Prognostic determinants of patients with lateral nodal involvement by rectal cancer

OBJECTIVE: To clarify the characteristics related to long-term survival in patients with lateral nodal involvement. SUMMARY BACKGROUND DATA: Few reports have addressed the prognostic determinants in patients with actual lateral nodal involvement, which are important in determining treatment. METHODS: Review of a prospective colorectal database at a single institution for a 10-year period (1987-1996) identified 53 patients with lateral nodal involvement. RESULTS: All nine patients who underwent resection of synchronous distant metastases developed recurrence and died within 3 years. Of the 44 patients without distant metastases, 25 (57%) developed locoregional recurrence, and the overall 5-year survival rate was 32%. Multivariate analysis showed that age, total number of involved nodes (mesorectal and lateral), and circumferential surgical margin involvement had independently predicted postoperative survival. Patients with three or fewer nodes involved accounted for one third of lateral-positive patients, with a 5-year survival rate of 75%, whereas the 18 patients with four or more involved nodes had a 5-year survival rate of 4%. All eight patients with circumferential margin involvement died of carcinoma, and seven developed locoregional recurrences. Involvement of other pelvic organs had no effect on prognosis, nor were adverse prognostic outcomes noted by the region of lateral involvement. CONCLUSIONS: For patients with lateral involvement, the most important prognostic variables are distant metastases, the total number of nodes involved, circumferential margin involvement, and age. Selection of patients based on these variables may lead to the identification of a subgroup for whom lateral nodal dissection could be the first treatment choice.     

Neuroprotective action of a novel compound–M50463–in primary cultured neurons

The neuroprotective effects of a novel synthetic compound, M50463, have been determined by using embryonic rat neocortical neurons in various culture conditions. M50463 was initially characterized as a potent specific ligand for a voltage-dependent sodium channel by radioligand binding studies. In fact, M50463 inhibited neuronal cell death induced by veratrine and inhibited an increase of the intracellular calcium level in neurons evoked by veratrine. In addition to such expected effects, M50463 had the ability to prevent glutamate neurotoxicity, to promote the neuronal survival in serum-deprived medium and to prevent nitric oxide-induced neurotoxicity. These results suggested that M50463 is not a simple sodium channel blocker, but a neuroprotective agent which has some crucial mechanism of action on neuronal death occurring in various situations, and it is a novel, innovative candidate for neuroprotective therapy for various neurodegenerative disorders.     

Absorption, plasma concentration, and excretion after single administration of 14C-(+-)-3-(benzylmethylamino)-2,2-dimethylpropyl methyl 4-(2-fluoro-5- nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate hydrochloride in rats and dogs.

The absorption, plasma concentrations, and excretion of a newly synthesized calcium antagonist, TC-81 ((+-)-3-(benzylmethylamino)-2,2-dimethylpropyl methyl 4-(2-fluoro-5-nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5- pyridinedicarboxylate hydrochloride, CAS 96515-74-1) were studied following a single oral or intravenous administration of 14C-labelled compound. After oral administration, 14C-TC-81 was rapidly and well absorbed from the gastrointestinal tract. The peak plasma concentrations of radioactivity were observed at 0.5-1 h (rats) and 1-2 h (dogs) h after dosing. The elimination of the radioactivity in plasma was biphasic with a half-life of 3.8-5.2 h (a phase) and 42.9-56.2 h (beta phase) in the rats or 3.2 h (a phase) and 61.5 h (beta phase) in dogs. Maximum plasma concentrations of unchanged drug after oral administration of TC-81 to male rats at the doses of 0.5, 1.0, and 3.0 mg/kg were 1.7, 7.3 and 15.6 ng/ml, respectively. They were attained at 0.5 h after dosing in every dose examined. Plasma levels of unchanged drug declined with a half-life of 0.39-1.15 h. When TC-81 was orally administered to male dogs at the doses of 0.1, 0.2 and 0.5 mg/kg, plasma concentrations of unchanged drug reached the maximum level at 0.5 h after dosing and the values were 0.8, 3.3 and 9.6 ng/ml, respectively. They were eliminated with a half-life of 2.4-2.8 h. The absolute bioavailability of unchanged drug was estimated to be 2.6-7.0% (rats) and 5.3-15.5% (dogs) of the dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reoperation in patients with biliary atresia

Twenty-seven reoperations were done on 23 patients among 100 infants with biliary atresia who have been treated at Tohoku University Hospital between 1971 and 1981. Nineteen patients had a single reoperation and 4 patients had 2 reoperations. We present the results and the role of reoperation in biliary atresia patients in our institution. Excellent bile drainage after reoperation was obtained in 13 of 15 patients with good bile flow after the initial operation. On the contrary, good bile drainage was not obtained by reoperation in 8 of 12 cases without active bile flow after the initial operation. Cessation of bile flow after successful initial operation is an absolute indication for reoperation. Aggressive reoperations under proper indications improve the surgical results in biliary atresia patients.     

Effective separation of human chorionic gonadotropin subunits by high performance gel permeation chromatography

Human chorionic gonadotropin (hCG) was effectively separated into alpha and beta subunits by treating with 8 M guanidine hydrochloride, followed by high performance gel permeation chromatography (GPC) on a 2.5 X 60 cm TSK G 3000 SW column in 6 M guanidine hydrochloride. Their molecular weights estimated by GPC were about 29,000 daltons for the beta subunit and 19,000 daltons for the alpha subunit. Both subunits were examined for SDS-polyacrylamide gel electrophoresis, amino acid analyses and radioimmunoassay, respectively. Neither subunit showed significant binding to the hCG-receptor fraction of rat Leydig cell in vitro. However, the separated subunits easily recombined and recovered about 90% of receptor binding activity of intact hCG. The present results indicate that the GPC technique is an effective, simple and non-denaturing method for the separation of hCG into alpha and beta subunits.     

Chemical and mutagenic properties of alpha-phosphonooxynitrosamines

The chemical and mutagenic properties of the products of solvolysis of alpha-acetoxynitrosamines in phosphate buffer were investigated. alpha-Acetoxynitrosamines decomposed in two ways: O-acyl fission yielded alpha-hydroxynitrosamines, which decomposed into aldehydes and alcohols, while O-alkyl fission gave a resonance hybrid of alpha-N-nitrosocarbonium and -iminium ions, which was trapped with phosphate and afforded alpha-phosphonooxynitrosamine. Formation of alpha-phosphonooxynitrosamines was dependent on the structure of alpha-acetoxynitrosamines; those with a secondary alpha-phosphonooxy group, including cyclic nitrosamines, were easily formed, while among those with a primary phosphonooxymethyl group, only those with an alkyl group containing a branched alpha-carbon as isopropyl, sec-butyl and tert-butyl were isolated. They were good substrates of alkaline phosphatase and showed a nuclear magnetic resonance spectrum due to the presence of a phosphorus atom. They were decomposed by acid catalysis, and the rate was dependent on the structure. They were directly mutagenic in bacterial tester strains, except for a compound with a tert-butyl group. The activity was similar or stronger in Salmonella typhimurium TA1535 and much weaker in Escherichia coli WP2 and WP2 hcr- than those of alpha-acetoxynitrosamines. Stability in neutral aqueous solution and the strong mutagenicity of alpha-phosphonooxynitrosamines suggested their possible involvement in metabolic activation as a precursor of alpha-hydroxynitrosamines, and also in the organotropic carcinogenicity of N-nitrosodialkylamines as a transport form.     

Analysis of the exercise-induced orthogonal P wave changes in normal subjects and patients with coronary artery disease

Near-maximal treadmill exercise testing was performed on 26 normal individuals (NL) and 78 patients with coronary artery disease (CAD) using a modified Bruce's protocol. Exercise-induced changes in orthogonal P wave measurements were made automatically, using an averaging technique, immediately before and 30 sec after treadmill exercise to assess their diagnostic significance in evaluation of left ventricular (LV) function in CAD patients. The maximal inferior and posterior components of the P wave and the maximal P-vector magnitude in the frontal and left sagittal planes showed a statistically significant increase after treadmill exercise both in NL and CAD patients. These changes were considered to be physiological responses of the P wave to dynamic exercise. The percent changes of the maximal horizontal P-vector magnitude (%Hmax) were significantly higher after treadmill exercise in CAD patients than in NL. In patients with effort angina pectoris and without a previous myocardial infarction, the %Hmax showed a highly significant negative correlation with the percent changes of the LV ejection fraction (r = 0.66, p less than 0.01), measured by exercise RI angiography. These results suggest that the exercise-induced increase in %Hmax reflects transient impairment of LV function during exercise. It was concluded that a %Hmax of more than 120% provided a useful, noninvasive index for assessing LV function in treadmill exercise testing.