Infantile convulsions with mild gastroenteritis

The development of sensitive new molecular genetic techniques has led to the detection of rotavirus in cerebrospinal fluid, stools and throat swabs from patients with gastroenteritis with accompanying clinical symptoms similar to infantile benign convulsions. Small round structured virus (SRSV) has also been found in stools of patients with similar clinical symptoms by a new procedure. However, the mechanism by which these viral infections induce benign convulsions remains to be elucidated. The present paper reviews recent virological and clinical studies of seizures probably caused by gastroenteritis viruses including rotavirus, SRSV and other viruses.     

K201 Improves norepinephrine‐induced diastolic dysfunction with preserved ejection fraction

Heart failure with preserved ejection fraction differs from systolic heart failure in pathogenesis, underlying disease, and prognosis; however, the onset mechanism of this type of heart failure remains unknown and there is no proven therapy. Recently, we showed that norepinephrine (NE) under Ca²⁺ loading induces severe diastolic dysfunction without a significant change in the left ventricular ejection fraction (LVEF), that is, increased left ventricular end‐diastolic pressure (LVEDP), norepinephrine‐induced diastolic contracture (NEIDC), and diastolic opening of the aortic valve. In this study, the effects of two benzothiazepine derivatives, K201 (JTV519) and diltiazem, on diastolic dysfunction were examined using this model. K201 significantly suppressed the increase in LVEDP, reduced the incidence of NEIDC, and significantly improved the Ea wave and DCT in a dose‐dependent manner, as well as reducing pulmonary hemorrhage. In contrast, diltiazem did not improve diastolic dysfunction and the mortality in the diltiazem group was 57%, compared to 0% in the K201 group. These results suggest that reduction of intracellular Ca²⁺ alone does not inhibit diastolic heart failure; in contrast, blocking of α‐adrenoceptors and regulation of proteins such as troponin I via protein kinase C are required for treatment of diastolic heart failure. These results also suggest that K201 may be an agent for treatment of diastolic heart failure. Drug Dev. Res. 67:852–861, 2006. © 2007 Wiley‐Liss, Inc.     

Influence of thoracoabdominal movement on pulmonary function in patients with Parkinson's disease: comparison with healthy subjects

Patients with Parkinson's disease (PD) may develop pulmonary dysfunction, but the pathogenesis remains unclear. We investigated a correlation between thoracoabdominal movements and pulmonary function in seven patients with PD and 14 healthy controls. We measured vital capacity (VC) and forced vital capacity (FVC) using an autospirometer, and measured chest and abdominal movements using a respiratory inductance plethysmography by fixing transducers on the rib cage and umbilicus. Patients with PD had significantly decreased % VC (90.3 +/- 17.1 vs 105.8 +/- 13.9%), chest movement (271.3 +/- 79.6 vs. 375.2 +/- 126.7% VT) and abdominal movement (217.6 +/- 93.5 vs. 247.4 +/- 100.2% VT) with 100% VT being an average volume of chest and abdomen at rest during measurement of VC. Patients with PD also had significantly decreased % FVC (74.4 +/- 20.6 vs. 97.6 +/- 14.1%), chest movement (246.2 +/- 115.2 vs. 344.5 +/- 126.4% VT) and abdominal movement (160.3 +/- 105.6 vs 207.6 +/- 104.7% VT) with 100% VT being an average volume of chest and abdomen at rest during forced maximal inspiration. Based on the results, we conclude that a reduction of % VC in patients with PD correlated with chest movements, while a reduction of % FVC correlated with abdominal movement in patients with PD.     

Familial spinal arachnoiditis with secondary syringomyelia: clinical studies and MRI findings

We report the clinical and MRI findings of two patients with familial spinal arachnoiditis. Although their initial symptoms were various, they both showed spastic paraparesis and sensory disturbance below the thoracic level. Cytokines and WBC in the CSF were studied, but they were not elevated at all. The spinal magnetic resonance images of each showed extensive arachnoiditis and a cystic structure. The other impressive features included: (i) an enhancement within the thickened arachnoid and an adhesion between the spinal cord and the dura mater, (ii) deformation of the thoracic cord where the arachnoid adhered, and (iii) secondary syrinx formation. Laminectomy may have an adverse outcome for such patients.     

Liposteroid therapy for refractory seizures in children

Liposteroid is dexamethasone palmitate incorporated into liposomes and was developed as an anti-inflammatory drug for targeting therapy mainly for rheumatoid arthritis. Recently, it was reported that liposteroid might be effective for the treatment of West syndrome, with fewer side effects than those of corticotropin therapy. We describe three patients, a 2-month-old boy with early infantile epileptic encephalopathy, a 4-month-old girl with symptomatic West syndrome, and a 2-year-old girl with symptomatic localization-related epilepsy, whose refractory seizures were treated with liposteroid according to the original method reported by Yamamoto and colleagues in 1998. Uncontrollable seizures ceased completely in two patients and the seizure frequency decreased markedly in the other patient. Electroencephalograms revealed marked improvement in all patients. They showed no relapse of the seizures, and all showed no adverse effects except for mild brain shrinkage in one patient. Our experience with these three patients suggests that liposteroid therapy might be a new option for the treatment of refractory seizures in children, as well as for West syndrome.     

Lymph node metastases identified with mediastinoscopy in a patient with superficial carcinoma of the esophagus

Superficial esophageal cancers limited to the lamina propria are not associated with lymph node metastases. Mediastinoscopic transhiatal esophagectomy was planned in a patient with widespread superficial cancer of the midthoracic esophagus. Sampling of the upper mediastinal lymph nodes revealed metastases. The operation was converted to a transthoracic esophagectomy with radical lymphadenectomy. Histopathologic examination of the resection specimen showed three metastatic lymph nodes, despite local invasion limited to the lamina propria. This is the first report of a patient with superficial esophageal cancer and lymph node metastases.     

Cloning of the 5' upstream region of the rat p16 gene and its role in silencing.

Hypermethylation of the 5' upstream region (5' region) of the human p16(CDKN2A) (p16) gene is known to cause silencing, which is involved in a wide range of human cancers. For the rat p16 gene, its 5' region has not been cloned, and it is uncertain whether surrogate use of exon 1 alpha is adequate for analysis of p16 silencing. In this study, we observed that methylation analysis of exon 1 alpha gave false positive results in three samples of normal rat mammary epithelia and in two of six primary mammary carcinomas. Therefore, we determined the nucleotide sequence of the 5' region of the rat p16 gene. To confirm that methylation status of the 5' region is correlated with p16 expression, the methylation status was analyzed by bisulfite sequencing and methylation-specific PCR in three samples of normal mammary glands, six samples of mammary carcinomas and four cell lines. The 5' region was demethylated in all of the three normal and six carcinoma samples that fully expressed p16. On the other hand, the 5' region was highly methylated in the 3Y1 cell line, which lacked p16 expression, but without deletion. These results showed that the methylation status of the 5' region was more closely correlated with p16 expression than that of the exon 1 alpha and analysis of the methylation status is useful in examining p16 silencing in various rat tumors.     

A novel SOD1 gene mutation in familial ALS with low penetrance in females

We identified a novel missense mutation in the Cu/Zn superoxide dismutase gene in a family with amyotrophic lateral sclerosis (ALS). The mutation was a transition of T to C, resulting in a substitution of leucine 126 to serine in exon 5. The family had very unique clinical features of extremely mild severity only in the legs of two male patients with onset of 42 and 52 years old, and their mothers did not develop any symptom even after reaching the age of 80 and carrying the same mutation. The present study suggests that there are other factors that delay or prevent the disease.