Axillary lymph-node metabolic activity assessment on 18F-FDG-PET/CT in rheumatoid arthritis patients treated with biologic therapies.

Objective: Recent studies have provided new insights into the role of lymph nodes (LNs) in rheumatoid arthritis (RA). The aim of this study was to evaluate the metabolic activity of the axillary LNs in relation to that of the upper limb joints and the clinical assessment of disease activity in RA patients treated with biologic therapies.Method: 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) scans were acquired for 64 patients with RA at baseline and after 6 months of biologic therapy, and the patients' clinical status was evaluated. The maximum standardized uptake value (SUVmax), metabolic active volume, and total lesion glycolysis (TLG) were used to assess glucose metabolism in the LNs and 12 joints. Clinical evaluations included serum markers and the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate (DAS28-ESR).Results: Changes in the SUVmax and TLG for the axillary LNs correlated significantly with those of the ipsilateral wrist joints. There was a positive correlation between the changes in the three metabolic parameters of the axillary LNs and the changes in disease activity after treatment. After 6 months of biologic therapy, all metabolic parameters for the axillary LNs in patients with a DAS28-ESR < 3.2 were significantly lower than those of patients with a DAS28-ESR ≥ 3.2.Conclusion: A relationship between the glucose metabolism of the axillary LNs and the ipsilateral wrist joints was demonstrated by the 18F-FDG-PET/CT parameters. The metabolic activity and active volume of axillary LNs may reflect the therapeutic response to the biologic treatment of RA.

A clinical and ultrasonographic study of risk factors for elbow injury in young baseball players.

PURPOSE: To determine the risk factors for elbow injury and its association with glenohumeral internal rotation deficit among young baseball players. METHODS: 229 baseball players aged 9 to 14 (mean, 11) years completed a self-administered questionnaire with items related to years of playing baseball, hours of training per weekday, days of training per week, and past and present experience of elbow pain. Two orthopaedic surgeons measured the range of motion of both shoulders and elbows. Another 2 orthopaedic surgeons performed ultrasonography to detect any elbow abnormality such as fragmentation of the medial epicondylar apophysis and osteochondritis dissecans of the capitellum. Using univariate and multivariable analyses, participants with or without elbow abnormality were compared to determine the risk factors for elbow abnormality. RESULTS: Elbow abnormality was detected in 100 of the participants and comprised osteochondritis dissecans of the capitellum (n=18) and fragmentation of the medial epicondylar apophysis (n=82). Elbow abnormality was associated with being a pitcher, past and present experience of elbow pain, loss of elbow extension, and the side-to-side internal rotation difference. The 100 participants with elbow abnormality were stratified into symptomatic (n=57) or asymptomatic (n=43) of elbow pain. Those with elbow abnormality and elbow pain was associated with being a pitcher. CONCLUSION: Being a pitcher was a risk factor for both elbow abnormality and elbow pain. Nonetheless, 43% of baseball players with elbow abnormality were asymptomatic. The use of ultrasonography was effective in detecting elbow abnormality and enabling early treatment.

F13459, a new derivative of mycophenolic acid. II. Physico-chemical properties and structural elucidation.

F13459 is a new inhibitor of synthesis and trafficking of virus glycoprotein isolated from the culture broth of a Penicillium sp. The molecular formula of F13459 was determined to be C27H28O11 by HRFAB-MS and NMR spectral analyses. The structure of F13459 was elucidated to be 3,4-dihydro-3,4,6,8-tetrahydroxy-3-methyl-1H-2-benzopyran-1-one 4-O-mycophenolate, an ester derivative of mycophenolic acid. F13459 was isolated as the optically inactive form. F13459 exists in epimeric mixtures at C-3' through relatively fast hemiacetal-ketone tautomerism and at C-4' through slow keto-enol tautomerism. Those epimerizations were confirmed by NOE differential experiments for fast chemical exchange and equilibrium and by deuteration experiments in NMR for slow chemical exchange.

Lupeol esters from the twig bark of Japanese pear (Pyrus serotina Rehd.) cv. Shinko.

Five new lupeol esters, lup-20(29)-ene-3beta-yl eicosanoate, docosanoate, tetracosanoate, hexacosanoate and octacosanoate, were isolated as a mixture from the twig bark of Japanese pear (Pyrus serotina Rehd.) cv. Shinko, together with lupeol and epifriedelinol. Their structures were determined by spectral analyses including 2D-NMR experiments.

Fibrolamellar carcinoma of the liver.

We report a resected case of fibrolamellar carcinoma (FLC) of the liver that occurred in a 21 year-old Japanese male with a normal liver. Lymph node metastases around the common hepatic artery and the hepatic hilum were revealed by a post-operative histological examination. He was in good health 7 months after the surgery. This case demonstrates typical findings of FLC, radiologically and histologically. The details are described in this report. Moreover, after reviewing 12 Japanese cases, we emphasize the differential diagnosis of focal nodular hyperplasia (FNH) as the following: 1) Calcification is frequently seen in FLC. 2) The central scar of FLC is visualized as an area of low intensity on T2-weighted magnetic resonance imaging (MRI).

Ocular activity of topically administered anandamide in the rabbit.

Marijuana and its psychoactive constituents, cannabinoids, reduce intraocular pressure (IOP) in humans and animals. Because anandamide, a recently discovered endogenous ligand of cannabinoid receptors, reportedly shows cannabimimetic pharmacological activity, we examined its effect on the eye. Varying amounts of anandamide, in 50 microL of light mineral oil, were topically applied to a rabbit eye and changes in IOP and ocular symptoms were monitored. Anandamide (50 micrograms to 1 mg) induced a significant decrease in IOP within 1 hour after administration; maximum reduction occurred at 2 hours; and there was a return to baseline by 7 hours following administration. A noticeable hyperemia of conjunctival blood vessels was also noted 2 hours after administration. Neither mineral oil alone or with palmitylethanolamide (an analogue of anandamide) caused a significant decrease in IOP or conjunctival hyperemia. This study indicates that anandamide does produce cannabimimetic effect in rabbit eyes.

Novel amino acid metabolite produced by Streptomyces sp.: I. Taxonomy, isolation, and structural elucidation.

A strain of streptomycete isolated from a soil sample was found to produce a novel amino acid metabolite. The compound was purified from the culture fluid by chromatography, using cation exchange resin, a synthetic adsorbent, and finally by preparative HPLC with a reverse-phase column. The structure of the compound was established as N(delta)-(5-methyl-4-oxo-2-imidazolin-2-yl)-L-ornithine on the basis of an analysis of the spectral data and chemical degradation. This was confirmed by comparing the NMR spectrum of the metabolite with that of the compound synthesized by treating methylglyoxal and N(alpha)-acetyl-L-arginine. The substance did not show any antimicrobial activity against bacteria, fungi and yeasts by the agar plate method, but exhibited a weak preventive effect on cucumber mildew disease in a pot test.

Adrenal metastasis from hepatocellular carcinoma--report of a case.

A 66-year-old man presented with an epigastric tumor demonstrated by both ultrasonography and computed tomography as hepatocellular carcinoma. He referred himself to a specialist at another hospital who performed transarterial embolization (TAE) of the hepatic artery. But the serum alpha fetoprotein (AFP) concentration gradually rose after the procedure. A right adrenal metastasis was discovered by computed tomography 9 months after his presentation, 8 months after first embolization. When TAE was performed for this metastasis, there was transverse palsy of the lower limb secondary to spinal artery embolization. He returned to our hospital where a right adrenectomy was performed 14 months after his first presentation. The operation was successful and he was discharged 6 weeks later. But he was readmitted in 8 months with an elevated serum AFP concentration and died within 2 weeks. The details of this case are presented, and the indications for resection of adrenal metastasis from hepatocellular carcinoma are discussed.

1'-Acetoxychavicol acetate as an inhibitor of phagocytosis of macrophages.

We screened extracts of edible plants for inhibitors of phagocytosis by peritoneal exudate macrophages. 1'-Acetoxychavicol acetate was isolated from the ethyl acetate extract of Languas galanga, and this compound strongly inhibited phagocytosis at an IC50 value of 1.2 microM with negligible effects on pinocytosis and cell viability. Target(s) of 1'-acetoxychavicol acetate was suggested to be downstream of the signal transduction pathway that is mediated by protein kinase C.

[An intracranial collision tumor composed of intrasellar gangliocytoma and pituitary adenoma].

The authors report a rare case of collision tumor composed of intrasellar gangliocytoma and pituitary adenoma. The patient was a 56-year-old woman, who had a mild acromegalic feature and slightly elevated plasma GH level. But she had no abnormal neurological findings. Transsphenoidal microsurgery was performed and an intrasellar tumor was totally removed. After the operation, plasma GH level decreased to within normal level. She was discharged with no neurological deficit. Histological examination showed two components. One of them was gangliocytoma composed of many large, and often binucleated cells with Nissl substance. The other had the appearance of chromophobe adenoma. In this part, some of the cells showed positive stain for GH. The clinical and histological features of this lesion are discussed and compared with 31 other cases of intrasellar ganglioglioma or gangliocytoma.

Immunohistochemical demonstration of S-100 protein in epithelial cells of bovine oviduct.

The present study deals with an immunohistochemical localization of S-100 protein in the bovine oviduct. The epithelium of the infundibulum, ampulla and isthmus showed a positive staining for S-100 protein. The immunoreactivity for S-100 was observed both in the ciliated and nonciliated (secretory) cells of the oviductal epithelium at any stages of the estrous cycle. The immunoreactivity was also found in nervous elements and endothelial cells of blood vessels. No cell outside these cells showed any immunoreactivity for S-100. Although the functional significance of S-100 protein in the oviductal epithelium remains to be elucidated, the present results introduce new perspectives into the investigation of function and localization of S-100 protein.

[Glial fibrillary acidic protein and neurofilament protein in medulloblastoma].

Medulloblastoma is the most common primitive neuroectodermal tumor (PNET) with the potential to differentiate along glial or neuronal lines. Thirty cases of medulloblastoma were tested by the peroxidase-antiperoxidase (PAP) method with anti-GFAP serum (DAKO) and by the avidin-biotin peroxidase complex (ABC) method with 68kd subunit of anti-NF antibody. All the cases were classified into three subtypes based on these immunohistochemical findings and were analyzed in relation to clinico-pathological features. Fifteen of thirty medulloblastomas contained GFAP positive cells, seventeen showed cells reacting to NF. The reactions for both proteins were present in eight medulloblastomas (PNET-BD, bipotential differentiation). Seventeen medulloblastomas reacted to only one protein (PNET-MD, monopotential differentiation). No reaction for either was found in five cases (PNET-NOS, not otherwise specified). The two year survival rate was 12.5% for PNET-BD compared to 49.2% for PNET-MD and 53.3% for PNET-NOS. Nine variables, i.e. age, tumor stage, metastatic stage, operation, radiotherapy, chemotherapy, histology, GFAP and NF, were analyzed using Cox's proportional hazard model. This revealed that the significant factors were tumor stage (p = 0.0002), GFAP (p = 0.0008) and operation (p less than 0.05). In conclusion, GFAP is the most important histological factor for prognosis and medulloblastoma without glial differentiation has a much better prognosis than one with glial differentiation.

[Clinicopathological study of oligodendroglioma with special reference to immunohistochemical investigation].

The present study was undertaken to evaluate the utility of pathologic features and specific immunohistochemical studies in estimating the prognosis of oligodendroglioma. The pathological diagnosis of an oligodendroglioma was made on HE stained-sections according to WHO classification. Sixteen oligodendrogliomas, twelve mixed oligoastrocytomas and ten anaplastic oligodendrogliomas were immunotested by the peroxidase-antiperoxidase (PAP) method with anti-GFAP serum, anti-S-100 serum and anti-MBP (Myelin basic protein) serum and by the avidin biotin peroxidase-complex (ABC) method with anti-vimentin serum and ant-Leu 7 monoclonal antibody. GFAP positive cells were interpreted as reactive astrocytes, neoplastic astrocytes and neoplastic oligodendrocytes, S-100 positive cells were interpreted as reactive astrocytes and neoplastic astrocytes. Leu 7 positive cells were found in only one case of anaplastic oligodendroglioma. Anti-Leu 7 could not be considered as a specific marker for oligodendroglioma. Of the anaplastic oligodendroglioma 60% displayed MBP positively and 70% displayed vimentin positively. NSE positive cells were found in a few anaplastic oligodendrogliomas. The present study has not so far uncovered any marker that is restricted to oligodendrogliomas. However GFAP may be useful to assess the extent of reactive astrocytes and neoplastic astrocytes in the oligodendroglioma or mixed oligoastrocytoma. MBP and vimentin will help to determine the malignancy of oligodendroglioma.

The experimental study of the coronary reperfusion in the acute myocardial ischemia: the feasibility of the myocardial salvage.

In order to know the feasibility of coronary reperfusion by thrombolysis or aorto-coronary bypass graft in the early stages of the acute myocardial infarction, we studied the effect of the coronary artery reperfusion to acutely ischemic myocardium induced by the coronary artery occlusion in ninety-five anesthetized open-chest dogs. The major factors determining the extent of the myocardial salvage by the reperfusion were the duration of the occlusion time and the degree of the reperfusion injury. These two determinants were analysed by coronary circulation, the regional myocardial function, the mitochondrial metabolism, mitochondrial Ca and Mg contents, and morphological findings of the myocardium by electron-microscopy. The regional myocardial contractility (% systolic shortening) and the mitochondrial metabolism (oxidative phosphorylation) were significantly damaged by the reperfusion more in 60 minute occlusion than in 30 minute occlusion, although the coronary circulation (coronary blood flow, regional myocardial blood flow and coronary vascular resistance) and myocardial gas contents (PO2, PCO2 and pH) in the ischemic myocardium induced by less than 60 minute occlusion were almost recovered to the pre-occluded level by 60 minutes after reperfusion. By 120 minute reperfusion, the ischemic damage calculated from mitochondrial Ca and Mg contents (MC index: 1-[Mg/Ca] ischemia/[Mg/Ca] non-ischemia) was not changed in 30 minute occlusion but was significantly deteriorated in 60 minute occlusion. Therefore, coronary reperfusion must be started within 60 minutes or less after occlusion. A supplementary way to protect the myocardium from ischemia is needed as soon as possible before reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Dialysis dysequilibrium syndrome in neurosurgical patients.

Four neurosurgical patients with acute renal failure are presented. Intracranial pressure (ICP), cerebrospinal fluid (CSF) osmolality, and plasma osmolality were measured before, during, and after hemodialysis. There was an increase in ICP during all six hemodialyses performed on these patients. An osmolality gradient was established between the plasma and the CSF during four hemodialyses performed on two patients but not during one hemodialysis on one other patient. Continuous ventricular drainage and ICP monitoring were simple and effective clinical methods to avoid irreversible herniation during hemodialysis in these patients. A review of the literature on, proposed pathogenesis of, and prophylactic possibilities for dialysis dysequilibrium syndrome in neurosurgical patients is presented.

[Treatment of malignant brain tumors with slowly releasing anticancer drug-polymer composites].

The purpose of this study is to present the methodology and results of a clinical trial of local chemotherapy of malignant brain tumors based on slowly-releasing anticancer drug-polymer composites. The slowly releasing drugs were prepared by combining and mutually dispersing anticancer agents with glassified monomers containing 10% polymetacrylic methyl acid and then this compound was frozen at -78 degrees C and exposed to 1 X 10(6) rad of gamma rays from cobalt 60. Thus we prepared a compound of polymers and anticancer agents. We used needle-shaped capsules of this compound. These capsules release the drug very slowly over 40 days. We administered locally to the malignant brain tumors with either slowly releasing mitomycin, slowly releasing adriamycin, slowly releasing ACNU or slowly releasing 5 Fu drugs. The following techniques were employed in implantation these capsules. Implantation into the remaining tumor wall at the time of excision. Implantation into the tumor by CT-guided stereotactic method. We implanted these drugs into tumor of 55 cases, thereafter we conducted both radiation and chemotherapy with ACNU in most patients. This method has the following advantages: It is possible to be employed to different types of anticancer agents. Both dosage and releasing time can be adjusted. It is possible to administer these capsules postoperatively by the stereotactic method. The clinical study consists of 55 patients, 20 cases of anaplastic astrocytoma, 23 cases of glioblastoma multiforme, 5 cases of oligodendroglioma, 3 cases of medulloblastoma and 4 cases of others. Survival rate estimated by Kaplan-Meier method was 47% in glioblastoma at 12 months and 91% in anaplastic astrocytoma at 18 months.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinicopathological study on malignant glioma--with special reference to GFAP].

In surgical specimens of 91 cases of malignant glial tumor, the correlation between the clinical malignancy of the tumors and the presence of GFA protein in the surgical specimen was examined. In anaplastic astrocytomas, 20 of 27 cases revealed positive staining of GFAP. In the cases of glioblastoma multiforme 27 of 35 cases showed GFAP positive staining. On the other hand, in medulloblastomas, all 29 cases were negative. In anaplastic astrocytomas and glioblastoma multiforms, the difference between the survival curves of GFAP positive groups and negative groups were examined. Between two groups, there was no statistical differences. In this study, the presence of GFAP was not proportional to the degree of tumor differentiation, and the GFAP staining of the tumor tissue was not a valuable examination showing the prognosis of the patient.