A distinctive glomerular lesion complicating placental site trophoblastic tumor: report of two cases

Renal disease with distinctive pathologic features developed in two young women who had placental site trophoblastic tumors. The renal abnormalities were manifested by proteinuria in both cases and by hematuria in one case; blood pressure was elevated in one of the patients. Pathologic examination of the kidneys showed distinctive glomerular abnormalities, characterized mainly by the presence of occlusive eosinophilic deposits in many of the glomerular capillary lumina, most of which stained for fibrinogen-related antigens and IgM by immunohistochemical techniques. Ultrastructural examination showed the deposits to consist mainly of granular material that contained packets of fibrillar material with the appearance of fibrin. The uterine tumors were composed of mononucleated and multinucleated cells with abundant cytoplasm that infiltrated between the muscle bundles of the myometrium; in both tumors there was prominent deposition of eosinophilic material that had the tinctorial properties of fibrin and that stained for fibrinogen and IgM in immunoperoxidase studies. The renal abnormalities disappeared after hysterectomy in one case; the other patient, who was receiving chemotherapy and had disseminated intravascular coagulation, died with leukopenia and sepsis. The clinical and pathologic features in these cases suggest that the renal abnormalities were related to the uterine tumors and that the production of immune complexes and/or the activation of intravascular coagulation by the tumors were pathogenetic mechanisms.     

Study of the HLA system in Burkitt's lymphoma

Seventy-eight patients with Burkitt's lymphoma and seventy controls from Ghana were typed for HLA-A, B, C and DR antigens, to determine whether there is an association between the HLA system and Burkitt's lymphoma. Increased relative risk was observed in Burkitt's lymphoma patients with DR7, HLA-A1 and B12 (BW44).     

Cell-mediated immunity in leprosy and transfer of delayed hypersensitivity reactions

Eighty-nine patients with leprosy, 65 classified as lepromatous and 24 as tuberculoid, were examined in this study. Skin test responses to protein antigens and dinitrochlorobenzene (DNCB) were depressed in lepromatous patients compared to controls. Tuberculoid patients did not exhibit a significant depression to microbial antigens, but they showed a definite depression in the ability to be sensitized with DNCB. The transfer of delayed hypersensitivity reactions to tuberculin, trichophytin, and lepromin (Fernandez and Mitsuda reactions) was accomplished in lepromatous and indeterminate leprosy patients using viable lymphocytes from donors presenting positive reactions to these antigens. The lepromin reaction was also transferred to patients with South American blastomycosis and cutaneous leishmaniasis. The positive reactions of adoptive immunity were confirmed by histologic examination of skin biopsies.     

Successful treatment of chronic idiopathic urticaria and angioedema with cimetidine alone

We have studied a 50-year-old white man with chronic urticaria and angioedema who has responded to treatment with cimetidine alone for over 2 yr. In a double-blind, placebo-controlled study, cimetidine alone was at least as effective as chlorpheniramine in relief of urticaria and angioedema. Additionally, cimetidine significantly inhibited (p less than 0.01) the wheal response to histamine when it was compared to placebo. The inhibition of wheal response to histamine by cimetidine was significantly higher (p less than 0.05) than chlorpheniramine. The presence of predominantly H2- rather than H1-histamine receptors in the cutaneous blood vessels may be responsible for the therapeutic effects of cimetidine in this patient.     

Chromosome abnormalities in chronic lymphocytic leukemia revealed by TPA as a mitogen

Bone marrow and peripheral blood cultures of chronic lymphocytic leukemia patients were mitogenically stimulated with TPA (12-0-tetradecanylphorbol-13-acetate). Clonal cytogenetic abnormalities were detected in frequencies varying from 15% to 100%, in five of the six patients studied. Parallel studies with pokeweek mitogen showed a much lower level of stimulation and only two abnormal clones were detected. The chromosome abnormalities described in this study are similar to those reported in CLL by other authors, particularly with respect to trisomy 12 and deletion 11q. A significant frequency of hypodiploidy and chromosome deletion was also detected in this study, and further studies are underway to determine the significance of these findings.     

Inhaled lodoxamide tromethamine in the treatment of perennial asthma: a double-blind placebo-controlled study

The efficacy of lodoxamide tromethamine in the treatment of asthma was studied in a 16-week double-blind, placebo-controlled study of 68 perennial allergic subjects with asthma. Patients received either lodoxamide tromethamine, 0.25 mg four times daily, or placebo, administered by metered-dose inhaler. Response to treatment was assessed by analyzing changes in asthma symptoms, inhaled bronchodilator requirements, and pulmonary function when compared to a 2-week baseline period. Patients treated with lodoxamide tromethamine demonstrated an improvement in daytime breathing difficulty, cough, sputum production, and sleep (p less than 0.01 to 0.05), but improvement was not significantly different from that demonstrated by placebo-treated patients. Patients from both treatment groups were able to reduce their inhaled bronchodilators (p less than 0.01), but again no significant difference was apparent between lodoxamide tromethamine and placebo treatment, nor were there any differences in peak expiratory flow rate or FEV1 between the two groups. Seven patients who received lodoxamide tromethamine withdrew because of a sensation of heat and gastrointestinal symptoms. Thus, although lodoxamide tromethamine possesses potent mast cell-stabilizing activity in vitro, we have failed to demonstrate any useful long-term effect in the treatment of mild allergic asthma.     

T suppressor lymphocytes reverse ongoing acute allograft rejection

(LEW X BN)F1 cardiac allografts are rejected within 8 days in untreated LEW recipients. At the critical time point of 5 days after transplantation, the obviously rejecting grafts are enlarged and maximally infiltrated by host cells as shown by 111In-labeled lymphocyte tracer studies. However, when such hearts were retransplanted back to naive (LEW X BN)F1 secondary hosts, they survive indefinitely, showing that even late rejection is reversible in the absence of sustained host immunological drive. Attempts were then made to abrogate this advanced immune responsiveness using Cyclosporine (CsA). CsA therapy (15 mg/kg/day for 7 days) starting from day 5 produced indefinite graft survival, similar as if initiated at the time of operation. Addition of exogenous IL-2, which drives the proliferation of Tc, could not reverse this effect. Serial changes in phenotype of lymphocyte subpopulations infiltrating both acutely rejecting and indefinitely functioning cardiac allografts in unmodified and CsA treated hosts, respectively, were then studied. Ratio of Th:Tc/s cells in acutely rejecting grafts was 1.6 by day 3; it inverted abruptly to 0.7 by day 5-6, suggesting predominance of Tc/s during the later stages of allograft rejection. Similarly, treatment with CsA produced a transient depression of Th, with recovery of original Th:Tc/s ratio during the next 2-3 weeks. Adoptive transfer experiments were then performed to investigate the functional significance of these findings.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circulating immune complexes during immunotherapy.

Chronic immunization may lead to the production of circulating immune complexes (CICs). This study was undertaken to determine the presence of circulating IgG immune complexes in 95 subjects with allergic rhinitis/asthma receiving immunotherapy, 46 individuals with similar diagnosis but not on immunotherapy, and 64 healthy controls. Modified Raji cell and murine leukemia cell (L-1210) assays, selected for a high density of Fc receptors and devoid of Epstein-Barr virus membrane antigen, were used. Other immunological parameters such as immunologlobulins G, A, M, E, and rheumatoid factor activity were also studied. The CIC concentrations in the treated group did not differ significantly from the untreated group, although both groups did have a significantly higher concentration than the healthy controls. The presence of CICs has no relationship with age or sex of patients, dosage of allergen administered, number and nature of allergens received, period between the time of last injection and the blood sampling, and the duration of immunotherapy. Serum IgG, IgA, IgM, and rheumatoid factor activity did not differ between the treated and untreated groups. IgE was significantly higher in the treated group when compared with the untreated, and IgE levels in treated patients with elevated CICs were significantly increased compared with CIC-negative treated patients. These data suggest that CICs are present in serum of atopic diseases such as allergic rhinitis/asthma. Significantly, an association of elevation of CICs with immunotherapy could not be demonstrated.     

In vivo and in vitro correlates of food allergy.

Sera of 86 patients clinically sensitive to foods were tested by passive sensitization of human and/or monkey lung (127 tests) and the radioallergosorbent test (RAST) (72 tests), using whole-food antigens; the results were compared with skin (prick) testing. Results of the prick test correlated with history in 76% of cases; lung sensitization correlated with history in 37% and with prick test in 57%; and RAST correlated with history in 54% and prick test in 72%. It is concluded that a very large percentage of adverse reactions to foods are IgE-mediated. The prick test is of use in diagnosis, particularly when combined with RAST; the lung sensitization test is technically impractical and not a reliable indicator. The best diagnostic method is careful history with food challenge and withdrawal and rechallenge; the latter is safe except in patients with a history of violent reaction.