Vascular endothelial growth factor restores erectile function through inhibition of apoptosis in diabetic rat penile crura

PURPOSE: Vascular endothelial growth factor (VEGF) is known as a multifunctional protein with roles in angiogenesis stimulation and apoptosis inhibition. We hypothesized that intracavernous administration of VEGF would recover erectile dysfunction due to diabetes by protection from apoptosis in the penile cavernosum. MATERIALS AND METHODS: A total of 30, 6-month-old male Sprague-Dawley rats were divided into 2 large groups, namely 20 with diabetes and 10 healthy controls. The diabetic group received intraperitoneal injection of streptozotocin (STZ) to induce diabetes. Intracavernous injection of VEGF was administered to randomly selected STZ diabetic rats 6 weeks after STZ injections. Erectile functional studies were performed in 10 STZ and 10 STZ plus VEGF rats at 12 weeks. After completion of the functional study the penile crura were collected for molecular and immunohistochemical studies. RESULTS: Mean intracavernous pressure in the diabetic group was significantly lower than in controls and low pressure was significantly recovered by VEGF treatment. Gene expression of pro-apoptotic and anti-apoptotic factors were present in the control, diabetic and VEGF treated groups. However, anti-apoptotic protein expression was lacking in the diabetic group and it was recovered by VEGF treatment. The apoptotic index in the diabetic group was significantly higher than in controls and this index was significantly decreased in the VEGF treated group. CONCLUSIONS: The decrease in and recovery of intracavernous pressure correlated significantly with a variation in anti-apoptotic protein expression in the diabetic and VEGF treated groups. To our knowledge this is the first study to show that intracavernous injection of VEGF restores erectile dysfunction through the inhibition of apoptosis in diabetic rats.     

Immune responses and immunosuppressive mechanisms in tumor-bearing hosts

In the 1980s, it was demonstrated that human tumors had tumor antigens, and immune responses against human tumor antigens were induced. These days, various new immunotherapies are attempted to enhance immune responses against tumors and prevent tumor growth and progression. Nonetheless, it is difficult to reject tumors by only immune responses. One of the reasons is an immunosuppressive state in tumor-bearing hosts. It is considered that an immunosuppressive state is induced by various factors from the tumor side or host side, but the precise mechanism is not clear. When we consider the effective immune responses against tumors, we need to make clear and improve the immunosuppressive state in the tumor-bearing hosts.     

Evaluation of coronary artery calcification by multi-detector row computed tomography for the detection of coronary artery stenosis in Japanese patients

BACKGROUND: The development of an efficient noninvasive examination to detect coronary atherosclerosis is needed as a strategy to prevent coronary heart disease. To evaluate the usefulness of calcium score measured by multi-detector row computed tomography (MDCT), we compared calcium score derived from MDCT with findings of coronary artery stenosis assessed by coronary angiography (CAG). METHODS: In 108 patients (94 men, 14 women; average age, 65.7 years), we performed unenhanced CT scans and calculated coronary artery calcium score in 259 vessels without previous intervention and severe motion artifact to determine the correlation with the degree of coronary stenosis by CAG. RESULTS: The sensitivity and the specificity of calcification (calcium score 0.1+) for severe stenosis (75+%) were 89% and 43%, respectively. All four vessels with calcium score 1000+ had a severe stenosis. The areas under the receiver operating characteristics curve of calcium score for severe stenosis were 0.80 +/- 0.04, indicating the efficacy of this technique. CONCLUSIONS: Coronary artery calcification and calcium score determined by MDCT were associated with coronary arteries with severe stenosis. This technique appears to be useful for the evaluation of coronary atherosclerosis.     

Sentinel surveillance for international Shigella by a quarantine station in Japan

The Japanese quarantine system monitors incoming passengers to detect imported pathogens at international airports. At one airport, we found that 74% of 13 315 travellers returning with diarrhoea had visited only one country before entering Japan. On the basis of our results, we hypothesized that the international distribution and potential source of bacterial strains could be inferred by analysing strains isolated from travellers returning to Japan. In order to demonstrate the potential for this system, we randomly selected five Shigella sonnei strains and examined their restriction fragment length polymorphism patterns. One set of strains appeared to be closely related, while three sets, isolated from travellers who visited different countries were possibly related. These results suggest that international distributions and potential sources of S. sonnei may be inferred by monitoring isolates from passengers arriving at a Japanese quarantine station.     

Adenosinergic modulation of ventilation in obese zucker rats

OBJECTIVES: The goal of our study was to determine whether altered adenosinergic mechanisms contribute to the depressed ventilatory response observed in obese Zucker rats. RESEARCH METHODS AND PROCEDURES: Eight lean and eight obese Zucker rats were studied at 7 to 8 weeks of age. Ventilation (V(E)) during room air, during 5-minute hypercapnic (7% CO(2), balance O(2)), and during 30-minute sustained hypoxic (10% O(2)) exposures were sequentially measured by the barometric method on three separate occasions after the randomized blinded administration of equal volumes of either saline (control), 8-(p-sulfophenyl)-theophylline (8-PST, 7 mg/kg, peripheral adenosine antagonist), or aminophylline (AMPH, 15 mg/kg, peripheral and central adenosine antagonist). RESULTS: During room air and hypercapnic exposures, AMPH (but not 8-PST) significantly (p < 0.05) increased V(E) in both lean and obese rats. During acute (2 minute) hypoxic exposure, 8-PST (but not AMPH) significantly depressed V(E) in lean rats. In contrast, AMPH (but not 8-PST) selectively increased V(E) in obese rats. During sustained (10 to 30 minutes) hypoxic exposure, neither AMPH nor 8-PST administration altered V(E) in lean rats. In contrast, AMPH (but not 8-PST) selectively increased V(E) during the late response in obese rats. DISCUSSION: Our findings indicate that obese rats possess altered adenosinergic modulation of ventilatory responses to acute and sustained hypoxia in two opposite ways. We conclude that the reduced hypoxic ventilatory response observed in obese Zucker rats is attributed to depressed adenosinergic peripheral excitatory mechanisms and to enhanced adenosinergic central depression mechanisms, both of which contribute to the blunted ventilatory response in obesity.     

Combined mediastinal node assessment by lymphadenectomy and intraoperative mediastinoscopy

The purpose of this study was to determine the importance of combined mediastinal node assessment by lymphadenectomy and intraoperative mediastinoscopy to patients with left lung cancer. Forty-one patients with left lung cancer were divided into a group of 13 and a group of 28: in the first group, the aortic arch was mobilized, while in the second group the aortic arch was not mobilized. The mediastinal nodes of both groups were then dissected and mediastinoscopes were inserted into the operation field with an approach through thoracotomy to biopsy each mediastinal node. We compared nodal pathological assessment in these two groups. In the group with mobilized aortic arches, pathological assessment of lymphadenectomy at Naruke's station 3 was 11/13 (85%) and combined with intraoperative mediastinoscopy was 12/13 (92%). In the group without mobilized aortic arches, pathological assessment of lymphadenectomy of station 3 was 14/28 (50%) and combined use of intraoperative mediastinoscopy significantly improved the diagnoses to 24/28 (86%) (P=0.004). Combined use of lymphadenectomy and intraoperative mediastinoscopy could improve the assessment of station 3 in left lung cancer without mobilizing aortic arch.     

Percutaneous leverage pinning in the treatment of Bennett’s fracture

Twelve patients (eleven males, one female; mean age 36 years) with Bennetts fracture having a gap or a step-off of more than 2mm and in whom maintenance of the reduced position was difficult were treated by percutaneous leverage pinning. Bone union was obtained in all patients, and the wire was removed 37 days on average after the initial treatment. On the final follow-up examination, mild pain with motion was noted in two patients, and moderate to severe pain was noted in one patient. The reduction of the articular surface of the carpometacarpal joint of the thumb was confirmed by radiography; it was less than 1mm in nine patients, less than 2mm in two, and more than 2mm in one. Because reduction and fixation are performed utilizing the leverage force of the wire inserted into the trapezium, percutaneous pinning has advantages, such as technical simplicity and the ability to apply tension to the fractured site.     

Adrenal ganglioneuroma: a case report

A patient with an incidentally diagnosed adrenal ganglioneuroma is reported. A 37-year-old man who underwent abdominal computed tomography (CT) in the course of evaluating liver dysfunction was found to have a right adrenal tumor. Laboratory data including results of endocrinologic tests were normal except for a slight elevation of plasma aldosterone. With a preoperative diagnosis of non-functioning right adrenal tumor, resection was performed. The tumor specimen was noncystic weighing 150 g and measuring 10 x 8 x 3 cm. The histopathologic diagnosis was ganglioneuroma originating from the adrenal gland. Adrenal ganglioneuroma is relatively rare, 147 cases including ours have been reported in Japan. Increasing numbers of these tumors are being found incidentally by ultrasonography or CT. Ganglioneuroma is a benign tumor, and disagreement exists concerning diagnosis and indications for surgery.     

Secondary reconstruction of failed esophageal reconstruction

Between June 1992 and November 2002, 17 patients underwent secondary reconstruction of circumferential esophageal defects due to the failure of immediate reconstruction following ablation of thoracic esophageal cancer. Salvage reconstruction was achieved using free jejunal transfer in 13 patients (including long segment with double vascular pedicle in 2 cases), skin and/or musculocutaneous flap in 2 cases, and jejunal pull-up in 2 cases. In 5 patients, the second salvage surgery was required because of the failed first salvage. However, successful restoration of the esophagus and peroral alimentation was finally achieved in 16 of 17 patients, except 1 patient with several salvage operations using skin and musculocutaneous flap because the gut was unusable. We concluded that the preferred first choice for salvage restoration is free jejunal transfer. If the length of the esophageal defect is extensive, colonic interposition or jejunal pedicle with microvascular anastomosis for supercharging is the next option. If these procedures cannot be used, the transfer of a long jejunal segment with double vascular pedicles is recommended. Reconstruction using skin and/or musculocutaneous flap is the final option. As primary wound closure is often difficult in secondary reconstruction of the esophagus, a pectoralis major musculocutaneous flap is reliable to cover the reconstructed esophagus because skin flaps located in the neck region may be damaged by neck dissection or irradiation, and coverage of the anastomosis with muscle between the digestive tracts is effective to prevent leakage.