Prevalence and clinical outcome of mitral-valve prolapse.

BACKGROUND: Mitral-valve prolapse has been described as a common disease with frequent complications. To determine the prevalence of mitral-valve prolapse in the general population, as diagnosed with the use of current two-dimensional echocardiographic criteria, we examined the echocardiograms of 1845 women and 1646 men (mean [+/-SD] age, 54.7+/-10.0 years) who participated in the fifth examination of the offspring cohort of the Framingham Heart Study. METHODS: Classic mitral-valve prolapse was defined as superior displacement of the mitral leaflets of more than 2 mm during systole and as a maximal leaflet thickness of at least 5 mm during diastasis, and nonclassic prolapse was defined as displacement of more than 2 mm, with a maximal thickness of less than 5 mm. RESULTS: A total of 84 subjects (2.4 percent) had mitral-valve prolapse: 47 (1.3 percent) had classic prolapse, and 37 (1.1 percent) had nonclassic prolapse. Their age and sex distributions were similar to those of the subjects without prolapse. None of the subjects with prolapse had a history of heart failure, one (1.2 percent) had atrial fibrillation, one (1.2 percent) had cerebrovascular disease, and three (3.6 percent) had syncope, as compared with unadjusted prevalences of these findings in the subjects without prolapse of 0.7, 1.7, 1.5, and 3.0 percent, respectively. The frequencies of chest pain, dyspnea, and electrocardiographic abnormalities were similar among subjects with prolapse and those without prolapse. The subjects with prolapse were leaner (P<0.001) and had a greater degree of mitral regurgitation than those without prolapse, but on average the regurgitation was classified as trace or mild. CONCLUSIONS: In a community based sample of the population, the prevalence of mitral-valve prolapse was lower than previously reported. The prevalence of adverse sequelae commonly associated with mitral-valve prolapse in studies of patients referred for that diagnosis was also low.

Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (the Framingham Heart Study)

Little information is available on the prevalence and determinants of valvular regurgitation in the general population. This study sought to assess the prevalence and clinical determinants of mitral (MR), tricuspid (TR), and aortic (AR) regurgitation in a population-based cohort. Color Doppler echocardiography was performed in 1,696 men and 1,893 women (aged 54 +/- 10 years) attending a routine examination at the Framingham Study. After excluding technically poor echocardiograms, MR, TR, and AR were qualitatively graded from trace to severe. Multiple logistic regression analysis was used to examine the association of clinical variables with MR and TR (more than or equal to mild severity) and AR (more than or equal to trace severity). MR and TR of more than or equal to mild severity was seen in 19.0% and 14.8% of men and 19.1% and 18.4% of women, respectively, and AR of more than or equal to trace severity in 13.0% of men and 8.5% of women. The clinical determinants of MR were age (odds ratio [OR] 1.3/9.9 years, 95% confidence interval [CI] 1.2 to 1.5), hypertension (OR 1.6; 95% CI 1.2 to 2.0), and body mass index (OR 0.8/4.3 kg/m2; 95% CI 0.7 to 0.9). The determinants of TR were age (OR 1.5/9.9 years; 95% CI 1.3 to 1.7), body mass index (OR 0.7/4.3 kg/m2; 95% CI 0.6 to 0.8), and female gender (OR 1.2; 95% CI 1.0 to 1.6). The determinants of AR were age (OR 2.3/9.9 years; 95% CI 2.0 to 2.7) and male gender (OR 1.6; 95% CI 1.2 to 2.1). A substantial proportion of healthy men and women had detectable valvular regurgitation by color Doppler echocardiography. These data provide population-based estimates for comparison with patients taking anorectic drugs.

Gender differences in presentation, management, and cardiac event-free survival in patients with syncope.

In a MEDLINE search of published English studies (1966 to 1996), no prior study was identified that examined gender-based differences in the management and prognosis of patients admitted with syncope. We studied 109 consecutive patients (48 women) admitted with syncope at the Massachusetts General Hospital (1989 to 1990). All patients underwent Holter monitoring, signal-averaged electrocardiography, and echocardiography according to study protocol. Follow-up was 100% complete (10 +/- 4 months). Women were older (74 +/- 2 vs 66 +/- 2 years, p <0.01) and less likely to have premonitory symptoms when compared with men (46% vs 66%, p <0.05). A greater proportion of men had left ventricular ejection fractions of <0.40 (18% vs 0%, p <0.01), abnormal signal-averaged electrocardiograms (28% vs 8%, p <0.01), and a cardiac cause for syncope (49% vs 25%, p <0.01). Although referral for diagnostic electrophysiologic testing was >3 times as frequent for men compared with women (20% of men vs 6% of women, p <0.05), this difference was not significant after adjustment for age, ventricular arrhythmia, and referral for coronary angiography. During follow-up, 21% of men versus 6% of women (p <0.05) had cardiac events (recurrent syncope, myocardial infarction, or sudden death). Cardiac event-free survival rates were worse for men (p = 0.045). Thus, we have identified gender-based differences in the clinical presentation of syncope for hospital admission. Left ventricular dysfunction and an abnormal signal-averaged electrocardiogram occur more frequently in men. Men are more likely to have cardiac syncope and worse cardiac event-free survival when compared with women.

Relation of ultra-low frequency heart rate variability to the clinical course of chronic aortic regurgitation.

We examined the relation of the standard deviation of the 5-minute mean RR intervals over 24 hours (SDANN), a measure of ultra-low frequency heart rate variability (HRV) (<0.0033 Hz), and other measures of HRV to clinical outcome events in 50 asymptomatic or minimally symptomatic patients with chronic severe aortic regurgitation (AR) who underwent ambulatory electrocardiography as part of a prospective study of the natural history of regurgitant valvular diseases. At entry, all patients were in sinus rhythm and had New York Heart Association functional class I or minimal II congestive heart failure, with left ventricular (LV) ejection fraction > or = 45% and LV end-diastolic dimension > or = 5.5 cm in women and > or = 5.9 cm in men. End points were defined as progression to aortic valve replacement (n = 19) or sudden cardiac death (n = 1) during the mean follow-up period of 8.1 +/- 3.8 years. With the median SDANN of 145 ms as a partition value, the average annual risk of end-point events in patients with low SDANN was significantly greater than the event rate in patients with high SDANN (11%/year vs 2%/year, p <0.0003). In multivariate analysis, reduced SDANN was associated with end-point events independent of LV function, LV end-systolic dimension, and symptom status (p = 0.001). We conclude that reduced ultra-low frequency HRV measured as SDANN is strongly related to progression to valve surgery in asymptomatic and minimally symptomatic patients with chronic AR.

Rhythm annotation and interobserver reproducibility of measures of heart rate variability.

Interobserver reproducibility is high for time domain and power spectral measures of heart rate variability, with greater reproducibility for low-frequency measures, and especially for the standard deviation of the 5-minute RR intervals over 24 hours, than for high-frequency measures. Overall interobserver variability of < 8% for these measures is largely (50% to 75%) explained by interobserver differences in annotation of supraventricular ectopy and sinus arrhythmia.

A PCR test for avian malaria in Hawaiian birds.

The decline of native Hawaiian forest birds since European contact is attributed to factors ranging from habitat destruction to interactions with introduced species. Remaining populations of Hawaiian honeycreepers (Fringillidae: Drepanidinae) are most abundant and diverse in high elevation refuges above the normal range of disease-carrying mosquitoes. Challenge experiments suggest that honeycreepers are highly susceptible to avian malaria (Plasmodium sp.) but resistance exists in some species. In order to detect low levels of malarial infection and quantify prevalence of Plasmodium in high elevation natural populations of Hawaiian birds, a polymerase chain reaction (PCR) based diagnostic test was developed that identifies rRNA genes of Plasmodium in avian blood samples. Quantitative competitive PCR (QC-PCR) experiments indicate that the detection limit of our test is an order of magnitude greater than that reported for human malaria DNA blot tests. Compared with standard histological methods, the PCR test detected a higher prevalence of diseased birds at mid-elevations. Malaria was detected in three species of native birds living in a high elevation wildlife refuge on the island of Hawaii and in four species from Maui. Our results show that avian malaria is more widespread in Hawaiian forests than previously thought, a finding that has important conservation implications for these threatened species.

Hippocampal laminar glucose utilization and theta rhythm following unilateral fimbria-fornix lesions in rats.

Laminar profiles of glucose utilization were related to the presence or absence of movement-related hippocampal theta rhythm in CA1 and dentate gyrus of rats after aspirative unilateral combined lesions of the fimbria-fornix and cingulum. Three groups were studied: (1) sham-operated rats, (2a) lesioned rats with an ipsilateral loss of theta activity at 4 weeks post-lesion that persisted at 12 weeks post-lesion, and (2b) lesioned rats with a loss of theta activity at 4 weeks post-lesion, but a recovery of theta rhythm at 12 weeks post-lesion. Fimbria-fornix/cingulum lesions served both to abolish ipsilateral theta rhythm and to decrease ipsilateral glucose metabolism in all cell layers of CA1 and the dentate gyrus, when normalized to the contralateral hemisphere. Although glucose metabolism in lesioned animals with a recovery of theta rhythm was not as high as control levels, in several laminae it was significantly higher than that of lesioned animals with persistent loss of theta rhythm. These laminae included the dentate hilus and strata oriens, pyramidale and lacunosum-moleculare of CA1. The increased glucose metabolism associated with the return of theta rhythm suggests a functional reinnervation of these layers of the hippocampus in such animals.

Structural and functional effects of prenatal cocaine exposure in adult rat brain.

The long-term effects of cocaine exposure early in development on the metabolic function of major central neuronal systems in the rat are reported in this study. Pregnant Wistar rats were administered either 60 mg/kg cocaine or the vehicle from gestation day (G) 8 through 22 via daily gastric intubation. Sixty-day-old male offspring were examined using the quantified deoxyglucose autoradiographic method. Of the 45 structures examined, 2 cortical and 14 subcortical structures showed statistically significant alterations in glucose metabolism compared to controls. The primary somatosensory and motor cortices showed significant decreases. The hypothalamus contained the greatest concentration of nuclei showing significant changes in activity. All of these changes were decreases. The nigrostriatal pathway, the medial forebrain bundle, the hippocampus, septum and amygdala were all significantly less metabolically active in the exposed offspring. The subcortical sensory systems did not appear to be affected at the dose of cocaine studied. Adjacent sections incubated in 1nM [3H]SCH 23390 showed an increase in the concentration of D1 receptors in the substantia nigra, pars reticulata. Forebrain dopaminergic regions which showed decreased glucose metabolism did not appear to have altered SCH 23390 binding. Although size determinations were made on several cortical and subcortical structures, none were significantly affected by prenatal cocaine. Effects of chronic prenatal cocaine exposure on adult brain metabolism in several neuronal systems were identified at doses which had no significant effects on adult brain or body size. These data support the hypothesis that cocaine use during pregnancy produces permanent neurological effects at doses below those which produce growth retardation and terata.

Arginine vasopressin and body fluid homeostasis in the fetal alcohol exposed rat.

Studies involving fluid homeostasis were carried out in adult Long-Evans rats born to mothers given liquid diets containing 35% of the calories derived from ethanol and compared to offspring of dams given isocaloric liquid diets containing no ethanol. Plasma levels of arginine vasopressin (AVP), plasma and urine osmolality, and urine production were determined in water-sated and water-deprived offspring. In the water-sated condition, the group exposed to alcohol prenatally had plasma levels of AVP seven-fold above control levels. This increase was associated with a large increase in within-group variability. Water consumption was also significantly elevated in the group of fetal alcohol exposed (FAE) rats. Plasma and urine osmolality and urine production were similar to control levels. In the control animals, 24-hr of water deprivation produced the expected increase in AVP, in plasma and urine osmolality, and decrease in urine production. The FAE animals, however, showed parallel changes in plasma and urine osmolality and urine production with no significant change in AVP. Examination of basal glucose metabolic rates in the cerebral structures involved in fluid homeostasis revealed that despite the large increase in AVP levels in the FAE rats, only the neurohypophysis and supraoptic nuclei showed significant increases in activity. These data suggest that fetal alcohol exposure causes a long-term disruption in the central mechanisms regulating vasopressin release and fluid homeostatic responses.

Regional brain glucose utilization during and following chronic naltrexone administration: preliminary observations in rat brain.

Experiments were conducted to determine some of the metabolic correlates of tonic opioid activity in the central nervous system under conditions previously examined for changes in monoamine levels. The glucose metabolic rates in seven brain regions were determined by autoradiographic visualization of 14C-deoxyglucose incorporation in female rats after 8 days of chronic exposure to naltrexone pellets and 10 days after pellet removal. Autoradiographs were analyzed on a region-by-region basis to correspond to areas previously dissected and analyzed for changes in monoamine content under similar experimental conditions. Chronic administration of naltrexone resulted in a significant decrease in the metabolic activity of neurons in the striatum. Other brain areas examined under this condition were not significantly affected. Ten days following pellet removal, 14C-deoxy-glucose incorporation was indistinguishable from that determined in placebo treated rats in all brain regions examined. These results indicate that tonic opioid input is an important determinant of metabolic activity in the striatum. In addition, these results indicate that conditions previously shown to alter regional content of monoamines do not necessarily produce concomitant changes in regional glucose utilization.

Stimulation of brain metabolism by perinatal cocaine exposure.

Cocaine was administered to neonatal rats between day 1 and day 10, which in the rat falls within a developmental stage roughly equivalent to the third trimester of gestation in human fetuses. At 60 days of age, when the animals had reached adulthood, cerebral glucose metabolic patterns were examined by quantitative autoradiography. Adult females, but not adult males, exhibited significant increases in metabolic activity in a number of cerebral structures, including those of the limbic, motor, and sensory systems. Many of these structures are the same as those which are excited in adult rats by the acute administration of cocaine and other stimulants. These data suggest that cocaine consumption during pregnancy may constitute a risk factor leading to long-term alterations in brain function in the adult.

Cerebral metabolic interactions between thyroid state and imipramine in the rat.

Local rates of cerebral glucose metabolism were determined in four groups of adult rats 4 weeks after surgery: sham-operation + saline; thyro-parathyroidectomy (TX) + saline; sham-operation + imipramine; or TX + imipramine. Daily i.p. injections, imipramine at 10 mg/kg or saline at 1 ml/kg b.w., were given during the 2 weeks before the deoxyglucose experiment. TX reduced glucose utilization in the limbic, motor, endocrine and auditory systems. Imipramine reduced glucose metabolism in the median eminence, both habenular nuclei and several limbic regions including the amygdala, hippocampus and parietal cortex. Five structures showed significant interactions between TX and imipramine. In three of these regions, the supraoptic nucleus, central amygdala and lateral habenula; TX and/or imipramine individually reduced metabolism and the combined treatment raised it back to within the normal range. In the dorsal raphe, TX and imipramine tended to increase metabolism and the combined treatment resulted in a decrease to within normal range. The neurohypophysis, unaffected by TX alone, showed a significant increase in activity when TX was combined with imipramine. These data indicate, in part, that both hypothyroidism and imipramine treatment alone depress metabolism in limbic forebrain and the major limbic-brainstem relay nuclei. Combined treatment normalizes metabolism in many of these limbic pathways. Hypothetically, hypothyroidism may alter central catecholamine function in such a way that the metabolic response to imipramine is reversed or altered.

Evolutionary ecology and radiation of Hawaiian passerine birds.

The Hawaiian islands contain the most spectacular variety of landbirds ever discovered on remote oceanic islands. The Hawaiian honeycreepers, having evolved from a presumably single founding species of cardueline finch, comprise most of this avifauna. Birds from at least three other families of passerines and five families of non-passerines also radiated in Hawaii. Recent discoveries of a fossil avifauna indicate that most radiations were more extensive than previously thought. Classical analysis of the radiation of Hawaiian birds, especially the honeycreepers, focused on characters related to acquisition of food. Recent studies of bill size and shape in relation to food resources, and of foraging mode in relation to interspecific competitors, provide models of how divergence in diet and/or bill morphology might have evolved. Studies of geographic variation among subspecies on different islands and among populations within islands have revealed extensive divergence in characters such as sexual chromatism, nest sites and nest morphology.