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Biomedical subjects

M MacPhee

Publications and source records attributed to M MacPhee.

At least 19 recordsLinked to original sources
PubMed2003

Inactivation of viral and prion pathogens by gamma-irradiation under conditions that maintain the integrity of human albumin.

BACKGROUND AND OBJECTIVES: The administration of therapeutic plasma protein concentrates has been associated with the real risk of transmitting viral diseases and the theoretical risks of prion transmission. Our objective was to determine if gamma-irradiation can inactivate viral or prion infectivity without damaging a protein biotherapeutically. MATERIALS AND METHODS: Human albumin 25% solution, spiked with four model viruses (including porcine parvovirus) or with brain homogenate from scrapie-infected hamsters, was gamma-irradiated at constant low-dose rates and assayed for viral and prion infectivity or for albumin integrity. RESULTS: At a radiation dose of 50 kGy, viruses were inactivated by >/= 3.2 to >/= 6.4 log10 and scrapie by an estimated 1.5 log10, whereas albumin was only moderately aggregated and fragmented. CONCLUSIONS: gamma-Irradiation can preferentially inactivate viral and prion pathogens without excessive damage to albumin structure.

Animals↗
PubMed2001

Development of an animal model for assessment of the hemostatic efficacy of fibrin sealant in vascular surgery.

PURPOSE: Sustained hemostatic function of fibrin sealant (FS) is crucial when it is used in cardiovascular surgery. The purpose of this study was to develop a model that can determine the long-term hemostatic efficacy of tissue sealants in a vascular surgery. METHODS: To determine the ability of the model to detect differences in FS performance, various concentrations of FS were prepared and tested. Tensile strength of FS clots was determined in vitro using a tensiometer. Laparotomy was performed on 49 anesthetized rabbits, and a segment of the aorta was occluded, transected, and then sutured in an end-to-end fashion with four or eight interrupted 9-O sutures. The four-suture repair was covered with FS or placebo, and blood flow restored. Spilled blood was absorbed with gauze and weighed to estimate blood loss. Four weeks after surgery the animals were euthanized and the vessels recovered for histology. RESULTS: Average tensile strength of FS clots at 120, 90, and 60 mg/ml topical fibrinogen complex (TFC) concentration was 0.42 +/- 0.07 N, with no significant difference among them. The lowest TFC concentration, 30 mg/ml, produced weaker clots than either 120 or 90 mg/ml (P < 0.05). All rabbits with four-suture anastomoses that were treated with placebo bled to death after the vessel was unclamped (n = 6). Treatment of suture line with standard FS concentration (120 mg/ml TFC, n = 8) sealed the anastomosis and prevented blood loss. Hemostasis was sustained for 4 weeks, allowing vascular healing. All rabbits with the eight-suture anastomosis survived the operation but lost 42 +/- 9.2 ml blood (n = 5). Hemostatic efficacy of FS was unchanged when TFC was diluted to 90 mg/ml (n = 6) but further dilution to 60 mg/ml with water (n = 8) produced significantly less effective clots, with an average blood loss of 5.5 +/- 7.6 ml (P < 0.05) and two fatal clot failures postoperatively. When FS was diluted to 60 mg/ml TFC with a buffer, it maintained its hemostatic strength (n = 6). Further TFC dilution to 30 mg/ml led to consistent bleeding with an average blood loss of 35.3 +/- 10.3 ml (P < 0.001, n = 6). CONCLUSIONS: The four-suture anastomosis of rabbit aorta offers a consistent and reliable method for evaluating the short- and long-term hemostatic efficacy of FS products. This model is not only able to determine the functional differences in various concentrations of FS, but it is also sensitive to detect the subtle changes in FS preparation (e.g., medium composition) that is not detected by in vitro testing.

Anastomosis, Surgical↗
PubMed2001

Potential uses of absorbable fibrin adhesive bandage for genitourinary trauma.

Fibrin sealants have become increasingly popular in nearly all surgical specialties. The absorbable fibrin adhesive bandage (AFAB) is a novel, potentially revolutionary product made from dried fibrinogen and thrombin. The AFAB appears to have excellent efficacy in producing rapid hemostasis in a variety of experimental major renal trauma models. The AFAB also appears to enhance healing of the urinary collecting system. Further study is essential to explore new urologic applications of this exciting technology.

Animals↗
PubMed2001

Tetracycline delivery from fibrin controls peritoneal infection without measurable systemic antibiotic.

The addition of antibiotics to an adhesive haemostat results in an ideal system for the treatment of a localized infectious disease. Fibrin sealant (FS) is a biocompatible, resorbable, adherent haemostat that can deliver antibiotics. Previous use of fibrin to deliver antibiotics resulted in rapid release and limited bioactivity. We have reported previously that poorly soluble antibiotics significantly retard release from FS, resulting in extended delivery in vitro, and overcome antibiotic-resistant infection. We now report that localized antibiotic delivery from FS controls peritoneal infection without measurable systemic antibiotic. Rats and mice were implanted with preformed FS discs containing tetracycline free-base to evaluate control of peritoneal sepsis and to measure serum tetracycline levels. Infection was initiated with Staphylococcus aureus. Morbidity and mortality were evaluated for 14 days. Serum was isolated from jugular vein blood with subsequent evaluation for antimicrobial activity. Mice prophylactically treated with FS-tetracycline (FS-TET) 500 mg/kg 2 days before infection cleared the S. aureus infection, resulting in 100% survival. Mice treated with FS-TET 500 mg/kg 7 days before infection survived. Mice treated with FS-TET 1750 mg/kg 35 days before infection also survived. Rats treated with FS-TET 500 mg/kg had undetectable serum tetracycline levels, whereas in vitro release of tetracycline from FS-TET pellets in rat serum was readily detected. We conclude that fibrin is an excellent vehicle for extended delivery of low solubility tetracycline. Tetracycline delivered from FS is an appropriate chemotherapy for S. aureus peritonitis. FS-TET controls localized infection without a measurable concentration of systemic tetracycline.

Animals↗
PubMed2000

Hospital networking. Comparing the work of nurses with flexible and traditional schedules.

OBJECTIVE: This research study was conducted to contrast workplace socialization of nurses working flexible (flex) and traditional schedules in an acute care setting. The study illustrates the types of social networks used by both types of nurses in a reengineered healthcare environment. SUMMARY BACKGROUND DATA: Reengineering strategies, such as flex nurse staffing, add a new dimension to workplace change and adaptation. Few studies have examined the similarities and differences between nurses working flex and traditional schedules. The research literature shows that workplace socialization significantly affects job satisfaction, organizational commitment, and retention. No studies have examined how the process of socialization--forming social networks--differs for nurses working traditional or flex schedules. METHODS AND SUBJECTS: A convenience sample of 120 nurses working traditional schedules and 46 nurses working flex schedules from a pediatric, tertiary care setting completed the Social Network Questionnaire (SNQ), a standardized instrument that records individuals' social network composition and function. RESULTS: No significant differences were found in the nurses' social network composition. Both types of nurses constructed peer-based networks and nurse managers were also present in their networks. Nurses working traditional schedules used significantly more peer members for different types of emotional support, such as reassurance and handling emotional upsets. CONCLUSIONS: Workplace networks are important to both types of nurses. Nurses on flex schedules may form less social attachments in order to manage the increased demands of moving among multiple units. This group of nurses can provide clues for adaptive change in reengineered environments.

Female↗
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↗
PubMed1999

Intraoperative use of the absorbable fibrin adhesive bandage: long term effects.

PURPOSE: The absorbable fibrin adhesive bandage (AFAB) reduces acute blood loss in experimental trauma models, but the effects on wound healing and subsequent function have heretofore not been investigated. Retropubic prostatectomy was selected to evaluate short and long term effects of using the AFAB intraoperatively. MATERIALS AND METHODS: Dogs undergoing prostatectomy were randomly assigned to one of four treatments: CONTROL- sponges and manual pressure were applied after transecting the prostatic pedicles. Sponges were removed when the prostate was delivered. Vessels were isolated and ligated if bleeding continued after removal. AFAB- hemostatically active bandages were applied to the prostatic bed prior to sponges and pressure. Additional bandages were applied at the urethrovesical junction after completing the anastomosis. PLACEBO- visually identical (hemostatically inert) bandages were applied in an identical fashion. LIQUID SEALANT- concentrated thrombin and fibrinogen solution was applied to the vessels prior to sponges and pressure. Additional sealant solution was applied around the anastomosis. RESULTS: Blood loss and time to achieve hemostasis were significantly less in the AFAB group compared with the other treatments. There were no differences in days to anastomotic integrity, continence, or intra-abdominal adhesions at necropsy six weeks later. CONCLUSIONS: The AFAB can reduce surgery time and blood loss, with no decrement in wound healing or subsequent function.

Animals↗
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↗