Severe Graves' ophthalmopathy accompanied by myasthenia gravis]

We report a 53-year-old woman with severe Graves' ophthalmopathy accompanied by uncontrolled myasthenia gravis. She presented remarkable exophthalmos, chemosis, and restriction of eye movement. Despite plasma exchange, steroid pulse therapy, local injection of steroid, and irradiation, ocular symptoms did not ameliorate. Since optic neuropathy was seen, orbital decompression surgery was performed in the left eye. Bilateral chemosis was improved after the surgery. Five years after surgery, there was no ocular palsy in the operated left eye, but in the contralateral eye. For the good prognosis of the eye movement, orbital decompression might be recommended in the severe Graves' ophthalmopathy accompanied by the optic neuropathy and/or ophthalmoplegia with proptosis.     

A study of non-aromatizing androgen 19-hydroxylase in sheep adrenal

We reported on the unusually high isotope effect of non-aromatizing androgen 19-hydroxylase in sheep and dog adrenals and the validity of the [3H] water method using [19-3H3] androgen. We have extended the study to examine whether this 19-hydroxylation is catalyzed by a cytochrome P-450 dependent enzyme. Sheep adrenal homogenate (1.65 mg prot.) was incubated in the presence of NADPH (5.6mM) with [19-3H3, 4-14C]-androstenedione (A) (3.2 microM, 8.24 x 10(4) dpm 3H/micrograms, 3H/14C = 17.2) in a total of 1.2 ml PO4 buffer under air at pH 7.4 for 2, 5 and 10 min. [19-3H2, 4-14C]-19-hydroxy-A (19-OHA) with added carrier was purified through extraction, TLC, acetylation to form 19-AcOA, and further TLC to give 19-hydroxylase activity as assessed by the product isolation method. Simultaneously, the [3H] water was measured by distillation, and with correction by the apparent kinetic isotope effect (KH/KT = 11.8), used for assessment of 19-hydroxylase activity. The effects on the hydroxylation by cofactor (NADPH, NADH), incubation atmosphere (N2, CO/O2), cytochrome P-450 inhibitors (metyrapone, clotrimazole) and heating were measured by both methods. Compared to the complete system (89.6pmol/min/mg as 100%), carbon monoxide suppressed 15.8, 59.3 and 86.4% of the 19-hydroxylation when a CO/O2 ratio of 0.1, 1 and 9 was used, respectively. Replacement to nitrogen atmosphere decreased the activity by 93.8%. Replacement of NADPH with NADH (7.5mM) caused more than a 92.1% decrease in activity. Metyrapone at 50 and 200 microM and and clotrimazole at 2.5 and 10 microM suppressed the activity by 82.8, 90.4, 85.4 and 94.9%, respectively. A larger scale sheep adrenal incubation of A (250 microM) under 18O2 atmosphere and isolation of 19-AcOA were carried out in a similar manner. The gas chromatography-mass spectrometry analysis of the purified product showed 48.5% of the product to be 18O-labeled as [M+ + 2], m/e 346. Thus, the non-aromatizing androgen 19-hydroxylase requires NADPH and molecular oxygen. It is strongly inhibited by carbon monoxide and cytochrome P-450 inhibitors. These results indicate that the enzyme system responsible for non-aromatizing androgen 19-hydroxylase in adrenal is a cytochrome P-450 dependent monooxygenase.     

Risk factors for invasive aspergillosis in living donor liver transplant recipients.

Invasive aspergillosis (IA) is a severe complication of liver transplantation. Risk factors for IA after deceased donor liver transplantation (DDLT) have been presented in several reports, but are not well established for living donor liver transplant recipients. Here, a retrospective case-control study was performed. Five cases with IA were investigated after living donor liver transplantation (LDLT) between January 1999 and December 2002 at Kyoto University Hospital. For comparison, living donor liver transplant recipients without IA were taken as controls. These patients had undergone LDLT 1 month before or after each IA case and had the same survival times as the latter. We evaluated the clinical and laboratory findings for both groups up until their demise. Patients with IA after LDLT had a very poor prognosis. By univariate analysis, risk factors for IA were preoperative intensive care unit stay (P = 0.02) and preoperative steroid administration (P = 0.02). Preoperative steroid administration for fulminant hepatitis possibly predisposed to the development of IA after LDLT.     

In Vivo Molecular Imaging Characterizes Pulmonary Gene Expression During Experimental Lung Transplantation

Experimental gene therapy is a promising strategy to prevent ischemia-reperfusion (I/R) injury and allograft rejection after lung transplantation, and methods will eventually be needed to characterize pulmonary transgene expression in vivo in humans. Therefore, we studied positron emission tomography (PET) as a means of performing in vivo molecular imaging in rodent models of lung transplantation. Rats were transfected endotracheally with adenovirus encoding a fusion gene of a mutant Herpes simplex virus-1 thymidine kinase and the green fluorescent protein gene (the former serving as an imaging reporter gene). Twenty-four hours after transfection, lungs were transplanted in groups representing normal transplantation, I/R injury and acute allograft rejection. Imaging was obtained either 24 h after transplantation to study reperfusion injury or 4 days after transplantation to study graft rejection. After imaging, lungs were excised and analyzed for thymidine kinase activity. Imaging detected transgene expression in transplanted lungs even in the presence of acute rejection or I/R injury. The PET imaging signal correlated with in vitro lung tissue assays of thymidine kinase activity (r(2) = 0.534). Thus, noninvasive molecular imaging with PET is a feasible, sensitive and quantitative method for characterizing pulmonary transgene expression in experimental lung transplantation.     

Case of acute urinary retention as a result of non-steroidal anti-inflammatory drugs

Abstract:   A 19-year-old woman presented at our hospital with acute urinary retention in September 2005. She had experienced the same chief complaint twice previously. She had used non-steroidal anti-inflammatory drugs before acute urinary retention. The results of physical examinations were unremarkable, and her neurologic signs were not remarkable. The basic laboratory test values were all normal and a psychiatric assessment indicated that her symptoms were not psychogenic. Magnetic resonance imaging was carried out, but revealed only a slight bulging in the L3/L4/L5 disk. Water cystometry showed acontractile detrusor. We made a diagnosis of acute urinary retention as a result of non-steroidal anti-inflammatory drugs because of her use of such drugs before the development of symptoms on multiple occasions. This patient was regularly followed up as an outpatient, and she could void smoothly in February 2006. This is the first report which acute urinary retention associated with non-steroidal anti-inflammatory drugs in Japan.     

Treatment of a patient with end-stage renal disease, severe iron overload and ascites by weekly phlebotomy combined with recombinant human erythropoietin

A 41-year-old hemodialyzed woman developed ascites and was found to have secondary iron overload. The dose of administered iron was approximately 11-12 g, and her serum ferritin level was 15,000 ng/ml (15,000 micrograms/l). There were no signs of congestive heart failure, fluid overload, or liver cirrhosis. A program of weekly phlebotomy combined with recombinant human erythropoietin (rhEPO) therapy was tried to eliminate the iron congestion. After 9 months of this therapy, about 5 g of iron had been removed. The ascites completely disappeared, and her serum ferritin level fell to 5,800 ng/ml (5,800 micrograms/l). This suggests that such combined therapy would be useful when iron overload must be corrected rapidly. Before therapy, the sterile ascitic fluid showed exudative characteristics with 3.7 g/dl (37 g/l) of total protein. The serum-ascites albumin difference was 0.6 g/dl (6 g/l), and the fluid contained 1,400 inflammatory cells/mm3 (1.4 X 10(9)/l). Notably, the serum-ascites albumin difference increased in parallel with iron elimination. These findings suggested that iron deposition may have played a role in changing the permeability of the peritoneum, or in impairing lymphatic drainage, both of which are presumed to be pathogenetic factors of nephrogenic ascites.     

Immunological study on chyluria

Immunological studies were performed in 87 patients with chyluria referred to our clinic from January 1982 to December 1988. White blood cell count in 78 patients was 5210.3 +/- 1440.9/mm3. The fraction and the number of lymphocyte were 18.7 +/- 9.5% and 934.1 +/- 521.6/mm3, respectively: they were lower than normal limit. The percentages of T and B lymphocytes studied in 46 patients were 79.3% +/- 11.2% (normal range: 76-86) and 10.4 +/- 7.9% (normal range: 8-16), respectively: both lymphocytes tended to decrease in percentage. Lymphocyte blast formation stimulated with phytohemagglutinin (PHA) was carried out in 20 patients. The mean of the blast formation was 17410.0 +/- 10275.1 c.p.m. (normal range: 377700-62400), and much lower than normal value. Of 22 patients who had PPD skin test, only 9 (40.9%) were positive. These findings signified that cellular immunity was suppressed in patients with chyluria. On the other hand, the value of immunoglobulin was within normal range (IgG: 1325.3 +/- 475.6 mg/dl, IgA: 242.0 +/- 98.3 mg/dl, IgM 130.4 +/- 95.9 mg/dl). Study on the values of laboratory examinations showed statistically positive correlation between total lymphocyte population and T cell number, and between total lymphocyte population and lymphocyte blast formation. In patients with chyluria, serious sequelae have not been reported. However, care should be taken for possible opportunistic infection and, particularly, malignant tumors because suppression of cellular immunity may be one of the promoting factors of malignant tumors.