New strategies in immunosuppression

This article reviews recent papers relating to immunosuppressives and attempts to categorise the bewildering number of new reagents according to their effects on the immune response. It is apparent that the majority of groups are concentrating on reagents which, like cyclosporin A, are predominantly directed at T cells (42% of the last 200 papers inTransplantation, Transplant International andTransplantation Proceedings). The major change in strategy which is occurring relates to the rapidly increasing use of reagents directed against T cell subsets, especially those directed against the interleukin-2 receptor and CD4-positive T cells. This groups's share of the market has risen from 2% to over 12% within 5 years. New successful monoclonal antibodies include reagents directed against antigen-presenting cells and against molecules directly involved in cell adherence. The use of donor bone marrow or subsets of cells from donor bone marrow as inducers of non-reactivity, especially to solid organ grafts, is certainly one of the most exciting of the non-antibody protocols. It is encouraging that relatively specific immunosuppression can be induced in animals by combinations of specific and non-specific reagents as well as by specific reagents alone. This will facilitate the introduction of specific protocols into the human situation, and this strategy holds out great hope for the future. Unfortunately, one of the most effective ingredients of such combination therapies in animal models (anti-CD4) appears to have its tolerogenic potential abrogated by cyclosporin A and FK-506. One area of immunosuppression which is receiving scant interest relates to antibody (especially non human leucocyte antigen antibody) production, but as the interest in xenotransplantation increases it is anticipated that major new interest will emerge in this area.     

Use of the KTP-532 Laser in Acoustic Neuroma Surgery

The potassium titanyl phosphate (KTP-532) laser has been applied to otologic surgery with a proven record of both safety and efficacy. The aim of this study was to demonstrate the use, safety, and advantages of laser dissection in the surgical treatment of acoustic neuromas. The authors' experience with 111 patients in whom laser surgery was used in acoustic neuroma is presented, with emphasis on surgical technique employed and facial nerve functional outcome. The method of laser dissection did not result in deleterious neurologic sequelae or laser-specific complications. In addition, laser dissection afforded certain advantages to traditional techniques, especially in larger tumors. The facial nerve functional outcome as assessed by the House-Brackmann grading system revealed that 90.2% of small tumors, 72.2% of medium tumors, and 75.0% of large tumors achieved satisfactory (grades I and II) functional results. These results compare favorably with the literature describing nonlaser dissection techniques. The observations and results reported in this article demonstrate the safety of the KTP-532 laser in the posterior cranial fossa, and specific advantages that this technology may offer to the surgical armamentarium of the neuro-otologist are outlined.     

Role of tyrosine kinase signaling for beta-cell replication and survival

Diabetes mellitus is commonly considered as a disease of a scant beta-cell mass that fails to respond adequately to the functional demand. Tyrosine kinases may play a role for beta-cell replication, differentiation (neoformation) and survival. Transfection of beta-cells with DNA constructs coding for tyrosine kinase receptors yields a ligand-dependent increase of DNA synthesis in beta-cells. A PCR-based technique was adopted to assess the repertoire of tyrosine kinases expressed in fetal islet-like structures, adult islets or RINm5F cells. Several tyrosine kinase receptors, such as the VEGFR-2 (vascular endothelial growth factor receptor 2) and c-Kit, were found to be present in pancreatic duct cells. Because ducts are thought to harbor beta-cell precursor cells, these receptors may play a role for the neoformation of beta-cells. The Src-like tyrosine kinase mouse Gtk (previously named Bsk/Iyk) is expressed in islet cells, and was found to inhibit cell proliferation. Furthermore, it conferred decreased viability in response to cytokine exposure. Shb is a Src homology 2 domain adaptor protein which participates in tyrosine kinase signaling. Transgenic mice overexpressing Shb in beta-cells exhibit an increase in the neonatal beta-cell mass, an improved glucose homeostasis, but also decreased survival in response to cytokines and streptozotocin. It is concluded that tyrosine kinase signaling may generate multiple responses in beta-cells, involving proliferation, survival and differentiation.     

Octreotide in the treatment of thoracic duct injuries

Anecdotal reports support the use of octreotide in the treatment of traumatic thoracic duct injuries and chylothorax, but no prospective studies have proved its efficacy. We evaluated the effects of octreotide in treating thoracic duct transection in a canine model. Eight mongrel dogs (27.8+/-5.1 kg) were fed one pint of 10.5 per cent milkfat 2 hours before operation. Through a left supraclavicular neck incision, the thoracic duct was identified and transected, producing free flow of chyle. A quarter-inch drain was tunneled subcutaneously from the wound and attached to closed suction. After wound closure dogs were randomized to a control group (n = 4) receiving sham injections of saline subcutaneously three times per day, or a treatment group (n = 4) given 3 microg/kg octreotide three times per day. Postoperatively all dogs were fed a standard low-fat (5-7%) crude fat diet. Drain output was measured each day, and on odd-numbered postoperative days the drainage was analyzed for cholesterol, triglycerides, albumin, and total protein. Fistula closure was defined as drainage <10 ml/24-hour period. Treated dogs achieved fistula closure significantly faster than controls: 3.5+/-1.3 days versus 7.8+/-1.0 days (P = 0.0037). Whereas equivalent amounts of drainage occurred on the day of surgery and on postoperative day one in both groups, by postoperative day 2 the treatment group had significantly less drainage over 24 hours: 63+/-69 ml versus 195+/-79 ml (P = 0.046); this significant difference persisted through postoperative day 5 when drainage began to decrease in the control group. No significant differences between groups were seen in levels of cholesterol, triglycerides, albumin, or protein in the drainage at any time point. We conclude that octreotide is effective in treating thoracic duct injury, leading to an early decrease in drainage and early fistula closure. The mechanism for this effect remains to be clarified.     

The future of criminal violence: juveniles tried as adults

Juveniles tried as adults (JTA) represent a select and small subsample of juvenile offenders. This study seeks to provide a profile of habitually violent JTAs transferred to the adult penal system and to compare them with their adult counterparts. Twenty-nine incarcerated violent male juveniles tried as adults were compared with a sample of 27 incarcerated violent male offenders across demographic, neuropsychological, criminal history, psychopathy, and substance abuse variables. The JTAs were characterized by a high rate of gang membership (96%), substance abuse (alcohol, marijuana, and phenylcyclidene), and use of guns. In the juvenile sample, 65 percent used guns in violence not leading to arrest, and 93 percent used guns in a violent crime leading to arrest. Juvenile offenders were similar to their adult counterparts in patterns of criminality, although adult offenders had higher psychopathy scores. Both groups revealed generally intact neuropsychological functioning with the exception of a higher rate of perseverative responses in the adult sample. The results are discussed in terms of the implication of the degree of violence in a young offender population.