[Scleral tattooing: A dangerous fashion trend]. / Tatouage scléral : une mode émergente dangereuse.

Tattooing of the glove is an old practice used 2000 years ago on the cornea to improve the appearance of unsightly corneal scars. Since 2007, tattoo artists have been performing scleral tattoos, also called "eyeball tattoos," despite the risks involved and the disapproval of health authorities and the medical community. We report the case of a 30-year-old man with bilateral black ink scleral tattoos who came to our ophthalmologic emergency service with episcleral nodules, which had appeared at the ink injection sites. The clinical course stabilized with topical anti-inflammatory treatment. Similar cases have been reported in the literature, in one of which the patient underwent surgical excision of a similar lesion. Histological analysis showed a lympho-histiocytic reaction without any signs of malignancy. To date, 20 cases of scleral tattoos have been reported in the international literature, often with severe complications. We see, on the one hand, complications related to perforating trauma, and on the other hand, acute and chronic complications inherent to the products used. Scleral tattooing is gaining popularity around the world despite significant risk exposure, including traumatic, inflammatory, immune, infectious and probably long-term neoplastic consequences. Ophthalmologists must be aware of this practice and its consequences in order to make the most appropriate therapeutic decisions.

NFκB2 Gene as a Novel Candidate that Epigenetically Responds to Interval Walking Training.

Physical fitness has been reported to decrease the risk of lifestyle-related diseases. The present study evaluated genome-wide methylation under the hypothesis that interval walking training (IWT) imparted beneficial effects on health, particularly by epigenetically ameliorating susceptibility to inflammation. We screened DNA from peripheral blood samples via genome-wide microarray for genes whose methylation was affected by IWT, paying special attention to promoter regions, and identified over 40 hyper- or hypo-methylated genes following IWT that were not witnessed in controls. We next selected genes in which the degree of methylation change in the promoter region was correlated with energy consumption following IWT. In this way, we found the NFκB2 gene to have increased methylation in multiple regions of its promoter sequence following participation in an exercise regimen. Next, IWT-induced NFκB2 hyper-methylation was confirmed by a quantitative PyroSequencing assessment of methylation in samples obtained from independent subjects who also underwent IWT. The increase in NFκB2 gene promoter methylation by IWT indicates that this regimen may suppress pro-inflammatory cytokines. Thus, these results provide an additional line of evidence that IWT is advantageous in promoting health from an epigenetic perspective by ameliorating susceptibility to inflammation.

Antiviral response by natural killer cells through TRAIL gene induction by IFN-alpha/beta.

Natural killer (NK) cells play an important role in early defense against viral infection. The cytotoxic activity of NK cells is increased by interferon-alpha/beta (IFN-alpha/beta), produced en masse in virally infected cells. However, the mechanism(s) by which IFN-alpha/beta contribute to the NK-cell-mediated antiviral response is not well understood. Here we provide evidence that the cytotoxicity of NK cells is enhanced by IFN-alpha/beta through induction of TNF-related apoptosis-inducing ligand (TRAIL). Isolation and analysis of the murine TRAIL promoter revealed the presence of an IFN-stimulated response element (ISRE), which binds to the transcription factor ISGF3 (interferon stimulated gene factor-3). This promoter is indeed activated by IFN-beta in ISGF3-dependent manner. We also show that virally infected cells, but not uninfected cells, are susceptible to TRAIL-mediated cytotoxicity in vitro, and that the TRAIL expressed in NK cells is indeed crucial in limiting virus replication in vivo. Thus, our study reveals a new molecular link between IFN-alpha/beta signaling and activation of NK cells in antiviral response of the host.

[Prognostic significance of myocardial imaging with iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid in patients with angina pectoris].

OBJECTIVES: To assess the clinical significance of iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid(BMIPP) single photon emission computed tomography(SPECT), the predictive value of BMIPP imaging in patients with angina pectoris was evaluated. METHODS: One hundred seventy-four patients who underwent BMIPP imaging in our institution were aged 61.8 +/- 11 years. One hundred thirty-five patients had stable angina and 39 had unstable angina at the time of examination. Patients with previous myocardial infarction or myocardial disorders were excluded. Early and delayed images were acquired in BMIPP SPECT, and the images were analyzed visually. Cardiac events were classified into hard and soft events: the former consisted of cardiac death and nonfatal myocardial infarction, and the latter included coronary revascularization and heart failure. RESULTS: The findings of BMIPP imaging were normal in 82 patients and abnormal in 92. During follow-up of 15.5 +/- 9.5 months, hard events were observed in 4 patients and soft events in 53. In patients with normal BMIPP imaging, soft events were observed in nine patients, but no hard event was encountered. Furthermore, in patients with both normal BMIPP and stress thallium imagings, no cardiac event was observed during 2 years. In contrast, 4 hard events and 44 soft events occurred in patients with abnormal BMIPP imaging. Patients with abnormal BMIPP imaging had a higher incidence of soft events than those with normal BMIPP imaging, regardless of the type of angina(16/62 vs 3/73, p < 0.0005 for stable angina; 28/30 vs 6/9, p < 0.0001 for unstable angina). CONCLUSIONS: The finding of BMIPP imaging correlates well with the mid-term prognosis of patients with angina pectoris. Since BMIPP SPECT is performed without stress to the patient, this imaging modality is important in evaluating patients with stable or unstable angina.

The influence of nitroglycerin and prostaglandin E1 on dynamic cerebral autoregulation in adult patients during propofol and fentanyl anaesthesia.

We investigated dynamic cerebral autoregulation in 24 normocapnic adult patients during propofol and fentanyl anaesthesia. Hypotension was induced, to a mean arterial pressure (MAP) of 60-65 mmHg, using nitroglycerin or prostaglandin E1. Time-averaged mean cerebral blood flow velocity in the right middle cerebral artery was measured continuously using transcranial Doppler sonography. Dynamic autoregulatory response was activated by a sudden decrease in MAP following release of bilateral thigh cuffs (thigh cuff test) and evaluated as a dynamic rate of autoregulation (dRoR in % x s(-1)). The cuff test was repeated to obtain two values of dRoR during baseline and during induced hypotension; the data were then averaged. The mean value of dRoR during baseline and during induced hypotension was 14.2 (2.9) and 14.2 (1.6) % x s(-1), respectively, in the nitroglycerin group, and 14.6 (2.6) and 14.4 (2.4) % x s(-1), in the prostaglandin E1 group. We were unable to demonstrate significant between- or within-group differences in dRoR. Thus, we conclude that nitroglycerin and prostaglandin E1 do not attenuate dynamic cerebral autoregulation.

Peripheral nerve lengthening by controlled isolated distraction: a new animal model.

We have developed a simple and effective animal model to study the distraction neurogenesis utilizing the sciatic nerve-lengthening technique in rats. The model allows macroscopic, physiological, and histological evaluation of the distraction site. Fourteen adult Harlan Sprague Dawley rats (300-350 g) were used in this study. A 10 mm segment of the right sciatic nerve of each animal in the nerve-lengthening group was resected. Gradual nerve lengthening was performed by advancing the proximal nerve stump at a rate of 1 mm/day. The proximal stump neuroma was then resected and a direct nerve anastomosis was performed. On the left side a standard autogenous nerve-grafting procedure was performed with a 10 mm segment of sciatic nerve used as an in situ nerve graft. Three months after the second surgery, the sciatic nerves were exposed and investigated by gross observation and EMG followed by histological processing and tissue analysis. Neomicrovascularization was observed surrounding the sciatic nerve anastomosis in all five specimens of the nerve-lengthening group as compared to the more white-colored scar tissue that was observed in the nerve-grafting group. The EMG results were similar for both groups. Histological studies of the lengthened nerves showed axon morphology equivalent to the grafted nerves. This study demonstrated a clear evidence of the successful nerve regeneration within a segmental nerve gap by nerve lengthening.

Telemedical support using real-time ultrasonography and endoscopy images.

We developed a telecommunications apparatus (TMS-6101, NIHON KOHDEN WELLNESS CORPORATION, Tokyo, Japan) and evaluated its clinical utility as a telemedical support system. It is capable of transmitting on a real-time basis such vital signs as blood pressure, arterial O2 saturation and ECG recordings, which are measured at bedside using the Life-Mate monitor (NIHON KOHDEN WELLNESS Co.). It is also capable of transmitting moving video-camera pictures in real time. In this study we assessed its application for telemedical supports with particular emphasis on ultrasonography and endoscopy images since reports of such applications are lacking. Employing this system, several kinds of technically demanding endoscopic procedures were supported successfully under the supervision of at least one off-site specialist physician. The system proved to be a very useful medical resource, since it facilitated high quality medical care and specialist consultation at any location without those specialists traveling to the scene.

[Cerebral autoregulation during sevoflurane or isoflurane anesthesia: evaluation with transient hyperemic response].

We investigated dynamic cerebral autoregulation during N2O-O2/fentanyl anesthesia (baseline) plus 1.0 and 2.0 minimum alveolar anesthetic concentrations (MAC) of sevoflurane or isoflurane anesthesia in 14 patients undergoing non-neurosurgical operation. Cerebral blood flow velocity in the right middle cerebral artery (Vmca) was measured continuously using transcranial Doppler ultrasonography. At normocapnia, dynamic cerebral autoregulation was tested by transient hyperemic response (a response of Vmca after a brief compression of the ipsilateral common carotid artery). For quantitative comparisons, ratio of systolic Vmca before, to immediately after compression (THRR) was calculated. Values of THRR were 1.14 +/- 0.03 (mean +/- SD), 1.15 +/- 0.04, and 1.12 +/- 0.03 during baseline, 1.0, and 2.0 MAC sevoflurane anesthesia, respectively. THRR was not significantly different among the 3 conditions. In contrast, THRR values were 1.17 +/- 0.03, 1.07 +/- 0.02, and 1.01 +/- 0.01 during baseline, 1.0, and 2.0 MAC isoflurane anesthesia, respectively. THRR was significantly attenuated in a dose dependent manner during isoflurane anesthesia. These results indicate that dynamic cerebral autoregulation is preserved during 2.0 MAC sevoflurane anesthesia, but not during 1.0 MAC isoflurane anesthesia.

T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma.

Bone resorption is regulated by the immune system, where T-cell expression of RANKL (receptor activator of nuclear factor (NF)-kappaB ligand), a member of the tumour-necrosis factor family that is essential for osteoclastogenesis, may contribute to pathological conditions, such as autoimmune arthritis. However, whether activated T cells maintain bone homeostasis by counterbalancing the action of RANKL remains unknown. Here we show that T-cell production of interferon (IFN)-gamma strongly suppresses osteoclastogenesis by interfering with the RANKL-RANK signalling pathway. IFN-gamma induces rapid degradation of the RANK adapter protein, TRAF6 (tumour necrosis factor receptor-associated factor 6), which results in strong inhibition of the RANKL-induced activation of the transcription factor NF-kappaB and JNK. This inhibition of osteoclastogenesis is rescued by overexpressing TRAF6 in precursor cells, which indicates that TRAF6 is the target critical for the IFN-gamma action. Furthermore, we provide evidence that the accelerated degradation of TRAF6 requires both its ubiquitination, which is initiated by RANKL, and IFN-gamma-induced activation of the ubiquitin-proteasome system. Our study shows that there is cross-talk between the tumour necrosis factor and IFN families of cytokines, through which IFN-gamma provides a negative link between T-cell activation and bone resorption. Our results may offer a therapeutic approach to treat the inflammation-induced tissue breakdown.

CD8(+) T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-alpha/beta signaling.

The balanced action of cytokines is known to be critical for the maintenance of homeostatic immune responses. Here, we report the development of an inflammatory skin disease involving CD8(+) T cells, in mice lacking the transcription factor, interferon regulatory factor-2 (IRF-2). CD8(+) T cells exhibit in vitro hyper-responsiveness to antigen stimulation, accompanied with a notable upregulation of the expression of genes induced by interferon-alpha/beta (IFN-alpha/beta). Furthermore, both disease development and CD8(+) T cell abnormality are suppressed by the introduction of nullizygosity to the genes that positively regulate the IFN-alpha/beta signaling pathway. IRF-2 may represent a unique negative regulator, attenuating IFN-alpha/beta-induced gene transcription, which is necessary for balancing the beneficial and harmful effects of IFN-alpha/beta signaling in the immune system.

Primary malignant melanoma of the male urethra.

BACKGROUND: We describe a rare case of malignant melanoma originating from the male urethra. METHODS/RESULTS: This case, which presented a tan-colored lesion at the distal urethra on urethroscopy, was considered as transitional cell carcinoma by transurethral biopsy. Pathologic examination of widely resected urethra revealed scattering cells, which included melanin granules in cytoplasm, and then immunohistochemical stains established the diagnosis as amelanotic melanoma. Although partial penectomy and inguinal lymph node dissection were subsequently performed, 7 months later, total cystourethrectomy was required because of multifocal recurrence at the residual urethra. CONCLUSIONS: In cases of amelanotic melanoma, it should be noted that a lack of melanin granules in tumor cells may lead pathologists and urologists to a misdiagnosis due to the histologic non-specific appearance. With respect to surgical management, of significance is the fact that malignant melanoma may progress multifocally along the total urethra; therefore, total urethrectomy should be considered as radical surgery for the primary site, even if the tumor is confined to the distal urethra.

[Papillary adenocarcinoma of the prostate: report of 3 cases].

We report here 3 cases of papillary adenocarcinoma of the prostate. In all 3 cases, the tumors were discernible on cystourethroscopy and transurethral biopsy established the diagnosis, whereas no significant finding was found on digital rectal examination. Although androgen deprivation therapy was administered in all cases, different surgical procedures were employed according to the stage in each case. In case 1, since the papillary tumor was confined within the prostatic urethra, complete resection was accomplished by transurethral resection (TUR). In case 2, since pelvic lymph nodes metastases were found, local radiation therapy was added. In case 3, since the patient had vesical invasion of tumor total cysto-prostatectomy was performed. Papillary adenocarcinoma of the prostate originates from the prostatic duct, resulting in existence at the "central portion" of the prostate gland. Cystourethroscopy and transurethral biopsy is helpful for diagnosis of this disease, whereas rectal digital examination is useless. As a surgical procedure for the primary site, TUR may be efficient for tumors confined within the prostatic urethra, although more extensive surgery may be necessary for those with a more invasive profile.

[Indication and effectiveness of endoscopic percutaneous gastrostomy as a route of parenteral alimentation for the home care patient].

We are managing 8 home care patients who have a gastrostomy made using an endoscopic percutaneous technique as a route of parenteral alimentation. Based on our experience, the preconditions for an endoscopic percutaneous gastrostomy as a route of parenteral alimentation are 1. normal gastrointestinal function, 2. difficulty in swallowing, 3. possibility that the caregiver can manage the gastrostomy. When we performed an endoscopic percutaneous gastrostomy as a route of parenteral alimentation for 8 home care patients, we obtained the several advantages mentioned below. 1. Swallowing pneumonia was prevented. 2. Adequate amount of alimental liquid could be infused. 3. Patient could take a bath or shower with the gastrostomy, and good QOL was realized. 4. The home care patient with the gastrostomy could have a satisfactorily long life.

Leiomyosarcoma of the spermatic cord.

BACKGROUND: A rare case of leiomyosarcoma from the spermatic cord is described. A 72-year-old man complained of a hard, golf-ball sized mass in the right inguinal canal. METHODS: Transinguinal radical orchiectomy was performed and histologic examination revealed leiomyosarcoma originating from the spermatic cord. Distant metastases were not observed by further examinations. Radiation as adjuvant therapy was carried out in order to prevent the local recurrence. RESULTS/DISCUSSION: The patient has been alive for 16 months with no evidence of disease. In leiomyosarcoma of the spermatic cord, locoregional recurrence is common. In addition to transinguinal radical orchiectomy, local radiation therapy should be carried out as an adjuvant.

[Telemedical support in emergency medicine].

In July 1997 we began support of paramedics who would respond to emergency scenes using a telecommunications system based in the hospital emergency unit. However, since no telecommunications system that could be employed on the actual clinical site was available, we had to develop a new system. Our telecommunications system (TMS-6101, NIHON KOHDEN WELLNES Co., Tokyo, Japan) can transmit vital signs in real time and interactively transmit several types of moving images. Because the current infrastructure for radio communications cannot provide adequate telemedical support for paramedics, we are using the new system for clinical support between our unit and associated hospitals. Based on 57 cases of clinical telemedical intervention, the system has enabled high-quality decision making by specialists without the need for them to travel to the scene or transport X-rays films, ultrasonographic reports, or endoscopic results. If this newly developed telecommunications system is employed for telemedical interventions in medical facilities in remote areas or on remote islands, medical consultations for Japanese individuals overseas, night-time first aid in urban areas, and in disaster situations, the physicians on both side of the line will be able to obtain a wealth of timely information, greatly influencing outcome in both emergency and nonemergency cases.

[Transitional cell carcinoma in the ureter showing inverted proliferation: a case report].

A case of transitional cell carcinoma in the ureter showing inverted proliferation is reported. A tumor in the middle third of the right ureter was found in a 67-year-old male complaining of gross hematuria. Since positive findings of malignancy were obtained in a washing examination of urine cytology, right nephroureterectomy was performed. The gross specimen consisted of a polypoid and pedunculated 22 x 8 mm tumor which showed a smooth surface as in normal ureteral mucosa. Histopathologically, the tumor was lined with normal transitional epithelium but filled with transitional cell carcinoma, grade 1. Diagnosis and treatment of ureteral tumors showing inverted proliferation are discussed.

[Anesthetic management for renal tumor extending to the inferior vena cava].

A 58 year-old woman underwent radical nephrectomy, thrombectomy and ileo-cecal resection for renal tumor with thrombus involving the inferior vena cava and ascending colon cancer. In a patient having tumor thrombus extending to the vena cava, recognition of the position of the thrombus is important for surgical and anesthetic management in pre- and intra-operative periods. Transesophageal echocardiography (TEE) enabled us to visualize the real-time movement and deformity of thrombus by surgical manipulation and compression during operation. TEE seemed also very useful not only in understanding the hemodynamics during operation but also in detecting the residual tumor and the blood flow in liver and the inferior vena cava after operation.

Requirement for IRF-1 in the microenvironment supporting development of natural killer cells.

Natural killer (NK) cells are critical for both innate and adaptive immunity. The development of NK cells requires interactions between their progenitors and the bone-marrow microenvironment; however, little is known about the molecular nature of such interactions. Mice that do not express the transcription factor interferon-regulatory factor-1 (IRF-1; such mice are IRF-1(-/-) mice) have been shown to exhibit a severe NK-cell deficiency. Here we demonstrate that the lack of IRF-1 affects the radiation-resistant cells that constitute the microenvironment required for NK-cell development, but not the NK-cell progenitors themselves. We also show that IRF-1(-/-) bone-marrow cells can generate functional NK cells when cultured with the cytokine interleukin-15 and that the interleukin-15 gene is transcriptionally regulated by IRF-1. These results reveal, for the first time, a molecular mechanism by which the bone-marrow microenvironment supports NK-cell development.

[Metastasis of renal cell carcinoma to ipsilateral adrenal residuum and contralateral adrenal gland after radical nephrectomy: a case report].

A 68-year-old woman had undergone radical nephrectomy via a transabdominal approach 4 years earlier for a 8 cm tumor located from the midportion to the upper pole of the right kidney. Pathological diagnosis was renal cell carcinoma (RCC), clear cell subtype, G2, pT2pN0M0. Four years postoperatively, followup computed tomography scan revealed masses in bilateral adrenal region (6 cm in diameter on the left side and 5 cm on the light). Bilateral adrenalectomy confirmed the diagnosis of adrenal metastases from clear cell carcinoma. It was concluded that the tumor had metastasized to the ipsilateral adrenal tissue as the residuum of the previous surgery. She has been treated by oral steroid supplementation without evidence of recurrence for 18 months.