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Biomedical subjects

A M Solinger

Publications and source records attributed to A M Solinger.

At least 19 recordsLinked to original sources

Clinical and immunologic effects of a PRIMATIZED anti-CD4 monoclonal antibody in active rheumatoid arthritis: results of a phase I, single dose, dose escalating trial.

OBJECTIVE: The goal of this single infusion, dose escalation study was to evaluate the safety of the PRIMATIZED anti-CD4 monoclonal antibody (Mab), IDEC-CE9.1, in patients with rheumatoid arthritis (RA). METHODS: Twenty-five patients received single infusions of IDEC-CE9.1 in dose escalation form (0.03 to 4 mg/kg). Cohorts consisted of 3 patients each with seropositive RA. Following treatment, patients were monitored for 2 weeks before initiation of treatment of the next cohort. Peripheral blood samples were taken during and after treatment to measure immune function. Flow cytometry of peripheral blood mononuclear cells and in vitro proliferative responses to antigens and recall antigens were assessed pre and post-treatment. Cell surface markers CD3, CD4 (OKT4 and Leu 3a), CD8, CD20, CD25, CD45Ro, CD45Ra and DR were analyzed, and proliferation to mitogens and recall antigens was measured. RESULTS: No infusion related adverse events were noted and other drug related adverse events were mild. Reduction in peripheral CD4 T cell number was brief (3 to 7 days) and not associated with infection. CD4 cell surface antigen downmodulation was observed postinfusion. Suppression of CD25 expression was associated with a positive clinical response. In vitro proliferative responses to mitogens and antigen were inhibited for up to one month with no association to positive clinical response. CONCLUSION: IDEC-CE9.1 appears to have a benign safety profile and may modulate immune function rather than deplete CD4+ T cells.

Adult↗

Rheumatic diseases and AIDS--is the association real?

There have been many reports of an association of certain musculoskeletal disorders especially Reiter's syndrome and psoriatic arthritis with human immunodeficiency virus (HIV) infection. A review of the first 1,100 HIV positive patients at the University of Cincinnati AIDS Clinic and Treatment Center has revealed 9 with psoriasis of whom 4 developed arthritis, 1 with Reiter's syndrome which predated HIV infection, 9 with nonspecific arthralgias, 7 with diffuse myalgias of whom 5 were AZT and one alpha-interferon related. Three patients with temporal arteritis/polymyalgia rheumatica, 2 of whom are biopsy proven, have been observed. The frequency distribution for race, age, sex for this population was contrasted to that expected. The only increased frequencies were in psoriatic arthritis with 4 cases observed and 0.73 expected and in temporal arteritis/polymyalgia rheumatica with 3 cases observed and 0.3 expected. Whether there is a coincidental or real increase is an important question requiring prospective, epidemiological studies to help determine if the differences reported are demographic or genetic.

Acquired Immunodeficiency Syndrome↗

Induction of autoantibodies by human immunodeficiency virus infection and their significance.

Although many of the changes in HIV and AIDS appear to be global, on closer investigation the defects are specific and can be explained by recognized mechanisms. Despite a demonstrated concurrent polyclonal B-cell activation, studies fail to show any evidence to date of significant dysregulation of the immune system leading to serologic or clinical autoimmunity.

Acquired Immunodeficiency Syndrome↗

Emergence of acyclovir-resistant varicella zoster virus in an AIDS patient on prolonged acyclovir therapy.

We demonstrate for the first time the appearance of acyclovir resistance in serial varicella zoster isolates from a patient treated with acyclovir. We recovered varicella zoster virus three times over a period of 5 months from the skin lesions of this patient with AIDS who was treated with three courses of intravenous acyclovir and prolonged low-dose oral acyclovir. The isolate recovered from a typical zoster lesion before acyclovir, and one obtained from a hyperkeratotic lesion 2 months later, after intravenous and oral acyclovir, were sensitive to acyclovir and produced normal amounts of thymidine kinase. In contrast, virus recovered from lesions 5 months after the onset, when the patient had received repeated courses of acyclovir, was acyclovir-resistant and thymidine-kinase-deficient. Resistance to acyclovir was associated with persistence of lesions which failed to improve with intravenous acyclovir, but was not associated with new lesion formation.

Acquired Immunodeficiency Syndrome↗

Prolonged cutaneous herpes zoster in acquired immunodeficiency syndrome.

We described the development of prolonged disseminated cutaneous herpes zoster in two patients with acquired immunodeficiency syndrome. Both patients developed hyperkeratotic, verrucous lesions that progressed despite acyclovir therapy. The biopsy specimens were typical of herpes infection. The development of acyclovir-resistant varicella-zoster virus during therapy was suspected clinically in the first patient and documented in vitro in the second patient. The inability to mount an effective cell-mediated immune response contributed to the prolonged course of cutaneous zoster in our patients. The hyperkeratotic nature of the skin lesions may reflect their chronic nature. Treatment with inadequate doses of acyclovir, allowing viral persistence and the selection of resistant strains of virus, may also be implicated. We recommend prolonged high-dose intravenous acyclovir therapy in the initial management of herpes zoster in patients with acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

HIV and arthritis.

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Arthritis, Infectious↗

Acquired immune deficiency syndrome (AIDS) and autoimmunity--mutually exclusive entities?

Loss of normal immune homeostasis occurs in acquired immune deficiency syndrome (AIDS). We evaluated patients at the University of Cincinnati and New York University Medical Centers for serologic evidence of autoimmune changes. Specifically, tests for antinuclear and organ-specific antibodies by immunofluorescence, antisperm and anti-seminal plasma antibodies, rheumatoid factor by latex and sensitized sheep cell agglutination techniques, anti-polyadenosine (poly A), and single-stranded DNA antibodies were performed in human immunodeficiency virus (HIV) antibody-positive sera. A parallel study of mitogen responsiveness was performed and showed inhibition of response by AIDS and AIDS-related complex (ARC) sera. In spite of evidence of polyclonal B-cell activation, hyperglobulinemia, and the presence of antibodies to many infectious agents, as well as the known cellular immune abnormalities, the patients tested had a striking absence of these autoantibodies. The only major difference noted from normal controls, was a low but significant level of antibody binding to poly A. The autoimmune connective tissue diseases were not observed in this group of patients.

Acquired Immunodeficiency Syndrome↗

Drug-related lupus. Clinical and etiologic considerations.

Drug-related lupus (DRL) was first described in 1945 in association with sulfadiazine. Since that time, more than 50 medications have been implicated in this syndrome and its associated laboratory abnormalities. Several mechanisms for these findings have been postulated, but no one mechanism has been established as pre-eminent. The clinical spectrum, when it does occur, is characterized by polyserositis: arthritis, pleuritis, pericarditis, and peritonitis. Many of the well-known features of SLE are rarely, if ever, seen in DRL.

Acylation↗

Indications for immunotherapy.

Underlying immunodeficiency should be suspected in every patient, irrespective of age, who has recurrent, persistent, severe, or unusual infections. Defects in immunity can be classified into primary or secondary disorders involving specific or nonspecific immune mechanisms. Several forms of primary and secondary immunodeficiency exist for which various immunotherapeutic modalities are available. Significant among these are immunoglobulins commercially available for intravenous infusion. Other therapies include transplantation of tissue such as bone marrow, fetal liver, and fetal thymus. Enzyme replacement therapy is being developed, as is the use of products unique to immunocompetent cells, such as thymus extract, thymosin, interleukins, and transfer factor. Forms of nonspecific immune modulators and stimulators are other possibilities, especially in the context of the immunotherapy of tumors.

Humans↗

Patients with collagen vascular disease and dyspnea. The value of gallium scanning and bronchoalveolar lavage in predicting response to steroid therapy and clinical outcome.

Patients with collagen vascular disease with or without pulmonary symptoms were studied to determine the value of gallium scan and bronchoalveolar lavage (BAL) in predicting clinical outcome and response to steroid therapy. Thirty-six subjects, 20 with progressive dyspnea, were studied. Gallium uptake was seen in the lung in 17 of the 20 progressively dyspneic patient's and none of the 16 nonprogressive patients (chi square = 22.5, p less than 0.001). The BAL fluid in the progressive patients had a higher percentage of neutrophils (13.4 percent +/- 2.88) and lymphocytes (16.1 percent +/- 2.75) than in the nonprogressive patients (neutrophils = 3.3 +/- 1.30 percent; lymphocytes = 5.6 +/- 1.57 percent, p less than 0.02 for both). Of the 19 progressive patients who were treated with steroids or cyclophosphamide, six had only increased neutrophils in their BAL fluid and all died. The remaining 13 treated progressive patients had increased lymphocytes or a normal BAL (two patients): six had improvement in their vital capacity, six have had stable function, and one died. We found gallium scan and BAL useful in assessing progressive pulmonary fibrosis in collagen vascular disease.

Adrenal Cortex Hormones↗

Immature T lymphocytes in human neonatal blood.

Thirty-two cord blood samples taken after caesarean section or vaginal delivery and concurrent venous blood samples obtained from normal adult controls were evaluated using monoclonal antibodies. The percentage of circulating pan-T-cell+ lymphocytes was significantly lower in cord blood (46%) compared with adult controls (72%). In the cord cells, 22% showed reactivity with the common thymocyte antigen compared with less than 1% in adult controls. The helper:suppressor ratio was lower in cord blood (1.71) compared with 1.98 for adult blood. These figures reflect a unique population (12%) of immature T cells in cord blood that coexpress helper and suppressor phenotypes. These features are not found in adult blood. These double-labeling studies characterized a previously undescribed blood T-cell phenotype which correlates negatively with gestational age (R = -0.93). These studies reveal the presence of an immature population of T cells in normal human neonatal blood that exhibit the phenotype characteristic of normal developing thymocytes.

Adult↗