Bilateral salpingectomy as an option of permanent contraception at time of caesarean section: A survey of practice.

BACKGROUND: Opportunistic bilateral salpingectomy during benign gynaecologic surgery is advocated as a risk-reducing strategy due to the inverse association of epithelial ovarian cancers observed in epidemiological studies in a low-risk setting. Currently, no formal guidance exists for permanent surgical contraception at time of caesarean section in Australia. AIMS: Our aim was to survey Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) regarding bilateral salpingectomy compared to other procedures offered for permanent contraception at the time of caesarean section. MATERIALS AND METHODS: An online survey was utilised to collect clinician demographics, opinions, barriers, and justifications in regard to options of permanent surgical contraception at time of caesarean section. RESULTS: Bilateral salpingectomy was identified as the most effective method of permanent contraception at time of caesarean section. However, only 62% of respondents offer the procedure as a method of permanent contraception. The two most common reasons for clinicians to offer bilateral salpingectomy at time of caesarean section were evidence suggesting a link between the fallopian tube and gynaecological cancer (80%) and efficacy as a permanent form of contraception (16%). The primary barrier identified by 51% of respondents was perceived increased risk of surgical complications, followed by reasoning that it would not allow the possibility of future tubal reversal. CONCLUSION: This study identifies diverse opinions on surgical approach to permanent contraception at time of caesarean section and offered by clinicians of RANZCOG. Further research is required to establish safety profiles and short- and long-term risks of bilateral salpingectomy.

Debridement and primary closure of a mesenteric duodenal perforation in a dog.

A 7-year-old male mixed intact breed dog was presented with a 6-day history of lethargy and anorexia. A linear foreign body was diagnosed and an exploratory laparotomy performed. The foreign body was pushed orad and removed via gastrotomy. Two mesenteric duodenal perforations were found: one at the level of the common bile duct and a second at the duodenal flexure. Both lesions were debrided and primarily closed in a simple interrupted appositional pattern. A gastrostomy tube and closed suction drain were placed routinely. The dog recovered without complications and ate voluntarily the first day postoperatively. The drain and gastrostomy tube were removed without incident at 4 and 15 days, respectively. Five months postoperatively the dog was reported to be clinically normal. Debridement and primary closure may represent an alternative to more extensive surgery with rerouting for duodenal perforations in select cases.

Effects of substance P on human cerebral microvascular endothelial cell line hCMEC/D3 are mediated exclusively through a truncated NK-1 receptor and depend on cell confluence.

The neuropeptide substance P (SP) mediates pain transmission, immune modulation, vasodilation and neurogenic inflammation. Its role in the peripheral nervous system has been well characterised. However, its actions on the blood-brain barrier (BBB) are less clear and warrant further study. The aim of this study was to characterise the effect of SP on the brain microvascular endothelial cells using the immortalized human brain microvascular endothelial cell line hCMEC/D3. As part of our studies, we have evaluated changes in expression, at mRNA and protein levels, of genes involved in the function of the blood-brain barrier such as occludin, induced by exposure to SP. We show that the effect of SP is dependent on cell confluence status. Thus, at low confluence but not at full confluence, SP treatment reduced occludin expression. The expression of the SP receptor, neurokinin-1 receptor (NK-1R) (the truncated form of the receptor expressed exclusively in this cell line) was also modulated in a similar pattern. SP treatment stimulated extracellular signal-regulated kinase (Erk2) phosphorylation which was not associated to changes in Interleukin-6 (IL-6), Interleukin-8 (IL-8), or Intercellular Adhesion Molecule 1 (ICAM-1) protein expression. In addition, SP treatment effectively recovered nitric oxide production on cells exposed to tumour necrosis factor alpha (TNF-α). SP did not trigger intracellular calcium release in hCMEC/D3 cells. We conclude that hCMEC/D3 cells are partially responsive to SP, that the effects are mediated through the truncated form of the receptor and are dependent on the confluence status of these cells.

Cangrelor Use Patterns and Transition to Oral P2Y12 Inhibitors Among Patients With Myocardial Infarction: Initial Results From the CAMEO Registry.

Background In clinical trials, cangrelor has been shown to reduce percutaneous coronary intervention-related ischemic complications without increasing major bleeding. This study was performed to examine cangrelor use and transition to oral P2Y12 inhibitors in routine clinical practice. Methods and Results The CAMEO (Cangrelor in Acute Myocardial Infarction: Effectiveness and Outcomes) registry is a multicenter, retrospective observational study of platelet inhibition strategies for patients with myocardial infarction undergoing percutaneous coronary intervention. In phase 1, data were collected on consecutive patients with myocardial infarction (n=482) treated with any P2Y12 inhibitor to understand cangrelor use by hospital. In phase 2, data were collected in a 2:1 (cangrelor-: non-cangrelor-treated) ratio of patients with myocardial infarction (n=873). In phase 1, cangrelor use varied across hospitals (overall, 50.4% [range, 6.0%-100%]). Of patients receiving cangrelor in both phases (n=819), 3.3% received either the bolus or infusion only. Cangrelor was infused for a median of 121 (76-196) minutes; and 38.3% received an infusion for <2 hours. Most patients transitioned from cangrelor to ticagrelor (ticagrelor, 85.3%; clopidogrel, 9.5%; prasugrel, 5.2%). Many patients (16.4%) had a >1-hour gap between cangrelor cessation and oral P2Y12 inhibitor initiation; this was highest among those transitioned to clopidogrel (56.6% versus 34.5% prasugrel versus 10.8% ticagrelor; P<0.001). Only 27.3% were dosed with cangrelor and transitioned to an oral P2Y12 inhibitor in a fashion consistent with the pivotal trials and US Food and Drug Administration label. Conclusions This multicenter registry demonstrated interhospital variability in how cangrelor was administered and transitioned to an oral P2Y12 inhibitor. These findings highlight opportunities for optimization of cangrelor dosing, infusion duration, and transition of care from the catheterization laboratory to the ward setting.

Non-invasive vagus nerve stimulation attenuates proinflammatory cytokines and augments antioxidant levels in the brainstem and forebrain regions of Dahl salt sensitive rats.

The anti-inflammatory effects of vagus nerve stimulation are well known. It has recently been shown that low-level, transcutaneous stimulation of vagus nerve at the tragus (LLTS) reduces cardiac inflammation in a rat model of heart failure with preserved ejection fraction (HFpEF). The mechanisms by which LLTS affect the central neural circuits within the brain regions that are important for the regulation of cardiac vagal tone are not clear. Female Dahl salt-sensitive rats were initially fed with either low salt (LS) or high salt (HS) diet for a period of 6 weeks, followed by sham or active stimulation (LLTS) for 30 min daily for 4 weeks. To study the central effects of LLTS, four brainstem (SP5, NAb, NTS, and RVLM) and two forebrain sites (PVN and SFO) were examined. HS diet significantly increased the gene expression of proinflammatory cytokines in the SP5 and SFO. LLTS reversed HS diet-induced changes at both these sites. Furthermore, LLTS augmented the levels of antioxidant Nrf2 in the SP5 and SFO. Taken together, these findings suggest that LLTS has central anti-inflammatory and antioxidant properties that could mediate the neuromodulation of cardiac vagal tone in the rat model of HFpEF.

Subclinical Retinal versus Brain Findings in Infants with Hypoxic Ischemic Encephalopathy.

PURPOSE: To detect retinal features and abnormalities on optical coherence tomography (OCT) without pupil dilation and relate these to brain injury in infants with a clinical diagnosis of hypoxic ischemic encephalopathy (HIE). METHODS: Under an institutional review board-approved protocol, we imaged eight infants without pharmacologic mydriasis, using handheld, non-contact spectral-domain (Leica Microsystems, IL) or investigational swept-source OCT at the bedside in an intensive care nursery, after birth (depending on primary clinical care team permission based on health status) and weekly until discharge. The newborn infant with HIE is neurologically unstable; therefore, pharmacologic mydriasis and stimulation with visible light for retinal examination are usually avoided. We analyzed images for retinal pathologies, central foveal thickness, and retinal nerve fiber layer (RNFL) thickness at the papillomacular bundle and compared them to historical controls and published normative data, HIE clinical assessment, and abnormalities on brain magnetic resonance imaging (MRI). RESULTS: On OCT, three of eight infants had bilateral multiple small macular and perimacular cystoid spaces; two of these three infants also had pronounced retinal ganglion cell layer thinning and severe brain injury on MRI and the third had bilateral paracentral acute middle maculopathy and mild brain injury on MRI. Other findings in HIE infant eyes included abnormally thin fovea and thin RNFL and markers of retinal immaturity such as the absence of sub-foveal photoreceptor development and sub-foveal fluid. CONCLUSIONS: Bedside handheld OCT imaging within the first 2 weeks of life revealed retinal injury in infants with HIE-related brain injury. Future studies may determine the relationship between acute/subacute retinal abnormalities and brain injury severity and neurodevelopmental outcomes in HIE.

Healthy shopper? Blood pressure testing in a shopping centre Pop-Up in England.

BACKGROUND: Improving detection of elevated blood pressure (BP) remains a public health need. We present results from a Pop-Up health check stationed in shopping centres in England. We hypothesise the rate of case detection is related to measurable 'unhealthiness' of the shopping centres. METHODS: A Pop-Up health check was sited in four and three shopping centres sampled from the top ten unhealthiest and top 15 healthiest shopping regions respectively, following a report ranking towns/cities based on their unhealthy and healthy retail outlets. On one day in each shopping centre, people were approached and consented to BP testing. Outcome measure was people flagged with BP ≥ 140/90 mmHg (cases). RESULTS: We detected 45 (22.6%) and 20 (13.1%) cases from testing 199 and 152 adults in the unhealthy and healthy locations respectively (relative risk 1.72; 95% confidence interval: 1.06 to 2.78). A measure of unhealthy retail outlets (e.g. fast-food outlets) within each shopping centre was associated with detection rate (R2 = 0.61; p = 0.04). CONCLUSION: An association exists between cases of suspect hypertension found in a health check Pop-Up and measured 'unhealthiness' of the shopping centre site. Results hint at strategies for public testing of BP, potentially in the context of reducing health inequalities.

Effect of Cord Blood Magnesium Level at Birth on Non-neurologic Neonatal Outcomes.

OBJECTIVE: We examined the effects of magnesium sulfate on non-neurologic neonatal outcomes with respect to cord blood magnesium level. STUDY DESIGN: We conducted a secondary analysis of the Maternal-Fetal Medicine Units Beneficial Effects of Antenatal Magnesium (MFMU BEAM) trial comparing the upper and lower quintiles of cord blood magnesium level. Outcomes included cerebral palsy (CP), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and assessments of mental and motor disability. Logistic regression was used to estimate adjusted odds ratios (aORs) of each outcome, controlling for gestational age (GA), birth weight, and treatment group (TG). RESULTS: A total of 1,254 women of the 2,444 included in the BEAM trial had cord blood magnesium levels recorded. GA and birth weight were lower and TG was more common in the upper quintile cohort (p < 0.001). Neonates in the upper quintile were more likely to have severe NEC (OR, 2.41, 95% confidence interval [CI]: 1.11-5.24), ROP (OR, 1.65, 95% CI: 1.05-2.59), and BPD (OR, 1.70, 95% CI: 1.04-2.73). Adjustment for covariates demonstrated no difference in the NEC, ROP, and BPD rates, although there was a decrease in rates of mental disability index < 70 which was not seen in the unadjusted analysis (aOR, 0.49, 95% CI: 0.25-0.99). CONCLUSION: Higher cord blood magnesium levels do not appear to have adverse non-neurologic effects on the neonate and may demonstrate improvement in neurologic outcomes.

MiR-126 and miR-126* regulate shear-resistant firm leukocyte adhesion to human brain endothelium.

Leukocyte adhesion to brain endothelial cells, the blood-brain barrier main component, is a critical step in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). Leukocyte adhesion is mediated mainly by selectins, cell adhesion molecules and chemokines induced by pro-inflammatory cytokines such as TNFα and IFNγ, but the regulation of this process is not fully clear. This study investigated the regulation of firm leukocyte adhesion to human brain endothelium by two different brain endothelial microRNAs (miRs), miR-126 and miR-126*, that are downregulated by TNFα and IFNγ in a human brain endothelial cell line, hCMEC/D3. Using a leukocyte adhesion in vitro assay under shear forces mimicking blood flow, we observed that reduction of endothelial miR-126 and miR-126* enhanced firm monocyte and T cell adhesion to hCMEC/D3 cells, whereas their increased expression partially prevented THP1, Jurkat and primary MS patient-derived PBMC firm adhesion. Furthermore, we observed that miR-126* and miR-126 downregulation increased E-selectin and VCAM1, respectively, while miR-126 overexpression reduced VCAM1 and CCL2 expression by hCMEC/D3 cells, suggesting that these miRs regulate leukocyte adhesion by modulating the expression of adhesion-associated endothelial mRNA targets. Hence, human brain endothelial miR-126 and miR-126* could be used as a therapeutic tool to reduce leukocyte adhesion and thus reduce neuroinflammation.

Profiling Humoral Immune Responses to Clostridium difficile-Specific Antigens by Protein Microarray Analysis.

Clostridium difficile is an anaerobic, Gram-positive, and spore-forming bacterium that is the leading worldwide infective cause of hospital-acquired and antibiotic-associated diarrhea. Several studies have reported associations between humoral immunity and the clinical course of C. difficile infection (CDI). Host humoral immune responses are determined using conventional enzyme-linked immunosorbent assay (ELISA) techniques. Herein, we report the first use of a novel protein microarray assay to determine systemic IgG antibody responses against a panel of highly purified C. difficile-specific antigens, including native toxins A and B (TcdA and TcdB, respectively), recombinant fragments of toxins A and B (TxA4 and TxB4, respectively), ribotype-specific surface layer proteins (SLPs; 001, 002, 027), and control proteins (tetanus toxoid and Candida albicans). Microarrays were probed with sera from a total of 327 individuals with CDI, cystic fibrosis without diarrhea, and healthy controls. For all antigens, precision profiles demonstrated <10% coefficient of variation (CV). Significant correlation was observed between microarray and ELISA in the quantification of antitoxin A and antitoxin B IgG. These results indicate that microarray is a suitable assay for defining humoral immune responses to C. difficile protein antigens and may have potential advantages in throughput, convenience, and cost.

Detection of Mycobacterium leprae by PCR testing of sputa from a patient with pulmonary cryptococcus coinfection in northern Australia.

A case of fever, sepsis, and chest lesions evident on a computed tomography scan of an indigenous man in northern Australia following burns to the feet is described. Sputum PCR testing revealed Mycobacterium leprae, and a fine-needle aspirate of the chest lesions demonstrated Cryptococcus coinfection.

A Newfoundland cohort of familial and sporadic idiopathic pulmonary fibrosis patients: clinical and genetic features.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an adult-onset Idiopathic Interstitial Pneumonia (IIP) usually diagnosed between age 50 to 70 years. Individuals with Familial Pulmonary Fibrosis (FPF) have at least one affected first or second-degree relative and account for 0.5-20% of cases. METHODS: We ascertained and collected DNA samples from a large population-based cohort of IPF patients from Newfoundland, Canada. For each proband, a family history was documented and medical records were reviewed. Each proband was classified as familial (28 patients) or sporadic (50 patients) and all 78 probands were screened for variants in four highly penetrant, adult-onset PF genes (SFTPC, SFTPA2, TERT,TERC). RESULTS: Seventy-eight IPF probands were enrolled of whom 28 (35.9%) had a positive family history. These 28 familial patients led to the recruitment of an additional 49 affected relatives (total of 77 FPF patients). By age 60 years, 42% of the familial cohort had been diagnosed with PF compared with only 16% of the sporadic patient collection (χ2 = 8.77, p = 0.003). Mean age of diagnosis in the familial group was significantly younger than the sporadic group (61.4 years vs. 66.6 yrs, p = 0.012) with a wider age range of diagnosis (19-92 years compared with 47-82 years). Thirty-three of 77 (42.8%) FPF patients had a tissue diagnosis and all but five had usual interstitial pneumonia histology. Compared with other published case series, the familial IIP histologies were more homogeneous. Three of 28 familial probands (10.7%) and none of the 50 sporadic probands had pathogenic variants in the four genes tested. All three familial probands had mutations in TERT. Other phenotypes associated with telomerase deficiency were present in these families including cirrhosis, bone marrow hypoplasia and premature graying. Telomere length assays were performed on mutation carriers from two families and confirmed telomere-related deficiency. CONCLUSION: The proportion of familial cases in our cohort is higher than any previously reported estimate and we suggest that this is due to the fact that Newfoundland cohort is ethnically homogeneous and drawn from a founder population. In our patient collection, diagnosis with IPF prior to age 45 years predicted familial disease. In two of the three TERT mutation families, the pedigree appearance is consistent with genetic anticipation. In the other 25 FPF families negative for mutations in known PF genes, we did not identify other telomerase associated medical problems (bone marrow dysfunction, cirrhosis) and we hypothesize that there are novel PF genes segregating in our population.

Orexin A (hypocretin-1) levels are not reduced while cocaine/amphetamine regulated transcript levels are increased in the cerebrospinal fluid of patients with multiple sclerosis: no correlation with fatigue and sleepiness.

BACKGROUND: Fatigue and sleep disturbance are common features of multiple sclerosis (MS). Our objectives were to determine cerebrospinal fluid levels of orexin A (hypocretin-1), a hypothalamic peptide involved in sleep, in patients with MS, and correlate them with fatigue, sleepiness, and levels of cocaine and amphetamine regulated transcript (CART) another neuropeptide regulating metabolism with wider nervous system distribution. METHODS: Consecutive patients with MS (n=34), other inflammatory (n=24) or non-inflammatory (n=42) neurological diseases, undergoing lumbar puncture were investigated. Orexin and CART were measured by RIA by investigators unaware of the patients' diagnosis. RESULTS: Orexin A was slightly decreased in the cerebrospinal fluid of patients with inflammatory disease. There was no evidence of orexin A deficiency in MS, although there was a non-significant trend toward a decrease compared to non-inflammatory neurological diseases (p=0.06). CART levels were increased in MS compared to the non-inflammatory disease group (p=0.03). There were no significant correlations between CSF levels of orexin A and CART, fatigue, and hypersomnolence. CONCLUSIONS: Cerebrospinal fluid orexin A is decreased in CNS inflammatory diseases other than MS, where it shows a trend toward reduction, but does not correlate significantly with CART or with measures of fatigue and hypersomnolence.

Structure and function of KH domains.

The hnRNP K homology (KH) domain was first identified in the protein human heterogeneous nuclear ribonucleoprotein K (hnRNP K) 14 years ago. Since then, KH domains have been identified as nucleic acid recognition motifs in proteins that perform a wide range of cellular functions. KH domains bind RNA or ssDNA, and are found in proteins associated with transcriptional and translational regulation, along with other cellular processes. Several diseases, e.g. fragile X mental retardation syndrome and paraneoplastic disease, are associated with the loss of function of a particular KH domain. Here we discuss the progress made towards understanding both general and specific features of the molecular recognition of nucleic acids by KH domains. The typical binding surface of KH domains is a cleft that is versatile but that can typically accommodate only four unpaired bases. Van der Waals forces and hydrophobic interactions and, to a lesser extent, electrostatic interactions, contribute to the nucleic acid binding affinity. 'Augmented' KH domains or multiple copies of KH domains within a protein are two strategies that are used to achieve greater affinity and specificity of nucleic acid binding. Isolated KH domains have been seen to crystallize as monomers, dimers and tetramers, but no published data support the formation of noncovalent higher-order oligomers by KH domains in solution. Much attention has been given in the literature to a conserved hydrophobic residue (typically Ile or Leu) that is present in most KH domains. The interest derives from the observation that an individual with this Ile mutated to Asn, in the KH2 domain of fragile X mental retardation protein, exhibits a particularly severe form of the syndrome. The structural effects of this mutation in the fragile X mental retardation protein KH2 domain have recently been reported. We discuss the use of analogous point mutations at this position in other KH domains to dissect both structure and function.

Cytochrome P450 17A1 and catechol O-methyltransferase polymorphisms and age at Lynch syndrome colon cancer onset in Newfoundland.

PURPOSE: Lynch syndrome is a cancer predisposition syndrome which includes colon cancer. It is caused by inherited defects in DNA mismatch repair genes. Sporadic colon cancers are influenced by exogenous hormones (e.g., postmenopausal hormones); we hypothesized that polymorphisms which influence endogenous hormones would therefore modify age at colon cancer onset among Lynch syndrome mutation carriers. EXPERIMENTAL DESIGN: We genotyped 146 Caucasian Lynch syndrome mutation carriers for a 5'-untranslated region polymorphism in cytochrome P450 17A1 (CYP17; c.-34T-->C) and an exon 4 polymorphism in catechol O-methyltransferase (COMT; c.472G-->A); 50 mutation carriers had developed colon or rectal cancer at last contact. We used chi(2) tests to assess differences in counts. Kaplan-Meier survival curves and Cox proportional hazard models assessed age at onset of colorectal cancer stratified by CYP17 and COMT genotypes. RESULTS: Homozygous carriers of the CYP17 C allele were diagnosed with colorectal cancer 18 years earlier than homozygous carriers of the T allele. Hazard ratios identified that, relative to homozygous carriers of the T allele (T/T), carriers of one copy (T/C) and two copies (C/C) of the rare allele were, respectively, at 1.9-fold and 2.9-fold increased the risk of colon cancer at any age. The COMT rare allele suggested a nonstatistically significant trend of decreased colon cancer risk. CONCLUSIONS: This study showed that a polymorphism in CYP17 (c.-34T-->C) modifies age at onset of Lynch syndrome. Because of the high risk of colorectal cancer among this group, knowledge of the CYP17 genotype is warranted for genetic counseling and risk assessment. Future work should assess polymorphisms associated with steroid hormones in Lynch syndrome mutation carriers.

Conserved C-terminal domains of mCenp-F (LEK1) regulate subcellular localization and mitotic checkpoint delay.

Centromeric Protein-F (Cenp-F) family members have been identified in organisms from yeast to human. Cenp-F proteins are a component of kinetochores during mitosis, bind to the Rb family of tumor suppressors, and have regulatory effects on the cell cycle and differentiation; however, their role in these processes has not been resolved. Here, we provide evidence that the role of murine Cenp-F (mCenp-F, also known as LEK1) remains largely conserved and that the domains within the C-terminus collectively function to regulate the G2/M cell cycle checkpoint. Overexpression of the C-terminal domain of mCenp-F decreases DNA synthesis. Analyses of deletion mutants of mCenp-F reveal that the complete C-terminal domain is required to delay cell cycle progression at G2/M. Signal transduction pathway profiling experiments indicate that the mCenp-F-mediated cell cycle delay does not involve transcriptional activity of key cell cycle regulators such as Rb, E2F, p53, or Myc. However, endogenous mCenp-F colocalizes with pRb and p107, which demonstrates in vivo protein-protein interaction during cell division. These observations suggest that the domains of the C-terminus of mCenp-F have a conserved function in control of mitotic progression through protein-protein interaction with pocket proteins, thus providing a direct connection between cell cycle regulation and mitotic progression.

A new variant database for mismatch repair genes associated with Lynch syndrome.

Mutations in some mismatch repair (MMR) genes are associated with Lynch syndrome (LS; also called hereditary nonpolyposis colorectal cancer [HNPCC]), an autosomal dominant cancer susceptibility syndrome. Colorectal cancer (CRC) is the most frequent cancer observed in LS. However, tumors occur at a variety of extracolonic sites and individuals may have multiple primary cancers. LS is the most common hereditary form of CRC, accounting for approximately 1% of all CRC. Since the first account of mutations in MSH2 causing this cancer susceptibility syndrome in 1993, mutations in three additional MMR genes, MLH1, MSH6, and PMS2, have been shown to cause LS. More than 1,500 different variants have been identified in these four genes and approximately 80% of the alterations have been identified in MLH1 and MSH2. There have been a few previous attempts to systematically record MMR variants associated with LS patients; however, they were not complete nor were they continuously updated. Thus, it was our goal to generate and maintain a comprehensive catalogue of MMR variants from genes known to be mutated in LS (http://www.med.mun.ca/MMRvariants; last accessed 8 February 2007). Providing such a resource should aid investigators in understanding the significance of the variants.

Development and characterization of a solvent extraction-gas chromatographic/mass spectrometric method for the analysis of perfluorooctanesulfonamide compounds in solid matrices.

A method utilizing solvent extraction and analysis by gas chromatography-positive chemical ionization mass spectrometry (SE-GC-PCIMS) was developed for the analysis of three neutral hydrophobic perfluorooctanesulfonamide compounds [perfluorooctanesulfonamide (PFOSA), N-ethyl perfluorooctanesulfonamide (N-EtPFOSA), and N,N-diethyl perfluorooctanesulfonamide (N,N-Et2PFOSA)]. These compounds are suspected metabolic precursors of perfluorooctane sulfonate. The SE-GC-PCI-MS method was used to analyze all three perfluorooctanesulfonamides in fast food, fish, and Arctic marine mammal liver samples. The SE-GC-PCI-MS method produced relatively higher recoveries of the analytes (averaging 83 +/- 6%, 84 +/- 9%, and 89 +/- 19% for N,N-Et2PFOSA, N-EtPFOSA, and PFOSA, respectively) with lower coefficients of variation, and less susceptibility to matrix effects, than ion pair extraction-liquid chromatography-tandem mass spectrometric methods. Method detection limits (MDLs) were 100, 120, and 250 pg/g for N,N-Et2PFOSA, N-EtPFOSA, and PFOSA, respectively. The three compounds were found at concentrations ranging from below the MDL to 22 ng/g wet weight in fast food, fish, and Arctic marine mammal liver samples.