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Biomedical subjects

M Clark

Publications and source records attributed to M Clark.

At least 37 records · Page 2Linked to original sources

The basis of the histamine assay in skin.

1. The assay of wheal response to histamine injected sub-epidermally has been reviewed. Several discrepant claims were found in earlier work. 2. The saline control injection may evoke a wheal, which if present should be allowed for in the assay procedure. 3. There was no evidence for a limb dominance effect. 4. Using a 3.26 mM (1 mg ml-1) standard solution of histamine acid phosphate (1.18 mM as free base) and 0.1 ml injections, the straight central portion of the assay curve was found to be between 0.3 and 2.3 x 10(-3) mM, as free base, with an ED50 of about 0.018 mM histamine base.

Histamine

The musculo-skeletal examination: a neglected clinical skill.

One hundred and sixty-six patients admitted to general medical wards of a teaching hospital were examined on the day of discharge to determine whether they had been assessed for musculoskeletal disorders during their admission. Of these patients, 54.8% had musculo-skeletal symptoms with 17.5% having a significant rheumatological disorder which had been ignored. A history of musculo-skeletal symptoms was recorded in 40.4% of all patients and the examination in only 14.5%. This contrasted with the documentation of the cardiovascular (99.4%), respiratory (100%), gastrointestinal (97.6%) and central nervous (53%) systems' examination. Eighty per cent of symptomatic patients received either no treatment for their rheumatic disorder, or treatment that we regarded as suboptimal or inappropriate. Musculo-skeletal symptoms are common in patients admitted to medical wards, but are being inadequately assessed or at worst ignored. The omission of the musculo-skeletal system examination, in contrast to the almost universal inclusion of other systems' examination, demands correction. Undergraduate and postgraduate training programmes require re-evaluation. The implications of these findings are discussed.

Adult

Effects of a take-home drug prevention program on drug-related communication and beliefs of parents and children.

Five hundred and eleven fourth, fifth, and sixth grade students and their parents from six schools in northwest Arkansas participated in this study. Students were blocked on school and grade level, then assigned randomly by class to either the intervention Keep A Clear Mind (KACM) program or a waiting list control. KACM students received four weekly correspondence lessons designed to be completed at home with a parent. KACM students reported significantly less perceived peer use of alcohol, tobacco, and marijuana, as well as significantly less peer pressure susceptibility to experiment with cigarettes. Mothers in the KACM program reported significantly more recent and frequent communication with their children about refusing drugs, and significantly greater discussions with their children regarding how to resist peer pressure to use alcohol, tobacco, and marijuana. Intervention program fathers reported significantly more communication with their children concerning how to resist peer pressure to drink alcohol and use tobacco, and significantly greater motivation to help their children avoid drug use. No significant differences were found between groups on student intentions to use drugs. These data suggest a print medium that emphasizes parent-child activities holds promise for accessing families and enhancing drug prevention communication.

Adult

Cystic ameloblastic fibroma.

A seven-year-old white male presented with an enlarging mass in the mandible which was a cystic ameloblastic fibroma. This case, the third reported in the literature, demonstrated several unusual histopathologic findings and presented several controversies in management.

Child

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

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

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

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

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

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

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

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

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