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R Hoyt

Publications and source records attributed to R Hoyt.

At least 19 recordsLinked to original sources
PubMed2006

The hyper-CVAD-rituximab chemotherapy programme followed by high-dose busulfan, melphalan and autologous stem cell transplantation produces excellent event-free survival in patients with previously untreated mantle cell lymphoma.

The hyper-CVAD + rituximab (R) programme consists of fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone + R alternating with high-dose methotrexate + cytarabine (HD MTX/ARA-C) + R. This regimen, when used as initial therapy for patients under 65 years of age with previously untreated mantle cell lymphoma (MCL), results in remission rates of > 85% with a median event-free survival (EFS) of > 50 months, but with a pattern of continuous relapse out to 60 months. We performed a study of hyper-CVAD + R, followed by consolidative peripheral blood progenitor cells autograft [autologous stem cell transplant (AuSCT)] with high-dose busulfan and melphalan (Bu/Mel) conditioning, in patients with responsive disease. Thirteen patients with a median age of 54 (range = 33-61) were treated. Complete remission (CR) was achieved in 12 patients (92%) after hyper-CVAD + R and 12 completed AuSCT after Bu/Mel conditioning. One patient died during the autograft and another declined AuSCT after achieving a CR with hyper-CVAD + R. With a median follow-up from diagnosis of 36 months (range = 16-53 months), the observed 36 months overall survival and EFS are both 92% for the whole cohort. These data confirm the excellent CR rates achieved by the use of hyper-CVAD + R in patients with MCL and suggest that consolidation with Bu/Mel and AuSCT may improve durable disease control when compared to published outcomes of hyper-CVAD + R alone.

Adult↗
PubMed2006

Donor methylenetetrahydrofolate reductase genotype is associated with graft-versus-host disease in hematopoietic stem cell transplant patients treated with methotrexate.

Methotrexate (MTX), used as a graft-versus-host disease (GvHD) prophylactic agent in hematopoietic stem cell transplantation (HSCT), exerts its effect via folate cycle inhibition. A critical enzyme involved in folate metabolism is 5,10-methylenetetrahydrofolate reductase (MTHFR). We examined the association of a single nucleotide polymorphism (SNP) at position 677 in the MTHFR gene on GvHD outcomes in allogeneic HSCT patients administered MTX. MTHFR genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 193 HSCT patients and donors. A total of 140 patients were transplanted with an HLA-matched related donor and 53 with an unrelated donor. GvHD outcomes were compared between genotypes by univariate and multivariate analysis. The combined donor 677CT and TT genotypes were associated with a decreased incidence of GvHD (acute and chronic combined) in HSCT recipients with an HLA-matched related donor (75% at 1 year in the CT and TT group compared with 91% in the wild type CC group, P=0.01), increased time to onset of first GvHD (P=0.001) and time to first GvHD treated with systemic therapy (P=0.022). Unrelated donor MTHFR genotype was not associated with outcome parameters and no associations of recipient genotype in either related or unrelated donor cohorts were observed.

Adolescent↗
PubMed2006

Reduced-intensity allogeneic haemopoietic stem cell transplantation induces durable responses in patients with chronic B-lymphoproliferative disorders.

Thirty-six patients with chronic B-lymphoproliferative disorders (B-LPD) underwent reduced-intensity allogeneic transplantation (RIT) from HLA-identical related donors. Diagnoses included follicular (n=17), mantle cell (n=9) and small lymphocytic lymphoma (n=2), and chronic lymphocytic leukaemia (n=8). Median age at transplant was 51 years (range, 30-66) and time from diagnosis was 3.4 years (range, 0.3-9.5). At transplant, 28% were in CR, 36% were in PR and 36% were chemorefractory. Conditioning therapy included fludarabine and either cyclophosphamide (n=27) or melphalan (n=9). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin (CsA)/methotrexate (n=21), CsA/mycophenolate mofetil (n=13) or CsA alone (n=2). Eight patients died owing to acute GVHD (n=3), infection in association with chronic GVHD (n=4) and intra-abdominal bleeding (n=1). Treatment-related mortality was 8% at day 100, and 17 and 20% at one and two years, respectively. The cumulative incidence of grade II-IV acute GVHD was 58%, whereas limited and extensive chronic GVHD occurred in 25 and 56%, respectively. No patient has relapsed or progressed. At a median follow-up of 48 months, overall survival probability is 80% (95% CI, 67-93%). We confirm that RIT in chronic B-LPD can result in high and durable CR rates but with significant incidences of acute and chronic GVHD.

Adolescent↗
PubMed2003

The incidence, pathogenesis and natural history of steatorrhea after bone marrow transplantation.

A small number of case reports of steatorrhoea after allogenic BMT have been published, but the incidence and natural history of this complication have not been defined. We reviewed the incidence of steatorrhoea in 184 consecutive allograft recipients surviving at least 100 days. Steatorrhoea was documented in five patients, a median of 5.5 months (range 4-14) post-transplant. All patients had recent or concomitant acute gut or liver graft versus host disease (GVHD). The probability of developing steatorrhoea by 2 years post-transplant was 3.3% (95% confidence interval (CI) +/- 2.9% in the group overall, rising to 4.8% (CI +/- 4.2%) in patients with acute and/or extensive chronic GVHD. All patients responded clinically to pancreatic enzyme supplements. While these observations are consistent with previously reported autopsy data suggesting that GVHD of the exocrine pancreas is likely to be predominant underlying pathological process, in two patients concomitant small bowel or hepatic dysfunction may have contributed to the severity of steatorrhoea. Enzyme supplements were subsequently ceased in three patients without return of steatorrhoea, suggesting that the process is usually reversible. Our data demonstrate that steatorrhoea is not infrequent complication in the 2 years postallograft, particularly in patients with GVHD.

Adult↗
PubMed2003

Successful peripheral blood stem cell mobilisation with filgrastim in patients with chronic myeloid leukaemia achieving complete cytogenetic response with imatinib, without increasing disease burden as measured by quantitative real-time PCR.

Imatinib mesylate (Glivec) is a selective inhibitor of bcr-abl tyrosine kinase, the product of the Philadelphia chromosome, which is the hallmark of chronic myeloid leukaemia (CML). With imatinib, complete cytogenetic response (CCR) can be achieved in over 70% of newly diagnosed patients with CML. However, the optimal long-term management of patients who achieve CCR after imatinib is unknown. With longer follow-up, it is anticipated that some patients are likely to progress and become candidates for autologous transplantation. We studied filgrastim (r-metHuG-CSF) mobilisation of peripheral blood stem cells (PBSC) in 32 patients who have achieved CCR with imatinib. Our data demonstrate that (1) the target CD34(+) cell yields of >/=2.0 x 10(6)/kg were attained with filgrastim 10 microg/kg/day, in 9/18 (50%) of patients during uninterrupted imatinib therapy, and in 10/14 (70%) when imatinib was temporarily withheld. The median CD34(+) cell yield per aphaeresis was 0.70 x 10(6)/kg (range 0.14-2.18) and 2.90 x 10(6)/kg (range 0.15-8.71) in the two groups, respectively (P&<0.005). (2) The cell yields did not correlate with the duration of imatinib administration. (3) There was no impact of the mobilisation procedure on the level of leukaemia as measured by serial blood bcr-abl levels using real-time quantitative PCR with either protocol. (4) bcr-abl remained detectable at low levels in the harvests in most but not all patients. In conclusion, filgrastim can safely be used to mobilise PBSC in patients who have achieved CCR with imatinib, but CD34(+) cell yields are significantly improved when imatinib is temporarily withheld.

Adult↗
PubMed2003

Morphological effects of imatinib mesylate (STI571) on the bone marrow and blood of patients with Philadelphia chromosome (Ph) positive chronic myeloid leukaemia.

There have been few reports on the morphological findings in patients with chronic myeloid leukaemia (CML) undergoing treatment with imatinib mesylate. We examined morphological changes in the marrow and peripheral blood of 27 patients with chronic phase (CP), accelerated phase (AP) and blastic phase (BP) CML, 3 and 6 months after treatment with imatinib. At 3 months there was a significant clearance of leukaemic cells as evidenced by a complete haematological response (CHR) in the peripheral blood in 25 patients, together with reduced marrow cellularity in 25 (median reduction CP 42%; AP/BP 68%) and a reduction in the number of megakaryocytes (13 of 18 CP: five of six AP/BP; three patients did not have an assessable marrow) with an increase in the amount of normal megakaryopoiesis. After 6 months, there was continued morphological improvement in eight of 17 CP patients (one patient died after 3 months) with continued cytogenetic response (7 out of 15 patients with assessable metaphases had no abnormal Ph+ cells and three had <35% Ph+ cells) and maintenance of haematologic response in all patients. After an initial response to treatment at 3 months in the AP/BP group, with CHR and a reduction in cellularity in all patients, we found morphological evidence of a loss of response to treatment, with an increase in leukaemic cells, as evidenced by loss of CHR in three of nine and an increase in median cellularity in five patients. No patient in this group achieved a complete cytogenetic response. In summary, in CML-CP patients treated with 6 months of imatinib, there was a significant reduction in leukaemic cells as evidenced by a haematolological response in the peripheral blood, together with reduced marrow cellularity, restoration of morphologically normal haemopoiesis and a meaningful cytogenetic response. Maintaining a response to treatment appeared less likely to occur in the AP/BP group patients, especially those who did not achieve any cytogenetic response to treatment.

Antineoplastic Agents↗
PubMed2001

Pedicled bone flap formation using transplanted bone marrow stromal cells.

HYPOTHESIS: Transplanted osteoprogenitor cells derived from cultured bone marrow stromal cells (BMSCs) can be used to fabricate pedicled bone flaps. DESIGN: Prospective, randomized experimental trials. SETTING: Basic science research laboratory. MATERIALS: Immunodeficient female NIH-Bg-Nu-Xid mice, aged 3 months. INTERVENTION: The BMSCs were harvested from the long bones of C57Bl/6 transgenic mice carrying the type Ialpha1 collagen-chloramphenicol acetyl transferase reporter gene construct; their numbers were expanded in tissue culture. Treated mice received BMSC transplantations around the common carotid artery and internal jugular vein, the aorta and its venae comitantes, or the saphenous artery and vein; control mice received a sham transplant in comparable recipient sites. MAIN OUTCOME MEASURES: Mice underwent harvesting from 4 weeks to 2 years after transplantation. Transplants were evaluated via histological, immunohistochemical, and angiographic analyses. RESULTS: Compared with the controls, which formed no bone, 32 of 37 BMSC-containing transplants formed a vascularized bone island that was perfused specifically and solely by its common carotid artery vascular source. Mature transplants consisted of well-developed lamellar, corticocancellous bone whose osteocytes were derived from the grafted BMSCs; hematopoietic tissue derived from the recipient mouse. Transplants formed as early as 4 weeks and remained stable in size as late as 108 weeks. CONCLUSIONS: Bone marrow stromal cells can be used to create vascularized bone flaps in mice; these bone constructs are vascularized by their pedicle and therefore can potentially be transferred to a recipient site using microsurgical techniques. These findings provide proof of principle of an additional clinical application of BMSC transplantation techniques.

Animals↗
PubMed2000

Initial clinical experience with ambulatory use of an implantable atrial defibrillator for conversion of atrial fibrillation. Metrix Investigators.

BACKGROUND: A recent study has shown that the implantable atrial defibrillator can restore sinus rhythm in patients with recurrent atrial fibrillation when therapy was delivered under physician observation. The objective of this study was to evaluate the safety and efficacy of ambulatory use of the implantable atrial defibrillator. METHODS AND RESULTS: An atrial defibrillator was implanted in 105 patients (75 men; mean age, 59+/-12 years) with recurrent, symptomatic, drug-refractory atrial fibrillation. After successful 3-month testing, patients could transition to ambulatory delivery of shock therapy. Patients completed questionnaires regarding shock therapy discomfort and therapy satisfaction using a 10-point visual-analog scale (1 represented "not at all," 10 represented "extremely") after each treated episode of atrial fibrillation. During a mean follow-up of 11.7 months, 48 of 105 patients satisfied criteria for transition and received therapy for 275 episodes of atrial fibrillation. Overall shock therapy efficacy was 90% with 1.6+/-1.2 shocks delivered per episode (median, 1). Patients rated shock discomfort as 5.2+/-2.4 for successful therapy and 4.2+/-2.2 for unsuccessful therapy (P:>0.05). The satisfaction score was higher for successful versus unsuccessful therapy (3.4+/-3. 3 versus 8.7+/-1.3, P:<0.05). There was no ventricular proarrhythmia observed throughout the course of this study. CONCLUSIONS: Ambulatory use of an implantable atrial defibrillator can safely and successfully convert most episodes of atrial fibrillation, often requiring only a single shock. Successful therapy is associated with high satisfaction and only moderate discomfort.

Adult↗
PubMed2000

Neurological events associated with the infusion of cryopreserved bone marrow and/or peripheral blood progenitor cells.

Reports of neurological toxicity of cryopreserved stem cell infusion are infrequent. Three of 179 consecutive patients experienced significant neurological events in this context. Transient global amnesia developed following infusion in one patient and in the other two, cerebral infarction occurred. Profound hypotension, bradyarrhythmias or hypoxia were not associated with any of these episodes. These events may have been related to infused DMSO, which in the non-transplant setting has been associated with neurological toxicity and local infusion of which has resulted in acute vasospasm in animal models. These cases suggest that infusion of cryopreserved stem cells may result in cerebrovascular ischaemia. Bone Marrow Transplantation (2000) 25, 1285-1287.

Bone Marrow↗
PubMed1989

Middle ear injury in animals exposed to complex blast waves inside an armored vehicle.

With greater reliance on armored vehicles of improved survivability, questions have arisen about the likelihood of the wounding of vehicle occupants from blast waves alone. In this study, we placed anesthetized animals (sheep or pigs) inside lightly armored vehicles and exposed them to the blast waves generated by one of three sizes of shaped-charge munitions. Sixty-seven animals were exposed and 15 served as controls. No difference was noted between exposed and control groups for blast injury to the respiratory or gastrointestinal tracts. In contrast, middle ear damage was observed exclusively in animals exposed to blast and was correlated strongly with the peak pressure. The ear is the organ most sensitive to blast damage, and if protectors are not used, military physicians can expect to see a high incidence of middle ear injury in modern combat. The operational consequences of such an injury are not known.

Animals↗
PubMed1984

Advance prediction of transthoracic impedance in human defibrillation and cardioversion: importance of impedance in determining the success of low-energy shocks.

The purposes of this study were to evaluate a method that predicts transthoracic impedance in advance of defibrillating shocks in humans and to assess the importance of transthoracic impedance in low-energy defibrillation. Via defibrillator electrodes we applied 31 kHz current to the chest during the defibrillator charge cycle, before the defibrillating shock was actually delivered. The current flow was limited by transthoracic impedance; a microprocessor monitored the predischarge current flow and determined the predischarge impedance by calibration against known resistance values. Actual impedance to the defibrillating shock was also determined and compared with the predicted impedance. With this approach we predicted impedance in 19 patients who received 66 shocks for ventricular and atrial arrhythmias. Predicted impedance (y) correlated very well with actual impedance (x):y = .90x + 11.3; r = .97. To determine the importance of impedance in defibrillation and cardioversion, we prospectively gathered data from 96 patients who received shocks of various energies for ventricular or atrial arrhythmias. In patients with high transthoracic impedance (greater than 97 omega), low-energy shocks (less than or equal to 100 J) for ventricular defibrillation had only a 20% success rate as opposed to a 70% success rate for low-energy shocks in patients with low or average impedance (p less than .05). We conclude that transthoracic impedance can be accurately predicted in advance of defibrillation and cardioversion. This method permits the preshock identification of patients with high impedance in whom attempts to defibrillate with low-energy shocks are inappropriate.

Arrhythmias, Cardiac↗
PubMed1983

Determinants of defibrillation: prospective analysis of 183 patients.

Previous studies have suggested that a number of factors may influence the ability to defibrillate: the transthoracic resistance and resultant current flow, the paddle electrode size, the duration of preshock ventricular fibrillation (VF) and cardiopulmonary resuscitation, metabolic abnormalities, body weight, the shock energy selected, and whether the patient is receiving lidocaine. To examine the effect of these variables, a prospective study was conducted of 183 patients who received direct-current shocks for VF. Overall defibrillation rates approached 90%, even in patients with secondary VF, but rates of successful resuscitation and survival were much lower. Patients who never defibrillated despite multiple shocks had a prolonged duration of cardiopulmonary resuscitation preceding the first shock (21 +/- 14 minutes) and systemic hypoxia and acidosis. These conditions tended to occur in patients who initially had cardiac arrest from causes other than VF: asystole, severe bradycardia and electromechanical dissociation. In such patients, VF developed only as a late event, which was then often unresponsive to attempted defibrillation. The other factors examined were not major determinants of defibrillation.

Body Weight↗
PubMed1983

Evaluation of a new defibrillation pathway--the tongue-epigastric route. I. Experimental studies in dogs.

The purpose of this study was to determine the efficacy of a tongue-epigastric defibrillation route in anesthetized dogs. Ventricular fibrillation was induced by rectangular pulses passed down a transvenous catheter into the right ventricle. Three groups of dogs were studied. Group I (15 dogs) received shocks from a 12 cm2 tongue electrode, a 50 cm2 circular, gelled self-adhesive electrode pad placed on the epigastrium and standard transthoracic defibrillator paddle electrodes. Shocks were given at energy levels of 50 to 460 joules (delivered energy, 50 ohm resistance). The success of the tongue-epigastric shocks in achieving defibrillation, and the resistance and current flow were determined at each energy level and compared with the same energy shocks from the standard transthoracic electrodes. In Group II (five dogs), comparisons were made between the 12 cm2 tongue electrode used in the first group of dogs and a larger tongue electrode of 40 cm2. In Group III (five dogs), intracardiac current flow (potential gradient) with tongue-epigastric and standard transthoracic electrodes was studied. In Group I, defibrillation success with the tongue-epigastric electrodes ranged from no success at 50 to 100 joules to 83% success at 460 joules. With standard transthoracic electrodes, success rates ranged from 65% at 50 joules to 100% at 300 joules. At all energies tested, the resistance was significantly higher and current significantly lower using tongue-epigastric compared with transthoracic electrodes. The higher tongue-epigastric resistance is probably related to the longer interelectrode distance; the correlation between interelectrode distance (x, in centimeters) and resistance (y, in ohms) in these dogs was y = 2.2x + 29.6, r = 0.78.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1983

Effect of ischemia, hypertrophy, hypoxia, acidosis, and alkalosis on canine defibrillation.

Our purpose was to assess the effect of myocardial ischemia, left ventricular hypertrophy, and systemic hypoxia and acid-base abnormalities on the energy requirements for defibrillation. We determined the defibrillation threshold (DFT), the minimum energy required to defibrillate. DFT was not significantly elevated after left anterior descending coronary occlusion, nor was there a relationship between the size of the occluded coronary distribution area (coronary risk area) and the change in DFT in individual animals. Renal hypertension and left ventricular hypertrophy were induced by unilateral nephrectomy and contralateral renal artery stenosis. DFT in left ventricular hypertrophy dogs was not significantly higher than in dogs without hypertrophy. Finally, we induced systemic hypoxia and acid-base abnormalities. Neither respiratory nor metabolic acid-base disturbances affected DFT, but during systemic hypoxia (O2 tension 45 +/- 2) DFT fell from 83 +/- 49 to 58 +/- 28 J (P less than 0.01). Thus in dogs, myocardial ischemia, left ventricular hypertrophy, and acid-base abnormalities do not elevate defibrillation energy requirements, whereas hypoxia reduces the energy needed to defibrillate.

Acidosis↗
PubMed1981

Elective cardioversion: influence of paddle-electrode location and size on success rates and energy requirements.

We compared the success rates and energy requirements of two electrode-paddle positions (anteroposterior vs. anterolateral) and different paddle sizes in the elective cardioversion of atrial arrhythmias. We prospectively studied 173 patients - 111 in atrial fibrillation and 62 in atrial flutter. The anterolateral paddles used were either two standard-size (8.5-cm diameter) paddles or one 13-cm diameter anterior paddle with one standard-size lateral paddle. The anteroposterior paddles used were either a standard-size or a 13-cm anterior paddle with 12-cm posterior paddle. Overall cardioversion success rates with either paddle position were similar (greater than 90 per cent). The larger paddles did not significantly reduce energy requirements for cardioversion of either arrhythmia. We conclude that anterolateral paddles are as effective as anteroposterior paddles for the elective cardioversion of atrial arrhythmias, and that there is no demonstrable advantage to using paddles that are larger than the standard size in either position.

Adult↗
PubMed1981

Transthoracic resistance in human defibrillation. Influence of body weight, chest size, serial shocks, paddle size and paddle contact pressure.

Successful defibrillation depends on delivery of adequate electrical current to the heart; one of the major determinants of current flow is transthoracic resistance (TTR). To study the factors influencing TTR, we prospectively collected data from 44 patients undergoing emergency defibrillation. Shocks of 94-450 J delivered energy were administered from specially calibrated Datascope defibrillators that displayed peak current flow, thereby permitting determination of TTR. Shocks were applied from standard (8.5-cm diameter) or large (13 cm) paddles placed anteriorly and laterally. First-shock TTR ranged from 15-143 omega. There was a weak correlation between TTR and body weight (r = 0.45, p less than 0.05) and a stronger correlation between TTR and chest width (r = 0.80, p less than 0.01). Twenty-three patients who were defibrillated using standard 8.5-cm paddles had a mean TTR of 67 +/- 36 omega (+/- SD), whereas 21 patients who received shocks using paddle pairs with at least one large (13 cm) paddle had a 21% lower TTR of 53 +/- 24 omega (p = 0.05, unpaired t test). Ten patients received first and second shocks at the same energy level; TTR declined only 8%, from 52 +/- 19 to 48 +/- 16 omega (p less than 0.01, paired t test). In closed chest dogs, shocks were administered using a spring apparatus that regulated paddle contact pressure against the thorax. Firmer contact pressure caused TTR to decrease 25%, from 48 +/- 22 to 36 +/- 17 omega (p less than 0.01, paired t test). Thus, human TTR varies widely and is related most closely to chest size. TTR declines only slightly with a second shock at the same energy level. More substantial reductions in TTR and declines only slightly with a second shock at the same energy level. More substantial reductions in TTR and increases in current flow can be achieved by using large paddles and applying firm paddle contact pressure.

Animals↗