In vitro maintenance of a pure-cone retina

The retina of the lizard, Sceloporus occidentalis, appears to have only cone photoreceptors. Eyecups from this animal were incubated in media containing Earle's Balanced Salts, supplemented with amino acids and vitamins, and gassed with 5% CO2/95% O2. Under these conditions, good morphology, protein synthesis, and normal cyclic AMP and cyclic GMP levels were maintained for 1-2 days. This in vitro preparation is likely to be useful for pharmacological studies of cone photoreceptors.     

Skin tumor initiating activities of the 9- and 10-fluoro derivatives of 7- or 12-methylbenz[a]anthracene and the 9- and 10-trifluoromethyl derivatives of 7,12-dimethylbenz[a]anthracene in SENCAR mice

We have determined the skin tumor initiating activity in SENCARmice of several 9- and 10-substituted mono- and dimethylbenz[a]anthracenederivatives. 9-fluoro-7-methylbenz[a]anthracene (9-F-7-MBA)was approximately as active as 7-MBA, whereas 10-F-7-MBA wasconsiderably more active as a skin tumor initiator than theparent compound. Initiating doses of 200 and 400 nmol per mouseof 10-F-7-MBA yielded 14.17 ± 0.16 and 22.47 ±1.64 papilliomas per mouse after 18 weeks of promotion with12-O-tetradecanoylphorbol-13-acetate, whereas comparable dosesof 7-MBA yield 2.13 ± 0.12 and 4.73 ± 0.68 papillomasper mouse respectively. The effect of fluoro substituents atpositions 9 and 10 of 12-MBA, a less potent tumor-initiatorthan 7-MBA, was also examined. 9-F-12-MBA was only slightlymore active than 12-MBA, whereas 10-F-12-MBA was again considerablymore active than the parent compound. Doses of 400 and 800 nmolper mouse of 10-F-12-MBA yielded 24.97 ± 2.18 and 22.20± 6.47 versus 1.13 ± 0.80 and 3.00 ± 0.17papillomas per mouse respectively for comparable initiatingdoses of 12-MBA. The effect of introducing a trifluoromethyl(CF₃) group at the 9 and 10 positions of 7,12-dimethylbenz[a]anthracenewas also examined. A (CF₃) group at either of these positionsessentially eliminated the tumor initiating activity of DMBAat the doses tested. These results when taken together withprevious results from our laboratory suggest that electron donatingsubstituents at positions 9 and 10 of the benz[a]anthracenenucleus either have no effect or enhance skin tumor initiatingactivity, whereas electron withdrawing groups at these positionsdramatically reduce or abolish tumor initiating activity.     

Phase II study of rituximab in combination with chop chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma.

PURPOSE: To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody Rituxan (rituximab, IDEC-C2B8; Genentech Inc, South San Francisco, CA) and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in patients with aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-three patients with previously untreated advanced aggressive B-cell NHL received six infusions of Rituxan (375 mg/m2 per dose) on day 1 of each cycle in combination with six doses of CHOP chemotherapy given on day 3 of each cycle. RESULTS: The ORR by investigator assessment confirmed by the sponsor was 94% (31 of 33 patients). Twenty patients experienced a complete response (CR) (61%), 11 patients had a partial response (PR) (33%), and two patients were classified as having progressive disease. In the 18 patients with an International Prognostic Index (IPI) score > or = 2, the combination of Rituxan plus CHOP achieved an ORR of 89% and CR of 56%. The median duration of response and time to progression had not been reached after a median observation time of 26 months. Twenty-nine of 31 responding patients remained in remission during this follow-up period, including 15 of 16 patients with an IPI score > or = 2. The most frequent adverse events attributed to Rituxan were fever and chills, primarily during the first infusion. Rituxan did not seem to compromise the ability of patients to tolerate CHOP; all patients completed the entire six courses of the combination. The bcl-2 translocation of blood or bone marrow was positive at baseline in 13 patients; 11 patients had follow-up specimens obtained (eight CR, three PR), and all had a negative bcl-2 status after therapy. Only one patient has reconverted to bcl-2 positivity, and all patients remain in clinical remission. CONCLUSION: This is the first report to demonstrate the safety and efficacy of the Rituxan chimeric anti-CD20 antibody in combination with standard-dose CHOP in the treatment of aggressive B-cell lymphoma. The clinical responses are at least comparable to those achieved with CHOP alone with no significant added toxicity. The presence or absence of the bcl-2 translocation did not affect the ability of patients to achieve a CR with this regimen. The ability to achieve sustained remissions in patients with an IPI score > or = 2 warrants further investigation with a randomized study.     

The relationship between cognitive failures, psychoneurotic symptoms and sex

As Broadbent et al's (1) original analysis of the relationship between the Cognitive Failures Questionnaire (CFQ) and the Middlesex Hospital Questionnaire (MHQ) was conducted on an altered version of the MHQ, the present study undertook this same analysis using the full MHQ. In addition, the relationship was examined to see if it was mediated by the differences in the scoring of males and females on each questionnaire. Our results support and strengthen Broadbent et al's conclusion that high rates of cognitive failure are associated with psychoneurotic symptoms. The sex difference on the CFQ is discussed in terms of vulnerability to stress to account for the higher incidence of psychoneurotic symptoms in females.     

Methotrexate, vinblastine, doxorubicin, and cisplatin in metastatic breast cancer. A phase II trial of the Hoosier Oncology Group

Forty-six eligible patients with metastatic breast cancer (MBC) were treated with a combination of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) as first-line chemotherapy. Of 44 patients evaluable for response, 28 (64%) had an objective response, including seven (16%) who had a complete response. The median duration of response was 4 months (range, 0 to 38 months), and the median survival from the time of entry was 14 months (range, less than 1 to greater than 45 months). Myelosuppression was the most common dose-limiting toxicity, with 54% of patients experiencing Grade 3 or 4 leukopenia (including 28% with granulocytopenic fever and one septic death), and cumulative Grade 3 anemia occurred in 28% of patients. Grades 3 to 4 stomatitis was observed in 18% of patients. An active, although highly toxic regimen when used as first-line therapy in MBC, M-VAC has a response rate and survival duration similar to existing, less toxic combination regimens. As such, M-VAC cannot be recommended in preference to other combination chemotherapy regimens in this clinical setting.     

What's new in plastic surgery?

Plastic and reconstructive surgery is benefiting from the ideas and achievements of its innovators, while at the same time exploiting collaborative efforts with private industry and with other surgical specialties. The result is better and faster problem-solving for patients with physical impairments.     

Partial denervation of the rat soleus muscle at two different developmental stages

Rat soleus muscles were partially denervated at two developmental stages. The L5 ventral ramus was sectioned in rats which were 4-6 days old, when the motor unit size of soleus muscles was still large, and at 17-19 days, when motor unit territory reached its adult value. The response of axons in the L4 ventral ramus to this procedure was then investigated. The removal of the L5 ventral ramus at 4-6 days results in an initial brief increase of motor unit size, after which the motor units retain the territory they occupied at 4-6 days. After removal of the L5 ventral ramus at 17-19 days, the L4 ventral ramus is able to expand to occupy a territory comparable in size to that of animals operated at 4-6 days. In both cases the final percentage of mean motor unit tension is two- to three-fold greater than that in normal muscles. Although the final motor unit territory is similar for both groups, it is achieved by different mechanisms. In animals operated on at 4-6 days the normal elimination of terminals does not occur, and the large neonatal motor units are retained, whereas in animals operated on at 17-19 days the peripheral field of L4 axons expands by axonal sprouting.