Early tracheostomy in closed head injuries: experience at a tertiary center in a developing country – a prospective study

Background

An important factor contributing to the high mortality in patients with severe head trauma is cerebral hypoxia. The mechanical ventilation helps both by reduction in the intracranial pressure and hypoxia. Ventilatory support is also required in these patients because of patient's inability to protect the airway, persistence of excessive secretions, and inadequacy of spontaneous ventilation. Prolonged endotracheal intubation is however associated with trauma to the larynx, trachea, and patient discomfort in addition to requirement of sedatives. Tracheostomy has been found to play an integral role in the airway management of such patients, but its timing remains subject to considerable practice variation. In a developing country like India where the intensive care facilities are scarce and rarely available, these critical patients have to be managed in high dependency cubicles in the ward, often with inadequately trained nursing staff and equipment to monitor them. An early tracheostomy in the selected group of patients based on Glasgow Coma Score(GCS) may prove to be life saving.Against this background a prospective study was contemplated to assess the role of early tracheostomy in patients with isolated closed head injury.

Methods

The series consisted of a cohort of 50 patients admitted to the surgical emergency with isolated closed head injury, that were not considered for surgery by the neuro-surgeon or shifted to ICU, but had GCS score of less than 8 and SAPS II score of more than 50. First 50 case records from January 2001 that fulfilled the criteria constituted the control group. The patients were managed as per ATLS protocol and intubated if required at any time before decision to perform tracheostomy was taken. These patients were serially assessed for GCS (worst score of the day as calculated by senior surgical resident) and SAPS scores till day 15 to chart any changes in their status of head injuries and predictive mortality. Those patients who continued to have a GCS score of <8 and SAPS score of >50 for more than 24 hours (to rule out concussion or recovery) underwent tracheostomy. All these patients were finally assessed for mortality rate and hospital stay, the statistical analysis was carried out using SPSS10 version. The final outcome (in terms of mortality) was analyzed utilizing chi-square test and p value <0.05 was considered significant.

Results

At admission both tracheostomy and non-tracheostomy groups were matched with respect to GCS score and SAPS score. The average day of tracheostomy was 2.18 ± 1.0038 days. The GCS scores on days 1, 2, 3, 4, 5, 10 between tracheostomy and non-tracheostomized group were comparable. However the difference in the GCS scores was statistically significant on day 15 being higher in the tracheostomy group.Thus early tracheostomy was observed to improve the mortality rate significantly in patients with isolated closed head injury

Conclusion

It may be concluded that early tracheostomy is beneficial in patients with isolated closed head injury which is severe enough to affect systemic physiological parameters, in terms of decreased mortality and intubation associated complications in centers where ICU care is not readily available. Also, in a selected group of patients, early tracheostomy may do away with the need for prolonged mechanical ventilation.     

Polyethylene glycol versus low-ionic-strength solution in pretransfusion testing: a blinded comparison study

BACKGROUND: Polyethylene glycol (PEG) has been shown to potentiate antigen-antibody reactions. STUDY DESIGN AND METHODS: To investigate the utility of PEG in pretransfusion testing, a blinded comparison study of PEG and a low-ionic-strength additive solution (LISS) was conducted. A total of 500 patient samples were tested in parallel with reagent antibody-detection cells using blind-coded PEG and LISS potentiators. RESULTS: In 34 (34%) of 100 samples with known antibodies in the Rh, Kell, Duffy, Kidd, and MNS systems, PEG antiglobulin reactions were stronger (total score, 382) than LISS antiglobulin reactions (total score, 216), and in 66 cases (66%), they were equal to those of LISS. Of 400 samples without detectable antibodies, 384 were negative with PEG and LISS, and 16 were positive in PEG tests and negative in LISS. Seven of the 16 were clinically important antibodies (D, 1; E, 3; Fya, 1; Jka; 1; Jkb, 1), and four were clinically benign antibodies (Le(a), 2; McCc, 1; Sda, 1). Five of the 16 demonstrated inconclusive PEG reactions, for a false-positive rate of 5 in 400 (1.3%). Of the 500 samples, none was negative in PEG tests and positive in LISS (0% false-negative rate). CONCLUSION: Although PEG demonstrates a relatively high false-positive rate, PEG is more sensitive than LISS in detecting clinically significant antibodies.     

Control of Emi2 activity and stability through Mos-mediated recruitment of PP2A

Before fertilization, vertebrate eggs are arrested in meiosis II by cytostatic factor (CSF), which holds the anaphase-promoting complex (APC) in an inactive state. It was recently reported that Mos, an integral component of CSF, acts in part by promoting the Rsk-mediated phosphorylation of the APC inhibitor Emi2/Erp1. We report here that Rsk phosphorylation of Emi2 promotes its interaction with the protein phosphatase PP2A. Emi2 residues adjacent to the Rsk phosphorylation site were important for PP2A binding. An Emi2 mutant that retained Rsk phosphorylation but lacked PP2A binding could not be modulated by Mos. PP2A bound to Emi2 acted on two distinct clusters of sites phosphorylated by Cdc2, one responsible for modulating its stability during CSF arrest and one that controls binding to the APC. These findings provide a molecular mechanism for Mos action in promoting CSF arrest and also define an unusual mechanism, whereby protein phosphorylation recruits a phosphatase for dephosphorylation of distinct sites phosphorylated by another kinase.     

Use of video capsule endoscopy in Crohn's disease

Capsule endoscopy has been available since 2001 to image the small intestine, a boon to practitioners managing patients with inflammatory bowel disease. During the last ten years, new technologies have been developed, including computed tomographic enterography, magnetic resonance enterography, in addition to our standard small bowel follow through, all of which image the small bowel. This has created a situation in which multiple options are available to the gastroenterologist to image the small bowel, each with strengths. This review focuses on capsule endoscopy as it pertains to the imaging of the small bowel in patients with known or suspected Crohn's disease. We will focus on comparative imaging data, how capsule endoscopy may aid in the prediction of disease type and course, the avoidance and meaning of capsule retention, along with cost considerations, and directions for the future.     

Contrast echocardiography is superior to tissue harmonics for assessment of left ventricular function in mechanically ventilated patients

BACKGROUND: Assessment of left ventricular function by echocardiography is frequently challenging in mechanically ventilated patients. We evaluated the potential value of contrast-enhanced imaging and tissue harmonic imaging over standard fundamental imaging for endocardial border detection (EBD) in these patients. METHODS AND RESULTS: Fifty patients underwent standard transthoracic 2D echocardiography and were imaged in fundamental and tissue harmonic modes and subsequently with intravenous contrast (Optison). Two echocardiographers reviewed all studies for ease of visualization of endocardial border segments and scoring of wall motion. EBD for each wall segment was graded from 1 to 4 (1 = excellent EBD). Wall motion was scored by a standard 16-segment model and 1 to 5 scale. Studies were categorized as nondiagnostic if 4 of 6 segments in the apical 4-chamber view were either poorly seen or not seen (EBD score 3 or 4). Quantification of ejection fraction was independently performed offline. Visualization of 68% of all segments improved with contrast echocardiography versus 17% improvement with tissue harmonics compared with fundamental mode. Significant improvement (poor/not seen to good/excellent) occurred in 60% of segments with contrast echocardiography versus 18% with tissue harmonics. A total of 850 segments were deemed poor/not seen, 78% of which improved to good/excellent with contrast echocardiography versus 23% with tissue harmonics. Interobserver agreement on EBD was 64% to 70%. Conversion of nondiagnostic to diagnostic studies occurred in 85% of patients with contrast echocardiography versus 15% of patients with tissue harmonics. Scoring of wall motion with fundamental mode, tissue harmonics, and contrast echocardiography was possible in 61%, 74%, and 95% of individual segments, respectively (P <.001). Wall motion scoring was altered in 17% of segments with contrast echocardiography and in 8% with tissue harmonics. Interobserver agreement on wall motion scoring was 84% to 88%. Contrast echocardiography permitted measurement of ejection fraction 45% (P =.003) more often over fundamental mode versus a 27% (P =.09) increase with tissue harmonics. CONCLUSIONS: Contrast echocardiography is superior to tissue harmonic imaging for EBD, wall motion scoring, and quantification of ejection fraction in mechanically ventilated patients.     

Characterization of avian and viral p60src proteins expressed in yeast.

Avian and viral p60src proteins were expressed from a galactose-inducible promoter in the yeast Saccharomyces cerevisiae. Both the viral and cellular src proteins produced in yeast cells were myristoylated at their amino termini, as is the case for src proteins expressed in chicken embryo fibroblasts. The viral src protein produced in yeast autophosphorylated at tyrosine-416 in vivo and had approximately the same level of in vitro kinase activity as p60v-src expressed in Rous sarcoma virus-transformed cells. Unlike p60c-src expressed in chicken cells, which is phosphorylated on tyrosine in vivo almost exclusively at tyrosine-527, p60c-src expressed in yeast was phosphorylated 2.5-3 times more at tyrosine-416 than at tyrosine-527. The specific activity of the p60c-src produced in yeast was 2.5-5.0 times higher than that of p60c-src overexpressed from a retroviral vector in chicken cells, implicating the altered state of in vivo phosphorylation in modulation of the in vitro kinase activity. The expression of p60v-src substantially slowed down the growth of the yeast cells, suggesting that phosphorylation of yeast proteins essential for cell growth may have interfered with their proper functioning.     

Molecular genetic rearrangements distinguish pre- and post-bone marrow transplantation lymphoproliferative processes

Chronic myelocytic leukemia (CML) may display a lymphoproliferative phase (lymphoid blast crisis) that is generally of B cell phenotype. Since lymphoproliferative disorders may occur following bone marrow transplantation (BMT), it may be difficult to distinguish posttransplant relapse of CML lymphoid blast crisis from de novo lymphoproliferation. Lymphoid blast crisis cells from a patient with CML displayed immunoglobulin heavy chain gene (C mu) rearrangement before BMT. Following BMT the patient developed a lymphoproliferative disorder involving multiple organs. Clonal rearrangement of C mu was demonstrated in several involved tissues. The rearranged C mu restriction fragment was distinct from that displayed before BMT. Additionally, rearrangement of the breakpoint cluster region (bcr) was demonstrated in the pretransplant blast crisis sample, but not in the posttransplant lymphoproliferation samples, thus confirming that these lymphoproliferative disorders were distinct. Molecular genetic techniques offer powerful diagnostic tools for monitoring the course of patients with CML undergoing BMT.     

Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

Two pathways of exocytosis of cytoplasmic granule contents and target cell killing by cytokine-induced CD3+ CD56+ killer cells

Cytokine-induced killer (CIK) cells are non-major histocompatibility complex-restricted cytotoxic cells generated by incubation of peripheral blood lymphocytes with anti-CD3 monoclonal antibody (MoAb), interleukin-2 (IL-2), IL-1, and interferon-gamma. Cells with the greatest effector function in CIK cultures coexpress CD3 and CD56 surface molecules. CIK cell cytotoxicity can be blocked by MoAbs directed against the cell surface protein leukocyte function associated antigen-1 but not by anti-CD3 MoAbs. CIK cells undergo release of cytoplasmic cytotoxic granule contents to the extracellular space upon stimulation with anti-CD3 MoAbs or susceptible target cells. Maximal granule release was observed from the CD3+ CD56+ subset of effector cells. The cytoplasmic granule contents are lytic to target cells. Treatment of the effector cells with a cell-permeable analog of cyclic adenosine monophosphate (cAMP) inhibited anti-CD3 MoAb and target cell- induced degranulation and cytotoxicity of CIK cells. The immunosuppressive drugs cyclosporin (CsA) and FK506 inhibited anti-CD3- mediated degranulation, but did not affect cytotoxicity of CIK cells against tumor target cells. In addition, degranulation induced by target cells was unaffected by CsA and FK506. Our results indicate that two mechanisms of cytoplasmic granule release are operative in the CD3+ CD56+ killer cells; however, cytotoxicity proceeds through a cAMP- sensitive, CsA- and FK506-insensitive pathway triggered by yet-to-be- identified target cell surface molecules.     

An expanding role for CD40L and other tumor necrosis factor superfamily ligands in HIV infection

Immunostimulatory members of the tumor necrosis factor (TNF) superfamily (TNFSF) of ligands are known to be important regulators of the immune system. These trimeric molecules interact with members of the TNF receptor superfamily (TNFRSF) to stimulate immune cells. Of the TNFSF molecules, CD40 ligand (CD40L, also called CD154 or TNFSF5) is the most crucial molecule for activating antigen-presenting cells (APCs) and thereby initiating the immune response. Evidence has accrued indicating that HIV infection either selectively depletes those CD4(+) T cells that express CD40L in response to antigen or down-regulates CD40L expression by these cells. Because CD40L expression is necessary for the immune defense against HIV and opportunistic infections, an insufficiency of CD40L could contribute to the progression of AIDS. CD40L contributes to the antiviral mechanisms of the host by inducing anti-HIV beta-chemokines and activating CD8(+) T cells. However, CD40L stimulation can lead to enhanced HIV replication under certain experimental conditions, due to its immune activating properties and the need for cellular activation for high-level HIV production. On balance, it is believed that reversing the relative CD40L deficiency seen in HIV infection will be important for immune restoration in AIDS. In addition, adding CD40L to a therapeutic or preventative vaccine could lead to strengthened antiviral immunity. Because of the complexities in delivering this molecule, a number of forms of CD40L have been developed, and one form of soluble CD40L has been tested in humans. New strategies are being developed to translate the profoundly immunostimulatory effects of CD40L found in animal models to humans with HIV infection.