A novel method of evaluating changes in intrinsic motivation during cognitive rehabilitation.

Motivation is one of the most important affecting rehabilitation outcomes. In present study, we propose a novel method to evaluate intrinsic motivation. We conducted experiments of simulated cognitive rehabilitation exercises. The results of these experiments demonstrate that intrinsic motivation is correlated to valence. Furthermore, CIM (Changes in intrinsic motivation) can be detected with up to 80% accuracy, using physiological states. The result showed that this method more precisely detects CIM than occupational therapists.Clinical Relevance-The proposed method enables to evaluate changes in intrinsic motivation during cognitive rehabilitation without disturbing or suspending rehabilitation.

Predictive value of von Willebrand factor for adverse clinical outcome in hypertensive patients with mild-to-moderate aortic regurgitation.

Plasma levels of von Willebrand factor (vWF), a marker of endothelial dysfunction/damage, are elevated in high-risk hypertensive patients and in patients with severe aortic regurgitation (AR). Patients with mild-to-moderate AR, frequently detected in hypertensive elderly, have additional left ventricular morphological and functional dysfunctions. We hypothesized that hypertensive patients with mild-to-moderate AR may have enhanced endothelial and/or left ventricular dysfunctions that may lead to a deteriorated prognosis. We measured vWF, prothrombin F1+2 (F 1+2) as a marker of thrombin generation, brain natriuretic peptide (BNP) in 104 hypertensive patients with mild-to-moderate AR and 66 hypertensive patients without AR. The left ventricular diameter at systole (LVDs) and left ventricular posterior wall thickness (LVWT) were determined by echocardiography and indexed by body surface area (LVDs/BSA and LVWT/BSA). VWF (median, interquartile range (IQR) 154, 120-196%) and BNP (34.7 pg ml(-1), 15-65%) levels were greater in patients with AR than in those without AR (135, 98-175% and 20, 10.3-49 pg ml(-1)). All patients were prospectively followed up for cardiac events during the period of median 43 months (IQR 31-81). Patients with AR had an increased risk of cardiac events (regression ratio (RR) 1.87, 95% confidence interval 1.28-2.87) when compared to those without AR. A multivariate Cox hazard analysis indicated that log vWF (RR 4.93) and log BNP (RR 1.9) were independent predictors in patients with AR. VWF was an independent predictor of clinical outcome in hypertensive patients with mild-to-moderate AR.

Effect of weight loss on blood pressure and drug consumption in normal weight patients.

The effect of weight loss on blood pressure and on antihypertensive drug consumption was examined in 81 nonobese subjects with essential hypertension who had been chronically treated with antihypertensive drugs. A hypocaloric diet was prescribed for 5 months. A weight loss greater than 2 kg in 5 months was considered significant. Quality and quantity of antihypertensive medications were scored according to a formula. In the subjects whose medication and weight did not change, mean arterial pressure remained unchanged, whereas it decreased significantly (-7.1 +/- 1.9 mm Hg) in those who showed significant weight loss (-3.28 +/- 0.34 kg) with no change in medication. Among the subjects whose antihypertensive medication remained constant during the diet program there was a significant correlation between the change in weight and mean arterial pressure (r = 0.45, p less than 0.01). Mean arterial pressure increased significantly (+5.1 +/- 1.7 mm Hg) in subjects whose weight remained unchanged with a decrease in medication, whereas it remained significantly lower than the control (by -3.1 +/- 2.0 mm Hg) in those whose weight decreased significantly (-4.57 +/- 0.69 kg) with the decrease in medication. The weight loss-induced decrease in blood pressure occurred independently of the initial degree of obesity and the initial level of mean arterial pressure. Urinary sodium excretion in the control period and at the end of the diet program did not differ significantly between subgroups. These results indicate that, even in subjects of normal weight with essential hypertension, weight loss can induce a fall in blood pressure that leads to a reduction of antihypertensive medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered circadian blood pressure rhythm in patients with Cushing's syndrome.

The circadian blood pressure rhythm was compared in patients with Cushing's syndrome, essential hypertension, and primary aldosteronism. In patients with essential hypertension or primary aldosteronism, a clear nocturnal fall in systolic and diastolic blood pressure and heart rate was observed. This fall was seen in untreated subjects as well as in patients receiving combined treatment with a calcium antagonist, diuretic, converting enzyme inhibitor, alpha-blocker and beta-blocker, or sympatholytic drug. In these groups, there was a positive correlation between heart rate and systolic or diastolic blood pressure. On the other hand, in patients with Cushing's syndrome, there was no nocturnal fall in blood pressure but in some patients a rise was observed. In all patients there was a nocturnal fall in heart rate. Thus, there was no significant correlation between heart rate and blood pressure in these patients. Exogenous glucocorticoid eliminated the normal nocturnal fall of blood pressure in patients with chronic glomerulonephritis or systemic lupus erythematosus. These results suggest that the changed circadian blood pressure pattern in patients with Cushing's syndrome is not due to antihypertensive treatment or to the mineralocorticoid excess accompanying this disease, but it is attributable to excess glucocorticoid or the associated disturbance in the adrenocorticotropic hormone-glucocorticoid system (or both). This conclusion also implies that the normal circadian rhythm of blood pressure may be regulated at least in part by the adrenocorticotropic hormone-glucocorticoid system.

Synthesis, Structure, and Redox Properties of [{(η(5) -C5 H5 )Co(S2 C6 H4 )}2 Mo(CO)2 ], a Novel Metalladithiolene Cluster.

Metal-metal bond formation by a cobaltadithiolene complex was observed for the first time in the reaction of [Co(η(5) -C5 H5 )(S2 C6 H4 )] with [Mo(CO)3 (py)3 ] and BF3 to give the Co-Mo-Co cluster 1. Cyclic voltammetry reveals that 1 undergoes two one-electron reduction steps at the Co centers, which is indicative of transmission of the Co-Co electronic interaction through the Mo center.

Exogenous glucocorticoid eliminates or reverses circadian blood pressure variations.

The effect of glucocorticoid on circadian variations of blood pressure was examined. In untreated patients with essential hypertension, a clear nocturnal fall in blood pressure and heart rate was observed and this was unaffected by combined treatment with antihypertensive drugs. The circadian blood pressure variation in patients with chronic glomerulonephritis (CGN) not receiving glucocorticoid treatment was essentially the same as that in patients with essential hypertension. In both groups there was a positive correlation between blood pressure and heart rate. On the other hand, in patients with CGN and systemic lupus erythematosus (SLE) who were treated with glucocorticoid, there was no nocturnal fall in blood pressure, and often a significant rise. In these patients the blood pressure was lowest in the afternoon and began to rise from then, and during the night, attaining a peak level in the morning. Despite this changed pattern of blood pressure variations, the heart rate in these patients was clearly reduced at night. In 10 patients with CGN and SLE, circadian rhythm of blood pressure and heart rate was examined before and during treatment with prednisolone (40.2 +/- 17.0 mg/day for 58.0 +/- 19.4 days, mean +/- s.d.). Prednisolone abolished the nocturnal fall of blood pressure, while the nocturnal fall of heart rate remained. There was no correlation between blood pressure and heart rate in patients with glucocorticoid treatment. These results suggest that the circadian blood pressure variation is influenced by the hypothalamo-pituitary-adrenal axis, probably through its action on the autonomic nervous system.

Hypertensive episodes and circadian fluctuations of blood pressure in patients with phaeochromocytoma: studies by long-term blood pressure monitoring based on a volume-oscillometric method.

A new portable device for the indirect measurement of arterial blood pressure was successfully applied to detect paroxysmal hypertension and circadian fluctuation of blood pressure in patients with phaeochromocytoma. The device utilizes the volume-oscillometric technique, it is equipped with a microprocessor and allows long-term automatic monitoring of indirect blood pressure in the human finger. Compared with conventional fully automated portable devices of the arm-cuff type, our current equipment is lighter, less noisy, and causes less discomfort. With this device repeated measurements can be made without causing stress or discomfort, and without disturbing sleep. The arterial pressure measurement obtained using this device was reliable and reproducible. In some patients certain symptoms, possibly due to phaeochromocytoma, had been observed for several years before the study, although hypertension had not been identified. While these patients had consistently high circulating catecholamine levels, nocturnal falls in blood pressure were clearly documented. This suggests that plasma catecholamines released from the phaeochromocytoma, though excessive, may be of less physiological importance than other regulatory mechanisms concerned with circadian fluctuation of blood pressure, e.g. the sympathetic nervous system and/or hypothalamo-pituitary-adrenal system. This new device has proved to be a reliable means of monitoring long-term blood pressure and is useful in the diagnosis of paroxysmal hypertension in patients with phaeochromocytoma.

N-methyl-D-aspartate receptor subunit changes are associated with lead-induced deficits of long-term potentiation and spatial learning.

The present study demonstrates that impairments of spatial learning and hippocampal long-term potentiation in rats chronically exposed to lead are associated with changes in gene and protein expression of N-methyl-D-aspartate receptor subunits. Rats exposed to 750 and 1500 ppm lead acetate were found to exhibit deficits in acquisition of a water maze spatial learning task. Furthermore, lead-exposed rats show dose-dependent reductions in the maintenance of in vivo hippocampal long-term potentiation induced in entorhinal cortex-dentate gyrus synapses. We found an unexpected, but significant (P<0.05), correlation between spatial learning and long-term potentiation when control and lead-exposed rats were analysed as a single, combined population. Dentate gyrus NR1 subunit messenger RNA was reduced 18% and 28% by exposure to 750 and 1500 ppm lead acetate, respectively. NR2A subunit messenger RNA was reduced 18% but only in the dentate gyrus of rats exposed to 1500 ppm lead acetate. No significant changes in dentate NR2B messenger RNA expression were measured in either of the lead-exposed groups. NR1 subunit protein was reduced 24% and 58% in hippocampal homogenates from rats exposed to 750 and 1500 ppm lead acetate. In contrast, no changes in NR2A or NR2B subunit protein were observed in the same hippocampal homogenates. These data show that reductions of specific N-methyl-D-aspartate receptor subunits are associated with deficits of both hippocampal long-term potentiation and spatial learning, induced in rats by chronic exposure to environmentally relevant levels of lead. These findings strongly suggest that the effects of lead on N-methyl-D-aspartate receptors may be the mechanistic basis for lead-induced deficits in cognitive function.

Methamphetamine-induced deficits of brain monoaminergic neuronal markers: distal axotomy or neuronal plasticity.

We examined the effects of methamphetamine (METH) on monoaminergic (i.e. dopamine and serotonin) axonal markers and glial cell activation in the rat brain. Our findings indicate that the loss of dopamine transporters (DAT), serotonin transporters (5-HTT), vesicular monoamine transporter type-2 (VMAT-2) and glial cell activation induced by METH in the striatum and in the central gray are consistent with a degenerative process. Our novel finding of METH effects on monoaminergic neurons in the central gray may have important implications on METH-induced hyperthermia. In other brain regions examined, DAT and 5-HTT deficits after METH administration were present in the absence of lasting changes in VMAT-2 levels or glial cell activation. Brain regions exhibiting protracted deficits in DAT and/or 5-HTT and VMAT-2 levels also expressed increased levels of [(3)H]-R-PK11195 binding to peripheral benzodiazepine receptors, a quantitative marker of glial cell activation. Immunohistochemical assessment of microglia and astrocytes confirmed the PBR results. Microglia activation was more pronounced than astrocytosis in affected regions in most METH-exposed brains with the exception of a small number of rats that were most severely affected by METH based on loss of body weight. In these rats, both microglia and astrocytes were highly activated and expressed a distinct regional pattern suggestive of widespread brain injury. The reason for the pattern of glial cell activation in this group of rats is not currently known but it may be associated with METH-induced hyperthermia. In summary, our findings suggest two neurotoxic endpoints in the brain of METH-exposed animals. Brain regions exhibiting DAT and 5-HTT deficits that co-localize with decreased VMAT-2 levels and glial cell activation may represent monoaminergic terminal degeneration. However, the DAT and 5-HTT deficits in brain regions lacking a deficit in VMAT-2 and glial cell activation may reflect drug-induced modulation of these plasma membrane proteins.

NMDAR-2A subunit protein expression is reduced in the hippocampus of rats exposed to Pb2+ during development.

Chronic exposure to lead (Pb2+) produces deficits of learning and memory in children and spatial learning deficits in developing rats. The N-methyl-D-aspartate receptor (NMDAR) has been identified as a principal target for Pb2+-induced neurotoxicity. Age-dependent changes in NMDAR subunit gene expression were observed in hippocampi of rats chronically exposed to Pb2+ during development [T.R. Guilarte, J.L. McGlothan, Hippocampal NMDA receptor mRNA undergoes subunit specific changes during developmental lead exposure, Brain Res. 790 (1998) 98-107]. These changes were present at blood Pb2+ levels ranging from 20-60 microg/dl. Littermates were used in the present study to determine whether the changes in gene expression were reflected in protein levels. NR1, NR2A, and NR2B subunit protein levels were measured in rat hippocampus and cortex at post-natal days (PND) 7, 14, 21, and 28 by Western blot and densitometric analysis. A treatment effect was apparent for NR2A subunit protein expression in the hippocampus (F1,28=10.224, p<0.01). NR2A subunit protein was reduced by 40%, 19%, and 27% from control levels in PND14, 21, and 28 Pb2+-exposed rats, respectively. Mean comparisons indicated that rats at PND14 exhibited the most significant reduction of NR2A (p<0.001). These data concur with our previous finding of reduced NR2A mRNA found in hippocampal pyramidal and granule cells of Pb2+-exposed rats. Pb2+ exposure during development had no effect on NR1 or NR2B subunit protein expression in the hippocampus at any age. No effect was observed on any subunit in the cortex at any age. The developmental profile of the NMDAR-2A subunit protein in the hippocampus is specifically changed by chronic exposure to Pb2+. These data suggest that composition of subunits comprising NMDAR may be altered in Pb2+-exposed rats.

Hippocampal expression of N-methyl-D-aspartate receptor (NMDAR1) subunit splice variant mRNA is altered by developmental exposure to Pb(2+).

N-methyl-D-aspartate receptors (NMDAR) play an important role in synaptic plasticity and brain development. We have previously shown that NR1-pan mRNA is significantly increased in the hippocampus of rats chronically exposed to low levels of lead (Pb(2+)) during development [T.R. Guilarte, J.L. McGlothan, Hippocampal NMDA receptor mRNA undergoes subunit specific changes during developmental lead exposure, Brain Res., 790 (1998) 98-107]. It is not known whether this Pb(2+)-induced increase in NR1-pan mRNA is associated with changes in specific splice isoforms. To study this effect, we used in situ hybridization of oligonucleotides to probe for the NR1-a, NR1-b, NR1-1, NR1-2, and NR1-4 isoforms which are most abundantly expressed in the rat hippocampus. Developmental exposure to increasing levels of Pb(2+) resulted in significant increases in NR1-a mRNA throughout the pyramidal and granule cell layers of the rat hippocampus at postnatal day 14 (PN14). NR1-b mRNA was increased in the pyramidal cell layer of Pb(2+)-exposed rats at PN21. Splicing of the C-terminus cassettes was also regulated by developmental exposure to Pb(2+). NR1-2 mRNA was increased in CA4 pyramidal cells and in dentate granule cells of PN21 Pb(2+)-exposed rats. Notably, expression of NR1-4 mRNA in CA3 pyramidal cells was increased in Pb(2+)-exposed rats at PN14 and decreased at PN21. No significant Pb(2+) effect was measured for NR1-1 mRNA expression. These data indicate that alternative splicing of the NR1 gene shows selective anatomical and temporal regulation by Pb(2+) in the developing rat hippocampus. This study provides further support to the hypothesis that NMDARs are important targets for Pb(2+)-induced neurotoxicity.

Determination of clinical accuracy and nocturnal blood pressure pattern by new portable device for monitoring indirect ambulatory blood pressure.

The accuracy and clinical application of a new portable device for measuring ambulatory blood pressure (BP) (ABPM 630, Nippon Colin, Nagoya, Japan) were assessed. The device uses a conventional arm cuff inflated by CO2 gas from a compact cartridge and is based on a cuff-oscillometric as well as a Korotkoff sound (microphone) technique. Blood pressure values obtained by ABPM 630 were compared with those measured by the auscultatory method. With the microphone method the mean differences from the auscultatory method were -0.28 +/- 6.15 mm Hg (mean +/- SD) for SBP and 0.96 +/- 6.28 mm Hg for DBP (n = 256), while for the cuff-oscillometric method the mean differences were -1.77 +/- 6.07 mm Hg for SBP and 3.06 +/- 6.87 mm Hg for DBP (n = 297). There was a highly significant correlation between BP values measured by the auscultatory method and ABPM 630. In 40 untreated subjects, 24 h BP was monitored simultaneously with the ABPM 630 and with a finger volume-oscillometric device (UBP-100, UEDA, Tokyo, Japan). The daytime average of SBP with the former (126 +/- 11.6 mm Hg) was almost the same as that with the latter (123 +/- 16.0 mm Hg), while the nighttime average in the former (117 +/- 9.7 mm Hg) was significantly higher than that in the latter (108 +/- 14.1 mm Hg, P less than .01). Only 4 out of 40 subjects experienced no sleep disturbance from the arm-cuff inflation. Five of the 40 subjects complained that their sleep was frequently interrupted by the arm-cuff inflation.(ABSTRACT TRUNCATED AT 250 WORDS)

Low level Pb(2+) exposure affects hippocampal protein kinase C gamma gene and protein expression in rats.

We examined the effect of chronic exposure to lead (Pb(2+)) on protein kinase C (PKC) in 50-day-old rat hippocampus. Cytosolic and membrane fractions of hippocampus from Pb(2+)-exposed rats showed reduced expression of PKC gamma protein. In contrast, a significant elevation of PKC gamma mRNA was observed in pyramidal and dentate granule cell layers. Protein expression of alpha, beta I, beta II and epsilon isoenzymes were unchanged in Pb(2+)-exposed rats, as was [(3)H]phorbol 12,13 dibutyrate (PDBu) binding in tissue slices. Differences were not observed in Ca(2+)-dependent or -independent PKC activity, or in PKC-specific back-phosphorylation of hippocampal homogenates from Pb(2+)-exposed rats. Reduced subcellular levels of PKC gamma in Pb(2+)-exposed rats suggest that signal transduction in the hippocampus may be selectively altered and may be important in manifesting Pb(2+)-induced impairments of synaptic plasticity, learning and memory.

Molecular changes in glutamatergic synapses induced by Pb2+: association with deficits of LTP and spatial learning.

What are the molecular bases for the neurotoxicity that occurs after developmental exposure to low levels of Pb2+, and are these effects persistent and detrimental in adults? Our inability to understand specific mechanisms behind Pb2+ neurotoxicity has long been one of many problem areas of this preventable childhood disease. The sensitivity of the developing brain to Pb2+-induced neurotoxicity is an outcome of the many unique characteristics that comprise the developing central nervous system. The developing brain can be exposed to significant concentrations of Pb2+ during vulnerable periods of development such as synapse formation, gene and protein expression, and other diverse molecular changes associated with these processes. Recently, changes in NMDA receptor subunits were identified in animals that showed cognitive deficits induced by exposure to Pb2+. This molecular association is important because it provides new evidence in the characterization of developmental Pb2+ neurotoxicity that supports physiological findings of impairments in synaptic plasticity and behavior. This review updates information from molecular studies that can be directly associated with impairments of behavior and synaptic plasticity, and outlines the functional consequences of molecular differences in Pb2+-exposed animals that illuminate potential mechanisms of Pb2+-induced neurotoxicity.

Squamous cell carcinoma of the breast. Report of a case diagnosed by fine needle aspiration cytology.

A 66-year-old woman presented with pure squamous cell carcinoma of the breast, a rare occurrence. The incidence of pure squamous cell carcinoma of the breast is lower than that of the mixed type. The preoperative diagnosis could be made by fine needle aspiration cytology. A modified radical mastectomy was performed. The patient was doing well, with no evidence of recurrence, 17 months after surgery.

[Efficacy of combination therapy consisting of cyclophosphamide, adriamycin, UFT and oophorectomy/tamoxifen for advanced or recurrent breast cancer].

Combination therapy consisting of cyclophosphamide (CPA), adriamycin (ADR), UFT and endocrine therapy of oophorectomy or tamoxifen (TAM) was given female patients with advanced or recurrent breast cancer. Premenopausal patients initially underwent oophorectomy, then were administered 300 mg/day of CPA and 30 mg/day of ADR intravenous injection every 2 weeks, and 300 mg/day of UFT orally every day. Postmenopausal patients, on the other hand, were administered the same three chemotherapeutic drugs and 30 mg/day of TAM orally every day instead of receiving castration. A total of 10 patients were registered, and nine of them were eligible. Premenopausal cases were six, and postmenopausal cases were three. The objective response rates were 50% (3/6) for premenopausal women and 33% (1/3) for postmenopausal women. Complete response was observed in one patient and partial response in three patients. The therapy was effective for lymph nodes (2/2), lung (3/4), breast (2/3), skin or subcutis (1/2), but it showed no effect on bone, pleural effusion or ascites. The overall 5-year survival rate was 53.3%. The main side effects of more than Grade 1 were leucopenia 33% (3/9), anorexia 22% (2/9) and malaise 22% (2/9). They were relatively mild for therapy involving ADR. This therapy was considered useful for advanced or recurrent breast cancer.

[Efficacy of Cepharanthin for preventing leukopenia and thrombocytopenia induced by chemotherapy in breast cancer patient--prospective randomized study].

A prospective randomized study was carried out to evaluate the efficacy of Cepharanthin (CEP) on leukocytopenia and thrombocytopenia during chemotherapy in breast cancer patients. The CEP group (51 patients) was administered CEP by 60 mg/day p.o.. The control group (55 patients) was not administered CEP in all the times. The rate of leukocytopenia was significantly lower (p less than 0.05) in the CEP group than in the control. But the recovery periods from nadir to normal range in WBC were not significantly different between the two groups. The average of nadir of WBC in the leukocytopenia patients was higher in the CEP group than in the control, but it was not significant. In MMVC group and MMC + TAM group, the rate of leukocytopenia was significantly lower in the CEP group than in the controls. The obvious efficacy of CEP for thrombocytopenia was not obtained in this study. We conclude that CEP showed an efficacy on preventing leukocytopenia induced by chemotherapy in breast cancer patients.

[The evaluation of pamidronate therapy for bone metastases from breast cancer].

We devised a method to evaluate comprehensively the therapy to alleviate the pain of bone metastases from breast cancer according to the three items of bone pain and effects of analgesia and radiology. In 12 patients, we evaluated the therapeutic effect of pamidronate as an alleviative treatment for the pain of bone metastases from breast cancer. Bone pain was evaluated on a 6-grade scale, as was use of analgesics. Improvement in bone pain, in addition to improvement in use of analgesia, was evaluated as markedly improved, improved, unchanged, aggravated, no pain or undeterminable. Radiological improvement in bone lesions was evaluated as markedly improved, improved, unchanged, aggravated or undeterminable. An overall evaluation was made by combining the above two. In this evaluation method, pamidronate therapy resulted in an evaluation of markedly improved in 2 patients, improved in 5, unchanged in 4 and aggravated in 1, demonstrating that the therapy was very useful as an alleviative treatment for the pain of bone metastases from breast cancer. The evaluation method, in which pain, a subjective complaint, is combined with use of analgesics, an objective factor, and to which radiological evaluation is added for further objectively, may in the future to be applicable for evaluation of various alleviative treatments of pain of bone metastases.

SLE-like and sicca symptoms in late component (C9) complement deficiency.

Hereditary deficiencies in early and late complement components are well known to predispose to SLE-like syndromes or recurrent infection. Hitherto reported C9 deficient cases have usually been healthy subjects, however, and it is not considered that C9 deficiency is associated with any specific disease. We describe a completely C9 deficient patient with possible Sjögren's syndrome and discuss the relationship.