PubMed Health⌕ Search

Biomedical subjects

A M Arnold

Publications and source records attributed to A M Arnold.

At least 37 records · Page 2Linked to original sources

Gender differences for coronary angioplasty.

To determine if differences in early and late outcome after angioplasty were related to gender or body surface area, 5,000 consecutive patients (1,274 women and 3,726 men) were studied. Baseline variables, procedural outcome, and long-term and event-free survival were assessed. Baseline variables included age, history of hypertension, diabetes mellitus, heart failure, myocardial infarction, prior angioplasty or bypass surgery, familial coronary disease, Canadian heart classification, extent of angioplasty, left ventricular function, and body surface area. Overall and event-free survival (freedom from infarction, repeat angioplasty, bypass surgery and death) were assessed at follow-up. The results showed that, compared with men, women were older (p < 0.0001), had a higher prevalence of diabetes (p < 0.0001), familial coronary disease (p = 0.002), hypertension (p < 0.0001), prior infarction (p = 0.004), and more involvement of the anterior descending artery (p = 0.017). Whereas men had similar extents of angioplasty and worse left ventricular function (p = 0.012), women more often had unstable angina (p < 0.0001). The success rates were similar, yet women had a higher procedural mortality (1.1% women, 0.3% men, p = 0.001). When corrected for body surface area, however, women were at no greater risk than men. Follow-up was complete for 97.4% of patients (mean 4 +/- 2 years). Event-free survival was significantly better in women, even after correcting for body surface area. Men were at higher risk for late death and repeat angioplasty on follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Differential expression of transforming growth factor-beta 1 and beta 3 as well as c-fos mRNA in normal human prostate, benign prostatic hyperplasia and prostatic cancer.

The discrepancy between the incidence of latent prostate cancer and that of clinically overt carcinoma suggests that there can be different courses in the biological progression of prostate cancer. As this cancer is detected increasingly at an infraclinical stage, markers are needed to indicate which lesions will progress and lead to the patient's death. To investigate the possibility that specific growth factors and/or proto-oncogenes are expressed differentially, we measured mRNA levels of transforming growth factors beta 1 (TGF-beta 1), TGF-beta 2 and TGF-beta 3 and of the c-fos and c-jun oncogenes by Northern blotting in normal prostate, benign prostatic hyperplasia (BPH) and prostate cancer. Our data demonstrate that expression of TGF-beta 1 increased, whereas that of TGF-beta 3 fell to an almost undetectable level in carcinoma. Expression of c-fos followed the TGF-beta 1 pattern, whereas no difference could be seen in c-jun expression in cancer as compared with BPH and normal prostate. The differential expression of TGF-beta 1, TGF-beta 3 and c-fos could possibly be used to improve the characterisation of prostate cancer. Long-term follow-up of patients may indicate whether mRNA levels of these growth factors and oncogenes correlate clinically and whether they can be used as markers for progression in human prostate cancer.

Adult↗

Risk stratification for long-term outcome after elective coronary angioplasty: a multivariate analysis of 5,000 patients.

OBJECTIVES: We attempted to develop a statistical model to facilitate risk stratification for long-term outcome after elective coronary angioplasty. BACKGROUND: Our understanding of factors related to long-term outcome after coronary angioplasty is limited. Adequate assessment of risk indexes could potentially lead to more appropriate use of percutaneous revascularization. METHODS: We studied 5,000 consecutive patients and assessed 19 clinical and anatomic variables as predictors of long-term event-free survival. Events were defined as death of any cause, myocardial infarction, bypass surgery or repeat percutaneous transluminal coronary angioplasty. Cox proportional hazards models were used to develop an equation for predicting event-free survival in a subset of 4,000 patients. The equation was validated with the remaining 1,000 patients. Variables that were significantly associated with an adverse outcome in the multivariate model included age > 60 years, extent of disease, Canadian Cardiovascular Society functional class, previous coronary angioplasty, male gender, history of diabetes mellitus, history of hypertension and history of congestive heart failure. RESULTS: The statistical model was used to develop a simplified scoring system, and the patients were assigned to three risk subgroups. Event-free survival curves for the three groups were significantly different (p = 0.0001). High risk patients had worse outcomes for each of the end points compared with low and moderate risk patients (p < 0.02). CONCLUSIONS: We demonstrated that clinical and anatomic variables can be used to risk-stratify long-term outcome after angioplasty, that a simplified scoring system can be used for risk stratification and that high risk patients have a low event-free survival.

Aged↗

Effects of testosterone on skeletal growth in lambs as assessed by labeling index of chondrocytes in the metacarpal bone growth plate.

The effects of testosterone on the epiphyseal growth plate of metacarpal bones of growing sheep were evaluated in 20 rams, 20 wethers, and 20 wethers receiving subcutaneous testosterone replacement therapy. Two animals from each testosterone treatment group were slaughtered at 14-d intervals from 49 to 133 d, and then at 28-d intervals until 217 d, for a total of 10 slaughter ages. Immediately after slaughter, the cannon bones were dissected of extraneous tissue, weighed, and their lengths measured. Growth plates from the metacarpal bones were isolated and explants were cultured for 24 h in medium containing [3H]thymidine. After autoradiography, labeling index was calculated as the ratio of labeled to total nuclei in the resting and proliferative zones of the growth plate. Testosterone increased (P < .03) weight and length of the metacarpal bone. Increased bone length due to testosterone was associated, in part, with a higher (P < .05) labeling index in chondrocytes of the proliferative zone of the growth plate. Labeling indices in the resting zone chondrocytes of rams were higher near the time of puberty. Accelerated growth followed by cessation of growth occurs concurrently with puberty in males of several species and is accompanied by an increase in the blood concentration of testosterone. Testosterone may mediate this accelerated growth by first increasing bone growth and then depleting the source of stem cells in the cartilage growth plate, the site where growth in length of long bones occurs.

Aging↗

The effect of the synthetic retinoid etretinate on sputum cytology: results from a randomised trial.

Laboratory studies, and one previous uncontrolled trial, have suggested that retinoids may reverse bronchial atypia, a putatively premalignant condition. Sputum sampling is a simple, non-invasive method of assessing atypia. Smokers with at least a 15 pack-year history were screened for sputum atypia. One hundred and fifty subjects' were randomised to receive the synthetic retinoid etretinate 25 mg orally or identical placebo daily for 6 months. Compliance was measured by performing pill counts and serum sampling every 2 months for etretinate levels. The outcomes assessed were, improvements in sputum atypia and toxicity. At baseline there was no significant difference between the two groups with respect to gender, smoking history or extent of atypia. Four of 75 subjects on etretinate and six of 75 on placebo dropped out before 6 months. Compliance as measured by pill counts and etretinate levels was high. Eighty-six per cent of subjects on etretinate took 90% or more of their prescribed medication and etretinate was detected in 245 of 264 samples. By contrast etretinate was detected in only six of 266 samples in the control group and probably did not represent true contamination. After 6 months on etretinate there was no difference in the degree of atypia between the two treatment arms. Toxicity was mild in both groups with considerable placebo effect noted. Etretinate, at the dose used in this study, had no impact on sputum atypia as detected by sputum sampling.

Administration, Oral↗

Energetic efficiency of rats fed low or high protein diets and grown at controlled rates from 80 to 205 grams.

Energetic efficiency of protein and lipid deposition was estimated based on the data from 53 rats fed purified diets. Intercepts of equations relating energy gain to metabolizable energy intake were different (P less than 0.002) for rats fed diets that contained 10 and 20% casein, so that metabolizable energy for maintenance was 118 and 108 kJ/day, respectively. Surprisingly, in view of the supposedly greater efficiency of lipid deposition, energetic efficiency above maintenance was constant at 0.38 +/- 0.02. Part of the reason is that composition of body gain was much less rigidly tied to daily energy intake--even across the wide range of data in this experiment--than is necessary to quantify reliably such an effect. Two methods of quantifying partial energetic efficiencies of protein and lipid deposition gave results that were comparable to previous estimates of about one-third and two-thirds, respectively. One of the methods used a more biological model but failed to fit data for rats fed the 10% casein diet. Because traditional statistical methods are unlikely to be extended much further to account for the many unsolved problems associated with estimating partial efficiencies, systems based at tissue and cellular levels are necessary to model detailed differences in energy utilization.

Animals↗

Chemoprevention for lung cancer--evidence for a high degree of compliance.

Studies of treatment efficacy are important for the development of cancer chemoprevention strategies. Recruitment aims for motivated, compliant subjects. The Concerned Smoker Study targets smokers with at least a 15-pack-year history and bronchial atypia on sputum sampling. Subjects receive etretinate 25 mg daily or identical placebo and are followed for 6 months. Compliance was monitored by assessing timely return for follow-up visits, return of monthly sputum samples, pill counts, and serum etretinate levels. Contamination, in the control group, was assessed by measuring etretinate levels. With half of the subjects having completed the study, this report assesses compliance: 88% follow-up visits occurred on schedule with only 9 missed visits of a possible total of 380; 443 (97.1%) of 456 possible sputum samples were returned. Pill counts indicated a high degree of compliance which was supported by the serum etretinate levels. Contamination was insignificant. The results suggest a very high degree of compliance. Only minor protocol changes will be required.

Etretinate↗

Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial.

The survival benefit of combination chemotherapy to patients with advanced non-small-cell carcinoma of the lung (NSCLC) is controversial. To study this question, the National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a prospective randomized trial comparing best supportive care (BSC) to two chemotherapy regimens, vindesine and cisplatin (VP), and cyclophosphamide, doxorubicin, and cisplatin (CAP). Between February 1983 and January 1986, 23 centers across Canada entered 251 patients on study. Eighteen centers participated in the three-arm schema (150 patients); centers choosing not to participate in a study with a no-chemotherapy arm followed a two-arm schema comparing VP with CAP (101 additional patients). Altogether, 233 patients were eligible. Patients had measurable or evaluable disease, with either distant metastases (82.5%) or bulky limited disease considered inoperable or unsuitable for radical radiotherapy. The treatment groups were comparable in terms of age, sex, performance status, histology, disease extent, and weight loss. The overall response rates (complete response [CR] plus partial response [PR]) on the chemotherapy arms were CAP, 15.3%, and VP, 25.3% (P = .06). Patients on the three-arm portion of the trial had a median survival of 32.6 weeks when treated with VP, 24.7 weeks with CAP, and 17 weeks with BSC. The significance of the differences in survival, adjusted for prognostic factors, is as follows: chemotherapy v BSC, P = .02; VP v BSC, P = .01; and CAP v BSC, P = .05. Toxicity on the chemotherapy arms was significant, with leukopenia of severe or greater degree occurring in 37.8% (CAP) and 40.0% (VP), severe vomiting in 12.2% (CAP) and 23.3% (VP), and severe neurotoxicity in 15.6% (VP).

Antineoplastic Combined Chemotherapy Protocols↗

Effects of gender, time of castration, genotype and feeding regimen on lamb growth and carcass fatness.

Two concurrent trials were conducted to examine the effects of gender, time of castration, genotype and feeding regimen on lamb growth rate and carcass fatness. Trial 1 compared Polypay and Coopworth x Polypay male lambs either left intact or castrated early, mid or late in growth. Trial 2 compared Hampshire-sired lambs (females, early castrate wethers and late castrate wethers) from Suffolk x Coopworth dams and whiteface x Coopworth dams. Gender and time of castration significantly affected growth rate in Trial 1 but not in Trial 2. Rams were more efficient than wethers, but no other gender or time of castration effects on feed efficiency were observed. Delaying castration and pasture grazing both reduced fatness. Lambs grazed on irrigated pastures until they weighed 41 kg then finished in drylot had a lower dressing percentage than lambs fed in the drylot throughout, but USDA quality grades were similar. Substitution of Polypay genes by Coopworth genes in crossbred lambs did not significantly alter any of the fatness traits measured but increased ribeye area. Hampshire-sired lambs grew faster than whiteface lambs, particularly in drylot. They had a higher dressing percentage without increased fatness, apparently because of greater muscling in ribeye and leg.

Adipose Tissue↗

Influences of gender, time of castration, genotype, birthtype and feeding regimen on lamb longissimus fiber type proportions.

Two trials examined genetic and environmental influences on muscle fiber type proportions. Trial 1 compared Polypay and Coopworth x Polypay male lambs either left intact or castrated early, mid or late in growth. Trial 2 compared Hampshire-sired lambs (females, early castrate wethers and late castrate wethers) from Suffolk x Coopworth dams and whiteface x Coopworth dams. Half the lambs in each trial were raised from weaning to 52 kg slaughter weight in drylot; the other half were reared to 41 kg on pasture before being finished in drylot. Analysis of longissimus tissue samples revealed no significant differences among rams, wethers and ewes in proportions of muscle fiber types. Early castration increased the proportion of alpha red fibers in Trial 1 (P less than .01) but not in Trial 2. Polypay lambs had a higher proportion of beta red fibers (P less than .05) than the Coopworth x Polypay lambs, but no differences were seen between the genotypes of Trial 2. Single-born lambs in Trial 1 had a 6% higher proportion of alpha white fibers (P less than .05) than twin-born lambs; however, this difference was not detected in Trial 2. Drylot lambs had a higher proportion of beta red fibers than pasture-reared lambs, the difference being 5% (P less than .01) in Trial 2. Muscle fiber type proportions were not found to be related to growth rate and carcass fatness, and no evidence of differential fiber transformation was found in this trial.

Animals↗

Late recurrence in Hodgkin's disease: a report of two cases.

Two cases of Hodgkin's disease are described who relapsed 22 and 19 years after regional radiation therapy. One of the patients also developed a carcinoma of the large bowel soon after first relapse. The importance of long follow-up and documentation of cause of death in Hodgkin's disease is stressed.

Adult↗

Retinoblastoma, eosinophilic granuloma, and malignant melanoma: a case report.

The case history of a patient treated for unilateral hereditary retinoblastoma who subsequently developed malignant melanoma and eosinophilic granuloma is presented. Although the association between retinoblastoma and second malignancies including malignant melanoma is established, we have found no reports of third malignancies occurring in such individuals.

Adult↗

Combination chemotherapy using high or low dose methotrexate for small cell carcinoma of the lung--a randomised trial.

Eighty-three patients with histologically proven small cell carcinoma of the lung were entered into a prospective randomised clinical trial to evaluate two induction regimes. A 'low' dose methotrexate regime which employed three cycles of etoposide, adriamycin and methotrexate given at conventional dosage was compared with a regime which employed three cycles of etoposide and adriamycin together with five courses of high dose methotrexate and folinic acid rescue. All patients achieving a complete response (CR) received prophylactic cranial irradiation. Patients with limited disease who achieved a CR received additional radiotherapy to the primary site. An alternative four drug regime (procarbazine, vincristine, cyclophosphamide and CCNU) was evaluated in patients failing to achieve or subsequently relapsing from a complete response. Response rates for the low dose and high dose methotrexate arms were 54 and 55% respectively with median survivals of 8.6 and 9.7 months. Median survival for complete and partial responders was 20.2 and 11 months respectively. The alternative four drug regime showed limited activity in patients failing to achieve a complete response after primary therapy. We conclude that high dose methotrexate as used in this study has no role in small cell lung cancer. The 'low' dose regime was well tolerated by outpatients, is effective and is suitable for generalised use in the palliation of small cell lung cancer.

Aged↗

Epileptic seizures associated with cisplatin administration.

Eighty-one patients with germ cell tumors or ovarian carcinoma were treated over a 4-year period with cisplatin-containing combination chemotherapy. Eight patients (9.8%) experienced epileptic seizures during or within 3 months of this chemotherapy. While a definite causal relationship between the seizures and cisplatin could not be established, we have rarely seen such episodes in relationship to other cytotoxic drugs. A number of possible contributing factors were apparent, including hyponatremia and pretreatment impairment of renal function.

Adult↗