Steroid-responsive encephalopathy associated with autoimmune thyroiditis presenting with diffusion MR imaging changes.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) presents with focal or diffuse nonenhancing MR imaging abnormalities in 50% of patients with SREAT during subacute exacerbation. Vasculitic changes in biopsy studies as well as the elevation of antithyroid antibodies and CSF protein suggests an inflammatory cause. We report the case of a patient with SREAT with changes on diffusion-weighted MR imaging, which improved with corticosteroid therapy and plasmapheresis, supporting the theory of inflammatory changes in exacerbation of presumptive SREAT.

Lack of isohemagglutinin production following minor ABO incompatible unrelated HLA mismatched umbilical cord blood transplantation.

While immune hemolysis due to donor isohemagglutinin (IH) production often complicates minor ABO incompatible peripheral blood hematopoietic stem cell transplantation (PBSCT), it is not known if this occurs with umbilical cord blood transplantation (UCBT). We compared IH production and hemolysis following minor ABO allogeneic PBSCT and UCBT. We reviewed 24 ABO minor incompatible allogeneic PBSCTs and 14 ABO minor incompatible UCBTs. Patients were evaluated for donor-derived IH by reverse ABO grouping. Evaluation of hemolysis was based on clinical and laboratory findings of anemia associated with increased RBC transfusion need, concomitant with the appearance of donor-derived IH. Of the 24 ABO minor incompatible allogeneic PBSCTs, 15 produced donor-derived IH from 6 to 88 days following transplantation, with seven of 15 patients exhibiting clinically evident hemolysis. There was no significant difference in days to leukocyte engraftment or infused CD34 cells in patients with or without donor-derived IH. None of the 14 patients receiving ABO incompatible UCBTs showed evidence of donor-derived IH following transplantation with a median follow-up of 60 days. We conclude that donor IHs are not produced in patients undergoing minor ABO incompatible UCBTs suggesting fundamental immunologic differences between allogeneic PBSCT and UCBT.

Consanguineous hemolytic uremic syndrome secondary to Escherichia coli O157:H7 infection treated with aggressive therapeutic plasma exchange.

We describe the successful management of an elderly husband and wife with Escherichia coli O157:H7 associated hemolytic uremic syndrome (HUS) treated with aggressive therapeutic plasma exchange (TPE) with replacement with fresh frozen plasma. Following twelve TPEs (three 1.5 volume; nine 1 volume), the husband's platelet count increased from 45 x 10(9)/L to 183 x 10(9)/L. Following ten 1.5 volume TPEs, the wife's platelet count increased from 30 x 10(9)/L to 193 x 10(9)/L. This is the first known occurrence of E. coli O157:H7 associated HUS in an elderly husband and wife successfully treated with aggressive TPE. We conclude that early, aggressive TPE should be considered and may be life-saving for E coli O157:H7 associated HUS in the elderly.

Pretransfusion compatibility testing for red blood cell administration.

The purpose of pretransfusion compatibility testing is to prevent incompatible red blood cell transfusions that could lead to immune mediated hemolytic transfusion reactions. Some hemolytic transfusion reactions may have serious sequelae including hemoglobinemia, disseminated intravascular coagulation, renal failure, and death. This article reviews the most comprehensive recent analyses of the laboratory methods used during pretransfusion compatibility testing in the United States. Most of the laboratory practice data have been published in the College of American Pathologists Transfusion Medicine Survey Sets and in a national survey called the Pre-Transfusion Testing Survey. This article couples and trends the data of these comprehensive surveys with an assessment of the literature to present the current practice of pretransfusion compatibility testing.

Pleomorphic liposarcoma: a clinicopathologic analysis of 19 cases.

Pleomorphic liposarcoma is a variant of liposarcoma defined morphologically by the presence of pleomorphic lipoblasts. Because of its rarity, there are limited studies with long-term follow-up information. Nineteen pleomorphic liposarcomas were studied. Unequivocal pleomorphic lipoblasts were required for inclusion. In each case, the following features were noted: tumor site; tumor size; tumor depth; predominant histologic pattern (epithelioid or malignant fibrous histiocytoma [MFH]-like); extent of necrosis (absent, less than 15%, or at least 15%); mitotic counts; treatment and clinical follow-up. Patients were 11 females and 8 males, aged 33-87 years (mean, 64.5 y; median, 70 y). Tumors involved the extremities (13 patients: intramuscular in 10, subcutaneous in 2, depth unknown in 1), retroperitoneum (4 patients), mediastinum (1 patient), and paratesticular region (1 patient). Size ranged from 4.5--31 cm (mean, 11.9 cm; median, 12.0 cm). Predominant pattern was epithelioid in 7 and MFH-like in 12. Necrosis was present in 15 (79%) and was extensive (36 15%) in 14 patients. Mitotic counts ranged from 0.2--3.4/10 high-power fields (mean, 1.4; median, 1.4) by the average-count method and from 1--6/10 high power fields by the highest count method (mean, 2.9; median, 3.0). All patients were treated surgically; 10 patients received adjuvant chemotherapy and/or radiation therapy. On follow-up of 18 patients (range, 2--129 mo; mean, 35.4 mo; median, 23 mo) nine (50%) were dead of disease (range, 2--48 mo; mean, 20.1 mo; median, 12 mo), one died of other causes 2 months after diagnosis, two were alive with disease, five were disease free, and one was alive at 129 months (tumor status unknown). Five had recurrences (range, 3--28 mo; mean, 14.4 mo; median, 8 mo), and four of five (80%) with recurrences were dead of disease. Metastases developed in eight patients (range, 4--48 mo; mean, 19.5 mo; median, 11.5 mo), most commonly to the lungs. In conclusion, pleomorphic liposarcoma is a rare tumor of adulthood that occurs most commonly in the deep, soft tissues of the extremities. It behaves as a high-grade sarcoma that frequently metastasizes, most commonly to the lungs. Although this tumor has a wide range of histologic appearances, no clinical or pathologic feature is predictive of a more aggressive clinical course.

Genetic control of pathogenic mechanisms in autoimmune demyelinating disease.

Multiple sclerosis is a disease of discrete phenotypes in different individuals. Animal models have been useful in identifying self-antigens that become the focus of autoimmune attack and genetic loci that control susceptibility to disease. We have previously demonstrated a role for Fas-dependent pathogenesis in the induction of EAE in B10.PL mice immunized with MBP. Others have indicated a Fas-independent mechanism predominates in SJL mice immunized with PLP. Here we compare the response of (B10.PLxSJL)F1 and parental mice under similar conditions for induction of EAE. The results indicate that immunodominance and dominant pathogenic mechanisms are both under genetic control, but can be inherited independently. The data also indicate that the dominant pathogenic mechanism can change during the course of disease in an individual. Elucidation of the genetic elements controlling pathogenesis during the course of disease would provide important information in designing therapeutic strategies for individuals in a heterogeneous patient population.

The role of fas ligand in vivo as a cause and regulator of pathogenesis.

Recent studies have significantly advanced our understanding of the physiological and pathogenic functions of Fas and Fas ligand (FasL) in vivo. In particular, roles for Fas-FasL interactions both in the induction and regulation of organ-specific autoimmune diseases have been defined and in some cases the specific targets and effectors of these interactions have been identified. Understanding the dynamic role of the Fas-FasL pathway in autoimmunity will provide insight into how best to modulate this interaction to achieve therapeutic benefits.

Dual role for Fas ligand in the initiation of and recovery from experimental allergic encephalomyelitis.

We have previously demonstrated a role for Fas and Fas ligand (FasL) in the pathogenesis of experimental allergic encephalomyelitis (EAE). However, using an active induction paradigm we could not distinguish between FasL expressed on activated CD4(+) T cells from that expressed on other inflammatory or resident central nervous system (CNS) cells. To address this issue, we have conducted reciprocal adoptive transfer experiments of nontransgenic or myelin basic protein-specific T cell receptor transgenic wild-type, lpr, or gld lymphocytes into congenic wild-type, lpr, and gld hosts. We found that FasL expressed on donor cells is important for the development of EAE, as FasL-deficient lymphocytes transfer attenuated disease. Furthermore, Fas expressed in the recipient animals is important for the progression of EAE, as clinical signs of disease in lpr recipients were dramatically attenuated after transfer of either wild-type or lpr T cells. Surprisingly, these experiments also identified CNS cells as a source of functional FasL. Host-derived FasL appears to be especially important in the recovery from EAE, as many gld recipients of wild-type lymphocytes develop prolonged clinical signs of disease. Thus it appears that FasL plays distinct roles in EAE during the initiation of and recovery from disease.

The role of the antigen-presenting cell in Fas-mediated direct and bystander killing: potential in vivo function of Fas in experimental allergic encephalomyelitis.

Costimulatory molecules are critical in mediating Fas-dependent direct and bystander lysis. In direct lysis, the APC is the Fas-positive target. It presents Ag to the T cell, thereby activating the T cell. The activated T cell then up-regulates FasL, allowing it to kill the APC. In bystander lysis, the APC again induces FasL expression on the T cell, but the target is a third Fas-positive cell that may lack the appropriate MHC-restricting element to activate the T cell. This study shows that ICAM-1 and B7-1 can serve as important adhesion molecules in direct killing using CD4+ T cell effectors. In bystander killing, B7-1 appears to act as a signaling molecule as well. It has been demonstrated that lpr and gld mice are less susceptible to experimental allergic encephalomyelitis than their wild-type counterparts. In this study, we show that although microglia are poor targets of direct killing, they are capable of stimulating myelin basic protein-specific T cells to kill innocent Fas-positive targets. This presents a possible mechanism for the pathogenesis of experimental allergic encephalomyelitis.

Role of Fas--FasL interactions in the pathogenesis and regulation of autoimmune demyelinating disease.

Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) represent complex processes that lead to destruction of oligodendrocytes (ODCs) and myelin. T cells are integral to the development of these diseases, but whether T cell-mediated cytolytic mechanisms are involved in the destruction of MHC Class II-negative targets, such as oligodendroglia and myelin, in the CNS is unclear. The primary lytic mechanism employed by CD4+ T cells is Fas-dependent, but can be MHC-unrestricted. Thus, T cell-mediated Fas-FasL interactions could directly contribute to the pathology of EAE and MS. This review summarizes studies from our laboratory and others that implicate Fas-FasL interactions in both the pathogenesis and regulation of demyelinating diseases.

Bizarre leiomyomas of the uterus: a comprehensive pathologic study of 24 cases with long-term follow-up.

A series of 24 bizarre (symplastic, pleomorphic) leiomyomas was analyzed to determine their spectrum of gross and microscopic features and to establish their clinical behavior by obtaining long-term follow-up. Patients' ages ranged from 25 to 51 years (mean 40.7). Maximum dimension of the tumors was about 1-14 cm (mean 4.2), with 83% measuring <5.5 cm and 8% > or = 10 cm. Grossly, the tumors generally resembled ordinary leiomyomas; one third had yellow or tan areas, two had hemorrhages, and a few had focal softening, cavitation or myxoid change. When evaluable (50%), the tumor border was generally circumscribed. Cellularity was 1+ in 21%, 2+ in 58%, and 3+ in 21%. Two tumors were predominantly of epithelioid cell type. Bizarre giant cells were unifocal in 12.5%, multifocal in 37.5%, and diffusely distributed in 50%. More than one third of the tumor contained giant cells in 67%. Degenerative changes occurred in 38%, usually hydropic change. One had infarct-type necrosis. None had tumor cell necrosis. Fibrinoid change of blood vessels occurred in 21%, usually accompanied by chronic inflammation. Mitosis counts ranged from zero to 2.8 mitotic figures (MFs)/10 high-power fields (HPFs) (mean 0.8) by the average count method. By the highest count method, the range was 0-7 MFs/10 HPFs (mean 1.6), with 13% having none and 29% having > or = 2 MFs/10 HPFs. Some pyknotic and karyorrhectic nuclei resembled abnormal MFs. Treatment was hysterectomy in 20 and myomectomy in six (including two with subsequent hysterectomy). Complete follow-up was available in 100%, ranging from 1 to 18.9 years (mean 11.2). Postoperative intervals were > or = 10 years in 58% and > or = 5 years in 83% of cases. All patients were alive and well. Although three patients subsequently developed unrelated second primary malignant neoplasms, none developed recurrence or metastasis of bizarre leiomyoma. Bizarre leiomyomas have a wider range of morphologic changes and mitotic activity than previously documented. This study firmly establishes the benign behavior of bizarre leiomyomas, even for those tumors with high cellularity, numerous widely distributed bizarre cells, and mitosis counts in the 2-7 MFs/10 HPFs range by the highest count method.