Biomedical subjects
Publications and source records attributed to K Webster.
Various implants have been used to repair defects in orbital walls. Few are fully biocompatible. The indications for repair of a defect of the orbital floor are reviewed, and the suitability in selected cases of placement of lyophilized porcine dermis (xenograft) is discussed.
Two cases of metastatic lesions presenting in the mandibular condyle as Temporo-Mandibular Joint Pain Dysfunction Syndrome are presented with a discussion on the mechanisms of tumour metastases to bone.
Lung strips from actively sensitized guinea pigs were repeatedly contracted by antigen (ovalbumin, OA) challenge in the presence of the antihistamine (H1) mepyramine. At lower concentrations of OA, hourly challenges gave reproducible and consistent responses. High-concentration OA resulted in desensitization, with two to six contractions being very weak. The antigen concentration affected not only the force of contraction, but other parameters including the time to peak effect, the protraction of the peak effect, and the repeatability of the force and time to peak. Low concentrations of OA induced a response which peaked by 6-8 min and decreased by about 30% after 15 min, while high-concentration OA resulted in a contraction which peaked later and did not relax. These data suggest that different 'early' and 'late' mediators may be involved depending on the 'activation state' or the mechanisms that predominate in the contraction response as a result of the amount of stimulation by antigen. Leukotriene apparently mediates the peak and the 15-min contraction since both were inhibited completely by FPL-55712 (IC50 = 8 microM) or NDGA (IC50 = 5 microM). These repeated, leukotriene-mediated contractions of isolated lung may mimic the clinical situation (chronic exposure to low amounts of antigen) of allergic disease and may be used to study the modulation of lung responses and desensitization phenomena.
A series of furo[3,2-b]indole carboxylic acids, tetrazoles, and carbamoyltetrazoles was prepared and tested in vitro with use of a model of active pulmonary anaphylaxis, the modified Schultz-Dale Test (SDT). In this model, isolated guinea pig lung strips are repeatedly challenged with antigen in the presence of an antihistamine (H1). Most of the acidic furo[3,2-b]indoles tested inhibited the leukotriene-mediated lung contraction in a dose-related manner. Compounds with an N-phenyl substituent were more potent (IC50 less than or equal to 5.0 microM) inhibitors of SDT than the N-methyl analogues (IC50 greater than or equal to 22.0 microM). Most of the N-phenyl analogues were more potent in SDT than Fisons' mediator-release inhibitor proxicromil (FPL-57,787; IC50 = 6.3 microM). The most potent furo[3,2-b]indoles were those unsubstituted at C-7 and with N-phenyl, 2-carbamoyltetrazole, and 3-alkoxy substituents. All of the carboxylic acid ester analogues tested were weak or inactive at concentrations of 10-30 microM.
Fifty-two cases of the rare entity, uterine endolymphatic stromal myosis, were evaluated in a collaborative study by gynecologic oncologists trained at the M. D. Anderson Tumor Institute. Fifty percent developed recurrent disease subsequent to initial surgical therapy. Of the surgical stage I cases, 47% developed pelvic recurrences, and 9% developed distant recurrences only after initial therapy. The five- and ten-year life-table survival of surgical stages I to IV were 88% for stage I, 66% for stage II, 100% for stage III, and 75% for stage IV. These long-term survival rates were due in part to the hormonal sensitivity of the recurrent tumors. Because of the high recurrence rate after initial therapy, a suggested plan of therapy is presented for patients with uterine endolymphatic stromal myosis.
A tumor colony assay (TCA) was evaluated for its ability to predict anticancer drug responses in an N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT)-induced murine bladder tumor (MBT) model. Ten anticancer drugs were evaluated in vivo and in vitro using four MBT cell lines (40 drug responses). Using the optimum criteria for drug response, the TCA accurately predicted drug responses in the murine model 65% of the time with a true-positive predictive rate of 54% and a true-negative predictive rate of 70%. Drug testing tumor cells immediately on removal from the mouse resulted in a true-positive predictive rate of 77% and a true-negative predictive rate of 100%. The authors conclude that the TCA can predict response to chemotherapy in the MBT model and may be useful in screening investigation compounds for the subsequent evaluation in this murine bladder tumor model.
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