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1.
Resuscitation ; 195: 110087, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38097108

ABSTRACT

Standardized reporting of data is crucial for out-of-hospital cardiac arrest (OHCA) research. While the implementation of first responder systems dispatching volunteers to OHCA is encouraged, there is currently no uniform reporting standard for describing these systems. A steering committee established a literature search to identify experts in smartphone alerting systems. These international experts were invited to a conference held in Hinterzarten, Germany, with 40 researchers from 13 countries in attendance. Prior to the conference, participants submitted proposals for parameters to be included in the reporting standard. The conference comprised five workshops covering different aspects of smartphone alerting systems. Proposed parameters were discussed, clarified, and consensus was achieved using the Nominal Group Technique. Participants voted in a modified Delphi approach on including each category as a core or supplementary element in the reporting standard. Results were presented, and a writing group developed definitions for all categories and items, which were sent to participants for revision and final voting using LimeSurvey web-based software. The resulting reporting standard consists of 68 core items and 21 supplementary items grouped into five topics (first responder system, first responder network, technology/algorithm/strategies, reporting data, and automated external defibrillators (AED)). This proposed reporting standard generated by an expert opinion group fills the gap in describing first responder systems. Its adoption in future research will facilitate comparison of systems and research outcomes, enhancing the transfer of scientific findings to clinical practice.


Subject(s)
Cardiopulmonary Resuscitation , Emergency Responders , Out-of-Hospital Cardiac Arrest , Humans , Smartphone , Cardiopulmonary Resuscitation/methods , Defibrillators , Out-of-Hospital Cardiac Arrest/therapy
2.
Article in German | MEDLINE | ID: mdl-37682284

ABSTRACT

BACKGROUND: This study evaluates the implementation of postcardiac-arrest-sedation (PCAS) and -care (PRC) by prehospital emergency physicians in Germany. MATERIALS AND METHODS: Analysis of a web-based survey from October to November 2022. Questions were asked about implementation, medications used, complications, motivation for implementing or not implementing PCAS, and measures and target parameters of PRC. RESULTS: A total of 500 emergency physicians participated in the survey. In all, 73.4% stated that they regularly performed PCAS (hypnotics: 84.7%; analgesics: 71.1%; relaxants: 29.7%). Indications were pressing against the respirator (88.3%), analgesia (74.1%), synchronization to respirator (59.5%), and change of airway device (52.6%). Reasons for not performing PCAS (26.6%) included unconscious patients (73.7%); concern about hypotension (31.6%), re-arrest (26.3%), and worsening neurological assessment (22.5%). Complications of PCAS were observed by 19.3% of participants (acute hypotension [74.6%]); (re-arrest [32.4%]). In addition to baseline monitoring, PRC included 12-lead-electrocardiogram (96.6%); capnography (91.6%); catecholamine therapy (77.6%); focused echocardiography (20.6%), lung ultrasound (12.0%) and abdominal ultrasound (5.6%); induction of hypothermia (13.6%) and blood gas analysis (7.4%). An etCO2 of 35-45 mm Hg was targeted by 40.6%, while 9.0% of participants targeted an SpO2 of 94-98% and 19.2% of participants targeted a systolic blood pressure of ≥ 100 mm Hg. CONCLUSIONS: Prehospital PRC in Germany is heterogeneous and deviations from its target parameters are frequent. PCAS is frequent and associated with relevant complications. The development of preclinical care algorithms for PCAS and PRC within preclinical care seems urgently needed.

5.
Oncogene ; 36(16): 2297-2308, 2017 04 20.
Article in English | MEDLINE | ID: mdl-27797378

ABSTRACT

Fibroblasts within the mammary tumor microenvironment are active participants in carcinogenesis mediating both tumor initiation and progression. Our group has previously demonstrated that genetic loss of phosphatase and tensin homolog (PTEN) in mammary fibroblasts induces an oncogenic secretome that remodels the extracellular milieu accelerating ErbB2-driven mammary tumor progression. While these prior studies highlighted a tumor suppressive role for stromal PTEN, how the adjacent normal epithelium transforms in response to PTEN loss was not previously addressed. To identify these early events, we have evaluated both phenotypic and genetic changes within the pre-neoplastic mammary epithelium of mice with and without stromal PTEN expression. We report that fibroblast-specific PTEN deletion greatly restricts mammary ductal elongation and induces aberrant alveolar side-branching. These mice concomitantly exhibit an expansion of the mammary epithelial stem cell (MaSC) enriched basal/myoepithelial population and an increase in in vitro stem cell activity. Further analysis revealed that NOTCH signaling, specifically through NOTCH3, is diminished in these cells. Mechanistically, JAGGED-1, a transmembrane ligand for the NOTCH receptor, is downregulated in the PTEN-null fibroblasts leading to a loss in the paracrine activation of NOTCH signaling from the surrounding stroma. Reintroduction of JAGGED-1 expression within the PTEN-null fibroblasts was sufficient to abrogate the observed increase in colony forming activity implying a direct role for stromal JAGGED-1 in regulation of MaSC properties. Importantly, breast cancer patients whose tumors express both low stromal JAG1 and low stromal PTEN exhibit a shorter time to recurrence than those whose tumors express low levels of either alone suggesting similar stromal signaling in advanced disease. Combined, these results unveil a novel stromal PTEN-to-JAGGED-1 axis in maintaining the MaSC niche, and subsequently inhibiting breast cancer initiation and disease progression.


Subject(s)
Epithelial Cells/cytology , Jagged-1 Protein/metabolism , Mammary Glands, Animal/cytology , Mammary Neoplasms, Animal/metabolism , PTEN Phosphohydrolase/physiology , Stem Cells/cytology , 3T3 Cells , Animals , Cancer-Associated Fibroblasts/metabolism , Cell Proliferation , Epithelial Cells/pathology , Female , Humans , Jagged-1 Protein/deficiency , Jagged-1 Protein/genetics , Mammary Glands, Animal/pathology , Mammary Neoplasms, Animal/genetics , Mammary Neoplasms, Animal/pathology , Mice , Mice, Transgenic , PTEN Phosphohydrolase/deficiency , PTEN Phosphohydrolase/metabolism , Receptor, Notch3/metabolism , Signal Transduction , Stromal Cells/cytology , Tumor Microenvironment
6.
Oncogene ; 34(28): 3651-61, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25241894

ABSTRACT

Metastasis of solid tumors is associated with poor prognosis and bleak survival rates. Tumor-infiltrating myeloid cells (TIMs) are known to promote metastasis, but the mechanisms underlying their collaboration with tumor cells remain unknown. Here, we report an oncogenic role for microRNA (miR) in driving M2 reprogramming in TIMs, characterized by the acquisition of pro-tumor and pro-angiogenic properties. The expression of miR-21, miR-29a, miR-142-3p and miR-223 increased in myeloid cells during tumor progression in mouse models of breast cancer and melanoma metastasis. Further, we show that these miRs are regulated by the CSF1-ETS2 pathway in macrophages. A loss-of-function approach utilizing selective depletion of the miR-processing enzyme Dicer in mature myeloid cells blocks angiogenesis and metastatic tumor growth. Ectopic expression of miR-21 and miR-29a promotes angiogenesis and tumor cell proliferation through the downregulation of anti-angiogenic genes such as Col4a2, Spry1 and Timp3, whereas knockdown of the miRs impedes these processes. miR-21 and miR-29a are expressed in Csf1r+ myeloid cells associated with human metastatic breast cancer, and levels of these miRs in CD115+ non-classical monocytes correlates with metastatic tumor burden in patients. Taken together, our results suggest that miR-21 and miR-29a are essential for the pro-tumor functions of myeloid cells and the CSF1-ETS2 pathway upstream of the miRs serves as an attractive therapeutic target for the inhibition of M2 remodeling of macrophages during malignancy. In addition, miR-21 and miR-29a in circulating myeloid cells may potentially serve as biomarkers to measure therapeutic efficacy of targeted therapies for CSF1 signaling.


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/pathology , Macrophages/metabolism , Melanoma, Experimental/genetics , MicroRNAs/genetics , Animals , Breast Neoplasms/blood supply , Breast Neoplasms/metabolism , Cell Line, Tumor , Cell Proliferation , Female , Humans , Macrophage Colony-Stimulating Factor/metabolism , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Melanoma, Experimental/secondary , Mice , Mice, Inbred C57BL , Neovascularization, Pathologic/genetics , Proto-Oncogene Protein c-ets-2/metabolism , Signal Transduction
10.
Berl Munch Tierarztl Wochenschr ; 121(11-12): 422-31, 2008.
Article in German | MEDLINE | ID: mdl-19086692

ABSTRACT

Scoring schemes for clinical, ultrasonographic and radiographic findings in pigs were developed based upon a standardized animal model for Actinobacillus pleuropneumoniae infection.The results of these methods were compared to each other as well as with the corresponding pathomorphological findings during necropsy. Altogether 69 pigs of different breeding lines (Hampshire, Pietrain and German Landrace were examined. Positive correlations were found between the results of all three methods as well as with the necropsy scores (p <0.0001). Different pathomorphological findings were detected either by radiographic or by ultrasonographic examination dependent upon the type of lung tissue alterations: Alterations of the pleura as well as sequestration of lung tissue on the lung surface could be clearly identified during the ultrasonographic examination while deep tissue alterations with no contact to the lung surface could be detected reliably by radiographic examination. Both methods complement each other, and the application of a combined ultrasonographic and radiographic examination of the thorax allows a comprehensive inspection of the lung condition. Particularly during the acute phase of the disease the extent of lung tissue damage can be estimated more precisely than by clinical examination alone.


Subject(s)
Actinobacillus Infections/veterinary , Actinobacillus pleuropneumoniae/pathogenicity , Swine Diseases/diagnosis , Actinobacillus Infections/diagnosis , Actinobacillus Infections/diagnostic imaging , Actinobacillus pleuropneumoniae/isolation & purification , Aerosols , Animals , Radiography, Thoracic/methods , Radiography, Thoracic/veterinary , Severity of Illness Index , Swine , Swine Diseases/diagnostic imaging , Swine Diseases/pathology , Ultrasonography/methods , Ultrasonography/veterinary
11.
Anaesthesist ; 56(11): 1147-54, 2007 Nov.
Article in German | MEDLINE | ID: mdl-17882389

ABSTRACT

Over the last 30 years the Advanced Trauma Life Support (ATLS) course has become the most successful training program in the world for the early care of severely injured patients. It has shaped trauma care systems in many countries and is now on the verge of being introduced into Germany by the German Society of Trauma Surgery (DGU). However, after publication of the latest edition in 2004 there are rising concerns regarding the lack of multi-disciplinarity, out-dated contents and lack of adaptability to regional needs. This article questions the beneficial effect of ATLS on the advanced German trauma care system and concludes that ATLS is not likely to improve trauma care in Germany.


Subject(s)
Emergency Medicine/education , Life Support Care/organization & administration , Life Support Care/standards , Algorithms , Europe , Germany , Humans , Shock/therapy , Trauma Centers , Wounds and Injuries/therapy
12.
Acta Anaesthesiol Belg ; 57(3): 271-5, 2006.
Article in English | MEDLINE | ID: mdl-17067139

ABSTRACT

Thoracic epidural anaesthesia in anaesthetized children requires a meticulous technique and may have an increased success rate when the distance between skin and epidural space is known. The objective of this observational study was to measure the skin to epidural distance (SED) during thoracic epidural puncture in 61 children. The epidural puncture was performed using the loss of resistance technique with saline 0.9%. The distance from the needle tip to the point where the needle emerged from the skin was measured. The post-operative analgesia parameters were also measured. Skin to epidural distance correlated significantly with the age and weight of the children. The equation for the relation between SED (cm) and age was 2.15 + (0.01 x months) and for SED vs weight was 1.95 + (0.045 x kg). Despite considerable variability among individuals, the observed correlation of SED with both age and weight shows that this parameter may be helpful to guide thoracic epidural puncture in anaesthetized children.


Subject(s)
Analgesia, Epidural/methods , Anesthesia, Epidural/methods , Epidural Space/anatomy & histology , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Linear Models , Male , Needles , Pain, Postoperative/drug therapy , Prospective Studies
13.
Ned Tijdschr Geneeskd ; 150(11): 635-6, 2006 Mar 18.
Article in Dutch | MEDLINE | ID: mdl-16610508

ABSTRACT

The medical benefits of nighttime missions by one single helicopter emergency medical service for trauma patients in the Netherlands are probably outweighed by the high risk for the crew and the general obstacles to nighttime flight operations. It is doubtful whether one nighttime trauma helicopter will have a favourable effect on the morbidity and mortality due to major trauma in the Netherlands. However, extending the role of regional centres in pre-hospital emergency medicine could be an approach to achieving long-term improvements in trauma care.


Subject(s)
Air Ambulances , Emergency Medical Services/statistics & numerical data , Humans , Mortality/trends , Netherlands , Transportation of Patients/methods
14.
J Sch Health ; 71(5): 167-72, 2001 May.
Article in English | MEDLINE | ID: mdl-11393927

ABSTRACT

An estimated 40% of children and adolescents with chronic health conditions such as cancer, diabetes, and hemophilia, experience school-related problems. Many children living with a chronic illness do not need or may not qualify for traditional special education programs, yet they may have unmet learning needs associated with chronic absenteeism, disease symptoms, or side effects of medical treatments. Using principles of family-centered schools, a coalition of schools, families, pediatricians, and nurses can work cooperatively to help students with chronic conditions succeed. This article describes the second phase of an ongoing initiative designed to support public schools in their efforts to meet the health and education needs of students with chronic health conditions.


Subject(s)
Chronic Disease , Disabled Children , Leadership , Learning , School Health Services/organization & administration , Adolescent , Child , Curriculum/standards , Family , Female , Humans , Male , New Hampshire , Program Evaluation
15.
Intensive Care Med ; 26(4): 462-5, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10872140

ABSTRACT

OBJECTIVE: Five commercially available oesophageal balloon catheters (OBCs) were tested to evaluate the accuracy in transmitting fast-changing pressure signals which can be observed, for example, during phrenic nerve stimulation. SETTING: Research laboratory of a university hospital. METHOD: The OBCs tested varied in length (900-1390 mm) and inner diameter (0.9-1.5 mm) as well as in balloon material [latex or polyvinylchloride (PVC)]. A 180-cm tube served as a control. A sudden pressure drop was generated by the explosion of a pressurized latex balloon. The time between the pressure drop and 75, 50, 25 and 10% of the maximal pressure was measured. RESULTS: The time intervals required to transduce a pressure drop of 90% varied between the different OBCs from 85 to 476 ms (control 32 ms). Transmission time was lower in OBCs with a larger inner diameter. Shortening the OBCs resulted in a further decrease in transmission time. CONCLUSION: The type of OBC used has an impact on signal processing. An OBCs with a short transmission time should be chosen, especially if fast pressure changes are to be evaluated such as during phrenic nerve stimulation.


Subject(s)
Catheterization/instrumentation , Esophagus/physiology , Manometry/instrumentation , Analysis of Variance , Humans , Signal Processing, Computer-Assisted , Time Factors , Transducers, Pressure , Work of Breathing
16.
J Emerg Med ; 18(1): 47-50, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10645837

ABSTRACT

Male infants under the age of 3 months presenting with pyelonephritis in the presence of urinary tract malformation (UTM) are prone to transient pseudohypoaldosteronism. This may resemble congenital adrenal hyperplasia (CAH). Hyponatremia, hyperkalemia, dehydration, and metabolic acidosis are the primary findings that permit the diagnosis of CAH. We report a case of transient pseudohypoaldosteronism resulting from pyelonephritis and vesicouretric reflux. The 17-day-old boy presented with a salt-losing episode simulating adrenal insufficiency. An initial diagnosis of CAH was made. The severe metabolic imbalance resulted in ventricular flutter that resolved after correction of the metabolic acidosis and the electrolyte and volume depletion. Early diagnosis is essential because both conditions are potentially fatal and treatment differs significantly. Differential diagnosis may be achieved by urinalysis and abdominal ultrasound scan.


Subject(s)
Arrhythmias, Cardiac/etiology , Pyelonephritis/complications , Ureter/abnormalities , Vesico-Ureteral Reflux/complications , Water-Electrolyte Imbalance/etiology , Acidosis/etiology , Child , Emergencies , Humans , Infant, Newborn , Male
17.
J Sch Health ; 69(10): 392-7, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10685375

ABSTRACT

Children and adolescents with chronic illness such as asthma, diabetes, and cancer are at the intersection of the health and education systems. At school, their health needs may be attended to by a school nurse, while their educational needs may be overlooked. This article helps school personnel become more proactive in identifying the educational implications of chronic illness in school children. The confusing array of terms used to refer to this population by health professionals and educators are clarified, and estimates of the size of the population are provided. The potential impact of some common disease processes, treatments, and medications are reviewed, as are the risks of chronic absenteeism. Suggestions for how school and health professionals can identify and work with this group of children are offered.


Subject(s)
Chronic Disease , Disabled Children , Education, Special/methods , Absenteeism , Adolescent , Child , Chronic Disease/epidemiology , Chronic Disease/therapy , Educational Status , Humans , Learning , Prevalence , Surveys and Questionnaires , United States/epidemiology
18.
Clin Nephrol ; 49(3): 186-92, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9543601

ABSTRACT

To evaluate storage iron deficiency and iron-deficient erythropoiesis we determined, in a cross-sectional study of 95 patients mainly including end-stage renal disease patients (ESRD) with (32) and without rh-EPO therapy (55), the following parameters: hemoglobin, mean corpuscular red cell volume, ferritin, transferrin saturation (TS), zinc protoporphyrin (ZPP) and soluble transferrin receptor (TfR). In the dialysis group the percentage of positive samples with each marker of tissue iron supply defined as TS < 20%, ZPP > 40 mumol/mol Heme and TfR > 3.05 microgram/ml was as follows: TS 43.7% and 32.2% at a diagnostic threshold level of < 16%, ZPP 33.3% and TfR 17.2%. Manifest storage iron deficiency defined as ferritin < 30 ng/ml was observed in 5.7% of the samples while the mean ferritin concentration of the rh-Epo treated dialysis patients was 509.3 ng/ml compared to 262.5 ng/ml in the group without rh-EPO therapy. These data reflect a generous iron substitution in our series taking a TS < 20% as an intervention criterion. Looking at the different results of the three markers the best correspondence was found between ZPP and TfR resulting in a weak positive correlation (+0.64). In conclusion, we found quite different results with different assays when evaluating endogenous iron availability in our series of mainly ESRD patients in a cross-sectional study. Because a gold-standard is not defined further firm conclusions cannot be drawn from this type of study. The adequacy of the different parameters of iron metabolism including threshold levels and, consequently, the decision and route of iron substitution deserve an evaluation in a longitudinal study to characterize the best marker or marker combination in this setting.


Subject(s)
Anemia, Iron-Deficiency/diagnosis , Kidney Failure, Chronic/complications , Protoporphyrins/blood , Receptors, Transferrin/blood , Adult , Aged , Aged, 80 and over , Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/etiology , Anemia, Iron-Deficiency/therapy , Biomarkers/blood , Erythrocyte Indices , Erythropoiesis , Erythropoietin/therapeutic use , Female , Ferritins/analysis , Hemoglobins/analysis , Humans , Iron/blood , Kidney Failure, Chronic/blood , Male , Middle Aged , Recombinant Proteins , Transferrin/analysis
19.
Blood ; 90(10): 3967-77, 1997 Nov 15.
Article in English | MEDLINE | ID: mdl-9354665

ABSTRACT

The factor XII gene from 31 unrelated factor XII-deficient patients from Germany, Switzerland, and Austria was screened for mutations at the genomic level. Several novel mutations were detected and their absence in a control group of 74 healthy unrelated individuals was checked. Most changes are in the serine protease domain affecting the catalytic triad His-393-Asp-442-Ser-544; two missense mutations, R398Q (arginine 398 to glutamine; gene bank accession no. U71276) and L395M (leucine 395 to methionine; gene bank accession no. U71277), are close to the active site histidine at position 393. Another mutation detected in a cross-reacting material (CRM)-positive female with a history of three abortions affects the active site aspartic acid by changing it to asparagine (D442N; gene bank accession no. U71275). The novel mutation G570R (glycine 570 to arginine; gene bank accession no. U71274) giving rise to a CRM-positive phenotype is located next to Cys571, which forms a vital disulfide bridge. Two mutations are causing reading frame shifts: one single basepair deletion in exon 12 [exon 12: 10590(DelC); gene bank accession no. U71278] and one acceptor splice site mutation [exon 14: 11397(G --> A); gene bank accession no. L43615]. The putative regulatory mutation exon 1:-8 (g --> c) in the upstream region of the gene is associated with an aberrant Taq I restriction site allele in intron B of the gene (gene bank accession no. X80393).


Subject(s)
Alleles , Factor XII/genetics , Mutation , Europe , Female , Genome, Human , Humans , Male , Pedigree
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