Cyanine fluorophores for cellular protection against ROS in stimulated macrophages and two-photon ROS detection.

We report the first example of a novel two-photon active, biocompatible, and macrophage cell-membrane permeable carbazole-based cyanine fluorophore for the detection of three biologically important ROS, namely, ˙OH, O2(-) and OCl(-) in solution. This versatile probe shows cellular protection not only in stimulated macrophages from phorbol-12-myristate-13-acetate-induced morphological changes but also lipopolysaccharide-induced cytotoxicity by quenching with the O2(-) and OCl(-) production, respectively. Such protection could be visualized by a distinct change in the fluorescence intensity of the probe.

Cost-consequence analysis comparing 2-octyl cyanoacrylate tissue adhesive and suture for closure of simple lacerations: a randomized controlled trial.

STUDY OBJECTIVE: We investigate the cost difference between conventional suture and tissue adhesive methods in simple wound closure. METHODS: A cost-consequence analysis was conducted alongside a nonblinded randomized controlled trial comparing 2-octyl cyanoacrylate tissue adhesive with conventional suture in simple lacerations closure in emergency departments (EDs) of a university teaching hospital and a major regional hospital in Hong Kong. One hundred eighty-six adult patients with simple lacerations of length within 8 cm were randomized to receive tissue adhesive (93 patients) or conventional suture (93 patients) for wound closure. The primary outcome measures were the costs to the Hospital Authority and the charges on participants incurred in each treatment method. The secondary outcome measures included the cosmetic visual analog scale, visual analog scale, Wound Evaluation Score, total time spent in each closure method, and the overall patients' satisfaction on the whole process of wound management. RESULTS: The 2 groups had similar baseline characteristics. The tissue adhesive method incurred a higher cost to the Hospital Authority (216.12 [US $27.70] versus 171.33 [US $21.96]; absolute difference 44.79 [US $5.74] [95% confidence interval (CI) 32.76 to 55.95 [US $4.20 to 7.14]]) but a lower charge to patients (109.68 [US $14.06] versus 156.96 [US $20.12]; absolute difference 47.28 [US $6.06] [95% CI, 35.58 to 58.98 [US $4.56 to 7.56]) than the conventional suture method. The mean cosmetic visual analog scale score, visual analog scale score, and Wound Evaluation Score of the 2 groups were similar at various intervals within 3 months after wound closure. Compared with the suture group, the tissue adhesive group had a shorter median procedure time, fewer patients had wound erythema or swelling after wound closure, fewer patients required analgesics on discharge at ED, and there was a higher overall patient satisfaction score. CONCLUSION: Simple wounds closed by tissue adhesives incur a higher cost to the Hospital Authority than the conventional suture but may be favored by patients because of lower personal charge.

Patients' perceptions of nasopharyngeal aspiration in the emergency department of a teaching hospital in Hong Kong.

Nasopharyngeal aspiration (NPA) is the preferred method for collecting specimens for viral culture in patients with respiratory tract infection. As virus identification may influence admission and treatment decisions, it is important to perform NPA in the emergency department. The test may be uncomfortable and poorly tolerated. This prospective study investigated patients' perceptions of NPA. Patients in the emergency department with upper respiratory tract infection undergoing NPA between 9 March 2005 and 12 August 2005 were included. 86 patients (mean (SD) age 47 (23) years; 49 women) were recruited. 22 (26%) patients complained that NPA was very uncomfortable, 59 (69%) reported that it was mildly uncomfortable and 5 (6%) patients reported no discomfort. On a 10-point scale, the median discomfort score was 4. 29 (34%) patients stated that NPA was more uncomfortable than blood taking, 19 (22%) patients felt that both were similar and 38 (44%) patients felt that NPA was less uncomfortable (p value not significant). NPA performed in the emergency department is well tolerated and should be considered in emergency departments when results may influence patient management.

Modulation by homocysteine of the iberiotoxin-sensitive, Ca2+ -activated K+ channels of porcine coronary artery smooth muscle cells.

We evaluated the acute effect of homocysteine on the iberiotoxin-sensitive, Ca(2+)-activated K(+) (BK(Ca)) channels of the porcine coronary artery smooth muscle cells. NS 1619 (1 to 30 microM) caused a concentration-dependent enhancement of the BK(Ca) amplitude (recorded using the whole-cell, membrane-rupture configuration) only with an elevated [Ca(2+)](i) of approximately 444 nM, but not with [Ca(2+)](i) of approximately 100 nM. Homocysteine (30 microM) caused a small inhibition ( approximately 16%) of the BK(Ca) amplitude ([Ca(2+)](i)= approximately 444 nM), and a greater inhibition ( approximately 77%) was observed with 100 microM NADH present in the pipette solution. The inhibition persisted after washing. With NADPH (100 microM), a smaller magnitude of inhibition ( approximately 34%) of the BK(Ca) amplitude was recorded. The NS 1619-mediated enhancement of the BK(Ca) amplitude (with elevated [Ca(2+)](i) plus NADH in the pipette) was attenuated by homocysteine. The homocysteine-mediated inhibition of the BK(Ca) amplitude was suppressed by Tiron (10 mM) or diphenylene iodonium (30 nM), applied alone, but not by superoxide dismutase (500 U/ml) and catalase (500 U/ml). Generation of superoxide (O(2)(-)) of the smooth muscle cells (with NADH presence), measured using the lucigenin-enhanced chemiluminescence, was markedly increased by angiotensin II (100 nM) and homocysteine (30 microM). The chemiluminescence signal was sensitive to apocynin (300 microM) or Tiron, applied alone, but not to superoxide dismutase and catalase. In conclusion, our results demonstrate that acute homocysteine application inhibits the iberiotoxin-sensitive BK(Ca) channels (with elevated [Ca(2+)](i) and NADH present) which is probably caused by the NADH oxidase activation and the concomitant generation of intracellular superoxide.

MR imaging of the brain in patients cured of acute lymphoblastic leukemia--the value of gradient echo imaging.

BACKGROUND AND PURPOSE: Hemosiderin and white matter lesions are 2 of the most common neurologic complications found on MR imaging that may be related to cranial irradiation and intrathecal methotrexate (MTX) therapy in childhood acute lymphoblastic leukemia (ALL). We evaluated the brains of patients previously treated for ALL with cranial irradiation and intrathecal MTX with MR imaging and tested the hypothesis that these patients have more MR evidence of central nervous system (CNS) injury than control patients who are in complete remission following systemic chemotherapy without cranial irradiation. METHODS AND MATERIALS: ALL patients recruited from a pediatric cancer center data base were examined at 1.5T by using T1-weighted, T2-weighted, gradient echo (GE), and fluid-attenuated inversion recovery sequences. Patients treated in childhood for solid extracranial neoplasms were used as controls. RESULTS: Lesions consistent with old hemorrhage were detected in 23 (55%) of the ALL patients and in none of the control patients (P <.001). Of the 62 hemorrhages detected on the GE images, only 9 (15%) were shown on T2-weighted images. White matter abnormalities were found in 2 ALL patients (5%) and one control patient (5%). Old infarcts were seen in 2 ALL patients (10%). CONCLUSION: Cerebral hemorrhages related to radiation-induced vascular malformations, most of which are asymptomatic, are much more common in survivors of childhood ALL than previously thought. GE sequencing is more sensitive in detecting hemorrhagic lesions than T2-weighted sequencing and is to be included in imaging protocols for follow-up study of patients after cerebral radiation therapy.

Successful treatment of spinal cord compression secondary to extramedullary hematopoietic mass by hypertransfusion in a patient with thalassemia major.

A 15-year-old girl with thalassemia major who suffered from paraparesis with a history of progressive lower limb weakness for 2 years immigrated from mainland China to Hong Kong. She had not received regular blood transfusion since the age of 6 years after splenectomy. MRI of the spine showed thoracic spinal cord compression secondary to extramedullary hematopoietic mass. She made significant recovery with hypertransfusion therapy alone. MRI of the spine repeated 3 months later showed nearly complete resolution of the extramedullary hematopoietic mass.

Photocatalytic degradation of water-soluble organic pollutants on TiO2 modified with gold nanoparticles.

Well characterised novel catalysts consisting of TiO2 modified with very small amounts of gold nanoparticles have been applied to the photocatalytic degradation of two important pollutants, methyl tert-butyl ether (MTBE) and 4-chlorophenol, in dilute aqueous solution using a fixed bed flow-through photocatalytic reactor. Although the thermal processing that was necessary for coating the reactor walls with the photocatalysts did lead to some loss of performance, the net gains in activity relative to unmodified TiO2 were nevertheless substantial and in excess of anything previously reported. Improvements in reaction rate by 50% and 100% for the removal of 4-chlorophenol and MTBE, respectively, were achieved. It was also found that effective removal of both pollutants could be achieved at water flow rates that are relevant to field applications involving the photocatalytic clean-up of contaminated groundwater. Due to their very small Au content, the cost of these materials is compatible with large scale use.

Radiation pneumonitis after selective internal radiation treatment with intraarterial 90yttrium-microspheres for inoperable hepatic tumors.

PURPOSE: To investigate the clinical, histopathological, and radiological features of radiation pneumonitis arising as a complication of selective internal radiation treatment for liver tumors. To correlate the development of radiation pneumonitis with the degree of lung shunting as assessed by 99mTechnetium-labeled macroaggregated albumin (Tc-MAA) scan. METHODS AND MATERIALS: Five out of 80 patients who had inoperable hepatic tumors and underwent treatment with intraarterial 90Yttrium- (90Y)-microspheres, developed progressive restrictive ventilatory dysfunction without an infective or cardiovascular cause. Histopathological evidence of a pneumonitis and the presence of microspheres in the lung tissue suggested a diagnosis of radiation pneumonitis. The clinical course, radiological and histopathological findings, percentage tumor shunting to the lungs (lung shunting, as predicted by gamma camera scanning after intraarterial Tc-MAA), and the estimated radiation dose to the lungs were analyzed. In an attempt to reduce pulmonary shunting of the microspheres, three patients received partial hepatic embolization with inert particles before selective internal radiation therapy. RESULTS: In the five patients who developed radiation pneumonitis, lung shunting percentages (as predicted by Tc-MAA scan) ranged from 13.1 to 45.6% (median 23.7%). The estimated whole lung radiation dose ranged from 10.43 Gy to 36.44 Gy (median 25.04 Gy). Among 75 patients who did not develop radiation pneumonitis, the percentage lung shunting ranged from less than 1% to 15% (median 6%). Nine patients had lung shunting greater than 13% and five of them developed radiation pneumonitis, whereas this developed in none of those in whom shunting was below 13%. The onset of radiation pneumonitis ranged from 1 to 6 months after internal radiation treatment. All five patients exhibited characteristic plain radiographic and computerized tomographic changes comprising extensive consolidation with well-defined lateral margins. Clinical improvement after corticosteroid treatment was seen in two patients. Three patients died from respiratory failure and two from other causes. Partial hepatic arterial embolization reduced the degree of lung shunting to less than 13%, but did not prevent the development of radiation pneumonitis. CONCLUSION: Radiation pneumonitis may become a complication after intraarterial 90Y-microspheres treatment when lung shunting, as assessed by Tc-MAA scan, is high (above 13%). Prescribed activity of 90Y and lung shunting of Tc-MAA should be considered together before giving selective internal radiation (SIR) therapy for hepatic tumors, and preferably avoided if the lung shunting is above 13%.

Histopathology of post-embolized meningiomas.

Although embolization of meningiomas has been performed for many years as a preoperative adjunct to reduce tumor vascularity and facilitate surgical excision, little has been written about the features of the histological artefacts introduced by the process. In particular, the fact that it may produce tumor necrosis may potentially cause confusion with atypical or malignant meningiomas. In this study, 25 meningeal tumors of different histological subtypes, all of which had been previously embolized, were reviewed histologically as well as with immunostaining for the MIBI antigen and proliferating cell nuclear antigen (PCNA). Necrosis, in the form of confluent necrosis as well as micronecrosis, was the most common feature (48%). Other characteristic features included florid ischemic changes (16%), intravascular Ivalon particles (24%), and fibrinoid necrosis of vascular walls (12%). Histological changes showed no obvious relationship with the interval between embolization and surgery. There was an increase in MIB1 and PCNA labelling indices in those tumor exhibiting necrotic foci, but it did not seem to have any prognostic significance. We believe pathologists should be familiar with the histological changes induced by embolization in meningiomas so that an erroneous diagnosis of a high-grade lesion will not be made.

Tests of scaling assumptions and construct validity of the Chinese (HK) version of the SF-36 Health Survey.

Few health-related quality of life (HRQOL) survey instruments are available to the Chinese, although many have been developed for Western populations. This article describes the testing of the acceptability, conceptual equivalence, scaling assumptions and construct validity of a Chinese (HK [Hong Kong]) version fo the MOS SF-36 Health Survey. A Chinese (HK) SF-36 survey form was developed by an iterative translation process. It was administered to 236 Chinese subjects who also rated the understanding, difficulty, relevance, and acceptability of each question. The scores were tested against the original scaling assumptions. The SF-36 profile of our subjects was compared to U.S. results for conceptual equivalence. Most subjects did not have any problem in understanding and answering the SF-36. Item means were generally clustered as hypothesized. All but a few items satisfied all scaling assumptions. The shape of the eight-scale SF-36 profile was similar to that of American patients, suggesting conceptual equivalence. We conclude that the Chinese (HK) version of the SF-36 Health Survey has achieved conceptual equivalence and satisfied the psychometric scaling assumptions well enough to warrant further use and testing, using the standard scoring algorithms.

Transmission patterns and the epidemiology of hookworm infection.

BACKGROUND: This paper presents a suite of models of hookworm transmission dynamics which vary the mixing patterns and rates of contamination and infection between children and adults. In this context mixing refers to the degree of epidemiological communication between children and adults, for example, whether adults are likely to get infected from infective material passed by children. METHODS: Three models are described which represent random mixing, no mixing and restricted mixing respectively. Child, adult and population targeted chemotherapy programmes are examined and compared between these models. Data from a hookworm control programme in Zimbabwe were analysed with respect to their fit to the various models. RESULTS: The analysis suggests that some mixing does occur and that in this study location, the sites where adults deposit faeces are more likely to lead to subsequent contamination than the sites children use. CONCLUSIONS: Mixing patterns may have a profound effect on transmission dynamics and should be considered in relation to design of control programmes.

Dynamic models of schistosomiasis morbidity.

Previous attempts to assess the health impact of schistosomiasis control programs on community morbidity have been limited by a lack of a theoretical framework that describes the dynamic relationships between infection and morbidity. In this paper, a model of schistosomal morbidity is developed and parameterized. Morbidity is divided into that due to current heavy infection, and early and late stages of chronic disease. The model was parameterized using data showing resolution of disease after treatment, correlations between prevalence of disease and intensity of infection and using age-morbidity profiles. The fitted parameters suggest that early manifestations of disease such as hepatomegaly in Schistosoma mansoni and S. japonicum infections would resolve relatively quickly following treatment whereas later forms of disease such as liver fibrosis resolve very slowly or not at all. Similar general conclusions were obtained with data on early and late forms of urinary tract morbidity in S. haematobium.

Epifil: a dynamic model of infection and disease in lymphatic filariasis.

The lack of a quantitative framework that describes the dynamic relationships between infection and morbidity has constrained efforts aimed at the community-level control of lymphatic filariasis. In this paper, we describe the development and validation of EPIFIL, a dynamic model of filariasis infection intensity and chronic disease. Infection dynamics are modeled using the well established immigration-death formulation, incorporating the acquisition of immunity to infective larvae over time. The dynamics of disease (lymphodema and hydrocele) are modeled as a catalytic function of a variety of factors, including worm load and the impact of immunopathological responses. The model was parameterized using age-stratified data collected from a Bancroftian filariasis endemic area in Pondicherry in southern India. The fitted parameters suggest that a relatively simple model including only acquired immunity to infection and irreversible progression to disease can satisfactorily explain the observed infection and disease patterns. Disease progression is assumed to be a consequence of worm induced damage and to occur at a high rate for hydrocele and a low rate for lymphodema. This suggests that immunopathology involvement may not be a necessary component of observed age-disease profiles. These findings support a central role for worm burden in the initiation and progression of chronic filarial disease.

Modelling the dynamic effects of community chemotherapy on patterns of morbidity due to Schistosoma mansoni.

This paper uses a mathematical framework to predict the long-term consequences of chemotherapy for the age distribution of schistosomiasis morbidity. The framework incorporates a previously validated transmission model, which is here extended to capture effects on 2 forms of Schistosoma mansoni morbidity: early disease exemplified by hepatomegaly and late disease exemplified by Symmer's fibrosis. The main aim of this analysis is to show how such an approach could be used to explore the probable public health consequences of decades of control. It is suggested that this procedure could usefully inform current approaches to the design of long-term control programmes.

Control of Ascaris infection by chemotherapy: which is the most cost-effective option?

Cost-effectiveness analysis is used to predict the optimal design of mass chemotherapy strategies in controlling Ascaris lumbricoides infection. The question of who to treat, how many to treat, and how often to treat are addressed using a population dynamic model of helminth transmission that assesses effectiveness in terms of disease reduction, combined with cost data from an actual control programme. Child-targeted treatment can be more cost-effective than population treatment in reducing the number of disease cases. The model also implies that, in the circumstances described here, enhancing coverage is a more cost-effective approach than increasing frequency of treatment.

Predicting the impact of school-based treatment for urinary schistosomiasis given by the Ghana Partnership for Child Development.

Mathematical models can be used to predict the impact of interventions to control infectious diseases. In this paper, an epidemiological model is used to predict the impact of chemotherapy of school-age children infected with Schistosoma haematobium, in a programme conducted by the Ghana Partnership for Child Development in the Volta Region, Ghana. Existing data were used to validate the predictions of the model, demonstrating convincingly the ability of the model to make correct predictions. Predictions of trends in mean egg count, infection prevalence and prevalence of heavy infection (> 50 eggs/10 mL urine) were then made for the period 1997-1999, and will be compared to the data collected in the programme in the future.

Dynamic aspects of morbidity and acquired immunity in schistosomiasis control.

In schistosomiasis control, rational planning of chemotherapy programmes is complicated by the dynamic interactions between treatment and levels of acquired immunity and morbidity in the community. In this paper, mathematical models that address the development of acquired immunity and the prevalence of morbidity are incorporated within an age-structured transmission framework to explore some of the dynamic complexities of long-term chemotherapy programmes. As well as illustrating some of the potential problems inherent in predicting the consequences of control measures, the model provides insights into the dynamics of schistosomiasis transmission and the parameters that need to be measured to further improve the design of community-based control programmes.

A stochastic model of schistosomiasis immuno-epidemiology.

Schistosomiasis is a helminth (worm) infection with approximately 200 million people infected worldwide. There is still controversy on whether differing worm burdens between individuals is a result of differing contact rates or of acquired immunity. In this paper, we present a stochastic modelling framework to address these issues. By using appropriate approximations for the higher moments of the joint distributions, differential equations for the means, variances and co-variances of infection and immunity can be obtained. Numerical solutions of these equations to obtain age profiles of the above properties were compared with Monte Carlo simulations of the stochastic process. Simulations showed that the results depended on whether between host heterogeneity was generated by differing contact rates or differing immune responses. Heterogeneity in contact rates produced a highly aggregated distribution of parasites with a large variance/mean ratio. Heterogeneity in the immune response had very little effect on the overall dynamics. This agrees with the predominant field evidence which would suggest that infection is mainly determined by ecology with a smaller contribution of immunity.

MR diffusion-weighted imaging of kidney: differentiation between hydronephrosis and pyonephrosis.

The objective of the study was to evaluate the capability and reliability of the magnetic resonance (MR) diffusion-weighted imaging (DWI) in differentiation between hydronephrosis and pyonephrosis. Single-shot echoplanar MR diffusion-weighted imaging was performed in 12 patients who had dilatation of the renal pelvis and calyces detected by ultrasonography (US). Microbiological tests confirmed that there were four cases of pyonephrosis and eight cases of hydronephrosis. Signal intensities of the collecting (pelvicalyceal) systems on the diffusion-weighted images and apparent diffusion coefficient (ADC) maps were noted. ADC values of the pelvicalyceal system in all patients were computed and compared using Student's t test. On diffusion-weighted images, the pelvicalyceal system of the hydronephrotic kidney was hypointense while the pelvicalyceal system of the pyonephrotic kidney was markedly hyperintense. The mean ADCs of the hydronephrotic and pyonephrotic renal pelvis were 2.98 +/- 0.65 x 10(-3) and 0.64 +/- 0.35 x 10(-3) mm(2)/s, respectively. The extremely low ADC of the renal pelvis of the pyonephrotic kidney accounted for its signal hyperintensity on diffusion-weighted images as well as signal hypointensity on ADC maps. In conclusion, the MR diffusion-weighted imaging may be a reliable tool to differentiate pyonephrosis from hydronephrosis.