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Biomedical subjects

J W Alexander

Publications and source records attributed to J W Alexander.

At least 19 recordsLinked to original sources
PubMed2005

African American renal transplant recipients benefit from early corticosteroid withdrawal under modern immunosuppression.

African Americans have historically been considered high-risk renal transplant recipients due to increased rejection rates and reduced long-term graft survival. Modern immunosuppression has reduced rejections and improved graft survival in African Americans and may allow successful corticosteroid withdrawal. Outcomes in 56 African Americans were compared to 56 non-African Americans enrolled in early withdrawal protocols. Results are reported as African American versus non-African American. Acute rejection at 1 year was 23% and 18% (P = NS), while patient and graft survival was 96% versus 98% and 91% versus 91% (P = NS), respectively. In conclusion, early withdrawal in African Americans is associated with acceptable rejection rates and excellent patient and graft survival, indicating that the risks and benefits of early withdrawal are similar between African Americans and non-African Americans. Additional followup is needed to determine long-term renal function, graft survival, and cardiovascular risk in African Americans with early steroid withdrawal.

Adrenal Cortex Hormones↗
PubMed2005

Corticosteroid avoidance ameliorates lymphocele formation and wound healing complications associated with sirolimus therapy.

INTRODUCTION: Sirolimus (RAPA) and corticosteroids (CS) both inhibit wound healing. To evaluate the possibility that RAPA and CS have additive effects on wound healing, we evaluated the effects of corticosteroid avoidance (CSAV) on wound healing complications in patients treated with RAPA. METHODS: One hundred nine patients treated with a CSAV regimen (no pretransplantation or posttransplantation CS) were compared with a historical control group (n = 72) that received cyclosporine (CsA), mycophenolate mofetil (MMF), and CS. The CSAV group received low-dose CsA, MMF, RAPA, and thymoglobulin induction. Complications were classified as follows: wound healing complications (WHC) or infectious wound complications (IWC). WHC included lymphocele, hernia, dehiscence, diastasis, and skin edge separation. IWC included wound abscess and empiric antibiotic therapy for wound erythema. RESULTS: The CSAV group was largely CS-free: 11% of patients received CS for rejection, 12% of patients received CS for recurrent disease, and 85% of patients are currently off CS. The CSAV group had a significantly lower incidence of WHC (13.7% vs 28%; P = .03) and lymphoceles (5.5% vs 16%; P = .02) than the control group. There was no difference in the incidence of IWC between the 2 groups. Patients who received CSAV were 18% less likely (P = .57) to develop any type of complication, 41% less likely (P = .20) to develop a WHC, and 71% less likely (P = .018) to develop a lymphocele. CONCLUSIONS: CSAV in a RAPA-based regimen results in a marked reduction in WHC and lymphoceles. Therefore, CSAV provides a promising approach for addressing WHC associated with RAPA therapy.

Adrenal Cortex Hormones↗
PubMed2005

A prospective, pilot study of early corticosteroid cessation in high-immunologic-risk patients: the Cincinnati experience.

BACKGROUND: The first prospective trial of steroid withdrawal dedicated to high-immunologic-risk patients is reported herein. METHODS: Twenty-five patients were enrolled prospectively in an IRB-approved HIPAA-compliant protocol. Immunosuppression included corticosteroid withdrawal (CSWD) at 7 days, tacrolimus (target trough level 4 to 8 ng/mL), sirolimus (target trough level 8 to 12 ng/mL), and Mycophenolate Mofetil (2 g/d). Induction with daclizumab (2 mg/kg) on posttransplant days (PTD) 0 and 14 was administered to the first 10 patients. The protocol for the next 15 patients was modified because of high acute rejection rates to include received T-cell-depleting antibody induction therapy with thymoglobulin (1.5 mg/kg) on PTDs 0 and 2 followed by daclizumab on Postoperative day (POD) 14. Recipient inclusion criteria included: (1) repeat transplant recipients; or (2) patients with a peak PRA > or =25%. All rejection episodes were diagnosed by biopsy and graded using Banff '97 criteria. RESULTS: Twenty-five patients were enrolled and median follow-up was 402 days. Forty percent of recipients were black, 68% of patients were repeat transplant recipients, 68% received deceased donor kidneys, and 36% had a peak flow PRA >25%. Overall acute rejection, graft survival, and patient survival rates of 40%, 88%, and 96%, respectively, were observed for the duration of the study. Acute rejection occurred in 6 of 10 patients (60%) with daclizumab induction; however, acute rejection rates fell to 27% when thymoglobulin was introduced (P = .1). CONCLUSIONS: This study supports our previous observations in a multivariate analysis of early CSWD patients, wherein polyclonal antibody induction therapy reduced acute rejection. High-immunologic-risk patients may be able to undergo early CSWD with acceptable rates of acute rejection.

Adrenal Cortex Hormones↗
PubMed2005

Global cardiovascular risk under early corticosteroid cessation decreases progressively in the first year following renal transplantation.

UNLABELLED: A primary reason to eliminate corticosteroids from immunosuppressive regimens in solid organ transplant recipients is improved cardiovascular risk profiles. Although a number of studies have documented that corticosteroid withdrawal (CSWD) regimens reduce hypertension, hyperlipidemia, diabetes, and weight gain, global assessments of cardiovascular risk under CSWD have not been reported. The purpose of this study was to document cardiovascular risk under CSWD using a global risk assessment by Framingham risk assessment. METHODS: Framingham global cardiovascular risk assessments were performed at baseline and 3, 6, and 12 months posttransplant on patients enrolled in prospective, IRB-approved early (<7 days of corticosteroids) CSWD trials. Framingham score was based on age, sex, presence of diabetes, HDL and total cholesterol, and systolic blood pressure. All patients were nonsmokers. Left ventricular hypertrophy assessment by EKG criteria was not available at all time points and therefore were not included. RESULTS: One hundred eighty-three patients were included in the analysis. Fourteen percent of patients had evidence of coronary heart disease (prior MI, CABG, PTCA, or significant cardiovascular disease as evidenced by angiography) prior to transplant. Complete information was available for 160 patients at baseline, 132 at 1, 3, and 6 months, and 93 at 12 months posttransplant. Mean 10-year risk (expressed as percent) for developing coronary heart disease decreased over time: 8.03 at baseline, 8.31 at 3 months, 7.40 at 6 months, and 7.20 at 12 months, indicating that global cardiovascular risk fell at 1 year posttransplant by about 10% in renal transplant recipients undergoing early CSWD. CONCLUSIONS: Estimation of cardiovascular risk by Framingham risk factor assessment allows incorporation of several cardiovascular risk factors into a single estimate, thereby accounting for differential effects of each individual factor on global cardiovascular risk. This experience indicates that global cardiovascular risk decreases by approximately 10% at 1 year posttransplant in renal transplant recipients who undergo early corticosteroid withdrawal (CSWD).

Adrenal Cortex Hormones↗
PubMed2005

Histocompatibility testing predicts acute rejection risk in early corticosteroid withdrawal regimens.

UNLABELLED: Histocompatibility testing has been shown to predict acute rejection risk in steroid-based immunosuppression. However, little evidence exists of its ability to predict acute rejection risk in corticosteroid-free patients, with no evidence in early corticosteroid withdrawal (CSWD) under modern immunosuppression. The purpose of this study was to evaluate the ability of histocompatibility testing to identify patients at high risk for acute rejection after early CSWD. METHODS: One hundred eighty-one patients were entered into six IRB-approved early CSWD regimens. Histocompatibility testing included serologic PRA, flow cytometric PRA testing by Class I and Class II MHC beads, and B cell crossmatching with pronase treatment. All rejection episodes were biopsy proven, and grading was assigned using Banff criteria. Influence of individual tests was examined using Chi square univariate and multivariate logistic regression analysis. RESULTS: Median follow-up was 23.5 months (range 7-48 months). Of 181 patients, 16% were repeat transplant recipients, 36% received deceased donor renal transplants, 48% received living related donor renal transplants, and 16% received living unrelated transplants. Overall patient survival was 97%, and death-censored graft survival was 96.5%. Acute rejection rates in the entire follow-up period were 17.7%. 12.4% in primary transplant recipients and 37% in repeat transplant recipients. Multivariate analysis revealed that HLA AB and DR locus mismatching were associated with increased acute rejection risk. Similarly, serologic PRA analysis predicted acute rejection risk; however, flow cytometry crossmatching did not predict acute rejection risk. The greatest single influence on acute rejection risk appeared to be a flow cytometric B cell crossmatch (7.94-fold increased risk). In conclusion, histocompatibility testing can identify patients at high risk for acute rejection following early CSWD. HLA matching, serologic PRA testing, and flow cytometry-based B cell crossmatching can all be used to predict acute rejection risk.

Adrenal Cortex Hormones↗
PubMed2004

Basic and clinical research in polyomavirus nephropathy.

Over the last decade, polyomavirus nephropathy (PVN) has emerged as an important cause of renal allograft dysfunction and graft loss. PVN occurs with a prevalence of 1%-8% in renal transplant recipients and is most commonly reported within the first 12 months posttransplant. The human polyomavirus, BK virus, is thought to be the primary etiologic agent of PVN. Risk factors for PVN are not well defined and are most likely a result of a complex interaction between multiple donor and recipient factors. Definitive diagnosis of PVN is made through histological assessment of a renal allograft biopsy. Recent studies have also evaluated noninvasive urine and serum markers for screening of BK virus replication and as adjunct tools in PVN diagnosis and monitoring. The principal treatment for PVN is immunosuppression reduction, but this must be balanced against the risks of rejection. If rejection occurs concurrently with PVN, a brief increase in immunosuppression to treat the rejection episode followed by a subsequent reduction in immunosuppression is recommended. No antiviral treatments for PVN have been approved by the Food and Drug Administration. Although the antiviral drug cidofovir has shown in vitro activity against murine polyomaviruses, and has been effective in some patients, it is associated with significant nephrotoxicity. Small series of patients treated with leflunomide and intravenous immune globulin therapy for PVN have also recently been reported. Retransplantation after graft loss due to PVN is feasible, but experience is limited. Current research is focusing on identifying PVN risk factors, refining screening, diagnostic and monitoring methods, and developing therapy for prophylaxis and treatment of PVN with the goals of decreasing the prevalence of PVN and improving allograft outcomes in renal transplant recipients diagnosed with PVN. This review will present recent advances in basic and clinical research related to PVN and renal transplantation.

Humans↗
PubMed2001

Interactive effects of tunnel dilation on the mechanical properties of hamstring grafts fixed in the tibia with interference screws.

The effect of dilation of the tibial tunnel on the strength of hamstring graft fixation using interference screws was evaluated. In all, 28 RCI screws were tested in male human tibia-hamstring constructs with tibial tunnels reamed or dilated to the respective size of the graft diameter. Dilation of the tibial tunnel failed to significantly enhance hamstring fixation. Grafts secured in dilated tunnels displayed an 11% greater resistance to the initiation of graft slippage (174+/-112 N) compared to their undilated controls (156+/-77 N, P=0.63). Dilation of the tibial tunnel increased the failure load by an average of 4%, independent of screw diameter (dilated specimens: 360+/-120 N, controls: 345+/-88 N, P=0.74). Biomechanical research on the effect of tibial tunnel dilation in hamstring fixation has not provided satisfactory evidence as to the benefits of this additional surgical step during anterior cruciate ligament (ACL) reconstruction.

Anterior Cruciate Ligament↗
PubMed2001

Using a management perspective to define and measure changes in nursing technology.

AIMS: The aims of this paper are to discuss the uses of the concept of technology from the medical science and the management perspectives; to propose a clear definition of nursing technology; and to present a study applying the use of the concept of nursing technology on nursing units. BACKGROUND: Nurse managers must use management terms correctly and the term technology may be misleading for some. A review of the nursing literature shows varied uses of the concept of technology. Thus a discussion of the dimensions, attributes, consequences, and definitions of nursing technology from the management perspective are given. DESIGN: A longitudinal study to measure the dimensions of nursing technology on nursing units 10 years apart. RESULTS: The findings suggest that the dimensions of nursing technology change over time and support the need for nurse managers to periodically assess nursing technology before making management changes at the level of the nursing unit. CONCLUSIONS: This study helps health care providers understand the unique role of nurses as healthcare professionals by identifying and measuring nursing technology on the nursing unit.

Data Interpretation, Statistical↗
PubMed2001

Immediate allograft dysfunction due to atheroembolic disease.

Atheroembolic disease is a known cause of renal failure following invasive vascular procedures in patients with atherosclerosis. It is, however, not generally associated with renal transplant dysfunction. We report on a case of donor-transmitted atheroembolic renal disease, which led to an immediate loss of the transplant kidney in the operating room. Risk factors associated with this condition and methods to prevent this complication are discussed.

Cadaver↗
PubMed2001

Comparison of translocation of different types of microorganisms from the intestinal tract of burned mice.

The aim of this study was to compare the ability of various microorganisms to translocate from the intestine to the mesenteric lymph nodes (MLNs), liver, and spleen in a burned mouse model. Balb/c mice were gavaged with 1 x 10(9) or 1 x 10(10) of one of 11 different microorganisms. All animals were then given a 20% burn. Survival after 10 days showed no significant difference between any of the groups at the 10(10) dose. At the 10(9) dose, significantly higher survival rates were found in three of the 11 strains. Microbial translocation (gavage of 10(10) 111In-labeled organisms) and host's ability to kill translocated bacteria (viable bacteria in tissues) were measured followed by burn injury and sacrifice four hours later. Translocation and killing of Staphylococcus epidermidis and Escherichia coli was high in the MLNs compared with all other groups but translocation was lower to the liver. Klebsiella, Pseudomonas, and Serratia translocated more evenly to all the tissues. However, these groups showed very high clearance of bacteria in the liver and spleen except for Klebsiella and one strain of Pseudomonas in the spleen. Candida showed poor translocation to all of the tissues and high clearance. It is concluded that various strains of bacteria translocate from the intestine to a similar degree after injury, but the tissues to which they translocate and the rate at which they are killed are somewhat strain dependent.

Animals↗
PubMed2000

Nutritional immunomodulation leads to enhanced allograft survival in combination with cyclosporine A and rapamycin, but not FK506.

BACKGROUND: Recently, specific immunonutrients were found to increase experimental allograft survival when combined with cyclosporine A (CsA). This study compared the effect on rat cardiac allograft survival when nutritional immunomodulation was used with CsA, rapamycin (Rapa), or tacrolimus (FK506). METHODS: Intra-abdominal ACI to Lewis cardiac allografts were performed and assessed daily by palpation. Study groups included untreated controls and those receiving CsA, Rapa, or FK506. Rats were fed ad libitum with Impact diet (fortified with fish oil, arginine, and RNA) or standard rat food. Further study groups were transplanted that received a donor-specific transfusion in addition to immunosuppression and diet. RESULTS: Allograft survival was extended by combining Impact with CsA (45.3+/-19 days) and Rapa (165.3+/-52 days), but not FK506 (12.4+/-3.2 days). Mean graft survival in the Rapa/Impact group met criteria for functional tolerance. The addition of a donor-specific transfusion did not lead to graft survival advantages over similar groups not receiving a donor-specific transfusion. CONCLUSIONS: The use of immunonutrients improves transplant outcome in animals treated with short courses of CsA and Rapa, but not FK506. These findings highlight the potential differences in the effects of nutritional immunomodulation with different immunosuppressive drugs in the treatment of transplant patients.

Animals↗
PubMed2000

Sodium arsenite induces the stress response in the gut and decreases bacterial translocation in a burned mouse model with gut-derived sepsis.

Bacteria translocation from the bowel to systemic organs after burn injury may contribute to or be a cause of sepsis and multiple organ failure. The stress response confers protection under stressful conditions that would otherwise lead to cell damage or death. We investigated whether prior induction of the stress response by sodium arsenite could affect bacterial translocation after thermal injury. HSP-70, a highly stress-inducible protein, was used as a marker for induction of the stress response. Balb/c mice were intravenously injected with 4 mg/kg of sodium arsenite and killed at selected times post-treatment. Other treated mice were then gavaged with 10(10) E. coil or 10(10) 111In-labeled E. coil followed by a 20% burn. Survival was observed for 10 days. Mice gavaged with radiolabeled E. coil were killed 4 h post-burn to determine the effect of HSP-70 induction on microbial translocation in mesenteric lymph nodes (MLN), liver, and spleen. Sodium arsenite-injected mice showed HSP-70 induction in the ileum that increased in a time-dependent manner with peak expression 12 h post-injection. Treated mice showed a significantly higher survival rate (93%) than controls (46%; P < 0.05), and detection of 111In-labeled E. coli was significantly less in the liver and spleen (P < 0.05). These data show that sodium arsenite induced HSP-70 expression in the small intestine. The stress response was associated with significantly increased survival and significant decrease in detection of 111In-labeled E. coil in the liver and spleen in a burned mouse model with gut-derived sepsis.

Animals↗
PubMed1999

Evaluation of pre- and posttransplant donor-specific transfusion/cyclosporine A in non-HLA identical living donor kidney transplant recipients. Cooperative Clinical Trials in Transplantation Research Group.

BACKGROUND: The beneficial effects of donor specific transfusion (DST) have become controversial in the cyclosporine era. This study was performed to evaluate the potential benefits of a new protocol for administering DSTs in the perioperative period. METHODS: Non-HLA identical living donor kidney transplant recipients were randomized prospectively to control or to receive a DST 24 hr before transplant and 7-10 days posttransplant. All patients received similar immunosuppression according to protocol. RESULTS: The protocol had 212 evaluable patients (115 transfused and 97 control). There were no differences in 1- and 2-year graft and patient survival, causes of graft failure, incidence and types of infection, repeat hospitalization, or the ability to withdraw steroids. Immunological hyporesponsiveness (by mixed lymphocyte culture) occurred more frequently in transfused patients (18%) than controls (3%) (P = 0.04). Blood stored for > or =3 days was associated with fewer early rejections than blood stored < or =2 days. Overall, class II antigen mismatches were associated with more rejection episodes than class I antigen mismatches. However, transfused patients, but not control patients, with more class I antigen mismatches were more likely to have rejections. CONCLUSIONS: Administration of DSTs by the method described had no practical influence on patient or graft survival for up to 2 years. However, donor-specific hyporesponsiveness was more common in transfused patients (18 vs. 3%). Longer follow-up will be needed to determine whether DST will be associated with long-term benefit.

Blood Preservation↗
PubMed1999

Use of percutaneous transpedicular external fixation pins to measure intervertebral motion.

STUDY DESIGN: Direct measurement of intervertebral motion was compared to motion determined by measuring the position of the exposed ends of the external fixation pins. OBJECTIVES: To verify the accuracy of this technique, so that this protocol can be used to study intervertebral motion in the clinical setting. SUMMARY OF BACKGROUND DATA: The transpedicular external fixation test has been shown to be a test that can predict the outcome of spinal fusion. In patients who are candidates for this test, intervertebral motion can be calculated from motion at the external ends of these pins. METHODS: Six fresh cadaveric spinal segments from L2 to L5 were instrumented with titanium Schanz screws. Reflective markers were placed on the tips of the pins, and intervertebral motion was measured using a noncontacting camera system. Computed tomography data were used to determine the position of the vertebra relative to the reflective markers. Intervertebral distances were calculated and compared with direct measurements obtained using a three-dimensional digitizing arm. RESULTS: There was an excellent correlation (r2 = 0.931) between the directly measured intervertebral motions and those that were indirectly calculated from measurements of motion at the end of the Schanz screws. CONCLUSIONS: Intervertebral motion can be measured by monitoring motion of the ends of transpedicular external fixation pins. Motion of anatomic landmarks on the vertebrae can be calculated from the pin end's motion if computed tomography data are used to determine the geometric relation between the vertebrae and the external fixation pins. This validation study supports the use of this method in clinical investigations of intervertebral motion in patients with low back pain and external fixation.

Aged↗
PubMed1999

The effect of nutritional immunomodulation on cardiac allograft survival in rats receiving mycophenolate mofetil, cyclosporine A, and donor-specific transfusion.

BACKGROUND: Immunosuppressive drugs continue to pose significant risks such as infection, toxicity, or neoplasia when used in long-term therapy. The investigation of newer and safer combined treatment strategies that decrease the need for these drugs is becoming increasingly important. Immunonutrients are known to have significant modulating effects on the immune system. Feeding with Impact, a commercially available diet enriched with arginine, omega-3 fatty acids, and RNA, recently has been shown to extend rat cardiac allograft survival when combined with a donor-specific transfusion (DST) and cyclosporine A (CsA). Because mycophenolate mofetil (MMF) is now commonly used in the clinical setting, the current study was designed to examine the effect on rat cardiac allograft survival when MMF was added to this immunosuppressive regimen. METHODS: Intra-abdominal ACI to Lewis heterotopic cardiac allografts were performed. Study groups included untreated controls and recipients receiving varying combinations of a DST (1 mL) on the day prior to engraftment, MMF 45 mg/kg/day from the day of transplant through postoperative day six, and CsA 10 mg/kg on the day prior to operation and 2.5 mg/kg from the day of transplant through postoperative day 6. Animals were fed ad libitum with Impact diet or standard lab chow. Graft survival was determined by cessation of a palpable heartbeat. RESULTS: Treatment with MMF led to a prolonged allograft survival over historical untreated controls. The combination of MMF with a donor-specific transfusion, Impact, or CsA was associated with an increase in graft survival over MMF alone. The addition of Impact to the combination of MMF and CsA resulted in further improvement. The most pronounced graft survival advantage was seen when Impact was combined with a DST and both of the immunosuppressive agents. One quarter of the animals in this group had a palpable donor heart beat at greater than 150 days, indicating functional tolerance in those animals. CONCLUSIONS: The administration of Impact diet to treatment groups in this study was associated with graft survival advantages when compared to most of the other study groups receiving a similar drug regimen and standard chow. These findings support the importance of nutritional influences on allograft survival, and highlight the potential of diet therapy when used with short courses of clinically relevant immunosuppressive drugs.

Adjuvants, Immunologic↗