Can serum IgE or blood eosinophil count predict postoperative oral corticosteroid response in chronic rhinosinusitis with nasal polyps?

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterised by inflammatory mucosa and polyp formation in the paranasal sinuses. The study's primary objective was to evaluate the outcomes of postoperative oral corticosteroid (OCS) in treating patients with bilateral CRSwNP. The secondary objective was to determine whether preoperative serum IgE levels (sIgE)and/or blood eosinophil count (BEC) correlate with postoperative outcomes following OCS use. METHODS: Patients with bilateral CRSwNP (n=236) who underwent endoscopic sinus surgery (ESS) were randomly assigned to receive 15 mg OCS twice daily or a placebo for 2 weeks. We investigated the treatment effects based on the subjective visual analogue scale (VAS), Sino-Nasal Outcome Test 22 (SNOT-22), and objective Lund-Kennedy Endoscopy Score (LKES) over 6 months; subgroups were stratified preoperatively as follows: sIgE <150 IU/mL, sIgE>=150 IU/mL, BEC <0.39x10(9) cells/L, and BEC>=0.39x10(9) cells/L. RESULTS: A total of 193 participants completed the study up to the 6-month follow-up; no apparent linear relationship was noted between sIgE and BEC. No significant differences in scores were noted upon assessment of the VAS, SNOT-22, and LKES among the follow-up timepoints in the primary analysis. However, in the primary or subgroup analyses with sIgE or BEC, significant differences in the longitudinal scores of sleep dysfunction were observed at the 1-month follow-up. CONCLUSION: Postoperative OCS did not significantly affect bilateral CRSwNP outcomes. sIgE levels and BEC may not be surrogate predictive biomarkers to assess the role of postoperative OCS use. OCS may increase the risk of transient sleep disturbance.

Add-on effect of clarithromycin to oral steroids as post- operative therapy for chronic rhinosinusitis with nasal polyps: a randomised controlled trial.

BACKGROUND: Evidence is lacking regarding the efficacy of macrolides and oral corticosteroids in chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery (ESS). Therefore, we examined the benefits of adding clarithromycin to oral pred- nisolone as post-ESS medical therapy in patients with CRSwNP. METHODS: In this randomised, double-blind, placebo-controlled trial, patients were enrolled and allocated to three study groups receiving different post-ESS medical therapies: group A (placebo for 14 weeks), group B (oral prednisolone [15 mg twice daily] for 2 weeks, followed by placebo for 12 weeks), and group C (oral prednisolone [15 mg twice daily] for 2 weeks, followed by clari- thromycin [500 mg daily] for 12 weeks). All enrolled patients received the perioperative care following a routine protocol, which included oral amoxicillin/clavulanate, and intranasal corticosteroid spray. The baseline and post-operative visual analogue scale (VAS) scores, Sino-nasal Outcome Test (SNOT-22) scores, and Lund-Kennedy endoscopy scores (LKES) were determined as the primary outcomes. RESULTS: One hundred twenty-six patients who received ESS for bilateral CRSwNP were randomised into group A (n=43), B (n=42), or C (n=41). Compared to groups A and B, group C showed greater VAS and SNOT-22 score improvement at 12 weeks after ESS. Group C showed significantly better LKES than did groups A and B at 8, 12, and 24 weeks after ESS. On stratifying the LKES results according to the presence/absence of tissue eosinophilia, greater add-on effects of clarithromycin were observed in the patient subgroup without tissue eosinophilia. CONCLUSIONS: Adding low-dose clarithromycin to oral corticosteroids as post-ESS therapy was well tolerated and showed benefi- cial subjective and objective outcomes in patients with CRSwNP, especially those without tissue eosinophilia.

[Clinical analysis of visual loss caused by facial cosmetic fillers injection].

Objective: To investigate the risk factors, clinical manifestations, and treatment of visual loss caused by cosmetic fillers injection. Methods: It was a retrospetive case series study. Collect the clinical data of 18 cases (18 eyes) which were diagnosed as visual loss caused by facial cosmetic fillers injection in the Second Hospital of Dalian Medical University during December, 2014 to June, 2016. Summarize the general condition, medical history, clinical examination results (including visual acuity, intraocular pressure, fundus condition, etc.) and the patient's facial appearance at the time of admission. Take the examinations such as VEP, FFA, OCT, etc. Confirm the composition of the fillers according to the medical history and the product packaging. After the diagnosis, all patients were treated generally combined with intraocular pressure reduction treatment and other treatment measures. Results: All the patients were female, 24-45 years old, with average age of 33.4. The fillers were mainly consisted of hyaluronic acid or autologous fat. For 6 patients the fillers were injected in the forehead, 8 patients were in the nose, the other 4 patients were in both sites. The mean time was 31.7 hours since the onset to the acceptance of medical treatment. All the patients manifested as no light perception, injection site ischemia, different degree of ptosis and fundus examination showed artery occlusion signs. Seventeen patients were central retinal artery occlusion, one was posterior ciliary artery occlusion. After active treatment, 2 patients' visual acuity improved to light perception, one improved to hand movements, while the others had no significant improvement. Conclusions: Most patients who suffered visual loss after cosmetic injections are young or middle-aged women, with most common injection sites at nose or forehead. The visual loss is mainly caused by central retinal artery occlusion which leads to an ineffective clinical treatment. The main factors that may induce artery occlusion are: injection done by informal medical organization, use of non-standard drugs, inadequate understanding of facial anatomy of the operator, and improper injection methods.(Chin J Ophthalmol, 2017, 53: 594-598).

[Clinical outcomes of early repair for open orbital fracture].

OBJECTIVE: To investigate the clinical outcomes following early repair for orbital fracture and soft tissue simultaneously for open orbital fractures. METHODS: Retrospective clinical study. This study comprised of 19 patients(20 eyes) with open orbital fracture who underwent surgery within 48 hours in the Second Hospital of Dalian Medical University between August 2011 and August 2014. The wounds were evaluated at the same time and the surgical debridement was done. The surgical exposure was achieved through direct approach and auxiliary cosmetic incisions. Titanium mesh and plate was used for orbital reconstruction. Local flaps or island flaps were used for soft tissue repair. With the post-operative CT scan, the condition of the soft tissue which was herniated, the orbital rim and orbital wall were observed. The measurement of the exophthalmos of both eyes was performed using Hertel exophthalmometer. Compared with the intact eye, the globe displacement (upward or downward) of the reconstructed eye was measured. The follow up duration was 12-24 months. The eye movement, diplopia, restriction of mouth opening, depression of midface, the condition of soft tissue and scar as well as post-operative complications were recorded. Comparison of the reconstructed eye's globe displacement before and after operation were analyzed with wilcoxon signed ranks test. Comparison of the exophthalmos of the reconstructed eye relative to the intact eye were analyzed with t-paired test. RESULTS: In all 19 cases (20 eyes), fractures were anatomically reconstructed, and no cases of infection, titanium mesh and plate migration and rejection occured during the follow-up. Seven cases had eyeball hypoglobus with median 3.0 mm (min 2.0 mm, max 4.0 mm) pre-operatively. The Reconstructed eye globe were corrected in 6 cases and 1 case had residual hypoglobus of 1.0 mm ,median 0.0 mm (min 0.0 mm, max 1.0 mm). The amount of the eye globe displacement between pre-and post-operation was statistically significant(z=-2.40, P<0.05). Enophthalmos was corrected in 16 cases (the mean of posterior globe displacement in reconstructed orbit relative to intact orbit was less than or equal to 2.0mm), but in 2 patients the residual enophthalmos was 3.0 mm. The difference of the exophthalmos of both eyes was not obvious (t=-0.46,P>0.05). Among 20 eyes, 16 patients had restrictive eye movement. After 12 months follow-up, 13 eyes with restrictive eye movement were corrected while the other 3 showed improvement. Eight patients of restriction of mouth opening or midface depression were corrected and no infection complications were noted. There was no flap necrosis in 13 patients of soft tissue defect. CONCLUSION: Surgical treatment of open orbital fractures with simultaneous repair of orbital fracture and soft tissue within 48 hours after trauma could correct enophthalmos, hypoglobus and eye movement function effectively and improve periorbital aesthetics. (Chin J Ophthalmol, 2016, 52: 273-277).

Occurrence of Phoma macdonaldii, the Causal Agent of Sunflower Black Stem Disease, in Sunflower Fields in China.

Phoma macdonaldii Boerma is the pathogen of sunflower black stem disease, causing dark black, oval to long lesions on stems of sunflower plants. Infection during early growth stages can reduce yield by 10 to 30% (3). This fungal disease is distributed mainly in North and South America and Europe. In China, the first case was reported in Xinjiang in 2008 (1), and was believed to be introduced as a result of hybrid sunflower seeds being imported from abroad. The Chinese government included this fungus into its quarantine pests list in 2010 (2). Since China imports a great number of sunflower seeds to grow in its Northern provinces from epidemic areas such as the United States, Argentina, and France, monitoring the disease occurrence in planting areas became crucial. During 2010 and 2011 growing seasons, surveys were conducted in 37 commercial farms or individual households in 12 counties of five areas (Xinjiang, Inner Mongolia, Ningxia, Hebei, and Beijing). A total of 185 suspicious samples of sunflower black stem disease were collected and all were found from imported hybrid seed fields. The presence of P. macdonaldii was confirmed as following: 4 mm2 tissue pieces cut from lesion margins were disinfected with 1% NaOCl, plated on APDA (acid potato dextrose agar, 4.5 to 5.0 pH adjusted with lactic acid), and incubated at 25°C with 12L:12D photoperiod. After 3 days of incubation, colonies were opalescent or ivory in color, and fluffy or flocculent in appearance. After 4 to 6 days, a large number of spherical or oblate black-brown pycnidia were formed separately or in clusters with thin wall and papillate ostiole in diameter of 135 to 324 µm (average 178 µm). A light pink or opalescent gelatinous substance (pycnidiospores) exuded from the ostiole. Pycnidiospores were single celled, oval or kidney-shaped and hyaline both with and without oil balls, and 1.5 to 3.0 µm × 3.0 to 6.5 µm (average 2.0 × 4.7 µm). Sequences of ITS1-5.8S- ITS2 rDNA fragment of all isolates (GenBank Accession No. JQ979487, JQ979488) were identical and had 100% homology with P. macdonaldii isolates from Xinjiang (HM003206) and Australia (DQ351823, DQ351825) and 99% homology with isolates from the former Yugoslavia (DQ351821, DQ351822) in GenBank. Pathogenicity studies of the isolate were performed by injecting 10 × 106/ml spore suspension into the hypocotyl of four true leaves of sunflower seedlings with a syringe. Sterile water was injected as control. After being inoculated in a plastic bag in the shade at room temperature for 48 h, the plastic bag was removed and the seedlings were grown under natural light. Symptoms of black stem disease were observed in all P. macdonaldii inoculated seedlings and the fungus was reisolated from the lesions for confirmation. The current survey found that 105 of 185 suspicious samples were P. macdonaldii positive and were all from four counties in Xinjiang, suggesting that the disease has not spread to other areas since its introduction. The monitoring of sunflower black stem disease is continuing, as is the research for measuring P. macdonaldii adaptability in China and the development of rapid molecular detection technology. References: (1) W. M. Chen et al. J. Yunnan Agric. Univ. 23:609, 2008. (2) J. Luo et al. Australas. Plant Pathol. 40:504, 2011. (3) E. Miric et al. Aust. J. Agr. Res. 50:325, 1999.

The use of dual-phase 18F-FDG PET in characterizing thyroid incidentalomas.

AIM: To examine the usefulness of dual-phase 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) for the evaluation of thyroid incidentalomas. MATERIALS AND METHODS: In this retrospective study, cases with focal thyroid lesions seen incidentally at FDG PET in which the histopathological diagnosis was available and in which dual-phase FDG PET imaging was performed at 1 and 2 h after FDG injection were reviewed. In the included cases, the 1 and 2 h maximal standard uptake value (1-hour maximal SUV and 2-hour maximal SUV, respectively) and retention index (RI) were calculated, and the differences between benign and malignant thyroid incidentalomas were analysed. Receiver operating characteristic (ROC) analysis was performed to evaluate the ability of 1-hour maximal SUV, 2-hour maximal SUV, and RI to discriminate benign from malignant lesions. RESULTS: A total of 39 patients (25 females, 14 males) with 45 lesions (17 malignant, 28 benign) were included. In malignant thyroid incidentalomas, the average 1-hour maximal SUV, 2-hour maximal SUV, and RI were 5.20, 5.72, and 7.67%, respectively, and in benign thyroid incidentalomas the values were 4.67, 4.97, and 7.38%, respectively. There were no significant differences in 1-hour maximal SUV, 2-hour maximal SUV, and RI between benign and malignant lesions. The area under the ROC curve did not differ from 0.5. CONCLUSION: Dual-phase FDG PET is not useful for differentiating benign from malignant thyroid incidentalomas.

First Report of Black Spot Caused by Colletotrichum gloeosporioides on Paper Mulberry in China.

Paper mulberry, Broussonetia papyrifera (L.) Venten. (family Moraceae), is a fast-growing tree with luxuriant branches and leaves. Because of strong adaptability and tolerance to unfavorable environmental conditions, it is an important tree species for shade or shelter and reforestation in mined areas and on hillsides. During the summer of 2010, brown-to-black spots were observed on leaves of paper mulberry in Baiwangshan Forest Park in Beijing, China. Early symptoms were round or elliptic, light brown, small lesions that later extended to round or irregular spots (4 to 6 × 4 to 8 mm) that were dark brown or black in the center with brown or light brown margins. Several dozen spots were found on severely infected leaves. Leaf tissues (2 × 2 mm), cut from the margins of lesions, were surface disinfected in 0.5% NaOCl solution for 3 min, rinsed three times with sterile water, plated on potato dextrose agar (PDA) and incubated at 25°C with a 12-h light and 12-h dark period. Numerous waxy subepidermal acervuli with setae were observed after 3 days. Acervuli were brown or black, round or elongate, and 100 to 250 µm in diameter. Setae were dark brown, erect straight or slightly curved, and 60 to 74 × 4 to 8 µm with one to two septa. Conidiophores were hyaline or light brown, short with no branches, and cylindrical with dimensions of 12 to 21 × 4 to 5 µm. Conidia were 11 to 21 × 3 to 6 µm, hyaline, aseptate, and cylindrical. Mycelia on PDA were off white-to-dark gray on the reverse side of the colony. Six isolates (BP21-1 to BP21-6) were obtained from different infected leaves and identified as Colletotrichum gloeosporioides (Penz.) Penz. & Sacc. (teleomorph Glomerella cingulata (Stonem.) Spaulding & Schrenk) on the basis of reverse colony color, dimensions and colors of acervuli, conidiophores, and conidia (3). ITS1-5.8S-ITS2 rDNA sequence analysis was performed on all six isolates. The resultant sequences were identical (GenBank Accession No. HQ 654780) and revealed 99% similarity (100% coverage) with C. gloeosporioides isolates in the GenBank (Accession Nos. EU371022.1 and AY376532.1) (2). Pathogenicity was demonstrated using six potted 3-month-old paper mulberry trees. Isolate BP21-2 was grown on PDA for 14 days and conidia were harvested to prepare a suspension of 106 conidia/ml. Three plants were sprayed with the conidial suspension and three were sprayed with sterile water. All trees were covered with plastic bags for 24 h to maintain high humidity and incubated at 25°C for 6 days. All conidia-inoculated trees showed identical symptoms as the infected leaves in the park, while the control trees remained symptom free. Reisolation of the fungus confirmed that the causal agent was C. gloeosporioides. C. gloeosporioides is distributed worldwide causing anthracnose on a wide variety of plants including members of mulberry family Moraceae, e.g., mortality of stem cuttings and death of saplings on mulberry (Morus alba L.) in India (1). To our knowledge, this is the first report of C. gloeosporioides causing black spots on paper mulberry in China. References: (1) V. P. Gupta et al. Indian Phytopathol. 50:402, 1997. (2) K. D. Hyde et al. Fungal Divers. 39:147, 2009. (3) J. E. M. Mordue. No. 315 in: Descriptions of Pathogenic Fungi and Bacteria. CMI. Kew, Surrey, UK, 1971.

First Report of Cochliobolus sativus Causing Leaf Spot on Paper Mulberry in China.

Paper mulberry, Broussonetia papyrifera (L.) Vent., is a highly adaptable, fast-growing tree that is native to eastern Asia. Its ability to absorb pollutants makes it ideal for ornamental landscapes, especially in industrial and mining areas. During the summer of 2010, brown lesions were observed on leaves of paper mulberry in Baiwangshan Forest Park, Beijing, China. These lesions were ovoid to fusiform and 4 to 9 × 2 to 4 mm with dark brown centers and light brown irregular edges. Spots on severely infected leaves sometimes coalesced to form long stripes with gray centers. To isolate the causal agent of the lesions, 4-mm2 pieces of diseased leaf tissue from 12 leaves were collected at the lesion margins and surface disinfected in 0.5% NaOCl for 3 min, rinsed three times with sterile water, plated on water agar, and incubated at 25°C with a 12-h photoperiod. After 5 days, the cultures, which became dark brown to black, were observed. Conidiophores (120 to 220 × 4 to 7 µm) were solitary or in groups of two to five, straight or flexuous with swollen bases, and light or dark brown. Conidia were dark olive brown, spindle- or oval-shaped with truncated ends (60 to 120 × 15 to 30 µm), slightly curved, and containing 3 to 12 distoseptate (mostly 6 to 10). Pseudothecia, produced after 14 days in culture, were dark brown to black and flask shaped (420 to 530 µm in diameter with 85 to 100 × 75 to 90 µm ostiolar beaks). Asci were cylindrical (100 to 220 × 30 to 40 µm) and contained eight ascospores. Ascospores were filiform, (150 to 360 × 6 to 9 µm), hyaline, with 6 to 11 septations. Isolates were identified as Cochliobolus sativus (Ito & Kurib.) Drechsler & Dastur (anamorph Bipolaris sorokiniana (Sacc. & Sorok.) Shoem.) on the basis of culture color and dimensions and colors of pseudothecia, asci, ascospores, conidiophores, and conidia (2,3). The identity of one isolate was confirmed by ITS1-5.8S-ITS2 rDNA sequence (GenBank Accession No. HQ 654781) analysis that showed 100% homology to C. sativus listed in Berbee et al. (1). Koch's postulates were performed with six potted 3-month-old paper mulberry plants. An isolate was grown on potato dextrose agar for 14 days to obtain conidia for a conidial suspension (3 × 104 conidia/ml). Three of the potted plants were sprayed with the conidial suspension and three were sprayed with sterile water as controls. Each plant was covered with a plastic bag for 24 h to maintain high humidity and incubated at 25°C with a 12-h photoperiod. After 7 days, the inoculated plants showed leaf symptoms identical to those previously observed on paper mulberry trees in the Baiwangshan Forest Park, while control trees remained symptom free. Reisolation of the fungus from the inoculated plants confirmed that the causal agent was C. sativus. C. sativus is widely distributed worldwide causing a variety of cereal diseases. Wheat and barley are the most economically important hosts. To our knowledge, this is the first report of C. sativus as a pathogen causing leaf spot of paper mulberry in China. References: (1) M. L. Berbee et al. Mycologia 91:964, 1999. (2) M. B. Ellis. Dematiaceous Hyphomycetes. CABI, Oxon, UK, 1971. (3) A. Sivanesan et al. No.701 in: Descriptions of Pathogenic Fungi and Bacteria. CAB, Kew, Surrey, U.K., 1981.

Osteoinductive effects of tantalum and titanium on bone mesenchymal stromal cells and bone formation in ovariectomized rats.

OBJECTIVE: Although Tantalum (Ta) exhibits better osteoinductivity in healthy subjects when compared with titanium (Ti), the relative effects in osteoporosis remain unknown. MATERIALS AND METHODS: In this study, bone mesenchymal stromal cells of ovariectomized rats (OVX-rBMSCs) were seeded on Ta and Ti substrates for in vitro evaluation of cell viability, reactive oxygen species (ROS) production, alkaline phosphatase (ALP) activity, extracellular mineralization osteogenic gene and protein expression involved in bone morphogenetic protein (BMP2)/small mothers against decapentaplegic homologs 1 (Smad1) pathway. For in vivo assessment, Ta and Ti implants were embedded in femur defects of ovariectomized rats, followed by sequential fluorochrome labeling and histological staining. RESULTS: Compared to Ti, the Ta substrates demonstrated higher viable cell percentages (96.5 ± 0.26 vs. 88.17 ± 2.23%), lower ROS levels (65% vs. Ti), and enhanced ALP activity and extracellular matrix calcification. Reverse Transcription-Polymerase Chain Reaction and Western blot assays validated the better osteoinductive effect of Ta regarding small mothers against decapentaplegic homologs 1 (Smad1), runt-related transcription factor 2, bone morphogenetic protein (BMP2), and ALP expression at both the mRNA (1.5-2-fold) and protein (1.2-1.8-fold) levels. BMP2/Smad1 signaling over-expression or knockdown yielded significantly enhanced or deteriorated OVX-rBMSC osteogenesis on the two surfaces. In addition, the Ta group revealed more new bone formation (1.3-1.5-fold vs. Ti) and slightly better bone-implant contact (31.82 ± 4.07 vs. 25.2-3.84% at 8 weeks post-implantation, p = 0.052) without the contribution of specific surface structures. CONCLUSIONS: In comparison to Ti, Ta reveals better biocompatibility and osteoinductivity to OVX-rBMSCs, and the preferential Ta osteoinductivity may reflect its greater potential to trigger the BMP2/Smad1 cascade. Thus," in front of "Ta". Ta appears preferable to Ti as a bone-implant surface material under osteoporosis conditions.

Overexpression of PER3 reverses paclitaxel resistance of prostate cancer cells by inhibiting the Notch pathway.

OBJECTIVE: To investigate the levels of period circadian protein homolog 3 (PER3) in paclitaxel-resistant prostate cancer patients and the effect of PER3 on paclitaxel-resistant prostate cancer cell lines. PATIENTS AND METHODS: A total of 38 patients diagnosed with prostate cancer in our hospital from June 2013 to June 2016 were divided into paclitaxel-resistant group (n=19) and non-resistant group (n=19) according to the follow-up treatment effects. Fluorescent quantitative polymerase chain reaction (PCR) was performed to evaluate the levels of PER3 in drug-resistant and non-resistant groups as well as the relative levels of PER3 before and after treatment. PER3 was overexpressed or knocked down in a paclitaxel-resistant prostate cancer cell line, followed by measuring its IC50 as well as changes in cell cycle and apoptosis. Using Western blot, we detected downregulation of Notch pathway and related receptor proteins when PER3 was overexpressed. RESULTS: The results of fluorescence quantitative PCR showed that the expression of PER3 in the paclitaxel-resistant prostate cancer group was lower than that in the non-resistant group, and the relative expression of PER3 was decreased after treatment. Fluorescent quantitative PCR and Western blot showed that the expression of PER3 in paclitaxel-resistant prostate cancer cells was higher than that of the untreated counterparts. After overexpression of PER3 by transfecting prostate cancer-resistant cell lines with plasmids, the IC50 was significantly reduced, the cell cycle was arrested, and the apoptosis was significantly increased. Subsequently, we detected decreased expression of Notch1 in PER3 over-expressed paclitaxel-resistant cell lines by Western blot; this attenuated resistance in paclitaxel-resistant cell lines. CONCLUSIONS: PER3 can induce sensitivity of paclitaxel-resistant cell lines to paclitaxel by inhibiting the expression of Notch1.

Study on the expression of VEGF and HIF-1α in infarct area of rats with AMI.

OBJECTIVE: To investigate the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α) in infarct area of rats with acute myocardial infarction (AMI). MATERIALS AND METHODS: A total of 36 healthy male Wistar rats weighing 180 g-220 g were included in our study and were randomly divided into two groups of 6 rats each: sham operation group and experiment group. In sham operation group, surgery was performed by opening chest without ligation of arteria coronaria while, in the experiment group, surgery was performed to produce AMI model. Animals were sacrificed immediately after the operation on day 7 and day 14, respectively. The serum troponin, myocardial infarct area, microvessel density in infarct area, VEGF and HIF-1α expression were analyzed. RESULTS: Differences in the serum troponin level, myocardial infarct area, microvessel density in infarct area, VEGF and HIF-1 expression level at different time points in sham and experiment groups had statistical significance (p < 0.05). On day 7, the serum troponin, myocardial infarct area, microvessel density in infarct area, VEGF and HIF-1 expression level were the highest and the level was second highest on day 14 while the levels were lowest immediately after the operation. The expression levels of VEGF and HIF-1α were positively related with the increasing density of microvessel in infarct area (p < 0.05). CONCLUSIONS: The expression of VEGF and HIF-1α might be involved with myocardial remodeling and angiogenesis.

Alpha 1-adrenergic stimulation inhibits 3,5,3'-triiodothyronine-induced expression of the rat heart sarcoplasmic reticulum Ca2+ adenosine triphosphatase gene.

The interactions between the beta-adrenergic system and thyroid hormone (T3) on cardiac function have been investigated in detail. In addition to beta-adrenoceptors, alpha 1-adrenergic receptors are present in the mammalian heart. The interactions between T3 and the alpha 1-adrenergic system remain, however, poorly understood. T3 stimulates the expression and transcription of the sarcoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA2) gene, a protein vital in the control of cardiac calcium transients and contractility. We show that in rat cardiac myocytes, the stimulatory effect of T3 on SERCA2 messenger RNA expression and gene transcription is inhibited by an alpha 1-adrenergic agonist. We demonstrate that direct activation of the alpha 1-adrenergic signaling pathway, using a mutant constitutively active G protein (Gq) similarly down-regulated the T3 effect on SERCA2 transcription. The combined effect of thyroid hormone receptor and retinoid X receptors on T3-stimulated SERCA2 gene transcription was also markedly attenuated by alpha 1-adrenergic stimulation. These results suggested that activation of the alpha 1-adrenergic signaling pathway has an inhibitor effect on T3-dependent SERCA2 gene transcription. As this inhibitory effect of alpha 1-adrenergic stimulation occurs when only one thyroid hormone response element (TRE) drives reporter expression, it is most likely mediated by an alteration of the nuclear factors binding to the TRE or by influencing the interaction of the TRE complex with the basal transcriptional machinery.

Frequent loss of heterozygosity on chromosomes 3p and 17p without VHL or p53 mutations suggests involvement of unidentified tumor suppressor genes in follicular thyroid carcinoma.

Follicular thyroid carcinoma (FTC) exhibits frequent loss of heterozygosity (LOH) on chromosomes 10q and 3p, suggesting involvement of tumor suppressor genes. We screened 14 FTC (10 Hurthle cell carcinomas and 4 nonoxyphilic FTC), 14 papillary thyroid carcinomas, and 7 follicular adenomas for LOH on chromosome arms 1p, 3p, 3q, 10p, 10q, 11p, 11q, 13q, 17p, and 17q. LOH was more frequent in FTC than in follicular adenoma or papillary thyroid carcinoma. In FTC, rates of LOH on 3p (86%), 17p (72%), and 10q (57%) were higher than the average rate of LOH (33%; P < 0.05). Most frequently involved were 3p21-25 and 17p13.1-13.3, the sites for the VHL (3p25-26) and p53 (17p13.1) tumor suppressors. We, therefore, characterized these genes by dideoxy fingerprinting and DNA sequencing. Two FTC had mutations in p53, but only 1 of these exhibited LOH at 17p. No VHL gene mutations were found. Thus, neither p53 nor VHL genes play a significant role in the pathogenesis of differentiated thyroid cancer. LOH on 17p, but not on 3p or 10q, was correlated with mortality. Accordingly, 3p and 10q LOH may represent early, and 17p LOH late, events in FTC development. The data suggest the presence of novel tumor suppressor genes on chromosomes 3p and 17p that may be important in the pathogenesis of FTC.

Roles of the AGE-RAGE system in vascular injury in diabetes.

This study concerns whether advanced glycation endproducts (AGE) are related to microvascular derangement in diabetes, exemplified by pericyte loss and angiogenesis in retinopathy and by mesangial expansion in nephropathy. AGE caused a decrease in viable pericytes cultivated from bovine retina. On the other hand, AGE stimulated the growth and tube formation of human microvascular endothelial cells (EC), this being mediated by autocrine vascular endothelial growth factor. In AGE-exposed rat mesangial cells, type IV collagen synthesis was induced. Those AGE actions were dependent on a cell surface receptor for AGE (RAGE), because they were abolished by RAGE antisense or ribozyme. The AGE-RAGE system may thus participate in the development of diabetic microangiopathy. This proposition was supported by experiments with animal models; several indices characteristic of retinopathy were correlated with circulating AGE levels in OLETF rats. The predisposition to nephropathy was augmented in RAGE transgenic mice when they became diabetic.

The clinical utility of a non-isotopic two-step assay (DELFIA) and an analogue radioimmunoassay (SimulTRAC) for free thyroxine compared.

The analytical and diagnostic performance of a new non-isotopic, two-step immunoassay (DELFIA) for the measurement of free thyroxine (free T4) in plasma or serum has been compared with an established second generation analogue radioimmunoassay (SimulTRAC). Both methods had a good diagnostic specificity in pregnancy, thyroid clinic patients, and patients taking anticonvulsant drugs. In patients presenting to a general medical ward the diagnostic specificity of both methods was poor. Two samples appeared to contain substances which produced assay interference by DELFIA but not by SimulTRAC assays. When free T4 was measured by equilibrium dialysis a clear association between sample dilution and free T4 concentration was demonstrated in sick euthyroid patients. In contrast, using samples obtained from patients with known thyroid disease, free T4 was little influenced by sample dilution. The effects of sample dilution on free T4 measured by DELFIA were similar to those found using equilibrium dialysis. It would appear that free T4 measurements have a relatively poor diagnostic specificity in non-thyroidal illness irrespective of the method used.

Clinical significance and outcome of one or two rib lesions on bone scans in breast cancer patients without known metastases.

The presence of one or two rib lesions on bone scans of post-treatment breast cancer patients without known metastases often makes clinical decision making problematic. The aim of this study was to identify skeletal metastasis predictors that might help the management of these patients. We recruited post-treatment breast cancer patients without overt metastases whose bone scans showed (1) one or two rib hot spots, or (2) one rib lesion and a concurrent bone abnormality. Their clinical and serial scintigraphic data were collected, reviewed and evaluated for correlations. After their first abnormal bone scans, 23 patients (11 of the 77 patients initially with one rib lesion (incidence, 14.3%), three of the 27 patients with two rib lesions (incidence, 11.1%), and nine of the 11 patients with one rib lesion plus a concurrent bone abnormality (incidence, 81.8%)) developed multiple bone metastases within 2 years of the initial rib lesions in all but one case. Univariate analyses revealed that a concurrent bone lesion other than the rib, direct tumour invasion to the chest wall or skin, and 10 or more lymph nodes involved were associated with increased risks of bone metastases whereas longer persistence of the rib lesions was associated with a lower risk. Multivariate proportional hazard analyses indicated that patients with a concurrent bone lesion other than the rib (relative risk (RR)=39.65; 95% confidence interval (CI)=8.13-193.28), 10 or more lymph nodes involved (RR=13.49; 95% CI=2.09-86.91), and no radiotherapy (RR=7.59; 95% CI=2.11-27.39) were more likely to have bone metastases, while those with longer persistence of the rib lesions (RR=0.92; 95% CI=0.84-0.98) and longer time interval between surgery and the rib lesion detection (RR=0.96; 95% CI=0.94-0.99) were less likely. We have identified clinical features applicable to risk stratification. High incidence of bone metastases was noted in patients with one rib lesion and a concurrent bone abnormality. Regular follow-up for 2 years after detection of rib lesions is recommended, especially for those with risk factors.

Evolution of differential renal function after acute pyelonephritis.

(99m)Tc dimercaptosuccinic acid (DMSA) renal scans can provide accurate diagnosis of acute pyelonephritis, its sequelae (renal scars) and differential renal function (DRF). The purposes of this retrospective study were (1) to assess the relationship between DRF obtained during acute pyelonephritis and at follow-up, and (2) to elucidate the value of initial DRF in predicting subsequent renal scars. A total of 47 children were enrolled. All had both unilateral acute pyelonephritis diagnosed by initial DMSA renal scans, and follow-up DMSA renal scans. We found the correlation between initial and follow-up DRF poor (adjusted R2 = 0.396). Whether or not renal scars developed determined the follow-up DRF. Vesicoureteral reflux was significantly more common in children who developed renal scars. In addition, the higher the grade of vesicoureteral reflux, the lower the follow-up DRF and the improvement in DRF. When using a DRF of 46% as the cut-off value to predict subsequent renal scars, the sensitivity and specificity were 47.8% and 83.3%, respectively. Owing to the low sensitivity, initial DRF is not suitable for predicting the occurrence of renal scars.

Pharmacological and pathological studies on hepatic protective crude drugs from Taiwan (V): The effects of Bombax malabarica and Scutellaria rivularis.

Bombax malabarica DC and Scutellaria rivularis B. were extracted in boiling water and concentrated into 1g/ml solution to investigate their hepatoprotective effect. Carbon tertrachloride (CCL4) was injected into rat subcutaneously with a dose of 3.0 ml/kg to induce experimental acute hepatotoxicity in the animal. The activities of serum glumtamic-oxaloacetic transaminase (SGOT) and serum glutamicpyruvic transaminase (SGPT) were measured after 72 hours of CCL4 administration. The hepatopathological changes of the liver tissue were observed simultaneously with liver enzyme activities determination. The pharmacological effect of B. malabarica and S. rivularis of Taiwan was compared with that of the Bupleurum chinense from mainland China. B malabarica (p < 0.001), S. rivularis (p < 0.001) and B. chinense (p < 0.05) all demonstrated a significant reduction in the CCL4-induced SGOT and SGPT. Pathological studies of these three drugs extracts demonstrated a marked hepato-protective effects on CCL4-induced liver fatty degeneration and cell necrosis.