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Biomedical subjects

M MacPhee

Publications and source records attributed to M MacPhee.

At least 19 recordsLinked to original sources
PubMed1999

Multicenter trial to evaluate the safety and potential efficacy of pooled human fibrin sealant for the treatment of burn wounds.

OBJECTIVE: The primary purpose of this multicenter study was to evaluate the safety and potential efficacy of a solvent/detergent-treated commercial fibrin sealant (human) for topical hemostasis in skin grafting. METHODS: The study involved a prospective evaluation of changes in viral titers in patients with burns less than 15% after treatment with fibrin sealant (human). Each patient served as his/her own control for an unblinded, randomized comparison of donor site hemostasis and healing. Preoperative serum was obtained to screen for viral titers. At autografting, the recipient site and one of two randomly chosen donor sites were treated with fibrin sealant (human). The use of other hemostatic agents, including epinephrine was prohibited. Each donor site was covered with gauze to collect blood for estimation of the relative amount of bleeding. The healing of the graft and donor sites was observed. Viral titers and wounds were checked monthly for 6 months, and at 9 and 12 months postoperatively. RESULTS: Viral titers for human immunodeficiency virus; hepatitis A, B, and C; Epstein-Barr virus; and cytomegalovirus were obtained before and after treatment. Of 47 patients, 34 completed the full year of observation. After treatment, there were no seroconversions to any of the aforementioned viruses. Bleeding at the recipient site appeared well controlled with fibrin sealant (human). Although investigators felt that fibrin sealant (human) improved donor site hemostasis, differences in hemoglobin measurements of blood-soaked dressings failed to reach significance. No differences were noted with regard to acceleration of donor site healing, graft take, or scar maturation at the two groups of donor sites. Anecdotally, the maturation of the recipient site appeared to be accelerated. CONCLUSION: Fibrin sealant (human) is safe for use during excision and grafting, and its topical hemostatic potential needs to be examined in patients with larger burns. Its role in scar maturation also needs to be investigated.

Adolescent↗
PubMed1998

Efficacy of a dry fibrin sealant dressing for hemorrhage control after ballistic injury.

OBJECTIVE: To determine if a dry fibrin sealant dressing (DFSD) will provide superior hemostasis when compared with regular gauze in a ballistic injury animal model. DESIGN: A nonsurvival randomized goat study. SETTING: A federal biomedical research institute. SUBJECTS: Eighteen anesthetized Angora goats. INTERVENTIONS: Uncontrolled hemorrhage was induced by a complex ballistic extremity injury. Control of hemorrhage was achieved by applying and holding pressure with the DFSD or regular gauze for 2 minutes. The dressings were left in place for 1 hour. MAIN OUTCOME MEASURES: Total blood loss, mean arterial pressure, ballistic injury, and mortality were recorded after 1 hour. RESULTS: The injuries were equivalent for the 2 groups. No animal mortality was seen. After 1 hour, the mean (+/-SEM) blood loss was 124+/-64 mL in the DFSD-treated group and 377+/-64 mL in the gauze dressings-treated group (P=.01). Twenty minutes after injury, the mean arterial pressure was 95.0 mm Hg (+/-SEM, +/-4.7 mm Hg) in the DFSD-treated group and 70.0+/-5.0 mm Hg in the gauze dressings-treated group. The difference persisted for the remainder of the study (P=.01). CONCLUSION: The DFSD was superior to gauze in decreasing blood loss and maintaining blood pressure while retaining the simplicity of standard dressing application.

Animals↗
PubMed1998

Novel delivery systems for coagulation proteins.

Long-term haemophilia prophylaxis with clotting factors administered by alternative delivery modes requires stable liquid formulations of these factors. We developed an aqueous-formulated human coagulation factor IX (hCFIX) with in vitro half-life (T 1/2) of 6 weeks at 37 degrees C and 18 months at 4 degrees C. Upon bolus subcutaneous (s.c.) injection in animals, hCFIX had a bioavailability of up to 16% compared to intravenous (i.v.) dose. When delivered by s.c. implanted pumps, hCFIX attained > 2% of normal human levels in the animal plasma. Hydrogels of hCFIX in a chitosan derivative, N,O-carboxymethyl chitosan (NOCC), released hCFIX slowly in vitro, and when injected s.c., gave prolonged plasma levels over those obtained by bolus i.v. or s.c. injection. Freeze-dried human coagulation factor VIII (hCFVIII) formulated in non-aqueous solvents had in vitro T 1/2 up to 80 days at 37 degrees C.

Administration, Cutaneous↗
PubMed1998

Haemophilia and advanced fibrin sealant technologies.

Fibrin sealant, which consists mainly of fibrinogen and thrombin, provides rapid haemostasis as well as tissue sealing and adhesion. Commercial, viral-inactivated products are available in Europe, Canada, and Japan. Liquid fibrin sealant (LFS) has been used clinically in haemophiliacs to perform dental procedures, orthopedic surgeries, non-orthopaedic surgeries, and circumcisions. LFS use is expected to increase as commercial products will soon be available in the US. Recombinant sources and transgenic animal bioreactor systems will replace plasma-derived products and become the predominant sources for this product in the next decade. Other areas of innovation include the development of fibrin sealant bandages or dressings, expandable foams, and spray powders which will provide the haemophiliac the ability to rapidly attain control of traumatic haemorrhages prior to hospital treatment with a significant reduction in the use of i.v. clotting factors. Fibrin sealant products have the potential to provide life-saving control of haemorrhage, reduction in factor dependency, lower viral exposure risk, and medical care cost reduction.

Drug Contamination↗
PubMed1998

Quality-of-life factors in adolescent inflammatory bowel disease.

Little is known about the specific psychosocial factors that influence quality of life in adolescents with newly diagnosed inflammatory bowel disease (IBD). We adapted a model by Garrett and Drossman to assess adolescent adjustment to recent-onset IBD. Thirty adolescent-parent pairs completed a set of standardized questionnaires. The inclusion criteria were adolescents 12-18 years of age with Crohn's disease or ulcerative colitis of < 5 years' duration. Adolescents' health-related quality-of-life scores significantly correlated with satisfaction and degree of closeness with their social support members, such as parents. An unexpected finding was that the adolescents included more extended family than peers in their social support networks. Also of note was that parental coping styles rather than adolescent coping styles significantly correlated with adolescents' quality-of-life health scores. Severity of illness did not correlate with adolescent quality-of-life health scores. There was significant agreement between adolescent and parental quality-of-life health scores and stressful event ratings. Adolescents with recent-onset IBD rely more on family members than their peers for emotional support, and they depend more on their parents' coping skills than their own. These findings may indicate lags in normal adolescent development. Adolescents and parents do communicate and share concerns with each other. Support programs for adolescents with IBD should reinforce existing coping skills and parent-adolescent communication while promoting normative development.

Adaptation, Psychological↗
PubMed1997

Tumorigenic transformation of immortalized ECV endothelial cells by cyclooxygenase-1 overexpression.

The cyclooxygenase (Cox) enzyme catalyzes the rate-limiting oxidative and peroxidative enzymatic steps in the biosynthesis of prostanoids. Both Cox-1 and -2 genes encode the two isoenzymes that carry out similar enzymatic steps. Enhanced Cox activity is associated with proliferative diseases such as colon cancer. To determine if a cause and effect relationship exists between Cox isoenzyme overexpression and tumorigenesis, the human Cox-1 and Cox-2 isoenzymes were transfected into ECV immortalized endothelial cells. Although numerous clones of Cox-1 expressing cells were obtained, Cox-2 overexpression resulted in growth disadvantage and increased cell death. In contrast, Cox-1 overexpressing cells expressed high levels of the functional Cox-1 polypeptide in the endoplasmic reticulum and the nucleus. In vitro proliferation of these cells was reduced compared with vector-transfected ECV cells. Cox-1 overexpression also enhanced the tumor necrosis factor-alpha-induced apoptosis of ECV cells 2-fold. In contrast to the in vitro behavior, ECV-Cox-1 cells proliferated aggressively and formed tumors in athymic "nude" mice, whereas the vector-transfected counterparts did not. The growth of Cox-1-induced tumors was not inhibited by indomethacin, suggesting a nonprostanoid function of Cox-1. ECV-Cox-1-derived tumors were angiosarcoma-like and contained numerous host-derived neovessels. These data suggest that Cox-1 overexpression in immortalized ECV endothelial cells results in nuclear localization of the polypeptide and tumorigenesis.

Animals↗
PubMed1996

A clinical tool for nonorganic failure-to-thrive feeding interactions.

An interdisciplinary team of professionals developed and piloted a clinical tool, the Feeding Checklist, for assisting observations of feeding interactions with nonorganic failure-to-thrive (NOFTT) clients. The piloting process involved two phases. During the development phase, content validity and reliability were established with three NOFTT experts. The tool was compared with a standardized feeding interaction assessment instrument to determine concurrent validity. Both tools revealed similar behavior patterns significantly differentiating between NOFTT and Thriving dyads. The results also concurred with NOFTT literature findings. During the second phase of the study, pediatric nursing staff significantly improved the nursing documentation of NOFTT feeding interactions when using the Feeding Checklist.

Adult↗
PubMed1996

Caring for head and neck oncology patients. Does social support lead to better quality of life?

OBJECTIVE: To determine whether social support contributes to better quality of life and psychological state of head and neck oncology patients. DESIGN: A structured questionnaire, administered orally to patients face-to-face, with specific questions about demographic and medical information and social support and two standardized scales; a cancer-specific quality of life scale and a depression scale. SETTING: Head and Neck Oncology Clinic, an institutional referral centre providing ambulatory care at the Camp Hill Medical Centre in Halifax, NS. PARTICIPANTS: Forty-five head and neck oncology patients (33 men, 12 women) who came for follow-up appointments at the clinic. One person did not complete the interview. Fifty patients were approached, but five were not included: one died before the interview, and four agreed to participate but were prevented by transportation or timing problems. MAIN OUTCOME MEASURES: Scores on the Functional Living Index-Cancer Scale and the Center for Epidemiologic Studies Depression scale. RESULTS: Four main factors predicted quality of life: satisfaction with family physician support, severity of cancer, sex of patient, and type of cancer. Three important predictors of psychological state were loss of appetite, family physician support, and sex of patient. CONCLUSION: Social support, particularly from family physicians, contributes greatly to better quality of life and psychological state for head and neck oncology patients.

Adult↗
PubMed1995

The secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of ApcMin-induced intestinal neoplasia.

Mutations in the APC gene are responsible for various familial and sporadic colorectal cancers. Min mice carry a dominant mutation in the homolog of the Apc gene and develop multiple adenomas throughout their small and large intestine. Quantitative trait loci studies have identified a locus, Mom1, which maps to the distal region of chromosome 4, that dramatically modifies Min-induced tumor number. We report here the identification of a candidate gene for Mom1. The gene for secretory type II phospholipase A2 (Pla2s) maps to the same region that contains Mom1 and displays 100% concordance between allele type and tumor susceptibility. Expression and sequence analysis revealed that Mom1 susceptible strains are most likely null for Pla2s activity. Our results indicate that Pla2s acts as a novel gene that modifies polyp number by altering the cellular microenvironment within the intestinal crypt.

Adenomatous Polyposis Coli↗
PubMed1995

Delivery of demineralized bone powder by fibrin sealant.

The main purpose of this study was to determine whether the use of fibrin sealant as a delivery vehicle for demineralized bone powder would result in bone induction in heterotopic and orthotopic sites. Rat demineralized bone powder alone or in different concentrations of fibrin sealant matrix (4, 8, 15, and 45 mg/ml) was bioassayed for bone induction by implantation in intramuscular sites. Distribution of treatment groups was as follows: demineralized bone powder alone (n = 12), demineralized bone powder plus 4 mg/ml fibrin sealant (n = 11), demineralized bone powder plus 8 mg/ml fibrin sealant (n = 11), demineralized bone powder plus 15 mg/ml fibrin sealant (n = 11), demineralized bone powder plus 45 mg/ml fibrin sealant (n = 10), 4 mg/ml fibrin sealant (n = 13), and 45 mg/ml fibrin sealant (n = 11). In a second group of rats, 8-mm critical-sized calvarial defects were created and treated with demineralized bone powder plus 30 mg/ml fibrin sealant. Intramuscular implants were retrieved after 28 days, while calvarial implants were retrieved at 28 days (n = 8), 3 months (n = 8), or 4 months (n = 5). Implants were then x-rayed and submitted for histology. Results showed bone formation as evidenced by radiopacity and histology. Radiopacity measurements of demineralized bone powder implants alone or in a fibrin sealant matrix were associated with immature woven bone at the implantation site. Fibrin sealant allowed bone formation by demineralized bone powder to occur, improved the handling of demineralized bone powder, and facilitated the shaping of implants.

Animals↗
PubMed1994

Change in the hospital setting: adopting a team approach for nonorganic failure-to-thrive.

The change process is described for the adoption of a multidisciplinary team approach to nonorganic failure-to-thrive (NOFTT) management at a pediatric care facility. A member of the nursing staff acted as a change agent. The need for change was documented with medical record audits. A team was developed and a management protocol derived from an external evaluation of successful programs described in the literature. Preliminary outcomes of the project are reported. Box 1 at the end of this article contains criteria for NOFTT diagnosis and an outline of the team's protocol.

Child↗
PubMed1993

Differential transforming abilities of non-secreted and secreted forms of human fibroblast growth factor-1.

Fibroblast growth factor (FGF)-1(1-154), the precursor for acidic FGF-1(21-154), is a potent angiogenic polypeptide, the structure of which lacks a signal peptide sequence for secretion. To investigate the biological significance of this structural feature, we have attempted forced secretion of FGF-1 through fusion of the entire FGF-1 coding frame with the signal peptide (sp) from the hst/KS3 gene, a secretory member of the heparin-binding growth factor family. We also studied the transforming ability of the signal-less forms of FGF-1 comprising FGF(1-154) and FGF-1(21-154). The presence of a soluble and biologically active form of FGF-1 was readily detected in the conditioned medium of NIH 3T3 cells transfected with sp-hst/KS3:FGF-1(1-154) as demonstrated by Western blot analysis and DNA synthesis assays, whereas sp-hst/KS3:FGF-1(21-154) was not detectable in conditioned medium even though the protein was detected in cellular extracts. The secreted form of sp-hst/KS3:FGF-1(1-154) stimulated the proliferation of human umbilical vein endothelial cells in vitro and was able to induce receptor-mediated tyrosine phosphorylation. Furthermore, the forced secretion of biologically active FGF-1 resulted in NIH 3T3 cell transformation as demonstrated by altered morphology in vitro, the formation of discrete colonies in soft agarose, growth under serum-free conditions, and ability to rapidly form highly vascular tumors in vivo. Interestingly, sp-hst/KS3:FGF-1(21-154) also mediated the transition to a transformed phenotype despite the inability to detect extracellular FGF-1 in the media conditioned by these NIH 3T3 cell transfectants. Although the transfection of FGF-1(21-154) yielded similar NIH 3T3 cell morphologic changes, these transfectants did not grow under serum-free conditions or yield colonies in soft agarose, and formed tumors in vivo with delayed kinetics. Furthermore, the FGF-1(1-154) NIH 3T3 cell transfectants did not exhibit morphologic changes, and this may be due to the inability of mRNA to express protein. These data suggest that although non-sp forms of FGF-1 may alter the monolayer phenotype of NIH 3T3 cells in vitro, the ability of FGF-1 to transform NIH 3T3 cells requires the function of a sp-directed secretory pathway and suggests that this pathway increases tumorigenicity in vivo.

3T3 Cells↗
PubMed1988

Quantitative and qualitative study of the restoration by cytokines of mononuclear cell delivery to skin test sites in anergic surgical patients.

We tested the hypothesis that anergy is associated with reduced delivery of mononuclear cells (MNCs) to delayed-type hypersensitivity sites and that cytokine (CK)-rich supernatants from mixed lymphocyte cultures overcome the defect. Significantly fewer MNCs were delivered to skin window chambers placed over purified protein derivative (PPD) injection sites of previously sensitized anergic patients compared with hospitalized PPD-reactive patients; coinjection of CK with PPD restored the MNC delivery in anergic patients to normal levels. The T cells cloned from a PPD + CK site of an anergic patient consisted of CD4+ and CD8+ cells whose capacities included cytotoxicity and lymphokine production. The frequency of PPD-reactive cells was 15 times greater than in the blood. Thus, the restoration by CK of the delivery of antigen-specific cells capable of participating in cell-mediated immunity in anergic patients may be feasible.

Adult↗
PubMedDate not supplied

Subverting bacterial resistance using high dose, low solubility antibiotics in fibrin.

Antibiotics (ABs) delivered from fibrin were evaluated for control of multi-drug resistant (MDR) Staphylococcus aureus. ABs having low aqueous solubility (< or = 1 mg/ml) were encapsulated by fibrin (composed of fibrinogen, thrombin, Factor XIIIa and calcium chloride) and examined. Electron microscopy revealed fibrin-caged, tetracycline crystals that were 0.26 to 2.8 microns in size and bound within the reticular matrix. Antibiograms documented that S. aureus ATCC 27659 was resistant to erythromycin (ERY), penicillin G (PEN), streptomycin (STR), sulfamethoxazole-trimethoprim (SXT) and tetracycline (TET). However, low solubility formulations of STR (10 mg/ml) or SXT (0.5 mg/ml), delivered from fibrin and evaluated by the agar disk diffusion assay, produced zones of growth inhibition after 18-24 h at 37 degrees C in vitro, indicating renewed susceptibility of S. aureus ATCC 27659 to these ABs. ERY, PEN and TET were unable to overcome resistance at concentrations up to 10 mg/ml. In vivo, intraperitoneal (i.p.) injection of 150 mg/kg STR delivered from fibrin resulted in 100% survival of rats with MDR S. aureus peritonitis as compared with control rats receiving i.p. STR (150 mg/kg) in 0.9% saline. The results demonstrate that some low solubility ABs delivered from fibrin are efficacious in controlling infection mediated by MDR S. aureus.

Animals↗
PubMedDate not supplied

Nursing case management for children with failure to thrive.

The case management approach is described for children with nonorganic failure to thrive in the pediatric tertiary care setting. An advanced practice nurse facilitated the organization of a planning committee, the construction of a care path, and the evaluation of the case management model. A 4-day care path is presented to show staff nursing functions in the nurse case manager role. Special issues are discussed for developing care paths for organic-based failure to thrive where parent reports can help guide health care interventions.

Case Management↗
PubMedDate not supplied

Teaching nurses about neuromotor development: an evaluative study.

A neuromotor screening tool, The Chandler Movement Assessment of Infants Screening Test (CMAI-ST), was selected to teach nurses who care for premature infants about neuromotor development. After training with the CMAI-ST, the nurses were more adept at recognizing major components of neuromotor development.

Child, Preschool↗