Large concentrations of nitrous oxide decrease the isoflurane minimum alveolar concentration sparing effect of morphine in the rat

Many adjuvant drugs have demonstrated anesthetic-sparing properties when combined with volatile anesthetics. Nitrous oxide is combined with volatile anesthetics to reduce the concentrations of volatile anesthetics required to produce anesthesia. Analgesic doses of opioids clearly reduce the requirement for inhaled anesthetics in both human patients and experimental animals. We performed this study to determine whether the combination of nitrous oxide and morphine decreased isoflurane minimum alveolar anesthetic concentration (MAC) even further in the rat. Fifty-eight female rats were used. The rats were divided into 8 groups: isoflurane in 4 possible nitrous oxide concentrations (0%, 30%, 50%, or 70%) with saline or morphine (1 mg/kg). Then the MAC of isoflurane (MAC(ISO))was determined from alveolar gas samples at the time of tail clamp. The MAC of isoflurane was significantly different at each nitrous oxide concentration, and increasing nitrous oxide concentrations reduced anesthetic requirements for isoflurane. The administration of morphine reduced the MAC(ISO) when used with 0% or 30% nitrous oxide. This MAC(ISO) by morphine reduction was less with 50% nitrous oxide and nonexistent at 70% nitrous oxide. However, with morphine present the MAC(ISO) was independent of the nitrous oxide concentration in the 30%-70% range.     

Second Biopsy of Axillary Sentinel Lymph Node for Reappearing Breast Cancer After Previous Sentinel Lymph Node Biopsy

Background Sentinel lymph node biopsy (SLNB) is a safe and accurate axillary staging procedure for patients with primary operable breast cancer. An increasing proportion of these patients undergo breast-conserving surgery, and 5% to 15% will develop local relapses that necessitate reoperation. Although a previous SLNB is often considered a contraindication for a subsequent SLNB, few data support this concern. Methods Between January 2000 and June 2004, 79 patients who were previously treated at our institution with breast-conserving surgery and who had a negative SLNB for early breast cancer developed, during follow-up, local recurrence that was amenable to reoperation. Eighteen of these patients were offered a second SLNB because of a clinically negative axillary status an average of 26.1 months after the primary event. Results In all 18 patients (7 with ductal carcinoma-in-situ and 11 with invasive recurrences), preoperative lymphoscintigraphy showed an axillary sentinel lymph node, with a preoperative identification rate of 100%, and 1 or more SLNs (an average of 1.3 per patient) were surgically removed. Sentinel lymph node metastases were detected in two patients with invasive recurrence, and a complete axillary dissection followed. At a median follow up of 12.7 months, no axillary recurrences have occurred in patients who did not undergo axillary dissection. Conclusions Second SLNB after previous SLNB is technically feasible and likely effective in selected breast cancer patients. A larger population and longer follow-up are necessary to confirm these preliminary data.     

Prevalence of GJB2 mutations and the del(GJB6-D13S1830) in Argentinean non-syndromic deaf patients

Genetically caused congenital deafness is a common trait affecting 1 in 2000 children and it is predominantly inherited in an autosomal recessive fashion. Several mutations in the GJB2 gene and a deletion of 342 kb in GJB6 (delGJB6-D13S1830) have been identified worldwide in patients with hearing impairment. The aim of this study was to determine the prevalence of these mutations in Argentina. Non-syndromic 46 probands (17 familial and 29 sporadic cases) were genetically evaluated. Mutations in GJB2 and/or delGJB6-D13S1830 were found in 19 patients, accounting for 41.3% of the sample. Of the 46 patients investigated in this study, 12 (26.1%) were diagnosed to carry sequence variations in both alleles; all but one, were considered causative for hearing impairment in those patients. In 7 out of 46 patients (15.2%) only one mutant allele was detected. Of their 38 chromosomes, 71% resulted with mutations in the GJB2 gene and 11% in GJB6. The most frequent mutation in GJB2 (24%) was c.35delG (11% homozygous and 13% heterozygous and compound heterozygous). In addition, 11 sequence variations different from c.35delG, were identified in the coding region of the GJB2 gene: T8M, V27I, M34T, E47X, R75W, W77R, I82M, L90P, E129K, V153I, M163V. The delGJB6-D13S1830 mutation was found in 4 patients (9%), 3 of them associated with GJB2 mutations, resulting in compound heterozygous for the DFNB1 locus. The present study demonstrates that mutations in the GJB2 gene and the delGJB6-D13S1830 are prevalent in the Argentinean population.     

Presence of nerve growth factor and TrkA expression in the SVZ of EAE rats: evidence for a possible functional significance

Nerve growth factor (NGF) is a well-characterized neurotrophic factor that plays a crucial role during development in the growth, differentiation, and maintenance of brain neurons as well as in the reparative response of the adult brain to neuronal damage. Recent studies have shown that acute axonal loss occurs in multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE), and that NGF suppresses clinical symptoms of EAE in nonhuman primates. Aim of the present study was to investigate the role of NGF in the regenerative response of the adult brain to neuronal damage occurring in EAE. Using EAE rats, we have found that exogenous NGF injection and NGF deprivation (NGF autoimmunization) can act on growth and differentiation of brain precursor cells in the subventricular zone (SVZ) of EAE rats. Moreover, NGF administration in brain of EAE rats stimulates the expression of early neuronal markers on proliferating precursor cells of the SVZ. The data obtained demonstrated that NGF and its antibody affect bromodeoxyuridine (BrdU) incorporation and NGF receptor expression by SVZ progenitor cells in the brain of EAE rats.     

Effect of supplementation with docosahexaenoic acid ethyl ester and sn-2 docosahexaenyl monoacylglyceride on plasma and erythrocyte fatty acids in rats

BACKGROUND/AIMS: Docosahexaenoic acid (C22:6, DHA) is an omega-3 fatty acid required for the normal development of the mammalian nervous and visual system. DHA is provided by the mother during pregnancy and lactating period. Mother's DHA supplementation during pregnancy, and even before pregnancy, has been suggested. DHA can be provided by marine oils, egg's yolk phospholipids, single cell algae oils, the pure fatty acid, or by the ethyl ester derivative (DHA-EE). Another way to provide DHA can be by sn-2 docosahexaenyl monoacylglyceride (DHA-MG), obtained by the treatment of fish oil with stereospecific lipases. sn-2 Fatty acid monoacylglycerides can be more easily absorbed at the intestine than other fatty acid derivatives. METHODS: Female rats fed with a synthetic, which provided essentially no DHA, received a 40-day supplementation of either DHA-EE or DHA-MG. Plasma and erythrocyte fatty acid composition were assessed by gas chromatography at day 0 and 40 of supplementation. RESULTS: DHA-EE increased plasma and erythrocyte DHA by 15 and 11.9%, respectively, with no modification of arachidonic acid (AA) content. DHA-MG supplementation increased plasma and erythrocyte DHA by 24 and 23.8%, respectively, but reduced AA by 5.5 and 3%, respectively. CONCLUSIONS: We conclude that in the rat, DHA-MG supplementation allows a higher plasma and erythrocyte DHA content than DHA-EE with minor modification of AA content.     

Proliferative high-risk lesions of the breast: contribution and limits of US-guided core biopsy

PURPOSE: To retrospectively correlate high-risk proliferative breast lesions (radial scar, atypical lobular hyperplasia, lobular carcinoma in situ and papillary lesions) diagnosed on core biopsy with the definitive histopathological diagnosis obtained after surgical excision or with the follow-up, in order to assess the role of core biopsy in such lesions. To discuss the management of the patient after a core biopsy diagnosis of high-risk proliferative breast lesion. MATERIAL AND METHODS: We evaluated 74 out of 1776 core biopsies consecutively performed on 67 patients. The histopathologic findings were as follows: 11 radial scars (RS), 3 atypical lobular hyperplasias (ALH), 3 lobular carcinomas in situ (LCIS), 57 benign papillary lesions. All patients underwent bilateral mammography, whole-breast ultrasound with a linear-array broadband transducer, and core biopsy with a 14 Gauge needle and a mean number of samples of 5 (range 4-7). Sixty-two of 67 patients, for a total of 69/74 lesions, underwent surgical biopsy despite benign histopathologic findings, mostly because of highly suspicious imaging for malignancy (BIRADS 4-5), whereas 5 patients refused surgery and have been followed up for a least 18 months and are still being followed up (2 with RS, 1 with ADH and 2 with papillary lesions). RESULTS: Among the core biopsied lesions with a diagnosis of RS (n = 11) pathology revealed one ductal carcinoma in situ (DCIS) (this case was characterized by granular microcalcifications on mammography and by a mass with irregular margins on ultrasound). Also in the group of ADH (n = 3) pathology revealed one DCIS (lesion not visible on mammography but depicted as a suspicious mass on US). In the group of LCIS (n = 3) pathologists found an invasive lobular carcinoma (ILC). Among the benign papillary lesions (n = 57) histopathologic analysis of the surgical specimen revealed 7 malignant lesions (4 papillary carcinomas and 3 DCIS), whose mammographic and ultrasound findings were indistinguishable from benign lesions. Altogether there were 10 false negative results (underestimation) out of 74 core biopsies with a diagnosis of high-risk proliferative breast lesions. CONCLUSION: The high rate of histological underestimation after core biopsy (10/74) (13.5%) demands a very careful management of patents with a core biopsy diagnosis of high-risk proliferative breast lesions, especially in the case of RS, lobular neoplasia and papillary lesions. However, the high imaging suspicion for malignancy prompts surgery. It is possible to assume that, when there is a low imaging suspicion for malignancy, when enough tissue has been sampled for pathology and no atypia is found within the lesions, surgery is not mandatory but a very careful follow-up is recommended. We must underline that there is no agreement regarding the quantity of tissue to sample. Vacuum-assisted biopsy may lead to better results, although there is as yet no proof that it can actually replace surgery in this group of lesions, since it seems only to reduce but not abolish the histological underestimation.     

Meloxicam, a specific COX-2 inhibitor, does not enhance the isoflurane minimum alveolar concentration reduction produced by morphine in the rat

A synergistic effect of nonselective cyclooxygenase (COX) inhibitors on morphine-induced decrease of isoflurane minimum alveolar concentration (MAC(ISO)) has been observed in the rat. We studied the influence of specific COX-2 inhibitors on this decrease of MAC. Sixty-four female rats were anesthetized with isoflurane in oxygen. The animals were grouped into saline solution, aspirin (30 mg/kg), morphine (1 mg/kg), morphine (1 mg/kg) + aspirin (30 mg/kg), meloxicam (1 and 3 mg/kg), and morphine (1 mg/kg) + meloxicam (1 and 3 mg/kg). Then the MAC(ISO) was determined from alveolar gas samples at the time of tail clamp. The groups treated with saline solution, aspirin, and 1 and 3 mg/kg meloxicam did not express any statistically relevant changes among them. The administration of morphine + meloxicam 1 or 3 mg/kg significantly reduced the MAC(ISO) just as in the group where only morphine was administered (morphine 1.35% +/- 0.07%, morphine + 1 mg/kg meloxicam 1.36% +/- 0.04%, and morphine + 3 mg/kg meloxicam 1.37% +/- 0.08%). The greatest reduction of MAC(ISO) was after administration of morphine + aspirin (1.19% +/- 0.05%). The administration of meloxicam does not potentiate the morphine-induced decrease of MAC(ISO) in the rat. IMPLICATIONS: A synergistic effect between morphine and aspirin on isoflurane minimum alveolar concentration has been observed in the rat--an effect that does not occur between morphine and meloxicam.     

Locally advanced breast cancer: comparison of mammography,sonography and MR imaging in evaluation of residual disease in women receiving neoadjuvant chemotherapy

The accuracy of mammography, sonography and magnetic resonance imaging (MRI) in identifying residual disease after neoadjuvant chemotherapy is evaluated and imaging findings are correlated with pathologic findings. Fifteen patients enrolled in an experimental protocol of preoperative neoadjuvant chemotherapy underwent clinical examination, mammography, sonography and dynamic MRI, performed in this order, before and respectively after 2 and 4 cycles of neoadjuvant chemotherapy. Four radiologists, two for mammography, one for sonography and one for MR, examined the images, blinded to the results of the other examinations. All patients underwent radical or conservative surgery, and imaging findings were compared with pathologic findings. MRI identified 2/15 (13.3.%) clinically complete response (CR), 9/15 (60%) partial response (PR), 3/15 (20%) stable disease (SD) and 1/15 (6.7%) progressive disease. Mammography identified 1/15 (6.7%) clinically CR, 8/15 (53.3%) PR and 4/15 (27%) SD, and was not able to evaluate the disease in 2/15 (13%) cases. Sonography presented the same results as MRI. Therefore, MRI and sonography compared to mammography correctly identified residual disease in 100 vs. 86%. MRI resulted in two false-negative results because of the presence of microfoci of in situ ductal carcinoma (DCIS) and invasive lobular carcinoma (LCI). MRI was superior to mammography in cases of multifocal or multicentric disease (83 vs. 33%). Sonography performed after MRI improves the accuracy in evaluation of uncertain foci of multifocal disease seen on MR images with an increase of diagnostic accuracy from 73 to 84.5%. MRI assesses response to neoadjuvant chemotherapy better than traditional methods of physical examination and mammography.     

Prophylactic antiemetics for laparoscopic cholecystectomy: droperidol, metoclopramide, and droperidol plus metoclopramide

BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the most significant problems in laparoscopic surgery. The antiemetic effects of metoclopramide and droperidol used alone or in combination for prevention of PONV after laparoscopic cholecystectomy (LC) were assessed in this prospective, double blind, placebo controlled randomized study. PATIENTS AND METHODS: A series of 140 patients, ASA physical status I or II, were included in the study. Patients were randomized to one of the following groups: 1, placebo; 2, metoclopramide 10 mg after the induction of anesthesia and placebo at 12 h postoperatively; 3, droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg at 12 h postoperatively; and 4, droperidol 1.25 mg plus metoclopramide 10 mg after the induction of anesthesia and droperidol 1.25 mg at 12 h postoperatively. Patients were observed for 24 hours for PONV, pain, need for rescue analgesics, and adverse events. RESULTS: Data were analyzed using the Student's t-test and chi-square test, with P < 0.05 considered statistically significant. The mean incidence of PONV was 54% with placebo, 42% with metoclopramide, 14% with two doses of droperidol alone, and 11% with a combination of metoclopramide plus droperidol. The patients receiving a combination of metoclopramide and droperidol had a significantly lower rate of PONV than those administered metoclopramide alone (P < 0.05) or placebo (P < 0.001). Those receiving two-dose droperidol alone also had a significantly lower incidence of PONV compared with metoclopramide (P < 0.05) and placebo (P < 0.001). There was no statistically significant difference between the metoclopramide and placebo groups. Sedation was significantly greater in patients administered droperidol 12 h postoperatively. CONCLUSION: The combination of metoclopramide and droperidol, and two-dose droperidol alone, were found to significantly decrease the incidence of PONV after LC, whereas metoclopramide alone proved inefficient.