The relationship between intraosseous catheter tip placement, flow rates, and infusion pressures in a high bone density cadaveric swine (Sus scrofa) model.

Background: Intraosseous (IO) infusion is a life-preserving technique when intravenous access is unobtainable. Successful IO infusion requires sufficiently high flow rates to preserve life but at low enough pressures to avoid complications. However, IO catheter tips are often misplaced, and the relative flow rates and pressures between IO catheter tips placed in medullary, trabecular, and cortical bone are not well described, which has important implications for clinical practice. Objectives: We developed the Zone Theory of IO Catheter Tip Placement based on bone density and proximity to the venous central sinus and then tested the influence of catheter tip placement locations on flow rates and pressures in a cadaveric swine model. Methods: Three cross-trained participants infused 500 mL of crystalloid fluid into cadaveric swine humerus and sternum (N = 210 trials total) using a push‒pull method with a 60 cm3 syringe. Computed tomography scans were scored by radiologists and categorized as zone 1 (medullary space), zone 2 (trabecular bone), or zone 3 (cortical bone) catheter tip placements. Differences between zones in flow rates, mean pressures, and peak pressures were assessed using analysis of variance and analysis of covariance to account for participant and site differences at the p < 0.05 threshold. Results: Zone 1 and zone 2 placements were essentially identical in flow rates, mean pressures, and peak pressures (each p > 0.05). Zone 1 and zone 2 placements were significantly higher in flow rates and lower in pressures than zone 3 placements (each p < 0.05 or less). Conclusion: Within the limitations of an unpressurized cadaveric swine model, the present findings suggest that IO catheter tip placements need not be perfect to acquire high flow rates at low pressures, only accurate enough to avoid the dense cortical bone of zone 3. Future research using in vivo animal and human models is needed to better define the clinical impact of IO catheter placement on infusion flow rates and pressures.

Application Times, Placement Accuracy, and User Ratings of Commercially Available Manual and Battery-Powered Intraosseous Catheters in a High Bone Density Cadaveric Swine Model.

INTRODUCTION: Intraosseous (IO) infusion, the pressurized injection of fluids into bone through a catheter, is a life-preserving resuscitative technique for treating trauma patients with severe hemorrhage. However, little is known regarding the application times, placement accuracy, and end-user ratings of battery-powered and manual IO access devices. This study was specifically designed to fill these knowledge gaps on six FDA-approved IO access devices. MATERIALS AND METHODS: Three experienced U.S. Navy Emergency Medicine residents each placed commercially available 15-gauge IO catheters in cadaveric swine (Sus scrofa) proximal humeri and sternums in a randomized prospective experimental design. Devices included the battery-powered EZ-IO Rapid Infuser and the manual Jamshidi IO, PerSys NIO, SAM Manual IO, Tactical Advanced Lifesaving IO Needle (TALON), and PYNG First Access for Shock and Trauma 1 (30 trials per device, 10 per user, 210 total trials). Application times, placement accuracy in medullary (zone 1) and trabecular (zone 2) bone while avoiding cortical (zone 3) bone, and eight subjective user ratings were analyzed using ANOVA and nonparametric statistics at P < .05. RESULTS: The EZ-IO demonstrated the fastest application times, high rates in avoiding zone 3, and the highest user ratings (P < .0001). The TALON conferred intermediate placement times, highest rates of avoiding zone 3, and second-highest user ratings. The SAM Manual IO and Jamshidi performed poorly, with mixed results for the PerSys NIO and PYNG First Access for Shock and Trauma 1. CONCLUSIONS: The battery-powered EZ-IO performed best and remains the IO access device of choice. The present findings suggest that the TALON should be considered as a manual backup to the EZ-IO.

Management of illicit substances in hospital: An evaluation of policy and procedure implementation.

Previous research has identified illicit substance use on hospital property as an ongoing concern, particularly in inpatient mental health units. This research, combined with concerns raised by healthcare providers, patients, and patients' families, resulted in one hospital in a medium-sized city in Canada enacting two internal strategies for the management of illicit substances on hospital property. The unit-based Green-Yellow-Red procedure employs environmental scanning and regular risk assessment to report the incidence rate of illicit substances suspected and/or found in the unit, to inform staff of the extent of necessary interventions which should ensue. The hospital-wide Management of Illicit Substances protocol includes ten steps which can be followed by any staff member who suspects they have found an illicit substance or related paraphernalia on hospital grounds. This paper discusses the creation and implementation of these two strategies, as well as associated challenges and outcomes of each. Overall, these strategies have effectively functioned to mitigate the potential dangers of exposure to illicit substances for staff and patients alike. These results stand to encourage other institutions to implement similar strategies in order to better manage situations in which illicit substances are suspected or discovered on hospital property.

The reciprocal relationship between cardiac baroreceptor sensitivity and cerebral autoregulation during simulated hemorrhage in humans.

A reciprocal relationship between the baroreflex and cerebral autoregulation (CA) has been demonstrated at rest and in response to acute hypotension. We hypothesized that the reciprocal relationship between cardiac baroreflex sensitivity (BRS) and CA would be maintained during sustained central hypovolemia induced by lower body negative pressure (LBNP), and that the strength of this relationship would be greater in subjects with higher tolerance to this stress. Healthy young adults (n = 51; 23F/28M) completed a LBNP protocol to presyncope. Subjects were classified as high tolerant (HT; completion of -60 mmHg LBNP stage, ≥20-min) or low tolerant (LT; did not complete -60 mmHg LBNP stage, <20-min). R-R intervals (RRI), systolic arterial pressure (SAP), mean arterial pressure (MAP), and middle cerebral artery velocity (MCAv) were measured continuously. Cardiac BRS was calculated in the time domain (ΔHR/ΔSAP) and frequency domain (RRI-SAP low frequency (LF) transfer function gain), and CA was calculated in the time domain (ΔMCAv/ΔMAP) and frequency domain (MAP-mean MCAv LF transfer function gain). There was a moderate relationship between cardiac BRS and CA for the group of 51 subjects in both the time (R = -0.54, P < 0.0001) and frequency (R = 0.61, P < 0.001) domains; there was a stronger relationship in the HT group (R = 0.73) compared to the LT group (R = 0.31) in the frequency domain (P = 0.08), but no difference between groups in the time domain (HT: R = -0.73 vs. LT: R = -0.63; P = 0.27). These findings suggest that an interaction between BRS and CA may be an important compensatory mechanism that contributes to tolerance to simulated hemorrhage in young healthy adults.

Tattoo Trouble: A Case of Drug-induced Thrombocytopenic Purpura.

Trimethoprim-sulfamethoxazole, otherwise known as Bactrim or Septra, is a commonly prescribed antibiotic for soft tissue infections. Drug-induced thrombocytopenia is a rare but serious adverse reaction to sulfonamide antibiotics like Bactrim/Septra. A 34-year-old active duty marine male with no significant past medical history presented with a chief complaint of a rash on his lower extremities. The patient stated that 2 weeks earlier, he was prescribed Bactrim for cellulitis at the site of a new tattoo. The intern noted a petechial rash that was pathognomonic for thrombocytopenia. Laboratory testing confirmed the patient's thrombocytopenia with platelets of 2,000/µL on initial complete blood count, without pancytopenia or other coagulopathies. The blood smear indicated a profound lack of platelets but otherwise normal cell counts and morphology. In the emergency department, the patient was typed and crossed, platelets were ordered, and hematology-oncology was consulted. Once admitted to the internal medicine ward, he was administered glucocorticoids as well as platelet transfusions. He was monitored for 3 days and discharged with a diagnosis of resolved drug-induced thrombocytopenia. This case illustrates the importance of conducting a thorough review of systems and physical examination in stable and otherwise healthy patients. In this case, the seemingly benign rash was one of the only clinical signs of severe thrombocytopenia, with a high risk of spontaneous bleeding in clinically significant organ systems. It is important to recognize immune thrombocytopenic purpura as a potential complication of Bactrim/Septra, as this antibiotic is widely used by military providers in operational settings.

MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration.

The human genome expresses thousands of natural antisense transcripts (NAT) that can regulate epigenetic state, transcription, RNA stability or translation of their overlapping genes1,2. Here we describe MAPT-AS1, a brain-enriched NAT that is conserved in primates and contains an embedded mammalian-wide interspersed repeat (MIR), which represses tau translation by competing for ribosomal RNA pairing with the MAPT mRNA internal ribosome entry site3. MAPT encodes tau, a neuronal intrinsically disordered protein (IDP) that stabilizes axonal microtubules. Hyperphosphorylated, aggregation-prone tau forms the hallmark inclusions of tauopathies4. Mutations in MAPT cause familial frontotemporal dementia, and common variations forming the MAPT H1 haplotype are a significant risk factor in many tauopathies5 and Parkinson's disease. Notably, expression of MAPT-AS1 or minimal essential sequences from MAPT-AS1 (including MIR) reduces-whereas silencing MAPT-AS1 expression increases-neuronal tau levels, and correlate with tau pathology in human brain. Moreover, we identified many additional NATs with embedded MIRs (MIR-NATs), which are overrepresented at coding genes linked to neurodegeneration and/or encoding IDPs, and confirmed MIR-NAT-mediated translational control of one such gene, PLCG1. These results demonstrate a key role for MAPT-AS1 in tauopathies and reveal a potentially broad contribution of MIR-NATs to the tightly controlled translation of IDPs6, with particular relevance for proteostasis in neurodegeneration.

The impact of acute central hypovolemia on cerebral hemodynamics: does sex matter?

Trauma-induced hemorrhage is a leading cause of disability and death due, in part, to impaired perfusion and oxygenation of the brain. It is unknown if cerebrovascular responses to blood loss are differentiated based on sex. We hypothesized that compared to males, females would have reduced tolerance to simulated hemorrhage induced by maximal lower body negative pressure (LBNP), and this would be associated with an earlier reduction in cerebral blood flow and cerebral oxygenation. Healthy young males (n = 29, 26 ± 4 yr) and females (n = 23, 27 ± 5 yr) completed a step-wise LBNP protocol to presyncope. Mean arterial pressure (MAP), stroke volume (SV), middle cerebral artery velocity (MCAv), end-tidal CO2 (etCO2), and cerebral oxygen saturation (ScO2) were measured continuously. Unexpectedly, tolerance to LBNP was similar between the sexes (males, 1,604 ± 68 s vs. females, 1,453 ± 78 s; P = 0.15). Accordingly, decreases (%Δ) in MAP, SV, MCAv, and ScO2 were similar between males and females throughout LBNP and at presyncope (P ≥ 0.20). Interestingly, although decreases in etCO2 were similar between the sexes throughout LBNP (P = 0.16), at presyncope, the %Δ etCO2 from baseline was greater in males compared to females (-30.8 ± 2.6% vs. -21.3 ± 3.0%; P = 0.02). Contrary to our hypothesis, sex does not influence tolerance, or the central or cerebral hemodynamic responses to simulated hemorrhage. However, the etCO2 responses at presyncope do suggest potential sex differences in cerebral vascular sensitivity to CO2 during central hypovolemia.NEW & NOTEWORTHY Tolerance and cerebral blood velocity responses to simulated hemorrhage (elicited by lower body negative pressure) were similar between male and female subjects. Interestingly, the change in etCO2 from baseline was greater in males compared to females at presyncope, suggesting potential sex differences in cerebral vascular sensitivity to CO2 during simulated hemorrhage. These findings may facilitate development of individualized therapeutic interventions to improve survival from hemorrhagic injuries in both men and women.

A comparison of protocols for simulating hemorrhage in humans: step versus ramp lower body negative pressure.

Lower body negative pressure (LBNP) elicits central hypovolemia, and it has been used to simulate the cardiovascular and cerebrovascular responses to hemorrhage in humans. LBNP protocols commonly use progressive stepwise reductions in chamber pressure for specific time periods. However, continuous ramp LBNP protocols have also been utilized to simulate the continuous nature of most bleeding injuries. The aim of this study was to compare tolerance and hemodynamic responses between these two LBNP profiles. Healthy human subjects (N = 19; age, 27 ± 4 y; 7 female/12 male) completed a 1) step LBNP protocol (5-min steps) and 2) continuous ramp LBNP protocol (3 mmHg/min), both to presyncope. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), middle and posterior cerebral artery velocity (MCAv and PCAv), cerebral oxygen saturation (ScO2), and end-tidal CO2 (etCO2) were measured. LBNP tolerance, via the cumulative stress index (CSI, summation of chamber pressure × time at each pressure), and hemodynamic responses were compared between the two protocols. The CSI (step: 911 ± 97 mmHg/min vs. ramp: 823 ± 83 mmHg/min; P = 0.12) and the magnitude of central hypovolemia (%Δ SV, step: -54.6% ± 2.6% vs. ramp: -52.1% ± 2.8%; P = 0.32) were similar between protocols. Although there were no differences between protocols for the maximal %Δ HR (P = 0.88), the %Δ MAP during the step protocol was attenuated (P = 0.05), and the reductions in MCAv, PCAv, ScO2, and etCO2 were greater (P ≤ 0.08) when compared with the ramp protocol at presyncope. These results indicate that when comparing cardiovascular responses to LBNP across different laboratories, the specific pressure profile must be considered as a potential confounding factor.NEW & NOTEWORTHY Ramp lower body negative pressure (LBNP) protocols have been utilized to simulate the continuous nature of bleeding injuries. However, it unknown if tolerance or the physiological responses to ramp LBNP are similar to the more common stepwise LBNP protocol. We report similar tolerance between the two protocols, but the step protocol elicited a greater increase in cerebral oxygen extraction in the presence of reduced blood flow, presumably facilitating the matching of metabolic supply and demand.

Factors affecting HLA expression: A review.

The detection and semiquantitative measurement of circulating human leucocyte antigen (HLA)-specific antibodies is essential for the management of patients before and after transplantation. In addition, the pretransplant cross-match to assess the reactivity of recipient HLA antibody against donor lymphocytes has long been the gold standard to prevent hyperacute rejection. Whilst both of these tests assume that recipient HLA-specific antibody is the only variable in the assessment of transplant risk, this is not the case. Transplant immunologists recognize that some HLA antigens are expressed at levels a magnitude lower than others (e.g., HLA-C, HLA-DQ), but within loci, and between different cell types there are many factors that influence HLA expression in both resting and activated cells. HLA is not usually expressed without the specific promoter proteins NLRC5, for HLA class I, and CIITA, for class II. The quantity of HLA protein production is then affected by factors including promoter region polymorphisms, alternative exon splice sites, methylation and microRNA-directed degradation. Different loci are influenced by multiple combinations of these control mechanisms making prediction of HLA regulation difficult, but an ability to measure the cellular expression of each HLA antigen, in conjunction with knowledge of circulating HLA-specific antibody, would lead to a more informed algorithm to assess transplant risk.

Hemorrhage simulated by lower body negative pressure provokes an oxidative stress response in healthy young adults.

IMPACT STATEMENT: We characterize the systemic oxidative stress response in young, healthy human subjects with exposure to simulated hemorrhage via application of lower body negative pressure (LBNP). Prior work has demonstrated that LBNP and actual blood loss evoke similar hemodynamic and immune responses (i.e. white blood cell count), but it is unknown whether LBNP elicits oxidative stress resembling that produced by blood loss. We show that LBNP induces a 29% increase in F2-isoprostanes, a systemic marker of oxidative stress. The findings of this investigation may have important implications for the study of hemorrhage using LBNP, including future assessments of targeted interventions that may reduce oxidative stress, such as novel fluid resuscitation approaches.

Cerebral oxygenation and regional cerebral perfusion responses with resistance breathing during central hypovolemia.

Resistance breathing improves tolerance to central hypovolemia induced by lower body negative pressure (LBNP), but this is not related to protection of anterior cerebral blood flow [indexed by mean middle cerebral artery velocity (MCAv)]. We hypothesized that inspiratory resistance breathing improves tolerance to central hypovolemia by maintaining cerebral oxygenation (ScO2), and protecting cerebral blood flow in the posterior cerebral circulation [indexed by posterior cerebral artery velocity (PCAv)]. Eight subjects (4 male/4 female) completed two experimental sessions of a presyncopal-limited LBNP protocol (3 mmHg/min onset rate) with and without (Control) resistance breathing via an impedance threshold device (ITD). ScO2 (via near-infrared spectroscopy), MCAv and PCAv (both via transcranial Doppler ultrasound), and arterial pressure (via finger photoplethysmography) were measured continuously. Hemodynamic responses were analyzed between the Control and ITD condition at baseline (T1) and the time representing 10 s before presyncope in the Control condition (T2). While breathing on the ITD increased LBNP tolerance from 1,506 ± 75 s to 1,704 ± 88 s (P = 0.003), both mean MCAv and mean PCAv were similar between conditions at T2 (P ≥ 0.46), and decreased by the same magnitude with and without ITD breathing (P ≥ 0.53). ScO2 also decreased by ~9% with or without ITD breathing at T2 (P = 0.97), and there were also no differences in deoxygenated (dHb) or oxygenated hemoglobin (HbO2) between conditions at T2 (P ≥ 0.43). There was no evidence that protection of regional cerebral blood velocity (i.e., anterior or posterior cerebral circulation) nor cerebral oxygen extraction played a key role in the determination of tolerance to central hypovolemia with resistance breathing.

The role of cerebral oxygenation and regional cerebral blood flow on tolerance to central hypovolemia.

Tolerance to central hypovolemia is highly variable, and accumulating evidence suggests that protection of anterior cerebral blood flow (CBF) is not an underlying mechanism. We hypothesized that individuals with high tolerance to central hypovolemia would exhibit protection of cerebral oxygenation (ScO2), and prolonged preservation of CBF in the posterior vs. anterior cerebral circulation. Eighteen subjects (7 male/11 female) completed a presyncope-limited lower body negative pressure (LBNP) protocol (3 mmHg/min onset rate). ScO2 (via near-infrared spectroscopy), middle cerebral artery velocity (MCAv), posterior cerebral artery velocity (PCAv) (both via transcranial Doppler ultrasound), and arterial pressure (via finger photoplethysmography) were measured continuously. Subjects who completed ≥70 mmHg LBNP were classified as high tolerant (HT; n = 7) and low tolerant (LT; n = 11) if they completed ≤60 mmHg LBNP. The minimum difference in LBNP tolerance between groups was 193 s (LT = 1,243 ± 185 s vs. HT = 1,996 ± 212 s; P < 0.001; Cohen's d = 3.8). Despite similar reductions in mean MCAv in both groups, ScO2 decreased in LT subjects from -15 mmHg LBNP (P = 0.002; Cohen's d=1.8), but was maintained at baseline values until -75 mmHg LBNP in HT subjects (P < 0.001; Cohen's d = 2.2); ScO2 was lower at -30 and -45 mmHg LBNP in LT subjects (P ≤ 0.02; Cohen's d ≥ 1.1). Similarly, mean PCAv decreased below baseline from -30 mmHg LBNP in LT subjects (P = 0.004; Cohen's d = 1.0), but remained unchanged from baseline in HT subjects until -75 mmHg (P = 0.006; Cohen's d = 2.0); PCAv was lower at -30 and -45 mmHg LBNP in LT subjects (P ≤ 0.01; Cohen's d ≥ 0.94). Individuals with higher tolerance to central hypovolemia exhibit prolonged preservation of CBF in the posterior cerebral circulation and sustained cerebral tissue oxygenation, both associated with a delay in the onset of presyncope.

Reproducibility of a continuous ramp lower body negative pressure protocol for simulating hemorrhage.

Central hypovolemia elicited by application of lower body negative pressure (LBNP) has been used extensively to simulate hemorrhage in human subjects. Traditional LBNP protocols incorporate progressive steps in pressure held for specific time intervals. The aim of this study was to assess the reproducibility of applying continuous LBNP at a constant rate until presyncope to replicate actual bleeding. During two trials (≥4 weeks intervening), LBNP was applied at a rate of 3 mmHg/min in 18 healthy human subjects (12M; 6F) until the onset of presyncopal symptoms. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), total peripheral resistance (TPR), mean middle and posterior cerebral artery velocities (MCAv, PCAv), and cerebral oxygen saturation (ScO2) were measured continuously. Time to presyncope (TTPS) and hemodynamic responses were compared between the two trials. TTPS (1649 ± 98 sec vs. 1690 ± 88 sec; P = 0.47 [t-test]; r = 0.77) and the subsequent magnitude of central hypovolemia (%Δ SV -54 ± 4% vs. -53 ± 4%; P = 0.55) were similar between trials. There were no statistically distinguishable differences at either baseline (P ≥ 0.17) or presyncope between trials for HR, MAP, TPR, mean MCAv, mean PCAv, or ScO2 (P ≥ 0.19). The rate of change from baseline to presyncope for all hemodynamic responses was also similar between trials (P ≥ 0.12). Continuous LBNP applied at a rate of 3 mmHg/min was reproducible in healthy human subjects, eliciting similar reductions in central blood volume and subsequent reflex hemodynamic responses.

Coupling between arterial pressure, cerebral blood velocity, and cerebral tissue oxygenation with spontaneous and forced oscillations.

We tested the hypothesis that transmission of arterial pressure to brain tissue oxygenation is low under conditions of arterial pressure instability. Two experimental models of hemodynamic instability were used in healthy human volunteers; (1) oscillatory lower body negative pressure (OLBNP) (N = 8; 5 male, 3 female), and; (2) maximal LBNP to presyncope (N = 21; 13 male, 8 female). Mean arterial pressure (MAP), middle cerebral artery velocity (MCAv), and cerebral tissue oxygen saturation (ScO2) were measured non-invasively. For the OLBNP protocol, between 0 and -60 mmHg negative pressure was applied for 20 cycles at 0.05 Hz, then 20 cycles at 0.1 Hz. For the maximal LBNP protocol, progressive 5 min stages of chamber decompression were applied until the onset of presyncope. Spectral power of MAP, mean MCAv, and ScO2 were calculated within the VLF (0.04-0.07 Hz), and LF (0.07-0.2 Hz) ranges, and cross-spectral coherence was calculated for MAP-mean MCAv, MAP-ScO2, and mean MCAv-ScO2 at baseline, during each OLBNP protocol, and at the level prior to pre-syncope during maximal LBNP (sub-max). The key findings are (1) both 0.1 Hz OLBNP and sub-max LBNP elicited increases in LF power for MAP, mean MCAv, and ScO2 (p ≤ 0.08); (2) 0.05 Hz OLBNP increased VLF power in MAP and ScO2 only (p ≤ 0.06); (3) coherence between MAP-mean MCAv was consistently higher (≥0.71) compared with MAP-ScO2, and mean MCAv-ScO2 (≤0.43) during both OLBNP protocols, and sub-max LBNP (p ≤ 0.04). These data indicate high linearity between pressure and cerebral blood flow variations, but reduced linearity between cerebral tissue oxygenation and both arterial pressure and cerebral blood flow. Measuring arterial pressure variability may not always provide adequate information about the downstream effects on cerebral tissue oxygenation, the key end-point of interest for neuronal viability.

Relaxin polymorphisms associated with metabolic disturbance in patients treated with antipsychotics.

People with schizophrenia have an increased risk of metabolic syndrome, with consequent elevated morbidity and mortality, largely due to cardiovascular disease. Metabolic disorders comprise obesity, dyslipidemia and elevated levels of triglycerides, hypertension, and disturbed insulin and glucose metabolism. The elevated risk of metabolic syndrome in individuals suffering from schizophrenia is believed to be multifactorial, related to a genetic predisposition, lifestyle characteristics and treatment with antipsychotic medications. Relaxin 3 (RLN3, also known as INSL7) is a recently identified member of the insulin/relaxin superfamily that plays a role in the regulation of appetite and body weight control. RLN3 stimulates relaxin-3 receptor 1 (relaxin/insulin-like family peptide receptor 3, RXFP3) and relaxin receptor 2 (relaxin/insulin-like family peptide receptor 4, RXFP4). We have investigated the role of ten polymorphisms in these genes (RLN3 rs12327666, rs1982632, and rs7249702, RLN3R1 rs42868, rs6861957, rs7702361, and rs35399, and RLN3R2 rs11264422, rs1018730 and rs12124383) in the occurrence of metabolic syndrome phenotypes (obesity, diabetes, hypercholesterolemia, hypertrigyceridemia, and hypertension) in a cross-sectional cohort of 419 US Caucasian patients treated with antipsychotic drugs. We found several associations between relaxin polymorphisms and hypecholesterolemia, obesity and diabetes, suggesting a role for the relaxin/insulin pathway in the development of metabolic disturbance observed in patients treated with antipsychotics.

Association of DRD2 variants and Gilles de la Tourette syndrome in a family-based sample from a South American population isolate.

Gilles de la Tourette Syndrome (GTS) is a chronic neuropsychiatric disorder characterized by motor and vocal tics. Epidemiological evidence supports the importance of genetic factors in disease susceptibility, whereas pharmacological and neuroimaging studies have suggested a defect in the dopamine system. The dopamine receptor D2 gene (DRD2) has been reported to be associated with GTS and related phenotypes. Here, we evaluate genetic association between DRD2 and GTS in a sample from a South American population isolate (Antioquia, Colombia). We genotyped nine single nucleotide polymorphisms (SNPs) across the DRD2 gene region in 69 GTS patients and their nuclear families and carried out both SNP and haplotype-based transmission distortion analysis. Evidence for association was found for three SNPs (rs6279, rs1079597 and rs4648318) and a five marker-haplotype comprising both rs6279 and rs1079597. Our findings replicate the association of DRD2 and GTS, and are consistent with the proposed connection between the dopamine system and this complex neuropsychiatric disease.