Multi-center analysis of calcinosis in children with juvenile dermatomyositis]

OBJECTIVES: To reveal the frequency and the clinical characteristics of dystrophic calcification that occurs in children with juvenile dermatomyositis, multi-center analysis was constructed. METHOD: Fifty children with JDM were enrolled, and 14 of them (28.0%) were complicated with calcinosis. Clinical symptoms and laboratory tests at onset, initial therapy and disease course were compared in children with and without calcinosis. RESULTS: The mean age of the onset of calcinosis was 4.78 +/- 3.33 years, and it was younger than those of children without calcinosis (8.66 +/- 3.85 years) (P = 0.0017). No differences of clinical manifestation except Gower's sign were observed. The frequency of positive anti-nuclear antibody was 7.1% in children with calcinosis and 52.9% without calcinosis (P = 0.0112). The initial therapy of methylprednisolon pulses gave no effects on prognosis of calcium deposition. The calcinosis appeared in 1.56 +/- 1.91 year after the onset of the disease. The various types of calcium deposition including large tumorous clumps, subcutaneous plaques or nodules, sheet-type calcification were deserved. They appeared over knee joints (64.3%), elbow joint (64.3%), and hip processes (50.0%). Calcinosis affecting the subcutaneous tissues frequently resulted in painful superficial ulceration of the overlying skin (42.9%), local infection (50.0%), and limitation of joint movement (14.3%). Although aluminum phosphate was effective in 2 children among 7, no other effective treatment was recommended. In 5 cases, surgical removal of tumorous clumps was operated. Thus, juvenile dermatomyositis is frequently complicated with calcinosis. This type of calcinosis was found to be unlikely to resolve completely, and resulted in severe disability in children.     

ENDOSCOPIC NASOBILIARY DRAINAGE: CURRENT INDICATIONS AND EVALUATION OF THE PRODUCTS

Endoscopic nasobiliary drainage (ENBD) is a well established mode of biliary decompression. Although ENBD is certainly an uncomfortable procedure with the potential risk of spontaneous dislocation or removal of the drainage catheter by disoriented patients, it has several advantages over endoscopic biliary drainage (EBD) using an indwelling stent. The current indications for ENBD are: (i) temporary drainage to treat obstructive jaundice and cholangitis caused by malignant or benign biliary stricture; (ii) urgent drainage to treat suppurative cholangitis primarily caused by common bile duct stones; (iii) temporary drainage after stone removal in patients with suspected incomplete clearance and/or with cholangitis; and (iv) biliary leaks that occur primarily after surgery, as well as other indications. Different types of nasobiliary catheters are currently available that have been designed with various diameters, shapes, and materials. However, the current catheters are not considered by most endoscopists to be sufficient. Further improvements are needed to achieve better drainage and better maneuverability.     

Locally applied cilostazol suppresses neointimal hyperplasia and medial thickening in a vein graft model.

BACKGROUND: Pathological changes in vein grafts begin immediately after arterial circulation is applied to the grafts. Chemical mediator stimulation and mechanical strain induce neointimal hyperplasia and medial thickening of the vein grafts, resulting in their failure. We investigated the inhibitory effect of locally applied cilostazol, an inhibitor of cyclic adenosine monophosphate phosphodiesterase III, on neointimal hyperplasia and medial thickening of the grafts. METHODS AND RESULTS: We established a distal anastomotic stricture model of femoral vein-abdominal aorta interposition grafting in rats. In this model, neointimal hyperplasia was observed not only at the distal anastomotic sites, but also in the graft body at postoperative day 14 and was markedly progressed at day 28. A strong expression of tenascin-C was found in the media and neointima of the graft body. In the grafts around which cilostazol was administered locally using Pluronic gel, neointimal hyperplasia was significantly suppressed compared with control grafts treated with the gel alone, with the mean neointimal cross-sectional area reduced by 87.1% for the graft body and by 78.9% for the distal anastomotic sites and mean medial cross-sectional area of the graft body reduced by 54.2% at day 28 versus the control. Cilostazol treatment decreased cell proliferation and the number of tenascin-C-producing cells seen by in situ hybridization, but the expression of tenascin-C protein was not suppressed. CONCLUSION: We concluded that a single perivascular application of cilostazol inhibits neointimal hyperplasia and medial thickening of vein grafts in a rat model.     

Lack of rapid initiating, promoting or sequential syncarcinogenic effects of di(2-ethylhexyl)phthalate in rat liver carcinogenesis

The effect of prolonged dietary administration of the peroxisomeproliferating plasticizer di(2-ethylhexy1)phthalate (DEHP wasstudied on liver carcinogenesis initiated by N-2- fltuorenylmxhmide(FAA) and with that of the neoplasm-promoter phenobarbital (PB).Also, DEHP was studied as an initiator by giving it in placeof FAA before PB. Male rats were fed FAA for 7 weeks to inducebepatocellular altered foci, and were subsequently given nochemical, 12 000 p.p.m. DEHP or 500 p.p.m. PB for 24 weeks inthe diet. In the rats fed DEHP, substantial hepatomegaly andperoxisome proliferation were induced. No evidence of indudionof hepatacellular altered foci or hepatic neoplasms was foundeither when DEHP was given alone for 24 weeks or for 7 weeksfollowed by PB. Also, DEHP fed for 24 weeks had no promotingeffect on liver altered foci that were induced by FAA and producedlittle or no enhancement of the occurrence of FAA-induced liverneoplasms. In contrast, PB exerted a marked enhancing effecton foci and substantially increased the incidence and multiplicityof liver neoplasms. Thus, the findings demonstrate that DEHPdid not have either a rapid initiating activity, a significantsequential syncarcinogenic activity, or a promoting effect onliver carcinogenesis under conditions in which numerous agentswith such activities have been identified.     

Alterations of nuclear pores in preneoplastic and neoplastic rat liver lesions induced by 2-acetylaminofluorene

The nuclear pore density and area were measured on freeze-fracturednuclei of ACI/N rat liver altered foci, adenomas and carcinomasinduced by 2-acetylaminofluorene, and compared with those ofnormal hepatocytes. The pore density of nuclei from these preneoplasticand neoplastic lesions was significantly higher than that ofhepatocytes, but there was no difference between lesions. Thearea of nuclear pores of the focus cells did not differ fromnormal hepatocytes, whereas the areas of pores of adenoma andcarcinoma cells were increased. Moreover, the nuclear pore areaof carcinomas was significantly greater than that of adenomas.These results suggest that some changes may occur in nuclearpores in the progress of tumorigenesis.     

A case-control study of breast cancer among Japanese women: with special reference to family history and reproductive and dietary factors

Summary To study the effects of family history and reproductive, anthropometric, and dietary factors on the risk of breast cancer among low risk populations, we conducted a hospital-based case-control study involving 908 patients with breast cancer and their matched controls, in Japan. A positive family history of breast cancer significantly increased the risk of breast cancer (odds ratio = 1.52, 95% confidence interval: 1.14–2.03). The risk further increased with increasing number of family members affected. Obesity, single marital status, fewer births, a late childbirth, and less consumption of green-yellow vegetables and dairy products were also associated with an increased risk of breast cancer. These associations were independent in multivariate analyses. There was no increase in risk associated with consumption of high fat foods. When analyzed by menopausal status, the association with family history of breast cancer, especially in the first degree of relatives, was more evident for premenopausal breast cancer. The associations with obesity and lower consumption of dairy products were more pronounced for postmenopausal breast cancer, while those with lower parity and single marital status were stronger for premenopausal breast cancer.     

Clinical Pharmacokinetics of Anti‐angiogenic Photodynamic Therapy with Benzoporphyrin Derivative Monoacid Ring‐A in Dogs Having Naturally Occurring Neoplasms

The aim of this study was to examine the pharmacokinetics of clinically applied benzoporphyrin derivative monoacid ring‐A (BPD‐MA; Verteporfin^®), a second‐generation photosensitizer, during a trial of photodynamic therapy (PDT) in nine dogs having naturally occurring neoplasms. After injecting BPD‐MA at 0.5 mg/kg intravenously, its mean half‐life (t_1/2) was found to be 8.14 ± 5.34 h, mean clearance (Cl) 35.13 ± 9.62 ml/(h kg), the mean value of the volume of distribution (V_c) 0.08 ± 0.01 l/kg and the mean steady state volume of distribution (V_ss) 0.38 ± 0.31 l/kg respectively. With the exception of a transitional increase in serum alkaline phosphatase activity, no other clinical abnormalities were observed. The t_1/2 in dogs with naturally occurring tumours was longer than that in humans, but similar to that in rats. The values of Cl and V_ss in dogs having naturally occurring neoplasms were lower than those in humans. It is suggested that the pharmacokinetics of BPD‐MA in tumour‐bearing dogs would be helpful in determining the protocol of a short drug‐light interval PDT with BPD‐MA that mainly targets the tumour vasculature.     

Immunocytochemical Evidence of Amyloid-enhancing Factor (AEF) in Polymorphonuclear Leukocytes

Amyloid enhancing factor (AEF) was extracted from spleens of mice that had received amyloidogenic stimulation. Sephacryl S 300 gel filtration of the crude AEF yielded five fractions, among which strong AEF activity was present in the first peak (Fl), and confirmed by an amyloid induction experiment. An anti AEF antiserum was obtained from a rabbit by immunization with Fl. This antibody reacted strongly with splenic polymorphonuclear leukocytes (PML) from mice given amyloidogenic stimulation, and weakly with those from normal untreated mice. Isoelectric focusing (IEF) analysis of both Fl and sera from mice given amyloidogenic stimulation was performed. A single band was observed on IEF analysis of Fl, whereas many bands were seen on IEF analysis of the sera. After the substances in the gel had been transferred to nitrocellulose membranes by capillary blotting, the membranes were made to react with the anti-AEF antiserum. The results suggested that AEF is a high molecular-weight substance derived from PML and increases in the serum at the time of, or shortly prior to, amyloid deposition in the spleen. Acta Pathol Jpn 39: 349∼355, 1989.     

A simple organ culture method for differentiation of melanocytes in mouse embryonic skin using “origami” membrane filter

Summary A simple organ culture method for culturing embryonic skin was developed. A piece of skin with a part of the neural tube from mouse embryo (11 to 12 d) was placed on a 25 mm d membrane filter. The filter was folded to wrap the explant and inserted into glass tubing. The explant and filter in the glass tubing were placed in a rotating tissue culture tube containing 5 ml culture medium (Ham's F12 supplemented with 15 to 20% fetal bovine serum) and filled with a mixture of 95% air:5% CO₂. In explants cultured for 6 d fully differentiated melanocytes were observed in the epidermis.     

A patient with hepatic granuloma formation and angiotensin-converting enzyme production by granuloma cells during clinical relapse of hepatitis A

Elevation of the serum angiotensin-converting enzyme (sACE) level and hepatic granulomas were found during a clinical relapse in a 22 year old patient with acute viral hepatitis type A (AVH-A). The serum transaminase level and sACE level remained high for more than 6 months. In the biopsied specimen of the liver, fibrous rings of granulomas composed of collagen types I, III, and V were observed. Furthermore, the localization of ACE was visible in the rough endoplasmic reticulum of epithelioid cells of granulomas in the liver under electron microscopy using the indirect immunoperoxidase method. These results suggest that granuloma cells in the liver caused by hepatitis A may be involved in ACE production. In addition, other diseases associated with the presence of granulomas in the liver, such as lymphoma, cytomegalovirus infection, visceral leishmaniasis, and lupoid hepatitis, were ruled out. However, the hepatic granulomas disappeared with the healing of AVH-A. In this regard, the present case is considered to be one of the very few cases of hepatic sarcoidosis.