Correlation between a Bedridden Status and the Long-term Outcome in Hemodialysis Patients after Intracerebral Hemorrhaging

Objective The quality of life and activities of daily living (ADL) are generally poor among dialysis patients after intracerebral hemorrhaging, and their precise clinical course remains unclear. In addition, the association between the severity of cerebral hemorrhaging and the long-term prognosis in these patients has not been fully elucidated. This study aimed to evaluate the subsequent prognosis of hemodialysis patients who survived the acute phase of intracerebral hemorrhaging. Methods We included hemodialysis patients who were admitted to Nagasaki University Hospital between 2007 and 2015 for intracerebral hemorrhaging treatment. After excluding cases of in-hospital death, survivors were classified using the 5-point modified Rankin Scale (mRS), which specifically measures the ADL in patients with cerebrovascular diseases. The patients were followed up at the medical facilities to which they were transferred in the same medical zone until 2017. Results Out of 91 patients with cerebral hemorrhaging (65±11 years old, 66% men, hemodialysis duration 108±91 months), 62 survived until discharge. Twenty-one patients died during observation, largely due to infectious diseases, such as sepsis and pneumonia (n=16, 76%). Compared to patients with mRS 0-4 (n=31), those with mRS 5 (n=31) showed a significantly poorer prognosis. The hazard ratio adjusted for age and antiplatelets was 13.7 (95% confidence interval: 3.88-63.7, p<0.001). Conclusion Hemodialysis patients with intracerebral hemorrhaging who were bedridden showed poor outcomes. The major causes of death were infections. Therefore, these patients should be carefully monitored for infections in order to improve their prognosis.     

Graded contusion model of the mouse spinal cord using a pneumatic impact device

OBJECTIVE: This study examined the effects of varying magnitudes of controlled spinal cord impact to the mouse spinal cord on neurological and histopathological variables to obtain a mouse model of spinal cord injury (SCI). METHODS: A laminectomy of the T10 vertebra was performed on anesthetized C57BL/6 mice. A pneumatic pressure-driven impact was performed on the spinal cord through the dura mater. Experimental groups were subdivided according to the energy of impact (0.25-mm-deep deformations): Group 1 (n = 5), impact velocity at 1 m/s; Group 2 (n = 5), impact velocity at 2 m/s; and Group 3 (n = 5), impact velocity at 3 m/s. Functional deficits over time were evaluated up to 28 days after SCI by testing hindlimb reflex and coordinated motor function. The extent of the lesions was analyzed histopathologically and quantified by a morphometric measurement. RESULTS: Mice of all groups exhibited profound functional deficits immediately after injury and subsequent gradual symptomatic recovery. The degrees of recovery were precisely correlated with the magnitudes of impact. The extent of resultant cord lesions was highly reproducible among animals, with little variance: means +/- standard deviation, 0.86 +/- 0.06/100 mm3 in Group 1; 2.4 +/- 0.28/100 mm3 in Group 2; and 11.0 +/- 1.0/100 mm3 in Group 3. CONCLUSION: Our results indicate that this model provides constant functional and histopathological lesions according to impact energy. This new mouse model of SCI opens a new avenue for studies investigating roles and/or effects of specific genes in the recovery process of SCI.     

Pouch operation for rectal cancer

Many retrospective studies have found that the functional outcome after a low anterior resection for rectal cancer is better with colonic J-pouch reconstruction than with conventional straight anastomosis. This advantage was demonstrated in prospective, randomized trials and meta-analyses. However, despite its increasing popularity there are several areas of controversy about the use of the colonic J-pouch reconstruction. These issues include anastomotic leaks, the part of the colon used for the pouch, the pouch size, causes of difficulty in evacuation, indications (the optimum level of anastomosis), appropriateness for the elderly, and long-term (2 years or more after surgery) functional outcome. All relevant articles identified from MEDLINE databases were reviewed. The incidence of anastomotic leaks is apparently reduced by colonic J-pouch reconstruction. A 5-cm colonic J-pouch using the sigmoid colon increases the reservoir function without compromising evacuation, and provides better functional outcome than straight anastomosis, even 2 years or more after surgery, in patients whose anastomosis is less than 8 cm from the anal verge. Patients with ultralow anastomoses, less than 4 cm from the verge, appear to benefit the most. At a time when the indications for abdominoperineal excision appear to be reduced for low rectal cancer, the demand for colonic J-pouch reconstruction (the best technique in pouch operations) is therefore likely to increase.     

Conus perimedullary arteriovenous fistula with multiple shunt points including the cauda equina: a case report

Perimedullary arteriovenous fistula (AVF) is usually located on the surface of the spinal cord and is fed by the anterior spinal artery and/or the posterior spinal artery. We report a rare case of Conus perimedullary AVF with multiple shunt points including the cauda equina. A 68-year-old man presented with leg pain when walking long distances. Magnetic resonance imaging at the thoracic and lumbar level revealed multiple signal voids with marked cord signal change. Angiography showed the perimedullary AVF fed by the anterior spinal artery from the right T9 intercostal artery at the level of the conus medullaris and the fistula fed by the left lateral sacral artery from the left internal iliac artery at the level of the cauda equina. In the first surgery, we performed surgical interruption of feeding arteries from the filum terminale and coagulated AV shunt of the conus medullaris. However residual perimedullary AVF was found at the conus medullaris in the postoperative angiography. Secondary surgery was carried out to treat residual AVF. Follow-up angiography showed complete disappearance of all AVFs. Postoperatively, the patient`s symptoms were improved. Because the Conus perimedullary AVF has the characteristics of multiple feeding arteies, multiple shunt points, and complex venous drainage, it must be kept in mind that other fistula could exist in the cauda equina or filum terminale.     

A neutralizing anti-fibroblast growth factor (FGF) 8 monoclonal antibody shows anti-tumor activity against FGF8b-expressing LNCaP xenografts in androgen-dependent and -independent conditions

BACKGROUNDS: Fibroblast growth factor 8-isoform b (FGF8b) has been detected in human clinical sex-organ related cancers including hormone-refractory prostate cancer. There are, however, few relevant experimental models. A murine monoclonal anti-FGF8 antibody, KM1334, has been shown to neutralize FGF8b and inhibit the growth of androgen-dependent mouse mammary SC-3 cells in vitro and in vivo. In the present study, we evaluated the anti-tumor activity of KM1334 against androgen-dependent and -independent progression of FGF8b-expressing human prostate cancer xenografts. METHODS: FGF8b cDNA was transfected into androgen-dependent human prostate cancer cell line LNCaP, and its xenograft tumors were established subcutaneously in SCID mice with or without castration. KM1334 at the dose of 400 microg/head was injected twice weekly. RESULTS: FGF8b-expressing LNCaP cells secreted FGF8b, showed enhanced level of Erk1/2 phosphorylation, and showed more potent growth properties than mock-expressing cells in vitro and in vivo. KM1334 reduced these properties in vitro, inhibited tumorigenecity in vivo (T/C=0.33), and showed anti-tumor activity against established tumors (T/C=0.47) of FGF8b-expressing cells. FGF8b-expressing LNCaP tumors were androgen-dependent. However, they recurred as androgen-independent FGF8b positive tumors after castration. KM1334 also inhibited the growth of established FGF8b-expressing tumors in the androgen-independent states (T/C=0.47). CONCLUSIONS: These results indicate that humanized monoclonal antibodies, conserving the paratope of KM1334, are a promising candidate for therapy of FGF8b-expressing clinical prostate cancers. Follow-up studies using xenograft models with clinical FGF8b-expressing tumors are required to validate these early findings.     

Predictors of Survival in Patients With Bone Metastasis of Lung Cancer

The prognosis of patients with bone metastasis from lung cancer has not been well documented. We assessed the survival rates after bone metastasis and prognostic factors in 118 patients with bone metastases from lung cancer. The cumulative survival rates after bone metastasis from lung cancer were 59.9% at 6 months, 31.6% at 1 year, and 11.3% at 2 years. The mean survival was 9.7 months (median, 7.2 months; range, 0.1-74.5 months). A favorable prognosis was more likely in women and patients with adenocarcinoma, solitary bone metastasis, no metastases to the appendicular bone, no pathologic fractures, performance status 1 or less, use of systemic chemotherapy, and use of an epithelial growth factor receptor inhibitor. Analyses of single and multiple variables indicated better prognoses for patients with adenocarcinoma, no evidence of appendicular bone metastases, and treatment with an epithelial growth factor receptor inhibitor. The mean survival period was longer in a small group treated with an epithelial growth factor receptor inhibitor than in the larger untreated group. The data preliminarily suggest treatment with an epithelial growth factor receptor inhibitor may improve survival after bone metastasis.     

Sling removal after the Vesica sling and tension-free vaginal tape (TVT) procedures

PURPOSE: We describe our experience of sling removal performed after either the Vesica sling procedure (due to vaginal erosion or at the time of reoperation for recurrent stress incontinence) or the tension-free vaginal tape (TVT) procedure (due to persistent urinary retention). MATERIALS AND METHODS: From May 1997 to December 2002, we performed 19 Vesica sling procedures and 66 TVT procedures for the treatment of urodynamic stress incontinence. In the former procedures, four patients (21%) developed vaginal erosion and underwent total or partial removal of sling material (Hemashield made from bovine-collagen-injected woven polyester). In another three patients, stress incontinence recurred 2-4 years after the Vesica sling procedure, and they underwent total sling removal and the TVT procedure. Before using the urethral pull-down process (UPDP) in TVT procedures, 2 out of 23 patients (8.7%) developed persistent urinary retention and underwent either sling release alone or partial sling removal concomitant with a second TVT procedure. After the introduction of the UPDP, no patient developed urinary retention. RESULTS: Three patients in whom total sling removal was performed due to vaginal erosion after a Vesica sling procedure developed recurrent stress incontinence. One patient who underwent partial sling removal remained continent, but vaginal erosion recurred 2 years later. Patients who had total sling removal and TVT procedures due to recurrent stress incontinence after Vesica sling procedure became continent with an uneventful postoperative course. One patient who underwent transvaginal release of TVT tape (polypropylene mesh) due to urinary retention after the TVT procedure developed recurrent stress incontinence, and the other who underwent partial removal of TVT tape and a second TVT procedure had resolution of urinary retention without recurrence of stress incontinence. CONCLUSION: Prompt and total sling removal should be recommended for vaginal erosion after the Vesica sling procedure. In patients with urinary retention after the TVT procedure, partial removal of TVT tape and a second TVT procedure using the UPDP to prevent overtightness may be a preferable choice to attain both continence and resolution of urinary retention.     

Local administration of hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds

Hepatocyte growth factor (HGF) has a number of biological activities, e.g., mitogenic, motogenic, antiapoptotic, antifibrous, and morphogenic. It also has angiogenic and angioprotective activities for endothelial cells. The aim of this study was to characterize the role of HGF in wound healing by administering the HGF gene locally to acute incisional skin wounds created on the backs of rats. To create wounds, the backs of Wistar rats were clipped and three 2-cm-long incisional wounds were made deep to the fascia. The wounds contained pannicrus carnosum and were created at intervals of 2 cm. After suturing, the HGF gene was then administered intradermally. Apoptotic cells in wound lesions were identified by TUNEL method as well as by immunological detection of active caspase-3. In the HGF-treated animals, we found almost complete suppression of apoptosis and well-organized wound healing. Histopathological examination revealed that the proliferation of fibroblasts was suppressed and that scar formation was less apparent in the HGF-treated animals compared to the controls. It is thought that administration of the HGF gene immediately after surgery may enhance the healing process through suppressing apoptosis, which occurred in the controls 1 week after suturing the incisional wound. In addition, locally increased HGF expression due to the introduction of the HGF gene to cells around wounds enhances dermal regeneration, possibly by promoting regeneration of dermal tissue, which results in less scarring due to its antifibrotic effect. Thus, HGF supplementation through gene therapy may be an effective strategy for treating wounds, as it increases the regeneration of the dermis to allow for "scarless wound healing."     

A case of thoracic disc herniation with sudden onset paraplegia on toilet straining: case report

Thoracic disc herniation is less common rather than cervical or lumbar herniation. Cases of sudden onset without trauma are especially rare. Generally, the neurological onset of disc herniation is caused by mechanical cord compression due to a protruded disc, and its onset is usually gradual. Ischemia is also considered as a factor of neurological onset. We report a case of a 78-year-old male with sudden paraplegia while straining at the toilet. T2 weighted MR image on admission showed mild disc protrusion at the level of Th8-9 and intramedullary high signal intensity below the Th8-9 level. We speculate that Valsalva-like maneuver had led to the congestion of vertebral venous plexus or compression of the anterior spinal artery, and spinal ischemia occurred.