Treatment of an established graft-versus-host reaction in AKR mice by adoptive immunotherapy.

A model system in AKR mice for the induction and cure of a clinically evident graft-versus-host disease is reported. Graft-versus-host disease is inititated by i.p. injections of ecyclophosphamide (250 mg/kg body weitht ) into female AKR mice, on Day 0. This is followed by i.v. injections of 45 x 10-6 normal spleen cells (NSC) from male C57BL/6J mice. Median survival time for these mice is 33.4 plus or minus 4.5 days. Following the administration of C57BL/6J NSC, AKR mice were rescued from graft-versus-host disease by the following treatment protocol: (a) Day 6, 35 x 10-6 DBA/2 NSC given i.v.; (b) Day 10, cyclophosphamide i.p. (150 mg/kg body weight); (c) Days 11 and 26, 35 x 10-6 AKR NSC given i.v. These experiments demonstrate that graft-versus-host reaction can be elminiated by coupling a graft-versus-host reaction with a graft-versus-graft reaction and restoring the host by immunocompetent syngeneic cells.

Graft versus leukemia without fatal graft-versus-host disease in AKR mice.

BW 5147 leukemia in AKR mice has been successfully treated by adoptive immunotherapy using allogeneic spleen cells from C57BL/6J mice. Graft-versus-host reaction was prevented by treatment with spleen cells from a second allogeneic strain (CBA, H-2 identical with AKR), followed by cycloposphamide and syngeneic spleen cells. Successful treatment of leukemia without graft-versus-host reaction is dependent upon a close relationship at the H-2 locus between the second allogeneic donor and the host AKR mice, since cells from a non-H-2 identical donor (DBA/2) do not increase survival. The doses of cyclophosphamide and of C57BL/6J spleen cells are also parameters of critical importance in successful treatment.

Further development of a successful protocol of graft versus leukemia without fatal graft-versus-host disease in AKR mice.

We previously reported a successful model for treatment of BW 5147 leukemia in AKR mice by adoptive immunotherapy using allogeneic spleen cells from C57BL/6 mice. The leukemia cells were given 3 days before initiation of therapy. Graft-versus-host reaction was prevented by treatment with spleen cells from a second allogeneic strain (CBA), followed by cyclophosphamide and syngeneic spleen cells. We now show that it is not necessary to use syngeneic spleen cells in the final transplant since H-2-compatible, allogeneic CBA cells are as effective. In addition, it is possible to initiate successful therapy 5 days after leukemia implantation providing that the initial cyclophosphamide, given in two doses of 100 mg/kg each and spaced 7 days apart, is administered prior to establishment of graft-versus-host reaction. Higher single doses of drugs were followed by fatal graft-versus-host disease.

Steroid-dependent nephrotic syndrome in lupus nephritis. Response to chlorambucil.

Nephrotic syndrome associated with mesangial lupus nephritis developed in a young woman. The heavy proteinuria exhibited a striking steroid-dependent course during a three-year period of time, with ten relapses occurring whenever attempts were made to withdraw prednisone therapy. A prolonged remission was induced by the administration of chlorambucil.

Sarcoid granulomatous nephritis occurring as isolated renal failure.

A woman had clinically isolated renal failure caused by granulomatous sarcoid nephritis. At the onset of her illness, there were no historical, physical, or clinical features to suggest a definite causative diagnosis. After a renal biopsy specimen disclosed noncaseating epithelioid granulomas, a course of steroid therapy resulted in prompt disappearance of uremic symptoms and amelioration of her renal failure. Although leukopenia, delayed cellular immunity, and the response to steroids increased the suspicion that the patient had sarcoidosis, it was not until identical granulomas were obtained via mediastinal node biopsy that the diagnosis was confirmed. Sarcoidosis may occur as isolated renal failure. Renal biopsy is indicated to ensure early diagnosis and prompt treatment of this steroid-responsive lesions.

Crescentic IgA nephropathy.

We report five cases of crescentic IgA nephropathy. All are males, 16-60 years of age. One case each came to medical attention with uremia, nephrotic syndrome, and gross hematuria; two cases presented with microhematuria and proteinuria on routine urinalysis. All had hypertension, azotemia (serum creatinine 1.6-9.4 mg/dl), proteinuria (greater than 6 g/24 hr in four cases), hypoalbuminemia (less than 3 g/dl), and hematuria (gross in two cases). All progressed to end-stage renal failure renal failure ending in dialysis (three cases) or death from unrelated causes (two cases). Prednisone, 60 mg/day for 1 month in two patients (with two 1-g doses of iv methylprednisolone in 1 case) did not improve the serum creatinine level, but one patient subsequently experienced a less rapid fall in renal function. A crescentic glomerulonephritis was present in all biopsies (crescents in 31-80% of glomeruli; mean, 50%). The size and stage of the crescents were variable. Numerous glomeruli had focal or diffuse sclerosis. In all cases, there was a 3 or 4+ deposition of IgA. Low-intensity staining for IgG and IgM was noted in four and three patients, respectively. On electron microscopy, dense granular mesangial deposits were noted in all cases and in four patients capillary subepithelial deposits were also observed. This form of IgA nephropathy is not common, but some studies indicate that it may occur in about 5% of patients with IgA nephropathy.

Fibrillary (immunotactoid) glomerulopathy. A possible role for kappa light chain in its etiology and/or pathogenesis.

The initial clinical manifestations, course, and immunopathologic findings of renal biopsies of nine patients with fibrillary glomerulopathy are reported. Their first symptoms and courses were variable, but proteinuria and renal failure were common. While some patients required hemodialysis soon after coming for treatment, others progressed to renal failure over several years. Three patients had monoclonal gammopathy; one of them had an isolated, transient, Bence-Jones proteinuria. The main pathologic features are glomerular enlargement, mesangial expansion, and mild hypercellularity. Congo red and thioflavin stains were negative. Kappa chain, either alone or with lambda chain and IgG, were the predominant immunoreactants. Ultrastructurally, the presence of coarse fibrils of 15-25 nm was characteristic, but there were also granular deposits in the capillary wall that occurred in a band-like pattern in the inner half of the glomerular basement membrane in a manner similar to the deposits seen in light chain deposit disease. The immunofluorescence and ultrastructural findings suggest that light chains (especially kappa) may be significant in the pathogenesis of fibrillary glomerulopathy and that there may be a relationship with light chain deposit disease.

Renal parenchymal malakoplakia. Histologic spectrum and its relationship to megalocytic interstitial nephritis and xanthogranulomatous pyelonephritis.

We report five cases of renal parenchymal malakoplakia. They represent a histologic spectrum of this uncommon inflammatory process as it involves the renal parenchyma. Only one of these five cases presented the classical histologic picture of malakoplakia ("diagnostic stage"). Two cases--although with similar cellular infiltrate--had a marked paucity of Michaelis-Gutmann bodies and thus might have been classified as megalocytic interstitial nephritis were it not for the identification of such calcific intracellular inclusions under the electron microscope. The fourth case presented a pseudosarcomatous morphology and is similar to what has been described as a late or fibrous stage in malakoplakia of the urinary bladder. The last case had a destructive, frankly granulomatous histologic picture with a preponderance of foamy histiocytes reminiscent of xanthogranulomatous pyelonephritis, but with clusters of von Kossa-positive Michaelis-Gutmann bodies. The last two forms of the disease have not been previously reported to occur in the kidney. We believe that these cases represent various stages of development of the disease.

Systemic mast cell disease presenting with peripheral blood eosinophilia.

Patients with mast cell disease most frequently present with skin lesions (urticaria pigmentosa), with systemic involvement in many cases. However, a small subset of patients with systemic mast cell disease lacks skin lesions and, in these patients the correct diagnosis may be difficult to establish. Patients with systemic mast cell disease commonly have hematologic abnormalities, including eosinophilia in up to 20% of cases, but isolated eosinophilia has been reported rarely. We describe an 82-year-old woman who was admitted to Rhode Island Hospital for coronary artery disease and unstable angina. Incidentally, an absolute eosinophil count of 7.84 x 10(9)/L (normal, < 0.45 x 10(9)/L) was detected with moderate thrombocytopenia and mild anemia. Review of earlier records revealed that absolute eosinophilia had been present for approximately 4 months, initially without other hematologic abnormalities. Clinical work-up showed left upper quadrant tenderness. No skin lesions were identified. Bone marrow core biopsy revealed paratrabecular, perivascular, and medullary mast cell aggregates with eosinophils, suggestive of mast cell disease. At autopsy the diagnosis was confirmed. Mast cell aggregates were found in the liver, spleen, lymph nodes, and bone marrow, and chloroacetate esterase stain highlighted mast cell granules. The bone marrow was also hypercellular with granulocytic and eosinophilic hyperplasia, suggestive of a poorly defined myeloproliferative disorder. Patients with systemic mast cell disease initially may present with peripheral eosinophilia. Clinical suspicion of the diagnosis facilitates proper handling of the bone marrow core biopsy specimen to allow the demonstration of mast cell granules.

Percutaneous large bore venotomy and tract creation: comparison of sequential dilator and angioplasty balloon methods in a porcine model. Preliminary report.

We used a pig model to evaluate the pathologic changes that occur during large caliber percutaneous venotomy and tract creation such as is necessary to deliver the Greenfield vena caval filter. Four sequential dilator and four angioplasty balloon tract creations were performed on eight external jugular veins in four adult pigs. Gross and microscopic evaluations of the veins and surrounding tissue followed the procedures. Morphometric measurements based on extent and severity of pathologic changes in the specimens were graded from 0 (normal) to 3 (severe and/or extensive). We found that while either technique entailed damage to the veins, the sequential dilator method produced substantially more smooth muscle stretching and tearing and disruption of the internal elastica. There also was greater perivascular and intramural hemorrhage. These changes extended as far distally as the catheters and sheaths were advanced. While the number of experimental samples is too small to allow valid statistical analysis, our results suggest that the angioplasty balloon technique may be superior for tract and venotomy creation. Furthermore, large sheaths should be advanced only enough to maintain venous access to limit the extent of potential venous damage.

Arteriosclerosis obliterans in a rabbit model.

RATIONALE AND OBJECTIVES: The authors induced atherosclerotic occlusions in a rabbit model, using and comparing different experimental methods. METHODS: Lesions were induced in 40 femoral arteries in 20 rabbits. Four combinations of lesion induction methods were used: 1) drying of the endothelium with carbon dioxide gas; 2) gas-drying of the artery plus mechanical injury; 3) gas-drying plus induced thrombosis of the treated segment using thrombin; and 4) gas-drying, mechanical injury, and induced thrombosis. All rabbits were fed a high-fat, high-cholesterol diet for 1 to 2 months after lesion induction. RESULTS: Seventeen rabbits were available for follow-up. Sixty-eight percent (13 of 19) of femoral arteries treated with thrombin-induced thrombosis demonstrated atherosclerotic occlusions, compared with 27% of those that did not receive this treatment (4 of 15; P < .01). CONCLUSIONS: Thrombin-induced thrombotic occlusion of a segment of artery which has been de-endothelialized, followed by a high-fat, high cholesterol diet, results in a higher yield of experimental occlusive atherosclerosis in rabbits than is achievable by other methods.

Computed tomography-guided percutaneous biopsy: a combined approach to the retroperitoneum.

When computed tomography (CT) is used to evaluate the lumbar spine in patients with low back pain, it is important to look at the adjacent retroperitoneum. CT is ideally suited to visualize the retroperitoneum and provide access for percutaneous needle biopsy.

Hemangioendothelioma of the spleen.

Hemangioendotheliomas of the spleen are rare and are considered to be of intermediate/borderline malignancy. We report such a case in a patient who presented with chronic anemia but who otherwise was asymptomatic. The tumor involved half the organ and was solitary and nonencapsulated. Microscopically, it was composed of vascular and stromal elements. Both types of elements showed moderate atypia and rare mitoses. The lining cells stained positively with antibodies to factor VIII-related antigen and Ulex europaeus lectin. The stromal component showed evidence of myofibroblastic differentiation. One year after splenectomy, all hematologic parameters slowly improved and returned to normal. The clinicopathologic differences between hemangioma, angiosarcoma, and hemangioendothelioma are discussed, and cases that have recently been reported in the literature are reviewed.

Proliferative glomerulonephritis with unusual, organized, cylindrical deposits associated with angioimmunoblastic lymphadenopathy-like T-cell lymphoma.

We describe an elderly man who developed angioimmunoblastic lymphadenopathy-like T-cell lymphoma, followed by acute renal failure 2 months later. Renal biopsy revealed proliferative glomerulonephritis, which was characterized by enlarged glomeruli with increased cellularity, thickened capillaries, intracapillary inflammatory cells, focal necrosis, and fibrin extravasation. Immunofluorescence studies revealed capillary and mesangial deposits of IgG, IgM, IgA, Ig kappa, Ig lambda, and C3. Electron microscopy revealed unusual, organized, electron-dense deposits in the capillary walls and mesangium. The deposits occurred as accumulations of large rigid tubules or cylinders, which, in longitudinal section, were double-walled. In transverse section, the deposits were annular or horseshoe shaped and occasionally had a central filament. The morphologic characteristics of these deposits are different from those seen in cryoglobulinemia or fibrillary and immunotactoid glomerulopathies. The significance of these deposits is uncertain; they may represent a cryoglobulin or an abnormal serum protein related to angioimmunoblastic lymphadenopathy-like T-cell lymphoma. The findings in this case expand the morphologic spectrum of glomerular lesions that may be associated with malignant lymphoproliferative disorders and, particularly, angioimmunoblastic lymphadenopathy-like T-cell lymphoma.

Solitary pleural amyloid nodules occurring as coin lesions diagnosed by fine-needle aspiration biopsy.

Solitary pleural amyloid nodule is rare and radiologically can mimic neoplastic lesions. This report describes two cases of this entity diagnosed by fine-needle aspiration biopsy in patients without systemic amyloid deposits. The histologic, ultrastructural, and cytologic features are described.

Cytologic diagnosis of cavernous hemangioma of the liver with fine-needle biopsy.

We present the cytopathologic findings in seven cases of cavernous hemangiomas of the liver diagnosed by direct "squash" smears made on tissue obtained through image-guided fine-needle biopsy. The diagnosis in each case was confirmed histologically. Utilizing this simple cytologic technique, the morphologic findings in these common hepatic lesions are as accurate and diagnostic as histologic examination.

Fine needle aspiration cytology of primary squamous cell carcinoma of the thymus. A case report.

We present the cytologic findings of a rare case of primary thymic squamous cell carcinoma with ultrastructural examination and histologic confirmation of the tumor. The clinicopathologic features of thymic carcinomas are discussed. Although the cytodiagnosis of squamous cell carcinomas in general is not difficult, we have observed some cytologic (and histologic) features that we think are distinctive in thymic squamous carcinoma.