Locally recurrent carcinoma of the breast. Results of radiation therapy

Local and regional recurrences are frequent problems in breast cancer management. Radiation therapy is effective in producing long term remission. This study evaluates the results of radiation therapy of 215 patients with recurrent disease limited to the chest wall and/or regional lymph node areas. The local results showed complete control in 67% of cases (mean and median durations 32 months and 22 months, respectively), partial control in 24% of cases (mean and median 11 and 8 months, respectively) and no control in the remaining 9%. The radiation dose recommended for the treatment of recurrent mammary carcinoma is 5000 rads in 5 weeks for relatively small lesions. Supplementary local doses of 500-1000 rads in 1 week may be given to bulky lesions as necessary for residual disease. Although local relapse indicates a poor prognosis, it is by no means totally hopeless. Of 215 patients treated 44 (21%) survived 5 years and 10 (5%) survived 10 years following radiation therapy of recurrent disease. There were seven patients, or 3%, who were free of cancer at 5 to 15 years. Radiation therapy was valuable in controlling local lesions, and thus, in improving quality of survival, even in those patients who eventually died of metastatic disease.     

Development of interpretive breakpoints for antifungal susceptibility testing: conceptual framework and analysis of in vitro-in vivo correlation data for fluconazole, itraconazole, and candida infections. Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards

The availability of reproducible antifungal susceptibility testing methods now permits analysis of data correlating susceptibility in vitro with outcome in vivo in order to define interpretive breakpoints. In this paper, we have examined the conceptual framework underlying interpretation of antimicrobial susceptibility testing results and then used these ideas to drive analysis of data packages developed by the respective manufacturers that correlate fluconazole and itraconazole MICs with outcome of candidal infections. Tentative fluconazole interpretive breakpoints for MICs determined by the National Committee for Clinical Laboratory Standards' M27-T broth macrodilution methodology are proposed: isolates for which MICs are < or = 8 microg/mL are susceptible to fluconazole, whereas those for which MICs are > or = 64 microg/mL appear resistant. Isolates for which the MIC of fluconazole is 16-32 microg/mL are considered susceptible dependent upon dose (S-DD), on the basis of data indicating clinical response when > 100 mg of fluconazole per day is given. These breakpoints do not, however, apply to Candida krusei, as it is considered inherently resistant to fluconazole. Tentative interpretive MIC breakpoints for itraconazole apply only to mucosal candidal infections and are as follows: susceptible, < or = 0.125 microg/mL; S-DD, 0.25-0.5 microg/mL; and resistant, > or = 1.0 microg/mL. These tentative breakpoints are now open for public commentary.     

An Eikenella corrodens toxin detected by plaque toxin-neutralizing monoclonal antibodies

Bacterial plaque from the gingival region of teeth contains cytotoxic agents which lyse undifferentiated human HL60 cells. A small panel of monoclonal antibodies (MAbs) was found to abrogate much of this activity and to detect antigens in certain strains of Streptococcus mitis and Eikenella corrodens. The aim of this study was to determine whether these bacterial antigens might be involved in HL60 cells cytolysis. Saline extracts were obtained by homogenizing washed, stationary-phase cells in 65 mM NaCl with a tight-fitting Potter-Elvehjem homogenizer. The extracts of E. corrodens were toxic to HL60 cells, whereas similar extracts of S. mitis were nontoxic. Adding plaque toxin-neutralizing MAb 3hE5 blocked the toxic effect of E. corrodens extract S. mitis extracts contained a single, strongly reactive antigen of 140 kDa (s140K antigen) detected on Western blots (immunoblots) by three MAbs from the panel. Rabbit antibodies raised to this antigen excised from the gel (anti-s140K serum) detected larger antigens in addition to s140K. E. corrodens extracts contained a number of antigens detected by the MAbs. Immunoglobulin G (IgG) was purified from anti-s140K serum by passage through DE52 cellulose. A 100-fold excess (by weight) of the purified IgG to E. corrodens protein specifically cross-precipitated an 80-kDa antigen plus a nonantigenic 16-kDa protein, presumably attached noncovalently. The remaining supernatant fraction had no toxic activity. A similar ratio of control IgG (from nonimmunized rabbits) did not precipitate these proteins, and the supernatant fraction had the same activity as the extract not treated with IgG. The proteins of 80 and 16 kDa were also detected in the anti-s140K immunoprecipitate by rabbit IgG antibodies to E. corrodens whole cells. The 80-kDa antigen, alone or complexed with the 16-kDa protein, may be involved in mediating the toxic activity in E. corrodens and plaque extracts.     

Evaluation of the gastrotoxicity of anti-inflammatory drugs: contribution of general registries of digestive endoscopy

The evaluation of the rate of gastroduodenal toxicity of anti inflammatory drugs is a difficult problem. We tried to analyse that question by studying the general endoscopic registers of the Gastro-Enterologic department of the hospital. This retrospective study concerns 2,945 endoscopies performed during the year 1988 and 1992 randomly chosen among the last 5 years. 992 results show injuries suggestive of non steroidal anti inflammatory drugs (NSAID) toxicity, however only in 65 cases the potential role of an anti inflammatory drug is mentioned: 36 men and 29 women, mean age: 50.6 +/- 19.6 years. Concerning the drugs, only the pharmacological classes they belong to are mentioned except for Aspirin. Acetyl salicylate acid 7 cases, NSAIDS 36 and Steroids 22. In the drug group 63% of injuries are located to the stomach (ulcers 13%, gastritis 50%), 37% to the duodenum (19% ulcers, 18% duodenitis). Compared to the groups with the same kind of injuries, but without any mention of drugs, there are no statistical difference in the proportion of ulcers. Aging and sex are not influent in our results on the genesis of drug induced ulcers. These results must be discussed because a lot of datas are missing in the registers and so the number of patients taking drugs is probably underestimated. This means that unless a prospective study is held with someone enquiring for all the risk factors, the study of the general endoscopic registers is not a good way to estimate gastrointestinal damages due to drugs.     

Association between serum amyloid A proteins and coronary artery disease: evidence from two distinct arteriosclerotic processes

BACKGROUND: Serum amyloid A (SAA) proteins are a family of inflammatory apolipoproteins that may modify high-density lipoprotein structure and function. Elevations of SAA have been reported in unstable coronary syndromes, but the levels and types of SAA protein in humans with spontaneous or transplant-associated coronary artery disease are not known. METHODS AND RESULTS: SAA levels were analyzed using an ELISA in 76 sera from 36 patients after cardiac transplantation and in 346 other individuals, 85 patients with atherosclerotic coronary disease plus 261 of their relatives. The mean SAA level was 5-fold higher in transplant patients (203+/-181 microg/mL [23 to 934 microg/mL]) compared with normal subjects without coronary disease (36+/-16 microg/mL [2.8 to 193 microg/mL], P<.005). The mean SAA level was significantly elevated in patients with transplant coronary disease (206+/-160 microg/mL, n=23) compared with those without (140+/-104 microg/mL, n=12, P=.02). Elevated SAA levels were associated with increased mortality after transplantation. On multiple regression analysis, SAA levels were predicted by corticosteroid dose, pretransplant diagnosis of atherosclerotic coronary artery disease, and the presence of transplant coronary disease. SAA levels were elevated in patients with spontaneous atherosclerotic coronary disease (49+/-31 microg/mL) compared with unaffected relatives (39+/-36 microg/mL, mean+/-SD, P=.02). There was no evidence for a genetic contribution to SAA levels. All inducible human SAA protein types were documented by immunoblotting in both spontaneous and transplant coronary disease. CONCLUSIONS: Environmentally determined elevations in SAA levels in patients with both spontaneous and transplant coronary artery disease provide further evidence for a potential pathophysiological link between inflammation, lipoprotein metabolism, and the development of atherosclerosis.