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Biomedical subjects

S M Wolff

Publications and source records attributed to S M Wolff.

At least 73 records · Page 4Linked to original sources
PubMed1981

Human cyclic neutropenia: clinical review and long-term follow-up of patients.

Human cyclic neutropenia is a distinctive disorder of unknown cause characterized by regularly recurrent episodes of profound neutropenia, which have a periodicity of about 3 weeks. This periodicity remains constant and is remarkably consistent among patients. Although blood elements other than neutrophils are nt depleted, essentially all patients experience a cycling of monocyte counts with monocyte cycles of the same length as but reciprocal to neutrophil cycles. Cycling of platelet and reticulocyte numbers also may occur. Patients experience a clinical syndrome of recurrent illness characterized by malaise, fever, aphthous stomatitis, and cervical adenopathy. Incidental infections may occur with neutropenia but respond readily to antibiotics. The clinical course is benign compared with others conditions in which similar degrees of neutropenia occur. The only life-threatening complication encountered during long-term follow-up of patients was the occurrence of spontaneous peritonitis, segmental bowel necrosis, and septicemia which required surgical intervention. Most patients develop the disease in childhood, but a significant number of patients develop the disease in adulthood as an apparently acquired condition. The disease occurs equally in both sexes and is familial in some. Studies of marrow morphology, myelopoiesis, and neotrophil kinetics have shown that cyclic neutropenia is primarily a disease of abnormally regulated neutrophil production. The judicious use of antibiotics, careful oral and dental care, and patient education are the mainstays of management. Alternate-day corticosteroids have been used successfully to abate the recurrent signs and symptoms, and in one patient the disease was gradually corrected by alternate day prednisolone. Human cyclic neutropenia is of special investigative interest because clarification of this disease may contribute greatly to an understanding of the normal control of myelopoiesis.

Agranulocytosis↗
PubMed1981

Demonstration of a circulating suppressor factor of thymocyte proliferation during endotoxin fever in humans.

Sub-pyrogenic levels of human leukocytic pyrogen (LP) have been shown to enhance phytohemagglutinin-induced murine thymocyte proliferation. It was concluded that LP is similar to lymphocyte-activating factor (LAF). Since endotoxin stimulates the production of LP and LAF, we attempted to employ in vitro thymocyte proliferation to detect circulating LP/LAF in 12 normal human subjects during experimental endotoxin fever. Sera obtained before and during fever were first mixed with an immunoadsorbent that binds human LP/LAF, and then the dissociated material was added to thymocyte cultures. Material derived from sera obtained during the maximum fever (3 to 4 hr after endotoxin) was markedly suppressive for thymocyte proliferation in vitro. The appearance of this suppressive effect correlated with the profound lymphopenia observed in the subjects. This suppressor factor(s) was nondialyzable and was destroyed at 70 degrees C, and its suppressive effects inhibited the lymphocyte-activating property of LP/LAF. In addition, the suppression of PHA responses did not appear to be modulated by prostaglandin synthesis. The results demonstrate that a factor circulates during endotoxin fever in humans that suppresses in vitro thymocyte proliferation.

Adult↗
PubMed1980

Recurrence of Wegener's granulomatosis after kidney transplantation. Successful re-induction of remission with cyclophosphamide.

A patient with Wegener's granulomatosis underwent successful kidney transplantation. After four years he had a recurrence of his disease while being maintained on azathiorpine. Substitution of cyclophosphamide for azathioprine resulted in a rapid remission of the Wegener's granulomatosis. Renal function has remained stable, and the patient has done well. As previous reports have suggested, it appears that cyclophosphamide is the immunosuppressive drug of choice in the treatment of Wegener's granulomatosis and that azathioprine is not as effective as cyclophosphamide in the treatment of this form of systemic vasculitis.

Adult↗
PubMed1980

Effect of indomethacin on increased resistance to bacterial infection and on febrile responses induced by muramyl dipeptide.

The pyrogenicity in the rabbit and the ability to stimulate nonspecific resistance to bacterial infection in the mouse of muramyl dipeptide (MDP), a synthetic immunoadjuvant, are known to be enhanced when the glycopeptide has been conjugated to a carrier. The effects of indomethacin on fever induced by MDP or its conjugated derivative were studied. Indomethacin reduced febrile responses to MDP or its derivative, although it did not decrease production of endogenous pyrogen in vivo or in vitro. When incubated with rabbit peritoneal cells, indomethacin suppressed the elevation in prostaglandin levels usually induced by MDP. When administered to mice, indomethacin alone stimulated resistance to bacterial infection and, under appropriate conditions, had a strong synergistic effect when combined with free or conjugated MDP. The results demonstrate that neither pyrogenicity nor increased prostaglandin levels are prerequisites for immunopotentiation by synthetic glycopeptides.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1980

Wegener's granulomatosis.

Wegener's granulomatosis is characterized by a necrotizing granulomatous vasculitis which can be found in both the upper and lower respiratory tracts and with either focal or proliferative glomerulonephritis. However, any organ system can be affected by the disease. Over the past 17 years, 47 patients with histologically proven Wegener's granulomatosis have been treated at the National Institute of Allergy and Infectious Disease. Since 1972, patients with head and neck manifestations have been managed in collaboration with the Department of Otolaryngology, National Naval Medical Center. Experiences with these patients have shown that all have had some degree of respiratory tract involvement, with 42/47 having disease in the nose or paranasal sinuses. An effective therapeutic regimen is possible with immunosuppressants (particularly cyclophosphamide) and locally supportive measures. As a result of such therapy, more than 80% of the patients treated have experienced long-term remissions. The clinical implications of this therapy are discussed, and a protocol for patient management presented.

Adolescent↗
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↗