractions, ventricular tachycardia, and death from 77.3 +/- 5.2 to 105.0 +/- 6.0; 84.9 +/- 5.2 to 132.7 +/- 9.1; and 108.8 +/- 4.0 to 165.7 +/- 10.4 micrograms/kg, respectively (P less than 0.05). When 6-hydroxydopamine (6OHDA; 20 mg/kg i.v.) was given 3 days prior to the experiment, the protective effect of reserpine was not evident. When bretylium (20 mg/kg i.v., 2 h prior to ouabain) was administered to animals previously treated with reserpine, the dose of ouabain which produced premature ventricular contractions, ventricular tachycardia, and death was increased to 109.0 +/- 7.2; 146.1 +/- 12.6; and 165.8 +/- 7.6 micrograms/kg, respectively (P less than 0.05). However, the magnitude of this protective action was similar to that produced by reserpine alone. Lathers et al. (Fed. Proc. 40, 672, 1981) reported that bretylium alone provides protection of a similar order of magnitude as reserpine. Thus, the effects of reserpine and bretylium were not additive; this indicates that the two agents may be acting on the same locus or they may be acting at different sites with the action of one drug masking or blocking the action of the other. Since 6OHDA prevented the action of reserpine on ouabain-induced ventricular arrhythmia and since 6OHDA only produces degeneration of adrenergic nerve terminals, it is probable that the protective effect of both reserpine and bretylium is due to an action at the adrenergic nerve terminal. The heart rate and blood pressure were not involved in the antiarrhythmic effects of reserpine.
The effects of increasing age were studied on rat atrial sensitivity to lidocaine by means of intracellular microelectrode recording of transmembrane electrical activity. Under control conditions, atrial resting potential and the maximum rate of rise of phase 0 (Vmax) were not influenced by increasing age (1 month to 24 months). However, the amplitude of the action potential and of the overshoot, and the duration of the action potential and the plateau phase decreased as a function of age. Lidocaine hydrochloride, 5 mg/L, did not alter resting potential, but decreased the amplitude of the action potential and of the overshoot, decreased the frequency of occurrence of an overshoot, decreased Vmax, and increased action potential duration and plateau duration. The effects of lidocaine to abolish the overshoot and prolong the duration of the action potential and the plateau phase increased with increasing age. Thus, it has been demonstrated that electrophysiological properties of rat atrial muscle undergo alterations in relation to increasing age. These alterations may be responsible for the observed age-related changes in atrial sensitivity to lidocaine.
Computed tomography (CT) was used in the evaluation of nine patients with nonopaque calculi in the upper urinary tract. In each case the calculus was identified as a very high density object (370-586 Hounsfield units) with calcium oxalate and cystine stones having somewhat higher attenuation values than uric acid or xanthine stones. The differentiation between calculi and other "radiolucent" filling defects was readily made since calculi had much higher attenuation values than blood clot or neoplasm. CT of the upper urinary tract may obviate the need for more invasive procedures such as retrograde pyelography when nonopaque filling defects require differentiation.
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Mouse P388 and L1210 leukemia cells grown in vitro were found to be 4 to 10 times more sensitive to 6-diazo-5-oxo-L-norleucine and 3 to 5 times more sensitive to Acivicin than were 3T3 and C57BL x DBA/2 F1 embryonic fibroblasts. The combined actions of succinylated Acinetobacter glutaminase-asparaginase and 6-diazo-5-oxo-L-norleucine or Acivicin produced synergistic inhibition of nucleic acid synthesis in P388 tumor cells. An uptake system for Acivicin is described. Its properties in P388 and 3T3 cells are similar in their strong temperature dependence, utilization of the "L" transport system, presumably competitive inhibition by glutamine, similar Km's (about 200 microM), and potent inhibition by p-chloromercuribenzene sulfonate, NA+. However, Acivicin uptake was inhibited in 3T3 (but not in P388) cells by KCN or 2,4-dinitrophenol. At equilibrium in P388 cells, the intracellular level of Acivicin was approximately 57-fold greater than was the extracellular concentration. The accumulated Acivicin was not metabolized by P388 cells, nor does exchange of 3H label into water occur. Rapid efflux of Acivicin occurred with both cell lines at 37 degrees, but efflux from 3T3 cells was greatly diminished at 0 degrees. The rate of efflux was accelerated by including glutamine or unlabeled Acivicin in the extracellular medium.
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The influence of maternal position during labor on comfort and uterine efficiency was studied by contrasting the influence of sitting in a chair with lying on the side during the first stage of labor. Nineteen primigravidas alternated between these two positions at 30 minute intervals for as long as this was possible during their labors. There was a significant difference in their preference to sit up during early labor (less than 6 cm dilation) and lie on their side during late labor (greater than 6 cm dilation). Uterine efficiency, however, was significantly less (p less than 0.05) in early labor in the sitting position than on the side. After labor was well established, ie after 6 cm dilation, the efficiency of uterine contractions to dilate the cervix was not significantly different between the 2 positions although it was less in the sitting position. The lateral recumbent position was accompanied by more efficient labor and was preferred by most women in late labor. Localization of pain and fetal position also seem to be associated with maternal position preference, and both factors require further investigation.
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Injection of a purified serotonin (and tryptophan)-degrading enzyme into mice produced a pronounced hypothermia when the mice were maintained at 22 degrees C, but not at 30 degrees C. Brain levels of serotonin and tryptophan were strikingly depleted, but concentrations of norepinephrine and dopamine remained unchanged.
The postneonatal death rate was studied for 332 infants from 160 families, ascertained through an abused proband. There were nine deaths compared with 2.9 expected from the legitimacy, social class, age, and parity distribution (p = 0.003). All but one of the babies died at home, and all were referred to a coroner or procurator fiscal. No adequate explanation of death could be found in four cases. Bonding problems probably existed in most of the nine families before death occurred.