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Biomedical subjects

M M Lederman

Publications and source records attributed to M M Lederman.

At least 109 records · Page 6Linked to original sources

Left-sided endocarditis due to Pseudomonas aeruginosa. A report of 10 cases and review of the literature.

Ten confirmed cases of left-sided endocarditis due to Pseudomonas aeruginosa were reported in detail and the English literature was reviewed. In recent years, venous access (usually illicit) has been the major predisposing factor to this infection and abuse of pentazocine and tripelennamine has been particularly associated with endocarditis due to this organism. This infection involves previously damaged as well as normal valves. The development of congestive heart failure did not adversely affect the prognosis of this infection. However, the development of azotemia was associated with a greater likelihood of a fatal outcome. In the current series, deaths were due to uncontrolled infection. This often occurred despite inhibitory and bactericidal activity in serum generally considered adequate for treatment of endocarditis. Medical treatment alone rarely produced cure of infection. Our experience with a high frequency of major vessel embolization (4/10) and the improved survival after medical/surgical treatment suggests that prompt valve replacement combined with high doses of an aminoglycoside plus carbenicillin or ticarcillin provide the best opportunity for successful outcome in patients with left-sided endocarditis due to P. aeruginosa.

Adult↗

Defective postbinding lysis underlies the impaired natural killer activity in factor VIII-treated, human T lymphotropic virus type III seropositive hemophiliacs.

We investigated the diminished natural killer (NK) activity in human T lymphotropic virus type III (HTLV-III) seropositive hemophiliacs. Despite normal percentages of NK cells, lymphocytes from five hemophiliacs showed impaired NK activity against K-562 tumor cells in 4-h chromium release microcytotoxicity assays. For example, at an effector-to-target cell ratio of 10:1, cells from patients caused 21.7 +/- 2.5% lysis of tumor targets compared with 47.9 +/- 5.1% lysis by cells from controls (mean +/- SEM, P less than 0.005). Cells from patients were as cytotoxic in 18 h as were cells from controls in 4 h. Binding to tumor targets was not impaired since 11.0 +/- 1.5% of cells from patients and 11.1 +/- 1.3% of cells from controls bound to K-562 cells. Patients' binding cells, however, showed defective killing of attached tumor cells at all time points tested from 0 to 18 h. At 4 h, for example, patients' cells had lysed 10.9 +/- 2.1% of attached tumor cells compared with 26.3 +/- 3.3% lysis by controls' cells (P less than 0.005). The percentage of lymphocytes which were active NK cells (i.e., cells that bound and lysed a tumor cell) was always lower for patients than for controls (1.17 +/- 0.25% vs. 2.82 +/- 0.33%, P less than 0.005). Two methods for estimating recycling of effector cells against multiple target cells demonstrated that active NK cells from patients could recycle as well as those from controls (approximately 3-4 times in 4 h). Mixing experiments showed no evidence for cellular suppression of NK activity. The lytic function of NK cells from HTLV-III seropositive hemophiliacs is thus heterogeneous. This is characterized by a defect in post-binding lysis, with relative sparing of binding capability and recycling capacity.

Adult↗

Inhibition of human lymphocyte proliferation by ultraviolet radiation: effects of ultraviolet B (290 to 320 nm) on T-lymphocytes, monocyte accessory function, and induction of suppressor mechanisms.

In vitro exposure of peripheral blood lymphocytes (PBLs) to doses of ultraviolet radiation (UVR) achievable during recreational sun exposure produces profound inhibition of lymphocyte blastogenesis. This study demonstrates that this inhibition is mediated by a direct dose-dependent effect on populations enriched for T-lymphocytes and is reversible after incubation of responder cells with phytohemagglutinin (PHA). In contrast, monocyte accessory function for both antigen- and mitogen-induced proliferation is relatively unaffected by in vitro exposure to UVR at doses up to 30 mJ/cm2. Exposure of PBL to UVR also results in the induction of a suppressor mechanism that inhibits the proliferation of unirradiated PBLs. In vitro exposure of human blood cells to UVR may provide a valuable tool for examining the cellular basis for the immunosuppressive effects of UVR.

Adult↗

Antihemophilic factor [factor VIII] preparations inhibit lymphocyte proliferation and production of interleukin-2.

To examine the role of antihemophilic factor (factor VIII) preparations in the pathogenesis of subclinical immunodeficiency in hemophilia, we tested the in vitro effects of these products on immune function. Both lyophilized antihemophilic factor (LAHF) and cryoprecipitates inhibited lymphocyte proliferation in a dose-dependent fashion. Further studies indicated that LAHF interfered with an early event in proliferation and also that prolonged incubation of human lymphocytes with LAHF resulted in an irreversible inhibition of lymphocyte proliferation without detectable cytotoxic effects. LAHF also inhibited the production of interleukin-2 (IL-2) by human lymphocytes and by Jurkat tumor cells, suggesting that inhibition of IL-2 production was not mediated through effects on interleukin-1. Gel filtration of LAHF revealed two peaks of inhibitory activity; one with mol wt greater than 2 X 10(6) comigrated with factor VIII coagulant activity and antigen, whereas another with mol wt approximately 6 X 10(5) was devoid of factor VIII activity and antigen. Further study will ascertain whether administration of factor VIII-containing preparations contributes to the subclinical immunodeficiency seen in patients with hemophilia or serves as a cofactor in the development of clinical immunodeficiency after exposure to the retrovirus human T-lymphotropic virus type III.

Acquired Immunodeficiency Syndrome↗

Preoperative use of povidone-iodine. A prospective, randomized study.

One hundred one adult orthopedic surgical patients were studied in a randomized, prospective clinical trial to compare the effectiveness of the standard povidone-iodine scrub and paint with povidone-iodine painting alone for presurgical skin preparation. No infections occurred in either group. The scrub-plus-paint group showed a 0.601 logarithmic reduction in bacteria counts, compared with 0.622 with painting alone. Further, 36.8% of the patients in the scrub-plus-paint group had skin counts that actually increased after preparation, compared with 13.8% of patients in the paint-only group. The preparation bacterial counts among inpatients, who received preoperative hexachlorophene showers, were significantly lower than that of outpatients, who did not receive preoperative showers. The data support the use of the preoperative hexachlorophene shower and the omission of scrubbing from the surgical skin preparation technique.

Ambulatory Care↗

Acquisition of antibody to lymphadenopathy-associated virus in patients with classic hemophilia (factor VIII deficiency).

Antibody to lymphadenopathy-associated virus (LAV) was assayed in 461 serum and plasma samples that had been obtained from 149 patients with classic hemophilia and 64 controls and stored for periods as long as 18 years. No control or patient samples obtained before 1980 contained antibody to this retrovirus. The prevalence of antibody to LAV in the patient samples rose from 15% (2 of 13) in 1980 to 62% (18 of 29) in 1984. During this time, none of 8 untreated hemophiliacs and none of 26 hemophiliacs treated solely with cryoprecipitates had antibody to LAV. In contrast, the prevalence of antibody to LAV among hemophiliacs treated with lyophilized antihemophilic factor rose from 25% (2 of 8) in 1980 to 78% (18 of 23) in 1984. These seropositive hemophiliacs had fewer OKT4 helper cells and lower proliferative responses to mitogen than similarly treated seronegative patients. Treatment with locally prepared cryoprecipitates was not associated with serologic evidence of virus exposure.

Antibodies, Viral↗

Impaired cell-mediated immunity in hemophilia. II. Persistence of subclinical immunodeficiency and enhancement of natural killer activity by lymphokines.

We performed follow-up studies in 11 patients with asymptomatic classic hemophilia, who on initial study 8 to 12 months previously had demonstrated abnormalities of lymphocyte phenotype and function. Although all subjects remained well, diminished lymphocyte proliferative responses, natural killer activity, and decreased ratios of OKT4 helper/OKT8 suppressor lymphocytes persisted. Moreover, the absolute number of OKT4 helper lymphocytes fell in the patients from a mean of 745 +/- 73/microliter in the first study to 585 +/- 50/microliter in the follow-up study, which was lower than the control value of 857 +/- 87 (P less than 0.02). Despite diminished natural killer activity, patients with hemophilia had at least normal numbers of natural killer cells as determined by the presence of the OKM1 antigens and Giemsa staining to identify large granular lymphocytes. Patients with hemophilia had more Leu 11a-positive cells than controls. Lymphocyte binding to tumor targets was not diminished, and removal of adherent cells did not increase patients' natural killer activity to control levels. Incubation of patients' lymphocytes with alpha-interferon, gamma-interferon, or interleukin-2 resulted in enhancement of natural killer activity but did not reach control levels. Thus the diminished natural killer activity in patients with hemophilia retained responsiveness to lymphokines and was caused either by an intrinsic or acquired defect in the natural killer cell or by modulation by a nonadherent cell. Subclinical immunodeficiency in patients with hemophilia is not transient and is associated with a diminished number of OKT4 helper cells, a finding often associated with clinical immunodeficiency.

Adult↗

Sputum elastin fibers and the diagnosis of necrotizing pneumonia.

Potassium hydroxide (KOH) preparations for elastin fibers on sputum obtained from 80 patients seen over a four-month period at two Cleveland hospitals were performed. The results were compared with roentgenographic evidence of necrosis and case diagnosis. Sixty-one patients had neither elastin in sputum nor roentgenographic evidence of cavitation; 11 had positive results using both methods. Two patients had no elastin fibers in sputum but had parenchymal pulmonary cavities on chest x-ray film. Six patients had elastin observed in KOH preparations of sputum, but no cavitation roentgenographically. The presence of elastin in sputum was strongly correlated with roentgenographic evidence of pulmonary necrosis (p = 5.7 X 10(-8]. Including patients seen before, after, and during the prospective study, we have observed a total of nine with positive sputum preparations for elastin and no cavitation on chest x-ray film for whom tissue was available for study. All had pulmonary necrosis histologically. Our observations suggest that the KOH preparation of sputum for elastin fibers may be more sensitive than the chest roentgenogram in the detection of pulmonary necrosis and may be a useful adjunct in the diagnosis of necrotizing disease.

Diagnosis, Differential↗

Pre-incubation of human monocytes results in loss of effector activity and diminished stimulation of the autologous mixed lymphocyte reaction.

Human monocytes were cultured at 37 degrees C for 72 h, washed, adjusted for viability and compared to freshly prepared monocytes for stimulation of the autologous mixed lymphocyte reaction (AMLR) and effector function. Pre-incubated monocytes were less potent AMLR stimulators than were freshly prepared cells. Pre-incubated monocytes demonstrated less antibody-dependent tumour killing of CCRF-CEM, less killing of Staphylococci and less spontaneous tumour killing of K-562 than did fresh monocytes. Pre-incubated monocytes produced less prostaglandin E2, demonstrated less surface Ia antigen and were less efficient accessory cells for antigen presentation than were fresh monocytes. AMLR stimulation correlated with monocyte killing (r = 0.95) and PGE2 production (r = 0.98). Thus, monocytes pre-incubated for 3 days are less active effector cells, display less surface Ia antigen and are less potent stimulators of the AMLR than fresh monocytes. Moreover, in this system, monocyte effector activity correlates with ability to stimulate the AMLR.

Antibody-Dependent Cell Cytotoxicity↗

Ultraviolet radiation inhibits human natural killer activity and lymphocyte proliferation.

Exposure to ultraviolet radiation (UVR) has been implicated in the predisposition to certain neoplasms and leads to viral reactivation. Natural killer (NK) activity may play a role in immunosurveillance and response to certain viral infections. We have evaluated the sensitivity to UVR of human NK activity, a nonproliferative function, and the proliferative response to the mitogen phytohemagglutinin (PHA). In vitro exposure to UVR resulted in a dose-dependent inhibition of NK activity and response to PHA. The wavelength dependence for UVR inhibition of NK activity and of the PHA response of lymphocytes were virtually superimposable at wavelengths at or above 300 nm, but NK activity was less sensitive to UVR at 260 and 280 nm. Maximal sensitivity for both functions was found at 260 nm, consistent with a nucleic acid chromophore mediating UVR inhibition of both activities. The DNA-directed drugs mitomycin C, acridine orange, and adriamycin at concentrations that inhibit proliferation are poor inhibitors of NK activity. These results suggest that UVR inhibition of NK activity as well as proliferation may be mediated by a nucleic acid chromophore. NK activity, however, is less sensitive to direct damage of DNA by alkylation, distortion, or oxidation. At 300 nm, the amount of radiation required to inhibit NK activity and proliferation is within the range penetrating to the dermis and capillaries during environmental exposure to sunlight.

Adult↗