High-dose chemotherapy and autologous peripheral blood stem cell transplantation for treatment of unspecified peripheral T-cell lymphoma presented with hepatosplenomegaly and hypercytokinemia syndrome: report of three cases.

We report here three cases of peripheral T-cell lymphoma unspecified (PTCL-US), which presented with bone marrow infiltration and hepatosplenomegaly and were successfully treated with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (auto-PBSCT). The patients were all characterized by cytokine-induced symptoms such as fever, anasarca, cytopenia, poor general condition, and disseminated intravascular coagulation syndrome. Laboratory data showed extremely high levels of soluble interleukin-2 receptor, beta(2)-microglobulin, and ferritin. All three patients were negative for anti-adult T-cell leukemia antibody. In one patient, hemophagocytosis was revealed by a histological examination of the bone marrow. The International Prognostic Index was high for all three patients, and they all achieved complete remission after the intensive chemotherapy for remission induction. During complete remission, they were treated with HDCT [modified interleukin-converting enzyme regimen] followed by auto-PBSCT. The recovery of hematopoiesis after auto-PBSCT was prompt and sustained engraftment was obtained. No serious adverse effects other than myelosuppression were noted. One patient died due to cerebrovascular disease without relapse 18 months after auto-PBSCT. The other two patients are still alive and have not suffered from relapse. Our observations suggest that auto-PBSCT following HDCT may be an effective and safe therapeutic modality for high-risk PTCL-US patients characterized by hepatosplenomegaly and cytokine-induced syndrome.

[Hemodynamic effects of STA-MCA anastomosis on patients with occlusion of the main cerebral artery].

PURPOSE: We studied cerebral circulation in patients with occlusion of the main cerebral artery and investigated the efficacy of STA-MCA anastomosis. PATIENTS AND METHODS: Thirty-six patients with occlusion of the main cerebral artery were studied. Twenty-three patients had occlusion of the internal carotid artery and 13 had occlusion of the middle cerebral artery. The mean age was 62 years. Cerebral blood flow (CBF) was measured in all patients and cerebrovascular reactivity (CVR) was examined in 11 patients by xenon enhanced CT. Intraoperatively, cortical arterial pressure and anastomotic flow were measured. RESULTS: There was no perioperative mortality or morbidity. There was no ipsilateral stroke recurrence during the follow-up period averaging 35.1 months. Patency of the anastomosis was verified in 91% of the patients by magnetic resonance angiography. Twenty-three (64%) patients showed decreased CBF before the operation and 57% of these patients showed improvement to the normal range after STA-MCA anastomosis. All of the eight patients with decreased CVR showed improvement after the operation. Anastomotic flow correlated significantly with the cortical arterial pressure. CONCLUSION: STA-MCA anastomosis could improve cerebral circulation of patients with low CBF or low CVR due to occlusion of the main cerebral arterial. It was concluded that STA-MCA anastomosis may contribute to the reduction of stroke recurrence, if perioperative complications are reduced.

Preparation of 4'-substituted thymidines by substitution of the thymidine 5'-esters.

tert-Butyl thymidylate 3 was prepared from thymidine 1 in six steps and 67% overall yield. When the lithium trianion of 3 (prepared by treatment of 3 with excess LDA and then excess tert-butyllithum) is reacted with electrophiles, trapping occurs stereoselectively from either the alpha- or beta-face depending on the electrophile (Scheme 1). Deuterioacetic acid in deuteriomethanol affords mainly the alpha-deuterated product (4a/4b = 2.4:1) while all other electrophiles, e.g., phenylselenenyl chloride, allyl bromide, and N-fluorobenzenesulfonimide (NFSI), give predominately (or completely) the products of attack from the beta-face (5bcd/4bcd = 3.7:1 to 100:0). The structures of the products were determined by coupling constant analysis of both the initial compounds and the diols 6bcd prepared by ester reduction and by formation of the acetonides 7bc. The methyl ester of the 3'-epimer of thymidylic acid 9 was also prepared from thymidine 1 in nine steps and 74% overall yield. When the lithium trianion of 9 (prepared by treatment of 9 with excess LDA and then excess tert-butyllithum) is reacted with electrophiles, trapping also occurs stereoselectively with attack on either the alpha- or beta-face depending on the electrophile (Scheme 2). Again, deuterioacetic acid in deuteriomethanol affords mainly the beta-deuterated product (11a/10a = 1.6:1) while all other electrophiles, e.g., phenylselenenyl chloride, methyl iodide, allyl bromide, and NFSI, gave predominately (or completely) the product of attack from the alpha-face (8.7:1 to 100: 0). Again, the structures of the products were determined by coupling constant analysis of both the initial compounds, and the diols 12b-e were prepared by reduction of the ester and by formation of the acetonides 13bcd. A rationale has been developed using molecular mechanics calculations to explain the diastereoselectivity that involves staggered axial attack on the sp(2) carbon opposite to the pseudoaxial alkoxy group in the most stable half-chair conformation of the enolates, as shown in Schemes 3-5.

[Macroscopic and pathohistological investigation of endarterial plaque after intraoperative balloon dilatation of the carotid artery during carotid endarterectomy].

Twelve patients associated with stenosis of the extracranial carotid artery underwent intraluminal balloon dilatation during carotid endarterectomy (CEA). There were 11 men and 1 woman, and age ranged from 56 to 73 years old. The rate of stenosis, shown by angiography, in each patient was from 60 to 85% in width. After securing carotid blood flow by a T-shaped shunt tube, a balloon catheter was inserted from the exposed common carotid artery into the internal carotid artery. The balloon was inflated three or four times with 2.5-3.5 atm. for 30-40 seconds. Immediately after balloon dilatation, endoscopic investigation was performed (Wolf; hard type endoscope, 2.7 mm diameter). Then CEA was performed using the usual procedure. The removed endarterial plaque was investigated pathohistologically. In macroscopic and endoscopic findings, there were 6 patients with mural thrombosis, 4 patients with laceration of the intima, and one patient with outflow of atheroma from the intima. Only 3 patients had increase in lumen after balloon dilatation. In pathohistological appearance, all patients had a moderate degree of fibrosis, calcification, and atheroma in the cross section of the plaque. Ten patients had intramural hemorrhage. Three typical patients were revealed by the use of angiographical, ultrasonographical, endoscopic, and pathohistological presentation. Case 10 showed laceration of the intima by balloon dilatation, and had moderate increase in lumen size macroscopically and endoscopically. There were moderate cases of fibrosis, calcification, atheroma, and intramural hemorrhage. Dilatation of the lumen seemed to be accomplished by a decrease in thickness of the atheroma and intramural hemorrhage. Case 8 demonstrated an increase in lumen size, but also laceration of the intima and outflow of atheroma from the arterial wall. There were much atheroma and large intramural hemorrhage in the intima, which might become a source of enbolism. Case 7 revealed no laceration of the intima and no increase in lumen size. Preoperative ultrasonography showed hyperechoic finding and postoperative pathohistological findings showed severe fibrosis and calcification, which were thought to have interrupted balloon dilatation. There have been small numbers of reports about pathohistological presentation after percutaneous transluminal angioplasty (PTA), because it is very difficult to take a specimen after PTA. In this report we were able to present the necessity of preoperative investigations by angiography, ultrasonography, and 3D-CT.

Essential oil constituents from Japanese and Indian Curcuma aromatica rhizomes.

The chemical compositions of the essential oils from rhizomes of Curcuma aromatica cultivated in Japan and India were analyzed by GC and GC/MS. These oils were extremely different. The major constituents in both oils from Japanese samples were curdione, germacrone, 1,8-cineole, (45,5S)-germacrone-4,5-epoxide, beta-elemene, and linalool, whereas those in the oil from Indian were beta-curcumene, ar-curcumene, xanthorrhizol, germacrone, camphor, and curzerenone.

[Angiographical evaluation of extracranial carotid artery: comparison between Japanese and Hungarian].

We investigated the cervical level of carotid bifurcation, diameter of common carotid artery (CCA) and internal carotid artery (ICA) in 147 Japanese patients (150 arteries, range of age 31-79) and in 490 Hungarian patients (517 arteries, range of age 12-77). The cervical level of carotid bifurcation was determined by comparison with cervical vertebra. The carotid bifurcation of Japanese was most frequent at the lower part of 3rd cervical vertebra but in Hungarian the bifurcation was most frequent at the middle part of 4th cervical vertebra. Japanese carotid bifurcation was high-positioned compared with Hungarian. The mean CCA diameter in Japanese was 7.47 mm in male and 7.07 mm in female, in Hungarian 9.24 mm in male and 7.80 mm in female. The mean ICA diameter in Japanese was 4.96 mm in male and 4.83 mm in female, in Hungarian 8.56 mm in male and 7.66 mm in female. CCA and ICA diameter were larger in male than in female. The diameter of CCA had a significantly positive correlation with age (p < 0.002) but ICA had no similar correlation.

Characteristics of IgA anti-HIV antibodies in plasma from patients with HIV infection.

The concentration of total IgA and the specificity and molecular size of IgA anti-human immunodeficiency virus (HIV) type-1 antibodies in plasma obtained from individuals at different stages of HIV infection were analyzed. The concentration of total IgA in the plasma was not decreased even in the late stage of HIV infection, in contrast with those of total IgG and IgM. The IgA anti-HIV antibodies differed to the IgG anti-HIV antibodies in their specificity as determined by Western blotting. The IgA antibodies mainly bind to Env glycoproteins. The IgA anti-HIV antibodies in plasma were detected between IgG and IgM by gel filtration, suggesting the presence of polymeric IgA anti-HIV antibodies. These results indicate that the production of non-specific IgA in plasma is enhanced by unknown mechanisms in every stages of HIV infection, and suggest that IgA anti-HIV antibodies in plasma which are possibly polymeric and have unique specificity may play an important role in HIV infection.

[Pharmacokinetic and clinical evaluation of cefozopran in premature and newborn patients].

Cefozopran (SCE-2787, CZOP), which is already on the market with a variety of approved indications in infectious diseases for adult patients, was administered to premature and newborn patients to evaluate the pharmacokinetics and the clinical efficacy. 1. Pharmacokinetics CZOP was intravenously administered at doses of 10.0 mg/kg, 21.4 mg/kg and 40.0 mg/kg to premature and newborn patients, and the blood concentrations and urinary excretion rate were examined. The blood CZOP concentrations were 31.7 and 65.5 micrograms/ml at 30 minutes after administration of 10.0 mg/kg and 40.0 mg/kg, respectively. The elimination half life was 1.78 hours and 2.31 hours, and the urinary recovery was 110.7% and 53.7% within 6 hours after administration, respectively. In the patient given 21.4 mg/kg, the blood CZOP concentration was 36.4 mg/kg at 1 an hour after administration and the elimination half life was 3.97 hours. The urinary recovery was 29.6% within 5 hours after administration. 2. Clinical results The clinical efficacy was evaluated in 19 patients and judged "good" or better in 13 of them with the efficacy rate or 68.4%. The bacteriological response was evaluated in 10 patients from whom Gram-positive cocci of S. aureus (6 strains), S. pneumoniae (1 strain) and E. faecalis (1 strain) and Gram-negative bacilli of H. influenzae (2 strains) and E. coli (2 strains) were isolated as possible causative organisms. With exception of 1 strain each of S aureus and H influenzae, which were not tested after the treatment with CZOP, all of these strains were found to be eradicated. 3. Adverse drug reactions (ADRs) of signs and symptoms and abnormal alterations of laboratory test values. Safety evaluation was made in 24 patients. ADRs of signs and symptoms were recognized in none of them. As abnormal alterations of laboratory test values, increased eosinophils in 3 patients, elevated GOT in one and elevated GPT in one were recognized. These results indicate that CZOP is a drug useful for treatment of infections in premature and newborn patients.

[Isolation and analysis of amino acid sequence of V3 region of HIV-1 from patients with HIV-infection in Hiroshima].

Isolation of HIV-1 was tried in PBMCs separated from 27 blood samples which were sent to Hiroshima Prefectural Institute for Health & Environment Science for anti-HIV antibody-test. 18 samples were positive for HIV-isolation (4 samples were Rapid/High type, 12 samples were Slow/Low type and 2 samples were intermediate). Compared with clinical stages of patients, samples from patients in CDC-II were 64% (14/22) positive and those in CDC-IV were 100% (3/ 3) positive in HIV-isolation. Improvement of the methods is to be required to isolate HIV from the samples of patient in the latent phase. Removal of CD8 positive cells from PBMCs of patients did not affect the efficiency of HIV-isolation by our methods. Three parts in amino acid sequence of V3 region in proviruses were different between Rapid/High type isolated and Slow/Low type isolates. The difference of amino acid may be related to the different phenotypes of the two viruses.

[Usefulness of reaction times in high-cortical recognition tasks].

We compared reaction times for high-cortical recognition tasks with kana-searching test in a group of 46 normal individuals aged 21 to 83 who gain a full score in Mini-Mental State. The following tasks of reaction time were used; simple reaction time (SRT), choice reaction time (CRT), memory scanning time (MST), and visual searching time (VST). The results were consistent and demonstrated that mean reaction time of 46 individuals increased in difficult tasks such as MST or VST. All reaction times increased depending on aging, which became longer in difficult tasks. Score of kana-searching test was correlated with MST and VST, but did not correlate with SRT and CRT. These findings suggest that reaction times may be useful for mass-screening of high-cortical functions in different ages as well as the kana-searching test.

[Morphological differences in carotid angiograms and their relation to age]. / Carotis angiogramokon mért alaki eltérések és azok összefüggése az életkorral.

The level of carotid bifurcation, frequency of the kinking of the internal carotid artery, correlation between the diameter of carotid arteries and the age of the Hungarians was examined. The cervical level of carotid bifurcation, diameter of extracranial carotid arteries, frequency of kinking of internal carotid arteries were measured on conventional carotid angiograms in 490 Hungarian patients (517 arteries, age range 12-77 yr). The cervical level of the carotid bifurcation was determined by comparison with cervical vertebra. The most frequent level of carotid bifurcation was found at the middle part of 4th cervical vertebra. The position shifted higher with ageing. The mean common carotid artery diameter was 9.24 +/- 1.58 mm in males and 7.80 +/- 1.10 mm in females. The mean internal carotid artery diameter was 8.56 +/- 1.84 in males and 7.66 +/- 1.39 in females. The mean external carotid artery diameter was 5.53 +/- 1.11 mm in males and 4.76 +/- 0.91 in females. The diameter of the common carotid artery has a significantly positive correlation with age (p < 0.05) but internal carotid artery and external carotid artery had no similar correlation. The kinking of internal carotid artery was observed frequently in patients who had higher level of carotid bifurcation.

Remarkable acceleration for the deamination of carbocyclic purine nucleosides by adenosine deaminase under high-pressure.

Deamination of an anti-HIV carbocyclic adenine nucleoside, 9-[c-4,t-5-bis(hydroxymethyl)cyclopent-2-en-r-1-yl]-9H-adenine [(+/-)-BCA] and (+/-)-diamino-carbovir by adenosine deaminase under high-pressure (4 kbar) was carried out. Deamination of the former gave the corresponding (-)-hypoxanthine derivative whereas that of the latter produced (-)-carbovir having anti-HIV activity. The enantiomeric excess (e.e.) of both products was nearly 100%.

Resolution of 9-(c-4,t-5-bishydroxymethylcyclopent-2-en-r-1-yl)-9H-adenine and selective inhibition of human immunodeficiency virus by the (-) enantiomer.

Two enantiomers of 9-(c-4,t-5-bishydroxymethylcyclopent-2-en-r-1-yl)-9H- adenine (BCA) which showed a potent and selective anti-HIV effects have been synthesized and evaluated against human immunodeficiency virus type 1. The result demonstrated that the potent-HIV activity of racemic BCA is expressed solely by the (-) isomer.

[Cerebral vasospasm after subarachnoid hemorrhage, and inhibitory effect of nicardipine investigated by means of transcranial Doppler ultrasonography].

Cerebral vasospasm is a major complication associated with subarachnoid hemorrhage (SAH). However, real-time evaluation of vasospasm is very difficult via angiography, CT scan, and cerebral blood flow. In this study, for the evaluation of the arterial narrowing, the flow velocity in the middle cerebral artery (MCAFV) was measured with transcranial Doppler ultrasonography (TCD) in 41 patients with ruptured cerebral aneurysms which were repaired surgically within 48 hours after SAH. MCAFV was measured daily until the 25th day after onset. All patients underwent CT scan, angiography, and neurological assessments upon admission. To clarify the morphological changes of the cerebral vessels due to SAH, angiography was performed again about 10 days after surgery. For evaluation of the efficacy of treatment for vasospasm, 21 out of 41 cases were administered a calcium antagonist (4mg of nicardipine) through the cisternal drain every 12 hours for an average of 10 days. The other 20 cases did not receive nicardipine and served as controls. 15 patients with clinical symptoms had a rapid increase in MCAFV from the 3rd to 6th day after onset, and a high velocity of more than 150cm/sec continued for 7.6 +/- 3.6 days on the average. In marked contrast, 26 patients without clinical symptoms showed only a small increase in MCAFV of less than 110cm/sec. There was a significant correlation between the arterial narrowing of MCA and MCAFV (gamma = 0.72, p less than 0.01) except for 5 cases (12%).(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis of purine bases having a di(hydroxymethyl)cyclopentenyl group by means of high-pressure reaction and their anti-HIV activity.

The 1'- and 5'-hydroxymethyl derivatives of carbovir and related purine derivatives were synthesized from 5-hydroxymethylcyclopentadiene. The anti-HIV activity evaluation of these compounds has revealed that 9-(c-4,t-5-dihydroxymethylcyclopent-2-en-r-1-yl)-9H-adenine is a prospective chemotherapeutic agent against AIDS.

[Meningioma of pineal region].

A 58-year-old man was admitted to our hospital upon his request for an operation on a hemifacial spasm that had developed twelve years ago. The hemifacial spasm on the left side was the only positive neurological findings at the time of admission. However, a pre-operative neuroradiological examination revealed a meningioma originating in the falco-tentorial junction. Left neurovascular decompression was initially performed and was followed by the excision of the tumor through a right parietooccipital approach. The pathological diagnosis was meningothelial meningioma. The patient was discharged with no neurological deficit. There have been only a few reports on pineal meningioma and even now this type of tumor is considered to be rare. Some similar cases reported in the literature are reviewed. The clinical aspects, clinical features and the pathological entity are discussed.