Cases reported "Disease Models, Animal"

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1/83. Single-vessel arteriovenous revascularization of the amputated ear.

    Successful single-vessel arteriovenous replantation of a completely amputated human ear is described. This result was followed by an experimental study using a rabbit model, to confirm that an amputated ear could survive replantation with only a single arteriovenous anastomosis. Fifteen animals were placed in one of two experimental groups: Group 1-arteriovenous replantation, no treatment (n = 6); and Group 2-arteriovenous replantation with medicinal leeching (n = 9). All ears demonstrated initial reperfusion of the replantation immediately following microanastomosis. Laser Doppler flow readings in the non-leeched replanted ears fell to zero by 8 hr and, by 12 hr, the non-leeched ears demonstrated signs of necrosis. All the leeched, replanted ears demonstrated perfusion and complete viability at the time of sacrifice. The case report, combined with the results from the experimental study, confirm that single-vessel arteriovenous replantation of an amputated ear is feasible.
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2/83. Tension pneumothorax.

    The diagnosis of tension pneumothorax has typically been taught as the presence of hemodynamic compromise with an expanding intrapleural space air mass. This may occur quickly or gradually, depending on the degree of lung injury and respiratory state of the patient. Experimentally, tension pneumothorax is a multifactorial event that manifests a state of central hypoxemia, compensatory mechanisms, and mechanical compression on intrathoracic structures. Studies using animal models suggest that over hypotension is a delayed finding that immediately precedes cardiorespiratory collapse. Recognition of early signs and symptoms associated with tension pneumothorax, e.g., progressive hypoxemia, tachycardia, and respiratory distress, can alert medical personnel to the need for rapid decompression before physiologic decompensation.
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3/83. Correction of ureagenesis after gene transfer in an animal model and after liver transplantation in humans with ornithine transcarbamylase deficiency.

    We report effects of gene transfer and liver transplantation on urea synthesis in ornithine transcarbamylase deficiency (OTCD). We measured the formation of [15N] urea after oral administration of 15NH4Cl in two girls with partial OTCD before and after liver transplantation. Ureagenesis was less than 20% of that observed in controls before transplantation, and was normalized afterward. Studies performed on the OTCD sparse fur (spf/Y) mouse showed discordance between OTC enzyme activity and ureagenesis with modest increases in OTC enzyme activity after gene transfer resulting in significant improvement in ureagenesis. This study suggests that both liver transplantation and gene therapy may be effective in improving ureagenesis in OTCD.
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4/83. Can early postnatal closed head injury induce cortical dysplasia.

    PURPOSE: Increased availability of surgically resected epileptogenic tissues reveals often unsuspected cortical dysplasia (CD). There is some controversy about the ontogenic stages in which these occur. Although most take place during neuroblast proliferation and migration, there is some evidence for some CD occurring during postmigrational intrinsic cortical organization. It has been shown that various kinds of focal cortical manipulations in rats, if performed within 3-4 postnatal days, lead to the genesis of various cortical malformations including a four-layered microgyrus or an unlayered CD. It is not known whether such events also might occur in the human brain. methods: Two children sustained minor head trauma within 4 postnatal days and later developed intractable epilepsy, which was relieved by surgery. Neuropathologic analysis of the resected tissues revealed an unsuspected microdysplastic cortex immediately adjacent to a focal, modest meningeal fibrosis, presumably secondary to the old closed head trauma. RESULTS: The main histologic features were a disorganized, unlayered cortex; abnormal clusters of neurons, often with complex, randomly oriented proximal dendritic patterns with absent apical orientation; the presence of a number of heterotopic small and large neurons in the white matter; absence of inflammatory infiltrates, of hemosiderine, of reactive gliosis, or of an excessive number of blood vessels. The morphologic features in these surgical specimens suggest that these focal malformations occur because of a regional disorder of postmigrational intrinsic cortical remodeling. CONCLUSIONS: The clinical histories and the pathologic findings lend some support to the hypothesis that minor morbid events occuring in the immediate postnatal period may lead to microdysplasia in the human similar to those induced in rat pups. The animal model could be helpful to clarify the genesis of some cases of CD and of the epileptogenicity often manifesting later in life.
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5/83. Therapy of iatrogenic subglottic stenosis: a steroid/antibiotic regimen.

    The authors have evaluated the efficacy of a medical regimen, consisting of systemic antibiotics and steroids, in the management of acute iatrogenic subglottic stenosis. The study consisted of the infliction of a standardized subglottic injury to three groups of five dogs: Group I animals were placed on prednisone 1 mg/kg/24 hours and potassium phenoxymethyl penicillin 50 mg/kg/24 hours from the day of the trauma. Group II were placed on a similar regimen from the eighth day after subglottic trauma. Group III received no medical therapy at all. Therapy was continued in treated Groups I and II for five weeks. At the end of the study the dogs were sacrificed and the final degree of subglottic stenosis evaluated, at which time the laryngotracheal complexes were submitted for pathological evaluation. A significant difference was found between the degree of stenosis attained in the three groups. The study suggests that the introduction of a steroid/antibiotic regimen has a beneficial effect in developing subglottic stenosis and that the timing of such therapy is of importance.
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6/83. Scopulariopsosis and hypersensitivity pneumonitis in an addict.

    Granulomatosis caused by fungal spores of a soil saprophyte is a newly recognized pulmonary complication of intravenous drug addiction. Brown, non-budding spores were histologically identified in necrotic tissue, inside giant cells of sarcoidlike granulomata, and in the vicinity of focal angiitic lesions. The fungus was identified by culture as the dematiaceous scopulariopsis brumptii. Cultural and histopathologic studies of lung biopsy specimens established the diagnosis. We showed precipitating antibodies to fungal antigen in the serum, prepared from the patient's isolate. Similar granulomatous pulmonary lesions were experimentally produced in mice by a single intravenous injection of spores of S. brumptii. The spores remained viable but did not show evidence of growth in the animal's tissue. Precipitating antibodies to fungal antigen and immediate wheal and late necrotizing type of skin reactions were shown in the challenged mice. The studies support the notion that pulmonary hypersensitivity to fungal spores was mediated by an Arthus'-type phenomenon.
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7/83. Is epilepsy a progressive disease? The neurobiological consequences of epilepsy.

    While primary, or idiopathic, epilepsies may exist, in the vast majority of cases epilepsy is a symptom of an underlying brain disease or injury. In these cases, it is difficult if not impossible to dissociate the consequences of epilepsy from the consequences of the underlying disease, the treatment of either the disease or the epilepsy, or the actual seizures themselves. Several cases of apparent complications of epilepsy are presented to illustrate the range of consequences encountered in clinical practice and the difficulty in assigning blame for progressive symptomatology in individual cases. Because of the difficulty in interpreting clinical material, many investigators have turned to epilepsy models in order to address the potential progressive consequences of recurrent seizures. The authors review experimental data, mainly from animal models, that illustrate short-, medium-, and long-term morphological and biochemical changes in the brain occurring after seizures, and attempt to relate these observations to the human condition.
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8/83. Osteopetrorickets: case report.

    We report the case of a baby girl who presented with rickets at 3 months. At the age of 5 months she was readmitted because of nystagmus and a diagnosis of osteopetrosis was made on the basis of clinical and radiological findings. rickets is a paradoxical feature of osteopetrosis resulting from inability to maintain a normal calcium-phosphorus balance. In our patient the onset of rickets before other symptoms of osteopetrosis suggests a primary defect. Conclusion: It is possible that patients with osteopetrosis and rickets (osteopetrorickets) represent a different mutation like the osteopetrosis mouse, which is the only animal mutation with rickets.
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9/83. pentoxifylline for sickle-cell disease.

    OBJECTIVE: To review the use of pentoxifylline for the prevention and treatment of acute vasoocclusive episodes (VOEs) in sickle-cell disease (SCD). DATA SOURCES: Searches of medline (1965-April 2000), International Pharmaceutical abstracts (1970-April 2000), and science Citation Index Expanded (1989-April 2000) were performed using the key search terms sickle-cell disease, pentoxifylline, oxypentifylline, and Trental. DATA SYNTHESIS: patients with SCD commonly suffer from painful VOEs. pentoxifylline may be useful in this condition due to its ability to increase red blood cell deformability and inhibit platelet aggregation. Laboratory evidence, an animal model, and case reports suggest a benefit, but available clinical studies are methodologically poor, and data analysis is often inappropriate or absent. Limited data suggest that pentoxifylline is beneficial for treatment of a VOE in progress, but no data exist demonstrating a reduction in the number of VOEs with chronic pentoxifylline therapy. CONCLUSIONS: documentation of the efficacy of pentoxifylline for VOE prevention and treatment of SCD is poor, further studies are needed before its routine use is recommended.
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10/83. Evaluating laryngotracheal stenosis in a canine model with virtual bronchoscopy.

    We performed a prospective masked animal study to determine whether virtual bronchoscopy, a noninvasive computed tomography technique, can accurately measure upper airway stenosis. Virtual bronchoscopy creates a 3-dimensional endoscopic image from spiral computed tomography data. Laryngotracheal stenosis was endoscopically induced in 18 dogs. The excised larynges were examined by endoscopy, virtual bronchoscopy, and macrodissection. Measurements were made of the anteroposterior (A-P) diameter, the left-right (L-R) diameter, the full length of stenosis in the sagittal plane, and the length of the tightest stenotic segment. Each measurement method was performed independently. All investigators were unaware of measurements made by others. The measurements obtained through virtual bronchoscopy and actual endoscopy were compared to those made at dissection by interclass correlation coefficients (ICCs). endoscopy was better than virtual bronchoscopy in measuring the A-P diameter (ICC = .79, p < .0001; ICC = .42, p = .01). Both were equally effective in measuring the L-R diameter (ICC = .53, p = .0062; ICC = .52, p = .0064). The endoscopes could not assess the full length of the stenosis, whereas virtual bronchoscopy measured it fairly accurately (ICC = .72, p = .0001). Virtual bronchoscopy relatively accurately measured the length of the tightest stenotic segment (ICC = .68, p = .0002), whereas endoscopy produced measurements in only 11 of 18 larynges, and the measurements were less accurate (ICC = .45, p = .0068). Virtual bronchoscopy can provide good measurements of stenotic lesions in the airway. It is more accurate than actual endoscopy in determining the length of stenosis. It may therefore be useful as an adjunct imaging method in preoperative planning for reconstructive surgery.
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