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Schwannomas of the sinonasal tract are rare, accounting for

Introduction The continuous supply of personal protective equipment (PPE) in the National Health Service (NHS) is paramount in order to sustain a safe level of staffing and to reduce transmission of COVID-19 to patients, public and staff. Method A 16-question survey was created to assess the availability and personal thoughts of healthcare professionals regarding PPE supply in England. The survey was distributed via social media (Facebook © and Twitter ©) to all UK COVID-19 healthcare professional groups, with responses collected over 3 weeks in March 2020 during the beginning of the pandemic. Results A total of 121 responses from physicians in 35 different hospitals were collected (105 inpatient wards, 16 from intensive care units). In inpatient wards, eye and face protection were unavailable to 19.1% of respondents. Masks were available to 97.7% of respondents and gloves in all respondents (100%). Body protection was available primarily as a plastic apron (83.8%). All of respondents working in intensive care had access to full-body PPE, except FFP3 respirator masks (available in 87.5%). PPE is ‘Always’ available for 29.8% of all respondents, and ‘Never’ or ‘Almost Never’ in 11.6%. There was a statistically significant difference between London and non-London responders that ‘Always’ had PPE available (43.9% versus 19.0%, p = 0.003). Conclusions This is the first survey to evaluate PPE supply in England during the COVID-19 pandemic. Our survey demonstrated an overall lack of PPE volume supply in the UK, with preferential distribution in London. Eye and full body protection are in most lack of supply.

Routine exercise has been established as an effective way to improve overall health. The value of exercise has been established in many diseases, however, there are no studies investigating the impact of exercise for individuals with primary immunodeficiency disease (PID). The purpose of this study was to investigate exercise perceptions and behaviors in individuals diagnosed with PID. An online survey was distributed over a four-week period. Of the 264 responses collected, most were females, 45–54 years old. Respondents reported a measurable loss of function impairing their daily activities due to loss of mobility/physical activity (41.32%), or loss of lung/pulmonary function (40.08%,). They felt exercise decreased stress level and improved their mental well-being (46.25%). Some indicated they participate in exercise (33.20%), while 36.84% had not participated in exercise for at least 1 year. Exercise was limited primarily due to fatigue (86.97%). Exercise is important for those with chronic medical conditions. Most individuals living with PID can participate in low/moderate physical activity, but struggle with vigorous physical activity, since fatigue is the greatest barrier. Respondents view exercise as beneficial, and would like to increase participation in an exercise program.

© 2018 Lee, Carella, Papa and Bubici. A marked increase in the rate of glycolysis is a key event in the pathogenesis of hepatocellular carcinoma (HCC), the main type of primary liver cancer. Liver cirrhosis is considered to be a key player in HCC pathogenesis as it precedes HCC in up to 90% of patients. Intriguingly, the biochemical events that underlie the progression of cirrhosis to HCC are not well understood. In this study, we examined the expression profile of metabolic gene transcripts in liver samples from patients with HCC and patients with cirrhosis. We found that gene expression of glycolytic enzymes is up-regulated in precancerous cirrhotic livers and significantly associated with an elevated risk for developing HCC. Surprisingly, expression levels of genes involved in mitochondrial oxidative metabolism are markedly increased in HCC compared to normal livers but remain unchanged in cirrhosis. Our findings suggest that key glycolytic enzymes such as hexokinase 2 (HK2), aldolase A (ALDOA), and pyruvate kinase M2 (PKM2) may represent potential markers and molecular targets for early detection and chemoprevention of HCC.

This abstract was withdrawn by the authors.

Despite the amenability of early-stage prostate cancer to surgery and radiation therapy, locally advanced and metastatic prostate cancer is clinically problematic. Chemical castration is often used as a first-line therapy for advanced disease, but progression to the castration-resistant prostate cancer phase occurs with dependable frequency, largely through mutations to the androgen receptor (AR), aberrant AR signaling, and AR-independent mechanisms, among other causes. Semaphorin 3C (SEMA3C) is a secreted signaling protein that is essential for cardiac and neuronal development and has been shown to be regulated by the AR, to drive epithelial-to-mesenchymal transition and stem features in prostate cells, to activate receptor tyrosine kinases, and to promote cancer progression. Given that SEMA3C is linked to several key aspects of prostate cancer progression, we set out to explore SEMA3C inhibition by small molecules as a prospective cancer therapy. A homology-based SEMA3C protein structure was created, and its interaction with the neuropilin (NRP)-1 receptor was modeled to guide the development of the corresponding disrupting compounds. Experimental screening of 146 in silico‒identified molecules from the National Cancer Institute library led to the discovery of four promising candidates that effectively bind to SEMA3C, inhibit its association with NRP1, and attenuate prostate cancer growth. These findings provide proof of concept for the feasibility of inhibiting SEMA3C with small molecules as a therapeutic approach for prostate cancer.

The mortality rate in patients with haemodynamically unstable pelvic fractures is as high as 40–60%. Despite the new advances in trauma care which are in phase in trauma centres in Hong Kong, the management of haemodynamically unstable pelvic fracture is still heterogeneous. The aim of this study is to review the results of management of haemodynamically unstable pelvic fracture patients in Hong Kong over a five year period. This is a retrospective multi-centred cohort study of patients with haemodynamic and mechanically unstable pelvic fractures from 1 January 2010 to 31 December 2014. The primary outcome investigated is mortality of patients (including overall, 30-day, 7-day and 24-hour mortalities). Implementation of three-in-one pelvic damage control protocol was identified to be a significant independent predictive factor for overall, 30-day, seven-day and 24-hour mortalities. The overall in-hospital and 30-day mortality rates for patients managed with three-in-one protocol was 12.5%, while it was 11% for seven day mortality and 6% for 24 hour mortality. There were no significant differences in demographic characteristics, physiological measurements, types of pelvic fracture, severity and mechanism of injury between patients managed with or without three-in-one protocol. Implementation of the multidisciplinary three-in-one pelvic damage control protocol reduces mortality and therefore should be highly recommended. The results are convincing as it has eliminated the limitations of our previous single-centred trial.

Background and Purpose The present study assessed the effects of cilostazol on LPS-stimulated TLR4 signal pathways in synovial macrophages from patients with rheumatoid arthritis (RA). These effects were confirmed in collagen-induced arthritis (CIA) in mice. Experimental Approach Expression of TLR4, PU.1, NF-κB p65 and IκBα on synovial fluid macrophages from RA patients was determined by Western blotting, and cytokines were measured by elisa. Anti-arthritic effects were evaluated in CIA mice. Key Results Intracellular cAMP was concentration-dependently raised by cilostazol (1–100 μM). Cilostazol significantly suppressed LPS-stimulated increase of TLR4 expression by blocking PU.1 transcriptional activity in RA macrophages. In addition, cilostazol decreased LPS-induced myeloid differentiation factor 88 (MyD88) expression, but not that of TNF receptor-associated factor 6 (TRAF6). Cilostazol also suppressed IkBα degradation and NF-κB p65 nuclear translocation. Moreover, LPS-induced increase of cytokine production (TNF-α, IL-1β) was inhibited by cilostazol, an effect which was accompanied by suppression of IκBα degradation, and NF-κB p65 nuclear translocation. However, expression of anti-inflammatory IL-10 was elevated by cilostazol and forskolin/IBMX. In mice with CIA, post-treatment with cilostazol (30 mg kg−1 day−1) decreased expression of TLR4 in knee joints in association with decreased recruitment of macrophages. Consequently, synovial inflammation, proteoglycan depletion and bone erosion were significantly inhibited by cilostazol treatment. Conclusions and Implications Cilostazol down-regulated LPS-stimulated PU.1-linked TLR4 expression and TLR4/MyD88/NF-κB signal pathways, and then suppressed inflammatory cytokine production in synovial macrophages from RA patients. Also cilostazol markedly inhibited the severity of CIA in mice.

The objectives of this study were to survey elementary school students regarding the environmental conditions of their elementary schools and to assess the relationship between air pollution and allergic disease using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Therefore, this study was designed as a cross-sectional study. In this study, seven elementary schools were selected and they were classified into three categories. The selection included one school with no traffic-related or other pollutants, three with traffic-related pollutants, and three with traffic-related and other pollutants from industrial and filling station sources. The ISAAC questionnaire survey was given to all of the students except to those in the 1st grade who were presumed to be less likely to be exposed to the school environment than the remainder of the students attending those seven schools. The assessment of allergic disease was conducted on a total of 4,545 students. Three school zones with critical exposure were selected within each school and they were evaluated based on the levels of black carbon (BC), PM10, SO2, NO2, and O3. There was a significant increase in the risks based on the odds ratios of treatment experiences (within 1 year) for allergy-related diseases such as asthma and allergic rhinitis (a) in the school group with traffic-related pollutants and the school group with complex pollutants were 2.12 (1.41-3.19) and 1.59 (1.06-2.37), respectively, in comparison to the school groups with no exposure to pollutants. This was determined based on the odds ratio of symptoms and treatment experiences for allergy-related diseases by group based on the home town zone as a reference. Also, in the case of atopic dermatitis, the odds ratio of treatment experiences (within 1 year) was 1.42 (1.02-1.97), which indicated elevated risks compared to the students in the S1 school. A regression analysis was used to assess the relationship between the substances and the symptomatic experiences within the last year. There were significant increases in the odds ratio of the symptoms associated with allergic rhinitis and the BC and SO2 in the complex pollution areas. The results of the assessment of the relationship between atopic dermatitis-associated symptoms and O3 showed that the odds ratio increased with statistical significance.

Tumours are comprised of a highly heterogeneous population of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumours in vivo. These cancer stem cells (CSCs) represent a significant clinical challenge as they are resistant to conventional cancer therapies and play essential roles in metastasis and tumour relapse. Despite this realization and great interest in CSCs, it has been difficult to develop CSC-targeted treatments due to our limited understanding of CSC biology. Here, we present evidence that specific histone deacetylases (HDACs) play essential roles in the CSC phenotype. Utilizing a novel CSC model, we discovered that the HDACs, HDAC1 and HDAC7, are specifically over-expressed in CSCs when compared to non-stem-tumour-cells (nsTCs). Furthermore, we determine that HDAC1 and HDAC7 are necessary to maintain CSCs, and that over-expression of HDAC7 is sufficient to augment the CSC phenotype. We also demonstrate that clinically available HDAC inhibitors (HDACi) targeting HDAC1 and HDAC7 can be used to preferentially target CSCs. These results provide actionable insights that can be rapidly translated into CSC-specific therapies.

Cathelicidin is a pleiotropic host defense peptide secreted by epithelial and immune cells. Whether endogenous cathelicidin is protective against ulcerative colitis, however, is unclear. Here we sought to delineate the role of endogenous murine cathelicidin (mCRAMP) and the therapeutic efficacy of intrarectal administration of mCRAMP-encoding plasmid in ulcerative colitis using dextran sulfate sodium (DSS)-challenged cathelicidin-knockout (Cnlp(-/-)) mice as a model. Cnlp(-/-) mice had more severe symptoms and mucosal disruption than the wild-type mice in response to DSS challenge. The tissue levels of interleukin-1β and tumor necrosis factor-α, myeloperoxidase activity and the number of apoptotic cells were increased in the colon of DSS-challenged Cnlp(-/-) mice. Moreover, mucus secretion and mucin gene expression were impaired in Cnlp(-/-) mice. All these abnormalities were reversed by the intrarectal administration of mCRAMP or mCRAMP-encoding plasmid. Taken together, endogenous cathelicidin may protect against ulcerative colitis through modulation of inflammation and mucus secretion.

Introduction Sarcopenia and osteoporosis are age-related declines in the quantity of muscle and bone, respectively. Both contribute in disability, fall, and hip fracture in the elderly. This study reported the prevalence of sarcopenia in Chinese geriatric patients with hip fracture, and the correlation between relative appendicular skeletal muscle mass index and other factors. Methods This case series was conducted in Kowloon West Cluster Orthopaedic Rehabilitation Centre in Hong Kong. Data of all geriatric patients with primary hip fracture admitted to the above Centre from June to December 2014 were studied. Isometric grip strength, the maximal handgrip strength, was measured using a JAMAR hand dynamometer. Body composition including appendicular and whole-body lean body mass was measured using dual-energy X-ray absorptiometry. Pearson's correlation was used to examine the correlation between relative appendicular skeletal muscle mass index and other factors. Results A total of 239 patients with a mean age of 82 years were included in the study. Stratifying patients as male or female, the mean (± standard deviation) hand grip strength was 20.6 ± 7.3 kg and 13.6 ± 4.5 kg, the mean relative appendicular skeletal muscle mass index was 5.72 ± 0.83 kg/m(2) and 4.87 ± 0.83 kg/m(2), and the mean hip bone mineral density was 0.696 ± 0.13 g/cm(2) and 0.622 ± 0.12 g/cm(2), respectively. The prevalence of sarcopenia based on relative appendicular skeletal muscle mass index and hand grip strength according to the Asian Working Group for Sarcopenia definition was 73.6% in males and 67.7% in females. According to the European Working Group on Sarcopenia definition, the prevalence of pre-sarcopenia was 20.8% in males and 12.4% in females. Relative appendicular skeletal muscle mass index was positively correlated with hand grip strength, body weight, hip bone mineral density, body mass index, and total fat mass in males; and hand grip strength, body weight, body height, body mass index, and total fat mass in females. Except for body height in females, all correlations were statistically significant. Conclusion The prevalence of sarcopenia was very high in geriatric hip fracture patients, and much higher than that in community-dwelling elderly population. Apart from the need to prescribe osteoporosis medicine, sarcopenia screening and treatment should be offered and is essential to reduce subsequent fall, subsequent fracture, fracture-related complications and economic burden to Hong Kong.

One of the groups with high risk for osteonecrosis is patients with systemic lupus erythematosus (SLE). No predictive test, however, is known to detect osteonecrosis. The purpose of this study was to evaluate haemodynamic flow to the proximal femur in SLE patients.Twenty-two SLE patients without osteonecrosis were evaluated in comparison with 15 healthy controls. Medial and lateral circumflex arteries of 44 hips in the 22 SLE patients and 30 hips in the healthy controls were examined using ultrasound equipment with colour and power Doppler capability. Arterial pulsatility index (PI) and peak systolic velocity (PSV) were determined with neutral and internal rotation positions (stimulated ischaemia).PSV was significantly increased in SLE patients compared to healthy controls in both the neutral position (70.6+/-40.4 vs. 46.9+/-19.3; p0.001) and after internal rotation of the femoral head (74.8+/-42.3 vs. 49.9+/-19.9; p0.001). PI was also higher in SLE patients than in healthy controls in both the neutral position (8.9+/-6.3 vs. 5.5+/-3.4; p0.001) and after internal rotation (8.1+/-7.1 vs. 3.9+/-2.4; p0.001).PSV and PI of arteries to the femur head in SLE patients were significantly higher than in healthy controls.

Survivin is a dual regulator of cell proliferation and cell viability overexpressed in most human tumors. Although strategies to lower survivin levels have been pursued for rational cancer therapy, the molecular circuitries controlling survivin expression in tumors have not been completely elucidated. Here, we show that stimulation with insulin-like growth factor-1 (IGF-1) results in increased survivin expression in prostate cancer cells. This response is independent of de novo gene transcription, changes in mRNA expression or modifications of survivin protein stability. Instead, IGF-1 induced persistence and translation of a pool of survivin mRNA, in a reaction abolished by the mTOR (mammalian target of rapamycin) inhibitor, rapamycin. Forced expression of the mTOR target p70S6K1 reproduced the increase in survivin expression in prostate cancer cells, whereas acute ablation of endogenous p70S6K1 by small interfering RNA downregulated survivin levels. Rapamycin, alone or in combination with suboptimal concentrations of taxol reduced survivin protein levels, and decreased viability of prostate cancer cells. Therefore, IGF-1/mTOR signaling elevates survivin in prostate cancer cells via rapid changes in mRNA translation. Antagonists of this pathway may be beneficial to lower an antiapoptotic threshold maintained by survivin in prostate cancer.

We reviewed the intraoperative anaesthetic management and outcome of seven consecutive cases of endovascular stent graft surgery for thoracic aortic aneurysms or dissections over a period of 20 months in our institution. Seven males (median age 63) underwent endovascular stent graft surgery of the thoracic aorta under general anaesthesia. Four were emergency procedures for acute dissection or leaks of thoracic aneurysms. The duration of the procedures ranged from 120 to 300 minutes. Intraoperative stent migration occurred in one patient. Induced hypotension and immobilization were critical during stent deployment. Six out of the seven patients were discharged home between three to 20 days postoperatively. There was no 30-day mortality. One patient died sixty days postoperatively. Anaemia and respiratory complications were the most common postoperative problems encountered. None of the patients sustained spinal cord ischaemia, acute myocardial infarction or renal impairment. Endovascular stent graft surgery of the thoracic aorta is a relatively new alternative to conventional open surgery. Our experience suggests satisfactory short-term outcome even for patients with acute dissection. However, long-term survival and results require further evaluation.

This study was carried out to test the hypothesis that palpation for lumps may be more difficult in large breasts than in small breasts, resulting in a delay in the detection and diagnosis of breast cancer, and to determine whether this hypothesis is confirmed in Asian women. Of 833 new breast cancer patients registered in the Daegu Cancer Registry in 1997-1999, 579 were used in the final data analysis, after excluding patient records containing many missing data on study variables related with cancer staging. There was no difference in means of body mass index (BMI) according to tumour, either in all cases or in those under 49 years of age. In the 50+ age group, the means+/-standard deviations of BMI of T1, T2 and T3 were 23.7+/-2.8, 24.2+/-3.0, and 26.2+/-4.3, respectively (P=0.01). In univariate logistic regression of tumour characteristics with BMI, no statistically significant odds ratios were found either by continuous or quartiles of BMI. In conclusion, these results suggest that the hypothesis is partially confirmed in Korean breast cancer patients and further studies are needed to clarify the relationship between BMI and tumour stage at diagnosis.

The RET proto-oncogene encodes two major isoforms, RET9 and RET51, which differ at the carboxyl-terminal. Loss-of-function mutations in RET result in gut aganglionosis while gain of function mutations result in cancer syndromes. From studies on transgenic mice, RET9 is important for early development of the kidney and the enteric nervous system. Little is known about the function of RET isoforms in later life. Here we report the expression of RET isoforms and its signalling complex, GDNF and GFRalpha1, in foetal and adult human kidneys. We found their expression in both the developing and the adult renal collecting system. We further show that only RET51 but not RET9 could promote the survival and tubulogenesis of mIMCD3 (mouse inner medullary collecting duct) cells in collagen gel. Our results agree with the hypothesis that RET51 signalling is related to differentiation events in later kidney organogenesis. In addition, it may also have a function in the adult kidney. We further extend our study by showing increased RET and GDNF expression in collecting duct cysts of polycystic kidney patients. This suggests that GDNF/RET signalling may contribute to proliferation of the collecting duct epithelium in an autocrine/paracrine manner.

Background and aims: Smoking tobacco has opposite effects on the different forms of inflammatory bowel disease (IBD). It predisposes to the development of Crohn's disease (CD) yet is associated with a reduced incidence of ulcerative colitis (UC). We have studied sib pairs discordant for both smoking and IBD phenotype (UC or CD) to investigate whether smoking determines the type of IBD that develops in individuals with very similar genetic susceptibility. Patients: Smoking habits and disease characteristics were analysed in 242 IBD pedigrees (658 patients). Within this group there were 339 affected sibling pairs of whom 89 were discordant for smoking when diagnosed. Results: Smoking at diagnosis was associated with development of CD (odds ratio (OR) 3.55; 95% confidence limits 2.50–5.02; p

SUMMARYAlcohol consumption is a possible co-factor of high-risk human papillomavirus (HR-HPV) persistence, a major step in cervical carcinogenesis, but the association between alcohol and continuous HPV infection remains unclear. This prospective study identified the association between alcohol consumption and HR-HPV persistence. Overall, 9230 women who underwent screening during 2002–2011 at the National Cancer Center, Korea were analysed in multivariate logistic regression. Current drinkers [odds ratio (OR) 2·49, 95% confidence interval (CI) 1·32–4·71] and drinkers for ⩾5 years (OR 2·33, 95% CI 1·17–4·63) had a higher risk of 2-year HR-HPV persistence (HPV positivity for 3 consecutive years) than non-drinkers and drinkers for vs. HPV negativity for 3 consecutive years). A high drinking frequency (⩾twice/week) and a high beer intake (⩾3 glasses/occasion) had higher risks of 1-year (OR 1·80, 95% CI 1·01–3·36) HPV positivity for 2 consecutive years) and 2-year HR-HPV persistence (OR 3·62, 95% CI 1·35–9·75) than non-drinkers. Of the HPV-positive subjects enrolled, drinking habit (OR 2·68, 95% CI 1·10–6·51) and high consumption of beer or soju (⩾2 glasses/occasion; OR 2·90, 95% CI 1·06–7·98) increased the risk of 2-year consecutive or alternate HR-HPV positivity (vs. consecutive HPV negativity). These findings suggest that alcohol consumption might increase the risk of cervical HR-HPV persistence in Korean women.

BACKGROUNDGenetic anticipation has been proposed to explain observed age differences at diagnosis of Crohn’s disease in affected parents and offspring.AIMSTo compare affected parent-child pairs with Crohn’s disease and ulcerative colitis with a control group of non-familial patients with inflammatory bowel disease (IBD) in order to quantify whether ascertainment bias could account for this effect.METHODS137 affected parent-child pairs from 96 families and 214 patients with sporadic IBD were studied. Age at onset of symptoms and diagnosis were ascertained by interview and disease confirmed from clinical records.RESULTSOf the 137 affected parent-child pairs, 50 had Crohn’s disease only, 51 had ulcerative colitis only, and in 36, one had Crohn’s disease and the other ulcerative colitis. The median age of parents at diagnosis was 17.5 years older, 16 years older, and 18 years older in the Crohn’s disease, ulcerative colitis, and mixed disease families respectively (pCONCLUSIONSThere was no evidence of genetic anticipation or genomic imprinting of age at diagnosis in this sample of IBD families. Ascertainment bias is responsible for the age differences at diagnosis between affected parents and children.

BACKGROUND & AIMS: Some families have multiple members with inflammatory bowel disease (IBD). Do clinical features of familial differ from sporadic cases? Is there concordance between affected family members? Do environmental factors affect familial clustering? METHODS: In 67 families, each with three or more first-degree relatives with IBD, the 213 affected family members were interviewed, and their case records were reviewed. RESULTS: The clinical manifestations of familial cases did not differ from IBD reported in a large series. There was concordance for type of disease (P

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that regulates lipid metabolism and inflammatory responses. Certain PPARgamma ligands improve nonalcoholic steatohepatitis (NASH). The role of PPARgamma itself in NASH remains poorly understood. The functional consequences of PPARgamma in the development of steatohepatitis through gene deficiency or gene overexpression of PPARgamma delivered by adenovirus (Ad-PPARgamma) were examined. Our results show that PPARgamma-deficient (PPARgamma(+/-)) mice fed the methionine- and choline-deficient (MCD) diet developed more severe steatohepatitis than wild-type mice, and were unaffected by PPARgamma ligand rosiglitazone. Overexpression of PPARgamma delivered by Ad-PPARgamma attenuated steatohepatitis. This effect was associated with redistribution of fatty acid from liver to adipose tissue by enhancing expression of fatty acid uptake genes (fatty acid binding protein-4 (aP2), fatty acid translocase (CD36), lipoprotein lipase (LPL) and fatty acid transport protein-1 (FATP-1)) and lipogenic genes (sterol regulatory element binding protein isoform-1 (SREBP-1) and stearoyl-CoA desaturase isoform-1 (SCD-1)) in adipose tissue and to a lesser extent in liver. The anti-steatohepatitis action of PPARgamma was also mediated via regulating adipokines through suppressing tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and inducing adiponectin. Moreover, PPARgamma activation suppressed hepatic lipoperoxide and reduced hepatic pro-inflammatory cytokines (TNF-alpha and IL-6) production. In conclusion, PPARgamma is an important endogenous regulator and potential therapeutic target for nutritional steatohepatitis.

Hepatitis B viral (HBV) infection in early childhood is one of the leading causes of chronic hepatitis and liver cirrhosis that eventually lead to hepatic carcinoma. Despite the nationwide immunization programs to curtail the vertical transmission of HBV, childhood HBV infection through mothers is still occurring in Korea. As one of the efforts to understand the childhood HBV infection in Korea, four HBV promoter sequences in the sera of the chronically infected children were analyzed. Children harbored diverse viral variants as most of the chronically infected adult patients, but the deletion mutations were rare. The dominant viral sequences in the children were highly similar to the ones in the respective mothers, indicating that the maternal viruses were most likely transmitted to the children. The mutations in X, S1, S2/S promoters did not seem to show any correlation to the severity of the disease nor ages of the children. The mutations that showed some correlation to the severity of the disease were the mutations in C promoter, but the mutations did not seem to be vertically transmitted. Finally, the children with the elevated ALT/AST levels tended to have more child-specific variants suggesting that the accumulation of host-specific mutations might be associated with the development of clinical symptoms.

A neonate with extensive stage III mesoblastic nephroma was confirmed at operation to have a tumor that was too infiltrative and too advanced for primary excision. The abdomen was closed after multiple biopsies. Vincristine (1.1 mg/m2) was given intravenously once a week for a total of eight doses. Repeat CT scan confirmed shrinkage of the tumor and a nephrectomy could be performed safely and the tumor removed at the second laparotomy. CT scan repeated 1 year later showed no recurrence. This case illustrates the effective use of a single drug pre-excision chemotherapy which allowed a nephrectomy for extensive stage III mesoblastic nephroma to be carried out safely. © 1995 Wi1ey-Liss Inc.

Successful hematopoietic cell transplantation in a child with sickle cell disease and systemic lupus erythematosus

BackgroundInvestigation of anti-colon antibodies may be simplified if a sensitive method and homogeneous source of antigen were available.AimsTo examine the anti-colon antibody response using human colonic carcinoma cell lines as antigen.SubjectsPatients with inflammatory bowel disease and other gastrointestinal disorders and healthy controls were studied.MethodsComparative enzyme linked immunosorbent assays (ELISAs) were performed to assess the value of whole Caco-2, HT-29, and LS-180 cells as antigen. The antigenic determinants of the immune response were characterised by western blot analysis.ResultsSera demonstrated immunoreactivity against each of the cell lines, but different epitopes were recognised. Applying whole Caco-2 cells as antigen in an ELISA, the prevalence of anti-colon antibodies was significantly greater in patients with ulcerative colitis (36%) than Crohn’s disease (13%), other gastrointestinal disorders (13%) and healthy controls (0) (pConclusionsFixed whole cell ELISA is a simple and feasible method for studying the anti-colon antibody response. This response is non-specific, being directed against multiple antigens, and is likely to be an epiphenomenon of inflammatory bowel disease, more so for ulcerative colitis than Crohn’s disease.

Adult polycystic kidney disease (APKD) is a common genetic disease with a frequency of 1:1000. Evidence suggests that transforming growth factor alpha (TGF alpha) signaling may contribute to the hyperproliferation of the cystic epithelia in APKD. TGF alpha and epidermal growth factor (EGF) are well known mitogens expressed in the kidney and both exert their biological activities through binding to the same EGF receptor. A transgenic mouse that over-expressed TGF alpha developed renal cysts; raised levels of TGF alpha and EGF receptor mRNA were found in kidneys from two autosomal dominant APKD patients. To study the role of TGF alpha in cyst formation, we analyzed nine anatomically diagnosed adult polycystic kidneys and four normal kidneys using immunohistochemistry. We also traced the possible origins of the cysts by staining with the proximal convoluted tubule (PCT) marker, gp330, and the distal convoluted tubule (DCT) and collecting tubule (CT) marker, peanut agglutinin (PNA). In normal kidneys, TGF alpha protein was concentrated in the DCT and CT and EGF receptor protein in all three tubule types. In the early cysts of APKD, the cystic epithelia showed strong positive staining with TGF alpha, EGF receptor and gp330 but negative with PNA. Strong TGF alpha and EGF receptor staining was also found in the mixture of advanced cysts in the end-stage cystic kidneys although the cysts are likely to be derived from different segment of the renal tubules. This increased TGF alpha and EGF receptor expression in all cases and all types of cysts suggests that autocrine/paracrine stimulation by TGF alpha may be a common mechanism in cyst development in APKD.

Case report description: A 75-year-old man presented to our department with incidental finding of pericardial effusion. He suffered from general malaise and body weight loss in recent 3 months. He had chronic hepatitis B and an abdominal computed tomography (CT) disclosed a new soft tissue nodule 1.7x1.3 cm in size over the S7 of liver and pericardial effusion. A transthoracic echocardiography showed a cyst-like lesion about 2.6x2.9 cm over right atrioventricular (AV) groove and moderate pericardial effusion. (Panel A and B) The patient received subsegmentectomy of liver and the pathology was compatible with hepatocellular carcinoma. A follow-up echocardiography showed progression of the lesion one month later. A cardiac CT disclosed a soft tissue mass spreading along the right AV groove and encasing the right coronary artery (RCA). (Panel D) A positron emission tomography (PET) scan disclosed increase of radiolabeled 18F-2-fluoro-deoxy-D-glucose uptake along the right AV groove. (Panel C) Hence, video-assisted thoracoscopic biopsy was done and the pathology findings were compatible with diffuse large B cell lymphoma. (Panel D and E) The patient was diagnosed as primary cardiac lymphoma (PCL) and received chemotherapy. A follow-up echocardiography showed markedly decrease of the tumor size 3 months after chemotherapy. (Panel G and H) Conclusion: Our case presented as hepatic nodule and cystic lesion encasing RCA with pericardial effusion, and finally diagnosed as double cancers, namely hepatocellular carcinoma and PCL. This case reminds us that an aggressive work-up can help a patient with unexplained intra-cardiac mass and pericardial effusion. ![Figure][1] Figure 1 [1]: pending:yes

BACKGROUND: Some metallic compounds, especially of zirconium, can cause cell mediated granulomatous inflammation of the skin. Pigment granules containing compounds of aluminium, silicon, and titanium have been observed within macrophages in the wall of the small intestine in health and in Crohn9s disease. Zirconium compounds can be ingested in toothpaste. AIM: To determine in a pilot study if granulomatous sensitivity can be detected to compounds of these metals or silicon after injection into the skin of patients with Crohn9s disease. SUBJECTS: Eight patients with Crohn9s disease known to have had granulomata in the intestine and not currently treated with corticosteroids, and two healthy controls. METHOD: Two intradermal injections each of 0.1 ml of a 0.02% suspension of one of the compounds made in the abdominal wall of each subject. The site was marked and full thickness skin biopsy performed six weeks later. RESULT: A foreign body granuloma was observed on histological examination of two biopsy specimens but no evidence of a cell mediated response in any subject. CONCLUSION: No support was found for the hypothesis that Crohn9s disease is due to a specific sensitivity to ingested metallic or silicon compounds.

The pathogenic changes of inflammatory bowel disease (IBD) depend on migration of circulating leucocytes into intestinal tissues. Although leucocyte rolling and tenuous adhesion are probably regulated by inducible selectins on vascular endothelia, little is known about the expression of these molecules in Crohn's disease and ulcerative colitis. Using immunohistochemistry on surgically resected specimens, this study investigated endothelial P-selectin (CD62, granular membrane protein-140) in frozen sections of histologically uninvolved tissues adjacent to inflammation (Crohn's disease = 10; ulcerative colitis = 10), from highly inflamed areas (Crohn's disease = 20; ulcerative colitis = 13), and from normal bowel (n = 20). By light microscopy, two forms of P-selectin immunoreactivity were detected that apparently corresponded ultrastructurally to stored and released distributions. Compared with the normal gut, there was a 3.7-fold increase of P-selectin immunoreactivity on veins (p < 0.0001), venules (p < 0.0001), and capillaries (p < 0.05) in the highly inflamed gut, without differences between Crohn's disease and ulcerative colitis. In the uninvolved gut, P-selectin expression was similar to that seen in normal controls, except for a focal increase of P-selectin in the vicinity of small lymphocyte aggregates. The dramatic upregulation of P-selectin in the inflamed tissue and its potential role in leucocyte trafficking support the concept of P-selectin blocking therapy for the control of active IBD.

An outbreak of Pneumocystis carinii pneumonia (PCP) in three patients within a 6 week period was reported. Two patients had acute lymphoblastic leukaemia and one had brain-stem glioma. They shared common features of immuno-suppression and absence of cotrimoxazole prophylaxis and had been nursed in the same room. The severity of PCP and its response to treatment may be related to the degree of immunosuppression. Because of the morbidity and mortality of PCP, chemoprophylaxis should be given to all at-risk cases. Furthermore, isolation of patients with PCP should be considered in view of increasing evidence of nosocomial transmission.

We report a Chinese girl with Epstein-Barr virus (EBV) associated aplastic anaemia and hepatitis. Epstein-Barr virus genome was demonstrated in her bone marrow cells and EBV-specific serology suggested reactivation of EBV infection. She was initially treated with anti-thymocyte globulin (ATG) and methylprednisolone but with no haematologic response, and liver function continued to deteriorate. She was then treated with acyclovir. Her aplastic anaemia improved and hepatitis resolved, and there was eradication of EBV genome from her bone marrow cells.

L-Asparaginase-induced pancreatitis is an uncommon but potentially lethal complication. An 8-year-old girl with acute lymphoblastic leukaemia developed acute pancreatitis following treatment with asparaginase. Clinical and laboratory improvements were evident after treatment with somatostatin, with no complications of pancreatitis. Induction therapy for the leukaemia was able to be continued and complete remission was documented during the course of pancreatitis and somatostatin treatment, suggesting a beneficial role of somatostatin in the management of asparaginase-induced pancreatitis. © 1994 Wiley-Liss, inc.

SUMMARY Adhesion of circulating cells to vascular endothelium occurs in the early phase orinfiammation, and is mediated by specific cell adhesion molecules. Many such adhesion molecules are increased in inflamed regions of ulcerative colitis (UC) and Crohn's disease (CD) but there is limited knowledge of their expression in the uninvolved gut, adjacent to inflammation. We investigated immunohisto-chemically the expression of platelet endoihelial cell adhesion moleculc-1 (PECAM-1), intercellular adhesion molecule-l (ICAM-l)and lymphocyte function-associated antigen-1 (LFA-1.) on resected specimens taken at a distance of 2-4 cm from the inflamed area and without histological signs of inflammation. Compared with normal gut. we found (i) a significant increase of PECAM-1-positive vessels in the mucosa of uninvolved UC (149.0 ± 24.1 vesscls/mm2 (mean ± s.d.); normal colon = 123.1 ± 21.6; P= 0.004); (ii)a significant decrease of ICAM-1-positive vessels in uninvolved CD (111.9 ± 22.6 vessels/mm2 normal ileum = 136.9 ± 27.6; P=0.04); and (iii) a moderate but statistically insignificant increase of LFA-1 -positive cells in the mucosa of uninvolved UC and Crohn's ileitis. This altered expression of cell adhesion molecules may contribute to the early lesion in inflammatory bowel disease and provide new therapeutic opportunities.

Ethanol and xylene vapours were found to interfere with the determination of formaldehyde vapour by the chromotropic acid method, whether water or a mixture of chromotropic and sulphuric acids were used as the scrubbing solution. The interference can be removed by a porous polymer sorbent, Tenax GC. Thus, with a Tenax GC pre-trap, the chromotropic acid method can be applied to the determination of formaldehyde vapour in clinical laboratories where alcohol and xylene vapours are often encountered. The advantages of selecting chromotropic-sulphuric acid instead of water as the scrubbing solution are discussed.