[Ventricular fibrillation or general seizure?]. / Kammerflimmern statt Krampfanfall.

HISTORY AND CLINICAL FINDINGS: A 78-year-old patient seemed to have recurrent seizures due to marginal hypoglycaemia. He was initially awake with stable circulation. Subsequently, he lost consciousness followed by extensie twitching arms of his arms and the upper part of his body. Thereafter, the patient was somnolent, but accessible. INVESTIGATIONS AND TREATMENT: Initially hypoglycemia was thought to have caused general seizures. But the ECG monitor showed repetitive ventricular fibrillation, which was terminated by a cardioverter-defibrillator that had been implanted 3 years previously because of dilatative cardiomyopathy. At admission to hospital, marked hypokalemia (1,8 mmol/l) was noted as the cause of ventricular fibrillation. After normalization of serum potassium no further events occurred. CONCLUSION: Disorders of consciousness always request an ECG for early diagnosis.

Electron transport in argon in crossed electric and magnetic fields

An investigation of electron transport in argon in the presence of crossed electric and magnetic fields is carried out over a wide range of values of electric and magnetic field strengths. Values of mean energy, ionization rate, drift velocity, and diffusion tensor are reported here. Two unexpected phenomena arise; for certain values of electric and magnetic field we find regions where the swarm mean energy decreases with increasing electric fields for a fixed magnetic field and regions where swarm mean energy increases with increasing magnetic field for a fixed electric field.

1H NMR spectroscopy studies of Huntington's disease: correlations with CAG repeat numbers.

Huntington's disease (HD) is the result of an expanded (CAG) repeat in a gene on chromosome 4. A consequence of the gene defect may be progressive impairment of energy metabolism. We previously showed increased occipital cortex lactate in HD using localized 1H spectroscopy. We have now extended these studies to show an almost threefold elevation in occipital cortex lactate in 31 HD patients as compared with 17 normal control subjects (p < 10(-11)). The spectra in three presymptomatic gene-positive patients were identical to normal control subjects in cortical regions, but three in eight showed elevated lactate in the striatum. Similar to recently reported increases in task-related activation of the striatum in the dominant hemisphere, we found that striatal lactate levels in HD patients were markedly asymmetric (higher on the left side). Markers of neuronal degeneration, decreased N-acetylaspartate (NAA)/creatine and increased choline/creatine levels, were symmetric. Both decreased NAA and increased lactate in the striatum significantly correlated with duration of symptoms. When divided by his or her age, an individual's striatal NAA loss and lactate increase were found to directly correlate with the subject's CAG repeat number, with correlation coefficients of 0.8 and 0.7, respectively. Similar correlations were noted between postmortem cell loss and age versus CAG repeat length. Together, these data provide further evidence for an interaction between neuronal activation and a defect in energy metabolism in HD that may extend to presymptomatic subjects.

[Brain structures of reading Japanese words with functional MRI].

This review examines recent progress in understanding mechanisms involved in language related brain functions using functional magnetic resonance imaging (fMRI). The main focus is to detect differences in reading processes between the ideogram (Japanese kanji) and the phonogram (Indo-European language or Japanese kana). Inferior temporal (IT) areas on the language dominant side are involved in reading both characters. A plasticity model is introduced to explain the different localizations that have been ascribed to kana or kanji, respectively. FMRI will be an important clinical application for the preoperative evaluation of patients with lesions adjacent to these areas in the near future. Activation studies involving visual imagery and other relevant clinical issues are also briefly reviewed.

Assessment of the pathological grade of astrocytic gliomas using an MRI score.

To evaluate the usefulness of an MRI score for identifying tumour tissue characteristics, 41 histologically verified supratentorial astrocytic gliomas, including 13 low-grade astrocytomas (LGA) 14 anaplastic astrocytomas (AA) and 14 glioblastoma multiformes (GBM), were examined with a 0.5T superconductive MR imager. Nine MRI criteria were used: heterogeneity (HET), cyst formation or necrosis (CN), haemorrhage (HEM), crossing the midline (CM), oedema or mass effect (EM), border definition (BD), flow void (FV), degree (CE-D) and heterogeneity (CE-HET) of contrast enhancement; Gd-enhanced T1-weighted images were obtained in 32 cases (10 LGA, 10 AA, and 12 GBM). Each of the criteria was scored and analysed statistically. The mean values of LGA, AA and GBM were 0.45 +/- 0.31, 1.18 +/- 0.20, and 1.47 +/- 0.22, respectively. The MRI score increased with the pathological grades (P < 0.01-0.001). LGA had significantly lower values than AA in five (HET, CN, EM, BD, CE-D) of the nine criteria (55.6%) and lower values than GBM in all except HEM (88.9%). Three criteria (33.3%): HET, CN, and FV were significantly higher in GBM than AA. CE-D, HET, EM, CN, and CE-HET proved to be related to the pathological grade by a multiple regression analysis (P < 0.001).

Effects of enalaprilat on circadian profiles in blood pressure and heart rate of spontaneously and transgenic hypertensive rats.

We investigated the dose-dependent cardiovascular effects of enalaprilat at different dosing times in two animal models of hypertension. Blood pressure (BP) and heart rate (HR) were measured telemetrically in 5 spontaneously hypertensive rats (SHR) and in 5 transgenic hypertensive rats (TGR) after intraperitoneal (i.p.) injection of enalaprilat either at 700 h or at 1900 h. In SHR, dosing of enalaprilat at the beginning of the resting period, i.e., at 700 h, significantly reduced BP but did not influence HR. After dosing at 1900 h, BP was unchanged, whereas HR increased, which might have resulted from reflexly increased sympathetic tone. In TGR, enalaprilat at either dosing time decreased BP dose dependently and to a higher extent than in SHR, but the effects were more pronounced after morning than after evening dosing. These findings demonstrate that in two animal models of hypertension the antihypertensive effects of enalaprilat depended on the time of drug dosing.

Astrocytic gliomas: MRI and pathological grade.

The relationship between MR configuration and pathological grade was studied in 41 histologically verified supratentorial astrocytic gliomas with a 0.5T superconductive MR system. The gliomas included 13 low-grade astrocytomas (LGAs), 14 anaplastic astrocytomas (AAs) and 14 glioblastoma multiformes (GBMs). MRI configurations were classified into nine criteria which were scored and statistically analyzed. The mean values of LGAs, AAs and GBMs were 0.45 +/- 0.31, 1.18 +/- 0.20 and 1.47 +/- 0.22. In each grade, MRI score increased as pathological grades increased (p < 0.01-0.001). LGAs had significantly lower values than AAs in five of the nine criteria (55.6%); heterogeneity, cyst or necrosis, edema or mass effect, border definition, and the degree of contrast enhancement, and lower values than GBMs in eight criteria (88.9%) except for hemorrhage. Three criteria (33.3%), heterogeneity, cyst or necrosis, and flow void sign were significantly higher in GBMs than AAs. The four variables, heterogeneity, cyst or necrosis, edema or mass effect and border definition, proved to be important factors related to the pathological grade in a multiple regression analysis.

Evaluation of MRI score in the differentiation between glioblastoma multiforme and metastatic adenocarcinoma of the brain.

The authors statistically analyzed the MR configurations of 14 glioblastoma multiformes (GBMs) and 15 metastatic adenocarcinomas (MACs) of the brain in order to distinguish these two histological types on MR images. MR configurations were classified and scored upon the 9 criteria of heterogeneity, cyst or necrosis, haemorrhage, crossing of the midline by the tumour, oedema or mass effect, border definition, flow void sign, degree and heterogeneity after contrast enhancement. The mean value of GBMs was 1.47 +/- 0.22, and that of MACs was 0.91 +/- 0.37 (P < 0.001). GBMs had significantly higher values in five out of the nine criteria: border definition, heterogeneity, crossing of the midline of the tumour, flow void sign, and degree of the contrast enhancement (P < 0.001-0.05). Border definition was the best criterion for distinguishing two histological types. Six cases of MACs displayed hypo-intense lesions on T2 weighted images in contrast to GBMs which showed hyperintense lesions in all cases. In 4 out of the 6 MACs which were shown as hyperintensities on T2 weighted images, a hypo-intense peritumoural rim was noticed between the tumour parenchyma and the surrounding oedema. These data strongly suggest that GBMs and MACs can be distinguished on MR image by using MRI score.

Configurational MR characteristics of metastatic brain tumors.

Magnetic resonance (MR) characteristics of metastatic brain tumors (MBTs) were studied using 15 cases (13 males and 2 females whose ages ranged from 32-78 yr, with the mean age of 57.8 yr; 12 adenocarcinomas, 2 squamous-cell carcinomas, 2 large-cell carcinomas). Nine cases showed hypointensities and five showed isointensities on T1-weighted images. Six cases showed markedly hypo- or hypointensities, two showed isointensities, and six showed markedly hyper- or hyperintensities on T2-weighted images. One case was markedly hyperintense on both T1- and T2-weighted images. The decrease of the signal intensity on the T2-weighted image was the main MR characteristic. A hypointense peritumoral rim was seen in four of the six hyperintense tumors on T2-weighted images. There was no correlation between the signal intensity and the histological classification.

Inhibitory effect of fibronectin and its recombinant polypeptides on the adhesion of metastatic melanoma cells to laminin.

We have utilized recombinant fibronectin fragments with cell-binding domain (C-274), heparin-binding domain (H-271) or CS1 peptide in type III connecting segment (IIICS) and their fusion polypeptides such as CH-296 (containing C-274, H-271 and CS1), CH-271 (containing C-274 and H-271) and C-CS1 (containing C-274 and CS1) to investigate the mechanism of the fibronectin-mediated inhibitory effect on tumor cell adhesion to laminin as well as fibronectin. These fragments retained cell adhesion-promoting and/or heparin-binding properties when they were immobilized on a surface. Pretreatment of tumor cells with CH-296 or CH-271 suppressed cell adhesion to both laminin and fibronectin. H-271 at the high concentration of 500 micrograms/ml slightly inhibited cell adhesion to laminin (but not to fibronectin), whereas C-274, C-CS1 or a mixture of C-274, H-271 and CS1 (similar molar ratio to CH-296) inhibited cell adhesion to fibronectin but not to laminin. On the other hand, tumor cell adhesion to laminin-substrate was also inhibited by heparin or heparan sulfate, which were able to bind to laminin, suggesting that heparin-like molecules on the cell surface may be included among the laminin receptors. These results indicated that the co-presence of cell- and heparin-binding domains of fibronectin may be required for the fibronectin-mediated inhibitory effect on tumor cell adhesion to laminin, and that the interaction of the heparin-binding domain of fibronectin with the cell surface leads to the inhibition of the cell adhesion to laminin.

Recombinant fusion polypeptide with cell- and heparin-binding domains of fibronectin inhibits liver metastasis of L5178Y-ML25 lymphoma cells.

We have investigated the effect of recombinant polypeptides with cell-binding domain (C-274) or with heparin-binding domain (H-271) and their fusion polypeptide (CH-271) on liver metastasis of murine lymphoid tumor. The polypeptides containing heparin-binding domain, H-271 and CH-271, were able to inhibit liver metastasis when co-injected i.v. with L5178Y-ML25 T-lymphoma cells, while C-274 with cell-binding domain showed much weaker antimetastatic activity. Treatment with H-271 or CH-271 substantially prolonged the survival time of mice injected i.v. with L5178Y-ML25 cells. CH-271, containing cell- and heparin-binding domains, was more antimetastatic than H-271. The reason why CH-271 was more effective in inhibiting liver metastasis than H-271 can not be explained in terms of a difference in the stability in the circulation or in the molecular size of the polypeptide. The polypeptides used in this study did not affect the tumor cell growth or viability in vitro. CH-271 was found to be still active in inhibiting liver metastasis even when natural killer cells or macrophages were removed from this system. Furthermore, multiple administrations of CH-271 after tumor implantation effectively inhibited liver metastasis and enhanced the survival rate as compared with H-271, C-274 and untreated control. Thus, the fusion of H-271 with C-274 (i.e. CH-271) augments the antimetastatic property of H-271, possibly through the interaction between tumor cells and the heparin-binding domain of fibronectin.

Inhibitory effect of antimetastatic fusion polypeptide of human fibronectin on tumor cell adhesion to extracellular matrices.

We investigated the inhibitory mechanism of liver metastasis by using recombinant fragments with cell- and/or heparin-binding domains (C-274, H-271 or the fusion fragment CH-271). Intravenous co-injection of L5178Y-ML25 cells with CH-271 was more effective for the inhibition of liver metastasis than C-274, H-271 or C-274 + H-271. Reduction of the arrest and retention of the radiolabeled tumor cells in the liver of mice was found when CH-271 was co-injected with tumor cells. L5178Y-ML25 cells adhered both concentration- and time-dependently to the substrates precoated with fibronectin, laminin and reconstituted basement membrane, Matrigel. The tumor cell adhesions to the substrates were inhibited in the presence of CH-271. The tumor cell interaction with CH-271-substrate was inhibited by heparin, and monoclonal antibodies (IST-1 or IST-2) against the heparin-binding domain of fibronectin. However, monoclonal antibodies against the cell-binding domain failed to block the interaction. Similarly, CH-271-mediated antimetastatic activity was also inhibited by the treatment of CH-271 with IST-1 before the co-injection with tumor cells, whereas monoclonal antibody against the cell-binding domain had no effect. Thus, the antimetastatic effect of CH-271 fusion fragment on liver metastasis of L5178Y-ML25 cells may be partly due to interference with the adhesive interaction of tumor cells with extracellular matrix or basement membrane components by a heparin-binding domain-dependent mechanism.

Inhibition of tumor-induced angiogenesis by sulfated chitin derivatives.

The effect of antimetastatic sulfated chitin derivatives (SCM-chitin III) on angiogenesis induced by B16-BL6 cells was examined in syngeneic mice. SCM-chitin III caused a marked decrease of the number of vessels toward tumor mass (angiogenic response) without affecting the tumor cell growth when coinjected with tumor cells (on day 0), or injected into tumor site on day 1 or 3 after tumor inoculation. In contrast, carboxymethyl chitin as well as heparin had no effect. Invasion of endothelial cells through reconstituted basement membrane (Matrigel) toward tumor-conditioned media was significantly inhibited by SCM-chitin III in a Transwell chamber assay. SCM-chitin III also inhibited the haptotactic migration of endothelial cells to fibronectin-substrate, but did not inhibit the chemotactic activity in tumor conditioned media in vitro. SCM-chitin III did not directly affect the viability and the growth of tumor cells and endothelial cells in vitro. These results suggest that inhibition of lung tumor metastasis by SCM-chitin III may in part be due to the inhibition of tumor-associated angiogenesis.

Inhibition of lung metastasis by synthetic and recombinant fragments of human fibronectin with functional domains.

We have investigated the antimetastatic effect of synthetic or recombinant peptides containing the functional domains of fibronectin on experimental and spontaneous lung metastases of murine tumor cells. CS1 peptide which is present within type III homology connecting segment (IIICS) as well as C-274 (cell-binding domain) were able to inhibit experimental lung metastasis when co-injected intravenously (iv) with B16-BL6 melanoma cells, while H-271 (heparin-binding domain) could not. In the spontaneous metastasis model, multiple iv administrations of CS1 or C-274 after surgical excision of primary tumors caused a significant reduction of metastatic colonies in the lung. Both CS1 and C-274 significantly inhibited cell adhesion and migration to fibronectin-coated substrates when added freely in solution. CS1 peptide also inhibited the cell adhesion and migration to laminin-coated substrates, but C-274 did not. H-271 did not have any inhibitory effect on cell adhesion or migration to either of the substrates. Similarly, CS1 inhibited tumor invasion to both Matrigel/fibronectin- and Matrigel/laminin-coated filters, whereas C-274 inhibited the invasion to only Matrigel/fibronectin-coated filter. These results indicate that CS1 peptide of fibronectin, lacking the Arg-Gly-Asp-containing domain, actively inhibits tumor metastases in spontaneous and experimental metastasis models. The use of such a peptide might offer a promising therapeutic approach for combatting or preventing cancer metastasis.