Timing of initiation of adjuvant chemotherapy for gastric cancer: A case-matched comparison study of laparoscopic vs. open surgery.

BACKGROUND: Laparoscopic gastrectomy (LG) is reported to be associated with faster recovery than open gastrectomy (OG); however, the influence of the surgical approach on initiation timing of adjuvant chemotherapy (AC) remains unclear. METHODS: This was a single-institutional retrospective observational study. Patients with pathological stage II/III gastric cancer undergoing LG with D2 lymphadenectomy (LG group: n = 74) were matched 1:1 with patients selected from 214 similar patients undergoing OG (OG group: n = 74), identically matching gender, age, pathological stage, and type of gastrectomy, and comparing AC initiation timing between the two groups. Factors associated with delayed initiation of AC were investigated in a multivariable analysis. RESULTS: AC was performed in 86.5% (LG) and 83.8% (OG) of patients (p = 0.64). The median time interval before AC was significantly shorter in the LG vs. OG group (5.7 vs. 6.6 weeks, respectively, p < 0.001), and significantly more patients received AC within 6 weeks (60.8% vs. 27.0%, p < 0.001). Independent factors associated with delayed initiation of AC (>6 weeks) were: morbidity (≥grade 3a; odds ratio (OR): 16.1, 95% confidence interval (CI): 1.86-143), open surgery (OR: 5.17, 95% CI: 2.50-13.1), and postoperative weight loss ≥ 8% (OR: 2.47, 95% CI: 1.07-5.71). CONCLUSIONS: LG may be associated with shorter intervals before AC. Postoperative morbidity should be reduced as much as possible.

Neurophysiological classification of myoclonus.

Myoclonus can be diagnosed and classified mainly based on clinical features. Neurophysiologic studies help confirm clinical diagnosis and classification, and understand underlying physiological mechanisms. The neurophysiologic classification of myoclonus is mainly based on surface EMG (individual EMG patterns, muscle spatial distribution and time sequence of muscle activation), EEG, EEG/EMG relationships (jerk-locked back-averaging, cortico-muscular coherence), somatosensory evoked potentials, and long-loop reflexes. Paired stimulation evoked response/long loop reflex and jerk-locked evoked responses evaluate the excitability changes of the primary somatosensory cortex. Transcranial magnetic stimulation can evaluate the excitability state of the primary motor cortex.

Effect of low-temperature degradation on the mechanical and microstructural properties of tooth-colored 3Y-TZP ceramics.

The aim of the present study was to evaluate the effects of low-temperature degradation (LTD) induced by autoclaving on the mechanical and microstructural properties of tooth-colored 3 mol% yttria-stabilized tetragonal zirconia polycrystals (3Y-TZP). In total, 162 disc-shaped 3Y-TZP specimens were prepared. Two-thirds of the specimens were shaded by either the infiltration or powder mixing methods while the remaining specimens were used without coloring. The specimens were autoclaved at 134 °C for 0, 10, and 100 h to induce LTD (n=18 for each group). Chemical compositions were analyzed with X-ray fluorescence spectroscopy. Biaxial flexural strength was measured using a piston-on-three-ball test. The surface fraction and penetration depth of the monoclinic phase were examined using X-ray diffraction and scanning electron microscopy, respectively. The tooth-colored 3Y-TZP specimens contained Fe2O3 and Er2O3 (infiltration technique), and Fe2O3 (powder mixing method) at concentrations of<0.5 wt%. The tooth-colored 3Y-TZP had higher strength than the non-colored material after 100 h of autoclaving. In terms of surface fraction and penetration depth, the generation of monoclinic phase was significantly lower in the tooth-colored 3Y-TZP than in the non-colored material. The tooth-colored 3Y-TZP possessed equivalent biaxial flexural strength to that of the non-colored material and higher resistance to LTD regardless of the coloring technique (infiltration technique or powder mixing method) when the coloring pigments were contained at concentrations used in the present study.

Expectation of pain enhances responses to nonpainful somatosensory stimulation in the anterior cingulate cortex and parietal operculum/posterior insula: an event-related functional magnetic resonance imaging study.

Although behavioral studies suggest that pain distress may alter the perception of somatic stimulation, neural correlates underlying such alteration remain to be clarified. The present study was aimed to test the hypothesis that expectation of pain might amplify brain responses to somatosensory stimulation in the anterior cingulate cortex (ACC) and the region including parietal operculum and posterior insula (PO/PI), both of which may play roles in regulating pain-dependent behavior. We compared brain responses with and subjective evaluation of physically identical nonpainful warm stimuli between two psychologically different contexts: one linked with pain expectation by presenting the nonpainful stimuli randomly intermixed with painful stimuli and the other without. By applying the event-related functional magnetic resonance imaging technique, brain responses to the stimuli were assessed with respect to signal changes and activated volume, setting regions of interest on activated clusters in ACC and bilateral PO/PI defined by painful stimuli. As a result, the uncertain expectation of painful stimulus enhanced transient brain responses to nonpainful stimulus in ACC and PO/PI. The enhanced responses were revealed as a higher intensity of signal change in ACC and larger volume of activated voxels in PO/PI. Behavioral measurements demonstrated that expectation of painful stimulus amplified perceived unpleasantness of innocuous stimulus. From these findings, it is suggested that ACC and PO/PI are involved in modulation of affective aspect of sensory perception by the uncertain expectation of painful stimulus.

Increased synchronization of cortical oscillatory activities between human supplementary motor and primary sensorimotor areas during voluntary movements.

In human, both primary and nonprimary motor areas are involved in the control of voluntary movements. However, the dynamics of functional coupling among different motor areas has not been fully clarified yet. Because it has been proposed that the functional coupling among cortical areas might be achieved by the synchronization of oscillatory activity, we investigated the electrocorticographic coherence between the supplementary motor and primary sensorimotor areas (SMA and S1-M1) by means of event-related partial coherence analysis in 11 intractable epilepsy patients. We found premovement increase of coherence between the SMA proper and S1-M1 at the frequency of 0-33 Hz and between the pre-SMA and S1-M1 at 0-18 Hz. Coherence between the SMA proper and M1 started to increase 0.9 sec before the movement onset and peaked 0.3 sec after the movement. There was no systematic difference within the SMA (SMA proper vs pre-SMA) or within the S1-M1, in terms of the time course as well as the peak value of coherence. The phase spectra revealed near-zero phase difference in 57% (20 of 35) of region pairs analyzed, and the remaining pairs showed inconsistent results. This increase of synchronization between multiple motor areas in the preparation and execution of voluntary movements may reflect the multiregional functional interactions in human motor behavior.

Neural mechanisms underlying the processing of Chinese words: an fMRI study.

The present study employed functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms underlying orthographic, phonological and semantic processing of single character Chinese words. Twelve right-handed native Chinese speakers participated in the study. Three fundamental linguistic tasks including orthographic judgment, phonological matching and semantic association task were used. Our results demonstrated robust activation in the left posterior inferior temporal cortex (BA 37) for all three tasks. While the phonological matching task produced left-lateralized activation in the inferior frontal and parietal regions, semantic association task showed considerable bilateral activation in the inferior frontal and occipito-parietal regions. Direct comparison between phonological matching and semantic association task yielded semantic related activation in the anterior portion of the left inferior frontal gyrus (BA 47) and the right inferior frontal region (Broca's homology; BA 45). Behaviorally, there was no difference in response time between phonological matching and semantic association task. Our findings suggested that differential neural pathways were involved in the processing of meaning and sound of single-character Chinese words. The present study provided systemic information of the neural substrates underlying the processing of different components of Chinese language.

Role of cerebral cortex in human postural control: an EEG study.

OBJECTIVE: It was our primary objective to provide evidence supporting the existence of neural detectors for postural instability that could trigger the compensatory adjustments to avoid falls. METHODS: Twelve young healthy subjects performed self-initiated oscillatory and discrete postural movements in the anterior-posterior (AP) directions with maximal range of motion predominantly at ankle joint. Movements were recorded by the system and included force plate and EMG, and EEG measures from 25 electrode sites. The center of pressure dynamics and stability index were calculated, and EEG potentials both in voltage and frequency domains were extracted by averaging and Morlet wavelet techniques, respectively. RESULTS: The initiation of self-paced postural movement was preceded by slow negative DC shift, similar to movement-related cortical potentials (MRCP) accompanying voluntary limb movement. A burst of gamma activity preceded the initiation of compensatory backward postural movement when balance was in danger. This was evident for both oscillatory and discrete AP postural movements. The spatial distribution of EEG patterns in postural actions approximated that previously observed during the postural perceptual tasks. CONCLUSIONS: The results suggest an important role of the higher cortical structures in regulation of posture equilibrium in dynamic stances. Postural reactions to prevent falls may be triggered by central command mechanisms identified by a burst of EEG gamma activity. SIGNIFICANCE: The results from this study contribute to our understanding of neurophysiological mechanisms underlying the cortical control of human upright posture in normal subjects.

Somatosensory conduction delay in central and peripheral nervous system of diabetic patients.

Fifty-four diabetic patients with or without clinical evidence of neuropathy and with no clinical evidence of CNS dysfunction were studied by somatosensory-evoked potentials after electrical stimulation of the median nerve at the wrist and recorded from the scalp electrode against a noncephalic reference. Peripheral conduction index, calculated as the distance from the wrist to the C7 spinous process divided by the P9 latency, was significantly decreased (P less than 0.01) in diabetic patients (69.81 +/- 6.47 m/s) compared with 28 age-matched nondiabetic subjects (76.85 +/- 5.65 m/s). The P11-P13 interpeak latency, representative of the transit time from the dorsal column at the level of the sensory input into the cervical cord to the brain stem along the somatosensory pathways (CCT1), and the P13-N19 interpeak latency, representative of the transit time from the brain stem to the somatosensory cortex (CCT2), were significantly increased in diabetic patients (CCT1, 2.51 +/- 0.63 ms; CCT2, 5.76 +/- 0.92 ms) compared with nondiabetic subjects (CCT1, 2.28 +/- 0.36 ms, P less than 0.05; CCT2, 5.18 +/- 0.51 ms, P less than 0.01). We conclude that, in diabetic patients, neurophysiological abnormalities may be present in two distinct parts of the CNS and the peripheral nervous system.

Decrease in cortical benzodiazepine receptors in symptomatic patients with leukoaraiosis: a positron emission tomography study.

BACKGROUND AND PURPOSE: [11C]flumazenil (FMZ), a ligand that selectively binds to the central benzodiazepine receptor in the neuronal membrane, is useful for evaluating neuronal viability in a positron emission tomography (PET) scan. Using this ligand, we investigated whether there was a correlation between neuronal integrity in various brain structures and dementia in patients with leukoaraiosis. METHODS: Twelve patients with extensive leukoaraiosis on magnetic resonance imaging were divided into groups of patients with or without dementia. Based on a 2-compartment, 2-parameter model that included metabolite-corrected arterial input and PET-measured cerebral radioactivity, the distribution volume of FMZ (FMZ-V(d)) was calculated in various regions of interest by nonlinear curve fitting. Additionally, tracer kinetic analysis was applied for voxel-by-voxel quantification of FMZ-V(d), and data analysis was performed by statistical parametric mapping. RESULTS: The presence of dementia was associated with a reduced FMZ-V(d) in widespread areas of the cerebral cortex, including the bilateral frontopolar and frontal/insular areas, the left temporo-occipital border areas, and the left marginal cortical areas. CONCLUSIONS: Differences in neuronal integrity in the cerebral cortex might determine whether patients with leukoaraiosis become symptomatic or not.

Minimal record of disability in multiple sclerosis--application to Japanese patients.

The Japanese version of Minimal Record of Disability in MS was applied to randomly selected Japanese MS cases in order to determine the applicability of the scales and also to get the general trends of the disabilities of Japanese MS. The scales did reflect impairment of functional systems, in which visual system was most severe. The average DSS was 4/10. Incapacity status or environment status were well correlated with impairment of pyramidal or bowel/bladder systems. They also correlated with DSS. Duration of the illness was correlated with the severity of impairment, disability or handicap. Accumulation of such a core data base may help in management of the MS problems in the world.

Brain perfusion SPECT with 99mTc-bicisate: comparison with PET measurement and linearization based on permeability-surface area product model.

To characterize a recently introduced cerebral perfusion tracer, 99mTc-bicisate, single photon emission computed tomography (SPECT) images of 99mTc-bicisate were compared with CBF images obtained by positron emission tomography (PET) using the 15O steady-state method in 10 cases of cerebrovascular disease and dementia. 99mTc-Bicisate SPECT and PET CBF images showed a similar distribution pattern except for two cases with subacute stroke, in which 99mTc-bicisate showed less uptake than CBF in the infarcted area where oxygen metabolism was severely diminished. Comparison of 99mTc-bicisate uptake and CBF in the other eight cases showed less contrast between high- and low-flow regions in 99mTc-bicisate SPECT. Although the SPECT count ratio of cerebral structures to cerebellum showed a good correlation with CBF ratio, it gradually deviated from the linear relationship in the high-flow range. Assuming this nonlinear relationship is due to the limited extraction of the tracer, we estimated the permeability-surface area product (PS) value by a nonlinear least-squares curve-fitting procedure. The correction of the nonlinear relationship using the estimated PS value and a table lookup method resulted in an excellent linear relationship between corrected SPECT counts and CBF.

Chronic cerebral hypoperfusion induces MMP-2 but not MMP-9 expression in the microglia and vascular endothelium of white matter.

White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, the authors examined the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the white matter in a rat model of chronic cerebral hypoperfusion. After bilateral clipping of the common carotid arteries, myelin staining revealed demyelinating changes in the optic tract and the corpus callosum on day 7. Zymographic analyses indicated an increase in the level of MMP-2, but not MMP-9, after the hypoperfusion. Immunohistochemical analyses revealed the presence (most abundantly on day 3) of MMP-2-expressing activated microglia in the optic tract and corpus callosum. In contrast, the capillary endothelial cells expressed MMP-2 later. IgM-immunoreactive glial cells were absent in the sham-operated animals, but were present in the hypoperfused animals by day 3, reflecting the disrupted blood-brain barrier. These findings suggest that the main sources of the elevated MMP-2 were the microglia and the endothelium, and that these cells may contribute to the remodeling of the white matter myelin and microvascular beds in chronic cerebral hypoperfusion.

Reduction of nerve growth factor level in the brain of genetically ataxic mice (weaver, reeler).

By a highly sensitive enzyme immunoassay we measured the level of nerve growth factor (NGF) in the cerebellum and cerebrum of the neurologically mutant mice, weaver, reeler and Purkinje cell degeneration (PCD). A significant decrease in NGF level was observed in both cerebellum and cerebrum of weaver and reeler mutants of either sex. However, there was no such difference between normals and mutants in the case of the PCD mice. These results show that weaver and reeler mice have abnormalities of NGF synthesis and/or degradation not only in the cerebellum but also in the cerebrum.

Amino acid sequence determination of the novel forms of Go alpha purified from bovine brain membranes.

Previously we have reported that there are at least four different forms of Go alpha in bovine brain membranes which can be distinguished by their elution profiles from Mono Q column and their immunological reactivities. The four alpha-subunits are referred to as alpha o1, alpha o2, alpha o3 and alpha o4 in their elution orders from the column. Partial amino acid sequences of the purified alpha o1 and alpha o2 were determined and compared with the predicted sequences of two classes of Go alpha cDNAs, termed Go alpha-1 and Go alpha-2. There were at least two unique fragments corresponding with the predicted amino acid sequence of the Go alpha-2 cDNA but different from that of the Go alpha-1 cDNA upon tryptic digestion of alpha o1- or alpha o2-subunit. The alpha o3- and alpha o4-subunits, but not alpha o1-and alpha o2-subunits, were recognized by an antibody raised against a unique amino acid sequence predicted from Go alpha-1 cDNA. These results suggest that alpha o1,2 subunits and alpha o3,4 subunits are encoded by Go alpha-2 cDNA and Go alpha-1 cDNA, respectively.

Characterization of four G0-type proteins purified from bovine brain membranes.

Recently we reported there were at least four types of G0 or G0-like proteins in bovine brain membranes based on their elution profiles from Mono Q columns and their immunological reactivities; one of the proteins was purified as an alpha-monomeric form, and the others as alpha beta gamma-trimers. The four proteins, of which alpha-subunits were confirmed to be a family of G0-type by an immunoblot analysis, were thus referred to as alpha (0)1, G(0)2, G(0)3 and G(0)4, respectively, in order of their elutions from the column. Immunostained peptide mappings arising from proteolytic digestions of the four alpha-subunits, together with their fragmentation patterns containing radiolabeled ADP-ribose that had been incorporated by pertussis toxin-catalyzed ADP-ribosylation, suggested that the four G0-alpha were classified into either of two groups such as alpha (0)1 and G(0)2-alpha, or G(0)3-alpha and G(0)4-alpha. The kinetic parameters of their GTPase activities, however, revealed that there were different properties between alpha (0)1 and G(0)2-alpha or G(0)3-alpha and G(0)4-alpha. Thus, the four G0-type proteins appeared to be different entities from one another.

Purification of GTP-binding proteins from bovine brain membranes. Identification of heterogeneity of the alpha-subunit of Go proteins.

Using high-resolution Mono Q column chromatography, we purified 6 distinct peaks of GTP-binding proteins from bovine brain membranes. Five of them consisted of 3 polypeptides with alpha beta gamma-subunits and served as the substrate of islet-activating protein (IAP), pertussis toxin. The other one was purified as alpha-subunit alone and was also ADP-ribosylated by IAP in the presence of beta gamma-subunits. When each alpha-subunit was characterized by immunoblot analysis using various antibodies with defined specificity, the two of them were identified as Gi-1 and Gi-2, and other 4 appeared to be Go or Go-like G proteins. The alpha-subunits of immunologically Go-like proteins were apparently distinguishable from one another on elution profiles from the Mono Q column. Thus, there was a heterogeneity of the alpha-subunit of Go in the brain membranes.

Reflex sympathetic dystrophy (causalgia) treatment with guanethidine.

Three cases of reflex sympathetic dystrophy (causalgia) were associated with cervical spondylosis. Two of them were related to sudden cervical trauma. Patients showed burning pain, hyperalgesia in a segmental distribution, and edema of the arms, hands, and fingers bilaterally. Oral administration of guanethidine sulfate was effective in all cases. Our results support the hypothesis that hypersensitivity to norepinephrine plays a role in reflex sympathetic dystrophy.

Oculomotor abnormalities in Parkinson's disease.

Ocular movement was studied in 19 patients with Parkinson's disease and in ten normal controls. Common abnormalities included "hypometric saccade" on the eye-tracking test and on command, "saccadic pursuit," and convergence paresis. Reaction time was longer in patients with Parkinson's disease than in controls for horizontal saccadic gaze, finger movements, and body movements. Maximal saccadic velocity of horizontal gaze was slower in patients with Parkinson's disease than in controls. Slowing of the horizontal saccadic movement correlated significantly with an increased reaction time of finger and body movements. Correlation of decreased saccadic velocity with increased reaction time of finger movement was found for the finger ipsilateral to the direction of horizontal gaze, but not for the contralateral finger. It is postulated from these facts that bradykinesia also exists in eye movements in Parkinson's disease.

Central vs peripheral nerve conduction. Before and after treatment of subacute combined degeneration.

Central and peripheral nerve conduction was studied in two patients with subacute combined degeneration by using the short-latency somatosensory evoked potentials and the peripheral nerve conduction study during treatment with cyanocobalamin. Before the treatment, somatosensory evoked potentials with median nerve stimulation were normal, but those with peroneal nerve stimulation revealed prolonged central conduction indicating dysfunction within the posterior column. Peripheral sensory and motor nerve action potentials were reduced with normal or slightly reduced conduction velocity. After treatment, marked shortening of the central conduction time (by 24% and 31%, respectively) was observed with mild or no recovery of peripheral nerve action potentials. These physiologic findings suggest that the main pathologic changes in the central nervous system may be demyelination in the posterior column in addition to axonal degeneration in the peripheral nerve. The former was responsive to treatment but the latter was poorly responsive to treatment. Sensory symptom in subacute combined degeneration appears to be, at least partially, attributed to the spinal cord lesion.

The coagulation-fibrinolysis system in patients with leukoaraiosis and Binswanger disease.

BACKGROUND: Hypercoagulability is observed in vascular dementia, including Binswanger disease. However, the correlation between hypercoagulability, leukoaraiosis, and dementia remains unclear. OBJECTIVE: To examine how activation of the coagulation fibrinolysis correlates with leukoaraiosis and dementia. PATIENTS AND METHODS: Thrombin-antithrombin complex (TAT), prothrombin fragment(1 + 2) (F1 + 2) and cross-linked D-dimer (XDP) were measured consecutively in 18 subjects without dementia and with leukoaraiosis, and in 29 subjects with subcortical vascular dementia and severe leukoaraiosis (Binswanger disease) at either stable or deteriorating stages. They were compared with 19 patients with old lacunar infarctions and 24 patients with other neurological diseases. We also examined the indices of cognitive impairment and brain atrophy. In each group, the ventricular area-cranial space area ratio was measured by an image analyzer. RESULTS: Patients with Binswanger disease who were exclusively at deteriorating stages showed increased TAT and XDP levels and an increased ventricular area-cranial space area ratio, as compared with the patients with other neurological diseases (P<.001). The index of cognitive impairment in patients at a deteriorating stage showed a decreasing trend vs that of patients in the stable stage. Among the variables that were significantly associated with a hypercoagulable condition (ie, age, scores on Mini-Mental State Examination or the Hasegawa Dementia Rating Scale, Revised [MMSE/HDRS], white matter lesions, ventricular area-cranial space area ratio, and C-reactive protein), age (odds ratio [OR], 2.82) and MMSE/HDSR scores (OR, 0.43) survived as predictors for coagulation activation, and C-reactive protein survived for fibrinolysis activation (OR, 4.63) in multivariate analysis. CONCLUSION: Hypercoagulability in a subgroup of patients with Binswanger disease and with more severe cognitive impairment and brain atrophy does not support a triggering role for a coagulation-fibrinolysis system, although it may contribute to worsening of neurological deficits.