Awareness of fertility preservation among Chinese medical students.

INTRODUCTION: The fertility preservation (FP) services offered in Hong Kong are underutilised. There have been no previous studies on Chinese medical students to investigate the underlying reasons for this underutilisation in terms of awareness, knowledge, and attitudes towards FP and age-related fertility. METHODS: This was a cross-sectional survey among Chinese medical students in Hong Kong. RESULTS: The majority of participants (77.8%) were not familiar with any clinics or specialists who provide FP services. The vast majority (88.1%) underestimated female infertility at age 45 years, and 89.8% overestimated the age of male fertility decline. The students' FP knowledge was mainly acquired from electronic media (58.4%) and medical school (57.6%). Medical students showed overwhelming support towards FP for medical reasons (97.9%) but had mixed responses about FP for elective reasons related to career development in women (58.8%). Of the participants, 80.2% agreed that the government should subsidise FP services for patients with medical reasons. CONCLUSION: This study highlights the limited awareness and knowledge of FP among Chinese medical students. There is a strong worldwide need to increase education about and exposure to FP in the medical curriculum and improve medical students' knowledge.

Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails.

The Membrane Attack Complex-Perforin (MACPF) family is ubiquitously found in all kingdoms. They have diverse cellular roles, however MACPFs with pore-forming toxic function in venoms and poisons are very rare in animals. Here we present the structure of PmPV2, a MACPF toxin from the poisonous apple snail eggs, that can affect the digestive and nervous systems of potential predators. We report the three-dimensional structure of PmPV2, at 17.2 Å resolution determined by negative-stain electron microscopy and its solution structure by small angle X-ray scattering (SAXS). We found that PV2s differ from nearly all MACPFs in two respects: it is a dimer in solution and protomers combine two immune proteins into an AB toxin. The MACPF chain is linked by a single disulfide bond to a tachylectin chain, and two heterodimers are arranged head-to-tail by non-covalent forces in the native protein. MACPF domain is fused with a putative new Ct-accessory domain exclusive to invertebrates. The tachylectin is a six-bladed ß-propeller, similar to animal tectonins. We experimentally validated the predicted functions of both subunits and demonstrated for the first time that PV2s are true pore-forming toxins. The tachylectin "B" delivery subunit would bind to target membranes, and then the MACPF "A" toxic subunit would disrupt lipid bilayers forming large pores altering the plasma membrane conductance. These results indicate that PV2s toxicity evolved by linking two immune proteins where their combined preexisting functions gave rise to a new toxic entity with a novel role in defense against predation. This structure is an unparalleled example of protein exaptation.

MeCP2-regulated miRNAs control early human neurogenesis through differential effects on ERK and AKT signaling.

Rett syndrome (RTT) is an X-linked, neurodevelopmental disorder caused primarily by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, which encodes a multifunctional epigenetic regulator with known links to a wide spectrum of neuropsychiatric disorders. Although postnatal functions of MeCP2 have been thoroughly investigated, its role in prenatal brain development remains poorly understood. Given the well-established importance of microRNAs (miRNAs) in neurogenesis, we employed isogenic human RTT patient-derived induced pluripotent stem cell (iPSC) and MeCP2 short hairpin RNA knockdown approaches to identify novel MeCP2-regulated miRNAs enriched during early human neuronal development. Focusing on the most dysregulated miRNAs, we found miR-199 and miR-214 to be increased during early brain development and to differentially regulate extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase and protein kinase B (PKB/AKT) signaling. In parallel, we characterized the effects on human neurogenesis and neuronal differentiation brought about by MeCP2 deficiency using both monolayer and three-dimensional (cerebral organoid) patient-derived and MeCP2-deficient neuronal culture models. Inhibiting miR-199 or miR-214 expression in iPSC-derived neural progenitors deficient in MeCP2 restored AKT and ERK activation, respectively, and ameliorated the observed alterations in neuronal differentiation. Moreover, overexpression of miR-199 or miR-214 in the wild-type mouse embryonic brains was sufficient to disturb neurogenesis and neuronal migration in a similar manner to Mecp2 knockdown. Taken together, our data support a novel miRNA-mediated pathway downstream of MeCP2 that influences neurogenesis via interactions with central molecular hubs linked to autism spectrum disorders.

Educational effectiveness of gynaecological teaching associates: a multi-centre randomised controlled trial.

OBJECTIVE: To evaluate, among medical students learning the female pelvic examination, the added benefits of training by gynaecological teaching associates compared with training involving a manikin only. DESIGN: Randomised controlled trial. SETTING: Nine university teaching hospitals. POPULATION: Ninety-four medical students recruited prior to commencing a 4-week obstetrics and gynaecology rotation. METHODS: The control training consisted of lectures, demonstration of the pelvic examination on a manikin, and opportunities to practise on this low-fidelity simulation (n = 40). The experimental group received additional gynaecological teaching associate training, delivered by pairs of experienced associates to groups of four medical students (n = 54). MAIN OUTCOME MEASURES: Outcomes measured at the end of the rotation included knowledge of the correct order of examination components (Yes/No), and student comfort [Likert scales anchored between 1 (very uncomfortable) and 4 (very comfortable) on four items] and confidence [Likert scales anchored between 1 (No) and 3 (Yes) on six items]. The primary outcome, measured at the end of the academic year, was the objective structured clinical examination of a female pelvis (score range 0-54). RESULTS: At baseline, the groups were similar in age, gender, and ethnicity. At the end of the clinical rotation, when compared with the control intervention, the experimental intervention had a moderate effect on student knowledge [difference 29.9% (95% CI 11.2-48.6%); P = 0.002] and confidence [difference 1 (95% CI 0-2); P < 0.001], and a large effect on student comfort [difference 1.8 (95% CI 0.6-3.0); P = 0.004]. At the end of the academic year, the experimental intervention had no impact on skills compared with the control [difference 2 (95% CI-1 to 4); P = 0.26]. CONCLUSIONS: Among medical students taught the female pelvic examination by low-fidelity simulation, additional training by gynaecology teaching associates improved knowledge, comfort, and confidence at the end of the clinical rotation but did not improve examination skills at end of the academic year.

Long noncoding RNA profiles of adrenocortical cancer can be used to predict recurrence.

Adrenocortical carcinoma (ACC) is an aggressive malignancy with high rates of recurrence following surgical resection. Long noncoding RNAs (lncRNAs) play an important role in cancer development. Pathogenesis of adrenal tumours have been characterised by mRNA, microRNA and methylation expression signatures, but it is unknown if this extends to lncRNAs. This study describes lncRNA expression signatures in ACC, adrenal cortical adenoma (ACA) and normal adrenal cortex (NAC) and presents lncRNAs associated with ACC recurrence to identify novel prognostic and therapeutic targets. RNA was extracted from freshly frozen tissue with confirmation of diagnosis by histopathology. Focused lncRNA and mRNA transcriptome analysis was performed using the ArrayStar Human LncRNA V3.0 microarray. Differentially expressed lncRNAs were validated using quantitative reverse transcriptase-PCR and correlated with clinical outcomes. Microarray of 21 samples (ten ACCs, five ACAs and six NACs) showed distinct patterns of lncRNA expression between each group. A total of 956 lncRNAs were differentially expressed between ACC and NAC, including known carcinogenesis-related lncRNAs such as H19, GAS5, MALAT1 and PRINS (P≤0.05); 85 lncRNAs were differentially expressed between ACC and ACA (P≤0.05). Hierarchical clustering and heat mapping showed ACC samples correctly grouped compared with NAC and ACA. Sixty-six differentially expressed lncRNAs were found to be associated with ACC recurrence (P≤0.05), one of which, PRINS, was validated in a group of 20 ACCs and also found to be associated with metastatic disease on presentation. The pathogenesis of adrenal tumours extends to lncRNA dysregulation and low expression of the lncRNA PRINS is associated with ACC recurrence.

Enteric outbreak surveillance in British Columbia, 2009-2013.

BACKGROUND: Understanding enteric disease outbreak sources, burden of illness, mode of transmission and use of interventions informs planning, policy development and prevention programs. OBJECTIVE: To describe trends in enteric disease outbreaks investigated in British Columbia (BC) between 2009 and 2013. METHODS: An analysis was conducted of enteric disease outbreaks that had been entered into a national, secure web-enabled outbreak reporting system using the Canadian Network for Public Health Intelligence (CNPHI) and investigated in BC between January 1, 2009 and December 31, 2013. The data included information on pathogen, number of cases, hospitalizations, deaths, setting, mode of transmission, source, factors that contributed to the outbreak and interventions. Residential facility-based viral outbreaks and outbreaks associated with international travel were excluded. RESULTS: There were 104 outbreaks investigated in BC between 2009 and 2013. Ninety-three were reported by BC organizations and 11 were national outbreak investigations reported by the Public Health Agency of Canada (PHAC). There was an average of 21 outbreaks per year. Overall, the annual rate of foodborne outbreaks in BC was 2.8 per one million population. Seventy-nine (76%) outbreaks had a pathogen identified, most commonly norovirus, Salmonella and E. coli. There was a total of 108 hospitalizations (3.8% of all cases) and two deaths (0.1% of all cases); one caused by botulism, the other by E. coli O157. Food service establishments were the most common setting (33.7%), followed by the community (24.0%) and private functions (12.5%). The food types most often reported were fruits and vegetables, meat and seafood. The data showed a pathogen-food source combination between Salmonella and eggs. CONCLUSION: This is the first publication summarizing trends in enteric disease outbreaks in BC including assessing sources, burden and interventions. Ongoing reporting and analysis of outbreak data in BC will allow for improved assessment of trends in sources and pathogens over time and further understanding of the effectiveness of interventions associated with outbreaks.

Identification of the midline by obese and non-obese women during late pregnancy.

During central neuraxial blockade, identifying the midline in parturients can be difficult, particularly if they are obese. We assessed the ability of women in late pregnancy, both obese and non-obese, to identify the midline of their own back by pointing and by pinprick discrimination with reference to the true midline identified by ultrasound. Thirteen out of 25 (52%) obese women were accurate to within 5 mm in identifying the midline of their back by pointing with their fingertip, compared with 21/25 (84%) non-obese women (p = 0.03). The median (IQR [range]) fingertip-midline distance was greater in obese women (5 (5-10 [0-10]) mm compared with non-obese women (2 (0-5 [0-12]) mm; p = 0.007). Identification of the midline using pinprick was poorer by obese women (median (IQR [range]) 33 (25-45 [3-85]) mm) than by non-obese women (18 (13-25 [8-40]) mm; p < 0.0001). However, women in both groups were correct > 99% of the time in identifying that a stimulus was either to the left or to the right side.

Efficacy of cardiopulmonary resuscitation in the supine position with manual displacement of the uterus vs lateral tilt using a firm wedge: a manikin study.

Prevention of aortocaval compression is essential for effective cardiopulmonary resuscitation in late pregnancy. This can be achieved by either lateral maternal tilt or lateral uterine displacement. Results from a previous manikin study show that a firm foam-rubber wedge allowed successful chest compressions whilst providing stable and reliable lateral tilt. However, it did not investigate resuscitation in the supine position with manual uterine displacement. The aim of this study was to compare the effectiveness of chest compressions in a manikin in the supine position vs lateral tilt using a foam-rubber wedge, both on the floor and on a typical patient bed. Overall, we found that compressions were easier to perform in the supine position (p = 0.007 (bed) and 0.048 (floor)), and with greater stability in the supine position on the floor (p = 0.011). The effectiveness of chest compressions was similar in both the supine/uterine displacement and the lateral tilt positions, suggesting that either method may be suitable for CPR.

Cardiopulmonary resuscitation in the pregnant patient: a manikin-based evaluation of methods for producing lateral tilt.

The importance of minimising aortocaval compression during cardiopulmonary resuscitation in late pregnancy is widely accepted. Current European guidelines suggest employing manual displacement of the uterus with left lateral tilt to achieve this. Several methods for producing lateral tilt have been described; however, the optimum method is unknown. By performing simulated cardiopulmonary resuscitation on a manikin, we compared four of these methods: a folded labour ward pillow; a pre-formed foam wedge; a custom-made hard wooden wedge; and the 'human wedge'. Primary outcome measures were maintenance of adequate tilt, stability and effectiveness of chest compressions (rate, depth and adequate release). Overall, the foam and wooden wedges were significantly more stable and reliable at maintaining tilt than the pillow (p<0.0001); the wooden wedge was more stable and effective than the foam wedge (p<0.0001). Chest compressions were least effective with the human wedge (p=0.02). Effectiveness of chest compressions with lateral tilt was comparable to that reported previously in supine manikin studies. We recommend the use of dedicated foam or hard wedges rather than pillows or the human wedge for producing lateral tilt during cardiopulmonary resuscitation.

Detection of inner tube defects in co-axial circle and Bain breathing systems: a comparison of occlusion and Pethick tests.

The performance of the occlusion and Pethick tests in detecting faulty inner tubes in co-axial circle and Bain systems was compared. Twelve co-axial circle and 12 Bain anaesthetic breathing systems were tested using the occlusion and the Pethick tests. For each system, three tubes were intact, and the remaining nine had a defect deliberately created in the inner tube (three proximal, three middle and three distal). The investigators were blinded to which of the tubes were defective, and to each other's results. The results showed 100% specificity for both tests. The sensitivity of the occlusion test for detecting faulty breathing systems was found to be good (98%). Our results suggest that the occlusion test should be performed in preference to the Pethick test when testing co-axial circle and Bain systems.

Ethnic differences in refraction and ocular biometry in a population-based sample of 11-15-year-old Australian children.

PURPOSE: To examine the prevalence of refractive error and distribution of ocular biometric parameters among major ethnic groups in a population-based sample of 11-15-year-old Australian children. METHODS: The Sydney Myopia Study examined 2353 students (75.3% response) from a random cluster-sample of 21 secondary schools across Sydney. Examinations included cycloplegic autorefraction, and measures of corneal radius of curvature, anterior chamber depth, and axial length. RESULTS: Participants mean age was 12.7 years (range 11.1-14.4); 49.4% were female. Overall, 60.0% of children had European Caucasian ethnicity, 15.0% East Asian, 7.1% Middle Eastern, and 5.5% South Asian. The most frequent refractive error was mild hyperopia (59.4%, 95% confidence interval (CI), 53.2-65.6), defined as spherical equivalent (SE) +0.50 to +1.99 D. Myopia (SE-0.50 D or less) was found in 11.9%, 95% (CI 6.6-17.2), and moderate hyperopia (SE> or =+2.00 D) in 3.5%, 95% (CI 2.8-4.1). Myopia prevalence was lower among European Caucasian children (4.6%, 95% CI 3.1-6.1) and Middle Eastern children (6.1%, 95% CI 1.3-11.0) than among East Asian (39.5%, 95%, CI 25.6-53.5) and South Asian (31.5%, 95%, CI 21.6-41.4) children. European Caucasian children had the most hyperopic mean SE (+0.82 D) and shortest mean axial length (23.23 mm). East Asian children had the most myopic mean SE (-0.69 D) and greatest mean axial length (23.86 mm). CONCLUSION: The overall myopia prevalence in this sample was lower than in recent similar-aged European Caucasian population samples. East Asian children in our sample had both a higher prevalence of myopia and longer mean axial length.

Prevalence and associations of anisometropia and aniso-astigmatism in a population based sample of 6 year old children.

AIM: To study the distribution of anisometropia and aniso-astigmatism in young Australian children, together with clinical and ocular biometry relations. METHOD: The Sydney Myopia Study examined 1765 predominantly 6 year old children from 34 randomly selected Sydney schools during 2003-4. Keratometry, cycloplegic autorefraction, and questionnaire data were collected. RESULTS: Spherical equivalent (SE) anisometropia (> or =1 dioptre) prevalence was 1.6% (95% confidence interval (CI) 1.1% to 2.4%). Aniso-astigmatism (>or =1D) prevalence was 1.0% (CI: 0.6% to 1.6%). Both conditions were significantly more prevalent among moderately hyperopic (SE > or =2.0D) than mildly hyperopic (SE 0.5-1.9D) children. Myopic children (SE < or =-0.5D) had higher anisometropia prevalence. Neither condition varied by age, sex, or ethnicity. In multivariate analyses, anisometropia was significantly associated with amblyopia, odds ratio (OR) 29, (CI: 8.7 to 99), exotropia (OR 7.7, CI: 1.2 to 50), and neonatal intensive care unit (NICU) admission (OR 3.6, CI: 1.1 to 12.6). Aniso-astigmatism was significantly associated with amblyopia (OR 8.2, CI: 1.4 to 47), maternal age >35 years (OR 4.0, CI: 1.3 to 11.9), and NICU admission (OR 4.6, CI: 1.2 to 17.2). Anisometropia resulted from relatively large interocular differences in axial length (p<0.0001) and anterior chamber depth (p = 0.0009). Aniso-astigmatism resulted from differences in corneal astigmatism (p<0.0001). CONCLUSION: In this predominantly 6 year old population, anisometropia and aniso-astigmatism were uncommon, had important birth and biometry associations, and were strongly related to amblyopia and strabismus.

The use of antiplatelet agents in cardiac disease.

In this clinical review, the authors focus on the process of platelet activation and thrombosis in acute and chronic coronary syndromes. New antithrombotic therapies have emerged for various cardiovascular diseases, based on the evolving concept of vascular injury and platelets and the knowledge of the pathophysiology of the underlying disease states. An understanding of these mechanisms is crucial to therapeutic decision making with antiplatelet regimens, which are also discussed in detail.

Enhanced infectivity of an R5-tropic simian/human immunodeficiency virus carrying human immunodeficiency virus type 1 subtype C envelope after serial passages in pig-tailed macaques (Macaca nemestrina).

The increasing prevalence of human immunodeficiency virus type 1 (HIV-1) subtype C infection worldwide calls for efforts to develop a relevant animal model for evaluating strategies against the transmission of the virus. A chimeric simian/human immunodeficiency virus (SHIV), SHIV(CHN19), was generated with a primary, non-syncytium-inducing HIV-1 subtype C envelope from a Chinese strain in the background of SHIV(33). Unlike R5-tropic SHIV(162), SHIV(CHN19) was not found to replicate in rhesus CD4(+) T lymphocytes. SHIV(CHN19) does, however, replicate in CD4(+) T lymphocytes of pig-tailed macaques (Macaca nemestrina). The observed replication competence of SHIV(CHN19) requires the full tat/rev genes and partial gp41 region derived from SHIV(33). To evaluate in vivo infectivity, SHIV(CHN19) was intravenously inoculated, at first, into two pig-tailed and two rhesus macaques. Although all four animals became infected, the virus replicated preferentially in pig-tailed macaques with an earlier plasma viral peak and a faster seroconversion. To determine whether in vivo adaptation would enhance the infectivity of SHIV(CHN19), passages were carried out serially in three groups of two pig-tailed macaques each, via intravenous blood-bone marrow transfusion. The passages greatly enhanced the infectivity of the virus as shown by the increasingly elevated viral loads during acute infection in animals with each passage. Moreover, the doubling time of plasma virus during acute infection became much shorter in passage 4 (P4) animals (0.2 day) in comparison to P1 animals (1 to 2 days). P2 to P4 animals all became seropositive around 2 to 3 weeks postinoculation and had a decline in CD4/CD8 T-cell ratio during the early phase of infection. In P4 animals, a profound depletion of CD4 T cells in the lamina propria of the jejunum was observed. Persistent plasma viremia has been found in most of the infected animals with sustained viral loads ranging from 10(3) to 10(5) per ml up to 6 months postinfection. Serial passages did not change the viral phenotype as confirmed by the persistence of the R5 tropism of SHIV(CHN19) isolated from P4 animals. In addition, the infectivity of SHIV(CHN19) in rhesus peripheral blood mononuclear cells was also increased after in vivo passages. Our data indicate that SHIV(CHN19) has adapted well to grow in macaque cells. This established R5-tropic SHIV(CHN19)/macaque model would be very useful for HIV-1 subtype C vaccine and pathogenesis studies.

HIV-1 drug resistance in newly infected individuals.

CONTEXT: There is concern that the widespread use of antiretroviral drugs to treat human immunodeficiency virus 1 (HIV-1) infection may result in the increased transmission of drug-resistant virus. OBJECTIVE: To determine the prevalence of drug resistance-conferring mutations and phenotypic resistance to antiretroviral agents in a cohort of individuals newly infected with HIV-1. DESIGN: Case series with genetic analyses of the HIV-1 plasma-derived pol gene using reverse transcriptase polymerase chain reaction followed by direct sequencing of polymerase chain reaction products. Phenotypic analysis was performed with a recombinant virus assay. SETTING AND PATIENTS: Eighty individuals referred, on average, 1.7 months after infection with HIV-1 to the Aaron Diamond AIDS Research Center between July 1995 and April 1999. Subjects were from large urban areas (65 from New York, NY; 11 from Los Angeles, Calif); 60 (75%) were white, and 75 (93.8%) were homosexual men. MAIN OUTCOME MEASURES: Prevalence of known resistance-conferring genotypes and reduced susceptibility to individual antiviral agents by phenotype. RESULTS: Thirteen individuals (16.3%) had genotypes associated with drug resistance to any antiretroviral agent. Virus with known resistance-conferring mutations to any nucleoside reverse transcriptase inhibitors was found in 10 individuals, to any nonnucleoside reverse transcriptase inhibitors in 6 subjects, and to any protease inhibitors in 2 cases. Multidrug-resistant virus was identified in 3 individuals (3.8%). Extensive polymorphism in the protease gene was identified. Interpretation of genotypes and phenotypes was concordant in 57 (85%) of the 67 cases in which both studies were performed. CONCLUSION: The prevalence of HIV-1 variants with known resistance-conferring genotypes to any antiretroviral agent in this cohort of 80 newly infected individuals is 16.3%. These data support expanded use of resistance testing in the setting of primary HIV-1 infection. Clinical trials should be initiated to establish whether therapy guided by resistance testing, compared with the use of empirical triple combination antiretroviral therapy, provides additional virological and immunological benefit when treating primary HIV-1 infection. Further efforts to expand the study of transmission of drug-resistant HIV-1 variants, particularly in cohorts with different epidemiological profiles, are indicated.

Oral d,l sotalol reduces the incidence of postoperative atrial fibrillation in coronary artery bypass surgery patients: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: The purpose of this prospective, randomized, double-blind, placebo-controlled study was to assess the efficacy of preoperatively and postoperatively administered oral d,l sotalol in preventing the occurrence of postoperative atrial fibrillation (AF). BACKGROUND: Atrial fibrillation is the most common arrhythmia following coronary artery bypass surgery (CABG). Its etiology, prevention and treatment remain highly controversial. Furthermore, its associated morbidity results in a prolongation of the length of hospital stay post-CABG. METHODS: A total of 85 patients, of which 73 were to undergo CABG and 12 CABG plus valvular surgery (ejection fraction > or = 28% and absence of clinical heart failure), were randomized to receive either sotalol (40 patients; mean dose = 190 +/- 43 mg/day) started 24 to 48 h before open heart surgery and continued for four days postoperatively, or placebo (45 patients, mean dose = 176 +/- 32 mg/day). RESULTS: Atrial fibrillation occurred in a total of 22/85 (26%) patients. The incidence of postoperative AF was significantly (p = 0.008) lower in patients on sotalol (12.5%) as compared with placebo (38%). Significant bradycardia/hypotension, necessitating drug withdrawal, occurred in 2 of 40 (5%) patients on sotalol and none in the placebo group (p = 0.2). None of the patients on sotalol developed Torsade de pointes or sustained ventricular arrhythmias. Postoperative mortality was not significantly different in sotalol versus placebo (0% vs. 2%, p = 1.0). Patients in the sotalol group had a nonsignificantly shorter length of hospital stay as compared with placebo (7 +/- 2 days vs. 8 +/- 4 days; p = 0.24). CONCLUSIONS: The administration of sotalol, in dosages ranging from 80 to 120 mg, was associated with a significant decrease (67%) in postoperative AF in patients undergoing CABG without appreciable side effects. Sotalol should be considered for the prevention of postoperative AF in patients undergoing CABG in the absence of heart failure and significant left ventricular dysfunction.

Utilization of impedance measurements in pallidotomy using a monopolar electrode.

OBJECT: This study was performed to evaluate the reliability and utility of using monopolar impedance monitoring for estimation of the location of the thermocouple electrode during a pallidotomy procedure. METHODS: In 26 patients, impedance profiles were measured at 2-mm intervals and anatomical boundaries were marked on postoperative MRI studies in 19 patients. The pattern of change in impedance as the electrode was towards the target coordinates in the globus pallidus was studied empirically in relation to MRI-defined anatomy and by electrical stimulations. The pattern of impedance change was of greater reliability than absolute impedance values. A drop in impedance was noted in 10 cases where the electrode entered the putamen or globus pallidus upon exiting the internal capsule, and in 9 of these this drop was measured before or at the distal boundary of the internal capsule. A variable pattern in the region of the base of the globus pallidus was observed, with 10 of 19 cases demonstrating a decrease and 8 cases an increase, consistent with the proximity of a CSF cistern in the former and the ansa lenticularis and optic tract in the latter. Simulations showed that the monopolar electrode was more sensitive to the approach of a boundary than the bipolar electrode. CONCLUSION: Our measurements and simulations suggest that a monopolar electrode could predict a nearby region of high or low impedance before penetrating it and a trend of decreasing impedance as the distal edge of the globus pallidus is approached.