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Biomedical subjects

S M Wolff

Publications and source records attributed to S M Wolff.

At least 19 recordsLinked to original sources
PubMed1992

Pharmacokinetics, safety and immunomodulatory effects of human recombinant interleukin-1 receptor antagonist in healthy humans.

A phase I study of human recombinant interleukin-1 receptor antagonist (IL-1ra) was conducted in healthy males between the ages of 18 and 30. Twenty-five volunteers received a single, 3 h continuous intravenous infusion of doses ranging between 1 mg/kg and 10 mg/kg IL-1ra. At 3 h into the infusion, plasma IL-1ra levels were 3.1 micrograms/ml and 29 micrograms/ml for the 1 mg/kg and 10 mg/kg doses, respectively. Post-infusion plasma IL-1ra levels declined rapidly, exhibiting an initial half-life of 21 min and a terminal half-life of 108 min. Clinical, hematological, biochemical, endocrinological and immunomodulatory effects were monitored over 72 h and compared to those of four subjects receiving a 3 h infusion of saline. There were no clinically significant differences between the drug and saline groups in symptoms, physical examinations, complete blood counts, mononuclear cell phenotypes, blood chemistry profiles, serum iron and serum cortisol levels. Peripheral blood mononuclear cells (PBMC) obtained after completion of the IL-1ra infusion synthesized significantly less interleukin 6 ex vivo than PBMC from saline-injected controls. These data suggest that transient blockade of interleukin 1 receptors is safe and does not significantly affect homeostasis.

Cytokines↗
PubMed1992

Foveal hypoplasia in complete oculocutaneous albinism. A histopathologic study.

Histopathologic and ultrastructural findings in an eye from a patient with complete oculocutaneous albinism are reported. Examination revealed posterior embryotoxon, high myopia, no foveal differentiation, and absence of melanin pigment in all ocular structures. A few nonmembrane-bound electron-dense granules of lipofuscin were present in the iris and retinal pigment epithelial cells.

Aged↗
PubMed1991

Production of interleukin-1-receptor antagonist during experimental endotoxaemia.

Interleukin-1 (IL-1) has been implicated in the pathogenesis of sepsis. IL-1-receptor antagonist (IL-1ra) is a naturally occurring inhibitor of IL-1 activity that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We induced endotoxaemia in 9 healthy human volunteers by injection of Escherichia coli endotoxin, and measured plasma concentrations of IL-1 and IL-1ra by radioimmunoassay during the next 24 h. Peak plasma concentrations of IL-1ra were about a hundred-fold greater than those of IL-1 beta. No IL-1 or IL-1ra were detectable in the plasma of 4 volunteers injected with saline. Our results suggest that the predominant natural response to endotoxin in man is the production of antagonist rather than agonist.

Adolescent↗
PubMed1991

Taurolidine, an analogue of the amino acid taurine, suppresses interleukin 1 and tumor necrosis factor synthesis in human peripheral blood mononuclear cells.

Taurolidine (Geistlich Pharm, AG, Wolhusen, Switzerland), a derivative of the amino acid taurine, is commonly used in some parts of the world as an adjunctive therapy for various infections. Its mechanism of action is thought to be related to its antimicrobial properties, including its ability to interfere with some of the biological activities of endotoxin (lipopolysaccharide, LPS). For example, taurolidine has been shown to protect animals against endotoxic shock and death. In this study we examined the ability of taurolidine to block LPS-induced tumor necrosis factor (TNF) and interleukin 1 (IL-1) synthesis in human peripheral blood mononuclear cells (PBMC) from 27 donors. We observed a dose-dependent reduction in the synthesis of these two cytokines when taurolidine was preincubated with LPS before being added to PBMC. This reduction was independent of the molar ratio of taurolidine to LPS but was related to the concentration of taurolidine present in the PBMC cultures. There was a 80 to 90% reduction in total IL-1 and TNF synthesis induced by LPS at concentrations of taurolidine of 40 to 100 micrograms/mL; the vehicle was without effect. Following a 30-min preincubation with PBMC, taurolidine could be washed from the cells and still suppress cytokine synthesis induced by LPS. Using release of lactic acid dehydrogenase, 100 micrograms/mL of taurolidine was not toxic for PBMC. Taurolidine also reduced IL-1 and TNF synthesis induced by the Staphylococcus aureus-derived toxic shock syndrome toxin-1 as well as that induced by nontoxic heat-killed Staphylococcus epidermidis organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyltransferases↗
PubMed1980

The Jeremiah Metzger Lecture. The pathogenesis of fever in human subjects.

The pathogenesis of fever in man begins with the production of endogenous pyrogen by phagocytic leukocytes in response to exogenous pyrogens (toxic, immunologic or infectious agents). Endogenous pyrogen, a protein, is released from a variety of phagocytic leukocytes and enters the circulation after new messenger RNA and protein are synthesized. Fever is caused by an interaction of endogenous pyrogen with specialized receptors on or near thermosensitive neurons in the thermoregulatory center of the anterior hypothalamus. This interaction may cause local hypothalamic production of prostaglandins, monoamines and, possibly, cyclic AMP. From the anterior hypothalamus, information is transmitted through the posterior hypothalamus to the vasomotor center, which directs sympathetic-nerve fibers to constrict peripheral vessels and decrease heat dissipation.

Animals↗
PubMed1979

Cyclophosphamide therapy of severe systemic necrotizing vasculitis.

We studied 17 patients with severe systemic necrotizing vasculitis over an 11-year-period. Sixteen patients were treated daily with cyclophosphamide (2 mg per kilogram per day), and one was treated with azathioprine (2 mg per kilogram per day). Before entering the study, all patients had active and progressive disease, even though 16 patients had been receiving corticosteroids that had caused severe and often incapacitating toxic side effects. Three patients died during the study. Complete and often dramatic remissions occurred in the surviving 14 patients, who were then placed on alternate-day corticosteroid treatment with continuation of cyclophosphamide. Corticosteroids were later discontinued in seven patients. The mean duration of remission was 22 months (range, two to 61). No patient showed recurrence of disease during treatment with cytotoxic agents.

Adolescent↗
PubMed1978

Correction of human cyclic neutropenia with prednisolone.

A 70-year-old woman with cyclic neutropenia was treated with 16 mg of etiocholanolone and 25 mg of prednisolone intramuscularly every other day. During 14 weeks' treatment amplitude of cyclic fluctuations in neutrophil counts gradually decreased, but pretreatment cycles returned promptly after treatment was stopped. Prednisolone alone every other day (25 mg) reproduced this result, and by 23 weeks, neutrophil counts became stable at about 1500 per cubic millimeter. tcycling of monocytes, platelets and reticulocytes was also eliminated, as were symptoms that had accompanied neutropenic periods. In addition, bone-marrow neutrophil precursors and neutrophil marrow reserves were stabilized. The patient was subsequently maintained satisfactorily with oral prednisolone, 20 mg every other day. These studies demonstrate that the discontinuous myeloid maturation that occurs in cyclic neutropenia can be corrected with prednisolone every other day.

Aged↗
PubMed1978

Cyclophosphamide-induced remissions in advanced polyarteritis nodosa.

Two patients with far advanced polyarteritis nodosa involving multiple organ systems and with aneurysm formation demonstrable by celiac axis and renal arteriograms were treated with oral cyclophosphamide, 1 to 2 mg/kg/day, and alternate day prednisone therapy. Dramatic remissions of disease activity were achieved within weeks of initiation of therapy. Repeat angiograms obtained after one year revealed complete resolution of all aneurysms. Both patients are now receiving only cyclophosphamide and are maintained in complete remission 27 and 18 months after the start of therapy. Cyclophosphamide therapy can thus be highly effective even in far advanced polyarteritis nodosa.

Adult↗
PubMed1978

Familial mediterranean fever: a status report.

The recent discovery that an age-old drug, colchicine, can control this enigmatic, often unrecognized, recurrent disease means that most affected individuals can now lead virtually normal lives. The research leading to this advance is described, as are the essentials of diagnosis, colchicine's possible mechanisms of action, and the relative merits of chronic vs intermittent colchicine therapy in the abortion of impending attacks.

Adolescent↗
PubMed1978

Lack of specificity of the limulus lysate test in the diagnosis of pyogenic arthritis.

The diagnosis of pyogenic arthritis may be difficult to confirm since culture results are sometimes negative. This study attempted to evaluate the utility of the limulus lysate assay for the early detection of pyogenic arthritis due to gram-negative organisms. Seven-one specimens of synovial fluid from 46 patients were evaluated for reactivity in the limulus test, pyrogenic responses in rabbits, total white blood cell count, total neutrophil count, total red blood cell count, and protein and glucose concentrations. All patients with culture-proven septic arthritis or presumptive septic arthritis had joint fluid specimens that yielded a positive result in the limulus assay (12 patients). However, 52.9% of patients (18 of 34) who had a nonseptic cause for their joint effusion also had a joint fluid specimen that was positive in the limulus test. A positive limulus test result showed a significant correlation with an elevated total white blood cell count (P less than 0.0005), an elevated absolute neutrophil count (P less than 0.0005), and a decreased concentration of glucose (P less than 0.005) in synovial fluid, and the production of fever in rabbits after injection of synovial fluid (P less than 0.05). Thus, this study suggests that a positive result in the limulus test on joint fluid is nonspecific for a septic process, but a negative result would be evidence against it.

Arthritis, Infectious↗
PubMed1978

The pyrogenicity of the synthetic adjuvant muramyl dipeptide and two structural analogues.

The pyrogenic efect of the synthetic adjuvant N-acetylmuramyl-L-alanine-D-isoglutamine, also known as muramyl dipeptide (MDP), was studied in rabbits. MDP induced biphasic fevers in rabbits, but two structural analogues, N-acetylmuramyl-L-alanine-D-glutamic acid (MDPA) and the dimethylester of MDPA, were 10 times less pyrogenic. This finding was supported by studies in which MDP and its analogues released leukocytic pyrogen (LP) from rabbit phagocytic cells in vitro. In addition, MDP released LP from human phagocytes. Human phagocytes, however, required a 10-fold greater concentration of MDP than did rabbit cells. The structural analogues were similarly less effective than the parent molecule in releasing LP from human cells. All preparations of MDP were negative in the limulus amebocyte lysate test and failed to show pyrogenic cross-tolerance with bacterial endotoxin. Thus MDP, which is a pyrogenic molecule, is also able to release LP from rabbit phagocytes and to a lesser degree from human phagocytes, but does not cause gelation of limulus amebocyte lysate.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1978

Computer assisted tomography of orbital lesions in Wegener's granulomatosis.

The orbital lesions in six patients with Wegener's granulomatosis were studied by computer assisted tomography (CAT). Four patients had active orbital disease and proptosis, and each was found to have orbital masses accompanied by varying degrees of bone and sinus destruction. Two additional patients with histories of proptosis had no orbital lesions at the time of CAT study.

Adult↗