ATG induction therapy: long-term effects on Th1 but not on Th2 responses

Antithymocyte globulin (ATG) induction therapy is associated with an increased long-term risk of infection- and cancer-related death. To analyze long-term effects of ATG induction on lymphocyte function, we prospectively assessed CD4 helper function, B-cell/monocyte and cytokine responses in 84 renal transplant recipients (ATG, n = 44) up to 1 year post-transplant. A PWM-driven allogeneic coculture system was used to assess helper function of CD4+ T cells and T-cell-dependent B-cell responses. SAC I was used for T-cell-independent stimulation of B-cell cultures. In vitro cytokine secretion and serum soluble CD30 (sCD30) were determined by enzyme-linked immunosorbent assay (ELISA). ATG induced a persistent decrease of peripheral blood lymphocyte counts compared with non-ATG treatment because of a predominant decrease of CD4+ T cells (4 months, 1 year; P < 0.0005) which was associated with a decreased CD28 expression (1 year, P = 0.02) and CD4 cell interleukin 2 (IL-2) response (4 months, P < 0.0005). However, Th2 responses (CD4 help, CD4 cell IL-4 and IL-10 responses, sCD30), which proved to be predictive of graft outcome, were not affected, and neither was the secretion of the lymphoma growth factors IL-6 and IL-10 by B cells and monocytes. Our data show that ATG induction therapy in immunological high-risk patients induces a profound long-term decrease in cell counts and Th1 but not Th2 responses of CD4+ T cells which may explain long-term effects on infection and post-transplant lymphoproliferative disease (PTLD) incidence because of inadequate T-cell control.     

Interactions between Antinociception Induced by Cholecystokinin Antagonists and GABA Agonists in the Tail-Flick Test

Abstract: In this work, the influences of cholecystokinin receptor antagonists L-365,260, MK-329 and proglumide on antinociception induced by baclofen and GABA uptake inhibitor 4, 5, 6, 7–tetrahydroisoxazolo [4, 5-c]pyridin-3-ol (THPO) in the tail flick test has been studied. Baclofen and THPO induced antinociception in the tail flick test. Morphine, and the CCK receptor antagonists, MK-329, L-365,260 and proglumide also induced antinociception. The CCK receptor antagonists potentiated antinociceptive response induced by both baclofen and THPO. It may be concluded that cholecystokinin receptor mechanism(s) may interact with antinociception induced by GABA receptor mechanism(s).     

Thiol adducts of ethacrynic acid increase outflow facility in enucleated calf eyes.

Ethacrynic acid (ECA), a sulfhydryl (SH)-reactive diuretic drug, has been shown to increase outflow facility (C) both in living monkey eyes and in the calf eye, in vitro (Epstein et al. 1987). In an attempt to increase the therapeutic index of this drug for potential clinical use in glaucoma, we explored the effect of various thiol adducts of ECA on C in the calf eye in vitro. These adducts might be expected to liberate ECA by a reversible retro-Michael type reaction. Enucleated calf eyes were perfused at 25 degrees C at 15 mm Hg for 5 hours with various ECA-thiol adducts. ECA-cysteine at 0.25 mM (for each) increased outflow facility 104% compared to 38% in sham manipulated eyes (n-10; p less than .005). A dose response effect was demonstrated from 0.01 mM to 0.25 mM. A relative potency table (for increasing C) was established for several ECA-thiol adducts: Cysteine = cysteamine greater than glutathione greater than N-Acetyl cysteine greater than thiosalicylic acid greater than N-Acetyl cysteamine. This study identifies the potential of utilizing various derivatives of ECA as outflow pathway acting agents.     

Versatility of vertical rectus abdominis musculocutaneous flaps

The purpose of the study was to demonstrate a variety of indications for the vertical rectus abdominis musculocutaneous (VRAM) flap with respect to donor-site morbidity and alternative procedures. Fifteen VRAM flaps were performed in 15 patients during a 4-year period. The average age of patients was 58 years (range, 34-76 years). Inferiorly based VRAM flaps were used for defect coverage after tumor resection and for penile reconstruction in 7 cases. Superiorly based VRAM flaps were performed in 7 cases for reconstruction of osteocutaneous defects following sternal osteomyelitis and tumor resection. Arterial and venous "supercharging" was necessary in one case. One free VRAM flap was performed in a patient suffering from an osteocutaneous defect after resection of a malignant melanoma metastasis with infiltration of the brain and skull. The reconstructive goals were achieved in all cases using VRAM flap procedures. No total flap loss occurred. Minor complications as well as abdominal wall bulging and hernias were observed in four cases. The pedicled VRAM flap provides a reliable tool for coverage of large soft-tissue defects of the chest wall, groin, hip, and perineum even in a high-risk population, in which a safe and fast forward flap procedure is the primary reconstructive goal. Arterial and/or venous supercharging may be necessary, particularly in superiorly based VRAM flaps. An inferiorly based VRAM flap is a reliable tool for phalloplasty under special circumstances. The indication for free VRAM flaps is given in rare clinical situations. Stabilization of the donor site using artificial mesh is highly recommended.