Severe aortic regurgitation in von Recklinghausen's disease--a case report.

A 71-year-old man with von Recklinghausen's disease presented with NYHA class II exertional dyspnea and easy fatigability since about 20 days. Echocardiography and angiography demonstrated dilatation of aortic root, ascending aorta, and left ventricle, together with severe aortic regurgitation. Because of very few cases of cardiovascular abnormalities having been reported with von Recklinghausen's disease, it is logical to concur that this is simply co-existence, whereas other possible mechanisms are endothelial dysfunction or sympathetic denervation.

Exercise-induced myocardial perfusion abnormalities in sickle beta-thalassemia: Tc-99m tetrofosmin gated SPECT imaging study.

PURPOSE: To determine the mechanism of myocardial ischemia in patients with sickle beta-thalassemia, we performed a scintigraphic evaluation of myocardial perfusion during exercise. SUBJECTS AND METHODS: We studied 30 patients with sickle beta-thalassemia, (mean [+/-SD] age, 37 +/- 10 years) who had no electrocardiographic (ECG), radiographic, or echo-Doppler signs of pulmonary hypertension, left ventricular hypertrophy, or impaired contractility. All patients had a hemoglobin level greater than 7 g/dL. Treadmill exercise test was performed according to the Bruce protocol. Myocardial perfusion was assessed by single-photon emission computed tomography, using Tetrofosmin Tc-99 m Myoview as radiotracer, at peak exercise and again 4 hours later. RESULTS: Eight patients (27%) developed stress-induced scintigraphic perfusion abnormalities that were reversible in all but 1 patient. Subsequent coronary angiograms were normal in all 8 patients. ST segment depression was seen during exercise in 5 of the 7 patients who had reversible perfusion defects. Except for a significantly greater white blood cell count, these 5 patients did not differ from the rest of patients by sex, age, hemoglobin level, percentage hemoglobin F, beta-thalassemia genotype, or risk factors for coronary artery disease. Three of the 5 patients with perfusion and ECG abnormalities (and another with only perfusion defects) developed a stress-induced sickling crisis. CONCLUSION: Physical stress may induce myocardial ischemia in sickle beta-thalassemia patients with normal coronary arteries and elicit painful crises. The sickling process, activated by exercise, could be the common underlying mechanism.

Noninvasive assessment of left ventricular systolic function by stress-shortening relation, rate of change of power, preload-adjusted maximal power, and ejection force in idiopathic dilated cardiomyopathy: prognostic implications.

Indexes of left ventricular systolic function that are considered relatively load-insensitive were assessed to determine their relation to the severity of heart failure symptoms and their ability to predict the outcome of idiopathic dilated cardiomyopathy. Stress, flow, power, and ejection force were calculated throughout ejection by echocardiography at rest in 35 patients with idiopathic dilated cardiomyopathy and in 20 control subjects. Patients were evaluated prospectively every 6 months for 2 years. Asymptomatic patients were separated most clearly from New York Heart Association (NYHA) class II by end-systolic stress; NYHA class II patients were separated from NYHA class III and the latter from NYHA class IV by peak rate of change of flow. Ten patients showed improvement in symptoms as well as in systolic indexes; none of them died during the follow-up. Improvement was unpredictable with the evaluated variables. One- and 2-year cardiovascular mortality rates were 17% and 26%, respectively. Patients whose condition did not improve after the first year had a 17% second-year mortality rate. Peak rate of change of power predicted death with 100% sensitivity, 56% specificity, and 64% positive predictive value in NYHA III and IV patients.

The Leros PIKPA asylum. Deinstitutionalisation and rehabilitation project.

A three-year deinstitutionalisation and rehabilitation pilot intervention project was implemented at Leros PIKPA for people with severe learning disabilities. Initial conditions at the asylum were appalling. Residents suffered severe deprivation, extreme institutionalisation, and violation of basic human rights. Intervention involved professionals from different disciplines, and involved residents, their families, care staff, the institution, and the local community. As a result, resident care and adaptive behaviour has started to improve. Communication between residents and families has increased. Owing to training and sensitisation, care staff's poor resident-management practices and negative attitudes toward disabled people have changed. Living and hygienic conditions have been upgraded and building renovation is under way. Asylum administration and the local community have been sensitised to residents' needs. Eleven residents have moved to the project's pilot community home in Athens; two others now live with foster families. The results suggest that deinstitutionalisation and rehabilitation can be successfully initiated even in residential institutions of the severest kind.

The psychosocial dynamics of change at Leros PIKPA asylum.

The pilot intervention project at Leros PIKPA asylum was resisted at all levels of its implementation. Resistance ranged from implicit and passive to explicit and hostile. It took the form of strong rejective attitudes, defensiveness, and repressed emotions of guilt, shame and fear. It was apparent in efforts to delay, obstruct or reverse the progress of the project and undermine the work of intervention team members. It was evident in the interactions of the intervention team with all parties involved in implementing the project: medical professionals and welfare services, the state and local administrations, the central and local administrations of PIKPA staff, the local community, and the asylum residents' families and relatives. It is argued that this resistance to change is due to the interplay of cultural/attitudinal, psychodynamic and socio-economic factors that are not unique to Leros or Greece. The analysis of the psychosocial processes involved in resistance to changing the Leros PIKPA asylum may offer insights to the deinstitutionalisation of custodial settings in general.

Change in care staff's attitudes towards people with learning disabilities following intervention at the Leros PIKPA asylum.

The pilot intervention project at Leros PIKPA asylum sought to change the management of residents by decreasing care staff's tendency to view people with learning disabilities with attitudes of custodial segregation (e.g. "they should all live in institutions") and categorisation (e.g. "they are all alike"). To that end, staff were trained on the job in resident management and participated in seminars, sensitisation groups, clinical case presentations and visits to model rehabilitation units. To investigate whether staff attitudes towards people with learning disabilities had been influenced, staff members responded to a questionnaire of such attitudes, in March 1991 (initial assessment) and a year later (reassessment). Factor analyses of attitude ratings at initial assessment revealed a strong negative attitudinal construct, "Rejective and custodial segregation--Categorisation", according to which institutionalisation was the only appropriate type of care for people with learning disabilities, regardless of individual differences. At reassessment, however, this factor had split into two independent ones, "Rejective and custodial segregation" and "Categorisation", suggesting that the staff had understood that custodial care did not apply to all persons with learning disabilities indiscriminately. Reassessment factors further indicated that staff had comprehended the appropriateness of alternative care forms--community and home care. Analysis of Categorisation and Custodial segregation attitude ratings showed that only staff's tendency to view the disabled as "all alike" (Categorisation) had decreased at reassessment. The latter change and the structural change revealed by the factor analyses imply that staff's attitudes underwent a small but significant modification.

Mortality among institutionalised people with learning disabilities in Greece: a 30-year survey at the Leros PIKPA asylum.

The life expectancy of institutionalised people with learning disabilities is shorter than that of the general population. Data on population dynamics in institutions for such people are vital for planning purposes. Mortality can be considered a crude measure of quality of health care. Mortality data on the 914 admissions to the Leros PIKPA asylum for children and young adults with learning disabilities and associated problems in the years 1961-91 were reviewed. The overall crude mortality rate was 59.2 deaths per 1000 person-years. Twenty-two per cent of the deaths occurred within a year after admission. Age-specific mortality rates were particularly high for those aged one to four years, and declined thereafter. Male residents had lower mortality than female residents in almost all of the age groups. Compared with sex- and age-specific mortality data for the general population of Greece, the observed rates were 20-150 times higher but still comparable to those reported for people with more severe learning disabilities in institutions in other countries. Lifetable analysis by length of stay showed that male residents had a statistically significant higher probability of survival than female residents, which could not be attributed to age-related differential mortality. Culture-specific differential admission criteria may account for the observed sex difference.

Normal and stenotic human aortic valve opening: in vitro assessment of orifice area changes with flow.

The ability to measure aortic valve area clinically has emphasized the need to understand the changes in aortic valve orifice area during flow. To compare the performance of normal and stenotic human aortic valves we used a pulsatile flow model that simulated in vivo flow conditions. Five normal autopsy specimens and 15 stenotic valves removed at operation were mounted into the model. Valve function was assessed by analysis of video recordings of valve leaflet motion during flow. Over the flow rates tested normal valves demonstrated a linear increase in orifice area. There was no resistance to leaflet opening and valve closure was rapid. The majority of stenotic valves demonstrated an increase in orifice area at low flow rates. No valve showed any increase in maximal area beyond flow rates of 3 l min-1. Increased leaflet resistance of these abnormal valves resulted in notably slower opening and closing rates. In patients with a high cardiac output and severe stenosis, overestimation of the anatomic orifice area derived by the Gorlin equation can result. This is not related to variability in maximal orifice area.

In vitro measurement of stenotic human aortic valve orifice area in a pulsatile flow model. Validation of the continuity equation.

Aortic valve orifice area estimation in patients with aortic stenosis may be obtained non-invasively using several Doppler echocardiographic methods. Their validity has been established by correlation with catheterization data using the Gorlin formula, with its inherent limitations, and small discrepancies between the methods are present. To evaluate these differences further, 15 patients with severe aortic stenosis (mean transvalvular gradient 70, range 40-130 mmHg) had aortic valve area estimations by Doppler echocardiography using two variations of the continuity equation. The intact valves removed at valve replacement surgery were then mounted in a pulsatile model and the anatomical area was measured (mean 0.67 +/- 0.17 cm-2) from video recordings during flow at 5.4 l min-1. Aortic valve area calculated using the integrals of the velocity-time curves measured at the left ventricular outflow tract and aortic jet (mean 0.65 +/- 0.17 cm2) correlated best with the anatomical area (r = 0.87, P less than 0.001). The area derived by using the ratio of maximum velocities from the left ventricular outflow tract and aortic jet (mean 0.69 +/- 0.18 cm2) also correlated well with the anatomical area (r = 0.79, P less than 0.001). The index between the left ventricular outflow tract and aortic jet maximum velocities was less than or equal to 0.25 in all. In patients with severe aortic stenosis the aortic valve area can be reliably estimated using Doppler echocardiography.

Balloon dilatation of the aortic valve in a pulsatile flow model: assessment of the mechanisms and the magnitude and duration of changes in valve area and gradient.

Eighteen stenotic aortic valves (17 removed at operation) mounted in a pulsatile flow duplicator were dilated with a balloon catheter. Sequential measurements showed that the valve area initially increased from a mean (SD) of 0.52 (0.16) to 0.78 (0.17) cm2. It was 0.73 (0.16) cm2 five minutes after dilatation and this was little changed at four weeks (0.70 (0.15) cm2). Initially the mean transvalvar gradient fell significantly from 54 (27) to 32 (8) mm Hg but increased to 35 (10) mm Hg at five minutes and to 40 (11) mm Hg at four weeks. In six valves stretching of the orifice was the only mechanism responsible for the changes while in the remainder there was tearing through commissures with a greater initial increase in area (0.31 v 0.18 cm2) and a smaller decrease in area at five minutes (0.03 v 0.08 cm2). Fractures of calcific deposits in non-commissural positions were seen in one valve only. This laboratory study of isolated aortic valves showed a significant but small increase in valve area after balloon dilatation, which was greater when commissural tearing had occurred. Recoil of the stretched orifice was complete at five minutes and there was little further change over the next four weeks.

Purification and characterization of a soluble and a particulate glutamate dehydrogenase from rat brain.

Glutamate dehydrogenase (GDH) activity was determined in high-speed fractions (100,000 g for 60 min) obtained from whole rat brain homogenates after removal of a low-speed pellet (480 g for 10 min). Approximately 60% of the high-speed GDH activity was particulate (associated with membrane) and the remaining was soluble (probably of mitochondrial matrix origin). Most of the particulate GDH activity resisted extraction by several commonly used detergents, high concentration of salt, and sonication; however, it was largely extractable with the cationic detergent cetyltrimethylammonium bromide (CTAB) in hypotonic buffer solution. The two GDH activities were purified using a combination of hydrophobic interaction, ion exchange, and hydroxyapatite chromatography. Throughout these purification steps the two activities showed similar behavior. Kinetic studies indicated similar Km values for the two GDH fractions for the substrates alpha-ketoglutarate, ammonia, and glutamate; however, there were small but significant differences in Km values for NADH and NADPH. Although the allosteric stimulation by ADP and L-leucine and inhibition by diethylstilbestrol was comparable, the two GDH components differed significantly in their susceptibility to GTP inhibition in the presence of 1 mM ADP, with apparent Ki values of 18.5 and 9.0 microM GTP for the soluble and particulate fractions, respectively. The Hill plot coefficient, binding constant, and cooperativity index for the GTP inhibition were also significantly different, indicating that the two GDH activities differ in their allosteric sites. In addition, enzyme activities of the two purified proteins exhibited a significant difference in thermal stability when inactivated at 45 degrees C and pH 7.4 in 50 mM phosphate buffer.

Effects of a prenatal androgen peak on rat brain sexual differentiation.

Exposure of the developing female brain to a 5 alpha-dihydrotestosterone surge on day 18 of gestation resulted in defeminization and slight masculinization of the brain. In contrast, abolition of the androgenic effects of the testosterone peak naturally occurring in male fetuses on day 18 of gestation by exposure of the developing male brain to cyproterone acetate, at that time, resulted in demasculinization while feminization was not affected. On the basis of these results, we suggest that both the prenatal testosterone peak and the high testosterone levels occurring in males neonatally are necessary for aromatization sufficient to effect complete male rat brain sexual differentiation.

Estimation of gestational age in the neonate: a comparison of clinical methods.

A combined evaluation of almost all the proposed morphologic and neurologic criteria for estimating gestational age in the neonate was performed on 710 newborns of 28 to 44 weeks' gestation. It is concluded that (1) the neurologic criteria used by Dubowitz et al in combination with the external (morphologic) criteria of Farr et al give very accurate results of estimation of the gestational age; (2) equally accurate results can be obtained if those criteria with the lowest correlation coefficients--namely, are and leg recoil, degree of edema, and appearance of the genitalia--are omitted; and (3) the use of only nine external criteria, the assessment of which is easier to perform on sick babies, gives an estimation of gestational age that is accurate for clinical purposes (r=0.878).