Citations

Background— Aortic valve calcification (AVC) is considered degenerative. Recent data suggested links to atherosclerosis or coronary disease (CAD). Methods and Results— AVC and coronary artery calcifications (CAC) were prospectively assessed by Electron-Beam-Computed-Tomography in 262 population-based research participants ≥60 years. AVC was frequent (27%) with aging ( P <0.01) and in men ( P <0.05). AVC was associated with diabetes, hypertension, higher body-mass-index, and serum glucose (all P <0.05). AVC was a marker of higher prevalence ( P <0.01) and severity of CAD (CAC score: 441±802 versus 265±566, P <0.05) independently of age. After follow-up of 3.8±0.9 years, AVC score increased (94±271 versus 54±173, P <0.01, +11±32 U/year), faster with higher baseline AVC score ( P <0.01). Compared with participants remaining free of AVC, de novo acquisition of AVC was associated with higher LDL-cholesterol (141±31 versus 121±27 mg/dL, P <0.05) and faster CAC progression (+78±87 versus +28±47 U/year, P <0.05). In multivariate analysis, LDL-cholesterol independently determined AVC acquisition while higher baseline AVC scores determined faster progression of existing AVC. Conclusion— In the population, AVC is frequent with aging and atherosclerotic risk factors. AVC is a marker of subclinical CAD. AVC is progressive, appearing de novo with progressive atherosclerosis whereas established AVC progresses independently of atherosclerotic risk factors and faster with increasing initial AVC loads.

Abstract In the smooth muscle of guinea-pig uterus (oestrogen dominated) both noradrenaline (Nor) (α-action) and acetylcholine (ACh) depolarized the membrane, reduced membrane resistance, accelerated spike discharge and increased isometric tension proportionately. The magnitude of the response to ACh was directly related to the dose of ACh, the duration remaining that of the period of drug application. The response to Nor was slow in onset and outlasted the period of drug application by several minutes. Increasing doses of Nor mainly prolonged the duration of the response. The magnitude of the response depended on whether the depolarization by Nor reached firing threshold. The phasic tension response to evoked spikes was increased by Nor. Cooling reduced, and at 6°C abolished the depolarization caused by Nor but did not significantly change the response to ACh. The results obtained with variations of external potassium and chloride indicate that both ACh and Nor increased the membrane permeability to potassium, but that the Nor effect was small and shortlasting. Chloride was not involved in the depolarization caused by ACh, while the magnitude of depolarization and of the increase in membrane conductance by Nor were a direct function of the external chloride concentration. The removal of sodium from the external medium slowed the relaxation of the phasic tension responses to evoked spikes and increased resting tension. In the absence of spikes the tissue relaxed. The depolarization and reduction of membrane resistance by ACh were directly related to the external sodium concentration regardless whether sucrose or tris-Cl were used as substitute. The depolarization and reduction of membrane resistance by Nor did not depend on external sodium (tris substitution) though in the simultaneous absence of sodium and chloride (sucrose substitution) the response to Nor was abolished. The results obtained when NaCl was replaced with tris-Cl suggest that ACh may, in the absence of sodium, increase the entry of calcium. The failure of calcium removal from the cytoplasm may explain the maintained contracture. The contracture produced by Nor was increased in the absence of sodium, suggesting that, in addition to an increased calcium entry from outside, there may have been a release of sequestered calcium.

Abstract The α action of catecholamines on oestrogen dominated guinea-pig uterus is stimulant. The cell membrane is depolarized, membrane conductance is increased, spike discharge is accelerated and tension develops. This action resembles that of acetylcholine though catecholamines are less potent, and, in equiactive concentrations, catecholamines have a longer latency and a longer duration of action. Evidence, obtained by modifications of the ionic environment, indicates that the depolarization by acetylcholine is due to an increase in sodium and calcium permeability and that acetylcholine can release calcium from intracellular stores. The depolarization by catecholamines is due to an increase in chloride permeability and, in addition, sodium is required for the ensuing increase of spike discharge. Catecholamines produce an increase in the force of contraction, long outlasting their immediate stimulation. Moreover, their effect on membrane potential and membrane conductance persists in the presence of lanthanum. These results suggest that Ca release from intracellular stores may be the primary effect produced by the α action of catecholamines and that the increase in the cytoplasmic Ca2+ concentration may cause the changes at the cell membrane.

Objective: Although the epidemiology of microscopic colitis has been described in Europe, no such data exist from North America. We studied the incidence, prevalence and temporal trends of microscopic colitis in a geographically defined US population. Design and setting: In this population based cohort study, residents of Olmsted County, Minnesota, with a new diagnosis of microscopic colitis, and all who had colon biopsies for evaluation of diarrhoea, between 1 January 1985 and 31 December 2001 were identified. Biopsies were reviewed for confirmation (cases) and to identify missed cases (diarrhoea biopsies). Main outcome measures: Incidence rates, age and sex adjusted to the 2000 US white population. Poisson regression assessed the association of calendar period, age and sex with incidence. Results: We identified 130 incident cases for an overall rate of 8.6 cases per 100 000 person-years. There was a significant secular trend, with incidence increasing from 1.1 per 100 000 early in the study to 19.6 per 100 000 by the end (p<0.001). Rates increased with age (p<0.001). By subtype, the incidence was 3.1 per 100 000 for collagenous colitis and 5.5 per 100 000 for lymphocytic colitis. Collagenous colitis was associated with female sex (p<0.001) but lymphocytic colitis was not. Prevalence (per 100 000 persons) on 31 December 2001 was 103.0 (39.3 for collagenous colitis and 63.7 for lymphocytic colitis). Conclusions: The incidence of microscopic colitis has increased significantly over time, and by the end of the study, the incidence and prevalence were significantly higher than reported previously. Microscopic colitis is associated with older age, and collagenous colitis is associated with female sex.