Comparing performance of Chromameter®, Mexameter® and full-field laser perfusion imaging for measurement of ultraviolet B light-induced erythema.

Erythema induced by ultraviolet (UV)B light is a common skin reaction. Currently, three techniques, the Chromameter(®) CR-400, the Mexameter(®) MX16 and full-field laser perfusion imaging (FLPI), are widely used for dermatological evaluation of UVB-induced erythema. However, there is little known about the comparative performance of these three techniques. This study was therefore designed to evaluate the effectiveness of the three techniques. Our findings showed that the performance of Chromameter and Mexameter for measurement of UVB-induced erythema was very similar, while FLPI indicated acute erythema at D1 with the greatest fold change. Further studies of UVB dose-dependence need to be carried out.

Adjuvant hepatic intra-arterial iodine-131-lipiodol following curative resection of hepatocellular carcinoma: a prospective randomized trial.

BACKGROUND: The purpose of the present study was to determine whether intrahepatic injection of (131)I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC). METHODS: From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4-6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan-Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong. RESULTS: The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46-1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51-1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by (131)I-lipiodol and hepatic artery dissection during angiography. CONCLUSIONS: The randomized trial provides insufficient evidence to recommend the routine use of (131)I-lipiodol in these patients.

Distribution of killer-cell immunoglobulin-like receptor genes in Eastern mainland Chinese Han and Taiwanese Han populations.

The interaction between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) molecules expressed on target cells is known to modulate the cytolytic activity of natural killer (NK) cells. To date, a wide range of KIR genotypes has been observed, which varies among different ethnic populations. We report here comparison of the KIR gene content and genotypic structure of KIRs in 106 individuals from Eastern mainland Chinese Han and 97 from Taiwanese Han. All 17 KIR genes were observed in the two populations. Framework genes 2DL4, 3DL2, 3DL3 and 3DP1 were present in all individuals. The two populations had very similar frequencies in most loci, however, significant differences were noted in the frequencies of KIR3DS1 and KIR2DS4D (KIR2DS4 deletant variant). A total of 35 and 29 genotypes were identified in the individuals from the Eastern mainland Chinese and the Taiwanese Hans, respectively. Some pairs of KIRs showed significant positive and negative linkage disequilibrium (LD). Our data showed that there were minor distinctions in KIR gene frequencies, genotypes and LD between the two populations, which shed light on a possible geographic genetic demarcation among different Chinese communities.

Next generation physiologically based kinetic (NG-PBK) models in support of regulatory decision making.

The fields of toxicology and chemical risk assessment seek to reduce, and eventually replace, the use of animals for the prediction of toxicity in humans. In this context, physiologically based kinetic (PBK) modelling based on in vitro and in silico kinetic data has the potential to a play significant role in reducing animal testing, by providing a methodology capable of incorporating in vitro human data to facilitate the development of in vitro to in vivo extrapolation of hazard information. In the present article, we discuss the challenges in: 1) applying PBK modelling to support regulatory decision making under the toxicology and risk-assessment paradigm shift towards animal replacement; 2) constructing PBK models without in vivo animal kinetic data, while relying solely on in vitro or in silico methods for model parameterization; and 3) assessing the validity and credibility of PBK models built largely using non-animal data. The strengths, uncertainties, and limitations of PBK models developed using in vitro or in silico data are discussed in an effort to establish a higher degree of confidence in the application of such models in a regulatory context. The article summarises the outcome of an expert workshop hosted by the European Commission Joint Research Centre (EC-JRC) - European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), on "Physiologically-Based Kinetic modelling in risk assessment - reaching a whole new level in regulatory decision-making" held in Ispra, Italy, in November 2016, along with results from an international survey conducted in 2017 and recently reported activities occurring within the PBK modelling field. The discussions presented herein highlight the potential applications of next generation (NG)-PBK modelling, based on new data streams.

[The effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation in acute leukemia].

Objective: To study the effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia (AL) and its significance as molecular marker to dynamically monitor minimal residual disease (MRD) . Methods: Retrospectively analyzed those AL patients who underwent allo-HSCT in the First Hospital Affiliated to Zhejiang University School of Medicine during Jan 2016 to Dec 2017, a total number of 314 cases, 163 males and 151 females, median age was 30 (9-64) years old. Comparing the difference of WT1 expression at diagnosed, pre-HSCT and after HSCT. Using the receiver operating characteristic (ROC) curve to determine the WT1 threshold at different time so as to predict relapse. The threshold of WT1 expression before transplantation was 1.010%, within 3 months after HSCT was 0.079% and 6 months after HSCT was 0.375%. According to these thresholds, WT1 positive patients were divided into low expression groups and high expression groups. Analyzed the relationship between overall survival (OS) , disease-free survival (DFS) , cumulative incidence of relapse (CIR) and WT1 expression. Results: The OS and DFS of high expression group pre-HSCT were lower than low expression group [69.2% (9/13) vs 89.1% (57/64) , χ(2)=4.086, P=0.043; 53.8% (7/13) vs 87.5% (56/64) , χ(2)=9.766, P=0.002], CIR was higher than low expression group [30.8% (4/13) vs 7.8% (5/64) , P=0.017]. There was no significant difference of OS and DFS between high expression and low expression group of 3 months after HSCT (P=0.558, P=0.269) . The OS and DFS of high expression group of 6 months after transplantation were both lower than low expression group (P=0.049, P=0.035) . Multivariate analysis showed that WT1>0.375% when 6 months after transplantation was the only independent prognostic factor for shorter DFS (P=0.022) . There was no statistically significant difference in CIR between the high-expression group and the low-expression group 3 months after transplantation and 6 months after transplantation (P=0.114, P=0.306) . Conclusion: High expression of WT1 before and after HSCT was an adverse prognosis factor. It is of clinical practical value to use WT1 as a transplant recommendation index for patients with acute leukemia and as a marker to monitor MRD dynamically.

Isolated haploinsufficiency of exon 1 of the SHOX gene in a patient with idiopathic short stature.

This paper reports the case of a 16-year-old woman with idiopathic short stature (ISS) who was detected to be haploinsufficient in only exon 1 of the short stature homeobox-containing (SHOX) gene by RQ-PCR and had two copies of the other six exons intact. The translation of the SHOX protein and of the SHOX promoter may be potentially affected if the deletion of exon 1 is extended further upstream. Further studies may help in determining the significance of partial exonic deletions of the SHOX gene in relation to ISS.

An audit of fusion CT-PET in the management of colorectal liver metastases.

AIM: To assess the use of positron emission tomography combined with computerized tomography (CT-PET) with fluoro-18-2-deoxy-d-glucose ((18)F-FDG) to identify hyper-metabolic tumours, especially colorectal metastases (CRM). METHODS: Patient particulars, diagnoses and clinical outcome for each patient were studied. Twenty-three patients underwent CT-PET, 10 males and 13 females, median age 59 (range 34-72). Fourteen patients presented with primary liver CRM and nine had undergone previous liver resections. Indications for CT-PET included; suspected extrahepatic disease in 13/23 patients, possible hepatic recurrence 5/23 and clinical suspicion in 8/23 patients. RESULTS: Seven patients had a major impact on their management. Unexpected (not seen on CT) findings in the CRM group included, 7/23 (30%) patients with extrahepatic disease, 3/23 with hepatic metastases, 8/23 suspected of having liver or distant metastases on CT had a negative study. A clinical decision, based on the CT-PET report, could be undertaken in 21/23 patients. CONCLUSION: CT-PET is useful in patients with CRM where conventional imaging presents dilemmas such as: assessment of suspected extrahepatic disease, recurrence in liver, patients with advanced or perforated initial tumours.

Clinico-pathological features of cystic pancreatic endocrine neoplasms and a comparison with their solid counterparts.

AIM: Pancreatic endocrine neoplasms (PENs) may occasionally manifest as cystic lesions of the pancreas. The aim of this study is to report our experience with cystic PENs and to compare their clinico-pathological features with their solid counterparts. MATERIALS AND METHODS: From 1990 to 2004, 38 patients with PENs were reviewed. Six of these tumours appeared on radiological imaging as a cystic lesion of the pancreas. RESULTS: Of the 38 patients with a PEN, 21 of the patients were female and with a median age of 54.5 (range, 33-83) years. Sixteen patients had functional endocrine tumours of which insulinoma was the most common. The six patients with cystic PEN had a median age of 55.5 (range, 41-70) years and half were female. Cystic PENs were significantly larger [48 (range, 25-170) mm vs 19 (range, 3-120) mm, P = 0.013] and were less likely to be benign (0 vs 50%, P = 0.017) compared to their solid counterparts. There was no difference between cystic and solid PENs in terms of age, sex, presence of symptoms, proportion of functioning tumours and location of tumours within the pancreas. CONCLUSION: Cystic PENs share many clinico-pathological features with solid PENs. These differ only in the cystic appearance and tend to be of a larger size. Hence, these findings suggest that cystic and solid PENs are unlikely to be distinct pathological entities but are likely to be morphological variants of the same entity.

Crohn's disease in adults: observations in a multiracial Asian population.

AIM: To determine the demography and clinical presentation of CD and secondly to determine any differences in the prevalence between the different ethnic groups in a multiracial Asian population. METHODS: Patients with CD who were seen in 2001-2003 in the University of Malaya Medical Centre (UMMC) were enrolled in this study. Prevalence of disease was calculated for the group as a whole and by race with hospital admissions per ethnic group as the denominator. RESULTS: Thirty-four patients were diagnosed to have CD. Basic demographic data of patients; male:female 17:17; mean age 29.1 years (+/-13.5 years); ethnic group: Malays 5 (14.7%), Chinese 12 (35.3%) and Indians 17 (50%).Twenty-six (76.5%) were diagnosed under the age of 40 and 8 (23.5%) were diagnosed over the age of 40. Location of the disease was as follows:ileocolonic 13 (38.2%), terminal ileum only 9 (26.5%), colon only 8 (23.5%), and upper gastrointestinal 4 (11.8%). Sixteen (47.1%) had penetrating disease, 9 (26.5%) had stricturing disease and 9 (26.5%) had non-penetrating and non-stricturing disease. The hospital admission prevalence of CD was 26.0 overall, Indians 52.6, Chinese 6.9, and Malays 9.3 per 10(5) admissions per ethnic group. The difference between Indians and Malays: [OR 5.67 (1.97, 17.53) P<0.001] was statistically significant but not between the Indians and the Chinese [OR 1.95 (0.89, 4.35) P=0.700]. The difference between the Chinese and the Malays was also not statistically significant. [OR 2.90 (0.95, 9.42) P=0.063]. CONCLUSION: The clinical presentation of CD is similar to the Western experience. Although the overall prevalence is low,there appears to be a clear racial predominance among the Indians.

Cystic neoplasms of the pancreas with mucin-production.

AIM: To compare the clinico-pathological features of intraductal papillary mucinous cystic tumours (IPMT) and mucinous cystic tumours (MCT) of the pancreas. METHODS: Eighteen patients with IPMT and 18 with MCT who underwent surgical resection between 1990 and 2004 were retrospectively reviewed. Their clinico-pathological features were compared using univariate analysis. Statistical analyses of potential predictive factors of malignancy for each of these two groups were also conducted. RESULTS: Patients with IPMT were found to be older (64+/-10 vs 43+/-18 years, p<0.001) and were predominantly male (male:female ratio, 5:4 vs 1:17, p=0.003) as compared to patients with MCT. MCTs were found in the body-tail region (100%) whereas IPMTs were more evenly distributed (50% in the head) (p=0.001). Pathologically, IPMT was distinct from MCT in terms of size (3.8+/-3.2 vs 9.1+/-4.4 cm, p=0.001), association with secondary pancreatitis (50 vs 0%, p=0.011), communication with the pancreatic duct (94 vs 0%, p<0.001), presence of a dilated main pancreatic duct (61 vs 0%, p<0.001) and the presence of ovarian-type stroma (0 vs 44%, p=0.003). CONCLUSION: IPMT and MCT are distinct clinico-pathological entities. This distinction is important as management and outcome of these entities may differ.

Atypical presentations of emphysematous cystitis.

Emphysematous cystitis is an uncommon infection of the bladder with the formation of carbon dioxide either within the bladder or within its wall. It is commonly seen in women and those with poorly controlled diabetes mellitus, in association with some form of urinary stasis and obstruction. The clinical features are very varied and the outcome is often unpredictable. Radiography may reveal a radiolucent line around the bladder wall or gas within the bladder. Occasionally, computed tomography scans are required to help in the diagnosis due to their atypical presentation with acute abdominal pain. Herein, we report three patients with such a condition who were treated with favourable outcomes. Of the three patients, two had to undergo exploratory laparotomy due to their initial presentations with acute abdomens.

Clinical mimicry of hepatocellular carcinoma: imaging-pathological correlation.

This pictorial essay aims to show the clinical mimicry of hepatocellular carcinoma (HCC) and its diagnostic difficulty, and to create awareness among clinicians and radiologists of potential diagnostic pitfalls. A selected consecutive series of hepatectomies with proven HCC over a three-year period, identifying clinical presentation, blood results and imaging of patients with difficult preoperative diagnosis, was reviewed. The imaging of the focal liver lesions is presented pictorially with pathological correlation. Six patients out of 34 cases of resected HCC were diagnosed to have benign (three liver abscesses) and neoplastic (one Klatskin tumour, one colorectal liver metastasis, one gallbladder cancer) conditions. Compared to the rest in the series, all six patients had normal serum alpha fetoprotein levels. On computed tomography, the mosaic appearance of HCC mimicked locules of liver abscess while HCC with pseudocapsule (rim enhancement) was misdiagnosed as unilocular abscess or metastatic lesion. Arterial enhancement on contrast-enhanced triphasic computed tomography was useful in diagnosis of HCC. In summary, HCC can mimic benign and neoplastic clinical syndromes. The diagnosis of liver abscess can delay subsequent diagnosis of HCC and potentially complicate the treatment plan. Contrast-enhanced triphasic computed tomography or magnetic resonance imaging is useful to resolve difficult diagnosis, especially when the serum alpha fetoprotein level is not raised.

Intrinsic functional plasticity of the sensory-motor network in patients with cervical spondylotic myelopathy.

Several neuroimaging studies have suggested brain reorganisation in patients with cervical spondylotic myelopathy (CSM); however, the changes in spontaneous neuronal activity that are associated with connectedness remain largely unknown. In this study, functional connectivity strength (FCS), a data-driven degree centrality method based on a theoretical approach, was applied for the first time to investigate changes in the sensory-motor network (SMN) at the voxel level. Comparatively, CSM not only showed significantly decreased FCS in the operculum-integrated regions, which exhibited reduced resting-state functional connectivity (rsFC) around the Rolandic sulcus, but it also showed increased FCS in the premotor, primary somatosensory, and parietal-integrated areas, which primarily showed an enhanced rsFC pattern. Correlation analysis showed that altered FCS (in the left premotor-ventral/precentral-operculum, right operculum-parietale 4, and right S1) was associated with worsening Japanese Orthopaedic Association scores and that the rsFC pattern was influenced by cervical cord micro-structural damage at the C2 level. Together, these findings suggest that during myelopathy, the intrinsic functional plasticity of the SMN responds to the insufficient sensory and motor experience in CSM patients. This knowledge may improve our understanding of the comprehensive functional defects found in CSM patients and may inspire the development of new therapeutic strategies in the future.

Autosomal dominant hypocalcemia: a novel activating mutation (E604K) in the cysteine-rich domain of the calcium-sensing receptor.

We report a novel activating mutation (E604K) of the calcium-sensing receptor in a family with autosomal dominant hypocalcemia. Whereas all affected individuals exhibited marked hypocalcemia, some cases with untreated hypocalcemia exhibited seizures in infancy, whereas others were largely asymptomatic from birth into adulthood. The missense mutation E604K (G2182A; GenBank accession no. U20759), which affects an amino acid residue in the C terminus of the cysteine-rich domain of the extracellular head, cosegregated with hypocalcemia in all seven individuals for whom DNA was available. Two unaffected, normocalcemic members of the family did not exhibit the mutation. The molecular impact of the mutation on two key components of the signaling response was assessed in HEK-293 cells transiently transfected with cDNA corresponding to either the wild-type calcium-sensing receptor or the E604K mutation derived by site-directed mutagenesis. There was a significant leftward shift in the concentration response curves for the effects of extracellular Ca(2+) on both intracellular Ca(2+) mobilization (determined by aequorin luminescence) and MAPK activity (determined by luciferase expression). The C terminus of the cysteine-rich domain of the extracellular head may normally act to suppress receptor activity in the presence of low extracellular Ca(2+) concentrations.

Management of inpatients exposed to an outbreak of severe acute respiratory syndrome (SARS).

This is a prospective observational study of a cohort of inpatients exposed to a severe acute respiratory syndrome (SARS) outbreak. Strict infection control policies were instituted. The 70 patients exposed to the SARS outbreak were isolated from the rest of the hospital. They were triaged, quarantined and cohorted in three open plan wards. Selective isolation was carried out immediately when symptoms and signs suspicious of SARS manifested clinically. The patients' ages ranged from 21 to 90 years and 56% had surgery before the quarantine. Sixteen patients with unexplained fever during the period of quarantine were isolated, seven of whom were eventually diagnosed with probable SARS. The crude incidence of SARS in our cohort was 10%. The SARS case fatality was 14%. No secondary transmission of the SARS virus within the cohort was observed. Strict infection control, together with appropriate triaging, cohorting and selective isolation, is an effective and practical model of intervention in cohorts exposed to a SARS outbreak. Such a management strategy eases the logistic constraints imposed by demands for large numbers of isolation facilities in the face of a massive outbreak.

Breast abscess as the initial presentation of squamous cell carcinoma of the breast.

Breast abscesses are common and rarely harbour an underlying malignancy. Antibiotics and drainage by aspiration are the mainstays of treatment. We encountered two post-menopausal patients aged 48 and 70 who presented with acute breast abscesses that had an underlying squamous cell carcinoma of the breast. Infective aetiology was considered in each case and pre-operative diagnosis is possible but requires a high level of suspicion to avoid a delay in diagnosis. Aspirate from the abscess should be sent for both culture and cytology and if drainage is done, then biopsy of the abscess cavity is essential. Clinicians should be aware of the association of this rare primary neoplasm of the breast.

Pyogenic liver abscess complicated by endogenous endophthalmitis.

BACKGROUND: Endogenous endophthalmitis is an inflammation of ocular tissues that can lead to deterioration of and loss of vision. Rarely, this can complicate the course of a patient with pyogenic liver abscess. METHODS: Over an 18-month period, 68 patients were treated for pyogenic liver abscesses. Three patients, all of whom were male and with diabetes, were diagnosed with a Klebsiella pneumoniae liver abscess complicated by endogenous endophthalmitis. Open surgical or percutaneous drainage of the liver abscess was undertaken and the symptomology and outcome of the endophthalmitis reviewed. RESULTS: There was no mortality in our series. Two patients presented with simultaneous abdominal and ocular symptoms and one patient had ocular symptoms 3 days after surgical drainage of the liver abscess. Despite aggressive treatment, all patients had permanent deterioration of visual function with one patient becoming blind and requiring evisceration of the infected eye. CONCLUSION: Ocular symptoms in patients treated for pyogenic abscesses must be dealt with urgently with an ophthalmologic consultation. Increased awareness of this complication and a high index of suspicion are paramount for salvage of visual function.

Does laparoscopic fenestration provide long-term alleviation for symptomatic cystic disease of the liver?

BACKGROUND: The use of laparoscopic technique for management of symptomatic liver cysts is documented to be a feasible and safe procedure with good short-term symptomatic relief. However, it cannot be recommended as the standard of care as long-term results are scarce. The present study was initiated to review the long-term results of this approach in the management of symptomatic liver cysts. METHODS: A retrospective review of all patients with symptomatic liver cysts that were treated by laparoscopic fenestration in our department over an 8-year period from 1993 to 2001. The clinical and radiographical data were analysed at follow-up to assess the -outcome. RESULTS: Eleven patients were treated using a laparoscopic approach; 10 patients with solitary cysts and one with adult polycystic liver disease. All patients achieved short-term alleviation of symptoms and an uneventful postoperative course. The mean hospital stay was 3 days. Long-term follow up was available for 9 patients with a mean of 44 months. Histologically, one of the patients was diagnosed with a biliary cystadenoma and she had a symptomatic recurrence and a liver resection at 20 months. In the other seven patients, there was no clinical recurrence but a radiographical recurrence of 28.5%. The patient with adult polycystic liver disease had two symptomatic recurrences: at 26 months where he underwent a repeat laparoscopic fenestration and at 43 months where he underwent an open fenestration. CONCLUSION: The present study confirms that with adequate patients election, long-term alleviation of symptoms can be achieved with the laparoscopic approach for solitary simple liver cysts but not for polycystic liver disease or cystic tumours of the liver.