Lecithinized superoxide dismutase retards wobbler mouse motoneuron disease.

Gene mutations of Cu/Zn superoxide dismutase (SOD) have been discovered in familial amyotrophic lateral sclerosis (ALS). Oxidative stress also plays a role in the pathogenesis of sporadic ALS. Whether antioxidant therapy is beneficial in this fatal disease is now crucial. We have shown that SOD treatment improves neuromuscular dysfunction and morphological changes in wobbler mouse motoneuron disease. Progressive spinal motor neuronopathy and axonopathy, predominantly in the cervical cord, occur at postnatal age 3-4 weeks, leading to muscle weakness and contracture of the forelimbs in this animal. These motor deficits rapidly increase by postnatal age 6-8 weeks, and then slowly progress. Wobbler mice were given two doses daily of phosphatidyl choline-bound Cu/Zn SOD (PC-SOD, 10(4), 10(5) U/kg) or a vehicle solution by intraperitoneal injection from postnatal 3-4 to postnatal 7-8 weeks of age. PC-SOD treatment attenuated progression of motor dysfunction, prevented denervation muscle atrophy, and delayed degeneration of spinal motoneurons in wobbler mice. This raises the possibility that PC-SOD may have therapeutic potential in human motoneuron disease.

Coadministration of interleukin-6 (IL-6) and soluble IL-6 receptor delays progression of wobbler mouse motor neuron disease.

Interleukin-6 (IL-6), a multipotential cytokine, initiates signal transduction pathways similar to those of ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF). These molecules share the signal transducing receptor component, gp130. IL-6 triggers homodimerization of gp130, whereas CNTF and LIF induce heterodimerization of gp130 and LIF receptor. Although CNTF or LIF treatment attenuates motor deficits in wobbler mouse motor neuron disease (MND), neuroprotective effects of IL-6 on this animal have not yet been clarified. Here we studied whether simultaneous treatment with IL-6 and soluble IL-6 receptor (sIL-6R) can ameliorate symptomatic and neuropathological changes in wobbler mouse MND. After clinical diagnosis at postnatal age 3-4 weeks, wobbler mice received subcutaneous injection with human recombinant IL-6 (1.0 mg/kg), human sIL-6R (0.5 mg/kg), IL-6 + sIL-6R or vehicle, daily for 4 weeks in a blind fashion. Compared to vehicle, coadministration with IL-6 and sIL-6R potentiated grip strength, attenuated muscle contractures in the forelimbs, reduced denervation muscle atrophy and prevented degeneration of spinal motor neurons. Single administration with IL-6 or sIL-6R did not retard the symptomatic and neuropathological progression, although IL-6-treated mice did not raise anti-IL-6 antibodies. Treatment with IL-6 + sIL-6R, but not with IL-6 or sIL-6R alone delayed progression of wobbler mouse MND. Our results indicate that the neuroprotective mechanism for IL-6/sIL-6R on wobbler mouse MND differs from that of CNTF or LIF alone. We hypothesize that IL-6/sIL-6R complex may function on motor neurons through activation and homodimerization of gp130.

Magnetic resonance imaging and neuropathological findings in two patients with Creutzfeldt-Jakob disease.

We report 2 autopsy-proven patients with Creutzfeldt-Jakob disease (CJD) showing bilateral decreased signal intensity in the thalamus on T2-weighted images. On post-mortem examination, all affected areas showed the characteristic features of CJD, such as neuronal loss, gliosis, and status spongiosus. These findings are another distinctive MRI appearance in CJD.

Effect of transforming growth factor beta 1 on spinal motor neurons after axotomy.

Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor beta (TGF-beta) family, has potent effects on developing motor neurons. TGF are pluripotent cytokines that exert biological effects on a variety of neurons. TGF beta 1, on the other hand, promotes motor neuron survival in vitro and saves motor neurons from naturally occurring cell death. Here we investigate the neurotrophic effects of TGF beta 1 for axotomized motor neuron death. The sciatic nerve was cut in newborn rats and TGF beta 1 was injected, either by intraperitoneally or by lesion site, for 14 days after transection. Two or six weeks postlesion, the number and the diameter of motor neurons was assessed. TGF beta 1 significantly attenuated axotomy induced motor neuron death by intraperitoneal administration or by lesion site administration at 2 weeks after neonatal axotomy in a similar way. However, no effect was observed at 6 weeks after nerve lesion, despite continuous application of TGF beta 1 daily for 14 days. These results indicate that TGF beta 1 can prevent the death of motor neurons in vivo, but it cannot permanently rescue lesioned motor neurons.

Deprenyl enhances neurite outgrowth in cultured rat spinal ventral horn neurons.

Deprenyl, a selective monoamine oxidase B inhibitor, is effective in Parkinson's disease, and can slow the cognitive deterioration in Alzheimer's disease. However, it is not known whether this agent has a trophic effect on spinal motor neurons. We have studied neurotrophic effects of deprenyl on spinal motor neurons, using explanted ventral spinal cord culture from 13-day-old rat embryos. Deprenyl-treated cultures significantly enhanced neurite outgrowth with cultures of ventral spinal cord. Our data suggest that deprenyl is one of the candidate for neurotrophic factors on spinal motor neurons in vitro. A possible role for deprenyl in amyotrophic lateral sclerosis remains to be defined.

Intra-abdominal hemorrhage due to rupture of a splenic vein aneurysm: a case report.

Splenic vein aneurysm (SVA) is extremely rare. Most patients with an SVA have portal hypertension. In this report we describe the first recorded case of intra-abdominal hemorrhage due to rupture of an SVA in a patient without evidence of portal hypertension. A 72-year-old man was admitted to our medical center in a state of shock, with complaints of acute abdominal pain and abdominal distention. Preoperatively, abdominal ultrasonography demonstrated an echo-free space in the abdomen, suggesting the presence of a fluid collection. In addition, computed tomography revealed an enhanced lesion with contrast material in the pancreatic tail. An emergency operation showed bleeding from the SVA near the pancreatic tail. Consequently, a distal pancreatectomy with splenectomy was performed. Histologically the lesion was diagnosed as an SVA surrounded by pancreatic tissue with chronic inflammatory changes. The patient's postoperative course was uneventful.

Basic fibroblast growth factor and platelet-derived growth factor prevent the death of spinal motor neurons after sciatic nerve transection in the neonatal rats.

In vivo, motor neurons are destined to die after axotomy. Several neuronal growth factors, such as ciliary neurotrophic factor, brain-derived neurotrophic factor, and leukemia inhibitory factor rescue neuronal death of axotomized motor neurons. Here, we report that systemically administered basic fibroblast growth factor and platelet-derived growth factor prevented spinal motor neuron death in neonatal rats following sciatic nerve resection. These data indicate that basic fibroblast growth factor and platelet derived growth factor play a role for motor neuron survival in vivo.

TRH-analog, TA-0910 (3-methyl-(s)-5,6-dihydroorotyl-L-histidyl-L-prolinamide) rescues motor neurons from axotomy-induced cell death.

TA-0910 (3-methyl-(s)-5,6-dihydroorotyl-L-histidyl-L-prolinamide) is a potent and long acting TRH analog. We have studied the effect of TA-0910 on axotomy-induced neuronal death. The left sciatic nerve was transected in neonatal rats. TA-0910 or vehicle was administered on consecutive 14 days with intraperitoneal injections. After the treatment, the number of spinal motor neurons and the motor neuron diameter was assessed at the level of L4-6 segments. In comparison with vehicle, TA-0910 significantly prevented the death of motor neurons and preserved the motor neuron diameter on the lesioned side. These results suggest that TA-0910 is a survival factor for developing spinal motor neurons.

Neuroprotective effect of basic fibroblast growth factor on wobbler mouse motor neuron disease.

Basic fibroblast growth factor (bFGF) possesses neuroprotective effects on a variety of neurons. Here we report that it delays progression of motor neuron disease (MND) in the wobbler mouse. After initial diagnosis of MND at post-natal age 3-4 weeks, wobbler mice receive either recombinant human bFGF (1 mg kg-1, n = 10) or vehicle (n = 10), daily for weeks by subcutaneous injection in a blind fashion. We performed symptomatic and neuropathological assessments in both groups. The treatment was fulfilled at 7-8 weeks of age. In comparison with vehicle, bFGF treatment potentiated grip strength (p < 0.008), attenuated forelimb contracture (p < 0.003), and increased weight of the biceps muscle (p < 0.008). bFGF-treated mice retarded denervation muscle atrophy (p < 0.001) and degeneration of spinal motoneurons (p < 0.001). Our study shows that bFGF treatment is beneficial in a murine MND model. We provide a rationale that bFGF may have therapeutic potential in peripheral motor neuropathy or MND.

Acidic and basic fibroblast growth factors enhance neurite outgrowth in cultured rat spinal cord neurons.

We have studied neurotrophic effects of acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) on explanted ventral and dorsal spinal cord cultures from 13- and 14-day-old rat embryos. Cultures treated with aFGF and bFGF significantly enhanced neurite outgrowth with cultures of ventral spinal cord, but not with cultures of dorsal spinal cord. Our data suggest that aFGF and bFGF are potent neurotrophic factors on rat ventral spinal cord neurons in vitro.

Bromocriptine prevents neuron damage following inhibition of superoxide dismutase in cultured ventral spinal cord neurons.

Rosen et al. have reported point mutations in the cytosolic Cu/Zn superoxide dismutase (SOD 1) gene in some families with familial amyotrophic lateral sclerosis (ALS). To determine whether decreased SOD activity could contribute to neuronal damage, rat embryo ventral spinal cord neurons were incubated with diethyldithiocarbamate (DDC), an inhibitor of SOD. There was a marked increase in neuronal damage in cultures exposed to DDC and this phenomenon was dose-related. In this paradigm, these deteriorative changes were prevented by bromocriptine. DDC-treated ventral spinal cord neurons provide an in vitro model of free radical neurotoxicity secondary to decreased SOD activity. Simultaneous treatment with bromocriptine and DDC reduced neurotoxicity, indicating that bromocriptine has a neuroprotective effect against free radicals.

Deprenyl and pergolide rescue spinal motor neurons from axotomy-induced neuronal death in the neonatal rat.

It has been reported that both the monoamine oxidase inhibitor, deprenyl and the dopamine receptor agonist, pergolide have neuroprotective actions. To investigate the effect of deprenyl and pergolide on axotomized motor neuron death, we examined the survival of spinal motor neurons after sciatic nerve transection in the neonatal rats. Newborn rats were anesthetized with hypothermia. Sciatic nerve was cut near the obturator tendon in the left thigh. Animals were then treated daily with deprenyl (10 mg kg(-1)), pergolide (5 mg kg(-1)), or PBS for 14 days with intraperitoneal injections in a blind fashion. After the treatment, the number of spinal motor neurons in the L 4-6 was counted. There was approximately a 50% loss of spinal motor neurons in PBS-treated group. By contrast, both deprenyl and pergolide prevents spinal motor neuron death after axotomy Co-administration of deprenyl and pergolide is more effective than either agent alone but not significant. These findings are consistent with the idea that deprenyl and pergolide are survival factors for developing spinal motor neurons.

Experience with endoscopic axillary lymphadenectomy using needlescopic instruments in patients with breast cancer: a preliminary report.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of endoscopic axillary lymphadenectomy using needlescopic instruments in patients with breast cancer. METHODS: Five patients with breast cancer were treated by partial mastectomy and endoscopic axillary lymphadenectomy. We evaluated the results of the surgical procedure and the postoperative course. RESULTS: In all the patients, endoscopic axillary lymphadenectomy was performed successfully. The mean duration of the operation was 105.4 min, the mean blood loss 19.4 ml, and the mean number of dissected axillary lymph nodes 13. There were no intra- or postoperative complications. The mean amount of lymphorrhea was 131.2 ml, and the mean duration of drainage was 3.6 days. No postoperative analgesics were administered. CONCLUSIONS: Endoscopic axillary lymphadenectomy can be performed safely with needlescopic instruments, but further study is needed to establish this technique.

Spleen-preserving laparoscopic distal pancreatectomy with conservation of the splenic artery and vein for a large insulinoma.

We report a successful spleen-preserving laparoscopic distal pancreatectomy for a large insulinoma with conservation of the splenic artery and vein. The patient was a 48-year-old man with syncope due to hypoglycemia. Abdominal computed tomography (CT) and ultrasonography revealed a large 6-cm mass located in the tail of the pancreas. We adopted the laparoscopic approach to remove the tumor. After careful dissection and an accurate hemostasis between the pancreas and splenic vessels, laparoscopic distal pancreatectomy was carried out using a linear stapler. There were no perioperative complications. The patient was discharged uneventfully. He had no hypoglycemic episodes or abdominal symptoms during 8 months of follow-up. When performed by experienced laparoscopic surgeons in conjunction with intraoperative ultrasonography, spleen-preserving laparoscopic distal pancreatectomy with conservation of the splenic artery and vein is a technically feasible procedure for the treatment of benign lesions of the tail or body of the pancreas.

Laparoscopic resection of gastrointestinal mesenchymal tumors located in the upper stomach.

BACKGROUND: The treatment strategy for a gastrointestinal mesenchymal tumor located close to the esophagogastric junction remains controversial. The authors evaluate the criteria indicating that a gastrointestinal mesenchymal tumor is suitable for laparoscopic resection and assess the surgical techniques on the basis of clinical outcomes. METHODS: The criteria specified a tumor more than 2 cm in diameter or a tendency for it to increase in size during the follow-up period. For eight patients in whom the tumor was located within 3 cm of the esophagogastric junction, an intragastric laparoscopic approach was used, whereas for seven patients in whom the tumor was further from the esophagogastric junction, an exogastric approach was used. RESULTS: In all 15 cases, the laparoscopic resection was successful, with no complications. The intragastric group had a mean maximal tumor size of 2.9 cm, a mean operation time of 168 min, and a mean postoperative hospital stay of 8.8 days, whereas these values in the exogastric group, were respectively, 3.9 cm, 121 min (p = 0.0442), and 9.6 days. There were no recurrences in either group during the follow-up period. CONCLUSION: The good clinical outcomes suggest hat the criteria used as an indication for laparoscopic resection and the surgical techniques applied were appropriate for the resection of gastrointestinal mesenchymal tumors.

Laparoscopic resection of a functional paraganglioma in the organ of Zuckerkandl.

We describe the successful laparoscopic resection of a functional paraganglioma in the organ of Zuckerkandl. A 47-year-old man with hypertension and diabetes mellitus was found to have an abdominal mass beside the aorta. The tumor was diagnosed as a functional paraganglioma by diagnostic imaging and biochemical tests. We then performed a transperitoneal laparoscopic resection for removal. After freeing the left ureter, resecting the inferior mesenteric artery, and dividing the small blood vessels, the tumor was isolated and found to be preserved in its capsule. It was retrieved in a bag through an enlarged incision. The operation time was 450 min and blood loss was 410 ml. The postoperative course was uneventful and there has been no local recurrence or distant metastasis during the 18-month follow-up period. Laparoscopic resection of functional extraadrenal paragangliomas is technically feasible and safe if adequate pre- and intraoperative medical management and a careful, steady surgical technique are used.

Laparoscopic intragastric resection of gastric leiomyoma using needlescopic instruments. Case report.

Laparoscopic intragastric resection of gastric leiomyoma was performed using needlescopic instruments. The patient was a 71-year-old man who had a 2-year history of gastric submucosal tumor 2 cm in diameter located near the esophagocardiac junction. After getting informed consent, we performed a laparoscopic intragastric tumor resection under an oral endoscope. There were no intra- or postoperative complications. The patient was discharged uneventfully. Histopathologic diagnosis of the tumor was leiomyoma. Laparoscopic intragastric resection of a benign gastric submucosal tumor using needlescopic instruments is technically feasible and as safe as a less invasive procedure.

Laparoscopic intragastric stapled resection of gastric submucosal tumors located near the esophagogastric junction.

BACKGROUND: Laparoscopic resection cannot be applied easily to tumors located near the esophagogastric junction or the pyloric ring. We evaluated our laparoscopic intragastric surgical technique for gastric submucosal tumors located near the esophagogastric junction and the results of a clinical study. MATERIALS AND METHODS: We performed our technique in six patients: one man and five woman with a mean age of 61 years. Using the laparoscopic procedure, after inflation of the stomach, we inserted two or three balloon-type ports into the stomach through the abdominal wall. RESULTS: A stapled resection of gastric submucosal tumors using a laparoscopic linear stapler was performed successfully in all the patients. Without exception, stapled resections were successfully performed. The mean operation time was 168 min, and the blood loss was minimal There were no intra- or postoperative complications. The mean postoperative hospital stay was 9.8 days. The mean maximal diameter size of the resected specimens was 2.4 cm. Histopathologic diagnoses were gastrointestinal stromal tumors in five cases and enterogenous cyst in one. There were no recurrences during a mean follow-up period of 27 +/- 11.6 months. CONCLUSION: Although we need to evaluate the long-term outcomes, our procedure is considered technically feasible, safe, and useful for the resection of gastric submucosal tumors located near the esophagogastric junction.

Laparoscopic resection of the pancreas and review of the literature.

BACKGROUND: Laparoscopic pancreatic surgery still is not a common procedure worldwide. Postoperative complications such as a pancreatic leakage cause a serious condition. We report our consecutive laparoscopic pancreatic resections of islet cell tumors or benign diseases and their outcomes. METHOD: Laparoscopic pancreatic resections were attempted in three patients. Preoperative diagnoses were insulinoma in two patients and cystadenoma in one patient. The lesions were located in the pancreas body in two patients and the pancreas tail in one patient. Their sizes ranged from 1 to 6 cm in diameter (mean, 3 cm). RESULTS: We performed distal pancreatectomy using an endoscopic linear stapler with conservation of the spleen in two patients and enucleation in one patient. Of the distal pancreatectomies, the splenic artery and vein were preserved in one patient, whereas in the other they were divided. There were no perioperative complications in any of the cases. The mean postoperative hospital stay was 10 days (range, 7-14 days). There were no episodes of hypoglycemia or recurrence during the mean follow-up period of 25 months (range, 11-36 months). CONCLUSIONS: Although laparoscopic pancreatic resection of selected patients is a feasible and safe procedure in the hands of experienced laparoscopic surgeons, patients must be carefully observed after surgery to avoid serious conditions by pancreatic fistula.