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Biomedical subjects

J C Nelson

Publications and source records attributed to J C Nelson.

At least 145 records · Page 8Linked to original sources
PubMed1989

Dependence of the thyroxin/thyroxin-binding globulin (TBG) ratio and the free thyroxin index on TBG concentrations.

We studied the dependence of the free thyroxin (T4) index and the ratio of T4 to thyroxin-binding globulin (TBG) on TBG concentrations, using sera from cases of congenital TBG deficiency and congenital TBG excess. Two such sera with similar concentrations of albumin, transthyretin, and free T4 were mixed to provide test samples with TBG concentrations covering the range of clinical interest without changes in the other T4-binding proteins. Total T4, free T4, TBG, triiodothyronine (T3) uptake, and the free fraction of T3 in serum were measured, and we calculated the free T4 indices, T4/TBG ratios, and the free fraction of T4. A 100-fold variation in TBG concentration was associated with a 10-fold variation in total T4, a fourfold variation in T3 uptake, and a 10-fold variation in the T4/TBG ratio. As TBG concentrations increased, the T4/TBG ratio decreased and the free T4 index increased. The free T4 index did not parallel the T4/TBG ratio, and neither the T4/TBG ratio nor the free T4 index reflected the concentrations of free T4 in serum.

Adult↗
PubMed1989

Stimulants in the treatment of depression: a critical overview.

The authors reviewed the efficacy and safety of stimulant drugs in the treatment of depression. Although uncontrolled studies were generally positive, the 10 placebo-controlled studies of stimulant drugs in primary depression, with one exception, indicated little advantage of drug over placebo. Although several of these studies were methodologically unsophisticated, they were comparable with and performed during the same period as studies establishing the efficacy of imipramine. Controlled studies of stimulants in apathetic or depressed geriatric patients were more likely to be positive, but outcome frequently consisted of partial improvement. Studies in medically ill patients with depression were promising but uncontrolled. Side effects have not been severe, and these drugs may pose less of a risk than tricyclics in the medically ill or elderly. Habituation is suggested, but there are no placebo-controlled studies to confirm this. In short, the stimulant drugs do not appear to be as effective as the conventional antidepressants in primary depression, but may be of value in refractory cases or in special cases, such as those involving the medically ill patient. Placebo-controlled trials are needed to explore these questions.

Antidepressive Agents, Tricyclic↗
PubMed1989

Erythropoietin controls heme metabolic enzymes in normal human bone marrow culture.

Erythropoietin (Epo) was found to act as a concentration-dependent inducer of aminolevulinic acid (ALA) synthase and porphobilinogen (PBG) deaminase in normal human bone marrow in culture. Epo increased enzymatic activities in individual plated nucleated cells. At a low concentration of Epo, heme oxygenase activity did not change in human bone marrow erythroid progenitor cells. However, Epo at a concentration of 2 U/ml increased heme oxygenase as demonstrated by an increase in both the enzyme protein and its mRNA. In experiments with an inhibitor of heme synthesis, succinylacetone (SA), Epo failed to stimulate erythroid colony-forming unit (CFU-E) growth, but this CFU-E inhibition by SA was completely overcome by the addition of hemin. Epo nevertheless potentiated induction of ALA synthase in the presence of SA. Hemin exerted its regulatory role by negative feedback on ALA synthase in the presence of SA and Epo. Heme potentiated Epo action and resulted in the increase of human marrow erythroid progenitor cell proliferation and differentiation and a concomitant stimulation of ALA synthase and PBG deaminase. The potentiating effects of hemin on CFU-E growth were observed in human bone marrow cells cultured in media supplemented with fetal calf serum or serum-free media with interleukin 3 (IL-3). These results indicate that Epo is a potent inducer of ALA synthase and PBG deaminase in normal human bone marrow. In addition, our results may explain the mechanisms by which heme potentiates Epo or IL-3 enhancement of erythropoiesis. 1) Heme may stimulate the translation of several globin and nonglobin mRNAs, including those of ALA synthase and PBG deaminase; 2) as endogenous cellular heme synthesis reaches optimal levels, heme exerts its regulatory role on ALA synthase by negative feedback inhibition. Additionally, an increase in cellular heme may lead to an increase in its own degradation by induction of heme oxygenase.

5-Aminolevulinate Synthetase↗
PubMed1989

Acquired toxoplasmic retinochoroiditis after platelet transfusions.

We present a rare well-documented case of acquired toxoplasmic retinochoroiditis transmitted by platelet transfusion. A 52-year-old woman developed severe thrombocytopenia shortly after receiving a sulfamethoxazole-containing antibiotic. This episode was treated with platelet transfusions and a three-day course of corticosteroids. Thirteen days later, she developed an acute febrile illness typical of the typhus-like form of toxoplasmosis. Fifty-six days later, while still taking corticosteroids for recurrent immune thrombocytopenia, she developed an acute macular retinochoroiditis OD. Serology showed recently acquired toxoplasmosis. Epidemiologic investigation revealed no possible source for the toxoplasmosis other than the platelet transfusion.

Adrenal Cortex Hormones↗
PubMed1988

Heme metabolism and in vitro erythropoiesis in anemia associated with hypochromic microcytosis.

Heme metabolism and in vitro erythropoietic growth (CFU-E, BFU-E) were examined in bone marrow cells taken from two siblings with apparent familial hypochromic microcytic anemia. Bone marrow cells from both patients grew adequate numbers of CFU-E and BFU-E colonies in culture in the presence of erythropoietin. In addition, small numbers of endogenous CFU-E were seen in 7-day cultures. Assays on bone marrow cells taken from both patients revealed that baseline delta-aminolevulinic synthase activity was considerably reduced, but increased six to seven fold (to normal levels) when patients' cells were exposed to pyridoxal phosphate (PLP). In both cases, ferrochelatase and delta-aminolevulinic acid dehydratase activities were normal. Bone marrow heme oxygenase showed no significant differences in activities between normals and patients values in the absence or presence of PLP. In contrast, heme synthesis by patients' bone marrow was less than that of normals. This study demonstrates that bone marrow cells from patients with this rare disorder have some disturbances in heme metabolism, whereas erythropoiesis appeared to be normal when cultured with adequate nutrients in vitro.

5-Aminolevulinate Synthetase↗
PubMed1988

Antidepressant activity of 2-hydroxydesipramine.

We describe the relationship of 2-hydroxydesipramine (OH-DMI) plasma levels and response in a prospective DMI study in which dosage was rapidly adjusted to achieve a relatively uniform DMI plasma level. In prior studies, OH-DMI plasma levels were not related to response, but in these fixed-dose protocols the effects of OH-DMI are easily obscured by the higher concentrations of the parent drug. We hypothesized that in this study a contribution of OH-DMI to response might become apparent because DMI levels were relatively constant. Inpatients with nonpsychotic, unipolar DSM-III major depression who remained depressed (Hamilton score greater than 18) after 1 week of hospitalization without medication received a 4-week DMI trial. Twenty-four-hour drug plasma levels were used to adjust dose to reach a target DMI steady-state plasma level. Twenty-seven patients completed the trial. On every measure of response, total drug levels (DMI + OH-DMI) were more strongly correlated with outcome than were DMI levels alone. With multiple regression, both DMI and OH-DMI levels were independently and significantly associated with response. These findings suggest that OH-DMI has antidepressant activity.

Adult↗
PubMed1988

Hereditary and environmental influences on the variation of thyroid hormones in normal male twins.

Heritability of the variation of the plasma total and unbound T4 (free T4), T3, T4-binding globulin (TBG), and TSH concentrations was investigated in 15 monozygotic and 15 dizygotic male twin pairs. The variability in plasma of total (58%) and free T4 (72%) concentrations was significantly less (P less than 0.01) in the twin pairs than in unrelated men. Half of the variability of T3 (P less than 0.05), TBG (P less than 0.05), and TSH (P less than 0.05) was affected by influences shared by the twin pairs in both monozygotic and dizygotic twin pairs. The heritability index for variability of the plasma total T4 and free T4 was greater than 28% (P less than 0.05), and it was 25% or less for T3 and TBG. Variation in TBG accounted for less than 20% (P less than 0.001) of the variation in thyroid hormone concentrations. The results indicate that familial factors, which are affected by genetic and/or environmental factors, influence the variation of plasma TBG, TSH, T4, free T4, and T3 concentrations among normal men. Genetic factors influenced the variation in plasma T4 and free T4 levels.

Humans↗
PubMed1988

Direct determination of free thyroxin in undiluted serum by equilibrium dialysis/radioimmunoassay.

We have designed a re-usable dialysis cell and a complex dialysis buffer, with which undiluted serum samples can be dialyzed with minimal changes in their serum matrix. Dialysate thyroxin (free T4) is then measured by a sensitive RIA for T4. The range of reportability was 2-128 ng/L, the normal range was 8-27 ng/L, and the interassay CV was 7%. Free T4 concentrations in various disorders were as follows: hyperthyroidism, 32-478 ng/L; in both excess thyroxin-binding globulin (TBG) and familial dysalbuminemic hyperthyroxinemia, 9-27 ng/L; primary hypothyroidism, less than 2-7 ng/L; central hypothyroidism, 4-6 ng/L; severe TBG deficiency, 9-25 ng/L; hypothyroxinemias of nonthyroidal illness, 8-35 ng/L. With this free-T4 assay, which is adaptable to clinical laboratory use, one can differentiate hyperthyroidism from the major euthyroid hyperthyroxinemias and hypothyroidism from the major euthyroid hypothyroxinemias.

Adult↗
PubMed1988

Hydroxydesipramine in the elderly.

Elevation of the hydroxy metabolites of the tricyclic antidepressants in the elderly has been demonstrated for nortriptyline and suggested for desipramine by a study reporting elevated hydroxydesipramine (OH-DMI) plasma levels in four older patients. In the current study, patients treated with desipramine (DMI) were studied to determine whether OH-DMI was elevated in two larger samples of depressed elderly patients and to determine the magnitude of the increase, if present. In Sample I, which consisted of 68 patients of whom 23 were over 60 years of age, a fixed target dose of DMI was employed. Sample II, in which 20 of the 56 patients were over 60, received a dose adjusted to attain a fixed target DMI blood level. OH-DMI levels were higher in patients over 60 than in younger patients but the differences were not significant in either sample individually. In the two samples combined, average OH-DMI levels were 11 ng/ml higher in patients over 60 and the difference was significant (t = 2.30, p = 0.02). If variations in dose are accounted for, OH-DMI concentrations are positively correlated with age in both samples. OH-DMI/DMI ratios were not higher in the patients over 60 in these samples, but OH-DMI/DMI ratios may be higher in patients on lower doses with low DMI levels, as is common in the treatment of elderly patients. If comparable dosage is administered, nonlinear increases in DMI levels result in lower OH-DMI/DMI ratios similar to those in younger patients. Although our findings of elevated hydroxy levels in the elderly are consistent with prior reports, the clinical importance of an 11 ng/ml difference, particularly in relation to total drug levels averaging 220 ng/ml, is questioned.

Administration, Oral↗
PubMed1987

Does the dexamethasone suppression test relate to subtypes, factors, symptoms, or severity?

Results of the dexamethasone suppression test (DST) are frequently abnormal in depression but not always. We performed the DST in 95 depressed inpatients to determine whether abnormal DST results were associated with individual symptoms of depression, latent behavioral "factors," melancholia, or severity of depression. Initial insomnia, agitation, loss of sexual interest, and weight loss correlated significantly with nonsuppression. Using multiple regression, these four symptoms contributed independently to the variance in DST results and more closely associated with the DST results than did severity or the diagnosis of melancholia or endogenous subtype. Factor analysis failed to identify a factor that correlated with the DST results more significantly than did the individual symptoms. Our findings and a literature review suggest that DST nonsuppression associates with certain vegetative signs of depression but not with such symptoms as loss of interest or anhedonia nor with "psychological" symptoms such as guilt, worthlessness, helplessness, hopelessness, or suicidal ideation.

Adolescent↗
PubMed1987

Criteria for the selection of 'early' carcinomas of the rectum. Are they valid?

We retrospectively reviewed 76 cases of adenocarcinoma of the lower rectum treated by abdominoperineal resection between 1975 and 1985 to elucidate the relationship between pathologic stage and both the size and histologic grade of the tumor. Our results showed evidence of lymphatic invasion in 50% of the 36 patients with tumors 4.0 cm or less in diameter, 51% of the 68 patients with tumors of either a high or moderate degree of differentiation, and an alarming 53% of the 34 patients whose tumors satisfied both criteria simultaneously. Finally, a substantial proportion (25%) of patients who had only partial invasion of the muscular layer also had lymphatic metastases. These results differ significantly from what has been previously reported and lead us to conclude that the commonly used criteria of size and histologic grade are inadequate criteria and do not allow confident selection of patients with lesions suitable for local treatment.

Adenocarcinoma↗
PubMed1987

Nonlinear desipramine kinetics: prevalence and importance.

Tricyclic antidepressant plasma levels have been used to guide dose adjustment in nonresponding patients, and recently 24-hour drug levels have been advocated for predicting therapeutic doses. Both methods of dose adjustment assume linear drug kinetics. Recent reports have suggested that desipramine kinetics are nonlinear, but the samples described were small, six subjects or fewer. In the current study, plasma desipramine concentrations were examined in 42 inpatients who were depressed who had achieved steady-state conditions with a low initial dose and subsequently with a higher dose. Desipramine concentrations increased significantly more than that predicted by the dose increase; however, only one third of the sample had substantial nonlinear changes (an increase in the concentration 50% greater than expected). In the remainder of the sample, disproportionate increases in plasma concentrations were not likely to be of clinical consequence.

Adolescent↗
PubMed1987

Enhancer of seizure: a new genetic locus in Drosophila melanogaster defined by interactions with temperature-sensitive paralytic mutations.

Mutations in the enhancer of seizure (e(sei] locus have been isolated on the basis of their ability to cause temperature-induced paralysis of alleles at the seizure (sei) locus at temperatures at which these mutations ordinarily do not paralyze. This enhancer is specific to the seizure locus and is without effect on other temperature-sensitive paralytic mutants including para, nap, tip-E and shi. This suggests that the enhancer responds specifically to the mechanism of paralysis mediated by the seizure mutations. The e(sei) is a recessive mutation which maps to 39.0 on the left arm of chromosome 3. Deficiency mapping has placed it at 69A4-B5 on the salivary gland polytene chromosome map. When a new enhancer allele was isolated following P-M hybrid dysgenesis, there was a concomitant P-element insertion at 69B. In the absence of seizure mutations, the enhancer mutation causes non-temperature dependent hyperactivity when agitated and interferes with the climbing response. Electrophysiological studies examined the effects of increasing temperature on electrical activity in the adult giant fiber/flight muscle system. Neuronal hyperactivity was seen in both e(sei) and sei single mutant homozygotes, but not in wild type. The hyperactivity was more severe in the sei;e(sei) double mutants. The correlation between the physiological effects and the mutant behavior suggests that both sei and e(sei) cause membrane excitability defects. Since previous work has shown that seizure mutants affect [3H]saxitoxin binding to the voltage-sensitive sodium channel, e(sei) may code for a gene product which interacts with this channel.

Alleles↗
PubMed1987

Rapid desipramine dose adjustment using 24-hour levels.

Prior work indicates that plasma tricyclic levels obtained 24 hours after a single dose correlate well with steady state levels achieved. Although this suggests that 24-hour levels could be used to predict the dose needed to reach a desired plasma level, this method has seldom been tested prospectively. In the current study we test this strategy and determine patients' tolerance of rapid dose adjustment. First, the relationship of 24-hour levels and steady state levels in a sample of 16 inpatients was determined using a fixed dose paradigm. In a second sample of 26 depressed inpatients, plasma desipramine levels obtained 24 hours after a single test dose were applied to the regression equation derived from the first sample in order to estimate the dose needed to achieve a steady state level of 140 ng/ml. Once determined, the full dose was then rapidly administered. Sixteen of the 18 (89%) patients who completed the dose adjustment study had steady state drug concentrations within a target range of 125 to 300 ng/ml. This distribution of levels differed significantly from that previously reported for a fixed dose sample in which only 19 of 83 (23%) patients had levels within this range. Dose adjustment using 24-hour levels was well tolerated and should help to attain a more rapid response to antidepressant treatment. This has important implications for reducing lengths of hospitalization for depressed inpatients. The technique should also prove useful in research where a uniform plasma level paradigm is desirable.

Adult↗