Increased expression and plasma levels of myeloperoxidase are closely related to the presence of angiographically-detected complex lesion morphology in unstable angina.

BACKGROUND: Myeloperoxidase (MPO) is a leucocyte enzyme that catalyses the formation of a number of reactive oxidant species. OBJECTIVE: The purpose of this study is to evaluate the relationship between angiographic coronary plaque morphology in patients with unstable angina pectoris (UAP) or stable angina pectoris (SAP) and MPO levels. PATIENTS AND DESIGN: Plasma MPO levels on admission were measured in 236 patients with UAP, 146 with SAP and 85 control subjects using an ELISA kit. The angiographic morphology of the culprit lesion was classified into two types, simple or complex, based on the Ambrose classification. In addition, 61 atherectomy specimens obtained from a different cohort of patients with UAP and SAP were studied immunohistochemically for MPO. RESULTS: Median (IQR) plasma MPO levels in patients with UAP with a complex lesion were significantly higher than in patients with a simple lesion (41.9 (21.7­73.7) ng/ml vs 20.5 (15.9­27.9) ng/ml, p<0.0001), but there was no significant difference between the two groups in patients with SAP. On multivariate analysis, raised plasma MPO levels and Braunwald class III were independent factors for angiographically-detected complex lesions (adjusted OR 12.49, 95% CI 3.24 to 48.17, p=0.0002). In the atherectomy specimens the number of MPO-positive cells in patients with UAP with complex lesions was significantly higher (p<0.0005) than in patients with simple lesions. Moreover, in this cohort, plasma MPO levels were positively correlated with the number of MPO-positive cells in atherectomy specimens (R=0.42, p=0.024). CONCLUSIONS: This study shows that increased expression and plasma MPO levels are closely related to the presence of angiographically-detected complex lesion morphology in patients with UAP.

Simultaneous production of sphingolipids and ethanol by Kluyveromyces thermotolerans.

Kluyveromyces thermotolerans strain NBRC 1674 was selected for the simultaneous production of sphingolipids and ethanol from beet molasses. The strain gradually synthesized ethanol with fermentation periods and attained a level slightly higher than that of the strain of Saccharomyces cerevisiae usually used for ethanol production. The sphingolipids accumulated in the cells were composed of almost equal amounts of free ceramides and glucosylceramides. The sphingoid bases and fatty acids of the two sphingolipids differed from each other and changed under aerobic and anaerobic growth conditions. Oxygen limitation may cause accumulation of sphinganine by inhibiting sphingolipid desaturases and enhance its proportion in both the sphingolipids.

[Combined operation for ischemic heart diseases and valvular heart diseases].

We performed combined operation for patients who have both ischemic heart disease and valvular heart disease in 21 cases from January 1991 to October 1999. This operation was 3.1% of 682 cases of coronary artery bypass grafting and 5.0% of 416 cases of operation for valvular heart disease during that period. The mean age of these patients was 67.9 +/- 9.1 years. The average number of grafts in the coronary artery bypass grafting was 1.5 +/- 0.6. Aortic valve replacement was performed in 6 cases, mitral valve replacement in 10 cases and mitral valve plasty in 5 cases. Together with this combined operation, ascending aorta and aortic arch replacement was done in 1 case and abdominal aortic replacement in 2 cases. Three patients died due to postoperative aortic rupture, cerebral infarction or excessive surgical intervention in ascending aorta and aortic arch replacement. Combined operation for ischemic heart diseases and valvular heart diseases can safely performed, but it appears necessary to pay attention to arteriosclerotic lesions.

[Double valve replacement without blood transfusion in a case complicated with liver cirrhosis and pancytopenia].

A 63-year-old woman complicated with liver cirrhosis and pancytopenia was admitted for aortic and mitral valve replacement. As laboratory findings at time of admission showed pancytopenia with Hb of 7.3 g/dl, WBC of 2,200/mm3, and platelet of 6.2 x 10(4)/mm3, splenectomy was first conducted and the blood cells and platelet increased in number. At 27 days after splenectomy, double vale replacement was performed without blood transfusion and her postoperative course was unevenfull. It is considered that preoperative splenectomy is useful in management of patients complicated with hypersplenism and pancytopenia.

Lung cancer associated with pulmonary bulla. case report and review of literature.

A few reports have suggested the possible association between lung cancer and bullous disease. We report a surgical case of lung adenocarcinoma located in close proximity to pulmonary bullae. A 48-year-old nonsmoker, asymptomatic male was found to have a pulmonary tumor mass and giant bulla in the right lung. Thoracotomy identified a tumor arising from a firm, scarred and contracted area close to the bulla wall. Based on this report and review of other cases in the literature, we emphasize the need for physicians to be aware of the potential development of lung cancer in patients with pulmonary bulla.

Benign asbestos pleural effusion associated with pulmonary aspergilloma.

A rare case of benign asbestos pleural effusion associated with aspergilloma is reported. A chest radiograph of a 75-year-old Japanese man who was admitted with right chest pain showed a right pleural effusion and nodular shadows in the right apex and left middle lung field. Thoracocentesis revealed an exudate with atypical mesothelial cells. An open lung biopsy showed aspergilloma in the right S2 area and no evidence of malignancy. Many reactive mesothelial cells were found in the pleura. A quantitative asbestos digestion study of the lung tissue biopsy showed high-grade asbestos exposure.

Effects of endoluminal stent-grafts on acute aortic dissection in dogs.

Acute aortic dissection is a life-threatening condition, and may be treated with aggressive hypotensive drug therapy, but emergency surgery is often necessary. We evaluated the effectiveness of stent-grafts for the treatment of acute aortic dissection. Aortic dissection was surgically created in the descending thoracic aorta in 20 adult mongrel dogs. A stent-graft was inserted in the entry position. The tested animals were divided into 4 groups based on re-entry type and blood pressure alteration rate (AR) after acute aortic dissection. After insertion of the stent, the following results were observed: a) AR improved; b) proximal descending aorta and superior mesenteric arterial flows increased; c) cardiac function improved; and d) the dissecting aortic diameter decreased in the presence of pressure gradient group. From these results, insertion of a stent-graft to treat acute aortic dissection was judged to be effective.

Effect of barrier opening on brain edema in human brain tumors.

Blood-brain barrier (BBB) opening was carried out in 10 patients with cerebral lesions, and the MRI findings were evaluated following the barrier opening. An intra-arterial injection of 10% glycerol (4 ml/kg, 1 approximately 2 ml/s) was given as a hyperosmotic solution. T2-weighted MRI was undertaken using a TOSHIBA 22A at 30 minutes after BBB opening. Barrier-opening MRI was performed 10 times in 10 patients, including 5 cases of glioblastoma multiforme, 2 cases of astrocytoma, 1 case of malignant lymphoma, 1 case of cerebral contusion and 1 case of neurinoma. The high-intensity area (HIA) was compared with that in MRI without barrier opening. Three types of changes of HIA in MRI were observed after BBB opening as follows. Type 1: Expansion of the HIA was noted in 4 of 5 cases of glioblastoma multiforme, the 1 case of malignant lymphoma and the 1 case of cerebral contusion. Type 2: Almost no change was observed in the 1 case of neuronoma. Type 3: A decrease in HIA was noted in the 2 cases of astrocytoma and in 1 case of glioblastoma multiforme. The MRI following BBB opening evidently showed 3 types of changes according to the degree of BBB disruption. Glioblastoma multiforme or contusion with a severely disrupted BBB revealed an increase in HIA following barrier opening. Benign posterior fossa neurinoma showed no change in HIA after barrier opening. Moderate malignant tumors exhibited a decrease in HIA on barrier-opening MRI. It was concluded that malignant tumors have a severely damaged BBB, which is readily disrupted by osmotic barrier opening.

Sequential change of brain edema by semiquantitative measurement on MRI in patients with hypertensive intracerebral hemorrhage.

The progression of brain edema in seven patients with hypertensive intracerebral hemorrhage (ICH) was evaluated. Five were of putaminal and two were of thalamic hemorrhage. The hematoma volume in the patients was 4 approximately 40 ml (18.9 +/- 8.0 ml). Sequential MRI (SE: 2000/40) was performed at one, two and four weeks after onset. The edema volume (EV) was calculated as 1/2.(long diameter).(short diameter).(thickness) of the high intensity area (HIA) on MRI. In comparison with the EV at one week after onset, the EV at two weeks was increased and the EV at four weeks returned to the same level of that at one week (132.3 +/- 26.1%, 100 +/- 10.6%, respectively). In contrast, the consciousness level and motor weakness of the patients had already improved at two weeks after onset. Our results demonstrate that progression of brain edema after small or medium size ICH may not bring about a deterioration of the clinical course. Moreover, progression of brain edema to the cerebral cortex and ventricle as indicated by MRI suggested an absorption pathway for the edema fluid, and implying that brain edema following ICH could play a part in the healing process after ICH.

A material-control single-case study of the efficacy of treatment for written and oral naming difficulties.

Twenty-two right-handed aphasics with written and/or oral naming difficulties were treated with a traditional language therapy: copying and repetition of words. The efficacy and maintainability of the treatment were evaluated using a variation of the single-case design, which was termed the material-control single-case design. Effectiveness of the treatment for written naming difficulty was demonstrated for 9 of 21 subjects in a first treatment and 3 of 14 subjects in a second treatment. Three of the 14 subjects benefitted overall from both treatments in written naming. In oral naming, 2 of 18 subjects responded well to the first treatment while 2 of 16 responded well to the second treatment. One of the 16 subjects showed benefits from both the first and second treatments in oral naming. Although written and oral naming disturbances were difficult to improve using ordinary language treatment, a small proportion of subjects clearly showed effectiveness of the therapy. Maintenance of the effects of treatment was observed in all of the improvers.

A critical appraisal of neuropsychological correlates of Japanese ideogram (kanji) and phonogram (kana) reading.

Owing to the Japanese language's unique writing system, which consists of phonograms and ideograms, reading impairments of Japanese brain-damaged patients have attracted the interest of many researchers. Past case reports as well as some widely accepted handbooks and textbooks have concluded that a specific aphasia type or lesion site is associated with a particular impairment pattern of phonograms and ideograms in reading. However, the methodology and analytical procedures in previous studies were inadequate for reliable generalizations to be made. First, the test materials were unspecified or inappropriate, or the number of test items was small. Secondly, the conclusions were presented without providing individual performance data to support them. Thirdly, in associating patterns of reading impairment with lesion sites, only single cases were reported. The present investigation was designed to overcome the omissions of previous studies, and examined the ability to read 46 single phonograms and 46 single ideograms aloud in four groups of sufficiently large numbers of patients; namely, seven pure alexics, 23 Broca aphasics, 13 Wernicke aphasics, and seven patients with alexia and agraphia. Ours are the first data to demonstrate unequivocally no consistent linkage between aphasia type and the patterns of impairment of phonogram and ideogram reading. The impairment patterns were not uniform across patients even in the same aphasia group. A majority of the cases in each group showed that phonograms and ideograms were unselectively impaired. However, ideogram reading was more difficult in three cases in the pure alexia and Broca aphasia groups, respectively, and in one case in the Wernicke aphasia group. Phonogram reading was more severely disturbed in four cases among the Broca aphasics and in one case among the patients with alexia with agraphia. An apparent variability of impairment patterns characterized the Broca aphasic group. These dyslexic patterns did not appear to correlate with the site and extent of lesions identified by computerized tomography scans. Past reports linking a particular impairment pattern of phonogram and ideogram reading and a specific lesion site were studies of single cases, and their conclusions seem oversimplified. While sensory and motor dysfunctions can usually be neuroanatomically localized in individuals, impairments of certain high cortical functions, such as the reading of phonograms and ideograms, may not be correlated with damage to definite neuroanatomical structures.

Reduced growth of Ehrlich ascites tumor cells in creatine depleted mice fed beta-guanidinopropionic acid.

The effect of implantation of Ehrlich ascites tumor (EAT) cells on creatine distribution was investigated. It was also studied how depletion of creatine by feeding creatine-analogue beta-guanidinopropionic acid (beta-GPA) affects the growth of EAT cells in mice. Enhanced mobilization of creatine from host tissues to EAT cells against a greater concentration gradient was observed. The creatine (but not creatinine) level in blood plasma was lowered to 22% of the normal value by beta-GPA feeding alone and assimilation of 14C-creatine into EAT cells was inhibited. The growth of EAT cells was significantly reduced and the duration of survival of mice after implantation of EAT cells was extended when the creatine concentration was decreased. A decrease in daily food consumption and the degree of muscle atrophy after implantation of EAT cells was less in beta-GPA than control groups. In the creatine-depleted mice, the rate of increase in total EAT cell number and the volume of abdominal ascites were approximately half of the control values, and more dead EAT cells were observed. These results suggest that supplementation of beta-GPA inhibits creatine transfer to EAT cells and reduces the growth of cancer cells.

[A case of neoplastic angioendotheliosis--serial study of magnetic resonance imaging].

The case of a 59-year-old man who was diagnosed as having neoplastic angioendotheliosis by biopsy of a small hemangioma on the skin is reported. The clinical features were characterized by hypersomnia, memory disturbance, disorientation to time and mild left hemiplegia including the face. Laboratory findings showed an elevated erythrocyte sedimentation rate, increased serum LDH, increased CSF protein and pleocytosis in the CSF. The CSF level of IgG was also elevated and was associated with the appearance of oligoclonal IgG bands. The biopsy specimen of the hemangioma on the skin revealed that some small vessels were packed with atypical mononuclear cells which were positive for anti-B cell antibody. Magnetic resonance imaging (MRI) of the brain detected multiple lesions located in the cerebellum, thalamus and caudate nucleus. The left paramedian thalamic lesion might be responsible for his characteristic mood and behavioral changes. The serial MRI study disclosed that some lesions progressively enlarged and duplicated in number. These findings might be typical for neoplastic angioendotheliosis, in which the rapidly proliferating cells occluded small vessels one after another in the central nervous system. The serial study of MRI may serve an important diagnostic purpose in this disease, although most patients with this disease, so far, have been diagnosed by autopsy.

Effect of glycerol on ischemic edema evaluated by somatosensory evoked potentials.

Glycerol is administered to reduce intracranial pressure by clinically enhancing cerebral edema. In this study, the effect of glycerol on ischemic edema was evaluated in 34 cerebral infarct patients by serial SEP. Evoked potentials were obtained by stimulating the hemiparetic median nerve 60 times with duration of 0.1 msec. N20 wave of SEP was analyzed by signal processor. SEP was monitored every 30 min for 3 hr after glycerol administration. Improvements of CCT, which means interpeak latency between N13 and N20, were observed in 14 patients. In seven patients, N20 waves were observed after IV administration of glycerol even though N20 waves were not observed before glycerol administration. The patients in acute stage or with the small infarction of basal ganglia showed these electrophysiological improvements. No CCT changes were observed in nine patients, and no N20 waves were obtained in two patients even after glycerol administration. In conclusion, electrophysiologically, glycerol effect on ischemic edema was well recognized in acute staged infarct patients and the patients with small infarction of basal ganglia.

Major prognostic factors of adult patients with advanced T-cell lymphoma/leukemia.

Eighty-one adult patients with advanced T-cell lymphoma/leukemia including 54 with adult T-cell leukemia/lymphoma (ATL), who were treated between 1981 and 1983 with vincristine, cyclophosphamide, prednisolone, and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M) in randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 39.5% and 19.4%, respectively, and 69% of 32 CR patients had relapses, indicating the need for development of new effective regimens for the disease. In a multiple logistic regression analysis, only three factors, leukemic manifestation, poor performance status (PS), and a high lactate dehydrogenase (LDH) level, were significantly associated with the poor response rate. In a Cox proportional hazards model analysis, shortened survival was again significantly associated with poor PS and a high LDH level, but not with a clinical diagnosis of ATL. The two factors, PS and LDH level, that were found to be significantly associated with both CR and survival rates, were used to construct a model containing six categories of patients at increasing risk for poor response and shortened survival. These categories divided the patients into three groups with respective CR and 4-year survival rates of 75% and 53% for low-risk, 45% and 15% for moderate-risk, and 15% and 0% for high-risk. The results indicate that PS and LDH levels were the most important in predicting the response and survival of an adult patient with advanced T-cell lymphoma/leukemia. The prognosis of patients with usual peripheral T-cell lymphoma, excluding ATL, was comparable with that of advanced B-cell lymphoma. These results have important implications for the design of new prospective therapeutic trials.

Major prognostic factors of adult patients with advanced B-cell lymphoma treated with vincristine, cyclophosphamide, prednisone and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M).

Eighty-two adult patients with advanced B-lymphoma, treated between 1981 and 1983 with VEPA (vincristine, cyclophosphamide, prednisolone and doxorubicin) or VEPA-M (VEPA plus methotrexate) in a prospective randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 74% and 45%, respectively. The relapse rate was 51%. Stage of disease only was negatively associated with the CR rate in a multivariate analysis. The primary extranodal tumor site other than upper gastrointestinal (GI) tract and high grade pathology were found to affect disease-free survival adversely in a Cox proportional hazards model. Poor performance status, advanced stage, primary extranodal tumor site other than upper GI tract, advanced age, high grade pathology and prior therapy by either surgery or radiation, were significantly associated with shortened survival in a Cox proportional hazards model. These results indicate advanced B-lymphoma in Japan to be generally similar to advanced non-Hodgkin's lymphoma in the West in terms of prognostic factor characteristics, but the importance of the primary site in predicting survival has not been reported in the West. Also, the lack of a survival plateau in patients with diffuse large cell lymphoma indicates more intensive chemotherapy regimens than VEPA or VEPA-M to be needed. It was also found that the significant prognostic factors in patients with advanced B-lymphoma were very different from those with T-lymphoma. The five factors: pathology, stage, primary site, age, prior therapy by surgery or radiation, for which the risk ratio was more than 2.3, were used to construct a model containing 23 categories of patients running an increasing risk of shortened survival; this divided patients into three groups. The CR and 4-year survival rates of low-, moderate- and high-risk groups were 90% and 74%, 74% and 58%, and 50% and 5%, respectively. The risk-grouping provides indications for determining optimal therapy for individual patients and the need for new therapeutic trials in patients at high risk.

Increase of plasma methionine-enkephalin levels in patients at the acute stage of cerebral infarction.

We investigated the participation of endogenous opioid peptide in cerebral ischaemia. In 13 patients with supratentorial infarction, the plasma immunoreactive methionine-enkephalin concentration at the acute stage (30.77 +/- 3.54 pg/ml) was significantly higher than that at the chronic stage (20.37 +/- 2.07 pg/ml) or that of the control subjects (19.64 +/- 1.71 pg/ml). However, it was unrelated to infarct size or patient severity. The increased methionine-enkephalin, which appears to originate from the sympatho-adrenal system or infarcted brain, may play a role in the evolution of cerebral ischaemia.

Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M.

One hundred sixty-three patients with advanced non-Hodgkin's lymphoma including adult T cell leukemia/lymphoma (ATL) were treated from 1981 to 1983 with VEPA (vincristine, cyclophosphamide, prednisolone, and doxorubicin) or VEPA-M (VEPA plus methotrexate) in randomized fashion after stratification by surface marker. The complete response (CR) rate and the 4-year survival rate of patients treated with VEPA-M was 62.2% and 36.9%, respectively, while for those treated with VEPA the rates were 51.9% and 26.6, respectively. The difference was not statistically significant, but pretreatment characteristics predictive for response and survival were interesting. Three factors, leukemic change, poor performance status (PS), and T cell marker, were negatively associated with both CR and survival rates, and high-grade pathology was adversely associated with survival rate in a multivariate analysis. These prognostic factors are somewhat different from those in Western lymphomas. This may be reflection of major differences in patients' characteristics between Japanese and Western lymphomas: in this study, there was a high incidence of T cell lymphoma/leukemia (50%) including ATL (33%), leukemic manifestation (34%), poor PS (34%), and a low incidence of follicular lymphoma (9%). The statistically significant three factors for both CR and survival rates were used to construct a model containing eight categories of patients at increasing risk for poor response and shortened survival. These categories were divided into four groups, with respective CR and 4-year survival rates of 91% and 73%, 67% and 35%, 27% and 7%, and 10% and 5%. Ninety-three patients in whom CR was induced by VEPA or VEPA-M therapy were evaluated for prognostic factors predictive for disease-free survival. A shorter period (less than 28 days) required to achieve CR, a clinical diagnosis of ATL, and a lower hemoglobin level were found to affect disease-free survival adversely. These results have important implications for both the design of prospective randomized therapeutic trials and the determination of optimal therapy for individual patients.

Electropalatographic analysis of apraxia of speech in a left hander and in a right hander.

Two cases with 'pure' apraxia of speech are reported. The articulatory disturbances were quite similar. One of the two cases was a left-handed male with a subcortical haemorrhage and the other a right-handed male with a cerebral infarct. The MRI and CT scans showed that the first case had a lesion that mainly involved the right precentral gyrus and its deep white matter, and that the second had a lesion mainly affecting the lower parts of the left precentral and postcentral gyri and their deep white matter. These findings and a literature review suggest that a corticosubcortical lesion of the lower part of the left precentral gyrus in most right handers and a lesion of the symmetric region in the right hemisphere in some left handers cause apraxia of speech. The omission errors for sounds articulated by the tongue and the hard palate were analysed using electropalatography, which records visually the dynamics of the palatolingual contact. The results demonstrated that there were three kinds of omission errors: true omissions (no palatolingual contact); omissions with incorrect contact (palatolingual contact for a different sound or undifferentiated sound); and omissions with correct contact (correct palatolingual contact for a target sound). The latter two types of omission error were observed for initial consonants and they were probably caused by a delay in air flow. The patients also showed a tendency to substitute one of the two consonants/t, t/for other sounds, which suggested that they had difficulty in the inhibition of tongue activity.