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Biomedical subjects

D S Feldman

Publications and source records attributed to D S Feldman.

At least 19 recordsLinked to original sources

Modification of fibrinogen with poly(ethylene glycol) and its effects on fibrin clot characteristics.

The suitability of existing topical fibrin glue preparations for tissue sealing or local drug delivery applications is greatly limited by their poor mechanical properties and the limited capacity of fibrinogen (Fgn) to actively bind growth factors or other therapeutic agents. Poly(ethylene glycol) (PEG) offers potential solutions to these problems by providing a mechanism for increasing the number of crosslinks between adjacent fibrin monomer molecules or for covalently crosslinking Fgn to therapeutic agents. The feasibility of this approach requires the full biological activity, or clottability, of PE glycolated Fgn. This study characterizes the clot characteristics of Fgn modified to varying degrees with monofunctional succinimidyl propionate PEG (5000 Da). The data indicate that, although thrombin clotting times are significantly altered, Fgn maintains 90% of its capacity to clot upon the addition of up to 5 PEG/Fgn. Further derivatization significantly decreases the Fgn clottability. The addition of up to 5 PEG/Fgn has little, if any, effect on the kinetics of degradation by plasmin. The results suggest that limited modification of Fgn with lysine-reactive PEG allows therapeutic enhancement of fibrin glues.

Biocompatible Materials↗

Subfascial implantation of intrathecal baclofen pumps in children: technical note.

OBJECTIVE: Indwelling intrathecal drug delivery systems are becoming increasingly important as a method of neuromodulation within the nervous system. In particular, intrathecal baclofen therapy has shown efficacy and safety in the management of spasticity and dystonia in children. The most common complications leading to explantation of the pumps are skin breakdown and infection at the pump implantation site. The pediatric population poses particular challenges with regard to these complications because appropriate candidates for intrathecal baclofen therapy are often undernourished and thus have a dearth of soft tissue mass to cover a subcutaneously implanted baclofen pump. We report a technique of subfascial implantation that provides greater soft tissue coverage of the pump, thereby reducing the potential for skin breakdown and improving the cosmetic appearance of the implantation site. METHODS: Eighteen consecutively treated children (average age, 8 yr, 7 mo) with spasticity and/or dystonia underwent subfascial implantation of a baclofen pump. These children's mean weight of 42.9 lb is less than the expected weight for a group of children in this age group, ranging from 4 years, 8 months, to 15 years, 7 months. In all patients, the pump was inserted into a pocket surgically constructed between the rectus abdominus and the external oblique muscles and the respective anterior fascial layers. RESULTS: At an average follow-up of 13.7 months, no infection or skin breakdown had occurred at the pump surgical site in any of the 18 patients. CONCLUSION: At this early follow-up, the subfascial implantation technique was associated with a reduced rate of local wound and pump infections and provided optimal cosmetic results as compared with that observed in retrospective cases.

Adolescent↗

Modulation of mechanical properties in multiple-component tissue adhesives.

In vitro, ex vivo, and in vivo studies were performed to investigate the effect of mixing upon the mechanical properties of a two-component tissue adhesive. The hypothesis investigated was that a more complete mixing of the two components would yield an increase in the mechanical performance of the adhesive. This in turn would be demonstrated by improved outcomes in models of clinical sealant application. In vitro stereological analysis of tissue adhesive mixed and delivered by several different applicators demonstrated variation in the amount of mixing provided by each type of delivery system. Ex vivo tensile adhesive strength showed that there was a correlation between the amount of mixing and bonding strength; that is, more thorough mixing demonstrated higher adhesive strength. No significant difference was seen, however, between the different applicator types and impact on in vivo dermal incisional closure strength. There was a correlation, though, in amount of mixing and in vivo hemostasis. In a rabbit spleen incision model, a more thoroughly mixed sealant corresponded with a decrease in time to obtain complete hemostasis, as well as less sealant used. The effects of mixing on tissue-adhesive mechanical performance were influenced somewhat by the amount of mixing provided by the applicator. This effect, however, was dependent upon the sealant formulation and the type of in vivo application.

Animals↗

Congenital pseudoarthrosis of the tibia.

Congenital pseudoarthrosis of the tibia remains one of the most difficult conditions to treat in orthopedic surgery. Seven cases were treated in our hospital by different methods. Three out of seven patients were healed, two of these refractured. At follow-up, the success rate was 14% (one out of seven cases). It is our recommendation that early primary amputation with an appropriate prosthesis should be considered, and that the final evaluation should not be based on obtaining bone union, but on the level of function of the lower extremity.

Adolescent↗

Fibrin scaffold as an effective vehicle for the delivery of acidic fibroblast growth factor (FGF-1).

The effect of wound healing by fibrin and acidic fibroblast growth factor (FGF-1) in an in vivo model was evaluated in this study. Four full-thickness wounds were made on the dorsum of each rabbit (n = 5). Each of these wounds had different treatment groups: control, topical FGF-1 (100 microg/9 cm2), fibrin (2.0 mL at 60 mg/mL fibrinogen), and FGF-1 (100 microg/9 cm2)/fibrin. The animals were sacrificed at the end of 2 weeks. Histomorphometric analysis and mechanical testing were conducted to assess the healing response. FGF-1/fibrin treatment improved the mechanical properties of the healed tissue. Fibrin scaffold exhibited the desired tissue response, as demonstrated by the lack of inflammation, and was deemed an effective carrier for FGF-1.

Animals↗

The effect of solvent extraction and sterilization procedure on the tissue response to Dacron velour.

The effects of solvent extraction and sterilization procedure on tissue response to Dacron velour were studied in a canine model, using histomorphometrical techniques. The solvents used for extraction of low molecular weight moieties were either ethanol or water: the sterilization techniques examined were ethylene oxide (ETO) treatment, steam sterilization, and radiofrequency glow discharge (RFGD) treatment. The effect of the sterilization procedure was most marked in the outermost regions (velour) of the implant; no sterilization effects were determined in the capsule or the knitted regions. Velour in the steam sterilized implants had the smallest blood vessel dimensions compared with those that were treated with ETO or RFGD. The effects of different extraction methodologies appeared to be more significant than sterilization effects and were detected further into the implant. That is, not only were extraction effects detected in the capsule and velour, they were also detected in the outer knitted region. Extraction with water resulted in histological responses considered more biologically desirable (thinner capsule, lower giant cell presence, and larger blood vessel diameters) than responses to extraction with ethanol. Neither extraction nor sterilization effects were detected in the inner layers of the knitted region, which were adjacent to the adhesive.

Animals↗

In vivo wound healing response to a modified degradable fibrin scaffold.

Pooled donor fibrin with an ultimate fibrinogen concentration of 60 mg/ml was used to study its effect on wound healing of surgically created ulcers in a rabbit ear. Water soluble polymer (PEG Mw = 20 KD) beads of 100-150 microns were added (12% by volume) to the fibrinogen to obtain a porous and rough structure. Five 6 mm-diameter ulcers to the depth of bare cartilage were created on each rabbit ear. There were two periods of study (4 and 8 days), with 15 ulcers in each time period, 5 of which were treated with a modified fibrin scaffold, 5 with a non-modified fibrin scaffold, and 5 served as control ulcers. The ulcer sites were subjected to routine histological processing and histomorphometrical quantification. Data analysis revealed significant increases in volume fraction of fibroblast and number of blood vessels in the modified fibrin scaffold treated ulcers over control and non-modified fibrin scaffold treated groups.

Animals↗

Stimulation of angiogenesis by FGF-1 delivered through a modified fibrin scaffold.

A few studies have indicated that repeated dosing of acidic fibroblast growth factor (FGF-1) is essential to be effective in modulating the wound-healing response. However, little investigation has been done to determine the effective dosing regimen of FGF-1 or the appropriate carrier vehicle for this growth factor. The main objective of this study was to determine the effective angiogenic stimulatatory dose of FGF-1 delivered through a modified fibrin matrix, using a rabbit ear ulcer model. Specifically, the aim was to test the effects of FGF-1 on the angiogenic, fibroblastic, and epithelial responses in a wound model. Five 6-mm diameter ulcers to the depth of bare cartilage were created on each rabbit ear. Four different combinations (0.8, 8, 80, and 800 micrograms/ml) of the growth factor were examined across two periods of study. Pooled modified fibrin was used to deliver the growth factor. Histomorphometrical quantification was conducted after routine histological processing of the ulcers sites. Data analysis indicated a strong correlation between concentration and the histomorphometric response. In general, the growth factor treatments affected the healing response and exhibited a dose-dependent behavior. The addition of FGF-1 led to an increase in the angiogenic and fibroblastic responses, as well as an increase in the epithelialization rate. The preferred dose of 8 micrograms initiated a high epithelialization rate, fibroblastic, and angiogenic responses, and was the lowest dose required to initiate these responses.

Animals↗

Spinal muscarinic, glutamatergic and GABAergic receptor systems in cardiovascular regulation.

The central administration of cholinergic agonists can produce a significant increase in arterial blood pressure by enhancing sympathetic vasomotor tone. The stimulation of spinal muscarinic receptors through intrathecal (i.t.) injection of carbachol in rats evoked a significant pressor response that returned to preinjection levels within 30 to 40 min. We investigated the roles of glutamatergic and GABAergic receptors in mediating the hypertensive response to i.t. injection of the muscarinic receptor agonist carbachol and in the maintenance of resting blood pressure and heart rate. The i.t. pretreatment with the N-methyl-D-aspartate (NMDA) receptor antagonists D-AP7 or MK801 maleate (dizocilipine) attenuated the pressor response to i.t. administration carbachol in a dose-dependent manner in conscious, freely moving rats. In contrast, i.t. pretreatment with 6-cyano-7-nitroquinoxaline-2,3-dione, a non-NMDA glutamate receptor antagonist, was not effective in this regard, indicating that the carbachol-evoked pressor response was not mediated through the quisqualate/kainate subtype of glutamate receptors. The i.t. pretreatment with the gamma-aminobutyric acid type B receptor agonist baclofen also inhibited the pressor response to i.t. injection of carbachol at doses that did not alter motor function. To determine whether the pressor response to stimulation of spinal muscarinic receptors required the participation of higher centers, rats received an intracisternal injection of either methylatropine or D-AP7 before the i.t. injection of carbachol. Both intracisternal pretreatments significantly reduced the expression of the pressor response to i.t. injection of carbachol. These findings are consistent with the presence of a powerful modulating spinobulbar muscarinic pressor system. Pharmacological activation of this system involves the participation of spinal and perhaps medullary glutamate-NMDA and gamma-aminobutyric acid type B receptor systems.

2-Amino-5-phosphonovalerate↗

Spinal muscarinic cholinergic and nitric oxide systems in cardiovascular regulation.

Pharmacological activation of muscarinic receptors located in the thoracic spinal cord evokes a marked increase in blood pressure and heart rate. We have previously demonstrated that the cardiovascular response to stimulation of spinal cord muscarinic cholinergic receptors is dependent upon a pharmacologically described ascending spino-bulbar pathway. The purpose of the study was to determine whether the blood pressure and heart rate responses to intrathecal (i.t.) injection of the muscarinic cholinergic receptor agonist carbachol are mediated by a local nitric oxide (NO)-generating system. Freely moving rats were previously prepared with chronic indwelling i.t. and intra-arterial catheters. Both the pressor and tachycardic responses produced by i.t. injection of carbachol were inhibited in a dose-dependent manner by i.t. pre-treatment with the NO synthase inhibitor N-omega-Nitro-L-arginine methylester (L-NAME). To confirm the site of action of the drugs employed in conscious rats, a separate group of rats was anesthetized, and using surgical procedures previously developed in this laboratory, drug distribution was limited specifically to the lower thoracic spinal cord. When carbachol was administered by i.t. injection and localized to the lower thoracic area, muscarinic cholinergic receptor stimulation again produced a marked pressor response, but without the accompanying tachycardia. The ability of N-omega-Nitro-L-arginine methylester (L-NAME) to inhibit the pressor response to carbachol in conscious rats was confirmed in anesthetized rats, although higher doses of L-NAME than those employed in conscious rats were required. L-NAME-induced inhibition of the carbachol-evoked pressor response was reversed by the L-, but not the D-isomer, of arginine. Moreover, i.t. pre-treatment with Methylene blue, that interferes with NO production and function, effectively inhibited the expression of the pressor response to i.t. injection of carbachol. The 'anti-muscarinic' action of L-NAME was not due to a direct interaction with spinal muscarinic receptors, as L-NAME did not significantly displace [3H]methyl-scopolamine from spinal cord membranes in vitro. The results of this study support the hypothesis that spinal muscarinic cholinergic receptors participate in a sympathoexcitatory pathway that interacts either directly or indirectly with a local NO-generating system involved in the regulation of blood pressure.

Animals↗

Analysis of a biodegradable composite for bone healing.

A degradable L-PLA/calcium carbonate composite made of interconnecting phases was examined. This structure was used both to slow the degradation rate and to reduce the brittleness of the ceramic. Both in vitro and in vivo degradation studies were performed. Samples were incubated in buffered saline or placed in the dorsum of rats for 0, 1, or 4 weeks. Mechanical testing was performed on both groups, volume fraction of each component was determined for in vitro samples, and histology was performed on in vivo samples. Failure load, tensile strength, and elastic modulus significantly decreased during the 1st week for both groups. Continued decreases were seen at 4 weeks for in vitro samples but not for in vivo. Failure strain and tensile strength decreased only for in vitro specimens. PLA fraction significantly decreased during the 1st week and then stabilized. Histology showed that tissue ingrowth occurred at 4 weeks. The decrease in mechanical properties was probably a result of the decreased PLA fraction. The stabilization and even a slight increase in tensile strength and failure strain in the in vivo samples was probably due to the tissue ingrowth forming an implant-tissue composite.

Animals↗

Fracture-dislocation of the neck of the talus in a ten-year-old child: a case report and review of the literature.

A ten-year-old female underwent open reduction and internal fixation of a Hawkins type III fracture of the talar neck. The fracture united within three months. However, avascular necrosis of the body of the talus occurred. Partial collapse of the talar body ensued despite protection from weight-bearing for eight months after surgery. This case illustrates that fracture-dislocation of the talus can occur in a child and has a guarded prognosis.

Child↗

The role of intraoperative frozen sections in revision total joint arthroplasty.

We performed a retrospective analysis of thirty-three consecutive total hip and knee (twenty-three hip and ten knee) revision arthroplasties during which intraoperative frozen sections were analyzed. Data for the study were collected by means of a review of the charts, radiographic analysis, and evaluation of both frozen and permanent histological sections. The frozen sections, of periprosthetic tissue at the bone-cement interface or the pseudocapsule, were considered positive for active infection if there were more than five polymorphonuclear leukocytes per high-power field in at least five distinct microscopic fields. All patients were available for follow-up, at an average of thirty-six months (range, seventeen to seventy-nine months) after the initial revision operation. The frozen sections from ten patients were positive for infection, and those from twenty-three patients were negative. Comparison of the results of the analyses of the frozen sections (both positive and negative) with those of the analyses of the permanent histological sections of similar tissue showed a correlation of 100 per cent (sensitivity, 1.00; specificity, 1.00; and accuracy, 1.00). Nine patients had positive intraoperative cultures, and all of them had positive frozen sections (sensitivity, 1.00). Of the twenty-four patients who had negative intraoperative cultures, twenty-three had negative frozen sections (specificity, 0.96). Of the nine patients who had positive intraoperative cultures, only two were found to have infection on intraoperative gram-staining. The surgeon's operative assessment regarding the presence of infection, compared with the final pathological diagnosis, demonstrated a sensitivity of 0.70, a specificity of 0.87, and an accuracy of 0.82. All ten patients who had positive frozen sections were managed with excision arthroplasty; six of them subsequently had reimplantation, and the excision was the definitive procedure in the remaining four. One patient who had had a delayed reimplantation had a secondary skin slough and eventually was managed with an arthrodesis of the knee. In the group that had negative frozen sections, eighteen patients had a primary exchange revision arthroplasty and five had a delayed reimplantation. At the time of follow-up, one patient who had had a delayed reimplantation had radiographic loosening of the femoral component and was asymptomatic. One patient who had had a primary exchange arthroplasty was managed with a second revision because of aseptic loosening. There was no clinical recurrence of infection in any patient. The data indicate that analysis of frozen sections of periprosthetic tissue is a reliable predictor of the presence of active infection during revision joint arthroplasty. We recommend its use to differentiate aseptic from septic loosening.

Adult↗

Localization of cholinergic neurons involved in the cardiovascular response to intrathecal injection of carbachol.

Recent studies in this laboratory have demonstrated the ability of acetylcholine receptor agonists to produce systemic arterial pressor responses through stimulation of spinal muscarinic receptors. In urethane-anesthetized rats a new surgical procedure was employed to permit microinjection of drugs into the cerebrospinal fluid surrounding the medulla without significant redistribution to spinal sites and vice versa. Pretreatment with intracisternal (medullary level) injection of 10 micrograms of atropine significantly inhibited the expression of the pressor response produced by intrathecal injection of 5 micrograms of carbachol. This inhibition was due at least partly to the interruption of a medullary component of a spinobulbar pathway involving medullary muscarinic receptors. It was not due to redistribution of atropine from medullary to spinal sites since significant levels of atropine were not detected in the spinal cord after intracisternal injection of the drug. The remainder of the pressor response to intrathecal carbachol after medullary muscarinic receptor blockade was most likely due to interactions within the spinal cord itself.

Animals↗

Plasma ascorbic acid concentrations relate inversely to blood pressure in human subjects.

This study relates antioxidant status and blood pressure (BP) in 168 healthy residents of Augusta, GA, following usual diets. BP ranges were systolic (S) 84-152, mean 112 +/- 1 mm Hg, and diastolic (D) 52-96, mean 72 +/- 1 mm Hg. Plasma concentrations of ascorbic acid (AA) were significantly inversely related to SBP (r = -0.18, P < 0.05) and DBP (r = -0.20, P < 0.01); with regression equations SBP vs AA = -0.083C + 116 and DBP = -0.077C + 76. Highest and lowest quintiles of AA differed significantly in mean SBP (108 +/- 2, 113 +/- 2 mm Hg) and DBP (69 +/- 1, 74 +/- 2), P < 0.05. Plasma AA concentrations were significantly lower in the smokers. By deleting smokers, the inverse relations of SBP and DBP with plasma AA and the slopes of the equation were enhanced. Plasma selenium, alpha-tocopherol, alpha-tocopherol:cholesterol ratio, retinol and taurine were not related to BP; whereas male gender, body mass index, body fat distribution, plasma cholesterol, low density lipoprotein cholesterol, and triglycerides correlated.

Adipose Tissue↗

Clinical efficacy of aspirin and dextran for thromboprophylaxis in geriatric hip fracture patients.

The clinical efficacy of thromboprophylaxis with aspirin and dextran 40 was compared in a prospective review of 530 geriatric hip fracture patients treated surgically. All patients were also treated with early mobilization with weight bearing as tolerated and above-knee elastic stockings. In addition to clinical efficacy in preventing thromboembolic complications [deep vein thrombosis (DVT), pulmonary embolism (PE)], safety and cost-effectiveness were also assessed. The overall incidence of clinical thromboembolic disease was 2.8% (DVT = 0.4%, PE = 2.4%). The incidence of DVT (0.5%) and PE (2.6%) in the aspirin group was essentially the same as the incidence of DVT (0.3%) and PE (2.4%) in the dextran group. The inhospital mortality rate (aspirin 4.6%, dextran 3.8%), wound drainage (aspirin 1.5%, dextran 0.9%), deep wound infection (aspirin 0.5%, dextran 0.3%), gastrointestinal bleeding (aspirin 2.1%, dextran 1.5%), and congestive heart failure (aspirin 2.6%, dextran 1.8%) did not differ significantly between the two groups. The intraoperative transfusion rate was similar in both groups (aspirin .65 units, dextran .55 units). However, postoperatively, the transfusion rate was significantly higher in the dextran group (aspirin .26 units, dextran .41 units, p < .05). The treatment of thromboembolic complications was the same for each group and therefore represents similar treatment costs. However, the cost of prophylaxis with dextran was $309 per patient and with aspirin was $1.79 per patient. Our findings suggest that, based on clinical diagnostic criteria, aspirin and dextran are equally effective thromboembolic prophylactic agents in geriatric hip fracture patients. The safety, cost, and ease of administration of aspirin may make its use more desirable.

Aged↗