Biomedical subjects

S E Gabriel

Publications and source records attributed to S E Gabriel.

At least 91 records · Page 5Linked to original sources

PubMed1995

Trends in the utilization of silicone breast implants, 1964-1991, and methodology for a population-based study of outcomes.

Using the unique data resources of the Rochester Epidemiology Project, we have designed a population-based retrospective cohort study to examine the risks and complications of silicone breast implants among 749 Olmsted County, Minnesota, women who received these devices between 1964 and 1991, and 1498 control women who did not receive such devices. In this paper, we present data describing the population-based trends in the utilization of these devices from 1964 to 1991. In addition, we discuss the case ascertainment, outcome assessment, and reliability of the data collection for the outcomes study. The utilization of breast implants increased markedly over the past 30 yr with the rate of new implants per 100,000 women (> or = 15 years of age) rising from 3.5 in 1964 to 95 in 1979, remaining stable thereafter. The prevalence of breast implants among Olmsted County women > or = 15 years of age on 1 January 1992 was approx. 1%. An examination of the characteristics of these women reveals that recent utilization of breast implants has increased more rapidly among rural than among urban women, that the proportion of women receiving implants for breast cancer mastectomy reconstruction has increased in recent years, and that the great majority of women receiving implants are married at the time of implant. These trends also revealed that the average age of women who receive implants is rising and that in more recent years both much younger and much older women are receiving implants.

Adolescent↗

PubMed1995

cAMP- but not Ca(2+)-regulated Cl- conductance in the oviduct is defective in mouse model of cystic fibrosis.

Defective adenosine 3',5'-cyclic monophosphate (cAMP)-mediated Cl- transport in cystic fibrosis (CF) reflects defects in the cystic fibrosis transmembrane conductance regulator (CFTR). A moderate level of CFTR mRNA expression has been found in rodent and human oviductal epithelium, but unlike other CFTR-expressing tissues, the oviduct in CF patients is apparently normal. The present study was carried out to investigate the relative magnitude of the cAMP- and intracellular Ca2+ (Cai2+)-regulated Cl- secretion in primary cultures of the oviduct from normal and CF mice generated by targeted disruption of the murine CF gene. Normal oviductal epithelium exhibited a basal equivalent short-circuit current (Ieq) of 20.3 +/- 1.7 muA/cm2. CF oviduct exhibited a lower basal Ieq of 4.5 +/- 1.9 muA/cm2. In normal mice, forskolin (10(-5) M, apical) elicited a slowly developing sustained rise in Ieq, whereas ionomycin (5 x 10(-6) M, apical) and ATP (10(-4) M, apical) induced larger increases in Ieq consisting of a prompt, transient response followed by a slowly decreasing component. The Ieq response to forskolin was totally abolished in CF mouse oviducts, but the magnitudes of the peak Ieq responses to ionomycin and ATP were not different from normal. The time courses of the ionomycin- and ATP-evoked responses, however, were significantly more transient in CF than in normal oviducts. These results demonstrate that CF mouse oviduct exhibits defective cAMP- but not Cai(2+)-mediated Cl- secretion. The relatively high level of functional expression of the alternative Cai(2+)-activated Cl- secretory pathway in the mouse oviduct may contribute to the absence of major pathology in the CF oviduct.

Adenosine Triphosphate↗

PubMed1995

Economic and quality-of-life impact of NSAIDs in rheumatoid arthritis: A conceptual framework and selected literature review.

In this review, we provide a conceptual framework of the ideal pharmacoeconomic model for nonsteroidal anti-inflammatory drug (NSAID) use in rheumatoid arthritis, together with a review of selected literature focusing on those areas identified in our model. An ideal pharmacoeconomic model fully accounts for the benefits and costs of this therapy. The benefits include: decreased pain and swelling; increased functional status, which may in turn lead to increased earnings potential; and decreased use of adjunctive therapies. The costs include costs for drug acquisition and administration, monitoring and treatment for adverse effects, as well as preventive measures. Noneconomic 'costs' (i.e. losses in quality of life and/or functional status) must also be included in this equation. Our literature review led to the following conclusions. NSAIDs are highly effective agents for the control of musculoskeletal pain and inflammation, and as such are among the most widely used drugs worldwide. It is well recognised that marked improvements in quality of life occur among arthritic patients receiving NSAIDs. Although careful patient selection and monitoring for potential adverse effects is essential, these drugs are well tolerated by most patients. NSAID-induced gastrointestinal events, ranging from dyspepsia to severe complications that can lead to hospitalisation, surgery and death, are reported more commonly than adverse effects from any other class of drugs. These events represent a substantial economic burden to society and have well documented negative effects on quality of life. Although misoprostol (a prostaglandin analogue) prevents the development of clinically defined NSAID-associated ulcers, its effectiveness on clinically important outcomes such as haemorrhage and perforation is somewhat more modest. Furthermore, there is evidence that some patients may experience substantial losses in quality of life because of the adverse effects of medication (particularly diarrhoea). Therefore, the widespread use of misoprostol prophylaxis not only has important economic consequences, but has important consequences for quality of life. More research is needed to address the critical trade-offs between cost and quality of life that are inherent in the use of NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1995

Economic evaluation using mathematical models: the case of misoprostol prophylaxis.

Using misoprostol prophylaxis as an example, many of the methods employed in economic analyses that incorporate mathematical models were described. These included: decision analysis, cost effectiveness analysis (including incremental cost effectiveness analysis), one-way, multi-way, and probabilistic sensitivity analysis, and the estimation of quality adjusted life years for use in cost utility analysis. In the case of misoprostol prophylaxis, the cost effectiveness analysis demonstrated that, compared to the no prophylaxis alternative, prophylaxis cost an extra $650, on average, for every additional ulcer prevented, and was potentially cost saving for some high risk groups. The cost utility analysis demonstrated that prophylaxis resulted (on average) in modest additional costs and no additional quality of life benefits. Sensitivity analysis demonstrated that, at worst, prophylaxis reduced quality of life; at best, the incremental cost effectiveness ratio was $9333 for each quality adjusted life-year gained by prophylaxis compared to no prophylaxis. The results of the cost utility analysis also showed that prophylaxis may be cost saving in high risk groups, confirming the results of the cost effectiveness analysis. Finally, and perhaps most importantly, this analysis illustrated the importance of incorporating measures of health related quality of life into economic evaluation.

Cost-Benefit Analysis↗

PubMed1995

The use of clinical characteristics to predict the results of temporal artery biopsy among patients with suspected giant cell arteritis.

OBJECTIVE: To develop a mathematical model which predicts temporal artery biopsy results. METHODS: We collected clinical and laboratory data as well as biopsy results among a consecutive cohort of all individuals who underwent temporal artery biopsy at Mayo Medical Center between January 1, 1988 and December 31, 1991. All biopsies were independently reviewed by one pathologist. Logistic regression was used to identify a set of variables which best predicted the biopsy results. This model was then used to identify patients who were highly likely (> or = 95% predictive value) to have either a negative or a positive biopsy. A receiver operating characteristic (ROC) curve was generated using the best fit model. RESULTS: Of the 525 people in the study, there were 187 men and 338 women. The logistic regression model and the ROC curve generated from this model were of modest value in predicting biopsy results from prebiopsy clinical characteristics. However, this model identified 60 (11%) individuals who had a > or = 95% probability of having a negative biopsy. None of these individuals had any symptoms of claudication, only 5 of 60 (8%) had temporal artery abnormalities on examination, 45 (75%) had synovitis (suggesting an alternate diagnosis), and their median erythrocyte sedimentation rate was only 31 mm/h (Westergren). CONCLUSIONS: In individuals with these findings, we recommend a careful search for other diagnoses before temporal artery biopsy.

Aged↗

PubMed1995

Giant cell arteritis involving the facial artery.

Jaw claudication in giant cell (temporal) arteritis (GCA) is believed to be due to vasculitic obstruction or stenosis of the arteries supplying the muscles of mastication, notably the facial and internal maxillary arteries and their branches. However, histologic documentation of this is rarely available because GCA is usually diagnosed by temporal artery biopsies. We describe a patient with jaw claudication and other clinical features of GCA in whom a facial artery biopsy confirmed involvement by GCA.

Aged↗

PubMed1995

Costs of osteoarthritis: estimates from a geographically defined population.

Using the population based data resources of the Rochester Epidemiology Project and a postal survey, we estimated all costs (direct medical, indirect medical, and nonmedical) incurred among a population based prevalence cohort of individuals with osteoarthritis (OA) and a nonarthritic comparison cohort. Cost estimates were compared between the 2 groups adjusting for age and sex differences. Our results demonstrated that people with OA incur substantial incremental medical costs, not only for arthritis care, but also for the care of neurological, gastrointestinal, cardiac, and respiratory conditions compared to nonarthritics. These data also demonstrated important and statistically significantly higher levels of work disability among people with OA compared to their age and sex adjusted peers without arthritis from the same community.

Adult↗

PubMed1994

Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model.

The effect of the number of cystic fibrosis (CF) alleles on cholera toxin (CT)-induced intestinal secretion was examined in the CF mouse model. CF mice that expressed no CF transmembrane conductance regulator (CFTR) protein did not secrete fluid in response to CT. Heterozygotes expressed 50 percent of the normal amount of CFTR protein in the intestinal epithelium and secreted 50 percent of the normal fluid and chloride ion in intestinal epithelium and secreted 50 percent of the normal fluid and chloride ion and fluid secretion suggests that CF heterozygotes might possess a selective advantage of resistance to cholera.

Alleles↗

PubMed1994

Risk of connective-tissue diseases and other disorders after breast implantation.

BACKGROUND: We conducted a population-based, retrospective study to examine the risk of a variety of connective-tissue diseases and other disorders after breast implantation. METHODS: All women in Olmsted County, Minnesota, who received a breast implant between January 1, 1964, and December 31, 1991 (the case subjects), were studied. For each case subject, two women of the same age (within three years) from the same population who had not received a breast implant and who underwent a medical evaluation within two years of the date of the implantation in the case subject were selected as control subjects. Each woman's inpatient and outpatient medical record was reviewed for the occurrence of various connective-tissue diseases, certain other disorders thought to have an autoimmune pathogenesis (e.g., Hashimoto's thyroiditis), and cancer other than breast cancer, as well as related symptoms and abnormal results of laboratory tests. The case subjects were categorized according to whether they received implants for cosmetic reasons, for reconstruction after mastectomy for breast cancer, or for reconstruction after subcutaneous mastectomy for cancer prophylaxis. Additional control subjects (women treated for breast cancer who did not have breast reconstruction) were studied for comparison with the case subjects. RESULTS: A total of 749 women who had received a breast implant were followed for a mean of 7.8 years, and 1498 community controls were followed for a mean of 8.3 years. In 5 case subjects, as compared with 10 subjects in the control group, one of the specified connective-tissue diseases was diagnosed (relative risk, 1.06; 95 percent confidence interval, 0.34 to 2.97). Twenty-five case subjects had signs or symptoms of arthritis, as compared with 39 control subjects (relative risk, 1.35; 95 percent confidence interval, 0.81 to 2.23). Among the various signs or symptoms examined, only morning stiffness was significantly increased among the women who had received a breast implant (relative risk, 1.81; 95 percent confidence interval, 1.11 to 2.95). CONCLUSIONS: We found no association between breast implants and the connective-tissue diseases and other disorders that were studied.

Adolescent↗

PubMed1994

How does previous corticosteroid treatment affect the biopsy findings in giant cell (temporal) arteritis?

OBJECTIVE: To determine the effect of previous corticosteroid treatment on the results of temporal artery biopsy. DESIGN: Consecutive case series. SETTING: Tertiary care center. PATIENTS: A consecutive cohort of 535 patients who had temporal artery biopsies at Mayo Clinic, Rochester, Minnesota, between 1 January 1988 and 31 December 1991. MEASUREMENTS AND RESULTS: The dose and duration of corticosteroid treatment received before temporal artery biopsy and detailed clinical and laboratory data were obtained from the patients' medical records. All temporal artery biopsy slides were re-evaluated by a pathologist blinded to clinical data, previous corticosteroid treatment information, and the original pathologic diagnosis. Biopsy specimens were classified as negative for arteritis, positive for typical temporal arteritis, or positive for atypical temporal arteritis. Biopsy results were positive for 31% of patients (89 of 286) who did not receive corticosteroids before biopsy and for 35% of those (86 of 249) who did receive corticosteroids before biopsy (P = 0.4; 95% confidence interval for the difference, -4.7% to 11.5%). Patients who received corticosteroids before biopsy tended to have clinical features more suggestive of arteritis. A multiple logistic regression analysis model, controlling for these differences in clinical and laboratory features, showed that the biopsy positivity rate was unrelated to previous corticosteroid treatment. CONCLUSIONS: Although these results do not prove that histologic features are unaffected by corticosteroids, they show that, in this large, consecutive sample, the positivity rates of temporal artery biopsy were similar in untreated and corticosteroid-treated patients. Temporal artery biopsy may show arteritis even after more than 14 days of corticosteroid therapy in the presence of clinical indications of active disease.

Adrenal Cortex Hormones↗

PubMed1994

Pyridine nucleotide redox potential modulates cystic fibrosis transmembrane conductance regulator Cl- conductance.

Cl- conductance of the apical membrane of airway epithelial cells has properties of a passive diffusion mechanism but is decreased by inhibition of oxidative metabolism. Recent reports that cAMP-dependent Cl- conductance also requires ATP at the intracellular domains of the cystic fibrosis transmembrane conductance regulator (CFTR) suggests that ATP concentration could mediate metabolic regulation of Cl- conductance. However, metabolic inhibitors affect processes other than ATP free energy levels, including notably the metabolic pathways that set the redox potential of pyridine nucleotides within the cell. We have investigated the possibility that CFTR-mediated Cl- conductance is affected by the ratio of oxidized to reduced intracellular pyridine nucleotides. CFTR was expressed in airway and heterologous cells and studied under whole cell voltage clamp conditions, which permitted the intracellular NAD(P)+/NAD(P)H ratio to be varied independently of ATP concentration. In three cell types expressing CFTR, whole cell dialysis with reduced pyridine nucleotides inhibited activation of Cl- currents by forskolin and 8-(4-chlorophenylthio)-cAMP (CPT-cAMP), whereas dialysis with oxidized pyridines increased both basal and stimulated CFTR-mediated Cl- conductance. In cell-attached membrane patches, the open probability of 5-6-picosiemens Cl- channels that had been activated by forskolin and CPT-cAMP was further and reversibly increased by permeant oxidants. Neither swelling-induced whole cell K+ currents in CFTR-expressing cells nor swelling-induced whole cell Cl- currents in multidrug resistance protein-expressing cells were affected by NADPH. Pyridine nucleotide redox potential had little effect on phosphorylation of histone by protein kinase A. We conclude that CFTR Cl- conductance function can be modulated by pyridine nucleotide redox potential. This effect points to the existence of a mechanism or mechanisms by which cytosolic nucleotides other than ATP can affect plasma membrane Cl- conductance and may help explain how a passive ion conductance is linked to cellular energy metabolism.

3T3 Cells↗

PubMed1994

A cost-utility analysis of misoprostol prophylaxis for rheumatoid arthritis patients receiving nonsteroidal antiinflammatory drugs.

OBJECTIVE: To determine the cost-utility of low-dose misoprostol prophylaxis in rheumatoid arthritis (RA) patients treated with nonsteroidal antiinflammatory drugs (NSAIDs). METHODS: Prospectively collected, population-based data on 57 RA patients' preferences (obtained using the category scaling and time trade-off techniques), charge data from a consecutive, population-based cohort of 36 RA patients with NSAID-related gastric ulcer, and literature-derived probability estimates were incorporated into a decision analysis model. RESULTS: Probabilistic sensitivity analysis using 10,000 Monte Carlo simulations demonstrated that, on average, prophylaxis resulted in modest additional costs and no additional quality-of-life benefits. At best, the incremental cost per quality-adjusted life year gained was $9,333. At worst, prophylaxis reduced quality of life. Prophylaxis was cost-saving if the ulcer complication rate was > 1.5%, or if the 3-month price of misoprostol was < or = $95. CONCLUSION: Whereas prophylaxis may be cost-saving among high-risk NSAID users, from some patients' perspective, it reduces quality of life. Although these data may not be generalizable to other clinical populations, they illustrate the importance of incorporating patient preferences into economic evaluations.

Adult↗

PubMed1994

The sensitivity and specificity of computerized databases for the diagnosis of rheumatoid arthritis.

OBJECTIVE: To examine the accuracy of a computerized medical database for the diagnosis of rheumatoid arthritis (RA). METHODS: The complete medical records of all prevalent cases of RA (according to the 1987 American College of Rheumatology diagnostic criteria) on January 1, 1987 were reviewed to determine the sensitivity, specificity, and predictive value of database diagnoses compared with those obtained by medical record review. Agreement between database and medical record diagnoses was calculated using the kappa statistic. RESULTS: Computerized database diagnoses of RA had a sensitivity of 89%, a specificity of 74%, a positive predictive value of 57%, and a negative predictive value of 94% compared with diagnoses based on clinical information abstracted from the complete medical record. Agreement between database and medical record diagnoses was poor (kappa = 0.54). CONCLUSION: The sole reliance on such databases for the diagnoses of RA can result in substantial misdiagnosis.

Adult↗

PubMed1994

Lack of evidence for gender bias in the utilization of total hip arthroplasty among Olmsted County, Minnesota residents with osteoarthritis.

OBJECTIVE: To evaluate whether women have more advanced osteoarthritis (OA) than men prior to total hip arthroplasty (THA). METHODS: Preoperative clinical and radiographic severity of hip OA was determined among Olmsted County, Minnesota residents who underwent THA. The time from first radiographic changes and first symptoms to THA was compared between genders. RESULTS: Fifty men and 80 women underwent their first THA between 1985 and 1990. Men had higher disease activity levels preoperatively; however, 16 other clinical severity variables and 2 summary measures of OA severity were similar for both genders. Men had radiographically more advanced hip OA preoperatively. The time from first symptom of hip OA to THA was similar for both genders, while the time from first radiographic change to THA was significantly longer for men. CONCLUSION: These results fail to support the hypothesis that hip OA prior to THA is more severe among women compared with men.

Bias↗

PubMed1994

Primary systemic amyloidosis presenting as giant cell arteritis and polymyalgia rheumatica.

Primary systemic amyloidosis may present with features suggesting a vasculitis, including giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). In this report, we describe the clinical characteristics, temporal artery biopsy findings, and the response of vascular and musculoskeletal symptoms to corticosteroid therapy in 4 patients with primary systemic amyloidosis who presented with manifestations of GCA or PMR.

Aged↗

PubMed1993

Functional consequences of heterologous expression of the cystic fibrosis transmembrane conductance regulator in fibroblasts.

We studied the consequences of cystic fibrosis transmembrane conductance regulator (CFTR) expression in NIH-3T3 fibroblasts as a model for the effects of virally transduced CFTR expression in non-epithelial cells. Fibroblasts were infected with a retrovirus vector that contained the human CFTR and neor cDNAs. We selected and expanded G418-resistant clones that encompassed a range of CFTR expression. CFTR-mediated Cl-conductance function was measured as whole cell current, and CFTR protein was quantitated by immunoblot analysis. Overall, there was a good relationship between CFTR protein levels and CFTR-mediated Cl- conductance. Some clones had consistently high basal levels of CFTR-mediated Cl- conductance. This variation in function was partially explained by CFTR protein levels and was not due to clonal variation in cAMP metabolism. High levels of CFTR expression were associated with depolarization of fibroblast membrane potential. The CFTR-expressing clones with the largest basally active CFTR Cl- conductances and the most depolarized membrane potentials also exhibited slower growth rates. These results suggest that potential side effects of gene replacement therapy for cystic fibrosis include functional consequences of CFTR expression in non-epithelial cells.

3T3 Cells↗

PubMed1993

CFTR and outward rectifying chloride channels are distinct proteins with a regulatory relationship.

In cystic fibrosis (CF), numerous epithelial cell functions are abnormal, including Cl- conductance, sodium absorption, mucin sulphation and enzyme secretion. Although the CF gene product, the cystic fibrosis transmembrane conductance regulator (CFTR), functions as a small linear Cl- channel, it is difficult to attribute such pleiotropic disease manifestations solely to a defect in Cl- conductance. This has led to speculation that CFTR regulates the activity of other proteins. One possible example is the protein kinase A activation of outward rectifying Cl- channels (ORCC), which is defective in membrane patches excised from CF cells. Whether CFTR regulates the activity of an independent anion channel is debatable, because ORCC occur exclusively in excised membrane patches and could be an excision-induced molecular derivative of CFTR. 'Knockout' mice that lack CFTR provide a means to define the relationship between CFTR and ORCC. Here we report that ORCC are present in CFTR(-/-) mouse nasal epithelial cells and thus cannot be a derivative of the CFTR molecule. Also ORCC were regulated by protein kinase A in membrane patches from normal but not CFTR(-/-) cells. These observations are the first, to our knowledge definitive demonstration that CFTR regulates the activity of another protein.

3T3 Cells↗

PubMed1993

The cost-effectiveness of misoprostol for nonsteroidal antiinflammatory drug-associated adverse gastrointestinal events.

OBJECTIVE: To compare, in a Canadian health care setting, the costs and consequences of 3 strategies of misoprostol prophylaxis for osteoarthritis patients: prophylaxis for all patients taking nonsteroidal antiinflammatory drugs (NSAIDs), for no patients taking NSAIDs, and for only elderly patients (age > or = 60) taking NSAIDs. METHODS: We designed a decision-analysis model which incorporated costs (estimated with ulcer patient profiles and medical records), review, and probabilities (estimated from a companion meta-analysis, selected literature review, and Ontario Ministry of Health Statistics). Effectiveness was defined as the number of episodes of gastric ulceration requiring hospitalization or outpatient management that were averted by each strategy. RESULTS: On average, prophylaxis cost an additional $650 for every additional gastrointestinal event prevented. Prophylaxis for elderly NSAID users was cost saving if the ulcer complication rate in this group exceeds 1.2%, or if either the charges for outpatient ulcer treatment exceed $2,000, or the 3-month price of misoprostol is < or = $90. CONCLUSION: Our results demonstrate that, in this setting, misoprostol prophylaxis may be highly cost effective.

Aged↗