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Biomedical subjects

J K Williams

Publications and source records attributed to J K Williams.

At least 91 records · Page 5Linked to original sources
PubMed1996

The effects of disease severity and sex on coronary endothelium-dependent vasomotor function in an atherosclerotic primate model.

BACKGROUND: The relationship between the extent of atherosclerosis and vascular reactivity is not known, since studies of humans have used indirect measures of the extent of atherosclerosis (angiography and ultrasound), and most patients studied had only minimal-to-moderate atherosclerosis. It is known that atherosclerosis impairs coronary vasodilatation in response to acetylcholine, and that estrogen improves vascular reactivity of atherosclerotic coronary arteries in women and perhaps in men. However, the effects of estrogen and sex on arteries with advanced, complicated plaques are not known. METHODS: We used quantitative coronary angiography to measure vascular reactivity to infusions of 10(-6) mol/l acetylcholine and 15 micrograms/min nitroglycerin in 70 segments of coronary arteries in 16 rhesus monkeys (12 males, five intact females, nine ovariectomized females) with a wide range of extents of atherosclerosis. The extent and severity of atherosclerotic plaque in each segment was quantified by histologic and histomorphometric methods. Effects of sex and ovariectomy on vascular reactivity were examined at low and high levels of plaque severity. RESULTS: Vascular responses ranged from constriction (by 18%) to dilatation (by 14%) compared with the control diameter. The magnitude of the vascular response to acetylcholine, either dilatation or constriction, decreased with increasing plaque severity (P < 0.01). At low severity, arteries of intact females dilated (by 7.2 +/- 2.1%), whereas those of males and ovariectomized females constricted (by 4.5 +/- 1.5% and 5.0 +/- 1.2%, respectively; P < 0.001, versus intact females). When lesions were severe, vascular responses did not differ among groups. CONCLUSIONS: Our results indicate that arteries became unresponsive to acetylcholine as atherosclerotic lesions progressed in size and complexity, and that sex and estrogen status affected vascular reactivity only when lesions were small. These findings may imply a limited range of lesion development within which vascular reactivity can be influenced by sex and estrogen status.

Acetylcholine↗
PubMed1996

Time course of cellular proliferation, intimal hyperplasia, and remodeling following angioplasty in monkeys with established atherosclerosis. A nonhuman primate model of restenosis.

Animal models of arterial injury have failed to predict effective therapy to prevent restenosis in humans. While this may relate to species differences in the control of smooth muscle cell growth, many studies have used nonatherosclerotic animals, thereby failing to consider the importance of atherosclerosis in the response to injury. In an attempt to model human restenosis more accurately, we characterized the response to angioplasty in atherosclerotic monkeys. Twenty-one cynomolgus monkeys were fed an atherogenic diet for 36 months (plasma cholesterol, 12 +/- 1 mmol/L [470 +/- 23 mg/dL]). Angioplasty was then performed in the left iliac artery. After 4, 7, 14, or 28 days, bromodeoxyuridine was given to label proliferating cells, and iliac arteries were fixed in situ at physiological pressure (5 or 6 animals at each time point). Comparisons were made between injured and uninjured iliac arteries within each animal. Angioplasty often fractured the intimal plaque and media, transiently increasing lumen caliber (4 days: lumen area, 232.5 +/- 80.3% of control) and artery size as reflected by external elastic lamina area (EEL). EEL and lumen caliber returned to baseline by 7 days. Proliferation was increased throughout the artery wall at 4 and 7 days and later declined to control rates (4 days, injured versus uninjured: adventitia, 45.0 +/- 6.2% versus 16.3 +/- 7.2%; media, 8.6 +/- 2.6% versus 0.6 +/- 0.1%; intima, 16.0 +/- 5.6% versus 7.8 +/- 3.1%). The intima thickened markedly from 14 to 28 days, but an increase in EEL generally prevented further loss of the short-term gain in lumen caliber (28 days, percent of control: intimal area, 342.8 +/- 88.9%; EEL area, 150.2 +/- 28.9%; lumen area, 119.3 +/- 21.3%). The response to angioplasty in atherosclerotic monkeys appears to closely resemble that in humans. Plaque fracture, delayed recoil, intimal hyperplasia, and remodeling may each be important in determining late lumen caliber. This primate model should prove valuable in defining cellular and biochemical mediators of human restenosis.

Angioplasty↗
PubMed1996

Esterified estrogens with and without methyltestosterone decrease arterial LDL metabolism in cynomolgus monkeys.

Although both epidemiological and experimental evidence suggests that estrogen replacement therapy reduces the risk of coronary heart disease, the mechanisms for this beneficial effect are largely unknown. Furthermore, the addition of progestins or androgens to estrogen replacement therapy is of concern. The objective of this study was to examine the effects of esterified estrogens alone or in combination with an androgen on arterial LDL metabolism and early atherogenesis in ovariectomized female cynomolgus monkeys. Arterial LDL metabolism was assessed by using dual-labeled LDL that was injected 24 hours before necropsy. Arterial LDL degradation was reduced by 64% to 84% and cholesteryl ester content was decreased by approximately 50% in the thoracic aorta in both treatment groups compared with controls. In addition, aortic lipid peroxidation products, as assessed by thiobarbituric acid reaction, were significantly lower in animals treated with esterified estrogens, with a similar trend for combined estrogen-androgen treatment. Both treatments also reduced plasma concentrations of apoB-containing lipoproteins, reduced LDL particle size, and increased total-body LDL catabolism. The combination of decreased arterial LDL metabolism, decreased arterial lipid peroxidation, and improved plasma lipoprotein metabolism may explain some of the protective effects of estrogens on coronary heart disease and indicate that beneficial actions extend to a combination of estrogen and androgen.

Animals↗
PubMed1996

Short gut syndrome: treatment by neovascularization of the small intestine.

Surgical treatment for short bowel syndrome has been directed toward slowing intestinal transit or increasing the absorptive surface area of the bowel. In the present work, we attempted to enhance bowel absorption by increasing vascularity, using the omentum's unique ability to revascularize incorporated tissue. After a 90% resection of small bowel with primary anastomosis in 5 mongrel dogs, an omental flap based on the right gastroepiploic vessels was incorporated into a seromuscular incision on the antimesenteric border of the remnant small bowel. Five control dogs underwent a similar resection and seromuscular incision with an omentectomy. Serum d-xylose assays, hemoglobin, and total protein levels were measured preoperatively and at 3, 6, 9, and 12 weeks postoperatively. Weekly weights were followed. The mean percent d-xylose absorption in the experimental group increased from 96% of the baseline at 3 weeks to 136%, 163%, and 179% at 6, 9, and 12 weeks respectively (p < 0.5). The control group maintained absorption levels between 54% and 74%. Weight loss in the experimental group was significantly less than the controls at weeks 6 and 9, but by 12 weeks, weights were similar for the two groups. Small bowel absorption of d-xylose was significantly enhanced by incorporation of the omentum into the bowel remnant.

Animals↗
PubMed1996

Rhegmatogenous retinal detachments in HIV-positive patients with ocular syphilis.

The purpose of this study is to report retinal manifestations of lues in human immunodeficiency virus (HIV)-positive patients and to suggest a method for treatment of rhegmatogenous retinal detachments in these patients. Two HIV-positive patients with bilateral retinitis were examined and treated at the authors' institution for a period of 14 months. Ocular syphilis was diagnosed clinically, confirmed by cerebrospinal fluid serologic testing, and treated with intravenous penicillin. Both patients experienced bilateral rhegmatogenous retinal detachments complicated by proliferative vitreoretinopathy after resolution of the active retinitis. All four eyes underwent surgical repair with trans pars plana vitrectomy, epiretinal membrane delamination, gas-fluid exchange, endolaser, scleral buckle, and silicone oil instillation. The recognition of ocular syphilis as a cause of retinal detachment in HIV-positive patients is important. Prompt intervention with the appropriate medical and surgical treatments may result in the preservation of vision in these patients.

Adult↗
PubMed1996

[The vasa vasorum of the arteries].

Nourishment of arteries is accomplished by diffusion from the lumen of the vessel and from vasa vasorum. Most normal arteries have an extensive network of vasa in the adventitia that arise from branch points of parent arteries. When the thickness of arteries exceeds the ability of simple diffusion of nutrients from the lumen (larger muscular of atherosclerotic arteries), vasa extend into the media and intima. Vasa in the intima-media arise predominantly from adventitial vasa, but can arise from the lumen in vascular grafts and recanalized arteries after thrombosis. Vasa respond to vasoactive stimuli, and can regress after they vascularize arterial grafts and in response to regression of the atherosclerotic lesions. Therefore, vasa can increase blood flow to the artery wall by dilation of existing arteries or by formation of new vessels (neovascularization). Conversely, vasa can reduce blood flow to the artery wall by active constriction or by regression (involution) of existing vasa. The pathophysiological significance of vasa vasorum in normal and diseased arteries is related to their structure. Vasa in the intima-media are thin-walled endothelial cell tubes with thin or absent medial smooth muscle cells. Therefore, they are prone to collapse and rupture in response to arterial pressure, mechanical forces in the artery, necrotic substances found in diseased arteries, and vasospasm. Vasa also provide the artery with a vast absorptive endothelial surface that may have important implications for arterial lipid kinetics, and delivery and removal of neurohumoral agents from the artery wall. These properties have lead to speculation about their role in the pathogenesis of atherosclerosis, plaque rupture and thrombosis, medial ischemia leading to arterial dissection and aneurysm, restenosis after angioplasty, and post-stenotic dilatation. Finally, larger veins also have an extensive network of vasa that have been implicated in the pathogenesis of venous thrombosis and varicose veins.

Aorta↗
PubMed1995

Fish oil treatment decreases superoxide anions in the myocardium and coronary arteries of atherosclerotic monkeys.

BACKGROUND: This experiment sought to determine the effects of fish oil on superoxide anion production in the myocardium and coronary arteries of atherosclerotic monkeys. Recent evidence indicates that dietary supplementation with fish oil preserves normal vasomotion of atherosclerotic coronary arteries and reduces damage to the myocardium after ischemia and reperfusion, although the mechanisms remain unclear. METHODS AND RESULTS: Adult male cynomolgus monkeys were fed an atherogenic diet with (n = 15) or without (n = 15) half the fat calories from fish oil. After 12 months, chemiluminescence of lucigenin was used to measure superoxide anion production in coronary arteries and myocardium after 1 hour of ischemia and 2 hours of reperfusion. The signals were calibrated with known quantities of xanthine and xanthine oxidase. Superoxide anion production in ischemic myocardium was (mean +/- SEM, nmol/mg dry wt per minute) 1 +/- 1 and 4 +/- 1 in monkeys fed fish oil and not fed fish oil, respectively (P < .05). Superoxide anion production in coronary arteries not exposed to ischemia and reperfusion was (nmol/mg dry wt per minute) 4 +/- 1 and 8 +/- 2 in monkeys fed fish oil and not fed fish oil, respectively (P < .05). Superoxide anion production in coronary arteries was (nmol/mg dry wt per minute) 5 +/- 2 and 16 +/- 3 in monkeys fed fish oil and not fed fish oil after ischemia and reperfusion, respectively (P < .05). CONCLUSIONS: Dietary supplementation with fish oil reduced vascular superoxide anion production and prevented the increase in vascular and myocardial superoxide anion production that accompanied ischemia and reperfusion. These phenomena may underlie some of the beneficial cardiovascular effects of fish oil.

Acridines↗
PubMed1995

TRAM flap breast reconstruction after radiation treatment.

OBJECTIVE: Patients with and without radiation treatment before their breast reconstruction were compared to study the relationship of radiation to flap-related complications. SUMMARY BACKGROUND DATA: The transverse rectus abdominis muscle (TRAM) flap for breast reconstruction involves a a vascular pedicle and recipient bed, both included in the radiated field of patients undergoing adjunctive therapy. Detailed reviews of flap-related complications in this subgroup of patients have been limited. METHODS: One hundred eight patients with radiation treatment who subsequently underwent a TRAM flap breast reconstruction were compared with 572 patients with no radiation treatment before similar reconstruction. Flap-related complications, radiation dosage, time, fields, relationships between risk factors, and complications were studied. RESULTS: Overall complication rates were comparable between the two groups. Only fat necrosis (> 10% of total reconstruction) was found to be statistically significant (17.6% vs. 10.1%, p = 0.03228). No difference was found for fat necrosis in unipedicled vs. bipedicled flaps controlled for radiation (17.7% vs. 17.4%). Obesity and radiation therapy were associated with fat necrosis and major infection in a logistic regression. Significant abdominal scarring was also associated with major infection (p = 0.0044). CONCLUSIONS: In this, the largest reported series, radiation therapy was associated with increased fat necrosis and major infection. The use of the TRAM flap was not found to be prohibitive in radiated patients and should still be the first choice in this subgroup of patients.

Breast Neoplasms↗
PubMed1995

Effects of androgens on coronary artery atherosclerosis and atherosclerosis-related impairment of vascular responsiveness.

The factors responsible for the marked gender differences in risk of coronary heart disease and atherosclerosis severity remain largely undetermined. While some clinical and experimental evidence supports a protective effect of endogenous estrogen on the initiation and progression of atherosclerosis and incidence of coronary heart disease, much of the epidemiological data do not support this conclusion. The possibility that endogenous androgens may have adverse effects on atherosclerosis progression and coronary risk has received little attention. We investigated the effects of experimentally induced hyperandrogenism in female cynomolgus monkeys with diet-induced atherosclerosis. Animals were assigned randomly to one of four treatment groups: (1) untreated controls, (2) ovariectomized (sex hormone-deficient) controls, (3) treated with androstenedione and estrone (mild hyperandrogenism), or (4) treated with testosterone (male plasma androgen pattern). At necropsy, coronary atherosclerosis was approximately twice as extensive (P < .05) in testosterone-treated animals relative to untreated controls, while treatment with androstenedione and estrone had no effect on atherosclerosis extent. Coronary plaque size was positively correlated with lumen size in intact and ovariectomized controls; however, there was no evidence of a similar relation between animals in either androgen treatment group. The atherogenic effects of testosterone were independent of variations in plasma lipoprotein and nonlipoprotein risk variables. Although chronic hyperandrogenism had adverse effects on atherosclerosis progression, it reversed (P < .03) atherosclerosis-related impairment of endothelium-dependent vasodilator responses. We conclude that an experimentally induced male plasma androgen pattern results in exacerbation of diet-induced atherosclerosis-related arterial remodeling in female monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗
PubMed1995

Regression of atherosclerosis in female monkeys.

The objective of this study was to determine the structural and functional changes that occur in the artery wall in response to plasma lipid lowering and hormone replacement in surgically postmenopausal monkeys with established coronary artery atherosclerosis. Eighty-eight surgically postmenopausal cynomolgus monkeys were fed an atherogenic diet for 24 months and were then allocated into 4 groups: group 1 (n = 20), a baseline necropsy group; group 2 (n = 25), a lipid-lowering diet only; group 3 (n = 22), lipid lowering plus conjugated equine estrogen treatment equivalent to 0.625 mg/d for a woman; and group 4 (n = 21), lipid lowering plus conjugated equine estrogen and medroxyprogesterone acetate treatment (equivalent to 2.5 mg/d for a woman). Treatment was for 30 months. Histomorphometric analysis of perfusion-fixed coronary arteries revealed that plaque size did not change significantly in any of the groups compared with group 1 (P > .20). Plasma lipid lowering permitted coronary artery remodeling to occur (coronary artery and lumen size doubled compared with group 1) (P < .05); however, hormone therapy did not augment remodeling. Quantitative angiographic analysis of coronary artery reactivity revealed that lipid lowering improved dilator responses to acetylcholine by 22 +/- 4% (P = .01) but not to nitroglycerin (P = .23). Hormone replacement did not further affect vascular reactivity to the agonists tested (P > .4), but addition of medroxyprogesterone acetate diminished the beneficial effects of conjugated estrogens on coronary flow reserve (P = .03). In summary, the major arterial sequelae of lipid lowering in female monkeys were artery and lumen enlargement and improved reactivity of large epicardial coronary arteries. Addition of hormone replacement to the dietary modification did not further augment these improvements, except for the dilator capacity of the coronary microcirculation.

Acetylcholine↗
PubMed1995

Chlamydia trachomatis. A trojan horse.

Chlamydia trachomatis is a prevalent and virulent pathogen in the genital tract of sexually active women. The sequelae are diverse and represent a significant source of morbidity. The Centers for Disease Control estimates 4 million new cases annually, making it the most prevalent sexually transmitted disease in the United States. Several risk factors are well-defined and the pathophysiology has become better understood, helping to improve the body of data concerning sequelae. Newer diagnostic methods, such as gene probes, ELISA, and PCR, are now available to aid in detection. Novel treatment regimens have been developed to improve eradication of the infection and compliance. There are still questions regarding this pathogen and its interaction with other lower genital tract pathogens. Improved detection, reporting and appropriate treatment can reduce the effect of Chlamydial infections on reproductive capacity.

Adolescent↗
PubMed1995

Applying new genetic technologies: assessment and ethical considerations.

Discovery of genes associated with clinical disorders increases the ability of clinicians to more accurately assess risk for their clients to develop or to be carriers of certain health problems. Estimating these risks has become more precise with the addition of genetic testing. The process of client assessment and considerations associated with genetic testing for cystic fibrosis and one form of colon cancer (familial adenomatous polyposis) are presented in a case study format. Ethical considerations in the use of genetic testing include protection of privacy, protection from coercion, and assuring client understanding of implications of test results. Practitioner responsibilities also include educating clients regarding benefits and limitations of testing, collaborating with genetic counseling resources, and monitoring the client for potential adverse outcomes of testing.

Adenomatous Polyposis Coli↗