Age-matched Normal Control Subjects Research Articles

Functional abnormalities of circulating natural killer cell subpopulations in patients with dilated cardiomyopathy.

We investigated abnormalities in natural killer (NK) cells in the myocardium and circulating blood of 38 patients with idiopathic dilated cardiomyopathy (DCM), 18 patients with hypertrophic cardiomyopathy, 8 patients with primary amyloidosis, and 12 age-matched normal control subjects. Immunohistochemical staining of myocardial biopsies revealed a significantly greater number of CD57-positive NK cells in patients with DCM than that in controls (3.7 +/- 2.7 v.s. 1.9 +/- 1.6, p < 0.05). The New York Heart Association functional class, left ventricular ejection fraction, myocardial fiber diameter, and interstitial fibrosis volume fraction did not differ significantly between the DCM patients who died within five years of diagnosis and the 31 surviving DCM patients. However, there were significantly fewer CD57-positive NK cells in patients who died than in surviving patients (p < 0.05). There were no significant differences in the peripheral NK cell activity or the number of NK subset cells between the 16 patients with DCM (n = 16) and the 12 age-matched normal controls. In normal controls, the number of some NK cell subpopulations (CD16+, CD57+, CD16+ CD57+, and CD8+ CD57+ cells) were positively correlated with NK cell activity. In patients with DCM, there was no correlation between the number of NK cell subpopulations and NK cell activity. Our findings indicate that functional abnormalities exist in NK cell subpopulations in patients with DCM, and that these abnormalities may be related to the pathogenesis of DCM.

Bacterial meningitis: T cell activation and immunoregulatory CD4 + T cell subset alteration

Meningitis is the most important cause of acquired postnatal deafness and neurologic disorders in children. To determine if cell-mediated immunity is casually related to the pathogenesis of bacterial meningitis, T cell subsets were quantitated from blood of the 29 children with clinical and bacteriologic diagnosis of Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis bacterial meningitis. The CD4 + T cells increased and CD8 + T cells decreased in patients with meningitis as compared to patient control subjects (bacterial infections without meningitis) and normal healthy control subjects. An elevated percentage of CD25 + (interleukin-2 receptors) and HLA-DR + (immune-response gene-associated antigen) T cells were detected from all patients with meningitis. All 29 patients with meningitis had highly elevated CD4 + CD45R + (suppressor-inducer) cells and reciprocally depressed CD4 + CDw29 + (helper-inducer) cells compared with healthy age-matched normal and patient control subjects. These findings indicate characteristic immunologic T cell abnormalities from meningitis. The abnormal increase in the CD4 + CD45R + suppressor-inducer or “virgin” cells and expression of activation antigens on T cells may be of help in future understanding of abnormal immune reactions from bacterial meningitis. However, deficiency of the CD4 + CDw29 + helper-inducer or “memory” cells may contribute to the impaired helper function for B cell-induced protective antibody synthesis to bacterial capsular polysaccharides found in this disease.

Positron emission tomography suggests that the rate of progression of idiopathic parkinsonism is slow

We performed sequential positron emission tomography scans with 6-[18F]fluoro-L-dopa in 9 patients with idiopathic parkinsonism and 7 age-matched normal control subjects to compare changes in the nigrostriatal dopaminergic pathway over time. The mean interval between the scans was 3.3 years for the group with idiopathic parkinsonism and 3.9 years for the control subjects. The scans were analyzed by calculating the ratio of striatal to background radioactivity. Both groups showed statistically significant reductions of striatal uptake over the interval. The rate of decrease was almost identical in each group (p = 0.6). We infer that the usual rate of loss of integrity of the dopaminergic nigrostriatal pathway in patients with idiopathic parkinsonism is slow and the rate of change between the two groups was comparable.

Cortical magnetic resonance imaging changes in elderly inpatients with major depression

The purpose of the study was to determine if magnetic resonance imaging (MRI) scans of elderly depressed patients differ from MRI scans of age-matched control subjects and age-matched patients with Alzheimer's disease. The authors studied 21 patients 60 years or older with major depression, 16 patients with Alzheimer's disease, and 14 age-matched control subjects. Compared to control subjects, depressed patients had greater cerebral sulcal and temporal sulcal atrophy; larger sylvian fissures, lateral ventricles, third ventricles, and temporal horns; and greater severity of subcortical white matter lesions. Depressed patients also had more basal ganglia lesions but similar levels of periventricular hyperintensity. There were no differences between depressed patients with and without delusions on any MRI measure. Depressed patients who received ECT had more temporal horn atrophy and greater subcortical abnormality summary scores than normal subjects. Cortical sulcal atrophy correlated with age at onset of depression. The findings suggest that elderly hospitalized depressed patients have greater cortical as well as subcortical atrophy and more basal ganglia lesions than age-matched normal control subjects. The correlation of these abnormalities with outcome remains unknown.

Quantitative assessment of ultrasonic myocardial reflectivity in hypertrophic cardiomyopathy

The purpose of this study was to investigate the relation between acoustic properties of the myocardium and magnitude of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy. An on-line radio frequency analysis system was used to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and posterior free wall in 25 patients with hypertrophic cardiomyopathy and 25 normal age-matched control subjects. The integrated values of the radio frequency signal were normalized for the pericardial interface and expressed in percent.Tissue reflectivity was significantly increased in the hypertrophied ventricular septum, as well as in the nonhypertrophied posterior free wall, in patients with hypertrophic cardiomyopathy (58 ± 15% and 37 ± 12%, respectively) compared with values in normal subjects (33 ± 10% and 18 ± 5%, respectively; p < 0.001). Furthermore, measurements of reflectivity of the septum or posterior free wall, or botl, were beyond 2 SD of normal values in >90% of the patients and were also abnormal in each of the five study patients who had only mild and localized left ventricular hypertrophy. No correlation was identified between myocardial tissue reflectivity and left ventricular wall thickness in the patients with hypertrophic cardiomyopathy (correlation coefficient r = 0.4; p = NS).These findings demonstrate that myocardial reflectivity is abnormal in most patients with hypertrophic cardiomyopathy and is largely independent of the magnitude of left ventricular hypertrophy. Moreover, quantitative analysis of ultrasonic reflectivity can differentiate patients with hypertrophic cardiomyopathy from normal subjects independently of clinical features and conventional echocardiographic measurements.

Abnormal collagen fibril structure of skin in chronic haemodialysis patients: An electron microscopic study

The structure of collagen fibrils of skin in chronic haemodialysis patients was studied by electron microscopy. Although, in all patients, the parallel packing of the fibrils remained, there were areas with disorganization. The periodicity D as well as the banding pattern were normal. The most conspicuous finding of the work presented here is that in all patients the fibril diameters were significantly smaller than those from normal age-matched control subjects. Also, the former showed a much higher degree of variability in width of collagen fibrils than the latter.

Spectral characteristics for place of articulation in the speech of young normal, moderately and profoundly hearing-impaired French Canadians

A group of 10 moderately hearing-impaired children aged 7-10 years (five boys, five girls), 10 profoundly hearing-impaired children (five boys, five girls), and 10 age-matched normal control subjects (five boys, five girls), were recorded producing the six occlusives / p t k b d g / before the vowel /a/. Five productions were elicited from each child for a total of 30 potential correct productions each. LPC spectral analyses were performed at the moment of release (the burst) to determine the degree to which Blumstein and Stevens' (1979) spectral place-of-articulation features were present in the speech of these normal and hearing-impaired children, and whether there were differences between groups. A static 'centroid' analysis was also performed. Results reveal that the moderately hearing-impaired children's productions were not significantly different from those of the normal controls, but that some aspects of the profoundly hearing-impaired children's productions did differ from those of the moderately hearing-impaired and normal children. The relationship between degree of hearing loss and severity of speech production deficits is discussed. Implications of the results for remediation are also considered.

Cerebral glucose hypermetabolism in Friedreich's ataxia detected with positron emission tomography

Local cerebral metabolic rate for glucose was studied with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in 22 patients with Friedreich's ataxia and 23 age-matched normal control subjects. The diagnosis of Friedreich's ataxia was established by the history and physical findings and by excluding other diseases through laboratory investigations. PET studies revealed a statistically significant widespread increase of local cerebral metabolic rate for glucose in the brains of patients with Friedreich's ataxia who were still ambulatory, in comparison with normal control subjects. Nonambulatory patients with Friedreich's ataxia, in comparison with normal control subjects, had significantly increased local cerebral metabolic rates for glucose in the caudate and lenticular nuclei, but not in the other structures studied. The rate was significantly greater in ambulatory patients with Friedreich's ataxia than in nonambulatory patients in all structures studied except the caudate and lenticular nuclei. The data suggest that early in the course of Friedreich's ataxia, the local cerebral metabolic rate for glucose is increased extensively in the central nervous system, and as the disease progresses, it decreases in a regionally specific manner.

A cross-sectional study of the effects of depression on REM latency

In a cross-sectional design to address the effects of the course of depression on rapid-eye-movement (REM) latency, we have matched patients in their first-episode with (1) age-matched patients with recurrent depression, (2) onset-matched patients with recurrent depression, and (3) age-matched normal control subjects. Patients were also matched for sex and treatment site (inpatient or outpatient). No differences were found in REM latency for the three depressed groups, and all had lower REM latency than normals. This finding is taken as support for stable REM latency throughout the course of depression.

Effect of inversion on memory for faces in Parkinson's disease and right-hemisphere stroke patients

Upright and upside-down photographs of faces, schematic drawings of faces, and photographs of houses were presented to patients with Parkinson's disease (PD), patients with right hemisphere stroke (RH), and age-matched normal control subjects (NC) in a forced- choice recognition paradigm. These slides were presented in four orientation conditions: upright at original presentation and at test, upside-down at both, upright initially and upside- down at test, and vice versa. NC subjects recognized faces most accurately when presented in the same orientation both times. This suggests that the information is resistant to mental rotation. Patients with PD recognized faces most accurately when they were presented upright both times, suggesting difficulty with any unusual orientation, consistent with an inability to shift mental set. RH patients, unlike the other groups, did not recognize faces presented upright both times more accurately than those in any other condirion. This supports previous studies suggesting a right hemisphere specialization for recognition of upright faces.

Exercise responses in patients with congenital heart disease after fontan repair: Patterns and determinants of performance

After a Fontan repair for congenital heart disease, 42 patients underwent graded supine bicycle exercise tests at levels relevant to normal daily activities. Results were compared with those of 28 age-matched normal control subjects. At rest, the cardiac index, stroke index and systolic blood pressure were comparable in both groups, but increases with exercise were smaller in the patients with a Fontan circulation. The heart rate at rest was higher in the Fontan group, but this difference disappeared as soon as exercise started. To determine whether there are limitations intrinsic to the Fontan circulation at these levels of exercise, the 10 best performers were compared with 10 age-matched control subjects; no differences were found in cardiac index, stroke index, heart rate or blood pressure at any exercise level. Analysis of the determinants of cardiac output showed that at the other end of the spectrum poor performance after a Fontan operation did not result from inadequate levels of heart rate, but from an inability to increase or maintain stroke volume. Multivariate analysis demonstrated that impairment of ventricular contractility, only when severe, predicted limited performance. There was no evidence of increased afterload, particularly in the poor performers. Therefore, ventricular filling, which is determined primarily by the pulmonary vascular bed, appears to be a major determinant of functional result after a Fontan repair.

Age-adjusted threshold values for reduced REM latency in unipolar depression using ROC analysis

To determine an age-adjusted, clinically meaningful depressive diathesis, we have implemented Receiver Operator Characteristic(ROC) analysis for mean rapid eye movement (REM) latency in patients with unipolar depression. Depressed patients were compared with age-matched normal control subjects. Sensitivity and specificity estimates were calculated for selected threshold values on the ROC curves as well as for the Research Diagnostic Criteria endogenous/nonendogenous subtype. The mean REM latency value of 65.0–66.0 min was most sensitive and specific for depressed patients aged 35–72. The threshold value of 70.0 min appeared optimally sensitive and specific for depressed patients aged 20–34. There was no effect of age on REM latency in the normal control sample. Among depressed patients there was an effect of age but this was clearly observable only in nonendogenous depressed patients.

The Contour of the Juxtapapillary Nerve Fiber Layer in Glaucoma

Reliable structural markers for early glaucomatous optic nerve damage would facilitate the diagnosis of glaucoma at an early stage, possibly before visual field loss occurs. Computerized image analyses were used to develop and analyze new structural parameters for glaucomatous optic nerve damage. Multiple measurements of relative juxtapapillary nerve fiber layer height were made in glaucoma patients (n =112), patients suspected of having glaucoma (n = 87), and in age-matched normal control subjects (n = 53). The average relative nerve fiber layer (NFL) height differed in glaucoma patients and normal subjects by 70 μm, but differences exceeded 100 μm at the superior and inferior poles of the disc. Mean values for “glaucoma suspects” were intermediate between those for the normal subjects and glaucoma groups. The ability of summary statistics of relative NFL height measurements to discriminate between normal and glaucomatous eyes was superior to that of the standard disc parameters cup-disc ratio, disc rim area, and cup volume. Measurements of relative NFL height correlated with indices of visual field loss; the strongest correlations occurred for measurements at the superior and inferior poles. Measurements of juxtapapillary NFL height may prove useful to detect glaucomatous optic nerve damage at an early stage and to accurately recognize progressive nerve damage over time.

An acoustic analysis of frontal misarticulation of /s/ in children

In an attempt to investigate the acquisition of fine phonetic control and the nature of phonological representations in children who exhibit speech sound production errors, this study explored temporal, amplitude, and spectral characteristics of frontally misarticulated /s/ and compared these parameters to those associated with correctly articulated /θ/. The subjects included two groups of misarticulating children, aged 5–6 years and 7–8 years and two groups of age-matched normal control subjects. Recordings of /s/ and / θ/ as produced by these subjects in a variety of vocalic contexts were analyzed acoustically; mean duration, amplitude, and centroid frequency measures for the frication noise, and measures of variability were computed and contrasted across the four groups. Results indicated that all groups distinguished /s/ and / θ/ to some extent on all parameters measured. However, centroid values for misarticulated /s/ were lower in frequency than were those for normally-articulated /s/. Results are discussed in relation to the nature of phonological targets in misarticulating children and to the acoustic characteristics of misarticulated /s/ in developing speech production.

Type 1 fiber abnormalities in skeletal muscle of patients with hypertrophic and dilated cardiomyopathy: Evidence of subclinical myogenic myopathy

Abnormalities of skeletal muscle have been described in patients with dilated and hypertrophic cardiomyopathy. Eleven patients with dilated and eight with hypertrophic cardiomyopathy without overt symptomatic skeletal myopathy underwent extensive neuromuscular studies. Quantitative electromyography showed abnormal reduction of motor unit potential duration, indicative of myogenic myopathy, in four patients (36%) with dilated and in three (37%) with hypertrophic cardiomyopathy. Values were 21% to 40% (mean 28%) lower than those in age-matched normal control subjects. The presence of normal nerve conduction velocities and of normal motor unit fiber density in all patients indicated lack of neurogenic abnormalities.Skeletal muscle biopsy was performed in five patients with dilated and in four with hypertrophic cardiomyopathy. In all nine patients light and electron microscopy showed central hyporeactive cores, selective atrophy and mitochondrial abnormalities of type 1 fibers but not of type 2 fibers. The degree of impairment of left ventricular function in patients with electromyographic abnormalities was similar to that of those without (percent fractional shortening at two-dimensional echocardiography 21 ± 9 versus 25 ± 10, ejection fraction at angiography 39 ± 13% versus 42 ± 13% and left ventricular end-diastolic pressure 21 ± 6 versus 21 ± 8 mm Hg) as well as symptom duration (9 ± 4 versus 12 ± 8 months).Thus, subclinical electromyographic alterations indicative of myogenic myopathy are frequent in patients with dilated and hypertrophic cardiomyopathy and are unrelated to the degree of impairment of left ventricular function. The concomitant histologic alterations, characterized by selective type 1 atrophy, are similar to those observed in congenital and idiopathic myopathies, but different from those described in secondary heart failure.

A new Doppler method of assessing left ventricular ejection force in chronic congestive heart failure

A noninvasive method using Doppler echocardiography was developed to determine the force exerted by the left ventricle in accelerating the Mood into the aorta. The value of this new Doppler ejection index in the assessment of left ventricular (LV) performance was tested in 36 patients with chronic congestive heart disease undergoing cardiac catheterization and in 11 age-matched normal control subjects. The 36 patients were subgrouped into 3 groups based on angiographic ejection fraction (LV ejection fraction >60, 41 to 60 and <40%). According to Newton's second law of motion (force = mass × acceleration), the LV ejection force was derived from the product of the mass of blood ejected during the acceleration time with the mean acceleration undergone during that time. In patients with LV ejection fraction <40%, LV ejection force, peak aortic velocity and mean acceleration were severely depressed when compared with the other groups (p <0.001). In patients with LV ejection fraction of 41 to 60%, LV ejection force was significantly reduced (22 ± 3 kdynes) when compared with normal subjects (29 ± 5 kdynes, p = 0.002) and with patients with LV ejection fraction >60% (29 ± 7 kdynes, p = 0.009); peak velocity and mean acceleration did not differ between these 3 groups. The LV ejection force showed a good linear correlation with LV ejection fraction (r = 0.86) and a better power fit (r = 0.91). Peak aortic blood velocity and mean acceleration showed less good linear correlations with LV ejection fraction (r = 0.73 and r = 0.66, respectively). The mass of blood ejected during the acceleration time also showed a weak linear correlation with LV ejection fraction (r = 0.64). An LV ejection force <20 kdynes was associated with a depressed LV performance (LV ejection fraction <50%) with 91% sensitivity and 90% specificity. Thus, these findings suggest that LV ejection force is a new Doppler ejection phase index that appears to be more accurate than peak aortic blood velocity and mean acceleration for the assessment of systolic LV function,

Neurohumoral and hemodynamic effects of lower body negative pressure in patients with congestive heart failure

Baroreflex modulation of forearm vascular resistance (FVR) has been reported to be abnormal in patients with congestive heart failure (CHF). However, the neurohumoral mechanisms for this impairment are not defined. We assessed the responses of arterial pressure, FVR, plasma norepinephrine, and plasma renin activity to lower body negative pressure in 29 patients with compensated CHF (New York Heart Association class III and IV) and in 11 normal age-matched control subjects. Baseline mean arterial pressure (83 ± 2 vs 84 ± 2 mm Hg) and mean arterial pressure during LBNP (−10, −20, and −40 mm Hg) were not significantly different in the two groups. Basal FVR (43.7 ± 4 vs 27 ± 2 units), plasma norepinephrine (605 ± 81 vs 155 ± 8 pg/ml), and plasma renin activity (8.3 ± 1.7 vs 1.2 ± 0.2 ng/ml/hr) were significantly ( p < 0.01) higher in patients with CHF. The relative increases in FVR responses during LBNP of −10, −20, and −40 mm Hg (10 ± 4% vs 70 ± 12%, 17 ± 6% vs 106 ± 21%, and 24 ± 9% vs 152 ± 28%) were markedly attenuated in patients with CHF compared to control subjects. Plasma norepinephrine and plasma renin activity responses during LBNP were also attenuated in patients with heart failure. Our results suggest that baroreflex control of FVR and plasma norepinephrine and plasma renin activity is impaired in CHF because of the inability of the cardiopulmonary baroreceptors to alter sympathetic outflow.

Exercise Responses during Incremental and High Intensity and Low Intensity Steady State Exercise in Patients with Obstructive Lung Disease and Normal Control Subjects

A study was undertaken to compare the cardiac and ventilatory responses to different types of exercise between 12 patients with COPD and ten normal age-matched control subjects. Both groups attained comparable heart rates and the percentage of their maximum predicted heart rate. Patients had a higher heart rate and VE with a lower O2P at every level of work load. Patients had a mean VT which approximated their FEV1 and increased their VE predominantly by increasing their respiratory frequency. During the low intensity test, despite the differences in work load, the patients had comparable heart rates and VE. No resting spirometric value accurately predicted work load, VE, or maximal VO2. We conclude that patients have a reduced work tolerance that is not adequately explained by their reduced lung function. Thus, cardiac factors, deconditioning, and the dyspneic sensation may be determinants of exercise limitation in some patients.

Neuroendocrine Responses to Physostigmine in Alzheimer's Disease

To assess central nervous system cholinergic neuroendocrine regulation in Alzheimer's disease (AD), we measured plasma arginine vasopressin, beta-endorphin, and epinephrine responses to a cholinergic challenge elicited by intravenous administration of the acetylcholinesterase inhibitor physostigmine (0.0125 mg/kg) in male patients with AD (n = 12) and compared their responses with those of age-matched normal control subjects (n = 12). Physostigmine promptly increased plasma arginine vasopressin (tenfold), beta-endorphin (twofold to threefold) and epinephrine (threefold) levels in elderly control subjects. In contrast, patients with AD showed attenuated responses to physostigmine. When controls and patients with AD who experienced nausea (n = 2 and n = 6, respectively) were excluded, the arginine vasopressin, beta-endorphin, and epinephrine responses of patients with AD were significantly less than those of control subjects. These data suggest that the central nervous system cholinergic deterioration of AD results in decreased responsiveness of neuroendocrine systems that are regulated by central cholinergic mechanisms.

Does the abnormal pattern of breathing in patients with interstitial lung disease persist in deep, non-rapid eye movement sleep?

Patients with interstitial lung disease (ILD) characteristically exhibit an increased ventilation and breathing frequency when awake. We wanted to see if these increases persisted during deep non-REM sleep. Using noninvasive techniques, we have quantified the pattern of breathing, arterial oxygen saturation, and transcutaneous PCO2 (PtcCO2) during standardized conditions of relaxed wakefulness and during Stage 4 (S4) sleep in eight patients with ILD and eight age-matched normal control subjects. The patients were given supplemental oxygen in order to prevent hypoxic ventilatory stimulation. The data were compared between the two groups during each of these states and also between states within each group. During wakefulness in the patients, respiratory frequency (f) and PtcCO2 were higher (p less than 0.001 and p less than 0.05, respectively) and inspiratory time (TI) and expiratory time (TE) were shorter (p less than 0.05 and p less than 0.001, respectively) than in the normal subjects. However, during S4 sleep, there were no significant differences between groups. Comparing wakefulness with S4 sleep: in the normal subjects during sleep, f and PtcCO2 were increased (p less than 0.01 and p less than 0.05, respectively), TE was shortened (p less than 0.01), and ventilation (VI) was unchanged. In contrast, in the patients, f decreased (p less than 0.001), TE lengthened (p less than 0.01), VI decreased (p less than 0.05), and the rise in PtcCO2 seen in the normal subjects during sleep did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)