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Biomedical subjects

M Barker

Publications and source records attributed to M Barker.

At least 19 recordsLinked to original sources

Experimental basis for increasing the therapeutic index of cis-diamminedicarboxylatocyclobutaneplatinum(II) in brain tumor therapy by a high-zinc diet.

Metallothionein (MT), a ubiquitous intracellular protein, confers resistance to the toxic effects of platinum compounds. Since a high-zinc diet has been shown to induce MT synthesis in extracerebral tissues but not in brain, we investigated whether it could provide an experimental basis for decreasing the hematotoxicity of carboplatin without impairing its activity against brain tumors. After 2 weeks on either a high-zinc diet or a control diet (zinc content, 180 vs 10 ppm), mice and rats received various doses of carboplatin or Hanks' balanced salt solution by i.p. injection. The hematotoxicity of carboplatin was evaluated with an assay of colony-forming units of granulocytes and mononuclear cells in mice. The high-zinc diet enabled a 50% increase in the carboplatin dose without increasing hematotoxicity. The antitumor activity was evaluated with an assay of the colony-forming efficiency of gliosarcoma cells from 9L brain tumors in rats. The high-zinc diet did not alter the efficacy of carboplatin against this brain tumor. Northern blot analysis confirmed that the high-zinc diet induced MT mRNA in the kidney but not in the brain of mice and rats; it also showed MT mRNA induction in bone marrow cells of mice but not in rat 9L brain tumors. These results suggest that increasing the dietary intake of zinc might increase the therapeutic index of carboplatin in the treatment of brain tumors.

Animals

A re-evaluation of the osteoarticular manifestations of psoriasis.

A distinctive peripheral arthropathy associated with psoriasis is well recognized, the classical pattern describing an asymmetrical oligoarthritis with predominant distal interphalangeal joint (DIP) involvement. There is some dispute about the frequency of this classical pattern and of the pattern of symmetrical polyarthritis resembling rheumatoid arthritis. Some of the dispute may be a result of loose definitions. In this clinical and scintigraphic study of 50 patients with psoriatic arthritis we have used tighter definitions of disease pattern and have found that 68% of this group had a symmetrical polyarthritis similar to that found in rheumatoid arthritis. Yet, arthritis associated with psoriasis differs from rheumatoid arthritis in a number of ways including the pattern of joint involvement, extra-articular osseous features, and radiological changes. Scintigraphic changes in psoriatic arthritis suggest that subclinical involvement of the manubriosternal and sternoclavicular joints is common, suggesting an association between psoriasis vulgaris and arthro-osteitis. A modified classification of the osteoarticular manifestations of psoriasis is proposed.

Adult

Functional use of the Nucleus 22-channel cochlear implant in the elderly.

A questionnaire was sent to 101 Nucleus 22-channel cochlear implant recipients aged 65 years and older to investigate the perceived impact of cochlear implantation on their quality of life. The questionnaire was designed to gain insight into the patient's daily use of the Nucleus implant. Sixty-seven questionnaires were returned over a 3-month period. The results of the survey showed that elderly cochlear implant patients obtained similar benefits to younger adult patients who were implanted with the same device. We believe that the results of this study will aid other centers when counseling elderly patients on the expected daily functional benefits of this device.

Aged

Laryngeal examination: a comparison of mirror examination with a rigid lens system.

Indirect mirror laryngoscopy is the standard screening examination used in patients with complaints referable to the larynx and upper aerodigestive tract. The purpose of this study was to prospectively evaluate, in 100 patients, the diagnostic accuracy and examination success rate of indirect laryngoscopy versus a rigid rod examination. Fifty-two percent of mirror examinations were successful as were 83% of rod exams. This was a significant difference in success rate. From the 29 patients who underwent direct laryngoscopy, one false negative and one false positive mirror examination and one false positive rod examination were found. We conclude that the mirror is a useful screening tool so long as strict examination criteria are used. The rigid rod adds further diagnostic information in those patients who cannot be evaluated with a mirror.

Equipment Design

Cell kinetics of rat 9L brain tumors determined by double labeling with iodo- and bromodeoxyuridine.

Rats with 9L brain tumors received intraperitoneal injections of iododeoxyuridine (IUdR) and bromodeoxyuridine (BUdR) to estimate the duration of the deoxyribonucleic acid (DNA) synthesis phase (Ts) and the potential doubling time (Tp) of individual tumors. Different sequences and intervals (2 or 3 hours) of IUdR and BUdR administration were evaluated. After denaturation, tumor sections were reacted with Br-3, a monoclonal antibody that identifies only BUdR, and then were stained immunohistochemically by the avidinbiotin complex method. An antibody that recognizes both IUdR and BUdR, IU-4, was applied to the sections and identified by the alkaline phosphatase-antialkaline phosphatase method. Nuclei labeled only with IUdR stained blue, while those labeled with BUdR or with BUdR and IUdR stained brown. The fraction of cells that either left or entered the S-phase during the time between administration of IUdR and BUdR was measured to calculate Ts and Tp, assuming that the labeled cohort completed the DNA synthesis at a constant rate. The Ts was 8.8 hours (coefficient of variation (cv) = 0.05) and the Tp was 64.2 hours (cv = 0.08). The sequence and interval of administration of IUdR and BUdR had a minimal effect on Ts and Tp. In studies of 9L cells in monolayer culture, the Ts was 9.6 hours (cv = 0.08) and the TP was 30.6 hours (cv = 0.06). Double labeling with BUdR and IUdR allows the duration of the S-phase and potential doubling time of individual brain tumors to be estimated in situ from a single biopsy specimen.

Animals

Blood-brain barrier to pertechnetate following drug-induced hypotension.

The integrity of the blood-brain barrier (BBB) was examined in rabbits, in terms of the partition of 99mTc-pertechnetate (99mTcO4-) between brain and blood, following intracarotid injection of hypertonic arabinose, hypertension (168 mm Hg and 10% inspired carbon dioxide), or hypotension (less than 20 mm Hg for 15 min). Corrections were made for changes in tissue blood contents, using chromium-51 as a red cell marker. In control animals the mean brain:blood ratio was 0.038 (range 0.027-0.052). Following arabinose there was a five-fold increase in mean BBB permeability (mean brain:blood ratio 0.192 (0.070-0.378)). There was no change after hypertension and carbon dioxide (mean ratio 0.034) or after hypotension (mean ratio 0.032), despite an increase in cerebral extracellular potassium. Examination of other tissues showed no change in the 99mTcO4- tissue/blood partition in heart muscle in any study but, following hypotension, ratios in the kidney (mean ratio 1.63) and, to a lesser extent, the liver (mean ratio 1.37) had increased, suggesting an abnormality of active transport under these conditions. We conclude that, while 99mTcO4- tissue/blood partitioning revealed osmotic disruption of the BBB, profound hypotension with evidence of brain cell damage did not change BBB permeability to the same marker. Hypotension may influence active transport of this ion in liver and kidney.

Animals

AIDS--what to do.

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Acquired Immunodeficiency Syndrome

A measurement of the process of adolescence: standardization and interpretation.

The Objective Measure of Ego Identity Status (Adams, Shea, & Fitch, 1979) was administered to 350 adolescents (12 to 18 years old) to test the Eriksonian theory of a developmental continuum from role diffusion to identity achievement. The results offer construct validity for the dynamic process proposed by Blos and Erikson, but do not support the categorization procedure as set forth by Adams, Shea, and Fitch. The OMEIS questionnaire lends itself to a qualitative and dynamic interpretation rather than to a quantitative and normative approach. It is suggested that the dynamic interpretation is more sensitive to the psychological reality of the developmental process.

Achievement

Enuresis.

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Age Factors

Use of a long acting somatostatin analogue in controlling life threatening ileostomy diarrhoea.

A woman presented with persistent ileostomy diarrhoea unresponsive to conventional drug treatment and necessitating parenteral nutrition. Output was four to six litres of watery fluid per 24 hours while she was receiving oral nutrition and two to three litres when she was starved. Treatment with a long acting analogue of somatostatin (50 micrograms subcutaneously every 12 hours) reduced the ileostomy output to 2.0-2.5 litres/24 hours with an oral diet and the effluent became semiformed. Parenteral fluids could be stopped. Somatostatin may have a role in the treatment of secretory diarrhoea, but prospective controlled trials are necessary.

Diarrhea

The 9L rat brain tumor: description and application of an animal model.

Animal models allow determination of tumor response to anticancer agents under various experimental conditions. The chemically induced 9L rat brian tumor has been developed as both in vivo and in vitro models. Animal survival, clonogenic cell survival, and tumor growth delay provide means to measure the effectiveness of treatment modalities in this tumor model. Monolayer cultures, multicellular spheroid cultures, brain tumors, and flank tumors have been used to study the influence of different biological entities of the 9L model on the response to treatment with radiation and/or BCNU (1,3-bis (2-chloroethyl)-1-nitrosourea).

Animals

Methylation of DNAase-digestible DNA and of RNA in chromatin from rats treated with dimethylnitrosamine.

After injecting rats with di[14C]methylnitrosamine we have prepared liver chromatin and have examined firstly, the methylation level of the DNAase I-degradable fraction of the DNA and secondly, the level of methylation and the stability of methylated sites in chromatin RNA. Our results show that the level of 7-methylguanine in the degradable DNA is about 1.3 times that of whole DNA; therefore in the 20% or so of the DNA which is undegradable by DNAase I, the level must be very low or zero. Experiments using chromatin from rats injected with unlabelled dimethylnitrosamine plus [3H]thymidine show that the specific activity is similar in the DNAase I degradable and undegradable fractions, suggesting that there is no preferential repair in the latter region. In chromatin RNA, the level of 7-methylguanine is higher than that of whole DNA and decreases fairly rapidly within 30 h after dimethylnitrosamine treatment. Our results indicate that this decrease is due to some type of excision or repair process rather than to normal turnover.

Animals

Symptoms and feeding patterns in the first year of life.

With the help of family doctors, mothers and infant welfare sisters, we report an analysis of symptom and food diaries maintained throughout the first twelve months of life on 482 infants. This reveals the existence of extensive symptomatology in the first year of life--most of which was clearly unrelated to ingestion of foods or cow's milk. Our efforts to define the true incidence of cow's milk allergy have been unsuccessful. Altogether, 77 of the 482 diaries have revealed symptomatology at some time in the year which could conceivably have been associated with cow's milk ingestion. But, in only one of these 77 children were withdrawal and challenge tests carried out to determine whether the symptomatology disappeared on withdrawal of cow's milk and reappeared on its reintroduction into the diet. Most of the remaining 76 children had long periods of complete freedom from symptoms whilst taking cow's milk, and the evidence of any association with cow's milk was generally very tenuous. Soya substitutes were introduced in 13 cases, and cow's milk was temporarily discontinued in another 11 cases. Only 16 of these 77 children continued to experience chronic symptoms during the last two weeks of their first year.

Animals

Effect of dibutyryl cAMP on cell cycle progression of rat brain tumor cells in vitro.

Autoradiographic and flow microfluorometry analyses have been applied to a study of perturbed cell kinetics in 9L rat brain tumor cells treated with dibutyryl cyclic AMP and theophylline alone and in combination in vitro. At a concentration of 1 mM each, cell growth ceased shortly after the administration of these drugs. The results indicate that cells in S and G2 phase at the time of drug administration can undergo mitosis even though a considerable prolongation of G2 phase was apparent. However, cells in G1 at the time of drug administration was arrested in that phase, whereas those cells in S or G2 were able to complete one mitosis before becoming arrested in the G1 phase. This blocking effect was reversible, and cells resumed proliferation at a normal rate shortly after the removal of these drugs.

Animals