Basic neuroscience

Poster Session 1

Basic neuroscience     

Ropivacaine or 2% mepivacaine for lower limb peripheral nerve blocks. Study Group on Orthopedic Anesthesia of the Italian Society of Anesthesia, Analgesia, and Intensive Care

BACKGROUND: Intra- and postoperative clinical properties of sciatic-femoral nerve block performed with either ropivacaine at different concentrations or mepivacaine have been evaluated in a multicenter, randomized, blinded study. METHODS: Adult patients scheduled for foot and ankle surgery were randomized to receive combined sciatic-femoral nerve block with 225 mg of either 0.5% (n = 83), 0.75% (n = 87), or 1% (n = 86) ropivacaine, or with 500 mg of 2% mepivacaine (n = 84). A thigh tourniquet was used in all patients. Onset time, adequacy of surgical anesthesia, time to offset of nerve block, and time until first postoperative requirement for pain medication were evaluated by a blinded observer. RESULTS: The adequacy of nerve block was similar in the four treatment groups (the ratios between adequate:inadequate: failed blocks were 74:9:0 with 0.5% ropivacaine, 74:13:0 with 0.75% ropivacaine, 78:8:0 with 1% ropivacaine, and 72:12:0 with 2% mepivacaine). The onset of the block was slower with 0.5% ropivacaine than with other anesthetic solutions (P < 0.001). Regardless of the concentration, ropivacaine produced a longer motor blockade (10.5+/-3.8 h, 10.3+/-4.3 h, and 10.2+/-5.1 h with 0.5%, 0.75%, and 1% ropivacaine, respectively) than with mepivacaine (4.3+/-2.6 h; P < 0.001). The duration of postoperative analgesia was shorter after mepivacaine (5.1+/-2.7 h) than after ropivacaine (12.2+/-4.1 h, 14.3+/-5 h, and 14.5+/-3.4 h, with 0.5%, 0.75%, or 1% ropivacaine, respectively; P < 0.001). Pain relief after 0.5% ropivacaine was 14% shorter than 0.75% or 1% ropivacaine (P < 0.05). During the first 24 h after surgery, 30-37% of patients receiving ropivacaine required no analgesics compared with 10% of those receiving mepivacaine (P < 0.001). CONCLUSIONS: This study suggests that 0.75% ropivacaine is the most suitable choice of local anesthetic for combined sciatic-femoral nerve block, providing an onset similar to mepivacaine and prolonged postoperative analgesia.     

Risk of hepatitis C virus infection in a population exposed to biological materials

BACKGROUND: Hepatitis C virus is an important cause of acute and chronic hepatitis and it is an agent parenterally transmitted. Workers handling biological materials may be exposed to high concentration of virus-infected fluids. METHODS: The seroprevalence of hepatitis C virus antibodies was investigated in a population of 809 subjects exposed to varying levels of biological risk owing to the handling of human fluids or tissues and in 408 controls. The exposed group was subdivided in three subgroups according to low and occasional (262), intermediate but continuous (311), and high (236) exposure to biological materials. RESULTS: The seroprevalence of hepatitis C antibodies was low (1.40%) in all subjects. The risk groups showed no significant differences with respect to the control group; the most exposed group showed a seroprevalence of 1.27%. Age but not sex appeared significantly correlated with seroprevalence of positive antibodies (chi 2 = 5.949, P < 0.025). Aspartate aminotransferase and alanine aminotransferase showed a highly significant increase (P < 0.01 and P < 0.001, respectively) in subjects with positive hepatitis C antibodies, other than a high significant prevalence of values above the normal limit (chi 2 = 26.613, P < 0.001 and chi 2 = 39.164, P < 0.001, respectively). Among 17 positive hepatitis C virus subjects, 8 (47.1%) were positive for hepatitis B virus, but not for its antigen. CONCLUSIONS: Hepatitis C virus infection appears to be a low risk for people employed in the biomedical field, yet infection is associated with a significant liver involvement.     

Studies on the role of serotonin receptor subtypes in the effect of sibutramine in various feeding paradigms in rats.

The effect of the 5-hydroxytryptamine (5-HT) and noradrenaline (NA) reuptake inhibitor sibutramine was studied in food deprived, neuropeptide Y (NPY)- or muscimol-injected rats. Sibutramine dose-dependently reduced feeding caused by food-deprivation (ED50 = 5.1+/-0.8 mg kg(-1)) or by NPY injection into the paraventricular nucleus of the hypothalamus (ED50 = 6.0+/-0.5 mg kg(-1)). The increase in food intake caused by muscimol injected into the dorsal raphe was not modified by sibutramine (1-10 mg kg(-1)). The hypophagic effect of 5.1 mg kg(-1) sibutramine in food-deprived rats was studied in rats pretreated with different serotonin receptor antagonists. Metergoline (non-selective, 0.3 and 1.0 mg kg(-1)), ritanserin (5-HT2A/2C, 0.5 and 1.0 mg kg(-1)) and GR127935 (5-HT1B/1D), 0.5 and 1.0 mg kg(-1)) did not modify the hypophagic effect of sibutramine, while SB206553 (5-HT2B/2C, 5 and 10 mg kg(-1)) slightly but significantly reduced it (Fint(2.53) = 3.4; P<0.05). The reduction in food intake caused by 6.0 mg kg(-1) sibutramine in NPY-injected rats was not modified by GR127935 (1.0 mg kg(-1)). The results suggest that, with the possible exception of a partial involvement of 5-HT2B/2C receptors in sibutramine's hypophagia in food-deprived rats, 5-HT1 and 5-HT2 receptor subtypes do not play an important role in the hypophagic effect of sibutramine, at least in the first 2 h after injection.     

Determination of vascularization of B-cell non-Hodgkin's lymphomas with four markers

We evaluated the microvessel area (an index of angiogenesis) by using the factor VIII-related antigen (factor VIII-RA), and the expression of three components of the subendothelial basement membrane, namely: tenascin, laminin and type IV collagen. The four markers were assessed by immunohistochemical methods in 57 B-cell non-Hodgkin's lymphomas (B-NHL) and 28 benign lymphadenopathies. We found that microvessel area and the basement membrane markers had a different distribution pattern in relation to the histological type and degree of malignancy. In reactive and atypical lymphoid hyperplasias and in follicular low- and intermediate-grade B-NHL, microvessels were distributed within the interfollicular zones. By contrast, diffuse intermediate-grade and high-grade B-NHL were highly vascularized and microvessels were closely related to the neoplastic cells. Microvessel area was significantly associated with tenascin expression in all histological grades. Conversely, it was not correlated to laminin and type IV collagen expression, especially in diffuse intermediate-grade and high-grade B-NHL, where the expression of these markers was poor and fragmented. Our study suggests that angiogenesis and tenascin expression are associated phenomena in B-NHL, and that both increase with the malignancy grade. The prognostic value of angiogenesis and tenascin in B-NHL warrants further assessment in follow-up studies.     

Detection and clinical implications of early systemic tumor cell dissemination in breast cancer.

Blood-borne distant metastasis is the leading cause of cancer-related death in breast cancer. The onset of this fundamental process can now be assessed in cancer patients using ultrasensitive immunocytochemical and molecular assays able to detect even single metastatic cells. Analyses of bone marrow (BM) samples show that disseminated cells are present in 20-40% of primary breast cancer patients without any clinical or histopathological signs of metastasis. The common homing of circulating breast cancer cells in BM is indicative for systemic tumor cell spread and predictive for growth of overt metastases in relevant organ sites such as bone, lung, or liver. Recent clinical studies involving more than 3000 breast cancer patients demonstrated that the presence of tumor cells in BM at primary diagnosis is an independent prognostic factor for unfavorable clinical outcome. To date, sampling of BM, however, is not a routine procedure in clinical management of breast cancer patients. Therefore, several research groups have developed sensitive assays for detection of circulating tumor cells in peripheral blood. Studies evaluating the clinical relevance of these blood assays are ongoing. Here, we will review the existing tumor cell assays and discuss their current clinical relevance and perspectives for the clinical management of breast cancer patients.     

The effects of the single or multiple injection technique on the onset time of femoral nerve blocks with 0.75% ropivacaine

We evaluated the effect of the injection technique on the onset time and efficacy of femoral nerve block performed with 0.75% ropivacaine. A total of 30 patients undergoing arthroscopic knee surgery were randomly allocated to receive femoral nerve blockade with 0.75% ropivacaine by using either a single injection (Single group, n = 15) or multiple injection (Multiple group, n = 15). Nerve blocks were placed by using a short-beveled, Teflon-coated, stimulating needle. The stimulation frequency was set at 2 Hz, and the intensity of stimulating current, initially set at 1 mA, was gradually decreased to <0.5 mA after each muscular twitch was observed. In the Single group, 12 mL of 0.75% ropivacaine was slowly injected, as soon as the first muscular twitch was observed. In the Multiple group, the stimulating needle was inserted and redirected, eliciting each of the following muscular twitches: contraction of vastus medialis, vastus intermedius, and vastus lateralis. At each muscular twitch, 4 mL of the study solution was injected. Placing the block required 4.2 +/- 1.7 min (median, 5 min; range, 2-8 min) in the Multiple group and 3.4 +/- 2.2 min (median, 3 min; range, 1-5 min) in the Single group (P = 0.02). Onset of nerve block (complete loss of pinprick sensation in the femoral nerve distribution with concomitant inability to elevate the leg from the operating table with the hip flexed) required 10 +/- 3.7 min in the Multiple group (median, 10 min; range, 5-20 min) and 30 +/- 11 min in the Single group (median, 30 min; range, 10-50 min) (P < 0.0005). Propofol sedation was never required to complete surgery; although 0.1 mg fentanyl at trocar insertion was required in two patients of the Multiple group (13%) and nine patients of the Single group (60%) (P = 0.02). We conclude that searching for multiple muscular twitches shortened the onset time and improved the quality of femoral nerve block performed with small volumes of 0.75% ropivacaine. IMPLICATIONS: This prospective, randomized, blinded study was conducted to evaluate the effect of searching for multiple muscular twitches when performing femoral nerve block with small volumes of 0. 75% ropivacaine. Our results demonstrated that multiple injections markedly shortened the onset time and improved the quality of nerve blockade. This technique-related effect must be carefully considered when different clinical studies evaluating the use of new local anesthetic solutions for peripheral nerve blocks are compared.     

Gender-specific gene expression in post-mortem human brain: localization to sex chromosomes.

Gender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sex-chromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences.     

Fractional CO₂ vaginal laser for the genitourinary syndrome of menopause in breast cancer survivors

Adjuvant chemotherapy and endocrine therapy can induce early iatrogenic menopause or worsen pre-existing menopausal symptoms in breast cancer survivors (BCS). The second most frequent menopausal symptom after hot flushes is the genitourinary syndrome (GSM). Since hormone replacement therapy is contraindicated in BCS, vaginal laser might represent a new nonhormonal option for GSM. This study aims at evaluating the effectiveness of the fractional CO₂ vaginal laser for GSM in BCS compared with healthy women. This is a retrospective study on 135 postmenopausal women (45 BCS and 90 healthy women) who underwent fractional CO₂ laser for GSM. Objective (VHI and VVHI) and subjective outcomes (VAS for dyspareunia and vaginal dryness and a pain questionnaire) were evaluated at baseline visit and at every follow-up visit. Subjective and objective parameters improved significantly in both groups after laser therapy. The improvement was progressive and long-lasting up to 12 months after the end of the treatment. No severe adverse events were observed during the treatment. Fractional CO₂ vaginal laser induces a significant and long-lasting improvement on GSM symptoms in BCS. However, this improvement is slower than in healthy women undergoing the same treatment. Laser therapy turns out to be safe and well-tolerated.