A multicenter study of transient global amnesia for the better detection of magnetic resonance imaging abnormalities.

BACKGROUND AND PURPOSE: The detection rate of diffusion-weighted (DWI) hyperintense lesions varies widely in patients with transient global amnesia (TGA). The aim was to examine the association of hyperintense lesions on DWI magnetic resonance imaging (MRI) with patient characteristics, precipitating factors, clinical presentation and MRI settings in patients with TGA. METHODS: In this multicenter retrospective observational study, using the standardized diagnosis entry system of electronic health records of four tertiary medical centers in the Kansai district of Japan, TGA patients (n = 261) who underwent brain MRI within 28 days of onset were examined. When the onset time was unavailable, the discovery time was used. RESULTS: Diffusion-weighted hyperintense lesions were observed in 79 patients (30%). There were no significant differences in age, sex, vascular risk factors, precipitating factors or clinical presentation between patients with and without DWI lesions. The detection rate increased linearly 24 h after onset and then reached a plateau of 60%-80% by 84 h. After 84 h, the detection rate decreased rapidly. In a multivariate logistic regression model, MRI examination 24-84 h after onset (odds ratio 7.00, 95% confidence interval 3.50-13.99) and a thin-slice (≤3 mm) DWI sequence (odds ratio 7.59, 95% confidence interval 3.05-18.88) were independent predictors of DWI lesions. CONCLUSIONS: This study suggests that DWI hyperintense lesions in TGA are not associated with patient characteristics and clinical presentation. Brain MRI examination 24-84 h after onset and thin-slice DWI sequences enhance the detection of DWI lesions in TGA patients.

Predicting the Readmission and Mortality in Older Patients Hospitalized with Pneumonia with Preadmission Frailty.

BACKGROUND: In older people, frailty has been recognized as an important prognostic factor. However, only a few studies have focused on multidimensional frailty as a predictor of mortality and readmission among inpatients with pneumonia. OBJECTIVE: The present study aimed to assess the association between preadmission frailty and clinical outcomes after the hospitalization of older patients with pneumonia. DESIGN: Single-center, retrospective case-control study. SETTING: Acute phase hospital at Kobe, Japan. PARTICIPANTS: The present study included 654 consecutive older inpatients with pneumonia. MEASUREMENTS: Frailty status before admission was assessed using total Kihon Checklist (KCL) score, which has been used as a self-administered questionnaire to assess comprehensive frailty, including physical, social, and cognitive status. The primary outcome was a composited 6-month mortality and readmission after discharge. RESULTS: In total, 330 patients were analyzed (median age: 79 years, male: 70.4%, median total KCL score: 10 points), of which 68 were readmitted and 10 died within 6 months. After multivariate analysis, total KCL score was associated with a composited 6-month mortality and readmission (adjusted hazard ratio, 1.07; 95% confidence interval, 1.02-1.12; p = 0.006). The cutoff value for total KCL score determined by receiver operating characteristic curve analysis was 15 points (area under the curve = 0.610). The group with a total KCL score ≥ 15 points had significantly higher readmission or mortality rates than the groups with a total KCL score < 15 points (p < 0.001). CONCLUSIONS: Preadmission frailty status in older patients with pneumonia was an independent risk factor for readmission and survival after hospitalization.

The persistence of drug-induced fever by teicoplanin--a case report.

OBJECTIVE: It was reported that the drug-induced fever of teicoplanin tended to persist after cessation of treatment. It is considered that the long half-life of teicoplanin causes the phenomenon. However there was no detailed report regarding plasma concentration of teicoplanin during onset of drug induced-fever. Therefore we investigated the relation between persistence of drug-induced fever and plasma concentration of teicoplanin. CASE: A 38-year-old male patient on the Left Ventricular Assist System (LVAS) was treated with teicoplanin for methicillin-resistant Staphylococcus aureus (MRSA) and he experienced drug-induced fever. Plasma concentrations of teicoplanin were measured not only during the treatment with the drug but also after it was discontinued. As such, plasma concentration was measured even when the fever had subsided. RESULTS: On Day 9 of treatment, the dose was increased from 400 to 600 mg, but the patient had a fever of about 38 - 39 °C. When the treatment was discontinued, it took 9 days for the fever to subside to a temperature of about 37 °C. The half-life of elimination of teicoplanin in the elimination phase is about 108 h, which is long. The fever persisted until the plasma concentration decreased to below 10 µg/ml, which is the effective trough concentration, and subsided when the estimated blood concentration was 7.5 µg/ml. CONCLUSIONS: We suggest that there is the possibility that the drug-induced fever due to teicoplanin persisted until the plasma concentration had decreased adequately. Close monitoring of plasma concentration is necessary, particularly when teicoplanin clearance is decreased such as in patients with renal dysfunction.

Neuroleptic malignant syndrome with prolonged catatonia in a dopa-responsive dystonia patient.

The authors describe a patient with dopa-responsive dystonia who developed neuroleptic malignant syndrome with prolonged catatonia following treatment with neuroleptic agents. Use of these agents probably expanded the patient's neuronal dysfunction beyond the nigrostriatal system to involve multiple dopaminergic systems. Electroconvulsive treatment alleviated the prolonged catatonia.

Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms.

Nasu-Hakola disease (NHD) is an autosomal recessive disorder characterized by presenile dementia and bone cysts. Finnish patients revealed a large deletion in DAP12 gene encoding a key element for transducing activation signal. The authors examined six Japanese cases for DAP12 alleles. Five of the six had loss-of-function mutation, either a single-base deletion or a novel point mutation. The single patient without mutation normally expressed DAP12 protein. Japanese NHD has at least three genetic forms regarding DAP12.

Comparison of therapeutic efficacies of type A and F botulinum toxins for blepharospasm: a double-blind, controlled study.

Type F botulinum toxin can be used for treating patients with dystonia who become refractory to type A toxin injection due to antibody development. We compared the therapeutic efficacy of type F botulinum toxin to that of type A toxin in a self-controlled, double-blind clinical trial. In nine patients with blepharospasm, we injected type A toxin on one side and the same units of type F toxin on the other side. Although the onset of clinical effect, maximal benefit, and adverse reactions were similar between type A and F toxins, the duration of the clinical effect was significantly shorter on the side injected with type F toxin. Although type F toxin proved its promise as an alternative to type A toxin, its usefulness is limited by the shorter duration of action.

A comparison of endocrine and exocrine function after pancreatic fragment autotransplantation into splenic pulp, portal vein, and hepatic parenchyma.

Three sites were evaluated for potential pancreatic fragment autotransplantation. Both endocrine and exocrine functions were evaluated following autotransplantation into splenic pulp, portal vein, or hepatic parenchyma in 44 pancreatectomized dogs. Cholecystic bile amylase concentrations in the hepatic parenchyma group surviving more than 2 months were elevated significantly, and choledochal bile amylase concentrations increased markedly following pancreozymin-secretin injection. In contrast, bile amylase concentrations in dogs with intrasplenic or intraportal implants were low and did not respond to PS injection. Histologically pancreatic autografts in hepatic parenchyma revealed marked proliferation of exocrine tissue with abundant zymogen granules and reconstruction of the acinar lobules with a few islets. These acinar cells in the hepatic parenchyma were ultrastructurally normal. Transplant endocrine function, estimated by K values, was significantly better after splenic pulp and portal vein than after a hepatic parenchyma implantation, but no group improved during 1-year follow-up. Glucose-stimulated initial insulin responses were abnormally low in all recipients. Islet B cells lacked mature insulin granules, such as seen in normal resting B cells. This ultrastructural finding implies a persistent demand on the B cells and may explain the spontaneous recurrence of hyperglycemia and the diminished initial insulin response to a glucose load. This study indicates that euglycemic recipients of pancreatic fragment autotransplantation remain unstable and prediabetic.

Frequency of apoptosis relates inversely to invasiveness and metastatic activity in human colorectal cancer.

The frequency of apoptosis was determined in 102 cases of human colorectal cancer. The results were correlated with the frequency of cell proliferation and with clinicopathological characteristics such as degree of differentiation, invasiveness and metastasis. As a marker of apoptosis, intranuclear DNA strand breaks were localized with in situ nick translation (ISNT). As a marker of proliferation, proliferating cell nuclear antigen (PCNA) was localized immunohistochemically. The numbers of nuclei positive with ISNT and for PCNA per 1,000 nuclei on tissue sections were obtained. The labelling indices were compared with clinicopathological characteristics for each tumour. The ISNT labelling index of well differentiated colon carcinomas was higher than that of poorly differentiated carcinomas. Among similarly differentiated cancers, ISNT L.I. of colon carcinomas classified as Dukes A was higher than Dukes B/C, and L.I. of carcinomas which did not metastasize to lymph node or liver was higher than that of carcinomas which metastasized. The PCNA labelling index did not correlate with any of the clinicopathological characteristics or with the ISNT labelling index. The data suggest that apoptosis indices severe as a marker of tumour progression.

Expression of p53 protein in gastric carcinomas is not independently prognostic.

BACKGROUND: Biologic significance of p53 protein expression in gastric carcinomas is unclear. The relationship between p53 expression and survival after curative operations for gastric carcinoma was evaluated. METHODS: Paraffin-embedded specimens from 135 patients who underwent curative resection of gastric carcinoma were analyzed immunohistochemically for p53 expression. RESULTS: Immunoreactivity of p53 was found in 37 of 135 gastric tumors. Six of 48 early gastric carcinomas expressed focally scattered p53. Pattern of p53 expression in the majority of advanced carcinomas was diffuse. In univariate analyses a significant relationship with survival was found for tumor size (p < 0.01), depth of invasion (p < 0.01), nodal involvement (p < 0.01), and p53 expression (p < 0.01). Significant relationships were found between p53 expression and nodal involvement (p < 0.01) and depth of invasion (p < 0.01). A multivariate analysis revealed that the independent predictors of recurrence were nodal involvement (p = 0.009) and depth of invasion (p = 0.009). In a logistic multiple regression analysis p53 expression was not independently related to the parameters, which suggests an aggressive tumor. CONCLUSIONS: Our results suggest that p53 expression did not correlate with the aggressiveness of gastric carcinomas and failed to be an independent predictor of outcome.

erbB-2 expression in well-differentiated adenocarcinoma of the stomach predicts shorter survival after curative resection.

BACKGROUND: Correlation between erbB-2 expression, histologic type of gastric carcinoma, and survival after curative resection was evaluated. METHODS: Paraffin-embedded specimens from 120 patients who underwent curative resection of gastric carcinoma were analyzed immunohistochemically for the expression of erbB-2. RESULTS: Enhanced erbB-2 expression correlated with tumor stage and depth of invasion. Well-differentiated adenocarcinomas had a higher incidence of erbB-2 expression than did poorly differentiated carcinomas. Survival rates of 33 patients with erbB-2-positive carcinomas were significantly lower than those of 87 with erbB-2-negative carcinomas (p < 0.001). Survival rates of patients with well-differentiated adenocarcinomas that were erbB-2 positive were significantly lower than those that were erbB-2 negative (p < 0.001). However, the presence of erbB-2 was not associated with altered survival in 46 patients with poorly differentiated carcinomas. Multivariate analysis of all 120 patients revealed that independent predictors of recurrent disease include nodal involvement (p = 0.003) and erbB-2 expression (p = 0.0051). CONCLUSIONS: Our results suggest that erbB-2 expression is a new marker associated with poor prognosis in well-differentiated gastric adenocarcinomas.

High-frequency SEP components generated in the somatosensory cortex of the monkey.

To investigate the origin of high-frequency somatosensory evoked potential (SEP) components, we recorded median nerve SEPs from the scalp and the depth in six monkeys. Laminar field potentials were analyzed in area 3b (N10; corresponding to human N20) and area 1 (P12; corresponding to human P25). After digital filtering (300-900 Hz), 4-6 components were identified, and the 1st to 4th peaks in area 3b (7-11 ms in latency) and the 3rd to 5th in area 1 (9-13 ms) showed clear polarity reversals between the surface and the depth of the cortex. These results provide direct evidence for intracortical origin of early high-frequency components in area 3b and of late ones in area 1.

Pre-movement gating of short-latency somatosensory evoked potentials.

Somatosensory evoked potentials (SEPs) are reduced in amplitude during movement (gating). The mechanism involves central gating of afferent input and competition from other afferents activated by the movement. We distinguished these two by giving 11 normal subjects a warning sound followed 1 s later by an electric stimulus to the right median nerve at the wrist. The latter served both as a cue to start a finger movement and as stimulation to evoke SEPs. Gating effects were widespread in frontal (N30) and central (N60) areas, but were also seen, albeit to a lesser extent, in the recordings at P3 (P30). Since finger movement began after the stimulus, such gating must have been purely central in origin, presumably reflecting motor preparation.

Expression of Kirsten-ras p21 in gastric cancer correlates with tumor progression and is prognostic.

The purpose of this study was to determine the correlation between expression of ras oncoproteins and the tumor stage or outcome of patients with gastric carcinoma. After the specificity of each anti-ras monoclonal antibody was confirmed by protein immunoblot analysis, immunohistochemical assays for a common-ras antigen present in N-, Harvey- and Kirsten (K)-ras oncoproteins, as well as for K-ras specific antigen, were performed on paraffin-embedded carcinoma tissue from 110 patients who underwent curative resection. By Western blot analysis, there was more p21 in fresh cancer specimens than in normal specimens. K-ras expression distinguished advanced from early gastric carcinoma and correlated with depth of cancer invasion. Among the 110 patients, survival rates of those with carcinomas positive for the common-ras or K-ras antigens were significantly lower than of those with antigen-negative carcinomas (p < 0.05). In a multivariate analysis, nodal involvement (p = 0.002), serosal invasion (p = 0.012) and K-ras p21 expression (p = 0.044) were independently predictive of the recurrence. These results suggest that K-ras p21 is a useful marker of tumor progression and poor prognosis after curative resection.

Myoclonus in Alzheimer's disease.

Myoclonus was studied electrophysiologically in seven patients with clinically diagnosed Alzheimer's disease. There seem to be at least two physiological types of myoclonus in Alzheimer's disease. Cerebral cortical structures might participate in the generation of myoclonus in one type, while the other type is probably generated by subcortical structures.

Endocrine and exocrine function of pancreatic fragments autotransplanted into hepatic parenchyma.

We studied the use of hepatic parenchyma as a recipient site for pancreatic fragment transplantation. Endocrine and exocrine pancreatic functions were evaluated following pancreatic autotransplantation in 26 mongrel dogs that had undergone total pancreatectomy. The endocrine function of the pancreatic tissue transplanted to hepatic parenchyma was significantly inferior to that of normal controls. Cholecystic bile amylase concentrations were markedly elevated in six dogs that had been implanted with pancreatic fragments in their hepatic parenchyma and had survived more than 2 months. Also, choledochal bile amylase concentrations increased significantly following pancreozymin-secretion (PS) injection. In contrast, cholecystic bile amylase concentrations in normal dogs were low and choledochal bile amylase concentrations did not respond to a PS load. Histological examination of pancreatic autografts in hepatic parenchyma revealed marked proliferation of exocrine tissue with abundant zymogen granules and reconstruction of pancreatic lobules with a few islets.

An electrophysiological study of the corticospinal projections in amyotrophic lateral sclerosis.

OBJECTIVE: To elucidate the pattern of corticospinal tract involvement in patients with amyotrophic lateral sclerosis (ALS), we analyzed motor evoked potential (MEP) waveforms and their relationship to the behaviour of single motor units using the peristimulus time histogram (PSTH) technique. METHODS: Abnormality of the corticospinal pathways was studied in 35 ALS patients using MEPs. PSTHs were also constructed to assess the effect of magnetic cortical stimulation on the discharge pattern of a voluntarily activated motor unit. RESULTS: MEPs showed a complex waveform in 10 out of 18 (56%) ALS patients with upper motor neuron signs (UMN). PSTHs revealed double primary peaks (PPs), PP1 and PP2, in 6 out of 16 motor units (38%) in ALS with UMN, as compared to only 2 out of 16 (13%) motor units in multiple sclerosis or cerebrovascular disease with UMN. None of the patients with lower motor neuron diseases or ALS without UMN had these abnormalities. The late component of complex MEPs showed a good correlation to PP2 (P < 0.0001), both probably being mediated by relatively preserved slower conducting corticospinal volleys. CONCLUSIONS: These findings suggest preferential involvement of the fast conducting direct corticospinal tracts, sparing the slower or polysynaptic projections in ALS.

Cortical potentials associated with voluntary mandibular movements.

Movement-related cortical potentials (MRCPs) are negative potentials over the scalp, which gradually increase prior to voluntary movements, and might be applied to elucidate the cortical efferent function of the mandibular movements. We compared the MRCPs accompanying various mandibular movements to study the motor control mechanism underlying these movements. Electroencephalograms (EEGs) were recorded from 11 electrodes placed over the scalp (F3, Fz, F4, T3, C3, Cz, C4, T4, P3, Pz, and P4), according to the International 10-20 System, and electromyograms (EMGs) were obtained from surface electrodes over the masseter muscle and the anterior belly of the digastric muscle. Ten healthy subjects were requested to make brisk and self-paced mandibular movements in 4 different directions (mouth-opening and -closing, and left and right lateral movements). We obtained MRCPs by averaging the EEG, using the visually determined EMG onset as a trigger signal. In all the movements, a slowly increasing, bilaterally widespread negativity starting 1.5 to 2.0 sec before the EMG onset (Bereitschaftspotential, or BP proper) was observed, with the maximum over the vertex region. The negative slope (NS') occurred about 300 to 700 msec before the EMG onset. The cortical maps of BP/NS' (BP and NS' combined), immediately prior to the mouth-opening and closing, showed a symmetrical distribution, whereas that for the lateral movements showed a tendency of predominance over the hemisphere ipsilateral to the direction of the movement. BP/NS' amplitudes at the onset of movement differed significantly or tended to do so between open, close, and lateral movements, suggesting that MRCP recordings may thus provide a means to explore the role of the cerebral cortex in the control of mandibular movements.

Expression of epidermal growth factor receptor messenger RNA in human colorectal carcinomas assessed by non-radioactive in-situ hybridization.

No consensus as to the involvement of the epidermal growth factor receptor (EGF-R) in colorectal carcinomas has yet been attained, although they are assumed to play a role in the metastasis to lymph nodes and recurrence of breast carcinoma and bladder carcinoma invasion. Knowing that Dukes' classification of colorectal carcinoma is closely related to prognosis, we examined whether there is a correlation between Dukes' classification and the expression of EGF-R in colorectal carcinoma. If there is a positive correlation, the involvement of EGF-R in the processes may be assumed and the expression of EGF-R may be used as a marker of their prognosis. To this end, the expression of EGF-R mRNA and protein by non-radioactive in-situ hybridization and immunohistochemistry, respectively, were determined on histological preparations of formalin-fixed paraffin-embedded colorectal surgical specimens. In 30 cases of colorectal carcinoma examined, mRNA and/or protein was detected in 33% (two of six) of Dukes' A, in 40% (four of 10) of Dukes' B, in 36% (four of 11) of Dukes' C, in 33% (one of three) of Dukes' D and in 0% of normal colon epithelial cells. Thus, there was no positive correlation between the Dukes' classification and the expression of EGF-R. It is concluded that the expression of EGF-R in colorectal carcinoma is not a promising marker of prognosis. However, the role of EGF-R in EGF-R positive tumours remains to be examined.

Cortical distribution of Bereitschaftspotential and negative slope potential preceding mouth-opening movements in humans.

Cortical potentials associated with the voluntary movement of various body parts are known as movement-related cortical potentials, which allow evaluation of the cortical efferent function and other higher functions controlling voluntary movement. The cortical potentials have three main components: the Bereitschaftspotential (or 'readiness potential'), the negative slope and the motor potential. Here, the cortical potentials preceding mouth-opening movements were recorded to investigate which of these components could be observed. Electroencephalograms (EEGs) were recorded from 11 electrodes placed over the scalp (F3, Fz, F4, T3, C3, Cz, C4, T4, P3, Pz and P4) according to the international 10-20 system. Electromyograms (EMGs) were recorded from the anterior belly of the digastric and the masseter. The 10 healthy participants were requested to make brisk and self-paced mouth-opening movements. All data were digitized with a sampling frequency of 200 Hz and stored for off-line analysis. Movement-related cortical potentials were obtained by averaging the EEG, using the digastric EMG onset as a trigger signal. The Bereitschaftspotential was recorded as a gradually increasing, bilaterally widespread negativity starting 1.7 s (mean) +/-0.23 s (S.D.) before the onset of the opening movement. The amplitude, which was measured at movement onset, was maximum at Cz (3.8 +/- 1.3 microV). The negative slope was observed 500-600 ms before the movement onset, and the motor potential was not clearly identified, because of postmotion artefacts. The cortical maps of the Bereitschaftspotential and negative slope combined together before to the mouth opening showed a symmetrical distribution with a maximum at the vertex region. The study reveals that the Bereitschaftspotential and the negative slope, two components of the movement-related cortical potentials, can be observed preceding mouth-opening movements and are similar to those associated with other voluntary movements. Findings such as distribution, amplitude and onset of the potentials could provide important information for studying the cortical control of mandibular movements.