Search PubMed⌕ Search

Biomedical subjects

C A Lawton

Publications and source records attributed to C A Lawton.

18 recordsLinked to original sources
PubMed1995

Androgen deprivation with radiation therapy compared with radiation therapy alone for locally advanced prostatic carcinoma: a randomized comparative trial of the Radiation Therapy Oncology Group.

OBJECTIVES: Androgen deprivation therapy before and during radiation therapy could, by reducing tumor volume, increase local tumor control, disease-free survival, and overall survival in patients with locally advanced adenocarcinomas of the prostate. METHODS: In a randomized controlled clinical trial, patients with large T2, T3, and T4 prostate tumors, but no evidence of osseous metastasis, were randomized to receive goserelin 3.6 mg subcutaneously every 4 weeks and flutamide 250 mg orally three times daily 2 months before and during the radiation therapy course (Arm I) compared with radiation therapy alone (Arm II). Pelvic irradiation was administered with 1.8 to 2.0 Gy per day to a total dose of 45 +/- 1 Gy followed by a boost to the prostate target volume to a total dose of 65 to 70 Gy. RESULTS: Of 471 randomized patients, 456 were evaluable, 226 on Arm I and 230 on Arm II. With a median potential follow-up of 4.5 years, the cumulative incidence of local progression at 5 years was 46% in Arm I and 71% in Arm II (P < 0.001). The 5-year incidence of distant metastasis on Arms I and II was 34% and 41%, respectively (P = 0.09). Progression-free survival rates including normal prostate-specific antigen (PSA) levels for 396 patients with at least one PSA recorded were 36% in Arm I and 15% in Arm II at 5 years (P < 0.001). At this time, no significant difference in overall survival could be detected (P = 0.7). CONCLUSIONS: Short-term androgen deprivation with radiation therapy results in a marked increase in local control and disease-free survival compared with pelvic irradiation alone in patients with locally advanced carcinoma of the prostate. Long-term surveillance is required to assess effects on overall survival.

Adenocarcinoma↗
PubMed1995

Bone marrow transplant nephropathy: radiation nephritis revisited.

Late-onset renal failure occurs in up to 20% of survivors of bone marrow transplantation. Total body irradiation is a major factor in this syndrome, so-called bone marrow transplant nephropathy (BMT NP), which is defined by disproportionate anemia, hypertension, and azotemia. Previous or concurrent chemotherapy may potentiate the effect of radiation on the kidney. Kidney function may decline acutely or more gradually, with eventual long-term stabilization. Patient survival is associated with control of the blood pressure. BMT NP is a recognized complication of bone marrow transplantation, which will require ongoing attention.

Adolescent↗
PubMed1994

Effect of nephrotoxic drugs on the development of radiation nephropathy after bone marrow transplantation.

PURPOSE: Chronic renal failure is a significant cause of late morbidity in bone marrow transplant patients whose conditioning regimen includes total body irradiation (TBI). Radiation is a major cause of this syndrome (bone marrow transplant nephropathy), but it may not be the only cause. These studies use a rat syngeneic bone marrow transplant model to determine whether nephrotoxic agents used in conjunction with bone marrow transplantation (BMT) could be enhancing or accelerating the development of radiation nephropathy. METHODS AND MATERIALS: Rats received 11-17 Gy TBI in six fractions over 3 days followed by syngeneic bone marrow transplant. In conjunction with the bone marrow transplants, animals received either no drugs, cyclosporine, amphotericin, gentamicin, or busulfan. Drugs were given in schedules analogous to their use in clinical bone marrow transplantation. Drug doses were chosen so that the drug regimen alone caused detectable acute nephrotoxicity. Animals were followed for 6 months with periodic renal function tests. RESULTS: Gentamicin had no apparent interactions with TBI. Amphotericin increased the incidence of engraftment failure, but did not enhance radiation nephropathy. Cyclosporin with TBI caused late morbidity that appeared to be due to neurological problems, but did not enhance radiation nephropathy. Busulfan resulted in a significant enhancement of radiation nephropathy. CONCLUSION: Of the nephrotoxins used in conjunction with bone marrow transplantation only radiation and busulfan were found to be risk factors for bone marrow transplant nephropathy.

Amphotericin B↗
PubMed1994

Prostate cancer: are racial differences in clinical stage and survival explained by differences in symptoms?

PURPOSE: To better understand racial differences in data for patients referred for definitive treatment of biopsy-proved adenocarcinoma of the prostate gland. MATERIALS AND METHODS: Two groups of patients were defined for further analysis. Group 1 comprised all patients who received definitive external beam irradiation of prostatic carcinoma; group 2 comprised all patients with prostatic carcinoma referred between January 1988 and December 1992 for examination at the first clinical indication of adenocarcinoma of the prostate. All patients were evaluated for age, race (black vs white), differentiation of tumor, date of diagnosis, and clinical stage. RESULTS: In group 1, black patients were significantly younger and presented with disease at higher clinical stage but equivalent grade and survival compared with white patients. In group 2, black patients were significantly younger and had similar differentiation of tumor but with significantly higher clinical stage compared with white patients and more often had obstructive symptoms and less often had been screened for elevated prostate-specific antigen levels. CONCLUSION: Black patients should undergo earlier screening for prostate cancer.

Adenocarcinoma↗
PubMed1994

PSA screening.

Explore the source record for details and available documents.

Adenocarcinoma↗
PubMed1993

Clinical course of late-onset bone marrow transplant nephropathy.

Late-onset renal insufficiency is an increasingly recognized complication of bone marrow transplantation (BMT) which occurs between 6 and 12 months after BMT. This syndrome, which has occurred in 25% of our 2-year survivors, is characterized by azotemia, hypertension, and disproportionate anemia. A minority of our subjects have had a presentation similar to hemolytic-uremic syndrome, with rapid decline in kidney function. The others have had slower declines in kidney function, without apparent ongoing hemolysis. Stabilization of function has occurred in about one third of cases. Light microscopy has shown mesangial and endothelial cell dropout with widening of glomerular capillary loops. Electron microscopy has shown a striking subendothelial expansion of the glomerular basement membrane. This syndrome is similar to acute radiation nephritis. Stabilization of kidney function has occurred in some cases, perhaps reflecting control of the blood pressure. Studies of the prevention of this condition are needed because of the frequency of its occurrence and the growing number of BMT worldwide.

Adolescent↗
PubMed1992

Is long-term survival possible with external beam irradiation for stage D1 adenocarcinoma of the prostate?

From 1972 to 1986, 354 patients with local and locoregional adenocarcinoma of the prostate were treated with curative intent at the Medical College of Wisconsin. Fifty-six of these patients were found to have Stage D1 disease (evidence of pelvic lymph node involvement). Using external beam irradiation alone, these patients were treated aggressively to the pelvis followed by a boost to the prostate. The median dose to the prostate was 6800 cGy, and to the pelvis, it was 5040 cGy. The median period of observation after treatment was 9 years. Actuarial survival was 76% at 5 years, and disease-free survival was 61% at 5 years. Twenty-three patients had biopsy-proved pelvic lymph node involvement; the other 33 were considered to have Stage D1 disease based on abnormal computed tomographic scans, lymphangiograms, or both. Actuarial survival and disease-free survival were calculated for both groups separately, and there was no statistical difference in the results. Major complications occurred in 3.6% (two patients) of this group with Stage D1 disease. These results support the continued use of aggressive external beam irradiation in patients with locoregional adenocarcinoma of the prostate.

Actuarial Analysis↗
PubMed1992

Influence of renal shielding on the incidence of late renal dysfunction associated with T-lymphocyte deplete bone marrow transplantation in adult patients.

Late renal dysfunction following allogeneic bone marrow transplantation has been described by a number of centers including our own. Total body irradiation appears to play a major causative role in the development of this syndrome. In an effort to decrease the incidence of this renal toxicity we have added customized partial transmission renal blocking to our total body irradiation regimen. This partial renal shielding decreases the total dose to the kidneys from 14 Gy to 12 Gy. This report compares 71 adult patients who have received total body irradiation associated with bone marrow transplantation using renal shielding with 72 adult patients who were treated without the shielding; all of the patients have survived a minimum of 100 days post-BMT. Eighteen months following BMT, 26% of patients who did not have renal shielding have developed late renal dysfunction compared to only 6% of patients with renal shielding (p less than .05). Median follow-up in the nonblocked patients is 536 days post-transplant versus 341 days for the blocked patients. This added renal blocking has not adversely affected engraftment rates or relapse rates to date. Customized renal shielding as part of 14 gray total body irradiation in preparation for bone marrow transplantation appears to have decreased the incidence of late renal dysfunction in this group of adult patients and should be considered for all patients undergoing total body irradiation in conjunction with bone marrow transplantation.

Adolescent↗
PubMed1991

Late renal dysfunction in adult survivors of bone marrow transplantation.

Until recently long-term renal toxicity has not been considered a major late complication of bone marrow transplantation (BMT). Late renal dysfunction has been described in a pediatric population status post-BMT which was attributable to the radiation in the preparatory regimen. A thorough review of adults with this type of late renal dysfunction has not previously been described. Fourteen of 103 evaluable adult patients undergoing allogeneic (96) or autologous (7) bone marrow transplantation, predominantly for leukemia and lymphomas, at the Medical College of Wisconsin (Milwaukee, WI) have had a syndrome of renal insufficiency characterized by increased serum creatinine, decreased glomerular filtration rate, anemia, and hypertension. This syndrome developed at a median of 9 months (range, 4.5 to 26 months) posttransplantation in the absence of specific identifiable causes. The cumulative probability of having this renal dysfunction is 20% at 1 year. Renal biopsies performed on seven of these cases showed the endothelium widely separated from the basement membrane, extreme thickening of the glomerular basement membrane, and microthrombi. Previous chemotherapy, antibiotics, and antifungals as well as cyclosporin may add to and possibly potentiate a primary chemoradiation marrow transplant renal injury, but this clinical syndrome is most analogous to clinical and experimental models of radiation nephritis. This late marrow transplant-associated nephritis should be recognized as a potentially limiting factor in the use of some intensive chemoradiation conditioning regimens used for BMT. Some selective attenuation of the radiation to the kidneys may decrease the incidence of this renal dysfunction.

Adolescent↗
PubMed1991

Twice-daily tapering dexamethasone treatment during cranial radiation for newly diagnosed brain metastases.

Twenty evaluable patients with newly diagnosed brain metastases underwent treatment with a novel dose/schedule of dexamethasone aimed at reducing steroid toxicity during palliative radiation therapy. All patients received twice daily dexamethasone starting at 8 mg bid for four days then 4 mg bid for four days then 2 mg bid until the last day of radiation therapy. The radiation prescriptions were not standardized varying from 2000 cGy/5 fractions to 5800 cGy/29 fractions. Fourteen patients received dexamethasone for a minimum of 24 hours before their first radiation treatment and 7 (50%) experienced improvement in neurologic symptoms/signs prior to starting radiation treatments. Fourteen patients completed the planned course of radiation and dexamethasone. Only 1 patient needed to restart dexamethasone within 30 days of finishing radiation because of steroid reversible neurologic deficits. Steroid toxicity was mild including hyperglycemia (1), candida esophagitis (1), steroid pseudorheumatism (2), peripheral edema (1) and steroid withdrawal syndrome (1). Only two toxic events were recorded in patients receiving steroids less than 21 days. Twice daily dexamethasone appears to provide good clinical results with minimal morbidity.

Administration, Oral↗
PubMed1991

Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706.

Significant late intestinal and urinary morbidity from external beam irradiation for adenocarcinoma of the prostate has been a constant concern of both the urologist and the radiation oncologist. We analyzed two large Radiation Therapy Oncology Group trials (7506 and 7706) using primary irradiation in the treatment of local or locoregional adenocarcinoma of the prostate to assess morbidity via the Radiation Therapy Oncology Group scoring scheme (grade 1-5). One thousand twenty patients were treated in total with a minimum follow-up of 7 years in the surviving patients. There was a 3.3% incidence of intestinal complications defined as grade 3 toxicity or more with .6% of patients experiencing bowel obstruction or perforation. Urinary complications defined as grade 3 toxicity or more were found in 7.7% of patients with only 0.5% experiencing morbidity that would require a major surgical intervention such as laparotomy, cystectomy, or prolonged hospitalization. Intestinal and urinary complications were evaluated in reference to several parameters that might have an impact on their incidence (i.e., previous laparotomy, stage of disease, hypertension, positive lymph nodes, previous transurethral resection, total dose, and energy of accelerator used). Only total dose (greater than 70 Gray) was found to have a significant impact on the incidence of the urinary complications. None of these factors had a significant impact on the incidence of intestinal complications. These data from two large multi-institutional trials represent a fair estimate of the actual incidence of major intestinal and urinary complications from external beam irradiation in the management of local and locoregional adenocarcinoma of the prostate. Since the incidence of these major complications remains very low, we believe that external beam irradiation remains an excellent alternative to radical prostatectomy in the management of these patients.

Adenocarcinoma↗
PubMed1991

Allogeneic bone marrow transplantation for relapsed and refractory lymphoma using genotypically HLA-identical and alternative donors.

Twenty-two patients, ages 16.6 to 43.9 years (median age, 30 years), with relapsed or refractory lymphoma were treated by allogeneic bone marrow transplantation after high-dose chemotherapy with or without total body irradiation (TBI). Seven patients had Hodgkin's disease, four had low-grade histology non-Hodgkin's lymphoma (NHL), seven had intermediate-grade NHL, and four had high-grade NHL. Of the 22 patients, 17 received T-cell (CD-3)-depleted marrow after intensive pretransplant chemoradiotherapy, and five received T-cell-replete grafts after chemotherapy-based preparative regimens. Five patients were transplanted from donors other than genotypically HLA-identical siblings: four from partially HLA-matched relatives, and one from a phenotypically HLA-identical unrelated donor. Acute graft-versus-host disease (GVHD) was less than or equal to grade II in all patients, and chronic GVHD was limited or absent in all but one patient. Of the 21 assessable patients, 17 (80.9%) achieved complete remissions. Death due to transplant-associated complications occurred in five patients, and five patients have relapsed. Thirteen patients are alive, and 12 are continuously relapse-free at a median follow-up of longer than 28 months (range, greater than 10 to greater than 58 months) from transplant. The cumulative probability of treatment failure from relapse or progression of lymphoma was 29% (95% confidence interval [CI], 12% to 51%), while the actuarial lymphoma-free (ie, event-free) survival plateau is 54.6% (95% CI, 34% to 76%). For young patients with advanced malignant lymphoma, allogeneic bone marrow transplantation appears superior to salvage chemotherapy for achievement of long-term, lymphoma-free survival and may be preferable to autologous bone marrow transplantation for selected patients.

Actuarial Analysis↗
PubMed1989

Technical modifications in hyperfractionated total body irradiation for T-lymphocyte deplete bone marrow transplant.

The Medical College of Wisconsin implemented a major bone marrow transplant (BMT) program in July 1985. The type of transplants to be focused on were allogeneic T-lymphocyte deplete. Total body irradiation (TBI) was initially patterned after the Memorial method. Patients received total body irradiation in a sitting position at a dose rate of 20-25 cGy/minute with 50% attenuation lung blocks used both anterior/posterior and posterior/anterior. Electron boosting was utilized for the ribs beneath the lung blocks. Occasionally, lower extremity boosting was required because of the sitting position. A dose of 14 Gy was chosen since T-lymphocyte deplete bone marrow transplant data suggest the need for higher total doses to consistently obtain engraftment. This dose was given in 3 equal daily fractions over 3 days following conditioning chemotherapy. Six of 11 patients treated in this manner developed lethal pulmonary events. In response to the pulmonary toxicity, partial lung shielding was increased to 60% attenuation. In the next 107 patients receiving this program of total body irradiation there was a reduced incidence of fatal pulmonary events (10 cases of fatal idiopathic interstitial pneumonitis and 12 cases of fatal pulmonary infections) after a median follow-up of 9 months. This was an obvious improvement over the initial group. A significant level of hepato-renal toxicity was also observed with 14 Gy total body irradiation when no liver or kidney blocking was used. Of the first 20 patients treated, three cases of fatal veno-occlusive disease resulted. Subsequently, a 10% attenuation right sided liver block was added. Five of 98 patients treated with this block have developed fatal hepatic dysfunction, (median follow-up of 7.2 months). This incidence is not statistically different from the initial group but favors the use of the liver block. Some renal toxicity was also detected with the earlier regimen, especially in pediatric patients. Partial kidney blocking has been implemented to minimize this toxicity. Our current dose rate has been reduced to 8 cGy/minute in a further attempt to reduce organ toxicity. To date, this selective blocking has not adversely affected the excellent rate (96%) of first time engraftments.

Adolescent↗
PubMed1986

Extended-field radiation therapy for prostatic carcinoma with para-aortic lymph node metastasis.

The finding of involvement of para-aortic lymph nodes in patients with adenocarcinoma of the prostate has been considered so ominous that further therapy has often only been palliative. What is the proportion of patients with carcinoma of the prostate with regional metastasis limited to the infra-diaphragmatic lymph nodes who might be cured or at least offered long-term progression-free survival by aggressive treatment? From June 1970 through March 1983, 114 patients were treated with curative intent for adenocarcinoma of the prostate, clinical Stage III, at the Medical College of Wisconsin Affiliated Hospitals. Twenty-three of these patients had evidence of metastasis to the para-aortic lymph nodes. These patients were treated aggressively with external radiation therapy to the entire pelvis and para-aortic region. The median dose to the prostate was 70 Gy, the pelvis 54 Gy, and the para-aortic region 50 Gy. The median period of observation after treatment was 53.5 months. The actuarial survival was 90% at 5 years and progression-free survival was 73% at 5 years. The rate of major complications was 4.3%. Although the number of patients is small, the data suggest that extended field radiation therapy can result in prolonged progression-free survival and perhaps cure many patients with juxtaregional dissemination of adenocarcinoma of the prostate.

Adenocarcinoma↗
PubMed1986

Hypothyroidism as a correlate of lateral ventricular enlargement in manic-depressive and neurotic illness.

Lateral ventricular size, as assessed by computed tomography, was not significantly greater in manic-depressive cases than in neurotic patients, but 19% of manic-depressive cases had ventricular brain ratios (VBR) more than two standard deviations above the neurotic mean. Few correlates of VBR were found in the features of the illness and the treatment given, apart from the fact that in the outpatient sample, there was a significant association between increased VBR and hypothyroidism. Hypothyroidism was relatively common in this sample, but was treated and not associated with cognitive impairment. There was no relationship between lithium administration and VBR.

Aged↗
PubMed1980

An analog of MSH/ACTH 4-9 enhances interpersonal and environmental awareness in mentally retarded adults.

In a double blind procedure, four doses (0, 5, 10 and 20 mg) of an orally active analog of ACTH/MSH 4-9 was administered to mentally retarded adults. Changes in behavior and in productivity were evaluated as subjects performed their job in a sheltered workshop. During the first week productivity suffered while behavior related to communication and sociability increased in clients receiving the peptide analog. During the second week, clients given the peptide were more productive and attentive to environmental events while differences in sociability stabilized. Five and 10 mg enhanced productivity of tasks requiring precision and concentration where 20 mg depressed performance of all tasks. Regression equations indicated that different doses of the peptide generated unique relationships between behavior and productivity with self-stimulation characterizing the clients given the peptide. The use of the peptide analog of ACTH/MSH as a potential treatment with the mentally retarded is encouraged by these findings.

Adrenocorticotropic Hormone↗
PubMed1978

Voluntary control of electrogastric activity.

The tonic component of the electrogastrogram (EGG) has been shown to differentiate duodenal ulcer patients from healthy individuals (15). It has therefore been of considerable interest to investigate the possibility that individuals can learn to modify electrogastric activity. Using a discriminative conditioning paradigm with analogue feedback (Experiment I), subjects were generally unsuccessful at controlling tonic EGG activity. However, when the conditioning paradigm was altered (Experiment II) it was clear that subjects were able to modify specific electrogastric changes. In addition to EGG, heart rate, respiration, abdominal muscle activity, and digital blood flow were measured in order to assess the physiological concomitants of learned control of gastrointestinal activity. Subjects who evidenced discriminative control also showed the least amount of abdominal muscle activity and reported being the most relaxed. The results of these studies suggest that exploration of the physiological processes underlying the electrical activity of the gastrointestinal system and the ability of individuals to modify this activity may lead to significant clinical and theoretical advances.

Abdominal Muscles↗