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Biomedical subjects

J David

Publications and source records attributed to J David.

At least 55 records · Page 3Linked to original sources
PubMed1996

Elevated levels of corticotrophin-releasing factor binding protein in the blood of patients suffering from arthritis and septicaemia and the presence of novel ligands in synovial fluid.

In view of the reported inflammatory effects of corticotrophin-releasing factor (CRF) and the associated regulatory elements in the gene of its binding protein (BP), we postulate that both BP as well as novel BP-ligands other than CRF may be involved in inflammatory disease. We have investigated BP in the blood of patients with arthritis and septicaemia and have attempted to identify CRF and other BP-ligands in synovial fluid. The BP was found to be significantly elevated in the blood of patients with rheumatoid arthritis and septicaemia. There was less BP-ligand and CRF in synovial fluid from patients with rheumatoid arthritis that from those with osteo- or psoriatic arthritis. There was at least 10-fold more BP-ligand than CRF in the fluid of all three groups of patients. A small amount of immunoreactive human (h)CRF, eluting in the expected position of CRF-41, was detected after high-pressure liquid chromatography of arthritic synovial fluid; however, the bulk of material with BP-ligand binding activity eluted earlier, suggesting that synovial fluid contained novel peptides that interacted with the BP. These results would suggest that the BP and its ligands could play an endocrine immunomodulatory role in inflammatory disease.

Acute Disease↗
PubMed1996

Lymphadenopathy.

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Child↗
PubMed1996

Modulation of Ca2+ and K+ conductances in an identified insect neurone by the activation of an alpha-bungarotoxin-resistant cholinergic receptor

The effects of activation of a population of [alpha]-bungarotoxin ([alpha]-bgt)-insensitive cholinergic receptors on the soma of the cockroach fast coxal depressor motor neurone (Df) have been examined under two-electrode voltage-clamp conditions. Activation of these receptors was achieved by bath-application either of acetylcholine (ACh) in the presence of [alpha]-bgt or of the muscarinic agonist McN-A-343 (McN). Since these receptors have been shown previously to respond to some nicotinic agonists, we refer to them as 'McN-sensitive or mixed pharmacological profile muscarinic receptors' (mMAChRs). Activation of these receptors normally results in a biphasic response consisting of an initial outward current component, which reverses near -70 mV, and a later (delayed) inwardly directed current, which is only observed at membrane potentials more positive than -40 to -20 mV. The initial outwardly directed component of the McN-induced current appears to result from an increase in K+ conductance since it reverses at potentials close to the K+ equilibrium potential (EK) (approximately -70 mV under the experimental conditions used) and is blocked by internal Cs+. This increase in K+ conductance is probably due to an increase in Ca2+-activated K+ current (IK,Ca) which is known to form a large proportion of the outward current observed when this neurone is depolarized. The delayed inwardly directed current induced by McN results from suppression of a Ca2+ current (ICa) which, in turn, causes a decrease in IK,Ca. The net effect is a reduction in outward current, because IK,Ca is considerably larger than ICa. Evidence for an action of McN upon Ca2+ channels is provided by experiments in which K+ currents have been suppressed by internal Cs+ to reveal inward currents produced by the movement of Ba2+ through voltage-dependent Ca2+ channels. Ba2+ currents observed under these conditions are suppressed by bath application of McN. The inwardly directed current component of the McN response is unlikely to involve direct regulation of IK,Ca, since McN has no effect upon this current when it is induced by brief intracellular Ca2+ injections. Both the initial outwardly directed component and the delayed inwardly directed component of the McN-induced current were suppressed by intracellular injection of the Ca2+ chelator BAPTA. These observations suggest that a rise in [Ca2+]i mediates the electrophysiological effects of McN in Df somata.

Journal Article↗
PubMed1996

[A combination of normal physiologic management of delivery and epidural analgesia].

From the anaesthesiological aspect the authors recommend the method of loss of resistance during verification of the epidural space as a safer method (lower percentage of perforations of the spinal dura mater). At the mentioned concentrations and dosage the authors did not observe any motor disorders of the lower extremities. The assembled experience with a combination of physiological delivery with emphasis on the second stage of labour and epidural analgesia justify not only the statement that this combination is possible but that it is favourable for mother and foetus. The combination reduces considerably the disadvantages of both types of management of labour, it used isolated. It puts, however, much greater demands on the staff and the costs are higher. These disadvantages should, however, not influence humanitarian trends in obstetrics.

Adult↗
PubMed1995

Diverticulitis.

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Aged↗
PubMed1995

Rheumatology.

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Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Inflammatory cytokine responses in juvenile chronic arthritis.

The inflammatory cytokines interleukin 1 beta (IL-1 beta) interleukin 6 (IL-6), tumour necrosis factor alpha (TNF alpha) and the anti-inflammatory peptide--the interleukin 1 (IL-1) receptor antagonist--were measured in the plasma of children with juvenile chronic arthritis (JCA). In the two subgroups studied (polyarticular JCA and systemic JCA), there was good correlation between laboratory measures of disease activity C-reactive protein (CRP), erythrocyte sedimentation rate and clinical scores for disease activity. Despite higher levels of CRP in the systemic group IL-1 beta levels were lower and regression analysis recorded a difference in the relationship between CRP and IL-1 beta within the two clinical groups. In contrast, IL-6 levels were high in the systemic group and correlated with disease activity. No such correlation was observed in the polyarticular group. Five children with systemic JCA were studied during the febrile phase of their illness. IL-6 levels rose and fell with the fever. TNF alpha levels also rose and fell but out of phase with the fever. In contrast IL-1 beta levels were either undetectable throughout the febrile episode or only became detectable as the temperature reduced to normal. The IL-1 receptor antagonist was usually found in 1000-fold excess over IL-1 beta, levels rising and falling with the fever. These results demonstrate difference in the cytokine profiles and acute phase protein responses in polyarticular and systemic JCA. This would suggest different pathogenic mechanisms for these two groups of JCA with IL-6 being the more important cytokine in systemic JCA.

Acute Disease↗
PubMed1995

Aminophylline alters pharmacokinetics of carbamazepine but not that of sodium valproate--a single dose pharmacokinetic study in human volunteers.

Pharmacokinetic interaction of aminophylline with single dose sodium valproate (400 mg) and carbamazepine (200 mg) was evaluated in normal healthy volunteers using a cross over design. Neither the serum concentrations nor the pharmacokinetic parameters of sodium valproate (SV) were altered by the coadministration of aminophylline (AMP). In contrast AMP significantly decreased the plasma concentrations of carbamazepine (CBZ). The Cmax of CBZ was significantly lowered from 1.73 +/- 0.18 to 0.94 +/- 0.08 microgram/ml and the AUC o-t was significantly decreased from 76.19 +/- 6.20 to 52.66 +/- 1.84 micrograms/h/ml (P < 0.05). The pharmacokinetic parameters of CBZ that were altered in the presence of AMP were: the Tmax and t1/2 which was prolonged about threefold from 5.60 +/- 1.60 to 16.80 +/- 7.94 h and 44.88 +/- 4.50 to 125.07 +/- 29.09 h, respectively. The Vd was marginally increased from 2.19 +/- 0.13 to 3.85 +/- 0.57 L/kg and the Cl was decreased from 34.07 +/- 3.78 to 25.26 +/- 5.15 mL/min. None of these alterations are statistically significant. Bioavailability of CBZ was reduced by 29% in the presence of AMP, while that of SV was increased by about 8%. Results are of clinical significance because simultaneous administration of CBZ and AMP may reduce the efficacy of CBZ in epileptic patients.

Administration, Oral↗
PubMed1994

Radiation effects on late cytopathological parameters in the murine lens relative to particle fluence.

Lenses of mice irradiated with 250 MeV protons, 670 MeV/amu 20Ne, 600 MeV/amu 56Fe, 600 MeV/amu 93Nb and 593 MeV/amu 139La ions were evaluated by analyzing cytopathological indicators which have been implicated in the cataractogenic process. The LETs ranged from 0.40 keV/micrometer to 953 keV/micrometer and fluences from 1.31 10(3)/mm2 to 4.99 x 10(7)/mm2. 60Co gamma-rays were used as the reference radiation. The doses ranged from 10 to 40 cGy. The lenses were assessed 64 weeks post irradiation in order to observe the late effects of LET and dose on the target cell population of the lens epithelium. Our study shows that growth dependent pathological changes occur at the cellular level as a function of dose and LET. The shapes of the RBE-LET and RBE-dose curves are consistent with previous work on eye and other biological systems done in both our laboratory and others. The RBEmax's were estimated, for the most radiation cataract related cytological changes, MN frequency and MR disorganization, by calculating the ratio of the initial slopes of dose effect curve for various heavy ions to that of 60Co gamma-ray. For each ion studied, the RBEmax derived from micronucleus (MN) frequency is similar to that derived from meridional row (MR) disorganization, suggesting that heavy ions are equally efficient at producing each type of damage. Furthermore, on a per particle basis (particle/cell nucleus), both MN frequency and MR disorganization are LET dependent indicating that these classic precataractogenic indicators are multi-gene effects. Poisson probability analysis of the particle number traversing cell nuclei (average area = 24 micrometers2) suggested that single nuclear traversals determine these changes. By virtue of their precataractogenic nature the data on these endpoints intimate that radiation cataract may also be the consequence of single hits. In any case, these observations are consistent with the current theory of the mechanism of radiation cataractogenesis, which proposes that genomic damage to the epithelial cells surviving the exposure is responsible for opacification.

Animals↗
PubMed1994

The functional and psychological outcomes of juvenile chronic arthritis in young adulthood.

The functional and psychological outcome of 43 patients with polyarticular juvenile arthritis was assessed in order to evaluate the impact of disease on their quality of life. Mean disease duration was 19.7 yr (range 10-39 yr), mean age 26.7 yr (range 18-54 yr) with sex ratio 1:3 (male:female). Severe disability was present in 8% of systemic onset, 34% of RF negative (Rh-P), 38% of RF positive (Rh+P) and 86% of extended pauci-articular (ExP) juvenile arthritics-this last high percentage was due to ocular impairment. The Rh+P had more hip (100% of the group) and knee prostheses (31%) compared with Rh-P (77 and 11% respectively). The Rh+P and ExP groups were the most disabled with the highest proportions of patients with currently active disease (85 and 71% respectively). Psychological testing showed that 21% of the patients were clinically depressed and the rate increased (P = 0.06) with the degree of disability. The proportion of patients demonstrating an anxious preoccupation with their disease increased (P = 0.002) with the degree of disability. Despite this, 66% of patients were employed and 38% felt that their arthritis had no effect on their ability to form relationships.

Adult↗
PubMed1994

An inexpensive method for fabrication of intracerebroventricular cannulae for rats.

An inexpensive and simple method to fabricate intracerebroventricular (i.c.v.) cannulae for rats with readily available material is described here. The procedure is cost effective and quick. The cannulae thus designed are suitable for injecting minute quantities (microliters) of drugs/chemicals interacerebroventricularly for acute or chronic experiments in rats.

Animals↗
PubMed1994

Involvement of adenosine in postictal events in rats given electroshock.

The effect of a selective adenosine antagonist, 8-cyclopentyl 1,3-dimethylxanthine (8-CPT) was used to examine involvement of adenosine in ictal and postictal events in rats subjected to maximal electroshock (MES). MES induces the ictal event of hindlimb tonic extension (HLTE) followed by postictal depression (PID). 8-CPT 10 mg/kg, ip produced maximal significant reduction of PID without affecting HLTE, further confirming involvement of adenosine in PID. Carbamazepine and sodium valproate were studied independently and were coadministered with 8-CPT to determine if their anticonvulsant activity was modulated by adenosine and if they altered PID. 8-CPT did not antagonize the seizure protection afforded by CBZ or SV. CBZ significantly reduced postictal events whereas SV had no significant effect. These observations further confirm a role for adenosine in postictal phenomena.

Adenosine↗