A comprehensive technique was developed for continuous electrophysiological monitoring of intrinsic brain stem motor function during surgery to remove space-occupying lesions in the fourth ventricle and brain stem. The technique is analogous to that used during surgery in the cerebellopontine angle; motor nuclei and peripheral pontine fiber tracts of Cranial Nerves III-XII are identified by the electrical stimulation of structures in the operative field and the evaluation of the compound muscle action potentials recorded from the corresponding muscles of the head. Nerve function is monitored continuously by recording the ongoing electromyographic activity in these same muscles. Broadcasting electromyographic responses through a loudspeaker gives the surgeon immediate feedback on the status of the motor nuclei being monitored. Advantages of this technique include 1) the positive, objective identification of the nuclei and fiber tracts; 2) the continuous feedback on the status of these structures; 3) a safe approach through the fourth ventricle to the lesions in the brain stem; 4) the positive identification of the boundaries between the neoplasm and the motor structures of the rhomboid fossa; and 5) a warning to the surgeon of potentially harmful nerve manipulations (contact, dissection, transection) during surgery. After this technique was used in 16 consecutive operations to remove cavernomas (n = 9), gliomas (n = 4), and other types of tumors (n = 3), surgical and neurological results showed the method to be reliable and simple to perform.
Circulating BMZ antibodies are significantly associated with chronic GvHD in contrast to uncomplicated HCT. Recurrent mucocutaneous lesions in chronic inflammatory skin disorders may liberate antigens, which may lead to production of BMZ antibodies, particularly in the context of GvHD-mediated reduced self-tolerance.
The successful engraftment in SCID mice of intraperitoneally (i.p.) injected human lymphocytes (hu-PBL-SCID) and the failure of intravenously injected peripheral blood lymphocytes (PBL) directed the present study to investigate the early events of donor cell proliferation in the peritoneal cavity. We found focal lymphocyte engraftment together with histio-monocytic interleukin (IL)-6+ cell phenotypes which must have been transferred with the human cell inoculum, which could explain certain immune functions observed in hu-PBL-SCID chimeras. Following i.p. injection of 10(8) PBL, human cells suspended in peritoneal fluid as well as those adherent to the serosal peritoneum and abdominal organs were investigated by immunocytology and immunohistology. Human cells were found to form foci consisting predominantly of proliferating human lymphoblastoid CD3+ cells, which were mostly activated HLA-DR+ CD8+ lymphocytes. Among the lymphoid cells larger epithelioid-like cells were found to belong to the monocytic series and to stain strongly with anti-HLA-DR and anti-CD11c antibodies. Some of these cells were also positive with anti-ICAM and anti-IL-6. Congenic as well as allogeneic mouse PBL, injected i.p. into SCID mice, temporarily produced analogous foci, which shifted later on to foci similar in appearance to milky spots. However, the human cell foci appeared less compact, more closely resembling in vitro-culture soft agar colonies. It is possible that cytokines in the human histio-monocytic cells of the foci may have a feeder effect on the human lymphocytes and be a prerequisite for proliferation of human PBL in SCID mice. The observed early HLA-DR activation of human lymphocytes in the peritoneal foci could reflect triggering of immune reactions like xenogeneic graft-versus-host reactions in the peritoneal site, where the human CD11c+ HLA-DR+ histio-monocytic cells may act as antigen-presenting cells.
This new approach significantly reduces surgical traumatization and destabilization of adjacent motion segments. An endoscopic operating sheath, adopted from thoracoscopic surgery, creates space for visualization and surgical manipulations. The newly defined anatomic landmarks provide guidance to the screw entry point into the pedicle in the center of the exposure. Observation of the exact corresponding angles of convergence during screw insertion by an inclinometer facilitates correct screw placement. In accordance with the initial anatomic studies, this approach was successfully performed on 12 cadavers and then used in six patients. Two illustrative cases are presented.
Surprisingly little graft-versus-host disease (GVHD) has been observed in severe combined immunodeficient (SCID) mice injected intraperitoneally (IP) with human blood lymphocytes (hu-PBL-SCID), which raised the question as to whether GVHD in such a distant species is sporadic or suppressed because of immunologic reasons. After screening for blood T-cell chimerism, we hereby describe generalized lethal xenogeneic human GVHD in unconditioned SCID chimeras, which resembles GVHD in SCID mice injected with allogeneic lymphocytes. We adapted an immunocytochemical slide method for minute cell numbers, which allowed us to follow, by multimarker phenotyping of weekly mouse- tail bleeds, the chimeric status of 100 hu-PBL-SCID injected with 10(7) or 10(8) hu-PBL of Epstein-Barr virus- (EBV-) donors. More than half of the mice showed no or less than 2% T cells. However, 13% to 21% developed substantial blood T-lymphocyte chimerism (10% to 80% human CD+ cells) and high mortality. Immunohistology showed more human CD8+ than CD4+ T cells in the splenic white pulp. The cells developed HLA-DR activation markers and infiltrated the red pulp where human B cells also appeared. Expression of activation and proliferation markers increased within 5 to 6 weeks. Many human CD3+ cells were also found in the portal triads of the liver and in the lung, pancreas, and kidney. The thymus also became heavily infiltrated. The intestines and skin of hu-PBL-SCID were less infiltrated by donor cells than in SCID with allogeneic GVHD. The tongue contained almost no human T cells. Our data show that a relatively low overall incidence of human xenogeneic GVHD, even when high numbers of human PBL are injected, is the consequence of a dichotomy between mice with no or transient T-cell chimerism and a minority of mice with high-blood T-lymphocyte chimerism and GVHD mortality.
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