A mathematical model for predicting outcome in preterm labour.

OBJECTIVE: This study aimed to develop a model for predicting the outcome and evaluating the treatment of patients with threatened of preterm labour. METHODS: Clinical data from 236 patients at <32 weeks gestation who were in preterm labour were analysed to develop a discriminant function using multiple logistic regression to identify significant risk factors. The function was validated retrospectively in a further 501 patients and prospectively in 63 patients with premature labour. RESULTS: Factors that increased the risk of preterm birth were premature rupture of the membranes, intrauterine infection, dilatation of the cervix and uterine bleeding. Factors that decreased the risk of preterm birth were hospital admission after 28 weeks of gestation and intravenous administration of ritodrine. The predictive accuracy of the function was 75.4% in the 236 patients analysed, 84.8% in the further 501 retrospectively studied patients and 85.7% in the prospective group. CONCLUSIONS: The discriminant function described was clinically useful for predicting the outcome of threatened preterm labour before initiating treatment and for determining the medical care of patients, including maternal transfer to a high-level perinatal care centre.

Stress distribution of faceted particles in a silo after its partial discharge.

We present experimental and numerical results of the effect that a partial discharge has on the morphological and micro-mechanical properties of non-spherical, convex particles in a silo. The comparison of the particle orientation after filling the silo and its subsequent partial discharge reveals important shear-induced orientation, which affects stress propagation. For elongated particles, the flow induces an increase in the packing disorder which leads to a reduction of the vertical stress propagation developed during the deposit generated prior to the partial discharge. For square particles, the flow favors particle alignment with the lateral walls promoting a behavior opposite to the one of the elongated particles: vertical force transmission, parallel to gravity, is induced. Hence, for elongated particles the flow developed during the partial discharge of the silo leads to force saturation with depth whereas for squares the flow induces hindering of the force saturation observed during the silo filling.

Multiple intravascular papillary endothelial hyperplasia affecting skin and bone.

We report a 75-year-old man with multiple recurrent black papules involving his entire body. In the course of 3 years, 20 lesions were resected, which were histologically confirmed as intravascular papillary endothelial hyperplasia (IPEH). A similar vascular lesion was found on his tibia. The occurrence of multiple IPEH affecting skin and bone is extremely rare. The patient's medical history included hepatitis C, hepatoma and associated coagulopathy. We suggest that this patient's multiple lesions were induced by microthrombus formation due to liver dysfunction.

Citrullinated antigens as C1q-binding and monoclonal rheumatoid factor (mRF)-binding peptides in synovial fluids from rheumatoid arthritis patients.

OBJECTIVE: Previous studies have demonstrated that immune complexes (ICs) may be involved in the pathogenesis of rheumatoid arthritis (RA). However, autoantigens contained in rheumatoid ICs remain to be elucidated. In the present study, we investigated whether the peptides captured by C1q and monoclonal rheumatoid factor (mRF), presumably associated with ICs, were citrullinated in synovial fluids from patients with RA. METHODS: Sixteen rheumatoid arthritis synovial fluids (RASFs), 7 osteoarthritis synovial fluids (OASFs), and 20 sera from RA patients were used for experiments. ICs were measured using commercially available kits based on the C1q-binding (C1q-IC) and mRF-binding (mRF-IC) assays. Citrullination of the peptides captured by C1q and mRF was detected by anti-modified citrulline antibody (Senshu Ab) after chemical modification. RESULTS: There was a significant correlation between levels of citrullination of C1q-binding peptides and those of mRF-binding peptides in RASFs (r=0.77), both of which were significantly higher than those in OASFs. No citrullinated Ags captured by C1q and mRF were detected in sera from patients with RA. CONCLUSIONS: We have demonstrated the presence of citrullinated Ags as C1q- and mRF-binding peptides in RASF. We suggest that citrullinated Ags may contribute to the pathogenesis of RA through IC formation in the joint.

9-Cis-retinoic acid exhibits antifibrotic activity via the induction of cyclooxygenase-2 expression and prostaglandin E2 production in scleroderma fibroblasts.

BACKGROUND: The pathogenesis of scleroderma (SSc) is not fully understood, and there is no effective treatment for this chronic disease. Retinoic acid (RA) can modulate connective tissue metabolism, exhibit antifibrotic activity and improve the clinical symptoms of patients with SSc. However, the mechanisms by which RA elicits its antifibrotic actions remain to be determined. OBJECTIVE: To elucidate the underlying mechanisms by which retinoids exert beneficial effects on SSc. METHODS: Cultured skin fibroblasts from patients with SSc were treated with retinoids (9-cis-, 13-cis- and all-trans-retinoic acid) and their effect on the expression of cyclooxygenase (COX)-2, connective tissue growth factor (CTGF) and type I and III collagen and on the production of PGE(2) was examined. COX-2 expression was analysed by western immunoblotting, PGE(2) production by enzyme immunoassay and CTGF expression, and type I and III collagen expression by reverse transcriptase PCR and western immunoblotting. RESULTS: In cultured SSc fibroblasts, 9-cis-RA significantly increased COX-2 protein expression and PGE(2) production and inhibited the expression of CTGF and type I and III collagen. We further found that expression of CTGF and of type I and III collagen mRNA was inhibited by exogenous PGE(2) in SSc fibroblasts. CONCLUSION: In vitro, 9-cis-RA induced COX-2 expression and PGE(2) production in SSc fibroblasts and PGE(2) downregulated CTGF expression, leading to the inhibition of type I and III collagen synthesis. Our results indicate that the clinical effects of 9-cis-RA on SSc are, at least in part, attributable to the induction of PGE(2) and the subsequent suppression of CTGF expression that results in the blockade of collagenogenesis.

Graft-versus-adult T-cell leukemia/lymphoma effect following allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven effective in adult T-cell leukemia/lymphoma (ATL) patients. To study the graft-versus-ATL (Gv-ATL) effects after allo-HSCT, we analyzed 21 ATL patients who had been treated at our hospital. Of these, 18 had acute-, 2 had lymphoma- and 1 had chronic-type ATL; at allo-HSCT, seven patients were in CR, one was in PR, five had stable disease (SD) and eight had progressive disease (PD). Disease state after allo-HSCT was CR in 14, PR in 3, SD in 1 and PD in 3 patients. Among 15 patients who survived longer than 100 days, ATL relapsed in 10 patients, skin relapsed in 9 patients and 5 had relapsed on the skin alone. After we discontinued immunosuppressant therapy in these 10 patients, 8 manifested GVHD; ATL was ameliorated to CR in 6 patients. Donor lymphocytes were infused into two patients who did not show GVHD; one obtained CR. In five patients with skin relapse alone, four patients achieved CR following the discontinuation of the immunosuppressants. Our results demonstrate that relapse of ATL after allo-HSCT tends to develop on skin, and Gv-ATL effects played a critical role in the outcome of allo-HSCT for ATL.

Transcripts of the human herpesvirus 8 genome in skin lesions and peripheral blood mononuclear cells of a patient with classic Kaposi's sarcoma.

We report a 75-year-old Japanese woman with classic Kaposi's sarcoma. PCR amplified human herpesvirus 8 (HHV-8) DNA sequences from her skin lesions and peripheral blood mononuclear cells (PBMC), but not her plasma, saliva or urine. An antibody test against HHV-8 lytic antigens was positive. Immunohistochemical staining detected latent antigen. There was no evidence of HHV-8 infection in her husband, sister or daughter. Genes coding for HHV-8-encoded viral interleukin-6, viral macrophage inflammatory protein I, viral G protein-coupled receptor, viral cyclin D and viral Bcl-2 were expressed to the same degree in both her skin lesion and PBMC. Latency-associated T0.7 mRNA and HHV-8-encoded viral tegument protein genes were expressed in her PBMC at levels lower than in the skin lesions. Based on the gene expression profile, we concluded that lytic HHV-8 infection was present in her skin lesions and PBMC.

Immunoelectron-microscopic detection of globotriaosylceramide accumulated in the skin of patients with Fabry disease.

BACKGROUND: Fabry disease is characterized by the systemic accumulation of glycosphingolipids, particularly in the lysosomes of vascular endothelial cells of most organs due to the deficient activity of alpha-galactosidase A. The major glycolipid accumulated in tissue is globotriaosylceramide (GL-3). To date, no direct detection of GL-3 by immunoelectron microscopy has been reported. OBJECTIVES: To examine whether GL-3 is accumulated exclusively in lysosomes of cutaneous cells using an anti-GL-3 monoclonal antibody (mAb) and immunoelectron microscopy. METHODS: Skin specimens from seven patients with Fabry disease were examined immunohistochemically by light and electron microscopy using an anti-GL-3 mAb. RESULTS: By light microscopy, the cytoplasm of vascular endothelial cells, eccrine gland cells, and perineurium was stained with mouse anti-GL-3 antibody. Electron microscopically, positive signals for GL-3 were limited to dilated lysosomes in the cytoplasm of endothelial cells, pericytes, eccrine gland cells, dermal fibroblasts and perineurium. CONCLUSIONS: Our results demonstrate that the cytoplasmic deposit in Fabry disease was GL-3 and the accumulated GL-3 was localized essentially to lysosomes.

Selenium deficiency: report of a case.

We report an 18-month-old Japanese boy with selenium deficiency. He had dry skin with irregularly shaped, erythematous changes on the cheeks, groin, hip, and extremities, erosions on the external urethral and anal orifices, and sparse, short, thin, light-coloured hair. He had received parenteral nutrition for 5 months because of juvenile polyposis. At presentation, his serum selenium level was less than 2.0 microg/dL (normal range, 10.6-17.4 microg/dL). His skin lesions responded well to supplementary treatment with sodium selenite. His skin symptoms were similar to those attributable to a deficiency of zinc which, like selenium, is an essential trace element. According to the literature, selenium deficiency is responsible for cardiomyopathy, which was diagnosed in our patient. The clinical similarity to zinc deficiency and the literature yielded important clues for a diagnosis of selenium deficiency in this patient.

The detection of IgG and IgA autoantibodies to desmocollins 1-3 by enzyme-linked immunosorbent assays using baculovirus-expressed proteins, in atypical pemphigus but not in typical pemphigus.

BACKGROUND: We have shown previously that human desmocollin (Dsc) 1 is recognized by IgA autoantibodies of subcorneal pustular dermatosis (SPD) type IgA pemphigus. However, the presence of IgG anti-Dsc autoantibodies is still controversial, and antibodies to Dsc2 and Dsc3 have not been clearly identified. OBJECTIVES: To investigate this by producing recombinant proteins consisting of the entire extracellular domains of human Dsc1, 2 and 3 in baculovirus, and to use them to establish an enzyme-linked immunosorbent assay (ELISA). METHODS: By this ELISA, we examined in total 165 cases of various types of autoimmune bullous diseases, as well as 23 normal controls. RESULTS: None of 45 sera of classical pemphigus showed either IgG or IgA antibodies to any Dsc. In contrast, one atypical pemphigus serum showed both IgG and IgA antibodies to Dsc1, which were adsorbed by incubation with Dsc1 baculoprotein. Furthermore, this ELISA detected both IgA and IgG anti-Dsc3 antibodies in one atypical case, and IgA antibodies to both Dsc2 and Dsc3 in another. This reactivity was confirmed by positive IgA immunofluorescence with Dsc2 and Dsc3 expressed on COS-7 cells. These results show that both IgG and IgA autoantibodies against all of Dsc1-3 are present in the sera of particular cases of nonclassical pemphigus, except for IgG antibodies to Dsc2, but that they are not detected in classical pemphigus. Unexpectedly, although IgA antibodies of all of eight SPD type IgA pemphigus sera reacted with Dsc1 expressed on COS-7 cells, only one serum was positive in Dsc1 ELISA for IgA. CONCLUSIONS: This result indicates either that Dscs expressed by baculovirus may not adopt the correct conformation or that Dscs may need association with other molecules to express all the epitopes for autoantibodies.

Improvement of adult Still's disease with granulocyte and monocyte adsorption apheresis.

Adult Still's disease is characterized by a high spiking fever, transient skin rash, and polyarthralgia. Joint pain is one of the major complaints and is often intractable. We assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) therapy for treating arthralgia in adult Still's disease. A 33-year-old woman with adult Still's disease who suffered from recalcitrant arthralgia resistant to systemic corticosteroids was treated with GCAP therapy. She underwent five GCAP treatments at 5-day intervals. Her joint pain responded dramatically to the GCAP therapy, suggesting that GCAP may be useful for treating adult Still's disease. We present a detailed description of the patient and this novel therapy.

Neurologic manifestations of Kanzaki disease.

We describe the neurologic findings in a patient with alpha-N-acetylgalactosaminidase deficiency (Kanzaki disease). Clinical and electrophysiologic studies revealed sensory-motor polyneuropathy, and sural nerve pathology showed decreased density of myelinated fibers with axonal degeneration. The patient had mildly impaired intellectual function with abnormal brain MRI and sensory-neuronal hearing impairment with repeated episodes of vertigo attacks. These findings suggest that Kanzaki disease may develop neurologic complications in the CNS and peripheral nervous system.

Classical juvenile pityriasis rubra pilaris in a patient with Down syndrome.

We report a case of classical juvenile pityriasis rubra pilaris (CJPRP) in a 15-year-old boy with Down syndrome. The rash was extensive, severe, accompanied by intense itching and responded to low-dose etretinate. Xerosis and cheilitis were also present, suggesting that keratinization defects associated with Down syndrome may be involved in the pathogenesis of CJPRP. PRP is a rare dermatological disorder and to the best of our knowledge, this is the first reported case of CJPRP in a patient with Down syndrome.