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[Effects of BMP-2 gene therapy on vascularization in repairing bone defects].

OBJECTIVE: To study the effects of BMP-2 gene therapy on vascularization in repairing bone defects. METHODS: The isolated rabbit mesenchymal stem cells (rBMSC), after being transfected by adenovirus carrying BMP-2 gene (Ad-BMP-2) and seeded on xenogeneic bone scaffolds, were used to repair 1.5 cm-long radius bone defects. Five methods were in use in the experiments: Ad-BMP-2 infected rBMSC plus antigen-free bovine cancellous bone (BCB, Group A), rBMSC-BCB plus reconstructed hBMP-2 (Group B1), Ad-LacZ infected rBMSC-BCB (Group C), rBMSC-BCB (Group D) and only BCB scaffolds (Group E). After 4, 8, and 12 weeks of the operations, capillary vessel ink infusion, vascular endothelial growth factor ( VEGF) immunohistochemical staining and histological examination were conducted. RESULTS: After 4 weeks of the operations, usually in Group A one newly formed artery was found in every pore between the trabeculae of the BCB. The density of these intraosseous vessels was high in the periphery and decreasing towards the center of the grafts; by transmission electron microscopy, osteoblasts were always next to vascular endothelial cells and gradually developed into osteocytes with the increase of capillary vessel; VEGF expression were apparently enhanced in mesenchymocytes. CONCLUSIONS: BMP-2 gene therapy, by up-regulating VEGF expression, indirectly induces vascularization of grafts and is of great value to the treatment of bone in union and bone defects.

Animals↗

Plasma atropine concentrations via intravenous, endotracheal, and intraosseous administration.

To date, there have been limited studies on the pharmacokinetics of intravenous atropine and no pharmacokinetic studies on the endotracheal or intraosseous administration of atropine. This study examines the time to peak plasma concentration of atropine following intravenous, endotracheal, and intraosseous administration in anesthetized monkeys using a triple crossover design. Plasma atropine was assayed by a radioreceptor method. The time to peak plasma concentration of atropine was shortest with intravenous administration; and longest with endotracheal administration. The mean plasma concentration of atropine was significantly higher in intravenous administrations than in endotracheal administrations at 0.75 and 2 minutes; compared to that noted in intraosseous administrations, the concentration was significantly higher only at 0.75 minutes. The mean plasma concentration of atropine administered intraosseously was significantly higher than that of endotracheal administrations at 5 minutes and was greater than that of intravenous and endotracheal administrations for the samples collected from 5 to 30 minutes. The endotracheal and intraosseous routes provide alternatives to the intravenous administration of atropine when intravenous access is limited or not available.

Animals↗

Intraosseous fluid administration in emergencies.

15 patients who needed prompt administration of fluids and in whom cannulation of a vein proved difficult were given various solutions and drugs by the intraosseous route. The results of this therapy were rewarding and no serious complications were attributed to the procedure.

Adolescent↗

Effect of simulated joint effusion on subchondral haemodynamics and metabolism.

The purpose of the present study was to investigate the effect of simulated joint effusion on pO2, pCO2, the regional blood flow and intraosseous bone marrow pressure in the subchondral bone of rabbit. Mass spectrometry was used for simultaneous and continuous registration of subchondral pO2 and pCO2, while the relative argon signal was used for qualitative estimation of regional bone blood flow. The bone marrow pressure was recorded continuously by pressure transducers. Isotonic sodium chloride infusion at a constant pressure of 75 mmHg into the knee joint cavity constituted the basis for joint effusion. An instant increase in the subchondral bone marrow pressure followed the joint effusion (P less than 0.001). This resulted in a significant (P less than 0.01) decrease in the qualitative bone blood flow, significant (P less than 0.01) hypoxia and significant (P less than 0.01) hypercapnia in the subchondral bone. Joint effusion always lasted 30 minutes. Following its release all changes were reversed to normal values within 15 minutes. Within the period of observation no nervous or humoral factors seem to be brought into action. It was concluded that regional venous stasis was responsible for all changes, and that joint effusion should not be left untreated for long periods.

Animals↗

Intraosseous transfusion in an anesthetized swine model using 51Cr-labeled autologous red blood cells.

Peripheral venous access can often be difficult to obtain in infants and young children. Landmark articles in the 1940s showed that the intraosseous (IO) route was a viable one for resuscitation. While anecdotal reports and clinical experience suggest that blood products can be transfused via the IO route, it has not been specifically studied nor documented. We performed a prospective study to document the feasibility of red blood cell transfusion via the IO space. We studied the rapid infusion of 51Cr-labeled red blood cells via the IO space through an 18-gauge IO needle in three normovolemic immature swine. Serial central venous samples were removed at 30 seconds and at 1, 5, 15, 30, and 60 minutes and analyzed for evidence of radiolabeling. Our results revealed rapid delivery of radiolabeled red blood cells into the central circulation with no evidence of early heomolysis. Highest counts were seen in samples taken at 30 seconds to 1 minute. We conclude that the IO route is a viable means for blood transfusion in a nonhemorrhagic model.

Animals↗

Evaluation of safety and pharmacokinetics of vancomycin after intraosseous regional limb perfusion and comparison of results with those obtained after intravenous regional limb perfusion in horses.

OBJECTIVE: To evaluate the clinical effects and pharmacokinetics of vancomycin in plasma and synovial fluid after intraosseous regional limb perfusion (IORLP) in horses and to compare results with those obtained after IV regional limb perfusion (IVRLP). ANIMALS: 6 horses. PROCEDURES: 1 forelimb of each horse received vancomycin hydrochloride (300 mg in 60 mL of saline [0.9% NaCl] solution) via IORLP; the contralateral limb received 60 mL of saline solution (control). Solutions were injected into the medullary cavity of the distal portion of the third metacarpal bone. Synovial fluid from the metacarpophalangeal (MTCP) and distal interphalangeal (DIP) joints and blood were collected prior to perfusion and 15, 30, 45, 65, and 90 minutes after beginning IORLP, and synovial fluid from the MTCP joint only and blood were collected 4, 8, 12, and 24 hours after beginning IORLP. Plasma urea and creatinine concentrations and clinical appearance of the MTCP joint region and infusion sites were determined daily for 7 days. Results were compared with those of a separate IVRLP study. RESULTS: Clinical complications were not observed after IORLP. Mean vancomycin concentration in the MTCP joint was 4 microg/mL for 24 hours after IORLP. Compared with IORLP, higher vancomycin concentrations were detected in the DIP joint after IVRLP. Compared with IVRLP, higher vancomycin concentrations were detected in the MTCP joint for a longer duration after IORLP. CONCLUSIONS AND CLINICAL RELEVANCE: IORLP with 300 mg of vancomycin in a 0.5% solution was safe and may be clinically useful in horses. Intravenous and intraosseous routes may be better indicated for infectious processes in the DIP and MTCP joints, respectively.

Animals↗

[Intraosseous puncture in preclinical emergency medicine. Ten years experience in air rescue service].

INTRODUCTION: The intraosseous puncture (IO) is a fast and safe alternative to the puncture of peripheral veins in emergency situations in children < or =6 years of age. The purpose of this paper is to summarize 10 years of experience on the prehospital use of the IO method by the Helicopter Emergency Medical Service (HEMS) "Christoph 22", Ulm. MATERIALS AND METHODS: This was a retrospective study from 1 January 1996 to 31 December 2005. RESULTS: Out of a total of 9,549 missions, the proportion of children was 11.1%. In 27 children (4.2% of the children < or =6 years of age) an IO puncture was performed. Patients of the IO group were younger (1.0 vs. 3.7 years of age; p<0.001) and showed a higher degree of injury severity (NACA 6 vs. 4; p<0.001) compared to the total children group. In all children of the IO group (100%), the intraosseous puncture was the method of first choice to obtain access to the vascular system by the HEMS team. In 96.4% of these cases (26/27), the first IO puncture attempt was successful - in one child, a second puncture attempt was necessary. A standardized puncture technique was performed using the proximal tibia. The time required for successful placement of the IO infusion line was 60 s or less in all cases. In 37% of the cases (10/27) the IO infusion line was used for induction of general anaesthesia; dosage and onset of administered drugs were described as being equivalent to a peripheral infusion line. In all cases, the IO needle was replaced in-hospital within 2 h by a central or peripheral iv line. No complications were observed. CONCLUSIONS: The IO infusion technique is a simple, fast and safe alternative method for emergency access to the vascular system in children < or =6 years of age in the prehospital setting.

Aircraft↗

Evaluation of intraosseous vs intravenous antibiotic levels in a porcine model.

OBJECTIVES: To compare intraosseous vs intravenous routes of administration and their effects on serum levels of four antibiotics in an animal model. DESIGN: Prospective controlled study comparing two routes of drug administration. SETTING: Research laboratories of a large pharmaceutical company. PARTICIPANTS: Twenty male and female domestic swine weighing 10 to 20 kg. INTERVENTIONS: The animals were anesthetized and treated with controlled ventilation. The animals were divided into one of four groups: (1) intravenous and intraosseous cefotaxime sodium (50 mg/kg), (2) intravenous and intraosseous chloramphenicol sodium succinate (25 mg/kg), (3) intravenous and intraosseous vancomycin hydrochloride (15 mg/kg), or (4) intravenous and intraosseous tobramycin sulfate (2.5 mg/kg). There was a 24-hour clearance period for groups 1 and 2 and a 48-hour clearance period for groups 3 and 4. Serum drug levels were measured at 1, 15, 30, 45, 60, 90, and 120 minutes after intravenous and intraosseous administration of the respective antibiotics. Control and treated tibias were sampled for drug levels at the end of the experiment. MEASUREMENTS AND MAIN RESULTS: - Peak serum concentrations for intravenously administered antibiotics were within the therapeutic range. Peak serum levels after intravenous and intraosseous administration were 102 and 82 mg/L, respectively for cefotaxime; 13.9 and 6.3 mg/L, respectively, for chloramphenicol; 24.5 and 3.8 mg/L, respectively, for vancomycin; and 7.1 and 1.3 mg/L, respectively, for tobramycin. CONCLUSIONS: Cefotaxime may be administered intraosseously when intravenous access is not possible. We cannot recommend chloramphenicol or vancomycin for intraosseous administration, because serum levels were not comparable with those following intravenous administration. Findings with tobramycin suggested a lack of achievement of serum levels comparable with those following intravenous administration.

Animals↗

Comparison of intraosseous, central, and peripheral routes of sodium bicarbonate administration during CPR in pigs.

Obtaining venous access continues to be one of the most difficult problems faced by a physician caring for the pediatric patient in cardiac arrest. Our study examined the use of the intraosseous route (through the bone) to obtain venous access for sodium bicarbonate administration in a cardiac arrest model. Ventricular fibrillation was induced in 23 domestic swine. Cardiopulmonary resuscitation was performed for five minutes and sodium bicarbonate (1 mEq/kg) was administered through a peripheral IV line (n = 6), a central IV line (n = 5), or intraosseously (n = 6). Controls (n = 6) did not receive bicarbonate. Blood pH was sampled every two minutes for 30 minutes from the right ventricle, left ventricle, and femoral artery. An analysis of variance revealed that the central and intraosseous routes were significantly different (P less than .05) from the peripheral group, and that all three groups were significantly different (P less than .05) from the control. Pathology studies revealed only minor damage to bone when sodium bicarbonate was administered intraosseously. These data demonstrate that the intraosseous route is a rapid and effective alternative for venous access in a cardiac arrest model.

Animals↗

Intraosseous anesthesia: implications, instrumentation and techniques.

BACKGROUND: The author reviews historical methods and the instruments used to bring about intraosseous anesthesia, or IOA; discusses the criteria for successful use of the intraosseous injection, or IOI, technique; and provides recommendations. TYPES OF STUDIES REVIEWED: Articles from before 1990 consisted of subjective reports of patient types and procedures performed using IOI as a primary technique. Studies published after 1990 yielded subjective findings on indications for expanded clinical use. The author discusses the expansion of the role of IOI relative to integrated local anesthetic delivery systems. RESULTS: The literature and studies verify the efficacy of IOI as a supplemental or primary technique. The author recommends anesthetics and infusion sites, and reports on the patients' perceptions of comfort. CONCLUSIONS AND CLINICAL IMPLICATIONS: IOI can be used as a supplemental or primary technique to bring about local anesthesia in routine dental procedures. It can be used as a supplemental technique with mandibular nerve blocks to enhance deep pulpal anesthesia. It can be used as a primary technique so that patients do not experience numb lips or tongues postoperatively. Dentists can appreciate the immediate onset of anesthesia and reduced dosage levels of anesthetics associated with using IOI.

Anesthesia, Dental↗

The use of skin allograft with donor-specific tolerance in a rabbit model of full-thickness burn.

UNLABELLED: Previous studies in our laboratory demonstrated that portal vein or intraosseous administration of donor bone marrow cells for modulation of the central immune system is likely to be beneficial for allograft tolerance induction in rabbits. We recently reported that the severity of host conditioning for donor-specific tolerance induction was reduced without loss of efficacy by using a single intraosseous injection of donor bone marrow cells without immunosuppressive agent administration or T cell depletion. We now further investigated the feasibility and effectiveness of skin allografting using donor-specific tolerance to treat full-thickness burns. MATERIALS AND METHODS: Dutch rabbits were used as recipients, and Japanese white rabbits were used as donors. Three experimental groups of burned rabbits were studied. Group I, allograft control; group II, allograft plus total-body irradiation; group III, allograft plus total-body irradiation and bone marrow infusion. Allograft survival times were determined by macroscopic and histopathologic examinations. RESULTS: Mean (S.D.) skin allograft survival was as follows: group I, 13.2 (4.1) days; group II, 15.2 (3.7) days; group III, 108.4 (14.3) days. CONCLUSION: We have shown the potential to perform long-term skin allografts by the induction of donor-specific tolerance in a rabbit model of burn.

Animals↗

The effects of ischemia on long bone vascular resistance.

An in vitro canine tibia model was used to assess the effects of 48 h of hypothermic (4 degrees C) ischemia on bone vascular resistance and on responsiveness of intraosseous blood vessels to circulating norepinephrine. Three groups of bones were studied: Group I (n = 11), 48 h hypothermic ischemia; Group II (n = 11), 48 h hypothermic ischemia with pretreatment with allopurinol and oxypurinol; and Group III (n = 10), no ischemia. Resting vascular resistance in both ischemic groups (79 and 74 mmHg/ml/min) was significantly higher (p less than 0.0001) than in the nonischemic group (22 mmHg/ml/min). Effects of norepinephrine on vascular resistance were significantly greater in both ischemic groups (p less than 0.004). In all three groups, acetylcholine infusion attenuated the increases in perfusion pressure caused by norepinephrine. This demonstrates secretion of endothelial-mediated relaxing factors (EDRF) and prostaglandin for up to 48 h of hypothermic ischemia. As no significant differences were detected between the two ischemic groups, this study failed to demonstrate any protective effect of xanthine oxidase inhibitors.

Acetylcholine↗

Hemodynamic effects of knee-joint tamponade. 99mTc-diphosphonate scintimetry in growing dogs.

We studied the influence of joint effusion on juxtaarticular vascularity and bone metabolism of the immature knee in puppies by dynamic and static 99mTc-diphosphonate scintimetry. Unilateral joint tamponade of 10 KPa (75 mmHg), introduced by intraarticular dextran-70 infusion, resulted in quantitatively similar scintimetric changes in an angiographic Phase I (0-20 sec), a blood pool Phase II (20-256 sec), and a bone-uptake Phase III (2 h). The uptake was reduced by 20 percent in the distal femoral epiphysis, by 15 percent in the distal femoral growth plate in Phases II-III, and by 8 percent in the proximal tibial growth plate in Phase III. The main part of scintimetric changes during joint tamponade could be ascribed to altered epiphyseal and metaphyseal intraosseous hemodynamics.

Animals↗

An investigation of the pathological and physiological effects of intraosseous sodium bicarbonate in pigs.

Recent interest in the intraosseous (IO) route as an alternative venous access for drug and fluid administration has increased. This study examined the physiological and skeletal pathological effects of IO NaHCO3 in pigs. In the pathological studies, swine (8-10 kg) received NaHCO3 (1 mEq/kg) in one tibia and saline (1 ml/kg) in the other tibia via an 18-gauge spinal needle inserted into the anteromedial surface of the bone. The animals were then observed for one month, sacrificed, and the tibias were isolated, sectioned, and stained for pathological examinations. The physiological effects of IO NaHCO3 infusion were studied and compared with that of intravenous (IV) administration using a cardiac arrest model as previously described. The results demonstrated that NaHCO3 had no effect on the mean arterial blood pressure and plasma catecholamine levels, but increased arterial pH values within two minutes of administration. Similar effects were found with IV NaHCO3. Pathological data indicated signs of minimal local increase in skeletal turnover associated with IO NaHCO3 infusion. It is concluded that the IO route is a safe alternative venous access for NaHCO3 administration in swine.

Animals↗

Review of the biological response to a novel bone cement containing poly(ethyl methacrylate) and n-butyl methacrylate.

This review describes work published independently elsewhere in which the biological reactions to poly(ethyl methacrylate) n-butyl methacrylate (PEMBMA) have been studied. This material has been compared throughout with conventional poly(methyl methacrylate) (PMMA). Butyl methacrylate monomer used in PEMBMA was slightly less toxic than methyl methacrylate monomer used in PMMA when injected intraperitoneally in mice. No differences in cardiorespiratory effects were found between n-butyl and methyl monomer infused intravenously into anaesthetized rabbits. The tissue reaction to the beaded polymers of poly(methyl methacrylate) and poly(ethyl methacrylate) implanted subcutaneously was identical. The surface appearance of the two materials differed significantly when viewed by scanning electron microscopy, showing a series of elevations resembling tightly packed spheres in the case of PMMA, but a smooth surface with only occasional smooth elevations in the case of PEMBMA. Intramuscular implantation showed more fibrous tissue and tissue damage in relation to PMMA cured in situ compared with PEMBMA and there was more bone necrosis and a thicker fibrous tissue layer adjacent to PMMA than PEMBMA when cured intraosseously.

Animals↗

Plasma catecholamines, pH, and blood pressure during cardiac arrest in pigs.

This study examined plasma epinephrine (E) and norepinephrine (NE) concentrations, pH, and mean arterial blood pressure (MAP) in a cardiac arrest model. Twenty-three domestic swine (15-26 kg) were anesthetized with ketamine 20 mg/kg, i.m. and alpha-chloralose 25 mg/kg, i.v. and ventilated with a respirator. Catheters were placed in the right ventricle, left ventricle and femoral arteries for MAP recordings and blood pH sampling every 2 min. Catecholamine samples were taken from the femoral artery every 2 min. Cardiac arrest was induced by endocardial stimulation with a Grass S88 stimulator. Five minute post arrest resuscitation was initiated with a mechanical resuscitator. Ten minute post arrest NaHCO3 1 mEq/kg was administered by the peripheral i.v. (P; n = 6), central (CE; n = 5), or intraosseous, via the tibia, (I; n = 6), route. Controls (C; n = 6) did not receive NaHCO3. MAP (mean +/- S.D.) prior to arrest was: C 144 +/- 16, P 139 +/- 11, CE 137 +/- 13 and I 133 +/- 11 mmHg. Five and 25 min post arrest it was: C 21 +/- 5 and 17 +/- 6, P 34 +/- 8 and 23 +/- 7, CE 17 +/- 7 and 14 +/- 10 and I 26 +/- 6 and 11 +/- 3 mmHg, respectively. A 2-way analysis of variance did not reveal any difference in MAP values in the four groups. In all groups the blood pH from the femoral artery demonstrated a respiratory alkalosis that peaked at approximately 7.48 5 min after initiation of mechanical resuscitation. In the groups receiving NaHCO3, it peaked at 7.77 +/- 0.09 CE and 7.65 +/- 0.06 P 2 min post infusion and at 7.71 +/- 0.06 I 8 min post infusion. An analysis of variance revealed that the CE and I routes were significantly different (P less than 0.05) from the P group and that all three groups were different (P less than 0.05) from the C. Plasma E and NE concentrations at 0, 6, 10, 12, 20 and 30 min post arrest in the C group were, respectively: 3 and 10, 94 and 327, 119 and 329, 92 and 234, 33 and 135, and 127 and 62 ng/ml, respectively. All 3 groups receiving NaHCO3 demonstrated similar patterns and were not significantly different from C when compared with a 2-way analysis of variance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[The intraosseous administration on kavinton in treating myeloradiculoischemia].

The authors present a comparative analysis of the efficacy of their method of administration of vasoactive drugs into the peridural venous system and traditional conservative therapy in radiculomyeloischemia of different etiology. The dynamics of the disease was evaluated both by clinical manifestations and by evoked spinal cord potentials, complex examination of the acid-base balance of the blood from the involved vascular territory and blood from extremities. Results of a detailed examination of 24 patients with myeloradiculopathy carried out by means of precise electrophysiological and laboratory methods permit to recommend this treatment in clinical conditions.

Adult↗

[Malignant tumors of long bones in children: differential diagnosis and the role of imaging methods].

PURPOSE OF THE STUDY: The aim of the study was to analyze primary malignant tumors and tumor-like lesions of long bones, in relation to their localization, characteristics and distribution in age groups, in children and young adults, and to assess the role of radiography and magnetic resonance imaging (MRI) in their diagnosis. MATERIAL: Sixty-four patients, aged between 3 and 20 years, who were referred to us with the diagnosis of a suspected malignant long-bone tumor of osseous or cartilage origin in the period from 2000 to 2004 were included in the study. METHODS: Plain radiography and MRI were carried out on the same day. For MRI, the Magnetom Open Viva system (magnetic field strength of 0.2 T) was used and examination comprised a conventional STIR (corresponding to fat saturation) and a T-weighed sequence. Most patients also underwent post-contrast examination with paramagnetic contrast medium infusion. RESULTS: In 26 children (40.6 %) a primary malignant tumor of osseous or cartilage origin was diagnosed; one child (1.5 %) had a giant-cell tumor. The definitive diagnoses in 37 children (57.9 %) included osteomyelitis in 12, fatigue fracture in 11, posttraumatic myositis ossificans in three children, and miscellaneous diagnoses in the remaining 11 children (one, cartilaginous exostosis; three, unicameral bone cyst; two, non-ossifying fibroma; one, fibrous dysplasia; one, subperiosteal abscess; one, histiocytosis; one, foreign body; one, negative MRI findings). CONCLUSIONS: To confirm the diagnosis of a malignant long-bone tumor, high quality X-ray and MRI are essential; CT examination is recommended in specific indications. The results of imaging methods cannot be assessed without reference to each other. Primary malignant tumors of long bones usually involve a large soft-tissue mass, and an exclusively intraosseous localization is rare. Osteosarcoma often invades the epiphysis. In making the differential diagnosis of primary malignant bone tumors, special attention must be paid to differentiation from osteomyelitis or fatigue fractures. The majority of juvenile bone lesions of any origin are usually detected between 10 and 13 years of age. These pathologic lesions are most frequently localized in the distal or proximal transition zones between the diaphysis and metaphysis.

Adolescent↗