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Biomedical subjects

G Warden

Publications and source records attributed to G Warden.

At least 19 recordsLinked to original sources
PubMed2001

A murine model of smoke inhalation.

The United States has one of the world's largest per capita fire death rates. House fires alone kill >9,000 Americans annually, and smoke inhalation is the leading cause of mortality from structural fires. Animal models are needed to develop therapies to combat this problem. We have developed a murine model of smoke inhalation through the design, construction, and use of a controlled-environment smoke chamber. There is a direct relationship between the quantity of wood combusted and mortality in mice. As with human victims, the primary cause of death from smoke inhalation is an elevated blood carboxyhemoglobin level. Lethal (78%) and sublethal (50%) carboxyhemoglobin levels were obtained in mice subjected to varying amounts of smoke. Mice exposed to wood smoke demonstrated more dramatic pathology than mice exposed to cotton or polyurethane smoke. A CD-1 model of wood smoke exposure was developed, demonstrating type II cell hypertrophy, cytoplasmic blebbing, cytoplasmic vacuolization, sloughing, hemorrhage, edema, macrophage infiltration, and lymphocyte infiltration. The bronchoalveolar lavage fluid of smoke-exposed mice demonstrated a significant increase in total cell counts compared with those in control mice. These findings are comparable to the lung tissue response observed in human victims of smoke inhalation.

Animals↗
PubMed1998

Current efforts toward implementation of an urban health strategy: the Henry Ford Health System.

The Henry Ford Health System is one of the nation's major comprehensive nonprofit health systems. Though it serves seven counties in southeastern Michigan, it is based in the heart of the city of Detroit. Detroit, like many of the nation's largest cities, has high rates of poverty, single-parent households, unemployment, and violence. The health status of the population is well below national norms and Healthy People 2000 goals. Through the combined efforts of public and private organizations and the people of southeastern Michigan, Detroit is experiencing a renaissance. Henry Ford Health System is contributing to this renaissance and is working to define its role in improving the health status and quality of life of Detroit's residents. The system's current strategy centers on moving beyond civic projects and philanthropic efforts to the incorporation of care for the uninsured and underinsured in its core operations and plans for growth. To make this change, we have developed a systemwide process that focuses on designing and implementing new delivery models, on partnership development with a variety of organizations, and on managing the care of populations. Our efforts are a work in progress, but they are having an impact on our patients, our organization, and our community.

Adult↗
PubMed1997

The expression of cytokines, growth factors and ICAM-1 in the healing of human cutaneous xenografts on nude mice.

We postulate that wound healing is an orderly process mediated by a programmed expression of cytokines and growth factors. We suggest that these factors are produced in a consistent sequence, in regulated quantities and eliminated when their function is complete. We report here the results of studies on several cytokines, growth factors and the intercellular adhesion molecule expressed during the healing of grafts were visible clinically around 3-5 days post-graft and were completed by 4 weeks post-graft. During the 1st 2 weeks, we observed the following. (i) K-14 keratin was prominent throughout the entire epidermis. Thereafter it was limited to basal cell layers. (ii) Langerhans cells were not detectable with anti-human CD1a antibodies during the first week of healing but were clearly detectable 2 weeks post-graft. (iii) DOPA (dihydroxy phenylalanine) positive melanocytes gradually increased with time. The epidermis 21 to 28 days post-graft clinically and histologically seemed to be morphologically intact. Interleukin-1 (IL-1) was clearly detected in some basal cells of the epidermis, especially in melanocytes and some keratinocytes during the early stage of healing. Transforming growth factor-alpha (TGF-alpha) was detected in epidermis first in melanocytes and some keratinocytes shortly after grafting and again in the late stage of healing. It was also found in some dermal cells. Its expression coincided with keratinocyte proliferation and melanocyte migration. TGF-beta was strongly expressed in the epidermis and dermis after the first week post graft. (iv) ICAM-1 was transiently expressed only at the onset of healing. We previously reported that pro-opiomelanocortin and its derivatives MSH/ ACTH are expressed strongly during the healing of human xenografts. The 4 additional molecules which are the subject of this report all are expressed in healing human skin in a predictable sequence and quantity (intensity of stain). Together these data support our hypothesis that healing is a highly regulated process mediated by numerous cytokines.

Animals↗
PubMed1996

Hyperpigmentation of human skin grafted on to athymic nude mice: immunohistochemical study.

Human skin grafted on to athymic nude mice (BALB/C-nu/nu) spontaneously hyperpigments. We wished to identify the morphological and molecular bases for the hyperpigmentation for this phenomenon. We present data on the relationship of healing, regeneration of melanocytes and production of some melanogenic stimuli. Biopsies were taken at preset times post-graft and studied by histological and immunohistochemical methods. DOPA-positive melanocytes first became visible 120 h post-graft and melanin deposition became visible along the basal cell layer 2 weeks post-graft and increased in quantity with time. By immunochemical stains the quantity of three melanocyte specific enzymes, i.e. tyrosinase, tyrosinase-related protein-1 (TRP-1) and DOPA-chrome tautomerase (TRP-2), was markedly enhanced 1 week after grafting and persisted until 4 weeks post-graft. alpha-Melanocyte-stimulating hormone and adrenocorticotrophic hormone were clearly detected in the epidermis soon after grafting. They were still strongly detected in the epidermis and in the dermis 2-4 weeks post-graft. We conclude that hyperpigmentation in the grafted skin accompanies a marked increase in the quantity of melanogenic enzymes and melanogenic peptides. The neuropeptides might be one of many factors which stimulate melanogenesis.

Adrenocorticotropic Hormone↗
PubMed1993

The AHA's new chairman-elect designate: Gail Warden. Interview by Mary Grayson.

Gail L. Warden, president and CEO of Henry Ford Health System, Detroit, has been named chairman-elect designate of the American Hospital Association. He will become chairman of the board of trustees in January 1995. In many ways, Warden is the right man at the right time to head the AHA. His integrated system is described by many as light-years ahead of others in health care. This, plus his background as president and CEO of Group Health Cooperative of Puget Sound, Seattle, makes him one of the field's leading experts on managed care. And at a time when the association itself is revisiting its mission and goals, he is uniquely qualified to offer guidance. A former executive vice president of the AHA, he is now a member of the board of trustees and has served on numerous councils and committees, most recently the Special Committee on New Directions Evaluation.

American Hospital Association↗
PubMed1993

Tissue expanders in the lower face and anterior neck in pediatric burn patients: limitations and pitfalls.

Radovan's 1982 landmark work on the clinical use of tissue expanders was felt to be a panacea for multiple reconstructive problems. We have used and probably overused tissue expanders for reconstruction of many complicated pediatric facial burn problems. This has enlightened us to some of the limitations of their use, and we have, therefore, reassessed our indications for their use. From 1984 through 1990, 52 tissue expanders were used in 37 pediatric patients for face and anterior neck burn scar resurfacing. This experience, combined with the unique problems encountered with face and neck tissue expansion, provided the groundwork for operative guidelines. The long-term effects of gravity, growth, and scarring on facial features adjacent to expanded skin led to the following principles. (1) Caution should be used in advancing expanded neck skin beyond the border of the mandible. The risk of scar widening or possible lip or eyelid ectropion needs to be considered when planning these flaps. Extreme overexpansion is necessary to advance unburned neck flaps over the mandibular border to avoid these problems. (2) After advancement or rotational flaps neck flaps to the face, vertically directed suture lines in the neck may need redirection to prevent linear contracture. This correction may be performed during the primary operation or during revisions. (3) Expanded cheek or neck skin should preferably replace burned areas, but at the same time, not violate unburned facial aesthetic units. (4) To counteract the affects of gravity, expanded cheek skin in conjunction with expanded neck skin, if unburned, may be the best choice for face or mandibular border scar replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Histological, biochemical, and ultrastructural studies on hyperpigmented human skin xenografts.

The mechanisms for hyperpigmentation observed in human cutaneous xenografts placed on athymic nude mice was investigated. Histologic, biochemical, histochemical, and ultrastructural examinations were performed on human skin prior to grafting and at various times ranging from 2 weeks to 30 weeks post-grafting (PG). Hyperpigmentation was macroscopically visible on the graft as early as 4-6 weeks. The number of Dopa-positive melanocytes per unit area was increased at 2 weeks PG and remained elevated until 20 weeks PG. The surface area of the melanocytes, a measure of the activity of the cells, also increased significantly and remained above the pre-grafting size throughout the study. Western blot analysis using tyrosinase specific antibody (alpha Ty-SP) revealed the presence of tyrosinase exclusively in the grafted skin from 2 weeks to 12 weeks PG tested. Histological and ultrastructural observations revealed the presence of numerous dendritic melanocytes, indeterminant clear cells suggestive of Langerhans cells, and dermal melanophages. The results of this study suggest that the observed hyperpigmentation in grafted tissue is caused by an increase in the number of Dopa-positive melanocytes and probably from enhanced melanin production. Extracts of proteins from the xenografts exhibited prominent differences in low and high molecular proteins between pre- and post-grafted skin. Among them, the exclusive appearance of a protein doublet with apparent mw approximately 14 kDa was found in grafted skin, and subsequent studies indicate it has potent effects on melanocyte function.

Animals↗
PubMed1992

Healthcare's survival in the information age.

Strategic planning, CEO leadership, user consensus and close collaboration with software vendors are keys to creating an effective information system, say two top executives at Henry Ford Health System.

Chief Executive Officers, Hospital↗
PubMed1991

Beta-endorphin: a highly selective endogenous opioid agonist for presynaptic mu opioid receptors.

In the presence of physiological cations (in Krebs-4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid buffer) at 37 degrees C the Ki value's of beta-endorphin for mu- and delta-opioid receptor binding sites in rat neocortical membranes, labeled with [3H][D-Ala2,MePhe4,Gly- ol5]enkephalin (DAMGO) and [3H][D-Ala2-D-Leu5]enkephalin (in the presence of unlabeled DAMGO), respectively, amounted to about 9 and 22 nM. Surprisingly, a very different selectivity pattern for the endogenous opioid peptide was found when the affinity of beta-endorphin for functional presynaptic opioid receptors was examined. Thus, beta-endorphin strongly inhibited the electrically evoked release of [3H]NE from rat neocortical slices with an IC50 value of about 0.5 nM, whereas [14C] acetylcholine release from neostriatal slices was inhibited with an IC50 value of about 100 nM. On the other hand, the electrically evoked release of [3H]dopamine from striatal slices was not affected by beta-endorphin. The inhibitory effects of DAMGO and beta-endorphin on [3H]NE release from neocortical slices were equally well antagonized by naloxone. Moreover, 10 nM of the highly selective mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen- Thr-NH2 antagonized competitively the inhibitory effect of beta-endorphin on [3H]NE release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Pharmacokinetics of continuous intravenous infusion of methadone in the early post-burn period.

The pharmacokinetics of methadone were studied in 14 patients with acute, severe burns and receiving an intravenous infusion of methadone to control their pain. Serum methadone concentrations were measured by gas chromatography on 5 mL arterial blood samples obtained at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0 and 24 hours after the start of infusion. Albumin and Alpha-1-Acid glycoprotein (AAG) were measured by radial immunodiffusion. Serum methadone concentration-time data were fit with the appropriate sum of exponentials equation using iterative nonlinear regression analysis. All serum methadone concentration-time data were best described by a monoexponential equation. Estimates of Vd (180 +/- 62 L) were not significantly different from those predicted for Vc from body weight using literature values (156 +/- 41). Estimates of Vd were, however, significantly lower than those predicted for Vz using literature values (282 +/- 74) (P less than 0.001). In addition, CL values (53.0 +/- 19.3 L/h) were significantly higher than those predicted from body weight using literature values (9.2 +/- 2.3 L/h) (P less than 0.001). These changes resulted in estimates of the elimination half-life for methadone of 2.6 +/- 1.1 h. Methadone protein binding was independent of both albumin and AAG concentration. Multiple regression demonstrated that the significant predictors of CL in the early post burn injury period were serum albumin, days post injury and age. The coefficient of determination (r2) for this model was 0.8190. In summary, methadone CL is markedly elevated while the Vc is essentially unchanged during the early post burn injury period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Artificial dermis for major burns. A multi-center randomized clinical trial.

This communication presents an 11-center prospective randomized trial using the artificial dermis invented by Burke and Yannas. Patients with life-threatening burns who underwent primary excision and grafting within 7 days of injury had comparable sites randomized to receive either the artificial dermis (study site) or the investigator's usual skin grafting material (control site). Control materials were autograft, allograft, xenograft, or a synthetic dressing. Epidermal grafts were applied to the study site during a second operation, and surviving patients were followed for 1 year after grafting. One hundred thirty-nine sites on 106 patients were studied. Mean burn size was 46.5 +/- 15% mean total body surface (TBSA). Overall mortality was 13%, and mean hospital stay was 68 +/- 45 days. Median artificial dermis take was 80% compared with 95% for all comparative sites, but the take was equivalent to that of all nonautograft control materials. Results with the artificial dermis improved slightly as the investigators became more familiar with the material. Donor site thickness for the study site averaged .006'' +/- .002'' compared to .013'' +/- .018'' for control (p less than .0001) and the epidermal donor site healed an average of 4 days sooner (10 +/- 6 vs. 14 +/- 8 days) (p less than .0001). As the wounds matured during the first year, both patients and surgeons felt that both sites became more comparable in appearance and function. At the completion of the study, there was less hypertrophic scarring of the artificial dermis, and more patients preferred the artificial dermis to the control graft. Artificial dermis with an epidermal graft provides a permanent cover that is at least as satisfactory as currently available skin grafting techniques, and uses donor grafts that are thinner and donor sites that heal faster.

Adolescent↗
PubMed1988

Complications of controlled tissue expansion in the pediatric burn patient.

All patients at the Burn Institute reconstructed with tissue expanders between June of 1984 and June of 1987 were included in this review. There were 122 expanders used in 77 patients. Complications were defined as "absolute" (23 of 122 expanders, 20 percent) if they resulted in loss of expanders or additional surgery or none of preoperative plan was satisfied or "relative" (14 of 122 expanders, 11 percent) if they included spotty alopecia or alopecia greater than 50 percent or the operative plan only partially satisfied, reflecting poor judgment. The most common absolute complication was prosthetic exposure secondary to wound dehiscence occurring in the scalp area. Complications relative to specific anatomic areas were neck and face, 2 of 20 (10 percent); lower extremity, 1 of 4 (25 percent); trunk, 0 of 6 (0 percent); and scalp, 20 of 92 (22 percent). We feel that this high complication rate in the use of tissue expanders may be unique to the pediatric burn patient. Knowledge of indications for use and potential complications is essential to add this entity to the armamentarium of the burn reconstructive surgeon.

Adolescent↗