Variations in radioiodine ablation: decision-making after total thyroidectomy.

BACKGROUND: The role of radioiodine treatment following total thyroidectomy for differentiated thyroid cancer is changing. The last major revision of the American Thyroid Association (ATA) Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer in 2015 changed treatment recommendations dramatically in comparison with the European Association of Nuclear Medicine (EANM) 2008 guidelines. We hypothesised that there is marked variability between the different treatment regimens used today. METHODS: We analysed decision-making in all Swiss hospitals offering radioiodine treatment to map current practice within the community and identify consensus and discrepancies. RESULTS AND CONCLUSION: We demonstrated that for low-risk DTC patients after thyroidectomy, some institutions offered only follow-up, while RIT with significant activities is recommended in others. For intermediate- and high-risk patients, radioiodine treatment is generally recommended. Dosing and treatment preparation (recombinant human thyroid stimulation hormone (rhTSH) vs. thyroid hormone withdrawal (THW)) vary significantly among centres.

GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder.

The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG-related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, P=3.3 × 10-8; rs191260602, P=3.9 × 10-8). We followed up on this finding in a larger dimensional ACQ sample (N=2547) and in independent samples with a dichotomous AG phenotype based on the Symptoms Checklist (SCL-90; N=3845) and a case-control sample with the categorical phenotype PD/AG (Ncombined =1012) obtaining highly significant P-values also for GLRB single-nucleotide variants rs17035816 (P=3.8 × 10-4) and rs7688285 (P=7.6 × 10-5). GLRB gene expression was found to be modulated by rs7688285 in brain tissue, as well as cell culture. Analyses of intermediate PD/AG phenotypes demonstrated increased startle reflex and increased fear network, as well as general sensory activation by GLRB risk gene variants rs78726293, rs191260602, rs17035816 and rs7688285. Partial Glrb knockout mice demonstrated an agoraphobic phenotype. In conjunction with the clinical observation that rare coding GLRB gene mutations are associated with the neurological disorder hyperekplexia characterized by a generalized startle reaction and agoraphobic behavior, our data provide evidence that non-coding, although functional GLRB gene polymorphisms may predispose to PD by increasing startle response and agoraphobic cognitions.

Intestinal regeneration, residual function and immunological priming following rescue therapy after rat small bowel transplantation.

Clinical evidence suggests that recurrent acute cellular rejection (ACR) may trigger chronic rejection and impair outcome after intestinal transplantation. To test this hypothesis and clarify underlying molecular mechanisms, orthotopic/allogenic intestinal transplantation was performed in rats. ACR was allowed to occur in a MHC-disparate combination (BN-LEW) and two rescue strategies (FK506monotherapy vs. FK506+infliximab) were tested against continuous immunosuppression without ACR, with observation for 7/14 and 21 days after transplantation. Both, FK506 and FK506+infliximab rescue therapy reversed ACR and resulted in improved histology and less cellular infiltration. Proinflammatory cytokines and chemotactic mediators in the muscle layer were significantly reduced in FK506 treated groups. Increased levels of CD4, FOXP3 and IL-17 (mRNA) were observed with infliximab. Contractile function improved significantly after FK506 rescue therapy, with a slight benefit from additional infliximab, but did not reach nontransplanted controls. Fibrosis onset was detected in both rescue groups by Sirius-Red staining with concomitant increase of the fibrogenic mediator VEGF. Recovery from ACR could be attained by both rescue therapy regimens, progressing steadily after initiation of immunosuppression. Reversal of ACR, however, resulted in early stage graft fibrosis. Additional infliximab treatment may enhance physiological recovery of the muscle layer and enteric nervous system independent of inflammatory reactions.

Perioperative infliximab application has marginal effects on ischemia-reperfusion injury in experimental small bowel transplantation in rats.

PURPOSE: Ischemia-reperfusion injury leads to impaired smooth muscle function and inflammatory reactions after intestinal transplantation. In previous studies, infliximab has been shown to effectively protect allogenic intestinal grafts in the early phase after transplantation with resulting improved contractility. This study was designed to reveal protective effects of infliximab on ischemia-reperfusion injury in isogenic transplantation. METHODS: Isogenic, orthotopic small bowel transplantation was performed in Lewis rats (3 h cold ischemia). Five groups were defined: non-transplanted animals with no treatment (group 1), isogenic transplanted animals with vehicle treatment (groups 2/3) or with infliximab treatment (5 mg/kg body weight intravenously, directly after reperfusion; groups 4/5). The treated animals were sacrificed after 3 (group 2/4) or 24 h (group 3/5). Histological and immunohistochemical analysis, TUNEL staining, real-time RT-PCR, and contractility measurements in a standard organ bath were used for determination of ischemia-reperfusion injury. RESULTS: All transplanted animals showed reduced smooth muscle function, while no significant advantage of infliximab treatment was observed. Reduced infiltration of neutrophils was noted in the early phase in animals treated with infliximab. The structural integrity of the bowel and infiltration of ED1-positive monocytes and macrophages did not improve with infliximab treatment. At 3 h after reperfusion, mRNA expression of interleukin (IL)-6, TNF-α, IL-10, and iNOS and MCP-1 displayed increased activation in the infliximab group. CONCLUSION: The protective effects of infliximab in the early phase after experimental small bowel transplantation seem to be unrelated to ischemia-reperfusion injury. The promising effects in allogenic transplantation indicate the need for further experiments with infliximab as complementary treatment under standard immunosuppressive therapy. Further experiments should focus on additional infliximab treatment in the setting of acute rejection.

Predictive value of sleep apnea screenings in cardiac surgery patients.

INTRODUCTION: Obstructive sleep apnea (OSA) is a highly prevalent disorder associated with increased cardiovascular risks. We explored the predictive value of OSA screening instruments in cardiac disease patients awaiting cardiac surgery. METHODS: In this prospective cohort, 107 participants awaiting cardiac surgery from Cleveland Clinic and Johns Hopkins underwent polysomnography after completing Epworth Sleepiness Scale (ESS), Sleep Apnea/Sleep Disorder Questionnaire (SA/SDQ), STOP, STOPBAG2 and Berlin questionnaires. Score comparisons between groups based on apnea-hypopnea index (AHI) ≥15 were performed. Logistic regression with receiver operating characteristic (ROC) analysis was used to investigate optimal threshold. RESULTS: Prevalence of OSA (AHI ≥5) was 71.9% (77/107) and 51 (47.7%) had moderate-to-severe disease (AHI ≥15). Participants were primarily male (57%) and Caucasian (76.6%). Mean age was 67.3 ± 13.3 years and BMI was 26.5 ± 6.6. Of the five screening tools, STOPBAG2 with a cut-point of 0.381 provided 78% sensitivity and 38% specificity (AUC 0.66, 95%CI 0.55-0.77). SA/SDQ yielded a cut-point of 32 for all subjects (AUC: 0.62, 95%CI 0.51-0.73) with sensitivity and specificity of 60% and 62% respectively, while STOP score ≥2 provided sensitivity and specificity of 67% and 52% respectively (AUC: 0.61, 95%CI 0.51-0.72). Among STOP items, "observed apnea" had the strongest correlation with AHI ≥15 (OR 3.67, 95%CI 1.57-8.54, p = 0.003). The ESS and Berlin were not useful in identifying moderate-to-severe OSA. CONCLUSION: Common screening tools had suboptimal performance in cardiac surgery patients. STOPBAG2 was better at predicting the probability of moderate-to-severe OSA in patients undergoing cardiac surgery compared to ESS, SA/SDQ, STOP and Berlin questionnaires.

Influence of immunosuppression on alloresponse, inflammation and contractile function of graft after intestinal transplantation.

In small bowel transplantation (SBTx), graft manipulation, ischemia/reperfusion injury and acute rejection initiate a severe cellular and molecular inflammatory response in the muscularis propria leading to impaired motility of the graft. This study examined and compared the effect of tacrolimus and sirolimus on inflammation in graft muscularis. After allogeneic orthotopic SBTx, recipient rats were treated with tacrolimus or sirolimus. Tacrolimus and sirolimus attenuated neutrophilic, macrophage and T-cell infiltration in graft muscularis, which was associated with reduced apoptotic cell death. Nonspecific inflammatory mediators (IL-6, MCP-1) and T-cell activation markers (IL-2, IFN-gamma) were highly upregulated in allogeneic control graft muscularis 24 h and 7 days after SBTx, and tacrolimus and sirolimus significantly suppressed upregulation of these mediators. In vitro organ bath method demonstrated a severe decrease in graft smooth muscle contractility in allogeneic control (22% of normal control). Correlating with attenuated upregulation of iNOS, tacrolimus and sirolimus treatment significantly improved contractility (64% and 72%, respectively). Although sirolimus reduced cellular and molecular inflammatory response more efficiently after 24 h, contrary tacrolimus prevented acute rejection more efficiently. In conclusion, tacrolimus and sirolimus attenuate cellular and molecular inflammatory response in graft muscularis and subsequent dysmotility of the graft after allogeneic SBTx.

Perioperative infliximab application ameliorates acute rejection associated inflammation after intestinal transplantation.

As we have shown in the past, acute rejection-related TNF-α upregulation in resident macrophages in the tunica muscularis after small bowel transplantation (SBTx) results in local amplification of inflammation, decisively contributing to graft dysmotility. Therefore, the aim of this study is to investigate the effectiveness of the chimeric-monoclonal-anti-TNF-α antibody infliximab as perioperative single shot treatment addressing inflammatory processes during acute rejection early after transplantation. Orthotopic, isogenic and allogenic SBTx was performed in rats (BN-Lewis/BN-BN) with infliximab treatment. Vehicle and IV-immunoglobulin-treated animals served as controls. Animals were sacrificed after 24 and 168 h. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry, mediator mRNA expression by Real-Time-RT-PCR, apoptosis by TUNEL and smooth muscle contractility in a standard organ bath. Both, infliximab and Sandoglobulin® revealed antiinflammatory effects. Infliximab resulted in significantly less leukocyte infiltration compared to allogenic controls and IV-immunoglobulin, which was accompanied by lower gene expression of MCP-1 (24 h), IFN-γ (168 h) and infiltration of CD8-positive cells. Smooth muscle contractility improved significantly after 24 h compared to all controls in infliximab treated animals accompanied by lower iNOS expression. Perioperative treatment with infliximab is a possible pharmaceutical approach to overcome graft dysmotility early after SBTx.

Risk-adapted FDG-PET/CT-based follow-up in patients with diffuse large B-cell lymphoma after first-line therapy.

BACKGROUND: The purpose of this study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) during follow-up of patients with diffuse large B-cell lymphoma (DLBCL) being in complete remission or unconfirmed complete remission after first-line therapy. PATIENTS AND METHODS: DLBCL patients receiving FDG-PET/CT during follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in cases of suspected disease recurrence. RESULTS: Seventy-five patients were analyzed and 23 (30%) had disease recurrence. The positive predictive value (PPV) of FDG-PET/CT was 0.85. Patients >60 years [P = 0.036, hazard ratio (HR) = 3.82, 95% confidence interval (CI) 1.02-7.77] and patients with symptoms indicative of a relapse (P = 0.015; HR = 4.1; 95% CI 1.20-14.03) had a significantly higher risk for relapse. A risk score on the basis of signs of relapse, age >60 years, or a combination of these factors identified patients at high risk for recurrence (P = 0.041). CONCLUSIONS: FDG-PET/CT detects recurrent DLBCL after first-line therapy with high PPV. However, it should not be used routinely and if only in selected high-risk patients to reduce radiation burden and costs. On the basis of our retrospective data, FDG-PET/CT during follow-up is indicated for patients <60 years with clinical signs of relapse and in patients >60 years with and without clinical signs of relapse.

Hodgkin's lymphoma in remission after first-line therapy: which patients need FDG-PET/CT for follow-up?

BACKGROUND: The purpose of the study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) during follow-up of patients with Hodgkin's lymphoma. PATIENTS AND METHODS: Patients in complete remission or an unconfirmed complete remission after first-line therapy who received FDG-PET/CT during their follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in case of recurrence. RESULTS: Overall, 134 patients were analyzed. Forty-two (31.3%) patients had a recurrence. The positive predictive value of FDG-PET/CT was 0.98. Single-factor analysis identified morphological residual mass [P = 0.0005, hazard ratio (HR) 3.4, 95% confidence interval (CI) 1.7-6.6] and symptoms (P < 0.0001, HR 4.9, 95% CI 2.4-9.9) as significant risk factors for relapse. By multivariate analysis, morphological residual mass was the only significant risk factor for early follow-up (<24 months) (P = 0.0019, HR 7.6, 95% CI 2.1-27.3). Advanced stage (P = 0.0426, HR 3.6, 95% CI 1.1-12.3) and the presence of symptoms (P = 0.0009, HR = 14.6, 95% CI 3.0-69.7) were found to be significant risk factors for later follow-up (>24 months). CONCLUSIONS: Asymptomatic patients without morphological residues and an early stage of disease do not need a routine FDG-PET/CT for follow-up. Asymptomatic patients with morphological residues should receive routine follow-up FDG-PET/CT for the first 24 months. Only patients with advanced initial stage do need a routine follow-up FDG-PET/CT beyond 24 months.

Energy transfer, volumetric expansion, and removal of oral biofilms by non-contact brushing.

Non-contact removal of oral biofilms offers advantages beyond the reach of bristles, but it is unknown how energy transfer for removal from brush-to-biofilm occurs. In the present study we evaluated non-contact, oral biofilm removal by oscillating-rotating and sonic toothbrushes, and their acoustic output up to 6 mm distance. Whereas some brushes removed biofilm when used at a distance of up to 6 mm, others lost efficacy at a distance of 2-4 mm from the biofilm. Loss of efficacy was accompanied with high standard deviations and volumetric biofilm expansion. Both sonic and oscillating-rotating brushes caused fluid flows and the inclusion of air-bubbles, while non-contact acoustic energy-transfer was demonstrated to decay with distance for both types of brushes. We put forward the following mechanism for non-contact removal: (i) brush energy is absorbed by biofilm, resulting in the visco-elastic expansion of the biofilm; (ii) if the energy absorbed is sufficient and deformation is beyond the yield point, biofilm removal occurs; and (iii) if deformation is in the plastic range but below the yield point (i.e. at the limiting distance for non-contact removal), biofilm is expanded but not removed.

177Lu radiolabeling and preclinical theranostic study of 1C1m-Fc: an anti-TEM-1 scFv-Fc fusion protein in soft tissue sarcoma.

PURPOSE: TEM-1 (tumor endothelial marker-1) is a single-pass transmembrane cell surface glycoprotein expressed at high levels by tumor vasculature and malignant cells. We aimed to perform a preclinical investigation of a novel anti-TEM-1 scFv-Fc fusion antibody, 1C1m-Fc, which was radiolabeled with 177Lu for use in soft tissue sarcomas models. METHODS: 1C1m-Fc was first conjugated to p-SCN-Bn-DOTA using different excess molar ratios and labeled with 177Lu. To determine radiolabeled antibody immunoreactivity, Lindmo assays were performed. The in vivo behavior of [177Lu]Lu-1C1m-Fc was characterized in mice bearing TEM-1 positive (SK-N-AS) and negative (HT-1080) tumors by biodistribution and single-photon emission SPECT/CT imaging studies. Estimated organ absorbed doses were obtained based on biodistribution results. RESULTS: The DOTA conjugation and the labeling with 177Lu were successful with a radiochemical purity of up to 95%. Immunoreactivity after radiolabeling was 86% ± 4%. Biodistribution showed a specific uptake in TEM-1 positive tumor versus liver as critical non-specific healthy organ, and this specificity is correlated to the number of chelates per antibody. A 1.9-fold higher signal at 72 h was observed in SPECT/CT imaging in TEM-1 positive tumors versus control tumors. CONCLUSION: TEM-1 is a promising target that could allow a theranostic approach to soft-tissue sarcoma, and 1C1m-Fc appears to be a suitable targeting candidate. In this study, we observed the influence of the ratio DOTA/antibody on the biodistribution. The next step will be to investigate the best conjugation to achieve an optimal tumor-to-organ radioactivity ratio and to perform therapy in murine xenograft models as a prelude to future translation in patients.

Influence of temporary abdominal wall repair on the intestinal integrity: an experimental study in the rat.

BACKGROUND AND AIMS: The aim of this study was to analyze intestinal integrity after temporary abdominal wall repair with absorbable mesh. METHODS: Rats underwent abdominal wall repair with absorbable mesh or sham operation. Myeloperoxidase-positive cells in the intestinal muscularis were histochemically quantified. Intestinal transit was visualized 48 h after surgery. Local and systemic inflammatory response was measured with TNF-alpha and IL-6 ELISA as well as malondialdehyde (MDA) expression in serum and peritoneal fluid. RESULTS: Neutrophil count of the intestinal muscularis revealed that infiltration in the mesh-implanted and in the mesh-free animals 48 h postoperatively was similar. Gastrointestinal transit was similarly unaffected 48 h after surgery, with or without mesh implantation. TNF-alpha, IL-6 and MDA concentration in serum and peritoneal fluid showed no significant differences between the two groups. CONCLUSION: Intestinal contractility and local and systemic inflammatory response remained unaffected. Therefore, absorbable mesh augmentation is a safe and reliable method for temporary repair of the abdominal wall without affecting the intestinal integrity.

Gastric stump carcinoma - epidemiology and current concepts in pathogenesis and treatment.

AIM: The aim of this article is to review the aetiology, pathology and treatment of gastric stump carcinoma (GSC). GSC is an uncommon tumour; however, the incidence is not declining, so this tumour entity will be encountered in the years to come. METHODS: The electronic literature search was performed in the MEDLINE database to identify relevant studies concerning epidemiology, prognosis, treatment, aetiology and pathology of GSC. The references reported in these studies were used to complete the literature search. RESULTS: Patients subjected to distal gastric resection have a 4-7-fold increased risk of developing GSC, which is attributed mainly to gastroduodenal reflux. Denervation during partial gastrectomy may also contribute to the risk of developing GSC. Gastroduodenal ulcers were the main reason for partial gastrectomy. Both ulcer locations have an increased risk of developing GSC after 20 years. In GSC, Helicobacter pylori seems not to be an important risk factor, contrary to primary gastric cancer, because gastroduodenal reflux impairs the growth of Helicobacter pylori. CONCLUSION: The treatment of choice for GSC should be the total removal of the gastric remnant including at least D2 lymphadenectomy. The pattern of lymph node metastases in GSC may differ from primary gastric cancer, as lymph node metastases have been reported in the jejunal mesentery and the lower mediastinum. Therefore, GSC may require a modified lymphadenectomy to include all important lymph node stations. After radical remnant gastrectomy, GSC has a prognosis not different from primary proximal gastric cancer.

Acute rejection in allogeneic rodent small bowel transplantation causes smooth muscle dysfunction via an inflammatory response within the intestinal muscularis.

INTRODUCTION: Isogeneic intestinal transplantation elicits an inflammatory response within the intestinal muscularis that is associated with dysmotility. Usually the inflammation and the postoperative motor dysfunction resolve within a few days after small bowel transplantation (SBTx). However, the onset of acute rejection in allogeneic SBTx is again associated with dysmotility. We hypothesized that dysmotility during acute rejection is based on coexpression of kinetically active mediators by the alloreactive leucocyte infiltrate. MATERIALS AND METHODS: Rat SBTx (BN to Lew and BN to BN) was performed without immunosuppression. Animals were sacrificed at 1, 4, and 7 days after SBTx. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry. Mediator mRNA expression was determined by reverse transcriptase polymerase chain reaction. Muscle contractility was assessed in a standard organ bath. RESULTS: Transplanted animals showed a significant inflammatory response within the muscularis at day 1 after SBTx. However, allogeneic transplanted animals exhibited a significant second inflammatory peak at day 7 (mRNA induction: iNOS 150-fold; tumor necrosis factor-alpha 18-fold; interferon-gamma 397-fold), parallel to the onset of rejection. This change was associated with a significant leukocyte infiltration. Compared to controls, allogeneic transplanted animals showed a 29% decrease in smooth muscle contractility on days 1 and 4 and a 71% decrease of contractility on postoperative day 7. CONCLUSIONS: The motor dysfunction of transplanted small bowel during acute rejection is associated with an inflammatory reaction in the intestinal muscularis. The initial unspecific inflammation process immediately after transplantation is reactivated and intensified during acute rejection.

Mechanism and impact of organ harvesting and ischemia-reperfusion injury within the graft muscularis in rat small bowel transplantation.

INTRODUCTION: Inflammatory events within the gut muscularis contribute to dysmotility. We hypothesized that manipulation during organ harvesting initiated an inflammatory response via muscularis macrophages and that this cascade was amplified during reperfusion. METHODS: Small bowel transplantation was performed in Lewis rats. To investigate the impact of organ harvesting on muscularis inflammation, cold whole-body perfusion was performed after versus prior to organ harvesting. The role of macrophages was investigated by transplantation of the macrophage-depleted gut. Leukocyte infiltration was investigated in muscularis whole mounts. Mediator mRNA expression was determined by real-time reverse transcriptase polymerase chain reaction. Contractility was assessed in a standard organ bath. RESULTS: Organ harvesting and ischemia-reperfusion induced leukocyte recruitment and mRNA upregulation in the muscularis: interleukin-6 12217-fold, monocyte chemoattractant protein-1 62-fold, ICAM-1 12-fold, cyclooxygenase-2: 8-fold, iNOS: 150-fold. Although organ harvesting with cold ischemia prevented early gene expression, peak expression at 3-hour reperfusion was not changed by modification of the harvesting technique. Compared to controls, transplanted animals showed a 63% decrease in smooth muscle contractility. In contrast, transplanted macrophage-depleted gut exhibited significantly fewer leukocytes and only a 16% decrease in contractility. CONCLUSIONS: Gut manipulation during organ harvesting initiates an inflammatory response within the muscularis that is massively intensified during reperfusion. This change contributes to muscular dysfunction. Furthermore, the results suggested that resident macrophages play a key role in initiating this process.

Improved efficiency of budesonide nebulization using surface-active agents.

Our aim was to improve the efficiency of nebulised budesonide using surface-active agents. Cationic, anionic, and nonionic detergents were added to commercial budesonide suspension, and the particle size distribution during nebulization was measured using both cascade impaction and laser diffraction. Our results showed that the emitted dose was increased after addition of cationic (p < 0.001) and nonionic detergents (p < 0.01) compared with the commercial formulation alone. The respirable fraction was increased for all detergent formulations (p < 0.001) compared with the commercial formulation. We concluded that cationic and nonionic detergent increased the total output of budesonide from the Sidestream. All detergent formulations increased the respirable fraction of nebulized budesonide.

Strength and ductility with {10͞11} - {10͞12} double twinning in a magnesium alloy.

Based on their high specific strength and stiffness, magnesium alloys are attractive for lightweight applications in aerospace and transportation, where weight saving is crucial for the reduction of carbon dioxide emissions. Unfortunately, the ductility of magnesium alloys is usually limited. It is thought that one reason for the lack of ductility is that the development of - double twins (DTW) cause premature failure of magnesium alloys. Here we show with a magnesium alloy containing 4 wt% lithium, that the same impressively large compression failure strains can be achieved with DTWs as without. The DTWs form stably across the microstructure and continuously throughout straining, forming three-dimensional intra-granular networks, a potential strengthening mechanism. We rationalize that relatively easier slip characteristic of this alloy plastically relaxed the localized stress concentrations that DTWs can generate. This result may provide key insight and an alternative perspective towards designing formable and strong magnesium alloys.

Crash characteristics and injuries of victims impaired by alcohol versus illicit drugs.

Alcohol has long been associated with injury, but the relationship between other drugs and injury is less clear. Blood samples from 894 patients presenting to two Emergency Departments for treatment of motor vehicle injury sustained in passenger cars, station wagons, vans and pickup trucks, were tested for alcohol and other drugs. Results were related to demographic characteristics, including prior history of alcohol and drug use; crash characteristics; and injury characteristics. Alcohol was associated with more severe crashes, but other drugs, in the absence of alcohol, were not. The crashes involving drugs but no alcohol were very similar to those involving neither alcohol nor drugs.