Response of human tumor cell lines in vitro to fractionated irradiation

The surviving fraction of human tumor cell lines after 2 Gy (SF2) varies between 0.1 and 0.8. It has been postulated that differences in inherent radiosensitivity of tumor cells are a major determinant of radiation response in vivo. Assays of inherent radiosensitivity based on acute survival are being developed as predictors of tumor response which often assume that the same inherent radiosensitivity persists throughout a fractionated treatment. We have investigated the response of 2 human tumor cell lines (A549 and MCF7) with different inherent radiosensitivities to in vitro fractionated irradiation. A549 cells had an SF2 of 0.62 and a mean inactivation dose (D) of 3.07 Gy whereas MCF7 cells had an SF2 of 0.30 and a D of 1.52 Gy. Split dose repair capacity (at equal survival levels) was less for A549 than for MCF7 cells and recovery kinetics for both cell lines were substantially longer than those of rodent cell lines. Survival after 5 fractions of 2 Gy given 12 hr apart at 37 degrees C was near to that predicted from the acute survival curve, assuming complete repair and no proliferation. Acute survival of A549 cells which survived 5 fractions of 2 Gy given 12 hr apart was similar to the acute survival of unirradiated cells. When A549 cells were incubated at 22 degrees C between 5 fractions of 2 Gy given 12 hr apart, proliferation and split dose repair were substantially inhibited. These studies support the proposals to use in vitro inherent radiosensitivity assays for the prediction of in vivo response of tumors to fractionated treatment.     

Protective effect of muramyl dipeptide analogs against infections of Pseudomonas aeruginosa or Candida albicans in mice.

Two analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide) were found to give better protection than muramyl dipeptide against intraperitoneal Pseudomonas aeruginosa infection or intravenous Candida albicans infection in mice. The analogs tested were N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine and N-acetylmuramyl-L-alpha-amino-butyryl-D-isoglutamine. The optimum treatment was 80 mg/kg per day given once daily for 4 consecutive days before infection by the intraperitoneal, intravenous, or subcutaneous route. Dose response was limited. The compounds were not orally active. Synergism was seen between N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine and gentamicin. No postinfection protection was observed. A nonspecific stimulation of macrophage cells by muramyl dipeptide analogs may contribute to the protection because antiinfective activity against Listeria monocytogenes given intraperitoneally was achieved with CBA mice.     

The management of intransigent desquamative gingivitis with Dapsone

Fifteen patients suffering from intransigent desquamative gingivitis due to lichen planus or benign mucous membrane pemphigoid were treated with dapsone (diphenylsulphapyridine) over a 3-month period. Twelve patients completed the trial. Therapeutic benefit was estimated clinically with the aid of 35mm color transparencies taken at 4-week intervals; and subjectively by the patients estimating their progress as worse, no change, some improvement or complete recovery. Taken as a whole, some 58% of patients had some benefit from therapy. Of the 7 patients with lichen planus, 1 showed complete recovery and 3 showed some improvement. In the 5 patients with desquamative gingivitis due to mucous membrane pemphigoid, 3 showed some improvement and 2 received no benefit. Three patients withdrew from the trial due to side effects of the dapsone such as headaches and nausea. It is concluded that dapsone therapy may be of some use in the management of desquamative gingivitis when traditional treatments have failed. Patients should be warned of the possibility of side effects.     

Experiences with three distinct types of total knee joint arthroplasty

Experience with three different designs of total knee systems indicates that generally excellent knee function can be afforded the majority of patients for many years. The identification of patients who presently cannot expect satisfactory long-term function (the young, muscular, or obese, yet otherwise normal, individual, for instance) and their exclusion as candidates is important for long-term success. The importance of postoperative limb alignment and component position is emphasized. Gross instability and great metaphyseal bone loss are identified as the indications for linked, primary, or revision total knee arthroplasty. The role of the dynamic behavior of trabecular bone is hypothesized to be of major importance in long-term prosthetic knee joint function.