Are there differences in outcome after elective sigmoidectomy for diverticular disease and for cancer? A national inpatient study.

AIM: The postoperative outcome after elective sigmoidectomy for diverticulitis has not been compared to that for cancer. The study aimed to evaluate the differences in the postoperative outcome after sigmoidectomy for diverticular disease and cancer. METHOD: The National Inpatient Sample Database was used to identify patients who underwent elective sigmoid resection for diverticular disease or cancer between 2004 and 2011. After excluding patients with metastatic cancer and preoperative weight loss, sigmoid cancer and diverticulitis patients were matched using propensity score, controlling for age, gender, race, type of operation (open vs laparoscopic) and comorbidities. The end-points of interest were infective complications, reoperation, anastomotic leakage, rebleeding, length of hospital stay and in-hospital mortality. RESULTS: After propensity score matching (diverticulitis 11 192 patients, sigmoid cancer 11 192 patients), the mean age was 65 ± 12.5 years, 53.8% were male and 61.5% were Caucasian. Only 18.0% of the operations were done by laparoscopy. The overall complication rate was 17.7% and the in-hospital mortality rate was 0.9%. The diverticulitis group had a higher rate of surgical site infection (3.2% vs 2.6%, P = 0.004), intra-abdominal abscess formation (1.2% vs 0.4%, P < 0.0001) and reoperation (6.1% vs 4.1%, P < 0.0001) compared with the cancer group. The cancer group had a higher incidence of pneumonia (1.9% vs 1.5%, P = 0.01) and anastomotic leakage (9.2% vs 8.3%, P = 0.001). There was no difference in sepsis, deep vein thrombosis, respiratory failure, renal failure, rebleeding, overall complication rate or length of hospital stay. Subgroup analysis showed a higher in-hospital mortality for cancer than for diverticulitis patients whether resected by open or by laparoscopic surgery. CONCLUSION: Although elective sigmoidectomy for diverticular disease has a higher risk of infective complications, elective sigmoidectomy for cancer has a higher risk of anastomotic leakage.

Depression in the elderly in Vellore, South India: the use of a two-question screen.

BACKGROUND: Depression in the elderly is a common and disabling condition. The aim of the study was to evaluate the sensitivity and specificity of a two-question screen to identify depression and common mental disorders in the elderly. METHOD: Residents of a ward in the town of Vellore were identified by a door-to-door survey from which 204 subjects aged over 60 years were selected for the study by systematic random sampling. They were screened using the two-question screen. The Revised Clinical Interview Schedule (CIS-R) was employed to confirm the diagnosis. RESULTS: The prevalence of depression and common mental disorder, using the CIS-R standard, was found to be 31.5%. The two-question screen has a sensitivity of 93.8% and specificity of 48.2%. CONCLUSIONS: The high sensitivity of the two-question screen makes it a useful screening method which can be employed by health workers in the field.

Accurate axillary nodal staging can be achieved after neoadjuvant therapy for locally advanced breast cancer.

Lymph node status remains the most important prognostic indicator for breast cancer. Recent reports have established that the accuracy of assessing lymph node status is proportional to the number of nodes dissected. The accuracy of axillary staging following neoadjuvant chemotherapy has been cited as a technical concern due to limited node retrieval. The current study attempts to evaluate the ability to perform sentinel node biopsy (SNB) and formal axillary node dissection (AND) following neoadjuvant chemotherapy and to compare these results with non-neoadjuvant patients. One hundred sixteen consecutive patients undergoing SNB with simultaneous AND were retrospectively reviewed. Forty-two of these patients were treated with neoadjuvant chemotherapy prior to AND. Overall success rate in performing SNB in the neoadjuvant group was 95 per cent, and no false negatives have been noted to date. The overall SNB success rate in the non-neoadjuvant group was also 95 per cent with a false negative rate of 3 per cent. After AND in each group, a mean of 21 nodes were retrieved in the neoadjuvant group and 17.9 nodes in the non-neoadjuvant group (P = 0.018). In the neoadjuvant group, there were 19 node positive patients (42%) and 21 patients (28%) in the non-neoadjuvant group (P = 0.16). The mean number of positive nodes per patient was also similar between the two groups (2.9 in the neoadjuvant group vs 1.67 in the non-neoadjuvant group, P = 0.10). Following neoadjuvant therapy, accurate evaluation of the axilla is feasible. In this study, the mean number of nodes is significantly different in favor of the neoadjuvant group, but there is no significant difference in the number of node positive patients identified or in the mean number of positive nodes identified per patient. SNB is technically feasible with accuracy similar to that seen in patients with no history of neoadjuvant therapy. Neoadjuvant chemotherapy extends the use of breast-conserving therapy without sacrificing the ability to accurately stage the axilla either by use of standard axillary dissection or SNB.

Neoadjuvant chemotherapy for locally advanced breast cancer results in alterations in preoperative tumor marker status.

Neoadjuvant therapy followed by breast-conserving surgery has become an acceptable option for patients with locally advanced breast cancer. Although a distinct survival benefit has not been demonstrated using this approach, several questions have been raised following such therapy including its effects on receptor status and tumor markers. The current study retrospectively reviews estrogen receptor (ER), progesterone receptor (PR), and HER2-neu status in 55 consecutive patients treated by neoadjuvant chemotherapy. Preoperative and postoperative tumor markers were available for 43 of the 55 patients (78%). The pathologic complete tumor response rate (pCR) for this group was 19 per cent (8/43). Of those patients who did not achieve a pCR (n = 35), a change in tumor markers was seen in 25.7 per cent (9/35) of patients. When compared to a control group not undergoing neoadjuvant therapy, a significantly higher percent change in marker expression was noted in the neoadjuvant group (25.7% vs 5.9%, P = 0.046). ER, PR, and HER2-neu status remain important prognostic indicators for breast cancer. Tumor markers are useful in planning adjuvant therapy regimens. In this review, nearly 19 per cent of patients achieved a pCR. In patients not achieving a pCR, one in four patients had at least one change in tumor marker status. This study demonstrates the importance of establishing receptor and marker status prior to neoadjuvant therapy, as many patients will achieve a pCR and make tumor analysis impossible. Postoperative marker studies should be performed given the possibility of a change in status. The clinical relevance of this data will require further long-term follow-up. Until such data becomes available, caution should be considered when basing adjuvant therapy regimens on preoperative tumor marker studies alone.

Dexamethasone affects cytokine-mediated adhesion of HL-60 human promyelocytic leukemia cells to cultured dermal microvascular endothelial cells.

Leukocyte endothelial adhesion (LEA) is the prelude to a complex cascade of reactions following an immunological challenge. Recently, LEA has been implicated in the molecular basis of several dermatological disorders. While the role of proinflammatory cytokines, such as interleukin-1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), in LEA has been investigated using nondermal models, limited data exist regarding their effects on LEA in dermal models. This study shows that cotreatment of cultured human dermal endothelial cells (CADMEC) with IL-1beta and TNF-alpha resulted in a marked increase in the adherence of human promyelocytic leukemia (HL-60) cells to CADMEC and an increase in expression of intercellular adhesion molecule-1 and E-selectin. Pretreatment of CADMEC with dexamethasone, a long-lasting glucocorticoid, resulted in a decrease in both HL-60 cell adhesion to CADMEC and adhesion molecule expression. Taken together, these data demonstrate that LEA may play a role in inflammatory skin conditions and in the mechanisms underlying the potential use of glucocorticoids as a treatment option.

Fimbria-mediated enhanced attachment of nontypeable Haemophilus influenzae to respiratory syncytial virus-infected respiratory epithelial cells.

Respiratory syncytial virus (RSV) infection is known to predispose children to otitis media and sinusitis due to bacteria such as nontypeable Haemophilus influenzae (NTHI). In this study, we investigated the role of NTHI surface outer membrane protein P5-homologous fimbriae (P5-fimbriae) in attachment to RSV-exposed A549 epithelial cells. Analysis by fluorescence flow cytometry showed that a live P5-fimbriated NTHI strain (NTHIF+) attached to a higher proportion of RSV-exposed A549 cells than to control cells (mean, 68% for RSV versus 29% for control; P = 0.008), while attachment of the P5-fimbriae-deficient isogenic mutant strain (NTHIF-) was significantly lower than in control cells and rose only slightly following RSV exposure (mean, 17% for RSV versus 10% for control, P = 0.229). Attachment of NTHIF+ did not correlate with the amount of RSV antigen expressed by A549 cells. Furthermore, paraformaldehyde-fixed NTHIF+ also demonstrated an enhanced binding to RSV-exposed cells. Observations by transmission electronic microscopy showed that the mean number of bacteria attached per 100 RSV-exposed A549 cells was higher for NTHIF+ than NTHIF- (99 versus 18; P < 0.001). No intracellular bacteria were identified. UV-irradiated conditioned supernatants collected from RSV-infected A549 cultures (UV-cRSV) also enhanced the attachment of NTHIF+ to A549, suggesting the presence of a preformed soluble mediator(s) in UV-cRSV that enhances the expression of receptors for P5-fimbriae on A549 cells. In summary, RSV infection significantly enhances NTHI attachment to respiratory epithelial cells. P5-fimbria is the critical appendage of NTHI that participates in this attachment. In clinical settings, blocking of the P5-fimbria-mediated attachment of NTHIF+ by passive or active immunity may reduce the morbidity due to NTHI during RSV infection.

Cytokine modulation of human corneal epithelial cell ICAM-1 (CD54) expression.

To determine whether pro-inflammatory cytokines modulate intercellular adhesion molecule-1 (ICAM-1; CD54) expression on cultured primary human corneal epithelial cells (HCEs), confluent HCEs were treated with various concentrations of interferon-gamma(IFN-gamma), interleukin-1alpha(IL-1alpha), IL-1beta, IL-4, tumor necrosis factor-alpha (TNF-alpha), or combinations over time. ICAM-1 expression was measured by flow cytometry and/or a cell-based ELISA using a monoclonal mouse anti-human CD54 antibody. The apparent MW of ICAM-1 protein was determined by immunoprecipitation of biotinylated HCEs. RT-PCR was used to detect ICAM-1 RNA. The mature cell surface form of HCE ICAM-1 was approximately 110 kDa as determined by immunoprecipitation. IFN-gammaand TNF-alpha induced both dose- and time-dependent increases in ICAM-1 expression. An approximately 20-fold increase in ICAM-1 was seen at 50-100 U IFN-gamma ml-1. ICAM-1 specific mRNA accumulated approximately 4.5-fold after IFN-gammatreatment. TNF-alpha(100 U ml-1) induced a consistent approximately 6.0-fold increase in ICAM-1 expression. When IFN-gammaand TNF-alpha were mixed, at sub-optimal concentrations of each, a synergistic effect on ICAM-1 expression was not detected. Neither IL-4, IL-1alpha nor IL-1beta affected ICAM-1 expression in a consistent fashion. In summary, ICAM-1 was modulated on primary human corneal epithelial cells by the cytokines IFN-gamma and TNF-alpha in a dose- and time-dependent fashion. Cytokine modulation of corneal epithelial cell ICAM-1 during inflammation may contribute to corneal epithelial cell injury by aiding the attachment of inflammatory cells such as eosinophils which express the receptor for ICAM-1, the beta2 integrins (CD11a,b,c/CD18).

Arachidonylethanolamide (AEA) activation of FOS proto-oncogene protein immunoreactivity in the rat brain.

It is thought that the physiological actions of endogenous cannabinoid arachidonylethanolamide (AEA), as well as exogenous cannabinoids such as Delta9-tetrahydrocannabinol (THC), are mediated by two subtypes of cannabinoid receptors, CB1 and CB2, which have recently been characterized. Injection of AEA leads to alterations in motor behavior and endocrine function. While these phenomena have been well characterized, the neuronal substrate of AEA's actions remains undetermined. In this study, FOS immunoreactivity (FOSir) was used to map rat brain nuclei that are responsive to a single intracerebroventricular injection of AEA. The results showed that FOSir was induced in several nuclei including the bed nucleus of the stria terminalis (BNST), paraventricular nucleus of the hypothalamus (PVN), central nucleus of the amygdala (Ce), periaqueductal gray area (PAG), dentate gyrus in the hippocampus (Dg), paraventricular nucleus of the thalamus (PVA), median preoptic nucleus (MnPO), periventricular nucleus (Pe), caudate putamen (CPU) and the ependymal lining of the ventricles. The pattern of activation identified correlates, in part, with the distribution of CB receptors. At the same time, a new subset of nuclei, without demonstrable CB receptors, have been shown to respond to an AEA challenge. Activation of these nuclei is consistent with the physiological effects of AEA. These findings provide valuable information on the response to AEA at the level of neuronal activation and provide the basis for a broader understanding of the possible role of CB receptors in the modulation of motor and endocrine function associated with the use of exogenous cannabinoids, such as marijuana.

Autocrine regulation and experimental modulation of interleukin-6 expression by human pulmonary epithelial cells infected with respiratory syncytial virus.

The mechanisms of regulation of interleukin-6 (IL-6) production in respiratory syncytial virus (RSV)-infected respiratory epithelial cells were evaluated in A549 cell cultures. Incubation with purified RSV resulted in significant production of IL-1alpha, IL-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha). Addition of saturating concentrations of neutralizing antibodies against IL-1alpha, IL-1beta, or TNF-alpha into purified RSV-infected cell cultures resulted in a significant inhibition of IL-6 production, although anti-IL-1alpha antibody had the most predominant effect (80% inhibition). Anti-IL-1alpha antibody also almost completely blocked the expression of mRNA for IL-6. Addition of therapeutic concentrations of dexamethasone (1 microM) or ribavirin (90 microg/ml), an antiviral agent, also significantly inhibited the synthesis of IL-6. Hence, in clinical settings, pharmacological agents such as the specific antagonists of IL-6-inducing cytokines, as well as dexamethasone and ribavirin, could be used to modulate IL-6 production.

Autocrine regulation of interleukin-8 by interleukin-1alpha in respiratory syncytial virus-infected pulmonary epithelial cells in vitro.

Respiratory epithelial cells infected with respiratory syncytial virus (RSV) produce interleukin-8 (IL-8); however, the mechanisms of RSV-induced regulation of IL-8 are poorly understood. In the present study, the regulation of IL-8 by RSV was evaluated using pulmonary type II-like epithelials (A549). Live purified RSV (pRSV) induced a significant increase in IL-8 after 8 hr of exposure, while conditioned supernatants from pRSV-infected A549 cells (cRSV) induced IL-8 production in fresh A549 cultures within 4 hr of infection. Furthermore, cRSV that had been rendered non-infectious by ultraviolet-irradiation (UV-cRSV) or ribavirin treatment also induced an increased production of IL-8 in fresh A549 cells, suggesting that RSV induced the synthesis of a soluble mediator(s) which in turn enhanced the synthesis of IL-8. We have previously shown that RSV-infected A549 cells produce IL-1alpha, IL-1-beta and tumour necrosis factor-alpha (TNF-alpha), which by themselves are known to induce the synthesis of IL-8. Preincubation of UV-cRSV or simultaneous incubation of pRSV with recombinant IL-1 receptor antagonist almost completely blocked (95-98%) the production of IL-8 by A549 cells. Furthermore, incubation with neutralizing antibodies against IL-1alpha, IL-1beta and TNF-alpha showed that IL-1alpha was the predominant soluble mediator that enhanced the mRNA expression and synthesis of IL-8. IL-1beta and TNF-alpha induced the synthesis of IL-8 at 24 hr, but partially inhibited the synthesis at 48 hr. In summary, these experiments provide direct evidence for an autocrine mechanism of enhanced IL-8 production in RSV-infected epithelial cells that is primarily mediated by IL-1alpha. In clinical settings, inhibitors of IL-1alpha may be useful in suppressing inflammation due to IL-1alpha as well as IL-8.

Transcription of genes encoding iron and heme acquisition proteins of Haemophilus influenzae during acute otitis media.

Unencapsulated Haemophilus influenzae is the second most common etiologic agent of otitis media in children. H. influenzae requires heme for aerobic growth in vitro and is able to utilize hemoglobin and complexes of heme-hemopexin, heme-albumin, and hemoglobin-haptoglobin and ferritransferrin as sources of iron and heme in vitro. Several of the acquisition mechanisms have been characterized and been shown to be heme repressible in vitro. However, little is known about the expression of heme and/or iron acquisition mechanisms during infections in the middle ear. This study was performed to determine if the genes encoding heme and iron acquisition proteins are transcribed during in vivo growth and to compare these findings with those for samples grown in vitro. Reverse transcriptase PCR (RT-PCR) was used to analyze total RNA fractions derived from in vitro- and in vivo-grown H. influenzae. Genes encoding the transferrin-binding proteins TbpA and TbpB, the 100-kDa hemopexin-binding protein HxuA, and the hemoglobin-binding protein HgpA were transcribed during otitis media. Twelve middle ear fluid samples were analyzed by blind RT-PCR to determine the transcriptional status of these genes in H. influenzae during otitis media. Five isolates had transcripts corresponding to tbpA, tbpB, and hxuA. The presence of hgpA transcripts was variable, depending on the presence of hgpA in the genome of the H. influenzae isolate. Samples without H. influenzae gene transcripts contained other etiologic agents commonly causing otitis media. These data demonstrate that H. influenzae iron and/or heme acquisition genes are transcribed during otitis media and suggest that the microenvironment during acute otitis media starves H. influenzae of heme.

Chronic exposure to morphine, but not ethanol, attenuates the expression of interleukin-1 beta converting enzyme in rat spleen.

IL-1 beta converting enzyme (ICE), a proteolytic enzyme that converts the inactive precursor of interleukin-1 beta (IL-1 beta) to its mature active form, has been abundantly detected in the IL-1 beta producing cells in the spleen. Since IL-1 beta is a potent neuro-endocrine-immuno modulator, alterations in the production of IL-1 beta by an exogenous factor, such as morphine or ethanol, may have deleterious effects on the system as a whole. In this study, we examined the expression of ICE in the spleens of rats given chronic treatment with morphine versus ethanol using reverse transcriptase-polymerase chain reaction (RT-PCR). The expression of ICE in the spleen of rats given chronic morphine was clearly less than that of the animals given placebo, however, it was similar for both rats on ethanol and control diets. These data suggest that chronic use of morphine, but not ethanol, attenuates the expression of ICE in the spleen.

Interleukin-1 alpha mediates the enhanced expression of intercellular adhesion molecule-1 in pulmonary epithelial cells infected with respiratory syncytial virus.

The mechanisms of virus-induced enhancement of intercellular adhesion molecule-1 (ICAM-1) expression in epithelial cells are unknown. In the present study, the effect of respiratory syncytial virus (RSV) infection on the expression of ICAM-1 in human pulmonary type II-like epithelial (A549) cells was evaluated. Conditioned RSV media (cRSV) produced from growth of RSV in A549 cells induced a significant increase in the expression of ICAM-1. Treatment of the cells with noninfectious cRSV prepared by ultraviolet (UV) irradiation (UV-cRSV) or ribavirin treatment resulted in the expression of ICAM-1 to a similar extent as infectious cRSV. These results suggested that RSV induces the synthesis of a soluble mediator(s) that regulates the expression of ICAM-1. Cytokine analysis by immunoassay and polymerase chain reaction showed that RSV induces the synthesis of interleukin (IL)-1 alpha and -beta, and tumor necrosis factor alpha (TNF-alpha). Preincubation of UV-cRSV with soluble IL-1 receptor (sIL-1r) almost completely blocked the enhancement of ICAM-1 expression. Furthermore, simultaneous incubation of infectious purified RSV with sIL-1r resulted in a significant reduction in enhancement of ICAM-1 expression. Preincubation with neutralizing antibodies to IL-1 alpha and -beta, and TNF-alpha showed that the predominant ICAM-1 enhancing soluble mediator in UV-cRSV was IL-1 alpha. These experiments provide direct evidence for an autocrine mechanism of enhanced ICAM-1 expression in RSV-infected epithelial cells that is mediated primarily by IL-1 alpha. Pulmonary epithelial cells may play an important immunoregulatory role in the microenvironment of the lower respiratory tract infected with RSV.

Presence of respiratory syncytial virus genomic sequences in middle ear fluid and its relationship to expression of cytokines and cell adhesion molecules.

The presence of respiratory syncytial virus (RSV) and several cytokines and cell adhesion molecules in middle ear effusions and mucosal tissues was evaluated using polymerase chain reaction. RSV genomic sequences were detected in 23 (52.7%) of 44 middle ear effusions tested. The sequences were detectable at an even higher rate (82.4%) in effusions of children in whom infectious virus was detected in the nasopharynx. All samples with the RSV genome contained the mRNA for interleukin-1 beta and -6 and tumor necrosis factor-alpha. The messages for these cytokines, together with intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, and vascular cell adhesion molecule-1, were detected in human middle ear mucosal organ cultures infected in vitro with RSV. Our results suggest that the enhanced synthesis of proinflammatory cytokines and cell adhesion molecules in the middle ear infected with RSV may contribute to the inflammatory processes in otitis media.

Doxylamine: a cause for false-positive gas chromatographic assay for phencyclidine.

A 25-year-old white woman ingested an unknown quantity of doxylamine succinate and flurazepam. Urine immunoassay screen (EMIT-dau) was positive for benzodiazopine and negative for phencyclidine. Subsequent gas chromatographic assay of the urine revealed a markedly positive assay for phencyclidine. Doxylamine was ultimately found to be the cause for the false-positive gas chromatographic assay for phencyclidine.