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Biomedical subjects

S E Gabriel

Publications and source records attributed to S E Gabriel.

At least 55 records · Page 3Linked to original sources
PubMed1999

Modeling the lifetime costs of rheumatoid arthritis.

OBJECTIVE: To develop an analytical approach for estimating the lifetime costs of rheumatoid arthritis (RA) using existing population based cross sectional data, and to use this estimate to describe the potential cost-effectiveness of bone marrow transplantation for RA. METHODS: Estimates of arthritis related costs (direct, indirect, and nonmedical) and mortality were obtained from previously assembled population based cohorts. A mathematical model was designed defining 25 hypothetical ratios (RA/NA) representing the proportionate excess cost of RA each year for the 25 years following a diagnosis of RA. Using age and sex-specific cost estimates, we then simulated a vector of 25 ratios 1000 times. Each age and sex-specific randomly generated variable was converted to an estimated dollar amount (in 1995 dollars US) of excess cost attributable to RA. All dollar amounts were discounted by 3% per year. Finally, each vector of 25 discounted dollar amounts was summed to yield an estimate of the total excess medical costs in 1995 dollars for the first 25 years of a person's lifetime following a diagnosis of RA. Because not every one of these hypothetical individuals would be expected to live all 25 years, we used the standardized mortality ratio for an individual with RA (from our inception cohort) and multiplied it by the age-specific 1990 mortality rates for Minnesota whites to estimate how many of the 1000 randomly generated hypothetical individuals could be expected to die during each of the 25 years. For these, the summation of estimated cost was truncated at the death year. This process yielded, for each age and sex, a sample of 1000 sums of 25 (or fewer) excess costs all in terms of 1995 dollars that correspond to the excess cost during the first 25 years after an RA diagnosis, adjusted for differential survival among patients with RA compared to nonarthritic controls. The distribution of these sums thus represented a distribution of the 1995 dollars that could be saved if RA could be "cured" soon after incidence. RESULTS: Our simulation analyses indicated that the median lifetime incremental costs of RA range roughly from ,$61,000 to $ 122,000. Incremental costs were higher for younger individuals compared to older individuals and were consistent over all percentiles and age groups. No systematic relationship between the incremental costs of females with RA compared to males was identified. CONCLUSION: These data suggest that interventions such as autologous bone marrow transplantation, which has recently been estimated to cost roughly $60,000, may be cost saving if they eliminate the downstream incremental costs of RA.

Adult↗
PubMed1999

Polymyalgia rheumatica with low erythrocyte sedimentation rate at diagnosis.

OBJECTIVE: To determine the frequency and clinical characteristics of polymyalgia rheumatica (PMR) with low erythrocyte sedimentation rate (ESR) at diagnosis in a community based cohort of 232 patients. METHODS: A retrospective review of medical records of all the patients with a diagnosis of PMR in Olmsted County, Minnesota, seen and followed over a 22 year period, from 1970 through 1991. RESULTS: Seventeen (7.3%) patients had ESR < 40 mm/h at diagnosis. The findings and outcome in these patients were compared with the others in the group. There was no difference in sex or age between the 2 groups. Both groups had the same delay to diagnosis, typical gradual onset of the disease, the same frequency of both proximal and distal stiffness/pain, and the same frequency of synovitis. Systemic features were less frequent in the low ESR group than in the high ESR group (59 vs 81%, p = 0.05). Mean ESR in the low ESR group was 26+/-9 mm/h versus 74+/-24 mm/h in the high ESR group. The mean hemoglobin concentration was significantly lower (p = 0.0015) in the high compared to the low ESR group (12.2+/-1.4 g/dl versus 13.3+/-1.3 g/dl). The frequency of positive temporal artery biopsy and of diagnosed giant cell arteritis was the same in the 2 groups. Initial response to therapy, frequency of relapses, number of patients going into remission, time to remission, and daily dose of steroids were the same in both groups. CONCLUSION: Other than more frequent systemic symptoms, our population of patients with PMR and low ESR at diagnosis had similar clinical characteristics and course of disease as patients with high ESR at diagnosis.

Adrenal Cortex Hormones↗
PubMed1999

Comorbidity in arthritis.

OBJECTIVE: To describe the relative frequency of selected comorbidities in 2 population based prevalence cohorts of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) compared to age and sex matched community controls. METHODS: Using the population based data resources of the Rochester Epidemiology Project, we assembled 3 prevalence cohorts of all residents of Olmsted County, Minnesota, with RA (1987 American College of Rheumatology criteria) and age and sex matched controls without arthritis on January 1, 1965, January 1, 1975, and January 1, 1985. Cases and controls were followed longitudinally through their complete (inpatient and outpatient) medical records beginning 10 years prior to the prevalence (or index) date until death, migration from the county, or January 1, 1995. Comorbidity was assessed yearly using the Charlson Comorbidity Index and the Index of Co-existent Diseases (ICED). Descriptive statistics were used to illustrate the baseline characteristics of the study population and the frequency of individual comorbidities in each of the 3 groups over the followup period. Cox proportional hazards modeling was used to assess the risk for each individual comorbidity among patients with arthritis compared to controls and to identify significant predictors of an increase in comorbidity level over time. RESULTS: Our study population included 450 RA, 441 OA, and 891 control subjects. The age and sex distributions of cases and their controls were similar. Over the followup period, patients with RA had a higher likelihood of developing congestive heart failure, chronic pulmonary disease, dementia, and peptic ulcer disease, while cases with OA had a significantly higher risk of developing peptic ulcer disease and renal disease. Among patients with either RA or OA, age, male sex, and baseline comorbidity were significant predictors of a rise in comorbidity. The presence of RA was a highly significant predictor of a rise in comorbidity from one year to the next, even after controlling for the effects of age, sex, and baseline comorbidity (p = 0.0004 for the Charlson and p = 0.006 for the ICED). CONCLUSION: These data indicate that the burden of illness among people with arthritis is higher than for nonarthritics and that this burden appears to be increasing over time, particularly in RA. These results suggest that specialized chronic disease care will be increasingly important for the future health care needs of people with RA.

Arthritis, Rheumatoid↗
PubMed1999

Mortality in rheumatoid arthritis: have we made an impact in 4 decades?

OBJECTIVE: To evaluate trends in survival among patients with rheumatoid arthritis (RA) over the past 4 decades. METHODS: Three population based prevalence cohorts of all Rochester, Minnesota, residents age > or =35 years with RA (1987 American College of Rheumatology criteria) on January 1, 1965, January 1, 1975, and January 1, 1985; and an incidence cohort of all new cases of RA occurring in the same population between January 1, 1955 and January 1, 1985, were followed longitudinally through their entire medical records (including all inpatient and outpatient care by any provider) until death or migration from the county. Mortality was described using the Kaplan-Meier method and the influence of age, sex, rheumatoid factor (RF) positivity, and comorbidity (using the Charlson Comorbidity Index) on mortality was analyzed using Cox proportional hazards models. RESULTS: Mortality was statistically significantly worse than expected for each of the cohorts (overall p<0.0001). A trend toward increased mortality in the 1975 and 1985 prevalence cohorts compared to the 1965 prevalence cohort was present, even after adjusting for significant predictors of mortality (age, RF positivity, and comorbidity). Survival for the general population of Rochester residents of similar age and sex improved in 1975 compared to 1965, and in 1985 compared to 1975. CONCLUSION: The excess mortality associated with RA has not changed in 4 decades. Moreover, people with RA have not enjoyed the same improvements in survival experienced by their non-RA peers. More attention should be paid to mortality as an outcome measure in RA.

Adult↗
PubMed1998

A clinical trial of a chest-pain observation unit for patients with unstable angina. Chest Pain Evaluation in the Emergency Room (CHEER) Investigators.

BACKGROUND: Nearly half of patients hospitalized with unstable angina eventually receive a non-cardiac-related diagnosis, yet 5 percent of patients with myocardial infarction are inappropriately discharged from the emergency department. We evaluated the safety, efficacy, and cost of admission to a chest-pain observation unit (CPU) located in the emergency department for such patients. METHODS: We performed a community-based, prospective, randomized trial of the safety, efficacy, and cost of admission to a CPU as compared with those of regular hospital admission for patients with unstable angina who were considered to be at intermediate risk for cardiovascular events in the short term. A total of 424 eligible patients were randomly assigned to routine hospital admission (a monitored bed under the care of the cardiology service) or admission to the CPU (where patients were cared for according to a strict protocol including aspirin, heparin, continuous ST-segment monitoring, determination of creatine kinase isoenzyme levels, six hours of observation, and a study of cardiac function). The CPU was managed by the emergency department staff. Patients whose test results were negative were discharged, and the others were hospitalized. Primary outcomes (nonfatal myocardial infarction, death, acute congestive heart failure, stroke, or out-of-hospital cardiac arrest) and use of resources were compared between the two groups. RESULTS: The 212 patients in the hospital-admission group had 15 primary events (13 myocardial infarctions and 2 cases of congestive heart failure), and the 212 patients in the CPU group had 7 events (5 myocardial infarctions, 1 death from cardiovascular causes, and 1 case of congestive heart failure). There was no significant difference in the rate of cardiac events between the two groups (odds ratio for the CPU group as compared with the hospital-admission group, 0.50; 95 percent confidence interval, 0.20 to 1.24). No primary events occurred among the 97 patients who were assigned to the CPU and discharged. Resource use during the first six months was greater among patients assigned to hospital admission than among those assigned to the CPU (P<0.01 by the rank-sum test). CONCLUSIONS: A CPU located in the emergency department can be a safe, effective, and cost-saving means of ensuring that patients with unstable angina who are considered to be at intermediate risk of cardiovascular events receive appropriate care.

Adult↗
PubMed1997

Complications leading to surgery after breast implantation.

BACKGROUND: Local complications that require additional surgical procedures are an important problem for women with breast implants. METHODS: We studied 749 women who lived in Olmsted County, Minnesota, and received a first breast implant at the Mayo Clinic between 1964 and 1991. We identified complications that occurred after the initial procedure and after any subsequent implantation. A complication was defined as a surgical procedure performed for any of the following reasons: capsular contracture; rupture of the implant; hematoma or bleeding; infection or seroma of the wound; chronic pain; extrusion, leakage, or sweating of the implant; necrosis of the nipple, areola, or flap; malfunction of the filler port of a tissue expander; and wound dehiscence. RESULTS: During follow-up (mean, 7.8 years; range, 0 to 25.8), 208 (27.8 percent) of the women underwent 450 additional implant-related surgical procedures. Ninety-one (20.2 percent) were anticipated, staged procedures or were done because the patient requested a size change or aesthetic improvement, and 359 procedures (79.8 percent) had at least one clinical indication (thus constituting a complication). Complications occurred in 178 (23.8 percent) of the 749 women and involved 274 (18.8 percent) of the 1454 breasts with implants and 321 (18.8 percent) of the 1703 implants. The most frequent problem was capsular contraction (272 cases), followed by rupture of the implant (60), hematoma (55), and wound infection (23). The rate of complications was significantly lower (P<0.001) among women with cosmetic implants (6.5 percent at one year, 12 percent at five years) than among women who underwent implantation after mastectomy for breast cancer (21.8 percent at one year, 34 percent at five years) or prophylactic mastectomy (17.3 percent at one year, 30.4 percent at five years). CONCLUSIONS: Women who have had breast implantation frequently experience local complications during the subsequent five years. Complications were significantly less frequent among patients who received implants for cosmetic reasons than among those who received implants after mastectomy for cancer or for cancer prophylaxis.

Adult↗
PubMed1997

CFTR-like chloride channels in non-ciliated bronchiolar epithelial (Clara) cells.

Distal airways are believed to be a major site of disease in cystic fibrosis. The product of the CF gene, CFTR, is expressed in non-ciliated bronchiolar epithelial (Clara) cells. Clara cells in primary culture are capable of Cl- secretion which can be stimulated by cAMP and extracellular nucleotides. We used the patch clamp technique to look for Cl- channels in the apical membrane of rabbit Clara cells. In cell-attached patches, we recorded Cl- channels with a conductance for outward currents of 7.5 +/- 0.4 pS (n = 10) and for inward currents of 3.2 +/- 0.5 pS (n = 10); these channels typically exhibited slow kinetics and were not inhibited by the Cl- channel blockers NPPB and DIDS. Channel activity was not noticeably dependent on pipette potential. Addition of chlorophenylthio-cyclic AMP (cpt-cAMP) to the bath increased the percentage of cell-attached patches with active channels (33.8% vs 56.7%; p< 0.05) and the channel open probability (0.49 +/- 0.03 vs 0.84 +/- 0.02; p< 0.05). Extracellular ATP increased the percentage of cell-attached patches with active channels (28.7% to 50.0%; p< 0.05) but had no significant effect on the channel open probability (0.62 +/- 0.07 vs 0.60 +/- 0.06). In conclusion, rabbit non-ciliated bronchiolar epithelial cells express low-conductance Cl- channels that share many similarities with the CFTR-related Cl- channel and are regulated by cAMP and extracellular ATP.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1997

Adverse outcomes of antiinflammatory therapy among patients with polymyalgia rheumatica.

OBJECTIVE: To evaluate the incidence and risks of adverse events associated with therapy (both corticosteroids [CS] and nonsteroidal antiinflammatory drugs [NSAIDs]) among a previously identified, population-based cohort of patients first diagnosed with polymyalgia rheumatica (PMR) between 1970 and 1991 who were followed up over the long term. METHODS: Information on demographics, PMR diagnosis, disease course, and drug therapy, in addition to data on adverse events commonly associated with CS and NSAID treatment, was obtained from the Rochester Epidemiology Project database. Cox proportional hazards and regression analysis models were used to evaluate the relationship between the occurrence of these events and therapy. RESULTS: Of the 232 patients (69 male, 163 female) included in the study, the mean age at PMR diagnosis was 72.9 years, the average followup was 8.0 years, and 30 patients were also diagnosed with giant cell (temporal) arteritis. Among the 175 patients (49 male, 126 female) treated with CS, the mean duration of CS therapy was 2.4 years, the average daily dose was 9.6 mg, and the mean cumulative dose was 8.4 gm. In total, 65% of the 124 patients treated with CS alone experienced at least 1 adverse event, compared with 67% of the 57 patients treated with NSAIDs alone and 80% of the 51 patients treated with CS and NSAIDs. The average time from initiation of therapy to the first adverse event was 1.6 years (n = 160). Proportional hazards modeling identified 3 variables that independently increased the risk of adverse events: age at PMR diagnosis, a cumulative dose of prednisone > or = 1,800 mg, and female sex. Person-year analysis revealed that the risks of diabetes mellitus, vertebral fractures, femoral neck fractures, and hip fractures were 2-5 times greater among PMR patients compared with age- and sex-matched individuals from the same population. Medical care or consultation by a rheumatologist was a highly significant predictor of a lower initial CS dose. CONCLUSION: The use of CS and NSAIDs in the treatment of PMR is associated with important long-term morbidity.

Adrenal Cortex Hormones↗
PubMed1997

Psychosocial outcomes and health status of adults who have had juvenile rheumatoid arthritis: a controlled, population-based study.

OBJECTIVE: The goal of this study was to evaluate the physical and psychosocial impact of juvenile rheumatoid arthritis (JRA) among a population-based cohort of adults who had the disease during childhood, compared with a control cohort of subjects with no history of JRA. METHODS: The Rochester Epidemiology Project database was used to identify all cases of JRA (based on the American College of Rheumatology [formerly, the American Rheumatism Association] 1977 criteria) among Rochester, Minnesota residents first diagnosed between January 1, 1960 and December 31, 1993. Controls were age- and sex-matched to the cases as of the date of diagnosis of JRA. A pretested postal survey was mailed to all adult cases (whose date of birth was before December 31, 1975) and matched controls from the same population, to obtain information on socioeconomic issues and functional status (using the Health Assessment Questionnaire and the Health Status Questionnaire). The complete medical records of all cases and controls were reviewed to obtain information on demographics and clinical manifestations of JRA. RESULTS: Of the 50 eligible cases, 44 (88%) responded to the survey. There were 102 age- and sex-matched controls (2-3 per case) who responded to the survey. Seventy-three percent of the cases had pauciarticular-onset JRA, 16% had polyarticular-onset JRA, and 11% had systemic-onset JRA. Average followup was 24.7 years and 24.5 years after the index date for cases and controls, respectively. Greater disability (P = 0.0002), more bodily pain (P = 0.0002), increased fatigue (P = 0.0112), poorer health perception (P = 0.0004), and decreased physical functioning (P = 0.0002) were reported by the cases compared with the controls. JRA cases reported significantly lower rates of employment (P = 0.015) and lower levels of exercise (P = 0.0002) than did controls. Level of educational achievement, annual income, health insurance status, and rate of pregnancy and childbirth were similar for both cases and controls. CONCLUSION: Adults who have had JRA during childhood experience long-term physical and psychosocial impairment.

Adolescent↗
PubMed1997

The feasibility and validity of studies comparing orthopedists and non-orthopedists caring for musculoskeletal injuries: results of a pilot study.

OBJECTIVE: To review care provided by orthopedists and non-orthopedists for a variety of common acute injuries to the shoulder, knee, and ankle; and to evaluate the difficulties in assessing results from diagnostic data collected for administrative reporting by comparing these data with data collected by medical record abstraction for the same patients. METHODS: The Rochester Epidemiology Project database was used to identify new cases of Colles fracture, knee sprain, ankle sprain, and shoulder sprain/rotator cuff injury among Olmsted county residents > 18 years of age, who were evaluated between January 1, 1990 and December 31, 1992. Data were collected from an administrative database and medical records. RESULTS: Although the diagnoses recorded in the administrative database and those obtained from medical record review were the same in 94% of the 500 cases reviewed, only 270 (67.7%) actually represented acute injuries. Medical record review showed that (for the shoulder and ankle) injury severity was highly correlated with treatment specialty: 13 of 15 severe injuries were cared for by orthopedists, while 64 of 68 mild injuries were treated by non-orthopedists. Diagnostic uncertainty was more common among non-orthopedists; in 21 of the 149 patients treated by non-orthopedists (15.1%), the final (i.e., recorded for coding) diagnosis was different from the initial diagnosis. In 14 of these cases, an orthopedist made the final diagnosis. None of the diagnoses made by orthopedists were revised. CONCLUSION: Current diagnostic coding does not capture injury acuity, severity, or diagnostic uncertainty. Studies that limit themselves to such data for diagnostic information are likely to suffer from biases which can skew results in unpredictable ways. Conclusions drawn from such studies are likely to be flawed.

Adolescent↗
PubMed1997

Polarized distribution of key membrane transport proteins in the rat submandibular gland.

Immunofluorescence labelling and confocal microscopy were employed to examine the polarized distribution of several membrane transport proteins believed to be essential for salivary secretion in the rat submandibular gland. The Na+/K+-ATPase, Na+/H+ exchanger isoform 1 (NHE1), and the secretory Na+/K+/2Cl- cotransporter isoform were all found in the basolateral membranes of acinar and intralobular duct cells. Anion exchanger isoform 2 (AE2) was found only in the basolateral membranes of acinar cells, while AE1 was absent from glandular epithelial cells. Aquaporin 5 was detected in the apical membranes of acinar cells, while the cystic fibrosis transmembrane conductance regulator was found only in apical membranes of intralobular duct cells. NHEs 2 and 3 were found in the apical membranes of both acinar and intralobular duct cells. Our results are generally consistent with the expected distribution of most transporters based on previous physiological and pharmacological experiments. However, the apical localization of NHEs 2 and 3, and the presence of the secretory isoform of the Na+/K+/2Cl- cotransporter in intralobular duct cells were not predicted.

Animals↗
PubMed1997

Intestinal physiology and pathology in gene-targeted mouse models of cystic fibrosis.

Cystic fibrosis (CF) is a fatal genetic disorder that affects approximately 1 in 2,500 live Caucasian births. The disease can be described as a generalized exocrine disease affecting a variety of epithelial tissues, with early manifestation as meconium ileus in a significant number of neonates. Cloning of the gene causing CF was accomplished in 1989, and the protein product, cystic fibrosis transmembrane conductance regulator (CFTR), has been conclusively shown to be an adenosine 3',5'-cyclic monophosphate (cAMP)-regulated Cl- channel. Subsequently, several mouse models of CF were generated by gene-targeting approaches in an attempt to further understand this disease. The initial excitement generated by the emergence of these mouse models was somewhat tempered by the finding that none of the models developed airway disease, which is currently responsible for most of the morbidity and mortality in the human CF population. However, the various CF mouse models, of which there are now 10, are remarkably similar to their human counterparts with respect to intestinal pathophysiology. Most importantly, the intestinal tract of the CF mouse models demonstrates the absence of cAMP-mediated Cl- transport, which is a hallmark of CF disease. Furthermore, the murine CF intestinal tract also shows an inability to secrete HCO3-, defective cAMP regulation of electroneutral NaCl absorption, and elevated electrogenic Na+ transport in the distal colon, as well as other ion transport perturbations. Besides the fundamental mechanisms of ion transport studied in the murine CF intestinal tract, these models have also been important in understanding other tissues with regard to CF. Mice heterozygous for the CFTR knockout gene have a reduced ability to secret Cl- and fluid and therefore provide further support for the CF "heterozygote advantage" hypothesis. Some CF mouse models maintain a limited ability to secrete Cl-, which may be due to accessory genes that are hypothesized to ameliorate disease severity in the intestines of these mice. This review describes the CF models generated and compares the murine defects in ion transport with observed abnormalities in the human CF intestine.

Animals↗