Search PubMed⌕ Search

Biomedical subjects

M Clark

Publications and source records attributed to M Clark.

At least 217 records · Page 12Linked to original sources

Comparison of contact pressures measured at the sacrum of young and elderly subjects.

Contact (interface) pressure measurements were made between the sacrum of groups of young and elderly subjects lying upon two special mattresses used to prevent pressure sores. One mattress was an alternating air pressure mattress, the other a foam mattress. Contact pressures were measured using a hydraulic sensor taped directly to the skin over the sacrum. All mean pressures and 'pressure impulses' (total applied pressure per standard time period) appeared higher when measured among the elderly subjects. Compared with the pressures measured from young subjects, the maximum contact pressures were significantly higher (p less than 0.05) on both mattresses, with the pressure impulse higher while lying upon the foam mattress (p less than 0.05).

Adult↗

Measurement of soft tissue thickness over the sacrum of elderly hospital patients using B-mode ultrasound.

The thickness of soft tissues over the sacrum of elderly hospital in-patients has been measured using B-mode ultrasound. Forty patients were scanned, of which nine had recognizable superficial pressure sores at the sacrum. No correlation was found between the depth of soft tissue and either age or Norton score. Patients with sores had less soft tissue over the sacrum (p less than 0.025). Excluding one patient whose sacral sore appeared to be the final stage of the healing process, the remaining eight all had less than 8.5 mm of sacral soft tissue cover. Five patients without sacral sores also had less than 8.5 mm of sacral soft tissue cover. However, a combination of the presence of incontinence and the depth of sacral soft tissue cover identified seven of the eight patients with sacral sores with no inclusion of patients without sores.

Aged↗

Preliminary evaluation of bereavement experiences in a hospice program.

The purpose of this study was to determine how the services of a bereavement program could be more helpful to survivors following the death of a spouse and/or significant other. Ninety-seven bereaved individuals were interviewed thirteen months after the death over a period of two years. The results of this pilot study revealed that most of the subjects were managing their lives and coping with their loss without undue stress. Overall, subjects were satisfied with the services of the hospice program and were experiencing recovery. Implications for further study and practice are discussed.

Adult↗

Effect of acute ethanol on release of endogenous adenosine from rat cerebellar synaptosomes.

The effects of pharmacologically relevant concentrations of ethanol on the release of endogenous adenosine from rat cerebellar synaptosomes were investigated. Release was conducted for 5, 10, 30, or 60 s after which time the incubation medium (containing the released adenosine) was rapidly separated from the synaptosomal membranes by vacuum filtration. The adenosine content of the filtrate was measured by HPLC-fluorescence detection. Both basal and KCl-stimulated adenosine release consisted of an initial rapid phase, for the first 10 s, that was followed by a relatively slower phase. Basal endogenous adenosine release was estimated as 199 +/- 14 pmol/mg protein/5 s. Potassium (chloride) increased adenosine release from the basal level to 433 +/- 83 pmol/mg protein/5 s. Ethanol caused a dose-dependent increase of adenosine release. The interaction between dilazep and ethanol indicates that ethanol-stimulated release does not involve the dilazep-sensitive transport system. The results support previous findings that indicate that cerebellar adenosine is involved in the mediation of ethanol-induced motor disturbances in the rat.

Adenosine↗

Effect of acute ethanol on uptake of [3H]adenosine by rat cerebellar synaptosomes.

Many classes of CNS-acting drugs have been suggested to act at least partially via inhibition of adenosine uptake. Synaptosomal uptake of [3H]adenosine and the effect of acute ethanol on it were studied in a rat brain area known to be involved in the coordination and modulation of normal motor activity, the cerebellum. Uptake of [3H]adenosine was found to be linear with time (about 40 sec) and increasing concentrations (up to 1.5 microM) of adenosine. The uptake of [3H]adenosine was inhibited by dilazep (IC50 = 2.5 x 10(-7) M) in a dose-dependent manner. Pharmacologically and/or toxicologically relevant concentrations of ethanol (2.5 to 100 mM) significantly inhibited the uptake of [3H]adenosine between 12 and 15%. Lineweaver-Burk plots indicated that both in vitro (25 mM) and in vivo (1.5 g/kg i.p.; 30 mM blood level) ethanol lowered Km as well as Vmax values for adenosine uptake to nearly the same extent. In the case of in vivo ethanol, no ethanol was present during the assay since synaptosome preparation would wash out residual ethanol. The results of the present study indicate possible membranal alterations by in vivo ethanol. It is concluded that the uptake of [3H]adenosine is inhibited by intoxicating concentrations of ethanol in vitro and by acute ethanol (1.5 g/kg) in vivo. This may partially explain the modulatory role of endogenous adenosine in ethanol-induced motor disturbances.

Adenosine↗

Changes in circulating equine erythrocytes induced by brief, high-speed exercise.

Five horses were exercised at 10m/sec at a 3 degree incline for 2 mins. Packed cell volume, erythrocyte count, haemoglobin concentration, mean corpuscular volume, plasma protein, total white cell count and lymphocytes increased significantly in blood samples taken after exercise, compared with those taken before exercise; but mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration decreased. Erythrocytes were more resistant to osmotic stress after exercise, but their shape and degree of deformity were unaffected by exercise.

Animals↗

Topical dexamethasone lowers rabbit ocular tension, as does topical mifepristone (RU 486), a peripheral blocker of dexamethasone and progesterone.

The variability of the response of the rabbit eye to topical 1% dexamethasone has been shown in two groups of 20 young albino rabbits each (total 40) tested in succession. The pressure anomalously fell significantly (but by only 1 mm Hg) in both groups in the first 4 weeks of administration, but not in subsequent weeks. Mifepristone (RU 486), a peripheral antagonist of dexamethasone and progesterone, reduced the pressure significantly, again by only 1 mm Hg, in the first group of 20 rabbits, not the second. Accordingly, no conclusion was possible on the originating question: does pre-treatment with mifepristone prevent the dexamethasone-induced rise in rabbit intra-ocular pressure?

Administration, Topical↗

Age-related hemodynamic, renal, and hormonal differences among patients with congestive heart failure.

The purpose of this study was to determine if there were characteristics that distinguish elderly patients with heart failure (greater than 65 years of age) from younger patients with heart failure. We studied 128 consecutively admitted patients with chronic congestive heart failure (CHF) under uniform conditions, with measurement of systemic hemodynamics, vasoactive hormones and sodium status, and renal function. Additional characterization included the hemodynamic response to gravitational stress (head-up tilt; n = 65), and renal blood flow and function by steady-state clearance techniques (n = 46). Compared with younger patients with CHF, there was a greater frequency of ischemic heart disease in the elderly patients with CHF. Within the CHF population there was an increase of systemic vascular resistance and a trend of decreased heart rate with aging. Heart rate responsiveness was attenuated during tilt according to age. Circulating norepinephrine increased with aging, but a clear-cut age-related effect was not observed for renin system activity or sodium status. Both serum urea nitrogen and serum creatinine increased with age. More detailed renal studies confirmed an age-related decrease of glomerular filtration rate and a noncompensatory filtration fraction, despite increasing renal vascular resistance. We conclude that elderly patients with CHF have relatively greater vasoconstriction (or decreased compliance) and blunted heart rate responsiveness associated with increased circulating norepinephrine. Furthermore, renal function in the elderly patient with CHF is markedly compromised. These findings are consistent with superimposition of an aging effect on the CHF process, which must be considered in evaluating the response to drug therapy and the outcome of multicenter CHF trials.

Adult↗

Preventing pressure sores: matching patient and mattress using interface pressure measurements.

An adapted version of the mattress system classification scheme described by Clark (1987; 1988) has been developed and its use illustrated with the classification of four mattress systems currently used in acute geriatric wards. The classification of these mattress systems was based upon measurements of trochanteric contact pressures. The verdicts of the classification scheme were compared with the established clinical use of each mattress, with broad agreement achieved. For example, a foam mattress used to protect patients at low risk of developing pressure sores was classified as suitable for use with "low" risk patients. However, several shortcomings to the classification of mattress systems solely upon trochanteric contact pressures were described in conjunction with requirements of a more comprehensive mattress system assessment.

Adolescent↗

Effects of benzylic hydroxyl substitution on the alpha-adrenoceptor blocking activity of tolazoline.

The R(-)- and S(+)-enantiomers of alpha-hydroxytolazoline, the benzylic hydroxy-substituted derivative of the alpha-adrenoceptor antagonist, tolazoline, were evaluated at alpha 1- and alpha 2-adrenoceptors in canine saphenous vein. Benzylic hydroxyl substitution of tolazoline in either the R(-) or S(+) configuration significantly decreased affinity at both alpha 1- and alpha 2-adrenoceptors. Differences in affinity between the R(-)- and S(+)-enantiomers were small, which is characteristic of imidazolines, but in marked contrast to phenethylamines where enantiomeric differences are large. The rank order of affinities at alpha 1- and alpha 2-adrenoceptors is tolazoline greater than S(+)-alpha-hydroxytolazoline = R(-)-alpha-hydroxytolazoline, which is different from that order predicted by the Easson-Stedman hypothesis (i.e., R(-) greater than S(+) = desoxy). The findings support our contention that phenethylamines and imidazolines interact differently with alpha-adrenoceptors.

Adrenergic beta-Antagonists↗

Reshaping human antibodies for therapy.

A human IgGI antibody has been reshaped for serotherapy in humans by introducing the six hypervariable regions from the heavy- and light-chain variable domains of a rat antibody directed against human lymphocytes. The reshaped human antibody is as effective as the rat antibody in complement and is more effective in cell-mediated lysis of human lymphocytes.

Amino Acid Sequence↗

The potential of hybrid antibodies secreted by hybrid-hybridomas in tumour therapy.

Using a simple method for the selection of hybrid cell growth from the cell fusion of pairs of existing hybridoma cell lines, 2 different hybrid-hybridoma cell lines were produced. Both hybrid-hybridomas secreted bi-specific antibody with similar specificity for human CD3 and for mouse Thy-l but in one case the parental antibody isotypes were both IgG2b and in the other case the CD3 antibody was IgG2b and the anti-Thy-l antibody was IgG2c. In a model in vitro system both bi-specific antibodies were able to elicit potent cell killing of a Thy-l expressing mouse tumour cell line by human effector cell blasts. The cell blasts were generated from resting peripheral blood mononuclear cells using a mitogenic monoclonal antibody (MAb) (YTH361). The parental anti-Thy-l IgG2b but not the IgG2c antibody was also able to mediate cell killing by ADCC. This ADCC killing was inhibited by a MAb to the CD16 Fc receptor but the killing elicited by the bi-specific antibodies was not. Both mechanisms of tumour cell killing may be of great potential in human tumour therapy with MAbs.

Animals↗

Mediation of acute ethanol-induced motor disturbances by cerebellar adenosine in rats.

The possible involvement of brain adenosine in acute ethanol-induced motor incoordination (MI) and inhibition of spontaneous motor activity (SMA) was investigated in male Sprague-Dawley rats. Pretreatment with theophylline or 7-(2-chloroethyl)-theophylline, adenosine antagonists, markedly reduced ethanol-induced MI and inhibition of SMA during a 60 min test period compared with saline + ethanol group. On the contrary, pretreatment with (-)-N6(R-phenylisopropyl)adenosine (R-PIA), an adenosine agonist, or dilazep, an adenosine uptake blocker, markedly potentiated the ethanol-induced MI as well as inhibition of SMA in a 60 min test period compared with saline + ethanol group. No effect on motor coordination was seen when the drug pretreatment was not followed by ethanol. However, the adenosine agonists and antagonists did alter SMA when the pretreatment with these drugs was not followed by ethanol. Ethanol clearance was not altered by the drug pretreatment as blood ethanol levels were similar in all groups except for lower ethanol levels in the R-PIA-treated group. Adenosine A1 binding studies, using 3H-R-PIA as the radioligand and crude membrane preparation from cerebellar cortex, revealed an increase in Bmax with no significant change in Kd in ethanol-treated animals vs. saline control. Theophylline pretreatment prevented the increase in Bmax elicited by ethanol. Collectively, the data suggest that endogenous cerebellar adenosine may be a participating factor in ethanol-induced motor dysfunctions.

Adenosine↗

The effects of various methods of sacrifice and of ethanol on adenosine levels in selected areas of rat brain.

The effect of acute ethanol on adenosine content in four motor areas of the male Sprague-Dawley rat brain was investigated using HPLC-fluorescence detection. Since basal adenosine levels are difficult to assess due to extremely rapid turnover of adenosine, four different methods of sacrifice were also evaluated for adenosine measurement. The rank order for best results in measuring adenosine content with the various methods of sacrifice was: focused microwave irradiation greater than decapitation into liquid nitrogen greater than immersion into liquid nitrogen greater than decapitation. These differences probably reflect differences in degree of hypoxia and postmortem anoxia, factors well known to elevate adenosine, associated with the sacrifice method. Focused microwave irradiation of appropriate duration was found to be the best method of sacrifice and the results probably most closely reflect true basal adenosine levels. No significant alteration in adenosine content in any brain region examined was observed due to ethanol administration.

Adenosine↗

Regulation of glomerular filtration rate in chronic congestive heart failure patients.

The purpose of this study was to identify the factor(s) that characterize impaired glomerular filtration rate (GFR) in congestive heart failure (CHF) patients. We studied 34 patients, measuring systemic hemodynamics, vasoactive hormones, and sodium and volume status. Renal plasma flow (para-aminohippurate) and GFR (inulin) were assessed by steady-state clearance techniques. Both linear and multiple regression analyses were performed. Impaired GFR was characterized by reduction of renal blood flow and renal fraction of cardiac output, and by an increase of renal vascular resistance. The correlation between GFR and filtration fraction (r = 0.492, P less than 0.003) indicated that individuals with greatest impairment of GFR had the lowest filtration fraction and increased overall renal vascular resistance, indicating dependence of GFR on afferent, rather than efferent vasoconstriction, under conditions of low renal perfusion. Mean vasoactive hormones and blood volume were increased, but without clear cut correlation with GFR. The greatest impairment of GFR was observed in elderly CHF patients, as renal blood flow and function demonstrated an age-dependent decline, in addition to the adverse effects of CHF. In a multiple regression model, renal blood flow and filtration fraction accounted for 69% and 25%, respectively, of the variability of GFR, with a co-linear influence of age. Thus, we have identified age-related, abnormal renal hemodynamic patterns in CHF, and the fragile nature of GFR in the elderly CHF population.

Adult↗