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Background Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients. Methods The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signalling pathways were investigated in vitro. Results The patients were well‐controlled, and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL‐5, IL‐13 and IL‐9 in response to IL‐25, IL‐33 plus IL‐2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL‐5, IL‐13 and IL‐9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signalling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment. Conclusion The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK‐STAT signalling pathways. This provides a new understanding of glucocorticoid application in regard to allergic diseases.

Recent advances in technology have enabled the development of various non-invasive skin imaging tools to aid real-time diagnosis of both benign and malignant skin tumours, minimizing the need for invasive skin biopsy. Multispectral optoacoustic tomography (MSOT) is a recently developed non-invasive imaging tool, which offers the unique capacity for high resolution three dimensional (3D) optical mapping of tissue by further delivering highly specific optical contrast from a depth of several millimetres to centimetres in living tissues. MSOT enables volumetric, spectroscopic differentiation of tissue, both in vivo and in real time, with and without the application of biomarker-specific probes, and is further able of providing spatial maps of skin chromophores, as well as underlying blood vasculature.Three patients with suspicious skin tumours consented to have their lesions imaged with MSOT prior to excision. The histological findings and measurements were compared.We demonstrated the first in vivo clinical use of MSOT for 3D reconstruction of skin tumours in three patients with good histological correlation.Our findings confirm the potential benefit of the new imaging method in guiding surgical intervention to achieve a more precise excision with better clearance and lower relapse rates. It can also potentially help to shorten the duration of Mohs' micrographic surgery. Further large-scale studies are necessary to ensure correlation between MSOT and histology.

Introduction of hydrophilic components, particularly amines and zwitterions, onto a degradable polymer platform, while maintaining precise control over the polymer composition, has been a challenge. Recognizing the importance of these hydrophilic residues in multiple aspects of the nanobiomedicine field, herein, a straightforward synthetic route to access well-defined amphiphilic and hydrophilic degradable block copolymers from diethanolamine-derived functional eight-membered N-substituted aliphatic cyclic carbonates is reported. By this route, tertiary amine, secondary amine, and zwitterion residues can be incorporated across the polymer backbone. Demonstration of pH-responsiveness of these hydrophilic residues and their utility in the development of drug-delivery vehicles, catered for the specific requirements of respective model drugs (doxorubicin and diclofenac sodium salt) are shown. As hydrophilic components in degradable polymers play crucial roles in the biological interactions, these materials offers opportunities to expand the scope and applicability of aliphatic cyclic carbonates. Our approach to these functional polycarbonates will expand the range of biocompatible and biodegradable synthetic materials available for nanobiomedicine, including drug and gene delivery, antimicrobials, and hydrophilic polymers as poly(ethylene glycol) (PEG) alternatives.

Summary The use of topical antiseptics in the treatment of atopic dermatitis (AD) has previously been explored. However, no triclosan-containing leave-on emollient has been evaluated previously, to our knowledge. The aims of this study were to assess the safety and efficacy of an emollient containing triclosan compared with the emollient alone (vehicle) for the treatment of AD. Eligible patients with mild to moderate AD were randomized to receive either the study cream or vehicle. All patients also received a low-potency corticosteroid cream to use during the treatment phase of the study if necessary. Patients were assessed for severity according to the SCORing Atopic Dermatitis (SCORAD) Index, amount of corticosteroid used, patient assessment of cream, and adverse events (AEs). In total, 60 patients received either the study cream or vehicle, and an intention-to-treat analysis was performed. At day 14, there was a significant decrease in SCORAD from baseline for the study cream compared with vehicle (P < 0.05). At day 27, although there was an improved mean reduction from baseline, this was no longer significant (P > 0.05). Only four patients had mild treatment-related AEs. The mean total amount of topical steroid applied by the patients using the study was significantly lower than that used by controls (P = 0.40). Triclosan-containing leave-on emollient was safe and highly acceptable to patients. However, the overall benefit on day 27 was not significant. Nevertheless, the amount of topical steroid used by patients was significantly less with the study cream than with the vehicle, thus further studies are needed to confirm its steroid-sparing effect.

Early detection of retinopathy of prematurity (ROP) in premature and very-low-birth-weight infants is crucial. In this retrospective study, 581 infants either with a birth weight below 1500 g or a gestational age of less than 32 weeks, or who did not fit these criteria but were judged to be at increased risk, were screened for ROP. ROP developed in 159 (27.4%). The incidence of ROP appeared to be inversely proportional to birth weight and gestational age. Infants with a birth weight below 750 g had a significantly higher risk of developing stage 3 and 4 ROP. The mean age at detection was 7.6 ± 1.6 weeks. Nearly all of the ROP cases and all of the stage 3 and 4 cases were detected between the 5th and 10th week. Because screening should be focused on these visionthreatening stages, ophthalmic examinations should be concentrated in, but not limited to, the period between the 5th and the 10th postnatal week.

To evaluate the effectiveness of CT and MRI at 0.5 T in the diagnosis and staging of retinoblastoma, we studied 11 patients in whom retinoblastoma was clinically suspected. Nine of the eleven had surgically proven retinoblastoma; in the other two a diagnosis of Coats' disease was made. MRI was not as specific as CT for diagnosing retinoblastoma, due to its lack of sensitivity in detecting calcification; it did, however, have superior contrast resolution. On MRI, Coats' disease was reliably diagnosed and easily differentiated from retinoblastoma. Moreover, the greater ability of MRI to differentiate subretinal fluid from tumour also confers high accuracy in measuring tumour size. CT is still the study of choice in the diagnosis of retinoblastoma, but when MRI is available, it should be performed for better differentiation from lesions such as Coats' disease.

Dermatofibrosarcoma protuberans (DFSP) has conventionally been treated with wide local excision. More recently Mohs micrographic surgery (MMS) has been advocated.To assess our departmental experience with DFSP in the context of a literature review relating to DFSP treated with MMS.This was a case review of 35 patients with DFSP treated between 1998 and 2009 with MMS using paraffin-embedded sections.Seventeen patients required one horizontal layer to clear their tumour, 10 patients needed two and eight patients needed three layers or more. The median preoperative clinical size was 6 cm(2) (range 0·75-54·8) and the median postoperative wound size was 46·8 cm(2) (range 4-145·2). Tumour persistence has not been observed in any of our patients after a median follow-up duration of 29·5 months (range 6-146).We present 35 DFSP patients, none of whom showed persistent tumour after treatment with 'slow' MMS using paraffin sections. We advocate MMS as the treatment of choice for DFSP, especially for tumours over the head and neck region where tissue conservation is particularly important.

Scrotal pyoderma gangrenosum is uncommon. We present a 17-year-old Chinese male patient with newly diagnosed Crohn's disease presenting with scrotal pyoderma gangrenosum. Biopsy and other investigations were done to diagnose and look for associated diseases of pyoderma gangrenosum. Treatment with high-dose prednisolone failed. Subsequent treatment with oral cyclosporine was successful.

Clinical and microscopic pigmentation may affect the treatment outcomes in basal cell carcinoma. However, there have not been any in-depth histopathological comparisons between clinically pigmented and non-pigmented basal cell carcinomas with regards to microscopic melanization. The aims of our study were to determine the proportion of pigmented basal cell carcinomas presenting to the National Skin Centre in Singapore, to characterize the histological pattern of melanization and to perform a semi-quantitative analysis of the degree of microscopic melanization of the tumours. Patients with clinical features and histologically confirmed basal cell carcinomas were recruited. Demographic data and clinical characteristics were recorded and basal cell carcinoma sections were examined for histological subtype and pattern of melanization. Twenty-five Chinese patients with 30 basal cell carcinomas were recruited. Three of the five clinically non-pigmented and all of the clinically pigmented basal cell carcinomas had microscopic evidence of melanization. Microscopic melanization in clinically non-pigmented basal cell carcinomas was present only focally or in the centre of the tumour mass. Both groups of basal cell carcinomas may be colonized by melanocytes. Two morphological types of melanocytes, a dendritic and round cell type, were identified. Future research is required to evaluate if the degree of microscopic melanization influences the treatment outcome of basal cell carcinomas.

A 53-year-old woman presented with a chronic, non-healing painless ulcer over her right clavicular area of a two-month duration. Skin biopsy, microbiological and radiological investigations confirmed the diagnosis of scrofuloderma arising from an underlying tuberculous infection of her acromioclavicular joint. She was treated successfully with anti-tuberculosis therapy with complete healing of the ulcer. Awareness of this uncommon presentation of osteoarticular tuberculosis may assist in earlier diagnosis.

Mechanical ventilation (MV) during exacerbation of asthma or chronic obstructive pulmonary disease (COPD) is unequivocally needed when apnoea, cardiorespiratory arrest, coma, hypoxia or treatment failure is present. The need is less clear when the patient can respond, has intact airway reflexes and spontaneous respiration. In this situation, acidosis is an important factor in the decision to institute MV. This study aimed to provide a clinical means of identifying patients with acute respiratory acidosis (ARA) in a setting where blood gas analysis is unavailable. We undertook a prospective, observational study of consecutive patients who presented to two emergency departments with severe and life-threatening exacerbation of asthma or COPD. Each underwent clinical assessment, treatment and blood gas analysis. The outcome measure was ARA or mixed ARA and metabolic acidosis. A total of 127 episodes in patients aged 15-90 years (65.3% males and 34.7% females) were included in the study. Of these, 62.2% had asthma and 37.8% had COPD; 71.7% had life-threatening and 28.3% had severe attacks. Overall, the adjusted odds ratio (and 95% confidence intervals) for predictors of ARA were 7.09 (1.79-28.06) for drowsiness, 4.11 (1.31-12.88) for flushing, 3.34 (1.01-11.02) for having COPD and 2.86 (1.01-8.07) for intercostal retractions. In conclusion, with drowsiness, the likelihood of ARA is about seven times higher. The presence of flushing, COPD and intercostal retractions also increase the risk of ARA.

Acute pulmonary thromboembolism (PE) has been considered rare among Asians. We aim to describe the frequency and clinical features of this condition in a hospital in Singapore. Among patients admitted by the Emergency Department (ED), comparisons were made between those primarily diagnosed in the ED and those who were not.Retrospective review of all cases of radiologically proven acute PE over a 20-month period.Sixty-two patients were identified. The mean age was 61.5 +/- 18.0 years with a female to male ratio of 1.8:1. There were more Malays compared to other races. There were also more Caucasians, given the proximity of the hospital to the airport and the inclusion of tourists. The commonest symptoms were dyspnoea and chest pain, while the commonest signs were tachycardia and tachypnoea. Prolonged immobilisation was the commonest risk factor. Electrocardiographic S1Q3T3 pattern was seen in more patients compared to Western studies. Cardiomegaly was the commonest chest X-ray finding. Thirty-two patients were identified to have a source of embolisation. Overall mortality rate was 21%. The ED diagnosed 36% of the cases. Alternative admitting diagnoses were predominantly ischaemic heart disease and pneumonia. The group diagnosed in the ED were notably female (P = 0.044), Caucasian (P = 0.002) and had prolonged immobilisation (P = 0.025) prior to the onset of PE.Acute PE is not as rare here as previously thought. Clinical features reveal more similarities than differences compared to other studies in the literature. We advocate a high index of suspicion for earlier diagnosis in the ED.

We report two cases of acute toluene poisoning occurring during parquet flooring. Inhalation is the major route of absorption in the workplace, owing to the high volatility of the compound. Such patients should be monitored closely for respiratory distress, central nervous system (CNS) depression and cardiac arrhythmias. Both our patients manifested signs of CNS depression and one had bronchospasm aborted by salbutamol Industries using toluene must ensure that precautions like adequate ventilation are taken to protect their workers.

We studied the appearance of retinoblastoma on unenhanced and gadolinium-enhanced images and the accuracy of tumour staging with MR imaging. The MR images were obtained in 18 children with retinoblastoma and compared with histopathological findings after enucleation. The MR imaging included T1-weighted and dual-echo T2-weighted images before, and T1-weighted images after, gadopentetate dimeglumine injection. The contrast between tumour and ipsilateral vitreous strongly increased (57 %) after gadolinium on T1-weighted images (p = 0.004). Tumour was strongly hypointense as compared with ipsilateral vitreous in all patients using heavily T2-weighted (TE = 120 ms) images (p = 0.001). The estimated T2 of tumour (mean 96 + 14 ms) did not correlate with histological grading or degree of calcification. Unenhanced T1-weighted MR images rightfully excluded extrascleral growth in 16 of 16 cases, but its presence was confirmed after enucleation in only one of 2 abnormal MR scans. Invasion of the optic nerve behind the cribriform plate was confirmed in 2 of 3 abnormal gadolinium-enhanced MR scans, but also in 1 of the 15 cases in which MR images were normal. The T2-weighted images were useful in assessing retinal detachment. We conclude that heavily T2-weighted images, unenhanced T1-weighted images and gadolinium-enhanced T1-weighted MR images are complementary in characterizing and staging retinoblastoma.

The purpose of this retrospective study is to investigate the influence of 45 Gy megavoltage external beam radiotherapy on the occurrence of second primary tumours in hereditary- and non-hereditary retinoblastoma patients. Eighty-seven hereditary and 19 non-hereditary patients were irradiated for retinoblastoma. The follow-up of the hereditary patients ranged from 4-23 years (mean 12.4 years), of the non-hereditary patients from 6-23 years (mean 12 years). In the hereditary group 4 patients developed a second primary tumour (2 rhabdomyosarcoma, 1 osteosarcoma, 1 malignant histiocytoma), and 5 patients developed a pineoblastoma. Three second primary tumours were situated inside the radiation field. The latency period ranged from 1.5 to 18 years (mean 4.8 years). None of the non-hereditary patients developed a second primary tumour. The actuarially calculated probability of being free from second primary tumours was 96.9% at 10 years and 89.4% at 20 years (pineoblastoma excluded). The survival was 91.2% at 10 years and 84.2% at 20 years (pineoblastoma excluded). From this study it is suggested that external beam irradiation has a potentiating effect in patients, with the genetic predispopsition for retinoblastoma and who are more susceptible to second primary malignancies.

We report a case of an unusual giant congential tumor presenting in a newborn infant as a large exophytic mass emerging from the left orbit. After enucleation orbital recurrence developed within 14 days. No anti-tumor treatment was given and the child died at the age of 4 weeks. The histopathological and cytogenetical analysis of the tumor is presented. The tumor was diagnosed as a retinoblastoma but we could not exclude the possibility of a neuroblastoma. (C) 1994 Wiley-Liss, Inc.

In 1975–1987 at least 84 children developed blindness or impaired vision due to retinopathy of prematurity (ROP) in the Netherlands. Neonatal data were obtained on 74 (86%). Unexpectedly most children (40 i.e. 54%) had been in level I and II hospitals after birth. Screening for ROP had been either insufficient or not timed according to present recommendations in 33 out of 40 children in level I and II hospitals and 25 out of 34 in level III hospitals. As the number of children with ROP has not changed appreciably over the last 40 years, while birth rates in the Netherlands have steadily decreased, the incidence of blindness/impaired vision due to ROP has probably increased. In the current population at risk of ROP which differs considerably from the one during the first epidemic, the disease may not be completely preventable. We conclude that improvements in screening procedures and timely treatment are crucial in order to improve the present situation.

In order to test histochemical fibre types in human extraocular muscles, 2000 fibres from 5 inferior oblique muscles were examined in serial sections for myosin ATP-ase following preincubation at pH 4.3, menadione-linked alpha-GPD and NADHTR activity. In ATP-ase 4.3, +/- 15% of fibres in central and peripheral areas stained dark, the other fibres were slightly stained or unstained. Nearly all fibres with high activity in ATP-ase 4.3 had type I-like histochemical characteristics with high or very high NADHTR activity and low alpha-GPD activity. Fibres with low activity in ATP-ase 4.3 had a spectrum-wide variation in activity of NADHTR and alpha-GPD and could be divided into 3 subtypes with IIA, IIB and IIC-like characteristics. The histochemical profile of the fibres with type IIC-like characteristics differed from that of type IIC fibres in other skeletal muscles, by a lower ATP-ase 4.3 activity. In the central areas all 3 subtypes were more or less equally represented. In the peripheral areas most fibres with low ATP-ase 4.3 activity belonged to the IIC-like subgroup.

It is generally stated in elementary lectures on sensory systems that the limits of the visible spectrum are 400 nm (violet) and 700 nm (red), although there are several exceptions to this generalization. Recently, the properties of ultraviolet (UV) vision in invertebrates, as well as vertebrates, have been better characterized, and it is worthwhile to examine visual phenomena in the UV region of the spectrum. The purpose of this review is to integrate what is known about UV vision in invertebrates, which have been particularly well studied, with a growing literature on UV sensitivity and UV effects in the visual systems of humans and other vertebrates.

Few data exist from which an optimal strategy for retinopathy of prematurity (ROP) screening can be deduced. This strategy should compromise between the dual purpose of screening, to wit monitoring the incidence of ROP and determining an optimal moment for therapeutic intervention. We recorded the timely incidence and course of ROP in all except four premature infants admitted during a 1-year period. The study results indicate that a single screening moment is not likely to detect more than 70% of all cases. When relying, however, on a single screening, the investigation should be performed between the 7th and 9th weeks. The unpredictable course of ROP, varying between early starting, rapidly progressing forms and very late starting, usually benign forms probably precludes the possibility of 100% ROP detection. Screening during the 4th to 5th, 8th, and 11th weeks probably gives the best chances for determination of an optimal moment for treatment and approximation of the incidence.

For a four-year period the development of retinopathy of prematurity (ROP) was determined among neonates considered at risk of acquiring this condition. Fifty-six out of 249 premature infants developed some degree of ROP. Comparison of these infants with a group of 56 controls, admitted to hospital in the same period and matched for sex, birth weight, and gestational age, showed significant differences for sepsis, blood transfusions, and the period of oxygen monitoring in relation to the period of oxygen administration. The most consistent factor associated with the development of ROP was gestational age at the time of birth, though no gestational age group was entirely devoid of ROP. This suggests that screening for ROP should not be restricted to high-risk premature infants only.

Material obtained from the inferior oblique muscle proved to give the best preparations for histological and histochemical investigation. The normal aspects of inferior oblique muscle are discussed. The usefulness of inferior oblique muscle biopsy in pathological material is illustrated by a biopsy of a 6-year-old boy operated on for strabismus due to congenital third nerve palsy.

In The Netherlands, retinoblastoma patients have been registered in the Utrecht national retinoblastoma registry since 1862. This register is virtually complete from 1945 onwards. We describe a unique epidemiological survey of the occurrence of non-ocular cancer in all patients registered during the period 1945-1970. The occurrence of non-ocular cancer in relatives of patients with hereditary retinoblastoma is also reported. One hundred and forty-one patients with hereditary retinoblastoma were studied for non-ocular second primary cancer. Nineteen patients died of retinoblastoma. The median follow-up of the surviving 122 patients was 25 years. Seventeen of these patients developed a second primary cancer, most frequently soft-tissue sarcoma. The cumulative incidence of non-ocular cancer was 19% at the age of 35, i.e., a 14-fold increase as compared to the general population. Twelve patients with hereditary retinoblastoma died of non-ocular cancer whereas none of 252 patients with non-hereditary retinoblastoma died of non-ocular cancer. Furthermore, among the parents of our hereditary retinoblastoma patients, 24 (born before 1945) had also been affected by retinoblastoma or had affected sibs. In the parents, 4 tumors occurred, of which 2 were rhabdomyosarcomas and 2 were urinary bladder cancers. Both types of non-ocular cancer were also encountered among the 122 patients with hereditary retinoblastoma. In 103 fathers and 103 mothers of patients with hereditary retinoblastoma who did not have retinoblastoma themselves, there was no previous family history of retinoblastoma. The fathers had a relative risk of 8.3 for pancreatic cancer compared to the general population. There was no significant increase in the number of non-ocular tumors in 332 sibs of patients with hereditary retinoblastoma.

Forty-two ex-prematures having had regressed forms ol retinopathy of prematurity (ROP) during the neonatal period were compared with 42 matched non-ROP expremature controls at ages 6 to 10 years. The overall incidence of ophthalmologic problems was 55% in the ROP and 36% in the non-ROP group. Strabismus, amblyopia, and refraction anomalies occurred more frequently in the ROP group. In this group, a significantly greater number of children had decreased vision in one or both eyes compared to the non-ROP group. Although the incidence of ophthalmologic problems in the ROP group was considerably higher, the incidence in the non-ROP group still turned out unexpectedly high. This implicates that non-ROP very low birth weight neonates should also be considered to be at a greatly increased risk for later visual problems. Regular ocular examinations, mandatory for the ROP group, thus should be included in follow-up programs of non-ROP very low birthweight neonates as well.

Widely differing screening routines for retinopathy of prematurity (ROP) are encountered in the literature. Because no standard pattern in the development of retinopathy of prematurity has so far been recognized and substantial differences exist between patient-populations, none of these procedures seem generally applicable. Diverse manifestations of this entity cast doubt upon the usefulness of rigid screening procedures. As illustrated by two cases, some retinas seem to be at risk of developing ROP over a considerable period of time which may even extend beyond term. It is suggested that very low birthweight neonates, suffering serious illness or undergoing anesthesia after the initial "routine" ROP screening, should be reexamined for ROP thereafter.

A high performance liquid chromatographic method (ultraviolet detection) for the determination of flecainide concentration in human plasma was reported. Flurazepam (dalmadorm) was used as the internal standard. A mixture of methanol and deionized water containing ion paired reagent served as the mobile phase. The regression equation of flecainide was: y = 0.0017x + 0.0131, r = 0.9975. The extraction recoveries exceeded 94%, and the coefficients of variation (both within the same day and in different days) were less than 5%. The pharmacokinetic parameters in Chinese volunteers after taking flecainide were: Ka = 0.908h-1, T1/2 = 8.131h, peats time = 3.487h, AUC = 441.8ng.h/ml. The mean plasma concentration of flecainide in cases responded well to this drug was 423.6 +/- 227.4ng/ml.

An epidemiological survey has been carried out to establish the incidence of second malignant neoplasms in hereditary retinoblastoma survivors in The Netherlands and the relative risk of cancer in non-affected relatives. The cumulative incidence of second neoplasms was 19% at the age of 35 years. Fathers, unaffected by retinoblastoma, were at risk for pancreatic cancer, the relative risk being 8.3.