[Recent advances in preoperative assessment of hepatic functional reserve for hepatectomy].

Hepatectomy represents the first choice of treatment for primary and secondary liver malignancies.However,post-hepatectomy liver failure(PHLF) remains a significant cause of morbidity and mortality after liver resection.Inadequate remnant liver volume and function are the determining factors of PHLF.Therefore,preoperative assessment of hepatic functional reserve is of paramount importance for prevention of PHLF.There are two main conventional assessment systems of preoperative hepatic functional reserve.The first is remnant liver volume(RLV) and its derivative indicators such as residual liver volume ratio,standardized residual liver volume ratio,RLV/body weight,and RLV/body surface area,calculated by imaging-based methods such as CT,that assess whether the volume of residual liver meets the requirements of safe hepatectomy.However,RLV is not an appropriate indicator of functional liver remnant,since the function of liver within equal volume among different persons is unequal due to the underlying liver diseases.Functional imaging techniques,such as 99Tcm-GSA,99Tcm-IDA and Gd-EOB-DTPA-enhanced MRI can simultaneously evaluate residual liver volume and function,leading to be a more appropriate indicator of functional liver remnant.The second is liver function tests,including serum biochemical parameters,clinical scoring systems and quantitative liver function tests.However,it can merely evaluate the overall liver function preoperatively,but not the residual one postoperatively.The residual liver function can be accurately measured by intraoperative indocyanine green clearance with the extrahepatic and intrahepatic blood flow of liver to be resected blocked.In addition,methods such as preoperative portal vein embolization and associating liver partition and portal vein ligation for staged hepatectomy,can be used for patients with a predicted inadequate RLV.Due to the unequal liver function within an equal volume increased by different methods,functional imaging techniques are more appropriate in predicting the increasing functional liver than traditional methods which just assess the increasing liver volume.

Household economic burden and outcomes of patients with schizophrenia after being unlocked and treated in rural China.

AIMS: Patients with severe mental disorders in low-resource settings have limited access to services, resulting in overwhelming caregiving burden for families. In extreme cases, this has led to the long-term restraining of patients in their homes. China underwent a nationwide initiative to unlock patients and provide continued treatment. This study aims to quantify household economic burden in families after unlocking and treatment, and to identify factors associated with increased burden due to schizophrenia. METHODS: A total of 264 subjects were enrolled from three geographically diverse provinces in 2012. Subjects were patients with schizophrenia who were previously put under restraints and had participated in the 'unlocking and treatment' intervention. The primary outcome was the current household economic burden, obtained from past year financial information collected through on-site interview. Patient disease characteristics, treatment, outcomes and family caregiving burden were collected as well. Univariate and multivariate linear regression were used to construct risk factor models for indirect economic burden. RESULTS: After participating in the intervention, 85% of patients continued to receive mental health services, 70% used medication as prescribed and 80% were never relocked. Family members reported significantly decreased caregiving burden after receiving the intervention. Mean direct and indirect household economic burdens were CNY963 (US$31.7) and CNY11 724 (US$1670) per year, respectively, while family total income was on average CNY12 108 (US$1913) per year. Greater disease severity and poorer patient psychosocial function at time of study were found to be independent factors related to increased indirect burden. CONCLUSIONS: The 'unlocking and treatment' intervention has improved the lives of patients and families. Indirect burden due to disease is still a major economic issue that needs to be addressed, potentially through improving treatment and patient functioning. Our findings contribute to the unravelling and eventual elimination of chronic restraining of mentally ill patients in low-resource settings.

[Spatial distribution of cancer-related burden in Guangzhou from 2010 to 2013].

Objective: To evaluate the burden and to describe the characteristics of spatial distribution caused by malignant tumors among different administrative areas in Guangzhou from 2010- 2013. Methods: Based on data from the Cancer Registry system and population in Guangzhou in 2010- 2013, disability-adjusted life year (DALY) was assessed on the disease burden of cancer, in accordance with the method used in the Global Burden of Disease study. Results: The crude incidence rates of cancer appeared as 256.22/10(5) in 2010-2011 and 270.04/10(5) in 2012-2013, with the crude mortality rates as 143.17/10(5) and 148.01/10(5), respectively, in Guangzhou. Cancers caused 606 238.95 DALYs in 2010-2011 and 623 763.80 DALYs in 2012-2013 for both sexes and 37.63 and 37.81 person year per 1 000 persons, with the standardized DALY rates as 34.51‰, 34.00‰ respectively. Three administrative districts (Yuexiu, Haizhu and Liwan) were with the largest disease burden of cancers that accounted for 45% of the DALYs for the whole Conghua district, with liver cancer was the leading cancer on DALYs, and tracheal, bronchus and lung cancer ranked the first in the other districts. Conclusions: In Guangzhou, disease burden caused by cancers was both prominently seen in the newly developed urban area and the old districts. It remains an arduous task to continue programs on control and prevention of cancers in this city.

Active monitoring versus direct active monitoring for Ebola virus disease in the United States: experiences and perceptions of former persons under monitoring in the District of Columbia and Indiana.

OBJECTIVES: During the 2014-2016 West Africa Ebola outbreak, the Centers for Disease Control and Prevention recommended daily monitoring and surveillance of persons arriving in the United States (US) from impacted areas through either active monitoring (phone calls, online platforms, and so on) or direct active monitoring (in-person or electronic visualization). Intensiveness of policies implemented by state/local jurisdictions varied markedly. To study the experiences and perceptions of active monitoring versus direct active monitoring on former persons under monitoring (FPUMs) in the US, we compared two jurisdictions that utilized distinct polices: the District of Columbia (DC) and Indiana (IN). STUDY DESIGN: Retrospective assessment survey of FPUMs. METHODS: FPUMs from both jurisdictions (DC 826 and IN 246) monitored from October 2014 to September 2015 were surveyed regarding their overall perception of monitoring, communications with jurisdictional staff, negative consequences experienced, and risk for and concern about Ebola virus disease. A total of 294 DC FPUMs and 52 IN FPUMs responded. RESULTS: Directly actively monitored FPUMs in IN were more likely to report monitoring was difficult (P < 0.01), not being allowed to return to work (P = 0.01), and faster response times when reaching out to their assigned health department (P < 0.01). Overall all FPUMs, regardless of the monitoring method they underwent, perceived little risk and reported they felt monitoring protected public health. CONCLUSIONS: Our results display that while FPUMs preferred active monitoring, both polices equally reduced their concern, suggesting that less intensive polices achieve the same level of perceived effectiveness by those monitored while also reducing the amount of negative consequences they may face.

Rationale and design for the community activation for prevention study (CAPs): A randomized controlled trial of community gardening.

BACKGROUND: Engaging in health-promoting behaviors (e.g., healthy fruit- and vegetable-rich diet, physical activity) and living in supportive social and built environments are consistently and significantly associated with reductions in cancer, heart disease, diabetes, and other chronic diseases. Interventions to change diet and physical activity behaviors should aim to educate individuals, change the environments in which people live, work and recreate, improve access, availability, and affordability of healthy foods, and create safe places the facilitate active lifestyles. This trial will assess whether community gardening increases fruit and vegetable consumption and physical activity, improves social support and mental health, and reduces age-associated weight gain and sedentary time among a multi-ethnic, mixed-income population. METHODS/DESIGN: A randomized controlled trial of community gardening began in Denver, Colorado in January 2017. Over 3 years, we will recruit 312 consenting participants on Denver Urban Gardens' waitlists and randomize them to garden or remain on the waitlist. At baseline (pre-gardening), harvest time, and post-intervention, study participants will complete three 24-hour dietary recalls, a 7-day activity monitoring period using accelerometry, a health interview and physical anthropometry. DISCUSSION: This project addresses health-promoting behaviors among a multi-ethnic, mixed-income adult population in a large metropolitan area. If successful, this trial will provide evidence that community gardening supports and sustains healthy and active lifestyles, which can reduce risk of cancer and other chronic diseases. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03089177: Registered on 03/17/17.

Influence of medical insurance schemes and charity assistance projects on regular prophylaxis treatment of the boys with severe haemophilia A in China.

OBJECTIVE: To explore the influence of medical insurance policy and charity assistance projects on the uptake and discontinuation of regular prophylaxis treatment in Chinese severe haemophilia A children. METHODOLOGY: This retrospective study was conducted on children with severe haemophilia A, who received FVIII prophylaxis treatment at 12 haemophilia centres in China from 1 November 2007 to 31 May 2013. RESULTS: The average duration of prophylaxis treatment received by haemophilia children significantly increased from 16.7 weeks in 2008 to 32.8 weeks in 2012 (P < .001). The main reason for prophylaxis acceptance included dissatisfaction with previous "on-demand" regimens, availability of improved local medical insurance policies and patient/family awareness of haemophilia. The main reason for subsequent discontinuation of prophylaxis was economic instability. The upper limit of insurance was up to RMB 150 000/y (~USD: 22 000/y) for 80.1% of the insured patients and would be sufficient to cover the continuous low-dose prophylaxis regimen. However, for many patients the burden of out-of-pocket copayment cost represented a risk for poor adherence to regular prophylaxis. In about two third of the patients, the annual out-of-pocket copayment cost amounted to >50% of their average annual disposable income. Many patients therefore required assistance from the charity assistance projects, but nonadherence remained prevalent. CONCLUSION: Medical insurance policy and charity assistance projects helped haemophilia children to accept and continue prophylaxis regimens. It was the proportion of the out-of-pocket copayment cost rather than the upper limit of insurance reimbursement that restricted long-term regular low-dose prophylaxis in China.

A prospective study of health-related quality of life of boys with severe haemophilia A in China: comparing on-demand to prophylaxis treatment.

INTRODUCTION: Treatment for boys with haemophilia in China is rapidly improving; however, comprehensive outcomes have not been examined prospectively. AIM: The aim of this study was to evaluate the effect of short-term full-dose prophylaxis compared to on-demand treatment, on the Health-Related Quality of Life (HR-QoL) of boys with severe haemophilia A (HA) in China. METHODS: Boys with severe HA (FVIII<1%) completed 3 months of on-demand treatment and 3 months of full-dose prophylaxis (25 FVIII IU per kg 3x per week). The primary outcomes were child- and parent-reported Canadian Hemophilia Outcomes - Kids Life Assessment Tool (CHO-KLAT) scores. The number and type of bleeds and Activities Scale for Kids (ASK) scores were also recorded. RESULTS: Analyses included 23 boys between 4 and 15.9 years of age. The number of bleeds decreased by 94% on prophylaxis (P < 0.0001, Wilcoxon Signed-Rank test). The mean child-reported CHO-KLAT scores for boys ≥7 years (n = 20) was 61.4 (±10.9) during on-demand treatment and 61.9 (±11.4) following short-term prophylaxis (P = 0.72, paired t-test). The mean parent-reported CHO-KLAT score during the on-demand phase was 54.4 (±10.5) with an increase of 3.8 points (±8.1; P = 0.04, paired t-test) following prophylaxis. CONCLUSIONS: Child-reported CHO-KLAT scores were lower in boys with severe HA in China than reported in countries with access to full-dose prophylaxis. Boys reported higher HR-QoL scores than their parents. Small improvements in ASK scores were noted following the prophylaxis phase. These changes were only significant in the parent-reported CHO-KLAT scores. Longer term prospective clinical trials are needed in China to determine the impact of prophylaxis on HR-QoL in boys with severe HA.

[Phonological assessment and voice analysis of thyroid surgery patients].

Objective:To investigate the changes of speech and voice acoustics in patients with thyroid disease before and after operation, get objective values, and conducive to guiding the clinical diagnosis and treatment and recurrent laryngeal nerve protection. Method:A total of 216 patients undergoing thyroid surgery from October 2015 to October 2016 were treated with TVQ and GRBAS at 1 day before surgery, 1 week, 1 month, and 3 months postoperatively to phonological assessment, and Praat software was used to collect and analyze the acoustic acoustics index for preoperative and postoperative comparative analysis. Result:All patients did not damage the recurrent laryngeal nerve, unilateral or bilateral thyroid subtotal resection (no exploration of recurrent laryngeal nerve) in patients with postoperative speech and voice index F0 was decreased at 1 week after surgery (P<0.05), the other indicators did not change significantly; difference was found out in single-sided total thyroidectomy+ipsilateral central area lymph node dissection, bilateral thyroidectomy+unilateral central area lymph node dissection (exploration of unilateral recurrent laryngeal nerve) in patients with TVQ, GRBAS and F0, HNR after surgery 1 week compared with preoperative (P<0.05), However, there was no significant difference 3 months; TVQ, GRBAS and F0, HNR were significantly changed in patients with bilateral thyroidectomy+bilateral central lymph node dissection (revealed bilateral recurrent laryngeal nerve) at 1 week after operation (P>0.05). F0 and HNR were lower than those before operation, and the patients were treated with Jitter and Shimmer. The patients were treated with TVQ, GRBAS, Jitter and Shimmer before operation, however, the majority of patients' TVQ, GRBAS, Jitter, Shimmer can be restored to preoperative level after surgery 3 months (P>0.05). Conclusion:The appearance of speech and voice problems in patients after thyroid surgery may increase with the expansion of the surgical range, the change in speech and voice after neck lymph node dissection is reversible.

A new virtual ring-based system matrix generator for iterative image reconstruction in high resolution small volume PET systems.

A common approach to improving the spatial resolution of small animal PET scanners is to reduce the size of scintillation crystals and/or employ high resolution pixellated semiconductor detectors. The large number of detector elements results in the system matrix--an essential part of statistical iterative reconstruction algorithms--becoming impractically large. In this paper, we propose a methodology for system matrix modelling which utilises a virtual single-layer detector ring to greatly reduce the size of the system matrix without sacrificing precision. Two methods for populating the system matrix are compared; the first utilises a geometrically-derived system matrix based on Siddon's ray tracer method with the addition of an accurate detector response function, while the second uses Monte Carlo simulation to populate the system matrix. The effectiveness of both variations of the proposed technique is demonstrated via simulations of PETiPIX, an ultra high spatial resolution small animal PET scanner featuring high-resolution DoI capabilities, which has previously been simulated and characterised using classical image reconstruction methods. Compression factors of 5 x 10(7) and 2.5 x 10(7)are achieved using this methodology for the system matrices produced using the geometric and Monte Carlo-based approaches, respectively, requiring a total of 0.5-1.2 GB of memory-resident storage. Images reconstructed from Monte Carlo simulations of various point source and phantom models, produced using system matrices generated via both geometric and simulation methods, are used to evaluate the quality of the resulting system matrix in terms of achievable spatial resolution and the CRC, CoV and CW-SSIM index image quality metrics. The Monte Carlo-based system matrix is shown to provide the best image quality at the cost of substantial one-off computational effort and a lower (but still practical) compression factor. Finally, a straightforward extension of the virtual ring method to a three dimensional virtual cylinder is demonstrated using a 3D DoI PET scanner.

Optimizing EEMCO guidance for the assessment of dry skin (xerosis) for pharmacies.

PURPOSE: People with dry skin (xerosis) are common in community pharmacies, but there is no consistent guidance for community pharmacists to evaluate and alleviate dry skin. Through evaluating any difference of the clinical scoring systems of EEMCO guidance between a dermatologist and pharmacists and the efficacy of moisturizers for the treatment of dry skin recommended by community pharmacists, we aim to validate a dry skin guidance through the help of community pharmacists. These results provide insight into how community pharmacists can help patients with dry skin. METHODS: The clinical scoring systems of EEMCO guidance used in this study comprised analog scales, the overall dry skin score (ODS), and the specific symptom sum score (SRRC) system. All pictures of the dry skin scored by pharmacists were visually evaluated by a dermatologist. The efficacy of the moisturizers was determined by the difference of the scales on day 0 and on day 28. RESULTS: In this study, 387 patients with dry skin from 157 community pharmacies were evaluated by pharmacists. Visual scale with divisions, ODS and SRRC that were evaluated by pharmacists on day 0 and day 28 were moderately reliable by a dermatologist. All parameters of dry skin were significantly improved by the moisturizers which were recommended by community pharmacists on day 28. CONCLUSION: Visual scale, ODS and SRRC can be generally measured to evaluate dry skin in community pharmacies with moderate degree of reliability. This finding has possible applications for investigating the assessment of the community pharmacists on clinical scoring system of dry skin and moisturizers.

Assessment of vasa vasorum in the walls of thrombophlebitic saphenous vein.

AIM: The purpose of this study was to investigate the proliferation of vasa vasorum (VV) in the walls of thrombophlebitic saphenous vein (TSV), and to evaluate the influence of high venous pressure and lack of oxygen on the VV. METHODS: The specimens of the great saphenous vein were collected: 11 primary varicose vein (PVV), 11 TSV and, as a control, eight normal great saphenous vein. Masson staining and immunohistochemistry for CD34 were used to observe the status of VV, and the number of VV were counted under light microscopy. RESULTS: VV of the thrombophlebitic saphenous vein group (TSVG) were clustered together in adventitia, increased linearly in media, and scattered appearance in intima, were increased partially in intima of thrombus rupturing. In TSVG, the number of VV observed in adventitia, media and intima was 16.738±7.685, 4.845±2.537, 2.448±3.030, respectively. In the primary varicose vein group (PVVG), the corresponding values were 14.280±4.440, 2.965±1.125, 0.500±0.548. And the number was 8.911±2.629, 0.150±0.424, 0±0 in the control group (CG). Significantly higher numbers of VV were observed in the TSVG as compared to the PVVG or CG (P<0.05). No significant difference was observed between intima and media (P>0.05). CONCLUSION: Thrombi in varicose veins can induce proliferation of VV, which may be involved in high venous pressure and hypoxia.

Medical waste production at hospitals and associated factors.

This study was conducted to evaluate the quantities of medical waste generated and the factors associated with the generation rate at medical establishments in Taiwan. Data on medical waste generation at 150 health care establishments were collected for analysis in 2003. General medical waste and infectious waste production at these establishments were examined statistically with the potential associated factors. These factors included the types of hospital and clinic, reimbursement payment by National Health Insurance, total number of beds, bed occupancy, number of infectious disease beds and outpatients per day. The average waste generation rates ranged from 2.41 to 3.26kg/bed/day for general medical wastes, and 0.19-0.88kg/bed/day for infectious wastes. The total average quantity of infectious wastes generated was the highest from medical centers, or 3.8 times higher than that from regional hospitals (267.8 vs. 70.3Tons/yr). The multivariate regression analysis was able to explain 92% of infectious wastes and 64% of general medical wastes, with the amount of insurance reimbursement and number of beds as significant prediction factors. This study suggests that large hospitals are the major source of medical waste in Taiwan. The fractions of medical waste treated as infectious at all levels of healthcare establishments are much greater than that recommended by the USCDC guidelines.

Worst, average or current pain in the Brief Pain Inventory: which should be used to calculate the response to palliative radiotherapy in patients with bone metastases?

AIMS: To determine which pain intensity scale in the Brief Pain Inventory correlates best with functional interference and should be used to calculate the response to palliative radiotherapy. To determine the differences in functional interference scores for patients classified as responders and non-responders to palliative radiotherapy. PATIENTS AND METHODS: All patients referred to the Rapid Response Radiotherapy Program for palliative radiotherapy of symptomatic bone metastases were considered for the study. Patients rated the intensity and functional interference of their pain at the irradiated sites according to the Brief Pain Inventory before and 2 months after radiotherapy. Worst, average and current pain scores were correlated with functional interference scores using Spearman rank coefficients. Responders and non-responders to palliative radiotherapy were defined for each pain intensity scale according to the end points specified by the International Bone Metastases Consensus Working Party. Average differences between responders and non-responders were compared using a Wilcoxon rank sum test. RESULTS: Between May 2003 and June 2005, 199 patients enrolled in the study (102 men and 97 women). Ninety-five patients returned complete questionnaires at 2 months of follow-up. All pain intensity and interference scores for evaluable patients were significantly lower at 2 months (P<0.0021). Response rates differed depending on the definition of pain intensity. An overall response rate was observed in 66, 58 and 54% of patients for worst, average and current pain, respectively. Worst pain showed the best correlation with functional interference. Responders reported significantly larger decreases in functional interference scores at follow-up in general activity, normal work, enjoyment of life and average functional interference. CONCLUSION: Worst pain intensity had higher correlations with all functional interference scores except relationships with others. Therefore, we recommend an 11-point scale measuring worst pain to evaluate response rates in future radiotherapy trials. The mean difference from baseline to follow-up in functional interference scores was significantly larger in patients who responded to radiotherapy treatment.

Diffusion tensor imaging in the assessment of normal-appearing brain tissue damage in relapsing neuromyelitis optica.

BACKGROUND AND PURPOSE: Normal-appearing brain tissue (NABT) damage was established in multiple sclerosis by histology, MR spectroscopy, magnetization transfer imaging and diffusion tensor imaging (DTI). However, whether this phenomenon can be detected in relapsing neuromyelitis optica (RNMO) remains unclear. The aim of this study was to use DTI to investigate the presence of NABT damage in RNMO patients and its possible mechanism. METHODS: Conventional MR imaging and DTI scans were performed in 16 patients with RNMO without visible lesions on brain MR imaging and in 16 sex- and age-matched healthy control subjects. Histogram analysis of mean diffusivity (MD) and fractional anisotropy (FA) was performed in the entire brain tissue (BT), white matter (WM), and gray matter (GM). Region of interest (ROI) analysis of MD and FA was also performed in WM regions connected with the spinal white matter tracts or optic nerve (including medulla oblongata, cerebral peduncle, internal capsule, and optic radiation), in corpus callosum without direct connection with them, and in some GM regions. RESULTS: From histogram analysis, we found the RNMO group had a higher average MD of the BT, WM, and GM, a lower average MD peak height and a higher average MD peak location of the GM, and a higher average FA peak height of the WM than did the control group. From ROI analysis, compared with control subjects, RNMO patients had a higher average MD and a lower average FA in ROIs of WM connected with the spinal white matter tracts or optic nerve and a normal average MD and FA in corpus callosum without direct connection with them. In addition, a high average MD was found in parietal GM in these patients. CONCLUSIONS: Our findings confirm the presence of abnormal diffusion in brain tissue in patients with RNMO and suggest that secondary degeneration caused by lesions in the spinal cord and optic nerve might be an important mechanism for this abnormality.

Ultrastructural assessment of Plasmodium falciparum in age-fractionated thalassaemic erythrocytes.

Culture of Plasmodium falciparum in age-fractionated thalassaemic red blood cells (RBC) has shown evidence of parasite damage on light microscopy in older cells during the third culture cycle (96-144 h). In this report, parasites growing in thalassaemic trait and normal RBC were examined ultrastructurally from 96 to 144 h. All parasite stages in old thalassaemic RBC showed evidence of damage worsening with culture duration. There were cytoplasmic alterations with ribosomal damage, and parasite cytoplasm became increasingly loose and grainy, with multiple fissures. Discontinuity of the nuclear membrane with an abnormal nucleolus was seen at l20 h. Cytosomes remained normal, but damage to the food vacuole and shrunken disintegrating parasites were observed at 144 h. These changes are compatible with cellular degeneration and developmental retardation and would account for the schizont maturation arrest and reduced reinvasion rates previously reported. Increased free radicals associated with thalassaemic erythrocytes would explain these changes, further supporting the role for oxidant stress in the protective mechanism.

Relationship between transferrin saturation and iron stores in the African American and US Caucasian populations: analysis of data from the third National Health and Nutrition Examination Survey.

In previous analyses of transferrin saturation data in African Americans and Caucasians from the second National Health and Nutrition Examination Survey (NHANES II), subpopulations were found consistent with population genetics for common loci that influence iron metabolism. The goal of this new study was to determine if these transferrin saturation subpopulations have different levels of iron stores. Statistical mixture modeling was applied to transferrin saturation data for African Americans and Caucasians from the third National Health and Nutrition Examination Survey (NHANES III), and then the mean serum ferritin concentrations were determined for the transferrin saturation subpopulations that were identified. After adjustment for diurnal variation, 3 subpopulations of transferrin saturation were identified in each racial group. Satisfying Hardy-Weinberg conditions for major locus effects, in both racial groups the sum of the square roots of the proportion with the lowest mean transferrin saturation and the proportion with the highest mean transferrin saturation was approximately 1. When weighted to reflect the US adult population as a whole, these subpopulations of increasing transferrin saturations had progressively increasing mean age-adjusted serum ferritin concentration values in each ethnic grouping as stratified by sex (trend test, P <.002 for all). These results are consistent with the concept that population transferrin saturation subpopulations reflect different levels of storage iron.

Parametric mapping of scaled fitting error in dynamic susceptibility contrast enhanced MR perfusion imaging.

The purpose of this study was to examine the benefits of routine generation of a parametric image of scaled curve fitting errors in the analysis of dynamic susceptibility contrast enhanced MR perfusion imaging. We describe the scaled fitting error (SFE), which reflects the magnitude of potential errors in the estimation of perfusion parameters from dynamic susceptibility contrast enhanced studies. The SFE is the root-mean-square error between the observed values in the time course of change of effective transverse relaxation rate (delta R2* (t)) in tissue and the theoretical values derived by gamma variate curve fitting, scaled with a simple function related to the area under the fitted gamma variate curve. The SFE was tested using Monte Carlo simulation and by observations in normal volunteers and patients. This demonstrated that the SFE was linearly related to uncertainties in calculation of the values of relative cerebral blood volume (rCBV) and relative mean transit time (rMTT). High spatial resolution SFE maps were obtained in all volunteers and patients. In normal brain, SFE was consistently higher in white matter than in grey matter. In 54/85 patients with neurodegenerative or vascular brain disease, SFE maps showed focal areas with high values owing to poor signal to noise ratio in delta R2*(t). Increased SFE was also found in 11/54 brain tumours owing to loss of conformance of delta R2*(t) to the gamma variate function. SFE mapping is simple to implement and the computational overhead is negligible. It is concluded that parametric maps of SFE allow visual and quantitative comparison of fitting errors with the theoretical gamma variate model between anatomical regions and provide a quality control device to rapidly assess the reliability of the associated rCBV and rMTT estimations.

Knowledge-based segmentation of thoracic computed tomography images for assessment of split lung function.

The assessment of differential left and right lung function is important for patients under consideration for lung resection procedures such as single lung transplantation. We developed an automated, knowledge-based segmentation algorithm for purposes of deriving functional information from dynamic computed tomography (CT) image data. Median lung attenuation (HU) and area measurements were automatically calculated for each lung from thoracic CT images acquired during a forced expiratory maneuver as indicators of the amount and rate of airflow. The accuracy of these derived measures from fully automated segmentation was validated against those from segmentation using manual editing by an expert observer. A total of 1313 axial images were analyzed from 49 patients. The images were segmented using our knowledge-based system that identifies the chest wall, mediastinum, trachea, large airways and lung parenchyma on CT images. The key components of the system are an anatomical model, an inference engine and image processing routines, and segmentation involves matching objects extracted from the image to anatomical objects described in the model. The segmentation results from all images were inspected by the expert observer. Manual editing was required to correct 183 (13.94%) of the images, and the sensitivity, specificity, and accuracy of the knowledge-based segmentation were greater than 98.55% in classifying pixels as lung or nonlung. There was no significant difference between median lung attenuation or area values from automated and edited segmentations (p > 0.70). Using the knowledge-based segmentation method we can automatically derive indirect quantitative measures of single lung function that cannot be obtained using conventional pulmonary function tests.

Technology evaluation: gene therapy (FGF-5), Vical.

Vical, in collaboration with Merck, is developing gene-based therapies, including its 'naked DNA', for the potential treatment of ischemic heart disease. Vical has obtained preclinical data in animal models showing that a gene for a potent growth factor, FGF-5, can be delivered and expressed in coronary arteries stimulating the formation of new blood vessels. This new blood vessel formation may provide supplemental blood flow and necessary cardiac tissue oxygenation in areas of the heart where atherosclerotic blockages are present. Vical anticipates that its FGF-5 gene-based product would be used in conjunction with balloon angioplasty to stimulate new blood vessel formation at the site of the blockage. A series of experiments have been conducted in rats, whereby genes encoding FGF-5 were injected directly into rat heart muscle. The DNA was absorbed and the FGF-5 protein was expressed by cardiac myocytes. Active FGF-5 was released into the extracellular spaces of the heart muscle cells and new blood vessels formed throughout the local area. Quantitative measurements of blood vessel formation indicated that capillary density increased significantly in the hearts of treated rats compared to untreated controls. Further studies are underway to evaluate the persistence of new blood vessels following FGF-5 gene injection, and measurements will be made to assess the extent of improved blood flow in the affected region [177118]. In December 1996, the US patent office issued patent number US-05580859, covering Vical's naked DNA technology [227199].

Flow cytometric assessment of oxidant stress in age-fractionated thalassaemic trait erythrocytes and its relationship to in vitro growth of Plasmodium falciparum.

The role of oxidant stress in mediating the protection against malaria in thalassaemic red blood cells (RBC) has been hypothesized. In this study we have assessed the relationship between oxidant stress, red cell age and malarial parasite activity in thalassaemic RBC. Using a flow cytometric method to assess lipid peroxidation, we have shown that the age-related increase in sensitivity to oxidative stress previously demonstrated in normal RBC also occurs in thalassaemic RBC. Invasion and growth of Plasmodium falciparum was also shown to deteriorate with increasing RBC age. This effect was more pronounced in thalassaemic RBC with associated schizont maturation arrest and abnormal parasite morphology. In addition, there was a slight but consistent inverse correlation between sensitivity to oxidant stress and parasite activity (R = -0.43; P = 0.03 for normal RBC and R = -0.42; P = 0.01 for thalassaemic RBC). Our findings indicate an association between red cell age, oxidant stress and P. falciparum growth, providing further support for the role of oxidant stress in mediating the protective effect against malaria in thalassaemic RBC.