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Biomedical subjects

S M Wolff

Publications and source records attributed to S M Wolff.

At least 109 records · Page 6Linked to original sources

Effect of induced fever on serum iron and ferritin concentrations in man.

Previous reports have shown that endotoxin decreases serum iron in experimental animals. In this study fever was produced in nine female and nine male normal subjects in order to define the temporal and quantitative changes in serum iron and ferritin concentrations. Six volunteers were randomly given bacterial endotoxin (5 ng/kg) or saline intravenously and received the alternative compound a week later. Serial blood samples were drawn at 4-hr intervals for a 24-hr period, beginning when the compound was administered, for the determination of serum iron and ferritin concentrations. The same study was performed with intramuscular etiocholanolone (0.3 mg/kg) or the vehicle, propylene glycol, as a control, but the first blood sample was obtained 9 hr after the compound was given. In addition, blood samples were obtained at 12-hr intervals in six volunteers for 11 days after an intramuscular injection of etiocholanolone. The results showed a significant increase (p less than 0.005 for etiocholanolone, P less than 0.01 for endotoxin) in serum ferritin and a significant decrease (p less than 0.005 for etiocholanolone, p less than 0.001 for endotoxin) in serum iron for both pyrogenic compounds compared with the control compounds. However, the amount of fever and the changes in the iron parameters were greater with etiocholanolone. One episode of induced fever with etiocholanolone effected changes in serum ferritin and iron concentrations that lasted 10 days. Thus this study demonstrated that a single episode of fever in man produced rapid and prolonged changes in serum iron and ferritin concentrations.

Adult↗

Successful renal transplantation in Wegener's granulomatosis.

Two patients with Wegener's granulomatosis, who were in complete remission secondary to cyclophosphamide therapy but who had end-stage renal failure, were treated with renal transplantation. Neither patient has clinical evidence of recurrent glomerulonephritis 10 and 28 months after receiving the renal transplants. Cytotoxic therapy has been proved to be highly effective in inducing and maintaining remission in patients with Wegener's granulomatosis; thus increasingly larger numbers of patients will be seen who, despite being maintained in complete remission, will have markedly impaired renal function due to previous acute damage. Renal transplantation can now be considered an acceptable alternative form of therapy in such patients.

Adult↗

Nonspecific resistance to infection induced in mice by a water-soluble adjuvant derived from Mycobacterium smegmatis.

The effect of a nontoxic, water-soluble adjuvant (Neo-WSA) from delipidated cells of Mycobacterium smegmatis on the susceptibility of mice to infection with four challenge organisms was studied. An intravenous dose of 1 mg of Neo-WSA per mouse 24 hr before challenge enhanced resistance to infection with a fungus (Candida albicans), a gram-negative bacterium (Klebsiella pneumoniae), and a gram-positive bacterium (Streptococcus pneumoniae). Protection by Neo-WSA was not significant when the mice were challenged with a malarial parasite. Plasmodium berghei. When 1 mg of Neo-WSA was given intravenously to mice 10 min before challenge with C. albicans, protection was significant, but when the same dose was given two or six days prior to challenge, mice were not protected. The concentration of iron in serum had not changed significantly 1 or 24 hr after the intravenous injection of 1 mg of Neo-WSA. Thus Neo-WSA is capable of inducing nonspecific resistance to certain experimental infections in mice. The protection afforded by administration of Neo-WSA 10 min before challenge, the lack of protection afforded by administration of Neo-WSA six days before challenge, and the lack of significant change in the serum iron concentration clearly separate this compound from bacterial endotoxins, which are classical inducers of nonspecific resistance to infection.

Adjuvants, Immunologic↗

Surface sulphydryl groups and hexose monophosphate pathway activity in resting human polymorphonuclear leucocytes.

The role of surface -SH groups on the hexose monophosphate pathway activity in resting human polymorphonuclear leucocytes was studied. Endotoxin, taurocholic acid and concanvalin A stimulated [I-14C]glucose oxidation to a greater degree than [6-14C]glucose oxidation. The stimulation of glucose-I-C-oxidation by endotoxin, taurocholic acid and concanavalin A could be prevented by p-chloromercurybenzene sulphonic acid, an inhibitor of surface -SH groups. In contrast, polymorphonuclear leucocytes from four patients with chronic granulomatous disease failed to show stimulation of glucose-I-C-oxidation by endotoxin, taurocholic acid or concanavalin A.

4-Chloromercuribenzenesulfonate↗

Changes in the composition of canine respiratory cells obtained by bronchial lavage following irradiation or drug immunosuppression.

Canine respiratory cells, obtained by bronchial lavage, and blood leukocytes were monitored to observe cellular changes following acute and chronic immunosuppression. Irradiation (350 R) produced bone marrow suppression and prompt peripheral blood leukopenia, but did not affect recovery of pulmonary alveolar macrophages or lymphocytes for 12 days after. Treatment for 6 weeks with daily methylprednisolone (1 mg/kg) caused a progressive decrease in the number of recoverable respiratory lymphocytes, whereas alternate day methylprednisolone (2 mg/kg) had less effect. Cyclophosphamide in combination with steroids generally augmented the progressive loss of blood and respiratiory lymphocytes. Recovery of alveolar macrophages was not changed appreciably. Thus, the population of lung macrophages, sampled by pulmonary lavage, withstood acute and chronic forms of immunosuppression very well. In contrast, canine lymphocytes seem more susceptible to injury, especially to drug regimens containing steroids.

Animals↗

Radiation therapy of midline granuloma.

During a 15-year period, 10 patients with well-documented midline granuloma were treated with high-dose, deep local irradiation and followed for extended periods of time. Long-term remissions were achieved in 7 patients, with a mean (+/- SEM) survival postirradiation of 7.4 (+/- 1.4) years in the 6 patients still alive. True midline granuloma, which is a localized, destructive, inflammatory process of the upper airways, can be distinguished from Wegener's granulomatosis and neoplasms of the upper respiratory tract by several clinicopathologic criteria. The cause of midline granuloma is unknown, but it most likely represents an abnormal accelerated hypersensitivity reaction to an unknown antigen(s). Although serious complications of high-dose local irradiation to the upper airways can occur, the risk is warranted because of the high, long-term remission rate in this previously uniformly fatal disease.

Adolescent↗

Chediak-Higashi syndrome: reversal of increased susceptibility to infection by bone marrow transplantation.

Transplantation of normal bone marrow to mice with the Chediak-Higashi syndrome (CHS) resulted in normal granulopoiesis and a reversal of their increased susceptibility to challenge with intravenous Candida albicans. These findings suggest that (1) the leukocyte defect in CHS can be reversed by marrow transplantation and (2) the mechanism for increased susceptibility to infection in these animals is due to a bone-marrow-derived cellular defect. Because of similarities between murine and human CHS, bone marrow transplantation might be considered as a mode of therapy in selected cases of the human disease.

Animals↗

Decreased nucleotide and serotonin storage associated with defective function in Chediak-Higashi syndrome cattle and human platelets.

Prolonged mean template bleeding time of 14 min observed in seven cattle with the Chediak-Higashi syndrome (CHS) prompted the examination of platelet function in these animals. There was no distinguishable difference in concentration of circulating platelets between CHS and control cattle. CHS bovine platelets failed to aggregate in vitro in response to concentrations of acid-soluble collagen which induced aggregation in all normal samples. The primary platelet response to 5 muM ADP was normal in CHS cattle. A markedly decreased amount of serotonin (1.2% of normal) was detected in CHS bovine platelets. Bovine CHS platelet ATP and ADP contents were significantly less than normal, and the ATP/ADP ratios were 5.04 in normal and 29.38 in CHS platelets. Results of these animal investigations prompted a similar study of two patients with CHS. In humans, an increased bleeding time greater than 15 min and an in vitro impaired aggregation response to acid-soluble collagen and 5 muM adrenaline were discovered. Both ATP and ADP were reduced in CHS human platelets, and the ATP/ADP ratio was 3.96, compared to a ratio of 1.52 for platelets of two normal subjects. These findings suggested the presence of a "storage pool disease" of CHS platelets.

Adenosine Diphosphate↗

Defective polymorphonuclear leukocyte chemotaxis and bactericidal capacity in a boy with recurrent pyogenic infections.

A 13-year-old boy with a history of recurrent pyogenic infections had abnormalities of polymorphonuclear leukocyte (PMN) function which probably accounted for his susceptibility to infection. PMN phagocytosis and nitroblue tetrazolium dye reduction were normal but glucose 14C oxidation was abnormally increased in resting cells. The patient's PMNs possessed decreased bactericidal activity against Staphylococcus aureus and Escherichia coli. Also documented were decreased PMN chemotactic activity and leukocyte accumulation in Rebuck skin windows. PMN random motility, PMN bone marrow reserve, PMN kinetics, lymphocyte blastogenesis, and delayed cutaneous hypersensitivity were normal. This patients represents another of the growing number of distinct granulocytopathies currently being recognized which may result in increased susceptibility to infection.

Adolescent↗

A platelet abnormality in the Chediak-Higashi syndrome of man.

Platelets from two probands homozygous for the Chediak-Higashi syndrome have approximately 10% of the normal number of serotonin-containing dense bodies as visualized electron microscopically in air-dried whole mounts. Since transport of serotonin across the platelet plasma membrane proceeds at a normal rate, and the few dense bodies present appear to store normal amounts of serotonin, the absence of dense bodies may account for the low platelet serotonin values found in these patients.

Blood Coagulation Disorders↗

Lack of clinical usefulness of the limulus test in the diagnosis of endotoxemia.

Studies of the clinical value of the limulus amebocyte lysate test for the detection of endotoxemia are inconsistent. In an attempt to define the value of this test, a total of 237 plasma samples from 111 patients were tested for endotoxin with seven different lysate preparations. A total of 48 plasma samples yielded a positive test with one or more of the seven preparations. Two of eight samples positive with all seven preparations were from ambulatory patients. A significant positive correlation of the test with bacteremia, neutrophilia and elevated serum alkaline phosphatase was found. Only three of the 48 positive tests occurred by four hours of incubation, and only 12 were associated with positive blood cultures (eight contained gram-negative bacteria). The test now available has no clinical usefulness in the detection of endotoxemia or gram-negative septicemia.

Adolescent↗

Effects of etiocholanolone-induced fever on plasma antipyrine half-lives and metabolic clearance.

The plasma half-life and metabolic clearance rate of antipyrine, a drug metabolized by hepatic microsomal enzymes, were determined in 33 normal volunteers during a basal state and during fever induced with a single intramuscular injection of etiocholanolone. Of the 14 normal volunteers who achieved significant fever (fever index greater than 50), in 11 plasma antipyrine half-life was prolonged after a single oral dose of 10 mg/kg and antipyrine metabolic clearance rate was decreased. There was no significant change of these mean values in 19 normal volunteers who failed to develop significant fever (fever index smaller than 50). Therefore, under the conditions of this study plasma antipyrine half-life was prolonged, probably due to impaired hepatic metabolism, during etiocholanolone-induced fever, although no correlation was observed between the magnitude of fever and the extent to which plasma antipyrine half-life was prolonged. Failure to obtain such a correlation may be attributable to the very small range of temperature elevation, extending from 37.9 degrees C to 39.2 degrees C, in the group of 14 subjects achieving significant etiocholanolone-induced fever (fever index greater than 50). A higher dose of antipyrine (18 mg/kg) suppressed induction of fever by etiocholanolone; antipyrine is the only orally administered drug thus far shown to be effective in repressing etiocholanolone-induced fever.

Adolescent↗

A primate model for the study of human fever.

The effect of semipurified human leukocytic pyrogen isolated in vitro from neutrophilic leukocytes was studied in awake, chair-restrained rhesus monkeys. Intravenously administered leukocytic pyrogen elicited (1) a monophasic fever of short duration and latency to onset that varied from animal to animal and (2) a febrile response that was much greater at night, when the base-line temperature is low, than during the day, when the base-line temperature is high. Intravenous indomethacin, in contrast to large intravenous doses of sodium salicylate, reduced the febrile response to leukocytic pyrogen. Rapid, repeated injections of leukocytic pyrogen prolonged the febrile response from 1 1/2 to 5 1/2 hr, at which point there was a sudden 300%-400% increase in fever increment over a 30-min period. Since the rhesus monkey is as sensitive to human leukocytic pyrogen as the rabbit, it is proposed that this primate might serve as a useful model in investigations directed toward the understanding of the pathophysiology of fever in human beings.

Animals↗

Radiographic changes in the sacroiliac joints in familial Mediterranean fever.

In a series of 43 patients with familial Mediterranean fever, six were found to have radiographic changes in the sacroiliac joints consisting of loss of normal cortical definition, sclerosis on both sides of the joint with or without erosions, and fusion. These changes were noted despite the absence of clinically symptomatic joint disease. The explanation for these findings is unknown.

Adult↗