Brain-specific Foxp1 deletion impairs neuronal development and causes autistic-like behaviour.

Neurodevelopmental disorders are multi-faceted and can lead to intellectual disability, autism spectrum disorder and language impairment. Mutations in the Forkhead box FOXP1 gene have been linked to all these disorders, suggesting that it may play a central role in various cognitive and social processes. To understand the role of Foxp1 in the context of neurodevelopment leading to alterations in cognition and behaviour, we generated mice with a brain-specific Foxp1 deletion (Nestin-Cre(Foxp1-/-)mice). The mutant mice were viable and allowed for the first time the analysis of pre- and postnatal neurodevelopmental phenotypes, which included a pronounced disruption of the developing striatum and more subtle alterations in the hippocampus. More detailed analysis in the CA1 region revealed abnormal neuronal morphogenesis that was associated with reduced excitability and an imbalance of excitatory to inhibitory input in CA1 hippocampal neurons in Nestin-Cre(Foxp1-/-) mice. Foxp1 ablation was also associated with various cognitive and social deficits, providing new insights into its behavioural importance.

Asymptomatic deep vein thrombosis and superficial vein thrombosis in ambulatory cancer patients: impact on short-term survival.

BACKGROUND: Asymptomatic venous thrombotic events (VTEs) are possible findings in ambulatory cancer patients. Data regarding the incidence and clinical impact of asymptomatic VTEs are conflicting. We therefore conducted a study to evaluate the occurrence of asymptomatic VTEs of the lower limbs in ambulatory cancer patients to further evaluate the association of these asymptomatic VTEs on survival during a 9-month follow-up period. METHODS: In our prospective cohort, we included 150 consecutive ambulatory cancer patients who were free of any clinical symptoms for VTEs. Compression ultrasound to detect deep vein thrombosis (DVT) and superficial venous thrombosis (SVT) of the lower limbs was performed by a vascular specialist in all patients at baseline. In case of pathological findings the patients were treated with low molecular weight heparin (LMWH) because of current established guidelines. The occurrence of death was investigated during a 9-month follow-up period. RESULTS: A total of 27 (18%) patients with VTEs were detected, which included 13 patients (8.7%) with a SVT and 16 patients (10.7%) showing a DVT. Two patients had both, a SVT and a DVT as well. During the 9-month follow-up period the occurrence of a VTE at baseline was associated with a 2.4-fold increased risk for death (HR 2.4 (1.2-5.3); P=0.03). CONCLUSION: Asymptomatic VTEs of the lower limbs in ambulatory cancer patients are frequently occurring concomitant features and are associated with poor survival during a 9-month follow-up period despite anticoagulation with LMWH.

Percutaneous transluminal angioplasty versus primary stenting in infrapopliteal arteries in critical limb ischemia.

BACKGROUND: In endovascular recanalisation of infrapopliteal arteries, studies have already pointed out the value of balloon angioplasty, but for stent implantation very few randomized controlled data exist so far. PATIENTS AND METHODS: We conducted a randomized controlled prospective trial in patients with critical limb ischemia (CLI) comparing the effect of percutaneous transluminal balloon angioplasty (PTA) versus primary stenting in infrapopliteal arteries, concerning 1-year clinical benefit and reobstruction rate. RESULTS: 54 patients were either randomized for primary stenting (balloon expandable stent) or PTA alone, 33 patients were assigned to the PTA group, 21 patients to the stent group. The whole follow up period of 12 months was completed by 46 patients. Improvement by at least one Rutherford classification was reached by a total of 33 (75.0 %) of patients at month 12, 22 (81.5 %) in the PTA group and 11 (64.7 %) in the stent group. A complete ulcer healing at month 12 showed 21 (63.6 %) of all patients, with a higher percentage in patients treated with PTA alone 16 (80.0 %) vs 5 (38.5 %). 50.0 % of all patients showed re-obstruction over the follow-up period, 39.4 % of the PTA and 66.7 % of the stent group. At month 3 primary patency rate was nearly equal in both groups (76.7 % PTA vs 75.0 % stent), but drifted apart with the duration of the follow-up period, with a primary patency at month 12 in the PTA group of 48,1 % vs 35,3 % in the stent group. As for secondary patency at month 12 the PTA group showed a patency rate of 70.4 %, vs 52.9 % in the stent group. CONCLUSIONS: Primary stenting with balloon expandable stents in the infrapopliteal arteries does not outway the benefit of PTA alone with the application of modern hydrophilic balloon catheters in patients with CLI.

Are flow-mediated vasodilatation and intima-media thickness of the brachial artery associated with restenosis after endovascular treatment of peripheral arterial occlusive disease?

OBJECTIVE: Restenosis after percutaneous angioplasty of peripheral arteries is still an unsolved matter. Previous studies reported an association between flow-mediated dilatation (FMD), a marker of endothelial dysfunction, and restenosis after coronary angioplasty. This study evaluates the influence of FMD and brachial intima-media thickness (B-IMT) on restenosis after angioplasty of peripheral arteries. METHODS: One hundred and eighty-four patients (124 male) with claudication related to peripheral arterial disease participated in this trial. FMD and B-IMT were assessed before endovascular revascularisation. In a 12-month follow-up duplex ultrasound examinations were performed to detect restenosis. Finally 128 patients (91male, 37 female) were eligible for statistical analysis. RESULTS: Restenosis was found in 54 patients (42.2%). Mean FMD was 3.53 ± 3.56%, with no difference between the patients with restenosis (3.55 ± 3.64%) and those without (3.52 ± 3.48%; p = 0.716). B-IMT had a mean value of 0.326 ± 0.134 mm. B-IMT significantly differed between the patients with restenosis (0.326 ± 0.134 mm) and those without (0.256 ± 0.133 mm; p = 0.007). We confirmed that a B-IMT over 0.21 mm was an independent risk factor for restenosis [OR 2.9 (1.3-6.3)]. CONCLUSION: Endothelial dysfunction is not associated with restenosis. Conversely patients with enlarged B-IMT are at risk of restenosis after angioplasty of peripheral arteries.

Proximal lower limb vein thrombosis following vipera berus hand bite.

Vipera berus has a wide geographical distribution throughout Central and Northern Europe. The symptoms after a bite usually are mild, life threatening symptoms are mainly described in children. We describe a case of popliteal vein thrombosis of the right leg after systemic envenoming with Vipera berus venom after a bite in the right hand by a female Vipera berus in the alpine region of Styria, Austria. Changes of the plasmatic coagulation system were obvious in our patient. These changes were due to an activation of the coagulation system and might be the reason for the thrombotic event in this usually healthy young male person.

Sustainable aquaculture through the One Health lens.

Aquaculture is predicted to supply the majority of aquatic dietary protein by 2050. For aquaculture to deliver significantly enhanced volumes of food in a sustainable manner, appropriate account needs to be taken of its impacts on environmental integrity, farmed organism health and welfare, and human health. Here, we explore increased aquaculture production through the One Health lens and define a set of success metrics - underpinned by evidence, policy and legislation - that must be embedded into aquaculture sustainability. We provide a framework for defining, monitoring and averting potential negative impacts of enhanced production - and consider interactions with land-based food systems. These metrics will inform national and international science and policy strategies to support improved aquatic food system design.

[Phantom studies using echo contrast media to improve the Doppler color sonographic imaging of the superficial femoral artery in the adductor canal]. / Phantomuntersuchungen mit echokontrastgebenden Substanzen zur Verbesserung der farb-doppler-sonographischen Darstellung der A. femoralis superficialis im Adduktorenkanal.

The adductor canal was simulated using 2.6 cm muscular tissue and 2 fasciae to analyse the limits of colour-coded Doppler sonography (angiodynography) in this region. Defects in the spectral signal cause a significant underestimation of mean, peak systolic and peak diastolic (backflow) velocities and of calculated blood flow. Furthermore the pulsatility index is overestimated and the colour-coded visualisation of the arteries is almost lost. For the most part, these changes can be compensated by administration of a sonographic contrast agent (SH U 454). A minimum of 9 mg microbubbles/ml blood is required. Nevertheless, the adjustment of system controls (e.g. transducer power) becomes more difficult and an ideal setting impossible.

Compliance with hepatitis B virus vaccination in a high-risk population.

OBJECTIVE: To quantify cultural barriers to hepatitis B virus (HBV) vaccination and parental compliance with a specific vaccination protocol among a primarily among population of infants born at a community hospital. METHODS: This study was concurrent with an immunogenicity study of two vaccination schedules and occurred prior to the inception of universal infant vaccination with hepatitis B vaccine (HepB). In this study, parental pairs were interviewed, consent obtained, subjects were randomly assigned to each group, and first immunization was administered in the hospital. Follow-up contacts required for completion were documented. RESULTS: Of 260 eligible parental pairs interviewed, 175 (67%) declined participation, mainly because of fears of vaccine side effects (55%) or ignorance of the hepatitis B virus (HBV) (30%). Of 85 infants enrolled in the study, 28 (33%) were later withdrawn from the study; 13 (46%) of these 28 infants were withdrawn at the request of parents. Each infant who completed the study received 5 postcards, 10 phone calls, and 3 home visits. CONCLUSIONS: Families were unaware of the risk of HBV infection and feared vaccination. Aversion to subjecting an infant to pain was a principal reason for failure to complete the study, and frequent contacts were required to ensure adherence. Existence of a safe and effective hepatitis B vaccine and universal vaccination is unlikely to change deeply felt attitudes against vaccination. Current vaccination strategies must take these prejudices into account.

Treatment of cyanide poisoning.

The object of this study was to evaluate the effectiveness of five regimens in treating cyanide poisoning. A series of anesthetized adult beagle dogs were instrumented to record hemodynamic and respiratory function and given 2.5 mg/kg sodium cyanide intravenously. The 10 control animals given only cyanide died at from 5 to 7 minutes. Therapy, as described below, was given to other groups at from 2 to 3 minutes following the cyanide administration. Artificial respiration did not alter the lethal effects of cyanide nor prolong survival time in any of the 10 animals. Amyl nitrite given by inhalation or by the intravenous route allowed survival of all 15 animals. Sodium nitrite (20 mg/kg), dimethylaminophenol (DMAP) (5 mg/kg), and hydroxylamine hydrochloride (5 mg/kg) given intravenously with no artificial ventilation also allowed for 100% survival (15 animals). Amyl nitrite, sodium nitrite, and sodium thiosulfate were ineffective when given intramuscularly (I.M.) (0 of 12 dogs); however, I.M. DMAP (5 mg/kg) and I.M. hydroxylamine hydrochloride (50 mg/kg) increased heart rate and blood pressure and restored spontaneous breathing. All 15 animals treated with I.M. doses of either of these drugs survived the lethal dose of cyanide. Results of these studies indicate that intravenous sodium nitrite, DMAP, and hydroxylamine hydrochloride, and amyl nitrite by inhalation, are all effective in reversing the lethal effects of cyanide poisoning. Only DMAP and hydroxylamine hydrochloride are effective when given by the intramuscular route. These results provide data to support an approach to therapy that is more practical and applicable where expert medical care may not be available following cyanide exposure.

Safety and efficacy of periprocedural anticoagulation with enoxaparin in patients undergoing peripheral endovascular revascularization.

BACKGROUND: Periprocedural anticoagulation is primarily used in endovascular procedures to prevent acute reocclusion of the target vessel, but periprocedural anticoagulation might also have an impact on long-term outcome. Consecutive bleeding events are feared complications. Despite changes in peripheral endovascular revascularizations (EVRs), the periprocedural management has remained unchanged for years. Unfractionated heparin is still the treatment of choice during and immediately after EVR. MATERIALS AND METHODS: We performed a prospective, single-center, open-label phase III study comparing 2 different regimes of enoxaparin peri-interventional to peripheral EVR stratified into low- and high-risk groups according to the acute and long-term reocclusion risk due to their vessel morphology. In both groups, 0.5 mg/kg of enoxaparin as a bolus was administered intravenously 10 to 15 minutes before the start of the procedure. In the low-risk group, 40 mg of enoxaparin were administered once daily for 7 days; whereas in the high-risk group, 1 mg/kg of enoxaparin was administered subcutaneously (sc) 2 times a day for 48 hours after the procedure and afterward 40 mg of enoxaparin was administered sc once daily for 5 days. RESULTS: For the analysis of the per protocol population, 44 patients remained in the low-risk group and 140 in the high-risk group. Concerning the primary safety end point, a total of 25 (13.59%) bleeding events occurred until day 30; 5 (11.36%) of them in the low-risk group and 20 (14.29%) in the high-risk group (P = .809 for low vs high risk). None of the bleeding events observed were major according to Thrombolysis In Myocardial Infarction criteria. Concerning our primary efficacy end point, none of the patients showed an acute reocclusion classified as a significant decrease in ankle-brachial index (ABI) or elevated peak systolic velocity ratio confirmed by duplex sonography until day 30. Concerning the second end point of prevention of chronic reobstruction, at day 180 ABI has decreased in the low-risk group from mean 0.94 at day 30 to mean 0.89 and from 1.28 at day 30 to 0.85 after 6 months in the high-risk group. No significant reobstruction was found in the low-risk group, whereas 5 significant reobstruction events were objectified in the high-risk group, all of them in the femoropopliteal arterial segment at day 180. CONCLUSION: We conclude that low-molecular-weight heparin either in a low-dose or high-dose regime during a peripheral EVR is safe concerning bleeding complications and acute reobstructions. The long-term follow-up showed no significant difference between our high- and low-risk groups concerning reobstruction. The periprocedural anticoagulation seems to have no influence on the long-term patency rate after peripheral EVR.

Unusual deep vein thrombosis sites: magnetic resonance venography in patients with negative compression ultrasound and symptomatic pulmonary embolism.

OBJECTIVES: To evaluate the clinical characteristics of patients with pulmonary embolism (PE), negative compression ultrasound (CUS) of the lower limbs and detection of unusual deep vein thrombosis (DVT) sites by means of magnetic resonance (MR) venography. METHODS: A retrospective data analysis of PE patients hospitalized at our institution from April 2009 to 2011. RESULTS: From April 2009 to 2011, a total of 762 PE patients were treated at our institution. In 169 of these patients CUS for DVT was negative. In these patients MR venography was performed for further evaluation. We found venous thrombosis at unusual sites in 12 of these patients. Due to free floating thrombus masses and fear of life-threatening PE progression we inserted an inferior vena cava filter in three of these 12 patients. The leading venous thromboembolism risk factor in our patients was immobilization (5 patients, 41.7%). CONCLUSIONS: We conclude that especially in patients with PE and negative CUS of the lower limbs a thrombosis of the pelvic veins should be considered in case of symptoms for venous thrombosis in this area. Further diagnostic work-up with MR venography should be scheduled in these patients especially in patients with risk factor immobilization as therapeutic consequences might occur.

Intra-arterial injection, a rare but serious complication of sclerotherapy.

Intra-arterial injections represent the most feared complication of sclerotherapy for varicose veins. We present a case of an inadvertent intra-arterial injection of polidocanol at the left medial calf in a 59-year-old woman with subsequent arterial occlusions of the posterior tibial artery and foot arteries. Despite several therapeutic interventions, lower-limb amputation could not be prevented. We conducted a PubMed search for articles reporting arterial complications related to sclerotherapy, in order to evaluate aetiology, clinical presentation, therapeutic management and outcome of sclerotherapy-associated intra-arterial injections during the past 50 years. Intra-arterial injection of a sclerosing solution was reported in 63 cases, mostly after injection near the ankle region or the distal medial calf. Clinical presentation was frequently characterized by immediate pain during injection and distal ischaemia with subsequent tissue loss. Despite several treatment approaches, amputation could not be prevented in 31 cases (52.5%). The pathophysiology of arterial complications related to intra-arterial injection and advisable therapeutic interventions are discussed. Inadvertent intra-arterial injection represents a limb-threatening complication of sclerotherapy. Target-oriented and prompt therapy seems inevitable in order to reduce the risk of permanent tissue loss and amputation.

A high CHA(2)DS(2)-VASc score is associated with a high risk for critical limb ischemia in peripheral arterial occlusive disease patients.

BACKGROUND: The CHA(2)DS(2)-VASc (congestive heart failure, hypertension, age ≥ 75 years (doubled), type 2 diabetes, previous stroke, transient ischemic attack, or thromboembolism (doubled), vascular disease, age 65-75 years, and sex category) score was published as a predictive scoring model for stroke in atrial fibrillation patients. As multiple vascular risk factors are included in this score we evaluated the occurrence of critical limb ischemia (CLI) in peripheral arterial occlusive disease (PAOD) patients according to their CHA(2)DS(2)-VASc score independent of a coexisting atrial fibrillation. METHODS: We evaluated 2237 PAOD patients treated at our institution from 2005 to 2010. CHA(2)DS(2)-VASc score was calculated and the occurrence of CLI was investigated. Furthermore all constituents of the score were investigated concerning association with CLI. RESULTS: Frequency of CLI was higher in patients with a high CHA(2)DS(2)-VASc score. Age ≥ 75 years was associated with an increased risk for CLI (OR 3.0), as was age 65-75 years (OR 1.8), type 2 diabetes (OR 2.8), and the factor previous stroke, transient ischemic attack, or thromboembolism (OR 1.4). The occurrence of arterial hypertension was protective for CLI (OR 0.6). Sex and congestive heart failure were not associated with an increased CLI risk. CONCLUSION: High CHA(2)DS(2)-VASc score is associated with a high CLI risk. As not all constituents are equally associated with CLI and some are even protective, a new score including only some of the factors should be evaluated for the prediction of CLI.

Arthus reaction to recombinant hepatitis B virus vaccine.

A severe, local, inflammatory, late-phase reaction accompanied by skin necrosis occurred after an infant was given an intramuscular injection of recombinant hepatitis B virus vaccine. The clinical course and appearance of the rash were typical of an Arthus reaction. Although not identical to this case, prior reported cases of complement-mediated reactions occurring after hepatitis B virus infection or vaccination provide theoretical support for this diagnosis.

Studies of cyanide poisoning.

The use of amyl nitrite and phenoxybenzamine in the treatment of acute cyanide poisoning was evaluated. Sixty anesthetized beagle dogs were injected i.v. with sodium cyanide (2.5 mg/kg) and were followed for changes in the heart rate, electrocardiogram, respiration, blood pressure and methemoglobin concentration. Twenty control dogs died within 5 to 7 min, showing severe bradycardia, a sharp drop in arterial blood pressure, and respiratory paralysis. Pretreatment with phenoxybenzamine (0.5 mg/kg) prevented these changes in 8 of 10 dogs; however, this drug was ineffective if given after the cyanide. In contrast, amyl nitrite given after cyanide administration reversed both the cardiovascular changes and the respiratory paralysis in 24 of the 30 dogs studied. These changes occurred before the formation of significant amounts of methemoglobin and indicate that early death caused by cyanide may be due in part to cardiovascular-respiratory failure in addition to the classic poisoning of the cytochrome oxidase system. These studies indicate that phenoxybenzamine prevents and amyl nitrite reverses the otherwise lethal effects of cyanide.

Economic impact of diagnosis-related groups and severity of illness on reimbursement for central nervous system infections.

Because the federal government's diagnosis-related group (DRG) classification system for prospective payment has not been widely applied to hospitalized pediatric patients, we analyzed the effectiveness of one DRG category (central nervous system infections) for a single year at a medium-sized children's hospital to control for patients' severity of illness and for hospital reimbursement. Several independent measures of severity of illness (length of stay, duration of fever, Physiologic Severity Index) showed that patients with bacterial meningitis and those with encephalitis (DRG 20) were more ill than those with aseptic meningitis (DRG 21) (p less than 0.001 for each measure). Cost analysis revealed that the hospital was only partially reimbursed for its charges (shortfall of $95,547) and that patients with Medicaid or no insurance accounted for 22% of discharges but 88% of losses. Reimbursement by DRG would have increased payment for DRG 21 but decreased that for DRG 20. If DRGs were applied to pediatric central nervous system infections and used in a prospective payment system, they would accurately predict disease severity between but not within groups, and significant financial losses for children's hospitals would still occur.

Targeted testing of children for tuberculosis: validation of a risk assessment questionnaire.

OBJECTIVE: Given the directive of the American Academy of Pediatrics to test children for tuberculosis (TB) only if they are at high risk for the disease, we sought to determine how well a risk assessment questionnaire can predict a positive tuberculin skin test (TST) result among children seen in a medical office setting. METHODS: In a prospective observational study, we identified 31 926 children who received well-child care in 18 pediatric offices of the Kaiser Permanente Northern California Region from August 1996 through November 1998 and who were due to receive a routine TST (Mantoux method) as part of universal screening. Parents were asked to complete a questionnaire about risk factors for TB infection that included demographic information. The TST result at 48 to 72 hours was compared with questionnaire responses to identify responses that were most highly associated with a positive TST result at both the 10-mm and 15-mm cutoffs. A concurrent study was conducted to determine whether parents can recognize induration. RESULTS: This population was diverse in age (range: 0-18 years), race/ethnicity (white: 37%; Hispanic: 26.4%; Asian: 15.0%; black: 11.8%; other: 8.4%; not stated by parent: 1.6%), and household annual income (range: $10 524-$175 282). Overall incidence of positive TST results was 1.0% at the 10-mm cutoff and 0.5% at the 15-mm cutoff. Positive predictive value of selected individual risk factors at the 10-mm cutoff were: child born outside the United States, 10.4%; history of receiving bacille Calmette-Guérin vaccine, 5.5%; and child having lived outside the United States, 5.3%. Using multivariate analysis, we selected a subset of risk factors that were independently and significantly associated with a positive TST result >/=10 mm: history of receiving bacille Calmette-Guérin vaccine (odds ratio [OR]: 2.31; 95% confidence interval [CI]: 1.70-3.13); household member with history of positive TST result or TB disease (OR: 1.53; 95% CI: 1.14-2.04); child born outside the United States (OR: 8.63; 95% CI: 6.16-12.09); child having lived outside the United States (OR: 2.06; 95% CI: 1.49-2.85); and race/ethnicity reported by parent as Asian (OR: 2.28; 95% CI: 1.59-3.27) or Hispanic (OR: 1.57; 95% CI: 1.09-2.26). Several factors were not statistically significant predictors of a positive TST result: age, sex, household annual income, household member infected with human immunodeficiency virus or who had stayed in a homeless shelter, and being an adopted or foster child. Overall sensitivity of the 9 main items on the questionnaire was 80.9%; when a subset of 4 of these questions plus the race/ethnicity questions were used, sensitivity of responses was 83.5%. Parents failed to recognize positive TST results at a rate of 9.9% (for the 10-mm cutoff) and 5.9% (at the 15-mm cutoff). CONCLUSION: A 5-question risk assessment questionnaire completed by parents can be used to accurately identify risk factors associated with TB infection in children. In our population, some risk factors suggested by the American Academy of Pediatrics could not be validated. Parents cannot be relied on to read TST results accurately. Screening for TB can be enabled by using a standardized, validated questionnaire to identify children who should be given tuberculin skin testing.