Tube Feed Necrosis after Major Gastrointestinal Oncologic Surgery: Institutional Lessons and a Review of the Literature.

BACKGROUND: Small bowel necrosis after enteral feeding through a jejunostomy tube (tube feed necrosis, TFN) is a rare, serious complication of major abdominal surgery. However, strategies to reduce the incidence and morbidity of TFN are not well established. Here, in the largest series of TFN presented to date, we report our institutional experience and a comprehensive review of the literature. METHODS: Eight patients who experienced TFN from 2000 to 2014 after major abdominal surgery for oncologic indications at the University of Cincinnati were reviewed. Characteristics of post-operative courses and outcomes were reviewed prior to and after a change in tube-feeding protocol. The existing literature addressing TFN over the last three decades was also reviewed. RESULTS: Patients with TFN ranged from 50 to 74 years old and presented with upper gastrointestinal tract malignancies amenable to surgical resection. Six and two cases of TFN occurred following pancreatectomy and esophagectomy, respectively. Prior to TF protocol changes, which included initiation at a low rate, titrating up more slowly and starting at one-half strength TF, three of six cases of TFN (50%) resulted in mortality. With the new TF protocol, there were no deaths, goal TF rate was achieved 3 days later, symptoms of TFN were recognized 3 days earlier, and re-operation was conducted 1 day earlier. CONCLUSION: This case series describes a change in clinical practice that is associated with decreased morbidity and mortality of TFN. Wider implementation and further refinement of this tube-feeding protocol may reduce TFN incidence at other institutions and in patients with other conditions requiring enteral nutrition.

Surprising similarity between mechanisms mediating low (1 Hz)-and high (100 Hz)-induced long-lasting synaptic potentiation in CA1 of the intact hippocampus.

It is generally assumed that long lasting synaptic potentiation (long-term potentiation, LTP) and depression (long-term depression, LTD) result from distinct patterns of afferent activity, with high and low frequency activity favouring LTP and LTD, respectively. However, a novel form of N-methyl-d-aspartate (NMDA) receptor-dependent synaptic potentiation in the hippocampal CA1 area in vivo induced by low frequency afferent stimulation has recently been demonstrated. Here, we further characterize the mechanisms mediating this low frequency stimulation (LFS)-induced LTP in area CA1 of intact, urethane-anesthetized preparations. Consistent with previous reports, alternating, low frequency (1 Hz) stimulation of CA1 afferents originating in the contralateral CA3 area and the medial septum resulted in gradually developing, long lasting (>2 h) LTP of field excitatory postsynaptic potentials (fEPSPs) recorded in CA1. Local application of the protein synthesis inhibitor anisomycin in CA1 blocked LFS-induced LTP, as did application of H89, an inhibitor of protein kinase A. Given the apparent overlap in molecular mechanisms mediating LFS-LTP and "classic" high-frequency stimulation (HFS)-induced LTP in CA1, we examined the relation between these forms of LTP by means of occlusion experiments. LFS, delivered to synapses saturated by initial HFS, resulted in a gradually developing LTD, rather than the normally seen LTP. Conversely, initial induction of LFS-LTP reduced the amount of subsequent HFS-LTP. Together, these experiments reveal a surprising similarity in the molecular mechanisms (dependence on NMDA receptors, protein kinase A, protein synthesis) mediating LTP induced by highly distinct (1 vs. 100 Hz) induction protocols. Importantly, these findings further challenge the "high-frequency-LTP, low-frequency LTD" dogma by demonstrating that this dichotomy does not account for all types of plasticity phenomena at central synapses.

Effectiveness of cognitive behaviour therapy in schoolchildren with depressive symptoms in Alexandria, Egypt.

We evaluated the effectiveness of cognitive behaviour therapy for 12-14-year-old school-children from a low socioeconomic area in Alexandria, Egypt during the academic year 2003-04. Our sample comprised 198 boys and 136 girls. Students were assessed using the Child Depression Inventory and the Coopersmith Self-Esteem Inventory. The frequency of depression was 9.6%; 7.1% in boys and 13.2% in girls. The 32 children with depression were offered cognitive behaviour therapy. Only 17 accepted the offer and received 9 sessions of therapy. They were assessed 3 months after the intervention using the same tools and the results indicate the short-term effectiveness of the therapy.

Large interarcuate spaces in the cervical vertebral column of the tyrolean mountain sheep.

Large interarcual spaces have been described between the arcus vertebrae C5/C6 and C6/C7 in the cervical vertebral column of Nubian goats. This aperture enables direct access to spinal cord and rootlets without the need to perform a hemilaminectomy. The present study was performed in order to determine whether these large interarcual spaces can also be found in the vertebral column of the Tyrolean mountain sheep, as this small ruminant, which is anatomically very similar to the Nubian goat, is frequently used for experimental purposes at the Surgical University Clinic in Austria. The carcasses of 10 sheep (six females, four males; range of age: 2.5-6 years, range of weight: 52-89 kg) were dissected and the vertebral column was exposed. All 10 sheep showed elliptic openings between the fourth cervical and the first thoracal vertebrae. Three sheep had additional openings between the first and the second thoracal vertebrae. All openings were covered solitarily by the ligamentum flavum and under this ligamentum lay the spinal cord without any further osseous or ligamentous protection. These findings are not mentioned in the common textbooks of veterinary anatomy and deserve attention, as they can be a step forward towards non-traumatic experimental surgery on the spinal cord.

Identification of a high affinity nucleocapsid protein binding element within the Moloney murine leukemia virus Psi-RNA packaging signal: implications for genome recognition.

Murine leukemia virus (MLV) is currently the most widely used gene delivery system in gene therapy trials. The simple retrovirus packages two copies of its RNA genome by a mechanism that involves interactions between the nucleocapsid (NC) domain of a virally-encoded Gag polyprotein and a segment of the RNA genome located just upstream of the Gag initiation codon, known as the Psi-site. Previous studies indicated that the MLV Psi-site contains three stem loops (SLB-SLD), and that stem loops SLC and SLD play prominent roles in packaging. We have developed a method for the preparation and purification of large quantities of recombinant Moloney MLV NC protein, and have studied its interactions with a series of oligoribonucleotides that contain one or more of the Psi-RNA stem loops. At RNA concentrations above approximately 0.3 mM, isolated stem loop SLB forms a duplex and stem loops SL-C and SL-D form kissing complexes, as expected from previous studies. However, neither the monomeric nor the dimeric forms of these isolated stem loops binds NC with significant affinity. Longer constructs containing two stem loops (SL-BC and SL-CD) also exhibit low affinities for NC. However, NC binds with high affinity and stoichiometrically to both the monomeric and dimeric forms of an RNA construct that contains all three stem loops (SL-BCD; K(d)=132(+/-55) nM). Titration of SL-BCD with NC also shifts monomer-dimer equilibrium toward the dimer. Mutagenesis experiments demonstrate that the conserved GACG tetraloops of stem loops C and D do not influence the monomer-dimer equilibrium of SL-BCD, that the tetraloop of stem loop B does not participate directly in NC binding, and that the tetraloops of stem loops C and D probably also do not bind to NC. These surprising results differ considerably from those observed for HIV-1, where NC binds to individual stem loops with high affinity via interactions with exposed residues of the tetraloops. The present results indicate that MLV NC binds to a pocket or surface that only exists in the presence of all three stem loops.

Biological characterization and chemokine receptor usage of HIV type 1 isolates prevalent in Brazil.

The human immunodeficiency virus type 1 (HIV-1), the etiological agent of the acquired immunodeficiency syndrome (AIDS), shows a variety of biological properties, which may constitute an obstacle to development of effective vaccines or antiretroviral therapy. To characterize Brazilian strains of HIV-1, we studied 24 viruses isolated from blood samples of HIV-1-positive patients from different regions of the country. To examine the cell tropism and the virus ability to form syncytia, primary macrophages and the CD4+ T cell line MT-2 were infected with these viruses. We found that 22 isolates replicated well in macrophages (macrophage-tropic isolates), 2 infected only MT-2 cells (T cell line tropic variants), while 6 of them grew in both cells. We found 8 syncytium-inducing (SI) and 16 non-SI (NSI) isolates. Continuous cultures of 18 isolates were established in the CCR5+/CXCR4+ cell line PM-1, and SI/NSI features of these viruses were confirmed by cell fusion assay with uninfected CD4+ T cell lines (PM-1, MT-2, H9, and SUP-T1). The coreceptor usage of 18 isolates was investigated by infecting U87 cells transfected with CD4 and chemokine receptors, and we found that 11 isolates infected only CCR5+ cells, 3 only CXCR4+ cells, whereas 4 used both coreceptors. We also observed that X4 isolates were more sensitive to neutralization by dextran sulfate than R5 or R5X4 viruses. Our findings show that the Brazilian isolates are phenotypically similar to those prevalent in other regions, which could mean that therapeutic strategies based on HIV-1 phenotypic properties would be efficient in Brazil, as in other countries.

Elevated serum and bronchoalveolar lavage fluid levels of interleukin 8 and granulocyte colony-stimulating factor associated with the acute chest syndrome in patients with sickle cell disease.

The role of cytokines in the development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) was studied. Serum interleukin 8 (IL-8) levels were elevated in 14 episodes and undetectable in six out of 20 episodes of ACS in 19 patients with SCD. In contrast, IL-8 levels were undetectable in the sera of 29 control patients with SCD studied during routine clinic visits or hospitalization for vaso-occlusive crises. The differences in mean IL-8 levels and the proportion of patients with detectable levels between the two groups were highly significant (P < 0.0001 and 0.04 respectively). The mean IL-8 level in bronchial fluid samples from children with ACS was also significantly higher than that in sickle cell patients undergoing elective surgery (5500 +/- 1400 pg/ml vs. 1900 +/- 470 pg/ml, P = 0.03). Granulocyte colony-stimulating factor (G-CSF) (2000 +/- 1700 pg/ml) was present in five out of six samples of bronchial fluid, but not serum, from children with ACS. All but one of the patients with ACS studied were negative for the Duffy red cell antigen, which is a receptor that binds and inactivates IL-8 and other chemokines. These findings suggest that IL-8 and G-CSF may play a role in the development of the ACS and the complications associated with it.

CD26 expression correlates with entry, replication and cytopathicity of monocytotropic HIV-1 strains in a T-cell line.

Experiments to identify cell determinants involved in HIV-1 tropism revealed a specific decrease in the expression of the T-cell activation antigen CD26 after monocytotropic (M-tropic) but not T-cell line-tropic (T-tropic) virus infection of the PM1 T-cell line. The level of CD26 expression in single-cell clones of PM1 correlated with the entry rate and cytopathicity of M-tropic HIV-1 variants, resulting in preferential survival of cells with low CD26 levels after infection. Experiments with recombinant viruses showed that the third hypervariable region of the envelope gp120 plays an important role in this selection process. This study identifies CD26 as a key marker for M-tropic human immunodeficiency virus type 1 (HIV-1) infection and suggests a mechanism for the early loss of CD26-expressing cells in HIV-1-infected individuals.

Immunosuppressive effect of paracoccidioidomycosis sera on the proliferative response of normal mononuclear cells. Identification of a Paracoccidioides brasiliensis 34-kDa polypeptide in circulating immune complexes.

In this paper we relate that sera from paracoccidioidomycosis patients inhibited the mitogen-induced proliferative responses of normal mononuclear cells. Treatment of these sera with 2.5% polyethyleneglycol (PEG), a method classically used to precipitate immune complexes, significantly reduced their inhibitory activity. Immunoblot analysis of the PEG precipitates identified a 34-kDa polypeptide, recognized by rabbit anti-P. brasiliensis IgG. Patient mononuclear cells showed partial restoration of their proliferative capacity after 24 h culture in medium alone, which suggests release of membrane-bound molecules in the culture medium. These findings indicate that circulating P. brasiliensis antigens, complexed or not with antibodies, may play a negative immunoregulatory effect in the mitogen-induced proliferative responses of paracoccidioidomycosis patients.

Neonatal adaptation: cardiac adrenergic effector mechanisms after birth in newborn sheep.

At birth, there is a marked increase in circulating plasma catecholamine concentrations. This increase is critical to many of the physiologic adjustments to postnatal life. Because the levels observed are higher than those seen in most other physiologic conditions in adults, previous investigators have suggested that the newborn is less sensitive to adrenergic stimulation or that desensitization to adrenergic stimulation occurs rapidly. To investigate this question, we designed experiments to measure myocardial beta-adrenergic receptor density and sensitivity before and after exposure to the catecholamine surge at birth in term newborn sheep. We also measured the status of sympathetic innervation, reflected by myocardial norepinephrine content. At birth, plasma catecholamines increased 4- to 6-fold with associated increases in heart rate, blood pressure, and cardiac output. Myocardial beta-adrenergic receptor at birth (135 fmol/mg protein) did not change significantly by 6 h of life (157 fmol/mg protein). Myocardial adenyl cyclase activity, reflecting receptor sensitivity, and myocardial sympathetic innervation also did not change. These results suggest that, despite exposure to sustained adrenergic stimulation, myocardial adrenergic effector mechanisms do not change in the newborn sheep at birth.

Glucose tolerance in pregnant women following treatment for sterility.

The incidence of glucose intolerance in 76 patients with polycystic ovary disease (PCOD) who became pregnant after treatment for ovulation was compared with that in 95 healthy women, matched with respect to age and diabetic background, who conceived without intervention. The incidence of abnormal glucose tolerance test results in the treated group was twice that in the normal group (19.7% vs. 9.5%; P less than .03). Moreover, within the treated group abnormal test results occurred more frequently in patients who became pregnant following induction of ovulation with human menopausal gonadotropin (29%) than in those who conceived as a result of other treatment modalities (12%).

Polyclonal B cell activation in paracoccidioidomycosis. Polyclonal activation in paracoccidioidomycosis.

Paracoccidioidomycosis (PCM) is often associated with hypergammaglobulinemia and increased serum levels of circulating immune complexes (CIC). In order to investigate whether polyclonal B lymphocyte activation (PBA) is a current process in PCM, we measured the numbers of IgG secreting cells (IgG SC) in the peripheral blood of 16 patients and of 8 healthy controls. The numbers of IgG SC were found to be significantly elevated in PCM patients. We also observed increased serum levels of IgG, IgA and CIC. These data reflect an activation of B lymphocytes in PCM patients.

The possible role of circulating immune complexes in the deficiency of cell-mediated immunity in paracoccidioidomycosis.

1. The nature and extent of immune abnormalities was studied in 28 untreated patients with a chronic moderate form of paracoccidioidomycosis (PCM). 2. The patients presented hyporeactivity to skin tests, diminished lymphocyte transformation by mitogens such as phytohemagglutinin-P and concanavalin A and by Paracoccidioides brasiliensis protein antigen. They also presented peripheral blood leukocytosis but normal absolute numbers of T-cell and T-cell subsets. 3. The patients had increased serum levels of C3d, as well as high levels of circulating immune complexes (CIC) detected by C1q-binding and protein A-binding assays. 4. There was a significant negative correlation between lymphocyte transformation by mitogens and CIC levels which suggested that CIC may be involved in the genesis of the depressed cell-mediated immunity in PCM patients.

The possible role of circulating immune complexes in the deficiency of cell-mediated immunity in paracoccidioidomycosis

1. The nature and extent of immune abnormalities was studied in 28 untreated patients with a chronic moderate form of paracoccidioidomycosis (PCM). 2. The patients presented hyporeactivity to skin tests, diminished lymphocyte transformation by mitogens such as phytohamgglutinin-P and concanavalin A and by Paracoccidioides brasiliensis protein antigen. They also presented peripheral blood leukocytosis but normal absolute numbers of T-cell and T-cell subsets. 3. The patients had increased serum levels of C3d, as well as high levels of circulating immune complexes (CIC) detected by C1q-binding and protein A-binding assays. 4. There was a significant negarive correlation between lymphocyte transformation by mitogens and CIC levels which suggested that CIC may be involved in the genesis of the depressed cell-mediated immunity in PCM patients

Production of a monoclonal anti-hamster thymocyte antibody with mitogenic properties.

A monoclonal antibody (MAb), designated H3, with specificity for hamster lymphocytes, was produced by somatic cell hybridization of myeloma Sp 2/0 and spleen cells of Balb/c mice immunized with suspensions of viable hamster thymocytes. The H3 MAb (IgG 3) reacted specifically with hamster thymocyte surface membranes (immunofluorescent assay). The antibody recognized a protein of an approximate molecular weight of 44,000 Daltons in immunoblots of hamster thymocyte extracts. The soluble H3 MAb presented potent mitogenic properties as indicated by the DNA synthesis induced in in vitro hamster lymphocyte cultures.

Spores, pollen, and microplankton from the horizon Beta outcrop.

Palynology was used for dating a pre-Pleistocene deep-sea organic lutite layer situated stratigraphically near seismic horizon beta, below horizon A. The spores and pollen are closely identified, quantitatively, with nonmarine and marine Middle Cretaceous assemblages (Albian-Cenomanian) on the continents, an age designation that is confirmed by the occurrence of dinoflagellate cysts, acritarchs, foraminifers, and coccoliths in the investigated cores. The abundance of these well-preserved, land-derived assemblages in an area far removed from a source suggests some tectonic displacement since their deposition.