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Biomedical subjects

R Mehra

Publications and source records attributed to R Mehra.

At least 73 records · Page 4Linked to original sources
PubMed1996

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↗
PubMed1996

Delayed effects of rhG-CSF mobilization treatment and apheresis on circulating CD34+ and CD34+ Thy-1dim CD38- progenitor cells, and lymphoid subsets in normal stem cell donors for allogeneic transplantation.

Allogeneic transplantation of peripheral blood progenitor cells (PBPC) is emerging as a new stem cell transplant modality. Rather than undergoing general anesthesia for bone marrow harvest, normal blood stem cell donors are subjected to rhG-CSF mobilization treatment followed by single or multiple apheresis. Whereas the effects of cytokine treatment and apheresis on stem cell peripheralization and collection have been described, little is known about delayed effects of rhG-CSF treatment and apheresis on a normal hematopoietic system, and there are no long-term data that address safety issues. Ten normal, patient-related donors underwent a 3 or 4 day rhG-CSF (filgrastim) treatment (12 micrograms/kg/day) followed by single or tandem apheresis. We monitored peripheral blood (PB) cellularity including CD34+ and lymphoid subsets at baseline, during cytokine treatment, prior to apheresis, and at days 2, 4, 7, 30 and 100 post-apheresis. The PB progenitor cell concentration peak prior to apheresis was followed by a nadir by day 7 and normalized by day 30, with the exception of the most primitive CD34+ Thy-1dim CD38- progenitor subset that reached a nadir by day 30. Lymphoid subsets such as CD3, 4, 8, suppressor cells (CD3+ 4- 8- TCR+ alpha beta), and B cells (CD19+) showed a similar pattern with a nadir concentration by day 7, followed, except for B cells, by a rebound by day 30 and subnormal counts at day 100. The PB concentrations of hemoglobin and platelets dropped mainly due to the apheresis procedure itself, and normalized by day 30. With cytokine treatment, the PB alkaline phosphatase and lactate dehydrogenase concentrations increased 2.2- and 2.8-fold, respectively, over baseline, and returned to normal range by day 30. Based on the preliminary nature of this study, the clinical relevance of these findings is still unclear.

ADP-ribosyl Cyclase↗
PubMed1995

CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation.

Donor lymphocyte infusions can reinduce complete remission in the majority of patients with chronic myelogenous leukemia (CML) who relapse into chronic phase after allogeneic bone marrow transplantation (BMT). Such infusions are associated with a high incidence of graft-versus-host disease (GVHD) and marrow aplasia. BMT using selective depletion of CD8+ lymphocytes from donor cells reduces the incidence of GVHD without an increase in leukemia relapse. We hypothesized that infusion of CD8-depleted donor peripheral blood lymphocytes could also reinduce complete remissions with a lesser potential to produce symptomatic GVHD in patients with CML who relapsed after allogeneic BMT. Ten patients with Ph(+) CML who relapsed a median of 353 days after BMT (range, 82 to 1,096 days) received donor lymphocyte infusions depleted of CD8+ cells. Nine patients received a single infusion and 1 received two infusions. Four patients were treated while in chronic phase with clonal evolution, 2 during accelerated phase, 3 during blast crisis, and 1 in a cytogenetic relapse. A mean of 0.9 +/- 0.3 x 10(8) mononuclear cells/kg were infused, containing 0.6 +/- 0.4 x 10(6) CD3+CD8+ cells/kg. Six patients achieved hematologic and cytogenetic remission at 4, 8, 11, 15, 39, and 54 weeks after lymphocyte infusion. Two patients developed > or = grade II acute GVHD, and 1 patient developed mild chronic GVHD. We conclude that donor lymphocyte infusions depleted of CD8+ cells can induce remissions with a low rate of severe acute GVHD in patients with CML who relapse after allogeneic BMT, supporting the hypothesis that CD8+ lymphocytes are important effectors of GVHD, but may not be essential for the graft-versus-leukemia effect against this disease. Further controlled studies are required to confirm these preliminary observations.

Acute Disease↗
PubMed1995

Clinical efficacy and safety of atrial defibrillation using biphasic shocks and current nonthoracotomy endocardial lead configurations.

We undertook a prospective randomized clinical trial evaluating efficacy and safety of internal atrial defibrillation in patients with drug-refractory atrial fibrillation (AF). Consecutive patients with paroxysmal or chronic AF were randomly tested with 3 internal atrial defibrillation lead configurations and biphasic shocks. Patients with implanted cardiac pacemakers were tested with the right atrium (RA) and left pulmonary artery or coronary sinus (CS) configuration. Shocks were initially delivered without anesthesia to assess patient tolerance. The need for backup ventricular defibrillation and pacing support was evaluated. Eighteen patients with (n = 15) or without (n = 3) structural heart disease, mean left ventricular ejection fraction 36 +/- 14%, and mean left atrial diameter 4.5 +/- 0.6 cm were studied. The mean defibrillation threshold in the best randomized lead configuration was 9.9 +/- 7.7 J. Mean defibrillation threshold for the right ventricle (RV) and superior vena cava configuration was 13.3 +/- 5 J, which was significantly lower than the RA and axilla configuration (20.1 +/- 7.4 J, p < 0.04) but not the RV to RA configuration (16.5 +/- 11 J, p > 0.2). The mean defibrillation threshold using the RA-left pulmonary artery/CS configuration was 8.9 +/- 9 J (p > 0.2 vs RV-superior vena cava). There was a bimodal distribution of defibrillation thresholds. Low atrial defibrillation thresholds correlated with absence of heart disease, higher ejection fraction, and smaller left ventricular end-diastolic diameter. Shocks were hemodynamically well tolerated, but 2 of 18 patients (11%) had nonsustained ventricular tachycardia after shock delivery. Six of 18 patients (33%) had postshock bradyarrhythmias. Fourteen of 16 patients perceived shocks > or = 3 J as intolerable.(ABSTRACT TRUNCATED AT 250 WORDS) [corrected]

Adult↗
PubMed1995

A prospective randomized comparison in humans of biphasic waveform 60-microF and 120-microF capacitance pulses using a unipolar defibrillation system.

BACKGROUND: Improving unipolar implantable cardioverter-defibrillator (ICD) effectiveness has favorable implications for ICD safety, efficacy, and size. Advances in defibrillation efficacy would accelerate ICD ease of use by decreasing device size and by minimizing morbidity and mortality related to an improved defibrillation safety margin. The specific purpose of the present study was to determine whether unipolar defibrillation efficacy could be improved further in humans by lowering biphasic waveform capacitance. METHODS AND RESULTS: We prospectively and randomly compared the defibrillation efficacy of a 60-microF and a 120-microF capacitance asymmetrical 65% tilt biphasic waveform using a unipolar defibrillation system in 38 consecutive cardiac arrest survivors before implantation of a presently available standard transvenous defibrillation system. The right ventricular defibrillation electrode had a 5-cm coil located on a 10.5F lead and was used as the anode. The system cathode was the electrically active 108-cm2 surface area shell (or "can") of a prototype titanium alloy pulse generator placed in a left infraclavicular pocket. The defibrillation pulse was derived from either a 60-microF or a 120-microF capacitance and was delivered from RV-->CAN. Defibrillation threshold (DFT) stored energy, delivered energy, leading-edge voltage and current, pulse resistance, and pulse width were measured for both capacitances examined. The 60-microF capacitance biphasic pulse resulted in a stored-energy DFT of 8.5 +/- 4.1 J and a delivered-energy DFT of 8.4 +/- 4.0 J. In 34 of 38 patients (89%), the stored-energy DFT was < 15 J. Leading-edge voltage at the DFT was 517 +/- 128 V. Mean pulse impedance for the 60-microF waveform was 60.6 +/- 7.1 omega. The 120-microF capacitance biphasic pulse resulted in a stored-energy DFT of 10.1 +/- 7.4 J and a delivered-energy DFT of 10.0 +/- 7.2 J (P = .13 and .13, respectively). In 28 of 38 patients (74%), the stored-energy DFT was < 15 J (P = .052). Leading-edge voltage at the DFT with the 120-microF capacitance pulse was 386 +/- 142 (P < .00001). Mean pulse impedance for the 120-microF waveform was 60.7 +/- 7.0 omega (P = .80). CONCLUSIONS: The results of the present study suggest that a relatively small capacitance, 60 microF, can be used for unipolar defibrillation systems without compromising defibrillation energy requirements compared with more typical ICD capacitance values, but this will require a higher circuit voltage. The use of lower capacitance also provides a modest increase in the percent of patients who have very low energy defibrillation requirements, an important issue should maximum ICD energy be decreased from the present level of 34 J. Such a move to smaller output devices could allow significant decreases in device size, a necessary feature of making cardioverter-defibrillator implantation comparable to that of standard pacemaker surgery.

Adult↗
PubMed1995

Intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation.

OBJECTIVES: To determine the minimal active dose and extent of activity of intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation. METHODS: Twenty-four adults with grade 3 or 4 hemorrhagic cystitis were treated. All but 2 had failed other local therapy. Treatment was initiated at a median of 32 days post-transplant. Eleven patients received carboprost intravesicularly at 0.2 mg/dL for 60 minutes every 6 hours, and the dose was escalated every 24 hours until a dose of 1.0 mg/dL was reached unless a response was achieved. Thirteen additional patients were treated at an initial dose of 0.8 mg/dL, with escalation to 1.0 mg/dL after four doses in the absence of a response. RESULTS: Overall, 15 of the 24 patients responded. In the dose-escalation setting, 0.8 mg/dL was the minimal active dose. The total response rate was 62% with doses at or above 0.8 mg/dL and 18% at lower doses. All but one response occurred with 7 or fewer days of therapy, and 9 patients relapsed later. Four additional patients were salvaged following cystoscopy with clot evacuation with or without alum or formalin instillation. In all but 1 patient, bladder spasms developed during treatment with carboprost, but were not sufficiently severe to discontinue therapy. CONCLUSIONS: Intravesicular carboprost at 1.0 mg/dL every 6 hours for no more than 7 days should be considered for a randomized study for treatment of refractory hemorrhagic cystitis. Cystoscopic examination and evacuation of clots prior to therapy may be required to achieve the full benefit of this treatment.

Administration, Intravesical↗
PubMed1995

Prospective randomized comparison of biphasic waveform tilt using a unipolar defibrillation system.

BACKGROUND: A unipolar defibrillation system using a single right ventricular (RV) electrode and the active shell or container of an implantable cardioverter defibrillator situated in a left infraclavicular pocket has been shown to be as efficient in defibrillation as an epicardial lead system. Additional improvements in this system would have favorable practice implications and could derive from alterations in pulse waveform shape. The specific purpose of this study is to determine whether defibrillation efficacy can be improved further in humans by lowering biphasic waveform tilt. METHODS: We prospectively and randomly compared the defibrillation efficacy of a 50% and a 65% tilt asymmetric biphasic waveform using the unipolar defibrillation system in 15 consecutive cardiac arrest survivors prior to implantation of a presently available standard transvenous defibrillation system. The RV defibrillation electrode has a 5-cm coil located on a 10.5 French lead and was used as the anode. The system cathode was the active 108 cm2 surface area shell (or "CAN") of a prototype titanium alloy pulse generator placed in the left infraclavicular pocket. The defibrillation pulse derived from a 120-microF capacitor and was delivered from RV-->CAN, with RV positive with respect to the CAN during the initial portion of the cycle. Defibrillation threshold (DFT) stored energy, delivered energy, leading edge voltage and current, pulse resistance, and pulse width were measured for both tilts examined. RESULTS: The unipolar single lead system, RV-->CAN, using a 65% tilt biphasic pulse resulted in a stored energy DFT of 8.7 +/- 5.7 J and a delivered energy DFT of 7.6 +/- 5.0 J. In all 15 patients, stored and delivered energy DFTs were < 20 J. The 50% tilt biphasic pulse resulted in a stored energy DFT of 8.2 +/- 5.4 J and a delivered energy DFT of 6.1 +/- 4.0 J; P = 0.69 and 0.17, respectively. As with the 65% tilt pulse, all 15 patients had stored and delivered energy DFTs < 20 J. CONCLUSION: The unipolar single lead transvenous defibrillation system provides defibrillation at energy levels comparable to that reported with epicardial lead systems. This system is not improved by use of a 50% tilt biphasic waveform instead of a standard 65% tilt biphasic pulse.

Adolescent↗
PubMed1995

Allogeneic bone marrow transplantation for refractory and recurrent low-grade lymphoma: the case for aggressive management.

PURPOSE: To evaluate the role of allogeneic bone marrow transplantation (BMT) in recurrent low-grade lymphoma. PATIENTS AND METHODS: Between 1989 and 1994, 10 patients with chemotherapy-refractory and recurrent low-grade lymphoma were treated with myeloablative therapy and allogeneic BMT. All patients had poor prognostic features and had been extensively pretreated. RESULTS: Eight patients achieved a complete remission and none have relapsed at a median follow-up time of 816 days (range, 346 to 1,865). Two patients died of early complications. The actuarial survival and failure-free survival rates are both 80% +/- 12.6%. For surviving patients, the duration of the current remission exceeds that of any previous remission achieved. CONCLUSION: These results compare favorably with those for autologous BMT. Allogeneic BMT offers considerable promise for the treatment of patients with poor-prognosis low-grade lymphoma. Its role should be further defined in prospective studies.

Adult↗
PubMed1995

A phase I-II study of high-dose thiotepa, busulfan and cyclophosphamide as a preparative regimen for autologous transplantation for malignant lymphoma.

Thirty-four adults with malignant lymphoma at high-risk for relapse were treated on a Phase I-II study of high-dose thiotepa (THIO), busulfan (BU) and cyclophosphamide (CYC) with autologous marrow or peripheral blood stem cell support. Four patients were in untreated relapse, 7 had stable or progressive disease, 12 were in partial remission, and 11 were in complete remission after reinduction chemotherapy before proceeding to the preparative regimen. Median follow-up time is 22 months. Grades 3-4 regimen-related toxicity occurred in 3 (14%) of 22 patients treated with THIO 250 mg/m2 x 3, BU 1 mg/kg x 10 and CYC 50 mg/kg x 3, and this was considered the maximal tolerated dose-schedule. Of the 23 patients with active disease at the time of transplantation, 52% (95% CI 31-73%) achieved a complete response, and 26% (95% CI 10-48%) achieved a partial response. For all patients, median time to progression was 13 months, median survival was 16 months, and disease-free survival at 18 months was 34% (95% CI 18-51%). The combination of THIO, BU and CYC is tolerable as a preparative regimen for lymphoma and has a high response rate, but further measures are needed to reduce the relapse rate for patients with advanced disease.

Adult↗
PubMed1995

High-dose chemotherapy with BEAC regimen and autologous bone marrow transplantation for intermediate grade and immunoblastic lymphoma: durable complete remissions, but a high rate of regimen-related toxicity.

Forty-eight adult patients with recurrent or refractory intermediate grade or immunoblastic lymphoma received high-dose carmustine (BCNU), etoposide, Ara C and cyclophosphamide (BEAC), followed by autologous bone marrow transplantation (BMT). Median follow-up is 906 days (range 613-2067 days). The complete remission rate was 42% and 22% had a partial response. Actuarial failure-free survival is 30% +/- 6.6%. Twenty one patients relapsed or progressed. Only one relapse occurred > 1 year after autologous BMT. Adverse prognostic factors for failure-free survival include high LDH at the time of autologous BMT, chemotherapy-refractory disease and multiple prior relapses. Patients with chemotherapy responsive first salvage (those achieving first CR only with salvage chemotherapy and those with first relapse, responding to salvage chemotherapy) had a failure-free survival of 52% +/- 10% vs 12% +/- 6% for those with more advanced disease. Of 13 patients who had no adverse factors, only two relapsed. Treatment-related mortality occurred in 23%, including infection (n = 4), cardiac toxicity (n = 4), pulmonary toxicity (n = 2) and hemorrhage (n = 1). Pulmonary toxicity was more common among patients who had received prior radiation-therapy to the chest. BEAC chemotherapy with autologous BMT is an effective but relatively toxic regimen for patients with relapsed or refractory lymphomas. The combination of chemotherapy-responsive disease after failure of one chemotherapy regimen and normal LDH identifies patients with a favorable prognosis. Alternative cytotoxic regimens require evaluation, with the goal of reducing treatment related mortality. More effective cytoreductive therapy is required for patient with poor prognostic features.

Adolescent↗
PubMed1995

Impaired pancreatic bicarbonate secretion in chronic malnutrition.

Twenty three children with recurrent episodes of diarrhea and chronic malnutrition were studied for pancreatic duct function. Those children were subjected to pancreatic stimulation with pancreozymin and secretin. Grade I malnourished children, as per Gomez classification, formed the control group. The water output from pancreas increased in malnourished children (p < 0.05). It correlated significantly to cationic transport (p < 0.01). Sodium and potassium together accounted for significant proportion of water output in pancreatic fluid. Potassium transport increased with increasing severity of malnutrition and may be responsible for the hypokalemia observed in malnourished children. Pancreatic secretion of bicarbonate decreased in severe malnutrition inspite of increased flow rate of pancreatic secretion. This is probably due to defective bicarbonate secretion likely to be located at pancreatic duct epithelial cell membrane.

Bicarbonates↗
PubMed1995

Interferon-alpha and interleukin-2 as treatment for leukemia relapse after allogeneic bone marrow transplantation.

We treated 12 patients with leukemia relapse after allogenic bone marrow transplantation with a combination of interferon-alpha (IFN-alpha) ((2.5-5.0) x 10(6) u/m2 subcutaneously three times a week) and interleukin-2 (IL-2) ((1.8-3.6) x 10(6) IU/m2 subcutaneously five times a week) to determine the toxicity and efficacy of combination cytokine therapy in this setting. The median age of the patients was 39 years (range: 16-50). There were nine females and three males. The median time to relapse from BMT was 98 days (range: 0-963). At the time of relapse, six patients had AML, four patients had CML (two in blast crisis and two in chronic phase with clonal evolution), and one patient had lymphoblastic lymphoma. Combination cytokine therapy was started a median of 108 days post BMT (range: 37-2404). Nine patients treated at the higher dose level required a 50% dose reduction because of toxicity or GVHD (three CNS, two GVHD, one high fever, one diarrhoea with hypotension, and one pericarditis). At a lower dose level, 2 of 10 patients had their treatment discontinued because of toxicity or GVHD. Six patients developed clinical findings consistent with acute GVHD while on combination cytokine therapy. Two patients responded to combination cytokine therapy: one with CML and one with AML. Combination cytokine therapy is feasible in the setting of relapse post allogeneic BMT. The combination of IL-2 1.8 x 10(6) IU/m2 five times a week with IFN-2 2.5 x 10(6) U/m2 three times a week seems to be tolerable, and merits further study in this setting.

Acute Disease↗
PubMed1994

Effect of shock timing on efficacy and safety of internal cardioversion for ventricular tachycardia.

OBJECTIVES: We examined the effect of shock timing within the QRS complex on cardioversion efficacy in a randomized crossover test of shocks delivered at two timing intervals relative to QRS onset. BACKGROUND: The local ventricular electrogram is used in implantable cardioverter-defibrillators to synchronize cardioversion shocks to terminate ventricular tachycardia. However, the timing of the local electrogram relative to global ventricular depolarization is variable, depending on the site of ventricular tachycardia origin. METHODS: Transvenous defibrillation leads were positioned in the right ventricular apex (cathode), coronary sinus and superior vena cava (anodes) of patients with sustained monomorphic ventricular tachycardia. After repeat ventricular tachycardia induction, sequential shocks with energy settings of 0.5 to 22 J were delivered simultaneously with QRS onset (QRS + 0 shock) or 100 ms after QRS onset (QRS + 100 shock). QRS onset was determined from the surface electrocardiogram. Cardioversion threshold, defined as the lowest shock energy for successful ventricular tachycardia termination, was measured for these two timings. RESULTS: Fifteen patients (13 men, 2 women; mean [+/- SD] age 60.5 +/- 7.7 years) completed testing. Cardioversion threshold was significantly lower with QRS + 100 shocks than QRS + 0 shocks (3.1 +/- 3.5 vs. 10.5 +/- 7.4 J, p < 0.01). Thirteen patients (87%) experienced ventricular tachycardia acceleration with QRS + 0 shocks, but only three patients (20%) had ventricular tachycardia acceleration using QRS + 100 shocks (p < 0.01). Of the 32 failed QRS + 0 shocks, 25 (78%) caused ventricular tachycardia acceleration, whereas only 5 (36%) of the 14 failed QRS + 100 shocks caused ventricular tachycardia acceleration (p < 0.05). Cardioversion threshold was not correlated with ventricular tachycardia cycle length, QRS duration, left ventricular ejection fraction or left ventricular diastolic volume (p = NS). CONCLUSIONS: Internal cardioversion shocks delivered late in the QRS complex during ventricular tachycardia are more effective and have a lower risk of ventricular tachycardia acceleration than those delivered near QRS onset.

Aged↗
PubMed1994

Combination biphasic waveform plus sequential pulse defibrillation improves defibrillation efficacy of a nonthoracotomy lead system.

OBJECTIVES: We hypothesized that combining biphasic waveform and sequential pulse defibrillation techniques would lower the defibrillation threshold of a nonthoracotomy lead system in humans below that obtained with biphasic or sequential pulse defibrillation alone. BACKGROUND: Previous studies have shown that sequential pulse monophasic shocks and biphasic waveform shocks are more effective than single monophasic shocks for ventricular defibrillation. METHODS: Thirteen patients aged 48 to 71 years undergoing nonthoracotomy defibrillation lead testing participated in the study. Transvenous electrodes were positioned in the right ventricular apex, superior vena cava and coronary sinus. A cutaneous patch electrode was placed on the left chest wall. All electrodes were connected to an external defibrillator. In random order, defibrillation threshold measurements were made for biphasic defibrillation alone, sequential defibrillation alone and combined biphasic plus sequential defibrillation. RESULTS: The mean defibrillation threshold-delivered energy was 18.0 +/- 11.9 J for biphasic defibrillation and 16.3 +/- 9.0 J for sequential defibrillation. Biphasic plus sequential defibrillation significantly reduced the threshold energy to 10.2 +/- 5.3 J (p < 0.001). Threshold peak voltage and current values showed corresponding reductions. The combined waveform resulted in a greater reduction in defibrillation threshold in patients with threshold energies > 18 J versus those with threshold values < or = 18 J for sequential (p = 0.001) or biphasic (p < 0.01) waveform alone. The nonthoracotomy lead implantation rate was improved from 62% with each of the single techniques (biphasic waveform or sequential pulse defibrillation) to 85% with the combined waveform. CONCLUSIONS: Adding biphasic waveform to sequential pulse defibrillation significantly reduced the defibrillation threshold compared with either technique alone, and nonthoracotomy lead system implantation can be enhanced by this combined technique.

Aged↗
PubMed1994

Prospective, randomized comparison in humans of a unipolar defibrillation system with that using an additional superior vena cava electrode.

BACKGROUND: A unipolar defibrillation system using a single right ventricular (RV) electrode and the active shell or "CAN" of the implantable cardioverter-defibrillator itself situated in a left infraclavicular pocket has been shown to be as efficient in defibrillation as an epicardial lead system. The purpose of this study was to determine whether defibrillation efficacy can be improved further by adding a superior vena cava (SVC) electrode to this already efficient defibrillation system. METHODS AND RESULTS: We prospectively and randomly compared the defibrillation efficacy of a simplified unipolar defibrillation system, RV-->CAN, with that of one incorporating a high SVC electrode, RV-->SVC + CAN, in 15 consecutive cardiac arrest survivors undergoing implantation of a presently available transvenous defibrillation system. The RV defibrillation electrode was a 5-cm coil located on a 10.5F lead used as the anode in both lead configurations examined. The active CAN was a 108-cm2 surface area shell of a titanium alloy pulse generator used as the cathode in both configurations and placed in a left infraclavicular pocket. The SVC electrode was a 6F 5-cm-long coil and was used as an additional cathode positioned at the junction of the SVC and the left innominate vein. The defibrillation pulse used was a 65% tilt, asymmetric biphasic waveform delivered from a 120-microF capacitor. The defibrillation threshold (DFT) stored energy, leading edge voltage, current, and pulsing resistance were measured for both lead systems. The single-lead unipolar system, RV-->CAN, resulted in a stored energy DFT of 7.4 +/- 5.2 J, and the three-electrode dual pathway system, RV-->SVC + CAN, resulted in a DFT of 6.0 +/- 3.4 J (P = .20). There was no difference in defibrillation efficacy with the more complicated three-electrode system over the unipolar system despite a decrease in pulsing resistance to 48.6 +/- 3.5 omega compared with 61.2 +/- 5.9 omega for the unipolar system (P < .0001) and a slight rise in delivered current to 6.3 +/- 1.8 A compared with 5.5 +/- 2.0 A for the unipolar system (P = .062). CONCLUSIONS: The unipolar single-lead transvenous defibrillation system provides defibrillation at energy levels comparable to that reported with present epicardial lead systems. Coupling of this lead system to a third SVC electrode increases system complexity but offers little defibrillation advantage despite a large decrease in pulsing resistance and a modest increase in delivered current.

Defibrillators, Implantable↗
PubMed1994

Efficacy of a single-lead unipolar transvenous defibrillator compared with a system employing an additional coronary sinus electrode. A prospective, randomized study.

BACKGROUND: Recent development of a prototype single-lead unipolar transvenous defibrillator offers the possibility of device implantation with the ease of a permanent pacemaker. Lowering defibrillation energy requirements would allow for a further reduction in defibrillator generator size and enhance the feasibility of pacemaker-like placement. However, if achieving a lower defibrillation energy requires placing additional intracardiac leads, the potential advantage of a smaller generator may be offset by the disadvantages of a more complex lead system. The purpose of this study was to compare defibrillation energy requirements of a single-lead unipolar defibrillator with a three-electrode system employing an additional lead in the coronary sinus. METHODS AND RESULTS: Testing of a single-lead unipolar biphasic pulse defibrillation system versus a three-electrode system with an additional coronary sinus lead was performed in prospective, randomized fashion in 15 patients with a history of ventricular tachycardia or fibrillation. Ventricular fibrillation was induced with alternating current, and defibrillation threshold was measured by a pulse given 10 seconds after arrhythmia induction. The mean defibrillation threshold stored energy and mean leading edge voltage did not significantly differ between the two systems (11.3 +/- 5.9 J versus 9.9 +/- 5.2 J and 418 +/- 118 V versus 390 +/- 112 V, respectively; P > .4). Using either defibrillation system, all patients were successfully defibrillated by < 24 J and over half of patients by < 10 J. CONCLUSIONS: A unipolar transvenous biphasic defibrillation system is an effective means of treating ventricular fibrillation. The added complexity of additional leads is not offset by any significant improvement in defibrillation efficacy or energy requirements. Given the simplicity and effectiveness of a single-lead system coupled with a small generator, placement of defibrillation systems may now approach the ease of pacemaker implantation.

Adult↗
PubMed1994

Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies.

PURPOSE: To determine the efficacy and toxicity of etoposide, cyclophosphamide, and fractionated total-body irradiation (TBI) as the conditioning regimen for allogeneic bone marrow transplantation (BMT) in patients with hematologic malignancies. PATIENTS AND METHODS: Seventy-nine patients underwent BMT from a human leukocyte antigen (HLA)-identical sibling using cyclosporine/methotrexate for graft-versus-host disease (GVHD) prophylaxis. Thirty-four patients had early leukemia (acute leukemia or lymphoblastic lymphoma in first remission, chronic myelogenous leukemia [CML], or refractory anemia [RA]), and 45 patients had more advanced disease. Patients received etoposide 1,500 mg/m2 on day -8, followed by cyclophosphamide 60 mg/kg/d on days -7 and -6, and 10.2 Gy of TBI administered in six fractions of 1.7 Gy given twice daily for 3 days from day -3 to -1. Donor bone marrow was harvested and infused on day 0. RESULTS: Patients with early leukemia had a disease-free survival rate of 53% +/- 9% and an overall survival rate of 57% +/- 10% at 3 years. Patients with advanced disease had a disease-free survival rate of 15% +/- 5% and overall survival rate of 17% +/- 5%. The actuarial relapse rate for the early-leukemia group is 33% +/- 9% versus 69% +/- 9% for patients with more advanced disease. Severe toxicity was most frequently manifested as pulmonary hemorrhage followed by multiorgan failure and death. The 100-day mortality rate for the early-leukemia group was 10% versus 50% for patients with more advanced disease. CONCLUSION: The combination of cyclophosphamide, etoposide, and TBI is a relatively safe and effective preparative regimen for patients with early hematologic malignancies. Controlled trials are needed to evaluate critically this combination versus other standard preparative regimens. Greater toxicity was observed in patients with advanced disease, and this program does not appear to offer any advantage over other regimens.

Adolescent↗