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Biomedical subjects

C Wright

Publications and source records attributed to C Wright.

At least 325 records · Page 18Linked to original sources
PubMed1986

Syndrome X: the haemodynamic significance of ST segment depression.

The relation between chest pain, ST segment depression, and changes in left ventricular function was assessed in six patients with angina, a positive exercise test, and normal coronary arteries as assessed by arteriography (syndrome X). In the six patients with syndrome X and in six controls there was no significant rise in pulmonary artery diastolic pressure during treadmill exercise, although there was ST segment depression (range 1-4.5 mm) in the patients with syndrome X. In 19 patients with coronary artery disease, however, the pulmonary artery diastolic pressure increased by a median 5 mm Hg (range 0-13.6 mm Hg) on treadmill exercise. In only one patient with coronary artery disease, who showed 1 mm ST segment depression, was there no rise in pulmonary artery diastolic pressure. During ambulatory monitoring in patients with syndrome X there were 12 episodes of ST segment depression (greater than 1 mm) (4 painful, 8 painless) in which there was no change in pulmonary artery diastolic pressure. In the patients with coronary artery disease there were 29 episodes of angina during ambulatory monitoring and during all of them pulmonary artery diastolic pressure rose by a median 7.5 mm Hg (range 1.8-19.7 mm Hg). Unlike the haemodynamic changes that usually occur during myocardial ischaemia in coronary artery disease, chest pain and ST segment changes in patients with syndrome X are not associated with impaired left ventricular function as assessed by ambulatory pulmonary artery pressure monitoring.

Ambulatory Care↗
PubMed1986

The haemodynamic response to myocardial ischaemia in ambulant patients with variant angina.

The haemodynamic response to myocardial ischaemia in patients with variant angina during ambulatory activity is unknown. Ambulatory pulmonary artery pressure monitoring with a transducer tipped catheter and simultaneous frequency modulated electrocardiograms was used to assess changes in left ventricular function in five male patients (mean age 51.8 years) during variant angina; four patients had coronary artery stenosis and one had normal coronary arteries. Two hundred and seventy hours of ambulatory recordings were analysed. Twenty episodes (12 painful, 8 silent) of ST segment change greater than 1 mm occurred. Episodes tended to occur more frequently in the early morning hours. Six episodes of painful ST elevation were associated with a rise in pulmonary artery diastolic pressure. In the remaining episodes ST segment elevation was of shorter duration and there was no rise in pulmonary artery diastolic pressure. Pain was usually a late feature. Silent ST segment elevation occurred at rest and pulmonary artery diastolic pressure increased in all but one episode. Silent exertional ST segment depression was associated with a greater increase in pulmonary artery diastolic pressure than that seen during ST segment elevation. ST segment depression preceded or followed ST segment elevation in two episodes. The onset of ST segment elevation nearly always preceded the onset of a rise in pulmonary artery diastolic pressure. Ergometrine maleate provocation produced a rise in pulmonary artery diastolic pressure in three patients. In one there was no response to 1000 micrograms but spontaneous episodes of ST segment elevation were recorded during ambulatory monitoring. Treadmill exercise resulted in both ST segment elevation and depression with a similar haemodynamic response during both types of electrocardiographic change. When there is important coronary artery disease in two or more vessels ST segment changes may occur in different territories during treadmill exercise and during spontaneous episodes. Ambulatory pulmonary artery diastolic pressure monitoring is a useful technique for the investigation of variant angina.

Adult↗
PubMed1986

The haemodynamic significance of asymptomatic ST segment depression assessed by ambulatory pulmonary artery pressure monitoring.

A transducer-tipped catheter with simultaneous frequency modulated electrocardiograms and a miniaturised tape recorder was used to record ambulatory pulmonary artery pressure for 24-48 hours in 19 men (mean age 57.7) with clinical and angiographic evidence of coronary artery disease. Sixty seven episodes of ST segment depression (greater than 1 mm) were recorded. Thirty five were accompanied by pain of which six occurred at night; in 34 pulmonary artery diastolic pressure rose significantly. In all but two of the 32 episodes of painless ST segment depression (four of which were at night) there was a significant rise in pulmonary artery diastolic pressure. No such rise was found in six normal subjects during exertion. ST segment changes tended to occur before (24 episodes) or at the same time (27 episodes) as changes in pulmonary artery diastolic pressure. ST segment depression followed an increase in pulmonary artery diastolic pressure in only 13 episodes. The times to maximum ST depression and maximum pulmonary artery diastolic pressure rise were similar. Painful and painless ST segment depression could not be distinguished on the basis of the configuration of the ST segment or in terms of the changes in the pulmonary artery diastolic pressure.

Aged↗
PubMed1986

Polyamines and autocrine control of tumor growth by prolactin in experimental breast cancer in culture.

We have previously observed that both polyamines and an autocrine mechanism are involved in the stimulation by ovine PRL (oPRL) of growth of the N-nitrosomethylurea-induced rat mammary tumor cultured in vitro in the soft agar clonogenic assay. These experiments were designed to test the interaction between these two pathways of oPRL action in this system. In agreement with previous findings in our laboratory, conditioned medium obtained from oPRL-treated (oPRL-CM), but not untreated, tumors consistently stimulated colony formation when added to N-nitrosomethylurea mammary tumors plated in soft agar under serum-free medium conditions. Administration of alpha-difluoromethyl-ornithine (DFMO), an irreversible inhibitor of polyamine biosynthesis, abolished the colony-stimulating effect of oPRL-CM. The inhibitory effect of DFMO was reversed in a dose-dependent fashion by the addition of spermidine, which entirely restored the growth-promoting action of oPRL-CM. In addition, the administration of increasing amounts of spermidine potentiated the colony-stimulating effect of suboptimal concentrations of oPRL-CM. In contrast, manipulation of the polyamine environment with DFMO and/or spermidine administration did not affect the number of colonies formed when conditioned medium from untreated tumors was added instead of oPRL-CM. We conclude that the polyamine pathways plays an essential role in the expression of autocrine control of tumor growth by oPRL.

Animals↗
PubMed1986

Autocrine stimulation by estradiol-regulated growth factors of rat hormone-responsive mammary cancer: interaction with the polyamine pathway.

We have recently shown that the integrity of the polyamine pathway is essential but not sufficient for expression of the mitogenic effect of estradiol (E2) in the N-nitrosomethylurea-induced rat mammary tumor grown in vitro in the soft agar clonogenic assay. To elucidate the mechanism of E2 action in this system, we tested whether E2 may stimulate tumor growth through induction of secretory growth factor(s), as already proposed for human breast cancer cell lines in culture. Furthermore, we investigated the potential interaction between such "autocrine" control of tumor growth by E2 and the polyamine pathway. Conditioned medium obtained from E2-treated tumors (E2-CM) but not from control tumors (C-CM) consistently stimulated colony formation when added to N-nitrosomethylurea-mammary tumors plated in soft agar under serum-free media conditions. Such growth-promoting effects of the E2-CM was found to increase with increasing protein concentrations of the medium and was abolished by pretreatment of the medium with concanavalin A, heat, and trypsin. The addition of the polyamine biosynthetic inhibitor alpha-difluoromethylornithine (1 mM) totally abolished the colony-stimulating effect of the E2-CM. Exogenous administration of spermidine (0.1 mM) reversed the inhibitory effect of alpha-difluoromethylornithine on colony formation and restored the action of the E2-CM. Although the addition of polyamines alone did not affect the number of colonies formed, the administration of spermidine was found to significantly enhance in a dose-dependent fashion the colony-stimulating effect of suboptimal concentrations of E2-CM. Attempts to identify the E2-inducible growth factor in the E2-CM and in N-nitrosomethylurea-mammary tumor specimens using monoclonal antibodies raised against the Mr 52,000 E2-inducible protein gave negative results. We conclude that autocrine stimulation of tumor growth by E2 is not limited to human breast cancer cell lines but also occurs in individual experimental mammary tumors grown in soft agar. Our results show that the polyamines must be present for the expression of this "autocrine" control of tumor growth by E2. Finally, the identity of the E2-induced growth factor operating in our system remains to be determined.

Animals↗
PubMed1986

Polyamines and hormonal regulation of N-nitrosomethylurea-induced rat mammary tumor growth in vivo.

We have observed that polyamines play an essential role in the expression of hormonal action on the growth of the N-nitrosomethylurea-induced mammary tumor cultured in soft agar. Since polyamine levels cannot be measured in this system, we could not determine whether tumor polyamine pools are under endocrine control. To test this hypothesis, the following experiments were conducted in N-nitrosomethylurea tumor-bearing rats in vivo. Both tamoxifen administration (200 micrograms/day) and ovariectomy produced dramatic reductions in tumor growth but neither treatment significantly altered tumor polyamine levels after either 7 or 21 days of treatment. Some decrease in tumor level of putrescine, spermidine, and spermine was observed 21 days after ovariectomy but it was not statistically significant. Exogenous administration of putrescine (300 mg/kg/day) reversed the antitumor effect of tamoxifen but did not prevent tumor regression induced by ovariectomy. This effect of putrescine was, however, variable in magnitude from experiment to experiment. To test whether the reversal of tamoxifen effect by putrescine might simply be due to interference with tamoxifen uptake by the tumor cells, we measured estrogen and progesterone receptors in the tumors of rats chronically treated with tamoxifen and tamoxifen plus putrescine. In both groups estrogen receptors are virtually undetectable, thus suggesting that putrescine had not inhibited tamoxifen entry into the cells and binding to estrogen receptors. Progesterone receptor levels were similarly high in both groups and not significantly different from control. These results indicate that at least under these experimental conditions N-nitrosomethylurea mammary tumor polyamine pools are not under ovarian hormone control. The mechanism by which putrescine reverses tamoxifen's effect remains unclear.

Animals↗
PubMed1986

Promotion by prolactin of the growth of human breast neoplasms cultured in vitro in the soft agar clonogenic assay.

The role of prolactin (PRL) in supporting the growth of human breast cancer is still unclear. The ability to grow primary breast cancer specimens in the soft agar clonogenic assay in the absence of serum gave us the opportunity to evaluate the growth-promoting effect of PRL and to compare it to that of estradiol in the same tumor samples. PRL was tested both at physiological concentrations (20 ng/ml) as well as in pharmacological amounts (200 ng/ml) comparable to circulating blood levels in hyperprolactinemic states. Estradiol was simultaneously tested in physiological amounts (10(-8)M). In 17 infiltrating ductal carcinomas, the lower dose of PRL stimulated colony formation to 126 +/- 5.2% (SE) of control, while the higher dose increased colony number to 159 +/- 10.4% of control. This latter effect was comparable to that observed with estradiol (159 +/- 8.5% of control). The effect of PRL was more pronounced in estrogen receptor-positive tumors. Nine of ten estrogen receptor-positive tumors were PRL sensitive, while three of seven estrogen receptor-negative tumors exhibited a clear response to PRL administration. PRL did not stimulate colony formation in a malignant cystosarcoma phylloides and in two benign lesions (fibroadenoma and fibrocystic disease). We conclude that, at least under the conditions of the soft agar clonogenic assay, PRL exerts a dose-dependent growth-promoting effect on human breast cancer. Such effect is comparable to that of estradiol when PRL is added in concentrations similar to circulating blood levels in hyperprolactinemic patients.

Adult↗
PubMed1985

Abnormal behavioural changes associated with vasopressin-induced barrel rotations.

Arginine-8-vasopressin (AVP) was injected into the cerebral ventricles of rats in order to characterize the dose-response relations of the convulsant actions of AVP and to obtain a detailed description of other acute behavioural effects. The incidence of barrel rotations, a violent and apparently uncontrolled motor activity during which rats rotate about their long axis, was found to be dose dependent, with a threshold of between 1 and 10 ng per rat. Other behavioural effects of AVP including immobility, titubation, ataxia, backward walking, and inhibition of exploratory activities and of grooming were seen at doses as low as 100 pg. These behavioural effects occurred within 9 min after injection, and thus have the same time course as barrel rotations. These acute actions of AVP may be significant in interpreting the effects of AVP on cognitive processes and memory and should also be taken into consideration in the clinical use of AVP as an anti-amnestic.

Animals↗
PubMed1985

Screening for cervical and breast cancer among Caribbean immigrants.

The yield of abnormal Pap tests was 13.3/1000 women screened; the yield of breast cancer was 2.2/1000 women examined. Approximately half of the Haitian immigrants (N = 361) had no prior Pap test, compared to one-quarter of the English-speaking Caribbean immigrants (N = 228) and one-tenth of the U.S.-born Black women (N = 264). Only 47% of Haitian women had a regular source of health care compared to 74% of the English speaking Caribbean women and 83% of the U.S.-born Black women. Haitian women were much less likely to practice breast self-examination or to use contraception than were U.S.-born Black women. This program reveals significant needs for preventive health services among low-income Caribbean immigrant women, and demonstrates that selective neighborhood-site programs can be effective in reaching those in need.

Breast Neoplasms↗
PubMed1985

Polyamines and estrogen control of growth of the NMU-induced rat mammary tumor.

Recent in vitro evidence suggests that polyamines play an important role in the growth of the N-nitrosomethyl-urea (NMU)-induced rat mammary tumor, and that they may be involved in mediating the effect of estrogens on tumor growth. In support of this hypothesis, we here show that inhibition of polyamine biosynthesis with alpha-difluoromethyl-ornithine (DFMO) blocks the mitogenic effect of estradiol-17 beta (E2) added to NMU-mammary tumors grown in soft agar in the presence of the antiestrogen tamoxifen (Tam). Exogenous polyamine administration reversed the inhibitory effect of DFMO and restored E2 action. Administration of polyamine inhibitors to NMU-tumor-bearing rats induced significant inhibition of tumor growth, although tumor ornithine decarboxylase (ODC) was not consistently suppressed. Under our experimental conditions, such treatment did not potentiate the antitumor effect of Tam. Tam alone was found to suppress tumor ODC, suggesting a possible involvement of the polyamine pathway in its antitumor action. These data suggest that the polyamines may play an important role in the hormonal control of the growth of this experimental breast cancer.

Animals↗
PubMed1985

Intradural cyst with compression of the cauda equina in ankylosing spondylitis.

A cauda equina syndrome complicating long-standing ankylosing spondylitis was found to be due to a large multiloculated cyst. This differed from posterior dural diverticula identified in similar cases in that the cyst filled the lumbar canal with erosion of the upper lumbar vertebral bodies and chronic inflammatory changes were evident in the cyst wall. Cauda equina compromise in ankylosing spondylitis has several possible mechanisms including fibrosis following arachnoiditis, root damage by dural diverticula, and direct compression by arachnoid cyst.

Aged↗
PubMed1985

Effects of combined alpha and beta adrenoceptor blockade in patients with angina pectoris. A double blind study comparing labetalol with placebo.

The effects of a combined alpha and beta receptor antagonist, labetalol, were investigated in 10 patients with chronic stable angina pectoris. The optimal dose was determined during an initial dose titration study when the patients were treated with 200 mg, 400 mg, and 600 mg (six patients) of labetalol a day. The effective dose was then compared with placebo in a double blind randomised study. The effects of the drug were monitored with angina diaries, treadmill exercise testing, and 48 hour ambulatory electrocardiographic ST segment monitoring. Plasma labetalol concentrations were measured during each treatment period. The mean effective antianginal dose of labetalol was 480 (SD 140) mg/day given by mouth twice a day. There was a dose related reduction in daytime and nocturnal heart rate, the frequency of pain was significantly reduced by 41%, and exercise duration was significantly increased by 44% with labetalol when compared with placebo. The frequency and duration of the episodes of ST segment depression were significantly reduced by 56% and 73% respectively with labetalol. Adverse effects resulted in a reduction of the dose of labetalol in two patients. Thus labetalol is an effective agent in the treatment of angina pectoris.

Adult↗
PubMed1985

Morphology of ambulatory ST segment changes in patients with varying severity of coronary artery disease. Investigation of the frequency of nocturnal ischaemia and coronary spasm.

The frequency and magnitude of objectively determined myocardial ischaemia during normal daily activities of patients with varying severity of coronary artery disease are unknown. Furthermore, the incidence of nocturnal resting myocardial ischaemia and frequency of coronary spasm in patients with normal coronary arteries and chest pain are also not known. One hundred consecutive patients with chest pain referred for coronary angiography were therefore investigated with exercise testing and ambulatory ST segment monitoring. Fifty two of 74 patients with significant coronary artery disease and six of 26 with no significant coronary narrowing had episodes of ST segment change during 48 hours of ambulatory monitoring. Two patients, one with normal coronary arteries and localised spasm and one with three vessel disease, had episodes of ST segment elevation, whereas all other patients had episodes of ST segment depression. The frequency, duration, and magnitude of ST segment changes were greater in patients with more severe types of coronary artery disease. Thus more than six episodes of ST segment change per day occurred in patients with two or three vessel disease or left main stem stenosis and in the only patient with coronary spasm and normal coronary arteries. Nocturnal ischaemia occurred in 15% of patients with coronary artery disease and was almost an invariable indicator of two or three vessel coronary artery disease or left main stem stenosis. Episodes of ST segment change occurred most commonly during the morning hours and least commonly during the night, in parallel with changes in basal hourly heart rates. The heart rate at the onset of ST segment change tended to be lower in patients with coronary artery disease than in those with normal coronary arteries. The duration of exercise to ST segment depression tended to be shorter in patients with more severe disease, but it could not predict patients with nocturnal myocardial ischaemia, left main stem stenosis, or coronary spasm, whereas ambulatory ST segment monitoring was able to identify most of these patients.

Activities of Daily Living↗
PubMed1985

Autocrine stimulation by prolactin of hormone-responsive breast cancer growth in culture.

Evidence obtained in human breast cancer cell lines in culture suggests that estradiol stimulates the synthesis of secretory proteins which may, in turn, mediate its mitogenic effect. We questioned whether a similar mechanism could mediate the growth-promoting effect of PRL in the N-nitrosomethylurea-induced rat mammary tumor grown in soft agar, where PRL exerts a dose-dependent colony-stimulating effect. Conditioned medium obtained from PRL-treated tumors, but not from control tumors, was found to exert a significant dose-dependent colony-stimulating effect when added to N-nitrosomethylurea-induced mammary tumors plated in soft agar under serum-free medium conditions. The growth-promoting action of conditioned medium from PRL-treated tumors was abolished by pretreatment with heat, trypsin, and Concanavalin-A, suggesting the possible glycoprotein nature of the oPRL-induced growth factor(s). These results provide support for the novel hypothesis that estradiol and PRL may support the growth of hormone-responsive breast cancer through a similar mechanism.

Animals↗
PubMed1985

Hormone dependency of human breast neoplasms cultured in vitro in the stem cell assay.

The stem cell soft agar culture system provides a biological tool with which to study tumor clones derived from heterogeneous tumor cell populations. For testing the feasibility of this approach in identifying hormone-responsive clones of mammary tumors, a study was done to determine whether estrogen deprivation or supplementation would alter colony formation in sequential breast neoplasms received in the Cell Kinetics Laboratory, The Pennsylvania State University. Single-cell suspensions obtained from 22 freshly excised breast neoplasms (20 malignant, 2 benign) were plated in soft agar with and without tamoxifen (Tam) (10(-7) M) with the use of serum-supplemented media and with and without 17 beta-estradiol (E2) (10(-8) M] under serum-free medium conditions. Twenty tumors successfully grew, producing 42 +/- 8 (mean +/- SEM) colonies in control dishes in the presence of serum and 27 +/- 5 in its absence (P less than .001). Tam inhibited colony formation in 78% of malignant tumors, whereas a stimulatory effect was observed with E2 in 94%. An increase in colony formation was induced by Tam in 4 tumors (2 benign and 2 malignant). The effects of E2 and Tam on tumor growth were not influenced by the estrogen and progesterone receptor status of the tumor. These preliminary results suggest that all tumors, irrespective of their receptor status, may contain clones of hormone-responsive cells.

Adenocarcinoma, Mucinous↗