EEG Changes during Awake Carotid Endarterectomy

To determine the reason for differing shunt rates based on electroencephalographic (EEG) and neurologic changes during general and regional anesthetic, respectively, we compared simultaneous EEG tracings and neurologic status in 135 patients undergoing carotid endarterectomy (CEA) under cervical block over a 30-month period. The decision to shunt in these patients was made on the basis of neurologic changes only irrespective of EEG findings. This group was then compared to the 288 patients undergoing CEA under general anesthetic with EEG monitoring over the same period. EEG changes occurred in 7.4% of awake patients and 15.3% of asleep patients (p <0.03). The rates of ipsilateral hemispheric changes were similar, but no awake patient manifested global EEG changes with clamping while 3.5% of patients under general anesthesia did (p <0.04). Global, but not hemispheric, changes were correlated with systolic blood pressure variability during clamping. This implies that global EEG changes in anesthetized patients may be the result of the anesthetic technique itself, and that cervical block may in fact be cerebroprotective.     

Pairings of ethanol sipper with food induces Pavlovian autoshaping of ethanol drinking in rats: evidence of long-term retention and effects of sipper duration

AIMS: This study asks if repeated Pavlovian pairings of a sipper tube (conditioned stimulus, CS) with food (unconditioned stimulus, US) will induce Pavlovian autoshaping conditioned responses (CRs), consisting of drinking of either 6% ethanol or water from the sipper CS. This study also tests predictions derived from the autoshaping model by asking if sipper CS-directed drinking will be retained, despite the absence of training for several weeks, and, in addition, if drinking rate is a negative function of sipper CS duration. METHODS: Autoshaping procedures, conducted in two daily sessions, consisted of the brief insertion of the sipper tube CS followed by the response-independent presentation of food US. For the Ethanol group (n = 8), the sipper CS contained 6% ethanol, whereas for the Water group (n = 8), the sipper CS contained tap water. Saccharin fading procedures were employed, whereas for both groups, during days 1-19, the sipper CS contained 0.1% saccharin, and thereafter across training days the concentration of saccharin was gradually reduced (0.07, 0.035, 0.0%). Following elimination of saccharin, both groups were maintained in their home cages during a 27-day retention interval, and then re-evaluated for autoshaping of drinking of unsweetened ethanol and water. Thereafter, across days, the duration of access to the sipper CS (5.0, 7.5, 10.0, 15.0 s) during each autoshaping trial was increased. RESULTS: Both groups increased drinking across the first 19 days of training with sipper CS-food US pairings, and, at 0.0% saccharin, the Ethanol group consumed 14.76 ml of 6% ethanol per day, resulting in a daily ethanol consumption of 2.77 g/kg. For both groups, daily levels of drinking before and after the 27-day retention interval were comparable, attesting to the durability of the acquired drinking effects. At each CS duration, the Ethanol group consumed more millilitres of fluid per day than did the Water group, and for the Ethanol group, peak drinking of 24.0 ml of 6% ethanol per day was observed at the 10 s CS duration. For both groups, drinking rate (millilitres of fluid consumed per second of CS duration), was a declining monotonic function of CS duration, resulting in a daily ethanol consumption of approximately 4.2 g/kg for the Ethanol group. CONCLUSIONS: These data reveal that these sipper CS-food US autoshaping procedures induce drinking in rats that is durable and negatively related to increasing CS duration. The effects of both variables are consistent with the hypothesis that drinking from the sipper CS is a Pavlovian autoshaping CR. Autoshaping of drinking in the Water group is observed despite the absence of water deprivation, and even more fluid is consumed by the Ethanol group than by the Water group. The high volumes of ethanol consumed during brief daily sessions suggest that Pavlovian autoshaping procedures may provide an animal learning model of binge drinking.     

Ubiquitination capabilities in response to neocarzinostatin and H(2)O(2) stress in cell lines from patients with ataxia-telangiectasia

The human genetic disorder ataxia-telangiectasia (A-T) is due to lack of functional ATM, a protein kinase which is involved in cellular responses to DNA double strand breaks (DSBs) and possibly other oxidative stresses, as well as in regulation of several fundamental cellular functions. Studies regarding responses in A-T cells to the induction of DSBs utilize ionizing radiation or radiomimetic chemicals, such as neocarzinostatin (NCS), which induce DNA DSBs. This critical DNA lesion activates many defense systems, such as the cell cycle checkpoints. The cell cycle is also regulated through a timed and coordinated degradation of regulatory proteins via the ubiquitin pathway. Our recent studies indicate that the ubiquitin pathway is influenced by the cellular redox status and that it is the major cellular pathway for removal of oxidized proteins. Accordingly, we hypothesized that the absence of a functional ATM protein might involve perturbations to the ubiquitin pathway as well. We show here that upon treatment with NCS, there was a transient 50-70% increase in endogenous ubiquitin conjugates in A-T and wt lymphoblastoid cells. Ubiquitin conjugation capabilities per se and levels of substrates for conjugation were also similarly enhanced in wt and A-T cells upon NCS treatment. We also compared the ubiquitination response in A-T and wt cells using H(2)O(2) as the stress, in view of preexisting evidence of the effects of H(2)O(2) on ubiquitination capabilities in other types of cells. As with NCS treatment, there was an approximately 45% increase in endogenous ubiquitin conjugates by 2-4 h after exposure to H(2)O(2). Both cell types showed a rapid 50-150% increase in de novo formed 125I-ubiquitin conjugates. As compared with wt cells, unexposed A-T cells had higher endogenous levels of conjugates and enhanced conjugation capability. However, A-T cells mounted a more muted ubiquitination response to the stress. The enhanced ubiquitin conjugation in unstressed A-T cells and attenuated ability of these cells to respond to stress are consistent with the A-T cells being under oxidative stress and with their having an 'aged' phenotype. The indication that ubiquitin conjugate levels and ubiquitin conjugation capabilities are enhanced upon oxidative stress without significant changes in GSSG/GSH ratios indicates that assays of ubiquitination provide a sensitive measure of cellular stress. The data also add support to the impression that potentiated ubiquitination response to mild oxidative stress is a generalizable phenomenon.     

Demented patients' participation in a clinical trial: factors affecting the caregivers' decision

Clinical trials for Alzheimer's disease take place in medical centers all over the world. Patients and caregivers have to decide whether or not to agree to participate in clinical trials. This study aimed to investigate the motivation that determines the caregivers' choice. Nineteen caregivers of demented patients who consented to participate in a clinical trial in our Memory Clinic and 10 caregivers who refused to participate were interviewed. The data were gathered by a self-report questionnaire covering various aspects of the caregivers' decision-making process. Among the reasons for agreeing to participate in the clinical trial were the respondents' belief that it would improve or help to maintain the patients' condition. Most of the respondents of both groups indicated that information regarding side effects and success probability was adequately provided in advance. The primary reason for refusal was the potential side effects of the drug. The implications of the findings are discussed.     

High prevalence of the prothrombin gene mutation in women with intrauterine growth retardation, abruptio placentae and second trimester loss

BACKGROUND: It has been reported recently that obstetric complications are associated with thrombophilias. Our objective was to investigate the association between pregnancy complications and the guanine 20210 adenine (G20210A) mutation in prothrombin gene. METHODS: Two hundred and twenty-two women (study group) with obstetric complications were tested for the prothrombin mutation. Indications for testing were: severe preeclampsia, mild preeclampsia, intrauterine growth retardation, severe abruptio placentae, unexplained stillbirth, second trimester loss, and three or more consecutive spontaneous abortions. We also tested 156 healthy women who had at least one normal pregnancy and comprised the control group. RESULTS: Demographic data of the study and control groups were similar. Twenty-eight women of the study group (13%) were found to be heterozygous carriers of the 20210 variant of the prothrombin gene compared to five (3.2%) of the control group, p=0.001, odds ratio (OR) 2.9; 95% confidence interval (CI) 1.3-6.5. Compared to the control women, the prothrombin gene mutation was significantly more prevalent in women with IUGR, abruptio placentae, and second trimester loss but not in women with mild or severe preeclampsia, stillbirth and habitual abortion. CONCLUSIONS: Our data demonstrate that the mutation in the prothrombin gene is associated with specific pregnancy complications.     

The effect of continuous intraabdominal nebulization of lidocaine during gynecological laparoscopic procedures- a pilot study

Although laparoscopic surgery is known to cause less postoperative pain when compared to laparotomy, some patients still suffer from excessive pain, especially during the first stages of recovery. The purpose of our study was to assess the effect of intraperitoneal nebulization of lidocaine during gynecological laparoscopic procedures on perioperative pain. The study was a prospective, randomized, double-blinded, placebo-controlled trial (Canadian task force classification I) that included 23 patients who underwent outpatient gynecological laparoscopic procedures. Patients were randomly assigned either to a study group that received 5 mg/kg of lidocaine intraperitonealy during surgery (n=15) or to a control group that received sterile water in the same manner (n=8). The fluid was infuslated along with the CO₂ through a Insuflow® device. All patients received the same anesthetic technique. Intraoperative pain as assessed by changes in the vital signs was treated with fentanyl. Postoperative pain was evaluated according to postoperative opioid requirements and by the Visual Analogue Scale (VAS) at 15 min, 1 h and 24 h postoperatively. The VAS score was found to be lower for the study group 1 h after surgery (p=0.023). There was no difference in the VAS scores at 15 min (p=0.9) and 24 h (p=0.11) after surgery. A correlation analysis showed no association between the amount of lidocaine insufflated and the severity of the postoperative pain. There was no difference in terms of fentanyl administration during surgery or opiod consumption following surgery between the groups. We concluded that continuous intraperitoneal insuflation of lidocaine using an Insuflow® device may significantly reduce pain in the initial stage of postoperative recovery.     

Impaired liver function tests in patients treated with antithymocyte globulin: Implication for liver transplantation

Antithymocyte globulin (ATG) is traditionally used as a conventional immunosuppression agent in various pathological states including severe aplastic anaemia (SAA), graft versus host disease (GVHD), and for the prevention and treatment of graft rejection and GVHD post bone marrow and liver transplantation. We reviewed the liver functions of 16 haematological patients with no previous liver disorders who received ATG as part of their pre-bone marrow transplantation (BMT) conditioning regimen, and the liver function tests of five SAA patients who received ATG as part of their treatment. Liver functions were evaluated at day — 1 pre-, and days +3 and +10 post-ATG treatment. All patients had normal liver functions before treatment. In the haematological patients, the mean serum lactic dehydrogenase (LDH) levels increased from 408.7 ± 37.7 U/l pre-treatment to 1394.4 ± 488.7 U/l 3 days post-treatment (n = 16;p < 0.029), and then declined to 561.4 ± 61.3 U/l 10 days post-treatment (n = 16;p < 0.043). The mean alanine aminotransferase (ALT) levels increased from 51.9 ± 11.3 U to 184.6 ± 74.6 U (n = 16;p < 0.036), and then declined to 121.9 ± 61.3 U (n = 16; NS). The mean aspartate amino transferase (AST) levels increased from 31.2 ± 5.7 U to 152.0 ± 67.0 U (n = 16;p < 0.44) and then declined to 46.0 ± 14 (n = 16;p < 0.049). The mean r-glutamyltransferase (GTP) levels increased from 93.0 ± 34 to 188.0 ±36 (n = 16;p < 0.02), and were 168.0 ± 37.0 at day +10 (n = 16; NS). The mean bilirubin levels increased from 18.0 ± 1.9μM I^-1 to 22.7 ± 2.8 (n = 16); NS), at day +3 and to 31.9 ± 6.9 at day +10 (n = 16; NS). In contrast, no significant changes in liver function tests were demonstrated in the SAA patients treated with ATG. The possible pathophysiologic mechanisms and the clinical implications for liver transplantation are discussed.