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Biomedical subjects

J C Nelson

Publications and source records attributed to J C Nelson.

At least 55 records · Page 3Linked to original sources
PubMed1998

The ratio of erythrocyte zinc-protoporphyrin to protoporphyrin IX in disease and its significance in the mechanism of lead toxicity on haem synthesis.

Protoporphyrin and zinc-protoporphyrin were measured in the erythrocytes of normal subjects, workers exposed to lead and patients with iron deficiency and erythropoietic protoporphyria (EPP). Results showed significantly higher levels of zinc-protoporphyrin in the lead-exposed workers (P < 0.0001), patients with iron deficiency (P < 0.0001) and EPP patients (P < 0.001) compared with normal subjects. The lead-exposed workers showed the highest levels of zinc-protoporphyrin, which were significantly greater than both the iron-deficient and EPP patients (P < 0.0001). They also showed a higher ratio of zinc-protoporphyrin to free protoporphyrin compared with normal subjects (P < 0.0001) but no significant difference in this ratio was found when compared with iron-deficient patients (P = 0.1). These results are discussed in light of the controversy concerning the mechanism of formation of zinc-protoporphyrin in lead exposure.

Adult↗
PubMed1998

Probing the order within neonatal heart rate variability.

The mechanism by which heart rate variability (HRV) changes during neonatal illness is not known. One possibility is that reduced HRV is merely a diminished or scaled-down version of normal. Another possibility is that there is a fundamental change in the mechanism underlying HRV, resulting in a change in the ordering of RR intervals. We investigated the nature and extents of order in RR interval time series from 25 Neonatal Intensive Care Unit patients with a spectrum of clinical illness severity and HRV. We measured predictability (deviation of predicted intervals from observed), and regularity (measured as approximate entropy) of RR interval time series showing different degrees of HRV. In RR interval time series where the effects of scaling were removed, we found 1) records showing normal HRV had more order than those showing low HRV; 2) the nature of the order was more like that of a periodic process with frequencies over a large range (time series whose log-log power spectrum had a 1/f distribution) than that of chaotic one (logistic map); and 3) the nature of order did not change greatly as HRV fell. We conclude that neonatal RR interval time series are ordered by periodic processes with frequencies over a large range, and that the extent of order is less during illness when HRV is low.

Algorithms↗
PubMed1998

The use of a sensitive equilibrium dialysis method for the measurement of free testosterone levels in healthy, cycling women and in human immunodeficiency virus-infected women.

Measurements of total and free testosterone levels in women have lacked precision and accuracy because of limited assay sensitivity. The paucity of normative data on total and free testosterone levels in healthy women has confounded interpretation of androgen levels in women with human immunodeficiency virus (HIV) infection and other disease states. Therefore, the objectives of this study were to develop sensitive assays for the measurement of the low total and free testosterone levels in women to define the range for these hormones during the normal menstrual cycle and assess the total and free testosterone levels in HIV-infected women. By using a larger volume of serum, increasing the incubation time, and reducing the antibody concentration, the sensitivity of the total testosterone assay was increased to 0.008 nmol/L, and that of the free testosterone assay was increased to 2 pmol/L. The mean percent free testosterone was 1.0 +/- 0.1% of the total testosterone. Serum total and free testosterone levels in the follicular and luteal phases were not significantly different, but both demonstrated a modest preovulatory increase, 3 days before the LH peak. Serum total [0.50 +/- 0.32 (14.60 +/- 9.22) vs. 1.2 +/- 0.7 nmol/L (34.3 +/- 21.0 ng/dL); P < 0.0001] and free testosterone levels (5.56 +/- 2.70 (1.58 +/- 0.80) vs. 12.8 +/- 5.5 pmol/L (3.4 +/- 1.7 pg/mL); P < 0.0001) were significantly lower in HIV-infected women (n = 37) than in healthy women (n = 34). Serum total and free testosterone levels were also significantly lower in HIV-infected women who were menstruating normally. There were no significant differences in serum total and free testosterone levels between those who had lost weight and those who had not. Testosterone levels correlated inversely with plasma HIV ribonucleic acid copy number. Serum FSH, but not LH, levels were significantly higher in HIV-infected women than in controls. Using assays with sufficient sensitivity, we defined the range for total and free testosterone levels during the normal menstrual cycle. Serum total and free testosterone levels are lower in HIV-infected women and correlate inversely with plasma HIV ribonucleic acid levels. The hypothesis that androgen deficiency contributes to wasting in HIV-infected women remains to be tested.

Adult↗
PubMed1998

Salsalate administration--a potential pharmacological model of the sick euthyroid syndrome.

This study examined salsalate ingestion as a model of the sequelae of acute inhibition of thyroid hormone binding to serum protein. One dose of salsalate (60-65 mg/kg) was administered to healthy volunteers. Serum salsalate concentrations peaked at 2 h (82 micrograms/mL), then declined at 8 h to 1.2 micrograms/mL. Serum total T4 (TT4) and total T3 (TT3) concentrations declined for 4 h, then recovered by 96 h, while T4 binding protein concentrations remained unchanged. TT3 was reduced to a greater extent than TT4 between 2 h and 72 h, and serum total reverse(r)T3 (TrT3) was transiently increased at 8 h. TSH concentrations fell while TT4 and TT3 fell, then recovered while TT4, TT3, and free T3, but not free T4, were still reduced. Subsequently, TSH overshot basal levels and continued to rise after 96 h while TT4, TT3, free T4, free T3, and TrT3 were all at basal levels. We postulate that an acute release of T4 and T3 from circulating transport proteins, induced by an inhibitor of binding, can result in large and rapid redistribution of T4 and T3 into tissue compartments associated with transiently reduced peripheral tissue 5'-monodeiodination and deranged TSH regulation.

Adult↗
PubMed1998

Differences in preconceptional and prenatal behaviors in women with intended and unintended pregnancies.

OBJECTIVES: This study examined whether pregnancy intention was associated with cigarette smoking, alcohol drinking, use of vitamins, and consumption of caffeinated drinks prior to pregnancy and in early pregnancy. METHODS: Data from a telephone survey of 7174 pregnant women were analyzed. RESULTS: In comparison with women whose pregnancies were intended, women with unintended pregnancies were more likely to report cigarette smoking and less likely to report daily vitamin use. Women with unintended pregnancies were also less likely to decrease consumption of caffeinated beverages or increase daily vitamin use. CONCLUSIONS: Pregnancy intention was associated with health behaviors, prior to pregnancy and in early pregnancy, that may influence pregnancy course and birth outcomes.

Adult↗
PubMed1998

Augmentation strategies with serotonergic-noradrenergic combinations.

Combinations of antidepressants with both serotonergic and noradrenergic activity may be especially effective and thus useful in treating refractory patients and severely depressed patients. In the current report, studies of combinations of serotonin selective reuptake inhibitors (SSRIs) and noradrenergic tricyclics or of SSRIs and bupropion are reviewed, and practical issues pertaining to their use are discussed.

Adrenergic Uptake Inhibitors↗
PubMed1998

Acute neuroleptic treatment in elderly patients without dementia.

Low doses of neuroleptics are the standard for treating psychosis in elderly patients because of concern about inducing adverse effects. The authors found that fixed, low-dose neuroleptic treatment (0.15 mg/kg/day) for 10 days resulted in low perphenazine levels and low rates of acute response (25%) in elderly patients with primary psychotic illness (without dementia). Increase in initial dose did not speed acute response and induced adverse effects that were absent or minimal with low-dose treatment. With higher-dose treatment, drug blood levels rose disproportionately, and level-to-dose ratios were higher than those observed in non-elderly adults. Naturalistic follow-up suggested that response may take longer to develop than in non-elderly adults and that low doses for a longer duration may provide effective treatment.

Aged↗
PubMed1998

Divalproex treatment of mania in elderly patients.

Because lithium is difficult to use, divalproex may be an effective alternative for elderly manic patients. In this study, the authors retrospectively assessed outcome of 21 patients, age 60 to 82 years, hospitalized for a manic episode and treated with divalproex. The mean final divalproex dose was 1,405 mg/day, and the mean serum level was 72 micrograms/ml; 20 patients also received concomitant neuroleptic medication. Overall, 19 of the 21 patients (90%) were rated as Much or Very Much Improved. The only remarkable side effect, sedation, occurred in two patients and improved with dose reduction. Although the study suggests that divalproex is an effective and well tolerated treatment for elderly manic patients, the retrospective nature of the study and the concomitant administration of neuroleptic medication suggest caution in interpreting the findings.

Aged↗
PubMed1998

Treatment of antidepressant nonresponders: augmentation or switch?

Selective serotonin reuptake inhibitors (SSRIs) are now commonly used in the treatment of major depression. In all patients starting treatment, the intent-to-treat response rate is about 50%. The other 50% will require some change in treatment, either augmentation or switch to a different agent. In this report, augmentation strategies are reviewed, with special attention to those strategies that have been used with the SSRIs. The data for switching antidepressants also are reviewed. Although there are no direct comparison studies of augmentation strategies versus switching that address the question of relative efficacy, the tactical issues that pertain to augmentation or switching are discussed.

Antidepressive Agents↗
PubMed1998

Overcoming treatment resistance in depression.

Treatment-resistant depression is commonly encountered by mental health professionals. Strategies for the treatment of resistant depression, including augmentation strategies and switching antidepressants, are reviewed. The potential advantages and disadvantages of each of these strategies are discussed.

Antidepressive Agents↗
PubMed1997

Solvophobically driven folding of nonbiological oligomers.

In solution, biopolymers commonly fold into well-defined three-dimensional structures, but only recently has analogous behavior been explored in synthetic chain molecules. An aromatic hydrocarbon backbone is described that spontaneously acquires a stable helical conformation having a large cavity. The chain does not form intramolecular hydrogen bonds, and solvophobic interactions drive the folding transition, which is sensitive to chain length, solvent quality, and temperature.

Acetonitriles↗
PubMed1997

Map of the synapses onto layer 4 basket cells of the primary visual cortex of the cat.

The pattern of excitatory and inhibitory inputs to the inhibitory neurons is largely unknown. We have set out to quantify the major excitatory and inhibitory inputs to layer 4 basket cells from the primary visual cortex of the cat. The synapses formed with the soma, and proximal and distal dendrites, were examined at the light and electron microscopic levels in four basket cells, recorded in vivo and filled with horseradish peroxidase. The major afferents of layer 4 have been well characterised, both at the light and electron microscopic levels. The sizes of the synaptic boutons of the major excitatory inputs to layer 4 from the thalamic relay cells, spiny stellate cells, and layer 6 pyramidal neurons are statistically different. Their distributions were compared to those of the boutons forming asymmetric contacts onto the basket cells, which were assumed to be provided by the same set of excitatory afferents. The best-fit results showed that about equal numbers of synapses were provided by the layer 6 pyramids (43%) and the spiny stellates (44%), whereas the thalamic afferents contributed only 13%. A similar analysis on the symmetric synaptic input to the basket cells indicated that as much as 79% of the symmetric synapses could have originated from layer 4 basket cells. Thalamic and spiny stellate synapses were preferentially located on the soma and proximal dendrites, regions that also had 76% of all the symmetric contracts.

Animals↗
PubMed1997

The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer's disease.

Centrally acting cholinergic drugs have been reported to increase regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) in brain regions affected by Alzheimer's disease (AD). We studied the effects of the acetylcholine releaser linopirdine (LPD) on SPECT rCBF in patients with probable AD. Twenty-four AD patients (12 M, 12 F; mean age +/- SD = 68.9 +/- 8.2 years) and 13 healthy controls (8 M, 5 F; 68.4 +/- 8.0 years) participated. AD patients were scanned with 20 mCi of Tc99m-ECD at baseline and following 4 weeks of treatment with LPD 40 mg TID (n = 15) or placebo TID (n = 9) in a double-blind trial. Healthy subjects were scanned for comparison with baseline AD scans. Cortical/cerebellar rCBF ratios were derived for nine cortical structures. The combined parietal association cortex showed a 20.6% reduction in patients relative to controls. Patients treated with LPD showed an increase in parietal rCBF of 4.1 +/- 5.8%; whereas those treated with placebo showed a decrease of -2.0 +/- 7.4% (F = 5.13; df = 1, 22; P = 0.03). These data support the conclusion that rCBF abnormalities in AD are, in part, truly "functional" and can be selectively altered with pharmacological interventions. The parietal activation seen with LPD and other cholinergic AD drug therapies suggests the importance of measuring parietal lobe neuropsychological function in the course of evaluating these drugs.

Acetylcholine↗
PubMed1997

Altered binding of serum thyroid hormone to thyroxine-binding globulin in women with functional hypothalamic amenorrhea.

OBJECTIVE: To further characterize hypothyroidemia with decreased serum concentrations of total triiodothyronine and total T4 in women with functional hypothalamic amenorrhea. DESIGN: Cohort study. SETTING: University of California San Diego Clinical Research Center. PATIENT(S): 8 women with functional hypothalamic amenorrhea (hypogonadotropic or normogonadotropic amenorrhea of at least 6 months duration) and 9 normal cycling women in the early follicular phase of their cycles. INTERVENTION(S): 24-hour frequent blood sampling. MAIN OUTCOME MEASURE(S): Comparison of levels of thyroid hormones and binding proteins between functional hypothalamic amenorrhea and normal cycling women. Measurements of serum free T4, free triiodothyronine, total T4, total triiodothyronine, reverse triiodothyronine, thyroid-binding globulin, albumin, and prealbumin levels and determination of T4 binding and binding affinity to each of the three binding proteins. RESULT(S): The results confirmed reduced levels of total triiodothyronine and total T4, but revealed no significant difference in free triiodothyronine and free T4, as well as reverse triiodothyronine, levels between functional hypothalamic amenorrhea and normal cycling women. Although serum levels of thyroid hormone-binding proteins were similar between normal cycling women and functional hypothalamic amenorrhea, a significant decrease in T4 bound to thyroid-binding globulin along with a decrease in apparent affinity of thyroid-binding globulin for T4 was present in functional hypothalamic amenorrhea. No differences in prealbumin- or albumin-T4 interactions were found. CONCLUSION(S): In functional hypothalamic amenorrhea, a reduced thyroid-binding globulin binding affinity appears to explain the disparity between normal levels of free triiodothyronine, free T4, and binding proteins in the face of reduced levels of total triiodothyronine and total T4.

Adult↗
PubMed1997

Serum free thyroxine concentration is not reduced in premature infants with respiratory distress syndrome.

OBJECTIVE: We used improved methods of assay to determine whether pituitary-thyroid function is altered in premature infants with respiratory distress syndrome (RDS) during the first week of postnatal life. METHODS: Serum free thyroxine (T4) was measured by direct equilibrium dialysis, total thyroxine (TT4) by radioimmunoassay, and thyrotropin by a sensitive immunometric assay in 90 premature infants (45 healthy control subjects and 45 with RDS) during their first week of life after 25 to 30 weeks of gestation. Infants in the RDS group received exogenous surfactant therapy. RESULTS: Free T4 and thyrotropin concentrations of infants were not significantly different between RDS and control groups. As expected, infants with RDS had significantly lower serum total T4 concentrations compared with control infants (p < 0.001). This difference was present even after stratification for gestational age (25- to 27-week group, p = 0.012; 28- to 30-week group, p = 0.002). Lower total T4 concentrations were attributable to lower T4 binding to serum proteins among infants with RDS compared with control subjects, especially in the 25- to 27-week gestation group (p = 0.0075). CONCLUSION: These data indicate that pituitary-thyroid function is not altered in premature infants with RDS. The low total T4 state in these premature infants is attributable solely to reduced serum T4 binding, as is often seen in acute nonthyroidal illnesses.

Case-Control Studies↗
PubMed1997

Thyroid function in very low birth weight infants.

OBJECTIVES: The purpose of this study was to test the hypothesis that low circulating thyroxine concentrations characteristic of very low birth weight (VLBW) neonates (< 1500 g) are the result of decreased protein binding of thyroid hormones and to elucidate the mechanism(s) responsible and possible significance thereof. DESIGN: Cross-sectional comparison of thyroid related measurements in cord blood specimens from VLBW infants and from full term infants. Longitudinal comparison in cord and 2- and 4-week blood specimens from VLBW infants. PATIENTS: Cord blood specimens were analysed from 47 VLBW and 45 full term infants weighing > or = 2500 g. Repeat analyses in venous bloods from 32 of the VLBW infants were analysed at 2 weeks of age and again at 4 weeks in 23. The first cohort of patients was studied in 1994 and comprised 28 VLBW and 24 full term infants (Cohort A). The studies were repeated in 1995-96 in 19 VLBW infants and 21 full term infants (Cohort B). MEASUREMENTS: T4, free T4 (FT4), T3, thyroxine binding globulin (TBG), and TSH were measured in cord blood and 2- and 4-week venous specimens from VLBW infants and in cord blood specimens of full term infants. Molar ratios of T4/TBG were calculated. RESULTS: (1) Cord blood TBG, T4 and T3 concentrations of VLBW infants were each 60% of those of term infants. TBG concentrations were 397 +/- 111 vs 680 +/- 172 nmol/l (P < 0.0005). T4 concentrations were 76 +/- 22 vs 139 +/- 26 nmol/l (P < 0.0005). FT4 concentrations were in the normal adult range in both neonatal groups. T4/TBG ratios did not differ between the neonatal groups but were significantly less than that of adults (P < 0.001). (2) TSH concentrations in VLBW infants at 2 and 4 weeks were less than 50% of cord blood values. At 2 weeks, TBG concentrations of VLBW infants were unchanged from cord blood concentrations but mean T4 concentration fell by 18% and T4/TBG ratios by 21% (P < 0.005). Mean FT4 rose by 78% (P < 0.02). The changes in mean T4 and FT4 were due largely to FT4 concentrations of 37-113 pmol/l and T4 concentrations of 13-48 nmol/l in 5 infants. These infants also had lower T4/TBG ratios and were smaller and more ill than the remainder of the cohort. The changes disappeared by 4 weeks in 3 of the 4 infants tested. CONCLUSIONS: Cord T4/TBG ratios are the same in very low birth weight and term infants and are significantly lower than in adult blood. These are more than compensated for in term infants by a 236% increase in thyroxine binding globulin concentrations. The lower thyroxine binding globulin concentrations in very low birth weight infants explain their much lower T4 concentrations. Cord FT4 concentrations of full term and very low birth weight infants are in the normal adult range. T4 concentrations are further depressed and free T4 concentrations elevated in the most ill very low birth weight infants at 2 weeks of age in a manner analogous to that of the 'sick euthyroid syndrome'.

Cross-Sectional Studies↗