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Biomedical subjects

D Clark

Publications and source records attributed to D Clark.

At least 163 records · Page 9Linked to original sources
PubMed1993

No major differences in energy metabolism between matched and unmatched groups of 'large-eating' and 'small-eating' men.

Rates of energy expenditure (J/kg fat-free mass (FFM) per min) in normal weight, 'small-eating' men were compared with those obtained for normal weight (n 8) and underweight (n 5) 'large-eating' men. For the matched groups of 'large-' and 'small-eaters' there were no differences in resting metabolic rate (RMR) measurements but during controlled daily activities there was a small but significant increase (P < 0.05) in energy expenditure in the 'large-eaters'. These results contrast with those obtained for the unmatched groups where energy requirements were about 10% (P < 0.01) higher in the underweight 'large-eaters' at rest but were not different during the more energetic (walking) activities. However, after adjustment for differences in FFM between these two groups, the resting energy expenditures of the 'large-eaters' (82.54 (SE 1.51) J/kg FFM per min) were similar to those of the 'small-eaters' (81.87 (SE 1.51) J/kg FFM per min). Oral temperatures were significantly higher in the matched (0.35-0.65 degrees) and unmatched (0.7-0.9 degrees) 'large-eaters' both at rest and during the different activities, but the thermic effect of food (50 kJ/kg FFM) was one fifth lower (not significant) in both groups of 'large-eaters'. These results provide little evidence for any major metabolic differences between groups of 'large-eating' and 'small-eating' men.

Adult↗
PubMed1993

Palliative care of patients with terminal cancer.

Palliative (terminal) care is now recognized worldwide as an important, multidisciplinary aspect of the continuing care of patients with incurable cancer. Symptom control and quality-of-life are of the essence. Various treatment methods are available, and radiotherapy and chemotherapy (used appropriately) are important modalities. Palliative care has to be set against a background of planning, development, and cost-benefit analyses.

Humans↗
PubMed1993

Subtle variations in living conditions influence behavioural response to d-amphetamine.

The influence of prior living conditions on behaviours related to the reinforcing properties of d-amphetamine was determined. Rats were housed either in bright light (BL) conditions at the top of a standard rack or in dim light (DL) conditions on the third row of the same rack. Although BL rats showed a higher locomotor response in the novel environment, they were less sensitive than DL rats to the locomotor activating effects of d-amphetamine. The groups did not differ in responding for a secondary reinforcer in a conditioned reinforcement paradigm. However, only in DL rats as the response for the secondary reinforcer enhanced by d-amphetamine. These findings indicate that subtle differences in housing conditions can influence behavioural responses to psychoactive drugs.

Amphetamine↗
PubMed1993

Subtypes of early age onset alcoholism.

Forty-three adolescents qualifying for a DSM-III-R diagnosis of alcohol abuse/dependence were classified according to the internalizing-externalizing behavior dimension. Two clusters were identified. The majority of subjects clustered into a group characterized by behavioral dyscontrol and hypophoria (history of suicide attempts) (cluster 2), whereas the other group was primarily featured by negative affect (cluster 1). Cluster 2 subjects demonstrated more severe alcohol and drug use-related problems, behavioral disturbances, and general psychopathology; lower prevalence of depressive disorders; and less severe anxiety disorders. These results, implicating two variants of adolescent alcohol abuse/dependence, suggest the need to tailor differential treatments to adolescents with alcohol abuse/dependence based on personality characteristics and clinical presentation.

Adolescent↗
PubMed1993

Behaviour in the novel environment predicts responsiveness to d-amphetamine in the rat: a multivariate approach.

The behaviour of rats in a novel environment was studied using a rapid time-sampling observation procedure followed by a principal component analysis (PCA) of the data. This approach revealed that novel environment behaviour can be described by two factors or principal components. The first factor comprised rearing, sniffing-up, ambulation and locomotion (photocell counts), and was termed "Escape". The second factor, which had high positive loadings of sniffing-down and locomotion and a high negative loading of immobility, was termed "Exploration". The scores of individual rats on the "Escape" factor predicted the stimulatory effect of acutely administered d-amphetamine (1.5mg/kg) on unconditioned behaviour. "Escape" high responders (HRs) showed more behavioural stimulation than "Escape" low responders (LRs). However, the locomotor stimulatory response of both groups increased after long-term, periodic administration of d-amphetamine and drug discrimination training, such that the level of drug-induced locomotor activity was now equivalent for the two groups. The same rats were tested twice with various doses of d-amphetamine after being trained to discriminate this drug (0.5mg/kg) from saline. "Escape" HRs were less sensitive than "Escape" LRs to the discriminative effects of 0.125-0.25mg/kg d-amphetamine. In contrast to these findings, "Exploration" HRs and LRs were not different on any of the dependent measures described above. These results are discussed in relation to the possibility that "Escape" factor scores are an indication of an animal's responsivity to novelty-induced stress. If this is the case, then animals which are more susceptible to the effects of novelty stress are more sensitive to the locomotor stimulating effects of acute d-amphetamine, but less sensitive to the cueing properties of low doses of this drug.

Journal Article↗
PubMed1993

Electrophysiological effects of putative autoreceptor-selective dopamine agonists on A10 dopamine neurons.

The dopamine (DA) hypothesis of schizophrenia proposes hyperactivity of the mesocorticolimbic DA system, originating within the A10 DA cells of the ventral tegmental area (VTA), as a pathophysiological mechanism. Thus, reduction of activity in this system, including that produced by putative "autoreceptor-selective" DA agonists, may be of clinical utility. The present studies compared the ability of eight D2 DA receptor agonists to inhibit the firing of rat A10 DA neurons after i.v. administration. Both N-n-propyl-N-phenylethyl-p(3-hydorxyphenyl)ethylamine hydrochloride (RU 24213) and 2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]- azepine dihydrochloride (B-HT 920) were potent, high-efficacy agonists which completely inhibited the firing of A10 DA cells. The putative autoreceptor-selective DA agonists 3-(4-(4-phenyl-1,2,3,6-tetrahydropyridyl-(1)-butyl)-indole hydrochloride (EMD 23,448) and (+)-3-(3-hydroxy-phenyl)-N-n-propylpiperidine [(+)-3-PPP] were considerably weaker than RU 24213 and B-HT 920, but also exhibited "full" efficacy (i.e., they completely suppressed cell firing). The putative autoreceptor agonist preclamol [(-)-3-PPP] and its trans-fused congener (-)-HW 165 were weak partial agonists that failed to completely inhibit A10 DA cells. The new putative autoreceptor agonist N-[(8-alpha)-2-chloro-6-methylergoline-8-yl]-2,3]dimethylopropa namide (SDZ 208-911) was also a weak partial agonist that exhibited partial antagonist effects (reversed inhibition produced by the D2 agonist quinpirole), whereas its structural analog N-[(8-alpha)-2-chloro-6-methylergoline-8-yl]-2,2-dimethylopropa namide (SDZ 208-912) was nearly inactive as an agonist, but was an effective antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Nonsurgical management of primary skin malignancies.

Cryosurgery, electrosurgery, radiotherapy, chemotherapy, and interferon therapy achieve high cure rates for primary skin malignancies. These techniques are readily mastered. They combine cost-effective use of time, space, and equipment. Proper patient selection maximizes safety, comesis, and cure rates.

Facial Neoplasms↗
PubMed1993

Cutaneous micrographic surgery.

Cutaneous micrographic surgery (CMS) is a highly effective method of treating cutaneous malignancy. With high cure rates and conservative removal of normal tissue. CMS is the treatment of choice for cutaneous malignancies that are difficult to treat. Basal cell and squamous cell carcinomas that are large, recurrent, or in high-risk locations; that have unfavorable histologies; or that have been treated previously with other modalities should be considered for treatment with CMS.

Facial Neoplasms↗
PubMed1993

What school nurses really do--a study of school nurse utilization.

The functions of twelve school nurses in a large metropolitan school district were examined in relation to utilization of health services and student time lost from school using health problem categories. Findings suggest absentee data and utilization are valuable outcome measures supporting the importance of school health programming.

Absenteeism↗
PubMed1992

Physical and biochemical characterization of five commercial resins for immunoaffinity purification of factor IX.

The American Red Cross has developed an immunoaffinity chromatography method to purify human coagulation factor IX (FIX) to homogeneity using monoclonal antibodies (MAb) that bind FIX in the presence of divalent cations. The MAb is immobilized on Sepharose CL2B, a soft gel with a low pressure tolerance as well as poor large-scale performance characteristics, including low reusability, and resin crumbling and deterioration. In this study, we examined several commercially available resin supports. Aside from Sepharose CL2B, we studied two other cross-linked agaroses, as well as two synthetic polymer supports. Immobilization chemistries included cyanogen bromide activation of agarose, 2-fluoro-2 methylpyridinium toluene-4-sulfonate activation of one of the synthetic polymer as well as aldehyde group reduction by NaCNBH3 to form secondary amine linkages on one of the cross-linked agaroses. To determine the feasibility of using the resins in large-scale immunoaffinity chromatographic purification of FIX, we studied physical and biochemical properties of the resins. The physical characteristics studied included the crushability of the resins under pressure as well as ability to support increasing flow-rates at increasing pressures. The biochemical examination of the various resins focused on efficiency of antigen capture by the immobilized antibody ligand and the effect of flow-rate on MAb efficiency, where we found that very low flow-rates slightly increased the capacity of the MAb. The results demonstrate a straightforward method of assessing the feasibility of using particular resins in large-scale affinity purification.

Antibodies, Monoclonal↗
PubMed1992

Neurokinin agonists differentially affect A9 and A10 dopamine cells in the rat.

The effect of selective neurokinin (NK) receptor agonists on the activity of A9 and A10 dopamine cells was assessed using extracellular recording. A higher proportion of A10 cells which were administered the NK1 receptor agonist GR73632 or the NK3 receptor agonist senktide showed an effect, whereas the NK2 receptor agonist GR64349 did not discriminate as clearly between the two cell groups. The most frequently encountered response in all cases was an increase in firing rate.

Animals↗
PubMed1992

Some effects of different extracellular proteins on oxygen consumption and heat production in isolated rat hepatocytes.

When hepatocytes prepared from 24-h-fasted rats were washed, suspended and incubated in Krebs-Henseleit bicarbonate-buffered saline, the endogenous rates of O2 consumption and heat production were 2.13 +/- 0.13 mumol/min per g wet wt. and 1.00 +/- 0.05 J/min per g wet wt. respectively. The inclusion of 2.5% (w/v) defatted and dialysed bovine serum albumin in either the cell suspension (washing) buffer or the cell incubation buffer produced a 20-25% increase in O2 consumption and heat production: these rates were increased by an additional 20-25% when the albumin (2.5%) was present in both the cell suspension and the cell incubation buffers. There was an inverse relationship between the increases in O2 consumption and heat production and the leakage of lactate dehydrogenase from the isolated hepatocytes: the inclusion of purified bovine serum albumin decreased lactate dehydrogenase leakage from 40% to 15% of total enzyme content. The calorimetric-respirometric ratios for hepatocytes incubated both in the absence (-461 +/- 19 kJ/mol O2) and presence (-477 +/- 8 kJ/mol O2) of the purified protein are very similar to the theoretical, thermochemically derived oxycaloric equivalents.

Animals↗
PubMed1992

Iontophoretically administered drugs acting at the N-methyl-D-aspartate receptor modulate burst firing in A9 dopamine neurons in the rat.

Extracellular single-unit recording and iontophoresis were used to examine the effect of N-methyl-D-aspartate (NMDA) and the competitive NMDA antagonist (+/-)-4-(3-phosphonopropyl)-2-piperazine carboxylic acid (CPP) on the firing rate and firing pattern of A9 dopamine (DA) neurons in the rat. Administration of NMDA produced a dose-dependent increase in firing rate (up to nearly 300% of baseline at the highest ejection current), which could be blocked by iontophoretic CPP. Low currents (less than 10 nA) were sufficient to induce apparent depolarisation inactivation in some neurons. In addition to this effect on firing rate, NMDA also caused a dramatic increase in burst firing, which was also dose dependent; cells made more bursts, and each burst consisted of more spikes. The only measured aspect of burst morphology that was not affected was the mean burst interspike interval. All nonbursting cells (n = 10) were converted to burst firing by the drug. CPP administered alone was found to reduce burst firing, without affecting the firing rate. These data suggest that a tonically active excitatory amino acid input to A9 DA neurons is responsible for inducing burst firing in vivo and that this input seems to operate via the NMDA receptor, possibly by virtue of its link to a Ca2+ ionophore.

Animals↗
PubMed1992

Electrophysiological evidence that intrastriatally administered N-methyl-D-aspartate augments striatal dopamine tone in the rat.

The firing rate and terminal excitability of identified nigrostriatal dopamine (DA) neurons was determined before, and over a 10-15 min period following, direct intrastriatal administration of the glutamate (GLU) agonist NMDA, or saline. NMDA (0.025 and 0.075 mumol) produced a short latency increase in DA cell firing rate. In 7/8 cases, this increase in firing rate was accompanied by a profound reduction in terminal excitability. The decrease in excitability usually outlasted the increase in firing rate (sometimes by more than 8 min), and was superseded at a later stage by a marked increase in excitability. None of these effects were seen with saline (n = 5), and they could all be blocked by preadministration of the competitive NMDA antagonist AP-7 (0.025 mumol; n = 6). The sequence of events leading to the observed results is argued to be as follows; NMDA initially excites striatal efferents to the DA cell, which through disinhibition and direct stimulation increase DA cell firing rate. Increased firing rate leads to enhanced striatal DA release. Dopamine's inhibitory influence pre-empts any effect NMDA itself may have on the terminals of nigrostriatal neurons, and counteracts NMDA's stimulatory effect on striatal output cells. Furthermore, the marked reduction in terminal excitability suggests that DA becomes the dominant influence in the striatum for a time. Hence, the net outcome of the injection is augmented striatal DA tone. Later, the effect of residual NMDA becomes predominant once more.

2-Amino-5-phosphonovalerate↗