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Biomedical subjects

K Mahoney

Publications and source records attributed to K Mahoney.

15 recordsLinked to original sources

Comparison of modelled and observed in vivo temperature elevations induced by focused ultrasound: implications for treatment planning.

Two numerical models for predicting the temperature elevations resulting from focused ultrasound heating of muscle tissue were tested against experimental data. Both models use the Rayleigh-Sommerfeld integral to calculate the pressure field from a source distribution. The first method assumes a source distribution derived from a uniformly radiating transducer whereas the second uses a source distribution obtained by numerically projecting pressure field measurements from an area near the focus backward toward the transducer surface. Both of these calculated ultrasound fields were used as heat sources in the bioheat equation to calculate the temperature elevation in vivo. Experimental results were obtained from in vivo rabbit experiments using eight-element sector-vortex transducers at 1.61 and 1.7 MHz and noninvasive temperature mapping with MRI. Results showed that the uniformly radiating transducer model over-predicted the peak temperature by a factor ranging from 1.4 to 2.8, depending on the operating mode. Simulations run using the back-projected sources were much closer to experimental values, ranging from 1.0 to 1.7 times the experimental results, again varying with mode. Thus, a significant improvement in the treatment planning can be obtained by using actual measured ultrasound field distributions in combination with backward projection.

Acoustics↗

Migration of distinct subsets of CD8+ blood T cells through endothelial cell monolayers in vitro.

The immune response in many infections and to allografts is dependent on CD8+ cytotoxic T lymphocytes (CTL). Influx of CD8+ CTL from the blood has been documented during antigen challenge. We have previously found that a subset of CD8+ T cells from normal blood can migrate through endothelial cell monolayers in vitro. To further characterize migration-prone CD8+ T cells from normal blood, we examined the expression of CD28 and a restricted epitope of CD18/CD11a (S6F1), a CTL marker. Although normal blood CD8bright+ T cells were heterogeneous in their expression of CD28, three populations could be identified (CD28low, CD28moderate, and CD28high). CD8+ cells migrating across endothelial cell monolayers were enriched for CD8bright+ CD28high cells and a subset of CD8dim+ cells, which were CD28high. Both adherent and migrating CD8+ cells were exclusively (> 95%) S6F1high. There was also preferential adhesion and migration of CD8+ cells expressing the low-molecular-weight form of the leukocyte common antigen, CD45RO. Cytokine activation of the endothelium did not significantly alter preferential migration of these subsets. These data suggest that certain subsets of CD8+ memory T cells in normal human blood are prone to, adhere to, and migrate through allogeneic endothelial cells and would thus be likely to be recruited to sites of antigen challenge.

Adult↗

The utility of a bilateral breast pumping system for mothers of premature infants.

Mothers of premature infants have difficulty maintaining their milk supply as a result of the separation that occurs between the mother and the baby. The hypothesis in the present investigation is that use of a bilateral (simultaneous) breast pumping system will increase the volume of milk expressed in these mothers. Thirty-two breastfeeding mothers of premature infants were randomly assigned to either the control (single) or the experimental (bilateral) breast pump group. Mothers pumped at least four times a day. Data collection included a daily milk production log, weekly serum prolactin levels, and a weekly State-Trait Anxiety Inventory (STAI). Participation lasted from four to six weeks. Data analysis included average STAI scores; average prolactin levels; and weekly averages for number of pumping sessions, hours of pumping, and milk production in milliliters. The two groups did not differ on several demographic characteristics, STAI scores, prolactin levels, number of pumping sessions per week, or weekly milk production. The amount of time spent pumping, however, was statistically less for mothers who used the bilateral pump (7.6 +/- 3.0 hours/week) versus those who used the single pump (11.1 +/- 3.1 hours/week) (p = .003). Although use of either the single pump or the bilateral electric pump resulted in similar milk production, the bilateral pump significantly reduced the time invested in pumping. Health professionals should advocate use of the bilateral pump for mothers of premature infants. Additional studies are needed to determine strategies for increasing milk production in this population.

Adult↗

Graves' IgG recognizes linear epitopes in the human thyrotropin receptor.

Twenty-nine peptides covering the full extracellular domain of the human thyrotropin receptor have been synthesized and tested for reactivity with Graves' patients' and normal sera in ELISA. Two peptides, amino acids 331-350 and the second extracellular loop of the transmembrane segment, bound IgG-s from 5 and 4 of 10 Graves' disease patients' sera, respectively. Neither of these two peptides showed enhanced binding to normal IgG. There were no apparent differences between the Graves' disease and normal group with respect to the other 27 peptides. We conclude that peptide 331-350 and the second extracellular loop carry important linear epitopes which may contribute to the disease process in selected Graves' patients.

Enzyme-Linked Immunosorbent Assay↗

Case management lessons from a public/private partnership to finance long-term care.

In June of 1987, Connecticut's State Task Force on Private and Public Responsibilities for Financing Long-Term Care for the Elderly released its final report. This Governor's Commission, concluding that neither the private nor the public sector had much short-term hope of solving this difficult problem alone, recommended the creation of a public/private partnership. As this partnership was forged, some unique insights were gained into the functions of case management. This case study shows how case management can help coordinate the private and public roles, but it also raises some research questions which must be tackled before case management can fulfill its promise to help stretch and conserve scarce resources.

Connecticut↗

Animal toxicology studies on new medicines and their relationship to clinical exposure: a review of international recommendations.

Written guidance on the toxicology studies which should be completed to support an application to market a new medicinal product in the EEC, Japan, and the USA is readily available, although the recommendations can vary significantly between the three markets. Less clear are the regulatory authorities' expectations concerning the timing of these studies relative to the clinical development programme. All available guidelines for premarketing toxicology requirements, and the portions thereof needed to support various stages of the clinical trials programme will be reviewed. Significant differences among the three markets and between written guidance and customary practice will be highlighted. The practical implications for the clinical development programme will be identified.

Animals↗

Characterization of lymphocytic infiltrates in normal, preneoplastic, and neoplastic mouse mammary tissues.

Lymphocytic infiltrates were isolated from normal, preneoplastic, and neoplastic mouse mammary tissues. The surface markers on the infiltrating lymphocytes were characterized by immunofluorescent staining and flow cytometry. Preneoplastic and neoplastic tissues contained 10- to 20-fold more in situ lymphocytes than did the normal pregnant gland. Most of these lympocytes were T-cells. Relative to the T-cells in normal gland, the T-cells in C4 preneoplastic hyperplastic alveolar nodules and their spontaneous tumors have shifted in favor of the killer-suppressor subpopulation. This shift of T-cell subpopulations was a localized phenomenon and was not seen in the lymph nodes of hyperplastic alveolar nodules and tumor bearing mice. C4 lesion infiltrating cells also contained a subpopulation of lymphocytes that expressed 5- to 6-fold more LFA-1 antigen (lymphocyte function associated antigen-1) than did normal lymph node cells. The infiltrating lymphocytes of mammary tumors from cloned cell lines, on the contrary, had the same staining profile as did the lymphocytes from normal gland. Since most studies with human breast cancer infiltrates have demonstrated increased killer/suppressor T-cells and the presence of activated lymphocytes (J. Hurlimann and P. Saraga, Int. J. Cancer, 35: 753-762, 1985; H.L. Whitwell, H.P.A. Hughes, M. Moore, and A. Ahmed, Br. J. Cancer, 49: 161-172, 1984; and J.A. Ledbetter, R.V. Rouse, H. Spedding Micklem, and L. Herzenberg, J. Exp. Med., 152: 280-295, 1980) the C4 hyperplastic alveolar nodules and spontaneous tumor system may be a more relevant model for studying breast cancer infiltrates.

Animals↗

A noninvasive positron computed tomography technique using oxygen-15--labeled water for the evaluation of neurobehavioral task batteries.

A technique is described that provides information about relative cerebral responses to differing neurobehavioral tasks in normal subjects studied with positron computed tomography and oxygen-15-labeled water. Simulation studies demonstrate that this technique is sensitive to changes in true local CBF within a physiological range and tends to underestimate relative flow changes at high flow values (greater than 30 ml min-1 100 g-1) and to overestimate these changes for flow values of less than 25 ml min-1 100 g-1. Image acquisition times of 60 s following the arrival of oxygen-15-labeled water in the brain were the most accurate for identifying such relative changes between radioisotope administrations and were not limited by statistical noise from total image counts. Studies in normal volunteers indicate that the technique is highly reproducible, demonstrating a coefficient of variation for small (less than 2 cm2) regions of 2.98 between studies in the same state. Visual stimulation studies in normal volunteers demonstrated relative radioisotope concentration changes between control and stimulated states that are in good agreement with similar results obtained using the same stimulation paradigm but with the use of fluorodeoxyglucose to determine cerebral glucose metabolism.

Adult↗

A comparative trial of ranitidine 300 mg at night with ranitidine 150 mg twice daily in the treatment of duodenal and gastric ulcer.

A multicenter double-blind comparative trial of oral ranitidine, 300 mg hs versus 150 mg bid, was conducted in 89 patients with duodenal ulcer (DU) and 54 with gastric ulcer (GU). Antacid tablets were prescribed prn. After 4 wk of treatment there were no statistically significant differences in the ulcer healing rates associated with the once daily (DU 86.4%, GU 62.5%) and the twice daily (DU 84.4%, GU 73.3%) regimens. Antacid consumption, by both DU and GU patients, was higher in the 150 mg bid group, but the differences did not achieve statistical significance. Further improvement in cumulative healing rates in response to both treatment regimens was observed following a second 4-wk treatment for those patients whose ulcers had failed to heal during the 1st month. Smoking adversely affected the rate of ulcer healing in DU patients, but had no significant effect on GU healing. No serious adverse effects or biochemical abnormalities were observed. Ranitidine 300 mg hs appears to be equally safe and effective as the standard regimen of 150 mg bid in the short-term treatment of uncomplicated gastroduodenal ulcer.

Adult↗

Toilet training of normal and retarded children.

Early elements in an operant chain of toilet behaviors were trained in three normal infants and five retarded children. Following that, eliminative behaviors were conditioned by operant procedures. Each child was equipped with an auditory signalling device that gave cues to the learner. Baseline behavior was recorded for a period of five days. The procedure for training consisted of two steps. First, a response was obtained through physical, verbal, and auditory prompts. Second, prompts were faded until the child responded in the presence of the auditory signal. When the device was removed the child performed without the auditory prompt. Parents were instructed in a similar procedure to enhance generalization in the home. Seven of the eight subjects reached a criterion and maintained that behavior during three criterion sessions.

Journal Article↗