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P Grigsby

Publications and source records attributed to P Grigsby.

17 recordsLinked to original sources
PubMed2006

Prostanoid receptors in human uterine myocytes: the effect of reproductive state and stretch.

In the human, prostanoids are known to be important mediators of uterine relaxation and contraction during pregnancy and parturition. We have previously shown that stretch of uterine smooth muscle cells increased prostaglandin H synthase 2 (PGHS-2) mRNA expression, PGHS-2 peptide synthesis and activity, however, the net effect on uterine contractility of this increase in prostaglandin synthesis would be determined by the expression of the different prostanoid receptors. Therefore, the aims of this study were to establish the expression of prostanoid receptor mRNA in uterine myocytes obtained from women in different reproductive states and to test the hypothesis that stretch of uterine myocytes alters prostanoid receptor mRNA expression to promote uterine contractility. Myocytes were isolated from women undergoing hysterectomy (NP) and pregnant women undergoing LSCS either before (NL) or after the onset of labour (L) and were subjected to 11% stretch for 1 h (n = 6 in all cases). Copy numbers of the individual receptors varied widely with reproductive state but followed the pattern: FP > IP = DP = EP-4 > TP = EP-3 = EP-2 > EP-1. FP mRNA expression was significantly lower in the NL group compared to the NP group and EP-3, EP-4 and TP mRNA expression was significantly lower in both NL and L groups compared to NP group levels. The level of mRNA expression of EP-1, EP-2, DP and IP did not differ between NP, NL and L groups. Stretch of cells derived from the NP group resulted in a significant decrease in EP-4 mRNA expression alone and of the NL group a significant decrease in EP-2 mRNA expression alone. Stretch had no effect on cells derived from the L group. These data show that pregnancy is associated with a significant reduction in 3 of 4 pro-contraction associated prostanoid receptor mRNA expression and 1 of 4 pro-relaxant. Stretch elicited no consistent change in prostanoid receptor mRNA expression.

DNA Primers↗
PubMed2003

Myometrial activation and preterm labour: evidence supporting a role for the prostaglandin F receptor--a review.

An increase in the myometrial expression of the prostaglandin (PG) receptors, and especially the PGF(2alpha) receptor (FP), may be an important component of the process initiating preterm labour. In this review of the literature and presentation of new possibilities, evidence will be discussed that demonstrates an increase in mouse uterine FP mRNA occurs at preterm birth whereas uterine PGF(2alpha) concentrations do not increase, suggesting elevated uterine receptor expression and sensitivity is a mechanism for preterm labour initiation. The first examination of the complete human myometrial FP promoter will be described and evidence presented that demonstrates the pro-inflammatory cytokine, interleukin-1beta, stimulates FP mRNA expression. Finally new data showing that administration of a specific FP antagonist delays preterm birth in sheep will be presented.

Animals↗
PubMed2000

Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix.

PURPOSE: To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma. PATIENTS AND METHODS: Patients with clinical stage IA(2), IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m(2) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT. RESULTS: Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P =.003) and 1.96 (P =. 007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group. CONCLUSION: The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.

Adult↗
PubMed1998

Cost minimization analysis and utility of pretreatment and posttreatment total body iodine-131 scans in patients with thyroid carcinoma.

BACKGROUND: The purpose of this study was to evaluate the utility of posttreatment total body iodine-131 (I-131) scans. METHODS: The records of 63 consecutive patients with thyroid carcinoma treated with surgery and postoperative I-131 were reviewed. Patients underwent a postoperative diagnostic total body I-131 scan. Subsequently, patients received therapeutic administration of I-131. Posttreatment total body I-131 scans were performed. RESULTS: The postoperative diagnostic total body I-131 scans revealed uptake in the neck in all 63 patients and also demonstrated lung and mediastinal uptake in 7 patients with known sites of metastatic disease. The posttreatment total body I-131 scans also revealed neck uptake in all patients and demonstrated uptake in the lung and mediastinum in those with known metastasis to those sites. Additional foci of neck uptake were revealed on the posttreatment total body I-131 scans in six patients. Stepwise logistic regression was performed to identify prognostic factors predictive of additional foci of uptake on the posttreatment total body I-131 scans compared with the pretreatment diagnostic total body I-131 scans. Variables found to correlate significantly with additional uptake on the posttreatment total body I-131 scans were tumor size > or = 2 cm, follicular histology, and multifocal disease. CONCLUSIONS: Posttreatment total body I-131 scans yielded additional information in only 10% (6 of 63) of the study patient population treated with postoperative I-131 for thyroid carcinoma. Therefore, the cost, and the associated inconvenience to the patient, of performing a posttreatment total body I-131 scan can be eliminated for most patients.

Adolescent↗
PubMed1997

Cost-utility analysis of a malignant glioma protocol.

PURPOSE: To perform a cost-utility analysis utilizing a cooperative group protocol and constrasting the results with the published quality adjusted survival. METHODS AND MATERIALS: A cost-utility analysis was performed on Radiation Therapy Oncology Group (RTOG) protocol 83-02. The quality-adjusted survival has been published previously. Pretreatment tests and chemotherapy costs are not considered, as these were similar across all treatment arms. Payor costs are calculated from Federal Register data for Medicare Region IV. Global charges are used to calculate the professional and technical charges. Costs are measured in relative value units (RVUs) and are tabulated assuming equal treatment complexity for all treatment arms. RESULTS: The number of RVUs calculated for each arm were 48 Gy--166.65; 54.4 Gy--182.17; 64.8 Gy--232.53; 72.0 Gy--272.19; 76.8 Gy--287.11; and 81.6 Gy--302.63. The RVU/QALY for the <50-year-old group were 48 Gy--119.03; 54.4 Gy--100.65; 64.8 Gy--104.78; 72.0 Gy--90.73; 76.8 Gy--193.99; and 81.6 Gy--165.37. The RVU/QALY for the >50-year-old group were 48 Gy--198.39; 54.4 Gy--276.85; 64.8 Gy--426.57; 72.0 Gy--423.71; 76.8 Gy--703.70; and 81.6 Gy--519.10. Sensitivity analysis of one treatment plan, simulation, and set of blocks for the 48 Gy and 54.4 Gy arms decreased the RVU/QALY to 105.34 and 90.05, respectively. DISCUSSION: Our analyses shows the experimental arm with the lowest RVU/QALY is also the arm with the longest quality-adjusted survival. This arm had the most efficient use of resources in this protocol. Prospective collection of all pertinent cost data is required for comparison of one treatment against another. All cooperative group protocols should have prospective quality of life and economic endpoints to allow for comparison of the most cost efficient treatment method.

Brain Neoplasms↗
PubMed1996

Phase III study of interstitial thermoradiotherapy compared with interstitial radiotherapy alone in the treatment of recurrent or persistent human tumors. A prospectively controlled randomized study by the Radiation Therapy Group.

PURPOSE: The objectives of this randomized trial were to determine if interstitial thermoradiotherapy (ITRT) improves tumor regression/control in accessible lesions in comparison with interstitial radiotherapy (IRT) alone and to assess the skin and soft tissue complications with either modality. METHODS AND MATERIALS: From January 1986 to June 1992, 184 patients with persistent or recurrent tumors after previous radiotherapy and/or surgery, which were amenable to interstitial radiotherapy, were accessioned to a protocol developed by the Radiation Therapy Oncology Group (RTOG). One hundred seventy-three cases were analyzed (87 patients in the IRT group and 86 in the ITRT arm). The two arms were well balanced regarding stratification criteria. Most tumors were in the head and neck (40% in the IRT group and 46% in the ITRT group), and pelvis (42% and 43%, respectively). Eighty-four percent of patients in both arms had prior radiation therapy (> or = 40 Gy); 50% and 40%, respectively, had prior surgery, and 34% in each arm had prior chemotherapy. The dose of radiation therapy administered was dependent on the previous radiation dose and did not exceed a total cumulative dose of 100 Gy. Hyperthermia was delivered in one or two sessions, either before or before and after interstitial implant. The intended goal of the hyperthermia was to maintain a minimal tumor temperature of 42.5 degrees C for 30 to 60 min. RESULTS: There was no difference in any of the study end points between the two arms. Complete response (CR) was 53% and 55% in both arms. Two-year survival was 34% and 35%, respectively. Complete response rate for persistent lesions was 69% and 63% in the two treatment arms as compared with 40% and 48% for recurrent lesions. A set of minimal adequacy criteria for the delivery of hyperthermia was developed. When these criteria were applied, only one patient had an adequate hyperthermia session. Acute Grade 3 and 4 toxicities were 12% for IRT and 22 % for ITRT. Late Grade 3 and 4 toxicities were 15% for IRT and 20% for ITRT. The difference was not significant. CONCLUSIONS: Interstitial hyperthermia, as applied in this randomized study, did not show any additional beneficial effects over interstitial radiotherapy alone. Delivery of hyperthermia remains a major obstacle (since only one patient met the basic minimum adequacy criteria as defined in this study). The benefit of hyperthermia in addition to radiation therapy still remains to be proven in properly randomized prospective clinical trials after substantial technical improvements in heat delivery and dosimetry are achieved.

Adult↗
PubMed1993

On-line image verification in radiation therapy: an early USA experience.

The intense effort in the past 5 to 10 years to develop on-line image verification (OLIV) systems is made partly in anticipation of the increased verification demands of complex 3-dimensional (3D) conformal radiation therapy, and partly to improve on the current practice of weekly treatment verification. These systems allow convenient acquisition of daily portal images or many images during one treatment session. Systems based on fluoroscopic and scanning approaches can now be purchased from various vendors and are being evaluated at several radiation therapy centers. The performances of these systems vary, but all appear to be adequate for clinical use. At the Mallinckrodt Institute of Radiology, we have been conducting clinical on-line imaging for the past 3 years using a fiber-optic fluoroscopic system. Daily operation of the system requires coordinated participation of the physics and radiation therapy technology staff. The major consideration is in the management and evaluation of the large amount of verification images about each individual patient. At present, it is not clear whether the technology would be cost-effective in the clinical setting. However, it is clear that OLIV provides a powerful tool in enhancing our knowledge of treatment variation. The information will be invaluable in the development of improved treatment techniques. It is also likely that these systems will play a important part in the verification of 3D conformal radiation therapy.

Calibration↗
PubMed1992

Design and implementation of a microcomputer-based tutorial in radiation oncology.

The design and implementation of a computer-based training system for radiation oncology was undertaken. A frame-based system was chosen, with factual information from Principles and Practices of Radiation Oncology, by Perez and Brady, as the body of knowledge. Each unit of the system was based on a site (chapter) and consists of three sections: text, review questions, and patient management problems. The text section contains text, tables, and references and defines the information upon which the review questions and clinical cases are based. The review questions are multiple choice and true-false, and immediate feedback is given for both correct and incorrect responses. The patient management problems are interactive and provide alternative methods of presenting information and stimulating problem-oriented thought. The emphasis in all sections is on learning rather than testing. Advantages of a computer-based tutorial include the ability to present large volumes of information easily, the capacity for immediate feedback, and the flexibility of format in presentation of material. Potential applications are discussed.

Computer-Assisted Instruction↗
PubMed1990

The costs of low dose rate remote afterloading compared to manual afterloading brachytherapy.

A relatively recent development in the United States in brachytherapy technology is the use of equipment to remotely afterload radioactive sources into the patient applicators. This technique competes with past practices where the source was placed by hand. With remote afterloading, the sources are automatically removed from the patient and placed into a lead safe whenever healthcare personnel enter the patient's room. The primary benefit of remote afterloading brachytherapy is to reduce the radiation exposure to the patient's visitors and healthcare providers. By comparing the operating and maintenance costs for remote afterloading brachytherapy (RAL) and manual afterloading (MAL) for patients receiving conventional low dose rate brachytherapy from interstitial and intracavitary implants, estimates of the prospective cost of this increased safety can be offered.

Brachytherapy↗
PubMed1989

Phase II study of multiple daily fractionations in the palliation of advanced pelvic malignancies: preliminary report of RTOG 8502.

This Phase II protocol was designed around the format of a previously reported study for the palliation of advanced pelvic malignancies (RTOG 7905). The large dose per fraction (1000 cGy) of the first study unexpectedly demonstrated frequent late gastrointestinal toxicity and was replaced in the present study by 2 days of twice daily fractionation (370 cGy/fraction totaling 1480 cGy/course) based on linear quadratic consideration of acute and late toxicities. The interval between courses of 4 weeks was retained and the total dose for three courses was 4440 cGy. A total of 152 patients were entered of which 142 have sufficient follow-up information for analysis. Fifty-nine percent of the patients completed all three courses, 20% completed two courses, and 20% received only one course. The primary sites were: gynecological (39.4%); colorectal (32.4%); genitourinary (24.7%); and other (2.8%). The best overall response was: complete remission (10%); partial remission (22%); no change (24%); progression (10%); and unknown (27%). For the patients completing all three courses, the response was: complete remission (14%); partial remission (31%); no change (40%); progression (7%); and unknown (8%). Median survival was 4.5 months and the actuarial survival at 12 months is 19%. In RTOG 7905, 90% of the late toxicities appeared by 12 months. For RTOG 8502, there were 32 patients alive at 9 months and 19 patients alive at 12 months available for evaluation of late toxicity. There has been one late grade 3 GI toxicity reported and only one acute grade 3 gastrointestinal toxicity. Even if the true rate of late toxicity for 8502 were 20%, the chance of seeing none or one toxicity would be 0.007. This toxicity report represents a marked reduction of the grade 3 and 4 late toxicity seen in RTOG 7905 (37% at 9 months and 45% at 12 months) without lowering the tumor response rate. The interval between courses in both protocols allows for potential tumor proliferation. To test for the effect of tumor proliferation, RTOG 8502 is continuing as a Phase III randomization between 4 weeks and 2 weeks separation.

Adult↗
PubMed1987

Hepatic adenoma within a spindle cell carcinoma in a woman with a long history of oral contraceptives.

The case of a young woman is presented who had a long history of oral contraceptive use and who was found to have a focal hepatic adenoma within a large spindle cell carcinoma of the liver. The pleomorphic tumor is positive for keratin and alpha 1-antitrypsin by immunohistochemistry, has intracellular lumina by electron microscopy, a moderately high thymidine labeling index, and is negative for estrogen and progesterone receptors. A review of the literature concerning liver tumors occurring in young patients indicates that there is an underlying disturbance of the hormonal milieu in all instances reported. The prognosis is widely variable and unpredictable.

Adult↗
PubMed1982

Toxicity and radiation protective effect of WR-77913 in BALB/c mice.

The toxicity and radiation protective effect obtained by intraperitoneal injection of WR-77913 have been investigated in BALB/c mice. The toxic LD50/30 was 3574 mg/kg. When WR-77913 was given 30 min before whole body irradiation adequate protection was observed against bone marrow and gut death. Dose modifying factors of 1.91 and 1.76 for bone marrow and 1.95 and 1.80 for gut death were obtained with drug doses roughly equivalent to one half and one quarter of the maximum tolerable doses (MTD). No protective effect was observed against central nervous system injury. Preliminary experiments with the EMT6 tumor show limited tumor protection with a dose of WR-77913 equivalent to 70 per cent of the MTD. Because of its low toxicity, adequate bone marrow and gut protection at doses equivalent to one quarter MTD and limited protection of the EMT6 tumor, WR-77913 deserves further investigation to determine its value in multiple drug dose regimens and its capability to protect other normal tissues.

Amifostine↗
PubMed1981

Modification of the oral radiation death syndrome with combined WR-2721 and misonidazole.

In order to investigate the combined use of radioprotective and radiosensitizing chemicals we have used WR--2721 and misonidazole to study their combined chemical toxicity and radiomodifying effects in our model using the oral radiation death (ORD) syndrome as the endpoint. Our data demonstrate that WR-2721 does protect against the ORD syndrome. Misonidazole does not protect against the ORD syndrome. Misonidazole does not sensitize the normal oral cavity to local irradiation. WR-2721 and misonidazole produce additive toxicity when injected simultaneously and the combination can provide an overall protective response to the ORD syndrome. We conclude that the combination may be potentially useful for the treatment of cancers of the oral cavity.

Amifostine↗
PubMedDate not supplied

Sodium hydrogen-S-(3-amino-2-hydroxypropyl) phosphorothioate (WR-77913): toxicity and bone marrow radioprotection.

Experiments have been carried out to compare the toxicity and radioprotective effect of sodium hydrogen-S-(3-amino-2-hydroxypropyl) phosphorothioate (WR-77913) with those of S-2-(3-aminopropylamino)ethyl phosphorothioic acid (WR-2721). The drugs were given intraperitoneally to 12 week-old female BALB/c mice 30 minutes before whole body irradiation. Lethality at 30 days was the endpoint used. The drug LD50/30 was 678 mg/kg for WR-2721 and 3574 mg/kg for WR-77913. The LD50/30 for WR-77913 combined with 500 mg/kg of WR-2721 was 3328 mg/kg. The LD50/30 for misonidazole was 380 mg/kg when given in combination with 500 mg/kg of WR-2721 and 801 mg/kg when combined with 2200 mg/kg of WR-77913. Protection of bone marrow by WR-77913 and WR-2721 was comparable at doses close to the maximum tolerable dose (MTD, drug dose lethal to 10% of the animals at 30 days), but WR-77913 gave better protection at 35% of the MTD. These characteristics of low toxicity, non-additive toxicity with WR-2721, less toxicity in combination with misonidazole and adequate bone marrow protection at 25% of the MTD, make WR-77913 a protector worthy of further investigation.

Amifostine↗
PubMedDate not supplied

Combined radiosensitization and radioprotection for oral cavity tumors: study with an oral cavity tumor model.

Adjuvant therapy with combined radioprotectors and radiosensitizers has not been extensively examined. We investigated the use of combined S-2-(3-aminopropylamino) ethylphosphorothioic acid (WR-2721), misonidazole (Ro-07-0582) and single dose radiotherapy in treating the EMT 6/Ky tumor implanted in the buccal mucosa of Balb/c mice. Our results demonstrate that single dose irradiation plus WR-2721 or misonidazole prolonged the mean survival time (MST) of EMT 6/Ky bearing Balb/c mice significantly compared to either controls or single dose irradiation plus WR-2721 and misonidazole.

Amifostine↗