Role of red blood cell deformation in toxicity of contrast media in cerebral angiography

The authors investigated the effect on the brain of red blood cells that had been modified by contrast media. Rat blood was mixed with an equivolume of contrast media, and up to 200 microL of the mixture was infused to the internal carotid artery of the rat. Evans blue was administered intravenously to assess the integrity of the blood-brain barrier (BBB). Immediately after the death of the animal, or 2.5 hours after the infusion, the brain was removed for evaluation of the degree of BBB destruction and edema. Extensive destruction of the BBB, cerebral edema, and death of the animals were induced by infusion of blood mixed with an ionic contrast medium, such as diatrizoate and iothalamate, which deformed red blood cells. Microscopic observation showed atrophy and necrosis of nerve cells and decomposition of nerve fibers in the affected area of the brain. Cerebral damage was not observed in rats injected with blood mixed with a nonionic contrast medium such as iopamidol, iopromide, or metrizamide, which had less effect on red blood cells. Cerebral damage also was observed in the rats injected with blood mixed with a hyperosmotic solution of mannitol, as well as washed red blood cells mixed with an ionic contrast medium. This study's results indicate that hyperosmotic ionic contrast media affect red blood cells and cause disturbance in cerebral circulation.     

Successful Treatment of Adult T-cell Leukemia/Lymphoma with MACOP-B,M-FEPA and VEPP-B Combination Chemotherapy

A 45-year-old man was referred to our department in March of 1989. Physical examination showed erythroderma, palmo-plantar hyperkeratosis, generalized lymphadenopathy, hepatosplenomegaly, and leukemic manifestation. The lymphocyte count in the peripheral blood before treatment was 1.7 × 10⁴ cells/mm³. Atypical lymphocytes such as flower cells and lobulated cells were seen in the peripheral blood. A sample excised from a lymph node showed immunoblastic, pleomorphic T cells by a modified classification scheme of the Working Formulation. A high level of serum LDH was detected (2.1 times the upper normal limit). Anti HTLV-1 antibody was also detected in the serum. The atypical lymphocytes were positive for CD3, CD4, CD5, CD7 and HLA-DR, and negative for CD8. Thus, the clinical, pathologic and immunologic features were those of typical acute-type ATL. The patient was treated with VEPA-M for three months starting in March of 1989. Because of poor response, the patient was then treated with MACOP-B, M-FEPA, and VEPP-B for about one year from June of 1989 and has been free of disease up to the time of writing, March of 1993.     

Low-level chemiluminescence and life span of Drosophila melanogaster.

Spontaneous photon emission (chemiluminescence, CL) as a monitor of free radical evolution in Drosophila melanogaster which had been maintained at 25 or 30 degrees C for 5 days after emergence was measured. When maintained at 30 degrees C the fly CL intensity was stronger than at 25 degrees C. Under the condition of the higher temperature, the fly life span was shorter (mean life span = 29 days at 30 degrees C and 63 days at 25 degrees C), and oxygen consumption (3.7 microliters/mg.h at 25 degrees C, 4.9 microliters/mg.h at 30 degrees C) and the mobility (movement distance = 25 mm/min at 25 degrees C, 700 mm/min at 30 degrees C) increased, together with augmentation of phospholipid hydroperoxide in the fly total lipids. The CL spontaneously emitted from fly homogenate was decreased by the free radical scavengers both in experiments in vivo and in vitro. The hypothesis is proposed that as the oxygen metabolism grows active, the chemiluminescent reactions that involve oxygen-dependent free radical metabolism, including membrane phospholipid hydroperoxidation, contribute to the acceleration of senescence of fly bodies.     

Clinical features of patients with obsessive-compulsive disorder showing different pharmacological responses]

BACKGROUND: Although selective serotonin reuptake inhibitors (SSRIs) are the mainstay of pharmacological treatment for obsessive-compulsive disorder (OCD), some OCD patients do not show improvement. Sometimes, the addition of a low-dose atypical antipsychotic, such as risperidone, or olanzapine, to ongoing SSRI treatment has been shown to be effective. However, there are patients who still show no response after trials with this augmentation therapy. In the present study, we examined the clinical features of OCD patients who showed different responses to pharmacological treatment. SUBJECTS AND METHOD: Fifty OCD patients were divided into three groups according to their pharmacological responses: responders to SSRI (group A: n= 25), responders to SSRI with an atypical antipsychotic (group B: n= 15), and non-responders to both SSRI and SSRI with an atypical antipsychotic (group C: n= 10). We examined the clinical features such as age, sex, age of onset, duration of illness, types of obsessive-compulsive symptoms, severity, improvement after treatment, insight into disease, depression, comorbidity, involving family members in compulsive or ritualistic behavior, and the level of social adaptation of each OCD group. RESULTS: Twenty five patients showed a good response to SSRI monotherapy, 15 showed a response to antipsychotic augmentation, and 10 were non-responders to both SSRI and SSRI with an atypical antipsychotic. Significantly lower insight levels were observed only in group B and higher depressive levels in group C. OCD patients who were refractory to SSRI monotherapy showed comorbidity at a significantly higher frequency. OCD patients in group A showed significantly greater improvement, and group B showed inferior social adaptation after treatment. There were no significant differences in age, sex, age of onset, duration of illness, severity, involving family members in compulsive or ritualistic behavior, and social adaptation before treatment in the three OCD groups. CONCLUSION: There were differences in the clinical features of OCD patients who showed different responses to pharmacological treatment. Our results suggest that OCD is clinically and biologically heterogeneous. It may be important to divide OCD patients into subgroups for future studies.     

Transient Brain Ischaemia Provokes Ca2+, PIP2 and Calpain Responses Prior to Delayed Neuronal Death in Monkeys

To clarify the mechanism of postischaemic delayed cornu Ammonis (CA)-1 neuronal death, we studied correlations among calpain activation and its subcellular localization, the immunoreactivity of phosphatidylinositol 4,5-bisphosphate (PIP₂) and Ca²⁺ mobilization in the monkey hippocampus by two independent experimental approaches: in vivo transient brain ischaemia and in vitro hypoxia-hypoglycaemia of hippocampal acute slices. The CA-1 sector undergoing 20 min of ischaemia in vivo showed microscopically a small number of neuronal deaths on day 1 and almost global neuronal loss on day 5 after ischaemia. Immediately after ischaemia, CA-1 neurons ultrastructurally showed vacuolation and/or disruption of the lysosomes. Western blotting using antibodies against inactivated or activated μ-calpain demonstrated μ-calpain activation specifically in the CA-1 sector immediately after ischaemia. This finding was confirmed in the perikarya of CA-1 neurons by immunohistochemistry. CA-1 neurons on day 1 showed sustained activation of μ-calpain, and increased immunostaining for inactivated and activated forms of μ- and m-calpains and for PIP₂. Activated μ-calpain and PIP₂ were found to be localized at the vacuolated lysosomal membrane or endoplasmic reticulum and mitochondrial membrane respectively, by immunoelectron microscopy. Calcium imaging data using hippocampal acute slices showed that hypoxia-hypoglycaemia in vitro provoked intense Ca²⁺ mobilization with increased PIP₂ immunostaining specifically in CA-1 neurons. These data suggest that transient brain ischaemia increases intracellular Ca²⁺ and PIP₂ breakdown, which will activate calpain proteolytic activity. Therefore, we suggest that activated calpain at the lysosomal membrane, with the possible release of biodegrading enzyme, will cause postischaemic CA-1 neuronal death.     

Effects of the synthetic proteinase inhibitor, FOY, on hypercoagulability after surgery for esophageal carcinoma

Hypercoagulability develops after surgery for esophageal carcinoma, and it related closely to postoperative complications. This study evaluated the effects of the synthetic proteinase inhibitor, Cabexate Mesilate (FOY), on this hypercoagulability. The subjects used were 25 patients with a mean age of 63 who had undergone surgery for esophageal carcinoma. Of these, eight patients (test group) received FOY (2,000 mg/day) for three to 23 days after surgery, but 17 (control group) did not. In the test group, FOY controlled aggregation and release of the platelets and minimized their exhaustion. FOY almost completely checked the abnormal increase in thrombin activity which might trigger the hypercoagulability. Also, FOY suppressed the fibrinolytic activity slightly. These results indicate that FOY is effective in controlling hypercoagulability after surgery for esophageal carcinoma and in suppressing activity of the proteinases that cause both blood coagulation and fibrinolysis.     

Sacrococcygeal teratoma of newborn infants; a report of two cases]

Two cases of sacrococcygeal teratoma in female infants are reported. Case 1. A newborn baby with a hemispheric mass on her hip underwent surgery 3 days after birth and the lesion proved to be an immature teratoma. The serum AFP level was very high but became normal one month after the operation. The child also had agenesis of the corpus callosum and arachnoid cysts in right middle fossa. She died after developing shunt infection. Case 2. A newborn baby with a mature teratoma was operated on the day following birth. The tumor was subtotally removed, and there has been no recurrence after 6 months. Sacrococcygeal teratoma in female infants is often associated with agenesis of the corpus callosum and arachnoid cysts. They tend to develop almost at the same time as the teratoma. It is often difficult to determine whether the infant should be treated by chemotherapy or not if the teratoma is immature, especially when it has been totally removed, the serum AFP is normal, and the tumor is pathologically of a low grade.