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Biomedical subjects

S Miller

Publications and source records attributed to S Miller.

At least 217 records · Page 12Linked to original sources
PubMed1997

Adverse effects of low dose amiodarone: a meta-analysis.

OBJECTIVES: We sought to assess the odds of experiencing adverse effects with low dose amiodarone therapy compared with placebo. BACKGROUND: An estimate of the likelihood of experiencing amiodarone-related adverse effects with exposure to low daily doses of the drug is lacking in the published reports, and little information is available on adverse effect event rates in control groups not receiving the drug. METHODS: Data from four published trials involving 1,465 patients were included in a meta-analysis design. The criteria for inclusion were 1) double-blind, placebo-controlled design; 2) absence of a crossover design between patient groups; 3) mean follow-up of at least 12 months; 4) maintenance amiodarone dose < or = 400 mg/day; and 5) presence of an explicit description of adverse effects. Data were pooled after testing for homogeneity of treatment effects across trials, and summary odds ratios were calculated by the Peto-modified Mantel-Haenszel method for each adverse effect. RESULTS: The mean amiodarone dose per day ranged from 152 to 330 mg; 738 patients were randomized to receive amiodarone and 727 placebo. Exposure to amiodarone in this dose range, for a minimal duration of 12 months, resulted in odds similar to those of placebo for hepatic and gastrointestinal adverse effects, but in significantly higher odds than those of placebo (p < 0.05) for experiencing thyroid (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.0 to 8.7), neurologic (OR 2.0, 95% CI 1.1 to 3.7), skin (OR 2.5, 95% CI 1.1 to 6.2), ocular (OR 3.4, 95% CI 1.2 to 9.6) and bradycardic (OR 2.2, 95% CI 1.1 to 4.3) adverse effects. A trend toward increased odds of pulmonary toxicity was noted (OR 2.0, 95% CI 0.9 to 5.3), but this did not reach statistical significance (p = 0.07). The unadjusted total incidence of drug discontinuation was 22.9% in the amiodarone group and 15.4% in the placebo group. The odds of discontinuing the drug in the amiodarone group was approximately 1.5 times that of the placebo group (OR 1.52, 95% CI 1.2 to 1.9) (p = 0.003). CONCLUSIONS: Compared with placebo, there is a higher likelihood of experiencing several amiodarone-related adverse effects with exposure to low daily doses of the drug. Thus, although low dose amiodarone may be well tolerated, it is not free of adverse effects.

Amiodarone↗
PubMed1997

Myelin proteolipid DM20: evidence for function independent of myelination.

DM20 is a proteolipid protein that has been extensively studied for its role in central nervous system myelination. We demonstrate that DM20 expression is widespread and independent of myelination. In the Schwann cells and neurons of the peripheral nervous system, DM20 is not incorporated into the membrane as it is in the central nervous system (CNS), but remains cytoplasmic. Mutations that severely reduce the amount of DM20 mRNA in CNS myelinating cells have little effect on DM20 expression in nonmyelinating cells of the peripheral nervous system and embryonic CNS. Most importantly, the combination of wild-type DM20 from the endogenous X-linked gene and mutant DM20 expressed from an autosomal transgene results in embryonic lethality. We propose a function for DM20 to explain these diverse findings based on the ability of DM20 to form multimeric complexes, and hypothesize that the DM20 complex participates in intracellular molecular transport.

Animals↗
PubMed1997

Alpha interferon gene deletions in post-transplant lymphoma.

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized complication of organ transplant and has been associated with high mortality using conventional chemotherapy. We have investigated 11 cases of PTLD for alterations to the interferon alpha (IFNA) and p16 genes on chromosome 9p using archival material. 4/9 (44%) cases had deletions of the IFNA genes, in contrast to 1/59 (1.7%) cases of intermediate/high-grade de novo NHL drawn from the same geographical region. PTLD may therefore represent a distinct NHL subgroup exhibiting distinct gene pathology.

Chromosomes, Human, Pair 9↗
PubMed1997

Metabotropic glutamate receptor mGluR5 in astrocytes: pharmacological properties and agonist regulation.

Metabotropic glutamate receptor (mGluR) agonists induce extensive phosphoinositide (PI) hydrolysis in astrocytes grown in a chemically defined medium with select growth factors. These astrocytes express mGluR5 transcripts, but none of the splice variants of mGluR1, thus permitting the characterization of mGluR5 in a native CNS cell without interference from mGluR1 activity. mGluR5 activation (1) was not associated with stimulation of cyclic AMP formation, (2) showed high sensitivity to the removal of extracellular versus intracellular Ca2+, (3) displayed high coupling efficiency relative to receptor density, and (4) induced PI hydrolysis that was suppressed by phorbol esters with low potency. The rank order of agonist potency was similar to that observed in mGluR1 and mGluR5 transfected cells. The phenylglycine antagonists tested were effective in blocking responses to 1-aminocyclopentane-1S,3R-dicarboxylic acid, but not to glutamate. Prolonged exposure to agonists induced a two-phase desensitization of mGluR5 function, an initial phase (completed by 1 h and plateaus for another 3 h) and a late phase (progressive decrease to approximately 30% of control levels by 24 h). Only the latter phase was associated with receptor down-regulation. Desensitization of mGluR5 function did not involve receptor internalization or phosphorylation mediated by protein kinase C or A; it was purely homologous, and reversible. Resensitization after short agonist treatment did not require prior receptor sequestration. Recovery after prolonged agonist exposure required new protein synthesis, but the restoration of function was more rapid than normalization of receptor protein levels, indicating that regulation also involves other components of the transduction system. The protracted desensitization of mGluR5 in astrocytes suggests that the functions mediated by this receptor are maintained under a variety of conditions ranging from repetitive stimulation to injury responses.

Animals↗
PubMed1997

[MR tomography studies of myocardial function and perfusion after myocardial infarct].

PURPOSE: With the advent of fast pulse sequences, MR imaging of myocardial function and perfusion in ischaemic heart disease has become possible. Prior studies examined either myocardial perfusion or systolic wall motion. We intended to establish an examination procedure to simultaneously investigate regional myocardial motility and perfusion in patients 7-14 days after myocardial infarction. METHODS: A Turbo-FLASH 2D sequence was optimised to maximise image contrast between normal and malperfused myocardium after Gd-injection using a calculation model basing on the Bloch equation. Calculated values for trigger delay TD, inversion time TI and flip angle alpha were confirmed in a Gd-phantom and healthy volunteers. Subsequently, myocardial motility was studied (cine FLASH 2D sequence) and in slice positions with reduced wall thickening first pass and post contrast studies after 2-10 minutes were performed using the optimised Turbo-FLASH sequence. RESULTS: First pass SI-differences of normal compared to malperfused myocardium vary in relation to TD, TI and alpha in a relevant degree. Reduced myocardial motility was found with a sensitivity of 81% and specificity of 96%. Pathological perfusion patterns were detectable in all of these patients. CONCLUSIONS: A combined examination of motility and perfusion is possible by means of MRI and information about the status of postinfarct myocardium can be obtained.

Adult↗
PubMed1997

Phase-contrast MR angiography for detection of arteriosclerotic renal artery stenosis.

PURPOSE: To compare the accuracy of 3-D phase-contrast (PC) MR imaging with a 2-D time-of-flight (TOF) technique in the detection of arteriosclerotic renal artery stenosis. MATERIAL AND METHODS: Twenty-two patients with 28 angiographically proven renal artery stenoses were examined in a prospective blinded fashion by using 2-D TOF MR angiography (MRA) with venous saturation (FLASH) and 3-D PC MRA. The renal arteries were subdivided into 3 segments and graded for the presence of stenoses on a scale of 0-4 by 3 radiologists in blind. RESULTS: The accuracy of TOF and PC imaging in detecting renal artery stenoses was 65% and 77% respectively. Both 2-D TOF and 3-D PC MRA depicted 84% of the stenoses of the proximal renal artery greater than 50% in diameter. Renal artery stenoses greater than 50% and more than 15 mm in distance from the aorta were detected in 40% of cases with the 2-D TOF sequence and in 76% with the 3-D PC technique (p < 0.05). The rate of false-negative results was 32%. CONCLUSION: PC MRA is better at visualizing stenoses in the middle segment of the renal arteries and supplements conventional TOF techniques with additional information. However, even when the two techniques are combined, the false-negative rate in the MR imaging of stenoses of the renal arteries still needs to be reduced.

Aged↗
PubMed1997

Science in the early Athenaeum: a mirror of crystallization.

The Athenaeum, one of the most influential weekly magazines of Victorian Britain, was launched in 1828, towards the end of the period which saw the crystallization of science out of eighteenth-century natural philosophy and the differentiation of the individual sciences one from another. We examine the magazine's coverage of specific scientific areas in the year from May 1828 to April 1829, looking at what it defined as science and how it arrived at its definitions. The picture that emerges is complex, influenzed by editorial preferences as well as more clearly discernible objective criteria. But, at this stage, The Athenaeum appears to be opposed to opening up a gulf between the scientifically literate and the rest of its readership, reminding science of its debt to earlier endeavours.

History, 19th Century↗
PubMed1997

Comparison of activation of corticospinal neurons and spinal motor neurons by magnetic and electrical transcranial stimulation in the lumbosacral cord of the anaesthetized monkey.

To illuminate the action of non-invasive stimuli on the human cerebral cortex, responses of corticospinal axons and of plantar alpha-motor neurons following transcranial magnetic (TMS) and electrical stimulation (TES) were recorded in the lumbosacral cord in the anaesthetized macaque monkey. A round coil was used for TMS, and the anode was located at the vertex for TES. The responses of 175 identified corticospinal axons (conduction velocities of 24-95 m/s) were recorded from the lateral corticospinal tract at the T12-L3 spinal level. A single magnetic or electrical stimulus could evoke an early spike corresponding to the direct (D) wave in surface recorded volleys and was termed a D response. In the same axon, up to four further spikes, termed indirect (I) responses, could also be evoked. At a given intensity of stimulation, D responses had clear thresholds and fixed latencies, whereas I responses were labile in both respects. For TMS and TES, the thresholds of both D and I responses were inversely correlated with axonal conduction velocity. For TMS, fast conducting axons (> 75 m/s) had lower thresholds for D responses, while more slowly conducting axons (< 55 m/s) had lower thresholds for I responses. Very few of the axons with a conduction velocity of < 40 m/s (three out of 23) gave a D response to TMS. For TES, the majority of axons had lower thresholds for D responses or a similar threshold for both D and I responses. At threshold, the latencies of D responses evoked by TMS and TES were consistent with activation within the cortex, while TES also excited some corticospinal axons deep to the cortex. At 2.5 times threshold for the D response, TMS still excited axons mostly within the cortex, but with TES the site of activation shifted by as much as 65 mm below the cortex (mode 20 mm). Intracellular responses were recorded in 23 plantar alpha motor neurons supplying intrinsic muscles of the foot. All showed monosynaptic excitatory post-synaptic potentials (EPSPs) to both TMS and TES with no significant differences in the rise times of the evoked EPSPs. At threshold for a surface corticospinal volley, the average EPSP to TES began 0.5 ms earlier than that to TMS, and 1.0 ms earlier at 2.5 times this threshold. The different sites of activation of corticospinal neurons by TMS and TES, as well as the different distribution of D and I responses that they evoke, may both contribute to the differences in the onset latencies of the EMG responses evoked by these methods in human subjects.

Action Potentials↗
PubMed1997

Confirmation of ethanol compressed gas standard concentrations by an NIST-traceable, absolute chemical method and comparison with wet breath alcohol simulators.

This study compares compressed-gas Ethanol Breath Standards (EBS) with wet simulators as calibration standards for breath alcohol analyzers. After reviewing the technical basis and traceability for the two calibration sources, new analytical data verifying the ethanol content of EBS gas are presented. Based on collection of ethanol in an impinger and titration using a modified California Department of Health method, the data confirm the alcohol content of EBS compressed gas standards by an absolute, wet chemical method. These results establish the concentration accuracy and the NIST traceability of the EBS gas by two independent methods, gas chromatographic analysis traceable to NIST standards and the new wet chemical method. Effluent gas from a wet simulator standard is then analyzed by the wet method to show its equivalence with EBS gas.

Breath Tests↗
PubMed1997

Source of inhibin in ovine fetal plasma and amniotic fluid during late gestation: half-life of fetal inhibin.

Immunoactive inhibin (ir-inhibin) concentrations were determined in chronically catheterized sheep between 120 and 145 days gestation. Maternal plasma ir-inhibin concentrations remained basal (0.19 +/- 0.05 ng/ml) throughout the period of study. Immunoactive inhibin concentrations in male and female fetal plasma were elevated above those observed in maternal plasma, with the concentrations in plasma of male fetuses (7.38 +/- 0.04 ng/ml) being significantly greater (p < 0.001) than those in female fetuses (1.07 +/- 0.14 ng/ml). The concentrations of ir-inhibin in amniotic fluid of ewes bearing male fetuses (10.93 +/- 1.55 ng/ml) were significantly greater than in ewes bearing female fetuses (2.81 +/- 0.32 ng/ml; p < 0.05) but not significantly different from the concentrations in male fetal plasma. Immunoactive inhibin concentrations decreased following surgery in gonadectomized fetuses, to 3.25 +/- 0.99 ng/ml within 6 h, and remained at a mean value of 0.75 +/- 0.38 ng/ml from 24 h after gonadectomy. The half-life of circulating inhibin in fetal plasma, estimated from the decay curve during the first 6 h after surgery, was 3.94 +/- 0.88 h. There was a significant (p < 0.05) decrease in the concentration of ir-inhibin in amniotic fluid after gonadectomy; however, this decrease occurred gradually over 7 days, and ir-inhibin concentrations did not fall to those concentrations observed in fetal circulation at any time after gonadectomy. It is concluded that the major source of circulating ir-inhibin in male fetal plasma, but not in amniotic fluid, is the gonads.

Amniotic Fluid↗
PubMed1997

Lymphocyte, monocyte, and natural killer cell reference ranges in postpartal women.

Normative values for immune-cell subsets in postpartal women, who are recovering from the relative immunosuppression of pregnancy, have not been established. Considerable differences in normative values for subsets of immune cells have been demonstrated based on sociodemographic factors, such as age and race. In order to make accurate clinical decisions about postpartal women, comparisons with normal reference ranges are necessary. Therefore, flow cytometric data for 51 healthy women at 4 months postpartum are presented and changes over the first 4 postpartal months are documented. The levels of some lymphocyte cell subsets, such as CD4+/CD45RA+ and Ia on lymphocytes, remained stable over time. The levels of other lymphocyte cell subsets, such as CD4+/CD29+, increased over the first 4 postpartal months, while those of other cell subsets, such as CD8 and CD11b, increased between delivery and 2 months postpartum and then dropped again by the fourth postpartal month. The levels of two natural killer cell subsets (CD3-/CD16+ and CD3-/CD57+) rose from delivery until 1 month postpartum and then plateaued. Comparisons were made with reference ranges of nonpostpartal groups provided in the literature and in a study of healthy women being conducted in the same laboratory, and postpartal women were found to have lower values of CD8, CD3-/CD16+, CD4+/CD45RA+, CD20, and CD11b than those reported in the literature.

Adult↗
PubMed1997

Developmental enamel defects in tuberous sclerosis: a clinical genetic marker?

Ten probands with tuberous sclerosis (TS) and 20 first degree relatives were examined for evidence of pitted enamel hypoplasia; 100% of TS patients had pitting, compared to 65% of relatives and 72% of 25 controls. We found that 70% of TS cases had more than 14 pits per person compared with only 5% of relatives and 4% of controls; 85% of relatives and 84% of controls had fewer than six pits per person. Our results confirm that significantly increased numbers of dental enamel pits are found in persons with TS compared to controls. These results suggest that examination for the presence or absence of dental enamel pits is not a useful screening test for first degree relatives to detect otherwise unsuspected subjects with tuberous sclerosis. However, the lack of pits in first degree relatives in our study is probably largely because none of the relatives appeared to carry the TS gene.

Dental Enamel↗
PubMed1997

Neurobiology of speech perception.

The mechanisms by which human speech is processed in the brain are reviewed from both behavioral and neurobiological perspectives. Special consideration is given to the separation of speech processing as a complex acoustic-processing task versus a linguistic task. Relevant animal research is reviewed, insofar as these data provide insight into the neurobiological basis of complex acoustic processing in the brain.

Brain↗
PubMed1997

Nutritional value of pearl millet for lactating and growing goats.

Studies were conducted to assess nutritional value of pearl millet grain (Pennisetum glaucum [L] R. Br.) for lactating and growing goats. Three complete diets containing either 40% corn, 40% pearl millet, or 40% corn and pearl millet mixed 1:1 (wt/wt) were balanced to contain 16% crude protein and 2.24 Mcal DE/kg on an air-dry basis. Forty-five does were blocked by kidding date and randomly assigned to diets for a 7-wk investigation. Feed intake and milk production were unaffected (P > .25) by treatment, and they averaged 2.86 and 2.47 kg daily, respectively. Thirty-three growing goats were blocked by sex and fed the same diets for 15 wk. Daily growth rate and feed to gain ratio were depressed (P < .05) by 25.4 and 19.0%, respectively, when corn was completely replaced with pearl millet. Digestion coefficients for DM, GE, CP, and NDF were reduced by over 10 percentage units with partial or complete replacement of corn by pearl millet. Ruminal acetate and ratio of acetate to propionate increased (P < .05) but butyrate, propionate, and ammonia were depressed (P < .05) with the pearl millet diets. Growing goats consumed 43 meals daily. They consumed 26.9, 32.6, 27.4, and 13.1% of their ration during the morning (0600 to 1200), afternoon (1200 to 1800), evening (1800 to 2400), and night (2400 to 0600), respectively. Pearl millet is a useful energy feed for mature, but not for growing, goats.

Acetates↗
PubMed1997

Evaluation of a rapid, new method for detecting serum IgG antibodies to Helicobacter pylori.

There is an increased need for rapid, inexpensive tests to diagnose Helicobacter pylori infection. Our objective was to determine the performance characteristics of an immunochromatographic test (ICT) for detection of anti-H. pylori IgG antibodies. A commercially available ICT kit (FlexSure HP) was tested with a well-characterized cohort of banked sera as well as with fresh serum from randomly selected symptomatic patients. The ICT was evaluated with 107 stored sera and 96 prospective patients. The test correctly identified 65 of 68 H. pylori-infected and 37 of 39 noninfected stored sera and 54 of 57 infected and 30 of 39 noninfected patients. Sensitivity, specificity, and positive and negative predictive values were 96%, 95%, 97%, and 93% in stored serum and 95%, 77%, 86%, and 91% in fresh serum, respectively. We concluded that the ICT, reported at 4 min, is highly sensitive for detecting anti-H. pylori IgG antibodies in human serum. With a high negative predictive value, the test may be used to exclude H. pylori infection in symptomatic patients.

Adult↗
PubMed1997

Heat-induced thermal tolerance and radiation resistance to apoptosis in human lymphocytes.

We have investigated heat- and radiation-induced apoptosis in human lymphocytes in vitro. We have previously shown that apoptosis was induced by radiation at doses as low as 0.05 Gy. Here we report that heat induced apoptosis in human lymphocytes in a temperature- and time-dependent manner. Temperatures at or below 42 degrees C, for up to 90 min, did not cause lymphocytes to undergo apoptosis, whereas temperatures at or above 43 degrees C, for 30 min and longer, did induce apoptosis. Lymphocytes were protected against apoptosis induced by 44 degrees C heat by a prior heat shock of 42 degrees C for 30 min. Heat-induced thermal tolerance developed immediately following the inducing heat shock, was greater after 4 h, and persisted for at least 24 h. While heat also induced radiation resistance, this change was minor and not apparent until about 24 h after the heat shock. Prior to the development of radiation resistance, heat shock sensitized lymphocytes to radiation-induced apoptosis. We have previously shown that radiation-induced apoptosis in lymphocytes varies between donors and therefore may be useful in assessing individual radiosensitivity. We report here that heat also induced variable levels of apoptosis in lymphocytes from different donors, although the range of responses was not as large as those observed with radiation-induced apoptosis. In summary, heat shock induces tolerance to heat-induced apoptosis and results first in sensitization and then protection of lymphocytes against radiation-induced apoptosis.

Apoptosis↗