Perioperative evaluation of carotid endarterectomy by 3D-CT angiography with refined reconstruction: preliminary experience of CEA without conventional angiography.

Three-dimensional CT angiography (3D-CTA) was employed for perioperative evaluation of carotid endarterectomy (CEA) as an alternative to conventional angiography. A total of 62 carotid arteries were examined before and after CEA, 26 with an early 3D-CT system and 36 with multidetector helical CT allowing sophisticated reconstruction by a personal workstation. In addition to patients who had undergone conventional angiography at other institutes, 10 subjects underwent CEA on the basis of 3D-CTA findings alone. The findings provided detailed information with an excellent view of carotid stenoses. Volume rendering images comprehensively visualized lesions and surrounding structures as well as calcifications, which were also well depicted by maximum intensity projection images. Evaluation of the cerebral circulation is one problem that still requires solution, although cerebral vessels were delineated by 3D-CTA. One patient experienced transient hemiparesis, but no significant permanent deficit. We conclude that 3D-CTA is a safe and accurate modality that is a practical alternative to conventional perioperative angiography.

Dissociation of hemopoietic chimerism and allograft tolerance after allogeneic bone marrow transplantation.

Creation of stable hemopoietic chimerism has been considered to be a prerequisite for allograft tolerance after bone marrow transplantation (BMT). In this study, we demonstrated that allogeneic BMT with bone marrow cells (BMC) prepared from either knockout mice deficient in both CD4 and CD8 T cells or CD3E-transgenic mice lacking both T cells and NK cells maintained a high degree of chimerism, but failed to induce tolerance to donor-specific wild-type skin grafts. Lymphocytes from mice reconstituted with T cell-deficient BMC proliferated when they were injected into irradiated donor strain mice, whereas lymphocytes from mice reconstituted with wild-type BMC were unresponsive to donor alloantigens. Donor-specific allograft tolerance was restored when donor-type T cells were adoptively transferred to recipient mice given T cell-deficient BMC. These results show that donor T cell engraftment is required for induction of allograft tolerance, but not for creation of continuous hemopoietic chimerism after allogeneic BMT, and that a high degree of chimerism is not necessarily associated with specific allograft tolerance.

Donor T cells are not required for induction of allograft tolerance in mice treated with antilymphocyte serum, rapamycin, and donor bone marrow cells.

BACKGROUND: Postgraft infusion of donor bone marrow cells (BMC) effectively induces tolerance to skin allografts in antilymphocyte serum- and rapamycin-treated recipients in fully major histocompatibility complex-mismatched mouse strain combinations. We used various gene knockout mice to examine the role of donor T cells and B cells in BMC-induced allograft tolerance. METHODS: All recipient mice received ALS on days -1 and 2 and rapamycin (6 mg/kg) on day 7 relative to fully major histocompatibility complex-mismatched skin grafting on day 0. Donor BMC prepared either from mice lacking CD4- and/or CD8a-, or CD3epsilon-expressing cells or B cells, or from corresponding wildtype mice, were given on day 7. The level and phenotypes of chimerism was determined by flow cytometry. RESULTS: All T cell- and B cell-deficient BMC were as effective as wild-type BMC in inducing prolongation of skin graft survival. A low degree of chimerism without donor type T cells was detected in tolerant mice given T cell-deficient BMC or wild-type BMC 60 days after transplantation. Chimeric cells were composed of B cells and macrophages/monocytes. Low level chimerism without donor T or B cells was also present in tolerant mice given B cell-deficient BMC. CONCLUSION: Donor type T cells and T cell chimerism are not required for induction of allograft tolerance by the antilymphocyte serum/rapamycin/donor BMC-infusion protocol. Donor B cells also do not participate in tolerance induction. Thus, infusion of T cell-depleted BMC in conjunction with conventional immunosuppressive regimens will be a simple, safe, and effective way to induce allograft tolerance in clinical organ transplantation.

Establishment of stable multilineage hematopoietic chimerism and donor-specific tolerance without irradiation.

BACKGROUND: Induction of tolerance to organ transplants will increase graft survival and decrease patient mortality and morbidity. Radiation-induced cytoreduction/ablation followed by donor hematopoietic cell reconstitution has been the most consistently successful approach to experimental tolerance induction. However, reluctance of clinicians to expose recipients to radiation has hampered its clinical application. METHODS: In the studies described, administration of polyclonal antilymphocyte serum (ALS), donor-specific bone marrow (DSBM) (150x10(6) cells), and sirolimus (24 mg/kg) in a completely mismatched murine model (B10.A donor, C57B/10 recipient) produced 100% indefinite (>250 days) skin graft survival. The level and character of donor-specific chimerism was evaluated with flow cytometry. RESULTS: Specific tolerance was confirmed by continued acceptance of primary and secondary donor-specific skin allografts and rejection of third-party grafts. The level and duration of chimerism induced was directly related to the dose of DSBM administered. Mice given 150x10(6) DSBM cells showed levels of 8-10% donor peripheral blood mononuclear cell chimerism by 30 days, and these levels persisted indefinitely (>250 days) in association with permanent tolerance of donor grafts. Eighty percent of donor chimeric cells were B lymphocytes (MHC class I and II positive, Fc receptor positive, CD45/B220 positive but negative for CD4, CD8 and Thy 1.2) and 20% were sorted in the macrophage monocyte population. CONCLUSIONS: These studies demonstrate for the first time that cytoreduction/ablation with ALS combined with sirolimus and reconstitution with donor bone marrow induces tolerance and chimerism in a completely mismatched murine combination. The use of ALS and sirolimus, currently employed therapies in clinical transplantation, and the lack of requirement for radiation make this tolerance protocol attractive for clinical application.

Donor MHC class II antigen is essential for induction of transplantation tolerance by bone marrow cells.

Posttransplant infusion of donor bone marrow cells (BMC) induces tolerance to allografts in adult mice, dogs, nonhuman primates, and probably humans. Here we used a mouse skin allograft model and an allogeneic radiation chimera model to examine the role of MHC Ags in tolerance induction. Infusion of MHC class II Ag-deficient (CIID) BMC failed to prolong C57BL/6 (B6) skin grafts in ALS- and rapamycin-treated B10.A mice, whereas wild-type B6 or MHC class I Ag-deficient BMC induced prolongation. Removal of class II Ag-bearing cells from donor BMC markedly reduced the tolerogenic effect compared with untreated BMC, although graft survival was significantly longer in mice given depleted BMC than that in control mice given no BMC. Infusion of CIID BMC into irradiated syngeneic B6 or allogeneic B10.A mice produced normal lymphoid cell reconstitution including CD4+ T cells except for the absence of class II Ag-positive cells. However, irradiated B10.A mice reconstituted with CIID BMC rejected all B6 and a majority of CIID skin grafts despite continued maintenance of high degree chimerism. B10.A mice reconstituted with B6 BMC maintained chimerism and accepted both B6 and CIID skin grafts. Thus, expression of MHC class II Ag on BMC is essential for allograft tolerance induction and peripheral chimerism with cells deficient in class II Ag does not guarantee allograft acceptance.

Crossed cerebellar hyperperfusion in symptomatic epilepsy--two case reports.

A 74-year-old female with cerebral infarction and a 78-year-old female with cerebral glioblastoma suffered complex partial seizure. Ictal perfusion single photon emission computed tomography in these patients showed the interesting phenomenon of 'crossed cerebellar hyperperfusion,' a reversed crossed cerebellar diaschisis. The mechanism is probably spread of electrical seizure through efferent projections, and may be related to the cerebellar atrophy seen in patients with long-standing partial epilepsy.

Visual disturbance by lymphocytic hypophysitis in a non-pregnant woman with systemic lupus erythematosus.

The authors present the case of a patient with systemic lupus erythematosus who developed visual disturbance and amenorrhea. Though the clinical and radiological findings resembled those of pituitary adenoma, the patient was finally diagnosed as having lymphocytic hypophysitis after the operation. We briefly describe this relatively rare entity in relation to its autoimmune pathogenesis.

[A case of rhinocerebral mucormycosis presenting orbital apex syndrome].

A 62-year-old man with untreated diabetes complained of diplopia and headache. Neurological examination demonstrated left abducens nerve palsy. MRI showed a mass lesion in the left orbital apex. Total left ophthalmoplegia and visual loss rapidly developed in the next two weeks. A craniotomy was performed to decompress the orbital apex and remove the mass. The optic nerve was tightly encased by fibrous tissue. The pathological diagnosis was mucormycosis. Systemic administration of amphotericin B and fluconazole was started immediately. But the lesion rapidly invaded the cavernous sinus and occluded the left internal carotid artery. Finally, the patient died with intracranial extension of mucormycosis four months after the operation. Rhinocerebral mucormycosis is a rapidly progressive fatal disease. Successful treatment seems to be based on early diagnosis, control of the underlying disease, radical surgical resection, and systemic administration of amphotericin B. Mucormycosis should be considered as a differential diagnosis of orbital apex syndrome.

Intravenously administered macrophage colony-stimulating factor (M-CSF) specifically acts on the spleen, resulting in the increasing and activating spleen macrophages for cytokine production in mice.

IL-6 was transiently expressed in sera of mice after a bolus intravenous injection with LPS and it peaked 2 h later. Intravenous administration of M-CSF at 250 micrograms/kg/day for 5 days prior to an injection of 25 micrograms/kg of LPS elevated the serum IL-6 level 10-fold higher than that of mice which were not given M-CSF. Although M-CSF had no effect on the number of macrophages in alveoli and peritoneal cavity, it tripled the number of spleen macrophages and increased macrophage-progenitor cells 7-fold when injected intravenously. Spleen macrophages from M-CSF-injected mice produced 5-fold more IL-6 in response to LPS-stimulation in-vitro. However, M-CSF-injection had lesser effects on LPS-induced IL-6 production from liver, alveolar and peritoneal macrophages. Exogenously administered M-CSF was detected at higher concentration and for longer duration in the spleen than in any other organs examined. Spleen macrophages incubated in-vitro with more than 1000 U/ml of M-CSF for 3 days also produced more LPS-induced IL-6 than untreated cells. These results indicate that intravenously administered M-CSF not only enhances macrophage development in the spleen, but also primes mature macrophages for cytokine production.

Pure amnesia caused by bilateral temporal lobe astrocytoma--case report.

A 32-year-old male presented with progressive pure amnesia caused by astrocytoma invading the bilateral medial temporal lobes. Methionine positron emission tomography demonstrated the extent of tumor invasion well. His memory impairment was partially improved by treatment for the astrocytoma. Lesion of the bilateral hippocampus causes memory impairment, but pure memory loss without other associated neurological sign or deterioration of consciousness is rare in a case of cerebral neoplasm.

Apophysitis of the acromion.

We treated three patients with apophysitis of the acromion. These patients were two male athletes 12 and 14 years of age, respectively, and one female athlete 13 years of age. They reported pain at the top of the shoulder during and after shoulder movement while playing sports but had no rest pain or disturbance of daily activities. Physical examination demonstrated marked local tenderness at the acromion and slight warmth. X-ray films showed sclerosis and irregularity of the secondary ossification center of the acromion. Bone scintigraphy carried out on one patient demonstrated increased uptake in that region. Conservative treatment was used for these patients. Recovery was gradual but satisfactory.

Effect of recombinant human macrophage-colony stimulating factor on marrow, splenic, and peripheral hematopoietic progenitor cells in mice.

The effects of human macrophage colony-stimulating factor (M-CSF) on marrow, splenic, and peripheral progenitor cells (CFU-M, CFU-GM, and CFU-G) were investigated in mice administered recombinant human M-CSF (8-4,000 micrograms/kg). Single injection of 4,000 micrograms/kg of M-CSF resulted in a decrease in the number of marrow progenitor cells (CFU-M, CFU-GM, and CFU-G) on day 2 followed by a gradual increase, returning to the original level on day 4 or 5. In contrast, each type of splenic progenitors tested for started to increase markedly on day 2, reaching a level 4- to 15-fold higher than that of the basal value on day 3 or 4. Peripheral CFU-M, CFU-GM, and CFU-G also increased on day 2. In addition, administration of 800 micrograms/kg of M-CSF in mice caused a decrease in marrow CFU-G, as well as an increase in splenic CFU-G. The present results indicate that treatments of mice with pharmacological concentrations of human M-CSF affect the number of progenitor cells not only of monocyte/macrophage lineage but also of granulocyte lineage. Also, the coincidence between decrease of marrow progenitor cells and increase of splenic and peripheral progenitor cells suggests that the progenitor cells are released from bone marrow to peripheral blood and reseeded to the spleen by the action of M-CSF.

[Roles of the sympathetic nervous system in the local release of vasoactive intestinal polypeptide (VIP) from the small intestine of anesthetized dogs].

To investigate roles of the sympathetic nervous system in the local release of VIP, pharmacological alpha (phenoxybenzamine), beta (propranolol) adrenergic blockade or surgical sympathectomy by the ganglionectomy of splanchnic plexus was performed in anesthetized dogs. Portal and venous plasma VIP levels during intrajejunal infusion of 0.1 N HCl solution at a rate 1.5 ml/min for 20 minutes were observed before and after these procedures. The plasma VIP levels during the intrajejunal HCl infusion were significantly increased after blocking of alpha-adrenoceptors and surgical sympathectomy but showed no change after blocking of beta-adrenoceptors. These results suggest the inhibitory mechanism of the sympathetic nervous system on the local release of VIP from the canine small intestine. In addition, the increase of portal blood flow and bile secretion, and the elevation of bicarbonate concentration in the secreted bile during the intrajejunal HCl infusion were significantly higher after surgical sympathectomy than before, and plasma VIP levels were also significantly higher.

Serum neuron-specific enolase levels after subarachnoid hemorrhage.

We examined serum levels of neuron-specific enolase by enzyme immunoassay in 29 patients with subarachnoid hemorrhage due to ruptured cerebral aneurysm. Serum neuron-specific enolase levels were significantly higher in patients with a poor neurological status than in patients with a good neurological status on admission, and the greater the amount of subarachnoid blood, the higher the serum neuron-specific enolase level. Patients with a good outcome had low serum neuron-specific enolase levels throughout their courses. Serum neuron-specific enolase levels increased with development of delayed ischemic neurological deficits and, especially in poor outcome patients, high levels persisted until 3 weeks after the subarachnoid hemorrhage.