Age-matched Normal Control Subjects Research Articles

Elemental imbalances in the olfactory pathway in Alzheimer's disease

Concentrations of 11 trace elements were determined in 56 control and 98 Alzheimer's disease (AD) olfactory bulb, olfactory tract, olfactory trigone, piriform cortex and amygdala specimens by instrumental neutron activation analysis. Iron and zinc were significantly elevated and bromine was significantly depleted in olfactory regions of AD patients, compared with normal age-matched control subjects. Elevated iron could possibly play a role in neuronal degeneration in AD by enhancing reactive free radical formation.

Left lateralized P300 amplitude deficit in schizophrenic patients depends on pitch disparity

The general reduction of P300 amplitude in response to auditory oddball stimuli is one of the most consistently replicated biological observations in schizophrenic patients. Several groups have reported a P300 asymmetry in schizophrenic patients, others have not been able to replicate this finding. In order to clarify this issue, we examined the effect of stimulus discriminability on P300 amplitude distribution in schizophrenic patients and in age-matched normal control subjects, using two different auditory oddball paradigms. The detection of the target tone was either simple or difficult, due to manipulation of pitch disparity. The P300 amplitude was comparatively smaller in the schizophrenic patient group compared to the healthy controls and in the difficult task compared to the simple. The schizophrenic patients showed a specific P300 amplitude reduction over left temporal electrode sites when the simple paradigm was used. The difficult paradigm did not elicit asymmetrical P300 amplitudes in schizophrenic patients.

Effect of an inelastic aortic synthetic vascular graft on exercise hemodynamics

This study compared aortic input impedance characteristics between patients with aortic interposition Dacron grafts placed for traumatic aortic injury and normal age-matched control subjects. All subjects were examined at rest and after treadmill exercise. Magnetic resonance imaging was conducted to rule out anatomic (stenosis) effects. Exercise increased characteristic impedance (ie, reduced aortic distensibility) by 29% and decreased total systemic arterial compliance by 21% in the patient group, whereas the normal control group showed insignificant change in these variables after exercise. Peripheral pressure wave reflection was reduced substantially with exercise (27%) in the control group, with much less reduction observed in the patient group. These abnormal vascular hemodynamics were associated with significantly high cardiac energetic costs in the patient group. A plausible explanation for the observed differences lies in the exaggerated vascular impedance mismatch between compliant aorta and inelastic graft, when cardiac output increases dramatically.

Increased nitric oxide in exhaled air of normal human subjects with upper respiratory tract infections.

Viral infection may induce the expression of nitric oxide (NO) synthase, resulting in increased NO formation that has an antiviral effect. NO may be produced by various cells of the upper and lower respiratory tract, and may be detected in the exhaled air. We have studied the levels of exhaled NO in 18 normal subjects during symptomatic upper respiratory tract infections and during recovery 3 weeks later. Exhaled NO was measured using a modified chemiluminescence analyser. At the time of symptoms of upper respiratory tract infection, the peak exhaled NO values were 315 +/- 57 ppb (mean +/- SEM) and decreased to 87 +/- 9 ppb during recovery. Recovery values of exhaled NO were similar to those reported in age-matched normal control subjects (88 +/- 3 ppb, n = 72). These findings suggest that symptomatic upper respiratory tract infections markedly increase the concentration of NO in exhaled air. This may reflect the induction of nitric oxide synthase (NOS) in upper and lower respiratory tract, and may be relevant to viral exacerbations of asthma.

Increased Numbers of Mast Cells in Pterygia

We examined the mast cells in 12 pterygium specimens of patients who underwent primary excisions and the conjunctival specimens of ten normal age-matched control subjects. The mean mast cell count per cubic millimeter was twice as high in the pterygium specimens as in the control specimens. Mast cell proliferation and activation may contribute to the pathogenesis of pterygium formation.

Peripheral Serotonin in Alzheimer’s Disease

The platelet has been suggested to be a peripheral model of the central serotonergic neuron. This investigation was carried out in order to test the hypothesis that levels of serotonin (5-HT) in the platelet will be decreased in Alzheimer's disease (AD) since neurochemical studies suggest that levels of 5-HT are decreased in the brain of AD patients. We investigated platelet and plasma 5-HT in a group of AD patients (n = 22) as well as in age-matched normal control subjects (n = 20). The results show that the platelet level of 5-HT was significantly reduced in AD (65.7 +/- 28.41 ng/10(8) platelets in AD vs. 112.9 +/- 35.11 ng/10(8) platelets in controls; p = 0.0001). There was no effect on the levels of its metabolite 5-hydroxyindoleacetic acid. These findings suggest that the peripheral serotonergic system in AD is adversely affected.

Regional cerebral blood flow during a self-paced sequential finger opposition task in patients with cerebellar degeneration.

The brain regions controlling self-paced sequential finger movements in patients with cerebellar degeneration were studied by measuring changes in regional cerebral blood flow (rCBF) in eight patients using bolus injections of H2(15)O and PET. The results were compared with those obtained in eight normal age-matched control subjects. Patients and control subjects performed a self-paced sequential finger opposition task with the right hand, completing a sequence of movements every 4-6 s. Both groups had strong increases in the adjusted rCBF contralaterally in the primary motor cortex (M1) and ventral premotor area (PMv), in the caudal supplementary motor area (SMA) and cingulate motor area (CMA), and bilaterally in the prefrontal cortex (PFC), the lobus parietalis inferior (LPI), putamen and cerebellum. The cerebellum, PMv, rostral CMA, PFC and LPI were more active in the control subjects than in the patients, and the M1, SMA, caudal CMA and putamen were more active in the patients than in the control subjects. The reduced activity of the cerebellar neurons in the patients produced a complex pattern of rCBF increases and decreases in other brain regions. Our results suggest that for the preparation and execution of sequential finger movements, patients with cerebellar degeneration use a medial premotor system, including the SMA and caudal CMA, as well as the M1 and putamen, rather than the PMv, PFC, LPI and rostral CMA.

Red blood cell membrane dynamics in schizophrenia. II. Fatty acid composition

Fatty acid compositions were determined in red blood cell (RBC) ghost membranes of schizophrenic patients before and after haloperidol withdrawal, as well as with age-matched normal male control subjects ( n=22). Patients on haloperidol (HD) received treatment in doses between 5 and 20 mg/day for at least 5 weeks ( n=24). Drug-free patients ( n=19) were free of all psychotropic medications for an average of 40 days. A highly significant decrease in the levels (nmol/ml packed RBC) of polyunsaturated fatty acids (PUFAs), particularly 18:2( n−6) and 20:4( n−6), was found in both HD-treated and drug-free patients. This decrease remained in those patients who had withdrawn from HD for more than 5 weeks ( n=10). Concomitantly, the percentage of saturated and monoenoic fatty acids to total fatty acids increased significantly in schizophrenic patients. The resultant fatty acid profile consequently lowers the unsaturation index (UI), which represents the average number of double bonds per fatty acid molecule, in RBC ghost membranes of schizophrenic patients. Furthermore, the decreases in UI were significantly correlated to the increases in “structure order” of RBC ghost membranes as measured by the steady-state fluorescence anisotropy ( r s) in normal control and drug-free schizophrenic subjects. Therefore, it is likely that decreased levels of PUFAs in schizophrenic patients might result from a defective uptake of 18:2( n−6) into RBC membrane phospholipids. Since fatty acid composition of membrane phospholipids affects the relative degree of membrane fluidity, the present results lend further support that RBC membrane dynamics are altered in schizophrenia.

Central and peripheral limitations to upright exercise in untrained cardiac transplant recipients.

Functional capacity and quality of life are subjectively improved after cardiac transplantation. However, the objective improvement in exercise tolerance after transplantation has been disappointing. The extent to which allograft diastolic dysfunction contributes to this exercise intolerance has not been defined. Thirty cardiac transplant recipients between 3 and 16 months after transplantation and 30 age-matched normal control subjects underwent maximal symptom-limited graded upright bicycle exercise testing with simultaneous radionuclide angiography, invasive hemodynamic monitoring, and breath-by-breath gas analysis. Mean blood pressure was higher in the transplant group at supine rest (112.1 versus 97.7 mm Hg), normalized with upright posture, and became lower than normal at peak exercise (121.1 versus 133.2 mm Hg). Systolic function as measured by ejection fraction was normal in both groups. However, the cardiac transplant recipients had significantly lower exercise tolerance, achieving a mean maximal work rate of 390 kilopond-meters per minute (kpm/min), compared with 825 kpm/min in the normal subjects. Peak oxygen consumption was 12.3 mL.min-1.kg-1 in the transplant group, 46% lower than the normal group's value of 22.9 mL.min-1.kg-1. The transplant patients had a resting tachycardia (94 beats per minute) and a 79% reduction in exercise heart rate reserve compared with normal. Despite this chronotropic incompetence, stroke index response to exercise was consistently lower after transplantation, accounting for a 41% reduction in cardiac index at maximal exercise. The lower stroke index was accompanied by a 32% lower end-diastolic volume index at rest and a 14% lower end-diastolic volume index at peak exercise. Despite the smaller ventricular volumes after transplantation, pulmonary capillary wedge pressure was 35% higher than normal at supine rest and 50% higher at maximal exercise. Right atrial and mean pulmonary arterial pressures were similarly elevated. The ratio of pulmonary capillary wedge pressure to end-diastolic volume index was significantly higher during the postural change and exercise, suggesting allograft diastolic dysfunction. Arteriovenous oxygen difference was similar between groups at rest and with submaximal exercise but was 24% lower at maximal exercise in the transplant group, suggesting an abnormality in peripheral oxygen uptake or utilization. Exercise tolerance is severely limited during the first 16 months after cardiac transplantation despite preservation of allograft left ventricular systolic function. This intolerance is due to an inadequate cardiac index response from a combination of chronotropic incompetence and diastolic dysfunction limiting the appropriate compensatory use of the Starling mechanism. In addition, there is a peripheral abnormality in oxygen transport or utilization that may partially reflect the effects of deconditioning.

Alzheimer's disease and Lewy body disease: a comparative clinicopathological study.

The exact nature of the relationship between Lewy body disease and Alzheimer's disease (AD) is unknown. To investigate this, we compared cases of pure Lewy body disease, mixed Lewy body disease with AD, and pure AD to see what pathological features were shared and how they differed. We counted neurons, Lewy bodies, diffuse and neuritic senile plaques, neurofibrillary tangles, and neuropil threads in the frontal and medial temporal cortex and hippocampus from 5 autopsied cases of Lewy body disease (without AD histopathology), 7 with combined Lewy body disease and AD, 6 with AD, and 5 age-matched normal control subjects. Average neuronal counts in the cases with Lewy body disease were indistinguishable from those of control subjects, but higher than those for AD and combined Lewy body disease and AD. Diffuse plaque densities were similar in all disease forms. Neuritic senile plaques, neurofibrillary tangles, and neuropil threads were numerous in AD and combined Lewy body disease and AD, but sparse or absent in Lewy body disease and controls. Pure Lewy body disease and AD appear to be distinct clinicopathological entities except for the common feature of diffuse plaques in both disorders.

Respiratory Dysrhythmias in Patients With Tardive Dyskinesia

Tardive dyskinesia (TD) is a disorder characterized by abnormal involuntary movements and associated with neuroleptic therapy. To determine whether the respiratory muscles are involved in this condition, we compared the breathing pattern of ten patients with TD with ten patients with chronic schizophrenia receiving neuroleptic therapy without evidence of TD, and ten age-matched normal control subjects during resting tidal breathing, forearm pronation-supination (a maneuver designed to elicit the abnormal movements of TD), and breathing to a set frequency. Breathing patterns were also assessed in seven patients with TD during a progressive incremental exercise test and an overnight polysomnogram. Patients with TD had an irregular tidal breathing pattern, with a greater variability in both tidal volume and time of the total respiratory cycle (TTOT). Both groups of patients receiving neuroleptic therapy had a rapid shallow breathing pattern when performing forearm pronation-supination compared with control subjects. There were no differences between any of the subject groups when breathing to a set frequency. The patients with TD had a normal response to progressive exercise and inspiratory time and TTOT values were less variable during non-rapid eye movement sleep compared with wakefulness. We conclude that patients with TD have irregular rapid shallow breathing which is less variable during sleep and does not limit their exercise performance.

Incomplete achromatopsia in alzheimer's disease

We report that patients with Alzheimer's disease (AD) have a selective selective deficit in blue hue discrimination, as assessed with three clinical measures of color vision. The Farnsworth D-15 Test, the Lanthony New Color Test, and the City University Color Vision Test were administered to 32 patients with AD (ranging in dementia severity from mild to severe) and 32 age-matched normal control subjects (NCS). Of the AD patients, 11 who were representative of the larger group for age, education level, and dementia severity received a complete neuro-ophthalmological examination that ruled out obvious disorders of the anterior visual structures. AD patients made significantly more tritan (blue) errors than NCS on all three color vision tests but did not make more protan (red) or deutan (green) errors on two of the three tests. The results support the conclusion that there is a deficit in color discrimination in AD that is specific to blue hues, and oppose the hypothesis that AD does not deleteriously affect the color-opponent visual channel. In the absence of obvious damage to anterior visual structures, the likely substrates for the observed deficit are peristriate and inferotemporal visual cortices, which are subject to significant neuropathology in AD.

Smooth pursuit and saccadic eye movements and Wisconsin card sorting test performance in obsessive- compulsive disorder

Smooth pursuit eye movements (SPEMs), voluntary saccadic eye movements (VSEMs), and neuropsychological test (Touluse-Pieron Test and Wisconsin Card Sorting Test) performance were studied in 23 patients with obsessive-compulsive disorder and 27 age-matched normal control subjects. The patients performed more poorly than the control subjects on the SPEM and, to a lesser degree, VSEM measures. They also showed impairment on some aspects of the neuropsychological tests. No relationship was found between eye movement performance and neuropsychological impairment.

Regional cerebral blood flow measured with N-isopropyl-p-[123I]iodoamphetamine and its redistribution in ischemic cerebrovascular disease.

The relation between the redistribution phenomenon and regional cerebral blood flow and its clinical significance were investigated in stroke patients. Single-photon emission computed tomography studies using N-isopropyl-p-[123I]iodoamphetamine were performed on 16 patients (26 to 77 years old) with chronic infarction and 10 age-matched normal control subjects. Regional cerebral blood flow was quantitatively measured by a microsphere model, and the redistribution on delayed images was analyzed in ischemic lesions. Supratentorial mean cerebral blood flow and the ratio of gray matter to white matter in normal subjects were 52.7 +/- 5.0 mL/100 g per minute and 2.34, respectively. Low-activity areas of ischemic lesions on early images were classified into two abnormal zones, an infarct area and a peri-infarct area. These regions were characterized by regional blood flow averaging 9 to 20 mL/100 g per minute and 22 to 41 mL/100 g per minute, respectively. Redistribution, which was minimally present in the infarct area, was markedly enhanced in the peri-infarct area. After bypass surgery, we observed a significant increase of blood flow (+22%) in the peri-infarct area. The data indicate that the redistribution phenomenon depends on the maintenance of a minimal blood flow that would sustain cellular function and that this phenomenon is useful to evaluate bypass surgery in patients with chronic infarction.

Assessment of depression in Alzheimer's disease: symptoms, syndrome, and computed tomography findings.

The Hamilton Rating Scale for Depression (HAM-D) and DSM-III-R criteria were simultaneously employed to assess the prevalence of depression in 26 outpatients with dementia of the Alzheimer type and 26 age-matched normal control subjects. Both assessment methods evidenced a higher frequency of depression during the severe stages of Alzheimer's disease. Among the Alzheimer patients, the prevalence rate of depression produced by the HAM-D (38%) was higher than the rate produced by DSM-III-R criteria (23%). Such a difference was due to the weight given by the HAM-D to the vegetative symptoms reported by the Alzheimer patients with more severe dementia. In a subgroup of 14 Alzheimer patients who underwent computed tomography, the volumetric measurement of CSF spaces did not reveal any difference between the depressed and nondepressed patients. On the basis of these results, the clinical problems related to the assessment of depression in Alzheimer's disease are discussed.

Prolactin responses to domperidone in chronic schizophrenia

The prolactin response to 20 mg of domperidone, a peripheral dopamine receptor antagonist, was evaluated in a group of 17 male, drug-free, elderly, chronic schizophrenic patients and 8 age-matched male normal control subjects. Both groups of subjects were receiving a variety of nonpsychotropic medications not known to affect the prolactin response to dopamine receptor antagonists. Basal plasma prolactin levels did not differ between the two groups. However, the prolactin response following domperidone was significantly greater in the schizophrenic patients, although plasma domperidone levels did not differ between the two groups. This effect is opposite to the previously reported effect of domperidone in young schizophrenic patients compared with age-matched control subjects (Nerozzi, 1990). The prolactin response to domperidone was markedly smaller in the old compared with the young normal control subjects, whereas the young and old schizophrenic patients had identical responses. Possible explanations for these results are considered, especially the possibility of abnormalities in the release of dopamine and pituitary D 2 dopamine receptors in the elderly schizophrenic patients compared with age-matched normal control subjects.

The agraphia of Alzheimer's disease

Hypothesizing that agraphia in Alzheimer's disease (AD) reflects disturbances in multiple cognitive domains, we evaluated writing samples from 33 patients meeting strict criteria for probable AD. We found agraphia to be common on a standard narrative writing task. When compared with 41 education- and age-matched normal control subjects, AD patients had significantly lower writing scores, wrote significantly fewer words, mentioned significantly fewer categories of information, and were significantly more likely to make writing errors. On stepwise regression procedures, neuropsychological measures of visuoperceptual impairment and disease severity were the strongest predictors of agraphia, but other analyses indicated that measures of language, praxis, and attention could also contribute significantly to agraphia. On two writing tasks, we failed to confirm the previous contention that agraphia is a marker for familial AD. However, there was a highly significant interaction between family history, oral naming, and writing: patients with nonfamilial AD, but not those with a family history of dementia, showed a strong correlation between naming and writing performance. We conclude that agraphia in AD can be variously determined and that agraphia is not a reliable marker for familial disease.

Exercise-induced conduction velocity increment: a marker of impaired peripheral nerve blood flow in diabetic neuropathy.

Severe microvascular disease exists at the stage of clinical diabetic neuropathy. A non-invasive test that will identify those diabetic subjects who will eventually develop neuropathy is essential for early intervention. Sural sensory conduction velocity was recorded (x3) in 12 non-neuropathic diabetic subjects, 15 diabetic subjects with established neuropathy and 16 age-matched normal control subjects, before and after exercise to 80% age/sex predicted maximum heart rate. Fixed sural electrodes were used. Subcutaneous temperature was recorded by a needle thermocouple placed near the sural nerve. Sural sensory conduction velocity increased significantly after exercise in normal subjects (p less than 0.01, mean increase 5.07 m/s) and non-neuropathic diabetic subjects (p less than 0.02, mean increase 3.99 m/s) but not in neuropathic subjects (mean increase 0.99 m/s). Subcutaneous temperature rose significantly in normal subjects (p less than 0.01, mean increase 2.07 degrees C) and non-neuropathic diabetic subjects (p less than 0.001, mean increase 2.52 degrees C) but not in neuropathic subjects (mean increase 0.15 degree C). However, sural sensory conduction velocity increased by 1.2 m.s-1.degree C-1 following direct warming of the limb in six neuropathic subjects which was comparable to that of normal and non-neuropathic subjects (1.49 and 1.48 m.s-1. degree C-1). The impairment of exercise conduction increment in diabetic neuropathy suggests impaired nerve blood flow in diabetic neuropathy.

Dobutamine stress echocardiography: A sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer

Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 ± 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg/m2of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10 μg/kg per min were administered. Echocardiographic Doppler studies were per formed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 μg/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms.The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings wert more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 ± 1.9 mm versus 13.1 ± 1.5 mm for control subjects (p < 0.01). End-systolic left ventricular posterior wall dimension at the 5- μg/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 ± 2.4 mm versus 19.3 ± 2.6 mm for control subjects (p < 0.01). Percent left ventricular posterior wall thickening at baseline for the doxorubicin-treated group was 78 ± 18% versus 97 ± 13% for the control group (p < 0.01). Percent left ventricular posterior wall thickening at the 5- μg/kg per min dobutamine infusion for the doxorubicin-treated group was 121 ± 37% versus 185 ± 20% for the control group (p < 0.01). Decreased left ventricular shortening fraction and increased left ventricular end-systolic meridional wall stress were demonstrated in doxorubicin-treated patients only during dobutamine infusion. No differences were found between results in control subjects and doxorubicin-treated patients for measured diastolic variables.Thus, asymptomatic long-term survivors of childhood cancer treated with doxorubicin may have latent decreased cardiac performance that is undetected by commonly used echocardiographic methods, including rest left ventricular shortening fraction and left ventricular end-systolic meriodional wall stress. Our data establish that evaluation of left ventricular systolic function by end-systolic posterior wall dimension, posterior wall thickening, end-systolic meridional wall stress and shortening fraction measured during inotropic stimulation with dobutamine provides a sensitive technique for examining the cardiac status of asymptomatic doxorubicin-treated patients.

Attentional cues in chronic schizophrenia: abnormal disengagement of attention.

Posner's (1980) reaction time (RT) paradigm was used to examine the engagement and disengagement operations of visual selective attention in patients with schizophrenia. In the 1st experiment, 14 medicated, chronic schizophrenic subjects (diagnosed by criteria of the Diagnostic and Statistical Manual of Mental Disorders; American Psychiatric Association, 1987) and 15 age-matched normal control subjects made a speeded response to a target preceded by a valid, an invalid, or no cue. Control subjects showed the expected advantage and disadvantage in RT for valid and invalid cues, which suggests intact engagement and disengagement operations. For schizophrenic patients, valid cues also enhanced RT, but invalid cues did not slow RT. Similar results were found in the 2nd experiment. The failure of unpredictable, invalid cues to inhibit RT in chronic schizophrenia may be related to an abnormality in the disengagement operation of selective attention.