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Multifrequency tympanometry and histopathology in chinchillas with experimentally produced middle ear pathologies.

Middle ear lesions were produced in chinchillas by introducing fascia, Gelfoam, silastic or a combination of these materials into the labyrinthine and mastoid bullae. After 1-2 months, conventional 226 Hz and multifrequency tympanometry (MFT) were performed and the animals were sacrificed for histopathological analysis of the middle ear. Specific middle ear lesions were created including abnormal tympanic membrane thickness, tympanic membrane mass, tympanic membrane adhesion, mastoid bulla obstruction, ossicular adhesions and reduced middle ear volume. Several potentially strong associations emerged between tympanometric measures and pathological conditions. The strongest were the combinations of thick tympanic membrane and irregular multifrequency tympanograms, tympanic membrane mass and notched 226 Hz admittance tympanograms, tympanic membrane adhesions and low 226 Hz admittance, and tympanic membrane adhesions and low resonant frequency. 226 Hz static admittance had a sensitivity of 0.73 and a specificity of 0.75 for detecting significant middle ear pathology. Tympanometric width was not an effective diagnostic test, separately or in combination with static admittance. The most effective test based on 226 Hz measures was the combination of low admittance or admittance notch. MFT was superior to 226 Hz tympanometry. The combination of low resonance or double resonance or irregular patterns had a sensitivity and specificity of 0.91 and 1.0, respectively. Combining 226 Hz tympanometry with MFT improved the performance relative to 226 Hz tympanometry alone but not relative to MFT alone. The results support clinical reports that multifrequency tympanometry detects some middle ear pathologies that are not detected by conventional 226 Hz tympanometry.

Acoustic Impedance Tests↗

Intravascular occlusive therapy: use of interventional radiology in cancer patients.

Selective transcatheter intravascular occlusion in the treatment of cancer patients is a valuable extension of interventional diagnostic radiology. Intra-arterial embolization may be performed with various substances, including autologous clot, autologous subcutaneous tissue, Gelfoam, and stainless steel coil. Clinical applications in cancer patients include control of gastrointestinal and genitourinary hemorrhage, preoperative reduction of tumor vascularity, control of local symptoms, and therapeutic reduction of tumor bulk. The technique has been used for preoperative and palliative treatment of neoplasms of the head and neck, kidney, liver, spleen, and soft tissue and bone. Transcatheter intravascular occlusion should be performed only by radiologists experienced in angiographic techniques. Inadvertent occlusion of a normal vessel and thromboembolism are possible complications.

Angiography↗

Long-term results in otosclerotic patients operated by stapedectomy or stapedotomy.

Stapedectomy and stapedotomy are the techniques currently used in the surgical treatment of otosclerosis. During the period 1977-81, a total of 60 consecutive patients were subjected to surgery for otosclerosis according to the method of Schuknecht (Gelfoam and wire prosthesis). Another 55 consecutive otosclerotic patients were operated on during 1987-91with stapedotomy, according to the method advocated by Fisch (Fisch-type piston). Independent of the surgical technique used, the maximal hearing gain was obtained 1 year after surgery. In the frequency range 0.5-3 kHz, the mean value of the averaged pure tone thresholds improved from 52 to 28 dB in the stapedectomy group and from 57 to 26 dB in the stapedotomy group. In the frequency range 4-6 kHz, the subjects' hearing was not significantly improved in the stapedectomy group, whereas the subjects' hearing in the stapedotomy group improved from 61 to 44 dB. Per- and postoperative complications were low in both groups, except for one patient in the stapedectomy group who experienced the serious complication of a deaf ear after surgery.

Adult↗

Percutaneous transcatheter embolization in arterial injuries of the lower limbs.

PURPOSE: To evaluate the efficacy and safety of percutaneous transcatheter arterial embolization (PTE) in lower extremity arterial injuries. MATERIAL AND METHODS: From January 2000 to June 2004, patients who presented with a penetrating trauma of the lower limbs, along with bleeding and with no sign of ischemia or hemodynamic instability, were included in the study. The injuries were embolized by coils and Gelfoam. The efficacy of PTE was defined as its ability to stop bleeding both radiographically and clinically, and its safety was determined by the complication rate. RESULTS: There were 10 embolizations, which consisted of 5 profundal femoral, 3 superior gluteal, and 2 inferior gluteal artery embolizations. PTE was effective in all patients. There were two inguinal hematomas, which did not require any intervention, and there was a temporary renal function alteration. The mean hospital stay of these patients was 2.67 +/- 0.91 days. CONCLUSION: PTE may be an effective and safe method of treatment in certain cases with lower limb arterial injuries. However, patients should be selected meticulously by both the vascular surgeon and the interventional radiologist, and PTE should be undertaken only in experienced hands.

Adolescent↗

Influence of bone marrow on membrane-guided bone regeneration of segmental long-bone defects in rabbits.

Defects 10 mm long were created in long bone in the diaphysis of both radii of 18 rabbits (test and control side). On the test side, ingrowth of bone marrow into the defects was hindered or delayed by: plugging the opening of the cut bone ends with gutta-percha points (n = 7); plugging with Gelfoam (n = 6); or by removing the bone marrow by flushing with saline (n = 5). The defects on both test and control side were covered with an expanded polytetrafluoroethylene membrane, shaped as a tube. Healing was followed with radiographs for four to five months, after which the animals were killed and ground sections of the areas of the defects were prepared for histological examination. On the control side, nine of 18 animals had complete osseous bridging of the defect, and a small transverse non-mineralised zone remained in the centre of the healed defect in the other animals. This zone consisted of loose connective and cartilagenous tissue as well as connective tissue obviously derived from the outside of the membrane. By preventing or delaying the ingrowth of bone marrow we retarded the regeneration of mineralised bone, particularly in the gutta-percha and flushed bone marrow groups. The principle of guided tissue regeneration may be used to achieve regeneration of extensive long-bone defects. Any attempts to delay or prevent bone marrow ingrowth into the defects did retard regeneration of segmental long-bone defects.

Animals↗

A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential.

Here a new, intrinsically pluripotent, CD45-negative population from human cord blood, termed unrestricted somatic stem cells (USSCs) is described. This rare population grows adherently and can be expanded to 10(15) cells without losing pluripotency. In vitro USSCs showed homogeneous differentiation into osteoblasts, chondroblasts, adipocytes, and hematopoietic and neural cells including astrocytes and neurons that express neurofilament, sodium channel protein, and various neurotransmitter phenotypes. Stereotactic implantation of USSCs into intact adult rat brain revealed that human Tau-positive cells persisted for up to 3 mo and showed migratory activity and a typical neuron-like morphology. In vivo differentiation of USSCs along mesodermal and endodermal pathways was demonstrated in animal models. Bony reconstitution was observed after transplantation of USSC-loaded calcium phosphate cylinders in nude rat femurs. Chondrogenesis occurred after transplanting cell-loaded gelfoam sponges into nude mice. Transplantation of USSCs in a noninjury model, the preimmune fetal sheep, resulted in up to 5% human hematopoietic engraftment. More than 20% albumin-producing human parenchymal hepatic cells with absence of cell fusion and substantial numbers of human cardiomyocytes in both atria and ventricles of the sheep heart were detected many months after USSC transplantation. No tumor formation was observed in any of these animals.

Adipocytes↗

Hand-assisted laparoscopic partial nephrectomy.

BACKGROUND AND PURPOSE: The indications for partial nephrectomy are expanding as newer and more complete data come forth. A partial nephrectomy has traditionally required a generous flank incision. We report our experience using hand-assisted laparoscopy (HAL) as a less-invasive approach to partial nephrectomies. PATIENTS AND METHODS: Between October 1999 and May 2000, we performed 11 HAL partial nephrectomies. The average age of the patients was 55.7 years, the average body mass index was 25.6, and the average ASA class was 2.2. The indications for partial nephrectomy were enhancing solid renal lesions (N = 9) and nonfunctioning renal moiety in a duplicated system (N = 2). In the majority of cases, access to the renal pedicle was obtained prior to the partial nephrectomy. However, in no case did the renal artery or vein require occlusion. Several excisional techniques were employed, but all relied heavily on the Harmonic Scalpel in conjunction with the argon beam coagulator. Different hemostatic agents were applied to the renal defect, including Surgicel, Avitene, and fibrin-soaked Gelfoam activated by thrombin. In several instances, pledget reinforced sutures were placed in the renal capsule to aid with hemostasis. RESULTS: The average operative time was 273 minutes, the estimated blood loss 319 mL, and the change in hematocrit 7.3 points. No patient required a transfusion, and there was one conversion to open. Postoperatively patients, required an average of 35.6 mg of morphine sulfate equivalent and 8.2 narcotic tablets, resumed oral intake in 1.7 days, and were discharged home in 3.3 days. There were no major complications and only two minor complications. Postoperatively, five lesions were found to be benign, four lesions were confirmed to be malignant, and two lesions were consistent with a nonfunctioning duplicated renal moiety. Specimen size averaged 180 cc, and the tumor diameter averaged 1.9 cm. There were no positive surgical margins. CONCLUSIONS: Hand-assisted laparoscopic partial nephrectomy is feasible and reproducible. The surgeon's hand in the operative field facilitates dissection, vascular control, hemostasis, and suturing. Further long-term and prospective studies are underway.

Adult↗

Nephron-sparing laparoscopic surgery: techniques to control the renal pedicle and manage parenchymal bleeding.

Laparoscopic nephron-sparing surgery has been limited by several factors, including problems in the control of the vascular pedicle and the management of parenchymal bleeding. In an effort to improve the efficacy of laparoscopic nephron-sparing surgery, we developed and tested several techniques to control and manage intraoperative renal bleeding while performing 30 laparoscopic anatrophic nephrolithotomies using the porcine model. Control of the renal pedicle and management of bleeding included the use of the following: (1) extracorporeally applied atraumatic vascular pedicle clamp; (2) Argon Beam Coagulator to perform the capsulotomy; (3) electrocautery scissors to perform the nephrotomy; (4) Gelfoam welded to the cut surface of the parenchyma with the argon beam coagulator; (5) Surgicel welded to the outer surface of the kidney with the Coagulator; and (6) laparoscopically applied bolster sutures to further stabilize the renal unit. All animals tolerated the procedure well and survived to their appointed date of sacrifice. We conclude that these techniques may improve the efficacy of laparoscopic renal surgery, including nephron-sparing procedures.

Animals↗

Laparoscopic renal cryotherapy in swine: comparison of puncture cryotherapy preceded by arterial embolization and contact cryotherapy.

Variable results of open, percutaneous, and laparoscopic cryosurgery of the kidney have been reported. Minimally invasive approaches to lower-pole renal ablation were prospectively compared in swine: laparoscopic puncture cryoablation preceded by arterial embolization, laparoscopic contact cryosurgery, and arterial embolization alone. Eighteen kidneys in nine domestic pigs were randomized to one of three treatment groups of six organs each: (1) puncture cryotherapy preceded by selective lower-pole arterial embolization; (2) contact cryotherapy alone; and (3) arterial embolization alone. Under general anesthesia, appropriate animals underwent selective arterial embolization of the lower pole via femoral cutdown using Gelfoam pledgets. Animals randomized to cryotherapy underwent dissection of the lower pole of the kidney using a single 12-mm umbilical and two midclavicular-line ports in the lateral position. Under external ultrasound guidance, two 3-mm cryoprobes (Cryomedical Sciences, Rockville, MD) were positioned in the lower pole of the kidney, and double-freeze technique to -190 degrees C was performed using puncture or contact application. Ultrasonography was used to guide probe insertion during puncture cryotherapy only. Kidneys were harvested 11 to 14 days after the procedure. Both puncture and contact kidneys demonstrated cell death and subsequent necrosis by light microscopy and electron micrography. On average, puncture lesions were heavier than contact lesions, 19.3 g v 10.1 g (P = 0.02; unpaired t-test), whereas the kidneys were equivalent in weight: 74.1 g v 74.1 g. Puncture lesions represented 26.4% of total kidney weight v 13.5% in the contact group (P = 0.002; unpaired t-test). Only focal infarcts were identified in the embolization group. No evidence of adjacent visceral injury was identified in any of the groups, and no animal required conversion to open laparotomy. One kidney bled after contact cryotherapy, and hemostasis was achieved laparoscopically. Laparoscopic cryotherapy is reproducible and effective using either the puncture technique preceded by arterial embolization or the contact technique, without evidence of damage to adjacent structures. Contact lesions were less voluminous and more peripheral than puncture lesions. Embolization alone produces focal infarcts and focal zones of cell death.

Animals↗

Topical axonal transport blocker vincristine prevents nerve injury-induced spinal neuron sensitization in rats.

The effect of vincristine (Vin, a fast axonal transport blocker) to prevent any alteration in the excitability of dorsal horn neurons, following peripheral nerve injury, was investigated on 31 rats: 20 with chronic constriction injury (CCI) of the sciatic nerve and 11 sham preparations. In 15 of the 20 CCI rats, a small piece of gelfoam soaked with Vin was applied to the sciatic nerve before ligation (Vin+); in the remaining 5 rats the nerve was ligated without Vin (Vin-). The 11 sham rats were 7 Vin+ and 4 Vin-. The dorsal horn neuronal activity was recorded after 2-3 postoperative (PO) weeks. In the CCI Vin- rats, the neurons showed increased spontaneous activity and hyperresponsiveness to noxious stimulus with prolonged afterdischarges, events considered to signal central neuron sensitization. In the CCI Vin+ rats, the neuronal spontaneous and stimulated activity values were significantly lower (p < 0.001) than in the CCI Vin- rats being comparable to normal values. In sham Vin+ and Vin- rats, the neuronal activities had normal values. Given the crucial role attributed to central neuron sensitization for the development of neuropathic pain, the possibility that vincristine, by blocking the axonal transport, exerts a preventive action on this syndrome is discussed.

Action Potentials↗

Alginate encapsulated BDNF-producing fibroblast grafts permit recovery of function after spinal cord injury in the absence of immune suppression.

Encapsulation of cells has the potential to provide a protective barrier against host immune cell interactions after grafting. Previously we have shown that alginate encapsulated BDNF-producing fibroblasts (Fb/BDNF) survived for one month in culture, made bioactive neurotrophins, survived transplantation into the injured spinal cord in the absence of immune suppression, and provided a permissive environment for host axon growth. We extend these studies by examining the effects of grafting encapsulated Fb/BDNF into a subtotal cervical hemisection on recovery of forelimb and hindlimb function and axonal growth in the absence of immune suppression. Grafting of encapsulated Fb/BDNF resulted in partial recovery of forelimb usage in a test of vertical exploration and of hindlimb function while crossing a horizontal rope. Recovery was significantly greater compared to animals that received unencapsulated Fb/BDNF without immune suppression, but similar to that of immune suppressed animals receiving unencapsulated Fb/BDNF. Immunocytochemical examination revealed neurofilament (RT-97), 5-HT, CGRP and GAP-43 containing axons surrounding encapsulated Fb/BDNF within the injury site, indicating axonal growth. BDA labeling however showed no evidence of regeneration of rubrospinal axons in recipients of encapsulated Fb/BDNF, presumably because the amounts of BDNF available from the encapsulated grafts are substantially less than those provided by the much larger numbers of Fb/BDNF grafted in a gelfoam matrix in the presence of immune suppression. These results suggest that plasticity elicited by the BDNF released from the encapsulated cells contributed to reorganization that led to behavioral recovery in these animals and that the behavioral recovery could proceed in the absence of rubrospinal tract regeneration. Alginate encapsulation is therefore a feasible strategy for delivery of therapeutic products produced by non-autologous engineered fibroblasts and provides an environment suitable for recovery of lost function in the injured spinal cord.

Alginates↗

Electroencephalographic effects of laudanosine in an animal model of epilepsy.

We examined the effects of laudanosine, one of the principal metabolites of atracurium, on the electroencephalogram (EEG) in an animal model of induced epilepsy. Fourteen rabbits were anaesthetized with 4% halothane in oxygen, the trachea intubated and the lungs ventilated mechanically with 30% oxygen and 1% halothane in nitrogen. Animals were assigned randomly to receive either an infusion of laudanosine (laudanosine group, n = 7) at a rate calculated to produce plasma concentrations similar to those found following the clinical use of atracurium, or an equal volume of normal saline (control group, n = 7). To induce an epileptogenic focus, gelfoam sponges soaked in a pH-adjusted 4% cefazolin solution were applied bilaterally to the parietal cortical surface. This resulted in the production of spike and burst EEG activity in all animals. However, scoring the frequency of the spikes and bursts revealed no significant differences between the laudanosine and control groups. We conclude that, in this animal model of epilepsy, no increased incidence of seizure activity was produced by mean plasma laudanosine concentrations as great as 0.8 micrograms ml-1. These results suggest that the routine use of atracurium is unlikely to provoke seizures, even in the presence of an epileptogenic focus.

Animals↗

Collateral bronchopulmonary circulation after spontaneous recanalisation of pulmonary thromboemboli in the dog.

STUDY OBJECTIVE: The aim was to study the fate of enlarged bronchial arteries after resolution of experimental pulmonary embolism. DESIGN: Embolisation of the pulmonary arteries of both lungs was performed with intravenous gelfoam. Pulmonary pressure and pulmonary arteriolar resistance were measured 1 h, 40 d and 80 d after embolisation. Pulmonary angiography and aortography were performed at the same time to evaluate the pulmonary emboli and the collateral bronchopulmonary circulation. Aortography and gross pathological and histological examination of the lungs was performed after 80 d. EXPERIMENTAL MATERIAL: 15 adult mongrel dogs of either sex were studied, weight 22-25 kg. Nine dogs were embolised and there were six controls. MEASUREMENTS AND MAIN RESULTS: All animals survived until 80 d. There was a rise (p less than 0.001) in mean pulmonary artery pressure and arteriolar resistance 1 h after embolisation. Pulmonary artery pressures and resistances were still raised 40 d after embolisation but had returned to normal after 80 d. Pulmonary arteriography at 1 h confirmed massive thromboembolism. After 40 d antegrade pulmonary blood flow was almost completely restored, and the thromboemboli had largely disappeared. Pulmonary angiograms were completely normal after 80 d. Aortography after 40 d showed a well developed collateral bronchopulmonary circulation, most pronounced in the lower lobes, which persisted unchanged until 80 d. Aortography and gross pathological and histological examination at necropsy confirmed the presence of hypertrophic well developed bronchial arteries to both lower lobes and to a lesser extent to the middle and upper lobes, with only a few organised and recanalised thrombi in segmental arteries of both lower lobes. CONCLUSIONS: Our data show a temporal dissociation between the resolution of pulmonary thromboemboli in the present model and the eventual regression of developed bronchopulmonary collateral vessels. The mechanism of this dissociation could not be elucidated.

Animals↗

Needle tract implantation of hepatocellular carcinoma after percutaneous liver biopsy.

The authors report a case of needle tract implantation of hepatocellular carcinoma following percutaneous biopsy of the liver. The patient, a 62-year-old Japanese male, was found to have a small hepatocellular carcinoma diagnosed by needle biopsy; this was followed by transcatheter chemoembolization, a combination of transcatheter arterial infusion of adriamycin and transcatheter arterial embolization of Gelfoam, and right lobectomy. Eight months after the biopsy and the lobectomy, a nodule of hepatocellular carcinoma, measuring 3.5 cm in diameter, was found at the site of the previous biopsy and excised. The patient is doing well without further recurrence of tumor 23 months after the lobectomy and 15 months after the excision of the implanted tumor in the subcutis.

Biopsy, Needle↗

Calvarial bone graft donor site: a histological study in a rabbit model.

Recently the calvarium has become a popular site for harvesting bone grafts because of its low incidence of morbidity, its proximity to the operative site, and the decreased amount of resorption as a result of its membranous nature. However, information regarding the phenomenon of repair at the donor site itself remains lacking. This investigation was initiated in 40 adult white New Zealand rabbits as an experimental model to study the process of repair at the donor site and to examine the possible use of hydroxyapatite to reconstruct the residual donor site deformity. Our experimental protocol closely followed our clinical procedure for the harvesting of split calvarial bone grafts. Our conclusions in the rabbit model were: (1) each of the commonly used hemostatic agents (bone wax and gelfoam) inhibit osteoneogenesis to varying degrees, (2) hydroxyapatite shows promise in the reconstruction of the donor site defect, and (3) if the periosteum comes in direct contact the defect repairs itself.

Animals↗

Comparison of various delivery systems for demineralized bone matrix in a rat cranial defect model.

Demineralized bone matrix (DBM) has been successfully used as a substitute for bone grafting. Autogenous bone grafts may cause site morbidity and undergo significant resorption. DBM may overcome these problems, but it has no mechanical stability until bone formation has occurred. We tested various alloplastic implants (i.e., Surgicel, polydioxanone [PDS], porous polyethylene [Medpor], and Gelfoam) in combination with DBM and compared it with DBM alone in a 9 x 9 mm rat cranial defect model. Histological and biomechanical measurements were performed at postoperative month 2. Among the study groups, Gelfoam/DBM inhibited bone formation to varying degrees and was the only group that displayed an inflammatory response. Mechanical pushout tests using a servohydraulic testing frame were conducted. The Medpor/DBM implant displayed the strongest support at 2 months; maximum load was 95% of intact skull. Surgicel/DBM and DBM alone were comparable; maximum load was 66% of intact skull. Gelfoam/DBM and PDS/DBM displayed the weakest support (48% of intact skull). We conclude that, after 2 months of implantation, alloplastic/DBM composites provide osseous structural integration. Gelfoam/DBM is not an effective delivery system for DBM in our model.

Analysis of Variance↗

Long-term survival effects of GDNF on neonatal rat facial motoneurons after axotomy.

Glial cell-line derived neurotrophic factor (GDNF) has survival promoting effects on axotomized neonatal motoneurons. We examined how long it could sustain motoneurons after postnatal day O (PND) facial nerve axotomy. GDNF, or cytochrome c as a negative control, were locally administered by Gelfoam implants at the time of axotomy and some were re-implanted on PND 14. The surviving motoneurons were quantified on PND 14 and 28. GDNF completely rescued lesioned motoneurons from axotomy-induced cell death at 14 days and was still effective (about 40%) at PND 28. GDNF also prevented axotomy-induced atrophy at both PND 14 and 28, indicating that the neurotrophic effects of GDNF on neonatal motoneurons are long-term.

Animals↗

Increased cytotoxicity and stability of Lipiodol-pirarubicin emulsion compared to classical doxorubicin-Lipiodol: potential advantage for chemoembolization of unresectable hepatocellular carcinoma.

There is no well-defined curative treatment for advanced and unresectable hepatocellular carcinoma. The widely used transarterial chemoembolization (TACE) with a doxorubicin-Lipiodol emulsion has not been shown to improve survival in randomized studies. Further, obstruction of the hepatic artery used in the procedure is badly tolerated in patients with cirrhosis. Drugs with a more rapid penetration into the cancer cells are likely to eliminate the need for obstruction of the hepatic artery. We therefore compared the cytotoxicity of another anthracycline pirarubicin with that of the commonly used doxorubicin. In this report, we show that pirarubicin has a greater in vitro cytotoxic effect than doxorubicin on the HepG2 and Hu-H7 human hepatoma cell lines. Pirarubicin emulsion with Lipiodol is more stable at 37 degrees C than doxorubicin-Lipiodol. Moreover, pirarubicin accumulates at a greater extent in the oil phase, permitting Lipiodol to act as a slow-releasing vector for the anthracycline. Further, amiodarone, a multidrug resistance inhibitor, was shown to decrease the intrinsic resistance of HepG2 and Hu-H7 cells to both anthracyclines, and the presence of polysorbate 80 in the amiodarone preparation increased the stability of the anthracycline-Lipiodol emulsions. We therefore conclude that pirarubicin is a better candidate for TACE than doxorubicin. The rapid and increased cytotoxicity of pirarubicin on hepatoma cancer cells and the stability of the pirarubicin-Lipiodol amiodarone emulsion could avoid the complete obstruction of the hepatic artery by Gelfoam sponges, and provide a better tolerated method of TACE in patients with latent liver insufficiency.

Amiodarone↗