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Biomedical subjects

R McMillan

Publications and source records attributed to R McMillan.

At least 37 records · Page 2Linked to original sources
PubMed1997

Preoperative vancomycin prophylaxis decreases incidence of postoperative hemodialysis vascular access infections.

The role of vancomycin in the treatment of infected arteriovenous chronic dialysis access is well established. However, the role of preoperative vancomycin administration in preventing infection in newly placed, revised, or surgically thrombectomized grafts has not been determined. We performed a prospective randomized study to examine whether vancomycin prophylaxis can decrease the incidence of postoperative graft infections. Over a 5-year period, 206 patients undergoing 408 permanent vascular access procedures were randomized into two groups. Group 1 (206 procedures) received a single intravenous dose of 750 mg of vancomycin approximately 6 to 12 hours before vascular access placement procedures, while group 2 (202 procedures) did not. Patients were evaluated for access infection within the following 30 days and before use of the access for chronic dialysis. Access infection developed in two patients (1%) in group 1 and in 12 patients (6%) in group 2 (P = 0.006). All 14 infections occurred in upper extremity polytetrafluoroethylene grafts. We conclude that the use of preoperative single-dose intravenous vancomycin prophylaxis for hemodialysis vascular graft procedures reduces the risk of postoperative access infection.

Adolescent↗
PubMed1997

International study to compare antigen-specific methods used for the measurement of antiplatelet autoantibodies.

Platelet-associated and plasma autoantibodies against platelet glycoproteins (GP) have been demonstrated in patients with autoimmune thrombocytopenia (AITP) using various methods. Eight laboratories in seven countries participated in this international study to evaluate the interlaboratory agreement using glycoprotein-specific immunoassays for these autoantibodies. The participating laboratories received blind samples of frozen washed platelets and plasma from 22 normal donors and 22 AITP patients. Platelet-associated and plasma autoantibodies against GPIIb-IIIa and GPIb-IX were measured by MAIPA, immunobead assay or modified antigen capture assay. Of the control samples, 96.0% and 97.2% of all results for platelet-associated and plasma autoantibodies to GPIIb-IIIa/ GPIb-IX, respectively, were negative. The mean variation coefficient of the control samples of platelet-associated and plasma autoantibodies was 89.5% (range 11.1-272.9%) and 46.5% (range 21.0-78.0%), respectively. In 20/22 patient samples, platelet-associated autoantibodies to either glycoprotein were noted by at least two laboratories. The mean degree of agreement in these samples was 74.0%. There was a significant correlation in the individual antibody measurements between all laboratories (Kendall coefficient of concordance 0.60 and 0.38, P < 0.001; Spearman rank order test, range of correlation coefficient 52.3-94.0% and 42.2-85.0%, P < 0.05, for anti-GPIIb-IIIa and anti-GPIb-IX, respectively). In contrast, plasma autoantibodies to either glycoprotein were noted by at least two laboratories in only 13/22 patient samples. Moreover, the degree of agreement was poor (50.1%) and a significant correlation was noted between only six pairs of laboratories. We conclude that methods used in this study yield good interlaboratory agreement in measuring platelet-associated autoantibodies against GPIIb-IIIa and GPIb-IX. In contrast, poor agreement was found in detecting plasma autoantibodies to the same glycoproteins.

Autoantibodies↗
PubMed1997

Outpatient high-dose chemotherapy with autologous stem-cell rescue for hematologic and nonhematologic malignancies.

PURPOSE: A prospective study to determine the feasibility of high-dose chemotherapy (HDC) and autologous stem-cell rescue (ASCR) in the outpatient setting. METHODS: One hundred thirteen consecutive patients underwent 165 cycles of HDC/ASCR for a variety of malignancies. HDC regimens were disease-specific. Initially, patients were hospitalized for HDC, discharged on completion, and maintained as outpatients unless toxicities required rehospitalization (subtotal outpatient transplantation [STOT]). Once this was established as safe, a total outpatient transplant (TOT) program was developed in which patients received all of the HDC, as well as supportive care, as outpatients. Patients who declined the outpatient programs received the same HDC and supportive care as inpatients. RESULTS: In 140 of 165 (85%) HDC cycles, patients agreed to participate in one of the outpatient transplant programs. Five patients in the STOT program could not be discharged from the hospital because of toxicities that developed during HDC; thus, 135 patients were monitored the outpatient setting, 95 (70%) of whom were never readmitted. The mean +/- SEM total hospital length of stay (LOS), including all readmissions and excess days after chemotherapy, was 18.33 +/- 5.06 days for patients who refused the outpatient program, 8.22 +/- 5.76 days for patients in the STOT program, and 2.81 +/- 7.66 days for those in the TOT program (P < .001). One treatment-related death occurred in each treatment setting: day 120 inpatient, day 17 STOT, and day 110 TOT. CONCLUSION: Outpatient management of HDC/ASCR is safe and acceptable for the vast majority of patients. The STOT program resulted in significant reduction in hospital LOS, while the TOT program appears equally safe and further reduces LOS. Hospitalization for HDC/ASCR is unnecessary in most patients.

Adult↗
PubMed1996

Characterization of autoantigenic epitopes on platelet glycoprotein IIb/IIIa using random peptide libraries.

Most patients with chronic immune thrombocytopenic purpura (ITP) have autoantibodies directed against the glycoprotein (GP) IIb/IIIa complex. We have used a filamentous phage library that displays random linear hexapeptides to identify peptide sequences recognized by these autoantibodies. Plasma antibody eluates from two patients were used to select for phage displaying autoantibody-reactive peptides. From patient ITP-1 (known to have two distinct autoantibodies), we identified anti-GPIIb/IIIa antibody-specific phage encoding the peptide sequences Arg-Glu-Lys-Ala-Lys-Trp (REKAKW) and Pro-Val-Val-Trp-Lys-Asn (PVVWKN). Patient ITP-2 bound phage encoding the hexapeptide sequence Arg-Glu-Leu-Leu-Lys-Met. Each phage showed saturable dose-dependent binding to immobilized autoantibody, and binding could be blocked with purified GPIIb/IIIa. Patient ITP-1 autoantibody recognition of phage encoding REKAKW could be blocked with a synthetic peptide derived from the GPIIIa cytoplasmic tail; however, the PVVWKN was not. Using sequential overlapping peptides from the GPIIIa cytoplasmic region, an epitope for ITP-1 was localized to the sequence Arg-Ala-Arg-Ala-Lys-Trp (GPIIIa 734-739). Inhibition studies using synthetic peptides showed that phage REKAKW and PVVWKN were recognized by distinct autoantibodies from patient ITP-1. To determine whether individual patients with ITP possessed autoantibodies that recognize similar antigenic determinants on GPIIb/IIIa, the three phage were tested for binding to five other ITP patient autoantibodies. The phage encoding the peptide PVVWKN was found to bind ITP-1 and one other patient autoantibody. This result suggests that ITP patients recognize a limited number of shared epitopes.

Amino Acid Sequence↗
PubMed1996

The treatment of chronic progressive multiple sclerosis with cladribine.

A 2-year, placebo-controlled, double-blind, crossover study was started in 1992 to evaluate cladribine, an immunosuppressive drug, in the treatment of chronic progressive multiple sclerosis. In the first year patients were given cladribine 0.10 mg/kg per day for 7 days as four monthly courses for a total of 2.8 mg/kg or placebo. During the second year patients treated with placebo during the first year were given i.v. infusions of 0.10 mg, 0.05 mg, and 0.05 mg of cladribine per kg of body weight per day for 7 consecutive days in three successive monthly courses, for a total dose of 1.4 mg/kg. Patients who had been treated previously with cladribine were crossed over to placebo. Analysis of the results revealed a favorable influence on the neurological performance scores, both in the Kurtze extended disability status and the Scripps neurological rating scale, and on MRI findings in patients treated with cladribine. In the first year the most striking finding was that while clinical deterioration continued in the placebo-treated patients, the condition of patients who received cladribine stabilized or even improved slightly. Toxicity and therapeutic response were dose-related.

Adult↗
PubMed1996

Prophylactic antibiotics eliminate bacteremia and allow safe outpatient management following high-dose chemotherapy and autologous stem cell rescue.

This study examines the effectiveness of prophylactic ciprofloxacin and rifampin following high-dose chemotherapy and autologous stem cell rescue (HDC/ ASCR). Specific endpoints included the incidence of fever, clinically documented infection, bacteremia, and readmission rates from an outpatient bone marrow transplant setting following infection or fever. A group of 97 patients receiving 134 cycles of HDC/ASCR were studied. Patients were given ciprofloxacin 750 mg p.o. twice daily and rifampin 300 mg p.o. twice daily beginning on the day of stem cell reinfusion (24-48 h after completion of high-dose chemotherapy). Most patients were either discharged to an outpatient setting following completion of their chemotherapy or received all of their chemotherapy in an outpatient setting. Febrile neutropenia was treated with empirical antibiotics in an outpatient setting unless it was complicated by hypotension, renal failure, severe mucositis or other problems. The median duration of neutropenia (absolute neutrophil count below 500/mm3) was 7 days. Neutropenic fever occurred in 62% of patients but clinically documented bacterial infection occurred in only 2 (1.5%) patients during their neutropenic period. No bacteremia was noted. Readmission to the hospital following fever or infection occurred in 26% of patients maintained in the outpatient setting. There were no deaths from a bacterial infection in this study although 1 patient (0.7%) died from aspergillosis. Prophylactic ciprofloxacin and rifampin is a well-tolerated and highly effective combination that effectively decreases the risk of both gram-positive and gram-negative bacterial infection following HDC/ASCR. It facilitates outpatient management of myelosuppressed patients receiving autologous stem cell rescue.

Ambulatory Care↗
PubMed1996

A non-thrombocytopenic bleeding disorder due to an IgG4-kappa anti-GPIIb/IIIa autoantibody.

Autoantibodies in chronic immune thrombocytopenic purpura occasionally interfere with platelet function. We describe a patient with a normal platelet count who had clinically significant mucosal bleeding, a prolonged bleeding time and abnormal platelet aggregation. The patient had high titres of an IgG4 kappa autoantibody, directed to a cation-dependent epitope on platelet glycoprotein IIb/IIIa, which blocked the binding of fibrinogen and fibronectin to this complex. Corticosteroid treatment resulted in clinical improvement and a marked drop in autoantibody concentration. The lack of thrombocytopenia in this patient, despite high autoantibody levels, is best explained by the poor recognition of IgG4 antibodies by phagocytic cells.

Autoantibodies↗
PubMed1996

Development of cladribine treatment in multiple sclerosis.

Cladribine is a new type of drug with properties of selective lymphocyte suppression that appear to favorably alter the clinical course of progressive multiple sclerosis (MS). The history of the development of cladribine treatment in chronic progressive MS is discussed, and the application of cladribine treatment to progressive multiple sclerosis in a double-blind, placebo crossover study is reviewed. Cladribine selectively targets both resting and dividing lymphocytes and may be able to destroy the activated lymphocytes that induce CNS demyelination, thus producing stabilization or improvement in chronic MS. Although the role of cladribine has not yet been fully defined, additional studies are underway to evaluate the efficacy and safety of cladribine in both progressive MS and relapsing-remitting MS.

Cladribine↗
PubMed1996

The frequency of homozygous deletion of a developmentally regulated Vh gene (Humhv3005) is increased in patients with chronic idiopathic thrombocytopenic purpura.

Little is known of the genetic factors that may contribute to the development of chronic idiopathic thrombocytopenic purpura (cITP). We have previously shown that a developmentally regulated Vh gene (Humhv3005) is absent in 10/41 (24%) of patients with systemic lupus erythematosus while it is absent in only 7/88 (8%) of normal controls. This finding suggests that a homozygous deletion of an Ig variable (V) gene may alter the immune system and thus predispose the host to an autoimmune disorder. We have analyzed the same gene in 44 patients with cITP and found that Humhv3005 and like genes were absent in a higher percentage of patients (14 of 44, 31.8%) than they were absent in either normals (7/88, 8%, p = 0.002) or thrombocytopenic patients without cITP (6/53, 11.3%, p = 0.042); the hv3005 deletion frequency in the latter group did not differ from that in normals (P = 0.74). These data suggest that deletions of Humhv3005 and/or highly homologous Vh genes may predispose individuals to the development of cITP, and may contribute toward production of pathogenic antiplatelet antibodies.

Chronic Disease↗
PubMed1996

Mobilized peripheral blood progenitor cells (PBPC) in support of tandem cycles of high-dose chemotherapy (HDC).

We evaluated the efficacy, toxicity and feasibility of two cycles of high-dose chemotherapy (HDC), each supported with mobilized peripheral blood progenitor cells (PBPC). Ninety-six patients with metastatic or high-risk cancers received disease-specific HDC regimens. The first cycle consisted of cyclophosphamide 6000 mg/m2, thiotepa 500 mg/m2 and carboplatin 1200 mg/m2. Alternatively, some patients received etoposide 1800 mg/m2 substituted for thiotepa. A second cycle was planned 6-8 weeks later and consisted of mitoxantrone 60 mg/m2 with either melphalan 140 mg/m2 or thiotepa 600 mg/m2. PBPC were mobilized with either growth factor alone or cyclophosphamide followed by growth factor(s). Thirty-four of 96 enrolled patients (35%) did not receive the second cycle. The reasons were: patient refusal (15); insurance refusal (three); toxicities of cycle 1 (seven); no response to cycle 1 (four); and inadequate mobilization or poor engraftment, (five). Of the 33 patients who entered cycle 2 with measurable disease, 28 demonstrated further response after cycle 2 (including 10 who entered CR). One patient died of toxicity after each cycle. Hematologic recovery was rapid and complete in most patients. Tandem cycles of high-dose chemotherapy supported by PBPC are feasible and safe, although many patients fail to receive the second treatment. Preliminary evaluation shows evidence of further antitumor efficacy following cycle 2.

Adult↗
PubMed1995

The risks, benefits, and costs of expanding donor criteria. A collaborative prospective three-year study.

The study purpose was to identify risks, benefits and costs associated with an expanded donor protocol. The protocol design evaluated organs rescued using expanded donor criteria and weighed all costs associated with doing so. Costs were measured against conditions experienced with expanded and traditional criteria and recipient outcome. Traditional donors were between 5 and 55, with negative serologies, and no history of hypertension or diabetes. "Expanded donors" were between 55 and 75 or less than 5, with a history of hypertension, diabetes and/or sero-positive for Hepatitis C. During this study 73 donors met criteria from which 200 organs were transplanted. Defined costs and outcomes for recipients were tracked. Using expanded criteria: costs averaged 20% more per organ; OPO personnel spent an average of 6 hours more time on-site; an additional 12-14 hours in placement activity; and average organs per donor decreased. Heart patient and graft survival rates for traditional and expanded donor organs were comparable. Kidney patients transplanted from this pool experienced a decrease in patient (P = .14) and a significant decrease in graft (P = .02) survival rates. Patient (P = .05) and graft (P = .01) survival rates were significantly lower in liver patients transplanted with expanded donor organs. Two hundred transplants occurred using expanded donor criteria. Costs for the OPO increased appreciably. Heart and kidney utilization from these donors seems justified. It is thought that liver recipients' results were due to utilizing them in sicker patients. Recovery of organs from donors using expanded criteria appears to be a reasonable way of increasing organ supply.

Adolescent↗
PubMed1995

Reactivity of autoantibodies from chronic ITP patients with recombinant glycoprotein IIIa peptides.

Chronic immune thrombocytopenia is an autoimmune disorder characterized by destructive thrombocytopenia due to the formation of autoantibodies against platelet-associated antigens. Most antiplatelet autoantibodies react with either the platelet glycoprotein IIb/IIIa or Ib/IX complex, whereas some plasma autoantibodies react with glycoprotein IIIa. Previous studies from our laboratory suggested that most platelet-associated autoantibodies to platelet GPIIb/IIIa, which bind to the intact complex, bind much less avidly to the EDTA-dissociated complex, suggesting that the epitopes were complex-dependent. To evaluate this further we have studied the binding of platelet-associated autoantibody and plasma auto- and alloantibody eluates to large recombinant GPIIIa peptides: peptide 1 (GPIIIa Gly1-Val200); peptide 2 (GPIIIa Arg150-Glu400); peptide 3 (GPIIIa Lys350-Asp550); peptide 4 (GPIIIa Asn450-Val700) and peptide 5 (GPIIIa Trp715-Thr762, cytoplasmic fragment). Of the 33 platelet-associated antibody eluates tested, all bound avidly to the GPIIb/IIIa complex, but only one showed significant binding (>3 SD above control values) to one of the immobilized peptides (peptide 3). Conversely, antibodies known to bind to specific regions of GPIIIa (murine monoclonal antibody, anti-LIBS2; plasma autoantibody against the GPIIIa cytoplasmic fragment and anti-P1A1 antibody) all bound avidly to the GPIIIa peptide containing the appropriate epitope. Based on these and our previous results, we conclude that platelet-associated antibodies from chronic ITP patients rarely bind to epitopes localized to GPIIIa alone.

Autoantibodies↗
PubMed1995

Liver transplantation. When is it indicated and what can be expected afterwards?

Orthotopic liver transplantation is an established form of therapy for selected patients who have chronic parenchymal liver disease with cirrhosis, a chronic cholestatic syndrome, fulminant hepatic failure, or unresectable hepatic malignant disease. In most centers with experienced staff, 5-year survival rates exceed 70%. For a good outcome, it is essential that the patient be referred to a transplant center early, before overt clinical deterioration occurs. Following transplantation, lifelong immunosuppression is required to prevent allograft rejection, and extensive follow-up is necessary for early reversal of complications. The primary care physician plays a critical role in identifying organ donors.

Humans↗
PubMed1994

Cladribine in treatment of chronic progressive multiple sclerosis.

Chronic progressive multiple sclerosis (MS) is a severely disabling demyelinating disease in which autoimmune processes seem to have a major role. The nucleoside drug cladribine is a potent lympholytic agent with few side-effects. We have studied its efficacy and safety in a randomised double-blind trial. 51 patients (48 entered as matched pairs) received four monthly courses of 0.7 mg/kg cladribine or placebo (saline) given through a surgically implanted central line. Neurologists with no knowledge of which medication the patient was receiving examined the patients monthly and noted two rating scale scores (Kurtzke and Scripps). Cerebrospinal fluid and brain magnetic resonance imaging (MRI) examinations were done at 6 and 12 months. Average neurological scores, demyelinated volumes on MRI, and concentrations of oligoclonal bands in cerebrospinal fluid were stable or improved in the patients receiving cladrabine but continued to deteriorate in patients on placebo. Mean paired (placebo minus matched cladribine) differences at 12 months relative to baseline were 1.0 (SE 0.4) for the Kurtzke scores, -13.9 (2.3) for the Scripps scores, 4.57 (1.17) mL for demyelinated volumes, and 7.3 (3.3) arbitrary units for concentrations of oligoclonal bands. Cladribine was generally well tolerated and clinically significant toxicity occurred in only 1 patient, in whom severe marrow suppression developed with complete recovery after several months. 1 patient died of newly acquired hepatitis B, an event unlikely to be related to cladribine. We conclude that the immunosuppressive drug cladribine influences favourably the course of chronic progressive MS.

Adult↗