Porfimer sodium-mediated photodynamic therapy in patients with head and neck squamous cell carcinoma.

BACKGROUND: Photodynamic therapy is a less invasive therapeutic procedure for carcinomas. The goal of this study was to evaluate the utility of Photofrin (porfimer sodium)-mediated photodynamic therapy in patients with head and neck squamous cell carcinoma. METHODS: Forty-two head and neck squamous cell carcinoma patients who underwent Photofrin-mediated photodynamic therapy were treated by intraoperative light activation at 630 nm via a fiber optic microlens, 48 h after injection. We evaluated the impact of age, sex, tumor stage, primary site, light dose, and cancer history on overall survival using a Cox proportional hazards model. Information on the survival status of patients was obtained after a mean follow-up period of 51 months (range, 6-180 months). RESULTS: The 5-year overall survival for all patients was 57.8 % (95 % confidence interval of the survival rate: 39.8 %-72.1 %). The complete response rate was 69.0 %, and the efficacy (complete response + partial response) was 97.6 %. Earlier tumor stage was associated with increased survival (p = 0.012). Diseases of the respiratory tract also showed significant association with survival as compared to those of the alimentary tract (p = 0.01). CONCLUSIONS: Photofrin-mediated photodynamic therapy is useful for treating head and neck squamous cell carcinomas, and provides an improved quality of life in patients with recurrent or residual disease.

FGF2-responsive genes in human dental pulp cells assessed using a rat spinal cord injury model.

The central nervous system in adult mammals does not heal spontaneously after spinal cord injury (SCI). However, SCI treatment has been improved recently following the development of cell transplantation therapy. We recently reported that fibroblast growth factor (FGF) 2-pretreated human dental pulp cells (hDPCs) can improve recovery in a rat model of SCI. This study aimed to investigate mechanisms underlying the curative effect of SCI enhanced via FGF2 pretreatment; we selected three hDPC lines upon screening for the presence of mesenchymal stem cell markers and of their functionality in a rat model of SCI, as assessed using the Basso, Beattie, and Bresnahan score of locomotor functional scale, electrophysiological tests, and morphological analyses. We identified FGF2-responsive genes via gene expression analyses in these lines. FGF2 treatment upregulated GABRB1, MMP1, and DRD2, which suggested to contribute to SCI or central the nervous system. In an expanded screening of additional lines, GABRB1 displayed rather unique and interesting behavior; two lines with the lowest sensitivity of GABRB1 to FGF2 treatment displayed an extremely minor effect in the SCI model. These findings provide insights into the role of FGF2-responsive genes, especially GABRB1, in recovery from SCI, using hDPCs treated with FGF2.

Hyperbaric Oxygen Therapy as Concurrent Treatment with Systemic Steroids for Idiopathic Sudden Sensorineural Hearing Loss: A Comparison of Three Different Steroid Treatments.

We analyzed 356 patients with idiopathic sudden sensorineural hearing loss treated with hyperbaric oxygen therapy and systemic steroids (n = 161), systemic steroids alone (n = 160), or intratympanic and systemic steroids (n = 35). The main outcome measure was the hearing recovery rate. The effect of other variables, including the initial averaged 5-frequency hearing level, patient age, interval between the onset of symptoms and treatment, presence of vertigo as a complication, presence of diabetes mellitus, smoking history, and presence of hypertension, on the hearing recovery rate was also evaluated. The overall hearing recovery rate was significantly higher for the patients treated with hyperbaric oxygen therapy and systemic steroids than for those treated with systemic steroids alone (p < 0.001) or systemic and intratympanic steroids (p < 0.001). The presence of vertigo negatively affected hearing recovery. Our findings suggest that hyperbaric oxygen therapy confers a significant additional therapeutic benefit when used in combination with steroid therapy for idiopathic sudden sensorineural hearing loss.

Hyperbaric Oxygen Therapy as Adjuvant Treatment for Idiopathic Sudden Sensorineural Hearing Loss after Failure of Systemic Steroids.

We evaluated the outcomes of and prognostic factors for idiopathic sudden sensorineural hearing loss (ISSNHL) treated with adjuvant hyperbaric oxygen therapy (HBOT). A retrospective review of clinical data was performed for 167 patients with ISSNHL who failed to respond to systemic steroids and were treated by adjuvant HBOT at Shizuoka Saiseikai General Hospital. We analysed the clinical outcomes, the averaged 5-frequency hearing level after systemic steroids, patient age, the interval between post-steroids and pre-HBOT, vertigo as a complication, the presence of diabetes mellitus, smoking history, and hypertension. Overall, after HBOT, complete recovery occurred in 16 (9.6%) of the patients, with definite improvement in 16 (9.6%) and slight improvement in 45 (26.9%). The overall rate of hearing improvement was higher in the study group (77/167 cases, 46.1%) than in the control group (52/160 cases, 32.5%; p = 0.021). If performed appropriately, HBOT should be able to improve hearing in many cases unresponsive to initial therapy.

Evaluation of blood group antibodies in ABO-incompatible living-donor kidney transplantation.

OBJECTIVE: To assess changes in anti-blood type antibody titers and postoperative outcomes (graft survival and rejection rates) at our center with the use of the immunosuppressant, rituximab, in ABO-incompatible kidney transplants from living donors. Confirming anti-donor blood group antibodies is important for avoiding humoral rejection in ABO-incompatible kidney transplants. Splenectomy has been carried out in our hospital according to Alexandre's policy in order to suppress the production of anti-donor blood group antibodies. However, splenectomy has recently been avoided due to the administration of the immunosuppressant rituximab, which gives satisfactory outcomes. Thus, pre- and postoperative anti-donor blood group antibodies were measured, and the outcomes achieved with rituximab were examined. METHODS: A total of 134 cases of ABO-incompatible kidney transplants were carried out at Toho University Omori Medical Center between March 1989 and February 2013. These cases were classified as follows: azathioprine group (n = 62 patients); mycophenolate mofetil group (n = 33 patients); rituximab group (n = 39 patients). The anti-donor blood group antibodies levels (immunoglobulin G and immunoglobulin M) were measured in all groups before antibody removal, immediately before surgery, and 1, 2, 4 weeks and 3 months after surgery, and then compared. RESULTS: Rates of antibody-mediated rejection, including hyperacute rejection, in the azathioprine, mycophenolate mofetil, and rituximab groups were 32.2%, 18.1% and 7.6%, respectively. Graft survival rates were higher in the mycophenolate mofetil and rituximab groups than in the azathioprine group, but were lower in patients with higher preoperative antibody titers (≥128-fold higher immunoglobulin G) than in those with lower titers (<128-fold higher immunoglobulin G). In addition, postoperative anti-blood type antibody titers were significantly suppressed in the rituximab group. CONCLUSIONS: Administration of rituximab results in better antibody control than previous protocols including splenectomy, even in the postoperative period during which humoral rejection often occurs. This protocol eliminates the physical invasiveness of pre-transplant splenectomy, and is expected to provide better outcomes in chronic renal failure patients who undergo kidney transplants.

Derivation of iPSCs after culture of human dental pulp cells under defined conditions.

Human dental pulp cells (hDPCs) are a promising resource for regenerative medicine and tissue engineering and can be used for derivation of induced pluripotent stem cells (iPSCs). However, current protocols use reagents of animal origin (mainly fetal bovine serum, FBS) that carry the potential risk of infectious diseases and unwanted immunogenicity. Here, we report a chemically defined protocol to isolate and maintain the growth and differentiation potential of hDPCs. hDPCs cultured under these conditions showed significantly less primary colony formation than those with FBS. Cell culture under stringently defined conditions revealed a donor-dependent growth capacity; however, once established, the differentiation capabilities of the hDPCs were comparable to those observed with FBS. DNA array analyses indicated that the culture conditions robustly altered hDPC gene expression patterns but, more importantly, had little effect on neither pluripotent gene expression nor the efficiency of iPSC induction. The chemically defined culture conditions described herein are not perfect serum replacements, but can be used for the safe establishment of iPSCs and will find utility in applications for cell-based regenerative medicine.

Clinical utility of diffusion tensor imaging and fibre tractography for evaluating diffuse axonal injury with hemiparesis.

Although diffuse axonal injury (DAI) frequently manifests as cognitive and/or motor disorders, abnormal brain findings are generally undetected by conventional imaging techniques. Here we report the case of a patient with DAI and hemiparesis. Although conventional MRI revealed no abnormalities, diffusion tensor imaging (DTI) and fibre tractography (FT) revealed the lesion speculated to be responsible for hemiparesis. A 37-year-old woman fell down the stairs, sustaining a traumatic injury to the head. Subsequently, she presented with mild cognitive disorders and left hemiparesis. DTI fractional anisotropy revealed changes in the right cerebral peduncle, the right posterior limb of the internal capsule, and the right corona radiata when compared with the corresponding structures observed on the patient's left side and in healthy controls. On FT evaluation, the right corticospinal tract (CST) was poorly visualised as compared with the left CST as well as the CST in healthy controls. These findings were considered as evidence that the patient's left hemiparesis stemmed from DAI-induced axonal damage in the right CST. Thus, DTI and FT represent useful techniques for the evaluation of patients with DAI and motor disorders.

[Surgical indications and approaches for parapharyngeal space tumors].

In the 20-years from 1991 to 2010, we pathologically diagnosed 24 subjects with parapharyngeal space tumors by biopsying and/or resecting of 24 tumors. Of these, 18 were benign and 6 malignant. Pleomorphic adenoma and schwannoma predominated, accounting for 7 cases each. Enhanced CT and MRI were very useful in diagnosis, judging involvement and localization, and assessing radiological and pathological tumor diagnosis. Important radiological factors are determining whether tumor origin is pre-or post-styloid, and how the tumor is enhanced in CT or MRI. We treated 15 subjects surgically, telling 9 the diagnosis, and used only biopsy or scans. It is vital in follow-up to determine long-term treatment response.

A right-sided fourth branchial cleft cyst: a case report.

Branchial anomalies are a consequence of abnormal development of the branchial apparatus during embryogenesis. Here, a pediatric case with a right-sided fourth branchial cyst that was discovered on fetal ultrasound scanning (US) is presented. The embryological basis for the occurrence of this cyst and definitive surgical management are discussed.

Clinical utility of diffusion tensor imaging for evaluating patients with diffuse axonal injury and cognitive disorders in the chronic stage.

Although diffuse axonal injury (DAI) usually ellicits cognitive disorders, abnormal brain findings are generally undetected by conventional imaging techniques. The aim of this study was to evaluate the feasibility of using diffusion tensor imaging (DTI) to detect lesions in DAI patients and to investigate the correlation between DAI lesions and cognitive disorders. We examined 16 healthy controls and 11 patients with DAI. Using voxel-based analysis, we found that there were significantly more brain regions with decreased fractional anisotropy (FA) in the brain but DAI patients compared to healthy controls (p < 0.001), whereas few lesions were detected via conventional magnetic resonance imaging. There was a significant relationship between the results of the Wechsler Adult Intelligence Scale-Revised, Trail Making Test, and some indices of the Wechsler Memory Scale-Revised and the decreased FA observed in various areas of the brain (p < 0.001). The total cognitive scores on the functional independence and functional assessment measures, which represent behavioral problems, were correlated with the cluster (number of DAI lesions, p = 0.007) and voxel numbers (total size of all DAI lesions, p = 0.001). In the fiber tractography-based analysis, DAI patients with memory disorders showed an interruption of fibers within the fornix compared to healthy controls. These results indicate that DTI is a useful technique not only for detecting DAI lesions but also for examining cognitive disorders in DAI patients.

Development of involuntary movements after ventriculoperitoneal shunting for normal pressure hydrocephalus in a patient with chronic-phase thalamic haemorrhage.

BACKGROUND: Delayed-onset involuntary movements have been described after thalamic stroke. METHODS: We treated a patient with involuntary movements that increased after ventriculoperitoneal shunting (VPS) for normal pressure hydrocephalus (NPH) following thalamic haemorrage. One and one-half years after right thalamic and intraventricular haemorrhage, NPH suggested clinical evaluation and neuroimaging studies in a 56-year-old man. RESULTS: Hemidystonia and pseudochoreoathetosis were evident in the left arm, leg and trunk. Proprioceptive impairment and mild cerebellar dysfunction affected the left upper and lower extremity. Yet the patient could walk unassisted and carry out activities of daily living (ADL) rated as 90 points according to the Barthel Index (BI). Lumbar puncture lessened both gait disturbance and cognitive impairment. After VPS, cognition and urinary continence improved, but involuntary movements worsened, precluding unaided ambulation and decreasing the BI score to 65 points. Computed tomography after VPS showed resolution of NPH, while single-photon emission computed tomography showed increased cerebral blood flow after VPS. CONCLUSION: Increased cerebral blood flow after VPS is suspected to have promoted development of abnormal neuronal circuitry.

Diffusion tensor imaging fiber tractography for evaluating diffuse axonal injury.

Patients with Diffuse axonal injury (DAI) frequently exhibit cognitive disorders chronically. Radiologic recognition of DAI can help understand the clinical syndrome and to make treatment decisions. However, CT and conventional MRI are often normal or demonstrate lesions that are poorly related to the cognitive disorders. Recently, diffusion tensor imaging (DTI) fiber tractography has been shown to be useful in detecting various types of white matter damage. The aim of this study was to evaluate the feasibility of using DTI fiber tractography to detect lesions in DAI patients, and to correlate the DAI lesions with the cognitive disorders. We investigated two patients with chronic DAI. Both had impaired intelligence, as well as attention and memory disorders that restricted their activities of daily living. In both patients, DTI fiber tractography revealed interruption of the white matter fibers in the corpus collosum and the fornix, while no lesions were found on conventional MRI. The interruption of the fornix which involves the circuit of Papez potentially correlates with the memory disorder. Therefore, DTI fiber tractography may be a useful technique for the evaluation of DAI patients with cognitive disorders.

Long-term effect of low-frequency repetitive transcranial magnetic stimulation over the unaffected posterior parietal cortex in patients with unilateral spatial neglect.

OBJECTIVE: To explore long-term effects on unilateral spatial neglect of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected posterior parietal cortex. DESIGN: Uncontrolled pilot study. SUBJECTS: Two chronic-phase patients with left-sided unilateral spatial neglect from cerebral infarction. METHODS: Six rTMS sessions were undertaken for 2 weeks. Each session included 900 stimuli applied over P5 at an intensity of 95% motor thresholds and a frequency of 0.9 Hz. The Behavioural Inattention Test, either the Mini-Mental State Examination or the Revised Hasegawa Dementia Scale, Brunnstrom Recovery Stage, and Barthel Index were evaluated at 2-week intervals until 6 weeks after rTMS sessions. Single-photon emission computed tomography was performed 2 weeks before and after rTMS. RESULTS: Behavioural Inattention Test scores improved remarkably, especially from 2 to 4 weeks after rTMS sessions. At 6 weeks, Behavioural Inattention Test scores still remained above pre-rTMS levels. Other clinical evaluations as well as single-photon emission computed tomography showed no significant change during the study. CONCLUSION: In this small pilot study, low-frequency rTMS over the unaffected posterior parietal cortex decreased unilateral spatial neglect for at least 6 weeks.

Clinical outcome and accommodation in ABO incompatible kidney transplantation.

We performed 84 ABO-incompatible kidney transplants at Toho University since 1989, with plasmapheresis and exchange replacing AB blood group plasma as pre-conditioning to reduce anti-donor blood group antibodies. Our current immunosuppression protocol consists of basiliximab, MMF, steroid, and cyclosporine or tacrolimus, including splenectomy. Overall patient/ graft survival rates (n=84) were 95/93 at one year, 94/92 at 3 years, 87/80 at 5 years, 87/75 at 7 years, and 83/67 at 10 years. The outcomes are similar to those of ABO-compatible living donor transplants. We have achieved 100% graft and patient survival rates (n=48) for the 7 years since January 1997. Our findings suggest that post-conditioning is not necessary to control titers of anti-donor blood group antibodies or to overcome acute humoral rejection. Infection control is critical in achieving good outcomes in ABO-incompatible transplants. We found that only anti-donor blood group antibodies in blood group O recipients of ABO-incompatible kidneys were specifically suppressed one year after transplantation. This appeared to be a type of accommodation in which there was no immunological response despite the co-existence of donor antigen and antibody, and might have been caused by down-regulation of B cells to produce anti-donor antibody.

Stereoselectivity in deoxygenation of 5-hydroxy-5-phosphinyl-hexofuranoses (alpha-hydroxyphosphonates).

The addition of dimethyl phosphonate to six different hexofuranos-5-uloses in the presence of DBU, followed by esterification with methoxalyl chloride and then radical reduction, afforded 5-deoxy-5-dimethoxyphosphinyl-D- and L-hexofuranoses. The stereoselectivity of the deoxygenation and possible transition-state models are discussed.

[Ureteral stricture after ESWL for ureteral calculi].

BACKGROUND: There are many reports on the effects of ESWL, but few reports on the complications, especially remaining ureteral stricture after this treatment. Therefore we have retrospectively reviewed our cases to define the predisposing factors of this complication. METHODS: Since 1991 we have treated urolithiasis with ESWL using a Siemens Lithostar for the first therapy. We had 16 cases of ureteral stricture after this treatment. Ureteral stricture is the most common complication after ESWL treatment. To define the risk factor of the stricture we have compared 549 cases that were successfully treated between 1994 and 1996 without this complication. In these two groups we examined ages, sexes, chief complaints, size, position and components of the calculi, the degree of hydronephrosis, the frequency of ESWL, the presence of urinary tract infection, the duration of stone impaction and the after endourological treatment using multiple logistic regression analysis. RESULTS: Patients with the stone incidentally found and those with the UTI seemed to be more frequently associated with ureteral stricture, however there was not a significant difference. The hydronephrosis more than grade 3 (p = 0.025), the frequency of ESWL (p = 0.0325) and the after endourological treatment, especially TUL (p = 0.0184) were statistically significant among the other factors. The stricture occurred in 5 out of 29 patients with the hydronephrosis of grade 4 and 5 between 1994 and 1996. CONCLUSION: We should carefully treat patients with grade 3 or more hydronephrosis with ESWL. We should not repeatedly treat the patients with ESWL. We should take care of TUL treatment after ESWL.

Mechanism underlying the prevention of aneurismal rupture by coil embolization.

OBJECT: Endovascular treatment with Guglielmi detachable coil has been developed as a less invasive treatment for cerebral aneurysm. The aim of this study is to clarify the mechanism of the preventive effect of coil embolization. METHOD: Two aneurysm models were employed. One was a T-shaped bifurcation tube with a spherical dome made of glass, which was used for the measurement of pressure and visualization of flow pattern. The other model was a T-shaped glass tube with a spherical elastic silicone dome, which was used for the measurement of aneurismal wall displacement due to pulsation of flow. RESULT: 1, Guglielmi detachable coil caused no change in intra-aneurismal fluid pressure. 2, Coil insertion obstructed and slowed intra-aneurismal flow. This flow stagnation in the aneurysm might promote thrombus formation. 3, With increase in numbers of coils anchored at the intra-aneurismal wall, the displacement of the wall was considerably depressed. This suggests that coil insertion decreases the stress on the aneurismal wall. CONCLUSION: 1, Coil insertion depresses the pulsatile aneurysm wall movement, and diminishes the stress of the aneurysm wall. 2, Coil insertion obstructs intra-aneurismal flow and facilitates thrombus formation in the aneurysm. These two factors may operate synergistically to prevent aneurysm rupture.