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Biomedical subjects

M Clark

Publications and source records attributed to M Clark.

At least 199 records · Page 11Linked to original sources
PubMed1991

In vitro autoradiographic evidence for adenosine modulation of ethanol-induced motor disturbances in rats.

It was previously shown that adenosine agonists and antagonists potentiate and decrease ethanol-induced motor disturbances, respectively. This interaction of adenosine and ethanol was functionally correlated with a significant increase in Bmax of cerebellar cortical high affinity adenosine A1 receptors after a single ethanol injection. Quantitative autoradiographic analysis of adenosine A1 and A2 binding sites in rat brain was carried out in animals treated acutely with saline or ethanol. Adenosine agonist binding at A1 receptors was increased in the molecular layer of cerebellum 15 min after ethanol injection. This increase returned to control values by 60 min. Adenosine antagonist binding at A1 receptors was not altered by ethanol treatment. Inclusion of a poorly hydrolyzable analogue of GTP in the incubation medium decreased binding throughout the brain for adenosine agonists but had less effect on agonist binding in the cerebellum and hippocampus of ethanol-treated rats 15 min after injection. The inhibitory effect of the GTP analogue was equal in saline- and ethanol-treated rats after 60 min. These findings suggest that acute ethanol treatment elicits a transitory increase in adenosine A1 receptor binding that is limited to the cerebellum and hippocampus and that this increased binding reflects an increased (or stabilized) coupling of the receptors to GTP-binding proteins. Acute ethanol treatment did not alter agonist binding at the high affinity A2a subtype of adenosine receptors in striatum.

Adenosine↗
PubMed1991

Deforming arthropathy complicating primary biliary cirrhosis.

A 53-year-old woman with concurrent systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) developed a deforming but minimally symptomatic arthropathy. The simultaneous occurrence of SLE and PBC is believed to be rare. Moreover, destructive arthritis, in the absence of serum rheumatoid factor, has not been previously reported with either disease. We review the association of liver disease with arthritis and propose a possible mechanism to account for the severe joint destruction seen in our patient.

Arthritis↗
PubMed1990

Sustained-release (+)-PHNO [MK-458 (HPMC)] in the treatment of Parkinson's disease: evidence for tolerance to a selective D2-receptor agonist administered as a long-acting formulation.

4-Propyl-9-hydroxynaphthoxazine, or MK-458 (HPMC), a selective, nonergot D2 agonist administered orally twice a day in sustained-release form, was studied as adjunctive therapy with carbidopa-levodopa (Sinemet) in 12 Parkinson's disease patients with motor response fluctuations. The dosage of agonist was gradually increased over 12 weeks to a maximum tolerated level of up to 60 mg/day, and that of Sinemet was reduced concurrently. After 8 weeks, reduction of Sinemet averaged 45.1%, but over the next 4 weeks, despite a continued increase in dosage of the agonist, patients were unable to decrease their Sinemet further, and by 12 weeks mean reduction in Sinemet was only 32%. Only five patients completed the planned 24-week study, mostly due to progressive loss of efficacy. The MK-458 is capable of partially substituting for Sinemet in dosages employed in this study. Reduced sensitivity to the drug can appear over a relatively short time, perhaps as a result of down-regulation of postsynaptic dopamine receptors.

Activities of Daily Living↗
PubMed1990

Results of long-term treatment with controlled-release levodopa/carbidopa (Sinemet CR).

35 Parkinson's disease patients with motor response fluctuations (RF) participated in controlled clinical trials comparing Sinemet CR to Standard Sinemet (STD) at our institutions. 13 of 25 eligible patients continued to two years (the longest possible follow-up from the second study), and 5 of 11 have continued taking CR up to 4 years. At the end of both two and four years, patients were taking significantly fewer medication doses, with a significantly longer interdose interval, and up to two years, experienced fewer "off" periods than when on Standard Sinemet (STD) alone. Most patients required STD at at least one dose each day to hasten to onset of antiparkinson effect. Sinemet CR is a useful adjunct in the long-term management of motor response fluctuations in Parkinson's disease.

Antiparkinson Agents↗
PubMed1990

The effects of intrauterine growth retardation on the structural development of cranial nerves (optic, trochlear) in fetal sheep.

A quantitative morphometric study of the development of myelinated fibres in the optic and trochlear nerves has been made in growth-retarded fetal sheep at 140 days gestation (term = 146 days). Intrauterine growth retardation was induced as a result of the reduction of placental mass, by prior removal of placentation sites in six ewes. In the optic nerve (central nervous system) the mean diameter of myelinated fibres was not significantly reduced but the thickness of the myelin sheath relative to axon diameter was disproportionately reduced. In the trochlear nerve (peripheral nervous system) there was a significant reduction of 23% (P less than 0.01) in the mean diameter of myelinated fibres; however the normal axon:myelin ratio was maintained. The total number of myelinated fibres in the trochlear nerve did not differ between the normal and growth-retarded group, indicating that there was not a greater than normal incidence of cell death during intrauterine growth retardation in the nucleus of the trochlear nerve. The differential effect of intrauterine growth retardation on myelination in the central and peripheral nervous systems suggests that chronic intrauterine deprivation affects oligodendrocyte activity but does not markedly affect the capacity of Schwann cells to produce myelin.

Animals↗
PubMed1990

Analgesic use in the emergency department.

The relief of pain is one of the most common reasons for seeking care in an emergency department. We conducted a retrospective chart review to see whether children received analgesic treatment similar to that of adults with the same acute, painful conditions. Charts of 112 pediatric patients from the Children's Hospital of Philadelphia ED and 156 patients from the Medical College of Pennsylvania ED were reviewed. Patient ages ranged from a few months to 97 years. All patients had acute pain due to sickle cell crises (20%), lower-extremity fractures (31%), or second- or third-degree burns (49%). Hospitalization was required in 15% of cases. In the ED, 60% of patients with painful conditions received no pain medication at all. When medications were given, they were usually narcotics. Children (aged 19 years or younger) were much less likely to receive pain medications than adults (P = .001). Those less than 2 years old received analgesics less often than older children (P less than .01). Senior citizens (aged 65 years or older) received analgesics as often as other adults. On discharge from the ED, 55% of all patients had no pain medications prescribed; and children were less likely than adults to receive analgesics at discharge (P less than .001). Pediatricians and emergency physicians are reluctant to use analgesics for children in pain. The data suggest that these physicians need additional education about management of acute pain.

Adolescent↗
PubMed1990

L-deprenyl, levodopa pharmacokinetics, and response fluctuations in Parkinson's disease.

Six patients with Parkinson's disease (PD) and therapeutic response fluctuations (RF) on levodopa treatment participated in an open-label trial of L-deprenyl (Eldepryl) in conjunction with Sinemet. Deprenyl (10 mg/day) allowed a slight but not statistically significant 22% reduction of total daily levodopa intake after 4 weeks of treatment, with a significant but unsustained reduction in the number of daily "off" periods and an increase in the portion of waking day spent "on." Pharmacokinetic studies revealed no effect of deprenyl on the plasma levodopa concentration vs. time curve, or the coefficient of variation (C.V.) of plasma levodopa levels measured over an 8-h period. Plasma DOPAC levels were unaffected, suggesting that the majority of peripheral DOPAC is generated by action of MAO-A. For most patients, benefit was not maintained. Two patients have continued taking the drug, and both have enjoyed significant reductions in total levodopa dose. Both have mild end-of-dose failure and little dyskinesia. Since no changes in peripheral pharmacokinetics of levodopa could be demonstrated, any therapeutic action of deprenyl in PD would appear to be due to prolongation of dopaminergic activity within the CNS.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Alteration of topoisomerase II action is a possible molecular mechanism of HL-60 cell differentiation.

The inhibition of differentiation and persistence of proliferation in cell transformation is probably not only caused by the mutation of single genes. An additional mechanism of transcriptional control, not only of single genes but of gene programs, is possibly the alteration of the topoisomerases. These enzymes regulate the conformation of DNA by twisting and unwinding the double strands. As has been shown previously, only the genes located in relaxed DNA areas are transcribed and, therefore, the topoisomerases can be described as a gene regulation device. We present the hypothesis that topoisomerase II action is not only altered in, but also necessary for, HL-60 granulocytic cell differentiation. Thus, alteration of topoisomerases may well be a molecular mechanism of cellular differentiation.

Binding Sites↗
PubMed1990

Hospital image and the positioning of service centers: an application in market analysis and strategy development.

The research confirms the coexistence of different images for hospitals, service centers within the same hospitals, and service programs offered by each of the service centers. The images of individual service centers are found not to be tied to the image of the host facility. Further, service centers and host facilities have differential rankings on the same service decision attributes. Managerial recommendations are offered for "image differentiation" between a hospital and its care centers.

Adult↗
PubMed1990

The effect of a pressure-relieving wound dressing on the interface pressures applied to the trochanter.

A pressure-relieving dressing (PRD/Coloplast A/S, Denmark) was tested on 12 healthy volunteers to determine trochanteric and peritrochanteric interface pressures. Use of the PRD reduced the maximum pressure applied to the apex of the trochanter from a mean of 64.2 mm Hg to a mean of 52.2 mm Hg. The author speculates that this statistically significant difference may have clinical relevance for 79% of pressure ulcers in England and Wales but not for the 21% of pressure ulcers with cavities.

Bandages, Hydrocolloid↗
PubMed1989

A matched set of rat/mouse chimeric antibodies. Identification and biological properties of rat H chain constant regions mu, gamma 1, gamma 2a, gamma 2b, gamma 2c, epsilon, and alpha.

Rat C regions mu, gamma 1, gamma 2a, gamma 2b, gamma 2c, epsilon, and alpha have been characterized by means of chimeric antibody technology. A set of rat/mouse Ag-specific (anti-4-hydroxy-3-nitrophenacetyl) antibodies was constructed that differ only in the H chain constant region but carry identical V region and L chain, both of which are of mouse origin. All rat constant regions could be expressed and m.w. were as expected from the protein sequence. A slight variation in mobility within the IgG subclasses allowed us to establish a hierarchy for the sizes of the four gamma H chains; gamma 2b greater than gamma 1 greater than gamma 2c greater than gamma 2a. Rat IgG2c and IgG2b could be purified on both protein A and protein G while rat IgG2a could only be purified on protein G. Rat IgM and IgG2b were the most potent in C-mediated hemolysis. This was not simply a consequence of the amount of C1q bound because IgG2c bound C1q efficiently but was relatively poor in cell lysis. In ADCC using human effector and target cells, IgG2b and IgG1 were the most effective.

Animals↗
PubMed1989

Splenectomy for massive splenomegaly.

Twenty-four patients who underwent resection of giant spleen (spleen weight greater than 1.5 kg) have been reviewed to determine the difficulties and benefits of the procedure and, in particular, whether the use of adrenaline injection into the splenic artery could safely reduce technical difficulty. Although morbidity was higher in patients with giant spleens compared with those undergoing resection of smaller spleens the incidence of serious complications was small, and there were no operative or in-hospital deaths. In addition, virtually all patients benefited either on the basis of minimized haematological defect, or palliation of symptoms. Further, the injection of 1 ml of 1:10,000 adrenaline into the splenic artery before splenic mobilization reduced the splenic volume by approximately 40 per cent on average, and resulted in improved exposure, thereby facilitating the procedure.

Aged↗
PubMed1989

The improved lytic function and in vivo efficacy of monovalent monoclonal CD3 antibodies.

A series of hybrid-hybridomas were derived by the cell fusion of a CD3 antibody-secreting hybridoma with other Ig-producing cell lines. The Ig molecules secreted by these hybrid-hybridomas were fractionated by ion-exchange chromatography, and fractions containing monovalent CD3 antibodies were tested for complement-mediated lysis of T cells. Two monovalent CD3 antibodies with mixed heavy chain isotypes were very poor in lysis but, in contrast, a monovalent antibody possessing two identical rat gamma 2b heavy chains but two non-identical light chains was found to be more lytic with human complement than the parental bivalent CD3 antibody. The difference in lysis was not readily explicable in terms of a difference in complement activation at the level of C1q binding or cell-associated C3. A highly purified batch of this lytic monovalent CD3 antibody was prepared in a form suitable for in vivo therapy. In a preliminary clinical study in one patient with a T lymphoma in leukemic phase this monovalent CD3 antibody was found to be very effective in depleting CD3+ tumor cells in the peripheral blood and bone marrow. The cells in the peripheral blood were completely cleared and there was no evidence for antigenic modulation. In addition the antibody was able to reverse cell-mediated kidney rejection in three kidney graft patients. These results suggest that monovalent antibody may be effective in vivo as well as in vitro and that a fuller clinical evaluation is justified.

Adolescent↗
PubMed1989

Release of endogenous glutamate from rat cerebellar synaptosomes: interactions with adenosine and ethanol.

The effects of ethanol and adenosine receptor agonist R-PIA and antagonist theophylline on release of endogenous glutamate were tested in rat cerebellar synaptosomal preparation. Release was carried out for 5 to 60 sec after which time the released glutamate was separated from the synaptosomal membranes by rapid filtration. The amount of released glutamate in the filtrate was measured by an enzyme-linked fluorometric assay. Basal endogenous glutamate release was estimated as 3.7 +/- 0.3 nmol/mg protein/5 sec and was stimulated by high K+. Glutamate release consisted of an initial rapid phase for the first 10 sec that was followed by a relatively slower phase. Both Ca2+-dependent and Ca2+-independent glutamate release were observed which suggested the involvement of both neuronal and glial constituents of the synaptosomal preparation, respectively. Pharmacologically relevant concentrations of ethanol (25-100 mM) caused a trend toward a dose-dependent inhibition of glutamate release. R-PIA and theophylline inhibited and stimulated, respectively, basal release of glutamate and R-PIA-inhibited release was blocked by theophylline. Ethanol (25 mM) blocked the stimulatory effect of theophylline and the results of experiments following the inclusion of adenosine deaminase suggested the involvement of adenosine in this effect of ethanol. The results support our previous findings that suggest an involvement of cerebellar adenosine in the motor disturbing effects of acute ethanol and extend those findings by indicating that ethanol inhibits glutamate release from granule cells of the cerebellar cortex through an adenosine-sensitive mechanism.

Adenosine↗