Biomedical subjects

B Drury

Publications and source records attributed to B Drury.

6 recordsLinked to original sources

PubMed1992

Analogs of the delta opioid receptor selective cyclic peptide [2-D-penicillamine,5-D-penicillamine]-enkephalin: 2',6'-dimethyltyrosine and Gly3-Phe4 amide bond isostere substitutions.

In order to develop systemically-active opioid peptides, the delta-selective, opioid pentapeptide [D-Pen2,D-Pen5]-enkephalin (DPDPE) was modified by esterification and by substitution of 2',6'-dimethyltyrosine for tyrosine to yield 4. Compound 4 was on the order of 8- and 800-fold more active than DPDPE in both delta and mu opioid radioligand binding assays, respectively, in rat neural membrane suspensions. Compound 4 was considerably more potent than DPDPE at inhibiting contractions of electrically-stimulated mouse vas deferens in vitro, and this effect was very sensitive to naltrindole, a delta-selective opioid antagonist. These observations can be taken as indication that 4 exerts its effects through delta opioid receptors. This interpretation is supported by the finding that the EC50 value of 4 derived in the smooth muscle assay is very similar to that derived in NG108-15 neuroblastoma cells, a preparation devoid of mu receptors. Unlike DPDPE, 4 exhibited significant, naloxone-sensitive, antinociceptive activity when administered systemically, as measured by inhibition of phenylbenzquinone-induced stretching in mice (ED50 = 2.1 mg/kg). Compound 4 also displayed significant antinociceptive activity following systemic administration as measured by its action in mice to increase latencies for tail withdrawal from radiant heat (ED50 = 50 mg/kg). Compound 4 did not produce morphine-like discriminative stimulus effects in rats trained to discriminate 3.0 mg/kg morphine from vehicle at doses ranging from 30 to 120 mg/kg. This observation can be interpreted as indication that within this dosage range there is an absence of morphine-like subjective effects. Physical dependence, however, could be induced in mice at higher doses of 4 under a progressively-graded, 4-day dose regimen. Congeners of 4 with amide bond surrogates for the Gly-Phe amide bond (oxymethylene, trans-double bond, and bismethylene isosteres) in the cyclic core of DPDPE were prepared in an attempt to increase the antinociceptive activity of 4. While some of the congeners were active in the in vitro assays, they did not display significant antinociceptive activity following systemic administration. The preparation of all the compounds was accomplished by solution-phase methods. The mechanisms which might underlie the biological and systemic activity of 4 are discussed.

Amides↗

PubMed1989

Computers in the medical workplace.

Whether your greatest need is to have a neatly typed letter or an accurately aged accounts receivable report, or it's critical that you create an electronic medical record for decision support, the computer in the medical workplace should: 1. Save time for staff and patients. 2. Be convenient to use. 3. Respond quickly to the user. 4. Be flexible. 5. Free staff for intelligent work. 6. Minimize or eliminate redundancy. 7. Allow retrospective retrieval. If your computer and software produces the above results, you've chosen appropriate software and right equipment for your specific needs and your work place.

Computers↗

PubMed1988

Thermal dose-response of magnetic-induction thermoradiotherapy.

Sixty-three patients with advanced cancer underwent greater than or equal to 5,000 cGy combined with Concentric Coil magnetic-induction localized hyperthermia. Tumor regression (CR + PR) was compared to thermal dose received, incorporating the premise that hyperthermia response is a function of time as well as temperature. A computer program was developed (after Sapareto and Dewey [2]) which stored minimum tumor temperatures recorded spatially and temporally during treatment and correlated response with T43 (equivalent minutes at 43 degrees C during the first treatment) and CT43 (cumulative T43, computed by multiplying T43 by the actual number of identical subsequent treatments received during the course of therapy). Those who responded--N = 46 (73%)--had significantly higher median thermal doses than those who did not respond. Comparison of T43 and CT43 thermal dose values between responders and nonresponders was significantly different at p values of 0.05 and 0.04, respectively. The data indicate that magnetic-induction hyperthermia and high-dose XRT was an effective treatment combination in advanced disease and that tumor response improved as thermal dose increased.

Combined Modality Therapy↗

PubMed1986

Effect of localized magnetic-induction hyperthermia on the brain. Temperature versus intracranial pressure.

Normal brain and brain tumor temperatures were studied for their effects on intracranial pressure (ICP) in 13 patients who received 37 localized thermochemotherapy treatments for recurrent primary or metastatic brain tumors. Two transient neurologic complications occurred in patients with an elevated initial ICP value; thus, the authors concluded that an initial ICP value of 30 cm H2O or greater may contraindicate brain hyperthermia. It appears that noninvasive brain hyperthermia by magnetic-loop induction can cause an initial rise in ICP value, although a protective mechanism(s) that tends to lower ICP occurs over time, and also at a normal brain temperature of approximately 42.0 degrees C. Possible mechanisms of ICP reduction include direct heating of the hypothalamus with a reduction in pCO2 and the development of tachypnea and hyperpnea with a reduction in pCO2. Hyperthermia applied to the brain should be undertaken only with adequate monitoring of ICP; in addition, extreme caution should be taken in patients with an elevated initial ICP value and in those patients in whom adaptation to elevated pressure does not occur.

Adult↗

PubMed1985

Phase I trial of thermochemotherapy for brain malignancy.

High-grade primary and refractory brain tumors and metastases to the brain from other primary sites are associated with a grave prognosis. Treatment, usually palliative, consists of some combination of surgery, radiation, and chemotherapy. Recently, noninvasive hyperthermia by magnetic-loop induction has been safely used to treat patients with advanced cancer in extracranial sites. Both disease regression and disease stabilization have been observed. This technique was recently applied to brain tumors in an animal model, and its safety was again demonstrated. As a result, a Phase I trial of noninvasive localized hyperthermia in combination with intravenous chemotherapy has been carried out in ten patients whose primary or metastatic brain tumors failed to respond to standard therapy. Ten patients underwent 23 thermochemotherapy sessions using the magnetic-loop induction device. The median, maximum temperature of normal brain after 1 hour of hyperthermia was 41.1 degrees C (range, 38.6 degrees C-43.4 degrees C); the median, maximum temperature of brain tumor was 42.5 degrees C (range, 38.8 degrees C-46.3 degrees C) (P less than 0.01). The temperatures of both the normal brain and brain tumor were obtained during 18 treatments. The tumor temperature was greater than the normal brain temperature in 15 of 18 treatments. In 78% of the treatments, the measured tumor temperature reached at least 42 degrees C, whereas the normal brain reached 42 degrees C in only 13% of the treatments. These data demonstrate the "selective inability" of brain tumor tissue to dissipate heat. Vital signs, intracranial pressure, and neurologic status were monitored throughout the hyperthermia treatments. No mortality or increase in chemotherapeutic toxicity could be attributed to the thermochemotherapy. In addition, there were no local complications or permanent neurologic complications. Two patients with elevated intracranial pressure before therapy had transient neurologic deficits that may have been exacerbated by the hyperthermia. It is concluded that this new, noninvasive modality not only produced effective intracranial tumor heating, but could be performed safely with the proper precautions. Phase II trials are warranted.

Adult↗

PubMed1984

Combination radiofrequency hyperthermia and chemotherapy (BCNU) for brain malignancy. Animal experience and two case reports.

Patients with high-grade primary and metastatic brain malignancies have a median survival time of 3-8 months, regardless of therapy. Because MagnetrodeTM hyperthermia provides safe, deep internal heating without normal-tissue injury, we studied its effects first on the brain and surrounding tissues of rabbits. The normal rabbit brain (n = 26) could be heated to potentially tumoricidal temperatures (42-43 degrees C) without apparent histopathologic or clinical damage to the brain, skull, external eye, subcutaneous tissue or skin. Intracranial pressure did not rise significantly. Using transplanted VX-2 carcinoma, we showed both the safety and potential efficacy of thermochemotherapy (IV BCNU: 14 mg/kg) in the presence of a solid brain tumor. The average maximum brain temperature achieved was 43.06 degrees C. Mean survival from the time of tumor implantation in the treated group (n = 16) was 18.56 days, compared to 9.3 days for untreated controls (n = 30) (p less than .0001). Two patients have been treated with localized brain hyperthermia combined with intravenous BCNU (80 mg/m2) for a total of eight treatments. Maximum normal brain temperature achieved was 40.0 degrees C in Patient #1 and 41.5 degrees C in Patient #2. A tumor temperature of 42.9 degrees C was achieved in Patient #2. Intracranial pressure remained within the upper limits of normal. Swan-Ganz monitoring in Patient #1 revealed a stable cardiac index and mean pulmonary artery pressure with mild fluctuations in the CVP, PAD, and PCW. No increase in chemotherapy toxicity was observed and no normal tissue injury occurred in either patient. We conclude that non-invasive localized radiofrequency hyperthermia to the brain is feasible and can be performed safely in the presence of a solid brain tumor.

Animals↗