Biomedical subjects
Publications and source records attributed to J K Williams.
Laparoscopic cholecystectomy was performed on a pregnant woman at 18 weeks of gestation without complications. Considering the risk/benefit ratio, laparoscopic cholecystectomy in pregnant women is preferable to conventional cholecystectomy.
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OBJECTIVES: We attempted to determine whether continuous and cyclic medroxyprogesterone acetate modulates the effects of estrogen on dilation of atherosclerotic coronary arteries in surgically postmenopausal female monkeys. BACKGROUND: Estrogen replacement in postmenopausal women preserves normal dilator responses of atherosclerotic coronary arteries. The effects of progestins on coronary artery reactivity have not been determined. METHODS: Repeated quantitative coronary angiography was used to study the effects after 1 month of 1) no hormone replacement (control) or oral administration of 2) continuous conjugated equine estrogens, 3) cyclic high dose medroxyprogesterone acetate (MPA) given on days 16 to 26 of the month, 4) conjugated equine estrogens plus continuous low dose MPA, or 5) conjugated equine estrogens plus cyclic high dose MPA on endothelium-mediated dilation of atherosclerotic coronary arteries in 12 cynomolgus monkeys. Change in diameter of the left circumflex coronary artery was measured in response to intracoronary infusions of acetylcholine (10(-6) mol/liter per min) and nitroglycerin (15 micrograms/min). RESULTS: Coronary arteries constricted during no hormone treatment (-8 +/- 3% [mean +/- SEM]), dilated during conjugated equine estrogen treatment (+3 +/- 1%, p < 0.05 vs. control) and constricted during cyclic MPA treatment (-3 +/- 2%). Addition of cyclic or continuous MPA to the conjugated equine estrogen regimen inhibited acetylcholine responses by 50% (p < 0.05 vs. conjugated equine estrogens). There was no effect of treatment on vascular response to nitroglycerin (p > 0.05). CONCLUSIONS: Treatment with conjugated equine estrogens, but not MPA, augmented endothelium-mediated dilation of atherosclerotic coronary arteries. Addition of cyclic or continuous MPA to the conjugated equine estrogen regimen diminished endothelium-mediated dilation.
BACKGROUND: Lymph-node metastasis is the single greatest predictor of survival in patients with oral cavity cancers. Tumor angiogenesis has been correlated with metastasis in breast cancer and may have prognostic value in other tumors. PATIENTS AND METHODS: Sixty-six patients with clinically node-negative oral cavity squamous cell cancers were reviewed. Samples were cut and stained for factor VIII. The percentage of area of tissue stained for factor VIII was quantitated by a computerized image analyzer. Tumor depth was measured with an ocular micrometer to the nearest 0.1 mm. Variables were statistically examined against regional recurrence. RESULTS: The probability of metastasis (%) was 2 for tumor staining of < or = 10% and 93 for tumor staining > 10% (P < 0.0001). The tumor depth was < or = 4 mm in 10 and > 4 mm in 83 (P < 0.0001). Patients with < or = 4 mm and < or = 10% staining had a 2% rate of recurrence, and patients with > 4 mm and > 10% staining had a 100% rate of recurrence (P < 0.0001). CONCLUSION: Although tumor thickness was suggestive of predictability, only angiogenesis was a statistically significant predictor of recurrence in a multivariate analysis (P < 0.0001). Angiogenesis showed a strong correlation with regional recurrence and may be used as an independent prognostic indicator.
BACKGROUND: The purpose of this study was to identify determinants of coronary artery reactivity among premenopausal female monkeys. Estrogen replacement therapy in postmenopausal females modulates reactivity of atherosclerotic coronary arteries. However, no studies have evaluated the factors that modulate coronary artery reactivity among premenopausal females. METHODS AND RESULTS: Twenty-five adult premenopausal female monkeys were fed an atherogenic diet for 32 months. During this time, monkeys were housed in small social groups and determined to be socially dominant (associated with normal ovarian function) or subordinate (associated with impaired ovarian function). After 32 months, coronary artery vasomotor responses to intracoronary acetylcholine, nitroglycerin, and serotonin were assessed by computer-assisted quantitative coronary angiography. Coronary arteries of dominant monkeys dilated (+9 +/- 2%), whereas those of subordinate monkeys constricted (-6 +/- 2%) in response to acetylcholine (P < .05). There was no effect of social status on vascular response to nitroglycerin or serotonin (P > .10). Vascular responses to acetylcholine were independent of social status effects on plasma lipids, blood pressure, and atherosclerosis extent. The correlation between acetylcholine responses and plasma estradiol concentration measured on the day of angiography was r = .7 (P = < .01). Furthermore, dilation occurred only if plasma estradiol concentrations were greater than 60 pg/mL. CONCLUSIONS: Psychosocial factors and endogenous estrogen production are important modulators of acetylcholine-mediated dilation of atherosclerotic coronary arteries among premenopausal female monkeys.
Children with Turner syndrome (TS) are at increased risk for cognitive deficits and behavioural problems. Although cognitive skills are similar to those found in children with nonverbal learning disabilities (NLD), comparisons of behavioral patterns in children with TS to those in children with NLD have not been reported. The purpose of this research was to describe behavioral patterns in school-aged females with TS and to determine if these patterns differed from those exhibited by females with NLD as measured on the Pediatric Behavior Scale, a parental report of childhood behaviors. Behavioral characteristics were identified in 10 children with TS, 10 with NLD, and 10 healthy children. Those with TS and with NLD were found to have increased levels of social isolation. In addition, children with TS had behavioral problems in the areas of impulsivity and medical noncompliance. Identification of behavioral characteristics of specific conditions is essential to guide counseling and interventions provided by nurses and other health professionals.
In the past, management of congenital absence of ovaries in women with Turner's syndrome (TS) was limited to replacement of ovarian hormones to initiate pubertal development. Until recently, adoption or stepparenting were the only parenting options. However, with new developments in assisted reproduction, women with TS may be able to successfully complete pregnancy and childbearing. There are specific nursing considerations for children and adolescents to follow: anticipatory guidance regarding sexual development; encouraging discussions of the range of options that are available for women with TS regarding reproduction; and assisting these children and adolescents in understanding the benefits and limitations associated with one reproductive option, in vitro fertilization.
Exogenous estrogen administration has been shown to reduce the risk of coronary heart disease in women. However, there are limited data in regard to the effects of estrogen on cardiovascular function and hemodynamics. This experiment sought to determine the effect of exogenous estrogen administration on systemic hemodynamic variables and cardiovascular responses to adrenergic and vasodilator agonists in premenopausal cynomolgus monkeys. Adult female monkeys were given weekly i.m. injections of 1) saline (control, n = 6), 2) estradiol cypionate (100 micrograms/kg, n = 6) or 3) estradiol cypionate (700 micrograms/kg, n = 5) for 6 weeks. A Swan-Ganz thermodilution catheter and arterial catheters were used to measure cardiovascular hemodynamic parameters in anesthetized monkeys before and during i.v. infusion of 1, 2, 4 and 8 micrograms kg-1 min-1 of isoproterenol, phenylephrine and nitroprusside. The high-dose estradiol group had a higher cardiac output index (0.6 +/- 0.1 versus 0.25 +/- 0.1 liter min-1 kg-1, mean +/- S.E.M.) and lower systemic vascular resistance index (628 +/- 160 versus 2630 +/- 872 dyne x cm-5 x sec-2 kg-1) than the control group at base line before infusion of agonists (P < .05). High-dose estradiol administration attenuated the mean arterial blood pressure, cardiac output and systemic vascular resistance changes in response to infusions of phenylephrine, isoproterenol and nitroprusside (P < .05 versus control). It was concluded that the administration of high-dose estradiol resulted in systemic arterial dilation, although changes in hemodynamic variables (systemic vascular resistance and cardiac output) were attenuated during adrenergic stimulation and vasodilation.
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To study the effects of dietary and social manipulations on lesion progression in male monkeys with established atherosclerosis, 83 animals fed a diet containing 1 mg cholesterol per kcal for 14 months were either necropsied (baseline group, n = 21) or assigned to one of three experimental conditions: 1) a diet containing a high amount of fat and cholesterol and a stressful social situation (HiFC-stress, n = 18); 2) a diet lower in fat and cholesterol and a stressful social situation (LoFC-stress, n = 21); or 3) the low-fat, low-cholesterol diet and a nonstressful social situation (LoFC-no stress, n = 23). After 28 months, all animals were necropsied. Coronary atherogenesis was arrested among monkeys in the LoFC-stress and LoFC-no stress conditions compared with that of animals in the baseline condition (plaque areas of 0.35 mm2, 0.30 mm2, and 0.38 mm2, respectively). Lesions in animals fed the LoFC diet (both stress and no-stress groups) were significantly smaller than those in monkeys in the HiFC-stress condition (0.96 mm2). Furthermore, aortic cholesterol content was significantly decreased and luminal areas were relatively larger among monkeys in both LoFC conditions compared with animals in the baseline and HiFC-stress conditions (p < 0.05 for all). The results demonstrate that a low-fat, low-cholesterol diet can halt plaque development, reduce arterial cholesterol content, and permit compensatory arterial enlargement, processes that were unaffected by social stress in this investigation.
Lipoprotein(a) (Lp[a]) is a newly recognized risk factor for the development of coronary heart disease and stroke in human beings; however, the mechanisms by which Lp(a) increases the risk of coronary heart disease remain unclear. The purpose of this study was to examine the effects of Lp(a) on the occurrence of occlusive arterial thrombosis. Occlusive arterial thrombus formation was examined in 18 cynomolgus monkeys with high plasma Lp(a) concentrations (> 35 mg/dL, n = 6), intermediate Lp(a) concentrations (20-25 mg/dL, n = 6), and low Lp(a) concentrations (< 12 mg/dL, n = 6). A Goldblatt clamp was positioned around the left common carotid artery to produce a stenotic segment, and the artery was pinch-injured with needle holders. A 20-MHz Doppler velocity crystal, placed distal to the stenosis/injury site, was used to detect cyclic flow reductions (indicative of transient thrombosis) or permanent cessation of flow velocity (indicative of more stable occlusive thrombosis). All monkeys with high Lp(a) concentrations developed permanent cessation of flow, whereas only one of six arteries from low-Lp(a) monkeys developed permanent cessation of flow (p < 0.05). Arteries from monkeys with intermediate Lp(a) concentrations developed pronounced cyclic reductions of flow but did not progress to permanent cessation of flow. There were no differences in plasma von Willebrand factor activity among the three groups. Immunohistochemical analysis of the damaged arterial segments indicated incorporation of Lp(a) into the adventitia, media, and intima of arteries from monkeys with low and high plasma Lp(a) concentrations, as well as the presence of an occlusive thrombus in arteries that developed permanent cessation of flow.(ABSTRACT TRUNCATED AT 250 WORDS)
The objectives of this study were to determine if psychosocial stress impairs dilation through endothelium-derived relaxing factor (EDRF)-mediated mechanisms and if this effect is long lasting. Monkeys were fed an atherogenic diet for 36 mo while in one of three experimental conditions: (a) stable social groups ("unstressed," n = 6); (b) unstable social groups for the first half of the experiment and stable groups for the second half ("early stress," n = 8); and (c) stable groups for the first half of the experiment and unstable groups for the second half ("late stress," n = 6). Iliac arteries were studied in organ chambers containing Krebs' buffer and 10(-6) M indomethacin. Arteries from the late stress group had impaired dilation (shift of the dose-response curve down and to the right) to acetylcholine and the calcium ionophore A23187 (for both, P < 0.05), but not to nitroprusside (P > 0.05), compared with unstressed or early stress monkeys. NG-methyl-L-arginine reduced the dose-response curve to both acetylcholine and A23187 in the unstressed group and resulted in similar vascular responses among all three groups (P > 0.05). We conclude that current, but not previous, exposure to chronic stress impairs endothelium-mediated dilation of atherosclerotic iliac arteries of cynomolgus monkeys through an EDRF-mediated mechanism.
The notion of using case managers to coordinate care and services to the elderly has become increasingly popular. Case management appears to be seen by some as the route to reform and rationalization of the financing and provision of services. Little systematic research can be cited in making claims for its organization, efficacy or efficiency, yet opinions in this regard abound. Research and demonstration projects provide some insights but few conclusions to support the rhetoric of case management. Case management principles are enunciated and program options flow from them. A case is made for flexibility of organization and sensibility of provision.
We describe multiple human cardiac and skeletal muscle spectrin isoforms. Cardiac muscle expresses five erythroid alpha,beta spectrin-reactive isoforms with estimated MR's of 280, 274, 270, 255, and 246 kD, respectively. At least one nonerythroid alpha-spectrin of MR 284 kD is expressed in heart. While skeletal muscle shares the 280, 270, and 246 kD erythroid spectrins, it expresses an immunologically distinct 284 kD nonerythroid alpha-spectrin isoform. The 255 kD erythroid beta-spectrin isoform is specific for cardiac tissue. By immunocytochemistry, both erythroid beta- and nonerythroid alpha-spectrins are localized to costameres, the plasma membrane, and the neuromuscular junctional region.
A randomized, double-blind trial was conducted to determine the effectiveness of intrapleural bupivacaine hydrochloride in the management of pain after thoracotomy. Thirty-three men and 7 women with a mean age of 62 years (range, 21 to 76 years) undergoing elective posterolateral thoracotomy were randomly allocated preoperatively to either a study group receiving 20 mL of 0.25% bupivacaine or a control group receiving 20 mL of 0.9% saline solution through a pleural catheter every 4 hours. Patients received supplementary doses of intramuscular papaveretum as required. Assessment of pain, somnolence, and breathing capacity was performed after the intrapleural injections at 4, 24, 48, and 72 hours postoperatively. Pain assessment, as measured by a linear analog scale, was lower in the bupivacaine group at all times, reaching significance at 4, 24, and 72 hours (p less than 0.05). The forced vital capacity and forced expiratory volume in 1 second at 6 weeks postoperatively remained significantly lower than preoperatively (p less than 0.05). The fall in forced vital capacity from this postoperative level was significantly less in the bupivacaine group at 4, 24, and 48 hours, and the fall in forced expiratory volume in 1 second was significantly less at 4 and 48 hours in the treated group. When used in conjunction with doses of parenteral narcotic, intrapleural bupivacaine gives better pain control with less respiratory depression than intermittent doses of narcotic alone.
The recent availability of a 99.9% UVA source has made possible studies that show that low energy wavelengths, previously considered innocuous, significantly affected wound healing in hairless guinea pigs. Decreased wound tensile strength and a slower rate of wound contraction in irradiated animals were among the changes noted. Because of their advocated role in the wound healing process, fibroblasts were chosen to study the effects of pure UVA exposure at a cellular level. 3H-thymidine uptake levels were measured in 8 groups of fibroblast cultures (12 samples/group). The cultures were exposed to varying concentrations of pure UVA. Previously incorporated 14C-thymidine levels were used to compensate for differences in cell numbers between samples. At a fluence of 3.65 x 10(-3) watts/cm2, a significant decrease in 3H-thymidine incorporation (compared to controls) was seen for all exposure periods and there was a dose-dependent decrease only in 3H-thymidine uptake for cells exposed to 1-4 min of UVA. Using post-exposure incubations of 2-16 h, a time-dependent recovery of 3H-thymidine uptake was also demonstrated, from 40% of control at 4 h, to 75% at 8 h, and 99% at 16 h. The near-complete recovery at 16 h was seen in exposures up to 2.73 joules/cm2 (12 min), whereas higher concentrations showed only partial recovery. These studies demonstrated the deleterious, though reversible, effects of UVA on fibroblasts and suggest a possible pathophysiologic process for UVA's effect on wound healing in this animal model.
OBJECTIVES: This experiment sought to determine the effect of short-term administration of estrogen on endothelium-dependent dilation in the coronary arteries of 13 surgically postmenopausal female cynomolgus monkeys. BACKGROUND: Long-term estrogen replacement therapy prevents impaired endothelium-dependent dilation of atherosclerotic coronary arteries in postmenopausal female monkeys. However, it remains unclear whether this action of estrogen is due to long-term effects on plasma lipids and atherogenesis or to direct short-term effects on the endothelium. METHODS: The monkeys consumed an atherogenic diet for 18 months after bilateral ovariectomy. Vascular responses were measured just before euthanasia and necropsy. Dextrose in water (control), acetylcholine, 10(-6)M, and nitroglycerin were infused for 2.5 min each both before and 20 min after intravenous injection of 54 ng ethinyl estradiol. RESULTS: Quantitative coronary angiography revealed that the arteries constricted (-17 +/- 3%) in response to intracoronary infusion of acetylcholine before estrogen treatment but dilated (+5 +/- 3%) 20 min after intravenous injection of ethinyl estradiol (p less than 0.05). Coronary arteries dilated in response to nitroglycerin both before and after administration of estrogen (p greater than 0.05). Vascular responses of coronary arteries, both before and after administration of estrogen, were not associated with variation in plasma lipid concentrations, blood pressure, heart rate or plaque size. CONCLUSIONS: Estrogen affects endothelium-dependent coronary dilation within 20 min of administration and may have rapid direct effects on the vascular endothelium.
This study examined the effects of a verbal mediation strategy on three groups of subjects who had visual-spatial deficits. Thirteen females with Turner syndrome, 13 females with nonverbal learning disabilities, and 14 males with nonverbal learning disabilities, who ranged in age from 7 to 14 years, were taught via a cognitive behavioral modification approach to verbally mediate a spatial matching task. Pretest and posttest performance differences on parallel forms of a visual-spatial orientation task were examined. All three groups showed significant improvement in visual-spatial task performance after the training. There were no significant differences in the degree of improvement among the three groups. The results suggest that children with Turner syndrome may benefit from problem-solving strategy training in a manner similar to children with nonverbal learning disabilities.