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Biomedical subjects

D Churchill

Publications and source records attributed to D Churchill.

At least 37 records · Page 2Linked to original sources
PubMed2000

Transradial coronary stent placement in a patient with severe idiopathic autoimmune thrombocytopenic purpura.

A 62-year-old man with refractory, idiopathic, autoimmune thrombocytopenic purpura developed unstable angina. Despite a platelet count of 3,000, transradial cardiac catheterization and coronary stent placement in the left anterior descending coronary artery were successfully performed. The patient was treated with clopidogrel for two weeks and aspirin for four weeks without adverse event.

Angina, Unstable↗
PubMed1999

Characterization of a chloride current in the larval epidermis of the beetle Tenebrio molitor.

Voltage-clamp analysis of single cuticle-attached epidermal cells dissected from the newly-ecdysed mealworm revealed the presence of a large inwardly-rectifying anion (i.e. outwardly-going) current. In many cells this current formed spontaneously on breaking into the cell with the patch pipette when the bath solution was isoosmotic with the pipette solution (415 mosmol/l). The current was evoked rapidly by electrical stimulation or by bathing the cells in hyposmotic saline (335 mosmol/l). The reversal potential of the activated current shifted in agreement with the Nernst prediction for Cl(-) when the transmembrane chloride gradient was altered by partially substituting bath or patch pipette Cl(-) with gluconate(-). Substitution of Na(+) with choline(+) or K(+) with TEA and Ba(+) in the bath or pipette solutions did not alter the reversal potential. Addition of 200 &mgr;mol/l cyclic AMP or 1 mmol/l cyclic GMP to the pipette solution increased the initial current strength and reduced the time taken to reach half peak amplitude from 117 sec to 49 sec and 41 sec, respectively. Cyclic AMP also raised the threshold at which the current developed under hyperosmotic conditions by about 20 mosmol/l. Addition of the Cl(-) channel blockers diphenylamine-2-carboxylic acid (200 &mgr;mmol/l) and diisothiocyanostilbene-2,2'-disulphonic acid (250 &mgr;mol/l) to the bath solution reduced the inwardly-rectifying anion current by 50%. This current was barely detectable in cells prepared from the mid-instar integument. This non-constitutive pattern of expression suggests that cellular Cl(-) efflux (and that of other anions) may be required during moult-cycle specific processes such as moulting fluid formation and cell volume regulation. As the strength of the epidermal anion current could be raised by the exogenous application of cytosolic cyclic nucleotides, the activity of the anion channels responsible for this current may normally be regulated by yet-to-be-identified hormone(s) or neuropeptide(s) acting on this tissue.

Journal Article↗
PubMed1998

Biophysical and pharmacological characterization of voltage-dependent Ca2+ channels in neurons isolated from rat nucleus accumbens.

The nucleus accumbens (NA) has an integrative role in behavior and may mediate addictive and psychotherapeutic drug action. Whole cell recording techniques were used to characterize electrophysiologically and pharmacologically high- and low-threshold voltage-dependent Ca2+ currents in isolated NA neurons. High-threshold Ca2+ currents, which were found in all neurons studied and include both sustained and inactivating components, activated at potentials greater than -50 mV and reached maximal activation at approximately 0 mV. In contrast, low-threshold Ca2+ currents activated at voltages greater than -64 mV with maximal activation occurring at -30 mV. These were observed in 42% of acutely isolated neurons. Further pharmacological characterization of high-threshold Ca2+ currents was attempted using nimodipine (Nim), omega-conotoxin-GVIA (omega-CgTx) and omega-agatoxin-IVA (omegaAga), which are thought to identify the L, N, and P/Q subtypes of Ca2+ currents, respectively. Nim (5-10 muM) blocked 18%, omegaCgTx (1-2 muM) blocked 25%, and omegaAga (200 nM) blocked 17% of total Ca2+ current. Nim primarily blocked a sustained high-threshold Ca2+ current in a partially reversible manner. In contrast, omegaCgTx irreversibly blocked both sustained and inactivating components. omegaAga irreversibly blocked only a sustained component. In all three of these Ca2+ channel blockers, plus 5 muM omega-conotoxin-MVIIC to eliminate a small unblocked Q-type Ca2+ current (7%), a toxin-resistant high-threshold Ca2+ current remained that was 32% of total Ca2+ current. This current inactivated much more rapidly than the other high-threshold Ca2+ currents, was depressed in 50 muM Ni2+ and reached maximal activation 5-10 mV negative to the toxin-sensitive high-threshold Ca2+ currents. Thus NA neurons have multiple types of high-threshold Ca2+ currents with a large component being the toxin-resistant "R" component.

Animals↗
PubMed1997

Effect of atenolol on birth weight.

To investigate the possible harmful effects of early antihypertensive drug therapy with atenolol versus other therapies on pregnancy outcome, we reviewed the records of 398 women referred to our antenatal hypertension clinic between 1980 and 1995. Babies born to women taking atenolol were significantly lighter than babies born to women taking other beta blockers, other antihypertensive drugs, or no therapy, suggesting that atenolol might be detrimental in early pregnancy.

Analysis of Variance↗
PubMed1997

Ambulatory blood pressure in pregnancy and fetal growth.

BACKGROUND: Retarded growth in utero has been linked with high blood pressure and other risk factors for cardiovascular disease in adult life. However, the influence on fetal growth of the maternal blood pressure during pregnancy is not well defined. In a prospective study, we examined the relation between maternal ambulatory blood pressure during pregnancy and indices of fetal growth. METHODS: We studied 209 healthy nulliparous pregnant women referred to an inner-city district general hospital (86% of 244 consecutively referred women who met the study criteria). 24 h ambulatory blood-pressure recordings were obtained in early (median 18 weeks [IQR 17-18]) mid (28 weeks [28]), and late (36 weeks [36]) gestation. Eight infants delivered before 32 weeks' gestation were excluded from the analysis. FINDINGS: A 5 mm Hg (1 SD) increase in mean 24 h diastolic blood pressure at 28 weeks' gestation was associated with a 68 g (95% Cl 3-132) decrease in birthweight; a similar change in diastolic pressure at 36 weeks' gestation was associated with a 76 g (24-129) decrease in birthweight. These associations were independent of potential confounders (maternal age, height, weight, cigarette smoking, alcohol intake, ethnic origin, pregnancy hypertension syndromes, and preterm birth). Maternal mean 24 h diastolic blood pressure at 28 weeks' gestation was also inversely associated with the infant's ponderal index at birth in multivariate analysis (p = 0.06). Higher maternal ambulatory blood pressure at 28 weeks' and 36 weeks' gestation also predicted lower head circumference, although these associations were dependent on birthweight. Associations between ambulatory systolic blood pressure and indices of fetal growth were weak and inconsistent and ambulatory blood pressure at 18 weeks' gestation did not predict fetal growth. INTERPRETATION: There is a continuous inverse association between fetal growth and maternal blood pressure, throughout the range seen in normal pregnancy. Maternal blood pressure may be an important confounding factor in the reported associations between fetal growth retardation and adult hypertension and cardiovascular disease.

Adult↗
PubMed1997

Neurotrophin modulation of NMDA receptors in cultured murine and isolated rat neurons.

Neurotrophin modulation of NMDA receptors in cultured murine and isolated rat neurons. J. Neurophysiol. 78: 2363-2371, 1997. Patch-clamp and calcium imaging techniques were used to assess the acute effects of the neurotrophins, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and nerve growth factor (NGF), on the responses of cultured and acutely isolated hippocampal and cultured striatal neurons to the glutamate receptor agonist N-methyl--aspartic acid (NMDA). The effects of BDNF on NMDA-activated currents were examined in greater detail. Currents evoked by NMDA, and the accompanying changes in intracellular calcium, were enhanced by low concentrations of the neurotrophins (1-20 ng/ml). The potentiation by the neurotrophins was rapid in onset and offset (<1 s). The neurotrophins also reduced desensitization of these currents in most cells. The enhancement of NMDA-activated currents by BDNF was observed using both perforated and whole cell patch recording techniques and could be demonstrated in outside-out patches. Furthermore, its effects were not attenuated by pretreatment with the protein kinase inhibitors genistein or 1-(5-isoquinolynesulfony)2-methylpiperazine (H7). Therefore, the actions of BDNF do not appear to be mediated by phosphorylation. Similar enhancements were observed with NT-3 and NT-4 and with NGF despite the fact that hippocampal neurons lack TrkA receptors. All together this evidence suggests that the enhancement of NMDA-evoked currents is unlikely to be mediated through the activation of growth factor receptors. Modulation of NMDA responses by BDNF was dependent on the concentration of extracellular glycine. The most pronounced potentiation by BDNF was observed at low concentrations, whereas no potentiation was observed in saturating concentrations of glycine, suggesting that BDNF may have increased the affinity of the NMDA receptor for glycine. However, the competitive glycine-site antagonist 7-chloro-kynurenic acid blocked the enhancement by BDNF without shifting the dose-inhibition relationship for this antagonist, and Mg2+ consistently depressed the potentiation of NMDA-evoked currents by BDNF, indicating that BDNF does not alter glycine affinity. BDNF also reversibly increased the probability of opening of NMDA channels recorded from outside-out patches taken from cultured hippocampal neurons. Other unrelated peptides including dynorphin and somatostatin also caused a glycine-dependent enhancement of NMDA currents and depressed the currents in saturating concentrations of glycine. In contrast, a shortened analogue dynorphin (6-17), which lacks N-terminus glycine residues, and another peptide met-enkephalin were without effects on NMDA currents recorded in low concentrations of glycine. Our results suggest that neurotrophins and other peptides can serve as glycine-like ligands for the NMDA receptor.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Differences between office and 24-hour ambulatory blood pressure measurement during pregnancy.

OBJECTIVE: To compare blood pressure (BP) measurements in ambulatory pregnant women with well-taken office readings. METHODS: A cohort of 209 nulliparous pregnant women who underwent 24-hour ambulatory BP monitoring throughout pregnancy was studied; 62 of these women were also studied 12 weeks after delivery. In addition, 30 nulligravid, nonpregnant women were studied as controls. RESULTS: The 24-hour median systolic and diastolic ambulatory pressures were higher than office pressures during pregnancy (the differences between the office and ambulatory systolic and diastolic BP measurements were +5 and +5.5 mmHg at 18 weeks, +3 and +6.5 mmHg at 28 weeks, and +5 and +5.5 mmHg at 36 weeks, P < .001). Ambulatory BP showed a consistent rise over the three measurement points, resulting in higher levels of pressure at 36 weeks than those found 12 weeks after delivery (the difference between ambulatory BP at these measurement points was +5 and +1 mmHg). At the postpartum measurement point, the relationship between ambulatory and office BP was similar to that in other surveys in nonpregnant women of comparable ages and in our own control group of nulligravidas (the difference between ambulatory and office BPs after delivery was +1.5 and +2 mmHg, a nonsignificant difference). CONCLUSION: There are important differences between ambulatory and office BPs measured throughout pregnancy, findings that could not be explained by activity or our present knowledge of cardiovascular hemodynamics in pregnancy. Ambulatory BP readings must be considered different entities than office BP readings. Care should be taken in predicting obstetric outcome from the results of ambulatory BP recordings.

Adult↗
PubMed1996

Summary of track B: clinical science.

AIM: To review Track B on clinical science. Major topics covered were quantitative HIV-1 plasma RNA measurement, combination antiretroviral therapy, protease inhibitors, treatment of primary HIV-1 infection, HIV-1 drug resistance, future use of antiretroviral drugs, paediatric HIV-1 infection, opportunistic infections and HIV/AIDS in developing countries. QUANTITATIVE HIV-1 PLASMA RNA MEASUREMENT: Quantification of HIV-1 RNA is a predictor of progression of immune deficiency and death in HIV-infected adults and children, and is useful in monitoring response to antiretroviral therapy. THERAPY: Combination antiretroviral therapy is now the standard of care, although questions about optimal starting time and the best initial regimen remain unresolved. Protease inhibitors are a powerful new class of antiretroviral agents which in combination with other drugs can produce profound reductions in plasma HIV-1 RNA levels. Trials are in progress of combination antiretroviral therapy, including protease inhibitors, in persons recently infected with HIV-1 to assess the feasibility of permanent suppression or eradication of HIV-1. Adherence to therapy and drug resistance will become increasingly important subjects. CONCLUSIONS: The genuine improvements in patient management are out of reach to the majority of the world's HIV-infected persons, a conclusion with implications which dampened the optimism generated by the conference.

Adult↗