Working memory and aging: a cross-sectional and longitudinal analysis using a self-ordered pointing task.

Age-related declines in working memory performance have been associated with deficits in inhibition, strategy use, processing speed, and monitoring. In the current study, cross-sectional and longitudinal methodologies were used to investigate the relative contribution of these components to age-related changes in working memory. In Experiment 1, a sample of 140 younger and 140 older adults completed an abstract design version of the Self-Ordered Pointing Task modeled after Shimamura and Jurica (1994). Experiment 1 revealed that only processing speed and monitoring explained age differences in SOPT performance. Participants in Experiment 2 were 53 older adults who returned 4 years after the initial testing and 53 young adults. A task that assessed the ability to generate and monitor an internal series of responses as compared to an externally imposed series of responses was also administered. Experiment 2 replicated the key findings from Experiment 1 and provided some further evidence for age-related internal monitoring difficulties. Furthermore, the exploratory longitudinal analysis revealed that older age and lower intellectual abilities tended to be associated with poorer performance on the SOPT at Time 2.     

The composite N1 component to gaps in noise.

OBJECTIVE: To indicate whether the double peaked N(1) to gaps in continuous white noise is a composite of onset and offset responses to transients or whether it reflects higher processing such as change or mismatch detection and to assess the role of attention in this process. METHODS: Evoked potentials were recorded to two binaural stimulus types: (1) gaps of different durations randomly distributed in continuous white noise; and (2) click pairs at intervals identical to those between gap onsets and offsets in the continuous noise stimulus. Potentials to these stimuli were recorded while subjects read a text and while detecting gaps in noise or click pairs. RESULTS: Potentials were detected to all click pairs and to gaps of 5 ms or longer, corresponding to the subjects' psychoacoustic gap detection threshold. With long gap durations of 200-800 ms, distinct potentials to gap onset and gap offset were observed. The waveforms to all click pairs and to offsets of long gaps were similar and single-peaked, while potentials to gaps of 10 ms and longer, and potentials to onsets of long gaps were double-peaked, consisting of two N(1) negativities, 60 ms apart, irrespective of gap duration. The first (N(1a)), was more frontal in its distribution and similar to that of clicks. The second (N(1b)) peak's distribution was more central/temporal and its source locations and time course of activity were distinct. No effects of attention on any of the varieties and constituents of N(1) were observed. CONCLUSIONS: Comparing potentials to gap onsets, to click pairs and to gap offsets, suggests that potentials to gap onsets involve not only sound onset/offset responses (N(1), N(1a)) but also the subsequent pre-attentive perception of the cessation of an ongoing sound (N(1b)). We propose that N(1b) is distinct from change or mismatch detection and is associated with termination of an ongoing continuous stimulus. We propose to call it the N(egation)-process. SIGNIFICANCE: A constituent of the N(1) complex is shown to be associated with the pre-attentive perception of termination of an ongoing stimulus and to have distinct scalp distribution and intracranial sources.     

Effects of renin-angiotensin system blockade on macrophage infiltration in patients with hypertensive nephrosclerosis.

The mechanisms of hypertensive nephrosclerosis are not fully understood. In experimental models of the disease, inflammatory reactions such as macrophage infiltration play an important role. In human hypertensive nephrosclerosis, however, there have been few studies examining the role of inflammation histologically. We investigated whether the number of infiltrating macrophages was increased in human hypertensive nephrosclerosis, and evaluated the effects of a blockade of the renin-angiotensin system on clinical and histological findings. We examined macrophage infiltration using immunohistochemistry in renal biopsy specimens obtained from 16 patients with hypertensive nephrosclerosis, 5 patients with IgA nephropathy, 5 patients with membranous nephropathy, and 5 patients with minimal change nephrotic syndrome. The number of infiltrating macrophages in glomeruli was significantly larger in the patients with hypertensive nephrosclerosis than in those with minimal change nephrotic syndrome. The patients with hypertensive nephrosclerosis were divided into groups based on their use of antihypertensive agents at the time of renal biopsy. We investigated the effects of antihypertensive agents on clinical findings, macrophage infiltration, and monocyte chemoattractant protein-1 expression. There was no difference in clinical findings between the hypertensive groups. The numbers of infiltrating macrophages and monocyte chemoattractant protein-1-positive cells in glomeruli were significantly smaller in patients treated with an angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker, whereas calcium channel blockers had no influence on histological findings. In conclusion, inflammation is involved in the progression of human hypertensive nephrosclerosis and the inflammatory process is inhibited by blocking the renin-angiotensin system.     

Predicting occupational performance: handwriting versus keyboarding.

PURPOSE: To determine whether there is a correlation between handwriting and keyboarding speed and accuracy, and whether handwriting and keyboarding share common underlying components. METHODS: Sixty-three typically developing 5th-grade students attended a series of 15 keyboarding lessons for a total of 5 hours. Prior to the lessons, cognitive, sensory, and motor skills related to handwriting were evaluated. Prior to and following the lessons keyboarding and handwriting accuracy and speed were also tested. Correlations were employed to examine relationships between handwriting and keyboarding skills and multiple regression analyses were used to examine the contribution of performance components to handwriting and keyboarding performance. RESULTS: Following keyboarding instruction, a significant correlation was found between handwriting and keyboarding speed, but not in accuracy of these tasks. Similarly, some of the specific tests measuring tactile and oculo-motor functions were found to be related to both handwriting and keyboarding speed, yet accuracy of these tasks did not share common underlying components. CONCLUSIONS: It appears that handwriting and keyboarding accuracy may entail different skills, suggesting that keyboarding may be a potential alternative writing tool for students with handwriting difficulties. It also appears that when students write slowly, handwriting speed should be considered prior to recommending keyboarding for these students. Additional research is required to further support these findings.     

Analysis of ischemia-reperfusion injury in a microcirculatory model of pressure ulcers

The aim of this study was to establish a pressure ulcer model that visualizes the microcirculation, and to examine the participation of ischemia-reperfusion injury in the pathophysiology of pressure ulcers. An original system composed of a new skin fold chamber and compression device allowed loading quantitative vertical stress to the skin. An intravital microscopic technique enabled direct visualization of the microcirculation in the physiological condition and in response to pressure application. To estimate the effect of ischemia-reperfusion injury, animals were divided into two groups: the compression-release group (n = 8), in which the animals received four cycles of compression-release which consisted of 2 hours of compression followed by 1 hour of pressure release; and the compression alone group (n = 8) in which the animals underwent continuous compression for 8 hours. Functional capillary density was quantified before the compression procedure and on day 1 (35 hours) after the first evaluation. The cyclic compression-release procedure significantly decreased functional capillary density as compared to continuous compression, indicating that in our experimental setting repetition of ischemia-reperfusion cycle more severely damaged the microcirculation than single prolonged ischemic insult. This finding supports the significant contribution of ischemia-reperfusion injury to the pathophysiology of pressure ulcers at the level of dynamic in vivo microcirculation.     

A case of small cell carcinoma of the lung associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome]

A 51-year-old male who showed severe ataxia, dysarthria, bilateral blepharoptosis, diplopia and nystagmus with the subacute onset was reported. The chest roentgenogram and CT scan revealed mass lesions at the hilus of the left lung. The tumor markers, NSE and ProGRP, were elevated; 12.8 ng/ml (< or = 10) and 140.7 pg/ml (< or = 46), respectively. The biopsy was performed surgically and the small cell carcinoma of the lung was confirmed pathologically. His cerebellar symptoms were considered to be caused by the paraneoplastc cerebellar degeneration. However, the blepharoptosis was peculiar. The electrophysiological studies were carried out The muscle strength test of the right APB muscle was 5. But the supramaximum stimulation of the right median nerve evoked only 2.0 mV of CMAP of the right APB muscle. The repetitive stimulation tests of the same nerve showed that 3 Hz stimulation resulted in 42% waning but 20 Hz stimulation evoked no waxing. The post-exercise test of the right APB muscle showed 73% increase of the CMAP. These findings indicated that he also suffered from Lambert-Eaton myasthenic syndrome. The titer of the antibody against the P/Q type voltage-gated calcium channel (VGCC) was remarkably elevated, 1,920 pM. None of the following antibodies were detected ; they included antibodies against acetylcholine receptor, Hu, Yo, Ri, Ma-2, CRMP-5, amphiphysin and glutamic acid dehydrogenase. The small cell carcinoma was treated with the combination of irinotecan hydrochloride and cisplatin, leading to the reduction of the mass lesions and the tumor markers. His cerebellar symptoms improved slightly but his blepharoptosis was unchanged. The titer of antibody against the P/Q type VGCC reduced remarkably to 451.8 pM. We reviewed reported cases associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome and discussed the relation between the paraneoplastic syndromes and autoantibodies.     

Validity and reliability of the Japanese version of the Neuropsychiatric Inventory Caregiver Distress Scale (NPI D) and the Neuropsychiatric Inventory Brief Questionnaire Form (NPI-Q)]

OBJECTIVE: Neuropsychiatric disturbances are common and burdensome symptoms of dementia. Assessment and measurement of neuropsychiatric disturbances are indispensable to the management of patients with dementia. Neuropsychiatric Inventory (NPI) is a comprehensive assessment tool that evaluates psychiatric symptoms in dementia. We translated the NPI-Caregiver Distress Scale part of NPI (NPI-D) and NPI-Brief Questionnaire Form (NPI-Q) into Japanese and examined their validity and reliability. SUBJECTS AND METHODS: The subjects were 152 demented patients and the caregivers who lived with them. These patients consisted of 76 women and 76 men; their mean age was 73.9 +/- 7.8 (S.D.; range: 49 to 93) years. Their caregivers consisted of 46 men and 106 women; their mean age was 65.0 +/- 11.4 (S.D.; range: 35 to 90) years. The Mini-Mental State Examination (MMSE) was conducted with all patients and NPI-Q, NPI, NPI-D, and the Zarit caregiver burden interview (ZBI) were conducted with all caregivers. We examined validity of NPI-D by comparing its score with the MMSE and ZBI scores, and the validity of NPI-Q by comparing its score with the NPI and NPI-D scores. In order to evaluate test-retest reliability, NPI-D was re-adopted to 30 randomly selected caregivers by a different examiner one month later and NPI-Q was re-executed by 27 randomly selected caregivers one day later. RESULTS: Total NPI-D score was significantly correlated with ZBI (rs = 0.59, p < 0.01). Test-retest reliability of NPI-D was adequate (ri = 0.47, p < 0.01). Total NPI-Q severity score and distress score were strongly correlated with NPI (r = 0.77, p < 0.01) and NPI-D (r = 0.80, p < 0.01) scores, respectively. Test-retest reliability of the scores of NPI-Q was acceptably high (the severity score; ri = 0.81, p < 0.01, the distress score; ri = 0.80, p < 0.01). CONCLUSION: The Japanese version of NPI-D and NPI-Q demonstrated sufficient validity and reliability as well as the original version of them. These are useful tools for evaluating psychiatric symptoms in demented patients and their caregivers' distress attributable to these symptoms.     

Correlation between inflammatory cellular responses and chemotactic activity in bronchoalveolar lavage fluid following intratracheal instillation of nickel sulfate in rats

In a preceding study, we reported that the numbers of macrophages and polymorphonuclear leukocytes (PMN) were increased in bronchoalveolar lavage fluid (BALF) following the intratracheal instillation of nickel sulfate (NiSO₄) in rats. In the present study, BALF chemotactic activities for both macrophages and PMN were measured to investigate if the increases of these inflammatory cells in BALF depend on increases in chemotactic activities in epithelial lining fluid (ELF) of the lung. Both the number of PMN and the PMN chemotactic activity peaked at 2 days post-instillation and they were significantly correlated. However, the PMN chemotactic activity was inversely correlated with concentration of leukotriene B₄ (LTB₄), a well-known chemotaxin. Although PMN were not observed in control BALF, LTB₄ concentration in the control ELF (ca. 5×10^–7 M) was estimated to have a potential to attract PMN chemotactically through a membrane in in vitro migration assay. These results suggest that the presence of LTB₄ in ELF itself does not trigger transpulmonary PMN infiltration. The rat BALF were fractionated by high performance liquid chromatography (HPLC), and PMN chemotactic activity of each fraction was measured. The elution profiles of PMN chemotactic activity showed that there were at least two different chemotaxins in BALF obtained from the NiSO₄-exposed rats. Macrophage chemotactic activity in BALF also peaked at 2 days post-instillation. However, the number of macrophages was not significantly correlated with the chemotactic activity for macrophage in BALF. The HPLC study showed that the macrophage chemotactic substance in the BALF obtained from NiSO₄-exposed rats was different from complement fragment (C5a) and its MW was estimated to be 10 – 12 kD. Received: 1 December 1993/Accepted: 16 March 1994