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71.
Carlos R Ferreira Kristina Kintzinger Mary E Hackbarth Ulrike Botschen Yvonne Nitschke M Zulf Mughal Genevieve Baujat Dirk Schnabel Eric Yuen William A Gahl Rachel I Gafni Qing Liu Pedro Huertas Gus Khursigara Frank Rutsch 《Journal of bone and mineral research》2021,36(11):2193-2202
Generalized arterial calcification of infancy (GACI) is a rare disorder caused by ENPP1 or ABCC6 variants. GACI is characterized by low pyrophosphate, arterial calcification, and high mortality during the first year of life, but the natural course and possible differences between the causative genes remain unknown. In all, 247 individual records for patients with GACI (from birth to 58.3 years of age) across 19 countries were reviewed. Overall mortality was 54.7% (13.4% in utero or stillborn), with a 50.4% probability of death before the age of 6 months (critical period). Contrary to previous publications, we found that bisphosphonate treatment had no survival benefit based on a start-time matched analysis and inconclusive results when initiated within 2 weeks of birth. Despite a similar prevalence of GACI phenotypes between ENPP1 and ABCC6 deficiencies, including arterial calcification (77.2% and 89.5%, respectively), organ calcification (65.8% and 84.2%, respectively), and cardiovascular complications (58.4% and 78.9%, respectively), mortality was higher for ENPP1 versus ABCC6 variants (40.5% versus 10.5%, respectively; p = 0.0157). Higher prevalence of rickets was reported in 70.8% of surviving affected individuals with ENPP1 compared with that of ABCC6 (11.8%; p = 0.0001). Eleven affected individuals presenting with rickets and without a GACI diagnosis, termed autosomal recessive hypophosphatemic rickets type 2 (ARHR2), all had confirmed ENPP1 variants. Approximately 70% of these patients demonstrated evidence of ectopic calcification or complications similar to those seen in individuals with GACI, which shows that ARHR2 is not a distinct condition from GACI but represents part of the spectrum of ENPP1 deficiency. Overall, this study identified an early mortality risk in GACI patients despite attempts to treat with bisphosphonates, high prevalence of rickets almost exclusive to ENPP1 deficiency, and a spectrum of heterogenous calcification and multiple organ complications with both ENPP1 and ABCC6 variants, which suggests an overlapping pathology. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA. 相似文献
72.
Rachel Wuerstlein Nadia Harbeck Eva-Maria Grischke Dirk Forstmeyer Raquel von Schumann Petra Krabisch Kerstin Lüdtke-Heckenkamp Andrea Stefek Oliver Stoetzer Andrea Grafe Gabriele Kaltenecker Helmut Forstbauer Doris Augustin Iris Schrader Joke Tio Ulrike Nitz Oleg Gluz Ronald E. Kates Monika Karla Graeser 《Breast care (Basel, Switzerland)》2021,16(1):50
BackgroundProtroca evaluated the efficacy and safety of primary and secondary prophylaxis of neutropenia with lipegfilgrastim (Lonquex®) in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy (CT).Patients and MethodsOf the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients for the per-protocol set. Primary and secondary end points after lipegfilgrastim treatment were assessed.ResultsNine patients of the ITT set receiving lipegfilgrastim as primary prophylaxis (n = 222) had febrile neutropenia of grade 3–4 (5 patients) or infection of grade 3–4 (4 patients); 1/26 of those receiving secondary prophylaxis had an event. Dose reductions were performed in 9.5% of the patients. Postponement of cancer CT cycles for >3 days occurred in <15% of patients; 10.8% (92/851 AEs) and 8% (2/25 SAEs) of documented adverse events and serious adverse events, respectively, were related to lipegfilgrastim.ConclusionsApplication of lipegfilgrastim was effective as primary and secondary prophylaxis in the prevention of CT-induced neutropenia in breast cancer. 相似文献
73.
During preparation of cells for experimentation a considerable amount of bound substance is lost. Our aim was to develop a protocol which retained lectin binding to an extent similar to living cells. This procedure would use fixation procedures suited for fluorescent lectin conjugates and gold-conjugates to be visualized by light- and electron microscopy, respectively. We tested glutaraldehyde and paraformaldehyde in different concentrations before and after lectin binding, different buffers and divalent cations, as additives, to determine the effects on preservation of lectin binding. Lectin binding was visualized and semiquantitatively evaluated by image analysis in the light microscope after silver enhancement of lectin-gold conjugates and by using tetramethyl rhodaminyl isothiocyanate (TRITC)-conjugated lectins. Preservation of lectin binding was best visualized with fluorescent lectin conjugates, whereas during silver enhancement procedures of gold-conjugated lectins, a considerable amount of bound lectins was lost. In general, lectin binding to living cells followed by fixation is superior to fixation before lectin binding. Unfavourable combinations of fixatives and buffers can cause a loss of more than 90% bound lectin. In our experiments with freshly isolated guinea pig cardiomyocytes, lectin binding was best when we used Na-cacodylate buffer with glutaraldehyde fixation (0.1%) after binding of lectins to the living cells. 相似文献
74.
Justin Leube Anton Mühlbauer Immanuel Andrä Madleen Biggel Dirk H. Busch Lorenz Kretschmer Veit R. Buchholz 《European journal of immunology》2023,53(3):2250009
T cell ignorance is a specific form of immunological tolerance. It describes the maintenance of naivety in antigen-specific T cells in vivo despite the presence of their target antigen. It is thought to mainly play a role during the steady state, when self-antigens are presented in absence of costimulatory signals and at low density or to T cells of low affinity. In how far antigen-specific T cells can also remain clonally ignorant to foreign antigens, presented in the inflammatory context of systemic infection, remains unclear. Using single-cell in vivo fate mapping and high throughput flow cytometric enrichment, we find that high-affinity antigen-specific CD8+ T cells are efficiently recruited upon systemic infection. In contrast, most low-affinity antigen-specific T cells ignore the priming antigen and persist in the naïve state while remaining fully responsive to subsequent immunization with a high-affinity ligand. These data establish the widespread clonal ignorance of low-affinity T cells as a major factor shaping the composition of antigen-specific CD8+ T cell responses to systemic infection. 相似文献
75.
Very-long-baseline radio interferometry (VLBI) observations of gamma-ray blazars: results from millimeter-VLBI observations 下载免费PDF全文
Krichbaum TP Britzen S Standke KJ Witzel A Schalinski CJ Zensus JA 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(25):11377-11380
VLBI observations of the extremely gamma-bright blazar PKS 0528+134 at 8, 22, 43, and 86 GHz reveal a strongly bent one-sided-core jet structure with at least three moving and two apparently stationary jet components. At the highest observing frequencies the brightest and most compact jet component (the VLBI core) is unresolved with an upper limit to its size of approximately 50 microarcsec corresponding to approximately 0.2 parsec [H0 = 100 km.s-1.Mpc-1 (megaparsec-1), q0 = 0.5, where H0 is Hubble constant and q0 is the deceleration parameter]. Two 86-GHz VLBI observations performed in 1993.3 and 1994.0 reveal a new jet component emerging with superluminal speed from the core. Linear back-extrapolation of its motion yields strong evidence that the ejection of this component is related to an outburst in the millimeter regime and a preceding intense flare of the gamma-flux density observed in early 1993. This and the radio/optical "light curves" and VLBI data for two other sources (S5 0836+710 and 3C 454.3) suggest that the observed gamma-radiation might be Doppler-boosted and perhaps is closely related to the physical processes acting near the "base" of the highly relativistic jets observed in quasars. 相似文献
76.
Nader Gordjani Rainer Burghard Dirk Müller Helga Mathäi Gunther Mergehenn Jekabs U. Leititis Matthias Brandis 《Pediatric nephrology (Berlin, Germany)》1995,9(4):419-422
The potential tubulotoxicity of tobramycin and cefotaxim were assessed in neonates by measuring the urinary level of adenosine deaminase binding protein (ABP) and urinary 1-microglobulin and 2-microglobulin. In a prospective study, 33 neonates who received tobramycin and cefotaxim for suspected neonatal sepsis were compared with 48 untreated newborns during the first 10 days of life. The urinary concentrations of ABP and its excretion rates, corrected for body weight and body surface area, were significantly increased from the 1st day of treatment. Urinary 1-microglobulin and 2-microglobulin were not elevated under tobramycin and cefotaxim during the first 2 days of treatment. We conclude that ABP may be a sensitive marker for the detection of proximal renal tubular injury during tobramycin and cefotaxim treatments of neonates. The increase in urinary ABP which occurs before an elevation of urinary 1-microglobulin and 2-microglobulin may reflect earlier structural than functional alterations. However, since none of the treated infants had signs of electrolyte disorders or glomerular dysfunction, the clinical relevance of ABP measurement should be reevaluated. 相似文献
77.
Walter L. Strohmaier Anemone M. Carl Dirk M. Wilbert K.-Horst Bichler 《The Journal of urology》1996,155(1):48-51
Purpose
There is ongoing controversy regarding blood pressure changes after extracorporeal shock wave lithotripsy (ESWL*). Experimental data suggest a role for renin but only few data are relevant to humans. It has been shown that renin secretion is stimulated by endothelin, a recently discovered peptide with strong vasoconstrictive properties and stimulating effects on renin secretion. Endothelin is relevant in the development of hypertension and acute renal failure.*Dornier Medical Systems, Inc., Marietta, Georgia.Materials and Methods
In a prospective study of 48 normotensive patients undergoing ESWL for renal stones the influence of high energy shock waves on plasma endothelin and active renin was analyzed. These substances are secreted by renal cells in response to hemodynamic alterations, and inflammatory and traumatic processes. Peripheral blood samples were analyzed for active renin and endothelin before, and immediately, 1, 3 and 5 days after ESWL. Blood pressure was measured before, and 1, 3 and 5 days after ESWL.Results
Only a slight and transient increase was noted in active renin, which was in the same range as that found after mental stress. Endothelin and blood pressure were not significantly influenced by ESWL. There was no correlation between endothelin and active renin. Thus, the increase in active renin was not mediated by endothelin.Conclusions
The transient increase in active renin cannot be attributed to the development of hypertension. The lack of influence of ESWL on endothelin indicates that ESWL, at least in the routine clinical setting, does not cause severe renal trauma. 相似文献78.
Udo Kaisers Dirk Pappert Jan M. Langrehr Horst Undi Peter Neuhaus Rolf Rossaint 《Transplant international》1996,9(3):214-220
The purpose of this study was to determine the effects of vasoactive treatment with dopamine (DO), dopexamine (DX), and dobutamine (DOB) on hemodynamics, oxygen transport and hepatic venous oxygen saturation (SvhO2) after orthotopic liver transplantation (OLT). A pulmonary artery catheter was inserted into the right hepatic vein of 17 OLT patients. Timed infusion of DO, DX, and DOB was performed at the following rates: DO at 4 and 8 g/kg per minute, and DOB at 5 and 10 g/kg per minute. Hemodynamics, oxygen transport variables, and SvhO2 were assessed. Each catecholamine induced a significant increase in cardiac index, oxygen delivery, and SvhO2. Mean arterial pressure was increased during DO and DOB, but significantly reduced during DX. Each inotrope increased oxygen delivery in parallel with SvhO2, suggesting a corresponding increase in hepatic oxygen supply. Therefore, it appears that each vasoactive drug may be utilized in OLT patients to provide oxgen delivery without impairment of splanchnic oxygenation. 相似文献
79.
Matthias C. Angermeyer Dirk R. Schwoon 《Social psychiatry and psychiatric epidemiology》1982,17(1):13-22
Zusammenfassung Mit Hilfe eines Persönlichkeitsfragebogens (Gießen-Test), der von beiden Eltern und dem schizophrenen Kranken bei dessen Entlassung aus der ersten stationären psychiatrischen Behandlung ausgefüllt worden war, wurde die Personenwahrnehmung und damit mittelbar die Beziehung in der Familie untersucht. Über alle drei Selbstbilder und sechs Fremdbilder von insgesamt 28 Familien mit einem schizophrenen Sohn sowie von 29 als Vergleichsgruppe dienenden Familien mit einem chirurgisch kranken Sohn wurde eine Clusteranalyse berechnet, die die Abgrenzung von fünf Clustern erlaubte, von denen zwei vor allem durch Familien mit Schizophrenen und zwei vor allem durch solche mit organisch kranken Söhnen gebildet wurden; ein Cluster war unspezifisch. Ein 2-Jahres-follow-up ergab, daß 13 schizophrene Kranke erneut die Klinik aufsuchen mußten. Es fand sich keine statistisch bedeutsame Beziehung zwischen den untersuchten psychiatrischen und soziodemographischen Parametern und dem Rehospitalisierungsrisiko. Als besonders gefährdet erwiesen sich jedoch Familien, in denen sich nach den Ergebnissen der Clusteranalyse ein Konflikt zwischen Eltern und Sohn um die Definition als Kranker auf dem Hintergrund rigider Normvorstellungen abbildete. Die Übernahme der Krankenrolle durch den Patienten ging hingegen nur in der Hälfte der Fälle mit einer Rehospitalisierung einher, führte also nicht zwangsläufig zur Ausgrenzung aus dem Familienverband. Söhne aus Familien, die als besonders gesund imponierten, aber auch Söhne aus Familien mit dominanten Müttern wurden im Untersuchungszeitraum nicht erneut in die Klinik aufgenommen.
Teil des von der Deutschen Forschungsgemeinschaft unterstützten Projektes Interaktion in Familien mit Schizophrenen 相似文献
Summary Patterns of personal relationships within the families of male schizophrenic patients, and their relationship to clinical course and outcome, were examined by means of a personality questionnaire (Gießen-Test), completed by both parents and by the schizophrenic patient himself at the time of discharge from his first psychiatric in-patient treatment. The test yields scores related to the self-perceptions of the individual and to his perceptions of the other nuclearfamily members. A cluster analysis was performed on all three self-perception scores and six scores of the perceptions the three family members had of each other, for a total of 28 families each with a schizophrenic son and for a control group of 29 families each with a surgically-ill son. This analysis allowed five clusters to be distinguished, two of which consisted predominantly of families with schizophrenic sons and two predominantly of families with surgically-ill sons. The remaining cluster comprised a mixed group. A two-year follow-up showed that 13 schizophrenic patients had been readmitted to hospital. There was no statistically significant relationship between the psychiatric and sociodemographic parameters examined and the re-hospitalization rate. Readmissions were, however, more frequent from families in which the research findings had indicated conflicting mutual perceptions of parents and sons, against a background of rigid notions of normality. Acceptance by the patient of the notion of being ill was associated with re-hospitalization in only about half of the cases, so that it had not necessarily led to rejection by the family unit. No patients were readmitted during the follow-up period from families which had represented themselves as particularly healthy, or from families with dominant mothers.
Teil des von der Deutschen Forschungsgemeinschaft unterstützten Projektes Interaktion in Familien mit Schizophrenen 相似文献
80.
Vermeiren R de Clippele A Deboutte D 《European archives of psychiatry and clinical neuroscience》2000,250(3):133-138
Clinicians working with young delinquents are concerned with finding methods to predict recidivism in these subjects. It
has not been investigated yet to what extent psychiatric assessment can be of any help in this field.
In this study, we investigated whether psychiatric assessment can help to predict recidivism in already delinquent adolescents.
By means of semi-structured psychiatric assessment (Child Assessment Schedule), developmental interview of the parents and
self-report instruments, we assessed the psychiatric status of 72 delinquent adolescents, adjudicated before the Juvenile
Court of Antwerp (Belgium). A follow-up of criminal status after eight months was conducted.
Self-report questionnaires by the subjects did not differentiate recidivists from non-recidivists, while parent questionnaires
did. Through a semi-structured interview, we found that a diagnosis of conduct disorder significantly predicts recidivism,
while subjects with ADHD and substance abuse show a tendency towards more recidivism. We were unable, however, due to the
small number of subjects showing a psychiatric disorder (e. g. ADHA and PTSD) unrelated to conduct disorder, to assess the
relative contribution of these disorders to the recidivism rate.
This study found that psychiatric assessment of delinquent adolescents could be of help in predicting recidivism. The necessity
of gathering information from parents and teachers is demonstrated. Future research should include a more extensive group
of a delinquent adolescent and should focus on the effect of therapeutic interventions.
Received: 29 June 1999 / Accepted: 1 February 2000 相似文献