Spinal anaesthesia but not general anaesthesia enhances neutrophil biocidal activity in hip arthroplasty patients

The purpose of this study was to compare neutrophil cidal activity during general or spinal anaesthesia. Assays were performed on neutrophils extracted from the blood of patients after surgery had been under way for one hour. First, the ability of the neutrophils to kill a standard laboratory strain of S. aureus was examined. Neutrophils extracted from the blood during surgery in the spinal anaesthetic group and incubated with the staphylococci for one hour killed twice as many bacteria than those from two groups of patients that received halothane or isoflurane general anaesthesia (P < 0.05). This effect persisted, to a lesser extent, in the spinal group neutrophils after two hours of incubation with the bacteria. Second, neutrophils from patients under the same conditions of surgery and anaesthesia were tested to examine the effect of the different anaesthetic techniques on neutrophil biocidal mechanisms. Neutrophils extracted during surgery in the spinal group released more superoxide in response to phorbol-12-myristate-13-acetate (PMA) than those from both groups of patients that received general anaesthesia (P < 0.05). It is concluded that there is an increased state of reactivity of the neutrophil cell membrane NADPH oxidase system in patients receiving spinal anaesthesia than in patients receiving general anaesthesia.     

Antibiotic Administration in Patients Undergoing Common Surgical Procedures in a Community Teaching Hospital: The Chaos Continues

The influence of recently published guidelines by the Surgical Infection Society (SIS) on current surgical practice are not well documented. The appropriateness of antibiotic administration in a cohort of surgical patients undergoing elective and emergency surgery in a department of surgery in an urban, community-based, private, 560-bed teaching hospital was retrospectively reviewed. The following were the criteria defining administration as appropriate as modified from SIS guidelines: Prophylactic use: (1) started prior to operation; (2) spectrum appropriate to the specific operation; (3) duration ≤ 24 hours. Therapeutic use: (1) started prior to operation; (2) spectrum appropriate to pathology; (3) Duration ≤ 24 hours for contamination or “resectable” infection and ≤ 5 days for established infection in the absence of clinical evidence of persisting infection. Any switchover from an appropriate agent to another appropriate or inappropriate agent in the same patient in the absence of microbiologic or clinical indication was considered inappropriate administration. We reviewed the charts of 211 randomly selected patients who underwent elective (n= 132) or emergency (n= 79) procedures during 1996. The operations included gastrectomy (n= 22), appendectomy (n= 27), open (n= 5) or laparoscopic (n= 27) cholecystectomy, colectomy (n= 28), hysterectomy (n= 8), laparotomy for intestinal obstruction (n= 11), mastectomy (n= 26), and ventral hernia repair (n= 37). A total of 17 antibiotics were used for prophylaxis and 21 for therapy. In 156 patients (74%) the administration was considered inappropriate. Eight patients in the inappropriate group developed diarrhea (two cases of Clostridium difficile-induced colitis) compared to two cases of diarrhea in the appropriate group (nonsignificant). The average duration of administration after elective and emergency operations was 3.3 and 5.7 days, respectively. The total expense for excessive duration of administration was $18,533. Many surgeons are not familiar with the spectrum of antimicrobials and often do not distinguish between prophylactic and therapeutic administration. Antibiotic usage in current surgical practice is often inappropriate, excessive, and chaotic.     

Comparing changes in transient-evoked otoacoustic emission and pure-tone audiometry following short exposure to industrial noise

It has been suggested that otoacoustic emissions, particularly transient-evoked otoacoustic emissions (TEOAE), might be more sensitive in assessment of changes to the cochlea caused by noise than pure-tone audiometry (PTA). The aim of the study was to compare temporary threshold shifts with the changes in TEOAE following a six-hour exposure to industrial noise at the intensity of 85-97 dB (A). Thirty two male employees of a metal factory were screened. TEOAE, PTA and tympanometry were included in the hearing test battery. Both, PTA and TEOAE showed significant reduction due to noise exposure, but no correlation between temporary threshold shifts and decreases in either the overall TOAE level or the level of otoacoustic emission in the frequency bands was found. Our results confirm the high sensitivity of TEOAE to short exposure to industrial noise. This study may recommend this measurement as a method of evaluation for TTS conditions for hearing conservation programme purposes, in addition to pure-tone audiometry.     

Low doses of oxytocin facilitate social recognition in rats

Social recognition of juveniles by adult male residents has been shown to be modulated by neurohypophyseal hormones. The decrease of social investigation behavior during a second encounter with the same juvenile serves as index for social recognition. In the present study it was found that low doses (0.09–6.0 ng · kg^–1) of oxytocin (OXT) given subcutaneously dose dependently facilitated social recognition. The effect of OXT appeared specific, since no change in social investigation was found when a novel juvenile was tested during the second encounter. No disturbances of social recognition by the low doses of OXT could be detected, in contrast to higher doses of this hormone. Other neurohypophyseal hormones, vasopressin and vasotocin, did not facilitate social recognition when tested in the same range of low doses.     

Shortlasting, Unilateral, Neuralgiform Headache Attacks With Conjunctival Injection, Tearing, and Subclinical Forehead Sweating ("Sunct" Syndrome): II. Changes in Heart Rate and Arterial Blood Pressure During Pain Paroxysms.

The recently described "Sunct" syndrome is a rare picture of unilateral, shortlasting headache attacks accompanied by autonomic phenomena (conjunctival injection, tearing, etc.) on the symptomatic side. Heart rate and blood pressure were monitored in two elderly "Sunct" patients during and outside headache attacks. An ultrasound Doppler servo method was used for the non-invasive, continuous, beat-to-beat determination of instantaneous arterial blood pressure. In a third patient, systolic and diastolic blood pressure, both outside and during pain paroxysms, were assessed using the standard Korotkoff method. Heart rate was found to be significantly decreased during pain paroxysms. Systolic blood pressure was observed to be significantly increased during attacks, when compared with the inter-attack period, while a less consistent pattern was observed for diastolic blood pressure. Some of the changes in the cardiovascular system seemed to start prior to pain onset. Therefore, it seems unlikely that these changes were caused by pain activation of the sympathetic nervous system or the oculocardiac reflex.     

Effect of agomelatine in the chronic mild stress model of depression in the rat.

Chronic mild stress (CMS), a well-validated model of depression, was used to study the effects of the melatonin agonist and selective 5-HT(2C) antagonist agomelatine (S 20098) in comparison with melatonin, imipramine, and fluoxetine. All drugs were administered either 2 h before (evening treatment) or 2 h after (morning treatment) the dark phase of the 12-h light/dark cycle. Chronic (5 weeks) evening treatment with agomelatine or melatonin (both at 10 and 50 mg/kg i.p.) dose-dependently reversed the CMS-induced reduction in sucrose consumption. The magnitude and time course of the action of both drugs was comparable to that of imipramine and fluoxetine (both at 10 mg/kg i.p.); however, melatonin was less active than agomelatine at this dose. The effect of evening administration of agomelatine and melatonin was completely inhibited by an acute injection of the MT(1)/MT(2) antagonist, S 22153 (20 mg/kg i.p.), while the antagonist had no effect in animals receiving fluoxetine or imipramine. When the drugs were administered in the morning, agomelatine caused effects similar to those observed after evening treatment (with onset of action faster than imipramine) but melatonin was ineffective. Moreover, melatonin antagonist, S 22153, did not modify the intakes in stressed animals receiving morning administration of agomelatine and in any other control and stressed groups tested in this study. These data demonstrate antidepressant-like activity of agomelatine in the rat CMS model of depression, which was independent of the time of drug administration. The efficacy of agomelatine is comparable to that of imipramine and fluoxetine, but greater than that of melatonin, which had no antidepressant-like activity after morning administration. While the evening efficacy of agomelatine can be related to its melatonin receptors agonistic properties, its morning activity, which was not inhibited by a melatonin antagonist, indicates that these receptors are certainly required, but not sufficient to sustain the agomelatine efficacy. It is therefore suggested that the antidepressant-like activity of agomelatine depends on some combination of its melatonin agonist and 5-HT(2C) antagonist properties.     

Interleukin 12-based immunotherapy improves the antitumor effectiveness of a low-dose 5-Aza-2'-deoxycitidine treatment in L1210 leukemia and B16F10 melanoma models in mice.

PURPOSE: Recent findings indicating that many genes related to cancer development are silenced by an aberrant DNA methylation suggest that inhibitors of this process may be effective cancer therapeutics. In this study we investigated the efficacy of low-dose 5-aza-2'-deoxycitydine (DAC), a methylation inhibitor, with interleukin (IL) 12, one of the most potent cytokines with antitumor activity. Experimental Design: Mice inoculated with L1210 leukemia cells or with B16F10 melanoma cells were treated with 7 daily injections of low-dose DAC (0.2 mg/kg) and/or 7 daily doses of IL-12 (100 ng/dose). Scid/scid mice as well as monoclonal antibodies against CD4, CD8, and NK1.1 were used to investigate the mechanisms of the antitumor effects of the combination treatment. The activity of murine lymphocytes was measured with enzyme-linked immunospot and (51)Cr release assays. RESULTS: Treatment with DAC or IL-12 given alone produced moderate antitumor effects. In both tumor models combined treatment resulted in potentiated antitumor effects and produced 70% long-term survivors among mice inoculated with L1210 cells. The antitumor efficacy of combined treatment was abrogated in scid/scid mice, and after depletion of CD4(+) and CD8(+) T cells. Mice inoculated with B16F10 melanoma cells had significantly delayed tumor growth after combined treatment with DAC and IL-12. Strong antitumor effect correlated with a significant activation of lymph node-derived CD8(+) and CD4(+) cells. Transient neutropenia was observed in mice under treatment of DAC alone, but remarkably this effect was not potentiated by IL-12. CONCLUSIONS: This study provides the first evidence that antitumor effects of DAC can be strongly potentiated by IL-12 and could be beneficial in an effective low-dose-based antitumor therapy.     

Inhibition of cyclooxygenase-2 indirectly potentiates antitumor effects of photodynamic therapy in mice.

PURPOSE: The aim of the present study was to potentiate the antitumor effectiveness of photodynamic therapy (PDT). A cDNA microarray analysis was used to evaluate the gene expression pattern after Photofrin-mediated PDT to find more effective combination treatment with PDT and inhibitor(s) of the identified gene product(s) overexpressed in tumor cells. EXPERIMENTAL DESIGN: Atlas Mouse Stress Array was used to compare the expression profile of control and PDT-treated C-26 cells. The microarray results have been confirmed using Western blotting. Cytostatic/cytotoxic in vitro assay as well as in vivo tumor models were used to investigate the antitumor effectiveness of PDT in combination with cyclooxygenase (COX) 2 inhibitors. RESULTS: PDT induced the expression of 5 of 140 stress-related genes. One of these genes encodes for COX-2, an enzyme important in the tumor progression. Inhibition of COX-2 in vitro with NS-398, rofecoxib, or nimesulide, or before PDT with nimesulide did not influence the therapeutic efficacy of the treatment. Administration of a selective COX-2 inhibitor after PDT produced potentiated antitumor effects leading to complete responses in the majority of treated animals. CONCLUSIONS: COX-2 inhibitors do not sensitize tumor cells to PDT-mediated killing. However, these drugs can be used to potentiate the antitumor effectiveness of this treatment regimen when administered after tumor illumination.     

Sexual Functioning in Female Patients Undergoing Surgical Treatment for Colorectal Cancer—A Single-Center,Prospective Triple Timepoint Yearly Follow-Up

The study was aimed at assessing the quality of sexual functioning in female patients having undergone surgical treatment for cancer depending on the type of surgery. The prospective cohort consisted of 48 female patients (23 patients with stoma [A2] and 25 patients with maintained continuity of the GI tract [A1]). Study methods included a diagnostic survey and the analysis of medical records of patients. Research tools consisted of a standardized FSFI questionnaire and a proprietary form for evaluation of sociodemographic data. Measurements were performed at threetimepoints: On the day before the surgery (Measurement I) as well as six and 12 months after the surgery (Measurements II and III, respectively). Statistically significant differences in results were observed in Measurements II and III in the subscales of arousal (II:p = 0.0068, III:p = 0.0018), lubrication (II:p = 0.0221, III:p = 0.0134), orgasm (II:p = 0.0044, III:p = 0.0021), satisfaction (II:p = 0.0021, III:p = 0.0433), and pain/discomfort (II:p = 0.0343, III:p = 0.0473). In all cases, lower scores corresponding to lower quality of sexual functioning were observed in patients in whom stoma had been performed. Statistically significant differences in sexual functioning were observed at Measurements II and III in each group, with the results being significantly (p > 0.05) worse in patients having undergone Hartmann’s procedure or abdominoperineal resection). Variables significantly affecting self-assessed sexual satisfaction included marital status, age, and modality of neoadjuvant treatment. Restoration of the continuity of the gastrointestinal tract is a chance for better self-assessment of the patient’s quality of life as regards sexual functioning.