Thromboelastography as a Predictor of Outcomes Following Liver Transplantation.

BACKGROUND: Thromboelastography (TEG) has been used perioperatively during liver transplantation (LT) to provide a real-time global hemostasis assessment for targeted blood product replacement. We aimed to analyze the relationship between post-LT TEG results and outcomes. METHODS: We retrospectively analyzed patients undergoing LT from November 2008 to December 2014 at Mayo Clinic Florida. All 441 single-organ 1st-time LT patients aged ≥18 years requiring post-LT intensive care unit management were included. TEG parameters including r time, k time, α angle, and maximum amplitude were measured regularly during the first 24 hours after LT. Outcomes included return to the operating room secondary to bleeding, length of hospitalization, survival, and early allograft dysfunction. RESULTS: A prolonged and/or lengthening r time, k time, and r+k time were all independently associated with increased length of hospitalization after LT. Increased maximum amplitude on the first post-LT TEG was associated with early allograft dysfunction. No notable associations of TEG parameters with survival or return to operating room were observed. CONCLUSIONS: The association of absolute and temporal TEG value changes with increased length of hospitalization and early allograft dysfunction suggests that TEG may have a role in identifying patients at high risk for these outcomes.

Low density lipoprotein receptor related protein 1 and 6 gene variants and ischaemic stroke risk.

BACKGROUND AND PURPOSE: Low density lipoprotein receptor related proteins (LRPs) 1 and 6 have been implicated in cerebral ischaemia. In addition, genetic variation in LRP1 and LRP6 has been linked with various factors that are related to risk of ischaemic stroke. The aim of this study was to examine the association of LRP1 and LRP6 gene variants with risk of ischaemic stroke as part of the Ischemic Stroke Genetics Study (ISGS). METHODS: A Caucasian series (434 stroke patients, 319 controls) and an African American series (161 stroke patients, 116 controls) were included. Fourteen LRP6 variants and three LRP1 variants were genotyped and assessed for association with ischaemic stroke. RESULTS: In the Caucasian series, significant associations with ischaemic stroke were observed for LRP6 rs2075241 [odds ratio (OR) 0.42, P = 0.023], rs2302685 (OR 0.44, P = 0.049), rs7975614 (OR 0.07, P = 0.017), rs10492120 (OR 0.62, P = 0.036) and rs10743980 (OR 0.66, P = 0.037). Risk of ischaemic stroke was significantly lower for carriers of any of these five protective LRP6 variants (24.0% of subjects) compared to non-carriers (OR 0.57, P = 0.003). The protective association for LRP6 rs2075241 was observed at a similar magnitude across ischaemic stroke subtypes, whilst the effects of rs23022685, rs10492120 and rs10743980 were most apparent for cardioembolic and large vessel stroke. In the African American series, LRP1 rs11172113 was associated with an increased risk of stroke (OR 1.89, P = 0.006). CONCLUSIONS: The results of our preliminary study provide evidence that LRP6 and LRP1 variants may be associated with risk of ischaemic stroke. Validation in larger studies is warranted.

Nutcracker esophagus: demographic, clinical features, and esophageal tests in 115 patients.

Nutcracker esophagus (NE) is a common esophageal motility disorder chacterized by high amplitude peristaltic contractions in the distal esophagus. While previous studies have examined selected aspects of this condition (e.g. pathogenesis and treatment), there is a paucity of data regarding demographic and clinical features in large cohorts of patients. The aim of this study was to describe demographics, clinical features, comorbidities, time to diagnosis, source of patient referral by specialty, and medication use in a large cohort of patients with NE. We retrospectively analyzed consecutive cases of NE diagnosed from 2008-2010. The electronic medical records of these patients were reviewed, and relevant information was extracted. We identified 115 patients with NE. The median age was 62 years (range 25-87 years), and 63% were female. The median time patients experienced symptoms prior to diagnosis was 24 months (0-480 months). Most patients presented to an internal medicine consultant (42%) or to a gastroenterologist (35%). Presenting symptoms were chest pain (31%) and dysphagia (21%). Gastroesophageal reflux disease (GERD) symptoms were common: heartburn occurred in 51% of patients, 77% had a prior history of GERD, and 78% were receiving acid suppressive medications. GERD was confirmed by testing in at least 35%. Psychiatric comorbidity occurred in 24% with half the patients receiving psychotropic medications. Irritable bowel syndrome (IBS) and fibromyalgia co-existed in 15% and 12% of patients, respectively. Surprisingly, opioids were prescribed to 26% of patients. No statistically significant correlation was found between esophageal motility parameters and symptoms. In this study, NE patients were more commonly middle-aged females experiencing a considerable amount of time between symptom onset and diagnosis. Many were initially evaluated by internists for dysphagia or chest pain and had a history of GERD. Medication prescribed prior to diagnoses frequently involved acid suppression, but narcotic and psychotropic prescriptions were also commonly used. Central sensitization syndromes (fibromyalgia and IBS), psychiatric comorbidity, and reflux commonly coexisted. Our study suggests that future investigations should address the role and interaction of GERD and psychiatric disorders in NE.

Obese men have more advanced and more aggressive prostate cancer at time of surgery than non-obese men after adjusting for screening PSA level and age: results from two independent nested case-control studies.

BACKGROUND: It remains unclear whether the hemodilution effect of body mass index (BMI) on PSA levels translates to inappropriate prostate cancer (PCa) screening in obese men. To address this, we conducted two nested case-control studies within prospective cohorts of men undergoing radical prostatectomy for newly diagnosed PCa. METHODS: We identified 1817 men with BMI 30 kg m(-2) (cases) and 1244 men with BMI <25 kg m(-2) (controls) who underwent surgery to treat PCa at Mayo Clinic in Rochester between 2000 and 2009. Cases and controls were frequency matched on age and PSA level. In a similar manner, we identified 206 cases and 133 controls treated at Mayo Clinic in Florida between 2006 and 2011. We employed logistic regression models to evaluate the association of pathologic features of aggressiveness with obesity status. RESULTS: After adjusting for age and PSA level, we noted that obese men in the Rochester population are more likely to present with Gleason grade 8-10 tumors (OR= 1.50; 95% CI 1.14-1.96; P=0.003) and pT3, pT4, pTxN+ stage disease (OR=1.30; 95% CI 1.05-1.62). We noted a similar association seminal vesicle involvement (OR= 1.41; 95% CI 1.03-1.92; P=0.03). Results from the smaller Florida population supported these same associations but did not achieve conventional statistical significance. CONCLUSIONS: Obese men present with more aggressive PCa tumors compared with non-obese men of similar age and PSA screening values. If confirmed, this would support the need to explore PSA-based screening in obese men to possibly account for a hemodilution effect.

Evaluation of risk factors for cytomegalovirus infection and disease occurring within 1 year of liver transplantation in high-risk patients.

BACKGROUND: Recent studies have demonstrated that cytomegalovirus (CMV) infection and disease are associated with increased risk of graft loss and death in high-risk (donor CMV seropositive/recipient CMV seronegative) liver transplant recipients (LTR) despite effective antiviral chemoprophylaxis. Predictors of CMV infection and disease in this important population are incompletely defined. METHODS: A retrospective cohort study of 227 high-risk first LTR who received primary anti-CMV chemoprophylaxis during the first 100 days after transplant was performed. A large number of patient, donor, operative, and post-transplant potential risk factors were collected. Associations of potential risk factors for CMV infection or disease that occurred during the first year after transplant were assessed using Cox regression models. After Bonferroni adjustment for multiple testing, P-values ≤0.00125 (associations with CMV infection) and ≤0.00122 (associations with CMV disease) were considered as statistically significant. RESULTS: CMV infection and disease occurred in 91 (40%) and 43 (19%) of LTR, respectively. In multivariable analysis, increased risk of CMV infection was observed for patients with lower model for end-stage liver disease (MELD) score (P = 0.025), lower total bilirubin (P = 0.014), and longer operative time (P = 0.038), whereas increased risk of CMV disease was seen in patients with lower MELD score (P = 0.026), lower total bilirubin (P = 0.044), and lower international normalized ratio (P = 0.043). However, after adjustment for multiple testing, none of these findings approached statistical significance. CONCLUSION: Our results suggest that interventions designed to prevent CMV infection and disease should be applied to all high-risk LTR until more definitive predictors of these complications are identified.

Genetic variants associated with myocardial infarction in the PSMA6 gene and Chr9p21 are also associated with ischaemic stroke.

BACKGROUND: Ischaemic stroke shares common traditional risk factors with coronary artery disease (CAD) and myocardial infarction (MI). This study evaluated whether genetic risk factors for CAD and MI also affect susceptibility to ischaemic stroke in Caucasians and African Americans. METHODS: Included in the study were a Caucasian series (713 ischaemic stroke patients, 708 controls) and a small African American series (166 ischaemic stroke patients, 117 controls). Twenty single-nucleotide polymorphisms (SNPs) previously shown to be associated with CAD or MI were genotyped and assessed for association with ischaemic stroke and ischaemic stroke subtypes using odds ratios (ORs) from multivariable logistic regression models. RESULTS: In Caucasians, four SNPs on chromosome 9p21 were significantly associated with risk of cardioembolic stroke, the strongest of which was rs1333040 (OR 1.55, P = 0.0007); similar but weaker trends were observed for small vessel stroke, with no associations observed regarding large vessel stroke. Chromosome 9p21 SNPs were also associated with risk of ischaemic stroke in African Americans (rs1333040, OR 0.65, P = 0.023; rs1333042, OR 0.55, P = 0.070; rs2383207, OR 0.55, P = 0.070). The PSMA6 SNP rs1048990 on chromosome 14q13 was associated with overall ischaemic stroke in both Caucasians (OR 0.80, P = 0.036) and African Americans (OR 0.31, P = 0.020). CONCLUSIONS: Our results provide evidence that chromosome 9p21 variants are associated with cardioembolic ischaemic stroke in Caucasians and with overall ischaemic stroke in African Americans. The PSMA6 variant rs1048990 also appears to affect susceptibility to ischaemic stroke in both populations. These findings require validation, particularly the preliminary findings regarding African Americans given the small size of that series.

Undetectable sensitive serum thyroglobulin (<0.1 ng/ml) in 163 patients with follicular cell-derived thyroid cancer: results of rhTSH stimulation and neck ultrasonography and long-term biochemical and clinical follow-up.

CONTEXT: Surveillance of patients with differentiated thyroid cancer (DTC) is achieved using serum thyroglobulin (Tg), neck ultrasonography (US), and recombinant human TSH (rhTSH)-stimulated Tg (Tg-stim). OBJECTIVE: Our primary aim was to assess the utility of rhTSH Tg-stim in patients with suppressed Tg (Tg-supp) below 0.1 ng/ml using a sensitive assay. Our secondary aims were to assess the utility of US and to summarize the profile of subsequent Tg-supp measures. DESIGN: This is a retrospective study conducted at two sites of an academic institution. PATIENTS: A total of 163 patients status after thyroidectomy and radioactive iodine treatment who had Tg-supp below 0.1 ng/ml and rhTSH Tg-stim within 60 d of each other were included. RESULTS: After rhTSH stimulation, Tg remained below 0.1 ng/ml in 94 (58%) and increased to 0.1-0.5 in 56 (34%), more than 0.5-2.0 in nine (6%), and above 2.0 ng/ml in four (2%) patients. Serial Tg-supp levels were obtained in 138 patients followed over a median of 3.6 yr. Neck US were performed on 153 patients; suspicious exams had fine-needle aspiration (FNA). All positive FNA were identified around the time of the initial rhTSH test. Six of seven recurrences were detected by US (Tg-stim >2.0 ng/ml in one, 0.8 in one and ≤ 0.5 in four). One stage IV patient had undetectable Tg-stim. CONCLUSION: In patients with DTC whose T(4)-suppressed serum Tg is below 0.1 ng/ml, long-term monitoring with annual Tg-supp and periodic neck US are adequate to detect recurrences. In our experience, rhTSH testing does not change management and is not needed in this group of patients.

Association of cytomegalovirus infection and disease with death and graft loss after liver transplant in high-risk recipients.

In the era of effective antiviral chemoprophylaxis, cytomegalovirus (CMV) disease has been inconsistently associated with increased mortality in liver transplant (LT) recipients. A retrospective study evaluating the association of CMV infection and disease occurring within 1 year of transplant with the endpoints of death or the combined endpoint of graft loss or death was undertaken in a cohort of 227 CMV donor seropositive, recipient seronegative first LT recipients. Associations were evaluated using Cox proportional hazards regression models. CMV infection and disease occurred in 91 (40%) and 43 (19%) patients, respectively. Forty-eight (21%) died while 58 (26%) sustained graft loss or death. In multivariable analysis, CMV infection was associated with an increased risk of death (RR: 2.24, p = 0.008) and graft loss or death (RR: 2.85, p < 0.001). CMV disease was also associated with an increased risk of death (RR: 2.73, p = 0.003) and graft loss or death (RR: 3.04, p = 0.001). CMV infection and disease occurring within the first year after LT in high-risk recipients is associated with increased risk of death and of graft loss or death. Investigation of strategies to further reduce the risk of CMV infection and disease in high-risk LT recipients is warranted.

Association of surgeon with surgical site infection after liver transplantation.

Surgical site infection (SSI) after liver transplantation has been associated with increased risk of allograft loss and death. Identification of modifiable risk factors for these infections is imperative. To our knowledge, intraoperative practices associated with transplant surgeons have not been assessed as a risk factor. A retrospective cohort study of risk factors for SSI after 1036 first liver transplantations completed by seven surgeons at a single center between 2003 and 2008 was undertaken. Cox proportional hazards models were used to evaluate the association between surgeons and SSIs. SSIs were identified in 166 of 1036 patients (16%). Single variable analysis showed strong evidence of an association between surgeon and SSI (p = 0.0007); the estimated cumulative incidence of SSI ranged from 7% to 24%. This result was consistent in multivariable analysis adjusting for potentially confounding variables (p = 0.002). The occurrence of organ-space or deep SSI varied significantly among surgeons in both single variable analysis (p = 0.005) and multivariable analysis (p = 0.006). These findings provide evidence that differences in the surgical practices of individual surgeons are associated with risk for SSI after liver transplantation. Identification of specific surgical practices associated with risk of SSI is warranted.

SNCA, MAPT, and GSK3B in Parkinson disease: a gene-gene interaction study.

BACKGROUND AND PURPOSE: Recent evidence suggests that variation in the SNCA, MAPT, and GSK3B genes interacts in affecting risk for Parkinson disease (PD). In the current study, we attempt to validate previously published findings, evaluating gene-gene interactions between SNCA, MAPT, and GSK3B in association with PD. METHODS: Three Caucasian PD patient-control series from the United States, Ireland, and Norway (combined n = 1020 patients and 1095 controls) were genotyped for SNCA rs356219, MAPT H1/H2-discriminating SNP rs1052553, and GSK3B rs334558 and rs6438552. RESULTS: Our findings indicate that as previously reported, the SNCA rs356219-G allele and MAPT rs1052553 (H1 haplotype) were both associated with an increased risk of PD, whilst contrary to previous reports, GSK3B variants were not. No pair-wise interaction was observed between SNCA, MAPT, and GSK3B; the risk effects of SNCA rs356219-G and MAPT rs1052553-H1 were seen in a similar manner across genotypes of other variants, with no evidence suggesting synergistic, antagonistic, or deferential effects. CONCLUSIONS: In the Caucasian patient-control series examined, risk for PD was influenced by variation in SNCA and MAPT but not GSK3B. Additionally, those three genes did not interact in determining disease risk.

Urine catecholamine levels as diagnostic markers for neuroblastoma in a defined population: implications for ophthalmic practice.

PURPOSE: although elevated urinary catecholamine levels have been reported in 90-95% of patients with neuroblastoma, more recent studies of pediatric Horner syndrome caused by an underling neuroblastoma have reported normal values at presentation. The purpose of this population-based study is to report the percentage of cases of neuroblastoma with elevated urinary catecholamine levels at presentation and to suggest a recommended work-up for cases of idiopathic pediatric Horner syndrome. METHODS: the medical records of all pediatric (<19 years) residents of Olmsted County, Minnesota diagnosed with neuroblastoma from 1 January 1969 through 31 December 2008 were retrospectively reviewed. RESULTS: a total of 14 patients <19 years of age were diagnosed with neuroblastoma as residents of Olmsted County, Minnesota, during the 40-year study period. A total of 10 (71%) of the 14 cases manifested elevated urinary catecholamine metabolites at the initial presentation. Urinary vanillylmandelic acid (VMA) levels were greater than twice the upper limit of normal in eight (57%) of 14 cases, whereas homovanillic acid (HVA) levels were greater than two times the upper limit of normal in 10 (71%) of the 14 cases. Three (75%) of the four cases without significantly elevated urinary VMA or HVA levels were diagnosed with stage IV disease, whereas one (25%) had stage II neuroblastoma. CONCLUSION: urinary catecholamine levels were significantly elevated at presentation in 10 (71%) of the 14 neuroblastoma cases during the 40-year study period, suggesting that greater emphasis be placed on performing a thorough physical examination and obtaining warranted imaging studies in cases of idiopathic pediatric Horner syndrome.

Immediate intraocular pressure changes following intravitreal injections of triamcinolone, pegaptanib, and bevacizumab.

PURPOSE: To assess the intraocular pressure (IOP) changes, within the first 30 min after intravitreal injection of 0.1 ml (4 mg) triamcinolone, 0.09 ml (0.3 mg) pegaptanib, and 0.05 ml (1.25 mg) bevacizumab. METHODS: Records of patients who received intravitreal triamcinolone, pegaptanib, and bevacizumab and who had their IOP measured post-injection were reviewed. RESULTS: A total of 212 injections were performed (76 bevacizumab in 63 patients, 42 triamcinolone in 41 patients, 94 pegaptanib in 74 patients). At 10 min, over 87% of eyes receiving each drug had an IOP of less than 35 mmHg. Three of the 42 eyes receiving intravitreal triamcinolone were treated with IOP-lowering drops for pressures of 44, 46, and 60 mmHg. No patients treated with intravitreal bevacizumab or pegaptanib received IOP-lowering drops. The number of eyes in each injection group that had an IOP rise >10 mmHg within 30 min after injection was 27.6% of eyes receiving bevacizumab, 33.3% of eyes receiving triamcinolone, and 36.2% of eyes receiving pegaptanib. At 10 min, eyes with glaucoma were less likely to have an IOP<35 mmHg, but this difference became less marked with time. CONCLUSION: In our series, most patients receiving intravitreal injections did not require IOP-lowering drops after injection, and none required a paracentesis.

The changing incidence of oesophageal and gastric adenocarcinoma by anatomic sub-site.

BACKGROUND: The incidence rates of gastric and oesophageal adenocarcinoma are changing significantly, but little is known about specific sub-sites. AIM: To use a population-based approach to describe the trends in the site-specific incidence of oesophageal and gastric adenocarcinoma. METHODS: Using the Rochester Epidemiology Project, all cases of gastric and oesophageal adenocarcinoma among Olmsted County, Minnesota, residents first diagnosed between 1971 and 2000 were identified (n = 186). Complete in-patient and out-patient records were reviewed and site determined from pathological, surgical, endoscopic and radiological reports. RESULTS: Between the decades of 1971-1980 and 1991-2000, the incidence of oesophageal adenocarcinoma increased significantly from 0.4 to 2.5 per 100 000 person-years. The incidence of adenocarcinoma of the oesophagogastric junction also increased from a rate of 0.6 to 2.2 per 100 000 person-years. The incidence rate of cancer involving the gastric cardia was stable but the incidence of adenocarcinoma involving distal gastric sites declined. Combined oesophageal and oesophagogastric junction adenocarcinoma (4.7 per 1 000 000 person-years) was as common as gastric adenocarcinoma (3.4 per 100 000 person-years) in 1991-2000. CONCLUSIONS: The incidence rates of adenocarcinoma involving proximal gastric sub-sites do not appear to be increasing in a manner similar to those involving oesophageal sub-sites.

Exercising caution: social physique anxiety and protective self-presentational behaviour.

This study examined relations among body mass index (BMI), social physique anxiety (SPA) and protective self-presentational exercise behaviours in a sample of 86 female participants in aerobics classes at a university fitness centre. Participants completed a questionnaire assessing demographic and exercise-related information, the 9-item version of the Social Physique Anxiety Scale, and measures of two forms of protective self-presentational exercise behaviour (i.e., preferring to stand away from the aerobics instructor and wearing concealing exercise attire). Consistent with previous research, SPA was positively associated with both preferred exercise studio floor position (r = .31, p < .05) and clothing concealingness (r = .25, p < .05). SPA did not mediate the relations between BMI and either of the two protective self-presentational behaviours. BMI was a better predictor of clothing concealingness than SPA, but the opposite was found for exercise studio floor position preferences (r = .31 with SPA versus r = .15 with BMI). The findings provide an enhanced understanding of factors associated with self-presentation in exercise.

A comparison of endoscopic ultrasound, magnetic resonance imaging, and exam under anesthesia for evaluation of Crohn's perianal fistulas.

BACKGROUND & AIMS: To determine accuracy of endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) for evaluation of Crohn's disease perianal fistulas. METHODS: Thirty-four patients with suspected Crohn's disease perianal fistulas were prospectively enrolled in a blinded study comparing EUS, MRI, and examination under anesthesia (EUA). Fistulas were classified according to Parks' criteria, and a consensus gold standard was determined for each patient. Acceptable accuracy was defined as agreement with the consensus gold standard for > or =85% of patients. RESULTS: Three patients did not undergo MRI; 1 did not undergo EUS or EUA; and consensus could not be reached for 1. Thirty-two patients had 39 fistulas (20 trans-sphincteric, 5 extra-sphincteric, 6 recto-vaginal, 8 others) and 13 abscesses. The accuracy of all 3 modalities was > or =85%: EUS 29 of 32 (91%, confidence interval [CI] 75%-98%), MRI 26 of 30 (87%, CI 69%-96%), and EUA 29 of 32 (91%, CI 75%-98%). Accuracy was 100% when any 2 tests were combined. CONCLUSIONS: EUS, MRI, and EUA are accurate tests for determining fistula anatomy in patients with perianal Crohn's disease. The optimal approach may be combining any 2 of the 3 methods.

Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: We evaluated etanercept, a human soluble tumor necrosis factor receptor: Fc fusion protein, for the treatment of active Crohn's disease. METHODS: Forty-three patients with moderate to severe Crohn's disease were enrolled in an 8-week placebo-controlled trial. Patients were randomized to subcutaneous etanercept 25 mg or placebo twice weekly. The primary outcome measure was clinical response at week 4, defined as a decrease in the baseline Crohn's Disease Activity Index score > or =70 points or a Crohn's Disease Activity Index score <150 points. RESULTS: At week 4, 39% of etanercept-treated patients had clinical response as compared with 45% of placebo-treated patients (P = 0.763). The frequency of common adverse events including headache, new injection site reaction, asthenia, abdominal pain, Crohn's disease-related anemia, and skin disorders was similar in both groups. Likewise, the frequency of severe or serious adverse events was similar in both groups. CONCLUSIONS: Subcutaneous etanercept at a dose of 25 mg twice weekly is safe, but not effective, for the treatment of patients with moderate to severe Crohn's disease. The dose of etanercept administered in this study is that approved for rheumatoid arthritis. Higher doses or more frequent dosing may be required to attain a response in patients with active Crohn's disease.

Barriers to bicycle helmet use.

OBJECTIVE: To determine why people do or do not wear helmets while bicycling. METHODS: A survey was conducted from August through October 1999. Two survey areas were chosen for this study: local public schools and paved bicycle trails. For the school arm of the study, 3 public elementary, middle, and high schools were selected from 3 different regions of Rochester, Minnesota, for participation in the study. For the bicycle arm of the study, 3 paved trails located in southeastern Minnesota were selected. A total of 2970 surveys were distributed to the public school system, and 463 surveys were collected from bicyclists on the paved bicycle trails. The survey population was split into 3 age categories for analysis: child (7-10), adolescent (11-19), and adult (older than 19). RESULTS: Of the 2970 surveys distributed to Rochester public schools, 2039 (69%) were returned for analysis. Seventy-eight of the surveys that were completed in the public school system were discarded for the following reasons: age <10 years (35), insufficient completion (24), and selection of every reason for not wearing a bicycle helmet (19). A total of 463 surveys were completed on the 3 paved bicycle trails. One survey from the paved bicycle trail arm of the study was discarded because of insufficient completion. The total number of surveys used for statistical analysis was 2424. The distribution of male (52.7%) and female (47.3%) participants was similar. No significant difference in bicycle helmet use was found between genders. The age groups with the highest rate of bicycle helmet use were 50 to 59 years (62%) and older than 59 years (70%). The age groups with the lowest rate of bicycle helmet use were 11 to 19 years (31%) and 30 to 39 years (30%). The most common reasons given for not wearing a bicycle helmet were "uncomfortable," "annoying," "it's hot," "don't need it," and "don't own one." Bicycle helmet use was significantly influenced by peer helmet use in all 3 age groups. Children also were more likely to wear a bicycle helmet when their parents wore bicycle helmets. A majority of respondents in all 3 age groups indicated that bicycle helmets provided either "moderate" or "great" protection from head injury, although significantly more adults (65.9%) than adolescents (43.9%) believed that the protection afforded by bicycle helmets was "great." Despite this belief, a majority of adolescents and adults indicated that there was only a "slight risk" of head injury when bicycling without a helmet. Participants in all 3 categories were more likely to wear a bicycle helmet when they indicated either that there was a "great risk" of head injury when bicycling without a helmet or that helmets provided "great protection" from head injury. Adolescents and adults who believed that bicycling without a helmet put one at "great risk" for head injury also were more likely to indicate that helmets provided "great protection" from head injury. CONCLUSIONS: The prevalence of bicycle helmet use remains low despite research indicating the high level of head injury risk when bicycling without a helmet and the significant protection afforded by bicycle helmets. With the information provided by this survey, a well-designed intervention to increase the use of bicycle helmets can be implemented. Suggestions for a campaign to promote an increase in bicycle helmet use include focusing efforts on males and females between 11 and 19 years and 30 and 39 years of age; educating the public on new bicycle helmet designs that address comfort, ventilation, and fashion; educating adolescents on the significant protection from head injury afforded by bicycle helmets; and educating the public on the risk and severity of head injury associated with bicycling without a helmet. The influence of parents and peers on bicycle helmet use may be targeted through education and statements such as, "If you wear a bicycle helmet, you are not only protecting yourself, you are also helping to protect your friends and/or children." bicycle, helmet, injury, accident, prevention.

Impairment in motor learning of somatostatin null mutant mice.

Somatostatin was first identified as a hypothalamic factor which inhibits the release of growth hormone from the anterior pituitary (somatotropin release inhibitory factor, SRIF). Both SRIF and its receptors were subsequently found widely distributed within and outside the nervous system, in the adult as well as in the developing organism. Reflecting this wide distribution, somatostatin has been implicated regulating a diverse array of biological processes. These include body growth, homeostasis, sensory perception, autonomous functions, rate of intestinal absorption, behavior, including cognition and memory, and developmental processes. We produced null mutant mice lacking somatostatin through targeted mutagenesis. The mutant mice are healthy, fertile, and superficially indistinguishable from their heterozygous and wildtype littermates. A 'first round' phenotype screen revealed that mice lacking somatostatin have elevated plasma growth hormone levels, despite normal body size, and have elevated basal plasma corticosterone levels. In order to uncover subtle and unexpected differences, we carried out a systematic behavioral phenotype screen which identified a significant impairment in motor learning revealed when increased demands were made on motor coordination. Motor coordination and motor learning require an intact cerebellum. While somatostatin is virtually absent from the adult cerebellum, the ligand and its receptor(s) are transiently expressed at high levels in the developing cerebellum. This result suggests the functional significance of transient expression of SRIF and its receptors in the development of the cerebellum.

Generation of dynorphin knockout mice.

The opioid system has important roles in controlling pain, reward and addiction, and is implicated in numerous other processes within and outside the nervous system, such as mood states, immune responses, and prenatal developmental processes. The effects of the opioid system are mediated by at least three ligands, enkephalin, endorphin, and dynorphin, which act through the opioid receptors mu, delta, and kappa. In order to dissect the roles of individual components of the opioid system, mutant mice lacking single ligands or receptors are instrumental. We report here on the generation and initial characterization of a mutant mouse strain lacking pre-prodynorphin. Dynorphin 'knockout' mice are viable, healthy, and fertile and show no overt behavioral differences to wildtype littermates. Dynorphin knockout mice constitute a valuable tool for many research areas, among them research into pain, substance abuse, and epilepsy.

Conference highlight: do T cells care about the mitogen-activated protein kinase signalling pathways?

Mitogen-activated protein (MAP) kinases, which include the extracellular response kinases, p38 and c-Jun amino terminal kinases (JNK), play a significant role in mediating signals triggered by cytokines, growth factors and environmental stress. The JNK and p38 MAP kinases have been involved in growth, differentiation and cell death in different cell types. In the present paper, we describe how the JNK and p38 MAP kinase signalling pathways are regulated and their role during thymocyte development and the activation and differentiation of T cells in the peripheral immune system. The results from these studies demonstrate that the JNK and p38 MAP kinase signalling pathways regulate different aspects of T-cell mediated immune responses.