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Landscape fires are a natural component of the Earth System. However, they are of growing global concern due to climate change exacerbating their multiple impacts on biodiversity, ecosystems, carbon storage, human health, economies, and wider society. Temperate regions are predicted to be at greatest risk of increasing fire activity due to climate change, where fires can seriously impact important ecosystems for biodiversity and carbon storage, such as peatlands and forests. There is insufficient literature on the background prevalence, distribution, and drivers of fires in these regions, especially within Europe, to assess and mitigate their risks. Using a global database of fire patches based on the MODIS FireCCI51 product, we address this knowledge gap by quantifying the current prevalence and size of fires in Polesia, a 150,000 km 2 area comprising a mosaic of peatland, forest, and agricultural habitats in northern Ukraine and southern Belarus. Between 2001 and 2019, fires burned 31,062 km 2 of land, and were most frequent in spring and autumn. Although most fires started in agricultural land, fires disproportionately affected natural and semi-natural land cover types, particularly in protected areas. Over one fifth of protected land burned. Coniferous forests were the most common land cover type in protected areas, but fires mostly occurred in meadows, open peatlands (especially fen and transition mires), and native deciduous forests. These land cover types were highly susceptible to fires under low soil moisture conditions, but the risk of fire was low under average or higher soil moisture conditions. Restoring and maintaining natural hydrological regimes could be an effective nature-based solution to increase the resilience of fire-vulnerable ecosystems and support global biodiversity and carbon storage commitments under the United Nations Framework Conventions on Climate Change and Convention on Biological Diversity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: A rare presentation of pheochromocytoma (PCC) is catecholamine-induced-cardiomyopathy, or Takotsubo cardiomyopathy (TCM). PCC-induced TCM(PCC-TCM) can present as a typical or atypical type, based on the location of cardiac wall motion abnormalities. In this review, we sought to assess features and outcomes for PCC-TCM, and to compare typical and atypical subtypes., Methods: A search was conducted on two databases (PubMed and Embase) for case series or reports on PCC-TCM from 2006 to 2020., Results: One-hundred-and-two papers with a total of 104 cases of PCC-TCM were retrieved: 67(64.4%) typical and 37(35.6%) atypical subtypes. Overall median age was 50[range:23-86] years, the atypical group about a decade younger(p < 0.001). A female preponderance was seen for either subtype (∼75%). The most common presentations were chest pain(n = 60;58%), dyspnoea(n = 46;44%), and headache(n = 41;39.4%). Those with atypical subtype more often presented with fluid overload (typical:3% versus atypical:60%); acute pulmonary oedema (35% versus 60%); and cardiogenic shock (22% versus 43%) (all p < 0.05). Six patients (6%) died pre-operatively (typical:8% versus atypical:3%; p = 0.32). Non-fatal pre-operative complications occurred more among those with atypical TCM(p < 0.001), specifically cardiac arrest (typical:5% versus atypical:32%) and respiratory failure (9% versus 24%; both p < 0.05). Overall, 98 underwent surgery, majority undergoing laparoscopic adrenalectomy (81%); similar among the subtypes(p = 0.71). No robust data was provided on short-term outcomes, although two patients suffered from post-operative complications., Conclusion: Although quite similar in presentation to either standalone TCM or PCC, PCC-TCM seems to be associated with a higher degree of morbidity and mortality. The atypical PCC-TCM subgroup seems to have a more severe course with possibly a poorer outcome. Further research is needed to make more reliable inferences., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To investigate the prevalence and magnetic resonance imaging (MRI) phenotype of retinoblastoma-associated orbital cellulitis. Additionally, this study aimed to identify postlaminar optic nerve enhancement (PLONE) patterns differentiating between inflammation and tumor invasion., Design: A monocenter cohort study assessed the prevalence of orbital cellulitis features on MRI in retinoblastoma patients. A multicenter case-control study compared MRI features of the retinoblastoma-associated orbital cellulitis cases with retinoblastoma controls., Participants: A consecutive retinoblastoma patient cohort of 236 patients (311 eyes) was retrospectively investigated. Subsequently, 30 retinoblastoma cases with orbital cellulitis were compared with 30 matched retinoblastoma controls without cellulitis., Methods: In the cohort study, retinoblastoma MRI scans were scored on presence of inflammatory features. In the case-control study, MRI scans were scored on intraocular features and PLONE patterns. Postlaminar enhancement patterns were compared with histopathologic assessment of postlaminar tumor invasion. Interreader agreement was assessed, and exact tests with Bonferroni correction were adopted for statistical comparisons., Main Outcome Measures: Prevalence of retinoblastoma-associated orbital cellulitis on MRI was calculated. Frequency of intraocular MRI features was compared between cases and controls. Sensitivity and specificity of postlaminar optic nerve patterns for detection of postlaminar tumor invasion were assessed., Results: The MRI prevalence of retinoblastoma-associated orbital cellulitis was 6.8% (16/236). Retinoblastoma with orbital cellulitis showed significantly more tumor necrosis, uveal abnormalities (inflammation, hemorrhage, and necrosis), lens luxation (all P &lt; 0.001), and a larger eye size (P = 0.012). The inflammatory pattern of optic nerve enhancement (strong enhancement similar to adjacent choroid) was solely found in orbital cellulitis cases, of which none (0/16) showed tumor invasion on histopathology. Invasive pattern enhancement was found in both cases and controls, of which 50% (5/10) showed tumor invasion on histopathology. Considering these different enhancement patterns suggestive for either inflammation or tumor invasion increased specificity for detection of postlaminar tumor invasion in orbital cellulitis cases from 32% (95% confidence interval [CI], 16-52) to 89% (95% CI, 72-98)., Conclusions: Retinoblastoma cases presenting with orbital cellulitis show MRI findings of a larger eye size, extensive tumor necrosis, uveal abnormalities, and lens luxation. Magnetic resonance imaging contrast-enhancement patterns within the postlaminar optic nerve can differentiate between tumor invasion and inflammatory changes., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Topic: To determine the age up to which children are at risk of trilateral retinoblastoma (TRb) developing, whether its onset is linked to the age at which intraocular retinoblastomas develop, and the lead time from a detectable pineal TRb to symptoms., Clinical Relevance: Approximately 45% of patients with retinoblastoma-those with a germline RB1 pathogenic variant-are at risk of pineal TRb developing. Early detection and treatment are essential for survival. Current evidence is unclear regarding the usefulness of screening for pineal TRb and, if useful, the age up to which screening should be continued., Methods: We conducted a study according to the Meta-analysis of Observational Studies in Epidemiology guidelines for reporting meta-analyses of observational studies. We searched PubMed and Embase between January 1, 1966, and February 27, 2019, for published literature. We considered articles reporting patients with TRb with survival and follow-up data. Inclusion of articles was performed separately and independently by 2 authors, and 2 authors also independently extracted the relevant data. They resolved discrepancies by consensus., Results: One hundred thirty-eight patients with pineal TRb were included. Of 22 asymptomatic patients, 21 (95%) were diagnosed before the age of 40 months (median, 16 months; interquartile range, 9-29 months). Age at diagnosis of pineal TRb in patients diagnosed with retinoblastoma at 6 months or younger versus older than 6 months were comparable (P = 0.44), suggesting independence between the ages at diagnosis of intraocular retinoblastoma and pineal TRb. The laterality of intraocular retinoblastoma and its treatment were not associated with the age at which pineal TRb was diagnosed. The lead time from asymptomatic to symptomatic pineal TRb was approximately 1 year. By performing a screening magnetic resonance imaging scan every 6 months after the diagnosis of heritable retinoblastoma (median age, 6 months) until 36 months of age, at least 311 and 776 scans would be required to detect 1 case of asymptomatic pineal TRb and to save a single life, respectively., Conclusions: Patients with retinoblastoma are at risk of pineal TRb developing for a shorter period than previously assumed, and the age at diagnosis of pineal TRb is independent of the age at diagnosis of retinoblastoma. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) level of evidence for these conclusions remains low., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

This systematic review gives an extensive overview of the current state of functional imaging during (chemo)radiotherapy to predict locoregional control (LRC) and overall survival (OS) for head and neck squamous cell carcinoma. MEDLINE and EMBASE were searched for literature until April 2018 assessing the predictive performance of functional imaging (computed tomography perfusion (CTp), MRI and positron-emission tomography (PET)) within 4 weeks after (chemo)radiotherapy initiation. Fifty-two studies (CTp: n = 4, MRI: n = 19, PET: n = 26, MRI/PET: n = 3) were included involving 1623 patients. Prognostic information was extracted according the PRISMA protocol. Pooled estimation and subgroup analyses were performed for comparable parameters and outcome. However, the heterogeneity of included studies limited the possibility for comparison. Early tumoral changes from (chemo)radiotherapy can be captured by functional MRI and 18 F-FDG-PET and could allow for personalized treatment adaptation. Lesions showed potentially prognostic intratreatment changes in perfusion, diffusion and metabolic activity. Intratreatment ADC mean increase (decrease of diffusion restriction) and low SUV max (persistent low or decrease of 18 F-FDG uptake) were most predictive of LRC. Intratreatment persistent high or increase of perfusion on CT/MRI (i.e. blood flow, volume, permeability) also predicted LRC. Low SUV max and total lesion glycolysis (TLG) predicted favorable OS. The optimal timing to perform functional imaging to predict LRC or OS was 2-3 weeks after treatment initiation., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The feasibility of the liver-first approach for synchronous colorectal liver metastases (CRLM) has been established. We sought to assess the short-term and long-term outcomes for these patients., Methods: Outcomes of patients who underwent a liver-first approach for CRLM between 2005 and 2015 were retrospectively evaluated from a prospective database., Results: Of the 92 patients planned to undergo the liver-first strategy, the paradigm could be completed in 76.1%. Patients with concurrent extrahepatic disease failed significantly more often in completing the protocol (67% versus 21%; p = 0.03). Postoperative morbidity and mortality were 31.5% and 3.3% following liver resection and 30.9% and 0% after colorectal surgery. Of the 70 patients in whom the paradigm was completed, 36 patients (51.4%) developed recurrent disease after a median interval of 20.9 months. The median overall survival on an intention-to-treat basis was 33.1 months (3- and 5-year overall survival: 48.5% and 33.1%). Patients who were not able to complete their therapeutic paradigm had a significantly worse overall outcome (p = 0.03)., Conclusion: The liver-first approach is feasible with acceptable perioperative morbidity and mortality rates. Despite the considerable overall-survival-benefit, recurrence rates remain high. Future research should focus on providing selection tools to enable the optimal treatment sequence for each patient with synchronous CRLM., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: Diagnosing residual malignancy after (chemo)radiotherapy presents a diagnostic challenge because of overlapping symptoms and imaging characteristics. We assessed the added diagnostic value of diffusion-weighted imaging (DWI) to positron emission tomography combined with computed tomography (PET-CT) in patients with head and neck squamous cell carcinoma (HNSCC) with residual fluorodeoxyglucose ( 18 F-FDG) uptake at the primary tumor site 3 months after (chemo)radiotherapy., Study Design: For this retrospective study from January 2010 to June 2012, 22 cases (median patient age of 61 years; range 41-77 years) were included for analysis. Both PET-CT and magnetic resonance imaging (MRI), including DWI, were performed as part of the institutional protocol and were qualitatively assessed for the presence of residual malignancy at the primary tumor site., Results: The sensitivity and specificity of PET-CT were 100% and 47%, respectively. For DWI, sensitivity and specificity were 80% and 82%, respectively. When DWI was added to PET-CT with residual 18 F-FDG uptake, and only a positive read on both PET-CT and DWI was considered to be overall positive, sensitivity remained 80% (95% confidence interval [CI] 28%-99%), and specificity was 88% (95% CI 64%-99%)., Conclusions: In this pilot study of the selected patients with residual 18 F-FDG uptake at the primary tumor site 3 months after (chemo)radiotherapy, we demonstrated that the addition of DWI to PET-CT has the potential to increase the specificity of the response evaluation with limited decrease in sensitivity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Intravoxel incoherent motion (IVIM) imaging is increasingly applied in the assessment of head and neck cancer (HNC). Our purpose was to determine the diagnostic and prognostic performance of IVIM in HNC by performing a critical review of the literature. Pubmed and EMBASE were searched until May 2016. Study and patients characteristics, imaging protocol and diagnostic or prognostic outcomes were extracted by 2 independent reviewers. The studied IVIM parameters were diffusion coefficient (D), pseudodiffusion coefficient (D∗), and perfusion fraction (f). We included 10 diagnostic studies, 5 prognostic studies and 2 studies assessing both. Studies were very heterogeneous in terms of applied b-values, imaging protocols, outcome measurements and reference standards; therefore we did not perform a meta-analysis. The most commonly used sequence was "spin-echo planar imaging". A median of 10.5 b-values (range, 3-17) were used. All but three studies included at least 4 b-values below b=200s/mm 2 . By combining IVIM-parameters squamous cell carcinomas, lymphomas, malignant salivary gland tumors, Warthin's tumors and pleomorphic adenomas could be differentiated with a sensitivity of 85-87% and specificity of 80-100%. Low pre-treatment D or f and an increase in D during treatment were associated with a favorable response to treatment. D∗ appeared to be the parameter with the lowest prognostic value. Future research should focus on finding the optimal IVIM protocol, using uniformly accepted study methods and larger patient populations., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Orbital tumor recurrence is a rare but serious complication in children with retinoblastoma, leading to a high risk of metastasis and death. Therefore, we assume that these recurrences have to be detected and treated as early as possible. Preliminary studies used magnetic resonance imaging (MRI) to evaluate postsurgical findings in the orbit. In this study, we assessed the diagnostic accuracy of high-resolution MRI to detect orbital tumor recurrence in children with retinoblastoma in a large study cohort., Design: Consecutive retrospective study (2007-2013) assessing MRI findings after enucleation., Participants: A total of 103 MRI examinations of 55 orbits (50 children, 27 male/23 female, mean age 16.3±12.4 months) with a median time of 8 months (range, 0-93) after enucleation for retinoblastoma., Methods: High-resolution MRI using orbital surface coils was performed on 1.5 Tesla MRI systems to assess abnormal orbital findings., Main Outcome Measures: Five European experts in retinoblastoma imaging evaluated the MRI examinations regarding the presence of abnormal orbital gadolinium enhancement and judged them as "definitive tumor," "suspicious of tumor," "postsurgical condition/scar formation," or "without pathologic findings." The findings were correlated to histopathology (if available), MRI, and clinical follow-up., Results: Abnormal orbital enhancement was a common finding after enucleation (100% in the first 3 months after enucleation, 64.3% >3 years after enucleation). All histopathologically confirmed tumor recurrences (3 of 55 orbits, 5.5%) were correctly judged as "definitive tumor" in MRI. Two orbits from 2 children rated as "suspicious of tumor" received intravenous chemotherapy without histopathologic confirmation; further follow-up (67 and 47 months) revealed no sign of tumor recurrence. In 90.2%, no tumor was suspected on MRI, which was clinically confirmed during follow-up (median follow-up after enucleation, 45 months; range, 8-126)., Conclusions: High-resolution MRI with orbital surface coils may reliably distinguish between common postsurgical contrast enhancement and orbital tumor recurrence, and therefore may be a useful tool to evaluate orbital tumor recurrence after enucleation in children with retinoblastoma. We recommend high-resolution MRI as a potential screening tool for the orbit in children with retinoblastoma to exclude tumor recurrence, especially in high-risk patients within the critical first 2 years after enucleation., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The transmission of infectious diseases of livestock does not differ in principle from disease transmission in any other animals, apart from that the aim of control is ultimately economic, with the influence of social, political and welfare constraints often poorly defined. Modelling of livestock diseases suffers simultaneously from a wealth and a lack of data. On the one hand, the ability to conduct transmission experiments, detailed within-host studies and track individual animals between geocoded locations make livestock diseases a particularly rich potential source of realistic data for illuminating biological mechanisms of transmission and conducting explicit analyses of contact networks. On the other hand, scarcity of funding, as compared to human diseases, often results in incomplete and partial data for many livestock diseases and regions of the world. In this overview of challenges in livestock disease modelling, we highlight eight areas unique to livestock that, if addressed, would mark major progress in the area., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

This systematic review gives an extensive overview of the current state of perfusion-weighted magnetic resonance imaging (MRI) for head and neck squamous cell carcinoma (HNSCC). Pubmed and Embase were searched for literature until July 2014 assessing the diagnostic and prognostic performance of perfusion-weighted MRI in HNSCC. Twenty-one diagnostic and 12 prognostic studies were included for qualitative analysis. Four studies used a T2(∗) sequence for dynamic susceptibility (DSC)-MRI, 29 studies used T1-based sequences for dynamic contrast enhanced (DCE)-MRI. Included studies suffered from a great deal of heterogeneity in study methods showing a wide range of diagnostic and prognostic performance. Therefore we could not perform any useful meta-analysis. Perfusion-weighted MRI shows potential in some aspects of diagnosing HNSCC and predicting prognosis. Three studies reported significant correlations between hypoxia and tumor heterogeneity in perfusion parameters (absolute correlation coefficient |ρ|>0.6, P<0.05). Two studies reported synergy between perfusion-weighted MRI and positron emission tomography (PET) parameters. Four studies showed a promising role for response prediction early after the start of chemoradiotherapy. In two studies perfusion-weighted MRI was useful in the detection of residual disease. However more research with uniform study and analysis protocols with larger sample sizes is needed before perfusion-weighted MRI can be used in clinical practice., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Currently, resection criteria for colorectal cancer liver metastases (CRCLM) are only limited by remnant liver function. Morbidity and survival after a partial hepatectomy with limited or extended indication criteria were compared., Methods/design: Between 1991 and 2010, patients undergoing a liver resection for CRCLM with limited (n = 169) or extended indication criteria (n = 129) were retrospectively identified in a prospectively collected single-centre database. Limited indication criteria were defined as less than three unilateral, not centrally located liver metastases in the absence of extra hepatic metastases. The extended criteria were only limited by predicted remnant liver volume and patients fitness. Data on co-morbidity, resection margin, short- and long-term morbidity, disease-free (DFS) and overall survival were compared., Results: Patients with limited indications had less major complications (19.5% vs. 33.1%, P < 0.01), longer overall survival of 68.8 months [confidence interval (CI) 46.5-91.1] vs. 41.4 months (CI 33.4-49.0, P ≤ 0.001) and longer median DFS of 22.0 months [confidence interval (CI) 15.8-28.2] vs 10.2 months (CI 8.4-11.9, P < 0.001) compared with the extended indication group. Cure rates, defined as 10-year DFS, were 35.5% and 15.8%, respectively. Fewer patients in the extended indication group underwent an R0 resection (92.9% vs. 77.5%, P < 0.001). Only 17% of all R1 resected patients had recurrences at the transection plane., Conclusion: A partial hepatectomy for CRCLM with extended indications seems justified but is associated with higher complication rates, earlier recurrence and lower overall survival compared with limited indications. However, the median 5-year survival was substantial and a cure was achieved in 15.8% of patients., (© 2013 International Hepato-Pancreato-Biliary Association.)

Purpose: To determine and compare the diagnostic performance of magnetic resonance imaging (MRI) and computed tomography (CT) for the diagnosis of tumor extent in advanced retinoblastoma, using histopathologic analysis as the reference standard., Design: Systematic review and meta-analysis., Participants: Patients with advanced retinoblastoma who underwent MRI, CT, or both for the detection of tumor extent from published diagnostic accuracy studies., Methods: Medline and Embase were searched for literature published through April 2013 assessing the diagnostic performance of MRI, CT, or both in detecting intraorbital and extraorbital tumor extension of retinoblastoma. Diagnostic accuracy data were extracted from included studies. Summary estimates were based on a random effects model. Intrastudy and interstudy heterogeneity were analyzed., Main Outcome Measures: Sensitivity and specificity of MRI and CT in detecting tumor extent., Results: Data of the following tumor-extent parameters were extracted: anterior eye segment involvement and ciliary body, optic nerve, choroidal, and (extra)scleral invasion. Articles on MRI reported results of 591 eyes from 14 studies, and articles on CT yielded 257 eyes from 4 studies. The summary estimates with their 95% confidence intervals (CIs) of the diagnostic accuracy of conventional MRI at detecting postlaminar optic nerve, choroidal, and scleral invasion showed sensitivities of 59% (95% CI, 37%-78%), 74% (95% CI, 52%-88%), and 88% (95% CI, 20%-100%), respectively, and specificities of 94% (95% CI, 84%-98%), 72% (95% CI, 31%-94%), and 99% (95% CI, 86%-100%), respectively. Magnetic resonance imaging with a high (versus a low) image quality showed higher diagnostic accuracies for detection of prelaminar optic nerve and choroidal invasion, but these differences were not statistically significant. Studies reporting the diagnostic accuracy of CT did not provide enough data to perform any meta-analyses., Conclusions: Magnetic resonance imaging is an important diagnostic tool for the detection of local tumor extent in advanced retinoblastoma, although its diagnostic accuracy shows room for improvement, especially with regard to sensitivity. With only a few-mostly old-studies, there is very little evidence on the diagnostic accuracy of CT, and generally these studies show low diagnostic accuracy. Future studies assessing the role of MRI in clinical decision making in terms of prognostic value for advanced retinoblastoma are needed., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Prevalence of, and risk factors for, carriage of extended-spectrum β-lactamase (ESBL) -producing Enterobacteriaceae were determined for 1025 Dutch adults in municipalities with either high or low broiler densities. Overall prevalence of ESBL carriage was 5.1%. The hypothesis that individuals in areas with high broiler densities are at greater risk for ESBL carriage was rejected, as the risk was lower (OR = 0.45; p 0.009) for these individuals. Owning a horse increased the risk (OR = 4.69; p ≤0.0001), but horse owners often owned multiple species of companion animals. Routes of transmission from animals to humans in the community, and the role of poultry in this process, remain to be elucidated., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Background: Sustainability of hepatic glutathione (GSH) homeostasis is an important cellular defense against oxidative stress. Therefore, knowledge of liver GSH status is important. However, measurement of plasma GSH and tissue is difficult due to its instability. Alternatively, ophthalmate (OPH), an endogenous tripeptide analog of GSH, has been suggested as a potential indicator to assess GSH depletion., Aim: To provide an overview of present knowledge with respect to the usefulness of OPH as a biomarker for oxidative stress and hepatic GSH homeostasis., Methods: A systematic, computerized search combined with a cross-reference search of the literature described in PubMed (January 1975 to January 2012) was conducted, key words: 'ophthalmate' and 'ophthalmic acid'., Results: Twenty-two articles were included. Hepatic OPH levels increase inversely proportional to a drop in hepatic GSH in mice with paracetamol (PCM) induced hepatotoxicity. Little is known about the stability of OPH in human plasma. To measure the very low physiological concentrations of plasma OPH, liquid chromatography-mass spectrometry techniques can be employed. OPH synthesis can be measured in humans, using stable isotope labeling with a deuterated water ((2)H2O) load., Conclusion: OPH may be a promising biomarker to indicate hepatic glutathione depletion, but the suggested biological pathways need further unraveling., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

In integrated small-scale aquaculture farming, animal and human excreta maybe used as fish feed and pond fertilizer, thereby enhancing transmission of fish-borne zoonotic trematodes (FZTs) from final hosts, like humans, pigs and chickens, to snails. Areas within a pond could vary in trematode egg-load due to the immediate bordering land, and this might provide implications for control of these trematodes or sampling in field studies measuring FZT prevalence in snails. We therefore estimated the effect of bordering land use on prevalence and FZT burden in snails in different areas within small-scale aquaculture ponds. Nine sampling areas within a pond were assigned in six ponds. For each sampling area, about 120 Melanoides tuberculata snails were collected. Based on land use bordering a sampling area, these were categorized in 5 risk-categories: low-risk (road, rice planted in pond, agriculture, or middle of pond), human access point to pond, livestock sty (pigs or poultry), both human access point and livestock sty, and water connection to canal. In total, 5392 snails were collected. Percentages of snails with parapleurolophocercous cercariae varied between 6% in areas categorized as low-risk and areas with livestock sty only to 15% in areas with both human access point and livestock sty; only this 15% was significantly different from the prevalence in the low-risk category. Percentages of snails with xiphidio cercariae did not differ between risk-categories and varied between 5% and 10%. Mean snail size was 15.2mm, and was significantly associated with both the probability of infection as well as parasite burden. Very small differences in parasite burden were found at different land use areas; the maximum difference was about 11 cercariae. This study demonstrated only small differences between areas surrounding a pond on risk of snails to be infected with fish-borne trematodes within different pond areas. In field studies on FZTs in M. tuberculata snails in ponds, sampling from ponds can therefore be done without considering areas within ponds., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Based on animal experimentations, ophthalmate (OPH) has recently been suggested as a potential plasma biomarker to probe hepatic GSH homeostasis. Up until now, the inability to accurately determine OPH concentrations in human plasma prohibited further studies of OPH metabolism in humans. This study therefore aimed to study the influence of delayed sample preparation on OPH concentrations using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Venous plasma samples from 5 healthy human volunteers were incubated for varying times (5, 30, 60 and 120 min) at temperatures of 4 °C and 37 °C to investigate potential enzymatic degradation. At 37 °C, the decrease in OPH reached significance after 120 min (74.6% (range: 56.2-100.0%; p<0.0001)). At 4 °C, the same trend was observed but did not reach significance. These findings indicate ongoing enzymatic activity, stressing the need for immediate sample deproteinization to obtain reliable plasma concentrations. To investigate the feasibility of the here developed method, baseline arterial plasma values of 21 patients scheduled for partial liver resection were determined to be 0.06±0.03 μmol/l (mean±s.d.). In addition, in pooled samples from 3 patients, an OPH calibration curve was spiked to arterial plasma, arterial whole blood and liver biopsy material, resulting in a linear calibration curve in all cases. Individual measurements of baseline samples revealed that both arterial whole blood and liver biopsy material contained significant levels of endogenous OPH, namely 16.1 (11.8-16.4) μmol/l and 80.0 (191.8-349.2) μmol/kg, respectively. In conclusion, the present LC-MS/MS assay enables the accurate measurement of OPH in human plasma, whole blood and liver biopsies. Freshly prepared samples and immediate deproteinization are mandatory to block enzymatic degradation., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The infection dynamics of Eimeria species determine the clinical manifestation of the disease coccidiosis in poultry flocks, and a better understanding of the dynamics may contribute to improvement of control measures. Our aim was to study the course of infection and the transmission of Eimeria acervulina in groups of broilers by quantifying the transmission rate parameter and oocyst output. Three transmission experiments were carried out with groups of 20 male SPF broilers. At 2 days of age, one bird in each trial was orally inoculated with five sporulated E. acervulina oocysts (D0 post-inoculation, pi). One day after inoculation (D1 pi), the inoculated bird was housed with 19 non-inoculated contact birds. Individual faecal droppings were examined daily from D3-D32 pi to quantify the number of oocysts per gram faeces. The inoculated bird started shedding oocysts at D5 pi and contact birds between D10 and D17 pi. Contact birds that became infected due to oocyst excretion by the inoculated bird were characterized as first generation contact birds (C1). Contact birds excreting from D15 pi onwards (C2) became infected after the first C1 birds had started shedding and were considered to belong to a successive generation of the flock infection. Oocyst output was significantly lower for C1 compared to C2 birds, but the transmission rate parameter remained constant for both infection generations. These results suggest that although oocyst load increases, the transmission rate of E. acervulina remains constant between successive generations of infection in a flock., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: For patients who present with synchronous colorectal carcinoma and colorectal liver metastasis (CRLM), a reversed treatment sequence in which the CRLM are resected before the primary carcinoma has been proposed (liver-first approach). The aim of the present study was to assess the feasibility and outcome of this approach for synchronous CRLM., Methods: Between 2005 and 2010, 22 patients were planned to undergo the liver-first approach. Feasibility and outcomes were prospectively evaluated., Results: Of the 22 patients planned to undergo the liver-first strategy, the approach was completed in 18 patients (81.8%). The main reason for treatment failure was disease progression. Patients who completed treatment and patients who deviated from the protocol had a similar location of the primary tumour, as well as comparable size, number and distribution of CRLM (all P > 0.05). Post-operative morbidity and mortality were 27.3% and 0% following liver resection and 44.4% and 5.6% after colorectal surgery, respectively. On an intention-to-treat-basis, overall 3-year survival was 41.1%. However, 37.5% of patients who completed the treatment had developed recurrent disease at the time of the last follow-up., Conclusions: The liver-first approach is feasible in approximately four-fifths of patients and can be performed with peri-operative mortality and morbidity similar to the traditional treatment paradigm. Patients treated with this novel strategy derive a considerable overall-survival-benefit, although disease-recurrence-rates remain relatively high, necessitating a multidisciplinary approach., (© 2011 International Hepato-Pancreato-Biliary Association.)

Background: As indications for liver resection expand, objective measures to assess the risk of peri-operative morbidity are needed. The impact of sarcopenia on patients undergoing liver resection for colorectal liver metastasis (CRLM) was investigated., Methods: Sarcopenia was assessed in 259 patients undergoing liver resection for CRLM by measuring total psoas area (TPA) on computed tomography (CT). The impact of sarcopenia was assessed after controlling for clinicopathological factors using multivariate modelling., Results: Median patient age was 58 years and most patients (60%) were male. Forty-one (16%) patients had sarcopenia (TPA ≤ 500 mm(2) /m(2) ). Post-operatively, 60 patients had a complication for an overall morbidity of 23%; 26 patients (10%) had a major complication (Clavien grade ≥3). The presence of sarcopenia was strongly associated with an increased risk of major post-operative complications [odds ratio (OR) 3.33; P= 0.008]. Patients with sarcopenia had longer hospital stays (6.6 vs. 5.4 days; P= 0.03) and a higher chance of an extended intensive care unit (ICU) stay (>2 days; P= 0.004). On multivariate analysis, sarcopenia remained independently associated with an increased risk of post-operative complications (OR 3.12; P= 0.02). Sarcopenia was not significantly associated with recurrence-free [hazard ratio (HR) = 1.07] or overall (HR = 1.05) survival (both P > 0.05)., Conclusions: Sarcopenia impacts short-, but not long-term outcomes after resection of CRLM. While patients with sarcopenia are at an increased risk of post-operative morbidity and longer hospital stay, long-term survival is not impacted by the presence of sarcopenia., (© 2011 International Hepato-Pancreato-Biliary Association.)

Heterogeneity in exposure to Eimeria spp. of chickens in a flock will result in differences between individual birds in oocyst output and acquired immunity, which subsequently affects transmission of the parasite in the population. The aim of this study was to quantify effects of previous infection of broilers with Eimeria acervulina on immune responses, oocyst output and transmission. A transmission experiment was carried out with pair-wise housed broilers, that differed in infection history. This "infection history" was achieved by establishment of a primary infection by inoculation of birds with 50,000 sporulated E. acervulina oocysts at day 6 of age ("primed"); the other birds did not receive a primary infection ("naïve"). The actual transmission experiment started at day 24 of age: one bird (I) was inoculated with 50,000 sporulated oocysts and was housed together with a non-inoculated contact bird (C). Oocyst excretion and parameters describing transmission, i.e. the number of infected C birds and time passed before start of excretion of C birds, were determined from day 28 to day 50 for six pairs of four different combinations of I and C birds (I-C): naïve-naïve, naïve-primed, primed-naïve and primed-primed. Immune parameters, CD4(+), CD8(+), αβTCR(+) and γδTCR(+) T cells and macrophages in duodenum, were determined in an additional 25 non-primed, non-inoculated control birds, and in the naïve-naïve and naïve-primed groups, each group consisting of 25 pairs. Although the numbers of CD4(+) T cells and γδTCR(+) T cells increased after primary infection, none of the immunological cell types provided an indication of differences in infectivity, susceptibility or transmission between birds. Oocyst output was significantly reduced in primed I and C birds. Transmission was reduced most in the primed-primed group, but nonetheless transmission occurred in all groups. This study also showed that acquired immunity significantly reduced oocyst output after inoculation and contact-infection, but not sufficiently to prevent transmission to contact-exposed birds., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: Malignant transformation of hepatocellular adenomas (HCAs) into hepatocellular carcinomas (HCCs) has been reported repeatedly and is considered to be one of the main reasons for surgical treatment. However, its actual risk is currently unknown., Objective: To provide an estimation of the frequency of malignant transformation of HCAs and to discuss its clinical implications., Methods: A systematic literature search was conducted using the following databases: The Cochrane Hepatobiliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE and EMBASE., Results: One hundred and fifty-seven relevant series and 17 case reports (a total of 1635 HCAs) were retrieved, reporting an overall frequency of malignant transformation of 4.2%. Only three cases (4.4%) of malignant alteration were reported in a tumour smaller than 5 cm in diameter., Discussion: Malignant transformation of HCAs into HCCs remains a rare phenomenon with a reported frequency of 4.2%. A better selection of exactly those patients presenting with an HCA with an amplified risk of malignant degeneration is advocated in order to reduce the number of liver resections and thus reducing the operative risk for these predominantly young patients. The Bordeaux adenoma tumour markers are a promising method of identifying these high-risk adenomas., (© 2010 International Hepato-Pancreato-Biliary Association.)

Background: Two-stage hepatectomy has been proposed for patients with bilateral colorectal liver metastases. The present study assesses the feasibility and outcome of two-stage hepatectomy for the treatment of colorectal liver metastases., Methods: From January 1994 to December 2008, 720 patients underwent liver resections at two institutions for colorectal liver metastases. The feasibility and outcomes of two-staged hepatectomies were evaluated., Results: Forty-five patients were eligible for the two-stage approach and both stages were completed in 35 patients (78%). Reasons for failure included disease progression (n= 7), poor performance status (n= 1) and death after the first stage (n= 2). Patients who completed both stages had significantly fewer lesions than patients who failed to complete the second stage (5 vs. 8; P= 0.02). No differences between the two groups were observed with regard to lesion size, receipt of radiofrequency ablation (RFA) or presence of extrahepatic disease. Post-operative morbidity (24% vs. 26%; P= 0.9) and mortality (4% vs. 5%; P= 0.8) was similar between the first and second stages. Median overall survival was 16 months. Three-year survival was significantly worse for patients failing to complete both stages (18%) compared with patients completing both stages (58%) (P < 0.001). Similar survival rates were observed between patients who completed two-stage vs. patients treated with a planned single-stage hepatectomy (58% vs. 53%; P= 0.34)., Conclusion: The two-stage strategy for colorectal liver metastases can be performed with acceptable morbidity and mortality. The second stage will not be feasible in 20-25% of patients. Patients who are able to complete the two-stage approach, however, may have long-term survival comparable to patients treated with a planned single-stage hepatectomy.

Coccidiosis is an economically important disease in chickens, caused by infection with Eimeria species parasites. Diagnosis of coccidiosis is frequently based on oocyst enumeration in pooled faecal samples or litter. In studies on infection dynamics and for monitoring in the field, samples from individual chickens may be more appropriate as these support the determination of infection status of individual birds and more accurately reflect oocyst output at time of sampling. Faecal samples from individual birds can be collected, but the counting procedure limits the number of samples that can be processed and unequivocal microscopic differentiation between Eimeria species is very difficult. A test that overcomes these drawbacks would improve efficiency and quality of the diagnosis. The aim of this study was to compare two methods for Eimeria oocyst quantification in samples from individual birds. A real-time PCR that quantifies oocysts in cloacal swabs (qPCR) and oocyst counts in single droppings were compared to the standard procedure of oocyst counts in bulked 24h faeces. Faecal samples were collected daily from 30 broiler chickens, inoculated with different doses of Eimeria acervulina. The three techniques produced comparable oocyst counts for all inoculation doses. Single dropping counts are applicable for small sample sizes and when a single Eimeria species is used. For larger sample sizes qPCR is preferable as it can be carried out on samples that have been frozen for storage. Furthermore, qPCR can identify and quantify different Eimeria species, which makes it a valuable diagnostic tool for field or experimental work.

In 2001 the epidemics of foot-and-mouth disease virus (FMDV) in Great Britain, The Netherlands and France have shown how fast FMDV may spread between farms. The massive socio-economic impact of these epidemics and the intervention measures taken demonstrate the need for quantitative assessments of the efficacy of candidate intervention strategies. Here we use a mathematical model to describe the spatial transmission of FMDV in The Netherlands and use the Dutch 2001 outbreak data to estimate model parameters. We assess the effect of ring culling strategies using a novel and fast approach producing risk maps, and discuss its consequences for ring vaccination. These risk maps identify both the geographical areas of low risk, where a given intervention strategy is likely to achieve epidemic control within only two or three farm-to-farm infection generations, and high-risk areas, where control is likely to take (much) longer. Our results indicate that certain densely populated livestock areas in the Netherlands remain high-risk areas even for strategies that extend EU minimum measures with culling or vaccination within a ring radius of several kilometres. Depending on an economic assessment, area-wide vaccination might be judged appropriate once an FMDV outbreak would have been confirmed in or close to such a high-density area. The modeling approach developed here could be readily applied to outbreak data for other diseases and in other countries., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: Impaired gaze following is an important hallmark of autism spectrum disorders (ASDs) in clinical settings. Yet, ASD subjects perform normally on laboratory tasks involving gaze shifts. We investigated this contradiction, hypothesizing that impaired gaze following in ASDs is not related to basic impairments in attention orienting but to impaired emotion perception and abnormal processing of spatial frequencies (i.e., local and global information)., Method: We tested 30 high-functioning, school-age children with ASDs and 30 age- and IQ-matched controls on a task involving gaze shifts that cue the location of targets. The cueing faces differed in emotionality and were filtered for different spatial frequencies. We recorded behavioral responses (reaction times) and brain responses (event-related potentials)., Results: ASD subjects performed normally when neutral faces were used. However, emotional faces elicited modified face and gaze cue processing in control subjects, but not in the ASD subjects. Furthermore, the control group was biased toward the use of low spatial frequencies (global information) to process gaze cues, whereas the ASD group was biased toward the use of high spatial frequencies (local information)., Conclusions: We conclude that impaired gaze following in ASDs is related to impaired emotion processing. Moreover, ASD subjects show an abnormal reliance on local information to process gaze cues.

Previous phenotypic selection on residual feed intake (RFI) identified 20 efficient R- chickens and 20 nonefficient R+ chickens. Residual feed intake was defined as the difference between observed feed intake (FI) and expected FI based on metabolic BW and BW gain, and was used as a measure for feed efficiency. Body weight and BW gain were similar for both groups. Feed intake and RFI were significantly higher in R+ birds. It is hypothesized that nonefficient R+ birds are more flexible to divert resources from production processes toward maintenance processes, thus being better capable of handling a bacterial challenge. Chickens of both groups were randomly allocated to immunization with heat-inactivated Salmonella enteritidis bacteria, or inoculation with live Salmonella bacteria. Transportation to the isolation units caused a decrease in FI in R+ birds. This may reflect a particular way of coping with stress in R+ birds. More R+ birds stopped bacterial shedding considering a nonshedding interval of 10 or 11 d (P = 0.041). Nonantigen-specific antibody responses against keyhole limpet hemocyanin (KLH) were higher in R- birds. We conclude that R+ birds are able to keep their metabolism at a higher level, as indicated by higher heart and liver weights, and that Salmonella infection leads to reduced heart, liver, and gizzard weights. Oviduct weight and number of small yellow follicles were reduced in infected birds. Antigen-specific antibody responses were not different between the groups, indicating high priority for this parameter as a life trait. Possible differences in stress susceptibility between efficient and nonefficient chickens need further examination.

According to the resource allocation theory, animals have to make a trade-off between resource-demanding life traits to obtain maximal fitness. Artificial selection toward efficient producing farm animals, however, may have created animals that have an impaired ability to divert resources to maintenance processes, such as responding to immune challenges. Residual feed intake (RFI), defined as the difference between observed feed intake (FI) and expected feed intake based on metabolic BW and growth, was used as a measure for feed efficiency. Individual BW and FI of 352 pullets were recorded weekly from 4 until 14 wk of age to estimate RFI. The top 50 efficient R- and the top 50 nonefficient R+ birds were selected. BW and BW gain in both groups were similar. FI and RFI, however, were significantly higher in R+ birds. Thirty animals out of every group were randomly allocated to 1 of 3 treatments: immunization with keyhole limpet hemocyanin (KLH), Mycobacterium butyricum, or heat-inactivated Salmonella enteritidis bacteria. Antibody titers against KLH, M. butyricum, or Salmonella lipopolysaccharide did not differ between R+ and R- birds. The antibody titer against Salmonella protein was higher in R+ birds. We concluded that a population of chickens from a commercial breed shows considerable variation in RFI. Specific antibody production against KLH, M. butyricum, and S. enteritidis lipopolysaccharide, however, is not influenced by efficiency in terms of RFI. R+ animals may have a higher level of nonantigen specific antibodies, as indicated by the higher antibody response to Salmonella protein.

The presence of Salmonella in chickens is a problem because poultry meat is recognized as a source of human salmonellosis. Fermented feed has characteristics like a high number of lactobacilli and high concentration of lactic acid, which could make chickens less susceptible for infection with Salmonella. Fermented feed might therefore prevent the colonization of chickens with Salmonella. Two studies were performed to quantify the effect of fermented liquid feed on the susceptibility of broilers for Salmonella. The fermented feed was prepared by fermenting a dry broiler feed supplemented with 1.4 parts of water. Lactobacillus plantarum was used for fermentation. The fermented liquid feed (FLF) contained 10(9) to 10(10) cfu lactobacilli per gram, and the pH was 4. Individually housed control chickens and FLF-fed chickens were inoculated with 10(2) to 10(7) cfu Salmonella enteritidis (SE). Colonization was estimated by cloacal swabs and quantitative caecal culture. The proportion of SE-shedding chickens was decreased in FLF-fed chickens. FLF-fed chickens required a longer time after inoculation or a higher inoculation dose to get the same proportion of infected chickens in comparison with dry feed-fed chickens. The level of cecal colonization with Salmonella in the ceca was not different at the end of the experimental period. The results indicate that FLF can hamper the introduction of Salmonella in broiler flocks because the chickens are less susceptible for infection. Fermented liquid feed might therefore be a new hurdle in the strategy to control Salmonella in chicken flocks.

This study characterized the high molecular mass BP180 complex that is observed when unheated sodium dodecyl sulfate extracts of human skin or keratinocytes are subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. In heated extracts BP180 is present as a monomer with a molecular weight of 180 kDa, in unheated extracts BP180 runs at a molecular weight position over 500 kDa. By preincubating the unheated extracts at temperatures between 31 degrees C and 40 degrees C, the high molecular weight complex could be "melted" down to monomeric BP180. Under the conditions employed the T1/2 of the dissociation process was between 35 degrees C and 36 degrees C. The temperature resistance of the high molecular weight complex was used to analyze its molecular composition by performing two-dimensional electrophoresis with a "low-temperature" first dimension step and a "high-temperature" second dimension step. Silver staining and immunoblotting of the two-dimensional gels revealed the high molecular weight complex to be composed of solely BP180, indicating that the complex is the nondissociated homotrimeric form of BP180. The 120 kDa linear IgA dermatosis antigen (LAD-1) is an collagenous anchoring filament protein with homology to the extracellular collagenous part of BP180. Two-dimensional immunoblotting showed that LAD-1, as BP180, is also present as a high molecular mass complex and does not form mixed complexes with BP180.

A method was developed for monitoring the feeding activity of larvae of the midge Chironomus riparius. The egestion rate (mg dry wt feces/mg dry wt larva/h) of the deposit-feeding larvae was measured and used as an indication of the feeding activity. Both the egestion rate and survival of several metal-adapted and reference larvae were measured in five test sediments with various Cd and Zn concentrations. The reference larvae suffered increased mortality in two contaminated sediments by comparison with field-exposed larvae. The feeding of all individuals decreased in the most polluted test sediment but also in another supposedly clean reference sediment. No differences were found in egestion rates between the reference and field-exposed larvae. This observation, however, does not reliably answer the hypothesis whether the feeding activity of the adapted and nonadapted midge larvae differs in metal-contaminated sediments because the data are based on total egestion during the short (96-h) experiment and the progress of feeding was not followed., (Copyright 1998 Academic Press.)

Growth failure is a psychosocial problem for many patients who have undergone renal transplantation. 18 adolescents (mean age 15.6, range 11.3-19.5) with severe growth retardation after renal transplantation were treated with biosynthetic growth hormone (GH) for 2 years. All received prednisone, administered daily or on alternate days, with azathioprine and/or cyclosporin A. 16 were blindly assigned to one of two GH doses (4 vs 8 IU per m2 per day). Growth, bone maturation, renal graft function, plasma insulin-like growth factors, serum binding proteins, and other biochemical parameters were checked regularly. Glomerular filtration rate and effective renal plasma flow were tested with 125I-Thalamate and 131I-Hippuran. Data on growth and glomerular filtration rate during GH treatment were also compared with those of matched non-GH-treated controls. Mean (standard deviation) increment in height after 2 years of GH was 15.7 (5.1) cm, significantly greater (p < 0.0001) than in matched controls, 5.8 (3.4) cm. Results were similar for the two GH dosage groups. Bone maturation was not accelerated. Glomerular filtration rate and effective renal plasma flow did not change significantly. The incidence of a > 25% reduction in glomerular filtration rate over 2 years was not significantly higher in GH-treated patients than in non-GH-treated controls (39% vs 32%, p = 0.97). Although a few patients had deterioration of graft function, we could not find a relation with GH treatment. Our results show that sustained improvement of height can be achieved with GH in severely growth-retarded adolescents after renal transplantation.

The integrin alpha 6 beta 4 is a member of the integrin family of adhesion receptors. The integrin alpha 6 beta 4 is preferentially expressed in stratified squamous epithelia, where it is localized in hemidesmosomes. A reduced number of rudimentary hemidesmosomes is often found in skin from patients with junctional epidermolysis bullosa (JEB). In this study we have investigated the expression of alpha 6 beta 4 in skin specimens of patients with junctional (one non-lethal, two lethal) and dystrophic (two) epidermolysis bullosa, using immunofluorescent (IF) staining with five different monoclonal antibodies against the alpha 6 and beta 4 subunits. The intensity of IF staining of the integrin alpha 6 beta 4 and bullous pemphigoid antigen (BPA) was unreduced along the epidermal basement membrane zone (EBMZ) of all EB patients, compared to that in skin of healthy human controls. However, in the skin of two patients with lethal (Herlitz) JEB, who did not express GB3, IF staining of integrin alpha 6 beta 4 and BPA showed a "stitchy" discontinuous linear pattern along the EBMZ with interruptions at the borders of adjoining basal keratinocytes. The same results were obtained by immunoelectron microscopy. They corresponded with freeze-induced partial cell detachment from the basement membrane at the ultimate baso-lateral edge of the basal keratinocytes in lethal JEB skin. The basal lamellipodia at that location almost completely lacked tonofilaments and hemidesmosomes. Furthermore, in JEB there was a split between the intra- and extracellular epitopes of the integrin alpha 6 beta 4 receptor, whereas the integrin remains intact in salt-split skin. This suggests that the defect is in alpha 6 beta 4 itself or perhaps its ligand.

Stunted growth is a serious problem for children with chronic renal failure (CRF) despite normal endogenous growth hormone secretion and normal or elevated plasma concentrations of insulin-like growth factors (IGF) I and II. Biosynthetic growth hormone (GH) was given to 20 prepubertal children (eleven boys, nine girls; mean age 9.5 years, range 4-16) with CRF and severe growth retardation in a placebo-controlled, double-blind, cross-over trial. 6 months of subcutaneous injection of GH (4 IU/m2 per day) was either preceded or followed by 6 months of placebo injection. The patients had a full examination every 3 months. Sixteen children completed the study. Height velocity improved significantly with GH therapy (p less than 0.0001) and placebo (p less than 0.04), but the GH-induced height-velocity increase exceeded that of placebo by 2.9 cm per 6 months. There was a positive relationship between prestudy height velocity and height-velocity increase. Bone maturation was not affected. GH caused a significant increase in IGF-I and a moderate increase in IGF-II plasma concentrations. The pretreatment elevation of IGF-binding protein-1 decreased by almost 50% during GH therapy, while IGF-binding protein-3 increased significantly in concentration, although this increase was significantly smaller than the GH-induced increase in IGF-I. Fructosamine, lipid, and parathyroid concentrations remained constant. Renal function deterioration did not accelerate. Impressive height-velocity increase can be achieved with GH therapy in children with CRF and growth retardation without changes in renal function. Bone maturation appears unaffected suggesting improved final height. Treatment is best started before growth retardation becomes considerable.

An essential prerequisite for the in situ enumeration of epidermal Langerhans cells (LCs) is the unequivocal identification of the desired cell type. We have examined over 250 cryostat sections of normal human skin to analyze morphologic and methodologic problems underlying the quantification of epidermal LCs, defined by anti-T6 (OKT6) and anti-HLA-DR (OKIal) immunoperoxidase staining. Our findings show that OKT6 reactivity of dendritic processes in cross-sectioned epidermis yields microscopic images which are not easy to analyze objectively. The morphology that we find leads us to categorize dendritic cells into 3 arbitrary types of T6+ LC profiles. In addition we describe criteria for the assessment of OKT6 staining patterns relating to the dendritic state of epidermal LCs. Preliminary quantitative data on this issue are discussed in relation to: epidermal thickness; the thickness of skin tissue sections; and the discrepancy between the number of T6+ and HLA-DR+ LCs. We hope that the principles outlined in this report may serve to overcome potential methodologic problems with quantitation of T6+ epidermal LCs in skin sections.

Recently proposed esterase staining methods for the cytochemical identification of human peripheral blood monocytes and lymphocytes in our hands gave suboptimal results. Cellular purification and recommended fixation procedures appeared to decrease the esterase reactivity of leucocyte preparations. Drying for 12-18 h without further fixation of cytocentrifuge smears was found to produce minimal loss of the staining capacity for 1-naphthyl butyrate esterase in mononuclear cells. It is hoped that the slightly modified procedure meets the need for a simple technique to define mononuclear blood cells for clinical purposes.