Effect of retinoids on the induction of colon cancer in F344 rats by N-methyl-N-nitrosourea or by 1,2-dimethyihydrazine

The possible modifying effect of synthetic and natural retinoidson the incidence of colon cancer in rats induced by 2 intrarectaldoses of 2.5 mg of N-methyl-N-nitrosourea (MNU) given once aweek for 2 successive weeks or a single 150 mg/kg body weightdose of 1,2-dime-thylhydrazine (DMH), s.c. was investigated.Emphasis was on the effect of the development of early tumorsas visualized by endoscopy. With the retinoids N-ethyl-retinamide,N-2-hydroxyethylretinamide, N-(4-hydro- xyphenyl)-all-trans-retinamide(RAHA), and retinyl acetate (RA) administered orally after thecarcinogens, significant differences in early developing tumorswere not found. At histopathological examination of the tumorsthe RAHA + DMH group had significantly fewer adenomas per animal.The percentage of adenoma bearing rats was significantly lowerin groups receiving RAHA + DMH or RA + DMH. However, food consumptionwas lower in rats consuming either RAHA or RA. Retinyl palmitate(RP) and RAHA was administered intrarectally to MNU-inducedrats either before or after the carcinogen. When administeredbefore MNU, RP caused a significant increase in the percentageof tumor bearing animals and the average number of tumors peranimal as visualized endos copically. At histopathological examination,all retinoid groups except RAHA given after the carcinogen,produced significantly more adenomas per animal and a significantlygreater adenoma incidence than did the control groups. Thus,in two systems, the oral administration of retinoids did notclearly inhibit the early or later stages of colon tumor development.Inirarectal infusion of two retinoids had no effect on colonicmor phology but at histopathological examination of later stagetumors there was an enhanced adenoma response.     

The heterogeneity of leukemic reticuloendotheliosis, "hairy cell leukemia". Evidence for its monocytic origin.

The presence of B, T, and monocyte markers were studied on the spleen and peripheral blood mononuclear cells from two patients with leukemic reticuloendotheliosis. A high proportion of cells from both patients bore a receptor for cytophilic antibody, both in suspension and frozen tissue section. Cells in suspension lacked surface immunoglobulins or a receptor for sheep red blood cells. These results favor the evidence that "hairy cells" are monocytic in origin.     

Cerebral atrophy in multiple system atrophy by MRI

Cranial magnetic resonance images (MRI) of the cerebral areas of 40 patients with multiple system atrophy (MSA) and of 61 age-matched controls were analyzed. The cerebral area of MSA patients was 131. 95+/-15.89 cm(2) (mean+/-S.D.), which was significantly smaller than that of normal controls at 149.01+/-10.93 cm(2) (P<0.0001). All 23 MSA cases subjected to the MRI study over a 1-year period showed progressive cerebral atrophy, and the atrophy rate was 2.46+/-1. 66%/year. There were no significant differences within the MSA subtypes or between gender. The progression of cerebral atrophy in MSA correlated more with duration (r=-0.634) than age (r=-0.421). We conclude that MRI findings throughout the course of MSA suggest progressive cerebral atrophy, which is common in all subtypes and reflects duration of the disease rather than age.     

Alpha-synuclein inclusions in amygdala in the brains of patients with the parkinsonism-dementia complex of Guam

We investigated by immunohistochemistry the deposition of alpha-synuclein in the brains of deceased patients with the parkinsonism-dementia complex (PDC) of Guam. Five of 13 PDC brains showed numerous alpha-synuclein positive neuronal inclusions and abnormal neurites, chiefly in the amygdala. Similar alpha-synuclein positive lesions were observed, although to a lesser extent, in the entorhinal cortex and the dorsal vagal nucleus. No alpha-synuclein positive inclusions were observed in motor cortex or locus coeruleus, and only a small number of positive inclusions were found in the Sommer's sector, temporal cortex, or substantia nigra. Some of the alpha-synuclein positive inclusions were reminiscent of cortical Lewy bodies (LB), but many of those in the amygdala coexisted with tau-positive pretangles and/or neurofibrillary tangles (NFT) within the same neurons. In these neurons, tau-positive shells encapsulated alpha-synuclein positive central cores or irregularly shaped alpha-synuclein-positive deposition intermingled with pretangles/NFT. Thus, the present study suggests that a common mechanism may govern aggregation of alpha-synuclein and tau in the amygdala, and that aggregation of alpha-synuclein may play some role in the neurodegenerative process of a tauopathy (i.e. PDC) in which Abeta deposition is virtually absent.     

Serial diffusion-weighted imaging in MELAS

Clinical features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) resemble those of cerebral infarcts, but the pathogenesis of infarct-like lesions is not fully understood. To characterise these infarct-like lesions, we studied two patients with MELAS using diffusion-weighted (DWI) MRI before and after stroke-like episodes and measured the apparent diffusion coefficient (ADC) in the new infarct-like lesions. These gave high signal on DWI and had much higher ADC than normal-appearing regions. The ADC remained high even 30 days after a stroke-like episode then decreased in lesions, with or without abnormality as shown by conventional MRI. We speculate that early elevation of ADC in the acute or subacute phase reflects vasogenic rather than cytotoxic edema. The ADC of the lesions, which disappeared almost completely with clinical improvement, returned to normal levels, which may reflect tissue recovery without severe damage. To our knowledge, this is the first study of DWI in MELAS. Received: 13 September 1999/Accepted: 7 January 2000     

Cerebral oximetry for the detection of cerebral ischemia during temporary carotid artery occlusion

The near-infrared spectroscopy cerebral oximeter was assessed as a monitoring device for detecting and/or predicting cerebral ischemia during carotid endarterectomy (CEA) and the balloon occlusion test in 24 patients, 12 males and 12 females aged 28 to 77 years (mean 59.9 years). Tolerance testing of complete internal carotid artery (ICA) occlusion by balloon inflation for 20 minutes was performed in nine patients (cerebral aneurysm 6, neck tumor 3) and CEA was performed in 15 patients. The probe of the cerebral oximeter was placed on the forehead of the affected side and regional cerebral oxygen saturation (rSO2) was monitored continuously during all procedures. Stump pressure was measured just after ICA occlusion. Collateral circulation detected by digital subtraction angiography was classified into three groups: good, moderate, or poor. Stump pressure was 41-90 mmHg (mean 61.3 mmHg) in the good collateral circulation group, 40-43 mmHg (41.5 mmHg) in the moderate group, and 14-30 mmHg (23.8 mmHg) in the poor group. Change in rSO2 after ICA occlusion was +3.5(-)-4.2% (mean -1.6%) in the good collateral circulation group, -1.2(-)-6.6% (-3.2%) in the moderate group, and -2.4(-)-10.2% (-6.6%) in the poor group. Changes in rSO2 were significantly different between the good and poor collateral circulation groups (p < 0.01). A greater than 5% fall in rSO2 was observed in 0 of 15 patients in the good collateral circulation group, one of five in the moderate group, and three of four in the poor group. The cerebral oximeter is a useful, real-time, non-invasive method to measure brain oxygenation during CEA, skull base surgery, or other procedures which need to evaluate brain ischemia. A fall of greater than 10% from the rSO2 baseline value is dangerous, but less than 5% is safe.     

Inhibitors on an elastase-like enzyme activity catalyzing Suc-Ala-Ala-Pro-Leu-pNA amidolysis in human seminal plasma

The behavior of some proteinase inhibitors toward the Suc-Ala-Ala-Pro-Leu-pNA amidolytic enzyme activity in human seminal plasma (HSP) was tested. [(2S, 3R)-3-Amino-2-hydroxy-5-methyl-hexanoyl]L-valyl-L-valyl-L-aspartic acid (Amastatin) and 3-[1-[(2-(hydroxymethyl)- -pyrolidinyl)-2-methylpropyl]-carbamoyl] octanohydroxamic acid (Actinonin) showed strong inhibitory effects. No inhibition of this present enzyme activity was seen with anti-human serum (whole), anti-human leukocyte elastase, phenyl-methyl sulfonyl fluoride, Elastatinal, ethyeneglycol bis(beta-aminoethyl ethyl)N,N,N:N'-tetra acetic acid, and [L-3-trans-ethoxycarbonyl-oxirane-2-carbonyl]1-L-leucine(3-methylbutyl)a mido (E-64). No relation was observed between human pancreatic elastase antigen and the Suc-Ala-Ala-Pro-Leu-pNA amidolytic enzyme enzyme activity in HSP. Two peaks of Suc-Ala-Ala-Leu-Pro-pNA amidolytic enzyme activity were separated by Cellulofine GCL-2000 gel filtration and these activities were completely abolished by addition of Amastatin. Suc-Ala-Ala-Pro-Leu-pNA amidolytic enzyme activity in HSP is not an elastase-like metalloproteinase but is rather an acyl amidase-like leucine aminopeptidase.     

The management of medial ligament tears in patients with combined anterior cruciate and medial ligament lesions

The management of patients with combined medial collateral (MCL) and anterior cruciate (ACL) rupture remains controversial. We studied 25 such patients who elected to have the ACL lesion treated conservatively; 14 underwent MCL repair with early mobilization and 11 were treated with immobilization for two weeks. The mean follow up was 5.9 years (2 to 11). There was no difference in the clinical assessment of ligamentous laxity, KT-1000 measurements or Tegner activity scores between the two groups but there were significantly higher Lysholm function scores in the operated group.

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Résumé Le traitement optimal des cas associant des lésions du ligament croisé antérieur (ACL) à des lésions médiales collatérales (MCL) est controversé. Nous avons réalisé une étude sur le suivi du traitement de telles lésions dans le but d’évaluer si le traitement opératoire des déchirures de MCL peut apporter une amélioration des résultats fonctionnels pour des patients choisissant de ne pas subir une reconstruction de ACL. Notre étude portait sur 14 patients ayant subi une reconstruction du MCL et 11 patients traités sans opération. Nous n’avons pas observé de différences significatives entre les deux groupes pour les tests de relachement manuel, ni pour les mesures KT-1000, ni pour les niveaux d’activité de Tegner. En revanche les patients du groupe opératoire ont obtenu un meilleur score fonctionnel de Lysholm.

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Accepted: 7 December 1999     

Geographic Clustering Patterns in Mortality from Biliary Tract Cancer in Japan

We calculated the standardized mortality ratios (SMRs) of biliary tract cancer (BTC) in Japan from 1981 to 1990 and statistically analyzed the results according to 333 Secondary Areas of Medical Care, as well as sex and subsite [gallbladder cancer (GBC) and extrahepatic bile duct cancer (BDC)], in order to examine geographic clustering patterns of BTC. In GBC in both sexes, the Secondary Areas of Medical Care with high SMRs were clustered in the eastern part of Japan. In BDC in both sexes, the Areas with high SMRs were clustered between the northern and eastern parts of Japan. In comparison with GBC, this clustering favored the northern part of Japan. In males, the clustering pattern in mortality from BTC was mainly due to the occurrence of BDC. In females, the clustering pattern in mortality from BTC reflected that of GBC. The clustering of BTC, especially GBC, seems to be related to the distribution of plains, basins, and rivers.