A considerable amount of research has claimed that animals’ foraging behaviors display movement lengths with power-law distributed tails, characteristic of Lévy flights and Lévy walks. Though these claims have recently come into question, the proposal that many animals forage using Lévy processes nonetheless remains. A Lévy process does not consider when or where resources are encountered, and samples movement lengths independently of past experience. However, Lévy processes too have come into question based on the observation that in patchy resource environments resource-sensitive foraging strategies, like area-restricted search, perform better than Lévy flights yet can still generate heavy-tailed distributions of movement lengths. To investigate these questions further, we tracked humans as they searched for hidden resources in an open-field virtual environment, with either patchy or dispersed resource distributions. Supporting previous research, for both conditions logarithmic binning methods were consistent with Lévy flights and rank-frequency methods–comparing alternative distributions using maximum likelihood methods–showed the strongest support for bounded power-law distributions (truncated Lévy flights). However, goodness-of-fit tests found that even bounded power-law distributions only accurately characterized movement behavior for 4 (out of 32) participants. Moreover, paths in the patchy environment (but not the dispersed environment) showed a transition to intensive search following resource encounters, characteristic of area-restricted search. Transferring paths between environments revealed that paths generated in the patchy environment were adapted to that environment. Our results suggest that though power-law distributions do not accurately reflect human search, Lévy processes may still describe movement in dispersed environments, but not in patchy environments–where search was area-restricted. Furthermore, our results indicate that search strategies cannot be inferred without knowing how organisms respond to resources–as both patched and dispersed conditions led to similar Lévy-like movement distributions.
Deficits in executive functioning are of great significance in attention-deficit/hyperactivity disorder (ADHD). One of these executive functions, working memory, plays an important role in academic performance and is often seen as the core deficit of this disorder. There are indications that working memory problems and academic performance can be improved by school-oriented interventions but this has not yet been studied systematically. In this study we will determine the short- and long-term effects of a working memory - and an executive function training applied in a school situation for children with AD(H)D, taking individual characteristics, the level of impairment and costs (stepped-care approach) into account.
The study consists of two parts: the first part is a randomised controlled trial with school-aged children (8–12 yrs) with AD(H)D. Two groups (each n = 50) will be randomly assigned to a well studied computerized working memory training ‘Cogmed’, or to the ‘Paying attention in class’ intervention which is an experimental school-based executive function training. Children will be selected from regular -and special education primary schools in the region of Amsterdam, the Netherlands. The second part of the study will determine which specific characteristics are related to non-response of the ‘Paying attention in class’ intervention. School-aged children (8–12 yrs) with AD(H)D will follow the experimental school-based executive function training ‘Paying attention in class’ (n = 175). Academic performance and neurocognitive functioning (primary outcomes) are assessed before, directly after and 6 months after training. Secondary outcome measures are: behaviour in class, behaviour problems and quality of life.
So far, there is limited but promising evidence that working memory – and other executive function interventions can improve academic performance. Little is know about the applicability and generalization effects of these interventions in a classroom situation. This study will contribute to this lack of information, especially information related to real classroom and academic situations. By taking into account the costs of both interventions, level of impairment and individual characteristics of the child (stepped-care approach) we will be able to address treatment more adequately for each individual in the future. Trial registration: Nederlands Trial Register NTR3415.
AD(H)D; School-aged children; Working memory training; Executive function training; Academic performance; Randomised controlled trial
Multiple myeloma (MM) is a heterogeneous plasma cell disorder characterized by genetic abnormalities, including chromosomal translocations, deletions, duplications and genetic mutations. Translocations involving the immunoglobulin heavy chain region at chromosome 14q32 are observed in approximately 40% of patients with MM. Translocation of oncogenes into this region may lead to their increased expression, contributing to disease initiation, disease progression and therapeutic resistance. The t(4;14) translocation is associated with upregulation of the fibroblast growth factor receptor 3 (FGFR3) and the myeloma SET domain protein. Patients with t(4;14) demonstrate an overall poor prognosis that is only partially mitigated by the use of the novel agents bortezomib and lenalidomide; as such, an unmet medical need remains for patients with this aberration. Preclinical studies of inhibitors of FGFR3 have shown promise in t(4;14) MM, and these studies have led to the initiation of clinical trials. Data from these trials will help to determine the clinical utility of FGFR3 inhibitors for patients with t(4;14) MM and may pave the way for personalized medicine in patients with this incurable disease.
multiple myeloma; translocation; t(4;14); FGFR3; MMSET
Objectives. This summary evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-positive patients in Germany. Methods. Retrospective chart analysis of HIV-positive patients, who had been liver-transplanted in Germany between July 1997 and July 2011. Results. 38 transplantations were performed in 32 patients at 9 German transplant centres. The reasons for OLT were end-stage liver disease (ESLD) and/or liver failure due to hepatitis C (HCV) (n = 19), hepatitis B (HBV) (n = 10), multiple viral infections of the liver (n = 2) and Budd-Chiari-Syndrome. In July 2011 19/32 (60%) of the transplanted patients were still alive with a median survival of 61 months (IQR (interquartile range): 41–86 months). 6 patients had died in the early post-transplantation period from septicaemia (n = 4), primary graft dysfunction (n = 1), and intrathoracal hemorrhage (n = 1). Later on 7 patients had died from septicaemia (n = 2), delayed graft failure (n = 2), recurrent HCC (n = 2), and renal failure (n = 1). Recurrent HBV infection was efficiently prevented in 11/12 patients; HCV reinfection occurred in all patients and contributed considerably to the overall mortality. Conclusions. Overall OLT is a feasible approach in HIV-infected patients with acceptable survival rates in Germany. Reinfection with HCV still remains a major clinical challenge in HIV/HCV coinfection after OLT.
Inflammatory events within the intestinal muscularis, including macrophage activation and leukocyte recruitment, have been demonstrated to participate in causing postoperative ileus. Recently, glycine has gained attention due to its beneficial immunomodulatory effects in transplantation, shock and sepsis.
The purpose of this study was to determine if pre-operative glycine administration would attenuate postoperative ileus in rodents.
Muscularis glycine receptors were investigated by immunohistochemistry. Gastrointestinal motility was assessed by in vivo transit distribution histograms with calculated geometric center analysis and jejunal circular smooth muscle contractility in a standard organ bath. The impact of glycine on the muscularis inflammatory responses to surgical manipulation of the intestine were measured by real time PCR, nitric oxide Griess reaction, prostaglandin ELISA, Luminex and histochemistry.
Glycine-gated chloride channels were immunohistochemically localized to muscularis macrophages and postoperative infiltrating leukocytes. Pre-operative glycine treatment significantly improved postoperative gastrointestinal transit and jejunal circular muscle contractility. Pre-operative glycine injection significantly reduced the induction of IL-6, TNF-α, iNOS and ICAM-1 mRNAs, which was associated with the attenuation in postoperative leukocyte recruitment. Nitric oxide and prostanoid release from the postsurgical inflamed muscularis was diminished by glycine. The secretion of the inflammatory proteins IL-6, MCP-1 and MIP-1α were also significantly decreased by glycine pretreatment.
The data indicate that pre-operative glycine reduces postoperative ileus via the early attenuation of primal inflammatory events within the surgically manipulated gut wall. Therapeutic modulation of resident macrophages by glycine is a potential novel pharmacological target for the prevention of postoperative ileus.
Glycine; macrophage; leukocytes; inflammation; postoperative ileus
Accurate determination of tumour size in lung adenocarcinoma with bronchoalveolar features (BAC) is important for the determination of TNM (tumour, nodes, metastasis) scores used in staging, prognosis and therapy response assessment. However, tumour sizes derived using lung window (LW) CT or soft-tissue/mediastinal window (MW) CT often give different results. This study examines which measurement correlates best with actual tumour size and which best identifies advanced disease. This retrospective study included 43 BAC patients who underwent surgical resection with mediastinal lymphadenectomy <4 weeks post CT scan. The largest unidimensional tumour diameter on each CT window was compared with actual histopathological tumour size (HP). LW, MW and HP size measurements and a recently described CT parameter – the modified tumour shadow disappearance rate (mTDR) = (1 – [MW/LW]) – were then used to determine which parameter best discriminated between the presence or absence of advanced disease. There was no difference between HP and LW sizes, but MW significantly underestimated HP size (p<0.0001). Unlike MW (p = 0.01) and mTDR (p = 0.001), neither HP (p = 0.14) nor LW (p = 0.10) distinguished between patients with or without advanced disease. On receiver operating characteristic (ROC) analysis at a cut-off of ≤0.13, the sensitivity and specificity of mTDR for detecting advanced disease were 69% and 89%, respectively. In patients with tumours ≤3 cm, only mTDR remained a significant predictor of advanced disease (p = 0.017), with best cut-off at ≤0.20, giving a sensitivity and specificity of 71% and 94%, respectively. MW better predicts advanced disease than LW and might also need to be recorded for RECIST (response evaluation criteria in solid tumours) assessment for T staging of BAC; however, mTDR appears to be an even better predictor and should also be used.
High levels of fatty acid synthase (FAS) expression have been reported in hormone receptor-positive tumors, including prostate, breast, and ovarian cancers, and its inhibition reduces tumor growth in vitro and in vivo. Similar to other hormone receptor-positive tumor types, meningiomas are progesterone receptor- and estrogen receptor-immunoreactive brain tumors. To define the role of FAS in human meningioma growth control, we first analyzed the FAS expression using a tissue microarray containing 38 meningiomas and showed increased FAS expression in 70% of atypical WHO grade II and anaplastic WHO grade III meningiomas compared with 10% of benign WHO grade I tumors. We next confirmed this finding by real-time PCR and Western blotting. Second, we demonstrated that treatment with the FAS inhibitor, cerulenin (Cer), significantly decreased meningioma cell survival in vitro. Third, we showed that Cer treatment reduced FAS expression by modulating Akt phosphorylation (activation). Fourth, we demonstrated that Cer treatment of mice bearing meningioma xenografts resulted in significantly reduced tumor volumes associated with increased meningioma cell death. Collectively, our data suggest that the increased FAS expression in human meningiomas represents a novel therapeutic target for the treatment of unresectable or malignant meningioma.
fatty acid synthase; meningioma; therapy
The surgical management of cervical spondylodiscitis consists of the resection of the affected disc, the decompression of the cervical spinal cord, followed by the stabilization using an autologous bone graft or a titanium implant combined with a ventral plate fixation. Until now, there were no studies about the practicability and putative safety of PEEK cages in cervical spine infection. Now, we present the history of five patients suffering from neurological deficits and septicemia caused by mono- or bisegmental pyogenic cervical discitis and intraspinal abscess without severe bone destruction. Patients were treated surgically by discectomy, decompression, and ventral spondylodesis. The disc was replaced by a PEEK cage without additional fixation. Progressive bony fusion and complete regression of the inflammatory changes was demonstrated 7–8 months later by a computer assisted tomography and contrast enhanced magnetic resonance imaging, respectively. The vertebral alignment changed minimally; the cages developed only a slight average subsidence. The clinical symptoms improved in all patients significantly. Neck pain or instability was never observed. Nevertheless, prospective investigations of a larger patient series are mandatory. We suppose that the use of PEEK cages represents a potential and safe alternative in the treatment of cervical spondylodiscitis in selected patients.
Cervical spondylodiscitis; Targeted antibiotic therapy; Sepsis; PEEK cage; Stabilization; Decompression
Abdominal surgery results in a molecular and cellular inflammatory response in the intestine, leading to postoperative ileus. It was hypothesised that resident macrophages within the intestinal muscularis have an important role in this local inflammation.
To investigate whether chemical or genetic depletion of resident muscularis macrophages would lead to a reduction in the local inflammation and smooth‐muscle dysfunction.
Two rodent models were used to deplete and inactivate macrophages: (1) a rat model in which resident macrophages were depleted by chlodronate liposomes; (2) a model of mice with osteopetrosis mice, completely lacking the resident muscularis macrophages, used as an additional genetic approach. Animals with normal or altered intestinal macrophages underwent surgical intestinal manipulation. The inflammatory response was investigated by quantitative reverse transcriptase‐polymerase chain reaction for mRNA of MIP‐1α, interleukin (IL)1β, IL6, intracellular adhesion molecule 1 (ICAM‐1) and monocyte chemotractant protein 1 (MCP)‐1 in the isolated small bowel muscularis. In addition, muscularis whole mounts were used for histochemical and immunohistochemical analysis to quantify leucocyte infiltration and detect cytokine expression. Subsequently, in vitro muscle contractility and in vivo gastrointestinal transit were measured.
Both models resulted in markedly decreased expression of MIP‐1α, IL1β, IL6, ICAM‐1 and MCP‐1 after manipulation compared with controls. In addition to this decrease in inflammatory mediators, recruitment of leucocytes into the muscularis was also diminished. Macrophage‐altered animals had near normal in vitro jejunal circular muscle function and gastrointestinal transit despite surgical manipulation.
Resident intestinal muscularis macrophages are initially involved in inflammatory responses resulting in postoperative ileus. Depletion and inactivation of the muscularis macrophage network prevents postoperative ileus.
Calcium ions are highly versatile spacial and temporal intracellular signals of non-excitable cells and have an important impact on nearly every aspect of cellular life controlling cell growth, metabolism, fluid secretion, information processing, transcription, apoptosis, and motility. Neurons and glia respond to stimuli, including neurotransmitters, neuromodulators, and hormones, which increase the intracellular calcium concentration. The function of intracellular calcium in gliomas is unknown. Lots of daily used drugs may act via receptors that can be linked to the intracellular calcium system and therefore could influence glioma biology.
Glioma cells were loaded with the calcium ion sensitive dye Fura 2-AM. Subsequently, cells were stimulated with 25 different medical drugs for 30 s. The increase of free intracellular calcium ions was measured and calculated by a microscope–camera–computer-unit.
Except for the buffer solution HEPES that served as negative control and for the cortisol derivative dexamethasone, all other 24 tested drugs induced a rise of intracellular calcium ions. The cellular calcium responses were classified into seven functional groups. The tested substances activated several types of calcium channels and receptors.
Our study impressively demonstrates that medical drugs are potent inducers of intracellular calcium signals. Totally unexpected, the results show a high amount of functional cellular receptors and channels on glioma cells, which could be responsible for certain biological effects like migration and cell growth. This calcium imaging study proves the usability of the calcium imaging as a screening system for functional receptors on human glioma cells.
Glioma; Calcium imaging; Drugs; Cell-surface receptors; Tumor proliferation; Tumor invasion
Chronic kidney disease is frequent in patients after orthotopic liver transplantation (OLT) and has impact on survival. Patients receiving calcineurin inhibitors (CNI) are at increased risk to develop impaired renal function. Early CNI reduction and concomitant use of mycophenolat mofetil (MMF) has been shown to improve renal function.
The aim of this trial was to compare dose-reduced CNI/MMF versus CNI-free MMF/prednisone-based treatment in stable patients after OLT with respect to glomerular filtration rate (GFR). 21 patients [GFR 44.9 ± 9.9 mL/min/1.73 m2 measured by 99m-Tc-DTPA-clearance, serum creatinine (SCr) 1.5 ± 0.42 mg/dL] were randomized either to exchange CNI for 10 mg prednisone (group 1; n = 8) or to receive CNI at 25% of the initial dose (group 2; n = 13) each in combination with 1000 mg MMF b.i.d.
At month 12 mean SCr (-0.3 ± 0.4 mg/dL, p = 0.031) and GFR improved (8.6 ± 13.1 mL/min/1.73 m2, p = 0.015) in group 2 but remained unchanged in group 1. Main side effects were gastroinstestinal symptoms (14.3%) and infections (4.8%). Two biopsy proven, steroid-responsive rejections occurred. In group 1 mean diastolic blood pressure (BP) increased by 11 ± 22 mmHg (p = 0.03).
Reduced dose CNI in combination with MMF but not CNI-free-immunosuppression leads to improvement of GFR in patients with moderately elevated SCr levels after OLT. Addition of steroids resulted in increased diastolic blood pressure presumably counterbalancing the benefits of CNI withdrawal on renal function.
calcineurin inhibitor; GFR; impaired renal function; liver transplantation; mycophenolate mofetil
We investigated the incidence of, outcome from and possible risk factors for readmission to the surgical intensive care unit (ICU) at Friedrich Schiller University Hospital, Jena, Germany.
We conducted an analysis of prospectively collected data from all patients admitted to the postoperative ICU between September 2004 and July 2006.
Of 3169 patients admitted to the ICU during the study period, 2852 were discharged to the hospital floor and these patients made up the study group (1828 male (64.1%), mean patient age 62 years). The readmission rate was 13.4% (n = 381): 314 (82.4%) were readmitted once, 39 (10.2%) were readmitted twice and 28 (7.3%) were readmitted more than twice. The first readmission to the ICU occurred within a median of seven days (range 5 to 14 days). Patients who were readmitted to the ICU had a higher simplified acute physiology II score (37 +/- 16 versus 33 +/- 16; p < 0.001) and sequential organ failure score (6 +/- 3 versus 5 +/- 3; p = 0.001) on initial admission to the ICU than those who were not readmitted. In-hospital mortality was significantly higher in patients readmitted to the ICU (17.1% versus 2.9%; p < 0.001) than in other patients. In a multivariate analysis, age (odds ratio (OR) = 1.13 per 10 years; 95% confidence interval (CI) = 1.03 to 1.24; p = 0.04), maximum sequential organ failure score (OR = 1.04 per point; 95% CI = 1.01 to 1.08; p = 0.04) and C-reactive protein levels on the day of discharge to the hospital floor (OR = 1.02; 95% CI = 1.01 to 1.04; p = 0.035) were independently associated with a higher risk of readmission to the ICU.
In this group of surgical ICU patients, readmission to the ICU was associated with a more than five-fold increase in hospital mortality. Older age, higher maximum sequential organ failure score and higher C-reactive protein levels on the day of discharge to the hospital floor were independently associated with a higher risk of readmission to the ICU.
OBJECTIVE—This study examined whether neighbourhood level socioeconomic variables have an independent effect on reported child behaviour problems over and above the effect of individual level measures of socioeconomic status.
DESIGN AND SETTING—Multilevel analysis of cross sectional survey data relating individual level child behavioural problems and parental measures of socioeconomic status with neighbourhood level measures of socioeconomic deprivation in the city of Maastricht, the Netherlands.
PARTICIPANTS—Children born in the years 1990-1991 attending the second grade of normal kindergarten schools in the city of Maastricht, the Netherlands. Out of 1417 eligible 5-7 year olds, the parents of 734 children (51.8%) agreed to participate.
MAIN RESULTS—Child behaviour problems were more frequent in families of low parental occupation and education (F=14.51, df 3, 721, p<0.001; F=12.20, df 3, 721, p<0.001, respectively) and in families living in deprived neighbourhoods (F=13.26, df 2, 722, p<0.001). Multilevel random effects regression analysis showed that the effect of neighbourhood level deprivation remained after adjustment for individual level socioeconomic status (B over three levels of deprivation: 1.36; 95%CI=0.28, 2.45).
CONCLUSIONS—Living in a more deprived neighbourhood is associated with higher levels of child problem behaviour, irrespective of individual level socioeconomic status. The additional effect of the neighbourhood may be attributable to contextual variables such as the level of social cohesion among residents.
Keywords: neighbourhood deprivation; behaviour problems; multilevel regression analysis
Positron emission tomography in combination with the newly introduced catecholamine analogue [11C]hydroxyephedrine ([11C]HED) enables the noninvasive delineation of sympathetic nerve terminals of the heart. To address the ongoing controversy over possible reinnervation of the human transplant, 5 healthy control subjects and 11 patients were studied after cardiac transplant by this imaging approach. Regional [11C]HED retention was compared to regional blood flow as assessed by rubidium-82. Transplant patients were divided into two groups. Group I had recent (less than 1 yr, 4.4 +/- 2.3 mo) surgery, while group II patients underwent cardiac transplantation more than 2 yr before imaging (3.5 +/- 1.3 yr). [11C]HED retention paralleled blood flow in normals, but was homogeneously reduced in group I. In contrast, group II patients revealed heterogeneous [11C]HED retention, with increased uptake in the proximal anterior and septal wall. Quantitative evaluation of [11C]HED retention revealed a 70% reduction in group I and 59% reduction in group II patients (P less than 0.001). In group II patients, [11C]HED retention reached 60% of normal in the proximal anterior wall. These data suggest the presence of neuronal tissue in the transplanted human heart, which may reflect regional sympathetic reinnervation.
We examined the effect of different sediment types on the staining effectiveness of the fluorochrome DAPI (4′-6-diamidino-2-phenylindole dihydrochloride) over a wide range of concentrations and on the masking effect of sediment particles on DAPI-stained bacteria. Sediment type greatly affects the staining efficiency of DAPI, and most published studies seem to have underestimated bacterial abundances by using suboptimal concentrations of the fluorochrome. A DAPI concentration of 5 μg ml−1 is required to effectively stain the bacteria in most sediments that can be sampled with a gravity corer. When the sediments are diluted 687 times (a dilution factor similar to those most often used in the literature), sediment particle masking of stained bacteria is highly variable for different sediment types. By using a measure of turbidity (A750) to indicate masking and the quartz-corrected water content as a measure of the initial (in situ) dilution of each sediment type, it becomes possible to show a linear relationship between masking and the integrated (initial × experimental) dilution of various sediments. This relationship allows the development of a correction procedure for masking which makes accurate and unbiased counts possible. Data so obtained show a strong relationship between bacteria (cells per milliliter of fresh sediment) and sediment organic matter (grams [dry weight] per milliliter of fresh sediment), one that is not discernable without the correction. The proposed method of staining and correction for sediment masking provides the basis for a standardized interpretation of sediment bacterial counts.
An earlier study of 25 patients who were investigated by radionuclide angiography after a Mustard procedure showed that they had had evidence of right and left ventricular dysfunction at rest and with exercise. Twenty one (mean age 17.0 years (range 13.7-20.6) 11 female patients) of the original 25 patients were followed up a mean of 4.3 years later (mean 14.6 years (range 12.5-16.0) after the procedure). The group means for resting right and left ventricular ejection fraction and exercise response were not significantly different from those reported five years before. Individual changes in values were within the normal variation seen in serial studies. This long term longitudinal follow up of patients after the Mustard operation showed that although some patients still had right and left ventricular dysfunction, resting ventricular function and exercise response remained stable over a five year period. This preservation of cardiac function may contribute to the long term survival of patients after the Mustard procedure.
Neighboring genes encoding the mouse sex-limited protein (Slp) and fourth component of complement (C4) show extensive homology. In contrast to C4, however, Slp is regulated by androgen. One region of the Slp gene capable of hormonal response following transfection was located about 2 kilobases upstream of the transcription start site, where the C4 and Slp sequences diverge. This region, delimited here to a 0.75-kilobase fragment, showed cryptic promoter activity as well as androgen responsiveness in either orientation in front of the bacterial chloramphenicol acetyltransferase coding region. When this fragment was placed upstream of a viral long terminal repeat, increased chloramphenicol acetyltransferase expression derived from the viral promoter. Proteins from nuclear extracts specifically bound to four sequences within the region, near sites that are DNase I hypersensitive in vivo and reflect the hormonal and developmental regulation of Slp. Like several other cellular enhancers, this androgen-responsive element seems to be modular in nature and complex in its function.
Genes of the mouse S locus encoding C4 (the fourth component complement) and Slp (sex-limited protein) show extensive homology but are distinct in their function and regulation. In some mouse strains, such as B10.D2, Slp is androgen regulated, whereas in others, such as B10.W7R, expression of Slp is constitutive. We have previously shown that the B10.W7R strain has multiple Slp genes. In this report, we present the structure of the single C4 and four Slp genes of the B10.W7R S locus and compare the upstream flanking regions by partial sequence analysis and function in transfection assays. Of the four Slp genes, three (Slpw7.A, Slpw7.B, and Slpw7.C) have upstream and promoter regions very similar to those of C4. The fourth Slp gene (Slpw7.D) is instead virtually identical to the androgen-regulated allele (Slpd from the B10.D2 mouse) in upstream regions. In particular, far-upstream sequences from both Slpd and Slpw7.D render the bacterial chloramphenicol acetyltransferase gene hormonally responsive upon transfection into mammary carcinoma cell lines. The upstream sequences between 2 to 3 kilobases of the Slp promoter initiate transcription from multiple sites when fused proximal to the chloramphenicol acetyltransferase gene, and these transcripts are threefold more abundant in the presence of androgen. This behavior is similar for Slpd and Slpw7.D, which suggests that Slpw7.D may be androgen regulated but that this is masked in vivo by constitutive expression of the other Slp genes. Nonhomologous recombination is implicated not only in expanding the copy number of C4 and Slp genes in the B10.W7R mouse but also in creating hybrid genes with regulatory features of C4 and structural features of Slp.
Radionuclide studies were performed to determine pulmonary blood flow in six children who had undergone surgery for pulmonary atresia, ventricular septal defect, and hypoplastic pulmonary arteries with or without major aortopulmonary collateral arteries. Lung blood flow was assessed from both particle perfusion lung scans and the pulmonary and systemic phase of a radionuclide dynamic flow study. Five patients had perfusion defects identified on the particle perfusion lung scan. In three of these, abnormal areas were perfused only during the systemic phase of the flow study, a combination of findings that indicate the presence of perfusion by collateral arteries. In one patient no systemic perfusion was noted and in one an initial particle perfusion study indicated the presence of a lung segment perfused by a collateral artery. In this last patient the particle perfusion scan after total correction showed a reduction in the size of the lung perfusion defect and no evidence of lung perfusion during the systemic phase of the flow study. The particle perfusion lung scan in the sixth patient showed pronounced asymmetry in blood flow to the lungs with no segmental perfusion defect on the particle perfusion scan and no abnormalities on the systemic flow study. It is concluded that radionuclide lung perfusion and flow studies provide useful information on lung perfusion and merit further evaluation to define their role in the management of these patients.