Treatment for nephrolithiasis has evolved because of the dissemination of less invasive techniques, such as ureteroscopy and shock wave lithotripsy. We examined temporal trends in PCNL use and ...characterized the determinants of a prolonged LOS and in-hospital mortality to provide insight into the evolution of practice patterns for nephrolithiasis treatment.
We abstracted data on 12,948 patients undergoing percutaneous procedures for urinary calculi between 1988 and 2002 from the Nationwide Inpatient Sample using International Classification of Disease, 9th revision, Clinical Modification procedure and diagnostic codes. A weighted sample was used to estimate national PCNL use rates. Adjusted models were constructed to measure the association of hospital structure and patient demographics with mortality and a prolonged LOS (greater than 90th percentile).
Annual PCNL use increased temporally during the study from 1.2/100,000 to 2.5/100,000 United States residents (p <0.0001). The in-hospital mortality rate was low at 0.2%, although a volume-outcome relationship was still evident (high and low volume 0.1% and 0.2%, respectively, p = 0.002). Treatment at hospitals with lower hospital PCNL volume and lower discharge volume (all diagnoses) was associated with an increasing likelihood of in-hospital mortality (each p <0.01).
Despite the advent of less invasive techniques PCNL remains a popular means of managing stone disease. Although mortality was rare, it was significantly lower at high than at low volume hospitals. Low short-term mortality rates coupled with shorter LOS and high success rates may make PCNL increasingly palatable from a patient perspective and provide a potential basis for its increasing use.
3YSZ green layers approximately 10 μm thick were screen printed onto 3YSZ substrates up to 300 μm in thickness. The stress induced by constrained sintering of the film (between 1150° and 1350°C) was ...measured by monitoring the bending displacement of vertical strips of bilayers using a long‐distance microscope. In order to deduce the stress it was first necessary to measure the creep properties of the substrates by monitoring the bending of horizontal beams under gravity. The creep strain rate of the 3YSZ substrates was linearly dependent on applied stress at the low stresses and strains involved in the present work. The creep viscosity appeared to increase with strain (time), which might be due to changes in grain‐boundary composition, and had higher activation energy at temperatures above approximately 1250°C. The magnitudes of the creep viscosities are in reasonable agreement with other creep data in the literature for 3YSZ.
The in‐plane stress induced during constrained sintering of the 3YSZ films had a maximum value of approximately 3 MPa at 1200°C. This behavior is consistent with literature results reported for constrained sintering of bulk alumina. The stress induced by the constraint is of a similar order to the estimated sintering potential.
The detection of leukemia cells on newborn genetic screening cards (“Guthrie cards”) of a small group of patients and several sets of identical twins developing acute lymphoblastic leukemia (ALL) ...with identical phenotypic and chromosomal markers has provided evidence that childhood ALL cases may arise in utero. We conducted a retrospective study of a randomly selected group of childhood B-precursor ALL patients to determine the frequency of the presence of “leukemic” clones prenatally in ALL cases by testing newborn screening cards. The 17 ALL patients analyzed had a median age of 46 months (range, 18 months to 13 years) and had median presenting white blood cell (WBC) counts of 10 950/µL (range, 2900-70 300/µL) at diagnosis. A clonal rearrangement of the immunoglobulin heavy chain (IgH) gene was identified in diagnostic lymphoblasts and sequenced and patient-specific primers were used to amplify DNA from blood samples on the patient's newborn screening cards. Twelve of the 17 (71%) analyzed newborn cards had detectable IgH rearrangements amplified by seminested polymerase chain reaction. DNA sequencing confirmed that the IgH rearrangements detected matched the IgH sequences identified from diagnostic leukemia cells, indicating the presence of a “leukemic” clone at birth. There were no differences in age or presenting WBC counts between the cases with or without positive newborn screening cards. All 6 patients with hyperdiploid ALL had detectable “leukemic” clones on their cards. The results of our study support the notion that a high proportion of childhood B-precursor ALL cases arise in utero, although postnatal events are also important factors in leukemogenesis.
Aging is the single largest risk factor for most chronic diseases, and thus possesses large socioeconomic interest to continuously aging societies. Consequently, the field of aging research is ...expanding alongside a growing focus from the industry and investors in aging research. This year's 8th Annual Aging Research and Drug Discovery (ARDD) meeting was organized as a hybrid meeting from August 30th to September 3rd 2021 with more than 130 attendees participating on-site at the Ceremonial Hall at University of Copenhagen, Denmark, and 1800 engaging online. The conference comprised of presentations from 75 speakers focusing on new research in topics including mechanisms of aging and how these can be modulated as well as the use of AI and new standards of practices within aging research. This year, a longevity workshop was included to build stronger connections with the clinical community.
The binding of fibrinogen to its platelet receptor, the glycoprotein IIb-IIIa complex, is mediated, in part, by an Arg-Gly-Asp (RGD) sequence within the fibrinogen Aα chain. PAC1 is an IgM-κ murine ...monoclonal antibody that binds to the platelet fibrinogen receptor, and its binding is inhibited by both fibrinogen and RGD-containing peptides. To identify the regions of PAC1 that interact with the fibrinogen receptor, we determined the mRNA sequences of PAC1 immunoglobulin heavy and light chain variable regions. Five out of the six complementarity-determining regions (CDRs) of PAC1 had entirely germline sequences with no regions of similarity to fibrinogen. However, CDR3 of the PAC1 heavy chain (H-CDR3) was very large and unique due to the insertion of a novel D region segment. H-CDR3 contained a sequence, Arg-Tyr-Asp (RYD), that, if present in the proper conformation, might behave like the RGD sequence in fibrinogen. A 21-residue synthetic peptide encompassing the H-CDR3 region inhibited fibrinogen-dependent platelet aggregation as well as the binding of PAC1 (Ki = 10 µM) and fibrinogen (Ki = 5 µM) to activated platelets. The RYD region of H-CDR3 appeared to be central to its function, because substitution of the tyrosine with glycine increased the inhibitory potency of the peptide by 10-fold, while replacing the tyrosine with D-alanine or inverting the RYD sequence sharply reduced the inhibitory potency. Thus, the linear sequence, RYD, within H-CDR3 of PAC1 appears to mimic the RGD receptor recognition sequence in fibrinogen. This type of immunologic approach could be useful in studying the structural basis of other receptor-ligand interactions.
Understanding the requirements for protection against pneumococcal carriage and pneumonia will greatly benefit efforts in controlling these diseases. Recently, it has been shown that genetic ...polymorphisms can result in diminished expression of CCL5, which results in increased susceptibility to and progression of infectious diseases. We show that CCL5, together with Th cytokine mRNA expression, is temporally up-regulated during pneumococcal carriage. To determine the contribution of CCL5 to pneumococcal surface antigen A-specific humoral and cellular pneumococcal immunity, mice were treated with anti-CCL5 or control Abs before and during Streptococcus pneumoniae strain EF3030-challenge for the initiation of carriage. CCL5 blockade resulted in a decrease of CD4(+) and CD8(+) T cells as well as CD11b(+) cells in the spleen, cervical lymph node, lung, and nasopharyngeal associated lymphoid tissue during the recognition phase of the pneumococcal adaptive immune response. CCL5 blockade significantly reduced the Ag-specific IgG2a and IgG1 Abs in serum and IgA Ab levels in nasal washes. These decreases also corresponded to reductions in Ag-specific T cell (mucosal and systemic) responses. CCL5 inhibition resulted in decreasing the quantity of IL-4- and IFN-gamma-secreting CD4(+) T cells and increasing the number of Ag-specific IL-10-producing CD4(+) T cells; these changes combined also corresponded with the transition from pneumococcal carriage to lethal pneumonia. These data suggest that CCL5 is an essential factor for the induction and maintenance of protective pneumococcal immunity.
Single injections of recombinant cytokines/chemokines into tissue have provided insights into their possible roles during the inflammatory response. Adenoviral technology may allow us to mimic the in ...vivo situation more closely, with protein generated in a continuous but transient fashion. Replication-deficient human type 5 adenovirus containing a rat macrophage inflammatory protein-2 (MIP-2) gene insertion and cytomegalovirus promoter was injected into the mouse brain to investigate the inflammatory response to continuous overproduction of MIP-2. Adenovirus with a LacZ gene insertion expressing beta-galactosidase was used as a control. At doses of 10(4) to 10(7) plaque-forming units, a minimal inflammatory response was detected to the LacZ virus, with leukocyte recruitment that was restricted to the injection site. A dose of 10(7) plaque-forming units of both the LacZ and the MIP-2 vector produced extensive transgene product expression that persisted for at least 7 days. Astrocytes, recognized by their morphology, were the predominant cell type expressing MIP-2 and beta-galactosidase. A dose of 10(7) plaque-forming units of MIP-2 vector caused dramatic polymorphonuclear leukocyte (PMN) recruitment to the brain parenchyma after 2 days. PMN recruitment was still observed after 4 and 7 days, but had become more localized to the injection site and was associated with numerous foam-like macrophages. At both 2 and 7 days the blood-brain barrier was breached in the region of leukocyte recruitment. Despite the extent of leukocyte recruitment there were no overt signs of neuronal degeneration or demyelination. Our findings demonstrate that continuous production of MIP-2 in the CNS results in persistent PMN recruitment to the brain parenchyma with no evidence of tachyphylaxis. The lack of PMN recruitment to the brain parenchyma following CNS injury may be a result of deficient production of PMN chemoattractants.
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