Patients with resolution of low-lying placenta and placenta previa remain at increased risk of postpartum hemorrhage.

OBJECTIVE: To determine whether women who experience resolution of low placentation (low-lying placenta or placenta previa) are at increased risk of postpartum hemorrhage compared to those with normal placentation throughout pregnancy. METHODS: This was a retrospective cohort study of women who delivered at Mount Sinai Hospital between 2015 and 2019, and who were diagnosed with low-lying placenta or placenta previa on transvaginal ultrasound at the time of the second-trimester anatomical survey, with resolution of low placentation on subsequent ultrasound examination. Women undergoing second-trimester anatomical survey who had normal placentation on transvaginal ultrasound 3 days before or after the cases were randomly identified for comparison. The primary outcome was the rate of postpartum hemorrhage. Secondary outcomes included the need for a blood transfusion, use of additional uterotonic medication, the need for additional procedures to control bleeding, and maternal admission to the intensive care unit. Outcomes were assessed using a multivariable logistic regression model. RESULTS: A total of 1256 women were identified for analysis, of whom 628 had resolved low placentation and 628 had normal placentation. Women with resolved low placentation, compared to those with normal placentation throughout pregnancy, had significantly higher mean age (33.0 ± 5.4 years vs 31.9 ± 5.5 years; P < 0.01) and lower mean body mass index at delivery (27.9 ± 5.5 kg/m2 vs 30.2 ± 5.7 kg/m2 ; P < 0.01), and were more likely to have undergone in-vitro fertilization, be of non-Hispanic white race, have posterior placental location (all P < 0.01) and have private/commercial health insurance (P = 0.04). Patients with resolved low placentation vs normal placentation had greater odds of postpartum hemorrhage (adjusted odds ratio (aOR), 3.5 (95% CI, 2.0-6.0); P < 0.01), use of additional uterotonic medication (aOR, 2.2 (95% CI, 1.5-3.1); P < 0.01) and increased rates of additional procedures to control bleeding (aOR, 4.0 (95% CI, 1.3-11.9); P = 0.01). CONCLUSION: Despite high rates of resolution of low-lying placenta and placenta previa by term, women with resolved low placentation remain at increased risk of postpartum hemorrhage compared to those with normal placentation throughout pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Close Cassini flybys of Saturn's ring moons Pan, Daphnis, Atlas, Pandora, and Epimetheus.

Saturn's main ring system is associated with a set of small moons that either are embedded within it or interact with the rings to alter their shape and composition. Five close flybys of the moons Pan, Daphnis, Atlas, Pandora, and Epimetheus were performed between December 2016 and April 2017 during the ring-grazing orbits of the Cassini mission. Data on the moons' morphology, structure, particle environment, and composition were returned, along with images in the ultraviolet and thermal infrared. We find that the optical properties of the moons' surfaces are determined by two competing processes: contamination by a red material formed in Saturn's main ring system and accretion of bright icy particles or water vapor from volcanic plumes originating on the moon Enceladus.

Alternaria alternata challenge at the nasal mucosa results in eosinophilic inflammation and increased susceptibility to influenza virus infection.

BACKGROUND: Eosinophils in the nasal mucosa are an elemental feature of allergic rhinitis. OBJECTIVE: Our objective was to explore eosinophilic inflammation and its impact on respiratory virus infection at the nasal mucosa. METHODS: Inflammation in the nasal mucosae of mice was evaluated in response to repetitive stimulation with strict intranasal volumes of a filtrate of Alternaria alternata. Mice were then challenged with influenza virus. RESULTS: Repetitive stimulation with A. alternata resulted in eosinophil recruitment to the nasal passages in association with elevated levels of IL-5, IL-13 and eotaxin-1; eosinophil recruitment was diminished in eotaxin-1-/- mice, and abolished in Rag1-/- mice. A. alternata also resulted in elevated levels of nasal wash IgA in both wild-type and eosinophil-deficient ∆dblGATA mice. Interestingly, A. alternata-treated mice responded to an influenza virus infection with profound weight loss and mortality compared to mice that received diluent alone (0% vs 100% survival, ***P < .001); the lethal response was blunted when A. alternata was heat-inactivated. Minimal differences in virus titre were detected, and eosinophils present in the nasal passages at the time of virus inoculation provided no protection against the lethal sequelae. Interestingly, nasal wash fluids from mice treated with A. alternata included more neutrophils and higher levels of pro-inflammatory mediators in response to virus challenge, among these, IL-6, a biomarker for disease severity in human influenza. CONCLUSIONS AND CLINICAL RELEVANCE: Repetitive administration of A. alternata resulted in inflammation of the nasal mucosae and unanticipated morbidity and mortality in response to subsequent challenge with influenza virus. Interestingly, and in contrast to findings in the lower airways, eosinophils recruited to the nasal passages provided no protection against lethal infection. As increased susceptibility to influenza virus among individuals with rhinitis has been the subject of several clinical reports, this model may be used for further exploration of these observations.

Eosinophil persistence in vivo and sustained viability ex vivo in response to respiratory challenge with fungal allergens.

BACKGROUND: Eosinophils are immunomodulatory leucocytes that contribute to the pathogenesis of Th2-driven asthma and allergic lung diseases. OBJECTIVE: Our goal was to identify unique properties of eosinophils recruited to the lungs and airways of mice in response to challenge with asthma-associated fungal allergens. METHODS: Mice were challenged intranasally on days 0, 3 and 6 with a filtrate of Alternaria alternata. Recruited eosinophils were enumerated in bronchoalveolar lavage fluid. Eosinophils were also isolated from lungs of mice sensitized and challenged with Aspergillus fumigatus and evaluated ex vivo in tissue culture. RESULTS: Eosinophils persist in the airways for several weeks in response to brief provocation with A. alternata in wild-type, Gm-csf- and eotaxin-1-gene-deleted mice, while eosinophils are recruited but do not persist in the absence of IL-13. Eosinophils isolated from the lungs A. alternata-challenged mice are cytokine-enriched compared to those from IL5tg mice, including 800-fold higher levels of eotaxin-1. Furthermore, eosinophils from the lungs and spleen of fungal allergen-challenged wild-type mice are capable of prolonged survival ex vivo, in contrast to eosinophils from both untreated and fungal allergen-challenged IL5tg mice, which undergo rapid demise in the absence of exogenous cytokine support. TNF-α (but not IL5, IL-3, eotaxin-1 or GM-CSF) was detected in supernatants of ex vivo eosinophil cultures from the lungs of fungal allergen-challenged wild-type mice. However, neither TNF-α gene deletion nor anti-TNF-α neutralizing antibodies had any impact sustained eosinophil survival ex vivo. CONCLUSION AND CLINICAL RELEVANCE: Eosinophils are phenotypically and functionally heterogeneous. As shown here, eosinophils from fungal allergen-challenged wild-type mice maintain a distinct cytokine profile, and, unlike eosinophils isolated from IL5tg mice, they survive ex vivo in the absence of exogenous pro-survival cytokine support. As treatments for asthma currently in development focus on limiting eosinophil viability via strategic cytokine blockade, the molecular mechanisms underlying differential survival merit further investigation.

Fatty liver disease, glucose tolerance and insulin resistance in obese adolescents.

BACKGROUND/OBJECTIVES: Adult studies suggest that intra-hepatic fat predicts 2-h blood glucose levels and type 2 diabetes, and may have a role in the development of insulin resistance. Our study objective was to explore relationships between intra-hepatic fat and (i) blood glucose levels and (ii) insulin resistance determined by homeostasis model assessment (HOMA) in a group of obese adolescents. METHODS: Subjects were 61 obese non-diabetic male and female volunteers aged 12-18 years inclusive with a body mass index >95th percentile for age and 2-h blood glucose <200 mg dL(-1) . Each subject underwent 2-h glucose tolerance testing and measurement of haemoglobin A1c, ultrasensitive C-reactive protein and fasting insulin. Visceral, subcutaneous abdominal and intra-hepatic fat were determined by magnetic resonance imaging. Intra-hepatic fat was measured by gradient echo chemical shift imaging. RESULTS: Alanine aminotransferase levels and hepatic phase difference were not significant correlates of fasting or 2-h glucose. In a multiple regression model including hepatic phase difference and visceral fat volume, visceral fat volume was the sole predictor of HOMA. CONCLUSIONS: This study provides no support to the notion that intra-hepatic fat has a role in the regulation of fasting blood glucose, 2-h postprandial blood glucose or systemic insulin resistance.

Early atherogenesis and visceral fat in obese adolescents.

BACKGROUND/OBJECTIVES: Little information is available as to the cause of increased thickening of the intima-media of the carotid artery (cIMT) in the pediatric population. Therefore, cIMT was compared in obese adolescents and normal-weight controls, and associations between cIMT and lipid and non-lipid cardiovascular risk factors were assessed. SUBJECTS/METHODS: Subjects included 61 obese non-diabetic male and female volunteers aged 12-18 years inclusive with a body mass index (BMI) >95th percentile for age and 2-h blood glucose <200 mg dl(-1) matched to 25 normal-weight control volunteers with normal glucose levels. Each subject underwent a 2-h glucose tolerance test and measurement of hemoglobin A1c, ultrasensitive C-reactive protein, fasting insulin, blood lipids, visceral, subcutaneous abdominal and hepatic fat, and cIMT. RESULTS: Maximum cIMT was 0.647±0.075 mm in the obese subjects versus 0.579±0.027 mm in normal-weight controls (P<0.001). There was no difference in maximum cIMT between male and female subjects. There were significant correlations between maximum cIMT and BMI z-score, 2-h glucose, fasting insulin, homeostasis model assessment (HOMA), total low-density lipoprotein (LDL) cholesterol, very LDL cholesterol, high-density lipoprotein (HDL) cholesterol, HDL2 cholesterol, HDL3 cholesterol, triglycerides, remnant lipoprotein cholesterol, intermediate-density lipoprotein cholesterol, lipoprotein(a), apoprotein B100, abdominal subcutaneous fat volume, visceral fat volume and hepatic phase difference. On multiple regression analysis, visceral fat was the most significant predictor of maximum cIMT. Two-hour blood glucose, HOMA and systolic blood pressure were also significant predictors of maximum cIMT. CONCLUSIONS: cIMT was increased in the obese adolescents compared with the normal-weight-matched controls. Visceral fat was a key predictor of arterial wall thickening in these subjects. The results suggest that the focus of cardiovascular disease prevention in the adolescent obese should be visceral obesity, and not blood lipids or lipid subclasses.

Inhibition of hepatocyte autophagy increases tumor necrosis factor-dependent liver injury by promoting caspase-8 activation.

Recent investigations have demonstrated a complex interrelationship between autophagy and cell death. A common mechanism of cell death in liver injury is tumor necrosis factor (TNF) cytotoxicity. To better delineate the in vivo function of autophagy in cell death, we examined the role of autophagy in TNF-induced hepatic injury. Atg7Δhep mice with a hepatocyte-specific knockout of the autophagy gene atg7 were generated and cotreated with D-galactosamine (GalN) and lipopolysaccharide (LPS). GalN/LPS-treated Atg7Δhep mice had increased serum alanine aminotransferase levels, histological injury, numbers of TUNEL (terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling)-positive cells and mortality as compared with littermate controls. Loss of hepatocyte autophagy similarly sensitized to GalN/TNF liver injury. GalN/LPS injury in knockout animals did not result from altered production of TNF or other cytokines. Atg7Δhep mice had accelerated activation of the mitochondrial death pathway and caspase-3 and -7 cleavage. Increased cell death did not occur from direct mitochondrial toxicity or a lack of mitophagy, but rather from increased activation of initiator caspase-8 causing Bid cleavage. GalN blocked LPS induction of hepatic autophagy, and increased autophagy from beclin 1 overexpression prevented GalN/LPS injury. Autophagy, therefore, mediates cellular resistance to TNF toxicity in vivo by blocking activation of caspase-8 and the mitochondrial death pathway, suggesting that autophagy is a therapeutic target in TNF-dependent tissue injury.

Inflammatory responses to respiratory syncytial virus (RSV) infection and the development of immunomodulatory pharmacotherapeutics.

Respiratory syncytial virus (RSV; Family Paramyxoviridae, Genus Pneumovirus) is a major respiratory pathogen of infants and children and an emerging pathogen of the elderly. Current management of RSV disease includes monoclonal antibody prophylaxis for infants identified as high risk and supportive care for those with active infection; there is no vaccine, although several are under study. In this manuscript, we review published findings from human autopsy studies, as well as experiments that focus on human clinical samples and mouse models of acute pneumovirus infection that elucidate basic principles of disease pathogenesis. Consideration of these data suggests that the inflammatory responses to RSV and related pneumoviral pathogens can be strong, persistent, and beyond the control of conventional antiviral and anti-inflammatory therapies, and can have profound negative consequences to the host. From this perspective, we consider the case for specific immunomodulatory strategies that may have the potential to alleviate some of the more serious sequelae of this disease.

Eosinophil-derived neurotoxin / RNase 2: connecting the past, the present and the future.

The eosinophil-derived neurotoxin (EDN, also known as eosinophil protein-X) is best-known as one of the four major proteins found in the large specific granules of human eosinophilic leukocytes. Although it was named for its discovery and initial characterization as a neurotoxin, it is also expressed constitutively in human liver tissue and its expression can be induced in macrophages by proinflammatory stimuli. EDN and its divergent orthologs in rodents have ribonuclease activity, and are members of the extensive RNase A superfamily, although the relationship between the characterized physiologic functions and enzymatic activity remains poorly understood. Recent explorations into potential physiologic functions for EDN have provided us with some insights into its role in antiviral host defense, as a chemoattractant for human dendritic cells, and most recently, as an endogenous ligand for toll-like receptor (TLR)2.

Valor de la biopsia prostática contemporánea durante prostatectomía radical / Contemporary prostatic biopsy value during radical prostatectomy

La presencia de márgenes positivos en la pieza quirúrgica es un factor pronóstico adverso. La realización de biopsia rápida prostática y resección de los márgenes comprometidos durante prostatectomía radical (PR) podría mejorar el pronóstico de los pacientes. El objetivo de este trabajo es estudiar la relevancia de la biopsia contemporánea y la resección de los márgenes comprometidos durante PR. Material y Métodos: De una serie de 442 pacientes pT2, operados entre abril de 1997 y septiembre de 2004, se seleccionaron al azar 53 pacientes con márgenes (-) y 56 pacientes con márgenes (+). De este último grupo, a 31 pacientes se les realizó biopsia prostática rápida y resección de los márgenes comprometidos, y a los 25 restantes no. Todos los pacientes cuentan con un seguimiento de al menos 12 meses. Se comparó sobrevida libre de enfermedad por medio de curvas de Kaplan-Meier. Resultados: De los 53 pacientes con márgenes (-), 5 (9,4 por ciento) presentaron recurrencia bioquímica a los 18,8 meses promedio; de los 31 pacientes a quienes se les realizó biopsia rápida y re-resección, 7 (22,5 por ciento) presentaron recurrencia bioquímica a los 23,2 meses promedio, en cambio, en el grupo con márgenes (+) y sin biopsia rápida, 11 (44 por ciento) presentaron recurrencia bioquímica en un tiempo promedio de 6,9 meses. Al comparar las curvas de sobrevida libre de enfermedad se observa una diferencia estadísticamente significativa (P=0,017) entre el grupo con re-resección de márgenes v/s el que no la tenía. Conclusión: La resección de los márgenes comprometidos en pacientes con biopsia rápida positiva, se asocia a una sobrevida libre de enfermedad mayor que cuando no se realiza.

Introduction: Positive margin in surgical piece is an adverse prognosis factor. A soon prostate biopsy andinvolved margins resection during radical prostatectomy (RP) could improve prognosis. The purpose of thiswork is to study the contemporary biopsy relevance and the resection of the involved margins during RP.Material and methods: 53(-) margins patients and 56 (+) margins patients were selected at random, from atotal of 442 pT2 patients operated between April 1997 and September 2004. 31 patients from the last group,were made frozen prostate biopsy and resection of the involved margins. All of them were followed-up during12 months, at least. Healthy survival was compared, by Kaplan-Meier curves. Results: 5 of the total of 53patients with (-) margins (9.4%) shown biochemical recurrence at 18.8 months average; 7 of the 31 (22.5%)patients who were made fast and re-resection, shown biochemical recurrence at 23.2 months average. 11(44%) of the group with margin (+) and without a frozen biopsy, shown biochemical recurrence at 6.9months average. Comparing healthy survival curves, there is a significative difference (P = 0.017) in groupsof margins re-resection v/s groups without them. Conclusion: Margins resection involved in patients withpositive frozen biopsy is associated to a more healthy survival than if it is not made.

Influence of the kidney histology at the time of donation on long term kidney function in living kidney donors.

Living donation is the best choice for kidney transplantation, obtaining long-lasting good results for the recipient. Some concern still remains regarding the donor's long-term health. Kidney biopsy was routinely performed in our donor population at the time of donation many years ago. We found the existence of morphological kidney disease in those samples, in spite of normal clinical evaluations before donation. We attempted to correlate those abnormalities with long-term clinical outcomes. Donors were at least 10 years after surgery. A medical interview, including the SF-36 Health Survey, laboratory evaluation, and ambulatory blood pressure monitoring was performed on 27 donors meeting the inclusion criteria. Two donors had died after donation from unrelated causes with no known nephropathy. Histological analysis showed abnormalities in 16 of 29 donors. We found an increased prevalence of hypertension compared to the general population. Interestingly, there was no proteinuria in the donor population, and none developed clinical nephropathy. All subjects felt emotionally rewarded with donation, stating that their lives had no limitations. Our results suggest that kidney biopsy is neither necessary nor useful prior to donation because, although many donors had morphological kidney disease, none developed clinical nephropathy in the long term.

Characterization of the divergent eosinophil ribonuclease, mEar 6, and its expression in response to Schistosoma mansoni infection in vivo.

The eosinophil-associated ribonucleases (Ears) are rapidly evolving proteins found in multigene clusters that are unique to each rodent species. Of the 15 independent genes in the Mus musculus cluster, only mEars 1 and 2 are expressed at significant levels at homeostasis. Here we characterize the expression of mEar 6 in the liver and spleen in mice in response to infection with the helminthic parasite, Schistosoma mansoni. Interestingly, expression of mEar 6 is not directly related to the elevated levels of serum IL-5 or tissue eosinophilia characteristic of this disease, as no mEar 6 transcripts were detected in the liver or the spleen from uninfected IL-5-transgenic mice. The coding sequence of mEar 6 has diverged under positive selection pressure (K(a)/K(s) > 1.0) and has a unique unpaired cysteine near the carboxy-terminus of the protein. The high catalytic efficiency of recombinant mEar 6 (k(cat)/K(m) = 0.9 x 10(6)/M/s) is similar to that of the cluster's closest human ortholog, eosinophil-derived neurotoxin (EDN/RNase 2). In summary, we have identified mEar 6 as one of only two RNase A superfamily ribonucleases known to be expressed specifically in response to pathophysiologic stress in vivo.

A double-blind, randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania.

OBJECTIVES: This randomized, double-blind, placebo-controlled study examined the efficacy and tolerability of quetiapine in combination with divalproex (DVP) for acute mania in adolescents with bipolar disorder. It was hypothesized that DVP in combination with quetiapine would be more effective than DVP alone for treating mania associated with adolescent bipolar disorder. Furthermore, it was hypothesized that quetiapine would be well tolerated. METHOD: Thirty manic or mixed bipolar I adolescents (12-18 years) received an initial DVP dose of 20 mg/kg and were randomly assigned to 6 weeks of combination therapy with quetiapine, which was titrated to 450 mg/day (n = 15) or placebo (n = 15). Primary efficacy measures were change from baseline to endpoint in Young Mania Rating Scale (YMRS) score and YMRS response rate. Safety and tolerability were assessed weekly. RESULTS: The DVP + quetiapine group demonstrated a statistically significantly greater reduction in YMRS scores from baseline to endpoint than the DVP + placebo group (F(1,27) = 5.04, p =.03). Moreover, YMRS response rate was significantly greater in the DVP + quetiapine group than in the DVP + placebo group (87% versus 53%; Fisher exact test, p =.05). No significant group differences from baseline to endpoint in safety measures were noted. Sedation, rated as mild or moderate, was significantly more common in the DVP + quetiapine group than in the DVP + placebo group. CONCLUSIONS: The findings of this study indicate that quetiapine in combination with DVP is more effective for the treatment of adolescent bipolar mania than DVP alone. In addition, the results suggest that quetiapine is well tolerated when used in combination with DVP for the treatment of mania.

Parental reports of executive dysfunction in adolescents with bipolar disorder.

Bipolar disorder (BPD) is a serious mental illness that affects children and adolescents at a rate similar to that seen in adults. Extremely little is known, however, about cognitive functioning in childhood and adolescent BPD. The present study represents an initial effort to examine executive functioning in adolescents with BPD who are in a manic or mixed mood state, by collecting data from caregivers about the participants' performance on everyday tasks thought to be mediated by executive functioning abilities, using the Behavior Rating Inventory of Executive Function. In comparison to healthy volunteers, adolescents with BPD exhibited significant elevations across all of the measured functional domains. These elevations were evident even in adolescents with BPD who did not have comorbid ADHD, although they were most prominent in those with comorbidity. The findings suggest that adolescents with BPD have functional deficits on tasks requiring executive functioning skills that are not explicable solely on the basis of comorbid ADHD.

Glucocorticoid administration accelerates mortality of pneumovirus-infected mice.

The use of glucocorticoids for the treatment of symptoms associated with respiratory syncytial virus (RSV) infection has been questioned. To evaluate the sequelae of glucocorticoid administration in the setting of pneumovirus infection in vivo, hydrocortisone was administered to mice infected with pneumonia virus of mice (PVM), a pneumovirus and natural rodent pathogen that is closely related to RSV and replicates the signs and symptoms of severe human RSV infection. Results showed that hydrocortisone spared the pulmonary neutrophilia but resulted in ablation of the pulmonary eosinophilia, despite continued production of the relevant chemoattractant, macrophage inflammatory protein-1alpha. Hydrocortisone also led to diminished production of inducible nitric oxide synthase and accumulation of reactive nitrogen species in lung tissue and bronchoalveolar lavage fluid and diminished lymphocyte recruitment. PVM-infected mice responded to hydrocortisone with enhanced viral replication and accelerated mortality. These results suggest several mechanisms to explain why glucocorticoid therapy may be of limited benefit in the overall picture of pneumovirus infection.

Gene expression in epithelial cells in response to pneumovirus infection.

Respiratory syncytial virus (RSV) and pneumonia virus of mice (PVM) are viruses of the family Paramyxoviridae, subfamily pneumovirus, which cause clinically important respiratory infections in humans and rodents, respectively. The respiratory epithelial target cells respond to viral infection with specific alterations in gene expression, including production of chemoattractant cytokines, adhesion molecules, elements that are related to the apoptosis response, and others that remain incompletely understood. Here we review our current understanding of these mucosal responses and discuss several genomic approaches, including differential display reverse transcription-polymerase chain reaction (PCR) and gene array strategies, that will permit us to unravel the nature of these responses in a more complete and systematic manner.

Is age associated with size of adult extrahepatic bile duct: sonographic study.

PURPOSE: To determine if the size of the extrahepatic bile duct increases with age in adults. MATERIALS AND METHODS: A total of 258 consecutive patients 18 years and older, without known biliary or pancreatic disease, who were fasting to undergo routine abdominal sonography were examined. The transverse and anteroposterior dimensions of the extrahepatic bile duct were measured proximally at the porta hepatis, at the middle above the head of the pancreas, and distally at the head of the pancreas. Simple linear regression of the average of these measurements against age tested the hypothesis of a slope of 1.0 mm per decade. RESULTS: The sample included a wide variety of ages: 55 years +/- 16 (mean +/- SD), with a range of 20-92 years, including 151 men and 107 women. One-tenth of the cohort were younger than 35 years old and one-tenth were older than 77 years old. The six measurements were proximal-transverse 3.5 mm +/- 1.0, proximal-anteroposterior 2.9 mm +/- 1.1, middle-transverse 3.9 mm +/- 1.2, middle-anteroposterior 3.4 mm +/- 1.2, distal-transverse 4.1 mm +/- 1.2, distal-anteroposterior 3.5 mm +/- 1.2. Least squares regression slope differed significantly from 0.1 mm per year (95% CI; -0.000703, +0.00110) and in fact contained zero. CONCLUSION: Findings were not able to help confirm an association between age and size of the extrahepatic bile duct in an asymptomatic adult population.

Influence of baseline hematocrit and hemodilution on BOLD fMRI activation.

Current understanding of blood oxygenation level dependent (BOLD) fMRI physiology predicts a close relationship between BOLD signal and blood hematocrit level. However, neither this relationship nor its effect on BOLD percent activation (BPA) has been empirically examined in man. To that end, BPA in primary visual cortex in response to photic stimulation was determined in a group of 24 normal subjects. A positive linear relationship between BPA and hematocrit was seen, particularly in men. To evaluate the effect of change in hematocrit on BPA, 9 men were studied before and following isotonic saline hemodilution, resulting in an average 6% reduction in hematocrit and an 8-31% reduction in BPA. No significant change in the number of activated pixels was seen. A model of predicted BPA as a function of hematocrit and vessel size was developed, and results from this model closely mirrored the empiric data. These results suggest that hematocrit significantly influences the magnitude of BPA and that such baseline factors should be accounted for when comparing BOLD data across groups of subjects, particularly in the many instances in which hematocrit may vary systematically. Such instances include several disease states as well as studies involving sex differences, drug administration, stress and other factors. Finally, the robust agreement between predicted and empiric data serves to validate a semiquantitative approach to the analysis of BOLD fMRI data.