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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

Response of 9L rat brain tumor multicellular spheroids to single and fractionated doses of 1,3-bis(2-chloroethyl)-1-nitrosourea.

This study was designed to examine the relative effect of each of four fractions of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) against 9L rat brain tumor multicellular spheroids and to compare the results of the cell survival and growth delay assays. Similar levels of cell kill resulted when BCNU was administered either as single fractions of 1.5, 3.0, 4.5, or 6.0 micrograms/ml for 1 hr or as one to four fractions of 1.5 micrograms/ml that were administered sequentially for 1 hr each. Survival was increased if the assay was delayed until 24 hr after drug treatment, which indicates that 9L cells in spheroids recover from BCNU-induced potentially lethal damage. When BCNU was administered in 1.5-micrograms/ml fractions, plating efficiencies depended markedly on the interval between the fractions. The 12-hr protocol produced an overall higher cell kill. Fractionation schedules of 24 and 36 hr produced less cell kill than did the other schedules. Survival plateaued for the last three treatments with BCNU in the 36-hr schedule. Cells in S phase at the time of administration of the initial 1.5-micrograms/ml fraction of BCNU moved into G1- and G2-M phases by 12 hr after treatment. For time periods longer than 12 hr, cells began to appear in the BCNU-resistant S phase. Thus, the movement of cells into the drug-sensitive and -resistant phases after the first fraction correlates well with the corresponding overall cytotoxic effect produced by treatment with the combined BCNU (1.5 micrograms/ml) fractions. For a higher concentration (3.0 micrograms/ml for 1 hr), maximum cell kill was reached within the 12- to 18-hr interval, after which cell kill plateaued. Cells were not found in the S-phase fraction 12 to 36 hr after the first treatment with 3.0 micrograms/ml; maximum cell kill for the fractionated protocols resulted at these times. Therefore, BCNU, which is classified as a cell cycle-nonspecific drug, can induce a partial synchrony in 9L spheroid cells, which determines the overall cytotoxicity produced by fractionated BCNU protocols. Although spheroids did not shrink during or after exposure to BCNU, growth was retarded by treatment with all doses and schedules. An optimum time point for growth delay measurement could not be determined from the data. However, correlations between cell survival and growth delay were obtained with arbitrarily chosen end point volumes of four and ten times the volume at the time of treatment.

Animals

Subhypothalamic grafts of human pituitary adenomas in total-body irradiated rats.

Human pituitary adenomas proliferate neither in cell culture nor in athymic "nude" mice. We propose that one or several of the humoral factors necessary for the growth of pituitary adenomas is missing in these experimental environments. The purpose of our experiments was to examine the possible influence of the hypothalamus in supporting cellular proliferation, and thus adenoma growth. Fragments from four human pituitary adenomas (three pituitary prolactinomas; one ACTH-secreting adenoma) were transplanted into the pituitary fossa of total-body irradiated, hypophysectomized rats. The rats were killed after two weeks and perfused with a mixture of formalin and India ink. Histologic examination of serial sagittal sections through the pituitary fossa and the adjacent brain showed: vascularization of the grafts from the pituitary stalk and from the scar tissue in the sphenoid bone; survival of some adenomas; and numerous mitoses in an ACTH-secreting specimen obtained from a patient who had Cushing's disease. We conclude from these experiments that as yet unidentified hypothalamus factors are essential for the growth of certain types of pituitary adenomas.

Adenoma