Tony Zerbe - Academia.edu (original) (raw)
Papers by Tony Zerbe
The Lancet, Oct 1, 1988
leaving a population of immature resistant cells which can be replenished from a pool of dormant ... more leaving a population of immature resistant cells which can be replenished from a pool of dormant rumour cells. Thus resistance in myeloma need not be acquired by changes in the phenotype of myeloma cells but may be endogenous, due to the differential drug sensitivity of subpopulations of cells within the tumour. It must be stressed, therefore, that effective drug treaOTIent must kill the more primitive cell types such as the lymphoplasmacytoid cell. Because myeloma exhibits a degree of differentiation in man, studies to find the stem cell of the disease are most important if future treaOTIents are to produce longer disease-free intervals. Furthennore it will be necessary to assess whether potential precursor cells (lymphoplasmacytoid) synthesise and secrete immunoglobulin so that the disease can be effectively monitored. We thank the Cancer Research Campaign, the M~ca1 R=rch Council, and the Leukaemia Research Fund for suppon and the theatre staff and nUl'les of the IBM Unit at the Royal Manden Hospital fOT their CXlOperation.
Asaio Journal, 1995
ABSTRACT
PubMed, May 1, 1992
Graft atherosclerosis after heart transplantation is a problem that may limit long-term survival.... more Graft atherosclerosis after heart transplantation is a problem that may limit long-term survival. The objective of this study was to establish whether an association exists between graft atherosclerosis, cellular rejection, HLA compatibility, or antilymphocyte antibodies in recipient serum. Results of cineangiograms from 306 recipients were available. Life table and logistic regression analysis identified only a significant effect of cellular rejection on development of angiogram-evident graft vessel disease. A total of 146 allografts obtained at another transplantation or autopsy were also available. Coronary vessel narrowing was measured by planimetry. Linear regression with coronary narrowing as dependent variable established a positive association with history of cellular rejection. No effect was documented for panel reactive antibody level obtained before or after transplantation. We also did not show an impact of HLA mismatch on this process. The lack of HLA antigen effect prompts us to be cautious about linking graft atherosclerosis directly to the rejection event.
Human Immunology, Oct 1, 1991
American Heart Journal, Feb 1, 1991
Background and Objectives: Some reports have suggested that coronary microvascular dysfunction pl... more Background and Objectives: Some reports have suggested that coronary microvascular dysfunction plays a role in the recovery of myocardial function in patients with obstructive coronary artery disease. Thrombolysis in myocardial infarction (TIMI) frame count (TFC) is regarded as a simple, reliable method for evaluating microvascular function. We evaluated microvascular function using TFC immediately after coronary intervention and compared TFC with left ventricular systolic function eight months later. Subjects and Methods: We studied 68 patients with obstructive coronary artery disease who underwent coronary intervention. Just after intervention, TFC was calculated with the standard method. Left ventricular systolic function was assessed with left ventricular diastolic dimension (LVEDd), ejection fraction (EF), and wall motion score index (WMSI). Eight months after intervention, we completed follow-up coronary angiography and echocardiography. We defined high TFC (HTFC) as a TFC greater than 18. Results: Ten patients were in the HTFC group, and 58 patients were in the low TFC (LTFC) group. There was no difference between the two groups with regard to baseline cardiovascular characteristics and angiographic findings. Just after intervention, the HTFC group showed significantly higher LVEDd (56.6±8.9 mm) and WMSI (1.60±0.65) compared to the LTFC group (50.3±5.9 mm, p<0.05; 1.34±0.29, p<0.05, respectively), but there was no significant difference in EF between the groups (49.3±18.6% vs. 56.2±14.8%, p> 0.05). Eight months after intervention, there was also a significant decrease in the WMSI in the LTFC group (1.23±0.25, p<0.05), but not in the HTFC group (1.57±0.62, p>0.05). Conclusion: Increased TFC immediately after coronary intervention is an important poor prognostic factor related to myocardial systolic function eight months after coronary intervention. Coronary microvascular dysfunction may influence myocardial recovery in the setting of obstructive coronary artery disease.
Human Immunology, Oct 1, 1991
PubMed, Oct 1, 1989
Endomyocardial biopsy histology and the in vitro propagation of biopsy-infiltrating alloreactive ... more Endomyocardial biopsy histology and the in vitro propagation of biopsy-infiltrating alloreactive T lymphocytes were analyzed in cardiac transplant patients on RATG (n = 24) and OKT3 (n = 9) immunoprophylaxis protocols. During the first three months posttransplant, 27% of the 167 biopsies in the RATG group showed histological grades of 2 or higher, significantly less than the 44% frequency of positive histology for biopsies in the OKT3 group (P = 0.035). For the histologically positive biopsies the frequency of lymphocyte growth, and the primed lymphocyte testing (PLT)* and CML activity of biopsy grown cells were similar in the RATG and OKT3 groups. However, for histologically negative biopsies, there was significantly more lymphocyte growth in the OKT3 than in the RATG groups (68% vs. 30%; P = 0.005). There was also significantly greater donor-specific CML activity of the biopsy-grown cultures in the OKT3 group. These data that suggest less cellular rejection is associated with RATG than with OKT3 immunoprophylaxis. They extend our previously reported clinical experience of a higher rejection-free survival in patients on the RATG protocol.
Transplantation proceedings, 1991
FK 506 has established itself as a promising immunosuppressive drug in organ transplantation and ... more FK 506 has established itself as a promising immunosuppressive drug in organ transplantation and in the treatment of autoimmune disease. Therapeutic monitoring of plasma concentrations of FK 506 is essential to ensure appropriate dosage for adequate immunosuppression and to minimize potential side effects. Routine monitoring of FK 506 plasma concentration is performed with an enzyme-linked immunoassay (ELISA) previously developed by Tamura et al 1 and modified by Cadoff et al.2 Plasma FK 506 levels also have been measured with an in vitro bioassay.3 This assay is based on the inhibition of the alloantigen driven proliferation of cloned alloreactive T cells. These activated lymphocytes show a narrow sensitivity range to FK 506 and the IC50 is 0.07 to 0.12 nmol/L. In liver allograft recipients. the FK 506 levels as determined by bioassay are consistently lower than those measured by ELISA (Fig 1). These results suggest that the plasma may contain biologically less active FK 506 metabolites, which can be detected by ELISA.
The Journal of Thoracic and Cardiovascular Surgery, Feb 1, 1991
Evolution of human cardiac myocyte dimension during prolonged mechanical support In animal models... more Evolution of human cardiac myocyte dimension during prolonged mechanical support In animal models using left ventricular assist systems over long time periods, myocardial cellular atrophy has been reported, raising concern that prolonged cHnicai use of such systems might lead to deterioration in left ventricular function. At the University of Pittsburgh, long-term cHnicai use of the Novacor (Baxter Healthcare Corp., Novacor Div., Oakland, Calif.) left ventricular support system for patients awaiting heart tramplants has allowed study of the effects of long-term mechanical support on human subjects. This study determined that cardiac myocyte dimension is initially greater in patients with end-stage cardiac disease who require support rather than in patients with the same disease who do not require such support. Although myocyte dimension does decrease within a few days of the inception of support, this decrease merely brings cell size closer to the values usual in patients with chronic end-stage cardiac disease, and no further shrinkage is observed. Tbus the Novacor left ventricular assist system does not appear associated with left ventricular atrophy, and its long-term use may not be detrimental to left ventricular function.
American Heart Journal, 1993
To examine the possible relationship between cardiac and skeletal muscle disease in systemic scle... more To examine the possible relationship between cardiac and skeletal muscle disease in systemic sclerosis, we reviewed computerized records of 1095 consecutive patients with systemic sclerosis. One hundred eighty three (17%) had skeletal myopathy. Thirty-nine (21%) of the 183 fulfilled criteria for myocardial disease, compared with 90 (10%) of the 912 without myopathy (p < 0.0001.) Nineteen (10%) of the 183 had clinical CHF compared with 38 (4%) of the remainder (p < 0.002.) Fifteen (8%) of the patients with myopathy died of cardiac causes compared with 27 (3%) of the 912 without myopathy (p < 0.002.) Twenty-five patients with coexistent myopathy and myocardial disease, in the absence of other identifiable contributing causes, were identified. This group was characterized by a high incidence of cardiac conduction abnormalities (60%) and by the severity of the myocardial dysfunction and arrhythmias, both atrial and ventricular that they experienced. Eighteen of these 25 patients died; 12 (67%) died suddenly. Eight of the 18 (44%) had intractable CHF, which directly contributed to their deaths. Myocardial fibrosis was the predominant histologic abnormality at autopsy. However, autopsy of a patient who died in the context of acute "myocarditis" showed severe myocytolysis with contraction band necrosis but without inflammation or fibrosis; this is consistent with possible ischemically mediated injury. We conclude that skeletal and cardiac muscle disease in systemic sclerosis are associated. Patients with myopathy are at increased risk for CHF, sustained symptomatic arrhythmias, and cardiac death, particularly sudden death.
Labmedicine, Mar 1, 1987
Ektachem bilirubin fractions of TBILI, DBILI, Bu, Be, and DELTA were evaluated in an adult outpat... more Ektachem bilirubin fractions of TBILI, DBILI, Bu, Be, and DELTA were evaluated in an adult outpatient population and compared with other bilirubin measurements obtained on ACA and Cobas analyzers. TBILI measured on the Ektachem compared well with the other total bilirubin measurements, while Ektachem DBILI showed varying degrees of proportional bias, depending on the methodology and instrument it was compared with. The relative proportion of DELTA and Be levels to rising levels of DBILI showed that both bilirubin factors increase as DBILI increases until each make up about 50% of DBILI. Using levels of DBILI and liver enzymes, we separated the samples into the following broad patient groups and diagnoses: transplant patients with liver impairment or damage, transplant and psychiatric patients with drug cytotoxicity, and patients with hepatitis. There was some indication that Be and DELTA levels, rather than DBILI, may be more sensitive in the clinical monitoring of patients with liver disease.
The Joint Commission journal on quality improvement, Jul 1, 1997
Internal customers viewed the central laboratorys core business as laboratory information managem... more Internal customers viewed the central laboratorys core business as laboratory information management, not laboratory testing.
Transplantation proceedings, 1989
The Lancet, Oct 1, 1988
leaving a population of immature resistant cells which can be replenished from a pool of dormant ... more leaving a population of immature resistant cells which can be replenished from a pool of dormant rumour cells. Thus resistance in myeloma need not be acquired by changes in the phenotype of myeloma cells but may be endogenous, due to the differential drug sensitivity of subpopulations of cells within the tumour. It must be stressed, therefore, that effective drug treaOTIent must kill the more primitive cell types such as the lymphoplasmacytoid cell. Because myeloma exhibits a degree of differentiation in man, studies to find the stem cell of the disease are most important if future treaOTIents are to produce longer disease-free intervals. Furthennore it will be necessary to assess whether potential precursor cells (lymphoplasmacytoid) synthesise and secrete immunoglobulin so that the disease can be effectively monitored. We thank the Cancer Research Campaign, the M~ca1 R=rch Council, and the Leukaemia Research Fund for suppon and the theatre staff and nUl'les of the IBM Unit at the Royal Manden Hospital fOT their CXlOperation.
Asaio Journal, 1995
ABSTRACT
PubMed, May 1, 1992
Graft atherosclerosis after heart transplantation is a problem that may limit long-term survival.... more Graft atherosclerosis after heart transplantation is a problem that may limit long-term survival. The objective of this study was to establish whether an association exists between graft atherosclerosis, cellular rejection, HLA compatibility, or antilymphocyte antibodies in recipient serum. Results of cineangiograms from 306 recipients were available. Life table and logistic regression analysis identified only a significant effect of cellular rejection on development of angiogram-evident graft vessel disease. A total of 146 allografts obtained at another transplantation or autopsy were also available. Coronary vessel narrowing was measured by planimetry. Linear regression with coronary narrowing as dependent variable established a positive association with history of cellular rejection. No effect was documented for panel reactive antibody level obtained before or after transplantation. We also did not show an impact of HLA mismatch on this process. The lack of HLA antigen effect prompts us to be cautious about linking graft atherosclerosis directly to the rejection event.
Human Immunology, Oct 1, 1991
American Heart Journal, Feb 1, 1991
Background and Objectives: Some reports have suggested that coronary microvascular dysfunction pl... more Background and Objectives: Some reports have suggested that coronary microvascular dysfunction plays a role in the recovery of myocardial function in patients with obstructive coronary artery disease. Thrombolysis in myocardial infarction (TIMI) frame count (TFC) is regarded as a simple, reliable method for evaluating microvascular function. We evaluated microvascular function using TFC immediately after coronary intervention and compared TFC with left ventricular systolic function eight months later. Subjects and Methods: We studied 68 patients with obstructive coronary artery disease who underwent coronary intervention. Just after intervention, TFC was calculated with the standard method. Left ventricular systolic function was assessed with left ventricular diastolic dimension (LVEDd), ejection fraction (EF), and wall motion score index (WMSI). Eight months after intervention, we completed follow-up coronary angiography and echocardiography. We defined high TFC (HTFC) as a TFC greater than 18. Results: Ten patients were in the HTFC group, and 58 patients were in the low TFC (LTFC) group. There was no difference between the two groups with regard to baseline cardiovascular characteristics and angiographic findings. Just after intervention, the HTFC group showed significantly higher LVEDd (56.6±8.9 mm) and WMSI (1.60±0.65) compared to the LTFC group (50.3±5.9 mm, p<0.05; 1.34±0.29, p<0.05, respectively), but there was no significant difference in EF between the groups (49.3±18.6% vs. 56.2±14.8%, p> 0.05). Eight months after intervention, there was also a significant decrease in the WMSI in the LTFC group (1.23±0.25, p<0.05), but not in the HTFC group (1.57±0.62, p>0.05). Conclusion: Increased TFC immediately after coronary intervention is an important poor prognostic factor related to myocardial systolic function eight months after coronary intervention. Coronary microvascular dysfunction may influence myocardial recovery in the setting of obstructive coronary artery disease.
Human Immunology, Oct 1, 1991
PubMed, Oct 1, 1989
Endomyocardial biopsy histology and the in vitro propagation of biopsy-infiltrating alloreactive ... more Endomyocardial biopsy histology and the in vitro propagation of biopsy-infiltrating alloreactive T lymphocytes were analyzed in cardiac transplant patients on RATG (n = 24) and OKT3 (n = 9) immunoprophylaxis protocols. During the first three months posttransplant, 27% of the 167 biopsies in the RATG group showed histological grades of 2 or higher, significantly less than the 44% frequency of positive histology for biopsies in the OKT3 group (P = 0.035). For the histologically positive biopsies the frequency of lymphocyte growth, and the primed lymphocyte testing (PLT)* and CML activity of biopsy grown cells were similar in the RATG and OKT3 groups. However, for histologically negative biopsies, there was significantly more lymphocyte growth in the OKT3 than in the RATG groups (68% vs. 30%; P = 0.005). There was also significantly greater donor-specific CML activity of the biopsy-grown cultures in the OKT3 group. These data that suggest less cellular rejection is associated with RATG than with OKT3 immunoprophylaxis. They extend our previously reported clinical experience of a higher rejection-free survival in patients on the RATG protocol.
Transplantation proceedings, 1991
FK 506 has established itself as a promising immunosuppressive drug in organ transplantation and ... more FK 506 has established itself as a promising immunosuppressive drug in organ transplantation and in the treatment of autoimmune disease. Therapeutic monitoring of plasma concentrations of FK 506 is essential to ensure appropriate dosage for adequate immunosuppression and to minimize potential side effects. Routine monitoring of FK 506 plasma concentration is performed with an enzyme-linked immunoassay (ELISA) previously developed by Tamura et al 1 and modified by Cadoff et al.2 Plasma FK 506 levels also have been measured with an in vitro bioassay.3 This assay is based on the inhibition of the alloantigen driven proliferation of cloned alloreactive T cells. These activated lymphocytes show a narrow sensitivity range to FK 506 and the IC50 is 0.07 to 0.12 nmol/L. In liver allograft recipients. the FK 506 levels as determined by bioassay are consistently lower than those measured by ELISA (Fig 1). These results suggest that the plasma may contain biologically less active FK 506 metabolites, which can be detected by ELISA.
The Journal of Thoracic and Cardiovascular Surgery, Feb 1, 1991
Evolution of human cardiac myocyte dimension during prolonged mechanical support In animal models... more Evolution of human cardiac myocyte dimension during prolonged mechanical support In animal models using left ventricular assist systems over long time periods, myocardial cellular atrophy has been reported, raising concern that prolonged cHnicai use of such systems might lead to deterioration in left ventricular function. At the University of Pittsburgh, long-term cHnicai use of the Novacor (Baxter Healthcare Corp., Novacor Div., Oakland, Calif.) left ventricular support system for patients awaiting heart tramplants has allowed study of the effects of long-term mechanical support on human subjects. This study determined that cardiac myocyte dimension is initially greater in patients with end-stage cardiac disease who require support rather than in patients with the same disease who do not require such support. Although myocyte dimension does decrease within a few days of the inception of support, this decrease merely brings cell size closer to the values usual in patients with chronic end-stage cardiac disease, and no further shrinkage is observed. Tbus the Novacor left ventricular assist system does not appear associated with left ventricular atrophy, and its long-term use may not be detrimental to left ventricular function.
American Heart Journal, 1993
To examine the possible relationship between cardiac and skeletal muscle disease in systemic scle... more To examine the possible relationship between cardiac and skeletal muscle disease in systemic sclerosis, we reviewed computerized records of 1095 consecutive patients with systemic sclerosis. One hundred eighty three (17%) had skeletal myopathy. Thirty-nine (21%) of the 183 fulfilled criteria for myocardial disease, compared with 90 (10%) of the 912 without myopathy (p < 0.0001.) Nineteen (10%) of the 183 had clinical CHF compared with 38 (4%) of the remainder (p < 0.002.) Fifteen (8%) of the patients with myopathy died of cardiac causes compared with 27 (3%) of the 912 without myopathy (p < 0.002.) Twenty-five patients with coexistent myopathy and myocardial disease, in the absence of other identifiable contributing causes, were identified. This group was characterized by a high incidence of cardiac conduction abnormalities (60%) and by the severity of the myocardial dysfunction and arrhythmias, both atrial and ventricular that they experienced. Eighteen of these 25 patients died; 12 (67%) died suddenly. Eight of the 18 (44%) had intractable CHF, which directly contributed to their deaths. Myocardial fibrosis was the predominant histologic abnormality at autopsy. However, autopsy of a patient who died in the context of acute "myocarditis" showed severe myocytolysis with contraction band necrosis but without inflammation or fibrosis; this is consistent with possible ischemically mediated injury. We conclude that skeletal and cardiac muscle disease in systemic sclerosis are associated. Patients with myopathy are at increased risk for CHF, sustained symptomatic arrhythmias, and cardiac death, particularly sudden death.
Labmedicine, Mar 1, 1987
Ektachem bilirubin fractions of TBILI, DBILI, Bu, Be, and DELTA were evaluated in an adult outpat... more Ektachem bilirubin fractions of TBILI, DBILI, Bu, Be, and DELTA were evaluated in an adult outpatient population and compared with other bilirubin measurements obtained on ACA and Cobas analyzers. TBILI measured on the Ektachem compared well with the other total bilirubin measurements, while Ektachem DBILI showed varying degrees of proportional bias, depending on the methodology and instrument it was compared with. The relative proportion of DELTA and Be levels to rising levels of DBILI showed that both bilirubin factors increase as DBILI increases until each make up about 50% of DBILI. Using levels of DBILI and liver enzymes, we separated the samples into the following broad patient groups and diagnoses: transplant patients with liver impairment or damage, transplant and psychiatric patients with drug cytotoxicity, and patients with hepatitis. There was some indication that Be and DELTA levels, rather than DBILI, may be more sensitive in the clinical monitoring of patients with liver disease.
The Joint Commission journal on quality improvement, Jul 1, 1997
Internal customers viewed the central laboratorys core business as laboratory information managem... more Internal customers viewed the central laboratorys core business as laboratory information management, not laboratory testing.
Transplantation proceedings, 1989