Biomedical subjects
Publications and source records attributed to D Aderka.
A 37-year-old man with plasma cell leukemia developed nonfatal septicemia caused by the gram-negative bacterium CDC IV c-2. Recovery followed appropriate treatment with antibiotics. The biochemical features of this organism are reviewed.
Interstitial pneumonitis developed in a patient one week after therapy with nalidixic acid was initiated. The causal association between the drug and the lung disease is based on the temporal relationship, an increased eosinophil count in both peripheral blood and fluid obtained by bronchoalveolar lavage, a positive migration inhibitory factor test with nalidixic acid, and exclusion of other causes. This is, to the best of our knowledge, the first report of a pulmonary hypersensitivity reaction to nalidixic acid.
Cloxacillin-induced cholestasis was diagnosed with the help of the macrophage inhibition factor and mast-cell degranulation tests. The simultaneous occurrence of both immediate type as well as cell-mediated hypersensitivity to the drug suggested that a defect in the histamine-induced suppressor cells may underly this cloxacillin-induced allergic reaction.
The migration inhibition factor (MIF) test detects the in vitro release of lymphokine from lymphocytes in in vitro contact with a drug that had sensitized them in vivo. The specificity and sensitivity of the MIF test in identifying a drug inducing an allergic reaction is presented. The MIF test detected the drugs responsible for 20 out of 21 allergic episodes (95.2%) while the basophil degranulation test detected only eight of them (P less than .001). The sensitivity of a positive MIF test was 95.2% and its specificity was 76.9%. The specificity of a negative MIF test was 94.7%. The positive MIF test assisted the physician in indicating the drugs responsible for an allergic reaction in half of the patients. The drugs for which the MIF test was negative could be considered innocent in 95% of the cases. It is concluded that although the results of the present studies are encouraging, the clinical utility of the MIF test is still limited and improvement of the test specificity is required.
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An accepted, although debatable explanation for fever of unexplained origin (FUO) in cancer patients is the presence of liver metastases. This controlled study was aimed to determine whether FUO is more common in patients with liver metastases (Group A) as compared to those without evidence of spread to the liver (Group B). One hundred forty-five patients were studied in each group. Fever of unknown origin was experienced by 45 patients of Group A (31%) and 39 of Group B (26.9%). The duration and the fever characteristics were comparable in both groups. There was no relationship between the extent of the liver metastases and the incidence of FUO. That FUO was not caused by the presence of liver metastases per se, is deduced also from the remission of fever in 18 preoperative episodes after the resection of the primary tumor only, in spite of the persistence of the liver metastases. The type of fever and its duration was similar in patients with or without liver metastases. Thirteen severe infectious conditions were missed by the premature adoption of the convenient diagnosis of "fever due to liver metastases." Indomethacin, administered to normalize the fever incorrectly attributed to the liver metastases, obscured four of the above infectious conditions, with a fatal outcome. The authors conclude that the existence of "fever due to liver metastases" as an entity is not supported by the current study, and that the premature adoption of this diagnosis further compromised the outcome of patients with liver metastases and unexplained fever.
The cytotoxic effect of lymphotoxin (LT) and its modulation by interferon (IFN) was quantitatively assessed in uninfected and vesicular stomatitis virus (VSV)-infected cultured cells. Preparations of human LT, which were depleted of IFN, had a significant cytotoxic effect on VSV-infected HeLa, SV-80, WISH, and Vero cells. IFN, most notably IFN-gamma, further potentiated destruction of the infected cells by these LT preparations, when applied on the cells at sub-antiviral IFN concentrations. In contrast, no cytotoxic effect could be observed in any of the examined cells, when applying LT, IFN, or their combination, in the absence of viral infection. Infected cells in which VSV replication was suppressed by treatment with antiviral concentrations of IFN also resisted destruction by LT. These findings indicate that LT cytotoxicity can be selectively directed against virus-infected cells and that IFN can augment this cell-killing mechanism when failing to exert an antiviral effect.
A human cytotoxin (CTX) with an Mr of 17,500 was purified to homogeneity from cytokine preparations by the use of a monoclonal antibody against that protein. Sendai virus and, to a lesser extent, the lectin phytohemagglutinin were found to induce effective production of that CTX in cultures of human peripheral-blood mononuclear cells, the first - by stimulating monocytes to produce the proteins, and the latter - by stimulating T cells. With both kinds of inducers, CTX production correlated to a marked increase in the cellular levels of mRNA for CTX, as quantitated by translation of that mRNA, to biologically active CTX, in microinjected Xenopus oocytes. Crude CTX preparations, as well as purified CTX, were found to be selectively cytotoxic to metabolically depressed and to virus infected target cells; they effectively killed cells which were treated with inhibitors of macromolecule synthesis, such as cycloheximide, or infected by viruses, such as VSV, but failed to exert a cytotoxic effect in the absence of such sensitizing treatments. IFN, most notably IFN-gamma, further potentiated destruction of virus-infected cells by the purified CTX, when applied on these cells at subantiviral concentrations, while uninfected cells remained resistant to CTX following treatment with IFN. Formation of the 17.5K CTX in response to viral infection and the selective cytotoxic effect of that protein on cells infected by viruses, indicate a role of CTX in the defense against viral infections.
Crude preparations of cytotoxins (CTXs) produced by human peripheral blood mononuclear cells exert a marked cytotoxic effect when applied to cells in the presence of cycloheximide but in its absence can induce resistance to cytotoxicity. To examine the relationship between these cytotoxic and protective activities, we attempted to fully dissociate the CTX from the other proteins secreted by mononuclear cells. Mice injected with preparations of the cytokines secreted by peripheral blood mononuclear cells developed significant titers of serum antibodies to CTX(s). Splenocytes of such immunized mice were fused with NSO myeloma cells; a few among the resulting hybridoma cells secreted CTX-binding antibodies. Immunoadsorbents constructed with a monoclonal antibody produced by one of these hybridomas were used to purify to homogeneity a CTX (Mr approximately 17,500) from crude preparations of cytokines, by a single adsorption and elution cycle. Purified CTX was cytotoxic in the presence of cycloheximide but in its absence induced resistance to cytotoxicity; this resistance was manifested by decreased vulnerability to CTX in a subsequent incubation in the presence of cycloheximide. We conclude that CTX itself can induce certain changes in cells, which are reflected in resistance to its own cytotoxic effect.
The possibility that fever may be an early manifestation of colorectal carcinoma was examined. Of 92 consecutive patients, 28 had preoperative fever. In four patients the fever was the presenting symptom of the colonic tumor, and in another six patients it preceded gastrointestinal complaints by 1 week to 4 months. Fever was thus the earliest manifestation of colorectal carcinoma in 10.8% of the patients. In 13 of the 28 patients the fever could not be explained by the intraoperative findings. We suggest that transient bacteremia may be a common but frequently overlooked manifestation of colonic cancer. Prognosis of the patient may be improved by alertness to the possibility that an episode of unexplained fever may be the first, and sometimes the only, manifestation of colorectal carcinoma.
Part of the "idiopathic" liver granulomas prove finally to be caused by infection, sarcoidosis, or malignancy. We looked for the initial admission parameters which may differentiate the idiopathic from the malignancy related granulomas. Patients with idiopathic granulomatous hepatitis had smaller spleen than of lymphoma related granulomas (2.15 +/- 2 versus 9.5 +/- 4.8 cm below the costal margin, p less than 0.01), smaller liver (2.61 +/- 2 cm versus 6.5 +/- 4.0 cm, p less than 0.05), a lower percent of eosinophils (2.3 +/- 1.4 versus 6.2 +/- 3.5%, p less than 0.05) and unlike patients with lymphoma, their fever did not persist beyond 4 wk (p = 0.03). Indeed, if the fever remitted spontaneously, it was likely that a benign condition was responsible for the granulomas (p less than 0.025). If fever persisted (4 wk), a liver or a spleen extending more than 4 cm below the costal margin and 4% eosinophils were attributed 1 point each; a score of 2 points had a specificity of 80 and a 100% sensitivity in detecting patients with lymphoma related liver granulomas. It is concluded that the size of the liver and spleen, the percentage of eosinophils, and the persistence of fever may differentiate between patients with idiopathic- versus lymphoma-related granulomatous hepatitis.
A new type of human interferon (IFN), IFN-alpha-C, produced in Escherichia coli and purified on monoclonal antibodies, was given at a dose of 3 X 10(6) u (3 micrograms)/day to a terminally ill unsplenectomized patient with hairy cell leukemia, who had had severe recurrent infections and pancytopenia. There was marked reduction in the size of the spleen after 2 weeks, and platelet counts returned to normal after 1 month of treatment. The IFN treatment also raised the granulocyte counts and hemoglobin levels, improved the normal repopulation of the bone marrow, and restored resistance to infections. IFN-alpha-C was well tolerated, without serious side effects, and treatment has been continued for 10 months.
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An 18-year-old man, admitted because of severe bleeding manifestations due to varicella thrombocytopenia was administered 800 mg/day adenine arabinoside (Ara-A) intravenously for 5 days. 2 days after the start of this treatment the bleeding phenomena became markedly reduced and a progressive increase in the platelet count was noted thereafter. Although a spontaneous improvement is known to occur in patients with varicella thrombocytopenia, the rapid clinical improvement after the Ara-A administration is suggestive for its beneficial effect in the presented patient.