Trends in incidence and clinical presentation of temporal arteritis in Olmsted County, Minnesota, 1950-1985

Ninety-four Olmsted County, Minnesota residents with temporal arteritis (TA) initially diagnosed between 1950 and 1985 (incidence cohort) were identified. The age- and sex-adjusted incidence of TA per 100,000 population age 50 years or older was 17.0 (95% confidence interval [CI] 13.6-20.5), with a marked increase in incidence with age and a threefold greater incidence in women (23.4, 95% CI 18.2-28.7) than in men (7.4, 95% CI 3.7-11.0). The previously described secular increase in TA incidence in Olmsted County women continued from 1970 through 1985, while TA incidence in men declined in this latter time period. Although the frequency of classic clinical manifestations of TA declined over time, the percentage of patients undergoing biopsy who have positive specimens remained relatively constant (women 41%, men 26%). The incidence rate of temporal artery biopsy also increased for women during this period, but declined for men, suggesting that the differing trends in TA incidence by sex may be partially attributable to a detection bias. Future research in TA etiology and epidemiology should focus on possible causal factors linked to the differential TA incidence by sex.     

Plasma HIV-1 RNA decline within the first two weeks of treatment is comparable for nevirapine, efavirenz, or both drugs combined and is not predictive of long-term virologic efficacy: A 2NN substudy

BACKGROUND: The initial rate of plasma HIV-1 RNA (pVL) decline has been proposed as a marker of early efficacy of antiretroviral therapy (ART) and a possible predictor of late efficacy. We compared the rate of pVL decline in patients starting ART with nevirapine (NVP), efavirenz (EFV), or both drugs combined in addition to lamivudine (3TC) and stavudine (d4T). METHODS: Analysis of the viral decay constant (VDc) during the first 2 weeks of treatment in patients enrolled in the 2NN study who remained on allocated treatment. RESULTS: The median VDc (log10 copies per day, [interquartile range]) was similar for NVP (0.30 [0.25-0.36], EFV (0.31 [0.27-0.37]), and NVP + EFV (0.30 [0.27-0.36]). Patients with a baseline pVL >100,000 copies/mL were 8.7 (95% confidence interval [CI]: 6.2-12.3) times more likely to have a VDc >75th percentile. A high VDc was not associated with plasma drug concentration or with a decreased risk of virologic failure at week 48 after the start of therapy (hazard ratio = 0.8, 95% CI: 0.6-1.2). CONCLUSION: NVP, EFV, or NVP + EFV in combination with 3TC and d4T show similar rates of pVL decline during the first 2 weeks of treatment. The VDc with these regimens is not predictive of late virologic efficacy.     

Longitudinal Pattern of Enzymatic and Absorptive Functions in the Small Intestine of Rats After Short-Term Exposure to Dietary Cadmium Chloride

In vitro and in situ findings suggest an impairment of digestive and absorptive functions in the small intestine by enteral cadmium salts. In the rat, diets with up to 1 mmol Cd/kg are well tolerated, however, so that the impairment might not be this drastic or compensated by adaptive changes. To elucidate whether small intestinal functions are altered, we studied the effect of dietary cadmium on the longitudinal pattern of mucosal enzymes and the in vitro uptake of methyl α-D-glucoside in the small intestine of female rats. Three groups of rats were employed, a control group and two groups receiving dietary CdCl₂ either at 0.3 or 1.0 mmol Cd/kg of diet. Rats were killed after 1 week of feeding. The entire small intestine was removed, rinsed with ice-cold saline and divided into 12 segments of equal length. Mucosal scrapings from each segment were used to measure mucosal cadmium levels, sucrase, lactase, alkaline phosphatase, glycylleucine-hydrolase, and diamine oxidase activities. Sugar uptake was determined in vitro in all segments using everted rings tissue accumulation method. Although cadmium levels in the mucosa were high (>100 ng Cd/mg protein or >100 μmol Cd/kg WW) most enzyme activities were only slightly changed. When significant decreases in activity were detected, they were only observed in the proximal small intestine. Sugar uptake was also impaired only in proximal segments, the maximal transport capacity was reduced by approximately 20%. These findings suggest that cadmium even at dietary levels of 1 mmol/kg do not lead to a drastic impairment of digestive and absorptive functions in the small intestine and that in the rat presently observed, mostly proximal impairments are easily compensated by unaltered distal functions. Certainly, absorption of micronutrients, for which an impaired proximal function cannot be compensated, e.g. iron, might be critical in this respect. Received: 27 July 1998/Accepted: 4 November 1998     

Giant cell (cranial) arteritis: a clinical review

Giant cell arteritis is a disease of the elderly which is more common than previously recognized. It is important to be aware of this condition because treatment effectively relieves symptoms and prevents serious complications. The disease is suggested when an elderly patient complains of constitutional symptoms, headache, jaw claudication, or the musculoskeletal manifestations of polymyalgia rheumatica. Abnormalities in temporal arteries or other cranial arteries, or evidence of large vessel involvement may be detected by physical examination. A markedly elevated sedimentation rate in association with other clinical features of the disease strongly suggests giant cell arteritis, but a biopsy should be performed to confirm the diagnosis. Corticosteroid therapy should be started promptly in high doses in order to prevent blindness. Prolonged treatment with lower dose corticosteroids is generally necessary for up to 1 to 2 years, and sometimes longer, for continued symptomatic relief. Long-term follow-up of treated patients has demonstrated no detectable effect on survivorship.     

The American College of Rheumatology 1990 criteria for the classification of Henoch-Sch?nlein purpura

Criteria for identifying Henoch-Sch?nlein Purpura (HSP) and distinguishing HSP from other forms of systemic arteritis were developed by comparing the manifestations in 85 patients who had HSP with those of 722 control patients with other forms of vasculitis. By the traditional format of choosing different combinations of candidate criteria and comparing the combinations for their ability to separate HSP cases from controls, 4 criteria were identified: age less than or equal to 20 years at disease onset, palpable purpura, acute abdominal pain, and biopsy showing granulocytes in the walls of small arterioles or venules. The presence of any 2 or more of these criteria distinguish HSP from other forms of vasculitis with a sensitivity of 87.1% and a specificity of 87.7%. The criteria selected by a classification tree method were similar: palpable purpura, age less than or equal to 20 years at disease onset, biopsy showing granulocytes around arterioles or venules, and gastrointestinal bleeding. These were able to distinguish HSP from other forms of vasculitis with a sensitivity of 89.4% and a specificity of 88.1%.     

Correlation of interleukin-6 production and disease activity in polymyalgia rheumatica and giant cell arteritis

Objective. To explore the role of proinflammatory cytokines in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR), two clinically related syndromes characterized by an intense acute-phase reaction. In particular, to determine plasma concentrations of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) and to correlate changes in plasma IL-6 levels with clinical symptoms during corticosteroid therapy. Methods. IL-6 and TNFα concentrations were determined in plasma samples from patients with untreated PMR or GCA, and plasma IL-6 levels were monitored in patients receiving long-term therapy (14 months) with corticosteroids. To identify IL-6–producing cells, the polymerase chain reaction was used to detect IL-6 messenger RNA. In vitro production of IL-6 and IL-2 by peripheral blood mononuclear cells (PBMC) from treated and untreated patients was quantified using IL-6– and IL-2–specific bioassay systems. Results. IL-6 concentrations were increased in PMR and GCA patients, whereas TNFα concentrations were similar to those in normal donors. Administration of corticosteroids rapidly reduced the levels of circulating IL-6 but did not correct the underlying mechanism inducing the increased IL-6 production. In individual patients, changes in plasma IL-6 levels and clinical manifestations during prolonged therapy were closely correlated. Short-term withdrawal of corticosteroids, even after several months of treatment, was followed by an immediate increase in plasma IL-6 concentrations. To identify the cellular source of plasma IL-6, PBMC from treated and untreated patients with PMR or GCA were analyzed for their ability to secrete IL-6 and the T cell–specific cytokine IL-2. Polyclonal T cell stimulation caused a rapid release of IL-6, which was shown to be derived exclusively from CD14+ cells. Conclusion. Increased production of IL-6, but not TNFα, is a characteristic finding in patients with PMR or GCA. Corticosteroids rapidly suppress IL-6 production but do not correct the underlying mechanism inducing the increased IL-6 production. The close correlation of plasma IL-6 concentrations with clinical symptoms suggests a direct contribution of this cytokine to the disease manifestations and presents the possibility that monitoring IL-6 levels would be useful in making decisions on adjustment of corticosteroid dosage in individual patients.     

Epidemiology of polymyalgia rheumatica in olmsted county,minnesota, 1970–1991

Objective. To determine the incidence, prevalence, and survival of polymyalgia rheumatica (PMR) over a 22-year period in Olmsted County, Minnesota. Methods. Using the unified record system at the Mayo Clinic for the Olmsted County population, we reviewed all medical records with a diagnosis of PMR from 1970 through 1991. Results. There were 245 (173 female; 72 male) incidence cases of PMR between 1970 and 1991. The average annual age- and sex-adjusted incidence of PMR per 100,000 population ≥ 50 years was 52.5 (95% confidence interval [CI] 45.9–59.2), with a significantly higher incidence in females (61.7; 95% CI 52.3–71.2) than in males (39.9; 95% CI 30.7–49.2). The incidence varied over the period of observation, but no significant trends were found. The prevalence of PMR among persons ≥ 50 years on January 1, 1992 was 6/1,000. There was a small but significantly increased survival rate among male PMR patients compared with the general population. Conclusion. Our data demonstrate that PMR is a common nonfatal disease in the elderly, the incidence and clinical manifestations of which have varied but remained relatively stable over the last 2 decades.     

Thoracic aortic aneurysm and rupture in giant cell arteritis. a descriptive study of 41 cases

Objective. To determine the features and outcomes of patients with giant cell arteritis (GCA) who have aneurysms or rupture of the thoracic aorta. Methods. Patients with GCA seen over a 40-year period who had aneurysms and/or rupture of the thoracic aorta were identified by assistance of a computerized indexing system. The presence of thoracic aortic aneurysms (TAA), with or without aortic valve insufficiency (AI), was determined by radiographs, computed tomography scans, and ultrasound studies of the thorax, angiograms of the aorta, and postmortem examination. Results. Ten men and 31 women with GCA were found to have TAA and/or rupture. Three developed TAA before GCA was diagnosed, 5 developed aortic findings near the time of the diagnosis, and 33 after the diagnosis of GCA (median of 7 years after diagnosis). Sixteen patients developed acute aortic dissection, which caused death in 8. Nineteen patients also had AI due to aortic root dilation, 15 of whom developed congestive heart failure. Eighteen patients underwent 21 surgical procedures for TAA resection and/or aortic valve replacement or repair. Aortitis was documented histologically in 10 cases. Conclusion. Thoracic aortic complications in GCA are associated with serious outcomes that have been underrecognized and may be fatal. Physicians should be alert to the development of these complications at any time in the course of GCA, even many years after usual symptoms have subsided.