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Biomedical subjects

C Heard

Publications and source records attributed to C Heard.

8 recordsLinked to original sources
PubMed2001

A review of modifications to recombinant antibodies: attempt to increase efficacy in oncology applications.

Although monoclonal antibodies have high specificity, their usefulness in the clinic, especially against solid tumors, has been limited. This arises in part from the inability of antibody molecules to penetrate into the tumor and kill the tumor cells. In addition, natural cytotoxic effects of antibodies, mediated through complement or Fc receptors, may not be sufficient to kill malignant cells. This review will present some of the antibody modifications used to increase efficacy. Modified recombinant antibodies have been designed to be more cytotoxic (immunotoxins), to increase natural effector functions (bivalent antibodies, antibody-fusion molecules, multimeric antibodies, directed mutations in Fc region), or to pretarget cells for concentration of cytotoxic drugs. This review will also focus on engineering of smaller versions of antibodies that retain specificity (single chain Fvs, Fabs, Fab(2)s, minibodies, domain deleted antibodies) and have increased penetrability of solid tumors. Many of these antibody modifications may result in antigenic compounds which can limit repeat administration. Clinical experiences will be highlighted if information is available.

Animals↗
PubMed2001

Complications in pediatric tracheostomies.

OBJECTIVE: To examine complications of pediatric tracheostomy. STUDY DESIGN: Retrospective. METHODS: Chart review of children undergoing tracheotomy or laryngeal diversion between 1990 and 1999. RESULTS: Charts of 142 children were examined. Average age was 2.64 years (standard deviation [SD], 4.73 y) at surgery. Duration of tracheostomy was 2.08 years (SD, 1.72 y) for those decannulated, 3.12 years (SD, 2.5 y) for those still with a stoma, and length of follow-up for the whole group was 4.14 years (SD, 8.69 y). At last follow-up, 56% had a tracheostomy, 29% had none, and 15% had died; one death was tracheostomy-related. Three percent had intraoperative complications, 11% had complications before the first tracheostomy tube change, and 63% had complications after the first tube change. Thirty-four percent had a trial of decannulation; 85% of these were successful. Fifty-four percent of those decannulated had complications. Number of complications was not related to duration of follow-up. In-hospital mortality was congruent to mortality predicted by PRISM (Pediatric Rate of Mortality) scores. CONCLUSIONS: Forty-three percent had serious complications involving loss of the tracheostomy airway (tube occlusion or accidental decannulation) or requiring a separate surgical procedure. Deaths directly attributable to tracheostomy complications occurred in 0.7%.

Child, Preschool↗
PubMed2000

Continuous remifentanil for pediatric neurosurgery patients.

OBJECTIVE: Remifentanil hydrochloride is a new titratable opioid agonist with rapid onset and offset of action. We present 2 cases of intracranial mass lesions in whom remifentanil was used to obtain serial neurological examinations. METHODS: Patients received bolus doses of remifentanil 1 microgram/kg followed by continuous infusions of 0.1-0.5 microgram/kg/min, titrated to effect. After the clinical examination, the remifentanil was restarted to the desired effect. CONCLUSION: The ultra-short duration of action of remifentanil makes it ideally suited for selected pediatric neurosurgical patients in whom frequent, serial neurological examinations are necessary. There were no side effects associated with the use of remifentanil.

Anesthetics, Intravenous↗
PubMed1999

Two neutralizing human anti-RSV antibodies: cloning, expression, and characterization.

BACKGROUND: Respiratory syncytial virus (RSV) infection is a major problem in the newborn and aging populations. Fully human monoclonal antibodies with the ability to neutralize RSV could have a major impact on the immunotherapy of the disease. The generation of human antibodies has been difficult because there exists no general way to activate B cells against an antigen of choice in vitro. MATERIALS AND METHODS: Human spleen cells from individuals exposed to RSV were used to repopulate SCID mice. Hu-SCID mice were boosted with RSV fusion (F)-protein and subsequently developed B cell tumors. The tumors were removed and cultured and subcloned in vitro, using a feeder layer of CD154-expressing T cells. Two of these tumors produced the antibodies designated RF-1 and RF-2. VL genes were isolated by standard PCR techniques, however, it was necessary to use high-temperature reverse transcriptase to clone the VH genes. RESULTS: RF-1 and RF-2 VH genes were both found to be closely related members of the VH2 family. Vk genes originated from the VK III family. RF-1 and RF-2 recombinant antibodies expressed in CHO cells (cRF-1 and cRF-2) were found to have affinities for RSV F-protein of 0.1 nM and 0.07 nM, respectively, and both were able to neutralize several A and B subtypes of RSV. CONCLUSION: The technique of immortalizing human B lymphocytes, by passage in SCID mice and expression as recombinant antibodies in CHO cells, provides a method by which high-affinity human antibodies can be developed for immunotherapy of viral diseases.

Aged↗
PubMed1992

"Primatization" of recombinant antibodies for immunotherapy of human diseases: a macaque/human chimeric antibody against human CD4.

Immunoglobulin variable region genes from non-human primates, cynomolgus macaques, were shown to have 85%-98% homology with human immunoglobulin sequences and yet macaques are phylogenetically distant enough to respond against conserved human antigens. Immunoglobulin genes were isolated from monkeys immunized with human CD4 antigen and a human/monkey chimeric anti-CD4 antibody with 91-92% homology to human immunoglobulin framework regions was cloned and expressed. The antibody has an apparent affinity of 3.2 x 10(-11) M and exhibits potent immunosuppressive properties in vitro.

Animals↗
PubMed1984

Evaluation of a computer-assisted medication refill reminder system for improving patient compliance.

Computer-generated refill reminder notices were mailed to patients receiving continual medication for cardiovascular diseases to measure improved compliance and to discover whether a computer-assisted program was economically viable. Guidelines were established to define compliance. A computer-assisted compliance intervention program did not significantly improve the rate at which patients had their prescriptions filled "on time" and the mean compliance rate for both experimental and control groups was greater than 79%. Also discussed were cost and compliance strategy implications and the receptiveness of patients to the reminder program.

Analysis of Variance↗
PubMed1977

Occupational role acquisition: a perspective on the chronically disabled.

Occupational therapists are aware that chronic disability restricts not only physical and mental skills, but also social skills and the resulting ability of the patient to function in society. The issue of quality of life for the chronically disabled requires assisting them in the acquisition of new, although not always remunerative, occupational roles. The occupational role defines daily activity and appropriation of time, as well as the contribution to society and societal worth. This article presents the sociological concepts of role, three critical points in conceptualization of the occupational role acquisition process, a model for evaluating and monitoring a patient's progress, and a case study.

Adolescent↗