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Local delivery of indomethacin by a polyorthoester inhibits reossification of experimental bone defects.

Inhibition of orthotopic reossification after surgical removal of bone is sometimes indicated and may be accomplished by implantation of interpositional materials or by systemic administration of indomethacin. However, implantation of nonresorbable foreign material may induce a chronic inflammation and predispose to infections; and systemic administration of indomethacin may induce systemic adverse effects. We studied the effect of local delivery of indomethacin by a bioerodible polyorthoester on the reossification of segmental defects of the radius in rats. We divided 45 Wistar rats into three groups, A-C. A 3.5 mm-long middiaphyseal osteoperiosteal resection of the right radius was made in each rat. The defect was filled with 15 mg of polyorthoester with 5% indomethacin in group A and 15 mg of polyorthoester without drug in group B. No material was implanted in the defects in the group C rats. The rats were killed 50 days postoperatively. The mean area of the residual defects were greater in the defects with the polyorthoester with 5% indomethacin compared with defects with polyorthoester without drug or without implant as judged by computer-assisted area measurements on radiographs. By light microscopy, no inflammation was seen and only traces of the polyorthoester could be detected in the defects filled with the polyorthoester with or without indomethacin. The results of this study suggest that the polyorthoester may be used as a bioerodible system for local delivery of indomethacin to inhibit reossification of skeletal defects without tissue reaction, unabsorbed carrier, or systemic effects.

Animals↗

Enhanced repair of extensive articular defects by insulin-like growth factor-I-laden fibrin composites.

Stem cells indigenous to the cancellous spaces of the bone bed in an acute injury provide an important source of pluripotent cells for cartilage repair. Insulin-like growth factor-I facilitates chondrogenesis of bone marrow-derived stem cells in long-term culture and may enhance chondrogenesis in healing cartilage lesions in vivo. This study examined the impact of insulin-like growth factor-I, gradually released from fibrin clots polymerized in situ, on the recruitable stem-cell pool in a full-thickness critical cartilage defect model. Twelve full-thickness 15-mm cartilage lesions in the femoropatellar articulations of six young mature horses were repaired by an injection of autogenous fibrin containing 25 microg of human recombinant insulin-like growth factor-I or, in control joints, fibrin without the growth factor. All horses were killed at 6 months, and cartilage repair tissue and surrounding cartilage were assessed by histology, histochemistry, types I and II collagen immunohistochemistry, types I and II collagen in situ hybridization, and matrix biochemical determinations. White tissue filled grafted and control lesions, with the growth factor-treated defects being more completely filled and securely attached to the subchondral bone. A moderately improved chondrocyte population, more columnar cellular organization, and better attachment to the underlying bone were evident on histological evaluation of growth factor-treated defects. Type-II procollagen mRNA was abundantly present in the deeper half of the treated sections compared with moderate message expression in control tissues. Immunolocalization of type-II collagen showed a preponderance of the collagen in growth factor-treated lesions, confirming translation of type-II message to protein. Composite histologic healing scores for treated defects were significantly improved over those for control defects. DNA content in the cartilage defects was similar in treated and control joints. Matrix proteoglycan content was similar in treated and control defects and lower in the defects than in the intact surrounding and remote cartilage of the treated and control joints. The proportion of type-II collagen significantly increased in growth factor-treated tissues. Fibrin polymers laden with insulin-like growth factor-I improved the histologic appearance and the proportion of type-II collagen in healing, full-thickness cartilage lesions. However, none of the biochemical or morphologic features were consistent with those of normal articular cartilage.

Animals↗

Healing of canine articular cartilage defects treated with microfracture, a type-II collagen matrix, or cultured autologous chondrocytes.

The effects of three different treatments on the healing of articular cartilage defects were compared with use of a previously developed canine model. In the articular surface of the trochlear grooves of 12 adult mongrel dogs, two 4-mm-diameter defects were made to the depth of the tidemark. Four dogs were assigned to each treatment group: (a) microfracture treatment, (b) microfracture with a type-II collagen matrix placed in the defect, and (c) type-II matrix seeded with cultured autologous chondrocytes. After 15 weeks, the defects were studied histologically. Data quantified on histological cross sections included areal or linear percentages of specific tissue types filling the defect, integration of reparative tissue with the calcified and the adjacent cartilage, and integrity of the subchondral plate. Total defect filling (i.e., the percentage of the cross-sectional area of the original defect filled with any type of reparative tissue) averaged 56-86%, with the greatest amount found in the dogs in the microfracture group implanted with a type-II collagen matrix. The profiles of tissue types for the dogs in each treatment group were similar: the tissue filling the defect was predominantly fibrocartilage, with the balance being fibrous tissue. There were no significant differences in the percentages of the various tissue types among dogs in the three groups.

Animals↗

Subacute reconstruction of lower leg and foot defects due to high velocity-high energy injuries caused by gunshots, missiles, and land mines.

The present study reviews 215 male patients suffering high velocity-high energy injuries of the lower leg or foot caused by war weapons such as missiles, gunshots, and land mines. They were treated in the Department of Plastic and Reconstructive Surgery at Gulhane Military Medical Academy (Ankara, Turkey) between November 1993-January 2001. Severe soft-tissue defects requiring flap coverage and associated open bone fractures that were treated 7-21 days (mean, 9.6 days) after the injury were included in the study. Twenty-three of 226 extremities (10.2%) underwent primary below-knee amputation. The number of debridements prior to definitive treatment was between 1-3 (mean, 1.9). Gustilo type III open tibia fractures accompanied 104 of 126 soft-tissue defects of the lower leg. Sixty-four bone defects accompanied 83 soft-tissue defects of the feet. Eighteen local pedicled muscle flaps and 208 free muscle flaps (latissimus dorsi, rectus abdominis, and gracilis) were used in soft-tissue coverage of 209 defects. Overall, the free muscle flap success rate was 91.3%. Bone defects were restored with 106 bone grafts, 25 free fibula flaps, and 14 distraction osteogenesis procedures. Osseous and soft-tissue defects were reconstructed simultaneously at the first definitive treatment in 94% of cases. The mean follow-up after definitive treatment was 25 (range, 9-47) months. The average full weight-bearing times for lower leg and feet injuries were 8.4 months and 4 months, respectively. Early, aggressive, and serial debridement of osseous and soft tissue, early restoration of bone and soft-tissue defects at the same stage, intensive rehabilitation, and patient education were the key points in the management of high velocity-high energy injuries of the lower leg and foot.

Adult↗

Preaxial ray reduction defects as part of valproic acid embryofetopathy.

It is well known that prenatal exposure of valproic acid (VPA) may be associated with the occurrence of neural tube defects (Robert and Gibaud, 1982). Additional adverse effects related to VPA exposure include craniofacial abnormalities, skeletal defects, brain defects, cardiovascular defects, and urogenital defects (DiLiberti et al., 1984; Winter et al., 1987; Huot et al., 1987; Jager-Roman et al., 1986; Martinez-Frias, 1990). Recently, radial ray reduction has been reported as a severe type of skeletal defect associated with VPA exposure (Jager-Roman et al., 1986; Huot et al., 1987; Verloes et al., 1990). We report two additional cases of this severe limb reduction defect as part of a broader pattern of altered morphogenesis in fetuses exposed to VPA and to confirm an association between such severe specific skeletal defects and VPA exposure. We briefly review teratologic studies in experimental animals which document the biologic plausibility of this association, and suggest that fetuses exposed to VPA undergo detailed prenatal ultrasonographic evaluation of the limbs.

Abnormalities, Drug-Induced↗

Characterization and identification of local defects in glass.

The most relevant defects in glasses are categorized and investigated by appropriate microanalytical techniques. Since these defects very often present a real challenge because of complex chemical and mineralogical properties, a multimethod approach is necessary to supplement or confirm the findings from scanning techniques. The combination of electron probe microanalysis/energy-dispersive x-ray (EPMA/EDX) and laser ablation inductively coupled plasma mass spectroscopy (LA-ICP-MS) allows the determination of element trace concentrations in a knot, a glassy defect, thus finally enabling the identification of a special source of the defect from otherwise nondistinguishable refractories. The type of crystals can be determined exactly by the use of EPMA and x-ray dispersion (XRD), stones (a crystalline agglomerate) are analyzed by EPMA/EDX pointing to a possible source for this defect; results on metallic inclusions, "filled bubbles," and surface defects are reported and defect sources are discussed. Since close cooperation with the production departments and knowledge of production techniques and conditions are necessary for the diagnosis to take appropriate countermeasures, an approach is presented which systematically accumulates all information into a data base. The structure of such "expert systems" is described, which leads to correlation of appearance, analytical data, and source of the defects for even more accurate diagnosis and faster reaction.

Journal Article↗

Normally occurring loss of single cells and repair of resulting defects in retinal pigment epithelium in situ.

The retinal pigment epithelial cells, which form a monolayer between the choroid and photoreceptor cell layer of the eye, generally do not divide after birth. There is, however, a gradual loss of retinal pigment epithelial cells die and the mechanism by which the integrity of retinal pigment epithelium is maintained after cell death has not been examined. Confocal laser scanning microscopy of whole mounts of retinal pigment epithelium of 12 to 16 day old chick embryos showed that among the great majority of retinal pigment epithelial cells which were regular in size and hexagonal in shape, single, scattered, irregularly shaped, dying cells are present. The distribution of the dying retinal pigment epithelial cells, their morphology and the presence of apoptotic bodies, including pyknotic and fragmented nuclei, above such defects suggests that the death occurs by apoptosis. The defects created by the dying or dead cells were repaired by spreading of the surrounding normal retinal pigment epithelial cells and a series of stages in the repair of the defects could be identified. During the repair of the defects, fine microfilament bundles running parallel to the edge of the defect in each of the surrounding retinal pigment epithelial cells could be detected by confocal laser scanning microscopy giving a 'spider-web' appearance to the region around the defect. Since induction of proliferation in retinal pigment epithelial cells during healing of the defect requires cell migration, we would not expect the spreading of retinal pigment epithelial cells into the single cell defects to trigger cell proliferation. The death of single cells and the spreading of adjacent ones in the absence of cell proliferation would however explain at least in part the increase in the average size of retinal pigment epithelial cells with age.

Actins↗

Fluorine-18 deoxyglucose PET for assessment of viable myocardium in perfusion defects in 99mTc-MIBI SPET: a comparative study in patients with coronary artery disease.

Extent and frequency of viable tissue in myocardial segments yielding a perfusion defect on technetium-99m methoxyisobutylisonitrile (99mTc-MIBI), single photon emission tomography (SPET) at rest was prospectively investigated with 2-18F-2-deoxyglucose (18FDG) positron emission tomography (PET) in 46 patients with chronic coronary artery disease (CAD). Of these, 43 had a history of old myocardial infarction. For comparative visual and quantitative evaluation of identical anatomical slices, PET image files were converted into the SPET file structure and into the same matrix size. SPET and PET images were documented and visually (9 segments/patient) or semiquantitatively evaluated by a target-like polar map. Relative perfusion was expressed in percentage of peak 99mTc-MIBI uptake. Sample 18FDG uptake was related to the 18FDG uptake in the area of such maximal perfusion (18FDG uptake was 100% at the 100% 99mTc-MIBI uptake area). Of 414 segments, 167 (40%) revealed a resting perfusion defect. 18FDG uptake was present in 38 (23%) of the defects, while another 40 (24%) segments yielded 18FDG uptake in the periphery of the defect. When grouped according to the degree of 99mTc-MIBI uptake-reduction (in percentage of peak activity), 80% of severe defects (less than or equal to 30% of peak uptake), 48% of moderate (31%-50% of peak uptake) and 31% of mild (greater than 50% of peak uptake) defects were considered as non-viable on the basis of 18FDG uptake. Complete viability was found in none of the severe defects in contrast to 29% of moderate and 35% of mild perfusion defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

Evaluation of ossification in jaw defects by radio-nuclide imaging.

The uptake of the bone-seeking radiopharmaceutical 99mTc-MDP in defects of the mandibula was quantitated from scintigraphic images. Activity ratios were calculated by means of ROI-technique. The four selected regions contained two control regions and two with mandibula defects. One defect was filled with a fibrin bonding agent and one remained unfilled. The time course of the ratios showed a significant higher uptake of 99mTc-MDP in the region of the filled defect in comparison with the unfilled defect. The measurement of the residual defect areas from histological sections prepared 18 weeks after introduction of the defects confirmed the much more intensive ossification in the filled defects which could also be derived from the evaluation of the scintigrams. The results indicate that it is possible to follow up osseous repair by quantitative evaluation of scintigraphic images.

Animals↗

The latissimus dorsi muscle flap is useful for the repair of tracheal defects--an experimental study.

An experiment was designed to evaluate the limitations of the muscle flap method in treating various locations and sizes of tracheal defects. Five groups of dogs with several types of tracheal defects were prepared. Each defect was covered by the latissimus dorsi muscle flap. Defects of the tracheal membrane (posterior one-third of the tracheal wall) were successfully repaired by the muscle flap without stenosis, even if they extended to 10 rings in length or were situated at the carina. Defects in the posterior one-half of the trachea, up to 5 rings long, were repaired, with minimal stenosis. Defects of the posterior two-thirds, or anterior one-third of the trachea, resulted in marked stenosis following muscle flap repair. Tracheal movement as seen in the saver sheath type of tracheomalasia was observed when anterior support of the trachea was lost. On the other hand, the movement seen in the crescent type of tracheomalasia was observed when posterior support of the trachea was lost. We concluded that a defect of less than the posterior one-half of the trachea can be repaired by muscle flap, without inducing respiratory insufficiency. Therefore, muscle flap coverage for tracheal defects should be a useful technique in the combined resection of the tracheobronchial tree in cases of esophageal cancer.

Animals↗

[Spontaneous defects of the lateral cranial base. 1. Clinical aspects, diagnosis and therapy].

BACKGROUND: Spontaneous cerebrospinal fluid otorrhea (SCFO) or rhinorrhea originating from laterobasal defects is uncommon. An immediate closure of the defect is mandatory due to the risk of life-threatening meningitis. The purpose of this paper is to review the literature and to present two additional case reports with emphasis on diagnostic problems and surgical techniques. PATIENTS AND METHODS: Two adults have been treated for SCFO in our clinic. A 62-year-old woman was complaining of pertinent otorrhea after placement of a ventilation tube and conservative treatment of serous otitis for 1 year elsewhere. A 66-year-old male patient had been treated for acute pneumococcal meningitis. He presented with unilateral deafness and vertigo 3 months later. High-Resolution-Computer-Tomography (HRCT) revealed a unilateral defect in the female and a bilateral defect in the male patient. A transmastoidal approach was used to amputate the meningoencephalocele and modified (Mini-Craniotomy) in the second (male) patient. The defect was closed in two layers using allogenic material and fibrin glue. RESULTS: One year after surgery both patients were free of symptoms and defect closure remained stable in HRCT and under microscopic view. CONCLUSIONS: SCFO from tegment defects is an uncommon cause of otorrhea and even rhinorrhea. History and clinical presentation of our patients can be regarded as typical for adults with SCFO. Evaluation of history, HRCT and a high index of suspicion is a prerequisite for correct diagnosis. The approach (transmastoidal, transtemporal, Mini-Craniotomy) to repair leaks of the tegmen should be related to the extent of the defect.

Aged↗

Sonographic diagnosis of paravaginal defects: a standardization of technique.

The qualitative and quantitative effects of bladder and vaginal balloon volumes on the sonographic diagnosis of paravaginal defects were evaluated. Transabdominal ultrasound measurements were performed on patients with stage 4 prolapse and coexisting paravaginal defects (study group) as well as on nulliparous patients without prolapse or paravaginal defects (control group). Paravaginal defects were measured, first without a water-filled condom in the vagina, and then sequentially with a 30, 60 and 90 ml water-filled balloon in the vagina at bladder volumes of 150 and 300 ml. Paravaginal defects were detected on transabdominal ultrasound in both groups. In both the study and the control groups the size of the paravaginal defect was directly related to the size of the balloon placed in the vagina (P<0.0001). There were no significant differences in the size of the paravaginal defects measured at a bladder volume of 150 ml compared to those measured at 300 ml. We conclude that transabdominal ultrasound is not useful in detecting paravaginal defects.

Abdomen↗

Persistent site-specific defects after reconstructive pelvic surgery.

Our objective was to determine the persistence rates of site-specific defects after reconstructive pelvic surgery. We conducted a retrospective analysis of the post-operative outcome for 77 patients with pelvic support defects. Forty-five patients in the abdominal group underwent a Burch procedure, paravaginal repair and sacral colpopexy when indicated; 32 patients in the vaginal group had a sacrospinous vault fixation with or without colporrhaphy. A chi2 test, Wilcoxon's two-sample test. Wilcoxon's signed-rank test and multivariate logistic regression model were used for data analysis. The two groups were similar in age, weight, parity and menopausal status. There was significant improvement of all defects except in the vaginal group, which showed a higher rate of persistent paravaginal defects (68.7 vs. 13.3%, P = 0.001). After adjusting for potential confounders, there was no difference in the rates of apical and anterior wall defects between the two groups. The odds ratio for persistent paravaginal defects in the vaginal group was 8.9 (95% CI: 2.3-34). The choice of surgical procedure is the most important factor determining the rate of persistent pelvic support defects. Lateral wall defects must be addressed at the time of reconstructive surgery.

Adult↗

Prevalence of symptomatic and silent stress-induced perfusion defects in diabetic patients with suspected coronary artery disease referred for myocardial perfusion scintigraphy.

PURPOSE: Silent myocardial ischaemia--as evaluated by stress-induced perfusion defects on myocardial perfusion scintigraphy (MPS) in patients without a history of chest pain--is frequent in diabetes and is associated with increased rates of cardiovascular events. Its prevalence has been determined in asymptomatic diabetic patients, but remains largely unknown in diabetic patients with suspected coronary artery disease (CAD) in the clinical setting. In this study we therefore sought (a) to determine the prevalence of symptomatic and silent perfusion defects in diabetic patients with suspected CAD and (b) to characterise the eventual predictors of abnormal perfusion. METHODS: The patient population comprised 133 consecutive diabetic patients with suspected CAD who had been referred for MPS. Studies were performed with exercise (41%) or pharmacological stress testing (1-day protocol, (99m)Tc-sestamibi, 201Tl or both). We used semi-quantitative analysis (20-segment polar maps) to derive the summed stress score (SSS) and the summed difference score (SDS). RESULTS: Abnormal MPS (SSS> or =4) was observed in 49 (37%) patients (SSS=4.9+/-8.4, SDS=2.4+/-4.7), reversible perfusion defects (SDS> or =2) in 40 (30%) patients [SSS=13.3+/-10.9; SDS=8.0+/-5.6; 20% moderate to severe (SDS>4), 7% multivessel] and fixed defects in 21 (16%) patients. Results were comparable between patients with and patients without a history of chest pain. Of 75 patients without a history of chest pain, 23 (31%, 95% CI=21-42%) presented reversible defects (SSS=13.9+/-11.3; SDS=7.4+/-1.2), indicative of silent ischaemia. Reversible defects were associated with inducible ST segment depression during MPS stress [odds ratio (OR)=3.2, p<0.01). Fixed defects were associated with erectile dysfunction in males (OR=3.7, p=0.02) and lower aspirin use (OR=0.25, p=0.02). CONCLUSION: Silent stress-induced perfusion defects occurred in 31% of the patients, a rate similar to that in patients with a history of chest pain. MPS could identify these patients with a potentially increased risk of cardiovascular events.

Adult↗

The frequency, appearance, and significance of splenic perfusion defects in CT arterial portography.

BACKGROUND: The purpose of this study was to determine the frequency, appearance, and significance of splenic perfusion defects on computed tomographic arterial portography (CTAP). METHODS: CTAP was performed with dynamic scanning at 1-cm increments on 46 consecutive patients prior to laparotomy. Two readers retrospectively reviewed these studies in consensus and recorded the number, size, and shape of focal splenic perfusion defects. These defects were later correlated with surgical findings and at least one of the following imaging modalities: delayed CT 4-6 h after CTAP, intravenously enhanced CT, sonography, or magnetic resonance imaging (MRI). RESULTS: Splenic perfusion defects were present in 14 of 46 CTAP studies (30%), and in seven patients these defects were multiple. Most defects were wedge-shaped and peripherally located, although several round defects simulating metastases were also present. The spleen was normal at surgery in all patients, and comparison imaging revealed only a small splenic infarct in one patient on MRI. CONCLUSIONS: Splenic perfusion defects occur in about one-third of patients referred for CTAP, are usually wedge-shaped but may be round, and should not be interpreted as metastases without other evidence of a space-occupying mass.

Contrast Media↗

Endoscopic endonasal approaches to anterior skull base defects in pediatric patients.

INTRODUCTION: We studied 12 pediatric patients with congenital or acquired anterior skull base defects. All subjects underwent surgery owing to progressive symptoms. The endoscopic endonasal approach is a new method in the treatment of this pathology in children. MATERIALS AND METHODS: Twelve children had surgery to correct anterior skull base defects: seven patients with a spontaneous anterior basal meningoencephalocele and five with posttraumatic cerebrospinal fluid (CSF) leakage. The defects were repaired using the endoscopic endonasal approach, which combined with the fluorescein diagnostic test, detects the exact location of the skull base defect. Different closure techniques were used to obtain a permanent graft, depending on the type, location, and size of the defect. An intraoperative fluorescein test confirmed the absence of CSF leakage after surgery. RESULTS: The follow-up period ranged from 3 to 72 months. Symptoms resolved in all patients after surgery and none of them experienced complications or recurrence of CSF leakage. Postoperative magnetic resonance scans showed that the defect had successfully been repaired in all patients. DISCUSSION: The surgical treatment of skull base defects in children reduces life-threatening risks, which include infections, CSF leaks, and enlargement or trauma of the sac. The endoscopic technique minimizes surgical scars and has little impact on brain tissue. The endoscopic endonasal approach to the anterior skull base helps to preserve the physiology of the nose and sinuses and reduces the impact on the still developing splanchnocranium in pediatric patients. It ensures a definitive repair of the defect and requires a very short inpatient period.

Adolescent↗

Role of metaphyseal cancellous bone defect size in secondary displacement in Colles' fracture.

The purpose of this study was to evaluate the role of the metaphyseal cancellous bone defect size in secondary dislocation of Colles' fracture. Thirty-five patients with a dislocated Colles' fracture were examined by computed tomography (CT) for metaphyseal bone defects. The size of the defect was assessed and related to the surface area of the cross-section of the distal radius at the site of the defect. The relative size of the defect correlated with the severity of dorsal angulation of the fracture but not with the shortening of the radius seen after cast immobilization. We concluded that secondary displacement of the distal radius is partly mediated through the metaphyseal cancellous bone defect, and to prevent malunion in dorsal angulation, operative treatment or possibly filling of the defect should be considered even as early as during primary reduction if a large defect is suspected.

Adult↗

Glaucomatous visual field defects in patients with migraine.

PURPOSE: To investigate the visual fields in patients with migraine in terms of glaucomatous visual field defects. METHOD: Patients who attended our Neurology outpatient clinic complaining of headache and were diagnosed as migraine were enrolled in the study. Each patient was questioned for the frequency, side, localisation and severeness of the pain as well as the onset and the duration of the symptoms, the existence of aura, the description of the aura - if present -, additional systemic problems, and family history of migraine and glaucoma. Detailed ophthalmological examinations and computerised visual field (VF) analysis were then performed on each patient in our Ophthalmology Clinic. The findings of 77 patients (61 female, 16 male) were evaluated and statistical comparisons were carried out between the group of patients with glaucomatous-like VF defects and the group without significant defects. RESULTS: VF tests revealed glaucomatous-like defects in 48 (62.3 %) patients. Intraocular pressure (IOP) levels were within normal limits in all cases. There were no statistically significant differences between the groups with and without VF defects in terms of sex, the localisation and severeness of pain, the existence and the description of aura, and family history of glaucoma, as well as the duration of migraine, IOP and cup/disc ratio. The glaucomatous group was significantly older, with a significantly higher age of onset for migraine. Risk of having glaucomatous-like defects was higher in patients who had migraine attacks once a month or less frequently. A tendency of pain and VF defects to develop ipsilaterally was noticed. DISCUSSION: A possible relationship between the pathophysiology of migraine, visual field defects and glaucomatous optic neuropathy is emphasized and VF screening for normal tension glaucoma is recommended in patients with migraine.

Adolescent↗