The GOFURTGO Study: AGITG phase II study of fixed dose rate gemcitabine-oxaliplatin integrated with concomitant 5FU and 3-D conformal radiotherapy for the treatment of localised pancreatic cancer.

BACKGROUND: Locally advanced inoperable pancreatic cancer (LAPC) has a poor prognosis. By increasing intensity of systemic therapy combined with an established safe chemoradiation technique, our intention was to enhance the outcomes of LAPC. In preparation for phase III evaluation, the feasibility and efficacy of our candidate regimen gemcitabine-oxaliplatin chemotherapy with sandwich 5-fluorouracil (5FU) and three-dimensional conformal radiotherapy (3DCRT) needs to be established. METHODS: A total of 48 patients with inoperable LAPC without metastases were given gemcitabine (1000 mg m(-2) d1 + d15 q28) and oxaliplatin (100 mg m(-2) d2 + d16 q28) in induction (one cycle) and consolidation (three cycles), and 5FU 200 mg m(-2) per day over 6 weeks during 3DCRT 54 Gy. RESULTS: Median duration of sustained local control (LC) was 15.8 months, progression-free survival (PFS) was 11.0 months, and overall survival was 15.7 months. Survival rates for 1, 2, and 3 years were 70.2%, 21.3%, and 12.8%, respectively. Global quality of life did not significantly decline from baseline during treatment, which was associated with modest treatment-related toxicity. CONCLUSION: Fixed-dose gemcitabine and oxaliplatin, combined with an effective and safe regimen of 5FU and 3DCRT radiotherapy, was feasible and reasonably tolerated. The observed improved duration of LC and PFS with more intensive therapy over previous trials may be due to patient selection, but suggest that further evaluation in phase III trials is warranted.

Risk of arterial thromboembolic events in patients with advanced colorectal cancer receiving bevacizumab.

BACKGROUND: Bevacizumab is an antiangiogenic mAb with efficacy against several cancers, but it is associated with risk of arterial thromboembolism (ATE). Further data are needed to determine the safety of bevacizumab. PATIENTS AND METHODS: We recorded grade 3, 4, or 5 ATE events and other data (including age, baseline cardiovascular risk factors, history of ATE, and aspirin use) from 471 patients with metastatic colorectal cancer in the MAX (Mitomycin, Avastin, Xeloda) trial of capecitabine monotherapy versus capecitabine with bevacizumab with or without mitomycin C. RESULTS: Bevacizumab-treated patients had 12 grade 3, 4, or 5 ATEs (3.8% incidence). ATEs occurred in 2.1% of patients >65 years, 5% of those with a history of ATE, and 5% of those with cardiac risk factors. Age, history of ATE, or vascular risk factors did not increase risk. Aspirin users had a higher incidence than nonusers (8.9% versus 2.7%) but had higher rates of vascular risk factors. CONCLUSIONS: Bevacizumab was associated with a modestly higher risk of ATE, but safety was not significantly worse in older patients or patients with a history of ATE or vascular risk factors. The effect of aspirin in preventing ATE in patients receiving bevacizumab could not be determined from this study.

Randomised, non-comparative phase II study of weekly docetaxel with cisplatin and 5-fluorouracil or with capecitabine in oesophagogastric cancer: the AGITG ATTAX trial.

BACKGROUND: Docetaxel administered 3-weekly with cisplatin and 5-fluorouracil leads to better survival than does standard therapy in patients with oesophagogastric cancer, but leads to high rates of haematological toxicity. Weekly docetaxel is associated with less haematological toxicity. This randomised phase II study tested weekly docetaxel-based combination chemotherapy regimens, with the aim of maintaining their activity while reducing toxicity. METHODS: Patients with histologically confirmed metastatic oesophageal or gastric carcinoma were randomised to receive weekly docetaxel (30 mg m(-2)) on days 1 and 8, cisplatin (60 mg m(-2)) on day 1, and 5-fluorouracil (200 mg m(-2) per day) continuously, every 3 weeks (weekly TCF, wTCF); or docetaxel (30 mg m(-2)) on days 1 and 8 and capecitabine (1600 mg m(-2) per day) on days 1-14, every 3 weeks (weekly TX, wTX). RESULTS: A total of 106 patients were enrolled (wTCF, n=50; wTX, n=56). Response rates, the primary end point, were 47% with wTCF and 26% with wTX. Rates of febrile neutropenia were low in each arm. Median progression-free and overall survival times were 5.9 and 11.2 months for wTCF and 4.6 and 10.1 months for wTX, respectively. CONCLUSION: Weekly TCF and TX have encouraging activity and less haematological toxicity than TCF administered 3-weekly. Weekly docetaxel-based combination regimens warrant further evaluation in this disease.

A point prevalence study to determine the inpatient rate of carbapenemase-producing organisms at a large London NHS Trust.

BACKGROUND: There has been an increase in the number of carbapenemase-producing organisms documented across the UK over the past 10 years. From these, the 'big five' carbapenemases (KPC, OXA-48, IMP, VIM, and NDM) are the most common types reported in the order Enterobacterales, identified from a variety of reactive screening, outbreak, inpatient surveillance, and diagnostic samples. AIM: To perform a point prevalence study to determine the inpatient carriage rate of carbapenemase-producing organisms at Barts Health NHS Trust, which encompasses 2.5 million patients across four London boroughs: Tower Hamlets, Newham, Redbridge, and Waltham Forest. METHODS: Rectal swabs were collected from consenting inpatients, alongside details of the ward's medical specialty, patient's country of birth, history of foreign travel, length of hospitalization, and history of prior hospitalization. Swabs were enriched and subcultured on to mSuperCARBA selective medium. All Enterobacterales, Acinetobacter, and Pseudomonas species were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy and underwent antibiotic susceptibility testing by disc diffusion, according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. All isolates were screened for the 'big five' carbapenemases using a modified version of a published reverse transcriptase-polymerase chain reaction assay. FINDINGS: Of the 977 inpatients tested, 35 CPOs were isolated from 30 patients. NDM was the most frequently detected carbapenemase, followed by OXA-48, with an overall prevalence of 3.1%. Organisms isolated included Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, and Escherichia coli. Renal and elderly care patients had the highest prevalences of CPOs, whereas the intensive care unit prevalence was low. Statistical analysis found that hospitalization abroad, any previous hospitalization, foreign travel and, specifically, travel to India, Pakistan, and Bangladesh were associated with increased risk of CPO carriage. CONCLUSION: The overall prevalence of CPOs at Barts Health Trust was 3.1%, comprising NDM and OXA-48-type carbapenemases, which is in line with other London-based studies. Renal patients and the elderly had the highest burden of CPOs, whereas previous hospitalization and foreign travel were associated with an increased risk of CPO carriage.

New Antheridiogen from the Fern Onoclea sensibilis.

An antheridium-inducing hormone (antheridiogen) derived from the fern species Onoclea sensibilis (Polypodiaceae) is chromatographically distinct from the native antheridiogen of Pteridium aquilinum (Polypodiaceae). It also differs from the native antheridiogens of Lygodium japonicum and Anemia phyllitidis (Schizaeaceae).

Assessing the biological efficacy and rate of recontamination following hydrogen peroxide vapour decontamination.

The inanimate hospital environment can become contaminated with nosocomial pathogens. Hydrogen peroxide vapour (HPV) decontamination has proven effective for the eradication of persistent environmental contamination. We investigated the extent of meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and gentamicin-resistant Gram-negative rod (GNR) contamination in a ward side-room occupied by a patient with a history of MRSA, VRE and GNR infection and colonisation and investigated the impact of HPV decontamination. Fifteen standardised sites in the room were sampled using a selective broth enrichment protocol to culture MRSA, VRE and GNR. Sampling was performed before cleaning, after cleaning, after HPV decontamination and at intervals over the subsequent 19 days on two separate occasions. Environmental contamination was identified before cleaning on 60, 30 and 6.7% of sites for MRSA, GNR and VRE, respectively, and 40, 10 and 6.7% of sites after cleaning. Only one site (3.3%) was contaminated with MRSA after HPV decontamination. No recontamination with VRE was identified and no recontamination with MRSA and GNR was identified during the two days following HPV decontamination. Substantial recontamination was identified approximately one week after HPV decontamination towards post-cleaning levels for GNR and towards pre-cleaning levels for MRSA. HPV is more effective than standard terminal cleaning for the eradication of nosocomial pathogens. Recontamination was not immediate for MRSA and GNR but contamination returned within a week in a room occupied by a patient colonised with MRSA and GNR. This finding has important implications for the optimal deployment of HPV decontamination in hospitals.

A tropomyosin-2 mutation suppresses a troponin I myopathy in Drosophila.

A suppressor mutation, D53, of the held-up(2) allele of the Drosophila melanogaster Troponin I (wupA) gene is described. D53, a missense mutation, S185F, of the tropomyosin-2, Tm2, gene fully suppresses all the phenotypic effects of held-up(2), including the destructive hypercontraction of the indirect flight muscles (IFMs), a lack of jumping, the progressive myopathy of the walking muscles, and reductions in larval crawling and feeding behavior. The suppressor restores normal function of the IFMs, but flight ability decreases with age and correlates with an unusual, progressive structural collapse of the myofibrillar lattice starting at the center. The S185F substitution in Tm2 is close to a troponin T binding site on tropomyosin. Models to explain suppression by D53, derived from current knowledge of the vertebrate troponin-tropomyosin complex structure and functions, are discussed. The effects of S185F are compared with those of two mutations in residues 175 and 180 of human alpha-tropomyosin 1 which cause familial hypertrophic cardiomyopathy (HCM).

Allogeneic stem cell transplantation for refractory acute myeloid leukemia in pediatric patients: the UK experience.

We report outcomes for 44 children who underwent stem cell transplantation (SCT) for refractory AML in the UK between 2000 and 2012. Median age at SCT was 11.5 years. Twenty-three patients had primary refractory and 21 relapsed refractory AML. Refractory disease was confirmed by cytogenetics/molecular genetics in 24 cases. Median follow-up of the whole cohort is 6.8 years (2.1-14.9 years). Thirty patients (68%) achieved a CR following SCT. Transplant-related mortality at 1 year was 18%. Acute GVHD incidence was 52% (grade ⩾III 19%), chronic 7%. Relapse was the major cause of treatment failure and occurred in 32% of patients at a median of 61 days post SCT. Five-year overall survival and leukemia-free survival (LFS) were 43% (95% CI 31-61%). All patients with favorable cytogenetics (n=6) are alive in CR. Outcomes in patients with primary refractory disease were equivalent to those with relapsed refractory AML. Blast percentage ⩽30% in the BM pre-SCT, myeloablative conditioning and acute GVHD proved to be favorable prognostic features. We could stratify patients according to age ⩾10 years and >30% blasts in BM pre-SCT. Patients with none/one of these risk factors were highly salvageable (5 years LFS 53%) whereas those with both factors had a very poor prognosis (5 years LFS 10%). This may facilitate decision making on whether it is appropriate to consider transplant in such patients.

Vaccination to improve the persistence of CD19CAR gene-modified T cells in relapsed pediatric acute lymphoblastic leukemia.

Trials with second generation CD19 chimeric antigen receptors (CAR) T-cells report unprecedented responses but are associated with risk of cytokine release syndrome (CRS). Instead, we studied the use of donor Epstein-Barr virus-specific T-cells (EBV CTL) transduced with a first generation CD19CAR, relying on the endogenous T-cell receptor for proliferation. We conducted a multi-center phase I/II study of donor CD19CAR transduced EBV CTL in pediatric acute lymphoblastic leukaemia (ALL). Patients were eligible pre-emptively if they developed molecular relapse (>5 × 10-4) post first stem cell transplant (SCT), or prophylactically post second SCT. An initial cohort showed poor expansion/persistence. We therefore investigated EBV-directed vaccination to enhance expansion/persistence. Eleven patients were treated. No CRS, neurotoxicity or graft versus host disease (GVHD) was observed. At 1 month, 5 patients were in CR (4 continuing, 1 de novo), 1 PR, 3 had stable disease and 3 no response. At a median follow-up of 12 months, 10 of 11 have relapsed, 2 are alive with disease and 1 alive in CR 3 years. Although CD19CAR CTL expansion was poor, persistence was enhanced by vaccination. Median persistence was 0 (range: 0-28) days without vaccination compared to 56 (range: 0-221) days with vaccination (P=0.06). This study demonstrates the feasibility of multi-center studies of CAR T cell therapy and the potential for enhancing persistence with vaccination.

Ibrutinib downregulates a subset of miRNA leading to upregulation of tumor suppressors and inhibition of cell proliferation in chronic lymphocytic leukemia.

The lymph node (LN) is the site of chronic lymphocytic leukemia (CLL) cell activation and proliferation. Aberrant microRNA (miRNA) expression has been shown to have a role in CLL pathogenesis; however, a comparison of miRNA expression between CLL cells in the LN and the peripheral blood (PB) has previously not been reported. On the basis of the analysis of 17 paired LN and PB samples from CLL patients, we identify a panel of miRNAs that are increased in LN CLL cells correlating with an activation phenotype. When evaluated in CLL cells from 38 patients pre and post treatment with ibrutinib, a subset of these miRNAs (miR-22, miR-34a, miR-146b and miR-181b) was significantly decreased in response to ibrutinib. A concomitant increase in putative miRNA target transcripts (ARID1B, ARID2, ATM, CYLD, FOXP1, HDAC1, IBTK, PTEN and SMAD4) was also observed. Functional studies confirmed targets of ibrutinib-responsive miRNAs to include messenger RNA transcripts of multiple tumor suppressors. Knockdown of endogenous miR-34a and miR146b resulted in increased transcription of tumor suppressors and inhibition of cell proliferation. These findings demonstrate that ibrutinib downregulates the expression of a subset of miRNAs related to B-cell activation leading to increased expression of miRNA targets including tumor suppressors and a reduction in cell proliferation.

Nursing Informatics Certification Worldwide: History, Pathway, Roles, and Motivation.

INTRODUCTION: Official recognition and certification for informatics professionals are essential aspects of workforce development. OBJECTIVE: To describe the history, pathways, and nuances of certification in nursing informatics across the globe; compare and contrast those with board certification in clinical informatics for physicians. METHODS: (1) A review of the representative literature on informatics certification and related competencies for nurses and physicians, and relevant websites for nursing informatics associations and societies worldwide; (2) similarities and differences between certification processes for nurses and physicians, and (3) perspectives on roles for nursing informatics professionals in healthcare Results: The literature search for 'nursing informatics certification' yielded few results in PubMed; Google Scholar yielded a large number of citations that extended to magazines and other non-peer reviewed sources. Worldwide, there are several nursing informatics associations, societies, and workgroups dedicated to nursing informatics associated with medical/health informatics societies. A formal certification program for nursing informatics appears to be available only in the United States. This certification was established in 1992, in concert with the formation and definition of nursing informatics as a specialty practice of nursing by the American Nurses Association. Although informatics is inherently interprofessional, certification pathways for nurses and physicians have developed separately, following long-standing professional structures, training, and pathways aligned with clinical licensure and direct patient care. There is substantial similarity with regard to the skills and competencies required for nurses and physicians to obtain informatics certification in their respective fields. Nurses may apply for and complete a certification examination if they have experience in the field, regardless of formal training. Increasing numbers of informatics nurses are pursuing certification. CONCLUSIONS: The pathway to certification is clear and wellestablished for U.S. based informatics nurses. The motivation for obtaining and maintaining nursing informatics certification appears to be stronger for nurses who do not have an advanced informatics degree. The primary difference between nursing and physician certification pathways relates to the requirement of formal training and level of informatics practice. Nurse informatics certification requires no formal education or training and verifies knowledge and skill at a more basic level. Physician informatics certification validates informatics knowledge and skill at a more advanced level; currently this requires documentation of practice and experience in clinical informatics and in the future will require successful completion of an accredited two-year fellowship in clinical informatics. For the profession of nursing, a graduate degree in nursing or biomedical informatics validates specialty knowledge at a level more comparable to the physician certification. As the field of informatics and its professional organization structures mature, a common certification pathway may be appropriate. Nurses, physicians, and other healthcare professionals with informatics training and certification are needed to contribute their expertise in clinical operations, teaching, research, and executive leadership.

Management of chronic myeloid leukaemia in relapse following donor lymphocyte infusion induced remission: a retrospective study of the Clinical Trials Committee of the British Society of Blood & Marrow Transplantation (BSBMT).

Donor lymphocyte infusion (DLI) can restore remission in a high percentage of patients with chronic myeloid leukaemia (CML) who relapse after allogeneic stem cell transplant (SCT). Subsequent relapses after a DLI-induced remission do occur and the optimal management of these patients is not defined. A retrospective study of the practice of UK transplant centres was conducted. In all, 13 patients from seven centres were identified: all were treated for relapse post allogeneic SCT with DLI and achieved either a complete cytogenetic (n=5) or molecular (n=8) remission. All patients subsequently had a second relapse, at molecular (n=7), cytogenetic (n=4) and haematological (n=2) levels. Further DLI was used in the treatment of 11 patients, imatinib mesylate in three and chemotherapy in two. The two patients with haematological relapse died of blastic disease. The remaining 11 patients achieved either a complete cytogenetic (n=2) or molecular (n=9) remission. Nine patients remain in molecular remission at a median follow-up of 29 months, seven of whom had received DLI alone as treatment for second relapse, one DLI plus imatinib and one imatinib alone. Toxicity following DLI for second relapse was low. Longer follow-up will be required to see if these second DLI-induced remissions will be durable.

Isochromosome of a deleted 20q: a rare but recurrent chromosome abnormality in myelodysplastic syndromes.

Interstitial deletion of the long arm of chromosome 20, as the sole abnormality, is commonly observed in myeloid malignancies, including myeloproliferative disorder, myelodysplastic syndrome, and acute myeloid leukemia. The breakpoints of the deletion are typically located in the region 20q11.2 approximately q13.3, although smaller deletions within this region have also been reported. We present here 4 patients with myelodysplastic syndrome with an isochromosome of the deleted long arm of chromosome 20: ider(20)(q10)del(20)(q11q13). Fluorescence in situ hybridization studies were performed on the bone marrow samples from these patients to prove the identity of this unusual chromosome abnormality.

Clinical variance in assessing risk of pressure ulcer development.

Nurses working in one area health service (AHS) in Sydney, Australia, expressed concern about the development of pressure ulcers in hospitalized patients. Anecdotal evidence suggested that a variety of approaches were being used to assess patients to identify those at risk of pressure ulcer development. A questionnaire was distributed to all registered nurses (n = 2113) in clinical settings within the AHS. Data were analysed using frequency distribution. The response rate was 40% (n = 850), of which 444 were useable. Nurses generally do not use a tool to assess pressure ulcer risk potential, but rely on a range of practice procedures and risk indicators. It is recommended that a pressure ulcer project group be established to evaluate existing tools or, if necessary, develop a tool for the assessment of patients to identify those at risk of developing pressure ulcers.

Correlation between microsatellite discrepancy scores and transplant outcome after haemopoietic SCT for pediatric ALL.

Microsatellite analyses show that self-reported ethnicity often correlates poorly with true genetic ancestry. As unknown ancestral differences could potentially have an impact on transplant outcome, we developed an average allele length discrepancy (AALD) score to assess allele length discrepancy between donor/recipient (D/R) using microsatellites analysed routinely in post-transplant chimeric assessment. This was then compared with outcome in a homogeneously treated cohort of pediatric patients undergoing high-resolution sibling or matched unrelated donor transplantation for acute lymphoblastic leukemia (ALL). AALD scores formed a numeric continuum ranging from 0 to 1.4 (median 0.76) for sibling pairs and 0.8-2.17 (median 1.6) for high-resolution matched unrelated donor (HR-MUD) pairs. There was a trend for worse OS with increasing AALD score, which reached statistical significance above a threshold of 1.7 for OS. Patients whose transplants had an AALD score of ⩾1.8 had a risk of non-relapse mortality 4.9 times greater (P=0.025) and relapse risk three times greater (P=0.058) than those scoring <1.8. This approach will now be explored in a Centre International for Blood and Marrow Transplantation Research (CIBMTR) study of 750 D/R pairs across all disease groups; if confirmed, it has the potential to improve donor selection for patients with multiple prospective donors.

Purinergic responses in HT29 colonic epithelial cells are mediated by G protein alpha -subunits.

Using Fura-2 to measure changes in intracellular calcium ([Ca(2+)](i)), we show that P(2U)receptors in HT29 cells trigger an increase in [Ca(2+)](i)by pertussis toxin-insensitive G proteins. We then use replication-deficient adenoviruses expressing wild-type and dominant negative mutants of G(alpha q)and G(alpha i2), antisense directed against G(alpha q)or the C-terminal fragment of beta-adrenergic receptor kinase (beta ARK-CT) to identify these G proteins. We find the [Ca(2+)](i)response to UTP is not affected by increased expression of the wild-type G(alpha q), wild-type G(alpha i2)or beta ARK-CT, while it is blocked by over-expression of dominant negative G(alpha q). The timecourse of the UTP response is, however, altered by wild-type G(alpha q)and is only weakly inhibited by antisense G(alpha q). This suggests that the P(2U)response is mediated, at least partially, by a G protein distinct from G(alpha q). In contrast, the M(3)muscarinic response is inhibited by over-expression of antisense against G(alpha q), or over-expression of beta ARK-CT, a finding in agreement with our previous observation that the muscarinic response in HT29 cells is mediated by the beta gamma-subunits of G(q). We also find that P(2U)and M(3)receptors do not control identical Ca(2+)stores, suggesting that differential activation of G proteins can lead to Ca(2+)release from distinct stores.

Low-dose oral use of human interferon-alpha in cancer patients.

In a double-blind placebo-controlled trial, 57 adult subjects with disseminated malignancies were given orally low doses of recombinant human interferon-alpha (rHuIFN-alpha) at 0.05 IU, 0.5 IU, or 5.0 IU/kg body weight. The objective was to determine the efficacy of orally administered rHuIFN-alpha on appetite stimulation and/or weight loss prevention in anorectic cancer patients. Almost two-thirds (64%) of the subjects given 5.0 IU/kg reported an increase in appetite or body weight after 5 weeks in contrast to only 29% of the placebo-treated subjects. However, at the end of the 91-day trial, no significant differences in appetite enhancement or weight gain were noted between these two groups. Additionally, the 5.0 IU/kg treated group experienced half as many deaths as the control group by the conclusion of this 91-day trial.

Treatment of primary Sjögren's syndrome with low-dose natural human interferon-alpha administered by the oral mucosal route: a phase II clinical trial. IFN Protocol Study Group.

The purpose of this investigation was to examine the safety and efficacy of four dosages of natural human interferon-alpha (nHuIFN-alpha) delivered over a 12-week period orally in lozenges (150 IU and 450 IU, once [QD] or three times [TID] daily) compared to placebo in subjects with primary Sjögren's syndrome. This randomized, double-blinded clinical trial demonstrated that nHuIFN-alpha at a dose of 150 IU administered TID by oral lozenge significantly improved stimulated whole saliva output compared to placebo after 12 weeks of treatment. The 150 IU TID dose also was suggestive of benefit for 5 of 7 subjective measures of oral and ocular comfort. IFN lozenges demonstrated a good safety profile, with no serious adverse events found in any treatment group. There were no significant differences between the placebo and the four doses of IFN for adverse events by total number, organ system, severity, dropouts, and number judged to be related to treatment. In conclusion, these results demonstrated that the use of 150 IU IFN lozenges TID for 12 weeks in subjects with primary Sjögren's syndrome improved salivary output and decreased complaints of xerostomia without causing significant adverse medical events.

Cytohormonal patterns in mature and pre-term babies.

Comparison of cytohormonal patterns in full-term and pre-term babies of both sexes showed significant differences. At birth, irrespective of gestational age, both groups had high oestrogen levels, reflecting the maternal hormonal environment, but whereas the mature neonates were capable of metabolising and excreting the excess hormone within the first week of life, the pre-term infants took much longer to do so. It is thought that immaturity or impairment of liver function is at least partially responsible for this finding.

The effect of high cervical cordotomy on portal vein plasma serotonin and 5-hydroxyindoleacetic acid levels in dogs with and without superior mesenteric artery occlusion.

In ten dogs undergoing high cervical cardotomy, there was a statistically significant fall in plasma serotonin (5-HT) levels in portal vein blood; no further change in plasma 5-HT occurred after superior mesenteric artery (SMA) occlusion, which is an effective stimulus for 5-HT release. In five dogs undergoing high cervical corotomy with no SMA occlusion, there was a comparable fall in portal vein plasma 5-HT levels. The 5-hydroxyindoleacetic acid (5-HIAA) values in portal vein blood in the two groups of dogs above fell to comparable levels. These findings indicate (1) that maintenance of the normal plasma 5-HT level in portal vein blood in this experimental model is dependent on the integrity of the spinal cord and (2) that SMA occlusion in animals with a high cervical cordotomy does not result in further changes in the plasma 5-HT level in portal vein blood.