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Biomedical subjects

J A Simon

Publications and source records attributed to J A Simon.

At least 55 records · Page 3Linked to original sources

Catastrophic failure of the acetabular component in a ceramic-polyethylene bearing total hip arthroplasty.

Recent research in total hip arthroplasty has focused on attempts to decrease wear at the femoral head-acetabulum articulation, to limit the production of debris that is believed to lead to osteolysis and prosthetic loosening. The use of ceramic-on-polyethylene bearing surfaces has been reported to produce lower wear rates and therefore may increase the life expectancy of the joint arthroplasty. Problems with this bearing have been reported to be due to ceramic femoral head fracture. Reported here are 2 cases of catastrophic failure of total hip arthroplasties, involving a ceramic femoral head, caused by failure of the polyethylene acetabular liner, with subsequent penetration of the femoral head through the acetabular shell.

Acetabulum↗

Ascorbic acid supplement use and the prevalence of gallbladder disease. Heart & Estrogen-Progestin Replacement Study (HERS) Research Group.

To investigate the relation of ascorbic acid supplement use to gallbladder disease and cholecystectomy, we conducted a cross-sectional analysis of baseline from 2744 postmenopausal women, aged 44-79 years, enrolled in the Heart & Estrogen-progestin Replacement Study (HERS), a secondary coronary heart disease prevention trial. A total of 629 HERS participants (23%) reported a history of gallbladder disease. Of these, 508 (19%) also reported a history of cholecystectomy. In bivariate models, ascorbic acid supplement use was associated with a decreased prevalence of gallbladder disease [odds ratio (OR)=0.74; 95% confidence interval (CI), 0.57, 0.96] and a trend toward a decreased prevalence of cholecystectomy (OR=0.77; 95% CI, 0.58, 1.02). Because we detected significant interactions between ascorbic acid supplement use and alcohol consumption, multivariate analyses were performed stratified by drinking status. After adjustment for potential confounding variables, use of ascorbic acid supplements among drinkers was associated with a decreased prevalence of gallbladder disease (adjusted OR=0.50; 95% CI, 0.31, 0.81) and cholecystectomy (adjusted OR=0.38; 95% CI, 0.21, 0.67). Use of ascorbic acid supplements among non-drinkers was not significantly associated with either prevalence of gallbladder disease or cholecystectomy. Further study is necessary to confirm our findings and, specifically, to examine the combined effects of ascorbic acid and alcohol on cholesterol metabolism.

Adult↗

Androgen effects on the central nervous system in the postmenopausal woman.

Interest in the effects of androgens on the central nervous system (CNS) in postmenopausal women dates back to at least fifty years. The mechanisms of action of androgens on the CNS are extremely complex and multi-faceted. Much data has been accumulated in recent years that suggest a beneficial role of androgens in several aspects of CNS function. These include positive effects on mood, cognition, memory, and libido. The information continues to be preliminary in nature and requires further investigations. There is evidence of altered androgen metabolism triggered by exogenous postmenopausal estrogen therapy. While promising, the current body of evidence does not yet support the routine addition of androgens to postmenopausal hormone therapy.

Adult↗

Relation of serum ascorbic acid to serum lipids and lipoproteins in US adults.

OBJECTIVE: To examine the relation of serum ascorbic acid level to serum lipid and lipoprotein levels among a random sample of the US adult population. METHODS: Using linear regression, the relation of serum ascorbic acid level to serum lipid and lipoprotein levels was examined among 5,412 women and 5,116 men enrolled in the Second National Health and Nutrition Examination Survey (NHANES II), 1976-1980. Age, race, body mass index, level of physical activity, level of education, alcohol intake, and dietary energy, cholesterol, and fat intakes, and other potential confounders were included in the multivariate models. RESULTS: Serum ascorbic acid level was independently associated with high-density lipoprotein cholesterol (HDL-C) among women; each 1 mg/dl increase in serum ascorbic acid level (range 0.1 to 2.7 mg/dl) was associated with a 2 mg/dl increase in HDL-C level (p = 0.001). Because other investigators have demonstrated an inverse relation between ascorbic acid intake or blood levels and total serum cholesterol in individuals with elevated total serum cholesterol levels, we analyzed four subgroups of NHANES II participants with total serum cholesterol levels > 200 mg/dl. Among women with total serum cholesterol levels > or = 200 mg/dl, each 1 mg/dl increase in serum ascorbic acid level was independently associated with an increase of 2 to 3 mg/dl in HDL-C level (p < or = 0.05). Serum ascorbic acid level was not significantly associated with other serum lipids or lipoproteins. CONCLUSIONS: If the observed associations are linked causally, they would suggest that ascorbic acid is a factor in cholesterol homeostasis among women and may be particularly important for women at increased risk for coronary heart disease.

Adolescent↗

Serum ascorbic acid and other correlates of gallbladder disease among US adults.

OBJECTIVES: This study examined the correlates of clinical gallbladder disease among US adults and whether serum ascorbic acid levels are associated with a decreased prevalence of gallbladder disease. METHODS: Cross-sectional analyses of data from the Second National Health and Nutrition Examination Survey were conducted. RESULTS: A total of 384 women (8%) and 107 men (3%) reported a history of gallstone disease, and 347 women (7%) and 81 men (2%) reported a history of cholecystectomy. An inverted U-shaped relation was found between serum ascorbic acid level and clinical gallbladder disease among women but not among men. CONCLUSIONS: Ascorbic acid, which affects the catabolism of cholesterol to bile acids and, in turn, the development of gallbladder disease in experimental animals, may reduce the risk of clinical gallbladder disease in humans.

Adult↗

Renal medullary carcinoma.

PURPOSE: Renal medullary carcinoma is a rare and extremely aggressive neoplasm that almost always develops in young patients with sickle cell trait. To our knowledge all cases to date have been metastatic at surgical resection. Pathological examination reveals an aggressive tumor mainly involving the renal medulla with a varied morphology. The prognosis is dismal. Mean survival from the time of resection is 15 weeks (range 2 to 52). The disease course has not been altered by surgery, radiotherapy or various regimens of chemotherapeutic agents. MATERIALS AND METHODS: We add to the literature our experience treating renal medullary carcinoma in 2 cases and review the existing literature on this disease. RESULTS: Both patients whom we treated died of the disease, as have the other 35 patients described in the literature. CONCLUSIONS: A high index of suspicion may lead to earlier diagnosis and treatment, and survival of patients with renal medullary carcinoma.

Adult↗

Serum ascorbic acid and cardiovascular disease prevalence in U.S. adults.

To examine the relation between serum ascorbic acid level and the prevalence of cardiovascular disease, we analyzed data from 6,624 U.S. men and women enrolled in the Second National Health and Nutrition Examination Survey. We calculated odds ratios and 95% confidence intervals to estimate the relative prevalence of cardiovascular disease, defined as self-reported coronary heart disease or stroke, or a diagnosis of peripheral vascular disease based on physical examination. Serum ascorbic acid levels were independently associated with prevalence of coronary heart disease and stroke; a 0.5-mg per dl increase in serum ascorbic acid level was associated with an 11% reduction in coronary heart disease and stroke prevalence. We also analyzed the relation of ascorbic acid, grouped into low to marginal, normal, and saturation serum categories, to cardiovascular disease. Compared with participants with low to marginally low serum ascorbic acid levels, we found a 27% decreased prevalence of coronary heart disease (95% confidence interval = 10-41%) and a 26% decreased prevalence of stroke (95% confidence interval = 3-44%) among participants in the highest serum ascorbic acid category. Serum ascorbic acid levels were not consistently associated with prevalence of peripheral vascular disease. These results are consistent with the hypothesis that increased ascorbic acid intake may decrease the risk of coronary heart disease and stroke.

Adult↗

Smoking cessation after surgery. A randomized trial.

BACKGROUND: Cigarette smoking is the greatest cause of preventable mortality in the United States. Because most smokers would like to quit and most hospitals are smoke free, surgical admissions represent a window of opportunity for tobacco cessation interventions. METHODS: A total of 324 patients (98% men), aged 25 to 82 years, who were current smokers and who underwent noncardiac surgery were enrolled in a randomized controlled trial at the Veterans Affairs Medical Center, San Francisco, Calif. One hundred sixty-eight participants (52%) received a multicomponent intervention designed to increase self-efficacy and coping skills that included face-to-face in-hospital counseling, viewing a smoking cessation videotape, self-help literature, nicotine replacement therapy, and 3 months of telephone follow-up. One hundred fifty-six participants (48%) received self-help literature and brief counseling lasting 10 minutes. Serum or saliva cotinine levels were measured to confirm self-reported smoking cessation. RESULTS: At 12 months of follow-up, the self-reported quit rate was 27% among the intervention group and 13% among the comparison group (relative risk, 2.1; 95% confidence interval, 1.2-3.5; P < .01). Based on biochemical confirmation, 15% of the intervention group, compared with 8% of the comparison group, quit smoking at 12 months (relative risk, 2.0; 95% confidence interval, 1.0-3.9; P = .04). CONCLUSIONS: A smoking cessation intervention targeted at smokers hospitalized for noncardiac surgery can increase long-term quit rates. Surgical hospitalizations provide an opportunity to reach smokers who want to quit smoking.

Adult↗

Distal femoral fixation: a biomechanical comparison of the standard condylar buttress plate, a locked buttress plate, and the 95-degree blade plate.

OBJECTIVES: This biomechanical cadaver study was performed to compare the fixation stability of a standard lateral condylar buttress plate with a similar condylar buttress plate with the distal screws locked to the plate. Then the study was repeated with six additional matched femoral pairs to compare the locked plate with a standard 95-degree blade plate. DESIGN: Six matched pairs of mildly osteopenic femurs were selected, and each side was assigned randomly to fixation with either a standard lateral condylar buttress plate or a modified lateral condylar buttress plate with locked distal screws. The experiment was repeated with six additional matched pairs of femurs instrumented with either a modified lateral condylar buttress plate with locked distal screws or a standard 95-degree blade plate. INTERVENTION: The femurs were instrumented, and a gap osteotomy was created at the distal femoral metaphysis. The instrumented femurs were then mechanically tested in axial compression and bending/torsional loading to determine fixation stability; then they were loaded at 1,000 newtons for 10(5) cycles and retested for stability. MAIN OUTCOME MEASUREMENT: The displacement across the osteotomy gap at 100-newton and 1,000-newton axial loads was measured directly for each specimen before and after cycling. In addition, resistance to displacement in bending/torsional loading (newtons/centimeter) was determined from load/displacement curves, before and after cycling. RESULTS: The locked buttress plate provided significantly greater fixation stability than the standard plate both before and after cycling in axial loading. The locked buttress plate also proved significantly more stable in axial loading than the blade plate both before and after cycling. CONCLUSION: A condylar buttress plate with locked screws is a valid concept for improving fixation stability.

Biomechanical Phenomena↗

Bioresorbable fracture fixation in orthopedics: a comprehensive review. Part I. Basic science and preclinical studies.

Metal alloys are currently the most popular materials for manufacture of fracture-fixation devices. Two major disadvantages of these materials are their extreme stiffness, which causes stress shielding of the underlying bone, and the necessity, in a significant number of cases, of removing metallic implants after fracture healing is complete. These shortcomings of metal alloys have led to the study of bioresorbable materials for use in fracture fixation. Currently, polylactic acid, polyglycolic acid, and polydioxanone implants are available to the orthopedic surgeon for the fixation of small cancellous bone fractures. Part I of this article provides an overview of the basic science of bioresorbable materials and presents a comprehensive review of preclinical studies reported in the orthopedic literature. Clinical studies will be reviewed in Part II.

Alloys↗

Bioresorbable fracture fixation in orthopedics: a comprehensive review. Part II. Clinical studies.

Bioresorbable materials overcome two major disadvantages of the metal alloys most commonly used in fracture-fixation devices: their extreme stiffness, which causes stress shielding of the underlying bone, and the necessity, in a significant number of cases, of removing metallic implants after fracture healing is complete. The orthopedic surgeon now has the use of polylactic acid, polyglycolic acid, and polydioxanone implants for the fixation of small cancellous bone fractures. The currently available bioresorbable materials lack strength and stiffness and are associated with inflammatory reactions and osteolysis in a significant number of cases. Surgeons should use the available pins and screws with extreme care and attention to the characteristics of each individual injury, particularly its healing characteristics, as well as to the material's initial mechanical properties, degradation rates, and associated complications.

Biocompatible Materials↗

Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis.

A two-hybrid system was used to screen yeast and human expression libraries for proteins that interact with mismatch repair proteins. PCNA was recovered from both libraries and shown in the case of yeast to interact with both MLH1 and MSH2. A yeast strain containing a mutation in the PCNA gene had a strongly elevated mutation rate in a dinucleotide repeat, and the rate was not further elevated in a strain also containing a mutation in MLH1. Mismatch repair activity was examined in human cell extracts using an assay that does not require DNA repair synthesis. Activity was inhibited by p21WAF1 or a p21 peptide, both of which bind to PCNA, and activity was restored to inhibited reactions by addition of PCNA. The data suggest a PCNA requirement in mismatch repair at a step preceding DNA resynthesis. The ability of PCNA to bind to MLH1 and MSH2 may reflect linkage between mismatch repair and replication and may be relevant to the roles of mismatch repair proteins in other DNA transactions.

Adaptor Proteins, Signal Transducing↗

Relation of smoking and alcohol consumption to serum fatty acids.

To examine the relation of cigarette smoking and alcohol consumption to serum fatty acid levels, the authors conducted a cross-sectional study of 190 men who were enrolled in the Multiple Risk Factor Intervention Trial between 1973 and 1976. After controlling for dietary fat, cholesterol, energy intake, and other potential confounders, the authors found that smoking and alcohol intake were associated with the serum cholesterol ester and phospholipid levels of several fatty acids. As the number of cigarettes smoked per day increased, the levels of cholesterol ester and phospholipid palmitoleic acid (16:1) and oleic acid (18:1) and the levels of phospholipid dihomogammalinolenic acid (20:3) and omega-9 eicosatrienoic acid (20:3) increased (all p's < or = 0.01). Serum levels of phospholipid omega-3 docosahexaenoic acid (22:6) and cholesterol ester and phospholipid arachidonic acid (20:4) were inversely associated with smoking (all p's < or = 0.01). As the number of alcoholic drinks per week increased, levels of cholesterol ester and phospholipid palmitic acid (16:0) and oleic acid (18:1), cholesterol ester myristic acid (14:0), and phospholipid palmitoleic acid (16:1), adrenic acid (22:4), and omega-9 eicosatrienoic acid (20:3) increased (all p's < 0.05), whereas levels of cholesterol ester and phospholipid linoleic acid (18:2) and phospholipid stearic acid (18:0) and the serum polyunsaturated fat: saturated fat ratio decreased (all p's < or = 0.01). These results suggest that smoking and alcohol consumption may influence the absorption, synthesis, or metabolism of serum fatty acids. Studies that use serum fatty acid levels as indicators of dietary fat intake should control for the effects of cigarette smoking and alcohol consumption.

Adult↗

Serum fatty acids and blood pressure.

To examine the relation between serum fatty acids and blood pressure, we conducted a cross-sectional study of 156 men who were enrolled in the Multiple Risk Factor Intervention Trial. After confirming the stability of the stored serum samples, we measured serum fatty acid levels by gas-liquid chromatography and examined their association with blood pressure. Using stepwise linear regression, we determined that each SD increase (1.9%) in the serum level of cholesterol ester palmitoleic acid (16:1) was associated with a systolic pressure increase of 3.3 mm Hg (95% confidence interval, 0.9 to 5.6 mm Hg) and each SD increase (0.1%) in phospholipid omega 9 eicosatrienoic acid (20:3) was associated with a diastolic pressure increase of 1.7 mm Hg (95% confidence interval, 0.5 to 2.9 mm Hg). Serum level of cholesterol ester steric acid (18:0) was inversely associated with diastolic pressure: each SD increase (0.2%) was associated with a decrease of 1.4 mm Hg (95% confidence interval, -2.5 to -0.2 mm Hg). In multivariate models that included dietary fat intake, cholesterol ester dihomogammalinolenic acid (20:3) was also associated with diastolic pressure: each SD increase (0.16%) was associated with an increase of 1.2 mm Hg (95% confidence interval, 0.1 to 2.4 mm Hg). Our results indicate that three nonessential fatty acids--stearic acid, palmitoleic acid, and omega 9 eicosatrienoic acid, and one essential fatty acid--dihomogammalinolenic acid, are independent correlates of blood pressure among middle-aged American men at high risk of coronary heart disease.

Adult↗

Sunlight and sunburn in human skin cancer: p53, apoptosis, and tumor promotion.

Sunlight is a carcinogen to which everyone is exposed. Epidemiology indicates that most carcinogenic sunlight exposure takes place several decades before the tumor arises. Some of the early events have been identified by searching for genes having ultraviolet (UV)-specific mutations. Over 90% of squamous cell carcinomas and more than 50% of basal cell carcinomas from New England patients contain UV-like mutations in the p53 tumor suppressor gene. From the mutation pattern, it can be concluded that the carcinogenic DNA lesions were pyrimidine-cytosine photoproducts caused by the UVB portion of sunlight. Particular codons of the p53 gene are most susceptible, apparently because of slower DNA repair at specific sites. Sunlight is sufficiently mutagenic often to mutate both p53 alleles. These mutations are also found in the precancer for squamous cell carcinoma, actinic keratosis, implying an early role. The function of p53 in normal skin is indicated by the observation that inactivating p53 in mouse skin reduces the appearance of sunburn cells, apoptotic keratinocytes generated by UV overexposure. Skin thus appears to possess a p53-dependent "cellular proofreading" response to DNA damage in which precancerous cells self-destruct. If this response is reduced in a single cell by a prior p53 mutation, sunburn can thereafter select for clonal expansion of the p53-mutated cell into an actinic keratosis. Sunlight appears to act twice: as tumor initiator and as tumor promoter.

Animals↗

Serum fatty acids and the risk of coronary heart disease.

To examine the relation between serum fatty acids and coronary heart disease (CHD), the authors conducted a nested case-control study of 94 men with incident CHD and 94 men without incident CHD who were enrolled in the Usual Care group of the Multiple Risk Factor Intervention Trial between December 1973 and February 1976. After confirming the stability of the stored serum samples, the authors measured serum fatty acid levels by gas-liquid chromatography and examined their association with CHD. In all multivariate models, levels of the cholesterol ester saturated fatty acid palmitic acid (16:0) were directly associated with CHD risk (standardized odds ratio = 1.68; 95% confidence interval 1.10-2.55 in the model that adjusted for total plasma cholesterol level). Levels of the phospholipid omega-3 fatty acid docosapentaenoic acid (22:5) were inversely associated with CHD risk in the two multivariate models that controlled for the effects of total plasma cholesterol level or high density lipoprotein cholesterol to total plasma cholesterol ratio (standardized odds ratio = 0.58; 95% confidence interval 0.38-0.89 in the first model that controlled for total plasma cholesterol level). In contrast to the first two multivariate models, levels of the docosahexaenoic acid (22:6) were inversely associated with CHD risk in a third multivariate model that controlled for the effects of high density lipoprotein cholesterol to low density lipoprotein cholesterol ratio (standardized odds ratio = 0.57; 95% confidence interval 0.36-0.90). These findings are consistent with other evidence indicating that saturated fatty acids are directly correlated with CHD and that omega-3 polyunsaturated fatty acids are inversely correlated with CHD. Because these associations were present after adjustment for blood lipid levels, other mechanisms, such as a direct effect on blood clotting, may be involved.

Adult↗