Pitfalls of pedicle screw fixation in the sacrum. A cadaver model.

Five male cadavers were used to evaluate anatomically structures at risk using sacral pedicle screw fixation. Risk was defined as the likelihood of penetration by K-wires placed through the pedicles and cortices at the S1, S2, and S3 levels. A scale based on the distance from the wire to the vital structure was developed to quantify risk. Instrument insertion techniques were classified as direct and lateral. The direct technique at S1 placed the left common iliac vein and the sympathetic chain at high risk. The sympathetic chain was also at high risk at the S2 and S3 levels. The lateral technique placed the lumbosacral trunk at high risk at the S1 level, as well as the S1 nerve root with screw placement at the S2 level. Anterior cortical penetration during sacral pedicle screw fixation places anatomic structures at variable risk depending on the technique used.

Effects of treatment with immunomodulatory drugs on thymus and spleen lymphocyte subpopulations and serum corticosterone levels.

Immunofluorescence was used to characterize the lymphocyte subpopulations of mice treated with six immunomodulatory drugs: hydrocortisone acetate (HCA), corticosterone acetate (corticosterone), cyclophosphamide, cytosine arabinoside (Ara-C), 15(S)-methyl prostaglandin E1 (15(S)-methyl PGE1), and 2-amino-5-bromo-6-phenyl-4-(3H)-pyrimidinone (ABPP). The number of thymus and spleen cells bearing Thy-1, Ig, Lyt-1 and Lyt-2 antigens and the density of the antigens on each cell (IF profiles) were determined. Microscopic examination of cells stained with rhodamine-labeled anti-Lyt-2 and fluorescein-labeled anti-Lyt-1 was used to measure the proportion of Lyt-1+2-, Lyt-1+2+, and Lyt-1-2+ cells in the spleen and thymus of drug-treated animals. The changes in lymphocyte subpopulations were compared with the varied effects of these drugs on antibody formation and graft vs host (GVH) reaction. Three immunosuppressive drugs, HCA, cyclophosphamide, and Ara-C, depleted the thymus of cells expressing a large quantity of Thy-1. The drug-resistant cells were larger and had more Lyt-1 than cells from control animals. HCA treatment depleted the thymus of Lyt-1+2+ cells; the cortisone resistant cells were primarily Lyt-1+2-. Cyclophosphamide and the antiviral immunostimulant, ABPP, caused similar, but less marked, alterations. The proportion of Lyt-1-2+ cells in the thymus was reduced by treatment with all the drugs, but the density of Lyt-2 on the drug-resistant cells was not altered. Treatment with Ara-C or 15(S)-methyl PGE1 produced a very modest evaluation in Lyt-1+2- cells. 15(S)-Methyl PGE1, which suppresses some immuno-inflammatory reactions, had no discernible effect on thymocyte size or the IF profile of Thy-1, Lyt-1, or Lyt-2. In the spleen, the amount of Thy-1 and of immunoglobulin on cells bearing these markers was changed very little by drug treatment. The proportion of splenic B cells was diminished by treatment with cyclophosphamide and, to a lesser extent, by HCA, while the proportion of spleen cells bearing detectable Thy-1 and Lyt-1 increased correspondingly. The proportion of cells bearing Lyt-2 was altered by only two drugs; cyclophosphamide increased both Lyt-1+2+ and Lyt-1-2+ spleen cells and ABPP (an interferon inducer which stimulates antibody formation) decreased both Lyt-2+ subpopulations. Treatment with two drugs caused the serum corticosterone concentration to rise: ABPP increased serum corticosterone substantially while the prostaglandin induced a smaller and more transitory increase. An indirect mechanism, via corticosteroid release, might explain the thymic depletion observed in mice treated with 15(S)-methyl PGE1 and ABPP, but neither the suppression of the GVH reaction by these drugs nor polyclonal activation of B cells by ABPP can be attributed to endogenous corticosteroids. Our data show that enumeration of splenic lymphocyte subpopulations by immunofluorescence techniques may aid in elucidating the mode of action of immunomodulatory drugs.

Membrane fluidity and cholesterol in thymus and spleen cells from mice treated with immunomodulatory drugs.

We have used spin labeling, fluorescence polarization, and chemical analysis to characterize membrane properties of thymocytes from mice treated with immunomodulatory drugs. The number of thymocytes was reduced 90-95% by treatment of 6-9 week old mice with hydrocortisone acetate (HCA) or methylprednisolone (both 125 mg/kg) or with cyclophosphamide (250 mg/kg). Electron spin resonance (esr) examination of thymocytes labeled with 5-nitroxyl stearic acid indicated that the membranes of cells remaining after treatment with any of these drugs were more rigid than those from saline-treated controls. The total cholesterol/phospholipid (C/PL) molar ratio of the HCA-resistant thymocytes was twice that of the control mice. Treatment of mice with other immunomodulatory drugs, cyclophosphamide, cytosine arabinoside (Ara-C), 2-amino-5-bromo-6-phenyl-4-(3H)-pyrimidinone (ABPP) and 15(S)-methyl prostaglandin E1 (15(S)-methyl PGE1), also altered the C/PL ratio in thymocytes and, in some cases, in spleen cells. Fluorescence polarization measurements of thymocytes labeled with 1,6-diphenyl-1,3,5-hexatriene (DPH) did not reveal the differences between cells from HCA-and saline-treated mice that were detected by spin labeling and chemical analysis. Our results indicate that the greater rigidity detected by spin labeling of hydrocortisone-resistant thymocytes may be due, at least in part, to greater membrane cholesterol content. Of the methods employed, chemical analysis was the most sensitive in revealing drug-induced alterations in thymocyte populations.