Development of a marrow transplant regimen for acute leukemia using targeted hematopoietic irradiation delivered by 131I-labeled anti-CD45 antibody, combined with cyclophosphamide and total body irradiation

In an attempt to decrease the relapse rate after bone marrow transplantation (BMT) for advanced acute leukemia, we initiated studies using 131I-labeled anti-CD45 antibody (BC8) to deliver radiation specifically to hematopoietic tissues, followed by a standard transplant preparative regimen. Biodistribution studies were performed in 23 patients using 0.5 mg/kg trace 131I-labeled BC8 antibody. The BC8 antibody was cleared rapidly from plasma with an initial disappearance half-time of 1.5 +/- 0.2 hours, presumably reflecting rapid antigen- specific binding. The mean radiation absorbed doses (cGy/mCi131I administered) were as follows: marrow, 7.1 +/- 0.8; spleen, 10.8 +/- 1.4; liver, 2.7 +/- 0.2; lungs, 2.1 +/- 0.1; kidneys, 0.7 +/- 0.1; and total body, 0.4 +/- 0.03. Patients with acute myelogenous leukemia (AML) in relapse had a higher marrow dose (11.4 cGy/mCi) than those in remission (5.2 cGy/mCi; P = .001) because of higher uptake and longer retention of radionuclide in marrow. Twenty patients were treated with a dose of 131I estimated to deliver 3.5 Gy (level 1) to 7 Gy (level 3) to liver, with marrow doses of 4 to 30 Gy and spleen doses of 7 to 60 Gy, followed by 120 mg/kg cyclophosphamide (CY) and 12 Gy total body irradiation (TBI). Nine of 13 patients with AML or refractory anemia with excess blasts (RAEB) and two of seven with acute lymphocytic leukemia (ALL) are alive disease-free at 8 to 41 months (median, 17 months) after BMT. Toxicity has not been measurably greater than that of CY/TBI alone, and the maximum tolerated dose has not been reached. This study demonstrates that with the use of 131I-BC8 substantially greater doses of radiation can be delivered to hematopoietic tissues as compared with liver, lung, or kidney, which may improve the efficacy of marrow transplantation.     

Long-term neurodevelopmental outcomes in children born with gastroschisis: the tiebreaker

PurposeWe evaluated 2-year neurodevelopmental outcomes in children with gastroschisis.MethodsWe reviewed the records of children with gastroschisis treated between August 2001 and July 2008. Children discharged from the neonatal intensive care unit were referred to the state-sponsored Developmental Tracking Infant Progress Statewide (TIPS) program. We reviewed TIPS assessments performed before age 2 years. School districts evaluated children referred by TIPS and determined their eligibility for early intervention services. Poor outcomes were defined as scores of “failure” or “moderate/high risk” on the screening assessment or enrollment in early intervention services by 2 years. Children with gastroschisis were compared with case-matched nonsurgical, nonsyndromic children of similar gestational age and birth weight.ResultsOne hundred five children were born with gastroschisis, and 46 were followed up with TIPS. There was no statistically significant difference in performance on screening assessments or in the rate of enrollment in early intervention services between the gastroschisis children and controls.ConclusionsChildren born with gastroschisis have similar 2-year neurodevelopmental outcomes as nonsurgical, nonsyndromic neonatal intensive care unit children of similar gestational age and birth weight. Both groups of children have a higher rate of enrollment in early intervention than their healthy peers. These data suggest that neurodevelopmental outcomes in gastroschisis children are delayed secondary to prematurity rather than the presence of the surgical disease.     

Prehospital emergency trauma care and management

Prehospital care of the trauma patient is continuing to evolve; however, the principles of airway maintenance, hemorrhage control, and appropriate resuscitative maneuvers remain central to the role of the emergency medical care provider. Recent changes in the regulations for research in emergency settings will allow randomized trials to proceed to test new devices, drugs, and resuscitative strategies in the prehospital environment. The creation of prehospital research networks will provide the appropriate infrastructure to greatly facilitate the development of new protocols and the execution of large-scale randomized trials with the potential to change current prehospital practice.     

How safe is diathermy in patients with cochlear implants?

INTRODUCTION

Cochlear implants are surgically inserted electrical devices that enable severely or profoundly deaf individuals to interpret sounds from their environment and communicate more effectively. As a result of their electrical nature, they are susceptible to electromagnetic interference and can be damaged by excessive electrical energy. Surgical diathermy is one source of such potentially damaging energy. The British Cochlear Implant Group guidelines advise that monopolar diathermy should not be used in the head and neck region in patients with cochlear implants and that bipolar diathermy should not be used within 2cm of the implant (http://www.bcig.org.uk/site/public/current/safety.htm).

METHODS

A questionnaire was provided to 36 surgeons working in different specialties in the head and neck region, inquiring as to their knowledge of the safety considerations when using diathermy in cochlear implant patients. Thirty-five surgeons provided responses.

RESULTS

Overall, 77% of the respondents were unaware of the existence of published guidelines. Even when given an option to seek advice, 11% erroneously felt it was safe to use monopolar diathermy above the clavicles with a cochlear implant in situ and 49% felt that there was no restriction on the use of bipolar diathermy.

CONCLUSIONS

There is a significant deficit in the knowledge of safe operating practice in the rapidly expanding population of patients with cochlear implants which threatens patient safety. Through this publication we aim to increase awareness of these guidelines among members of the surgical community and this paper is intended to act as a point of reference to link through to the published safety guidelines.     

Erythropoietin structure-function relationships: high degree of sequence homology among mammals

To investigate structure-function relationships of erythropoietin (Epo), we have obtained cDNA sequences that encode the mature Epo protein of a variety of mammals. A first set of primers, corresponding to conserved nucleotide sequences between mouse and human DNAs, allowed us to amplify by polymerase chain reaction (PCR) intron 1/exon 2 fragments from genomic DNA of the hamster, cat, lion, dog, horse, sheep, dolphin, and pig. Sequencing of these fragments permitted the design of a second generation of species-specific primers. RNA was prepared from anemic kidneys and reverse-transcribed. Using our battery of species-specific 5' primers, we were able to successfully PCR- amplify Epo cDNA from Rhesus monkey, rat, sheep, dog, cat, and pig. Deduced amino acid sequences of mature Epo proteins from these animals, in combination with known sequences for human, Cynomolgus monkey, and mouse, showed a high degree of homology, which explains the biologic and immunological cross-reactivity that has been observed in a number of species. Human Epo is 91% identical to monkey Epo, 85% to cat and dog Epo, and 80% to 82% to pig, sheep, mouse, and rat Epos. There was full conservation of (1) the disulfide bridge linking the NH2 and COOH termini; (2) N-glycosylation sites; and (3) predicted amphipathic alpha- helices. In contrast, the short disulfide bridge (C29/C33 in humans) is not invariant. Cys33 was replaced by a Pro in rodents. Most of the amino acid replacements were conservative. The C-terminal part of the loop between the C and D helices showed the most variation, with several amino acid substitutions, deletions, and/or insertions. Calculations of maximum parsimony for intron 1/exon 2 sequences as well as coding sequences enabled the construction of cladograms that are in good agreement with known phylogenetic relationships.     

Dialogue and direction: A new focus for occupational therapy academic programmes in Australia

The present article profiles the development of a key professional group in Australia and New Zealand occupational therapy, the Australian New Zealand Council of Occupational Therapy Education (ANZCOTE). It identifies key issues of importance to this organization that can impact on the profession at large.     

Development and preliminary evaluation of an early childhood community occupational therapy programme

Community-based occupational therapy must be efficient, effective and of high quality. An innovative community health strategy was developed and implemented to meet the needs of early childhood agencies in the Macarthur community for a more accessible occupational therapy service for preschool children. This paper first describes the needs assessment that underpinned programme development. It then describes the planning and implementation phases of the programme. Finally, the paper outlines the preliminary phase of programme evaluation. This involved a survey of stakeholders to determine their views of the programme and the aspects of the programme that they felt should be included in a later evaluation phase. Stakeholders recommended evaluation of quality and design issues, strengths and weaknesses of programme components, stated aims, use of the programme, and client satisfaction. This programme development and evaluation experience supports the need for systematic, multi-method planning and evaluation strategies in community occupational therapy programmes to ensure effective high quality services.