O’Fallon, W. Michael

Abstract While severe primary hyperparathyroidism (HPT) is clearly associated with osteitis fibrosa cystica, it remains uncertain whether mild, asymptomatic primary HPT adversely affects the skeleton. Thus, we assessed the incidence of age-related fractures in a large, population-based inception cohort of 407 cases of primary HPT (93 men and 314 women) recognized during the 28-year period, 1965–1992. Fracture risk was assessed by comparing new fractures at each site to the number expected from gender- and age-specific fracture incidence rates for the general population (standardized incidence ratios, SIRs). These community patients with primary HPT mostly had mild disease (mean ± SD serum calcium, 10.9 ± 0.6 mg/dl). Altogether, 471 fractures occurred during 5766 person-years of follow-up. Overall fracture risk was significantly increased in these patients (SIR 1.3, 95% confidence interval [CI] 1.1–1.5). Primary HPT was associated with an increased risk of vertebral (SIR 3.2, 95% CI 2.5–4.0), distal forearm (SIR 2.2, 95% CI 1.6–2.9), rib (SIR 2.7, 95% CI 2.1–3.5), and pelvic fractures (SIR 2.1, 95% CI 1.1–3.5). The risk of proximal femur fractures was only marginally increased (SIR 1.4, 95% CI 1.0–2.0). By univariate analysis, increasing age and female gender were significant predictors of fracture risk, although higher serum calcium levels were also associated with increased fracture risk, and parathyroid surgery may have had a protective effect. By multivariate analysis, however, only age (relative hazard [RH] per 10-year increase, 1.6, 95% CI 1.4–1.9) and female gender (RH 2.3, 95% CI 1.2–4.1) remained significant independent predictors of fracture risk. Thus, primary HPT among unselected patients in the community is associated with a significant increase in the risk of vertebral, Colles', rib, and pelvic fractures. These data have important implications for the current trend to recommend nonsurgical management for patients with mild primary HPT.

Abstract OBJECTIVE To report presenting clinical symptoms, previous medical history, and survival rates for people with saccular intracranial aneurysms (IAs), in a defined population. METHODS The medical records of all residents of Olmsted County, Minnesota, with possible IAs were reviewed. Clinical manifestations at the time of diagnosis, previous medical history, demographic factors, and survival rates after diagnosis were determined. RESULTS Of 270 people with IAs detected between 1965 and 1995, 188 exhibited symptoms at the time of diagnosis, including 74% of women and 63% of men (P = 0.054). Intracranial hemorrhage (ICH) was the most common presenting symptom (60% of all patients and 86% of patients who exhibited symptoms), followed by cranial nerve palsy, transient ischemic attacks, and seizures. Survival rates after detection (with the exclusion of cases that were first detected during autopsies) were dependent on the occurrence of ICH; 23% of patients who presented with ICH died by 1 day after diagnosis, compared with 5% of those who did not exhibit symptoms or exhibited symptoms but without ICH at presentation. At 5 years, 44.7% of patients with hemorrhage had died, compared with 29.4% of patients with symptoms other than hemorrhage. After the first 24 hours after detection, survival rates did not differ significantly for those presenting with or without hemorrhage. Predictors of better survival rates also included lower age and later calendar year of presentation. CONCLUSION This study provides the first data on aneurysm characteristics, clinical symptoms, and survival rates among people with IAs in a defined population. During the study period, most aneurysms were detected in the context of an aneurysm-related symptom (particularly among women), with a large proportion of patients presenting with ICH. After the acute phase of hemorrhage, long-term survival rates among people with IAs were similar for those presenting with or without ICH.

Background and Purpose— Mortality after cerebral infarction (CI) has remained unchanged during the past 20 years, despite advances in neurologic care. Key factors affecting survival may be underrecognized. The purpose of this study was to determine the rate and cause of mortality after first CI. Methods— In this case-control, population-based study, all available medical records were reviewed for Rochester (Minnesota) residents with a first CI between 1985 and 1989 to identify morbidities and cause of death. Predictors for mortality were analyzed. Results— First CI was recorded for 444 patients. Survival was 83% at 1 month, 71% at 1 year, and 46% at 5 years. The most frequent causes of death were cardiovascular events (22%), respiratory infection (21%), and initial stroke complications (14%). Recurrent stroke and cancer accounted for 9% and 7.5% of deaths, respectively. In the first month after CI, 51% of deaths were attributed to the initial CI, 22% to respiratory infections, and 12% to cardiovascular events. During the first year, 26% of deaths resulted from respiratory infections and 28% from cardiovascular disease. Mortality was higher among patients than controls for at least 2 years after CI. Age, cardiac comorbid conditions, CI severity, stroke recurrence, seizures, and respiratory and cardiovascular morbidities were independent predictors of death. Conclusions— In the first month after CI, mortality resulted predominantly from neurologic complications. Later mortality remained high because of respiratory and cardiovascular causes. To improve long-term survival after CI, aggressive management of pulmonary and cardiac disease is as important as secondary stroke prevention.

The immune system is equipped with an extremely large spectrum of structurally diverse receptors to recognize all potential antigens. This fundamental principle of receptor diversity is no longer upheld in patients with rheumatoid arthritis (RA), who have a marked contraction of the T cell receptor repertoire. In this study, the ability of RA patients to produce T cells and to maintain T cell homeostasis was examined. CD4 T cells containing T cell receptor rearrangement excision circles (TREC) were substantially reduced in RA patients; TREC levels in young adult patients matched those of controls 20 years older. Increased self-replication of T cells in RA was indicated by age-inappropriate erosion of telomeres in circulating T cells with almost complete attrition of telomeric reserves in patients 20–30 yr of age. The degree of telomere loss was not related to disease duration or the use of disease-modifying medication and was most pronounced in CD4 + CD45RO null (naive) T cells. The loss of TREC-positive T cells could be a consequence of a primary defect in peripheral T cell homeostasis. Alternatively, RA patients may have impaired thymic function with the increased turnover of peripheral T cells being a secondary compensatory event.