Economic Credentialing

In the 1990s, hospital management and trustees introduced the concept of evaluating physicians for appointment, reappointment, and privilege delineation with the addition of financial criteria. Although emergency physicians are advocates for cost-effective care, they must make certain that credentials are determined by the provision of quality medical care, and that if economic criteria are used, the criteria chosen truly reflect quality of care. [Schafermeyer RW: Economic credentialing. Ann Emerg Med December 1997; 30:759-764.]     

Prevention of duodenal ulcer occurrence. Double-blind comparison of ranitidine and cimetidine

We compared ranitidine and cimetidine in maintenance therapy to prevent duodenal ulcer recurrence over a period of 24 months. Endoscopic examination at the end of 12 months showed that the ulcers of 26 of 31 patients (84%) on ranitidine in a dose of 150 mg remained healed and of 10 of 13 (77%) patients on cimetidine in a dose of 400 mg at night remained healed. Thirty-four patients continued in an open evaluation of ranitidine in a dose of 150 mg at night for a further 12-month period, and during this time there were four further recurrences. Life table estimates of duodenal ulcer recurrence during the 2-year period showed no significant difference between the two forms of treatment.     

Therapeutic immunization against Helicobacter mustelae in naturally infected ferrets

BACKGROUND & AIMS: Helicobacter infection of the gastric antrum is responsible for a number of gastric disorders. Antibiotic therapy is lengthy and is not always effective. It has been shown previously that oral immunization against Helicobacter felis in mice can prevent colonization after challenge. The aim of this study was to investigate the efficacy of therapeutic immunization in eradicating an established Helicobacter infection and in reducing gastritis. METHODS: Domestic ferrets, confirmed to be infected with Helicobacter mustelae by gastric endoscopy, were orally immunized with varying doses of purified Helicobacter pylori urease in combination with the mucosal adjuvant cholera toxin. Ferrets were assessed 1 week and 6 weeks after treatment for infection and pathology. RESULTS: Therapeutic immunization eradicated Helicobacter colonization in 30% of all immunized ferrets, although there was no difference in efficacy between the varying doses of antigen tested. The difference was statistically significant when compared with animals administered cholera toxin alone or buffer (P = 0.04). The intensity of inflammation was also significantly reduced in immunized animals (P = 0.0003). CONCLUSIONS: Oral immunization with purified H. pylori urease and cholera toxin can eradicate H. mustelae in a natural host pathogen model. Oral immunization of chronically infected animals markedly reduced gastric inflammation. (Gastroenterology 1996 Jun;110(6):1770-5)     

Covalent crosslinking of human coagulation factor V by activated factor XIII from guinea pig megakaryocytes and human plasma

Coagulation factor V (FV) has been shown to be synthesized in both the liver and megakaryocytes. We now present evidence that FV can be covalently crosslinked by an enzyme originating from megakaryocytes to form polymeric multimers of factor V. The guinea pig megakaryocyte enzyme appears to be factor XIIIa since the FV-crosslinking activity (1) had an absolute requirement for Ca++, (2) was completely inhibited by iodoacetamide, 5,5'-dithiobis- (2-nitrobenzoic acid), p- chloromercuribenzene sulfonic acid, and N-ethylmaleimide, all known alkylators of the thiol group at the active site of the factor XIIIa, (3) was blocked by known pseudoamine donor substrates of factor XIIIa including dansylcadaverine and putrescine, and (4) could be directly demonstrated in the guinea pig megakaryocyte lysate by a specific activity staining procedure. No tranglutaminase was detected in guinea pig megakaryocytes in contrast to red cells and liver. A similar pattern of covalent crosslinking of human FV by purified activated human plasma factor XIII was also demonstrated. Analysis of the crosslinked products of FV formed by the guinea pig enzyme by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) indicates the formation of intermediate as well as higher molecular weight polymers, suggesting that the crosslinking is a stepwise polymerization process.     

Heterogeneity in a lymphoid tumor: coexpression of T and B surface markers

Heterogeneity of leukemic cells was defined in a case of lymphoma. Four phenotypically distinct subpopulations of leukemic cells were identified. One subpopulation was observed to simultaneously express B- and T-cell characteristics. B-cell characteristics included monoclonal IgM (lambda) surface immunoglobulin, HLA-DR antigens, and expression of the B-cell antigen identified by the BA-1 monoclonal antibody. T-cell characteristics included E-rosette formation, expression of the pan-T- associated antigens recognized by the Leu-1 and OKT-11 monoclonal antibodies, and expression of the suppressor cytotoxic T-cell- associated antigen recognized by the Leu-2 and OKT-8 monoclonal antibodies. In addition to this subpopulation, three other phenotypically distinct subpopulations were identified, two of which expressed monoclonal IgM (lambda) surface immunoglobulin. The results of this investigation indicates that three phenotypically distinct lymphoid subpopulations bearing B-cell characteristics, and probably a fourth T-cell subgroup, were derived from a common lineage. These findings suggest that the malignancy involved a lymphoid progenitor cell that may possess diverse maturational capacity.     

Mode-of-action and human relevance framework analysis for rat Leydig cell tumors associated with sulfoxaflor

Abstract

Sulfoxaflor, a molecule that targets sap-feeding insects, was assessed for carcinogenic potential in groups of 50 Fischer rats fed with diets containing 0, 25, 100, 500 (males), or 750 (females) ppm sulfoxaflor for 2 years according to OECD 453. Sulfoxaflor did not alter the number of rats with Leydig cell tumors (LCTs: 88% of controls and 90–92% in treated groups). The size of LCT was increased at 100 and 500 ppm. The spontaneous incidence of LCT in Fischer rat is 75–100% compared with less than 0.01% in humans. These fundamental interspecies differences in spontaneous incidence of LCT are the result of quantitative and qualitative differences in Leydig cell response to hormonal stimuli. There are nine known modes of actions (MoA) for LCT induction. Analysis sulfoxaflor data suggested a hormone-based dopamine enhancement MoA causing the LCT effect through: 1) increased neuronal dopamine release via specific dopaminergic neuron-based nicotinic acetylcholine receptor (nAChR) agonism, leading to 2) decreased serum prolactin (Prl) levels, 3) downregulation of luteinizing hormone receptor (LHR) gene expression in Leydig cells, 4) transient decreases in serum testosterone, 5) increased serum LH levels, and 6) promotion of LCTs. The analysis suggested that sulfoxaflor promoted LCTs through a subtle stimulation of dopamine release. The MoA for LCT promotion in the carcinogenicity study is considered to have no relevance to humans due to qualitative and quantitative differences between rat and human Leydig cells. Therefore, the Fischer 344 rat LCT promotion associated with lifetime administration of high-dose levels of sulfoxaflor would not pose a cancer hazard to humans.     

Modification of conventional glass-ionomer cements with N-vinylpyrrolidone containing polyacids, nano-hydroxy and fluoroapatite to improve mechanical properties

OBJECTIVE: The objective of this study was to enhance the mechanical strength of glass-ionomer cements, while preserving their unique clinical properties. METHODS: Copolymers incorporating several different segments including N-vinylpyrrolidone (NVP) in different molar ratios were synthesized. The synthesized polymers were copolymers of acrylic acid and NVP with side chains containing itaconic acid. In addition, nano-hydroxyapatite and fluoroapatite were synthesized using an ethanol-based sol-gel technique. The synthesized polymers were used in glass-ionomer cement formulations (Fuji II commercial GIC) and the synthesized nanoceramic particles (nano-hydroxy or fluoroapatite) were also incorporated into commercial glass-ionomer powder, respectively. The synthesized materials were characterized using FTIR and Raman spectroscopy and scanning electron microscopy. Compressive, diametral tensile and biaxial flexural strengths of the modified glass-ionomer cements were evaluated. RESULTS: After 24h setting, the NVP modified glass-ionomer cements exhibited higher compressive strength (163-167MPa), higher diametral tensile strength (DTS) (13-17MPa) and much higher biaxial flexural strength (23-26MPa) in comparison to Fuji II GIC (160MPa in CS, 12MPa in DTS and 15MPa in biaxial flexural strength). The nano-hydroxyapatite/fluoroapatite added cements also exhibited higher CS (177-179MPa), higher DTS (19-20MPa) and much higher biaxial flexural strength (28-30MPa) as compared to the control group. The highest values for CS, DTS and BFS were found for NVP-nanoceramic powder modified cements (184MPa for CS, 22MPa for DTS and 33MPa for BFS) which were statistically higher than control group. CONCLUSION: It was concluded that, both NVP modified and nano-HA/FA added glass-ionomer cements are promising restorative dental materials with improved mechanical properties.     

Direct evidence for the interaction of the nucleotide affinity analog 5'-p-fluorosulfonylbenzoyl adenosine with a platelet ADP receptor

Previous reports have indicated that the nucleotide affinity analog 5'- p-fluorosulfonylbenzoyl adenosine (FSBA) at concentrations between 40 and 100 mumol/L and at times greater than 20 minutes covalently modifies a single protein component on the external platelet membrane surface and that adenosine diphosphate (ADP) protects against this reaction. That this protein is an ADP receptor linked to platelet activation is shown by FSBA inhibition of ADP-mediated platelet shape change, aggregation, and fibrinogen receptor exposure. In this report, further evidence for the interaction of FSBA with the ADP receptor on platelets is provided by the observation that FSBA at high concentrations (100 to 500 mumol/L) behaves as a weak agonist to produce platelet shape change within one minute as detected by spectroscopic assay and scanning electron microscopy with concomitant phosphorylation of the light chain of platelet myosin. The specificity of FSBA as an agonist is demonstrated by inhibition of FSBA-induced shape change by ATP and the covalent incorporation of SBA as well as the failure of 5'-fluorosulfonylbenozoyl guanosine (FSBG) to cause shape change. In contrast, incubation of platelets with low concentrations of [3H]-FSBA (40 mol/L) is not associated with stimulation of platelet shape change or myosin light chain phosphorylation.