PubMed Health⌕ Search

Biomedical subjects

P C Taylor

Publications and source records attributed to P C Taylor.

At least 19 recordsLinked to original sources
PubMed1999

Effects of treatment of rheumatoid arthritis patients with an antibody against tumour necrosis factor alpha on reticuloendothelial and intrapulmonary granulocyte traffic.

The therapeutic effects of a monoclonal antibody against tumour necrosis factor alpha (TNFalpha) were evaluated objectively in 10 patients with rheumatoid arthritis by 111In-labelled granulocyte imaging before and after treatment, and compared with changes in granulocyte kinetics with respect to the liver, spleen and lungs. Anti-TNFalpha resulted in a decrease in the size of the whole-body pool of marginating granulocytes, as reflected by a significant increase in the 30 min intravascular recovery of labelled granulocytes from 40% (S.D. 10) to 47% (S.D. 16) of injected activity (P<0.02). The 111In contents of the spleen, liver and lungs were unchanged, so the origin of the increment in recovery was presumed to be a reduction in granulocyte margination in inflamed synovium, although this was not quantifiable. The sizes of the granulocyte pools in the liver and lungs, expressed as the 111In content of the organ per unit of circulating 111In-labelled cells, were not significantly different after treatment, but the splenic granulocyte pool decreased by 16% (S.D. 19) (P<0.05). Individual changes in the size of the splenic pool showed no significant correlation with corresponding changes in 30 min recovery or with corresponding indices of inflammation (24 h 111In-granulocyte joint activity and C-reactive protein). We conclude that anti-TNFalpha produces an obvious resolution in inflammatory joint activity that is accompanied by an increased circulating component of the total blood granulocyte pool, as a result of decreased margination at sites of inflammation. Anti-TNFalpha may also produce a specific decrease in splenic granulocyte pooling, independent of any anti-inflammatory effects, although a similar decrease in the lungs, which might be anticipated as a result of reduced cytokine-induced granulocyte activation, could not be detected.

Aged↗
PubMed1998

Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men.

This study was conducted to determine the effects of arachidonic acid (AA) supplementation on human immune response (IR) and on the secretion of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4). Ten healthy men (20-38 yr) participated in the study and lived at the Metabolic Suite of the Western Human Nutrition Research Center. They were fed a basal diet (57, 27, and 16 energy percentage from carbohydrate, fat, and protein, respectively, and AA 200 mg/d) for the first 15 d of the study. Additional AA (1.5 g/d) was added to the diet of six men from day 16 to 65, while the remaining four subjects remained on the basal diet. The diets of the two groups were crossed-over from day 66 to 115. In vitro indices of IR were examined using blood drawn on days 15, 58, 65, 108, and 115. Influenza antibody titers were determined in the sera prepared from blood drawn on days 92 and 115 (23 d postimmunization). AA supplementation caused significant increases in the in vitro secretion of LTB4, and PGE2, but it did not alter the in vitro secretion of tumor necrosis factor alpha; interleukins 1 beta, 2, 6; and the receptor for interleukin 2. Nor did it change the number of circulating lymphocytes bearing markers for specific subsets (B, T, helper, suppressor, natural killer) and the serum antibody titers against influenza vaccine. The opposing effects of PGE2 and LTB4 may have led to the lack of change in immune functions tested.

Adult↗
PubMed1998

Dietary docosahexaenoic acid and immunocompetence in young healthy men.

The purpose of this study was to examine the effect of dietary docosahexaenoic acid (DHA), in the absence of eicosapentaenoic acid, on human immune response (IR). A 120-d study with 11 healthy men was conducted at the Metabolic Research Unit of the Western Human Nutrition Research Center. Four subjects (control group) were fed the stabilization or basal diet (15, 30, and 55% energy from protein, fat, and carbohydrate, respectively) throughout the study; the remaining seven subjects (DHA group) were fed the basal diet for the first 30 d, followed by 6 g DHA/d for the next 90 d. DHA replaced an equivalent amount of linoleic acid; the two diets were comparable in their total fat and all other nutrients. Both diets were supplemented with 20 mg d-alpha-tocopherol acetate per day. Indices of IR were examined on study day 22, 30, 78, 85, 106, and 113. Addition of DHA at moderately high levels did not alter the proliferation of peripheral blood mononuclear cells cultured with phytohemagglutinin or concanavalin A, or the delayed hypersensitivity skin response. Also, additional DHA did not alter the number of T cells producing interleukin 2 (IL2), the ratio between the helper/suppressor T cells in circulation, or the serum concentrations of immunoglobulin G, C3, and interleukin 2 receptor (IL2R). DHA supplementation, however, caused a significant (P = 0.0001) decrease in the number of circulating white blood cells which was mainly due to a decrease in the number of circulating granulocytes. The number of lymphocytes in peripheral circulation was not affected by Dietary DHA enrichment, but the percentage of lymphocytes in white blood cells increased because of a reduction in granulocyte numbers. None of these indices was changed in the control group. Our results show that when total fat intake is low and held constant, DHA consumption does not inhibit many of the lymphocyte functions which have been reported to be inhibited by fish oil consumption.

Adult↗
PubMed1998

Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women.

To determine the human folate requirement on the basis of changes in biochemical pathways, we studied the effect of controlled folate intakes on plasma homocysteine and lymphocyte DNA methylation and deoxynucleotide content in healthy postmenopausal women. Eight women (49-63 y of age) were housed in a metabolic unit and fed a low folate diet containing 56 microg/d of folate for 91 d. Folate intake was varied by supplementing 55-460 microg/d of folic acid (pteroylglutamic acid) to the diet to provide total folate intake periods of 5 wk at 56 microg/d, 4 wk at 111 microg/d and 3 wk at 286-516 microg/d. A subclinical folate deficiency with decreased plasma folate was created during the first two periods. This resulted in significantly elevated plasma homocysteine and urinary malondialdehyde, and lymphocyte DNA hypomethylation. The folate depletion also resulted in an increased ratio of dUTP/dTTP in mitogen-stimulated lymphocyte DNA and decreased lymphocyte NAD, changes suggesting misincorporation of uracil into DNA and increased DNA repair activity. The DNA hypomethylation was reversed with 286-516 microg/d of folate repletion, whereas the elevated homocysteine decreased with 516 but not 286 microg/d of folate. The results indicate that marginal folate deficiency may alter DNA composition and that the current RDA of 180 microg/d may not be sufficient to maintain low plasma homocysteine concentrations of some postmenopausal women.

Creatinine↗
PubMed1997

Clonal analysis of immunoglobulin mRNA in rheumatoid arthritis synovium: characterization of expanded IgG3 populations.

Plasma cells secreting IgG, M, and A abound in the synovium of patients with rheumatoid arthritis, yet their immunoglobulin repertoire and clonal relationship remain to be elucidated. Locally synthesized immunoglobulins probably contribute to the chronic joint inflammatory processes which are characteristic of these patients. To determine whether B lymphocyte proliferation contributes to the synovial plasma cell infiltrate, the clonality of IgG mRNA in individual synovial biopsies from an actively inflamed joint of patients with rheumatoid arthritis was investigated by a combination of cDNA length analysis and DNA sequencing. Particular sizes of immunoglobulin cDNA, detectable in subclasses 1, 3, or 4, were expressed in most synovial biopsies from one patient, suggesting their origin from expanded clones present in each biopsy. To prove a clonal relationship between recurrent cDNA lengths, immunoglobulin cDNA was cloned from three regions of synovium in three patients. The sequence of clones with a recurrent cDNA length was determined. An IgG3 clone found in most synovial biopsies of one patient was encoded by an unmutated copy of the V(H)1 gene, DP7. In contrast, IgG3 clones encoded by mutated versions of the V(H)3 gene DP49 or the V(H)4 gene DP63 were expanded in the other two patients. Different somatic mutants of these clones were isolated from different sites in these patients. The ratio of replacement/silent somatic mutations in these two families of clones suggests that the selective clonal expansion in the synovium of patients with rheumatoid arthritis is due to an antigen-driven immune response.

Adult↗
PubMed1997

Effects of dietary arachidonic acid on human immune response.

Arachidonic acid (AA) is a precursor of eicosanoids, which influence human health and the in vitro activity of immune cells. We therefore examined the effects of dietary AA on the immune response (IR) of 10 healthy men living at our metabolic suite for 130 d. All subjects were fed a basal diet containing 27 energy percentage (en%) fat, 57 en% carbohydrate, and 16 en% protein (AA, 200 mg/d) for the first and last 15 d of the study. Additional AA (1.5 g/d) was incorporated into the diet of six men from day 16 to 65 while the remaining four subjects continued to eat the basal diet. The diets of the two groups were crossed-over from day 66 to 115. In vitro indexes of IR were examined using the blood samples drawn on days 15, 58, 65, 108, 115, and 127. The subjects were immunized with the measles/mumps/rubella vaccine on day 35 and with the influenza vaccine on day 92. Dietary AA did not influence many indexes of IR (peripheral blood mononuclear cell proliferation in response to phytohemagglutinin, Concanavalin A, pokeweed, measles/mumps/rubella, and influenza vaccines prior to immunization, and natural killer cell activity). The post-immunization proliferation in response to influenza vaccine was about fourfold higher in the group receiving high-AA diet compared to the group receiving low-AA diet (P = 0.02). Analysis of variance of the data pooled from both groups showed that the number of circulating granulocytes was significantly (P = 0.03) more when the subjects were fed the high-AA diet than when they were fed the low-AA diet. The small increases in granulocyte count and the in vitro proliferation in response to influenza vaccine caused by dietary AA may not be of clinical significance. However, the lack of any adverse effects on IR indicates that supplementation with AA may be done safely when needed for other health reasons.

Adult↗
PubMed1997

Is there an advantage to repairing infected mitral valves?

BACKGROUND: The therapy for native mitral valve endocarditis is in evolution. Antibiotics have significantly improved survival rates, but patients with complications of endocarditis may require surgical treatment. METHODS: Between January 1985 and December 1995, 146 patients underwent surgical therapy (repair or replacement) for native mitral valve endocarditis. All patients had documented bacterial endocarditis. Univariate and multivariate analyses were performed to determine predictors of hospital death, long-term event-free survival, and probability of repair. Patients were evaluated in three groups: all patients, patients with acute endocarditis, and patients with chronic endocarditis. RESULTS: There were ten hospital deaths (6.8%). Patients undergoing repair had a lower hospital mortality rate (p = 0.008) then those having replacement. Event-free survival was improved after mitral valve repair in the overall group (p = 0.02) and in the group with healed (chronic) endocarditis (p = 0.05). Although the acute endocarditis group demonstrated an improved event-free survival rate after mitral valve repair versus replacement (74% versus 20% at 6 years), this did not reach statistical significance. CONCLUSIONS: We conclude that mitral valve repair is preferable to mitral valve replacement when possible, in patients with complications of endocarditis, as repair results in a lower hospital mortality and an improved long-term survival.

Adolescent↗
PubMed1997

Third coronary artery bypass operations: risks and costs.

BACKGROUND: Third coronary artery bypass operations are technically difficult and are associated with increased risk. METHODS: We reviewed the cases of 469 patients who had undergone a third isolated coronary artery bypass operation and used univariate and multivariate testing to examine the effect of preoperative and operative variables on outcome and costs. RESULTS: The in-hospital mortality was 7.0% (33 patients). Advanced age and severe symptoms were found to increase risk (both p < 0.05): the mortality was 14% (n = 74) in patients 70 years old or older who had severe symptoms. However, the overall mortality for 1993 through 1995 was 4.3% (5/117) and only one death (1.3%) occurred among the 79 patients who were less than 70 years old. The late survival rate was 94%, 84%, and 66% at 1, 5, and 10 postoperative years, respectively, and predictors of decreased late survival were advanced age, abnormal left ventricular function, and diabetes (all p < 0.05). Again, age of 70 years or more was a predictor of a poor outcome. Only 52% of patients in that subgroup (including both early and late mortality) were alive 5 years after operation. Analysis of direct hospital costs showed that the mean costs of third coronary artery bypass operations were 21% higher than the mean costs of primary operations but that the elevation in the mean costs for third operations was related to very high costs in 4 patients. Sex was found to influence the cost of both primary and third operations (increased cost for women). CONCLUSIONS: Unfavorable outcomes after third coronary artery bypass operations have been associated with preoperatively definable variables, particularly age of 70 years or more. The in-hospital mortality in patients younger than 70 was low, and long-term survival in this group has been favorable. The increased hospital costs associated with third operations are related to high costs in only a few patients and have been unpredictable.

Age Factors↗
PubMed1997

Reoperation for failure of mitral valve repair.

BACKGROUND AND OBJECTIVE: Mitral valve repair is the procedure of choice to correct mitral regurgitation of all types. Up to 10% of patients who undergo mitral valvuloplasty require late reoperation for recurrent mitral valve dysfunction. To determine the causes of failed mitral valve repair, we examined the surgical pathology of patients who underwent reoperation for failed mitral valve repair. PATIENTS AND RESULTS: From 1986 to 1994, 81 patients had 86 reoperations for recurrent mitral regurgitation after mitral valve repair. Mean age was 59.2 +/- 1.4 years; 55 were men. Primary valve disease was degenerative in 48 patients (59%), rheumatic in 16 (20%), ischemic in 13 (16%), endocarditic in 3 (4%), and congenital in 1 (1%). Mean time interval between initial mitral valve repair and reoperation was 15.6 +/- 2.5 months. Causes of repair failure were procedure-related (50 cases, 58%), valve-related (33 cases, 38%), or unknown (3 cases, 3%). Procedure-related valve failure was caused by suture dehiscence (21 cases), rupture of previously shortened chordae (19 cases), or incomplete initial correction (10 cases). Valve-related repair failure was caused by progressive primary valve disease (27 cases), endocarditis (5 cases), or extensive leaflet retraction (1 case). Repair failure was procedure-related in 70% of patients with degenerative valvular disease versus only 13% of patients with rheumatic valvular disease (p = 0.0001). At reoperation, mitral valve replacement was performed in 64 patients (79%) and repeat mitral valve repair in 17 (21%). CONCLUSION: We conclude that (1) most mitral valve repair failures are procedure-related in degenerative disease and valve-related in rheumatic disease; (2) rupture of previously shortened chordae is a common cause of late failure in patients with degenerative mitral valve disease; and (3) repeat mitral valve repair results in successful treatment for a minority of patients.

Adolescent↗
PubMed1996

Decrease in cellularity and expression of adhesion molecules by anti-tumor necrosis factor alpha monoclonal antibody treatment in patients with rheumatoid arthritis.

OBJECTIVE: The effect of chimeric anti-tumor necrosis factor alpha (TNF alpha) monoclonal antibody (MAb) therapy on synovial inflammation was studied in order to address the hypothesis that anti-TNF alpha therapy leads to down-regulation of adhesion molecules and a decrease in inflammatory cell influx in synovial tissue (ST). METHODS: The immunohistologic features of synovial biopsy specimens, both before and 4 weeks after anti-TNF alpha MAb (cA2) therapy, were studied in 14 patients with rheumatoid arthritis (RA). The patients either received a placebo (n = 2), or were given intravenous doses of cA2 at 10 mg/kg (n = 5) or 20 mg/kg (n = 7). RESULTS: A significant (P < 0.03) reduction in the mean scores for T cells and for the adhesion molecules, vascular cell adhesion molecule 1 and E-selectin, was observed after therapy with 10 mg/kg or 20 mg/kg of cA2 in RA patients. CONCLUSION: The reduced expression of adhesion molecules, and the decrease in cellularity of rheumatoid ST after cA2 administration support the hypothesis that the antiinflammatory effect of anti-TNF alpha therapy might be partly explained by down-regulation of cytokine-inducible vascular adhesion molecules in ST, with a consequent reduction of cell traffic into joints.

Antibodies, Monoclonal↗
PubMed1996

Repair of anterior leaflet prolapse: chordal transfer is superior to chordal shortening.

UNLABELLED: Several techniques are currently used to repair anterior leaflets with elongated or ruptured chordae. To evaluate the efficacy of these techniques, we analyzed the case histories of 108 patients operated on from 1989 through 1992 with degenerative mitral valve disease and prolapse of the anterior leaflet. The mean age was 59 +/- 15 years (range 18 to 87 years) and 74 (69%) were male. METHODS: Chordal shortening was performed in 31 (29%) and chordal transfer in 77 (71%) of the repairs. Of the transfers, 58 (75%) were from the posterior to the anterior leaflet and 16 (21%) were from the secondary to the primary position of the anterior leaflet. Three patients had both types of transfers. Seventy-one (66%) patients had isolated repairs and the remainder had associated procedures. The degree of preoperative mitral regurgitation was 3+ or greater for 107 (99%) of the patients, mean 3.4 for shortening and 3.7 for transfer. RESULTS: Four (4.0%) hospital deaths occurred, none after isolated repair. Follow-up of hospital survivors was 100% complete at a mean of 4.0 years. A total of 421 patient-years of follow-up were available for analysis. There were seven late deaths, for a 5-year actuarial survival of 93%. Eleven patients underwent reoperation for recurrent mitral regurgitation. Five-year actuarial freedom from reoperation was 90%-96% after chordal transfer and 74% after chordal shortening, p = 0.003. Independent predictors for reoperation include chordal shortening and preoperative New York Heart Association functional class III or IV. The mechanism of valve failure in six of seven patients undergoing reoperation after chordal shortening was rupture of the previously shortened chordae. CONCLUSIONS: We conclude that chordal transfer is superior to chordal shortening, providing a more predictable correction of mitral regurgitation and a lower incidence of reoperation. Reoperations after chordal shortening are a result of rupture of the previously shortened chordae.

Actuarial Analysis↗
PubMed1996

Surgical treatment of prosthetic valve endocarditis.

From 1975 through 1992, we reoperated on 146 patients for the treatment of prosthetic valve endocarditis. Prosthetic valve endocarditis was considered to be early (< 1 year after operation) in 46 cases and active in 103 cases. The extent of the infection was prosthesis only in 66 patients, anulus in 46, and cardiac invasion in 34. Surgical techniques evolved in the direction of increasingly radical débridement of infected tissue and reconstruction with biologic materials. All patients were treated with prolonged postoperative antibiotic therapy. There were 19 (13%) in-hospital deaths. Univariate analyses demonstrated trends toward increasing risk for patients with active endocarditis and extension of infection beyond the prosthesis; however, the only variables with a significant (p < 0.05) association with increased in-hospital mortality confirmed with multivariate testing were impaired left ventricular function, preoperative heart block, coronary artery disease, and culture of organisms from the surgical specimen. During the study period, mortality decreased from 20% (1975 to 1984) to 10% (1984 to 1992). For hospital survivors the mean length of stay was 25 days. Follow-up (mean interval 62 months) documented a late survival of 82% at 5 postoperative years and 60% at 10 years. Older age was the only factor associated (p = 0.006) with late death. Nineteen patients needed at least one further operation; reoperation-free survival was 75% at 5 and 50% at 10 postoperative years. Fever in the immediate preoperative period was the only factor associated with decreased late reoperation-free survival (p = 0.032). Prosthetic valve endocarditis remains a serious complication of valve replacement, but the in-hospital mortality of reoperations for prosthetic valve endocarditis has declined. With extensive débridement of infected tissue and postoperative antibiotic therapy, the extent and activity of prosthetic valve endocarditis does not appear to have a major impact on late outcome, and the majority of patients with this complication survive for 10 years after the operation.

Adult↗
PubMed1996

Efficacy of recombinant interferon-alpha (rIFN-alpha) in polycythaemia vera: a study of 17 patients and an analysis of published data.

The efficacy and tolerability of rIFN-alpha has been evaluated in 17 selected patients with symptomatic polycythaemia vera, diagnosed according to the PRV Study Group criteria. Complete disease control (CR) was achieved, after 1-12 months, in nine patients, with partial control in a further five cases. Three patients failed to respond. Pruritus significantly improved in 83% (10/12) of cases, following 1-28 weeks of treatment. Six patients (35%), however, were unable to tolerate rIFN-alpha, on account of weight loss, myalgia and mental changes. Overall, alpha-interferon therapy significantly improved venesection requirements, MCV and PCV values, platelet counts, pruritus scores and the degree of splenomegaly. Analysis of pooled published data (100 evaluable patients, including the present study) revealed an overall CR of 60%, a PR of 27%, and a failure rate of 13%. Significant pruritus control (> 50% improvement) occurred in 77% of cases. rIFN-alpha appears to be an effective therapy for PV-associated myeloproliferation and/or pruritus, although side-effects remain a concern. Long-term studies are now indicated to determine if the natural history of the disease is altered, in particular whether the incidence of myelofibrosis and/or leukaemic transformation is reduced.

Adult↗
PubMed1996

Transfer of type II collagen-induced arthritis from DBA/1 to severe combined immunodeficiency mice can be prevented by blockade of Mac-1.

Collagen-induced arthritis in susceptible mice is widely accepted as an experimental model for human rheumatoid arthritis (RA). We have investigated the role of the Mac-1 integrin beta 2 in the development and maintenance of arthritis by means of in vivo administration of 5C6 monoclonal antibody (mAb) to block this receptor. Injection of a single dose of 5C6 mAb (0.5 mg, intraperitoneally) prior to the expected onset of collagen-induced arthritis in DBA/1 mice diminished the severity of subsequent disease in these animals, as assessed both clinically and histologically (P < 0.01, chi 2). In the DBA/1 to severe combined immunodeficiency (SCID) transfer model of arthritis, the incidence of clinical arthritis was significantly reduced in SCID mice receiving maintained 5C6 treatment commencing the day prior to administration of donor splenocytes. Histological evaluation of joints from animals without clinically evident arthritis confirmed the absence of an inflammatory infiltrate in 22/27 joints examined. In a minority of these joints, however, synovial hyperplasia was apparent. In contrast, delaying antibody administration until 10 days after donor spleen cell transfer failed to protect three of five SCID recipients. These results confirm a functional role for Mac-1 in the generation of collagen-induced arthritis in mice. Since mAb 5C6 is non-cytotoxic, its action must be by blockade of the interactions between Mac-1 and its natural ligand(s). Our findings support the hypothesis that cells expressing Mac-1 play an important role in the induction and maintenance of joint damage in collagen-induced arthritis.

Animals↗
PubMed1996

Sternotomy infection with Mycoplasma hominis: a cause of "culture negative" wound infection.

Wound infections with Mycoplasma species are unusual; diagnosis may be delayed because of the growth characteristics of this organism. We report Mycoplasma hominis infection of sternotomy wounds in two patients. The first presented with fever and drainage from the incision 1 week after coronary artery bypass grafting. The other patient presented with drainage from the incision three weeks after double-lung transplantation. In both cases, initial cultures were negative, but the typical colonial morphology of M. hominis was subsequently detected. Successful treatment consisted of debridement and long courses of antibiotic therapy; omental flap grafting was eventually required for the second patient. Other published cases were reviewed and compared with the newly reported cases.

Aged↗
PubMed1995

The role of the B cells in the adoptive transfer of collagen-induced arthritis from DBA/1 (H-2q) to SCID (H-2d) mice.

Collagen-induced arthritis (CIA) can be transferred from DBA/1 to SCID mice when native type II collagen (CII) is administered together with spleen cells, arthritis appearing some 14 days after cell transfer. In the present study, we demonstrate that both donor T- and B-lymphocyte populations play a role in this model, and that arthritis arises in SCID recipients of either murine or bovine native CII. Furthermore, the requirement for administration of soluble native CII can be replaced by subarthritogenic doses of serum from Wistar rats with CIA. In this case a fully developed arthritis appears as early as 2 days after cell transfer. However, protein G-purified IgG from CIA rat serum together with splenocytes from arthritic DBA/1 mice does not transfer arthritis. A key role of B cells in this model appears to be the production of a humoral arthritogenic factor since arthritis can be successfully transferred to SCID mice by CIA rat serum administered together with a B cell-depleted splenocyte population consisting of T cells and donor-histocompatible antigen-presenting cells. By contrast, transfer of disease cannot be achieved by co-administration of CIA rat serum and purified donor T cells, indicating that the presence of donor antigen-presenting cells is a requirement for adoptive transfer of arthritis. We propose that joint damage initiated by arthritogenic product(s) of the B cell lineage releases soluble antigens that are presented to T cells which perpetuate the disease. The finding that arthritis can be generated in SCID recipients of CIA rat serum together with splenocytes from non-arthritic DBA/1 mice immunized with denatured CII supports the hypothesis that T cells with specificity for denatured joint components perpetuate disease initiated by humoral factors.

Animals↗