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Biomedical subjects

R S Bush

Publications and source records attributed to R S Bush.

At least 19 recordsLinked to original sources

Analysis of complications in patients treated with abdomino-pelvic radiation therapy for ovarian carcinoma.

Between 1971 and 1985, 598 patients with ovarian carcinoma were treated with abdomino-pelvic radiation therapy. Acute complications included nausea and vomiting in 364 patients (61%) which were severe in 36, and diarrhea in 407 patients (68%), severe in 35. Leukopenia (less than 2.0 x 10(9) cells/liter) and thrombocytopenia (less than 100 x 10(9) cells/liter) occurred in 64 patients (11%) each. Treatment interruptions occurred in 136 patients (23%), and 62 patients (10%) did not complete treatment. In both situations the most common cause was myelosuppression. Late complications included chronic diarrhea in 85 patients (14%), transient hepatic enzyme elevation in 224 (44%), and symptomatic basal pneumonitis in 23 (4%). Serious late bowel complications were infrequent: 25 patients (4.2%) developed bowel obstruction and 16 required operation. Multivariate analysis was unable to determine any significant prognostic factors for bowel obstruction; however, the moving-strip technique of radiation therapy was associated with a significantly greater risk of developing chronic diarrhea, pneumonitis, and hepatic enzyme elevation than was the open beam technique. We conclude that abdomino-pelvic radiation therapy as used in these patients is associated with modest acute complications and a low risk of serious late toxicity.

Abdomen

Complications of whole abdominal and pelvic radiotherapy following chemotherapy for advanced ovarian cancer.

We examined the records of 105 patients with advanced ovarian cancer who had been treated with cisplatin combination chemotherapy followed by abdominopelvic radiotherapy. The purpose was to define the morbidity of this approach, and identify those factors predictive of toxicity. Acute toxicity resulting in delay or failure to complete treatment was most commonly due to myelosuppression. Nine of 105 patients (8.6%) required surgery for bowel obstruction that was not due to recurrent disease, 3 had an episode of bowel obstruction that settled conservatively, and a further 5 underwent surgery for obstruction due to recurrent tumor. The presence of both a dose of abdominopelvic radiotherapy over 2250 cGy, as well as a second-look laparotomy prior to radiotherapy, was associated with an increased risk of serious bowel complications. The increased frequency of late bowel morbidity seen in the combined modality group is likely explained by the presence of these two factors, rather than the exposure to chemotherapeutic agents per se. These observations are supported by the published literature.

Abdomen

Effects of raw pea flour on nutrient digestibility and immune responses in the preruminant calf.

Two milk substitute diets for which the protein was provided either exclusively by skim milk powder (control) or partially (34%) by dehulled raw pea flour were given for 2 and 4 wk, respectively, to five preruminant calves, each fitted with a reentrant ileocecal cannula. Ileal apparent digestibility was lower with the pea diet during wk 1 than with the control diet. Four of the cannulated calves exhibited significant intolerance to the pea diet, resulting in lower digestibility during wk 4. In contrast, fecal digestibility of the pea diet, measured in four additional calves without reentrant cannulas, did not significantly decrease between wk 1 and 4. The AA composition of ileal digesta from the first group of calves did not vary greatly, suggesting that the differences observed in their apparent digestibility of proteins were due mainly to changes in the loss of endogenous proteins. However, pea legumin survived digestion in the small intestine in amounts generally equivalent to 1 to 3% of intake. Most of that undigested fraction was smaller than the native legumin: 40 to 200 kDa instead of 360 kDa. Also, a 45-kDa fragment was detected in the urine. Increased intestinal permeability could have favored the development of the high systemic anti-pea antibody titers that were observed in all of the calves.

Amino Acids

Ovarian carcinoma: improved survival following abdominopelvic irradiation in patients with a completed pelvic operation.

A prospective, stratified, randomized study of 190 postoperative ovarian patients with Stages IB, II, and III (asymptomatic) presentations is reported. The median time of follow-up was 52 months. Patients in whom bilateral salpingo-oophorectomy and hysterectomy (BSOH) could not be completed because of extensive pelvic tumor had a poor prognosis which did not differ for any of the therapied tested. When BSOH was completed, pelvic plus abdominopelvic irradiation (P + AB) with no diaphragmatic shielding significnatly improved patient survival rate and long-term control of occult upper abdominal disease in approximately 25% more patients than pelvic irradiation alone or followed by adjuvant daily chlorambucil therapy. The effectiveness of P + AB in BSOH-completed patients was independent of stage or tumor grade and was most clearly appreciated in patients with all gross tumor removed. Chlorambucil added to pelvic irradiation delayed the time to treatment failure without reducing the number of treatment failures.

Abdomen

Ovarian irradiation and prednisone therapy following surgery and radiotherapy for carcinoma of the breast.

Following mastectomy, patients with operable breast cancer underwent postoperative irradiation of the chest wall and regional lymph nodes. They were then assigned at random to receive no further therapy, ovarian irradiation (2000 rads in 5 days) or ovarian irradiation in the same dosage plus prednisone, 7.5 mg daily. A total of 705 patients received the randomly assigned treatment and were followed for up to 10 years. In premenopausal patients who received ovarian irradiation the recurrence of breast cancer was delayed and survival prolonged, but not significantly. In premenopausal women aged 45 years or more ovarian irradiation plus prednisone therapy significantly delayed the recurrence of breast cancer (P = 0.02) and prolonged survival (P = 0.02); the survival expectancy of these patients was similar to that of the general population of the same age from the third year after the cancer operation. No value was demonstrated for ovarian irradiation with or without prednisone therapy in postmenopausal patients.

Adult

The Princess Margaret Hospital study of ovarian cancer: stages I, II, and asymptomatic III presentations.

An analysis of 231 patients with stages I, II, and asymptomatic III ovarian cancer, studied in a prospective randomized-stratified trial, is presented. None of the stage IA patients with well-differentiated tumors have had disease relapses; one fourth of the patients with poorly differentiated tumors have had disease relapses throughout the peritoneal cavity. There is therefore little justification for pelvic radiation alone as postoperative therapy for stage IA ovarian carcinoma. For stage IB, II, and asymptomatic III presentations, patients with an incomplete initial pelvic operation had poor survival characteristics with all tested therapies. For patients in whom the operation was completed, abdominopelvic radiation was superior to pelvic radiation alone or followed by chlorambucil, with respect to long-term survival and control of abdominal disease. The effectiveness of abdominopelvic radiation was independent of stage or histology. The value of abdominopelvic radiation was most strikingly seen in patients with no visible residual tumor.

Cell Differentiation

Carcinoembryonic antigen (CEA) and other tumor markers in ovarian and cervical cancer.

Combinations of carcinoembryonic antigen (CEA), gamma glutamyl transpeptidase (GGT), pregnancy-associated macroglobulin (PAM) and placenta-like alkaline phosphatase (PLAP) were studied in groups of patients with ovarian and cervical cancer. In ovarian cancer, only CEA and PLAP levels appeared to reflect tumor burden and were complementary in detecting active disease. In cervical cancer, CEA and GGT reflected tumor burden, while PLAP showed just the reverse--the highest degree of positivity being present in minimal disease. PLAP positivity was even more pronounced in patients with cervical dysplasia and carcinoma in situ while CEA and GGT were negative. The data indicate that the use of marker combinations can improve our capacity to detect minimal disease and provide information regarding tumor biology that may not be available by studying individual markers or by other means. It remains to be determined whether the use of tumor markers can influence existing therapy sufficiently to alter the outcome in cancers which are notoriously difficult to treat.

Alkaline Phosphatase

Effects of age, sex and starvation on the turnover of plasma, liver and breast muscle proteins in the Japanese quail.

Half-lives of the plasma, liver and breast muscle proteins in female, old male, young male and starved young male Japanese quail were measured by following the changes in protein specific radioactivity over a period of 7 days. The female birds showed the shortest half-lives for plasma and liver proteins and very long half-lives for breast muscle proteins. Compared to the proteins from the female birds, the old and young male birds showed slightly longer half-lives for plasma and insoluble liver proteins and shorter half-lives for soluble liver and breast muscle proteins. Starved birds showed greatly increased half-lives for all proteins when compared to the corresponding proteins from the other groups of quail. In general, the trends shown for the turnover of proteins from plasma, liver and breast muscle of the four groups of quail were similar to turnovers reported for rats under similar treatment conditions.

Aging

The effect of chronic reductions in the arterial partial pressure of oxygen on the radiation response of an experimental tumour.

A previous study by the same authors has reported the effect of acute reductions in the arterial partial pressure of oxygen (PaO2) on tumour response to radiation. The results have been extended in the present paper to investigate tumour response to radiation in animals in which the PaO2 is chronically reduced. The purpose of these experiments was to simulate the condition of cancer patients undergoing radiotherapy in the presence of chronically low PaO2 values as might be expected in patients with chronic respiratory disease. Mice bearing transplantable KHT sarcomas were kept in a 12% O2 environment prior to (10--16 days), during and following the radiation treatment of their tumours. During the period of low PaO2 (about 50 mm Hg) exposure, the mice were found to increase their haemoglobin (Hg) levels by approximately 50%. Because of this increase, the response, determined using a growth delay assay of the tumours irradiated at reduced PaO2 was found to be the same as that observed for tumours in mice breathing air throughout the experiment. In mice with reduced PaO2 levels maintained at normal Hb concentrations by periodic bleeding, tumour response was found to be similar to that of mice with acute PaO2 reductions. These results indicate that chronic PaO2 reductions in the absence of Hb compensation may have a detrimental effect on the success of a radiation treatment.

Animals

The effect of misonidazole in combination with radiation dose fractionation.

Single doses or multiple fractions of 2, 3, 5 or 10 Gy were given daily to KHT Sarcomas, growing in C3H mice, in combination with a misonidazole dose of 0.5 mg/g body weight administered 30--40 min before each radiation dose. Cell survival assays were performed on groups of tumours after different total doses to determine tumour cell survival curves for each fractionation schedule. The results indicate that misonidazole is effective in sensitizing the tumours to single doses and to large dose fractions, but that the degree of sensitization declines with fraction size such that there is no difference between the survival curves obtained for 2 Gy fractions given with or without prior drug treatment. Comparison of iso-effect curves, derived from the data, with those for normal skin suggests that, even though misonidazole increases the effect of the radiation on the tumour when large dose fractions are used, the small dose fractions probably still give a better "therapeutic ratio".

Animals

Definitive evidence for hypoxic cells influencing cure in cancer therapy.

From an analysis of 2803 patients with carcinoma of the cervix treated by radiation therapy, a 62% cure rate can be shown. In those patients with Stage IIb and III disease, a haemoglobin level during treatment of below 12 g% was associated with a significantly higher pelvic recurrence rate, and also lower cure rate, than for those with a haemoglobin level 12g% or more. A prospective study shows that the correction of anaemia is associated with a decreased pelvic recurrence rate and an increased cure rate consistent with tumour hypoxia being greater in anaemic patients than in those with a normal haemoglobin level. It is also consistent with the thesis that hypoxia controls the radiation local control rate in patients with advanced carcinoma of the cervix.

Female

Evidence for separate enzymes of pyruvate decarboxylation and pyruvate synthesis in soluble extracts of Clostridium pasteurianum.

Additional evidence to that already presented (Sauer, F. D., Bush, R. S., and Stevenson, I. L. (1976) Biochim. Biophys. Acta 445, 518-520) suggests that pyruvate-ferredoxin oxidoreductase isolated from Clostridium pasteurianum consists of two separate enzymes: (a) pyruvate lyase, which catalyzes the CoA and electron acceptor-dependent decarboxylation of pyruvate, and (b) pyruvate synthase, which catalyzes the reduced ferredoxin-dependent carboxylation of acetyl-CoA to pyruvate. The enzymes separated on Sephadex G-200 and with acrylamide gel electrophoresis but complete separation of one enzyme free of the other was not achieved. Extensive purification procedures were not used because both enzymes are unstable. The results confirm published reports that pyruvate lyase contains thiamin and a chromophore which participates in electron transfer. Pyruvate synthase, however, did not appear to be a thiamin enzyme and there was no evidence to indicate participation of an enzyme chromophore in the pyruvate synthase reaction.

Carboxy-Lyases