Gonadal hormone substitutes: effects on the cardiovascular system.
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Animals↗
Biomedical subjects
J K Williams
Publications and source records attributed to J K Williams.
Tumor angiogenesis as a prognostic factor in laryngeal cancer.
BACKGROUND: Lymph node metastasis is the single greatest predictor of recurrence in laryngeal cancer. Prognostic factors are needed to target patients who may benefit from adjuvant therapy. Tumor angiogenesis correlates with metastasis in breast, bladder, and oral cavity cancer and may have prognostic value in other tumors. METHODS: In order to examine the relationship of tumor angiogenesis to recurrence, 51 patients with squamous cell carcinoma of the larynx were reviewed. In a blinded design, previously sectioned slides were chosen for advanced tumor and highest vessel concentration. Samples were cut and immunocytochemically stained for CD-31 (an endothelial marker). A computer image analyzer quantitated the percent area of staining. Variables were statistically examined against recurrence. RESULTS: Patients were stratified by percent tumor staining. Nodal involvement was seen in 9 (36%) patients with tumor staining < or = 20% and in 20 (77%) with tumor staining > 20% (P = 0.003). Patients with < or = 20% staining and without metastasis had a 13% rate of recurrence whereas patients with > 20% staining and without metastasis had a 67% rate of recurrence (P = 0.025). CONCLUSIONS: Though nodal status was suggestive of predictability, only angiogenesis is a statistically significant predictor of recurrence in node negative patients (P = 0.025). Angiogenesis shows strong correlation with regional recurrence and may be used as an independent prognostic indicator to determine clinically node negative patients who may be at higher risk for metastasis and require adjuvant therapy.
Carcinoma, Squamous Cell↗
Soy isoflavones enhance coronary vascular reactivity in atherosclerotic female macaques.
OBJECTIVE: To examine the effects of soy phytoestrogens on coronary vascular reactivity in atherosclerotic male and female rhesus monkeys. DESIGN: A prospective, randomized, blinded, controlled study. SETTING: Comparative Medicine Clinical Research Center of an academic medical center. PATIENT(S): Twenty-two young adult rhesus monkeys with pre-existing diet-induced atherosclerosis. INTERVENTION(S): Monkeys were fed soy-based diets for 6 months identical in composition, except that the isoflavones were extracted from one flow-isoflavone) and intact in the other (high-isoflavone). Quantitative coronary angiography was performed at the end of the study period. Females in the low-isoflavone group under went a second angiography after an acute IV dose of genistein. MAIN OUTCOME MEASURE(S): Percent change in diameter of the proximal left circumflex coronary artery in response to intracoronary acetylcholine and nitroglycerin, compared with control diameter. RESULT(S): Arteries from males constricted in response to acetylcholine. Arteries from females in the low-isoflavone group constricted (-6.2% +/- 2.8%, mean +/- SEM), whereas arteries from females in the high-isoflavone group dilated (6.4% +/- 1.2%, mean +/- SEM). Intravenous administration of genistein caused dilation in the previously constricting low-isoflavone females (3.3% +/- 2.8%). CONCLUSION(S): Like mammalian estrogens, dietary soy isoflavones enhance the dilator response to acetylcholine of atherosclerotic arteries in female monkeys.
Animals↗
Structural determinants of lumen narrowing after angioplasty in atherosclerotic nonhuman primates.
PURPOSE: The relationship between lumen narrowing, intimal hyperplasia, and wall remodeling after angioplasty was explored in a nonhuman primate model of atherosclerosis. METHODS: Cynomolgus monkeys (n = 37) used in long-term atherosclerosis studies underwent left iliac artery balloon injury. The uninjured right iliac artery served as a reference segment for intraanimal comparisons. One month later iliac arteries were fixed by perfusion (100 mm Hg) and removed for cross-sectional analysis to determine mean values for lumen area (LA), intimal area (IA), internal elastic lamina area (IELA), plaque burden (IA/IELA), and depth of wall injury. Values for each balloon-injured iliac artery were normalized to the contralateral uninjured iliac artery (percent of control), and linear regression analysis was performed comparing LA with IA, with IELA, and with depth of injury. Comparisons were also made between those arteries that remained dilated 1 month after balloon injury (LA > or = 140%; n = 13) and those that renarrowed (LA < or = 100%; n = 14). RESULTS: For all 37 animals, LA 1 month after balloon injury correlated well with IELA (r = 0.72; p < 0.001) but not with IA (r = 0.10; p = 0.54), suggesting that changes in artery size rather than neointimal mass determined lumen caliber. When comparing arteries that remained dilated (n = 13) with those that renarrowed (n = 14), there were no differences in depth of wall injury (injury depth: 0, no injury; 1, intima; 2, IEL; 3, media; 4, EEL; 2.1 +/- 0.3 vs 1.6 +/- 0.3; p = 0.12), neointimal accumulation (IA, 507% +/- 118% vs. 421% +/- 81% of control; p = 0.55), or plaque burden (IA/IELA, 0.39 +/- 0.04 vs 0.37 +/- 0.06; p = 0.71), respectively. However, wall size defined as IELA was significantly smaller in arteries that renarrowed than in those that remained dilated (IELA, 115% +/- 14% vs 230% +/- 19% of control; p < 0.001). CONCLUSIONS: Restenosis after angioplasty has been attributed to intimal hyperplasia, equating loss of lumen caliber with neointimal mass. The data presented herein suggest that lumen narrowing after arterial wall injury may have little to do with intimal mass per se, but rather that a change in wall caliber or wall narrowing is the cause of restenosis.
Angioplasty, Balloon↗
Principles of genetics and cancer.
OBJECTIVES: To discuss basic principles of inheritance as they relate to cancer genetics. DATA SOURCES: Current research and professional literature that are necessary to understand genetics and cancer. CONCLUSIONS: Studies of the human genome are identifying the location and sequence of genes that influence how cells grow and function, and relationships between genetic information and cancer development. IMPLICATIONS FOR NURSING PRACTICE: Understanding basic genetic information is an essential foundation of current and future oncology nursing practice.
Chromosomes↗
Shifting attention in visual space: tests of moving-spotlight models versus an activity-distribution model.
Participants were induced to concentrate preparatory attention at a central location, to identify a letter there, to identify a 2nd letter to the extreme left or right of a central horizontal range of 5 locations, and then to identify a 3rd letter at 1 of the central 5 locations. Analog and discrete versions of the moving-spotlight model predict that response times to the 3rd letter will be most rapid at the location of the 2nd letter, whereas an activity-distribution model predicts that the most rapid responses to the 3rd letter will be at the central location, where preparatory attention is strongest. The data from 3 experiments, taken together, are inconsistent with the moving-spotlight models and are consistent with the activity-distribution model.
Adult↗
Estrogens, progestins and coronary artery reactivity.
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Cardiovascular Diseases↗
The tensor fascia lata free flap in abdominal-wall reconstruction.
The pedicled tensor fascia lata flap (TFL flap) is a method of choice for abdominal-wall reconstruction. Frequently, the size and location of the defect produce this option. Microsurgical transfer may overcome these disadvantages. Therefore, the ability of the TFL free flap to reconstruct complex abdominal wounds was evaluated. Seven patients with full-thickness abdominal-wall defects reconstructed by TFL free flaps were reviewed. Their average age was 44.6 years (range: 27 years to 59 years); follow-up averaged 10.5 months (range: 2 months to 18 months). Fifty-seven percent of the wounds were either infected or contaminated; the defect averaged 15 cm x 26 cm Six 85.7 percent) of the wounds involved the epigastrum. No total flap loss was seen, but three flaps developed distal tip necrosis (42.9%). Microsurgical transfer of the TFL free flap overcomes the limitations of the arc of rotation seen with the pedicled flap. It increases the vascularity of the distal portion of the flap. The TFL free flap is therefore an option in abdominal wounds, particularly those with defects of large size or supraumbilical location.
Abdominal Injuries↗
Intracranial hypertension in a patient with craniofacial synostosis and patent sutures.
Craniosynostosis is often associated with restrictive cranial vault deformities, diminished intracranial volume, and intracranial hypertension. Advances in imaging techniques have provided a method of intracranial volume analysis that has demonstrated a more complicated relationship between craniofacial abnormalities and elevated intracranial pressures. Studies have confirmed a decrease in intracranial volume in the presence of craniosynostosis, but this association is not found in every patient. We report an unusual case of elevated intracranial pressure in a patient with the clinical stigmata of Crouzon's syndrome but with patent cranial vault sutures.
Cranial Sutures↗
Unilateral cleft lip repair in the presence of a vermilion hemangioma.
This case describes a repair of a unilateral cleft lip complicated by a lip hemangioma. The relevant issues regarding timing of the repair include safety of the procedure by minimizing blood loss during excision of the hemangioma and minimizing anesthesia risk. In obtaining a lasting cosmetic result, excision of the hemangioma would need to be done when the potential for residual tumor growth would be least likely (during tumor involution). Finally, the difficult issue of psychosocial concerns would balance the need for traditional early cleft repair with a definitive repair prior to increased social interaction in school. All these concerns were met with a delayed single-stage repair after partial involution of the hemangioma. We feel that a single-stage excision and lip repair is an acceptable option. It is reasonable to delay the cleft lip repair until significant involution of the hemangioma has occurred. An acceptable aesthetic result is obtainable.
Child, Preschool↗
A longitudinal, statistical study of reoperation rates in craniosynostosis.
A prospective, statistical study of reoperation rates was done in the treatment of 167 consecutive children with nonsyndromic and syndromic craniosynostosis over a 6-year period at Scottish Rite Children's Medical Center in Atlanta, Georgia. Mean length of follow-up was 2.8 years, with a range of 3 months to 6 years. Reoperation equal to or exceeding the magnitude of the original procedure occurred in 7 percent of cases. Multiple regression analysis revealed several factors associated with reoperation: Females and children with syndromic synostoses were more likely to require reoperation. Total reoperation rates for syndromic and nonsyndromic synostoses were 27.3 and 5.9 percent, respectively. Age at initial surgery, length of operation, and estimated blood loss did not predict a higher reoperation rate.
Child↗
The effects of radiation treatment after TRAM flap breast reconstruction.
A subgroup of mastectomy patients receives adjuvant radiation therapy after autogenous breast reconstruction for locoregional control of cancer. The effects of radiation therapy on pedicled transverse rectus abdominis musculocutaneous (TRAM) flaps were determined to evaluate complication rates and aesthetic results. Nineteen patients from 1981 to 1994 receiving radiation therapy after a pedicled TRAM flap reconstruction were compared with 108 patients who received radiation prior to reconstruction and 572 patients who underwent breast reconstruction without radiation. Retrospective reviews of patient charts were completed. Adjuvant radiation therapy was given for chest-wall recurrence in 13 of 19 patients. With a mean follow-up of 47.6 months from the time of reconstruction, 10 patients (52.6 percent) demonstrated postradiation changes in the TRAM flap reconstruction, and 6 required surgical intervention (31.6 percent). Overall complication rates were increased but were not found to be statistically significant between the radiated TRAM flap group and patients with preoperative radiation followed by TRAM flap reconstruction (31 versus 25 percent). Fibrosis was not found in patients with pre-TRAM flap radiation or in patients without radiation but was seen in 31.6 percent of patients who received radiation after the reconstruction. Fat necrosis was not significantly increased between the two groups of radiated patients. The complication rate does not change whether a patient receives radiation before or after her reconstruction; only the nature of the complication changes (fat necrosis to fibrosis).
Breast Neoplasms↗
Medroxyprogesterone acetate antagonizes inhibitory effects of conjugated equine estrogens on coronary artery atherosclerosis.
Although estrogen replacement therapy is associated with reduced risk of coronary heart disease and reduced extent of coronary artery atherosclerosis, the effects of combined (estrogen plus progestin) hormone-replacement therapy are uncertain. Some observational data indicate that users of combined hormone replacement consisting of continuously administered oral conjugated equine estrogens (CEE) and oral sequentially administered (7 to 14 days per month) medroxyprogesterone acetate (MPA) experience a reduction in risk similar to that of users of CEE alone. However, the effects of combined, continuously administered CEE plus MPA (a prescribing pattern that has gained favor) on the risk of coronary heart disease or atherosclerosis are not known. We studied the effects of CEE (monkey equivalent of 0.625 mg/d) and MPA (monkey equivalent of 2.5 mg/d), administered separately or in combination, on the extent of coronary artery atherosclerosis (average plaque size) in surgically postmenopausal cynomolgus monkeys fed atherogenic diets and treated with these hormones for 30 months. Treatment with CEE alone resulted in atherosclerosis extent that was reduced 72% relative to untreated (estrogen-deficient) controls (P < .004). Atherosclerosis extent in animals treated with CEE plus MPA or MPA alone did not differ from that of untreated controls. Although treatment had marked effects on plasma lipoprotein patterns, statistical adjustment for variation in plasma lipoproteins did not alter the between-group relationships in atherosclerotic plaque size, suggesting that these factors do not explain substantially the atheroprotective effect of estrogen or the MPA-associated antagonism. Although the mechanism(s) remains unclear, we conclude that oral CEE inhibits the initiation and progression of coronary artery atherosclerosis and that continuously administered oral MPA antagonizes this atheroprotective effect.
Administration, Oral↗
Tamoxifen inhibits arterial accumulation of LDL degradation products and progression of coronary artery atherosclerosis in monkeys.
Estrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women and inhibits progression of coronary artery atherosclerosis in monkeys. Tamoxifen is a nonsteroidal compound with mixed estrogen agonist and antagonist properties. Its antagonist activity is useful in chemotherapy of breast cancer and may have protective effects on plasma lipid concentrations, but its effects on atherogenesis have not been defined. The goal of this study was to examine the effect of tamoxifen on plasma lipids, arterial and hepatic LDL metabolism, and progression of coronary artery atherosclerosis in surgically postmenopausal female monkeys. Thirty-five monkeys were fed an atherogenic diet containing 1.3 mg.kg-1.d-1 tamoxifen (equivalent to the usual dose of 20 mg/d given to women). Thirty-one monkeys were fed the same atherogenic diet with no tamoxifen. Ten monkeys from each treatment group were fed the test diets for 12 weeks to examine the short-term effects of tamoxifen on arterial LDL metabolism. The rest of the monkeys were fed the test diets for 3 years to study the long-term effects of tamoxifen on development of atherosclerosis. In the short term, tamoxifen inhibited the rate of arterial accumulation of LDL degradation products overall (P = .03) and decreased hepatic cholesterol content (P = .003). In the long term, tamoxifen increased plasma concentrations of triglycerides (0.60 +/- 0.67 versus 0.23 +/- 0.02 mmol/L, P = .001) and reduced average LDL molecular weight (5.3 +/- 0.2 versus 4.8 +/- 0.1 g/mumol, P = 0.004) but had no effects on plasma total, LDL, or HDL cholesterol concentrations. Coronary artery atherosclerosis (intimal area, mean +/- SEM) was 0.25 +/- 0.06 mm2 in control monkeys and 0.12 +/- 0.03 mm2 in tamoxifen-treated monkeys (P = .057). We conclude that tamoxifen has antiatherogenic effects that may be modulated in part through direct effects on arterial LDL metabolism.
Animals↗
Benefits and burdens of genetic carrier identification.
This qualitative study examined experiences of adults requesting genetic-carrier testing for four autosomal-recessive and X-linked-recessive disorders. The sample consisted of 34 adults with a positive family history or membership in an ethnic group at risk for the inherited disorder. A semistructured interview guide was used to collect data during an interview 1 month after receipt of test results. Noncarriers experienced benefits of emotional relief and freedom to move ahead with reproductive planning. Carriers experienced burdens of sadness and loss of reproductive expectations. Some subjects in both groups experienced difficulty disclosing results to selected family members and expressed concerns regarding disclosure of testing to insurance providers.
Adult↗
The Roy Adaptation model and patient/family experiences.
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Adaptation, Psychological↗
Adeno-associated virus vectors for vascular gene delivery.
A variety of delivery systems have been used to genetically modify vascular endothelial cells and smooth muscle cells (SMCs), but currently available systems suffer from either inefficient in vivo gene transfer, transient episomal vector expression, or significant immune responses and inflammation. In the present study, we evaluated an alternate vector system, recombinant adeno-associated virus (rAAV) for transduction of vascular cells in culture and in vivo. Primary cultures of rabbit, monkey, and human SMCs; macaque and human microvascular endothelial cells; and human umbilical vein endothelial cells were efficiently transduced at a dose of 100 to 1000 DNase-resistant particles per cell. rAAV-mediated transduction of the vasculature in vivo was observed after intraluminal gene delivery or after intra-adventitial injection in carotid arteries of atherosclerotic cynomolgus monkeys. Whether vector delivery was intraluminal or adventitial, transduction was observed in the adventitia, particularly within microvessels (vasa vasorum) but not in cells of the intima or media. Transduction of adventitial microvessels was enhanced by balloon injury 4 days before gene transfer. This was particularly true for adventitial delivery. We have previously shown that adventitial cell proliferation increases significantly 4 days after balloon injury (45%) in this animal model. Together, these data suggest that cell proliferation may enhance AAV transduction in vivo in the vasculature. AAV vectors exhibited a tropism in vivo for the microvascular endothelium at the doses used in the present study, which may provide the opportunity for targeting gene delivery. In summary, we have demonstrated the utility of rAAV vectors for ex vivo vascular cell gene delivery and present an initial experience with rAAV for in vivo vascular gene delivery. This alternate vector system may overcome some of the limitations hampering the development of gene therapy for vascular disorders.
Animals↗
Prepatellar bursitis: a unique presentation of tophaceous gout in an normouricemic patient.
We describe a patient with no history of gout and persistently normal serum uric acid concentrations in whom septic acute prepatellar bursitis was diagnosed initially, but empiric antibiotic therapy failed. Urate crystals were detected when the prepatellar bursa was aspirated for the 3rd time, and the diagnosis was changed to gouty bursitis. The case illustrates the importance of repeatedly aspirating suspicious sites to establish the diagnosis in elusive cases of crystal deposition disease.
Aged↗