Hyperuricemia and Acute Renal Failure in Renal Transplant Recipients Treated With High-Dose Mizoribine.

BACKGROUND: Hyperuricemia is a common adverse event frequently found in renal transplant recipients with mizoribine (MZ). Hyperuricemia itself will be a cause of renal dysfunction, and renal dysfunction also will be a cause of hyperuricemia simultaneously. This study investigates frequency of hyperuricemia and renal failure in renal transplant recipients treated with high-dose MZ. PATIENTS AND METHODS: From December 2007 to October 2015, there was a total of 32 living related renal transplant recipients treated with high-dose MZ. Of the 32 patients, 28 were treated with urate-lowering medications. RESULTS: One patient received allopurinol (AP) and 13 patients received benzbromarone (BB). For 6 of them, their urate-lowering medications were converted to febuxostat (FX) form AP or BB. In the remaining 14 patients, FX was administered from the beginning. In 2 cases of ABO-incompatible living related renal transplant recipients who were maintained with high-dose MZ and BB, severe hyperuricemia and acute renal failure occurred. One patient was a 48-year-old man, and his creatinine (Cr) level increased to 8.14 mg/dL and his serum uric acid (UA) was 24.6 mg/dL. Another patient was a 57-year-old man, and his Cr level increased to 3.59 mg/dL and his UA was 13.2 mg/dL. In both cases Cr and UA were improved, and no finding of acute rejection and drug toxicity was observed in graft biopsy specimens. BB was switched to FX and discontinuance or reduction of MZ was done. CONCLUSION: Combination of MZ and BB has the risk of acute renal dysfunction after renal transplantation. Latent renal dysfunction should be watched for in renal transplant recipients receiving high-dose MZ.

How long should we follow the post-transplantation patient after graft loss? A case report of renal cancer in the grafted kidney that occurred 16 years after graft loss.

BACKGROUND: Renal cancers commonly occur in the native kidneys of renal transplant recipients, whereas renal cancer in the grafted kidney has been reported occasionally. Renal cancer in the grafted kidney occurred 16 years after graft loss in this case, which would be a more rare case. CASE REPORT: A 60-year-old man who had a kidney transplant from his mother at the age of 31 years and had hemodialysis again because of chronic rejection from the age of 44 years had right lower abdominal pain. Computerized tomography (CT) showed tumor involvement in the grafted kidney. Positron-emission tomography-CT also showed hot spots in the liver, cervical vertebra, and costal bone. Needle biopsy for grafted kidney and liver tumors were done, and pathologic findings revealed renal cancer of grafted kidney and metastatic liver tumor. Graftectomy was done, and renal cancer was diagnosed as spindle cell carcinoma. Irradiation for cervical bone metastasis was done after the surgery. He complained of abdominal pain and eating disturbance 2 months after the surgery. CT showed a huge recurrence tumor and multiple tumor dissemination. Small intestine was involved and obstructed by the main tumor. He died of recurrence of renal cancer 3 months after the surgery. CONCLUSIONS: It is reported that the rate of renal cell carcinoma in the grafted kidney was 0.19%-0.5% and it occurred at a mean of 12.6 years after renal transplantation. Herein, we report a rare case of renal cancer that occurred 29 years after renal transplantation. Long-term observation should be required for recipients who had rehemodialysis.

Acute renal failure caused by hyperuremic acidemia in ABO-incompatible kidney transplant maintained with cyclosporine and high-dose mizoribine: a case report.

INTRODUCTION: The shortage of cadaver organs has led to expansion of living donor kidney transplantations with, 30% increase among ABO-incompatible cases in Japan and the use of marginal extended donors. Herein we have reported the outcome after an ABO-incompatible kidney transplantation from an aged living-related donor who suffered from mild diabetes mellitus and hypertension. CASE REPORT: A 48-year-old man underwent ABO-incompatible kidney transplantation from his 76-year-old father, using anti-CD20 antibody induction, followed by cyclosporine (CsA), mycophenolate mofetil (MMF), and prednisolone. After the operation, MMF was switched to high-dose mizoribine (MZ). He was discharged from the hospital on postoperative day (POD) 28 with a serum creatinine (sCr) of 1.47 mg/dL. On POD 34 when the sCr was 8.14 mg/dL, his urine examination showed uric acid crystals with serum uric acid of 24.6 mg/dL. Biopsy findings showed no evidence of acute rejection but mild tubulointerstitial injury. Hemodialysis performed twice to reduce uric acid was accompanied by hydration. CsA/MZ was switched to tacrolims/MMF; benzbromarone, to febuxostat to treat hyperuric acidemia. On POD 58, sCr reduced to 1.75 mg/dL he was discharged. On POD 416, graft function was stable with sCr of 1.70 mg/dL. CONCLUSION: Common side effect of MZ is hyperuricemia which presumably caused acute renal failure of this aged marginal donor kidney.

[Arch translocation method for an arch aneurysm with open stent grafting using a nephrostomy catheter].

An 81-year-old female found to have an aneurysm in the distal aortic arch was successfully treated with arch translocation method. Under selective cerebral perfusion, a stent graft bound to a nephrostomy balloon catheter with a chainstitch was inserted from the ascending aorta into the descending aorta and its proximal end was sutured together with the distal aortic stump. Then a 4-branched Dacron graft replaced the ascending aorta reconstructing cephalobracheal branches individually. Each proximal end of cephalobracheal branches was ligated. The patient had no neurological deficit except for recurrence nerve palsy that had already existed before the operation. Postoperative angiography revealed complete thrombocclusion of the aneurysm.

Tuberculous pseudoaneurysm of the ascending aorta associated with intracranial tuberculoma.

A tuberculous aneurysm is rare and fatal because it may lead to a rupture due to the forming of a pseudoaneurysm. A lesion is especially uncommon in the ascending aorta. We report an unusual case of tuberculous pseudoaneurysm of the ascending aorta which developed 7 months after the onset of multiple intracranial tuberculoma in a 59-year-old man. He was treated for multiple intracranial tuberculomas in another hospital because of headache and left homonymous hemianopia. The temporal intracranial tuberculomas were reduced after antituberculous drug administration. However, they enlarged again shortly thereafter. At that time, a pseudoaneurysm of the ascending aorta was found, so he was introduced to our department. Intensive antituberculous drugs were administered perioperatively and postoperatively. The intracranial tuberculoma was reduced preoperatively. After that, the ascending aorta was successfully replaced with a Dacron graft. A hole was noted in the back of the ascending aorta. Three years after the operation, no symptoms of recurrence have been recognized. A tuberculous pseudoaneurysm of the ascending aorta may easily cause systemic tuberculosis or rupture, therefore it should be treated as early as possible.

Early and long-term results of cardiovascular surgery in octogenarians.

The purpose of this study was to evaluate characteristics and outcomes of octogenarians undergoing cardiovascular surgery with cardiopulmonary bypass in a Japanese population. Thirty-one consecutive patients over 80 years of age underwent coronary artery bypass grafting 19 (61%), combined coronary artery bypass grafting and ventricular septal perforation closure 1 (3%), valve replacement 3 (10%), and prosthetic graft replacement 8 (26%). The early mortality rate was 16.1%. Survival estimates were 74% after 1 year, 74% after 3 year, and 64% after 5 years. Emergency and urgent cases involved 16 (51.6%), and 2 patients (6.5%), respectively. Multivariate analyses revealed that predictors of early mortality was preoperative left ventricular ejection fraction. Predictors of hospital death (within 3 months after surgery) were preoperative renal dysfunction, intraaortic balloon pumping, and age. Predictors of late mortality were chronic lung disease and age. Twenty-one patients expected to have died before surgery were living at home, and 9 (40.9%) patients were completely autonomous. Multivariate analyses revealed diabetes mellitus and a small number of bypass grafts were predictive risk factors for postoperative autonomy. Thus, cardiovascular surgery can be performed in octogenarians under 85 years of age with a favorable long-term outcome, when appropriately applied in selective octogenarians without significant comorbidity. If patients are over 85 years of age or have significant comorbidity, clinical treatment recommendations should be individually tailored while evaluating the risk of having or not having surgery and their life expectancy. QOL of survivors was almost satisfactory and significantly improved compared with a preoperative state.

Left ventricular free wall rupture possibly induced by coronary spasm. Surgical repair in the emergency room.

A 68-year-old woman complained of chest discomfort after a traffic accident in which she driving hit a child. At about twenty-five minutes later, she went into sudden cardiogenic shock due to acute myocardial infarction caused by non-occlusive intracoronary thrombosis without significant organic coronary stenosis and without any sign of extraluminal contrast pooling on coronary angiography. She was transported to our emergency room by ambulance because of cardiac tamponade caused by a left ventricular free wall rupture following the acute myocardial infarction. On arrival, she was near cardio-pulmonary arrest on intraaortic balloon pumping. We performed emergency open cardiac massage and pericardiotomy. The hairline perforation responsible for the blowout-type left ventricular free wall rupture was successfully closed with Teflon-reinforced sutures. In conclusion, it was strongly suspected that the present case of left ventricular free wall rupture was caused by acute myocardial infarction due to intracoronary thrombosis following coronary spasm without significant organic coronary stenosis or rupture of atheromatous plaque.

Stented elephant trunk method for multiple thoracic aneurysms.

Stent-grafting and open graft replacement was introduced to reduce the complications of suture anastomosis in the descending aorta. We applied this technique in the treatment of a patient with multiple thoracic aneurysms. The elephant trunk procedure was used for thromboexclusion. A single branched graft was placed easily without twisting. In patients with aneurysms at both the proximal and distal thoracic aorta, combined stent-grafting and open graft replacement is an excellent approach.

[A case report of Ebstein's anomaly treated with Hetzer's procedure].

A 27-year-old male who had been diagnosed with Ebstein's anomaly was admitted with uncontrollable congestive heart failure. The echocardiogram revealed severe tricuspid valve incompetence and the electrocardiogram showed atrial fibrillation. He underwent Hetzer's repair procedure for tricuspid valve incompetence and Minzioni's right atrial isolation technique to restore sinus rhythm. His congestive heart failure quickly disappeared and sinus rhythm was restored after operation. He was discharged 3 weeks postoperatively and remains well 22 months after his operation. Hetzer's technique for tricuspid valve repair in Ebstein's anomaly restructures the valve mechanism at the level of the true tricuspid anulus by using the most mobile leaflet for valve closure without plication of the atrialized chamber. We conclude that Hetzer's procedure is an effective operation for Ebstein's anomaly.

Atherosclerotic aneurysm of the intrathoracic segment of the subclavian artery: a case report.

True aneurysms of the intrathoracic segment of the subclavian artery are extremely rare. Atherosclerosis is the most common etiology. The surgical approach and timing of repair remain controversial. We successfully treated a patient with a large proximal subclavian artery aneurysm which was secondary to atherosclerosis. The patient was asymptomatic for 30 years as the aneurysm enlarged. Three-dimensional computed tomography provided the most useful information regarding anatomy of the cervical vasculature. The patient underwent closure of the inlet port of the aneurysm and repair using a 6-mm Dacron bypass graft (Gelsoft , VASCTEK, Scotland) via a minimally invasive surgical approach.

Surgical treatment of abdominal aortic aneurysms located close to the visceral arteries: report of three cases.

The standard surgical treatment for abdominal aortic aneurysms (AAA) is in situ replacement of the infrarenal aorta, which is associated with a low mortality rate. On the other hand, thoracoabdominal aortic aneurysms (TAA) remain a formidable challenge and the complications that can occur may be severe including neurologic dysfunction and renal failure. We report herein three cases of patients with AAA located very close to the visceral arteries, for which in situ replacement of the infrarenal aorta was not feasible due to severe inflammation and adhesion. Therefore, aortic stump closure and in situ bypass grafting was performed to avoid reconstruction of the visceral arteries. No major complications or operation-related deaths occurred. Thus, while in situ replacement is usually recommended over bypass grafting for patients whose aneurysms are located very close to the visceral arteries, aortic stump closure and in situ bypass grafting should be considered as a more effective surgical option.

Familial hyperparathyroidism: report of a case.

We report herein a case of familial primary hyperparathyroidism diagnosed in a 23-year-old woman who presented with hypercalcemia and urolithiasis. The parathyroid gland was removed, and pathological examination revealed chief cell adenoma. The proband's younger sister had undergone surgery for parathyroid adenoma at the age of 19, and her aunt had a history of urolithiasis with a high level of serum parathyroid hormone. We have not yet found evidence of any other endocrine disorders suggesting multiple endocrine neoplasia (MEN) type 1 in this pedigree.

Azathioprine-induced megaloblastic anemia with pancytopenia 22 years after living-related renal transplantation.

Macrocytosis and megaloblastic changes in the bone marrow are frequently seen in renal transplant recipients treated with azathioprine (Az). However, severe anemia is a rare side effect of Az. We recently observed a case of severe megaloblastic anemia with pancytopenia in a renal transplant recipient who had been receiving Az therapy for 22 years. The patient was a 46-year-old woman who had been administered Az and prednisolone at a dose of approximately 1.7 mg/kg and 0.17 mg/kg daily, respectively. A bone marrow aspiration revealed megaloblastic anemia with the depletion of myeloid cells and megakaryocytes. She did not have vitamin B12 or folate deficiency. Therefore, FK506 (tacrolimus), a macrolide produced by Streptomyces tsukubaensis, which acts directly on T cells and is known to have less myelosuppression than Az, was substituted for Az. Although the leukopenia improved, the anemia and thrombocytopenia did not improve in the short term. She developed dyspnea and severe subcutaneous bleeding of the right lower extremity due to knee contusions. Hemodialysis was started to treat her uremic state. Although it was impossible to evaluate the long-term effects of FK506 therapy for the pancytopenia in our case, the conversion from Az to a less myelosuppressive drug, such as FK506, should be considered in renal transplant recipients with severe myelosuppression caused by long-term Az treatment.

Modulation of cardiac Ca2+ channels by isoproterenol studied in transgenic mice with altered SR Ca2+ content.

Phospholamban (PLB) ablation is associated with enhanced sarcoplasmic reticulum (SR) Ca2+ uptake and attenuation of the cardiac contractile responses to beta-adrenergic agonists. In the present study, we compared the effects of isoproterenol (Iso) on the Ca2+ currents (ICa) of ventricular myocytes isolated from wild-type (WT) and PLB knockout (PLB-KO) mice. Current density and voltage dependence of ICa were similar between WT and PLB-KO cells. However, ICa recorded from PLB-KO myocytes had significantly faster decay kinetics. Iso increased ICa amplitude in both groups in a dose-dependent manner (50% effective concentration, 57.1 nM). Iso did not alter the rate of ICa inactivation in WT cells but significantly prolonged the rate of inactivation in PLB-KO cells. When Ba2+ was used as the charge carrier, Iso slowed the decay of the current in both WT and PLB-KO cells. Depletion of SR Ca2+ by ryanodine also slowed the rate of inactivation of ICa, and subsequent application of Iso further reduced the inactivation rate of both groups. These results suggest that enhanced Ca2+ release from the SR offsets the slowing effects of beta-adrenergic receptor stimulation on the rate of inactivation of ICa.

cAMP-dependent regulation of cardiac L-type Ca2+ channels requires membrane targeting of PKA and phosphorylation of channel subunits.

The cardiac L-type Ca2+ channel is a textbook example of an ion channel regulated by protein phosphorylation; however, the molecular events that underlie its regulation remain unknown. Here, we report that in transiently transfected HEK293 cells expressing L-type channels, elevations in cAMP resulted in phosphorylation of the alpha1C and beta2a channel subunits and increases in channel activity. Channel phosphorylation and regulation were facilitated by submembrane targeting of protein kinase A (PKA), through association with an A-kinase anchoring protein called AKAP79. In transfected cells expressing a mutant AKAP79 that is unable to bind PKA, phosphorylation of the alpha1C subunit and regulation of channel activity were not observed. Furthermore, we have demonstrated that the association of an AKAP with PKA was required for beta-adrenergic receptor-mediated regulation of L-type channels in native cardiac myocytes, illustrating that the events observed in the heterologous expression system reflect those occurring in the native system. Mutation of Ser1928 to alanine in the C-terminus of the alpha1C subunit resulted in a complete loss of cAMP-mediated phosphorylation and a loss of channel regulation. Thus, the PKA-mediated regulation of L-type Ca2+ channels is critically dependent on a functional AKAP and phosphorylation of the alpha1C subunit at Ser1928.

Benign cervical teratoma in an adult: report of a case.

Cervical teratomas are rarely encountered in adults. We report herein the case of a 21-year-old woman who was admitted to our hospital for surgical treatment of a neck tumor, 7.5 x 4.5 x 2.7 cm in size, located in the left lower pole of the thyroid. Ultrasonography (US) and computed tomography (CT) revealed a multicystic tumor. The levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and squamous cell carcinoma-related antigen (SCC) in the cystic fluid were extremely elevated in contrast to the normal levels found in the serum. The tumor was completely excised and histological examination revealed it to be composed of elements derived from the three germ layers, confirming a diagnosis of benign cystic teratoma.

Iliac artery dissection originating in a true aneurysm. A case report.

The spontaneous dissection of a peripheral artery not involving the aorta is rare and usually does not arise from a true aneurysm. This is the first report of a spontaneous external iliac artery dissection originating in a true aneurysm.

[A clinical study of recurrent breast cancer].

In a recent 14-year period from December 1978 to December 1993, 180 patients with breast cancer were treated at the hospital, and out of these 180 patients, 38 patients (21.1%) who had a recurrent breast cancer were clinically evaluated. The first recurrence occurred in the local skin in 13 patients, regional lymph node in 1, bone in 13, lung in 4, liver in 4 and in other areas in 3. Histologically, the incidence of scirrhous carcinoma recurrence was higher than that of papillotubular carcinomas. There was no recurrence in mucinous carcinomas. The frequency of recurrence became higher in accordance with TNM classification, namely, 6.7% in Stage I, 23.7% in Stage II, 37.5% in Stage IIIa, and 47.1% in Stage IIIb cancers. An increasing tendency in the recurrence rate was also noted with an increase of tumor diameter or lymph node metastasis. Otherwise, there was no difference in cumulative survival after recurrence between TNM classification. There were no correlations between the estrogen receptor and incidence of recurrence or 5-year survival rate. The disease free interval (DFI) was less than 2 years in about 60% of the recurrent cases. DFI of bone metastasis was longer than for the other sites of recurrence. The survival rate increased according to prolongation of DFI. After through evaluation of these results, one should pay close attention to follow-up after mastectomy.

[A case of aortic dissection associated with congenital bicuspid aortic valve].

It is known that bicuspid aortic valve with dilatation of the ascending aorta is one of risk factors of the aortic dissection. A case of acute aortic dissection (DeBakey type-II) associated with bicuspid aortic valve who underwent successfully operation 8 hours after onset is reported. This patient went into cardiogenic shock because of cardiac tamponade and aortic valve regurgitation immediately after onset. Aortic valve and the ascending aorta were replaced using composite graft (#23 SJM prosthetic aortic valve and 26 mm woven Dacron vascular graft) combined with coronary artery reconstruction by Cabrol's technique. Aortic valve showed bicuspid and histological examination revealed cystic medionecrosis and loss of elastic fiber. Postoperative course was uneventful and this patients is doing well 3 years after the operation.

Repair of a ruptured aortic arch aneurysm complicated by postoperative paraplegia: report of a case.

We report herein the rare case of a 79-year-old man who suffered permanent paraplegia after undergoing an otherwise successful total arch replacement for a ruptured aortic arch aneurysm. During cardiopulmonary bypass, perfusion to the distal aorta was maintained from the femoral artery, and postoperative aortography showed intact tributaries from the aorta including the intercostal arteries. Postoperative paraplegia is an extremely rare complication of operations on the aortic arch; however, we speculate that the paraplegia in this patient could be attributed either to a steal phenomenon involving the radicular artery, or to the anatomical particularity of the spinal cord artery described by Cole and Gutelius as the "segmental system".