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Biomedical subjects

R Mehra

Publications and source records attributed to R Mehra.

At least 55 records · Page 3Linked to original sources

Effects of high-frequency atrial pacing in atypical atrial flutter and atrial fibrillation.

Atypical atrial flutter has, hitherto, been relatively refractory to termination by rapid atrial pacing. High-frequency pacing (HFP) in the atrium, for termination of atrial flutter or atrial fibrillation (AF), and the electrophysiologic effects related to it have not been examined. We examined the clinical efficacy, safety, and electrophysiologic mechanisms of HFP using 50-Hz bursts at 10 mA applied at the high right atrium in patients with atypical atrial flutter (group 1) or AF (group 2), using a prospective randomized study protocol. Four burst durations (500, 1000, 2000, and 4000 ms) were applied at the high right atrium repetitively in random sequence in 22 patients with spontaneous atrial flutter or AF. Local and distant right and left atrial electrogram recordings were analyzed during and after HFP. HFP resulted in local and distant right and left atrial electrogram acceleration in 8 of 10 patients (80%) in group 1 but caused less frequent local atrial electrogram acceleration (6 of 12 patients) and no distant atrial electrogram effects in group 2 (p < .05 versus group 1). The HFP protocol was effective in arrhythmia termination in 6 of 10 patients in group 1 but in no patient in group 2 (p < .05 versus group 1). Standard HFP protocol applied at the high right atrium can frequently alter atrial activation in both atria and can terminate atypical atrial flutter. Efficacy in AF is limited, probably due to limited electrophysiologic actions beyond the local pacing site.

Adult↗

Bone marrow transplantation after failure of autologous transplant for non-Hodgkin's lymphoma.

We evaluated the response to and toxicity of allogeneic or autologous bone marrow transplantation (BMT) for patients with non-Hodgkin's lymphoma (NHL) who relapsed after autologous BMT. Since 1990, 172 patients have received autologous BMTs in NHL at the MD Anderson Cancer Center and 75 have relapsed. Twelve patients (median age, 42 years), with disease recurrence underwent either allogeneic BMT (eight patients) or a second autologous BMT (four patients). Ten patients received thiotepa, busulfan and cyclophosphamide as conditioning, one patient received cyclophosphamide and total body irradiation and one received BCNU, etoposide, Ara-c and melphalan. The median interval between the first and second transplants was 23.5 months (range 5-80 months). Three patients who underwent allogeneic BMT had refractory relapses, three had a responsive relapse and two were in complete response (CR) at the time of BMT. Five patients received peripheral blood stem cells and three patients, allogeneic bone marrow. Three patients are alive and disease-free at 25, 22 and 7 months after allogeneic BMT. Four patients died of treatment-related causes and one from disease recurrence. All four patients undergoing autologous BMT had responsive relapses. Three patients received peripheral blood stem cells and one patient bone marrow. Two patients are alive and disease-free at 12 and 30 months after autologous transplants. There were no treatment-related deaths; two patients died of disease recurrence. This retrospective study shows that in selected patients, allogeneic or autologous BMT is an effective salvage therapy for NHL which recurs after autologous BMT.

Adult↗

Allogeneic blood stem cell transplantation in advanced hematologic cancers.

Allogeneic bone marrow transplantation for advanced hematologic cancer is associated with a high risk of early treatment-related morbidity and mortality. To determine the short-term benefits of allogeneic blood stem cell transplants when compared to bone marrow transplants, we reviewed outcomes of 74 adults with advanced hematologic cancer transplanted from HLA-matched related donors after conditioning with thiotepa, busulfan and cyclophosphamide. There were three cohorts: group 1 received bone marrow transplants with cyclosporine (CsA) and methotrexate (MTX) for GVHD prophylaxis; group 2 received bone marrow transplants with CsA and methylprednisolone (MP); and group 3 received blood stem cells with CsA and MP. All patients received filgrastim post-transplant. Median times (range) to neutrophils > or = 0.5 x 10(9)/l were 17 (8-30), 9 (8-16) and 10 (8-13) days post-transplant, and to platelets > or = 20 x 10(9)/l were 28 (14-100+), 19 (13-100+) and 14 (9-86) days post-transplant for groups 1, 2 and 3, respectively (P < 0.05 only for group 1 vs group 3 for both outcomes). Blood stem cell recipients had the least regimen-related toxicity, fewest early deaths and earliest discharge. There was no significant difference in acute GVHD between the three groups. One hundred and eighty-day survivals (95% CI) were 53% (35-72%), 32% (10-53%), and 68% (49-87%) for groups 1, 2 and 3, respectively (P < 0.05 only for group 2 vs group 3). For allogeneic transplantation, use of blood stem cell grafts has substantial advantages over marrow grafts.

Adolescent↗

Headache, circumoral paresthesia, and facial flushing associated with high-dose carmustine infusion.

We describe seven patients who developed symptoms including severe headache, circumoral paresthesia, and facial flushing during high-dose carmustine (BCNU) infusion as part of the preparative regimen for autologous peripheral blood stem cell (PBSC) transplantation for metastatic breast cancer. Five patients responded to pain medications, including partial and complete opiate receptor agonists. Premedication of subsequent doses of BCNU with corticosteroids, pain medications, or benzodiazepines lessened, but did not prevent the same symptoms from recurring. The incidence and mechanism of this toxicity are unknown, but this adverse syndrome should be considered when administering high-dose BCNU infusions.

Antineoplastic Agents, Alkylating↗

Management of lymphoma recurrence after allogeneic transplantation: the relevance of graft-versus-lymphoma effect.

Donor lymphocyte infusions, by virtue of a graft-versus-tumor effect, have been shown to induce remissions in leukemia that recurs after allogeneic bone marrow transplantation. Similar effects have been postulated to contribute to the decreased recurrence rate observed after allogeneic transplantation in non-Hodgkin's lymphoma. This lower recurrence rate may be due to a variety of other mechanisms. We aimed to evaluate the role of graft-versus-lymphoma effects in patients in whom lymphomas recur after allogeneic transplantation. At the time of recurrence, immunosuppressive therapy was withheld. Patients with non-responding disease received an infusion of donor lymphocytes. Patients were observed for response and graft-versus-host disease. Disease in four of nine patients responded to withdrawal of immunosuppressive therapy. A minor response was observed in one of three recipients of donor lymphocyte infusions. Responses were observed among two patients with follicular lymphoma, one with large cell lymphoma and one with lymphoblastic lymphoma. A minor response was observed in a patient with prolymphocytic leukemia/lymphoma. We conclude that withdrawal of immunosuppressive therapy and donor lymphocyte infusion can induce durable remissions in patients with recurrent lymphoma after allogeneic transplantation.

Adult↗

Foscarnet for prevention of cytomegalovirus infection in allogeneic marrow transplant recipients unable to receive ganciclovir.

Cytomegalovirus (CMV) disease can be prevented by administration of ganciclovir prophylactically post-transplant. However, up to 30% of patients discontinue use of ganciclovir as a result of profound neutropenia and may subsequently develop CMV infections while unprotected. To prevent reactivation of CMV, we administered foscarnet to 39 adults unable to receive ganciclovir due to delayed engraftment or ganciclovir-induced neutropenia. Twenty-four (62%) of the patients had received T cell-depleted marrow transplants. Foscarnet sodium 60 mg/kg i.v. daily was continued until the neutropenia resolved, at which time ganciclovir was resumed. CMV prophylaxis commenced at a median of 28 days following transplantation. Median time to initiation of foscarnet was day 60 post-transplant, and the median duration of treatment was 22 days. Foscarnet was well-tolerated. Six (15%) patients had CMV detected while receiving prophylaxis, and CMV-related mortality was 5%. Foscarnet is a safe and effective agent for prevention of CMV disease in allogeneic transplant recipients unable to receive ganciclovir.

Actuarial Analysis↗

Derivation of a defibrillator implant criterion based on probability of successful defibrillation.

Common criteria for implant of a cardioverter defibrillator include verification of a 2:1 energy safety margin or a fixed safety margin of 10 joules. These criteria have been established empirically. We present a statistically model based on defibrillation efficacy curves which may be used to establish a criterion which would meet a predetermined target. As an example, an implant criterion is derived based on a goal of 1-year sudden cardiac death survival of at least 99% by selecting an expected first-shock efficacy to meet that target. Logistic regression was performed on data from over 1,500 defibrillator implants including successful epicardial and transvenous electrode system implants as well as data from unsuccessful implants. A random sample from these curves was used to generate a representative sample of 1,000 potential implant candidates. By assuming successful defibrillation using a series of shocks at specified energies, i.e., choosing an implant criterion, the probability of successful defibrillation of the patient by a single shock at a predetermined maximum output can be established. Independent data are used to validate the model's accuracy in predicting defibrillation efficacy within the derived example.

Clinical Protocols↗

Phase I trial of cyclosporine-induced autologous graft-versus-host disease in patients with multiple myeloma undergoing high-dose chemotherapy with autologous stem-cell rescue.

PURPOSE: To determine the feasibility and toxicity of inducing autologous graft-versus-host disease (GVHD) with cyclosporine in patients with multiple myeloma undergoing autologous stem-cell transplantation. PATIENTS AND METHODS: Fourteen multiple myeloma patients with a median age of 50 years (range, 41 to 63) were enrolled. The median time from diagnosis to transplant was 651 days (range, 229 to 3,353). Ten patients had primary refractory disease, two were in first remission, and two were responsive to salvage therapy. The preparative regimen consisted of thiotepa, busulfan, and cyclophosphamide. Cyclosporine was administered daily for 28 days after the stem-cell infusion, and the dose was adjusted to maintain whole-blood cyclosporine levels between 50 and 150 ng/dL in the first seven patients (low-level group) and between 150 and 300 ng/dL in the other seven patients (high-level group). RESULTS: All patients achieved neutrophil engraftment a median of 11 days after transplant. Four patients developed > or = grade 2 hepatic toxicity, six developed > or = grade 2 nephrotoxicity, and four developed reversible cardiac toxicity. Only one treatment-related death occurred. Cyclosporine was withheld in seven patients for a median of 6 days because of renal and/or liver dysfunction. One patient developed clinical skin GVHD, which responded to corticosteroid therapy. Six patients developed histologic evidence of GVHD without clinical signs of GVHD (subclinical GVHD). The incidence of clinical and subclinical GVHD was similar in both cyclosporine groups. Three of 11 patients assessable for response achieved remissions. Three patients experienced disease progression 80, 160, and 354 days after transplant. Ten patients are alive without progression between 56 and 444 days after transplant. CONCLUSION: Induction of autologous GVHD by posttransplant cyclosporine is feasible and well tolerated in patients with multiple myeloma.

Adult↗

Analysis of chimerism following allogeneic bone marrow transplantation by fluorescent-in-situ hybridization.

Twelve patients (9 males and 3 females) with chronic myelogenous leukemia, underwent CD8+ T cell depleted allogeneic bone marrow transplantation with a sex-mismatched donor. To assess chimerism we performed fluorescent in-situ hybridization for the X and Y chromosome at different time points after BMT. Patient median age was 33 years (range, 27-48); median time to transplant was 28 months (range, 5-87). All patients received thiotepa 10 mg/kg; cyclophosphamide 120 mg/kg and 12.0 Gy of fractionated total body irradiation. CD8+ cells were depleted from the normal donor marrow with anti-CD8 murine monoclonal antibodies and immunomagnetic beads. Bone marrow aspirates were studied at <60, 60-140, 140-300, and >300 days post BMT. Hybridization was done on mononuclear cells and a median of 518 cells were counted per slide with a fluorescent microscope. The median percentage of donor cells was 99.04%, 98.21%, 98.15%, and 99.52% at <60, 60-140, 140-300, and >300 days after BMT. Mixed chimerism was a rare occurrence after CD8 depleted allogeneic BMT and occured only at low levels. Inhibition of repopulation by host hematopoietic cells may be associated with the graft-versus-leukemia effect against CML.

Adult↗

Allogeneic transplantation for recurrent or refractory non-Hodgkin's lymphoma with poor prognostic features after conditioning with thiotepa, busulfan, and cyclophosphamide: experience in 44 consecutive patients.

We report the outcomes of 44 consecutive patients with non-Hodgkin's lymphoma (NHL) who participated in prospective studies of allogeneic transplantation after conditioning with thiotepa, busulfan and cyclophosphamide. Within a range of 27-57 years, the median age was 37. Of the 44 patients, 12 (27.2%) had high-grade lymphomas, 27 (61.4%) had intermediate-grade lymphomas, and five (11.3%) had low-grade lymphomas. Twenty-eight (63.6%) patients had chemotherapy refractory disease. Thirty (68.2%) patients had stage IV disease at the time of transplantation, involving the bone marrow in 19 (43.2%). Eight (18.1%) patients had undergone previous transplantation, and 13 (29.5%) patients had received high-dose CVP as induction within 2 months prior to transplantation. Thirty-eight (86.3%) patients had an HLA-identical donor, and 6 (13.6%) had a one-antigen mismatched related donor. Twenty (45.4%) patients received bone marrow and 24 (54.6%) received granulocyte colony-stimulating factor (G-CSF) mobilized stem cells. The graft-versus-host disease (GVHD) prophylaxis contained cyclosporine or tacrolimus in combination with either methylprednisolone in 32 (72.7%) patients or with methotrexate in 12 (27.2%) patients. The actuarial probability of disease-free survival at 2 years is 23% (95% CI 13%-40%). Donor stem cell use was associated with a significantly decreased risk of treatment-related toxicity (p < 0.001), but with an increased risk for GVHD and delayed fungal and viral infections. These infections are linked not only to the use of donor-stem cells, but also to the methylprednisolone in the GVHD prophylaxis regimen. Improvements in the outcome of patients with advanced NHL and undergoing allogeneic transplantation will depend on the development of effective and non-toxic regimens for conditioning, GVHD prophylaxis, and opportunistic infections prophylaxis.

Adult↗

Phase I/II study of dose-intense doxorubicin/paclitaxel/cyclophosphamide with peripheral blood progenitor cells and cytokine support in patients with metastatic breast cancer.

Relapse following complete remission achieved with a single course of high-dose chemotherapy continues to be the main cause of treatment failure in patients with metastatic breast cancer. A phase I/II trial was initiated that combined the two most active drugs against breast cancer, doxorubicin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), with cyclophosphamide, and delivered four cycles of these drugs with peripheral blood progenitor cells (PBPCs) and granulocyte colony-stimulating factor support in an outpatient setting. Patients with untreated metastatic breast cancer received two cycles of doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2. During recovery from the second cycle, PBPCs were harvested. Responding patients were then admitted for a day to receive escalating-dose doxorubicin, paclitaxel, and cyclophosphamide followed by PBPC reinfusion on day 3 as outpatients. Seventeen patients have been enrolled to date. Ten patients completed treatment and received 34 cycles of high-dose chemotherapy every 21 days (range, 21 to 28 days). The median age was 47 years (range, 26 to 56 years) and the median number of metastatic sites was two (range, one to three). Five patients had received adjuvant chemotherapy (four cyclophosphamide/methotrexate/5-fluorouracil and one mitoxantrone-based). The most common toxic reactions were nausea and vomiting (75% of courses) and neurosensory (50% of courses). No patients had a decreased ejection fraction or overt congestive heart failure. Ten patients underwent cardiac biopsy (median doxorubicin, 253 mg/m2; range, 120 to 312 mg/m2); only one showed grade 1 cytotoxic changes with doxorubicin 240 mg/ m2. Six patients were admitted for neutropenic fever. Eight of 10 patients responded (two pathologically confirmed complete remissions in liver). At these doses, four cycles of doxorubicin, paclitaxel, and cyclophosphamide with PBPC and granulocyte colony-stimulating factor support every 21 days was well tolerated and showed evidence of activity. Enrollment at higher dose levels continues so that maximum tolerated dose can be defined.

Adult↗

Allogeneic transplantation for advanced leukemia: improved short-term outcome with blood stem cell grafts and tacrolimus.

We have evaluated the use of blood stem cell grafts for rapid hematopoietic recovery and tacrolimus (FK506) as GVHD prophylaxis to reduce early mortality after allogeneic transplantation. Eighty-five adults with advanced leukemia received high-dose thiotepa, busulfan, and cyclophosphamide as a preparative regimen in a prospective Phase II study. All donors were HLA-matched and related. Marrow (BMT) was used for 44 patients and filgrastim-mobilized blood stem cells (SCT) for 41 patients. GVHD prophylaxis consisted of cyclosporine (CsA) or FK506 with methotrexate (MTX) or methylprednisolone (MP). The median time to neutrophil recovery was earlier after SCT than after BMT (day 10 vs. 17, P<0.001), but this was due to the selective use of MTX only in the BMT patients. The risk of grades 2-4 GVHD was lower with FK506 than with CsA (16% vs. 45%, P=0.02) and was the same for SCT recipients as for BMT recipients (33% vs. 34%). Regimen-related toxicity was significantly lower after SCT than after BMT but did not differ between the FK506 and CsA patients. In comparison with those receiving the standard transplant (BMT with CsA and MTX), only the SCT recipients using FK506 and MP had a significantly higher survival at day 180 posttransplant (84% vs. 53%, P=0.014). In multivariate analyses, use of FK506 was associated with a lower risk of treatment-related mortality and a higher survival at day 180, while the diagnosis of acute lymphoblastic leukemia was associated with a higher risk of treatment-related mortality. These data suggest that the use of blood stem cell grafts and FK506 can reduce the early mortality after allogeneic transplantation for advanced leukemia.

Adolescent↗

Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after matched unrelated donor marrow transplantation.

Thirty adults with leukemia or lymphoma undergoing marrow transplantation from HLA-compatible unrelated donors received tacrolimus (FK506), a new immunosuppressive macrolide lactone, and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 36 years (range 21 to 49 years). Twenty-four patients had advanced disease, and 11 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/d intravenously (i.v.) by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued through day 180 posttransplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6, and 11. All patients engrafted. Grades 2-4 GVHD occurred in 34% (95% CI, 17% to 52%), and grades 3-4 GVHD in 17% (95% CI, 3% to 31%). Mild renal toxicity was common before day 100; 63% of patients had a doubling of creatinine, and 52% had a peak creatinine greater than 2 mg/dL, but only one patient was dialyzed. The median last i.v. dose of tacrolimus was 53% of the scheduled dose, and the median oral dose on day 100 was 41% of that scheduled. Overall survival at 1 year was 47% (95% CI, 27% to 66%). We conclude that tacrolimus can be combined safely with minidose methotrexate, and the combination has substantial activity in preventing acute GVHD after unrelated donor marrow transplantation.

Actuarial Analysis↗

Prevention of recurrent atrial fibrillation with chronic dual-site right atrial pacing.

OBJECTIVES: We investigated 1) the feasibility, safety and efficacy of multisite right atrial pacing for prevention of atrial fibrillation (AF); and 2) the ability of atrial pacing in single- and dual-site modes to increase arrhythmia-free intervals in patients with drug-refractory AF. BACKGROUND: We recently developed and applied a novel technique of dual-site right atrial pacing in an unselected group of consecutive patients with AF requiring demand pacing. A prospective crossover study design was used to evaluate single- and dual-site right atrial pacing modes. METHODS: The frequency of AF during the 3 months before pacemaker implantation was analyzed. Consecutive consenting patients underwent insertion of two atrial leads and one ventricular lead with a DDDR pulse generator. Patients were placed in a dual-site pacing mode for the first 3 months and subsequently mode switched to single site pacing for 3 months. Mode switching was repeated at 6-month intervals thereafter. RESULTS: Atrial pacing resulted in a marked decline in AF recurrences (p < 0.001). During dual-site pacing with an optimal drug regimen, there was no AF recurrence in any patient compared with five recurrences in 12 patients during single-site pacing (p = 0.03). The mean (+/-SD) arrhythmia-free interval before pacing (14 +/- 14 days) was prolonged with dual- (89 +/- 7 days, p < 0.0001) and single-site pacing (76 +/- 27 days, p < 0.0001). Symptomatic AF episodes showed a declining trend during dual- and single-site pacing compared with those during the preimplantation period (p = 0.10). Mean antiarrhythmic drug use for all classes declined from 4 +/- 1.9 drugs before implantation to 1.5 +/- 0.5 (p < 0.01) drugs after implantation. Twelve (80%) of 15 patients remained in atrial paced rhythm at 13 +/- 3 months. CONCLUSIONS: We conclude that multisite right atrial pacing is feasible, effective and safe for long-term application. Atrial pacing significantly prolongs arrhythmia-free intervals in patients with drug-refractory paroxysmal AF. Dual-site right atrial pacing may offer additional benefits and should be considered either as the primary mode or in patients unresponsive to single-site pacing.

Adult↗

Development and evaluation of a new 3-D digitization and computer graphic system to study the anatomic tissue and restoration surfaces.

It is necessary to visualize and reconstruct tissue anatomic surfaces accurately for a variety of oral rehabilitation applications such as surface wear characterization and automated fabrication of dental restorations, accuracy of reproduction of impression and die materials, etc. In this investigation, a 3-D digitization and computer-graphic system was developed for surface characterization. The hardware consists of a profiler assembly for digitization in an MTS biomechanical test system with an artificial mouth, an IBM PS/2 computer model 70 for data processing and a Hewlett-Packard laser printer for hardcopy outputs. The software used includes a commercially available Surfer 3-D graphics package, a public domain data-fitting alignment software and an inhouse Pascal program for intercommunication plus some other limited tasks. Surfaces were digitized before and after rotation by angular displacement, the digital data were interpolated by Surfer to provide a data grid and the surfaces were computer graphically reconstructed: Misaligned surfaces were aligned by the data-fitting alignment software under different choices of parameters. The effect of different interpolation parameters (e.g. grid size, method of interpolation) and extent of rotation on the alignment accuracy was determined. The results indicate that improved alignment accuracy results from optimization of interpolation parameters and minimization of the initial misorientation between the digitized surfaces. The method provides important advantages for surface reconstruction and visualization, such as overlay of sequentially generated surfaces and accurate alignment of pairs of surfaces with small misalignment.

Computer Communication Networks↗

Impact of preexisting CNS involvement on the outcome of bone marrow transplantation in adult hematologic malignancies.

PURPOSE: To determine the impact of prior or current CNS disease on the outcome of high-dose chemotherapy for patients with hematologic malignancies. PATIENTS AND METHODS: In a 54-month period, 373 patients with hematologic malignancies underwent allogeneic or autologous bone marrow transplantation (BMT) or blood stem-cell transplantation using high-dose thiotepa, busulfan, and cyclophosphamide (TBC) as the preparative regimen. Four patients with active CNS disease at BMT and 20 patients with a history of prior CNS disease were identified. The outcomes of those with a history of CNS disease were compared with those of a matched control group. RESULTS: Of four patients with active CNS disease at the time of BMT, two had CNS recurrences and one recurred in the bone marrow. One patient died of treatment-related toxicity. Four of 20 patients with prior CNS involvement currently remain free of disease. At 2 years, the disease-free survival (DFS) rate was 23% +/- 19%, and the DFS rate for the control group 39% +/- 24% (P = .053). An increased rate of treatment-related toxicity and especially grades II to IV CNS toxicity accounted for the poorer outcome of patients who had a history of CNS disease. Recurrence rates were not significantly different between the two groups. Prior radiation to the CNS correlated with CNS complications posttransplant (p = .01). CONCLUSION: Consolidation with TBC and BMT can induce prolonged DFS in a proportion of patients with a history of CNS disease. Such patients are at increased risk for CNS complications that lead to an inferior overall outcome when compared with a control group.

Adolescent↗

Effect of a whey protein concentrate used as a colostrum substitute or supplement on calf immunity, weight gain, and health.

The efficacy of a whey protein concentrate was evaluated as a colostrum substitute or supplement in two experiments using four groups of 29 calves. In Experiment 1, calves were fed either 2 L of pooled colostrum (group 1) or 500 g of whey protein concentrate (group 2). A mean total of 123.6 and 17.7 g of Ig was fed to calves in groups 1 and 2, respectively. Mean serum IgG, total protein, and globulin concentrations and Ig antibody activities to Escherichia coli K99 and rotavirus were significantly higher for calves in group 1 at 24 to 36 h and at 3 wk of age. Weight gain from birth to 3 wk of age was significantly lower for calves in group 2. The incidence of diarrhea was high but not different between treatments. The mortality rate (0 to 3 wk) was significantly higher for calves in group 2 (27.6%) than for calves in group 1 (3.4%). In Experiment 2, calves were fed either 2 L of pooled colostrum (group 3) or a solution of 1 L of pooled colostrum plus 500 g of whey protein concentrate (group 4). A mean total of 117.2 and 69.1 g of Ig was fed to calves in groups 3 and 4, respectively. Absorption rate of IgG was significantly lower for calves in group 4. Mean serum IgG, total protein, and globulin concentrations and Ig antibody activities to E. coli K99 and rotavirus were significantly higher for calves in group 3 at 24 to 36 h and at 3 wk of age. Mortality rate, BW gain, and incidence of diarrhea did not differ significantly between groups.

Animal Feed↗

Allogeneic peripheral blood stem cell transplantation using normal patient-related pediatric donors.

Successful allogeneic peripheral blood progenitor cell (PBPC) transplantation has recently been reported by several transplant centers. This is a first report describing allogeneic PBPC transplantation in five patients using related pediatric donors between the ages of 4 and 13 years. Donors underwent 3 or 4 days of rhG-CSF treatment (6 micrograms/kg q 12 h) for stem cell peripheralization prior to PBPC collection, which was performed by continuous-flow apheresis on day 4 or 5. Venous access was exclusively by ante-cubital veins. A median of 2.2 times (range 1.4-3.6) the donor's total blood volume (TBV) was processed per procedure. In cases where the donor's TBV was < 2 liters, the blood cell separator was primed with human serum albumin (HSA-5%), and anticoagulation was performed using a combination of heparin (pre-apheresis bolus + continuous infusion (CI)) and/or ACD-A (CI at a reduced rate). The median number of CD34+ cells collected per kg of donor body weight (b.w.) and per liter of donor blood processed during each procedure was 128 x 10(4) (range 58 x 10(4)-314 x 10(4)). Between one and two aphereses were sufficient to collect a safe CD34+ cell engraftment dose of 3 or 4 x 10(6)/kg of recipient b.w. Two PBPC recipients were parents, and three were siblings. After freezing and thawing, the median number of CD34+ cells per kg of recipient b.w. thawed and transfused was 8.5 x 10(6) (range 3.2 x 10(6)-9.7 x 10(6)). The time to PMN > 1000/microliters was between 10 and 16 days (four out of five evaluable patients), and platelets > 20000/microliters were reached between day 13 and 14 post-transplantation (three out of five evaluable patients). Two out of three evaluable patients developed grades one and three acute GVHD, and one out of three developed chronic GVHD. Two patients died of sepsis and VOD at day 10 and 19, respectively. Two adult patients are alive and in cytogenetic and molecular remission of CML at +339 and +227 days post-allotransplantation. One 3-year-old girl with hemophagocytic lymphohistiocytosis is in remission at +304 days post-transplantation. Using pediatric donors for allogeneic PBPC transplantation appears to be safe, yields a sufficient amount of progenitors for prompt engraftment, and results in clinical outcome similar to adult PBPC allotransplantation.

Adult↗