Biomedical subjects

C R Freeman

Publications and source records attributed to C R Freeman.

At least 55 records · Page 3Linked to original sources

PubMed1988

Prognostic criteria for experimental protocols in pediatric brainstem gliomas.

Prognostic criteria were developed to select children with high-risk brainstem gliomas for experimental treatment with hyperfractionated radiation. Patients were required to have (a) tumors confined primarily to the brainstem; (b) positive findings in two of three groups of neurologic signs (cranial nerve deficits and long-tract and cerebellar signs), and (c) symptom duration of less than 6 months. The 18-month survival of only 1 of 33 evaluable patients suggests that these criteria did in fact select tumors of poor prognosis. Such noninvasive predictors provide a valuable means of selecting for experimental treatment those children who would not be expected to benefit from standard therapies for malignant brainstem tumors. These criteria do not require routine biopsy for prognostic purposes, and avoid exposing the children to unnecessary risk.

Adolescent↗

PubMed1988

Hyperfractionated radiotherapy in brain stem tumors: results of a Pediatric Oncology Group study.

Between September 1984 and January 1986, 38 patients were entered onto the first phase of a Pediatric Oncology Group study designed to test the feasibility of treating children with brain stem tumors with hyperfractioned (twice daily) radiotherapy, to assess the early and late morbidity and efficacy of such treatment, and to test the feasibility of dose escalation in this group of patients. Of the 34 patients considered eligible after neuroradiology review, two did not complete planned radiotherapy because of progressive disease; both died of disease at 4 weeks and 9 months following initiation of treatment. The remainder were treated with 1.1 Gy twice daily, with an interval of 4 to 6 hours, to a total dose of 66 Gy in 60 fractions over 6 weeks. The majority of patients (24/34, 71%) improved clinically during the course of treatment; two remained stable, seven deteriorated, and for one the clinical response was unknown. By CT scan and/or MRI, no patient showed complete regression of disease; five showed a partial response to treatment, twenty fell into a stable disease category, eight patients developed progressive disease by the time of their first follow-up radiologic examination, and one patient was not evaluable for response, having been lost to follow-up immediately after completion of treatment. All five patients who achieved partial response and 17/20 patients in the stable, disease category subsequently progressed, after a median interval of 6.5 months. The median survival time was 11 months and survival at 1 year was 48% (SE 0.08). Morbidity of treatment consisted of an enhanced skin reaction in three patients, otitis media and/or externa in nine, and complications related to steroid intake in four, including diabetic ketoacidosis (two patients), Pneumocystis pneumonia (one patient), and disseminated varicella (one patient). Protracted use of steroids in 13 patients was associated in all instances with non responding or progressive disease. No patient developed signs or symptoms suggestive of CNS damage, and tissue obtained by biopsy at the time of progression in three patients and at autopsy in five failed to demonstrate any evidence of injury attributable to the radiotherapy. A dose escalation to 70.2 Gy in 60 fractions over 6 weeks was implemented as planned.

Adolescent↗

PubMed1988

Distribution of pulmonary vascular resistance in experimental fibrosis.

To elucidate mechanisms of pulmonary hypertension in interstitial fibrosis, we compared the left lower lobes (LLL) of six dogs in which fibrosis was induced by radiation and bleomycin with the normal right lower lobes (RLL) for 1) slope and intercept of the vascular pressure-flow (P-Q) curves, 2) segmental resistances with arterial and venous occlusion under base-line conditions, after serotonin and vasodilators, and 3) light-microscopic morphology and morphometry. We found that 1) the total volume and vascular compliance of the fibrotic LLL were five and four times less, respectively, than controls, 2) the slope and intercept of the P-Q curves in the LLL were 154.0 +/- 65.8 (SE) mmHg.l-1.min-1 and 8.2 +/- 1.5 mmHg, respectively, compared with 18.3 +/- 2.3 and 3.2 +/- 0.9 for the RLL, 3) the resistance of the arterial, middle, and venous segments in the LLL were higher than in the RLL, but middle segment resistance rose disproportionately, and 4) constriction of the arterial segment with serotonin was similar in LLL and RLL, and vasodilators were ineffective. Histologically, fibrosis involved 36% of the lung, and the capillary bed was severely obliterated. Arteries showed an increased percentage of medial and intimal thickening and peripheral muscularization; venous abnormalities were less marked. We conclude that pulmonary fibrosis increases vascular resistance mainly in the middle segment, largely by loss of tissue and obliteration of the microvasculature.

Animals↗

PubMed1987

Maturation of cerebellar neuroblastoma into ganglioneuroma with melanosis. A histologic, immunocytochemical, and ultrastructural study.

A ganglioneuroma with areas of melanosis was resected from the cerebellum of a 6.5-year-old girl. At 2.5 years of age, she was diagnosed to have cerebellar neuroblastoma, which was incompletely resected and then radiated. Histologic, ultrastructural, and immunocytochemical studies undertaken on tissue from both stages of the tumor demonstrated a neuroblastic origin and differentiation into a predominantly neuronal tumor with limited astroglial participation. In addition, widespread deposition of basal lamina material, perineuronal distribution of S-100 protein-bearing cells and melanosis were found. The various features and unusual biology of the tumor are discussed in the light of a review of the literature.

Cerebellar Neoplasms↗

PubMed1987

Hodgkin's disease following Wilms' tumor: a case report.

A patient is described who developed Hodgkin's disease 16 years after treatment of Wilms' tumor with radiation and actinomycin D. The issues relating to Hodgkin's disease as a second malignancy are reviewed. The need for long-term surveillance of patients with malignant disease for late effects of the cancer and its treatment is emphasized.

Adolescent↗

PubMed1986

Primary malignant lymphoma of the central nervous system.

Between 1960 and 1983, 19 patients with primary malignant lymphoma of the central nervous system (CNS) were seen at McGill University Hospitals. The diagnosis was made at autopsy in 3 patients, and by biopsy in 16. Results of treatment were poor. All four patient who underwent surgery alone died within 2 months of diagnosis. Of 12 patients who underwent surgery and postoperative radiotherapy, 11 died between 2 and 56 months (median, 12 months) following diagnosis, and one is alive with disease at 47 months. Patterns of involvement at first recurrence and/or at autopsy were analyzed for 13 patients. Failure at the original site of involvement was unusual after treatment consisting of surgery and radiotherapy. In contrast, failure in the brain at sites other than those originally involved was common in spite of the use of whole brain irradiation. Local leptomeningeal involvement was seen in one patient whose diagnosis was made at autopsy, and cerebral spinal fluid seeding was seen in two additional patients, one within 1 month of diagnosis and one at relapse at 6 months after diagnosis. No patient developed disease outside the CNS. The limitations of current therapy for this disease are discussed, and certain suggestions made regarding the management of future patients with this diagnosis.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Prophylaxis against radiation injury. The use of elemental diet prior to and during radiotherapy for invasive bladder cancer and in early postoperative feeding following radical cystectomy and ileal conduit.

Previous studies done in animals have shown that significant prophylaxis against radiation injury could be afforded by feeding an elemental diet (ED) for three days before and during radiation. In the present study 20 patients were fed an ED for three days before and for the four days during radiotherapy (five fractions of 400 rad [4 Gy] each) prior to radical cystectomy and ileal conduit for invasive bladder cancer; ED feeding was recommenced 24 hours postoperatively via a feeding jejunostomy. The ED-fed patients exhibited positive nitrogen balance preoperatively and had an early return to positive nitrogen balance postoperatively (3.60 +/- 0.32 days). There was also prompt return of bowel sounds (3.00 +/- 0.32 days). Histologically and ultrastructurally, biopsy specimens of the ileal mucosa showed normal morphologic findings, with maintenance of normal levels of enzyme activity in the brush border. Severe or bloody diarrhea was absent in these patients. These data suggest that ED feeding provides prophylaxis against the acute phase of radiation injury in patients undergoing high-dose, short-course radiotherapy for invasive bladder cancer and that it is a safe and feasible means of postoperative nutritional support, even in the presence of a fresh bowel anastomosis.

Aged↗

PubMed1986

Brain stem tumors in children: results of a survey of 62 patients treated with radiotherapy.

A survey was conducted by the Radiation Oncology Discipline Committee of the Pediatric Oncology Group to provide an estimate of the outcome of treatment with modern radiotherapy of brain stem tumors in children. Thirteen of thirty-eight institutions submitted data for 62 patients who had been diagnosed between 1972 and 1981, who had completed planned treatment with radiotherapy, and for whom follow-up information was available. The results were poor. Fourteen patients were alive with no evidence of recurrence between 11 and 154 (median 50.5) months post-treatment, two were alive with disease at 22 and 24 months, and forty-six died of disease at intervals ranging from 2 to 30 (median 8.7) months from initiation of treatment. Actuarial survival was 50% at 1 year, 29% at 2 years, and 23% at 5 years. The age of the patient, the surgical approach, and the volume and dose of radiotherapy all appeared to correlate with outcome on univariate analysis; but on multivariate analysis a statistically significant survival advantage was found only for patients greater than 5 years of age who had undergone surgery as part of their treatment. Possible explanations for these findings are discussed, and the roles of surgery, radiotherapy, and chemotherapy are reviewed.

Adolescent↗

PubMed1985

Elemental diet as prophylaxis against radiation injury. Histological and ultrastructural studies.

We investigated whether elemental diet feeding would protect the intestine from radiation injury. Five dogs were fed an elemental diet for three days before receiving pelvic irradiation (500 rad/day for four days) and were maintained on the diet during the days of irradiation. These dogs were compared with five dogs that were fed normal kennel ration, but were treated similarly otherwise. One day and five days following completion of the radiation treatment, the dogs were anesthetized and a biopsy specimen of terminal ileum was taken for histologic and electron microscopic studies. In the dogs fed the elemental diet, there was no significant damage to the intestine seen on histological examination, and electron microscopy disclosed elongated microvilli and no organelle damage. However, both histological and electron microscopic examination of the intestine from dogs maintained on normal kennel ration showed that severe damage had occurred from the irradiation procedure. It seems, therefore, that the feeding of an elemental diet to dogs as a prophylaxis can afford protection to the intestine from the acute phase of radiation injury.

Animals↗

PubMed1985

Interstitial pneumonitis following total body irradiation for bone marrow transplantation using two different dose rates.

A total of 22 patients with leukemia (10 ALL, 11 AML, 1 CML) have undergone allogeneic bone marrow transplantation (BMT) by the Quebec Co-operative Group for Marrow Transplantation from 1980 to 1982. All patients received 900 cGy total body irradiation (TBI), in a single fraction, on the day preceding BMT. The first 11 patients were treated on a cobalt unit at a constant dose rate of 4.7 to 6.3 cGy/min. Six of these patients developed interstitial pneumonitis (IP). The clinical course of three patients, two with idiopathic and one with drug-induced pneumonitis, was mild and recovery was complete in all. The other three patients developed severe infectious IP and two died. The next 11 patients were treated with a sweeping beam technique on a 4 MV linear accelerator delivering a total tumor dose of 900 cGy at an average dose rate of 6.0 to 6.5 cGy/min but an instantaneous dose rate of 21.0 to 23.5 cGy/min. Eight patients developed severe IP. Five of these were idiopathic and four died. Three were infectious and all died. The fatality of interstitial pneumonitis appeared to be greater in the group treated with the sweeping beam technique.

Adolescent↗

PubMed1985

Growth and development of long-term survivors of childhood acute lymphoblastic leukemia treated with and without prophylactic radiation of the central nervous system.

Two groups of patients with at least four years of remission following treatment of acute lymphoblastic leukemia with or without prophylactic cranial irradiation (mean interval of 8 years from diagnosis) were studied. Out of 41 eligible patients, 22 patients were assessed for pubertal staging, growth velocity, cranial computed tomography scanning, and complete endocrinologic status following stimulation with arginine or insulin hypoglycemia, TRH and LHRH. Group I (N = 9, 4 male, 5 female) had received systemic chemotherapy and intratheral methotrexate, but no cranial irradiation. Group II (N = 13, 9 male: 4 female) had additionally received central nervous system irradiation (2400 rads). All patients had undergone normal spontaneous puberty, and had normal levels of thyroxine, thyrotropin, dihydroepiandrosterone sulfate, testosterone or estrogens, luteinizing hormone, follicle stimulating hormone, prolactin, and cortisol. In Group I only one patient decreased his percentile height greater than 25% but he had normal growth hormone responses. In Group II, two younger patients showed growth deceleration with inadequate provocative growth hormone responses, whereas two pubertal patients developed growth arrest post diagnosis and treatment but had normal growth hormone responses. When Groups I and II and controls were compared as to the number of growth hormone samples greater than 5 ng/ml, the peak growth hormone value, or the mean growth hormone concentration during the combined arginine-insulin test, no significant differences were noted. Brain scan abnormalities were noted in 3 out of 9 patients in Group I (33%) and in 5 out of 11 patients in Group II (45%). There was no correlation in either group between abnormal computed tomography scans and abnormal growth hormone secretory dynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1984

Unilateral radiation nephropathy--the long-term significance.

Eighteen patients with gastrointestinal and retroperitoneal non-Hodgkin's lymphoma received abdominal radiotherapy as their primary treatment. Each patient received a total tumor dose of 2200 to 4500 cGy in 5 to 9 weeks to the whole or half of one kidney. Nine patients developed unilateral radiation nephropathy demonstrable on post-treatment evaluation with 99m Tc glucoheptonate blood flow, delayed static scan, and an I-131 radio-hippurate renal perfusion study. The tests were periodically repeated over periods ranging from 5 to 8 years. Six patients with nephropathy and 4 patients without nephropathy were followed 5 years or longer. The minimum nephro-pathogenic irradiation dose was 2200 cGy delivered in 59 days. The incidence of nephropathy is higher with increase in the total dose. Short term recovery in function was observed in 3 patients and long-term complete recovery was observed in one patient. Atrophic renal change was irreversible and progressive in 3 patients over a 6 to 7 year follow-up period. In this group of patients, an abnormal creatinine clearance and serum beta-2 microglobulin level was indicative of vascular damage. Elevated arterial blood pressure was seen in 5 patients. All were controlled medically, without nephrectomy. There was no other clinically significant problem resulting from the unilateral nephropathy in this group of patients.

Follow-Up Studies↗

PubMed1984

A simple isocentric technique for irradiation of the breast, chest wall and peripheral lymphatics.

The major problem with the standard technique for irradiation of the breast or chest wall and peripheral lymphatics is field matching at the junction between the supraclavicular and tangential fields. Overdosing or under-dosing across the junctions is unavoidable because of beam divergence. Various techniques using a half-blocked supraclavicular field in conjunction with special tangential fields have been introduced recently to eliminate the junction problem; they are, however, complicated, involving couch motions and machine isocentre repositioning when changing from the supraclavicular to the tangential fields. The breast treatment technique which we have used over the past twelve months utilises a supraclavicular half-blocked field, two tangential half-blocked fields and an optional posterior axillary field. The technique is simple and easy to set up since the same machine isocentre is used for all treatment fields and no couch movement or patient repositioning is required. The same half-block collimator which is used to define the caudad border of the supraclavicular field is used to define the cephalad edges of the two tangential fields. The margin of error of treatment is reduced and the dose measurements demonstrate excellent dose homogeneity through the entire treatment volume with no overdose or underdose at the field junction.

Breast Neoplasms↗

PubMed1982

Non-Hodgkin's lymphoma in couples.

The occurrence of identical non-Hodgkin lymphomas in three couples related only by marriage, is reported. The couples had lived together for 25 years or longer and there was a five to eight year delay in onset of the lymphoma between each of the members of the couple. The pathologic finding in two of the three couples was a nodular poorly differentiated lymphocytic (NPDL) type in the third a diffuse histiocytic (DHL) type (Rappaport's classification). All cases are believed to be of B-cell origin. The unusual clustering in their cases suggests an infections agent and/or environmental factor may be playing a role in the etiologic causes of some non-Hodgkin's lymphomas.

Aged↗

PubMed1982

Free flaps and irradiated recipient vessels: an experimental study in rabbits.

In an experimental study in rabbits the effect of previous irradiation to the recipient vessels on the survival rate of free flaps was evaluated. Pre-operative radiotherapy was given in a single anterior neck field using a Cobalt60 unit, 1.25 MeV, SSD 80 cm in a fractionated dose corresponding to 5000 rad/5 weeks. An experimental model using paired data was established using two epigastric free flaps in each animal: one anastomosed to the irradiated vessels (carotid and jugular vein) and implanted outside the irradiated field and the other flap anastomosed to the normal femoral vessels and also implanted outside the irradiated field. In a sequential analysis it was found that free flaps anastomosed to irradiated recipient vessels within 12 weeks from the start of radiotherapy failed significantly more often than free flaps anastomosed to normal recipient vessels (p less than 0.10). This supports the view that preference should be given to the use of non-irradiated recipient vessels for microvascular transfer of free flaps.

Animals↗

PubMed1982

Healing of microvascular anastomoses. A comparative study using normal and irradiated recipient vessels for experimental free flaps in rabbits.

A comparative study was undertaken to evaluate the possible effect of previous radiotherapy on the healing of subsequently performed microvascular anastomoses between irradiated recipient vessels and normal flap vessels in rabbits. Radiotherapy was given preoperatively to a single anterior neck field using a Cobalt 60 unit, 1.25 MeV, SSD 80 cm in a fractionated dose corresponding to 5,000 rad/5 weeks. An experimental model using paired data was established using two epigastric free island flaps in each animal: one anastomosed to the irradiated vessels (carotid artery and jugular vein) and the other anastomosed to the normal opposite femoral vessels. Results did not show any marked difference in the healing pattern during the first 3-week period postoperatively except for a higher rate of thrombosis, when irradiated recipient vessels were used in end-to-end anastomoses, while no difference in healing pattern or rate of thrombosis were found using telescoped arterial anastomoses.

Animals↗

PubMed1982

Lung scanning with 67gallium citrate for detection of acute radiation changes.

Radiogallium imaging plays a growing role in the investigation of acute and chronic inflammatory diseases of the lung. We studied a series of patients undergoing radiation treatment for carcinoma of the breast to evaluate the usefulness of imaging with 67gallium citrate in the detection of early radiation changes in the pulmonary parenchyma. In a series of 12 patients there was no correlation between the clinical and radiographic manifestations of radiation pneumonitis and the gallium scan.

Breast Neoplasms↗

PubMed1982

Gastrointestinal complications after radiotherapy for carcinoma of the uterine cervix.

Radiotherapy for invasive carcinoma of the uterine cervix caused gastrointestinal complications in 52 of 441 patients. External beam and intracavitary radiation together caused greater bowel damage than either method alone. Twenty-eight of the 52 patients required surgical intervention. Ileal stenosis in nine patients required primary resection with anastomosis in seven while the stenosis was bypassed in the other two. Acute perforation with peritonitis would require a diverting ileostomy and creation of a mucous fistula. A defunctioning colostomy was indicated for relief of pain, bleeding and stenosis of the rectum in 11 of 15 patients; 2 patients were treated by primary resection, 1 underwent abdominoperineal resection and another a pelvic exenteration. Of four patients with ileal and rectal involvement, one underwent right hemicolectomy and transverse colostomy, two had ileal resection and sigmoid colostomy and the other had hemicolectomy and rectal resection. All patients were well at follow-up from 3 to 120 months after operation. A Hartmann's procedure is indicated when it appears that primary closure may not succeed. Individualized management is essential.

Female↗