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Biomedical subjects

R R Perry

Publications and source records attributed to R R Perry.

17 recordsLinked to original sources
PubMed1992

Effect of treatment duration and glutathione depletion on mitomycin C cytotoxicity in vitro.

Glutathione (GSH) has been shown to modulate the cytotoxicity of a variety of chemotherapeutic agents. The effect of mitomycin C (MMC) treatment duration and the effect of GSH depletion on in vitro cytotoxicity against the human colon cancer cell line HT-29 was studied under aerobic conditions. Continuous-exposure experiments revealed that the cytotoxicity of 0.1 microM MMC, as measured by clonogenic cell survival, exhibited a shoulder until exposure time was at least 12 h, after which time exponential cytotoxicity was observed. Lowering GSH levels to less than 3% of control using buthionine sulfoximine (BSO) did not enhance cytotoxicity of MMC given for 1 h or continuously for less than 12 h. However, GSH depletion did enhance cytotoxicity of MMC given continuously for at least 12 h, with a dose-modifying factor at 1% survival of 1.4 for a 24-h treatment. GSH depletion under these conditions enhanced cytotoxicity of even minimally cytotoxic MMC concentrations (0.02 microM). Absolute levels of GSH-related enzymes, including glutathione-S-transferase, and the MMC-metabolizing enzyme DT-diaphorase did not change appreciably. A tetrazolium [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay was used to verify the results further and to determine the optimal sequence of BSO administration with a 24-h MMC treatment. BSO added simultaneously with MMC did not increase cytotoxicity, compared to MMC alone. BSO added and then removed prior to MMC was effective (dose-modifying factor at 50% survival = 1.3), but the greatest cytotoxicity was noted when BSO was present before and during MMC treatment (dose-modifying factor = 1.5). GSH depletion in another cell line (SW480) showed similar enhancement of 24-h MMC cytotoxicity. These studies show that aerobic cytotoxicity of MMC is improved by administration of the drug in continuous fashion for at least 12 h, as opposed to continuous administration for shorter periods or 1-h bolus administration. Cytotoxicity of continuous (at least 12-h) MMC treatment can be modestly enhanced by GSH depletion, which must precede MMC exposure in order to be effective.

Buthionine Sulfoximine↗
PubMed1991

Intravenous vs intraperitoneal sensitizer: implications for intraperitoneal photodynamic therapy.

Photodynamic therapy (PDT) is a potential treatment for peritoneal carcinomatosis. However, little data is available regarding the relative distribution of sensitizer to tumor and intra-abdominal organs, optimal route of sensitizer administration, and maximal tolerated light dose. Tumor and normal tissue sensitizer levels were measured by tissue extraction 3, 24, 48 and 72 h after 10 mg/kg of Photofrin II was given intraperitoneally (IP) or intravenously (IV) in a mouse peritoneal tumor model, and the maximal tolerated PDT light dose determined. Equivalent tumor sensitizer levels were obtained regardless of the route of sensitizer administration. Route of administration, however, did affect the kinetics of tumor sensitizer elimination, with the half-time for elimination (T1/2) 113.6 h for IP drug and 60.6 h for IV drug. Route of administration also affected sensitizer levels in several intra-abdominal organs, resulting in somewhat higher tumor to liver and kidney levels at 24 and 72 h after IP sensitizer administration. Despite these tissue distribution differences, route of sensitizer administration did not significantly affect PDT toxicity or mortality when mice were treated with 630 nm light. The maximum tolerated light dose was 1.04 J/cm2. These parameters will prove helpful in designing large scale animal trials assessing the efficacy and safety of intra-abdominal PDT.

Animals↗
PubMed1990

Sensitivity of different human lung cancer histologies to photodynamic therapy.

The relative sensitivities of different cancer histologies in a single site to photodynamic therapy (PDT) are unknown and methods to predict PDT sensitivity have not been described. The in vitro response to PDT of six established human lung cancer cell lines and one normal lung fibroblast cell line was studied using the clonogenic assay. Dose-response curves were determined for cells incubated in 25 micrograms/ml of Photofrin II for 2 h, followed by exposure to 630-nm light to total energies of 0-3150 J/m2. None of the cell lines were sensitive to sensitizer alone or light alone. Differences in inherent PDT sensitivities as evaluated by survival curve parameters n, Do, and light dose to yield 1% survival were observed among the cell lines. No clear correlation was found when inherent PDT sensitivity was compared with sensitizer uptake; however, a general association was noted between PDT sensitivity and the plating efficiency of the cell line. These data illustrate that differences in inherent PDT exist for in vitro systems. Such differences may explain some of the failures seen in clinical PDT.

Cell Line↗
PubMed1990

Survival after surgical resection for high-grade chest wall sarcomas.

Indications for chest wall resection of metastatic or locally recurrent sarcoma and for subsequent bony reconstruction are controversial. Twenty-eight patients had chest wall resection for high-grade primary, metastatic, or recurrent sarcoma. In all patients, resection with selective reconstruction of the bony thorax was performed without operative mortality. Since 1980, only patients with four or more ribs resected have had selective bony reconstruction. Follow-up ranged from 8 to 132 months (median follow-up, 42 months). All deaths were related to sarcoma recurrence. The overall actuarial survival rate was 85% at 1 year, 65% at 3 years, and 59% at more than 5 years. The overall actuarial proportion without disease recurrence was 64% at 1 year, 52% at 3 years, and 40% at more than 5 years. There was no significant difference in overall or disease-free survival for patients with primary, metastatic, or recurrent tumors. The most important prognostic factors were positive margins and concomitant pulmonary resection for synchronous lung metastases. These data support aggressive resection to obtain pathologically tumor-free margins for chest wall sarcomas, whether primary, metastatic or recurrent. Reconstruction can be individualized based on the extent of resection.

Adolescent↗
PubMed1990

Surgical management of pheochromocytoma with the use of metyrosine.

Despite recommended preoperative preparation with alpha-adrenergic blockers, severe hemodynamic instability may occur during operations to resect pheochromocytoma. We combined the alpha-blocker phenoxybenzamine with the tyrosine hydroxylase inhibitor metyrosine in an attempt to better manage the hypertension of patients with pheochromocytoma undergoing surgical resection. This report reviews the cases of 25 consecutive patients undergoing surgery for known intra-abdominal pheochromocytoma. Each patient had elevated serum or urine levels of catecholamines or their metabolites. Nineteen patients were prepared before operation with phenoxybenzamine and metyrosine and six patients were given phenoxybenzamine alone. There were no significant differences in maximum, minimum, or mean blood pressure before or after tumor resection between patients who received metyrosine and those who did not. However careful review suggested that those who received metyrosine had more severe disease as judged by biochemical criteria. Study of selected patients matched for age and severity of disease suggested that the intraoperative blood pressure management of patients prepared with phenoxybenzamine and metyrosine was facilitated. In addition metyrosine-prepared patients lost less blood and required less volume replacement during surgery than did non-metyrosine-prepared patients. There were no apparent differences in postoperative fluid requirements. Although the study is not a prospective randomized trial, a retrospective review of patients managed with the combination of phenoxybenzamine and metyrosine suggests that surgery to resect pheochromocytoma can be better performed with both drugs than with phenoxybenzamine alone. The combination regimen appears to result in better blood pressure control, less blood loss, and the need for less intraoperative fluid replacement than does the traditional method of single-agent alpha-adrenergic blockade.

Adrenal Gland Neoplasms↗
PubMed1989

In vitro photodynamic therapy of human lung cancer: investigation of dose-rate effects.

The influence of light dose-rate delivery was studied in human lung adenocarcinoma A549 cells treated with hematoporphyrin derivative (Photofrin II)-based photodynamic therapy. Clonogenic cell survival curves were generated for cells treated for 2 h with 25 micrograms/ml of Photofrin II followed by exposure to light delivered at 0.3, 0.15, 0.075, or 0.0375 milliwatts/cm2. Cellular sensitizer levels, as determined by fluorescence measurements, remained constant over the entire time course of all light exposures. As the dose rate of light delivery was decreased, a significant increase in cell survival was observed at equal light energies (225 mJ/cm2). The enhancement in survival from the highest to the lowest dose rate used was 1.6-fold (at the 50% survival level). These findings may have important clinical implications relating to photodynamic therapy of tumors and may provide a partial explanation for treatment failure.

Adenocarcinoma↗
PubMed1989

Potentiation of phototherapy cytotoxicity with light scattering media.

Lung cancer cells are susceptible to photodynamic therapy (PDT) using 630 nm light and dihematoporphyrin ether (DHE). A light scattering media, intralipid (IL), was compared to balanced salt solution (PBS) for PDT of A549 human lung cancer cells. Differences in cellular DHE content after IL or PBS exposure were determined. Cells were incubated in 25 micrograms/ml DHE for 2 hr and then incubated in various concentrations of IL or PBS at room temperature for 2.5 to 10.0 min. Significant amounts of DHE were lost from IL-incubated cells compared to cells incubated in PBS. After 5 min in 1% IL, cellular DHE content was 0.32 +/- 0.04 microgram DHE/10(6) cells compared to 0.56 +/- 0.11 microgram DHE/10(6) cells in PBS-incubated cells (P less than 0.05). Despite this, superior PDT cytotoxicity was noted when cells were treated in IL with energy densities greater than or equal to 105 mJ/cm2. At an energy density of 210 mJ/cm2, the survival fraction (SF) of cells treated in 1% IL was 0.004 +/- 0.001 compared to 0.071 +/- 0.022 in PBS-treated cells (P less than 0.05). SF was dependent upon the IL concentration with the greatest cell killing noted with 1% IL. An apparent loss of cellular DHE ("DHE washout") was confirmed by demonstration of a higher SF of cells incubated in IL, rinsed, and subsequently PDT-treated in PBS with 157.5 mJ/cm2 (SF = 0.85 +/- 0.11) compared to cells incubated and treated in PBS (SF = 0.50 +/- 0.03, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Survival↗
PubMed1989

Primary adrenal causes of Cushing's syndrome. Diagnosis and surgical management.

Cushing's syndrome is rare with only 20% of patients having a primary adrenal cause of hypercortisolism. We have developed a strategy to evaluate patients with suspected Cushing's syndrome and to localize the pathologic condition responsible for the hypercortisolism. This report reviews the last 11 consecutive patients who had a primary adrenal cause of hypercortisolism. Each patient had elevated 24-hour urine free cortisol and 17-hydroxycorticosteroid excretion consistent with hypercortisolism. All but one patient had undetectable plasma ACTH levels. No patient suppressed urinary steroid levels with high-dose dexamethasone and only one patient increased plasma ACTH or cortisol levels with oCRH, findings that were consistent with a pituitary-independent form of hypercortisolism. No patient had a pituitary tumor detected by computed tomography or magnetic resonance imaging, and eight patients had adrenal tumors accurately imaged. MRI of the adrenal glands correctly diagnosed adenoma in 5 of 6 patients with adenomas, carcinoma in 1 patient, and ACTH-producing pheochromocytoma in 1 patient. One tumor classified as carcinoma by MRI appeared on pathologic examination to be an adenoma. Three patients underwent petrosal sinus sampling for measurement of ACTH before and after oCRH administration, and each had petrosal sinus ACTH levels equal to peripheral levels, consistent with a primary adrenal cause of hypercortisolism. Two of these patients had typical bilateral pigmented micronodular adrenocortical disease and the third patient had macronodular adrenocortical hyperplasia. Each of the 11 patients was cured of hypercortisolism by unilateral or bilateral adrenalectomy and no patient has developed recurrent disease during the 7 to 29 month follow-up period. New modalities including the ovine CRH test, MRI, and petrosal sinus sampling have improved the evaluation of certain patients with Cushing's syndrome.

Adolescent↗
PubMed1989

Tracheoesophageal fistula in the patient with lymphoma: case report and review of the literature.

Tracheoesophageal fistula (TEF) occurs only rarely in the patient with lymphoma. Two cases are presented to illustrate the challenges in managing TEF in this patient population. Most of the 38 previously reported cases have occurred in patients who have undergone radiation therapy, although several patients have had TEF as an initial manifestation of lymphoma. TEF is usually, but not universally, associated with the presence of active lymphoma. The surgical approach should be individualized, based on the patient's overall condition, the site and size of the fistula, and sites of disease. Often a conservative surgical approach is warranted with the expectation that many of these fistulas will close after radiation therapy or chemotherapy. Patients with lymphoma-related TEF have a better prognosis than do those with TEF caused by carcinoma of the lung or esophagus.

Adult↗
PubMed1986

Role of metabolism in effects of diflubenzuron on growth of B16 melanomas in mice.

The insect growth regulator diflubenzuron (DFB), which also inhibits growth of experimental tumors in mice, was studied to determine the influence of in vivo microsomal metabolism on its antitumor activity. DFB inhibits chitin synthesis and growth of imaginal epidermis in insects and suppresses melanogenesis and uptake of nucleosides in mouse melanoma cells, but the means of cell growth regulation and the role of metabolism of DFB in such regulation have not been established. Five daily injections of DFB (total of 4000 mg/kg) into C57BL/6 mice with B16 melanomas induced an acute 11-20% decrease in tumor volume and a 2-3 day increase in the initial tumor volume doubling time (Td), but at mid-treatment tumors regained maximum (control-like) rate of volume increase. Tumors in mice conditioned with a mixed function oxidase inhibitor (CoCl2) and treated with DFB did not decrease in mean volume, but their rate of volume increase was reduced by about 75% and the Td was increased by 4.2 days. In contrast, induction of mixed function oxidase with 3-methylcholanthrene (3-MC) or beta-napthaflavone (B-NF) enhanced the effects of DFB by a factor of 1.5 to 2.0. Therefore, aromatic hydroxylation of DFB may be required for tumor growth regulation. Three metabolites of DFB--two hydroxylated forms and a scission product, 4-chlorophenylurea (CPU), were also tested for tumor growth regulation. CPU was ineffective; a form oxidized at the 3 carbon of the phenyl ring (3-OH-DFB) was only marginally effective; but the 2-carbon form (2-OH-DFB) induced a 24% decrease in mean tumor volume and a 2.4 day increase in Td. Pretreatment with 3-MC and treatment with 2-OH-DFB also resulted in a 24% decrease in tumor volume and a 2.2 day increase in Td, but also reduced tumor volume increase to 20% between the 5th and 10th days after the initial 2-OH-DFB injection, compared to a 125% increase without 3-MC. Further, 3-MC pretreatment caused the otherwise marginally effective 3-OH-DFB to become almost as effective as 2-OH-DFB. These data support our previous report that DFB alters tumor growth and show that mixed function oxidase enhances effects of DFB, 2-OH-DFB and 3-OH-DFB.

Animals↗
PubMed1986

Blood flow to transplanted fetal rat intestine.

Avascular fetal rat intestine becomes vascularized and grows and develops certain properties of normal small intestine when transplanted into the subcutaneous tissues of host syngeneic rats. We quantified the blood flow to this transplanted intestine (called "neogut") to clarify the role of angiogenesis in its growth and development. Additionally, we correlated blood flow and the growth of neogut into either patent tubular segments or large saccular segments with associated strictures. Blood flow was studied using 141Ce or 85Sr labeled microspheres. Blood flows are expressed as mean +/- SEM in (ml/min X g). Neogut blood flow (0.19 +/- 0.02) was greater than that of adjacent subcutaneous tissue (0.03 +/- 0.00, P less than 0.01) but less than that of native small bowel (0.85 +/- 0.07, P less than 0.01). The blood flow to the large saccular segments (0.10 +/- 0.01) was less than that to the tubular portions (0.27 +/- 0.02, P less than 0.01). The weight of neogut was comparable to that of native small bowel. These findings demonstrate that neogut implants stimulate angiogenesis to a degree which may be sufficient for it to absorb nutrients. Furthermore, ischemia is present in large saccular neogut segments with associated strictures. Additional investigation appears warranted to see if neogut can serve as a clinically useful small bowel substitute.

Animals↗
PubMed1986

Differential response to gamma radiation of human stomach cancer cells in vitro.

In vitro effects of radiation were studied in two permanent cell lines (AGS and SII) from two patients with adenocarcinoma of the stomach and three permanent sublines from each cell line. Radiation survival parameters for AGS and SII parent cell lines and sublines were determined after in vitro irradiation of their cells with 0.5 to 10 Gy of 60Co gamma rays. The AGS and SII cell lines had different growth properties, DNA contents and radiation survival curves. Surviving fractions of SII parent cells (76 chromosomes) after 2.0 and 10 Gy were 1.22 and 17.8 times greater, respectively, than values for AGS parent cells (47 chromosomes). Sensitivities (D0) were 1.08 and 1.45 Gy for AGS and SII parent lines, respectively. The D0 values for AGS parent cells and sublines were similar (1.01 to 1.08 Gy), but SII parent cells and sublines had D0 values of 1.45, 1.36, 1.37 and 1.12 Gy (for SII-A). Also, the SII parent cells had survival fractions after 2.0 and 10 Gy that were 1.3 and 11.3 times greater, respectively, than values for the SII-A cells. These data show differences in radiation responses among stomach cancer cell lines and sublines that may relate to DNA content, but there was no consistent correlation between radiation response and a particular cell characteristic.

Adenocarcinoma↗
PubMed1976

Lymphocyte response in patients with head and neck cancer: effect of clinical stage and radiotherapy.

Ffty-three patients with head and neck cancer tested before radiation treatment to determine numbers of blood lymphocytes and immunologic responses to mitogens of lymphocytes in whole-blood cultures had mean values that were 19% to 26% less than values for healthy individuals. Thirty patients whose disease was in stages III or IV had values similar to those in 23 patients whose disease was in stages I or II. Values for 45 patients tested at end of radiotherapy decreased to about 50% of pretreatment values; however, patients with advanced lesions experienced greater decreases (to 24% to 50%) than patients with localized lesions (to 71% to 84%). Patients with advanced lesions usually received radiation to larger areas than patients with localized lesions; therefore, the extent of decline in laboratory values was most likely dependent on volume of tissue treated.

Concanavalin A↗
PubMed1976

A follow-up evaluation of a summer health career program for minority students.

In an effort to attract minority students to health careers, a special summer education health career experience was developed. A matched comparison group design was utilized to determine the value of this program. Data were collected on both the participants and a matched comparison group three months before and six months after the program. Differences on most of the measures were not significant; however, there was a significant difference on stability of first career choice, indicating that a special summer program can and does have an effect on the participants. The study makes it clear that program effects cannot be assumed unless a follow-up evaluation is undertaken.

Career Choice↗
PubMed1976

A formative and summative evaluation model for special educational programs.

During the past two decades the problems of recruiting minority students into careers in the health fields have been addressed by many educators and various special study groups. Recent efforts by schools of medicine and allied health sciences to find viable solutions to the problem have facilitated implementation of career exploration and study-skills programs. Although the focus and sophistication of evaluation designs vary substantially among educational programs of this type, all share some common problems. The positions taken by the authors is that evaluation, both during and at the end of a program, is an essential aspect of the program and that the use of a systematic evaluation model is central to this effort. Data are presented which illustrate the utility of a systematic evaluation model when applied in a realistic test situation (an operational program for minority students). Several advantages of using this model are discussed.

Career Choice↗