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Biomedical subjects

L S Cook

Publications and source records attributed to L S Cook.

At least 37 records · Page 2Linked to original sources
PubMed1996

A population-based study of contralateral breast cancer following a first primary breast cancer (Washington, United States)

To evaluate predictors of contralateral breast cancer risk, we examined data from a nested case-control study of second primary cancers among a cohort of women in western Washington (United States) diagnosed with breast cancer during 1978 through 1990 and identified through a population-based cancer registry. Cases included all women in the cohort who subsequently developed contralateral breast cancer at least six months after the initial diagnosis, but prior to 1992 (n = 234). Controls were sampled randomly from the cohort, matched to cases on age, stage, and year of initial breast cancer diagnosis. Information on potential risk factors for second primary cancer was obtained through medical record abstractions and physician questionnaires. Women who were postmenopausal due to a bilateral oophorectomy (i.e., a surgical menopause) at initial breast cancer diagnosis had a reduction in contralateral breast cancer risk compared with premenopausal women (matched odds ratio [mOR] = 0.25, 95 percent confidence interval [CI] = 0.09-0.68), whereas no reduction in risk was noted among postmenopausal women who had had a natural menopause (mOR = 0.90, CI = 0.39-2.09). Among postmenopausal women, there was a suggestion of a lower risk associated with relatively high parity (2+). A family history of breast cancer was associated with an increased risk (mOR = 1.96, CI = 1.22-5.15) and varied little by menopausal status. Having an initial tumor with a lobular component (c.f. a ductal histology) was not related strongly to risk (mOR = 1.47, CI = 0.79-2.74). The results of the present and earlier studies argue that we have limited ability to predict the occurrence of a contralateral breast tumor. Better predictors will be required before diagnostic and preventive interventions can be targeted to subgroups of patients with unilateral breast cancer.

Adult↗
PubMed1995

Population-based study of tamoxifen therapy and subsequent ovarian, endometrial, and breast cancers.

BACKGROUND: The success of tamoxifen in reducing the occurrence of contralateral breast cancer among breast cancer patients in clinical trials has prompted the study of its use in the primary prevention of breast cancer. Long-term risks associated with tamoxifen therapy, however, are still being evaluated, particularly with respect to subsequent cancer occurrence at sites other than the breast. PURPOSE: This population-based, nested case-control study investigated the risks of second primary cancers of the ovary, endometrium, and contralateral breast among women receiving tamoxifen for breast cancer in conventional medical practice. METHODS: A cohort of women diagnosed with breast cancer during 1978 through 1990 was identified from a population-based cancer registry. Case subjects included all women in the cohort who subsequently developed second primary ovarian (n = 39), endometrial (n = 42), or contralateral breast (n = 234) cancer prior to 1992. Control subjects were a random sample of the cohort who did not develop a second primary malignancy; they were matched to the case subjects on age, disease stage, and year of initial breast cancer diagnosis (approximately two control subjects per case subject). Information on tamoxifen use as well as on potential risk factors for the second primary cancers was obtained through medical record abstractions and physician questionnaires. RESULTS: The percentage of women who had received tamoxifen was 18% and 20%, respectively, among ovarian cancer case subjects and control subjects; 26% and 31%, respectively, among endometrial cancer case subjects and control subjects; and 10% and 18%, respectively, among contralateral breast cancer case subjects and control subjects. The mean duration of tamoxifen use was less than 2 years for all groups. The relative risks for ovarian and endometrial cancers in women who took tamoxifen were relatively low but were consistent with no association (for ovarian cancer, matched odds ratio [mOR] = 0.6 and 95% confidence interval [CI] = 0.2-1.8; for endometrial cancer, mOR = 0.6 and 95% CI = 0.2-1.9). Tamoxifen therapy was associated with a decreased risk of contralateral breast cancer (mOR = 0.5; 95% CI = 0.3-0.9), especially if the drug had been taken for more than 1 year (mOR = 0.4; 95% CI = 0.2-0.9) or if the women were postmenopausal at initial breast cancer diagnosis (mOR = 0.4; 95% CI = 0.2-0.8). CONCLUSIONS AND IMPLICATIONS: These data suggest that short durations of tamoxifen therapy are not associated with an increased risk of endometrial or ovarian cancer but are associated with a reduction in contralateral breast cancer risk. It would not be appropriate, however, to generalize these results to women who receive tamoxifen for longer periods.

Adult↗
PubMed1994

The incidence of hepatocellular carcinoma in US white women with breast cancer after the introduction of tamoxifen in 1977.

It has been hypothesized that hepatocellular carcinoma might be a long-term adverse effect of tamoxifen therapy. Data from nine population-based cancer registries in the United States were used to investigate time trends in the incidence of hepatocellular carcinoma in white women previously diagnosed with invasive breast cancer during 1974-1987 and followed until 1989. Of particular interest were the rates after 1977, the year tamoxifen was licensed by the FDA. Compared to rates in all white women, no increased risk of hepatocellular carcinoma was found in women most likely to have received tamoxifen--those 50 years of age or more at diagnosis of breast cancer and diagnosed after 1977. These results suggest that tamoxifen does not cause a large increase in the incidence of hepatocellular carcinoma within the first decade after use. However, smaller and/or later increases in the risk for hepatocellular carcinoma are possible and warrant continued monitoring of women treated with tamoxifen.

Adult↗
PubMed1994

Circumcision and sexually transmitted diseases.

OBJECTIVES: New evidence linking lack of circumcision with sexually transmitted human immunodeficiency virus revives concerns about circumcision and other sexually transmitted diseases. This study was undertaken to assess the relationship between circumcision and syphilis, gonorrhea, chlamydial infection, genital herpes, nongonococcal urethritis, and exophytic genital warts. METHODS: A cross-sectional study of 2776 heterosexual men attending a sexually transmitted disease clinic in 1988 was used to investigate the relationship between circumcision and sexually transmitted diseases. Subjects with specific sexually transmitted diseases and those without such diseases were compared after adjustment for age, race, zip code of residence, other sexually transmitted diseases, and number of sexual partners. RESULTS: A positive relationship was observed between uncircumcised status and both syphilis and gonorrhea. A negative relationship was found between warts and lack of circumcision. No apparent relationship was noted between uncircumcised status and genital herpes, chlamydial infection, or nongonococcal urethritis. CONCLUSIONS: Uncircumcised men were more likely than circumcised men to have syphilis and gonorrhea and were less likely to have visible warts.

Adolescent↗
PubMed1993

Clinical presentation of genital warts among circumcised and uncircumcised heterosexual men attending an urban STD clinic.

INTRODUCTION: A recent study comparing heterosexual men with and without confirmed sexually transmitted diseases (STDs) in an urban STD clinic showed that uncircumcised men were less likely than circumcised men to have genital warts detectable by clinical examination (adjusted odds ratio 0.7, 95% confidence interval 0.4, 0.9). Based on these initial findings we hypothesised that the appearance and anatomic distribution of genital warts, and possibly treatment response, may be different for circumcised and uncircumcised men. METHODS: The anatomic location, appearance, number of warts, and response to treatment was investigated through review of medical records of 459 heterosexual men with genital warts detected in 1988. RESULTS: Age- and race-adjusted estimates indicated that among men with genital warts, warts were detected much more commonly on the distal penis--that is, the corona, frenulum, glans or urethral meatus-, among uncircumcised men (26%) than among circumcised men (3%) (OR 10.0, 95% CI 3.9, 25.7). Where the appearance was specified, warts were more often described as condylomatous in uncircumcised men and slightly more often as papular in circumcised men. No significant difference between circumcised and uncircumcised men was seen in the number of return visits to the clinic for persistent warts after treatment with liquid nitrogen: 2.2 visits for 19 uncircumcised men and 2.3 visits for 149 circumcised men. CONCLUSION: Circumcised men were more likely than uncircumcised men to have genital warts, but when present, warts were more often located on the distal portion of the penis among uncircumcised men. This paradox is not understood, but could reflect either nonspecific resistance to proximal penile warts conferred by the foreskin, or heightened susceptibility to various HPV types in uncircumcised men, some of which may confer subsequent immunity to genital warts.

Adolescent↗
PubMed1989

Neonatal aortic thrombosis complicating umbilical artery catheterization: successful treatment with retroperitoneal aortic thrombectomy.

A newborn infant with a history of umbilical artery catheterization had renal vascular hypertension and congestive heart failure. An abdominal ultrasound examination revealed aortic thrombosis extending from the celiac axis to the aortic bifurcation. Retroperitoneal aortic thrombectomy was performed without difficulty. The infant's hypertension and cardiac failure resolved. The retroperitoneal approach allowed excellent exposure of the aorta and avoided the postoperative gastrointestinal morbidity associated with a transperitoneal approach.

Aorta, Abdominal↗
PubMed1988

Oxygen regulation of ribulose 1,5-bisphosphate carboxylase activity in Rhodospirillum rubrum.

The carboxylase activity of ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBPC/O) decreased when an anaerobic culture of Rhodospirillum rubrum was exposed to atmospheric levels of oxygen. From 70 to 80% of the activity was lost within 12 to 24 h. Inactivation was apparent when the enzyme was assayed in situ (in whole cells) and when activity was measured in dialyzed crude extracts. The quantity of enzyme protein, as estimated from sodium dodecyl sulfate-polyacrylamide gels or as quantified immunologically, did not decrease within 24 h of exposure to air. Following extended exposure to aerobic conditions (48 to 72 h), degradation of enzyme occurred. These results indicate that the inactivation of RuBPC/O in R. rubrum may be due to an alteration or modification of the preformed enzyme, followed by eventual degradation of the inactive enzyme. When shifted back to anaerobic conditions (under an argon atmosphere), the RuBPC/O activity increased rapidly. This increase appeared to be due to de novo synthesis of enzyme. The increase in activity was not observed when the culture was maintained in the dark or in the absence of a suitable carbon source. Thus, the oxygen-mediated inactivation of RuBPC/O appeared to be due to some form of irreversible modification. The cloned R. rubrum RuBPC/O gene, expressed in Escherichia coli, yielded functional enzyme that was not affected by oxygen, indicating that inactivation in R. rubrum is mediated by a gene product(s) not found in E. coli.

Aerobiosis↗
PubMed1988

Oxygen-dependent inactivation of ribulose 1,5-bisphosphate carboxylase/oxygenase in crude extracts of Rhodospirillum rubrum and establishment of a model inactivation system with purified enzyme.

Ribulose 1,5-bisphosphate (RuBP) carboxylase/oxygenase (RuBPC/O) was inactivated in crude extracts of Rhodospirillum rubrum under atmospheric levels of oxygen; no inactivation occurred under an atmosphere of argon. RuBP carboxylase activity did not decrease in dialyzed extracts, indicating that a dialyzable factor was required for inactivation. The inactivation was inhibited by catalase. Purified RuBPC/O is relatively oxygen stable, as no loss of activity was observed after 4 h under an oxygen atmosphere. The aerobic inactivation catalyzed by endogenous factors in crude extracts was mimicked by using a model system containing purified enzyme, ascorbate, and FeSO4 or FeCl3. Dithiothreitol was found to substitute for ascorbate in the model system. Preincubation of the purified enzyme with RuBP led to enhanced inactivation, whereas Mg2+ and HCO3- significantly protected against inactivation. Unlike the inactivation catalyzed by endogenous factors from extracts of R. rubrum, inactivation in the model system was not inhibited by catalase. It is proposed that ascorbate and iron, in the presence of oxygen, generate a reactive oxygen species which reacts with a residue at the activation site, rendering the enzyme inactive.

Ascorbic Acid↗
PubMed1987

Cardiovascular time course after digoxin administration in left ventricular dysfunction after coronary artery bypass grafting.

Intravenous digoxin, 1 mg, was administered over 8 hours to 10 cardiac patients with left ventricular (LV) dysfunction after coronary artery bypass grafting. The cardiovascular effects of digoxin were monitored over 20 hours by indwelling pulmonary artery and radial artery lines and were compared with those of a control group of 10 patients who had normal postoperative LV function. Digoxin administration produced an increased cardiac index and mean arterial blood pressure within 2 hours. Within 4 hours after digoxin administration pulmonary artery wedge pressure in patients receiving digoxin was significantly lower than in control patients. At 16 hours there was a significant increase in both the LV stroke work and LV stroke work index in patients receiving digoxin vs control patients. Two patients receiving digoxin and 3 control patients had changes in cardiac rhythm during the study. Thus, digoxin can be safely administered to postoperative patients with LV dysfunction and is an acceptable inotropic agent.

Arrhythmias, Cardiac↗
PubMed1986

Cardiovascular effects of atropine in postoperative cardiac patients receiving digoxin for ventricular dysfunction.

Digoxin is clinically useful as a cardiac antiarrhythmic and inotropic agent. Its antiarrhythmic actions are mediated through the cholinergic nervous system. The cholinergic system, when activated, can depress ventricular function. We have sought to further increase the cardiovascular effects of digoxin by blocking its cholinergic effects with atropine. Atropine, 1 mg intravenously, was given to 10 postoperative cardiac patients. The cardiovascular time course was monitored by an ECG, radial arterial line, and pulmonary artery thermodilution catheter for 8 hours. A significant increase (p less than 0.05) in the cardiac output (CO), from 5.98 +/- 0.24 L/min to 6.60 +/- 0.34 L/min, was evident within 2 hours after atropine administration. The CO returned to control levels by 6 hours. There were no significant changes in heart rate, systemic vascular resistance, pulmonary artery wedge pressure, or systemic blood pressure. The results indicate that the cholinergic blockade of digoxin with atropine will acutely increase the cardiac output in postoperative cardiac patients.

Atropine↗
PubMed1984

Comparison of the canine tissue distribution of digoxin after acute and chronic administration: implications for digitalis therapy.

Digoxin is often used as an antiarrhythmic and inotropic agent. It produces significant neuroexcitatory responses that influence both its therapeutic and toxic effects. Patients receiving digoxin can be separated into 2 groups: those who receive it acutely and those who receive it chronically. The therapeutic and toxic responses to digoxin vary between these groups. The neural tissue distribution of digoxin was compared in dogs after both acute and chronic injections. Acute administration of digitalis in this study was associated with preferential uptake of digoxin into peripheral sympathetic nerves. Chronic administration was associated with continued selective uptake into the central nervous system despite decreasing serum levels. Therefore, acute (experimental or suicidal) or chronic (maintenance) digoxin administration produces different neural responses. The peripheral sympathetic nervous system will be the primary area of interaction with acute digoxin administration and the central nervous system will have a greater involvement with chronic digoxin administration. Our results indicate that the uptake of digoxin into the peripheral nervous system and central nervous system depends upon the duration of digoxin administration. The time course of digoxin accumulation influences both its therapeutic and toxic actions.

Animals↗
PubMed1984

Cardiovascular parameters after acute myocardial infarction and streptokinase administration in patients receiving coronary artery bypass grafts.

In 16 patients requiring coronary artery bypass grafting (10 control and 6 streptokinase patients), we compared the preoperative, operative, and postoperative cardiovascular parameters. Streptokinase patients had an acute myocardial infarction and attempted reperfusion with streptokinase before coronary artery bypass grafting. One patient failed to recannalize with streptokinase and one patient had reocclusion after withdrawal of heparin necessitating coronary artery bypass grafting. Examination of hemodynamic parameters revealed a lower preoperative mean blood pressure and an elevated pulmonary artery wedge pressure in streptokinase patients. The elevated pulmonary artery wedge pressure persisted through the postoperative period of observation. These results indicate that only minor differences exist between control and streptokinase patients. Emergency and elective coronary artery bypass grafting can be safely performed in patients treated with streptokinase for acute myocardial infarction without associated cardiogenic shock.

Blood Pressure↗
PubMed1983

Hemodynamic effects of combined digoxin and dopamine administration in postoperative patients with cardiac dysfunction.

In 10 patients with postoperative cardiac dysfunction which required dopamine for inotropic and hemodynamic support, we observed the cardiovascular effects of short-term digoxin administration. The average dosage of dopamine was 7.45 micrograms/kg per minute and was maintained while the patients were given 1 mg of digoxin over 8 hours. The dosage of dopamine was then tapered over the next 4 hours. We observed a significant increase in the cardiac index (4 hours) and a reduction in the heart rate (8 hours) before the dopamine dosage was reduced. After a reduction in dopamine dosage to 2.28 micrograms/kg per minute, these effects persisted. No significant changes were noted in systemic vascular resistance or pulmonary artery diastolic pressure during digoxin administration. These results indicate that the inotropic effects of dopamine and digoxin are additive when given in combination and that digoxin can be used to significantly reduce the dopamine dosage in patients with postoperative cardiac failure. Thus, the combination of an acute inotropic agent, dopamine, and a chronic inotropic agent, digoxin, appears to be clinically useful in postoperative cardiac dysfunction.

Cardiac Output↗
PubMed1982

Adrenergic and cholinergic mechanisms in digitalis inotropy.

In anesthetized dogs, the effects of peripheral cardiac nerves upon cardiotonic steroid-induced contractile force increases were determined by comparing the effects seen with cardiac nerves intact, cardiac denervation, stellate ganglia removed or vagi sectioned. Additionally, structure-activity relationships among four cardiotonic steroids were determined by comparing the contractile force effects of bolus i.v. injections of digitoxigenin (the genin), digitoxigenin-galactose (genin-neutral sugar combination), digitoxigenin-aminogalactose (ASI-222, genin-aminosugar combination) and digoxin. The effects of these drugs upon cardiac rate, mean blood pressure and cardiac contractile force were recorded. Cardiotonic steroids differ in their interaction with cardiac nerves. Digitoxigenin, in addition to its direct contractile force effect on the myocardium, modulates contractile force through adrenergic mechanisms. In contrast, both digoxin and ASI-222 influence their direct inotropic responses through cholinergic mechanisms. Neither adrenergic nor cholinergic mechanisms significantly affect the peak inotropic response of digitoxigenin-galactose. Our data indicate that alterations in both the aglycone and the sugar moieties can significantly alter the contribution of the autonomic nervous system to the contractile force response.

Animals↗
PubMed1981

Digoxin uptake into peripheral autonomic cardiac nerves: possible mechanism of digitalis-induced antiarrhythmic and toxic electrophysiologic actions.

It is generally accepted that certain cardiac rhythm disturbances are due to imbalances between the sympathetic and parasympathetic nervous systems. We have provided evidence that digoxin is concentrated in the peripheral nervous system of the heart as well as in the central nervous system. Previous findings have indicated that cardiac glycosides may directly or indirectly affect autonomic neurotransmitters. Therefore the uptake of digoxin into the peripheral cardiac nervous system may play an important role in both the antiarrhythmic and toxic electrophysiologic actions of digoxin.

Animals↗