BKV in Simultaneous Pancreas-Kidney Transplant Recipients: A Leading Cause of Renal Graft Loss in First 2 Years Post-Transplant

With the introduction of more potent immunosuppressive agents, rejection has decreased in simultaneous pancreas/kidney transplant (SPK) recipients. However, as a consequence, opportunistic infections have increased. The purpose of this report is to outline the course of SPK patients who developed polyomavirus-associated nephropathy (PVAN). A retrospective review of 146 consecutive SPK recipients from January 1, 1996 to December 31, 2002 was performed. Immunosuppression, rejection and development of PVAN were reviewed. Nine patients were identified. All received induction with either OKT3 or thymoglobulin. Immunosuppression included tacrolimus/cyclosporine, MMF/azathioprine and sirolimus/prednisone. Two patients were treated for kidney rejection prior to the diagnosis of PVAN. Time to diagnosis was an average of 359.3 days post-transplantation. Immunosuppression was decreased but five ultimately lost function. However, none developed pancreatic abnormalities as demonstrated by normal glucose and amylase. Two underwent renal retransplantation after PVAN diagnosis and both have normal kidney function. PVAN was the leading cause of renal loss in SPK patients in the first 2 years after transplantation and is a serious concern for SPK recipients. The pancreas, however, is spared from evidence of infection, and no pancreatic rejection occurred when immunosuppression was decreased.     

Effects of ONO-3708, an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, on platelet aggregation and thrombosis

The beneficial effects of an antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, 7-[2 alpha,4 alpha-(dimethylmethano)-6 beta-(2-cyclopentyl-2 beta- hydroxyacetamido)-1 alpha-cyclohexyl]-5(Z)-heptenoic acid (ONO-3708) on thrombosis were examined. ONO-3708 at 0.1-3 microM inhibited the human platelet aggregation induced by thromboxane A2, prostaglandin H2, collagen, ADP (secondary phase) and epinephrine (secondary phase) without affecting prostanoid synthesis and the content of cyclic AMP in platelets. The in vivo effects, on coronary thrombosis in this case, were examined in two canine models. ONO-3708, 3 to 300 micrograms/kg i.v., prevented dose dependently the coronary thrombosis induced by partial obstruction of the coronary artery. ONO-3708, 3 micrograms/kg per min i.v., significantly prevented electrically stimulated coronary thrombosis without affecting systemic blood pressure and heart rate. These results indicate that the thromboxane A2/prostaglandin endoperoxide receptor could play an important role in the pathogenesis of thrombosis and that ONO-3708 may have therapeutic advantages in preventing thrombosis.     

Gd-DTPA-cascade-polymer: Potential blood pool contrast agent for MR imaging

Gadolinium-DTPA (diethylenetriaminepentaacetic acid)-cascade-polymer, a potential new blood pool contrast agent for magnetic resonance (MR) imaging, was compared with a known blood pool agent, Gd-DTPA-polylysine, in an animal model. The relative signal intensities of liver, renal cortex, pancreas, and trunk muscle were assessed in 12 pigs between 4 seconds and 120 minutes after injection of a 20 μmol/kg dose of each contrast agent, by using a FLASH (fast low-angle shot) sequence. Except for muscle, all tissues showed visible enhancement after injection of either contrast agent. After injection of Gd-DTPA-polymer, enhancement patterns in the liver, renal cortex, and pancreas were similar to those seen after injection of Gd-DTPA-polylysine. No statistically significant differences in enhancement between the two contrast agents were found at any time point. The authors conclude that the contrast kinetics of Gd-DTPA-cascade-polymer are similar to those of Gd-DTPA-polylysine and that this agent may also be used as a blood pool contrast agent for MR imaging.     

Simple screening test for risk of falls in the elderly

Background:   The aim of this study is to construct a simple screening test for the risk of falls in community-dwelling elder persons.
Methods:   A total of 1378 community-dwelling people aged 65 years and older in five different communities in Japan were asked to answer a self rated questionnaire including 22 items covering physical, cognitive, emotional and social aspects of functioning and environmental factors. At a six-month follow-up, the outcome of fall occurrence and the number of falls was ascertained by social workers, health visitors or nurses.
Results:   Five out of 22 items were selected using a logistic regression model. Using this five-item version, a screening test was constructed, and at the best cut-off point, the sensitivity and specificity were 68% and 70%, respectively. The validity of this scale was tested on persons with cognitive dysfunction.
Conclusion:   The simplicity and the predictive validity of the screening test support the use of this test in health check ups or general outpatient facilities.     

Eosinophilic fasciitis associated with Borrelia afzelii infection]

A 58-year-old woman suffered from stiffness, swelling, rubor and muscle pain in the extremities one month after she climbed a mountain in Kyushu, an island in southern Japan. On admission, mild proximal weakness was present in the extremities. Her range of motion in the extremities was limited due to firm skin and subcutaneous stiffness which was similar to scleroderma. She showed peripheral blood eosinophilia and hypergammaglobulinemia as well as a high erythrocyte sedimentation rate. An IgM antibody against Borrelia afzelii was positive. MRI of the skeletal muscles demonstrated enhancing fascia around the biceps brachii muscle, and a biopsy specimen revealed perivascular infiltration of mononuclear cells within the hypertrophic fascia. Eosinophilic infiltration was absent. We treated the patient with prednisolone, doxycycline and amoxicillin, which alleviated the symptoms. This is the first report to show that Borrelia afzelii was involved in eosinophilic fasciitis.     

HTLV-I, HIV-I, and Hepatitis B and C Viruses in Western Province, Papua New Guinea: A Serological Survey

Seven hundred and twenty-three serum samples from individuals in 13 Gidra-speaking villages in Western Province, Papua New Guinea were tested for evidence of infection with human T- lymphotropic virus type I (HTLV-I), human immunodeficiency virus type I (HIV-I), hepatitis B virus (HBV) and hepatitis C virus (HCV). No samples were positive for antibodies to HIV-I. Antibodies to HTLV-I were found in 13 samples (1.8%), HBV surface antigens (HBsAg) were found in 86 samples (11.9%), and antibodies to HCV were found in 30 samples (4.1%). Six (46.2%) of 13 HTLV-I positive samples were positive for HCV or HBsAg. The seropositive rate varied in different villages and the incidence of HTLV-I and HCV was higher in coastal and riverine areas than inland.     

A case of brachial amyotrophic diplegia accompanied with Sj?gren's syndrome presenting good response to immunotherapies in the early course of the disease]

A 74-year-old woman suffered from progressive muscle atrophy and weakness of her arms since she was seventy two years old. Before referral to our department, she was diagnosed as having cervical spondylotic myeloradiculopathy and received spinal fusion. Though spinal decompression was successful, muscle weakness of her upper limbs were progressive even after the surgery. On admission, neurological examinations revealed marked atrophy and weakness of her bilateral upper limbs with absent deep tendon reflexes showing man-in-the-barrel syndrome. Her lower extremities had normal muscle strength, but fasciculations were seen in her all four limbs. Electrophysiologically, motor nerve conduction velocity was almost normal but the amplitude was remarkably decreased, conduction block was not detected, and electromyography showed neurogenic patterns on her all extremities. Spinal progressive musclar atrophy (SPMA) accompanied with Sj?gren's syndrome was the likely diagnosis. Because 50 kDa anti-neuronal antibodies were found in her serum, we assumed that anterior horn cells were impaired by an autoimmune mechanism. Thus we treated her with corticosteroid pulse therapy, plasma exchange (PE) and intravenous immunoglobulin infusion therapy (IVIG). Although steroid pulse therapy only had a minimal effect, PE and IVIG promoted a remarkable improvement on her weakness, and the effect lasted for about three months. This is the first case of SPMA with Sj?gren's syndrome which showed good response to PE and IVIG in the early course of the disease. We considered that some SPMA-like motor neuron syndrome accompanied with autoimmune features may require immunomodulating therapies.     

Takayasu arteritis: Follow-up studies for 20 years

We reviewed retrospectively 126 (5 male, 121 female) patients suffering from Takayasu arteritis who had been treated in our clinics from 1971 to 1990. The patients' ages ranged from 19 to 80yrs old (1990) with a mean age of 48.7 ± 11.8 years. HLA typing analysis in 98 patients revealed that 45 patients (47%) were confirmed as carrying the Bw52 antigen, a high result that is statistically significant as compared with that in healthy Japanese. Arteriograms (performed in 75 patients) revealed that 28 patients (37%) were affected in the aorta and its main branches by this disease (type IV by Nasu's classification) and 23 patients (31%) were affected only in the main branches (type I). The C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) improved significantly from 2.55 ± 0.28(+) and 57.0 ± 5.69 mm/hr to 0.53 ± 0.12(+) and 31.2 ± 3.45 mm/hr, respectively after treatment including steroid and antiplatelet therapy (P < 0.01).=" patients=" with=" bw52=" exhibited=" more=" severe=" inflammatory=" conditions=" than=" those=" without=" bw52.=" lung=" scintillations=" performed=" in=" 81=" patients=" showed=" pulmonary=" arterial=" lesions=" in=" 50=" patients=" (62%).=" echocardiograms=" revealed=" aortic=" regurgitation=" (ar)=" in=" 44=" patients=" (35%),=" with=" a=" significant=" difference=" noted=" between=" the=" bw52=" positive=" group=" and=" the=" bw52=" negative=" group=" [29/40=" (73%)=" versus=" 11/47=" (23%),=">P < 0.001].=" patients=" with=" bw52=" were=" prescribed=" higher=" doses=" of=" steroids=">P < 0.05)=" for=" longer=" periods=">P < 0.01)=" than=" those=" without=" bw52.=" of=" 11=" patients=" who=" died=" during=" our=" study=" period,=" 7=" died=" of=" cardiac=" complications,=" all=" of=" whom=" were=" suffering=" from=" ar.=" hla=" analysis=" performed=" in=" 6=" of=" these=" 7=" patients=" revealed=" that=" all=" carried=" the=" bw52=" antigen.=" in=" conclusion,=" the=" retrospective=" survey=" revealed=" that=" patients=" carrying=" the=" bw52=" antigen=" showed=" more=" severe=" inflammatory=" conditions=" and=" progressed=" more=" rapidly=" to=" complications=" and=" the=" fatal=" morbid=" condition,=" as=" compared=" with=" those=" without=" bw52.=" this=" suggests=" the=" important=" role=" of=" gene=" disequilibrium=" with=" this=" hla=">     

No difference in serum leptin concentrations between urban-dwelling Austronesians and Non-Austronesians in Papua New Guinea.

Pacific Islands populations can be broadly divided into Austronesians (AN) and Non-Austronesians (NAN); obesity and type 2 diabetes are prevalent in the former, although leptin levels in both groups have seldom been investigated. Thirty-seven (20 male and 17 female) adult pairs, matched by age and percent body fat, from AN-speaking Balopa and NAN-speaking Huli, all of whom migrated to settle in Port Moresby, the capital of Papua New Guinea, were selected for comparison of their serum leptin concentrations. The Balopa did not differ significantly from the Huli in age (30.5 +/- 9.7 and 30.0 +/- 8.7 years for males, 33.7 +/- 8.9 and 34.1 +/- 7.5 years for females, respectively) or percent body fat (19.4 +/- 5.6 and 18.8 +/- 4.6 for males, 34.1 +/- 6.2 and 33.3 +/- 5.0 for females), although the BMI of females was lower in the Balopa (26.4 +/- 4.9) than in the Huli (29.7 +/- 4.7) (P = 0.02). In both ethnic groups, females had markedly higher leptin concentrations than males, but there was no significant inter-group difference in males (3.5 +/- 2.6 and 3.1 +/- 4.7 ng/ml, P = 0.14) or females (22.7 +/- 12.9 and 19.7 +/- 11.9 ng/ml, P = 0.40), after controlling for lifestyle factors and serum lipids. Multiple regression analysis revealed that significant predictors of leptin concentration were % body fat (beta = 0.58), sex (male, 0; female, 1; beta = 0.27), and smoker status (non-smoker, 0; smoker, 1; beta = -0.15) (R(2) = 0.80), implying that the leptin concentration was primarily determined by lifestyle-derived body fatness. In conclusion, the NAN populations do not endogenously differ in leptin status from the AN populations, who have been recognized as a typical group with a "thrifty" genotype.