Anterior mediastinal solid tumours in adults: characterisation using dynamic contrast-enhanced MRI, diffusion-weighted MRI, and FDG-PET/CT.

AIM: To find significant parameters to characterise anterior mediastinal solid tumours in adults using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted MRI (DWI), and combined 2-[(18)F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS: Forty-eight histologically confirmed anterior mediastinal solid tumours in 48 patients (24 men, 24 women; age range 21-83 years, mean 50.7 years) were examined. The parameters analysed were maximal diameter, presence of capsule/septa on T2-weighted images, time-signal intensity curves (TICs), apparent diffusion coefficient (ADC), and maximum standardised uptake value (SUVmax). Also examined was whether any differences between histological types could be seen in these parameters. In a validation study, 42 anterior mediastinal solid tumours in 42 patients were examined consecutively. RESULTS: The washout pattern on TIC was seen only in thymic epithelial tumours (20/32). SUVmax of lymphoma (mean, 17.9), malignant germ cell tumours (14.2), and thymic carcinomas (15.6) were significantly higher than that of thymomas (6.1). The mean maximal diameter of thymic epithelial tumours was significantly smaller than that of lymphomas (p<0.01) and malignant germ cell tumours (p<0.05). The validation study also yielded high accuracy (38/42, 91%) in differentiation among the anterior mediastinal solid tumours. CONCLUSION: The SUVmax, TIC pattern on DCE-MRI, and maximal diameter might be useful to differentiate anterior mediastinal solid tumours in adults.

Living donor kidney transplantation preceding pancreas transplantation reduces mortality in type 1 diabetics with end-stage renal disease.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) is a definitive treatment for type 1 diabetics with end-stage renal disease (ESRD). Because of the shortage of deceased donors in Japan, the mortality rate during the waiting period is high. We evaluated mortality risk in patients with type 1 diabetes waiting for SPK, and the benefit of living-donor kidney transplantation (LDK) preceding pancreas transplantation, which may reduce mortality in patients awaiting SPK. METHODS: This retrospective study included 71 patients with type 1 diabetes. Twenty-six patients underwent SPK, 15 underwent LDK, and 30 were waiting for SPK. Their cumulative patient and graft survival rates were retrospectively evaluated. Risk factors contributing to mortality in patients with type 1 diabetes awaiting SPK were evaluated with the use of a Cox proportional hazards model. RESULTS: The 5-year cumulative patient survival rates in the SPK and LDK groups were 100% and 93.3%, respectively (P = .19), and 5-year kidney graft survival rates were 95.7% and 100% (P = .46), respectively. The cumulative survival rate in patients awaiting SPK was 77.7% at 5 years after registration. Duration of dialysis was the only factor significantly associated with patient and graft survivals according to both univariate and multivariate analyses. CONCLUSIONS: Patient and graft survival rates were similar in the SPK and LDK groups, but the survival rate of patients awaiting SPK decreased over time. Duration of dialysis was an independent risk factor for patient and graft survival. LDK preceding pancreas transplantation may be an effective therapeutic option for patients with type 1 diabetes and ESRD.

Outcome of renal transplantation in patients with type 2 diabetic nephropathy: a single-center experience.

BACKGROUND: Renal transplantation has been established as a treatment for end-stage renal disease (ESRD) due to diabetic nephropathy. However, few studies have focused on the outcome after renal transplantation in patients with ESRD and type 2 diabetic nephropathy. To investigate the effect of renal transplantation on ESRD with type 2 diabetic nephropathy, we retrospectively analyzed patients who received renal transplantation at our facility. This study aimed to compare the outcome of renal transplantation for type 2 diabetic nephropathy with that for nondiabetic nephropathy. METHODS: We studied 290 adult patients, including 65 with type 2 diabetic nephropathy (DM group) and 225 with nondiabetic nephropathy (NDM group), who underwent living-donor renal transplantation at our facility from February 2008 to March 2013. We compared the 2 groups retrospectively. RESULTS: In the DM and NDM groups, the 5-year patient survival rates were 96.6% and 98.7%, and the 5-year graft survival rates were 96.8% and 98.0%, respectively, with no significant differences between the groups. There were no significant differences in the rates of surgical complications, rejection, and infection. The cumulative incidence of postoperative cardiovascular events was higher in the DM group than in the NDM group (8.5% vs 0.49% at 5 years; P = .002). CONCLUSIONS: Patient and graft survival rates after renal transplantation for type 2 diabetic nephropathy are not inferior to those for recipients without diabetic nephropathy. Considering the poor prognosis of patients with diabetic nephropathy on dialysis, renal transplantation can provide significant benefits for these patients.

Nonneoplastic and nonhyperplastic thymus in myasthenia gravis. An immunohistochemical study with double immunoenzymatic labeling of basement membrane and cellular components.

Histologically normal thymus (type A) in patients with myasthenia gravis (MG) was immunohistochemically compared with hyperplastic MG thymus (type B) and normal non-MG thymus. In formalin-fixed, paraffin-embedded sections of ten type A, ten type B, and eight non-MG cases, the thymic epithelium and other cellular components were stained in conjunction with the basement membrane by a double immunoenzymatic method. This technique demonstrated a moderate architectural disturbance in type A thymus, with distended perivascular space (PVS), elongated medullary epithelium, and disrupted basement membrane. These changes were more prominent in type B thymus but were minimal to lacking in non-MG thymus. Compared with those in non-MG thymus, the myoid cells in MG thymuses of both types tended to cluster around the Hassall's corpuscles, with a slight decrease in number in type B but not in type A. B-lymphocytes were present in type B, type A, and non-MG thymuses in that order of abundance; the cells were confined to the medullary parenchyma in the non-MG group but were numerous both in the PVS and medulla in the MG groups. T-lymphocytes were increased in the expanded PVS of type A and B MG thymuses. The number of interdigitating reticulum cells was similar in the three groups, but the cellular distribution was more dispersed in MG thymuses of both types. These findings, although previously described in type B thymus, have not been well recognized in type A thymus. They support the view that a common abnormality (presumably chronic thymitis), differing in degree only, underlies MG thymuses regardless of the presence of follicular hyperplasia.

Leucocyte migration inhibition in myasthenia gravis. The effect of thymectomy.

Cellular hypersensitivity in myasthenia gravis (MG) to the thymus, muscles and peripheral nerves was examined by the method of the leucocyte migration inhibition test. The group of MG patients without thymoma had inhibition of leucocyte migration by thymus antigens. After thymectomy, they had a normal value of leucocyte migration. However, in the group of MG patients with thymoma, the inhibition of leucocyte migration by thymus antigens was observed after thymectomy. No significant inhibition of leucocyte migration was observed using muscle and peripheral nerve antigens. Cellular immunity in myasthenia gravis and the pathogenesis of the disease was discussed.

Acetylcholine-receptor-like protein from human thymoma associated with myasthenia gravis.

Cobrotoxin-binding protein was isolated by affinity chromatography from human thymoma which had been surgically removed from patients with myasthenia gravis. The protein was composed of polypeptides with a molecular mass of 40, 51, 65, and 74 kilodaltons as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulphate. Isoelectric focusing of the protein gave pI values of 5.2-5.6 and 11. This is the first report of the isolation of the protein from human thymoma. These findings suggest that the cobrotoxin-binding protein from human thymoma patients with myasthenia gravis has subunits similar to those of fish electric organs or mammalian muscles.

Isolation and characterization of nicotinic acetylcholine receptor-like protein from fetal calf thymus.

A nicotinic acetylcholine receptor-like protein (AChR-LP) was isolated from fetal calf thymus by affinity chromatography using cobrotoxin-Sepharose after alkaline extraction and solubilization with Triton X-100. The AChR-LP had a specificity of 1.61 +/- 1.12 nmol of alpha-bungarotoxin binding sites per mg of protein. The isoelectric point, sedimentation coefficient and amino acid composition of the purified AChR-LP were very similar to those of muscle and electric organ AChRs. Upon SDS-polyacrylamide gel electrophoresis purified thymus AChR-LP preparations contained up to 6 polypeptide bands of molecular weights of 40,000, 43,000, 51,000, 56,000, 58,000, and 66,000, respectively. The peptides of 40,000, 51,000, 56,000, and 66,000 dalton cross-reacted with the four subunits of Torpedo californica and fetal calf muscle AChR.

CT and MRI manifestations of primary pulmonary plasmacytoma.

Primary pulmonary plasmacytoma (PPP) is rare and its radiographic appearances have been seldom described. We report on a patient with PPP presenting with a hilar mass on chest radiograph. The diagnosis was confirmed by immunohistochemical study of the resected specimen. The computed tomographic and magnetic resonance imaging findings are presented.

[A case of sarcoidosis with cranial mononeuritis multiplex and peripheral polyneuropathy].

A 67-year-old woman with sarcoidosis, cranial mononeuritis multiplex and peripheral neuropathy was reported. The initial presentation of her sarcoidosis was a subcutaneous nodule of left knee joint on June, 1990. The number of subcutaneous nodules increased. Sarcoidosis was diagnosed by biopsy of the subcutaneous nodule. Paresthesia of the face and limbs appeared from November, 1991 and one month later, left abducens palsy and hearing disturbances were added. Alternate day therapy of 20mg prednisolone was effective in improvement of symptoms. The case of sarcoidosis with cranial mononeuritis multiplex and peripheral polyneuropathy was rarely found in 6 to 25% of patients with sarcoid neuropathy in the previous reports. Angiotensin-converting enzyme (ACE) in cerebro-spinal fluid not only raised on exacerbation also lowered with improvement of symptoms after steroid therapy. The ACE, which had a selective activity in the central nervous system, seemed to contribute to the index of treatment for sarcoidosis.

[Clinical usefulness of half-dose gadolinium-enhanced MR angiography of portal venous system (MR portography)--combined use with conventional dynamic MR imaging].

The clinical usefulness of half-dose Gadolinium-enhanced MR portography combined with the conventional full-dose dynamic MR imaging was evaluated on normal volunteers and patients. Half-dose MR portography was performed immediately following conventional full-dose Gd-enhanced dynamic MR imaging. The visualization of the extrahepatic portal system was either good or excellent in most cases excluding the splenic vein which was poor in 20.7%. That of the right and left main portal branches was also excellent. As for segmental branches, the visualization was poor of the left lobe. The comparison with digital subtraction angiography showed that the visualization of the right and left main portal branches was mostly equal. That of the splenic vein alone was worse on MR portography. We conclude that half-dose Gadolinium-enhanced MR portography is useful for the overall assessment of the portal venous system and can be added to the conventional dynamic MR imaging.

[Adaptation of dental home care--report number 1: Limitation of dental home care].

In 1985, we established a home care team which treats elderly and handicapped patients who cannot easily come to our clinic for treatments. The demand for home care is increasing, and 70% of this demand is related to dentures-i.e., adjusting dentures or making new dentures. Through the use of portable equipment, the home care team is able to cope effectively with this demand. However, some patients who experience difficulty eating as a result of their dental conditions require immediate attention. Furthermore, some patients require frequent follow-up. In such cases, time becomes more of an issue. Cases which were found to be difficult for the home care team include: treatments involving existing teeth where more than one tooth was involved, severe cares requiring surgical treatment, and cases requiring close monitoring of a patient's physical conditions. From our experience we know there is a great demand for home care, especially among elderly and handicapped patients; we also know that the risk factors increase and that there are limitations to the kind of care we can effectively deliver. Therefore in order to ensure the patient's safety and conduct effective treatment, it is critical that we evaluate each patient's condition carefully and thoroughly. Furthermore, it is important to develop a treatment plan and to conduct treatment while comprehensively monitoring the patient's condition.

[Adaptation of dental home care--report number 2: Attempt at a new system of dental home care].

In the first report we revealed some problems in visiting dental treatment, and concluded that a new dental care system should be constructed for the solution of those problems. Therefore, we started a new system which included dental treatment under hospitalization in our dental hospital. For home patients this system aims at treating, managing smoothly and providing better dental treatment, due to the choice of hospitalization, outpatient care, or home visits in the medical process. In the period from March, 1993, when our dental hospital was established, until December, 1998 treatment was given 1,527 times with 420 patients under this system, and 127 of these patients chose dental treatment under hospitalization. Dental treatment under hospitalization is the management method not found in usual dental treatment, but it is indispensable to our system. When we decide hospitalization, we must make an overall estimate of the patient's general condition, contents of treatment, eating function and nutritional condition, background, and the wishes of the patient and family. In principle, visiting dental treatment is intended for a patient who has finished dental treatment. When treatment is necessary, it should be limited to simple treatment, first aid and maintenance. The oral care of many home patients under the present circumstances is not practiced sufficiently, and cooperation of medical and welfare workers is required to improve such conditions.

Experimental autoimmune myasthenia gravis induced by thymic acetylcholine receptor-like protein.

The trigger mechanism of autoimmunity in myasthenia gravis (MG) has yet to be elucidated. To determine the function of the thymus in the pathogenesis of MG, we tried to produce chronic experimental autoimmune myasthenia gravis (EAMG) using nicotinic acetylcholine receptor-like protein (n-AChR-LP) isolated from the fetal calf thymus (FCT) by affinity chromatography with Sepharose-4B bound cobrotoxin. Lewis rats were inoculated with n-AChR-LP emulsified in Freund's complete adjuvant and later received two booster immunizations. The immunized rats developed generalized hypotonia at seven to ten days and then recovered spontaneously within two weeks. In the fourth week, flaccid paresis with either a hunched posture or waddling gait appeared in half of the rats, these symptoms improved transiently after treatment with neostigmine. At this time, evoked EMG showed decremental responses after curare sensitization, while anti-n-AChR-LP antibody, measured by enzyme-linked immunosorbent assay (ELISA), increased significantly. These findings therefore suggest that the n-AChR-LP from the thymus includes antigens to induce EAMG.

Homology between Fas and nicotinic acetylcholine receptor protein in a thymoma with myasthenia gravis--immunohistochemical and biochemical study.

Nicotinic acetylcholine receptor (nAChR) protein and Fas were detected in a cortical type thymoma from a patient with myasthenia gravis (MG). Immunohistochemical study showed the presence of these two antigens in the neoplastic thymic epithelial cells. This was confirmed by immunoblot analysis of the thymoma extract using polyclonal anti-nAChR (FCT) antibody and two monoclonal anti-Fas antibodies. A homology search between each of five subunits of nAChR and Fas in sequences of nucleotides and amino acids were performed. In nucleotides the percent identity revealed 44.1 and 44.4 in the alpha and gamma subunits, respectively. The places of homology in amino acids sequences between nAChR and Fas were found in alpha 316-355 and Fas 232-271, gamma 321-352 and Fas 3-34. These portions with homology include previously reported T-cell epitopes, alpha 320-337 and gamma 321-340. These two antigens may play a role in triggerring autoimmunity in MG.

Fas and nicotinic acetylcholine receptor in human myasthenic thymus--immunohistochemical study.

We studied the immunohistochemical localization of Fas and nicotinic acetylcholine receptor (nAChR) in the human thymus with myasthenia gravis (MG). Thymuses were obtained from thirteen patients with MG, (thymic hyperplasia 8; thymoma 5) and six normal controls. Antibodies against Fas, nAChR protein isolated from fetal calf thymus (nAChR-FCT), CD3, CD4, and CD8 were used. In both hyperplastic thymus and controls, Fas antigen was found in medullary epithelial cells especially in those around Hassall's corpuscle, in subcapsular epithelial cells, and partially in the cortex. There were no apparent differences between myasthenic thymus and the controls. In the thymic medulla the anti-nAChR-FCT antibody showed a similar staining pattern to the antibody against Fas. The nAChR and the Fas were suggested to be present in the same cell. Then six thymomas were double immunostained with antibodies against Fas and nAChR-FCT. A part of neoplastic epithelial cells were double positive for both Fas and nAChR. The present results show the first observation on the colocalization of the Fas and nAChR in thymic epithelial cells. These antigens were supposed to work on triggering mechanism of autoimmunity in MG.

Effect of cell permeable peptide of c-Jun NH2-terminal kinase inhibitor on the attenuation of renal ischemia-reperfusion injury in pigs.

The outcomes of organ transplantation have improved due to better immunosuppressive drugs, surgical techniques, and management of complications. However, ischemia-reperfusion injury remains a challenge affecting graft survival. In this study, we employed injection of a protein transduction domain (PTD) to inhibit the c-Jun NH2-terminal kinase (JNK) pathway thereby attenuating ischemia-reperfusion injury in a porcine model. The PTD-JNK inhibitor (JNKI) was administered into the renal artery, allowing it to be taken into various elements including vascular endothelial cells by endocytosis via the PTD. Serum creatinine and blood urea nitrogen concentrations were lower among PTD-JNKI than controls. In addition, renal tissue blood flow was maintained in the PTD-JNKI group, resulting in less tissue injury and fewer apoptotic cells. These results suggested that the PTD technique improved renal transplantation outcomes.

Effect of milrinone on ischemia-reperfusion injury in the rat kidney.

BACKGROUND: Milrinone (MIL), a phosphodiesterase (PDE) 3 inhibitor, exhibits cardiotonic and angioectatic effects. Various PDE inhibitors have been shown to suppress inflammatory cytokines. In this study, we evaluated the angioectatic and anti-inflammatory cytokine effects of MIL on renal function after warm ischemia in a rat ischemia-reperfusion (I-R) injury model. MATERIALS AND METHODS: MIL or control solution was perfused from the left renal artery to the right kidney, and the left kidney was excised. The right renal artery, vein, and ureter were clamped and then released after 50 minutes to produce warm ischemia. We evaluated control (n = 7), MIL (n = 7), and sham operation (n = 7) groups for serum creatinine, blood urea nitrogen (BUN), blood flow, expression of tumor necrosis factor (TNF)-α mRNA, apoptosis index, and histological evidence of acute tubular necrosis. RESULTS: Serum creatinine and BUN concentrations peaked at 24 hours after reperfusion. MIL treatment significantly reduced serum creatinine (control group 1.27 ± 0.45 mg/dL vs MIL group 0.77 ± 0.19 mg/dL, P < .05; sham 0.35 ± 0.2 mg/dL) and BUN (control 67.6 ± 13.6 mg/dL vs MIL 51.0 ± 8.8 mg/dL, P < .05; sham 23.0 ± 4.2 mg/dL) levels at 24 hours. Thereafter, serum creatinine and BUN concentrations in the MIL group remained significantly lower compared with the control group for 120 hours (P < .05). MIL group exhibited significantly higher tissue blood flow, less acute tubular necrosis, lower expression of TNF-α mRNA in renal tissue, and lower apoptotic index (P < .05). CONCLUSIONS: MIL maintained renal tissue blood flow by its vasodilatory effect, suppressed expression of TNF-α mRNA by increasing intracellular cyclic adenosine monophosphate, and ultimately decreased tubular cell apoptosis, thus protecting renal function after warm I-R injury.

Living donor renal transplantation using grafts with multiple arteries procured by laparoscopic nephrectomy.

OBJECTIVE: Kidney grafts with multiple renal arteries (MRAs) are not uncommon, but they do make transplantation more difficult. Laparoscopic graft nephrectomy has become the standard; however, the safety and reliability must be maintained for both a donor and a recipient even in case of MRAs. This study evaluated the short-term outcomes of living donor renal transplant using grafts with MRAs procured by laparoscopic nephrectomy. PATIENTS AND METHODS: This study reviewed all living donor kidney transplantations performed from January 2008 to June 2009, which were divided into 3 groups according to the number of renal graft arteries. The serum creatinine level, warm ischemic time (WIT), rewarming time, total ischemic time (TIT), operative time, acute rejection episodes, and complications in each group were evaluated. RESULTS: The serum creatinine level showed no difference among the groups. Longer TIT was observed in the MRAs group, but WIT and rewarming time did not differ. The acute rejection rate was not different. There were no vessel complications in any donors and recipients. CONCLUSION: Harvesting kidney grafts with MRAs by laparoscopic nephrectomy requires a longer TIT; however, transplantation can be performed safely and reliably for both donors and recipients.