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Biomedical subjects

J Hollinger

Publications and source records attributed to J Hollinger.

18 recordsLinked to original sources

Recombinant human acidic fibroblast growth factor and fibrin carrier regenerates bone.

Bone regeneration promoted by acidic recombinant human fibroblast growth factor (rhFGF-1), rabbit demineralized bone matrix (rDBM), and a fibrin (f) delivery system was measured in critical-sized defects in rabbits' radii. A unilateral segmental defect 20 mm in length was prepared in radii of 48 skeletally mature New Zealand White rabbits divided equally between 4- and 8-week cohorts. The temporal cohorts were divided equally among four treatment groups: rDBM, rDBM/f, rDBM/rhFGF-1/f, and rhFGF-1/f. Data for the fifth group, untreated critical-sized defects, were exploited from previous published reports from this laboratory. In response to experimental treatments, radiomorphometric and histomorphometric methods were used to derive quantitative outcome data that were tested by analysis of variance and post hoc multiple comparison tests (significance p </= 0.05). Radiomorphometric data (percentage of radiopacity of defect) were acquired at the day of the operation and every 2 weeks thereafter, whereas histomorphometric data (square millimeters of new bone formation) were determined at term. The objective for the study was to develop candidate bone regenerative therapies. Therefore, the hypotheses were that experimental treatments would promote bone formation within critical-sized defects and that one treatment would be superior to the rest. Testing hypotheses was achieved with quantitative methodology, and data were subjected to statistical models. Radiopacity at each 2-week period was greater in treated defects than in untreated critical-sized defects. The amount of radiopacity promoted by rDBM/f and rhFGF-1/f at 8 weeks was equivalent and was greater than antecedent times. Histomorphometric data analyses indicated that rDBM/f and rDBM evoked the same quantity of new bone formation at 4 weeks; by 8 weeks, all treatments except rDBM/f had more new bone within the critical-sized defects in comparison to untreated defects. That rDBM/f promoted less new bone than rDBM alone may suggest fibrin decreases bone formation, perhaps by impeding local solubility of endogenous and rDBM-containing signaling molecules. However, rhFGF-1/f promoted a significant and unexpected increase in bone formation response that could refute the previous notion. In conclusion, the combination of rDBM/rhFGF-1/f may represent a significant, new osteogenic therapeutic regimen. Additional assessments in higher order species must be accomplished to corroborate efficacy.

Animals↗

Critical aspects of tissue-engineered therapy for bone regeneration.

Recent advances in bone tissue engineering are established on the understanding of an engineered scaffold, the molecular milieu within the osteogenic site, and the cell(s) predisposed to an osteogenic lineage. Advances in the incorporation of a generative vehicle into a skeletal defect require temporal and spatial distribution of the scaffold, growth factor, and cell compatible with enhanced bone healing. Monitoring events culminating in osteogenesis has focused on phenotypic and intracellular indicators. Phenotypic and intracellular indicators include the presence of receptors and intracellular signals that enable cell proliferation and differentiation. Progress in the areas of scaffold design, growth factor utilization, bone cell lineage, and intracellular signaling are reviewed.

Animals↗

Assessment of an experimental bone wax polymer plus TGF-beta 1 implanted into calvarial defects.

The study reported describes an experimental biodegradable polymer ceramic composite with wax-like handling properties that was combined with 2.0 micrograms of recombinant human transforming growth factor beta (rhTGF-beta(1)). The polymer/rhTGF-beta(1) combination was introduced into standard-sized calvarial defects in rabbits to evaluate biodegradability, biocompatibility, hemostasis control, and bone promotion. The experimental wound model was a standard-size circular calvarial defect 8 mm in diameter. The experimental design included 24 skeletally mature New Zealand white rabbits divided evenly between two time periods (6 and 12 weeks) and among three experimental treatments (untreated defects and defects treated with polymer with or without rhTGF-beta(1)). Evaluations consisted of clinical examinations, standarized radiography, radiomorphometry, as well as histology and histomorphometry. Data were analyzed by an Analysis of Variance (ANOVA) and Fisher's Protected Least Significant Difference test at each time period (level of significance p < or = 0.05). Radiomorphometry data indicated that standard-sized defects treated with the wax-like polymer alone and the polymer plus 2.0 micrograms of TGF-beta(1) were significantly more radiopaque than control sites at both 6 and 12 weeks. Histomorphometric data revealed the amount of new bone was significantly greater at 6 weeks in the polymer plus 2.0 micrograms of TGF-beta(1) and in the control group than in the polymer alone. Moreover, at 12 weeks, there was significantly more new bone in the control than in either the polymer alone or the polymer plus 2.0 micrograms of TGF-beta(1). We speculate the incomplete biodegradation of the polymer ceramic composite contributed to the radiopacity and may have retarded osseous regeneration. It is important that the bone wax-like polymer material was biocompatible and acted as a hemostatic agent.

Animals↗

Charged beads enhance cutaneous wound healing in rhesus non-human primates.

Enhanced cutaneous wound healing by positively charged cross-linked diethylaminoethyl dextran beads (CLDD) was studied in a standardized incisional wound model in 20 adult and 20 geriatric Macaca mulatta (rhesus) partitioned equally over five time periods. Physiologic saline served as a control. Soft-tissue linear incisions were prepared between and 1 cm inferior to the scapulae. There were four incisions per rhesus; each incision was 1.5 cm long with 1 cm of undisturbed tissue between incisions, and both the experimental CLDD and physiologic saline treatments were administered to each rhesus. The incision treatments were either CLDD and soft-tissue closure with 4-0 BioSyn sutures or sterile physiologic saline and closure with 4-0 BioSyn sutures. The hypothesis was CLDD would enhance cutaneous wound repair. Verification of the hypothesis consisted of clinical examinations and histologic and tensiometric evaluations on biopsy specimens at 10 and 15 days, whereas 5-day and 2- and 4-month groups were assessed clinically and biopsy specimens were assessed histologically. The clinical course of healing for all groups was unremarkable. At 10 days, incisions in adult rhesus treated with CLDD had a 30-percent greater tensile strength compared with the physiologic saline-treated incisions (p = 0.01), whereas for geriatric rhesus, the CLDD treatment proved to be 15 percent greater in tensile strength compared with the physiologic saline cohort (p = 0.11). By day 15, incisions in adult rhesus were 26 percent stronger than the saline treatment group (p = 0.07), and the difference was 36 percent (p = 0.02) for the geriatric rhesus. From 5 through 15 days, histologic observations revealed a gradual decrease in quantity and integrity of CLDD, with no remnants of CLDD at either 2 or 4 months. Macrophages and multinucleated giant cells were localized in the dermis and were associated with the CLDD. These cells decreased commensurately with the decrease of CLDD beads. The data suggest that CLDD can enhance significantly the tensile properties of healing cutaneous wounds in both adult and geriatric rhesus. Moreover, if the wound healing is enhanced in geriatric patients, this finding may be clinically germane to conditions where wound healing is compromised, such as in diabetics and patients on steroids.

Animals↗

The integrated processes of hard tissue regeneration with special emphasis on fracture healing.

When bone is fractured, a sequence of dynamic events ensue to restore form and therefore function. Many key biologic cell regulators for these events have been identified, expressed through recombinant technology, and their roles posited. Moreover, the availability of recombinantly engineered molecules, such as the bone morphogenetic proteins with their potential to benefit patient care, has ushered in an important era in clinical dentistry that may eliminate either autografting or bank bone allografts. Therefore, in this review article, we have highlighted some of the exciting biologic regulators relevant to bone fracture healing and outlined the dynamic elements in this process.

Animals↗

Grief and AIDS: surviving catastrophic multiple loss.

This article explores the issues of grief brought about by the AIDS epidemic. As people affected by the epidemic experience multiple deaths in both their personal and professional lives, the parallel epidemic of grief is reaching crisis proportions. Traditional grief responses are compared with multiple loss grief and appropriate clinical interventions are explored. The phenomena of trauma, survivor guilt, Post-Traumatic Stress Disorder and other historic examples of multiple loss (holocausts) are examined. The existential questions of how to hold hope as we live in an "abyss of trauma, death and grief" concludes this article.

Acquired Immunodeficiency Syndrome↗

Maxillary alveolar cleft repair in dogs using recombinant human bone morphogenetic protein-2 and a polymer carrier.

Recombinant human bone morphogenetic protein-2 was evaluated in maxillary alveolar clefts in 24 adult, skeletally mature Foxhound dogs. Bilateral clefts were prepared, 1 cm in bony width, lined with healthy epithelium with functional teeth on each side, and were expected not to heal spontaneously with new bone. Preparation of bilateral clefts in 24 dogs permitted 48 recipient sites divided evenly among four treatment and two time periods (2 and 4 months), yielding six replicates per treatment per time. The overall goal for the study was to regenerate bone in the cleft using one of three treatments: (2) 200 microgram recombinant human bone morphogenetic protein-2 combined with the copolymer poly(lactide-co-glycolide) and autogenous blood, (2) poly(lactide-co-glycolide) and autogenous blood, or (3) an autograft from the posterior iliac crest. A fourth group consisted of untreated alveolar cleft defects. At designated times, dogs were euthanized, and the recipient beds with contiguous bone were recovered, processed, and assessed radiographically and histologically. Autograft-treated defects had more bone than other treatments at 2 months; however, by 4 months, there were no differences among treatments, except for the poly(lactide-co-glycolide) group, which had the least amount of bone. Response to the recombinant human bone morphogenetic protein-2 may have been suboptimal either because the dose was too low or because the poly(lactide-co-glycolide)-autogenous blood delivery system did not temporally maintain and spatially position recombinant human bone morphogenetic protein-2 at the recipient bed. In addition, the development of a nonhealing, critical-sized defect in the maxilla of the dog appears to require a more aggressive resection of bone to preclude spontaneous osseous regeneration.

Alveolar Process↗

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↗

Factors for osseous repair and delivery. Part I.

The healing fracture, autograft, and allograft repair are associated with a panoply of unique biochemical and cellular processes. Temporal harmony between the components of these processes can ensure restoration of form and function to bony deficiencies incurred as a consequence of developmental deformity, traumatic incident, or surgical resection. Part I of this editorial describes the chronobiology of the stages of several types of naturally occurring bone repair materials and the interaction of the component cells and their biochemical products. The emphasis is on growth and inductive factors, which are keys to promoting bone regeneration.

Animals↗

The healing sternum: a comparison of osseous healing with wire versus rigid fixation.

Although median sternotomy is used for most cardiac procedures, postoperative dehiscence remains a serious and persistent problem. This investigation was designed to assess new bone formation and sternal healing across the linear osteotomy of the sternum and to determine if rigid fixation would enhance bony healing and thus decrease unfavorable sequelae. To test this hypothesis, 14 skeletally mature baboons (Papio anubis) underwent standard median sternotomy; seven sternotomies were closed with interrupted 24-gauge cerclage wires, and seven, with thin Vitallium compression miniplates and transverse lag screws. The sterna from each group were harvested en bloc at 4 and 8 weeks, radiographed, processed, and serially sectioned and stained for histomorphometry to assess the quantity of new bone across the linear osteotomy. Clinical stability was superior with the plated and lag screw group at 4 weeks; however, by 8 weeks, no clinical difference between treatments was apparent. Histomorphometric analysis indicated that the linear osteotomy gap treated with plates and screws was less than the gap associated with the wire group. Rigid fixation of the sternum resulted in earlier union with primary osseous healing, suggesting greater inherent stability. these factors may decrease adverse sequelae for this procedure.

Animals↗

Calvarial bone regeneration using osteogenin.

This experimental study reports on the application of a partially purified noncollagenous protein extracted from cortical bone to restore craniotomy defects in Papio species (baboon). The partially purified protein (osteogenin) produced significantly more bone formation in calvarial wounds than was found in the untreated controls. There were no adverse tissue reactions from the implanted xenogeneic osteogenin.

Animals↗

[The critical 3-day fever-exanthema in young children (exanthema subitum, Zahorsky roseola infantum)--what is new?].

As to the present knowledge the critical rose rash of infants (exanthema subitum, roseola infantum) means to be an exanthematous infectious disease that, occurring preferably in elder babes and younger infants (1st--3rd year of life), is caused by the newly detected herpesvirus (now the sixth one) pathogenic for man. The natural contamination in our latitude is intense (60-75%), and the probably lifelong immunity in the majority of cases is acquired in infancy. Though experts in the clinical subject do stress all the time the exanthema subitum to be the most frequent exanthematous disease in early infancy and infancy, infection chains tested to exanthema, respectively epidemics are observed decidedly seldom. Consequently, most of all infections use to develop clinically inperceptibly or even with other symptoms (and without an exanthema); the exanthema up to now obligatory for establishing the diagnosis uses to appear only in the minority of all cases and in the great majority of them the seroconversion is clinically silent. The prognosis of the exanthema subitum is in force to be good; the disease is the special field of activity for ambulatorily acting physicians (paediatrist, general practitioner). To begin with, the status diagnostically unclear and high-febrile for several days, the central-nervous excitability occurring in many cases, and in some children the appearing of dramatic febrile convulsions, as well as gastroenteric symptoms perpetually give rise to differential diagnostic considerations and sometimes even to a (false) antibiotic therapy. In case of an affection by herpesviruses principally a latency (persistence) of the virus lasting for years (possibly even lasting for life) in human beings is to be taken into account; this condition is also current for HHV 6. On occurring of an immune debility a release and a discharge of herpesviruses--not only by children suffering from an exanthema subitum (!)--are possible so that human beings of each age may come into question to be the source of infection. Double infections of human immune cells (for instance HHV 6 and HIV 1 simultaneously) already have been found. The necessary studies in order to clarify essential clinical and virological problems are world-widely in full activity, and new cognitions (further symptoms of diseases associated with HHV 6, possibly affections in prenatal infections and so on) are soon to be taken into account.

Child, Preschool↗

[New knowledge of Zahorsky exanthema subitum (critical 3-day fever-exanthema, roseola infantum].

A survey is given on the history, characteristic symptoms and recent data of the etiology of exanthem subitum (Zahorsky's disease, sixth disease, roseola infantum). Some cases are presented and modern diagnostic techniques for atypical cases are discussed. The disease is caused by an infection with the human herpesvirus-6 (HHV 6; syn.:, "human B-lymphotropic virus", HBLV). Most babies and small children have an asymptomatic infection usually leading to lifelong immunity. The typical "exanthem subitum" develops only in a minority of the infected and susceptible persons. We suggest that the novel human herpesvirus-6 also has the potential of lifelong persistence in humans and can then be shedd at any age in case of acquired immunodeficiencies. World-wide research in this field is carried out by several working groups and new data will be available in a few years.

Antibodies, Viral↗

A review of the incidence of pain after an operation treatment visit: Part I.

This review presented some typically encountered painful sequellae from routine restorative dental treatment. A brief description of the importance of Tomes' processes and free nerve endings were mentioned also. This review should serve as a background for a clinical study concerning posttreatment pain that will be described in a later article.

Dental Restoration, Permanent↗