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Biomedical subjects

M Price

Publications and source records attributed to M Price.

At least 109 records · Page 6Linked to original sources

Kappa opiate receptor multiplicity: evidence for two U50,488-sensitive kappa 1 subtypes and a novel kappa 3 subtype.

Kappa receptor multiplicity is a complex area. We now present evidence from binding studies suggesting the existence of four kappa receptor subtypes. The guinea pig cerebellum contains high levels of U50,488-sensitive, or kappa 1, receptors. Kappa opiates (U50,488, tifluadom, Mr2034, Mr2266 and Win44,441) compete [3H]ethylketocyclazocine binding to kappa 1 receptors with kappa, values under 10 nM and Hill coefficients of approximately one, as does dynorphin A (kappa 1, 0.27 +/- 0.05 nM; Hill coefficient, 0.83 +/- 0.20, n = 4). However, competition studies with dynorphin B yield a Hill coefficient of 0.46 +/- 0.03 (n = 5) and nonlinear regression analysis of the competition curve is best fit by two sites. alpha-Neoendorphin Neoendorphin competition curves (Hill coefficient, 0.46 +/- 0.07; n = 3) also were best fit with two components. Competition studies with both alpha-neoendorphin and dynorphin B together suggest that both compounds label the same site with high affinity. Similar results were obtained using [3H]U69,593. Dynorphin B and alpha-neoendorphin competed binding with Hill coefficients of 0.45 +/- 0.04 (n = 3) and 0.59 +/- 0.09 (n = 3), respectively. These data suggest two subtypes of kappa 1 receptors in the guinea pig cerebellum: kappa 1a and kappa 1b. Classical kappa opiates and dynorphin A have high affinity for both subtypes whereas dynorphin B and alpha-neoendorphin label kappa 1b over 50-fold more potently than kappa 1a sites. [3H]Naloxone benzoylhydrazone [( 3H]NalBzoH) labels a novel, U50,488-insensitive kappa receptor subtype, kappa 3, in membranes from calf striatum, rat and mouse brain. We now have developed a relatively selective assay in calf striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

The pattern electroretinogram and visual-evoked potential in glaucoma.

The pattern electroretinogram (PERG) may reflect ganglion cell or inner retinal layer activity. The most sensitive spatial and temporal variables for testing patients with glaucoma have not yet been identified. Fifty-two glaucoma suspects, 51 glaucoma patients, and 28 normal subjects were studied with the PERG and VEP, using three repetition rates and three spatial frequencies. Fast Fourier transforms were calculated at each spatial frequency and reversal rate. An analysis of variance revealed that normals could be differentiated from ocular hypertension and glaucoma patients using the amplitude of the PERG (second and fourth harmonic). Abnormalities in phase of the PERG between groups were also detected. A discriminant analysis of all amplitude and phase data revealed that the phase shift of the response of the second harmonic at 11 alternations/s (15-min checks) and at 5.5 alternations/s (15-min checks) correctly identified 81% of the normal and 75% of the glaucoma patients. The phase shift determinations of the VEP revealed significant abnormalities using 2 and 1/2 standard deviation confidence limits. There was significant overlap in the pattern ERG amplitude and phase shift in all three groups.

Analysis of Variance↗

Ultrasound attenuation of the os calcis in women with osteoporosis and hip fractures.

Bone ultrasound attenuation of the calcaneus, and vertebral and femoral bone density measured by dual photon absorption were determined in 22 women with osteoporosis, 10 women with hip fractures, and 29 normal, age-matched controls to determine the utility of the ultrasound technique as an indicator of axial osteopenia. Vertebral and femoral neck density and bone ultrasound attenuation were significantly decreased (P less than 0.01) in the women with osteoporosis and those with hip fractures. The sensitivity and specificity of bone ultrasound attenuation was 80% at a value of 50 dB/MHz. At 90% specificity the sensitivity of bone ultrasound attenuation was 65%. The results of this pilot study suggest that ultrasound attenuation, a safe, simple, and radiation-free procedure, may be utilized as an indicator of decreased axial bone mass.

Aged↗

Irreversible opiate agonists and antagonists: V. Hydrazone and acylhydrazone derivatives of naltrexone.

We have synthesized a series of hydrazones and acylhydrazones of naltrexone. These substitutions had modest effects on competition of mu binding but many greatly enhanced the relative potency of the compounds for delta receptors. Increased delta affinity was most prominent with the acylhydrazones. Many of the derivatives elicited a wash-resistant inhibition of binding which was restricted to mu, not delta, binding sites. This wash-resistant inhibition of binding did not correlate with affinity, as determined by IC50 values, implying that the inhibition could not be explained simply by slow rate of dissociation due to increased affinity.

Animals↗

Fever alters characteristics of sleep in rats.

This study examined the effects of a fungal infection on body temperature (Tb) and sleep states. Tb and sleep were recorded in male rats for 24 hr after a saline injection and 48 hr after a subcutaneous injection of live brewer's yeast, at ambient temperatures (Ta's) of 20 degrees and 30 degrees C. Peak fevers of 1.6-3.1 degrees C occurred within 6-10 hr at both Ta's. The rats remained febrile for the next 12-24 hr. For the first 24 hr postyeast, amounts of SWS increased by 19 +/- 3% at 20 degrees C and 12 +/- 2% at 30 degrees C. Specifically, SWS was significantly increased from hr 5-8 (lights-on) and 13-24 (lights-off) at 20 degrees, and from hr 5-8 and 17-24 at 30 degrees C. Ta did not affect the changes in Tb or the changes in SWS after either saline or yeast. Duration of REMS varied with Ta after saline. After yeast, REMS increased by 21 +/- 12% at 20 degrees and decreased by 28 +/- 6% at 30 degrees C, with the net result that REMS at the two Ta's was equal during the fever. Furthermore, while the rats were febrile the normal diurnal variation in REMS was eliminated. Sleep and Tb returned to control values during the second fever day. These results suggest that an activated immune system both increases SWS and overrides the diurnal and thermoregulatory modulations of REMS.

Animals↗

The consequences of health service privatisation for equality and equity in health care in South Africa.

The trend towards the privatisation of health services in South Africa reflects a growing use of private sources of finance and the growing proportion of privately owned fee-for-service providers and facilities. Fee-for-service methods of reimbursement aggravate the geographical maldistribution of personnel and facilities, and the competition for scarce personnel resources aggravates the difference in the quality of the public and private services. Thus the growth in demand for these types of providers may be expected to increase inequality of access in these two respects. The potential expansion of medical scheme coverage is shown to be limited to well under 50% of the population, leaving the majority of the population without access to private sector health care. Even for members of the medical schemes, benefits are linked to income, thus clashing with the principle of equal care for equal need. The public funds needed to overcome financial obstacles to access to private providers could be more efficiently deployed by financing publicly owned and controlled health services directly. Taxation also offers the most equitable method of financing health services. Finally, attention is drawn to the dilemma resulting from the strengthening of the private health sector; while in the short term this can offer better care to more people on a racially non-discriminatory basis, in the long term, health care for the population as a whole may become more unequal and for those dependent on the public sector it may even deteriorate.

Black People↗

Health surveys in developing countries: the objectives and design of an international programme.

There have been calls recently for a major international effort to collect epidemiological information in developing countries. One approach to a World Health Survey is considered, namely single-round retrospective interview surveys. Surveys can contribute to the improvement of national health information systems by providing person-based, rather than episode-based, measures related to health that apply to the entire population. A programme of health interview surveys could be used to ascertain patterns of morbidity and mortality, to measure access to and use of health services and to develop and disseminate methodologies for collecting and analysing health related data. Single-round surveys could not be used to evaluate the impact of investments on health and would be of limited use for improving our understanding of the determinants of ill health. Attention is drawn to a number of conceptual, technical and logistic issues to be considered in the design of a World Health Survey.

Attitude to Health↗

Improving recovery following cardiac surgery: a randomized clinical trial.

To enhance individual and family health during recovery from heart surgery, this study employed nursing interventions based on self-efficacy and family stress theory during the hospitalization period and for 3 months thereafter. The effectiveness of the interventions were assessed through a randomized trial in which 67 prospective bypass and valve surgery patients, aged 30-77 years, and their spouses, were allocated either the experimental interventions or usual care and followed for 6 months. At 3 months post-surgery, the only statistically significant differences between the experimentals and controls were on perceived self-efficacy for lifting and tolerating emotional distress. At 6 months no significant differences were found on individual or family measures. Analyses revealed that age, gender and preoperative cardiac status significantly affected individual recovery. The study is continuing with a larger sample in order to explicate the recovery process and to better determine whether a low intensity nursing intervention can effect changes in individual and family recovery.

Adult↗

Volume response of quiescent and interleukin 2-stimulated T-lymphocytes to hypotonicity.

Regulatory volume decreased (RVD) in lymphocytes in response to hyptonically induced swelling is dependent on the membrane permeabilities of K+, Cl-, and H2O. We used electronic cell sizing, cell water determination, and the whole cell patch-clamp method to study these membrane permeabilities in the cloned mouse T-lymphocyte, L2. Quiescent L2 cells express low levels of a voltage-gated K+ channel and show no RVD at 25 degrees C. In contrast, L2 cells stimulated to proliferate with the growth factor interleukin 2 have increased K+ conductance and show RVD in response to hypotonicity. RVD in stimulated cells is blocked by quinine and verapamil at levels that also completely block the voltage-gated K+ conductance. Swollen, unstimulated L2 cells can be induced to shrink by addition of the monovalent cation ionophore gramicidin in the presence of impermeant extracellular organic cations; gramicidin also enhances the rate of RVD in stimulated cells. Additionally, the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) blocks this gramicidin-facilitated RVD. These results suggest that a minimum requisite Cl- permeability is present even in the unstimulated L2 cells, that a necessary and limiting K+ permeability determines the rate of RVD, and that this K+ permeability increases after growth-factor stimulation as predicted from the direct measurement of voltage-gated K+ conductance. The hydraulic permeability is approximately 70% greater in proliferating L2 cells than in quiescent cells. At 37 degrees C, some RVD occurs in unstimulated L2 cells, and stimulated cells show faster and more complete shrinkage. These results are discussed with respect to the underlying membrane permeabilities and their relation to stimulated cell proliferation.

Animals↗

MK-801 powerfully protects against N-methyl aspartate neurotoxicity.

Using the ex vivo chick embryo retina to study the efficacy of antagonists in blocking the excitotoxic effects of excitatory amino acid agonists, we previously identified phencyclidine as the most powerful known anti-excitotoxin. Here we show that MK-801 is 5 times more powerful than phencyclidine as an anti-excitotoxin, that its antagonism is specific for N-methyl-asparate toxicity, is non-competitive and does not entail inhibition of excitatory amino acid receptor binding.

Animals↗

Selectivity of pirenzepine in the central nervous system. III. Differential effects of multiple pirenzepine and scopolamine administrations on muscarinic receptors as measured autoradiographically.

The effects of intrahippocampal injections of scopolamine and pirenzepine on muscarinic receptor binding were examined by quantitative autoradiographic techniques. Brain slices from animals which had received 7 injections of either scopolamine (n = 5) or pirenzepine (n = 5) over a 22-day injection schedule were compared with slices from 5 saline-injected controls for receptor binding to the whole slice and within selected regions of the brain as measured autoradiographically. The total number of receptors was determined from direct binding assays with 1-[3H]quinuclidinyl-benzilate ([3H]-1-QNB), while the binding of the selective ligands pirenzepine, carbamylcholine, and scopolamine was examined through inhibition studies. The data from the whole slices indicated that pirenzepine-treated animals contained more receptors for [3H]-1-QNB than either saline- or scopolamine-injected controls. Slices from the same animals also displayed a lower affinity for pirenzepine. Slices from scopolamine-injected animals revealed neither an increase in receptor number nor a decrease in antagonist affinity, although the binding of the agonist carbamylcholine was increased. Quantitative analysis of the autoradiograms generated from the slices indicated that the increase in receptor number for pirenzepine-injected animals was predominantly within the cerebral and cingulate cortices. The inhibition by pirenzepine was also lower in these areas in the same group of animals. Agonist inhibition was altered in the central layers of the cerebral cortex and in the pretectal area in scopolamine-treated animals. The results suggest separate mechanisms of drug action and adaptation for pirenzepine and scopolamine.

Animals↗

The use of psychophysical, structural, and electrodiagnostic parameters to identify glaucomatous damage.

Fifty-one patients with early glaucoma and 29 patients without the disease had their contrast sensitivity, colour vision, differential light threshold, neuroretinal rim area, retinal nerve fibre layer, pattern-reversal electrogram and visually evoked potential examined. A stepwise discriminant analysis found that the combination of the vertical cup disc ratio, the diffuse nerve fibre layer score and the localized nerve fibre layer score correctly identified 98% of the normals and 84% of the glaucoma patients. Single parameters and various combinations of parameters were also examined for their ability to discriminate between the two groups. Fifty-two glaucoma suspects were similarly examined and were classified into those whose discriminant functions were normal or abnormal.

Electrodiagnosis↗

Drug reviews.

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Aged↗