Prescription patterns of psychotropics in patients receiving synthetic glucocorticoids.

OBJECTIVE: Synthetic glucocorticoids cause various psychiatric symptoms. Prescription of psychotropic drugs could be considered to be a proxy for manifestation of psychiatric symptoms. The aim of this study was to investigate the prescriptions of psychotropics in outpatients receiving synthetic glucocorticoids. METHODS: We used the claims sampling data during January 2015 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan made by the Ministry of Health, Labor, and Welfare in Japan. We compared the prescription rates of psychotropics between outpatients receiving oral synthetic glucocorticoids and age- and sex-matched controls and the prescription rates of psychotropics among the eight dosage groups of synthetic glucocorticoids by chi-squared test, and chlorpromazine/imipramine/diazepam equivalent doses (or daily defined doses) of respective psychotropics among these groups using Welch's t-test. RESULTS: Synthetic glucocorticoids were prescribed to 3.1% (n = 18 122) of 581 990 patients. The prescription rates of psychotropics were significantly higher among the synthetic glucocorticoid recipients than among the non-recipients: antipsychotics, 1.8% (n = 321) vs. 1.1% (n = 201) (P = 1.4 × 10-7 ); antidepressants, 4.0% (n = 724) vs. 2.0% (n = 359) (P = 8.7 × 10-30 ); anxiolytics/hypnotics, 16.7% (n = 3029) vs. 10.2% (n = 1841) (P = 2.7 × 10-75 ); and mood stabilizers, 1.3% (n = 238) vs. 0.7% (n = 120) (P = 3.6 × 10-10 ) respectively. There was no significant difference in the prescription rates of any psychotropic drugs, other than anxiolytics/hypnotics, among the eight synthetic glucocorticoid dosage groups. CONCLUSION: Prescriptions of oral synthetic glucocorticoids were found to be associated with the use of any of the types of psychotropic drugs, other than anxiolytics/hypnotics, although a causal relationship could not be confirmed due to the retrospective and cross-sectional nature of this study.

[Penile skin metastasis of gastric carcinoma associated with prostate carcinoma: a case report].

Skin metastasis of internal carcinoma is a rare situation and its risk is reported as 0.7-9%. The site of skin metastasis is more popular at upper part of the body such as neck and face. We report a case of perineal and penile skin metastases of gastric carcinoma associated with prostatic carcinoma. A 72-year-old man, who underwent total gastrectomy for gastric carcinoma 4 years ago, was found to have sclerotic change at perineal and penile skin. As his serum PSA level was 10.6 ng/ml, transrectal prostate biopsy and penile skin biopsy were performed. The prostate tissue pathologically demonstrated moderately differentiated adenocarcinoma and it was positive for both anti-PSA and anti-CEA antibody by immunohistochemical staining. The skin tissue was found to be infiltrative adenocarcinoma, negative for PSA and positive for CEA, which was compatible with the primary gastric carcinoma specimen. The patient had been treated for 7 months with administration of Doxifluridine and injection of LH-RH agonist, but died for progression of gastric carcinoma. A risk of skin metastasis of gastric carcinoma is reported as 6%, however, its metastasis to perineal and penile skin is the first case reported in the literature.

Vasculitis associated with septicemia: case report and review of the literature.

We report an unusual case in which infectious endocarditis presented systemic vasculitis and glomerulonephritis as the initial manifestation of the disease. The patient was a 16-year-old girl with congenital cyanotic heart disease who presented with skin purpura, proteinuria, and hematuria. She had hypergammaglobulinemia, cryoglobulinemia, and positive circulating immune complexes. Renal biopsy revealed crescentic glomerulonephritis. Her serum C3 level, which was initially normal, became decreased, and prednisolone and azathioprine were administered with a tentative diagnosis of systemic lupus erythematosus (SLE). Soon after, she developed fever and renal failure. Blood culture grew Streptococcus pyogenes, and the diagnosis of infectious endocarditis was made. Eight cases of systemic vasculitis and glomerulonephritis associated with infectious endocarditis have been described in the literature. Infectious endocarditis should be included in the differential diagnosis of systemic vasculitis and glomerulonephritis.

Thymoma with pemphigus foliaceus.

A 75-year-old Japanese woman was referred to us because of an anterior mediastinal mass. Crusts and shallow erosions developed 10 months earlier on her upper chest, back, and scalp. Pemphigus foliaceus was diagnosed based on histological examination of skin biopsy specimens and positivity for serum anti-desmoglein 1 antibody by enzyme-linked immunosorbent assay. Neurological examination and electromyography ruled out myasthenia gravis. Total thymectomy was performed, and the postoperative pathology studies showed mixed lymphoepithelial thymoma. One year after the resection, the eruption and alopecia improved and the serum anti-desmoglein 1 antibody titer decreased, suggesting a beneficial effect of thymectomy on thymoma-related pemphigus.

Expression of mitogen-activated protein kinase family in rat renal development.

BACKGROUND: Among mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinase (ERK) promotes proliferation or differentiation, whereas c-Jun N-terminal kinase (JNK) and p38 MAPK (p38) are thought to inhibit cell growth and induce apoptosis. MAPK phosphatase-1 (MKP-1) inactivates and modulates MAPKs. During renal development, large scale proliferation and apoptosis occur. We investigated the temporal and spatial expression patterns of MAPKs and MKP-1 in rat kidney during development. METHODS: Western blot analysis and immunohistochemistry were performed in the developing and mature kidney of the rat. RESULTS: The expression of ERK, p38, and MKP-1 were high in developing kidney. On the other hand, JNK was abundantly expressed in adult kidney. Active forms of ERK, p38, and JNK correlated with the protein expression levels. Immunohistochemical studies revealed that ERK was strongly expressed by blastema cells, mesenchymal cells, and ureteric bud tips in nephrogenic zone of embryonic kidney. In neonatal kidney, ERK was more abundant in the deep cortex and the medulla corresponding to tubule maturation. p38 and MKP-1 were detected uniformly in mesenchymal cells, mesangial cells, and ureteric bud epithelia of fetal kidney without an obvious correlation with the occurrence of apoptosis. JNK was expressed by tubular cells and podocytes of adult kidney. CONCLUSIONS: ERK, p38, and MKP-1 are strongly expressed in developing kidney, and JNK is detected predominantly in adult kidney. Both the temporal and spatial expression of ERK coincides with the maturation of the kidney.

An adult patient with hypersensitivity to mosquito bites developing mantle cell lymphoma.

Hypersensitivity to mosquito bites (HMB) has been known to occur exclusively in the first 2 decades of life and is frequently associated with Epstein-Barr virus (EBV) infection and lymphoproliferative diseases. We report here the first adult patient with HMB, a 61-year-old Japanese man who developed mantle cell lymphoma. EBV was detected in the lymph node by polymerase chain reaction and by in situ hybridization. Serum levels of interleukin (IL)-4, IL-6, and IL-10 were markedly increased, and the T-helper cell (Th)1/Th2 balance determined by intracellular cytokine levels was polarized to Th2. These findings suggest that the Th1/Th2 imbalance could partly be involved in the pathogenesis of HMB.

Two cases of ectopic hamartomatous thymoma.

Ectopic hamartomatous thymoma (EHT) is a rare benign neoplasm. Since it was named by Rosai et al. in 1984, 24 cases have been reported. We herein report two cases of EHT, one of which presented with massive myoid cells, and review the literature related to EHT. Both of our cases displayed the typical features of EHT: (1) nests of epithelial cells, including solid, cystic, or glandular epithelial islands; (2) spindle cells dominating the microscopic picture; and (3) adipose cells which intermingle haphazardly to impart a hamartomatous quality to the tumor. In this paper, we observed massive myoid cells and the transition from spindle epithelial cell to myoid cell in one of our cases. Immunohistochemical examinations showed that the main component of EHT, spindle cells, was positive for cytokeratin and epithelial membrane antigen (EMA). Intriguingly, the myoid cells simultaneously expressed cytokeratin, EMA, myoglobin, and creatine kinase-mm, suggesting that myoid cells may originate from epithelial cells and are an intermediate state between epithelial cells and muscular cells.

Distal tubular dysfunction in lupus nephritis of childhood and adolescence.

We describe a girl with lupus nephritis who presented with distal renal tubular acidosis and hyporeninemic hypoaldosteronism. While distal tubular dysfunction is well recognized in adult systemic lupus erythematosus (SLE), only a few pediatric patients have been reported. Evaluation of five pediatric patients with SLE revealed that distal tubular dysfunction in childhood and adolescence is rare.

Association of a novel 3-amino acid deletion mutation of apolipoprotein E (Apo E Tokyo) with lipoprotein glomerulopathy.

Lipoprotein glomerulopathy (LPG) is a newly recognized renal disease characterized by abnormal lipoprotein deposition in the glomeruli, dysbetalipoproteinemia, and a high level of plasma apolipoprotein (apo) E. We identified a novel apo E mutation in a 56-year-old Japanese male with LPG. Although the plasma cholesterol and triglyceride levels were normal, the levels of intermediate-density lipoprotein cholesterol and apo E were elevated to 13 mg/dl (0.336 mmol/l; 4.2+/-2.9 mg/dl, mean +/- SD, in 12 normolipidemic controls) and 9.2 mg/dl, respectively. Biochemical analysis revealed an unusual apo E phenotype (E1/3). Apo E genotyping using DNA digested by a restriction enzyme (HhaI) identified a 66-bp fragment which was not seen with any of the common alleles. Sequence analysis of the amplified genomic DNA fragments showed a 9-bp deletion in exon 4 of the apo E gene resulting in a 3-amino acid deletion (residues 141-143). This novel mutation involves the region of the apo E molecule known to be critically involved in binding to its receptor, and this may well transform the apo E molecule, an inefficient ligand, to its receptor(s). How this mutations causes glomerular damage remains to be determined.

Takayasu's aortitis with dissection in systemic lupus erythematosus.

A forty-seven-year-old Japanese woman under treatment for systemic lupus erythematosus (SLE), complained of severe back pain. Chest X-ray and MRI showed an aneurysmal dilatation of the ascending aorta. Subsequently an aortic replacement was performed. Microscopically, the resected aorta showed Takayasu's aortitis with chronic dissection. Both aortitis and dissection are rare events in SLE patients. To our knowledge, this is the first report of Takayasu's aortitis with dissection in a patient with SLE.

Molecular cloning of the human gene STK10 encoding lymphocyte-oriented kinase, and comparative chromosomal mapping of the human, mouse, and rat homologues.

LOK is a new and unique member of the STE20 family with serine/threonine kinase activity, and its expression is restricted mostly to lymphoid cells in mice. We cloned the cDNA encoding the human homologue of LOK. The amino acid sequence deduced from the cDNA shows a high similarity to that of mouse LOK, with 88% identity as a whole. The kinase domains at the N-terminus and the coiled-coil regions at the C-terminus are particularly conserved, showing 98% and 93% identity, respectively. Western blot analysis with mouse LOK-specific antibody detected 130 000 Mr LOK proteins in human and rat lymphoid cell lines and tissues. The gene encoding the LOK (STK10/Stk10) gene was mapped by fluorescence in situ hybridization to chromosome 5q35.1 in human, chromosome 11A4 in mouse, and chromosome 10q12.3 in rat. By virtue of polymorphic CA repeats found in the 3' untranslated region of the mouse Stk10 gene, the Stk10 locus was further pinpointed to chromosome 11 between D11Mit53 and D11Mit84, using the intersubspecific backcross mapping panel. These results established STK10 as a new marker of human chromosome 5 to define the syntenic boundary of human chromosomes 5 and 16 on mouse chromosome 11.

Localized hypertrophic mononeuropathy involving the femoral nerve.

The authors report a case of localized hypertrophic mononeuropathy involving the femoral nerve in a 20-year-old woman referred because of progressive weakness and atrophy of the left thigh. MRI showed an enlarged femoral nerve and biopsies of fascicles displayed a concentric pattern of cells resembling an onion bulb. These cells were positive for epithelial membrane antigen immunostaining and had an incomplete basal lamina.

[Two cases of polymyositis associated with interstitial pneumonia with anti-OJ (isoleucyl tRNA synthetase) antibodies].

We present two cases of polymyositis (PM) associated with interstitial pneumonia (IP) whose sera contain autoantibodies to OJ (isoleucyl tRNA synthetase). The first patient is a 51 year-old female who was diagnosed as rheumatoid arthritis (RA) and treated with gold and corticosteroid at another hospital. She was admitted to Keio University Hospital due to worsening of dyspnea on exertion and polyarthritis. Laboratory findings revealed elevation of serum CK and LDH. A diagnosis of PM was made based on the myogenic pattern of EMG and pathological feature by muscle biopsy. Chest radiography and CT showed interstitial fibrosis. Because of clinical deterioration, the dose of corticosteroid was increased (prednisolone 50 mg/day) and her symptom was stabilized. The second patient, a 62 year-old male, was admitted to Kawasaki Municipal Hospital because of dyspnea on exertion, polyarthritis, and fever. He was diagnosed as PM associated with IP on the basis of his clinical and laboratory findings, and chest radiography. He was treated with methylprednisolone pulse therapy (800 mg/day for three days) and his symptoms were improved. Both patients were found to have autoantibodies to OJ. Autoantibodies to aminoacyl tRNA synthetase have been described to be associated with myositis and/or IP. In North American, it was reported that all patients with anti-OJ had either myositis or IP or both. This suggests that anti-OJ was commonly associated with the anti-synthetase syndrome observed with other anti-synthetases. This is the first report of Japanese patients with anti-OJ antibody. The clinical features of these patients were likely to be similar to those observed in North American patients. However, further studies are necessary to clarify the precise clinical significance of this antibody.

Isolated periarteritis nodosa of the spermatic cord presenting as a scrotal mass: report of a case.

We report a 57-year-old man who visited a local hospital because of a fist-sized swelling and pain in his right scrotum. Surgically resected tissue revealed necrotizing arteritis in a small spermatic artery. As systemic symptoms for angiitis were not present, this is thought to be the second case of isolated angiitis occurring in the spermatic cord.

Secretory carcinoma of the breast in a 51-year-old male.

Approximately 100 female secretory carcinoma cases have been reported. Although this tumor was initially termed juvenile carcinoma as the patients were all children and adolescent females, subsequent reports demonstrated that it occurs in females of all ages. Moreover, to date, only five males with this tumor have been reported. As with the initial female secretory carcinoma cases, all five were children or young adults. A very rare case of non-invasive secretory carcinoma of the breast arising in a 51-year-old Japanese male is described. He presented with a lump in his left breast. The surgically resected tumor was a typical secretory carcinoma histologically, except that there was no infiltration of the surrounding stroma, and was composed of tumor cells with vacuolated cytoplasm that contained secretory materials. This case, the first recorded secretory carcinoma of the breast in a middle-aged male, demonstrates that this tumor may also arise in mature males, as is the case in females. Physicians should not rule out the possibility of a secretory carcinoma of the breast regardless of patient age and gender.

The relationship between primary splenic malignant lymphoma and chronic liver disease associated with hepatitis C virus infection.

BACKGROUND: An etiologically important role has been suggested for hepatitis C virus (HCV) infection in the development of B-cell non-Hodgkin's lymphoma (NHL). HCV has been recognized as the major cause of non-A, non-B chronic hepatitis throughout the world. Moreover, the occurrence of primary splenic malignant lymphoma (PSML) has been demonstrated in patients with chronic liver disease. METHODS: In this study, the authors describe three patients with PSML. The clinical, histologic, and immunohistochemical features of the lymphomas were studied. Clonal immunoglobulin heavy chain gene rearrangement was investigated by polymerase chain reaction. RESULTS: All three cases of PSML were detected by imaging studies performed in routine follow-up of cases of chronic liver disease associated with HCV infection. Macronodular lesions were found in the three spleens; two of them were of normal weight and another was moderately enlarged. The former two were the smallest PSMLs reported to date. The histology was B-cell NHL in all cases. All 3 patients were alive after splenectomy with an average follow-up of 51.7 months (range, 35-74 months). CONCLUSIONS: HCV infection may play an etiologic role in the development of splenic B-cell lymphoma. The long survival of the patients in this study may have been due to early splenectomy.