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R C Woodman

Publications and source records attributed to R C Woodman.

9 recordsLinked to original sources
PubMed1992

Prolonged recombinant interferon-gamma therapy in chronic granulomatous disease: evidence against enhanced neutrophil oxidase activity.

Recombinant interferon-gamma (rIFN-gamma) therapy has become an effective form of prophylaxis for patients with chronic granulomatous disease (CGD). Preliminary studies with CGD suggested that rIFN-gamma treatment enhanced phagocyte oxidase activity and increased superoxide (O2-) production. We evaluated several aspects of neutrophil NADPH oxidase activity in 19 CGD patients (representing all four known types of CGD) receiving prolonged rIFN-gamma therapy (6 to 27 months). In contrast to earlier studies, we failed to detect any improvement in neutrophil NADPH oxidase activity in 18 of the 19 CGD patients as determined by (1) intact cell O2- production (continuous assay), (2) nitroblue tetrazolium (NBT) staining, (3) cytochrome b558 spectroscopy, and (4) activity levels of cytosol and membrane oxidase components using a cell-free activation system. One patient with a variant form of X-linked CGD had a transient increase in neutrophil O2- production following 3 months of rIFN-gamma therapy. However, this was not sustained, and was not associated with any change in cytochrome b levels. In some patients, rIFN-gamma therapy was associated with the appearance of a small subset of circulating monocytes (1% to 20%) that were NBT-positive. Although the functional significance of this monocyte subpopulation needs to be determined, these results suggest that one possible mechanism by which rIFN-gamma may benefit CGD patients is by partially correcting the respiratory burst defect in a subset of monocytes. We conclude that the clinical benefit of prolonged rIFN-gamma therapy in the vast majority of CGD patients is not due to enhanced neutrophil NADPH oxidase activity. The mechanism of action of rIFN-gamma in most CGD patients remains unknown.

Child↗
PubMed1992

Allogeneic bone-marrow transplantation without protective isolation in adults with malignant disease.

Bone-marrow transplant (BMT) patients are severely immunocompromised immediately after the procedure and they are commonly nursed in strict protective isolation to reduce the risk of both infection and graft-versus-host disease (GvHD). We have studied a consecutive series of patients to see whether protective isolation is of benefit as prophylaxis against infectious complications of BMT. 50 consecutive patients who had malignant disease and received their first BMT from siblings or unrelated donors were nursed in standard single rooms with visitors instructed to wash their hands. A subset of 20 patients living locally spent a median of 25 days in hospital after BMT; they also spent some time at home on a median of 8 days before engraftment and 3 patients went home on more than 90% of their hospital days. 16 patients (32%) had positive bacterial cultures and/or focal infection. Gram-positive bacteraemia was found in 12 subjects (24%) but there were no gram-negative or deep fungal infections. Grade II or III acute GvHD developed in 17 patients (34%). There were no deaths from infection or acute GvHD. Transplant-related mortality was 6% in the first 100 days and 18% overall with a median follow-up of 22 months. Our mortality data compare favourably with those from institutions with strict isolation procedures. We conclude that BMT may be safely completed in some institutions without either protective isolation or the need to confine patients continuously in hospital.

Acute Disease↗
PubMed1991

Respiratory burst oxidase and three of four oxidase-related polypeptides are associated with the cytoskeleton of human neutrophils.

Resting and phorbol-activated human neutrophils were separated by treatment with Triton X-100 into detergent-extractable and cytoskeleton fractions. Respiratory burst oxidase activity was restricted entirely to the cytoskeleton. The cytoskeleton also contained approximately 15% of the neutrophil cytochrome b558, an oxidase-associated heme protein, as well as most of the oxidase-related cytosolic polypeptide p67phox. In contrast, the components of the oxidase-associated phosphoprotein family p47phox were found almost exclusively in the detergent extract, suggesting that p47phox is needed for oxidase activation but not for O2- production by the activated oxidase. Activation of the oxidase had no apparent effect on the distribution of any of these species between the cytoskeleton and the detergent extract. Our results support earlier studies implying that the cytoskeleton participates in an important way in regulating the activity of the O2(-)-forming respiratory burst oxidase of neutrophils.

Blotting, Western↗
PubMed1990

Bleeding complications associated with cardiopulmonary bypass.

Bleeding after CPB has been difficult to characterize and its treatment equally difficult to standardize. The complexity of this problem is related to the hemostatic process, the technical variations in the operative procedures, and the many uncontrolled variables associated with CPB, including the effects of anesthetic or pharmacologic agents, the nature of the priming solution, hemodilution, hypothermia, the type of oxygenator, and the use of transfused blood products. Although there are multiple and generally predictable complex changes in the hemostatic mechanism during CPB, the temporary loss of platelet function is the most common and clinically relevant. This transient platelet dysfunction occurs in all patients undergoing CPB; however, it only causes excessive bleeding in a small percentage of patients. Unfortunately, it has not yet been possible to predict which patients will develop hemorrhagic complications, although prolonged pump times are a contributing risk factor. Over the past decade there has been extensive investigation into the management of bleeding associated with CPB, provoked primarily by the increased awareness of transfusion-transmitted viral diseases and the inappropriately excessive use of homologous blood products. Several approaches to autotransfusion of shed blood and autologus blood donation have been developed to minimize perioperative homologous blood transfusion. Pharmacologic agents such as desmopressin, aprotinin, and topical fibrin glues have also been introduced to improve hemostasis during CPB. The protease inhibitor aprotinin is particularly promising in the reduction of bleeding associated with CPB when given prophylactically. Aprotinin may provide new insights into the mechanism of CPB-induced platelet dysfunction. Desmopressin is indicated only for the treatment of bleeding after CPB. The management of bleeding associated with CPB will undoubtedly

Cardiopulmonary Bypass↗
PubMed1988

Evidence that de novo protein synthesis participates in a time-dependent augmentation of the chemotactic peptide-induced respiratory burst in neutrophils. Effects of recombinant human colony stimulating factors and dihydrocytochalasin B.

We examined the effects of the recombinant human colony stimulating factors GM-CSF and G-CSF, cycloheximide (a protein synthesis inhibitor) and dihydrocytochalasin B (a microfilament disrupting agent) upon FMLP (N-formyl-methionyl-leucylphenylalanine)-stimulated O2- production by neutrophils. We confirmed a time dependent augmentation of O2- production following preincubation of neutrophils either alone or with colony stimulating factors. Furthermore, we found that GM-CSF, but not G-CSF, increased O2- production at some concentrations of the stimulus. Preincubation of neutrophils with cycloheximide in the absence of CSF caused a marked fall in O2- -production that was first evident at 2 hours. The fall in O2- -forming capacity caused by cycloheximide was much less pronounced if dihydrocytochalasin B was also included in the preincubation buffer. These findings suggest a previously unrecognized role for de novo protein synthesis in maintaining the ability of neutrophils to manufacture O2-, and support earlier studies indicating that the cycling of FMLP receptors between the cell membrane and an intracellular compartment is important in determining the magnitude of the respiratory burst in FMLP-stimulated neutrophils.

Blood Proteins↗
PubMed1986

Papular leukemids.

Skin lesions occurring in patients with leukemia may represent specific leukemic infiltrates or may manifest as nonspecific lesions not related to leukemic cell infiltration. Included in the latter are a number of nonspecific papular and nodular lesions generally called "leukemids." We present two patients with lesions we have categorized as papular leukemids.

Aged↗