Attosecond nonlinear polarization and light-matter energy transfer in solids.

Electric-field-induced charge separation (polarization) is the most fundamental manifestation of the interaction of light with matter and a phenomenon of great technological relevance. Nonlinear optical polarization produces coherent radiation in spectral ranges inaccessible by lasers and constitutes the key to ultimate-speed signal manipulation. Terahertz techniques have provided experimental access to this important observable up to frequencies of several terahertz. Here we demonstrate that attosecond metrology extends the resolution to petahertz frequencies of visible light. Attosecond polarization spectroscopy allows measurement of the response of the electronic system of silica to strong (more than one volt per ångström) few-cycle optical (about 750 nanometres) fields. Our proof-of-concept study provides time-resolved insight into the attosecond nonlinear polarization and the light-matter energy transfer dynamics behind the optical Kerr effect and multi-photon absorption. Timing the nonlinear polarization relative to the driving laser electric field with sub-30-attosecond accuracy yields direct quantitative access to both the reversible and irreversible energy exchange between visible-infrared light and electrons. Quantitative determination of dissipation within a signal manipulation cycle of only a few femtoseconds duration (by measurement and ab initio calculation) reveals the feasibility of dielectric optical switching at clock rates above 100 terahertz. The observed sub-femtosecond rise of energy transfer from the field to the material (for a peak electric field strength exceeding 2.5 volts per ångström) in turn indicates the viability of petahertz-bandwidth metrology with a solid-state device.

[Appropriate allocation of resources for interhospital transfer in emergency medical service-is a physician in the dispatch center helpful?] / Indikationsgerechte Durchführung von Sekundärtransporten im Rettungsdienst ­ Hilft der Arzt in der Leitstelle?

BACKGROUND: The number of interhospital transfers is constantly increasing because of specialization of medical facilities, capacity balancing between intensive care units as well as earlier rehabilitation procedures. This leads to an increase in requests for emergency physicians to accompany patient transfers. This study investigated whether clarification of interhospital transport by an emergency physician at the dispatch center can optimize the use of emergency services resources. METHOD: All transport clarifications performed by a tele-emergency physician between 1 January 2018 and 31 December 2019 were retrospectively analyzed as well as the transport request forms. Furthermore, all data on the number and alarmed rescue resources for interhospital transfers in the city of Aachen from 2013 onwards were exported from the dispatch center databank and included in the evaluation. RESULTS: In total 2333 requests for interhospital patient transfers from 2018 and 2019 were analyzed as well as 10,923 transports recorded from 2013 to 2019. The number of patient transfers accompanied by an emergency physician from 2013 to 2019 was significantly reduced from 786 (68.2%) to 495 (30.5%, p > 0.001). The correct resources of rescue vehicles and staff was requested in 1816 cases (77.8%). The urgency of emergency patient transfers was correctly evaluated in 567 (89.2%) cases. In total 526 assignments were carried out without an emergency physician and 315 of these patients were accompanied by a tele-emergency physician during transfer. CONCLUSION: The immediate clarification of interhospital transport requests by an emergency physician at the dispatch center leads to a significant reduction in unnecessary medical accompaniment of patient transfers. The choice of an appropriate transfer vehicle and staff should not be left to the requesting hospital physician alone.

De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females.

Variants in CLCN4, which encodes the chloride/hydrogen ion exchanger CIC-4 prominently expressed in brain, were recently described to cause X-linked intellectual disability and epilepsy. We present detailed phenotypic information on 52 individuals from 16 families with CLCN4-related disorder: 5 affected females and 2 affected males with a de novo variant in CLCN4 (6 individuals previously unreported) and 27 affected males, 3 affected females and 15 asymptomatic female carriers from 9 families with inherited CLCN4 variants (4 families previously unreported). Intellectual disability ranged from borderline to profound. Behavioral and psychiatric disorders were common in both child- and adulthood, and included autistic features, mood disorders, obsessive-compulsive behaviors and hetero- and autoaggression. Epilepsy was common, with severity ranging from epileptic encephalopathy to well-controlled seizures. Several affected individuals showed white matter changes on cerebral neuroimaging and progressive neurological symptoms, including movement disorders and spasticity. Heterozygous females can be as severely affected as males. The variability of symptoms in females is not correlated with the X inactivation pattern studied in their blood. The mutation spectrum includes frameshift, missense and splice site variants and one single-exon deletion. All missense variants were predicted to affect CLCN4's function based on in silico tools and either segregated with the phenotype in the family or were de novo. Pathogenicity of all previously unreported missense variants was further supported by electrophysiological studies in Xenopus laevis oocytes. We compare CLCN4-related disorder with conditions related to dysfunction of other members of the CLC family.

[Analgesia in the emergency medical service: comparison between tele-emergency physician and call back procedure with respect to application safety, effectiveness and tolerance]. / Analgesie im Rettungsdienst: Vergleich zwischen Telenotarzt- und Callback-Verfahren hinsichtlich Anwendungssicherheit, Wirksamkeit und Verträglichkeit.

BACKGROUND: Acute pain is a common reason for calling emergency medical services (EMS) and can require medication depending on the pain intensity. German EMS personnel feel strong pressure to reduce a patient's pain but are restricted by law. Currently, German federal law only allows the administration of opioid-containing drugs by or on the order of a physician, while in other European countries (e.g. Switzerland and The Netherlands) the administration of opioid-based analgesia by trained and certified paramedics is common practice. Consequently, a patient in Germany experiencing acute pain needs the attendance of an emergency physician in EMS missions. According to international standards pain reduction on the numeric rating scale (NRS) score by ≥2 or a NRS score ≤4 at the end of the patient transport is considered to be adequate. OBJECTIVE: Comparison of two different algorithm-based concepts for analgesia with consultation of a physician analyzing the efficacy, tolerance and safety of application. MATERIAL AND METHODS: In a retrospective cohort study in two different regions, two physician-supported algorithm-based analgesia concepts, a call back-supported concept (EMS Schleswig-Holstein: RKiSH) and a tele-EMS physician-based concept (EMS Aachen: RDAC), were compared over 2 years. The call back-supported concept is based on specific algorithms and certification of EMS personnel. In Aachen, the tele-EMS physician is integrated into the routine EMS system and includes immediate vital data transmission. RESULTS: Over a period of 2 years call back-supported analgesia was administered in 878 cases (2016: 428, 2017: 450) and telemedically assisted analgesia was used in 728 cases (2015: 226, 2016: 502). Call back vs. telemedicine: initial NRS scores were 9 (8-10) and 8 (6-9), respectively (p < 0.0001); NRS scores were reduced by 4 (3-5) and 5 (3-6), respectively (p = 0.0002), leading to mean NRS scores of 4 (3-6) vs. 3 (2-4), respectively (p < 0.0001) at patient handover/emergency room arrival. Clinically relevant pain reduction was achieved in both groups. Complete NRS documentation was conducted in 753 (85.8%) vs. 673 (92.4%) cases, respectively, p = 0. Severe adverse events did not occur in either of the groups. CONCLUSION: The administration of analgesia by EMS personnel with teleconsultation of a physician is effective and has a low rate of complications, particularly morphine. Overall, algorithm-based call back-supported as well as telemedically supported analgesia concepts based on regular training improve the management of pain in the prehospital setting. In addition, the resources of the emergency physician remain available for life-threatening emergencies. The training, certification and supervision of EMS personnel is very important in both systems to ensure the best pain management care and patient safety. Adjustments to the federal law on the administration of analgesics would facilitate the realization of algorithm-based concepts by paramedics as pain reduction could be performed with delegation by a medical director without consulting another physician.

Eight-year follow-up of a randomized clinical trial comparing ultrasound-guided foam sclerotherapy with surgical stripping of the great saphenous vein.

BACKGROUND: This was an 8-year follow-up of an RCT comparing ultrasound-guided foam sclerotherapy (UGFS) with high ligation and surgical stripping (HL/S) of the great saphenous vein (GSV). METHODS: Patients were randomized to UGFS or HL/S of the GSV. The primary outcome was the recurrence of symptomatic GSV reflux. Secondary outcomes were patterns of reflux according to recurrent varices after surgery, Clinical Etiologic Anatomic Pathophysiologic (CEAP) classification, Venous Clinical Severity Score (VCSS) and EuroQol Five Dimensions (EQ-5D™) quality-of-life scores. RESULTS: Of 430 patients originally randomized (230 UGFS, 200 HL/S), 227 (52·8 per cent; 123 UGFS, 103 HL/S) were available for analysis after 8 years. The proportion of patients free from symptomatic GSV reflux at 8 years was lower after UGFS than HL/S (55·1 versus 72·1 per cent; P = 0·024). The rate of absence of GSV reflux, irrespective of venous symptoms, at 8 years was 33·1 and 49·7 per cent respectively (P = 0·009). More saphenofemoral junction (SFJ) failure (65·8 versus 41·7 per cent; P = 0·001) and recurrent reflux in the above-knee GSV (72·5 versus 20·4 per cent; P = 0·001) was evident in the UGFS group. The VCSS was worse than preoperative scores in both groups after 8 years; CEAP classification and EQ-5D® scores were similar in the two groups. CONCLUSION: Surgical stripping had a technically better outcome in terms of recurrence of GSV and SFJ reflux than UGFS in the long term. Long-term follow-up suggests significant clinical progression of venous disease measured by VCSS in both groups, but less after surgery. Registration number: NCT02304146 (http://www.clinicaltrials.gov).

Strengths and limitations of coronary angiography with turbo high-pitch third-generation dual-source CT.

AIM: To define practical limitations of diagnostic image quality for recently introduced turbo high-pitch scan mode (THP) in third-generation dual-source computed tomography (CT). MATERIALS AND METHODS: Two hundred and twenty-nine consecutive patients undergoing CT coronary angiography were included in this retrospective single-centre analysis. A contrast-enhanced volume dataset was acquired in THP. Image quality of coronary segments was classified as diagnostic or non-diagnostic by three blinded readers. Segments were stated as non-diagnostic if at least one of three readers could neither exclude nor confirm significant stenoses. Multivariable logistic regression was used to assess relationships between number of non-diagnostic segments and common influencing factors. RESULTS: Median effective radiation dose was 0.6 (interquartile range [IQR], 0.4-0.8) mSv overall and 0.3 (IQR, 0.3-0.4) mSv in the 70 kV subgroup of this middle aged, predominantly pre-obese cohort (age: 61 [IQR, 52-67] years; body mass index [BMI]: 26 [IQR, 23-29] kg/m2) with a low-moderate median Agatston score (AS) 0 (IQR, 0-70). Diagnostic image quality was found in 98.1% of 3,678 coronary segments. AS was independently associated with diagnostic image quality (B=0.34; p=0.02), whereas heart rate, BMI, and presence of arrhythmia were not. The portion of diagnostic coronary segments decreased slightly in obese patients with heart rates >65 beats/min and dropped significantly in patients with an AS >600 (p=0.003). CONCLUSION: THP enables CT coronary angiography with minimal radiation exposure and is most appropriate in non-obese patients with stable sinus rhythm ≤65 beats/min and a calcium score ≤600.

Persistent infections with infectious pancreatic necrosis virus (IPNV) of different virulence in Atlantic salmon, Salmo salar L.

Infectious pancreatic necrosis virus (IPNV) is a prevalent pathogen in fish worldwide. The virus causes substantial mortality in Atlantic salmon juveniles and smolts when transferred to sea water and persistent infection in surviving fish after disease outbreaks. Here, we have investigated the occurrence of the virus as well as the innate immune marker Mx in the head kidney (HK) of Atlantic salmon throughout an experimental challenge covering both a fresh and a seawater phase. The fish were challenged with a high (HV) and low virulence (LV) IPNV. Both isolates caused mortality due to reactivation of the virus after transfer to sea water. In the freshwater phase, higher levels of virus transcripts were detected in the HK of fish infected with LV IPNV compared to HV, suggesting that the HV isolate is able to limit its own replication to a level where the innate immune system is not alerted. Further, ex vivoHK leucocytes derived from fish infected with the two isolates were stimulated with CpG DNA. Significantly, higher IFN levels were found in the LV compared to the HV group in the freshwater phase. This suggests that the viruses attenuate the antiviral host immune response at different levels which may contribute to the observed differences in disease outcome.

Ulcer recurrence after in-hospital treatment for recalcitrant venous leg ulceration.

BACKGROUND: Leg ulceration caused by chronic venous disease occurs in 1% of the adult Western population. A majority of these patients is successfully treated in the outpatient setting. A minority of patients is hospitalized, most frequently because of the lack of healing tendency. The literature provides recurrence rates for ulcer disease, but lacks specific data on recurrence rates after in-hospital treatment of recalcitrant venous leg ulcers. OBJECTIVES: To investigate time to ulcer recurrence after in-hospital treatment of venous leg ulceration. METHODS: A multicentre, retrospective cohort study of patients admitted for leg ulceration between 1996 and 2007 was conducted. RESULTS: Data could be collected for 107 of the patients. Of these, 27 had conservative treatment (bed rest, local wound care, pain management) and 48 patients underwent surgical ulcer treatment with (n = 19) or without (n = 29) initial vacuum-assisted closure (VAC) treatment. The treatment method was 'miscellaneous' in the remaining 32 patients. Median admission time was 30 days, median percentage of closure at discharge was 95%, and median time to ulcer recurrence 60 days. The Mann-Whitney U-test showed significant differences between the conservative group and the surgery group, the latter having a longer length of hospital stay (P < 0.0001) and a higher percentage of ulcer closure (P < 0.0001), but there was no difference in time to ulcer recurrence (P = 0.273). Comparable differences were demonstrated between the conservative group and the VAC plus surgery group. No significant differences could be demonstrated between the surgically treated patients and those treated by VAC and surgery. CONCLUSIONS: Hospital stay is significantly shorter in cases of surgical treatment of recalcitrant venous leg ulcers. Most ulcers recur within 2 months after hospital discharge. Recurrence of venous leg ulcers after hospital admission is independent of the method of treatment and cause of ulceration.

Establishing a cell line from Atlantic cod as a novel tool for in vitro studies.

The present work describes the generation of a cell line from newly hatched Atlantic cod (Gadus morhua) larvae (ACL cells). Primary cultures were initiated by explant outgrowth from partially minced tissues and subcultured cells were exposed to UV radiation. After a substantial period of growth lag, cells started to proliferate and different growth conditions were tested to establish the cell line. At present, the ACL cell line has been subcultured for more than 100 passages. ACL cells had a polygonal shape and the morphology appeared homogenous with epithelial-like cells. Cell growth was dependent on the presence of foetal bovine serum and cells proliferated in a wide temperature range with optimal growth at 15 °C. By exposure to a viral dsRNA mimic (poly I:C) the cells expressed high levels of a repertoire of genes comprising both inflammatory mediators and interferon stimulated genes. Infection studies with two different viruses showed that infectious pancreatic necrosis virus (IPNV) propagated efficiently, and induced low level expression of genes of both pathways before the cells rapidly died. No productive infection was obtained with nervous necrosis virus (NNV), but a transient increase in the viral RNA level, followed by a high increase in expression of selected ISGs, suggests that the virus enters the cells but is unable to complete its replication cycle. To our knowledge, ACL cells are at the moment the only existing cell line from Atlantic cod. Our results demonstrate that ACL cells can be a useful research tool for further exploration of host-pathogen interactions and it is believed that this cell line will serve as a valuable tool also for studies within other research areas.

Study of virulence in field isolates of infectious pancreatic necrosis virus obtained from the northern part of Norway.

In order to study the variety of infectious pancreatic necrosis virus (IPNV) strains involved in outbreaks of infectious pancreatic necrosis (IPN) in Atlantic salmon fish farms, samples were collected from 19 different outbreaks of IPN in the northern part of Norway. The main objective of this study was to examine whether IPNV isolates of different virulence were involved in the outbreaks and could explain the variable IPN protection observed in vaccinated post-smolts in the field. Both the molecular basis of virulence of all field isolates and virulence expressed by mortality after bath challenge of unvaccinated post-smolts with eight of the isolates were studied. Very little variation among the field isolates was detected when the 578-bp variable region encoding the VP2 protein known to be involved in virulence was sequenced. The cumulative mortality after experimental challenge with field isolates genetically characterized as highly virulent was always high (40-56%), while the cumulative mortality of the same strains in vaccinated post-smolts during the field outbreaks varied from 1 to 50%. Although the tested samples came from fish vaccinated with the same vaccine product, the protection against IPN varied. These results demonstrate that differences in virulence of the isolates were not the main reason for the variation in mortality in the field outbreaks. Most of the field isolates were of high virulence, which is shown in experimental challenges to be important for mortality, but clearly other factors that might affect the susceptibility of IPN also play an important role in the outcome of an IPNV infection.

Maternal but not paternal transmission of 15q11-13-linked nondeletion Angelman syndrome leads to phenotypic expression.

Angelman syndrome (AS) may result from either maternally inherited deletions of chromosome 15q11-13 or from paternal uniparental disomy for chromosome 15. This is in contrast to Prader-Willi syndrome (PWS), which is caused by either paternal deletion of this region or maternal disomy for chromosome 15. However, 40% of AS patients inherit an apparently intact copy of chromosome 15 from each parent. We now describe a family in which three sisters have given birth to four AS offspring who have no evidence of deletion or paternal disomy. We show that AS in this family is caused by a mutation in 15q11-13 that results in AS when transmitted from mother to child, but no phenotype when transmitted paternally. These results suggest that the loci responsible for AS and PWS, although closely linked, are distinct.

Quantitative and molecular aspects of water intake in meat-type chickens.

Even though water is the most essential nutrient for poultry production, adequate data on individual water intake in broiler chickens and its relationship with other traits of economic importance is scant. Water is provided to chickens in an unrestricted manner in spite of being a finite resource. Climate change continues to affect water sources and efficient bird use of water is long overdue. Understanding the biological basis of water intake is essential for sustainability of the poultry industry. Individual water and feed intake, and growth data was collected on 520 commercial broilers aged 14 to 42 days. We introduced the concepts of water conversion ratio (WCR) and residual water intake (RWI) as parameters that can be used to assess water intake efficiency. Water conversion ratio was defined as the amount of water consumed per unit of body weight gain, and RWI was defined as the difference between the actual water intake (WI) of a given bird and the expected WI by an average bird from the population with the same metabolic body weight, feed intake (FI) and body weight gain (BWG). The correlation between WI and FI was positive (r=0.77; P<0.0001), and the correlation between WI and BWG was positive (r=0.80; P<0.0001). Based on the distribution of RWI, the bottom 5 birds (LRWI) and the top 5 birds (HRWI) for RWI were selected for mRNA expression differences. The average broiler consumed about 7.8 L (± 1L) of water from 14 to 42 days of age. The mRNA expression of arginine vasopressin (AVP) antidiuretic hormone, calcium sensing receptor (CasR), sodium channel epithelial 1 subunit alpha (SCNN1A) and SCNN1D in the hypothalamus was upregulated in the LRWI group compared to the HRWI group. Similarly, kidney aquaporins (AQP) 2, 3, and 4 were upregulated in the LRWI group compared with the HRWI group. Given that water was provided ad libitum, the up-regulation of AVP and AQP gene mRNA expressions seem to indicate that the LRWI birds were more efficient in water reabsorption in the kidney compared to their HRWI counterparts. Increased water reabsorption will reduce the amount of water consumed to attain hydration. The water reabsorption potential was reflected in the excreta moisture levels as the LRWI birds had significantly lower excreta moisture than the HRWI birds. Excreta moisture level require further studies and could be considered as a potential proxy trait for water intake.

Randomized clinical trial of ultrasound-guided foam sclerotherapy versus surgery for the incompetent great saphenous vein.

BACKGROUND: New minimally invasive treatment modalities, such as ultrasound-guided foam sclerotherapy (UGFS), are becoming more popular. In a multicentre randomized controlled non-inferiority trial, the effectiveness and costs of UGFS and surgery for treatment of the incompetent great saphenous vein (GSV) were compared. METHODS: Patients with primary great saphenous varicose veins were assigned randomly to either UGFS or surgical stripping with high ligation. Recurrence, defined as reflux combined with venous symptoms, was determined on colour duplex scans at baseline, 3 months, 1 year and 2 years after initial treatment. Secondary outcomes were presence of recurrent reflux (irrespective of symptoms), reduction of symptoms, health-related quality of life (EQ-5D(™)), adverse events and direct hospital costs. RESULTS: Two hundred and thirty patients were treated by UGFS and 200 underwent GSV stripping. The 2-year probability of recurrence was similar in the UGFS and surgery groups: 11·3 per cent (24 of 213) and 9·0 per cent (16 of 177) respectively (P = 0·407). At 2 years, reflux irrespective of venous symptoms was significantly more frequent in the UGFS group (35·0 per cent) than in the surgery group (21·0 per cent) (P = 0·003). Mean(s.d.) hospital costs per patient over 2 years were €774(344) per patient for UGFS and €1824(141) for stripping. CONCLUSION: At 2-year follow-up, UGFS was not inferior to surgery when reflux associated with venous symptoms was the clinical outcome of interest. UGFS has the potential to be a cost-effective approach to a common health problem. Registration numbers: NCT01103258 (http://www.clinicaltrials.gov) and NTR654 (http://www.trialregister.nl).

Supplementation with vitamin A early in life and subsequent risk of asthma.

Animal models suggest that vitamin A deficiency affects lung development adversely and promotes airway hyperresponsiveness, and may predispose to an increased risk of asthma. We examined the long-term effects of vitamin A supplementation early in life on later asthma risk. In 2006-2008, we revisited participants from two cohorts in rural Nepal who were enrolled in randomised trials of vitamin A supplementation. The first cohort received vitamin A or placebo for <16 months during their pre-school years (1989-1991). The second cohort was born to mothers who received vitamin A, ß-carotene or placebo before, during and after pregnancy (1994-1997). At follow-up, we asked about asthma symptoms and performed spirometry. Out of 6,421 subjects eligible to participate, 5,430 (85%) responded to our respiratory survey. Wheezing prevalence during the previous year was 4.8% in participants aged 9-13 yrs and 6.6% in participants aged 14-23 yrs. We found no differences between the vitamin A supplemented and placebo groups from either trial in the prevalence of lifetime or current asthma and wheeze or in spirometric indices of obstruction (p ≥ 0.12 for all comparisons). Vitamin A supplementation early in life was not associated with a decreased risk of asthma in an area with chronic vitamin A deficiency.

[Intraosseous infusion in the pediatric emergency medical service. Analysis of emergency medical missions 1990-2009]. / Einsatz der intraossären Infusion im pädiatrischen Notarztdienst. Analyse von Notarzteinsätzen 1990-2009.

BACKGROUND: Timely establishment of venous access in infants and toddlers during emergency medical care can be a particularly challenging task. Alternative routes for drug and fluid administration, such as endobronchial, intramuscular, central venous or venous cut-down do not offer reliable solutions. Intraosseous infusion (IOI) has become established as an effective alternative intravascular access for rapid and efficient drug delivery. IOI was introduced in our local emergency medical service (EMS) in 1993 and was assigned a high priority in international guidelines for pediatric emergency medical care in 2000 and 2005. The aim of this study was to review the impact of the introduction of IOI on drug administration routes during prehospital emergency treatment of critically ill or severely injured pediatric patients (NACA index V-VII) in our tertiary medical care centre over a period of 20 years. METHODS: Pediatric prehospital emergency medical protocols from 1990 to 2009 were analyzed with respect to the administration routes for fluids and medications in severely injured or critically ill children with NACA severity scores V-VII. The frequency and mode of vascular access during prehospital treatment including IOI, endobronchial administration, central venous catheterization (CVC) and intramuscular administration as well as prehospital treatment and transportation without vascular access were analyzed. Two groups were compared: the introduction phase of IOI between 1990 and 1999 and the phase of growing IOI routine after introducing guidelines and regular staff IOI technique training between 2000 and 2009. Demographic data and drug administration routes in the two different time periods were analyzed using the Mann-Whitney-u test and t-test or χ(2)-test, respectively. A p-value <0.05 was regarded as significant. RESULTS: A total of 5,279 pediatric prehospital emergency charts were analyzed and 401 patients (7.6%) were scored as NACA V-VII. At the emergency scene 299 patients (75%) received a peripheral intravenous access, 3 (0.7%) a central venous line access, 77 (19%) an intraosseous needle and in 22 (5.4%) no vascular or intraosseous access was used during the course of prehospital treatment (NACA VII - 13 patients, NACA VI - 2 patients, NACA V - 7 patients). Of the NACA VII patients 3 were transported under continuous cardiopulmonary resuscitation without vascular access. After 2002 all patients with NACA index VII were treated with vascular or intraosseous access. In 48 patients (12%) at least initial medication was given by the endobronchial or alternative route but within the last 3 years endobronchial drug administration was no longer reported. Thus, in 124 critically ill patients (31%) routine peripheral venous access could not be established initially or until the end of treatment (77 times IOI, 22 times no access over the course of treatment, 3 times CVC and 22 times initial endobronchial followed by peripheral venous access). Over the reviewed period the use of IOI increased significantly (p<0.001), while the incidence of lacking vascular access (p<0.05) and alternative drug administration routes (p<0.001) continuously decreased. CONCLUSION: The IOI technique has not only been assigned a high priority in the guidelines for pediatric emergency care of critically ill children with difficult or failed venous access but has also significantly influenced current prehospital care. The introduction of the IOI technique in our prehospital pediatric emergency system has markedly reduced the number of critically ill or severely injured pediatric patients without vascular access or with less reliable alternative administration routes in the last 20 years.

Blocking the saphenofemoral junction during ultrasound-guided foam sclerotherapy-- assessment of a presumed safety-measure procedure.

OBJECTIVES: Ultrasound-guided foam sclerotherapy (UGFS) is a technique in which a mixture of sclerosing drug and gas is used to treat varicose veins. Several authors have demonstrated transient systemic effects after UGFS. These effects are not well understood but probably originate from a systemic distribution of the sclerosing foam. Therefore, safety measures have been developed to prevent foam from flowing into the deep venous system. The aim of the study is to evaluate whether blockage of the saphenofemoral (SF) junction by either manual compression or surgical ligation prevents microbubbles from leaking into the deep venous circulation. METHODS: To detect the distribution of microbubbles, radioactive pertechnetate (99mTcO4-) was added to the foam solution. Initially, in vitro trials were performed in the laboratory to investigate the effect of 99mTc on foam stability. The time taken for foam to liquefy was measured for foam alone and for the mixture with 99mTc. In subsequent research, eight varicose great saphenous veins (GSVs) were treated by UGFS. In three patients, this treatment was preceded by surgical ligation of the SF junction. In three patients, the groin was manually compressed during UGFS. In two patients, UGFS was performed without compression of the groin. RESULTS: In vitro, 99mTc did not influence foam stability; after 2.6 min all foam had reduced to liquid, regardless of whether 99mTc had been added or not. In vivo trials showed that all patients showed a decrease in the cumulative amount of 99mTc detected in the GSV following polidocanol-99mTc mixture injection. However, the decrease of radioactivity was slightly reduced when compression or ligation of the SF junction was performed. CONCLUSIONS: Blocking the SF junction during UGFS using either manual compression or ligation does not prevent, but may reduce the flow of foam into the femoral vein.

[Botulinum toxin for overactive bladder]. / Botulinumtoxin bei überaktiver Blase.

Idiopathic overactive bladder (OAB) is defined as a symptom complex characterized by urinary urgency with or without urinary incontinence, nycturia and increased frequency of micturition without the presence of an infection or other pathological conditions, especially a neurological disease. It is a diagnosis by exclusion. If conservative treatment with behavioral therapy and pelvic floor muscle training alone is not successful, pharmaceutical treatment is recommended according to the OAB staged treatment. For treatment refractory OAB, intravesical injection of onabotulinum toxin A is recommended according to the current guidelines (recommendation level A). The approved dose is 100 U botulinum toxin and is transurethrally injected into the detrusor muscle. The treatment effect lasts on average for 6-9 months and injections can be repeated without limitations. Due to the low rate of complications, the good success rate and the low invasiveness, botulinum toxin offers a good treatment option for treatment refractory OAB.

Endothelial cell-derived heparan sulfate binds basic fibroblast growth factor and protects it from proteolytic degradation.

Cultured bovine capillary endothelial (BCE) cells were found to synthesize and secrete high molecular mass heparan sulfate proteoglycans and glycosaminoglycans, which bound basic fibroblast growth factor (bFGF). The secreted heparan sulfate molecules were purified by DEAE cellulose chromatography, followed by Sepharose 4B chromatography and affinity chromatography on immobilized bFGF. Most of the heparinase-sensitive sulfated molecules secreted into the medium by BCE cells bound to immobilized bFGF at low salt concentrations. However, elution from bFGF with increasing salt concentrations demonstrated varying affinities for bFGF among the secreted heparan sulfate molecules, with part of the heparan sulfate requiring NaCl concentrations between 1.0 and 1.5 M for elution. Cell extracts prepared from BCE cells also contained a bFGF-binding heparan sulfate proteoglycan, which could be released from the intact cells by a short proteinase treatment. The purified bFGF-binding heparan sulfate competed with 125I-bFGF for binding to low-affinity binding sites but not to high-affinity sites on the cells. Heparan sulfate did not interfere with bFGF stimulation of plasminogen activator activity in BCE cells in agreement with its lack of effect on binding of 125I-bFGF to high-affinity sites. Soluble bFGF was readily degraded by plasmin, whereas bFGF bound to heparan sulfate was protected from proteolytic degradation. Treatment of the heparan sulfate with heparinase before addition of plasmin abolished the protection and resulted in degradation of bFGF by the added proteinase. The results suggest that heparan sulfate released either directly by cells or through proteolytic degradation of their extracellular milieu may act as carrier for bFGF and facilitate the diffusion of locally produced growth factor by competing with its binding to surrounding matrix structures. Simultaneously, the secreted heparan sulfate glycosaminoglycans protect the growth factor from proteolytic degradation by extracellular proteinases, which are abundant at sites of neovascularization or cell invasion.

Influence of promethazine on cardiac repolarisation: a double-blind, midazolam-controlled study.

Drugs used in anaesthesia may provoke torsadogenic changes in cardiac repolarisation. The aim of this study was to assess the effect of promethazine on the parameters of ventricular repolarisation: QTc interval and transmural dispersion of repolarisation. Forty patients were randomly allocated to receive promethazine (25 mg) or midazolam (2.5 mg). Changes in the ECG and arterial blood pressure were recorded. Correction of QT interval was calculated using Bazett's formula and Fridericia's correction; transmural dispersion of repolarisation was determined as T(peak)-T(end) time. Significant prolongation of QT interval, corrected with both formulae, was detected in patients receiving promethazine, while no change in the QTc value was observed in the midazolam group. There were no significant differences in T(peak)-T(end) time either between or within the groups. In conclusion, promethazine induces significant QTc prolongation but the lack of influence on transmural dispersion of repolarisation makes the risk of its torsadogenic action very low.

Effects of combined recombinant insulin-like growth factor (IGF)-I and IGF binding protein-3 in type 2 diabetic patients on glycemic control and distribution of IGF-I and IGF-II among serum binding protein complexes.

CONTEXT: Administration of recombinant human IGF-I (rhIGF-I)/recombinant human IGF binding protein-3 (rhIGFBP-3) to patients with type 2 diabetes improves blood glucose and enhances insulin sensitivity. The changes in various components of the IGF system that occur in response to rhIGF-I/rhIGFBP-3 as well as the minimum effective dose have not been determined. OBJECTIVES: The aim was to determine the dose of rhIGF-I/rh-IGFBP-3 necessary to achieve a significant decrease in glucose and to determine the changes that occur in the IGF-II and acid labile subunit in response to treatment. DESIGN: A total of 39 insulin-requiring type 2 diabetics were randomized to placebo or one of six groups that received different dosages of rhIGF-I/rhIGFBP-3. After 3 d in which insulin doses were adjusted to improve glucose control, a variable insulin dosage regimen was continued, and either placebo or one of six dosages (0.125-2.0 mg/kg.d) of rhIGF-I/rhIGFBP-3 was administered for 7 d. All subjects were hospitalized, and dietary intake as well as insulin dosage were controlled with instructions to treat to normal range targets. RESULTS: Fasting glucose was reduced in the groups that received either 1 (32 +/- 5% reduction) or 2 mg/kg.d (40 +/- 6% reduction) of the complex. Mean daily glucose (four determinations) was reduced by 26 +/- 4% in the 1 mg/kg group and by 33 +/- 5% in the 2 mg/kg group compared with 18 +/- 4% in the placebo group. Total serum IGF-I increased between 2.0 +/- 0.3- and 5.7 +/- 1.3-fold by d 8. IGFBP-3 concentrations increased significantly only in the 2 mg/kg group. IGF-II concentrations declined to values that were between 27 +/- 4% and 64 +/- 7% below baseline. Acid labile subunit concentrations declined significantly in the three highest dose groups. The sum of the IGF-I + IGF-II concentrations was significantly increased at the two highest dosages. There were very few drug-associated adverse events reported in this study with the exception of hypoglycemia, which occurred in 15 subjects who had received rhIGF-I/rhIGFBP-3 treatment. CONCLUSIONS: Administration of rhIGF-I/rhIGFBP-3 resulted in a redistribution of the amount of IGF-I and IGF-II that bound to IGFBP-3. Fasting and mean daily blood glucose were reduced significantly in the two highest dosage groups. The results suggest that both the total concentration of IGF-I as well as its distribution in blood may determine the extent to which insulin sensitivity is enhanced.