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Biomedical subjects

P McCarthy

Publications and source records attributed to P McCarthy.

At least 19 recordsLinked to original sources
PubMed2005

Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma.

PURPOSE: To evaluate the safety and efficacy of fludarabine plus rituximab in treatment-naive or relapsed patients with low-grade and/or follicular non-Hodgkin's lymphoma. PATIENTS AND METHODS: This was an open-label, single-arm, single-center phase II study enrolling 40 patients. During the first week of the study, patients received two infusions of rituximab 375 mg/m2 administered 4 days apart. Seventy-two hours after the second infusion of rituximab, patients received the first of six cycles of fludarabine chemotherapy (25 mg/m2/d for 5 days on a 28-day cycle). Single infusions of rituximab were administered 72 hours before the second, fourth, and sixth cycles of fludarabine, and two infusions of rituximab were given 4 weeks after the last cycle of fludarabine. Treatment duration was 26 weeks. RESULTS: An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naive and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal. CONCLUSION: Rituximab plus fludarabine was well tolerated and associated with an excellent complete response rate, including molecular remissions, in patients with low-grade or follicular lymphoma.

Adult↗
PubMed2001

High-efficiency electrotransfection of human primary hematopoietic stem cells.

A major obstacle to gene transfer into hematopoietic stem cells, a key step for many gene therapy and tissue replacement applications, is its low efficiency. High cell mortality is responsible for the low efficiency of electrotransfection when this technique is applied to certain 'refractory' cell types such as hematopoietic stem cells. Using human primary CD-34+ cells from peripheral blood as a model, we found that transfection-induced apoptosis and, to a lesser extent, postpulse colloidal-osmotic swelling are two main factors for the poor transfection of these cells. By applying caspase inhibitors (B-D-Fluomethyl Ketone and Z-VAD-FMK) to reduce apoptosis, and by using the postpulse pelleting method to suppress colloidal-osmotic swelling, we achieved a transfection efficiency of ~20%, regardless of the presence of cytokines in the suspension medium. This effort brings the ex vivo electrotransfection efficiency within the reach of therapeutic applications.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Hypogammaglobulinemia after heart transplantation: impact of pre-emptive use of immunoglobulin replacement (CytoGam) on infection and rejection outcomes.

Hypogammaglobulinemia (HGG) in solid organ transplant (SOT) patients confers an increased risk of opportunistic infections and poorer outcomes. Severe HGG (IgG < 350 mg/dL) after heart transplantation may follow intensification of immunosuppressive therapy and the resultant increased risk of opportunistic infections, particularly cytomegalovirus (CMV) disease. Evaluation of the effects of replacement therapy using intravenous immunoglobulin (CMV-IGIV, CytoGam) was conducted in cardiac transplant recipients and the data matched with a historical control group. Patients with severe HGG who received pre-emptive replacement therapy had significantly fewer opportunistic infections (P < 0.001) and episodes of rejection (grade > or = 3; P = 0.03 and grade > or = 2; P = 0.04) compared with the control group.

Adult↗
PubMed2001

Association between plaque instability, angiogenesis and symptomatic carotid occlusive disease.

BACKGROUND: Angiogenesis is a recognized feature of the atherosclerotic process and has been described in the context of unstable coronary atherosclerotic lesions. The aim of this study was to assess the association between angiogenesis in atherosclerotic carotid plaques and microscopic features of plaque instability, in particular intraplaque haemorrhage. METHODS: Consecutive patients undergoing carotid endarterectomy were included. Endarterectomy specimens were divided into their constituent atherosclerotic lesions. Histological sections were prepared and stained with haematoxylin and eosin, and immunohistochemically with an endothelial cell marker (CD34). The quantity of intraplaque haemorrhage was measured in transverse histological sections using computerized image analysis. Microvessel counts were performed in CD34-stained sections and were verified through computerized image analysis. RESULTS: Some 239 atherosclerotic lesions from 73 patients were available for analysis; 73 were early lesions, 74 were raised fibroatheromas and 92 were unstable atherosclerotic plaques. One hundred and fifty lesions were not haemorrhagic; 89 exhibited intraplaque haemorrhage, of which 28 involved less than 50 per cent of the plaque sectional area. There were higher microvessel counts in plaques containing over 50 per cent haemorrhage (P < 0.0001), unstable atherosclerotic lesions (P < 0.0001) and atherosclerotic lesions obtained from symptomatic patients (P < 0.001). CONCLUSION: There are strong associations between plaque vascularity, quantity of intraplaque haemorrhage and presence of symptomatic carotid occlusive disease.

Aged↗
PubMed2001

Multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system in patients awaiting heart transplantation.

BACKGROUND: Despite advances in heart transplantation and mechanical circulatory support, mortality among transplant candidates remains high. Better ways are needed to ensure the survival of transplant candidates both inside and outside the hospital. METHODS: In a prospective, multicenter clinical trial conducted at 24 centers in the United States, 280 transplant candidates (232 men, 48 women; median age, 55 years; range, 11-72 years) unresponsive to inotropic drugs, intra-aortic balloon counterpulsation, or both, were treated with the HeartMate Vented Electric Left Ventricular Assist System (VE LVAS). A cohort of 48 patients (40 men, 8 women; median age, 50 years; range, 21-67 years) not supported with an LVAS served as a historical control group. Outcomes were measured in terms of laboratory data (hemodynamic, hematologic, and biochemical), adverse events, New York Heart Association functional class, and survival. RESULTS: The VE LVAS-treated and non-VE LVAS-treated (control) groups were similar in terms of age, sex, and distribution of patients by diagnosis (ischemic cardiomyopathy, idiopathic cardiomyopathy, and subacute myocardial infarction). VE LVAS support lasted an average of 112 days (range, < 1-691 days), with 54 patients supported for > 180 days. Mean VE LVAS flow (expressed as pump index) throughout support was 2.8 L x min(-1) x m(-2). Median total bilirubin values decreased from 1.2 mg/dL at baseline to 0.7 mg/dL (P =.0001); median creatinine values decreased from 1.5 mg/dL at baseline to 1.1 mg/dL (P =.0001). VE LVAS-related adverse events included bleeding in 31 patients (11%), infection in 113 (40%), neurologic dysfunction in 14 (5%), and thromboembolic events in 17 (6%). A total of 160 (58%) patients were enrolled in a hospital release program. Twenty-nine percent of the VE LVAS-treated patients (82/280) died before receiving a transplant, compared with 67% of controls (32/48) (P <.001). Conversely, 71% of the VE LVAS-treated patients (198/280) survived: 67% (188/280) ultimately received a heart transplant, and 4% (10/280) had the device removed electively. One-year post-transplant survival of VE LVAS-treated patients was significantly better than that of controls (84% [158/188] vs 63% [10/16]; log rank analysis P =.0197). CONCLUSION: The HeartMate VE LVAS provides adequate hemodynamic support, has an acceptably low incidence of adverse effects, and improves survival in heart transplant candidates both inside and outside the hospital. The studies of the HeartMate LVAS (both pneumatic and electric) for Food and Drug Administration approval are the only studies with a valid control group to show a survival benefit for cardiac transplantation.

Cohort Studies↗
PubMed2001

Occipital fixation: effect of inner occipital protuberance alignment on screw position.

Previous authors have demonstrated that the optimum position for screw placement in the occiput is in the inner occipital crest. The position of this structure is usually taken as being in the midline; however, this has not been previously validated. Computerized tomography (CT) of the occipital region was performed prospectively according to a standard protocol. The study included 100 patients (53 female and 47 male, 18-75 years of age). CT images were analyzed to determine the position of the inner occipital crest in relation to the midline. The inner occipital crest is located off the midline (> or = 2 degrees ) in 48% of patients. Preoperative CT evaluation may be helpful prior to occipitocervical fixation on the basis of this study.

Adult↗
PubMed2000

The impact of routine mycophenolate mofetil drug monitoring on the treatment of cardiac allograft rejection.

INTRODUCTION: Mycophenolate mofetil (MMF) is a unique immunosupressive agent that has been shown to be efficacious in the treatment of cardiac allograft rejection. The utility of therapeutic drug monitoring on rejection prophylaxis and treatment is inconclusive. This study was undertaken to evaluate the incidence of rejection in relation to MMF trough level following heart transplantation. METHODS: Between May 1998 and February 1999, we retrospectively analyzed the clinical outcome of 215 heart transplant patients who had routine monitoring of MMF trough level at the time of scheduled endomyocardial biopsy. Patients were divided into three groups according to the time interval post transplant, and were evaluated in relation to the MMF trough level. Group I, 104 patients within 6 months of transplant; Group II, 90 patients, 6-12 months post transplant; and Group III, 71 patients beyond one year of transplant. Fifty patients had samples in more than one group. Rejection was defined as Grade > or = 3A based on ISHLT criteria. Mean follow-up period was 179+/-52 days. RESULTS: A significantly decreased incidence of rejection was noted in the samples with MMF trough level > or = mg/l compared to those with less than 2 mg/l inpatients evaluated within the first year of transplant (Group I: 8.8% vs. 14.9%, Group II: 4.2% vs. 11.3%, both P=0.05). In the presence of therapeutic cyclosporine (CSA) or tacrolimus (FK) blood levels, the incidence of rejection decreased significantly when MMF trough level was > or = 2 mg/l compared to samples with MMF trough level <2 mg/l (3.6% vs. 14.4%, P=0.005). No significant difference was noted in the presence of subtherapeutic CSA or FK levels (15.4% vs. 13.9%, P=NS). CONCLUSIONS: Monitoring of MMF trough levels may play a role in the management of cardiac transplant recipients during the first year post transplant.

Adult↗
PubMed2000

Efficacy of tacrolimus in patients with steroid-resistant cardiac allograft cellular rejection.

BACKGROUND: Tacrolimus is an immunosuppressive agent that is gaining widespread use in solid organ transplantation. This study was undertaken to evaluate the efficacy of tacrolimus in treating steroid-resistant cellular myocardial rejection. METHODS: We retrospectively analyzed the incidence of rejection and clinical outcome of 21 heart transplant recipients who were electively converted from cyclosporine to tacrolimus for recurrent episodes of steroid-resistant cellular rejection. These were compared to a historic group of 6 hemodynamically stable patients who were treated electively with Orthoclone OKT3 (Muromonab/CD3) for recurrent rejection. RESULTS: Eighty five percent (56/66) of the episodes of rejection occurred within the first 3 months after heart transplantation. Tacrolimus was started 2. 4 +/- 2.0 months post-transplant, and the mean follow-up duration on tacrolimus was 11.0 +/- 7.0 months. After conversion, a significant decline was noted in both the number of episodes of acute rejection per patient (3.14 +/- 0.85-0.57 +/- 0.87, p < 0.0001), and the incidence of acute rejection per 100 patient-days (6.39 +/- 3.96-0. 25 +/- 0.47, p < 0.0001). In comparison, OKT3 was started 5.25 +/- 9. 20 months post-transplant. Similarly, there was a significant decrease in the incidence of acute rejection per 100 patient-days (8. 69 +/- 5.65-0.20 +/- 0.23, p < 0.0001). The average hospital charges per patient for the OKT3-treated group was $33,339 +/- $10,511. There was no significant difference in the actuarial 1-year survival between the tacrolimus and OKT3-treated groups (93% vs 80%, p = 0.5). CONCLUSIONS: Outpatient conversion to tacrolimus is safe, well tolerated, and an effective therapeutic strategy for the treatment of steroid-resistant cellular rejection in heart transplant recipients. It is more cost-effective than OKT3 in the hemodynamically stable patient and outcomes are similar.

Adult↗
PubMed2000

Significant post-transplant hypogammaglobulinemia in six heart transplant recipients: an emerging clinical phenomenon?

BACKGROUND: The recent development of powerful agents such as mycophenolate mofetil and tacrolimus has altered current regimens for the prevention and treatment of allograft rejection. Questions have been raised about these newer regimens in terms of susceptibility to opportunistic infections and effects on host defenses. Severe hypogammaglobulinemia has been infrequently described in solid organ transplant recipients, but has been recently noted in six heart transplant recipients at one center, of whom five were receiving a combination of tacrolimus, mycophenolate mofetil, and prednisone. METHODS: Case summaries of six recent heart transplant recipients with total immunoglobulin G (IgG) levels of less than 310 mg/dl, five of whom had cytomegalovirus (CMV) infection and three of whom had multiple infections including Nocardia, invasive Trichophyton, and Acinetobacter bacteremia. Previous literature was reviewed with the aid of a Medline search using the search terms hypogammaglobulinemia; kidney, liver, heart, lung, and organ transplantation; mycophenolate mofetil; tacrolimus; cyclosporine; azathioprine; and nocardiosis. RESULTS: We here report six cardiac transplant recipients seen over a period of one year who were found to have immunoglobulin G levels of 310 mg/dl or below (normal: 717-1400 mg/dl). The first five patients were diagnosed because of evaluation for infections; the sixth, who was asymptomatic with an IgG level of 175, was found during screening for hypogammaglobulinemia instituted as a result of these first five patients. All six patients had received steroid pulses for rejection; all received mycophenolate mofetil; and 5/6 had been switched from cyclosporine to tacrolimus because of steroid-resistant rejection. Transient neutropenia (absolute neutrophil count less than 1000) was observed in 2/6; 3/6 had received OKT3 therapy for refractory rejection. These six patients were treated with a combination of antimicrobials, immunoglobulin replacement, and decrease in immunosuppressive therapy. CONCLUSION: The finding of unexpected hypogammaglobulinemia and concomitant infectious complications in six heart transplant recipients highlights a possible complication in a subset of patients receiving newer immunosuppressive agents. A larger prospective study is underway to determine risk factors for development of post-transplant hypogammaglobulinemia and to assess pre-transplant immune status of these recipients. Monitoring of immunoglobulin levels in high-risk patients receiving intensified immunosuppressive therapy for rejection may help to prevent infectious complications.

Acinetobacter Infections↗
PubMed2000

Severe respiratory depression after dimethylsulphoxide-containing autologous stem cell infusion in a patient with AL amyloidosis.

Adverse reactions with DMSO-cryopreserved stem cell infusion are well-recognized. However, severe, life-threatening anaphylactic reactions with DMSO are very rarely described in the literature. We report here a 58-year-old female with AL amyloidosis who developed an unexpected episode of respiratory arrest a few seconds after the beginning of thawed stem cell product infusion. Fortunately, the patient was resuscitated successfully without the need for intubation. The prompt development of the reaction just a few seconds after the stem cell infusion convincingly implicates DMSO as the potential suspect. The presence of amyloid cardiomyopathy might have also contributed to this adverse event. Bone Marrow Transplantation (2000) 25, 1299-1301.

Amyloidosis↗
PubMed2000

Uptake of Down syndrome screening in an Australian Vietnamese population.

It has been previously shown that the uptake of prenatal diagnosis by Victorian women of a non-English speaking background is significantly lower than that of comparable English speaking women. To explore this further we have examined the uptake of Down syndrome screening and diagnosis by Vietnamese women attending a community-based antenatal clinic in metropolitan Melbourne over a two year period. Of the 207 women studied, 161 (78%) were offered screening or diagnosis and of these women 139 (86%, 95%CI 81-92%) accepted the offer, representing 67% (95%CI 61-74%) of the entire population. Of the 127 women who had screening, rather than diagnosis, 12 (9%) had an 'increased risk' result. Eleven of these women accepted diagnosis. We also explored the reasons why 45 (22%) of women were not offered screening. Almost half (44%) of these women first attended the clinic at a too advanced stage of gestation but in 25 women there were no obvious reasons. These results are discussed in the context of current prenatal screening and diagnostic practice in Victoria and simple recommendations made.

Adult↗
PubMed2000

The mother-child interaction and clinical judgment during acute pediatric illnesses.

OBJECTIVES: For acutely ill children living in less than optimal environments, mothers and pediatricians may have a heightened perception of illness severity, a lower specificity of clinical judgments, and a tendency to over-utilize resources. We examined the mother-child interaction in order to understand the relation of less optimal environments to clinical judgment and resource use. STUDY DESIGN: At the 2-week and 6-, 15-, and 24-month well child visits of 316 children, the mother-well child interaction was assessed by using the Biringen's Emotional Availability Scales (EAS). Data were gathered regarding maternal depression and sense of competence, infant temperament, maternal social support, life events, the home environment, and demographics. At ill visits, the mother-ill child interaction was assessed by using the EAS, and mothers and pediatricians independently assessed illness severity using the Acute Illness Observation Scales. Resource use during the illness was evaluated. RESULTS: One thousand nine hundred eight-three acute illnesses were assessed. A less optimal mother-child interaction was significantly (P <.05 for all comparisons) associated with poorer reliability of mothers' judgments, lower specificity of mothers' judgments (71% vs 85%) and pediatricians' judgments (92% vs 97%), and greater use of resources (eg, for hospitalizations, 2.6% of visits vs 0.7%). Adverse maternal, infant, and demographic characteristics were associated with a less optimal mother-well child (r = 0.68) and mother-ill child (r = 0.80) interaction, a heightened perception of illness severity, and greater resource use. CONCLUSION: Less optimal environments adversely affect the mother-child interaction; a poor mother-child interaction is correlated with low specificity of clinical judgment and over-utilization of resources.

Acute Disease↗
PubMed1999

Outcome of de novo hepatitis C virus infection in heart transplant recipients.

The outcome of de novo hepatitis C virus (HCV) infection in heart transplant recipients of HCV-antibody positive organs is not known. The aim of the study was to determine the short-term outcome of de novo HCV infection in recipients of HCV-positive donor organs. HCV-antibody negative recipients of HCV-antibody positive hearts were identified from January 1, 1991 to February 28, 1998. Control patients matched for year of transplantation were also identified. Twenty-eight patients (22 males, mean age of 56 +/- 11 SD) received hearts from HCV-antibody-positive donors. The control group was similar to the patients in all clinical and demographic aspects. Twenty-three patients had detectable viremia by reverse-transcription polymerase chain reaction (RT-PCR). Of these 23 patients with de novo HCV infection, 7 (30%) developed HCV-related liver disease. Three patients (13%) had chronic hepatitis and 4 patients (17%) developed severe acute cholestatic hepatitis (ACH). Mycophenolate mofetil (MMF) use (P =.04) and high viral load at onset of acute liver disease (P =.02) were associated with ACH. Overall survival was similar between patients with de novo HCV infection and controls (P =.20). Development of ACH (P =.02) and MMF use (P =.0009) were associated with decreased survival in patients with de novo HCV infection. The present study showed that survival of patients with de novo HCV infection was similar to a matched control group. HCV-related severe ACH is associated with a poor short-term outcome in patients with de novo HCV infection. MMF use may be associated with a higher incidence of HCV-related severe ACH and a poor short-term outcome.

Actuarial Analysis↗