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Biomedical subjects

C Orton

Publications and source records attributed to C Orton.

At least 37 records · Page 2Linked to original sources
PubMed1991

Neonatal calves develop airflow limitation due to chronic hypobaric hypoxia.

Neonates and infants presenting with pulmonary hypertension and chronic hypoxia often exhibit airway obstruction. To investigate this association, we utilized a system in which neonatal calves are exposed to chronic hypobaric hypoxia and develop severe pulmonary hypertension. For the present study, one of each pair of six age-matched pairs of neonatal calves was continuously exposed to hypobaric hypoxia at 4,500 m (CH); the other remained at 1,500 m. At 2 wk of age, mean pulmonary arterial pressure (MPAP), dynamic lung compliance (Cdyn), resistance (RL), and static respiratory system compliance (Crs) were measured at 4,500 m in both CH and control calves exposed acutely to hypoxia (C). These measurements were repeated after cumulative administrations of nebulized methacholine (MCh). Tissues were removed for histological examination and assessment of bronchial ring contractility to MCh and KCl. After 2 wk of hypobaric hypoxia, MPAP (C 35 +/- 1.7 vs. CH 120 +/- 7 mmHg, P less than 0.001) and RL (C 2.64 +/- 0.16 vs CH 4.99 +/- 0.47 cmH2O.l-1s, P less than 0.001) increased. Cdyn (C 0.100 +/- 0.01 vs. CH 0.082 +/- 0.007 l/cmH2O) and Crs (CH 0.46 +/- 0.003 vs. C 0.59 +/- 0.009 l/cmH2O) were not significantly different. Compared with airways of C calves, airways of CH animals did not exhibit in vivo or in vitro MCh hyperresponsiveness; however, in vitro contractility to KCl of airways from CH animals was significantly increased. Histologically, airways from the CH calves showed increases in airway fibrous tissue and smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1988

Separating output factor into collimator factor and phantom scatter factor for megavoltage photon calculations.

Output factor has been used in megavoltage dosage calculations because collimator factor and backscatter factor are considered individually indeterminable. Output factor reflects the normalized product of backscatter factor and collimator factor for the most common treatment geometry. A method has been found for independently measuring collimator factors for megavoltage photons. Using a build-up cap of high density tissue equivalent material, we have measured the relative collimator factors for various units with photon energies up to 15 MV. Utilizing measured values for output factor and collimator factor relative backscatter factors have been determined.

Humans↗
PubMed1986

Randomized study of Corynebacterium parvum adjuvant therapy following surgery for (stage II) malignant melanoma.

One hundred and fifteen patients with histologically proven primary cutaneous melanoma were entered into a randomized prospective study following surgical removal of clinically obvious regional metastases. The study started in 1977 and was completed in June 1982. Fifty-eight patients (10 with regional skin metastases and 48 with regional node metastases) were in the control group and 57 (15 regional skin, and 42 regional node metastases) received adjuvant C. parvum. Other clinical features were well balanced for each group. C. parvum, 2 mg/m2 IV was repeated eight times at three weekly intervals. The schedule was based on previous work which indicated significant increase in killer cell activity. There was no serious toxicity and 22 patients exhibited tachyphylaxis. Seventeen patients in the control group (11 tumour free) are alive at 24-80 months, and 20 patients in the C. parvum group (12 tumour free) are alive 24-76 months from randomization. No statistically significant difference (P greater than 0.05) was observed between the two patient groups for overall survival (median 26 months) or relapse free survival (median 8 months) from the date of randomization. Nor was the overall survival from the date of primary surgery (median 52 months, range 4-237) or the relapse free survival, median 28 months, range 2-225, significantly different between the two groups of patients. The relapse pattern in the two groups, and survival after relapse were no different though the response rate to actinomycin D and DTIC chemotherapy was significantly higher in the control (48 per cent) than in the C. parvum (23 per cent) group. Toxicity to chemotherapy was not significantly affected by previous C. parvum treatment. Although there were trends for better survival, in the C. parvum patient group, statistically significant activity has not been noted in this study.

Adjuvants, Immunologic↗
PubMed1986

Corynebacterium parvum followed by chemotherapy (actinomycin D and DTIC) compared with chemotherapy alone for metastatic malignant melanoma.

Seventy-nine patients with Stage III widely metastatic melanoma were prospectively randomised to a 'no treatment' control group who received on tumour progression DTIC (250 mg/m2 i.v. daily X 5) and Actinomycin D 1.5 mg/m2 on Day 1. A total of six courses at 3-week intervals was given. Chemotherapy was only given on progression of disease. The other group received initially Corynebacterium parvum (2 mg/m2) every 3 weeks for a maximum of eight courses and then the same chemotherapy on evidence of progressive disease. Minimum follow up time is 3 yr. The chemotherapy response rate (control 37%, C. parvum 24%) was not statistically different nor was the effect of chemotherapy on the site of individual metastases. Radiotherapy responses for irradiated soft tissue disease again were not significantly different, between the two patient groups. No significant differences in survival (control group median, 4 months, range 1-46; C. parvum median 3 months range 1-35) were observed and only one patient is alive at 35 months. The pattern of relapse was also similar in both groups. Reduction in haematological toxicity consequent on chemotherapy was not observed in the C. parvum-treated patients. No additional benefit was observed when C. parvum was followed by DTIC and Actinomycin D chemotherapy compared with the results from the chemotherapy given alone, although C. parvum on this schedule had minimal toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Nasal carriage and antibiotic susceptibility of Staphylococcus aureus in general practice.

The incidence of nasal carriage of Staphylococcus aureus and the in vitro susceptibility of isolates to fusidic acid, penicillin, erythromycin, methicillin and tetracycline was determined in 204 patients who had been treated previously with a short course of a topical preparation of Fucidin for acute skin sepsis, and in an equal number of control subjects. Staphylococcus aureus was isolated from 36 per cent and 34 per cent of patients in the Fucidin and control groups respectively. Only one of the 144 isolates was resistant to fusidic acid. Short, single courses of topical therapy in general practice are unlikely to be epidemiologically hazardous in the long term. Evidence of possible cross-infection in general practice was obtained.

Administration, Topical↗
PubMed1975

Venous diversion trapping and growth of blood-borne cancer cells en route to the lungs.

A proportion of W-256 tumour cells injected intravenously into a tail vein of the rat are diverted into venous plexuses en route to the lungs; here tumour cells remain trapped, proliferate and form invasive solid tumours in the pelvis and hindquarters, which cause paraplegia, metastases and death. Also, cells trapped in veins produce tumour nodules distributed along the length of the tail; this effect in markedly enhanced by temporarily arresting the outflow of blood from the tail for a few seconds only immediately after cells are injected. Continous monitoring of the radioactive signal over the lungs after W-256 cells labelled with 125IUDR were injected showed that massaging the tail or intravenously injecting isotonic saline into the tail dislodged cells trapped in veins. In heparinized rats, tail trapping was markedly reduced, although not entirely abolished, and venous trapping in vertebral and pravertebral regions was decreased. The anatomical distribution of growth of the trapped cells in rats closely resembled metastases involving dissemination via the "vertebral venous system" produced by certain cancers in man. Labelled tumour cells trapped in the lungs of untreated mature rats commenced dying rapidly in situ wiht 1-2 h after injection; the majority had disappeared within 24 h, and less than 1% of the injected tumour cells survived to form lung colonies. Experimental evidence is presented which indicates that the lungs play a vital role in rapidly eliminating a high proportion of blood-borne cancer cells in the adult individual.

Animals↗
PubMed1974

Promotion of growth of tumour cells in acutely inflamed tissues.

Acute inflammatory reactions were induced in rats by the intravenous injection of cellulose sulphate (CS) or an extract of normal rat lung homogenate (LH), or by intraperitoneal injections of Compound 48/80. These treatments greatly increased survival and clonogenic growth in the lungs of rats of intravenously injected allogeneic W-256 and Y-P388 tumour cells. Increase in the dose of intravenously injected CS caused a logarithmic increase in colony forming efficiency (CFE) of tumour cells in the lungs. CFE was not stimulated by the intravenous injection of rats with pharmacological mediators of inflammation (histamine, 5-hydroxytryptamine, bradykinin and prostaglandins PGE(1) and PGF(2α)) which are released from tissues by agents which induce inflammation. Stimulation of CFE by CS occurred in adrenalectomized rats but was inhibited by treatment of rats with an anti-inflammatory steroid, dexamethasone. CFE was stimulated by CS in tumour immunized rats; the inflammatory state did not prevent the expression of immunity but "rescued" a proportion (approximately 20%) of the injected tumour cells from immunodestruction in the lungs. A higher proportion of tumours grew in the paws of rats when a small number of W-256 cells were injected interdigitally into the acute inflammatory swellings produced by the local injection of paws with LH or CS.CS is a "synthetic heparin" which causes marked prolongation of blood clotting time and also increases fibrinolytic activity of the blood. Anticoagulant treatment of rats with heparin did not affect CFE. Thus, there was no direct correlation between blood clotting time and CFE of blood borne tumour cells in the rat.The mechanisms which may be responsible for the nonspecific growth promoting effects of inflammatory reactions induced by various types of tissue injury on tumour induction and growth are discussed.

Adrenalectomy↗
PubMed1974

Reduction by anti-inflammatory corticosteroids of clonogenic growth of allogeneic tumour cells in normal and irradiated tissues of the rat.

Anti-inflammatory corticosteroids administered to rats in high dosages before intravenous injection of allogeneic tumour cells caused 5-10 fold reductions in "take" and clonogenic growth of the cells in lung and kidney and decreased growth and spread of the cells transplanted to leg muscle. Steroid therapy also reduced the effect of local irradiation of lung tissues in increasing tumour colony efficiency (CFE) in the lungs; it also tended to reduce similar effects of sublethal whole body irradiation. A non-steroidal anti-inflammatory drug, phenylbutazone, also reduced CFE in locally irradiated lungs in the rat.The results obtained indicate that corticosteroids do not stimulate the growth of implanted tumour cells by suppressing host immunity but decrease their clonogenic growth by inhibiting local inflammatory reactions to cell arrest, and similarly to local tissue damage caused by x-irradiation; it is asserted that such inflammatory reactions are growth promoting and thereby stimulate regeneration of stroma (repair) and also support survival and early growth of the tumour cell.

Animals↗
PubMed1973

Macrocolony assays in the rat of allogeneic Y-P388 and W-256 tumour cells injected intravenously: dependence of colony forming efficiency on age of host and immunity.

Two rapidly growing allogeneic tumours, sublines of Yoshida (Y-P388) and Walker (W-256) injected intravenously in single cell suspensions produced tumour macrocolonies in the lungs of rats within 7 days. Y-P388 produced similar but fewer colonies in the kidneys. Colony forming efficiency (CFE) in lung was high in weanling rats given either sublethal whole body irradiation (WBI) or a single dose of rabbit anti-rat lymphocytic serum (ALS) to suppress immunity. In immunologically intact weanlings CFE was much lower and many 7-day old colonies showed signs of regression. CFE for primary tumour cell challenges decreased rapidly and markedly with increase in age of host during the first 1-2 weeks after weaning. This resistance to growth of a primary challenge in lungs of older rats was not significantly reduced by WBI but was decreased by ALS. CFE of a secondary challenge of tumour cells injected intravenously in rats which had been previously immunized with heavily irradiated (HR) tumour cells was very low; it was not significantly increased by WBI but was moderately increased by ALS. In weanling rats given lethal (900 rad) WBI, 1 hour before intravenous injection of tumour cells, treatment with bone marrow (BM) cells derived from normal adult donors increased CFE, whereas BM (or spleen) cells from immunized donors decreased CFE. The results suggest that ALS and WBI not only increase tumour CFE by suppressing immunity to tumour growth but also "condition" host tissue (tumour bed) in such a way as to facilitate the survival, "take" and initial replication of grafted tumour cells before the rats recover from the immunosuppressive effects of these treatments.

Age Factors↗
PubMed1973

Stimulation of clonogenic growth of tumour cells and metastases in the lungs by local x-radiation.

Single cell suspensions of two allogeneic tumours (W-256 and Y-P388) injected intravenously produced macrocolonies in the lungs of rats. Colony forming efficiency (CFE, the number of colonies produced by each viable cell injected) was low in 6-week or older rats but was markedly increased by 1000-1500 rad local thoracic irradiation (LTI) given 7-14 days before the tumour cell injection, or by antilymphocytic serum (ALS) but not by sublethal whole body irradiation (WBI). Similarly, LTI increased the incidence of pulmonary metastases produced by a solid tumour growing in the leg muscle. Stimulation of CFE by LTI was a strictly local phenomenon and not due to effects of irradiation on thymus, spleen or other tissues of the rat. LTI failed to increase CFE in immunized rats. It is concluded that (1) LTI stimulates clonogenic growth of tumour cells arrested in the lungs, by causing inflammatory reactions accompanied by regenerative cellular proliferation of lung tissue, which increases the "plating" efficiency of tumour cells, (2) the increase in CFE in lungs is not due to suppression of immunity to tumour growth by LTI.

Animals↗
PubMed1972

Production of metastases by a primary tumour irradiated under aerobic and anaerobic conditions in vivo.

The effect of local irradiation of a rapidly metastasizing sarcoma in the leg of the rat was measured in terms of (a) regression of the primary tumour and (b) growth of metastases produced in lymph nodes and lungs, by dissemination occurring after irradiation of the primary tumour. These effects on rats which had been irradiated while breathing air were compared with rats breathing 10% O(2)/90% N(2) in which a tourniquet had been applied proximal to the tumour to arrest blood flow during irradiation. Tourniquet anoxia increased radioresistance of growth of primary tumour by (OER) factors of 2·9-3·3. Corresponding factors for inhibition of growth of metastases in abdominal lymph nodes, and for the reduction in incidence of lung metastases produced by single tumour cells, were 2·7 and 2·4 respectively. These results suggest that this tumour was radiobiologically well oxygenated when it was irradiated in a poorly vascularized stage of growth where tumour necrosis had developed.

Aerobiosis↗