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Biomedical subjects

J L Garrison

Publications and source records attributed to J L Garrison.

12 recordsLinked to original sources
PubMed2001

Selection of cell binding and internalizing epidermal growth factor receptor antibodies from a phage display library.

The first step in developing a targeted cancer therapeutic is generating a ligand that binds to a receptor which is either tumor specific or sufficiently overexpressed in tumors to provide targeting specificity. For this work, we generated human monoclonal antibodies to the EGF receptor (EGFR), an antigen overexpressed on many solid tumors. Single chain Fv (scFv) antibody fragments were directly selected by panning a phage display library on tumor cells (A431) overexpressing EGFR or Chinese hamster ovary cells (CHO/EGFR cells) transfected with the EGFR gene and recovering endocytosed phage from within the cell. Three unique scFvs were isolated, two from selections on A431 cells and two from selections on CHO/EGFR cells. All three scFv bound native receptor as expressed on a panel of tumor cells and did not bind EGFR negative cells. Phage antibodies and multivalent immunoliposomes constructed from scFv were endocytosed by EGFR expressing cells as shown by confocal microscopy. Native scFv primarily stained the cell surface, with less staining intracellularly. The results demonstrate how phage antibodies binding native cell surface receptors can be directly selected on overexpressing cell lines or transfected cells. Use of a transfected cell line allows selection of antibodies to native receptors without the need for protein expression and purification, significantly speeding the generation of targeting antibodies to genomic sequences. Depending upon the format used, the antibodies can be used to deliver molecules to the cell surface or intracellularly.

Animals↗
PubMed1999

The clinical, histologic, and ultrastructural presentation of polyvinyl sponge (Ivalon) breast prostheses removed for massive fluid accumulation.

The current study describes what we believe is the first report of bilateral massive seromas associated with open-cell Ivalon sponges. Additionally, the gross, histologic, and ultrastructural features consistent with previous reports of polyvinyl alcohol prostheses are presented. Despite the reported chemical inertness of polyvinyl alcohol, this material may incite a biologic response in some patients, leading to dense fibrosis and occasional foreign-body giant-cell reaction. It is postulated that the molecular breakdown products of the polyvinyl alcohol polymer may create an osmotic gradient across the periprosthetic capsule, which may lead to intracapsular fluid accumulation, as presented in this case.

Aged↗
PubMed1995

Improved large burn therapy with reduced mortality following an associated septic challenge by early excision and skin allografting using donor-specific tolerance.

These studies demonstrate clearly that the creation of donor-specific tolerance in animals permits the long-term survival of incompatible skin grafts placed following a burn with early eschar excision. Furthermore, the studies demonstrate graphically that such replacement can be done without any increase in the septic mortality in these animals and strongly suggest that such a treatment would be potentially efficacious as a therapy for large body burns that could not be successfully covered with autografts. When animals were observed either in the potentially septic milieu of a large 30% body burn or in a situation of a deliberate attempt to create a septic state using the septic challenge of CLP, the placement of a full-thickness skin graft that survived was clearly beneficial to the animal in reducing mortality. In addition, the donor-specific tolerance technique described permits long-term survival of these skin grafts, which in some of the earlier laboratory studies were able to survive permanently and might well achieve permanent survival in a clinical situation. However, a prolonged graft survival of 90 to 100 days, considering the ability to develop new split thickness skin grafts providing dermal cover at 20- to 25-day intervals, would provide opportunity for a least four "croppings" of the skins. Thus, for example, a small area of remaining autograft skin of 20% in an 80% burn patient could potentially be cropped four times to achieve close to 80% coverage. Coverage would be easier and more successful in the more common burns of less than 70% of TBSA. It is of interest to us that there is virtually no well-developed literature on the use of donor-specific tolerance to aid skin graft survival. There would seem to be a reasonable rationale for considering such therapy since septic problems should not be significantly increased during induction of skin graft tolerance. Once the skin grafting has produced a significant increase in functionally covered skin, the risk of sepsis should decrease markedly. Because sepsis is currently the major factor in 75% of burn deaths, donor-specific tolerance for skins grafts appears to be eminently reasonable for future consideration. Expanded animal studies are probably necessary before clinical trials are undertaken, although skin grafting with immunosuppression has already been tried in patients.

Animals↗
PubMed1994

Simultaneous quantitation of facial movements: the maximal static response assay of facial nerve function.

An assay is described that enables the simultaneous measurement of bilateral facial movements within zones relevant to facial nerve function. The assay allows the accurate quantitation of movement of the eyebrows, radix, lower eyelids, philtrum, mentum, and oral commissures relative to these points on the resting face. Global or region-specific facial nerve dysfunction is detectable using this assay, as shown in examples of patients having single branch facial nerve palsy and bilateral facial palsy (Möbius syndrome variant). Because facial movement is tested by region, with the remainder of the face relaxed, synkinesis can be detected when present. The assay has potential to be used as an adjunct to the presently used ordinal scales of facial nerve function, by allowing actual quantitation of region-specific facial movement. This feature may prove helpful in vector planning for reanimation procedures and may allow the tracking of functional responses after such procedures, thereby providing a measurement of their efficacy.

Adult↗
PubMed1992

Biomechanical analysis of a step-cut technique for flexor tendon repair.

We compared the strength of a new step-cut technique for flexor tendon repair with that of the widely used Kessler-Tajima technique, giving special attention to the relative contributions of the core and epitendinous sutures. 36 flexor digitorum profundus tendons from human cadavers were used. Corresponding digits from the same donor were paired, and the two tendons of each pair were placed in the Kessler-Tajima and step-cut groups, respectively. Each group had three subcategories of repair: (1) core repair alone; (2) epitendinous repair alone; and (3) full repair. In the Kessler-Tajima repair, the core stitch contributed more to ultimate tensile strength, while the epitendinous stitch contributed more to gap formation resistance. In the step-cut repair, however, the epitendinous stitch contributed more to both measures of strength. The full step-cut repair was 65% stronger in resisting gap formation and had 84% more ultimate tensile strength than the full Kessler-Tajima repair. We attribute the greater strength of the step-cut repair to the additional number of epitendinous loops, which lie perpendicular to the long axis of the tendon.

Cadaver↗
PubMed1990

Donor-specific tolerance permits burn allografting without increased sepsis.

Early excision and allografting of massive burns is beneficial. However, chronic immunosuppression, utilized to prolong allograft survival, increases the potential risk of infection. We have previously shown long-term skin allograft survival in mice with a 30% total body surface area (TBSA) burn by inducing donor-specific tolerance (DST) using only perigrafting administration of antithymocyte globulin (ATG) and donor bone marrow (DBM). Chronic immunosuppression is avoided. This study tests whether induction of DST compromises host resistance to infection. Resistance to a septic challenge created by cecal ligation and puncture (CLP) 10 days after a 30% TBSA burn was investigated in the following groups of mice: [table: see text] Positive blood cultures were documented for 97% of mortalities. Burn excision and grafting significantly (P less than or equal to 0.05) decreased mortality. No increased mortality was seen in allografted mice receiving ATG or ATG and DBM compared to isografted mice receiving no immunosuppression. These studies suggest that skin allografting with DST may permit the benefits of burn excision without the risks of infection seen with chronic immunosuppression.

Animals↗
PubMedDate not supplied

[Cross infection in a high risk nursery: comparison of two epidemiologic surveillance methods].

Two methods of surveillance for nosocomial infection--routine notification and active case finding--were compared during three consecutive months at the high risk newborn unit of the Hospital de Base of the Federal District, involving 66 newborns, which represented 93% of the total patient population referred to that unit for specialized care. Our purpose was to measure the efficiency of routine notification. While this method involved infection notification forms routinely filled by the physician at discharge time, active surveillance consisted of physical examination and chart review of all the newborns, carried out, independently, twice a week: routine notification estimated a 27.3 per cent prevalence rate, versus a 30.3 per cent by active-case finding, considered by the authors a superior surveillance method. Although infection rates were similar, routine surveillance resulted in many false-positive and false-negative notifications, reaching a sensitivity of 60.0 per cent and a specificity of 86.9 per cent. The resulting positive predictive value was 66.7 per cent and negative, 83.3 per cent. The data collected by routine notification was often incomplete and inconsistent. In conclusion, the results seem to indicate that control programs based solely on routine surveillance could be producing inaccurate nosocomial infection rates and, consequently inadequate control measures.

Analysis of Variance↗