Atsunori Yoshino

Growth hormone therapy and scoliosis in patients with Prader–Willi syndrome

Growth hormone (GH) therapy for short stature in patients with Prader–Willi syndrome (PWS) has started worldwide, and various favorable effects have been reported. However, the possibility of progression of scoliosis arises as a new problem of the GH therapy. In this study, we analyzed whether 72 patients who have been followed up in our hospital have such a problem. They included 46 males and 26 females (41 patients with the GH therapy and 31 without it) aged from one to 49 years. Consequently, 33 (45.8%) of 72 patients had scoliosis with the Cobb angle of >10 degrees. Twenty (48.8%) of forty‐one patients who received a GH therapy and 13 (41.9%) of 31 patients without the therapy had scoliosis, the frequency of scoliosis between the two groups showing no statistical difference (P = 0.56). Height velocity of scoliotic and non‐scoliotic patients during the first year of the therapy was 8.59 ± 1.92 and 10.70 ± 2.54 cm, respectively, showing a significant difference (P < 0.001). This shows that accelerated height velocity may not induce scoliosis. Comparison of starting age of a GH treatment revealed that non‐scoliotic patients received the therapy earlier than scoliotic patients (P = 0.021). Among 20 scoliotic patients who received the GH therapy, the degree of scoliosis progressed during the therapy in six patients, improved in three and fluctuated in one. Many patients showed progression of scoliosis with age irrespective of the use of GH, and some patients improved their scoliosis during the GH therapy. These findings showed that a GH therapy increases height velocity of PWS patients but does not necessarily develop scoliosis, and early start of the therapy may not be an exacerbating factor of scoliosis.

Effects of 5 Years Growth Hormone Treatment in Patients with Prader-Willi Syndrome

BACKGROUND Short-term studies showed favorable effects of growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS). AIMS To evaluate the long-term effects of GH therapy in patients with PWS retrospectively. PATIENTS AND METHODS Effects of GH treatment (0.5 IU/kg/w s.c.) for a period of 1 to 5 years were assessed for 37 Japanese patients with PWS aged 3-(9/12) to 21-(3/12) years. Height and weight were expressed as standard deviation scores (SDSs) of Japanese PWS patients. Height velocity, final height, body mass index (BMI) and Rohrer index were also evaluated. RESULTS After 1 year of treatment, the mean height velocity improved significantly from 4.32 to 8.69 cm per year (p < 00001). After 5 years of treatment, mean height SDS increased from -0.99 to +0.88 (p = 0.003). Mean final height of treated patients was 158.0 cm in males and 147.7 cm in females. Mean Rohrer index improved from 182 to 164 (p < 0.0001) after 1 year of treatment and stayed stable thereafter. CONCLUSIONS Long-term treatment with GH in patients with PWS improved height velocity, height SDS, final height, and the degree of obesity. These data encourage the long-term use of GH in these patients.

A Case of Membranous Glomerulonephropathy Associated with Takayasu's Arteritis.

Glomerulonephropathy is a rare complication of Takayasus arteritis (TA). To date, most glomerulonephropathies associated with TA show the histological feature of mesangial proliferation. Membranous glomerulonephropathy (MG) is a form of glomerulonephropathy in which the mesangial proliferation is not conspicuous and its association with TA is extremely rare. A 54-year-old man was referred to our hospital due to progressive edema in the lower limbs and nephrotic range proteinuria. Five years previously, he underwent percutaneous angioplasty for left subclavian artery stenosis. Kidney biopsy revealed stage II MG. General examination including enhanced CT scan confirmed the presence of TA. He started oral prednisolone therapy at a dose of 40 mg daily. The C-reactive protein level normalized 7 days after the prednisolone therapy. Three months later, proteinuria had remitted. Though the true relationship between MG and TA was not revealed in present case, considering the fact that complete remission of nephrotic syndrome occurred following the improvement of C-reactive protein level in response to steroid therapy, TA might be the secondary cause of MG. To our best knowledge, only two case reports described the association of MG and TA previously. Those two patients, however, also demonstrated the feature of systemic lupus erythematosus in addition to TA. This is the first case report that describes a patient who presented as MG associated with TA, but not complicated by systemic lupus erythematosus.

Eosinophilic Granulomatous Polyangitis with Renal Granulomatous Angitis and Interstitial Eosinophilic Infiltration without Lung Granuloma

Eosinophilic granulomatous with polyangiitis (EGPA) is systemic vasculitis characterized by concomitant symptoms of asthma, allergic rhinitis, and marked increase in peripheral eosinophilia. It was previously known as Churg-Strauss syndrome. EGPA incidence in Japan is very low, with only approximately 1,800 cases reported. Renal involvement occurs in approximately 20-25% of EGPA patients, and the most typical expression is pauciimmune crescentic glomerulonephritis. We herein report a case of 69-year-old Japanese woman with fever and high titer of myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) and eosinophilia. Her renal biopsy showed massive interstitial nephritis with granulomatous vasculitis like lesion without apparent active crescent formation in glomeruli. Immediately after steroid treatment (prednisolone [PSL] 30 mg/day), she had symptomatic relief and was discharged with a reduction in MPO-ANCA.

Expression of Tight Junction Protein Claudin-1 in Human Crescentic Glomerulonephritis

The origin of crescent forming cells in human glomerulonephritis (GN) remains unknown. Some animal studies demonstrated that parietal epithelial cells of Bowmans capsule (PECs) were the main component of proliferating cells and PEC-specific tight junction protein claudin-1 was expressed in crescentic lesions. We investigated the expression of claudin-1 in human GN. Immunohistochemistry for claudin-1 was performed on 17 kidney biopsy samples with crescent formation. Colocalization of claudin-1 with intracellular tight junction protein ZO-1 was also evaluated by immunofluorescence double staining. Claudin-1 is expressed mainly at the cell to cell contact site of proliferating cells in cellular crescentic lesions in patients with these forms of human GN. Small numbers of crescent forming cells showed extrajunctional localization of claudin-1. Colocalization of claudin-1 with ZO-1 was found at cell to cell contact sites of adjacent proliferating cells. In control samples, staining of claudin-1 was positive in PECs, but not in podocytes. Our findings suggest that claudin-1 contributes to crescent formation as a component of the tight junction protein complex that includes ZO-1. Co-localization of claudin-1 with ZO-1 implies the formation of functional tight junction complexes in crescentic lesions to prevent the interstitial damage caused by penetration of filtered molecules from Bowmans space.