Glial cell line-derived neurotrophic factor and chronic electrical stimulation prevent VIII cranial nerve degeneration following denervation

As with other cranial nerves and many CNS neurons, primary auditory neurons degenerate as a consequence of loss of input from their target cells, the inner hair cells (IHCs). Electrical stimulation (ES) of spiral ganglion cells (SGCs) has been shown to enhance their survival. Glial cell line-derived neurotrophic factor (GDNF) has also been shown to increase survival of SGCs following IHC loss. In this study, the combined effects of the GDNF transgene delivered by adenoviral vectors (Ad-GDNF) and ES were tested on SGCs after first eliminating the IHCs. Animal groups received Ad-GDNF or ES or both. Ad-GDNF was inoculated into the cochlea of guinea pigs after deafening, to overexpress human GDNF. ES-treated animals were implanted with a cochlear implant electrode and chronically stimulated. A third group of animals received both Ad-GDNF and ES (GDNF/ES). Electrically evoked auditory brainstem responses were recorded from ES-treated animals at the start and end of the stimulation period. Animals were sacrificed 43 days after deafening and their ears prepared for evaluation of IHC survival and SGC counts. Treated ears exhibited significantly greater SGC survival than nontreated ears. The GDNF/ES combination provided significantly better preservation of SGC density than either treatment alone. Insofar as ES parameters were optimized for maximal protection (saturated effect), the further augmentation of the protection by GDNF suggests that the mechanisms of GDNF- and ES-mediated SGC protection are, at least in part, independent. We suggest that GDNF/ES combined treatment in cochlear implant recipients will improve auditory perception. These findings may have implications for the prevention and treatment of other neurodegenerative processes. .     

Role of TLR4/MD-2 and RP105/MD-1 in innate recognition of lipopolysaccharide

TLR4 and RP105 are unique members of the Toll-like receptor (TLR) family molecules. They are associated with small molecules called MD-2 and MD-1, respectively, to form heterodimers (TLR4/MD-2 and RP105/MD-1) and function as recognition/signaling molecules of lipopolysaccharide (LPS), a membrane component of Gram-negative bacteria. Analysis of transfectant cell lines and gene-targeted mice revealed that both MD-2 and MD-1 are involved in the recognition of LPS as well as in the regulation of intracellular distribution and the surface expression of TLR4 and RP105, respectively. Since RP105 or MD-1-deficient mice show a reduced but not complete lack of LPS responsiveness, there may be functional associations between TLR4/MD-2 and RP105/MD-1. In addition, there was an increased frequency of RP105-negative B-lymphocytes in the peripheral blood in several rheumatic diseases, such as systemic lupus erythematosus, suggesting the involvement of RP105 in the pathophysiology of autoimmunity. Further analysis of the structure and function of TLR4/MD-2 and RP105/MD-1 will provide a better understanding of the pathophysiology, and a chance to develop evidence-based treatments for septic shock syndrome and autoimmunity.     

A prematurely terminated phase III trial of intraoperative intrapleural hypotonic cisplatin treatment in patients with resected non-small cell lung cancer with positive pleural lavage cytology: the incidence of carcinomatous pleuritis after surgical intervention

BACKGROUND: The prognosis of patients with resected non-small cell lung cancer without carcinomatous pleuritis whose intrapleural cancer cells were detected by means of a cytologic examination of pleural lavage fluid obtained immediately after a thoracotomy has been reported to be poor. METHODS: The Japan Clinical Oncology Group conducted a phase III trial for a 3-year period starting from October 1994 to determine whether intraoperative intrapleural hypotonic cisplatin treatment could effectively control pleural disease and thereby prolong the survival of these patients. The patients were randomized to receive either intraoperative intrapleural hypotonic cisplatin treatment or no treatment before closure of the open thorax. The intraoperative intrapleural hypotonic cisplatin treatment consisted of exposing the entire thorax to cisplatin (50 microg/mL) in distilled water for 15 minutes. RESULTS: Because of the slow registration pace, the study was prematurely terminated in January 1998. During the 41-month period from the start of the registration, 49 patients were entered into the study, and all were eligible. Twenty-five and 24 patients were randomly assigned to the treatment and control groups, respectively. No statistically significant difference in the overall survival and disease-free survival between the 2 groups was observed. However, the appearance of carcinomatous pleuritis was suppressed by the hypotonic cisplatin treatment (42% of the control group vs 8% of the treatment group, P =.008). CONCLUSIONS: Although the randomized trial was prematurely terminated, the intraoperative intrapleural hypotonic cisplatin treatment was found to effectively suppress the appearance of carcinomatous pleuritis in resected patients who demonstrated a positive pleural lavage cytology finding.     

Intraoperative lavage cytologic analysis of surgical margins as a predictor of local recurrence in pulmonary metastasectomy

HYPOTHESIS: Cytologic analysis of intraoperative lavage at the surgical margin during wedge or segmental resection for pulmonary metastatic lesions predicts postoperative local failure at the surgical margin of the pulmonary parenchyma. DESIGN: Prospective nonrandomized trial. SETTINGS: Institution-based study. PATIENTS: Fifty-one consecutive patients undergoing wedge or segmental resection for 87 pulmonary metastatic lesions of various primary tumor types from November 1, 1997, through January 31, 2001, were prospectively enrolled. INTERVENTIONS: An intraoperative lavage cytologic technique at the surgical margin for each pulmonary metastasis was performed as described previously. MAIN OUTCOME MEASURES: Incidence of positive cytologic findings and postoperative local recurrence at the surgical margin. RESULTS: Of the examined lesions, 10 (11%) showed positive cytologic results at the surgical margin, despite a macroscopically safe margin in the attempted resection. Of these, metastasectomy was converted to segmentectomy in 3. An additional wedge resection and evaporation using an Nd:YAG laser in the surgical margin were performed in 1 and 4 lesions, respectively. Complications precluded further treatment in 2 lesions. By July 2001, although no local recurrence at the surgical margin area was found among the lesions with negative cytologic results, recurrence at the surgical margin occurred in 2 with positive cytologic results, including 1 receiving no treatment and 1 receiving Nd:YAG laser evaporation, indicating that a significant difference in the recurrence rate according to lavage cytologic status (P<.001). CONCLUSIONS: This intraoperative lavage cytologic technique in wedge or segmental resection of pulmonary metastases of various primary tumors may be a useful predictor of local recurrence at the surgical margin. With these test results, local recurrence at the surgical margin may be controllable in patients undergoing pulmonary metastasectomy.     

Rapid expansion of benign scalp neurofibroma caused by massive intratumoral hemorrhage--case report

A 62-year-old man with neurofibromatosis type 1 presented with rapid growth of a scalp mass. Head computed tomography demonstrated a large extracranial tumor of soft tissue density with massive intratumoral hematoma. Cerebral angiography demonstrated remarkable hypervascularity of the tumor. Preoperative embolization and total removal of the tumor was performed. The tumor contained a large amount of intratumoral hematoma (500 ml). The histological diagnosis was neurofibroma without malignant transformation. Benign scalp neurofibroma showing massive intratumoral hemorrhage is rare. Rapid growth or intratumoral hemorrhage in neurofibroma may be an indicator of malignant transformation.     

Practical usefulness of bipolar scissors in hepatectomy

BACKGROUND/AIMS: Because less surgical stress might preserve quality of life of patients, it is more desirable to decrease both intraoperative blood loss and liver injury especially in hepatectomy. For the patients with hepatocellular carcinoma based on chronic liver dysfunction, it is more essential to control bleeding and reduce liver injury in hepatectomy than in other diseases. In the present study, a retrospective comparison about usefulness was made in hepatectomy between using bipolar scissors and using conventional procedure. Before 1997, in our hospital, we had dissected the liver by using the crushing clamp method in combination with cauterization by microwave coagulator for the purpose of reducing intraoperative blood loss. Since 1998, bipolar scissors have been introduced toward hepatectomy as a new, simple and easy device to use. METHODOLOGY: Fifty-three consecutive patients with primary hepatocellular carcinoma at TNM stage I/II who underwent partial hepatectomy between 1996 and 1999 were enrolled in the study. Thirty-two patients (1996-1997) were treated by using a conventional method (group CM) and 21 patients (1998-1999) were treated by using bipolar scissors (group BS). The factors related to surgical stress were compared between the two groups. RESULTS: The amounts of blood loss/transfusion were lower in group BS (641/100 mL) than in group CM (1112/450 mL). The percentages of patients who lost more than 1000 mL of blood were lower in group BS (19%) than in group CM (47%) (P = 0.04). An intraabdominal drainage was needed for 9.0 +/- 6.6 days in group BS, and the drainage period was shorter than that in group CM (15.0 +/- 8.7 days) (P = 0.01). CONCLUSIONS: These results indicated the superiority of bipolar scissors in decreasing blood loss and liver injury to the conventional method, suggesting the worth of performing the prospective randomized study.     

Formation of the biopulsatile vascular pump by cardiomyocyte transplants circumvallating the abdominal aorta

In spite of the fact that patients with heart diseases requiring heart transplantation are increasing in the world, there are a lack of donors, which makes it hard to offer them these life-saving transplants. As a way to overcome this dilemma, we have researched the addition of the new biopump, which consists of the cultured embryonic cardiomyocytes grafted around the abdominal aorta and contracts spontaneously, which subsequently supports the function of the host heart. Ventricular tissues from ICR 14-day-old embryos were cultured and were injected to BALB/c nude mice (male, 8-week-old) subperitoneally around the abdominal aorta. At 3 and 7 days after implantation, action potential of the grafts was measured. Grafts were prepared for histological study. The grafts survived, showed vigorous angiogenesis, and contracted spontaneously. The cardiomyocytes in the grafts showed irregular arrangement, containing myofibrils with sarcomeres and intercalated disks. It was confirmed by immunohistochemistry that the cardiomyocytes in the grafts matured in accordance with normal development. The grafts were very quickly invaded by small vessels from the surrounding tissues showing the formation of new circulation. Embryonic cardiomyocytes have the ability to remodel the abdominal aorta into a spontaneous pulsating apparatus and to function as a vascular pump.