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Biomedical subjects

R A Harvey

Publications and source records attributed to R A Harvey.

At least 19 recordsLinked to original sources
PubMed1998

Sensitivity of mononuclear leucocytes to glucocorticoids in elderly hip-fracture patients resistant to suppression of plasma cortisol by dexamethasone.

OBJECTIVE: Elderly women with proximal femur fracture show a prolonged increase in plasma cortisol, which could have undesirable catabolic effects. Suppression of cortisol by dexamethasone is impaired, suggesting resistance to glucocorticoid effects at feedback inhibitory sites. We therefore wished to find out whether peripheral glucocorticoid sensitivity is normal. DESIGN: Peripheral blood mononuclear leucocytes were used as a model tissue. Blood samples were taken from elderly women about 2 weeks after hip fracture and from elderly control women. Each patient was then given 1 mg dexamethasone at 2300 h followed by further sampling at 0800 and 1600 h the next day. METHODS: Glucocorticoid-receptor binding parameters were measured by incubating whole cells with [3H]dexamethasone for 2 h at 37 degrees C. Inhibition of cell proliferation by dexamethasone was assessed by addition of [3H]thymidine to cells cultured for 65 h with concanavalin A. Cortisol and dexamethasone concentrations were measured in the dexamethasone suppression test. RESULTS: As expected, the hip-fracture patients had raised morning cortisol concentrations and impaired suppression by dexamethasone. The cells of the patients had similar numbers of glucocorticoid receptors to those of the control subjects but higher values for Kd (i.e. a lower binding affinity). The cells of the patients incorporated less [3H]thymidine than the control cells in the absence of dexamethasone. The percentage inhibition by a saturating concentration of dexamethasone was unchanged but the concentration giving half-maximal inhibition was decreased (sensitivity was increased) at the higher of the two concanavalin A concentrations used. CONCLUSIONS: These experiments in mononuclear leucocytes give no evidence of peripheral resistance to glucocorticoids in hip-fracture patients with impaired suppression of cortisol by dexamethasone.

Aged↗
PubMed1995

Patency of a small vessel prosthesis bonded to tissue plasminogen activator and iloprost.

To test the thrombosis resistance of a vascular prosthesis coated with antithrombogenic agents, we evaluated a small vessel prosthesis of expanded polytetrafluoroethylene (ePTFE) implanted in the rat aorta and removed 1 week following surgery. Control grafts consisted of 1 mm internal diameter ePTFE. Experimental grafts consisted of 1 mm internal diameter ePTFE noncovalently bonded to tissue plasminogen activator (tPA) and iloprost using the surfactant tridodecylmethylammonium chloride. After 1 week the grafts were harvested, patency was determined, and histologic specimens were prepared for electron microscopy. Six of 10 control grafts were thrombosed, whereas 9 of 10 tPA-iloprost-bonded grafts were patent (p < 0.03). Of concern, there was an unexpectedly high mortality rate in the tPA-iloprost group compared to the control group among animals that died before completion of the study. Evaluation of the safety of these drugs must, therefore, be an early component of future experiments. Nevertheless, these studies indicate that a small vessel prosthesis bonded to tPA and iloprost may ameliorate some of the complications associated with early graft failure.

Animals↗
PubMed1992

The "S" Quattro in the management of fractures in the hand.

The "S" Quattro has shown its value in the management of displaced comminuted intra-articular phalangeal fracture dislocations. Since then the system has been used as a dynamic flexible external fixator in the treatment of five maluniting phalangeal fractures, five comminuted condylar and four severe compound fractures. These challenging fractures have been dealt with by easy operations, taking full advantage of the versatility of the "S" Quattro to achieve good results.

Adult↗
PubMed1992

Emergency medical systems in Czechoslovakia.

The year 1987 witnessed the "velvet revolution" of Vaclav Havel and the beginning of democratic reform in Czechoslovakia. As the country struggles to build a market-based economy, it maintains a well-developed socialist system of health care that is patterned after the former Soviet system and is free to all (Am J Emerg Med 1984; 2:455-456). Formal private medical practice does not exist. Non-emergency care is provided by multispecialty, primary-care oriented clinics (polyklinka) where after-hours visits are possible due to the presence of on-call physicians. In small towns such an on-call doctor would be a general practitioner, but in large cities an internist, pediatrician, and surgeon might all be available.

Czechoslovakia↗
PubMed1991

Cat-scratch disease: an unusual cause of combative behavior.

Acute encephalitis is an unusual manifestation of cat-scratch disease. The authors present the case of a 27-year-old man who exhibited the acute onset of encephalitis manifested by violent behavior and confusion. The diagnosis of drug abuse was presumed initially, but a careful examination revealed the true cause to be cat-scratch disease. Emergency physicians are frequently faced with the challenging task of evaluating confused and combative patients. This case demonstrates the importance of a complete physical examination and a thorough laboratory evaluation.

Adult↗
PubMed1990

Failure of demonstrated clinical efficacy of antibiotic-bonded continuous ambulatory peritoneal dialysis (CAPD) catheters.

Previous in vitro, in vivo, and a preliminary clinical report have demonstrated efficacy of noncovalently bonding antibiotics to the surface of continuous ambulatory peritoneal dialysis (CAPD) catheters in decreasing infectious complications. A larger prospective randomized clinical trial was completed. Eighty-six patients with chronic renal failure were enrolled in the study and randomized to receive either a surfactant treated or untreated control catheter. All catheters were soaked in cefoxitin at the time of insertion. Groups were comparable in terms of pre-existing illnesses, age, and gender. No differences were shown in the incidence of catheter-tract infections, peritonitis or mechanical complications. There was also no differences in microbiologic culture results. Therefore, it is concluded that this clinical trial did not demonstrate a reduction in catheter-related infectious complications by antibiotic bonding.

Bacterial Infections↗
PubMed1989

Binding of tissue plasminogen activator to vascular grafts.

Tissue plasminogen activator labeled with radioactive iodine (125I-tPA) was immobilized on vascular prostheses chemically modified with a thin coating of water-insoluble surfactant, tridodecylmethylammonium chloride (TDMAC). Surfactant-treated Dacron, polytetrafluoroethylene (PTFE), silastic, polyethylene and polyurethane bound appreciable amounts of 125I-tPA (5-30 micrograms 125I-tPA/cm2). Upon exposure to human plasma, the amount of 125I-tPA bound to the surface shows an initial drop during the first hour of incubation, followed by a slower, roughly exponential release with a t 1/2 of approximately 75 hours. Prostheses containing bound tPA show fibrinolytic activity as measured both by lysis of clots formed in vitro, and by hydrolysis of a synthetic polypeptide substrate. Prior to incubation in plasma, tPA bound to a polymer surface has an enzymic activity similar, if not identical to that of the native enzyme in buffered solution. However, exposure to plasma causes a decrease in the fibrinolytic activity of both bound tPA and enzyme released from the surface of the polymer. These data demonstrate that surfactant-treated prostheses can bind tPA, and that these chemically modified devices can act as a slow-release drug delivery system with the potential for reducing prosthesis-induced thromboembolism.

Antigens↗
PubMed1988

Prevention of vascular prosthetic infection with an antibiotic-bonded Dacron graft.

Surfactant-mediated antibiotic bonding was used in an animal model of aortic prosthetic infection. Control grafts, control plus parenteral oxacillin, and oxacillin-bonded Dacron grafts were challenged by local inoculation with Staphylococcus aureus. Ninety percent of controls, 80% of parenteral antibiotic recipients, and only 30% of antibiotic-bonded Dacron grafts became infected (p less than 0.01, p less than 0.03). Antibiotic-bonded grafts were also superior in terms of suture line cultures and patency. In separate experiments in a subcutaneous pouch model, antibiotic bonding significantly improved the median infective dose of Dacron over that of controls and Dacron soaked in cephalosporin. These studies demonstrate that antibiotic-bonded Dacron implants are highly resistant to infection. A multicenter clinical trial is planned.

Animals↗
PubMed1987

Infection-resistant continuous peritoneal dialysis catheters.

The techniques of bonding of anionic antibiotics by treatment with cationic surfactants were applied to continuous ambulatory peritoneal dialysis (CAPD) catheters. The elution of 14C-penicillin from tridodecylmethylammonium chloride (TDMAC) treated silicone elastomer catheters in dialysis solution was biphasic, with 95% dissociated from the catheter by 48 h. Forty percent of the TDMAC left the catheter surface during the initial 2 days. The ability of the surfactant TDMAC to bind antibiotics after incubation in dialysis solution correlated directly with the amount of surfactant remaining. Rats with intraperitoneal dialysis catheters were inoculated with exit site and intraluminal bacterial challenges. Intraperitoneal catheter tips treated with TDMAC-penicillin were rendered more resistant to colonization after exit site and intraluminal bacterial challenges.

Animals↗
PubMed1985

The application of antibiotic bonding to the treatment of established vascular prosthetic infection.

We used surfactant-mediated antibiotic bonding to treat established vascular prosthetic infections in an animal model. The infrarenal aorta of dogs was replaced with a polytef (PTFE) graft locally contaminated with Staphylococcus aureus. Infected grafts were then replaced with control polytef or polytef bonded with benzylkonium chloride and penicillin G tagged with radioactive carbon, or polytef bonded with tridodecylmethylammonium chloride and penicillin G tagged with radioactive carbon. Both types of antibiotic-bonded grafts had significantly fewer infections than control grafts did. The labeled penicillin G remained bound to both groups of antibiotic-bonded grafts for at least three weeks. In a second group of studies, surfactant-treated polytef adsorbed parenterally administered labeled penicillin G in highly significant concentrations compared with control grafts. These studies suggest the possibility that human vascular prosthetic infection may be treated with an antibiotic-bonded graft.

Animals↗
PubMed1985

Prevention of catheter sepsis by antibiotic bonding.

The techniques of antibiotic bonding were applied to the problem of hyperalimentation catheter sepsis. Pretreatment with tridodecylmethylammonium chloride (TDMAC) increased the bonding of 14C-penicillin to polyethylene catheter segments from 3.1 to 212 micrograms/cm and to silicone elastomer catheter segments from 0.09 to 181 micrograms/cm. The elution of the bound ligands from silicone elastomer catheter segments in the presence of plasma was studied. At 2 weeks more than 60% of the bound TDMAC remained adherent to the catheter. The elution of the bonded penicillin from the silicone elastomer catheters was biphasic, initially 95% dissociated after 48 hours of incubation. A bioassay revealed that the dissociated penicillin was bacteriocidal. Polyethylene catheters were placed in the jugular vein of rats and positioned in the right atrium. The catheters were tunneled posteriorly, exited between the forelimb shoulder girdles, and connected to a swivel mechanism. The exit site was inoculated before closure with 1 X 10(8) Staphylococcus aureus. Five days after insertion the catheters were removed via sterile thoracotomy and the tips cultured. Untreated control catheters, catheters treated by antibiotic soaking, and catheters pretreated with TDMAC all had high rates of catheter colonization (60% to 80)%. TDMAC-penicillin-bonded catheters did not become colonized. This difference was significant (p less than 0.005). Antibiotic bonding may prove effective in preventing hyperalimentation catheter sepsis.

Animals↗
PubMed1984

Noncovalent bonding of penicillin and cefazolin to dacron.

Dacron grafts treated with the surfactant, benzalkonium chloride or TDMAC bind significant quantities of penicillin-14C or cefazolin-14C. The treated grafts showed strong antibacterial activity which indicated that bound radioactivity corresponds to the reversible adsorption of biologically active molecules. Bound penicillin-14C or cefazolin-14C slowly dissociates when the grafts are placed in a surgically prepared muscle pouch in the rat. This slow release of antibiotic produces therapeutic levels of antibiotic in the adjacent tissue. Binding can also be achieved by in situ irrigation of surfactant treated grafts with antibiotic or by injection of the antibiotic.

Adsorption↗
PubMed1984

The biochemical bonding of cefoxitin to a microporous polytetrafluoroethylene surface.

Cefoxitin was bound to a microporous polytetrafluoroethylene (PTFE) surface with tridodecylmethylammonium chloride (TDMAC). Bactericidal concentrations of cefoxitin were achieved with very small doses of the antibiotic. Elution of cefoxitin from microporous PTFE occurs by two concurrent first-order processes, each occurring at a different rate constant. Bound cefoxitin inhibits the growth of Staphylococcus aureus in a bioassay. Finally, cefoxitin can be adsorbed to TDMAC-treated microporous PTFE in vivo when the antibiotic is administered locally or intravenously. The application of antibiotic bonding to the prevention of vascular prosthetic infections is discussed.

Animals↗
PubMed1984

Stability of antibiotics bound to polytetrafluoroethylene with cationic surfactants.

This study evaluated the effect of prolonged storage and sterilization on the noncovalent bonding of penicillin to polytetrafluoroethylene grafts. The surfactant tridodecylmethylammonium chloride was unaffected by prolonged storage or sterilization, and its ability to bind penicillin remained constant for as long as 3 months. Steam or ethylene oxide sterilization markedly diminished the antibacterial activity of bound penicillin. However, the antibacterial properties of penicillin remained constant for up to 12 weeks when the grafts were stored at either 4 degrees C or room temperature. Thus, the bonding process appears to increase the stability of the antibiotic, and the data presented suggest that vascular prostheses can be treated with a surfactant, sterilized, and stored for at least 3 months. Grafts can then be treated with an antibiotic in the operating room, washed, and implanted.

Blood Vessel Prosthesis↗
PubMed1982

The role of antibiotic bonding in the prevention of vascular prosthetic infections.

Oxacillin, a negatively charged antibiotic, was bonded to polytetrafluoroethylene (PTFE) grafts using the cationic surfactant, benzalkonium chloride. Control PTFE grafts and bonded grafts prepared at room temperature and at 90 C were placed in the infrarenal aorta of dogs and challenged by local contamination with Staphylococcus aureus. Bonded grafts were superior to controls in negative cultures, patency, and survival. The possible role of antibiotic bonding in the prevention of vascular prosthetic infection is discussed.

Animals↗