Effect of OPC-8212 (2(1H)-quinolinone), a new inotropic agent, on myocardial energy metabolism in patients with coronary heart disease

We examined the effects of a new inotrope, OPC-8212 (OPC: 2(1H)-quinolinone), on coronary sinus flow (CSF), myocardial oxygen consumption, myocardial lactate extraction ratio (LER), cardiac index (CI) and pulmonary arterial diastolic pressure (PADP) in eleven patients with prior myocardial infarction. Measurements were taken before (control) and 8 hours after administration of OPC (480 mg, p.o.). A cardiac function curve was obtained in each stage with rapid intravenous administration of 500 ml of saline (loaded state) after baseline measurements. There was a significant increase in the cardiac index and decrease in the pulmonary arterial diastolic pressure in the loaded state after OPC. Thus the ventricular function curve was shifted to the left and showed a steep incline, indicating an increased inotropic state. On the other hand, myocardial oxygen consumption and myocardial lactate extraction ratio were unchanged. Thus we concluded that OPC improved cardiac performance without increasing myocardial oxygen consumption.     

Tc-99m tetrofosmin myocardial perfusion SPECT after dipyridamole combined with low-level exercise in the diagnosis of coronary artery disease

Tc-99m tetrofosmin is a lipophilic, cationic perfusion imaging agent that changes to Tl-201 in detecting coronary artery disease during exercise testing. The purpose of this study is to evaluate the usefulness of Tc-99m tetrofosmin dipyridamole stress imaging combined with low level exercise for the detection of coronary artery disease. We examined 42 patients and 10 normal volunteers who also underwent coronary angiography. A one-day protocol was used: in the stress study, 296 MBq of tetrofosmin was injected and in the rest study 888 MBq was injected. After intravenous administration of dipyridamole (0.142 mg/kg/min for 4 minutes), the patient was exercised on a bicycle ergometer for 3 min (25 Watts). Tetrofosmin was injected 2 minutes after dipyridamole infusion during the exercise. Single photon emission computed tomographic images were obtained 30 minutes after the tracer injection. Images were interpreted as abnormal in 36 of 42 patients with coronary artery disease, and normal in all of 10 normal volunteers. The overall sensitivity of detection of coronary artery disease was 83.3% and the normalcy rate was 100%. The diagnostic values for the detection of significant stenosis in the three major arteries were: LAD sensitivity 83%, specificity 92%; LCX sensitivity 47%, specificity 91%; RCA sensitivity 75%, specificity 83%. Of the 66 arteries with more than 50% stenosis, 48 arteries were correctly identified. Of the 36 with more than 70% stenosis, 31 were identified. Scintigraphic evidence of multivessel disease was found in only 9 patients (50%). A protocol of Tc-99m tetrofosmin SPECT combined with low level exercise after dipyridamole is therefore useful for the detection of the coronary artery disease.     

A case of middle-aged onset sialidosis type I]

We reported a patient with middle-aged onset sialidosis type I. A 52-year-old Japanese man was referred to our hospital because of dysarthria, involuntary movement of his extremities and gait disturbance since the age of 46 years. On admission, neurological examination revealed scanning speech, action myoclonus, cerebellar ataxia and cherry-red spots. Vacuolated lymphocytes were found in peripheral blood. Brain 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) showed decreased glucose metabolism in the cerebellum. Enzymological analysis using his skin fibroblasts revealed primary deficiency of sialidase activity. Sialidase gene analysis identified compound heterozygotes for base substitusions of 239T-to-C and 649G-to-A, which resulted in amino acid alterations of P80L and V217M, respectively. These mutations have been reported in Japanese sialidosis type II (P80L) and I (V217M). Further studies are required to reveal effects of gene mutations on residual enzyme activities and phenotypes.     

An autopsy case of Degos disease with neurological symptoms--neuropathological observations and increased platelet aggregation]

We reported clinical and neuropathological observations of a 41-year-old man with Degos disease. He first noted painless skin lesions over the upper extremities in January, 1982. Three years later he was diagnosed as Degos disease by skin biopsy, and treatment with aspirin was started. In September, 1985, he complained of paresthesia on his right arm, followed by a series of new neurological manifestations suggesting multifocal spinal cord lesions. On October 28, examination of admission showed papules with central umblication over the whole body except the head, face, palms, soles and scrotum. Neurological examination revealed no weakness, diminished right biceps reflex, exaggerated patellar reflexes and Achilles reflexes, left extensor plantar reflex, hypesthesia and hypalgesia to the level of Th8, mild left spastic gait, and retention of urine. In November, he had paraparesis, loss of vibration sense of lower extremities, hypesthesia and hypalgesia to the level of TH4, and weakness of right upper extremity. In December, he showed tetraplegia, left-sided facial palsy, and hypesthesia and hypalgesia to the level of C5. In January, 1986, he showed right facial palsy, left facial hypesthesia, pseudobulbar palsy. In February, he had bilateral abducens nerve palsy and hiccups. On February 18, he died of intracranial hemorrhages. He had episodic abdominal pain several times during admission. His condition deteriorated progressively in four months after the first manifestation of neurological symptoms, despite the therapy with heparin, urokinase, ticlopidine, dipyridamole, and prednisolone. Laboratory studies showed gradual increase of CSF proteins (from 156 mg/dl to 602 mg/dl) and extremely increased platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathogenesis of Mucocutaneous Lesions in Behçet's Disease

Behcet's disease (BD) is characterized by recurrent oral aphthae, skin lesions, eye lesions, and genital ulceration. To determine the pathogenesis of BD, we performed histological and immunohistochemical studies of these mucocutaneous lesions, an assay of neutrophil activity, and HLA typing. Dense dermal or subcutaneous infiltrations of polymorphonuclear cells (PMN) without leukocytoclastic vasculitis were found in 28 of 57 lesions. Immunohistochemically, deposits of C3 on the vessels were found in 12 of 31 lesions. Deposits of immunoglobulin were not found except for one of IgM. C3 deposits and PMN infiltrations were significantly related (p<0.05). PMN activity by polarization was enhanced; however, the results did not show a significant relationship with the PMN infiltrations or the C3 deposits. The incidence of HLA-B51 was significantly high in BD, but no significant relationship was found between HLA-B51 and the results of other examinations. These results suggest that the pathogenesis of BD lesions differs from that of collagen diseases and that C3 deposits on the vessels may play an important role in the development of mucocutaneous lesions where PMN have mainly infiltrated.     

Diversity in DNA rearrangements and in RNA expressions of immunoglobulin gene on common variable immunodeficiency.

Six heterogeneous common variable immunodeficiency (CVID) patients were analysed for germ-line DNA, DNA rearrangements, and RNA expressions of immunoglobulin (Ig) gene by Southern or northern blotting using appropriate probes. We detected no polymorphism in neutrophil DNA hybridized to a C mu and a C gamma probe. In three patients, both serum Ig and Ig-bearing cells were scarcely detected, and by northern hybridization methods, neither mu mRNA, gamma mRNA, alpha mRNA nor kappa mRNA was detected. However, one Epstein-Barr virus-transformed B lymphoblastoid cell line (LCL) of these three patients was different from the germ line in the region of JH, C gamma, and C kappa, and expressed mu mRNA at a higher level. The B cell defects of these three patients lay on the B cell maturation stage similar to X-linked agammaglobulinaemia (XLA). In two others among the six CVID patients, serum IgM and IgM-bearing cells were detected to a certain degree, and by northern hybridization, mu mRNA was detected at a lower level, but neither mu mRNA, alpha mRNA, nor kappa mRNA was detected. One LCL of these two patients could express mu mRNA at the normal level. In the last patient, the serum IgM was normal, serum IgG and IgA were somewhat low, Ig-bearing cells were normal, mu mRNA and kappa mRNA were detected at the normal level, and gamma mRNA and alpha mRNA were detected at a lower level. The defect of this patient affected the class switch stage. These results showed that primary B cell defects in CVID occurred at several B cell differentiation stages which could be classified by expression of the Ig gene, and at the degree of clonal diversity in the B cell repertoire. Furthermore, this study provides support for the idea that the CVID defect is related to a more generalized cellular function, such as regulating the proliferation and/or clonal expansion of cells of the B lymphoid lineage.