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Biomedical subjects

I R Crocker

Publications and source records attributed to I R Crocker.

29 records · Page 2Linked to original sources
PubMed1995

Intracoronary radiation before stent implantation inhibits neointima formation in stented porcine coronary arteries.

BACKGROUND: Stent implantation has been shown to reduce restenosis by establishing a larger lumen but not by reducing neointima formation. We have previously shown that ionizing radiation reduced neointima formation after balloon injury in a swine model of restenosis. The purpose of this study was to determine whether endovascular irradiation of the coronary artery before stent implantation would affect neointima formation. METHODS AND RESULTS: Nine normolipemic pigs underwent coronary angiography, and segments of the left anterior descending and left circumflex arteries were chosen as targets for stenting. A high-activity 192Ir source was used to deliver 14 Gy by random assignment to one of the vessels. After this, 3.5-mm tantalum stents were implanted in both arteries. Three additional pigs were treated with a 90Sr/Y source (a pure beta-emitter) delivering 14 Gy to five segments of coronary vessels that were stented immediately after irradiation. Stent-to-artery ratio was similar in the radiated and the control arteries. Animals received aspirin 325 mg daily and were killed at 28 days. The intimal area was significantly reduced in the irradiated stented arteries compared with control arteries treated with stent only (1.98 mm2 with 192Ir and 2.53 mm2 with 90Sr/Y versus 3.82 mm2 in the control stented arteries, P < .005). CONCLUSIONS: Endovascular radiation before coronary stenting reduces neointima formation and may further reduce the restenosis rate after stent implantation.

Animals↗
PubMed1995

Endovascular low-dose irradiation inhibits neointima formation after coronary artery balloon injury in swine. A possible role for radiation therapy in restenosis prevention.

BACKGROUND: Restenosis after percutaneous transluminal coronary angioplasty remains a major limitation of the long-term success of this procedure. Restenosis is a form of wound healing. Low-dose ionizing radiation has been effective in inhibiting exuberant wound healing responses in a variety of clinical situations. METHODS AND RESULTS: Vascular neointimal lesions resembling human restenosis were created in the coronary arteries of normal pigs by overstretch balloon angioplasty injury. To test the effect of low-dose endovascular gamma radiation on lesion formation, a high-activity 192Ir source was introduced into one of the injured arteries in each animal and left in place for a period sufficient to deliver one of three doses: 350, 700, or 1400 cGy. To test potential benefits of delayed irradiation, 700 cGy was given in another group 2 days after injury. Animals were killed 14 days after balloon injury and the coronary vasculature was pressure-perfusion fixed. To test the late effect and safety of endovascular low-dose irradiation, 700 or 1400 cGy was given in miniswine coronary arteries after injury as well as in noninjured carotid arteries; this group was followed up for 6 months. Tissue sections were measured by computer-assisted planimetry. All arteries treated with radiation demonstrated significantly decreased neointima formation compared with control arteries. The ratio of intimal area-to-medial fracture length (IA/FL) was inversely correlated with the different radiation doses: control, 0.59; 350 cGy, 0.38; 700 cGy, 0.42; and 1400 cGy, 0.17 (r = -0.75, P < .0001). Delay of 700-cGy irradiation for 2 days after injury significantly decreased neointima formation compared with the same dose given immediately after injury. Analysis of long-term specimens showed reduction of IA/FL in the arteries irradiated with 700 cGy (0.3, P = .009) and 1400 cGy (0.31, P = .001) compared with control arteries (0.50). There was no excess fibrosis in the media, adventitia, or perivascular space of the coronary arteries or adjacent myocardium in pigs that received radiation compared with control animals. CONCLUSIONS: Low-dose intracoronary irradiation delivered to the site of coronary arterial overstretch balloon injury in pigs inhibited subsequent intimal thickening (hyperplasia). A dose-response relationship was demonstrated, and delay of treatment for 48 hours appeared to augment the inhibitory effect. Six months of follow-up without fibrosis or arteriosclerosis demonstrated the durability of the beneficial effect in the treated group. These data suggest that intracoronary irradiation therapy may aid in preventing clinical restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1995

Conservative treatment of early-stage breast cancer in a medically indigent population.

The compliance with a program of breast-conservation treatment for early-stage breast cancer and the results of that treatment among women treated between January 1983 and January 1992 was investigated in a large inner-city public hospital serving a primarily black population. Medical records and charts were reviewed for 25 consecutive patients with stage I and II breast cancer seen in consultation in the radiation oncology department. Of those 25 patients, 20 underwent lumpectomy and radiation therapy. Survival, disease-free survival, and local recurrence-free survival were computed using the Kaplan-Meier method. Compliance was evaluated based on time to complete the prescribed course of radiotherapy after a lumpectomy. Five-year local recurrence-free survival for stage I and II patients was 95% (confidence interval [CI]: 71% to 99%). Five-year overall survival for stage II patients was 71% (CI: 31% to 92%), and disease-free survival was 74% (CI: 36% to 91%). This study demonstrates that a program of breast-conservation treatment for early-stage breast cancer can be implemented with good results, excellent treatment compliance, and 100% follow-up in a population of medically indigent women.

Adult↗
PubMed1992

An adjustable collimator for stereotactic radiosurgery.

Stereotactic radiosurgery utilizing a linear accelerator is now carried out using small non-coplanar beams to produce a high-dose volume that is approximately spherical in shape. It is desirable to shape the high-dose region so that it is similar to the target volume thereby reducing the amount of healthy tissue irradiated by a high dose. An adjustable collimator has been developed that can be employed to control the target volume height and diameter. Based on film dosimetry and measurements made with a small parallel-plate ionization chamber it was determined that the beams produced by the collimator have properties that make them suitable for radiosurgery. The basic dosimetry parameters (output factors and tissue maximum ratios, TMR) needed for patient treatment were evaluated. It was found that the diameter and length of the high-dose region produced by the patient rotation method are related to the light-field size at 100 cm from the x-ray target. A more favourable dose distribution was found for the adjustable collimator as compared to treating the same volume by use of the two-target method.

Humans↗
PubMed1990

A patient rotator for stereotactic radiosurgery.

A new technique for stereotactic radiosurgery by use of a patient rotator is described. Using the rotator with a small collimated beam of 6 MV x-rays, a small well-defined region of the brain can be irradiated to a high dose with rapid fall off of the dose outside the target volume. Since the linear accelerator gantry does not move during therapy the possibility of a collision between the gantry and the patient or stereotactic equipment is eliminated. The system is also independent of the rotational stability of the linear accelerator gantry axis and turntable axis. Dose distributions measured in a Lucite head phantom with film exhibited properties well suited for radiotherapy. Tests carried out to evaluate the ability to irradiate a selected target point within the brain with the rotator system showed a maximum positional error of 1.0 and 2.0 mm for angiography and CT localisation respectively.

Brain Diseases↗
PubMed1990

Transforming growth factor-beta 1 expression in irradiated liver.

The expression of transforming growth factor-beta 1 (TGF-beta 1) in the liver of irradiated rats was increased in a dose-dependent fashion 9 months after irradiation. Expression of TGF-beta 1 was confined primarily to hepatocytes in the pericentral region of the liver, and the percentage of hepatocytes strongly positive for TGF-beta 1 was significantly correlated with the extent of fibrosis. We further showed that a localized injection of TGF-beta 1 into normal rat liver elicited a strong fibrotic reaction at the injection site. These results suggest that the increased hepatic concentration of TGF-beta 1 in response to radiation injury may be important in the pathogenesis of radiation hepatitis. TGF-beta 1 was also found to be present at a significantly higher concentration in unirradiated human hepatocytes than in normal rat hepatocytes, implying that the propensity for humans to develop radiation hepatitis may result in part from the elevated levels of TGF-beta 1 normally found in human liver.

Animals↗
PubMed1987

A prospective study of squamous head and neck carcinoma. Immunologic aberrations in patients who develop recurrent disease.

In a prospective study of squamous head and neck cancer, the pretreatment peripheral blood of 125 patients was examined for lymphocyte subclass and in vitro immunologic function. After 4 years of follow-up, 49 recurrences of disease were observed. Lymphocytes from patients with recurrent disease showed elevated interleukin-2 (IL-2) production and a tendency towards increased response to mitogens in comparison to those without recurrence. When disease-free survival is analyzed on the basis of IL-2 levels, patients with high relative IL-2 synthesis (greater than or equal to 1) had a 40% poorer prognosis than patients with low relative IL-2 levels (less than 1). The difference is significant at a P value of 0.02. Since IL-2 synthesis occurs with antigenic stimulation, it is postulated that patients who have a high IL-2 synthesis in their pretreatment lymphocytes may have had prior stimulation by circulating tumor antigen. Such immune response by the host may be successful in destroying the antigenic tumor cells but may leave the undifferentiated, less antigenic tumor cells to grow and metastasize. Thus, elevated IL-2 synthesis in pretreatment lymphocytes predicts a poorer prognosis.

Carcinoma, Squamous Cell↗
PubMed1987

Early results with combined modality therapy for carcinoma of the esophagus.

Since January 1984, 74 patients (61 men, 13 women; age range: 43-76 years) with carcinoma of the esophagus were evaluated. Fifty-two patients had squamous cell carcinoma and 22 patients had adenocarcinoma. Sixty-three patients had preoperative chemotherapy and radiation that consisted of cis-platinum and VP-16 for squamous cell carcinoma and cis-platinum 5-FU for adenocarcinoma combined with 4500-6000 rads. Thirty-four patients were staged inoperable at the completion of the 4-month treatment regimen. Eleven patients had surgery alone because they refused or were not candidates for the preoperative regimen. Twenty-nine patients completed the combined modality regimen and have had esophagogastrostomy. All patients receiving chemotherapy and radiation demonstrated improved swallowing and a dramatic reduction of tumor mass early in the course of therapy and have been able to maintain oral nutrition without other support in the posttreatment period. Of the 34 patients who had chemotherapy and radiation therapy as palliation, 18 are currently living. One patient died secondary to complications of chemotherapy, another patient died at 9 months of myocardial infarction. The remaining patients died secondary to their disease. Of the 29 patients who had radiation therapy and chemotherapy plus esophagogastrostomy, 25 are alive. There were no operative deaths. One patient died at 9 months of stroke. Three other patients had recurrence and died 1 year after surgery. Of the 11 patients who had surgery alone, two have died of the disease. Of the 29 patients who completed the integrated therapy, 10 had no evidence of residual tumor in the specimen, and in an additional five patients only microscopic foci were evident. These early results are an encouragement to continue the multidiscipline approach to carcinoma of the esophagus in the hope that the quality of life and disease-free interval, as well as ultimate survival, will be enhanced.

Adenocarcinoma↗
PubMed1986

Primary cutaneous lymphoma of the head and neck.

One hundred three patients with Stage I and II extranodal primary lymphomas of the head and neck were reviewed. Six patients (5%) presented with cutaneous lesions, five with single site and one with multiple sites of involvement. Histopathology was malignant lymphoma (ML) large cell (3), ML small cleaved cell (1), ML small lymphocytic (1), and ML mixed large and small cell (1). Five of six patients relapsed following initial treatment. Four patients were treated with primary radiation therapy, three of which had relapses outside the treatment area. One patient was treated with intralesional steroid injection and also recurred outside the treated area. One patient was treated with radiation and chemotherapy and recurred outside the treatment area. Three patients are alive without disease, two died of disseminated disease, and one died of unrelated causes. Isolated cutaneous presentation of head and neck lymphoma is uncommon. Radiation therapy appears to have been curative in one patient with localized disease. Four patients recurred outside the radiation portals despite careful staging, suggesting that systemic therapy may be necessary for disease control.

Aged↗
PubMed1985

Radiation protection of rat parenchymal hepatocytes with S-2-(3-aminopropylamino)ethylphosphorothioic acid.

The ability to protect parenchymal hepatocytes from ionizing radiation damage with S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR-2721) was investigated. The clonogenic survival of irradiated hepatocytes was determined with an in vivo transplantation assay system. Injection of WR-2721 (400 mg/kg) immediately after irradiation was without protective effect. In contrast, an intraperitoneal (IP) injection of WR-2721 30 min prior to 60Co irradiation resulted in a significant protection of parenchymal hepatocytes. The mean lethal dose (Do) and extrapolation number (n) of the survival curve for unprotected hepatocytes as 2.9 Gy and 1.8, respectively. The Do and n values for hepatocytes protected with WR-2721 were 5.7 Gy and 1.8, respectively. Thus, WR-2721 at a concentration of 400 mg/kg acted as a dose modifying agent with a dose modifying factor of approximately 2.0. Decreasing the concentration of WR-2721 to 200 mg/kg did not significantly reduce the radioprotective effectiveness of the drug. However, at concentrations less than 200 mg/kg, the radioprotective effect decreased in a dose-response manner with a concentration of 150 mg/kg providing 50% of the maximum effect observed.

Amifostine↗