The effect of chlorhexidine and dimethyl sulfoxide on long-term sealing ability of two calcium silicate cements in root canal.

OBJECTIVES: To evaluate the long-term effect of chlorhexidine (CHX) and dimethyl sulfoxide (DMSO) on the sealing ability and biomineralization of two different calcium silicate cements (CSC) in root canal. METHODS: Sixty human third molar root canals were obturated with ProRoot MTA or Biodentine. Before obturation the canals were irrigated with saline (control), 2% CHX or 5% DMSO. Microleakage was tested after three days and after six months. After additional six months (12 months after root filling) the roots were cut into 2 mm thick dentine discs. The discs were stored in artificial saliva for one year. The bond strength was measured with the push-out method, and the failure mode was evaluated with a stereomicroscope. The most apical disc of each tooth was used for Vickers hardness test. RESULTS: No significant differences between the groups was found in initial microleakage. The leakage increased significantly during the 6-month storage in all groups except in Biodentine-CHX group and Biodentine-DMSO group. CHX and DMSO irrigation significantly increased the leakage with ProRoot MTA with time, but there was no statistically significant difference compared to the ProRoot MTA-control group at six months' time point. CHX significantly reduced the push-out bond strength of ProRoot MTA. With Biodentine irrigation with CHX or DMSO resulted with significantly higher push-out strength compared to the Biodentine control group. Fracture analysis showed statistically significant difference in the distribution of the fractures between the groups, but neither CHX nor DMSO change the fracture pattern statistically significantly. With Vickers hardness test ProRoot MTA with and without DMSO as the final irrigant showed significantly higher dentin hardness than any Biodentine-group. SIGNIFICANCE: Considering that aging increased the leakage in all groups except with Biodentine-DMSO and the differences in the push-out strength and surface microhardness data, it appears that the time-related biomineralizing effect of MTA and Biodentine does not improve sealing to dentin. CHX significantly reduced ProRoot MTA bond strength and increased pure adhesive failures with both cements.

Clofazimine for Treatment of Cryptosporidiosis in Human Immunodeficiency Virus Infected Adults: An Experimental Medicine, Randomized, Double-blind, Placebo-controlled Phase 2a Trial.

BACKGROUND: We evaluated the efficacy, pharmacokinetics (PK), and safety of clofazimine (CFZ) in patients living with human immunodeficiency virus (HIV) with cryptosporidiosis. METHODS: We performed a randomized, double-blind, placebo-controlled study. Primary outcomes in part A were reduction in Cryptosporidium shedding, safety, and PK. Primary analysis was according to protocol (ATP). Part B of the study compared CFZ PK in matched individuals living with HIV without cryptosporidiosis. RESULTS: Twenty part A and 10 part B participants completed the study ATP. Almost all part A participants had high viral loads and low CD4 counts, consistent with failure of antiretroviral (ARV) therapy. At study entry, the part A CFZ group had higher Cryptosporidium shedding, total stool weight, and more diarrheal episodes compared with the placebo group. Over the inpatient period, compared with those who received placebo, the CFZ group Cryptosporidium shedding increased by 2.17 log2 Cryptosporidium per gram stool (95% upper confidence limit, 3.82), total stool weight decreased by 45.3 g (P = .37), and number of diarrheal episodes increased by 2.32 (P = .87). The most frequent solicited adverse effects were diarrhea, abdominal pain, and malaise. One placebo and 3 CFZ participants died during the study. Plasma levels of CFZ in participants with cryptosporidiosis were 2-fold lower than in part B controls. CONCLUSIONS: Our findings do not support the efficacy of CFZ for the treatment of cryptosporidiosis in a severely immunocompromised HIV population. However, this trial demonstrates a pathway to assess the therapeutic potential of drugs for cryptosporidiosis treatment. Screening persons living with HIV for diarrhea, and especially Cryptosporidium infection, may identify those failing ARV therapy. CLINICAL TRIALS REGISTRATION: NCT03341767.

X-Ray Absorption Spectrum of the N_{2}

The x-ray absorption spectrum of N_{2}^{+} in the K-edge region has been measured by irradiation of ions stored in a cryogenic radio frequency ion trap with synchrotron radiation. We interpret the experimental results with the help of restricted active space multiconfiguration theory. Spectroscopic constants of the 1σ_{u}^{-1} ^{2}Σ_{u}^{+} state, and the two 1σ_{u}^{-1}3σ_{g}^{-1}1π_{g} ^{2}Π_{u} states are determined from the measurements. The charge of the ground state together with spin coupling involving several open shells give rise to double excitations and configuration mixing, and a complete breakdown of the orbital picture for higher lying core-excited states.

The Effect of Chlorhexidine and Dimethyl Sulfoxide on Long-Term Microleakage of Two Different Sealers in Root Canals.

OBJECTIVE: The aim of root canal obturation is to prevent leakage and inhibit microbial invasion. This study aimed to determine the effect of chlorhexidine (CHX) and dimethyl sulfoxide (DMSO) as final irrigants on microleakage of root filling immediately and after 18 months. The hypothesis was that either CHX or DMSO would not affect the immediate or long-term microleakage. METHODS: A total of 120 human third molar root canals were obturated with RealSeal SE or Topseal and gutta percha. Before obturation, the canals were irrigated with saline (control), 2% CHX or 5% DMSO. Microleakage of half of each groups (n=10) was measured after 3 days, and of the other half was measured after 18 months with fluid filtration method. RESULTS: In immediate measurements, RealSeal SE performed significantly better in CHX-irrigated group (p=0.035; Mann-Whitney test). For both sealers, DMSO had the lowest mean microleakage values, which were also statistically significantly lower than with CHX irrigation within sealers (p<0.009 for Topseal and p=0.04 for RealSeal SE; Mann-Whitney test). With RealSeal SE, the microleakage with CHX was significantly higher than that in controls (p=0.022; Mann-Whitney test). CONCLUSION: Neither final irrigant showed statistically significant differences in the immediate microleakage within the two sealers. Irrigation with DMSO caused significantly less microleakage than CHX for both sealers after 18 months.

Electronic ground state of Ni2.

The Φ9/24 ground state of the Ni2+ diatomic molecular cation is determined experimentally from temperature and magnetic-field-dependent x-ray magnetic circular dichroism spectroscopy in a cryogenic ion trap, where an electronic and rotational temperature of 7.4±0.2 K was reached by buffer gas cooling of the molecular ion. The contribution of the spin dipole operator to the x-ray magnetic circular dichroism spin sum rule amounts to 7Tz=0.17±0.06µB per atom, approximately 11% of the spin magnetic moment. We find that, in general, homonuclear diatomic molecular cations of 3d transition metals seem to adopt maximum spin magnetic moments in their electronic ground states.

Component-resolved analysis of IgA, IgE, and IgG4 during egg OIT identifies markers associated with sustained unresponsiveness.

BACKGROUND: In a previously reported CoFAR study, 55 subjects with egg allergy underwent randomized, placebo-controlled egg oral immunotherapy (eOIT). Active treatment induced desensitization in most and sustained unresponsiveness (SU) in a smaller subset. We hypothesized that component-resolved analysis of IgE, IgG4, IgA, IgA1, and IgA2 may identify potential biomarkers of SU in OIT subjects. METHODS: Longitudinal samples for 51 egg-allergic subjects (37 active and 14 placebo) were available. Egg white (EW)-, ovalbumin (OVA)-, and ovomucoid (OVM)-specific levels of IgA, IgA1, and IgA2 were quantified by ELISA. IgE and IgG4 to these antigens were quantified using ImmunoCAP® . Clinical responders achieved SU to egg; all others were considered nonresponders. Between-group comparisons were made among active and placebo, as well as responders and nonresponders. RESULTS: No placebo subjects achieved responder status. Through month 48, among the 37 active subjects, baseline IgE-OVM was lower in responders (median 3.97 kU/l, n = 19) than in nonresponders (10.9 kU/l, n = 18, P = 0.010). Logistic regression analysis revealed that lower baseline IgE-EW (P = 0.038), IgE-OVM (P = 0.032), and a higher IgG4/IgE-OVM ratio (P = 0.013) were associated with clinical response. Relative increases in IgG4-EW, IgA-EW, and IgA2-EW were observed in responders (P = 0.024, 0.024, and 0.029, respectively). IgG4/IgE, IgA/IgE, and IgA2/IgE ratios for EW and IgA/IgE ratio for OVA were found to be significantly elevated among responders (P = 0.004, 0.009, 0.028, and 0.008, respectively). CONCLUSIONS: Increased IgG4-EW, IgA-EW, and IgA2-EW during eOIT are associated with clinical response to eOIT. Lower pretreatment IgE-EW and IgE-OVM are also associated with SU. Future studies are needed to evaluate and validate these potential biomarkers.

A phase 1 study of heat/phenol-killed, E. coli-encapsulated, recombinant modified peanut proteins Ara h 1, Ara h 2, and Ara h 3 (EMP-123) for the treatment of peanut allergy.

BACKGROUND: Immunotherapy for peanut allergy may be limited by the risk of adverse reactions. OBJECTIVE: To investigate the safety and immunologic effects of a vaccine containing modified peanut proteins. METHODS: This was a phase 1 trial of EMP-123, a rectally administered suspension of recombinant Ara h 1, Ara h 2, and Ara h 3, modified by amino acid substitutions at major IgE-binding epitopes, encapsulated in heat/phenol-killed E. coli. Five healthy adults were treated with 4 weekly escalating doses after which 10 peanut-allergic adults received weekly dose escalations over 10 weeks from 10 mcg to 3063 mcg, followed by three biweekly doses of 3063 mcg. RESULTS: There were no significant adverse effects in the healthy volunteers. Of the 10 peanut-allergic subjects [4 with intermittent asthma, median peanut IgE 33.3 kUA /l (7.2-120.2), and median peanut skin prick test wheal 11.3 mm (6.5-18)]; four experienced no symptoms; one had mild rectal symptoms; and the remaining five experienced adverse reactions preventing completion of dosing. Two were categorized as mild, but the remaining three were more severe, including one moderate reaction and two anaphylactic reactions. Baseline peanut IgE was significantly higher in the five reactive subjects (median 82.4 vs 17.2 kUA /l, P = 0.032), as was baseline anti-Ara h 2 IgE (43.3 versus 8.3, P = 0.036). Peanut skin test titration and basophil activation (at a single dilution) were significantly reduced after treatment, but no significant changes were detected for total IgE, peanut IgE, or peanut IgG4. CONCLUSIONS: Rectal administration of EMP-123 resulted in frequent adverse reactions, including severe allergic reactions in 20%.

A multicenter comparison study between the Endosafe PTS rapid-release testing system and traditional methods for detecting endotoxin in cell-therapy products.

BACKGROUND: Rapid-release testing reduces the waiting period for administration of time-sensitive cell-therapy products. Current assay systems are labor intensive and time consuming. The Endosafe portable test system (PTS) is a chromogenic Limulus amebocyte lysate (LAL) portable endotoxin detection system that provides quantitative results in approximately 15 min. To evaluate Endosafe performance with cell-therapy products, side-by-side testing of traditional LAL systems and the Endosafe system was conducted at the Production Assistance for Cellular Therapies (PACT) facilities and the National Institutes of Health's Department of Transfusion Medicine, USA. METHODS: Charles River Laboratories provided each center with a PTS reader and two commercially prepared lyophilized reference standard endotoxin (RSE) vials. All samples tested with the Endosafe system used 0.05-5.0 endotoxin unit/mL (EU/mL) sensitivity cartridges provided by Charles River. Each vial was reconstituted with LAL water and tested in triplicate using the Endosafe and in-house LAL methods. Subsequently, each center tested the endotoxin content of standard dilutions of cell-therapy products, thus creating paired test results for each sample. Additionally, fabricated endotoxin-positive samples containing varying concentrations of endotoxin were prepared and shipped to all centers to perform blinded testing. RESULTS: Valid paired results, based on each center's LAL method and the Endosafe system criteria, were analyzed. Endotoxin detection between paired results was equivalent in most cases. DISCUSSION: The Endosafe system provided reliable results with products typically produced in cell-therapy manufacturing facilities, and would be an appropriate test on which to base the release of time-sensitive cell-therapy products.

Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids.

Pediatric renal transplant recipients were enrolled in a multicenter, randomized, double-blind trial of steroid withdrawal. Subjects received basiliximab, calcineurin inhibitor, sirolimus and steroids. Of 274 subjects enrolled, 19 (6.9%) subjects developed posttransplant lymphoproliferative disorder (PTLD). The relative hazard (RH) for PTLD was 5.3-fold higher in children aged < or =5 versus those >12 years (p = 0.0017). EBV seronegative subjects had a 4.7-fold higher RH compared to EBV positive subjects (p = 0.02). Among EBV donor+/recipient- (D+/R-) subjects, the RH increased by 6.1-fold (p = 0.0001). In a multivariate model, risk factors included recipient age < or =5 years (RH 3.2, 95% CI: 1.1-9.6, p = 0.034) and EBV D+/R- status (RH 7.7, 95% CI: 1.6-35.9, p = 0.010). Of 19 patients with PTLD, 17 are alive with functioning grafts and 2 lost their grafts, 1 of whom subsequently died of recurrent PTLD. This 'robust' immunosuppression protocol was associated with low rejection rates but an unacceptably high incidence of PTLD. The combination of basiliximab, calcineurin inhibitor, sirolimus and steroids resulted in over-immunosuppression in a high-risk pediatric population and we do not recommend its use. Future studies must include routine viral monitoring to permit early identification of viral activity and a protocol driven reduction of immunosuppression aimed at avoiding complications.

Applicability of NINDS-sponsored studies to community-based physician involvement.

BACKGROUND: The National Institute of Neurological Disorders and Stroke (NINDS) Clinical Trials Group established the Clinical Research Collaboration (CRC) Project in 2005 to increase community-based physician involvement in NINDS-sponsored research. METHODS: We assessed a random sample of 112 of the more than 1,000 current NINDS-sponsored clinical research studies to determine which could involve community physicians in enrollment or follow-up. Scoring factors were based on the premise that participation is feasible for noninvasive studies with simple screening, and follow-up criteria and visit frequency consistent with usual care. Scored studies included 26 Phase III, 31 Phase I/II, and 55 nonclinical trials. RESULTS: Overall, 41% of the sampled research studies were considered conducive to community physician participation that exceeds referral only; 21% with participation in all study activities and 20% with ability to provide some follow-up. Specialized neuropsychological or neurologic scale testing was judged to exclude community physician participation in 16% of studies. CONCLUSION: Many National Institute of Neurological Disorders and Stroke studies are available in which community-based physicians could participate. Involving community physicians may increase efficiency of completing clinical research and encourage application of research findings in community practices.

Empiric monotherapy for febrile neutropenia--a randomized study comparing meropenem with ceftazidime.

In this Swedish multicentre study we compared the efficacy of meropenem with ceftazidime for treatment of febrile neutropenia. 192 patients were randomized and the number of evaluable patients was 92 in the meropenem group and 95 in the ceftazidime group. 40 (43%) patients in the meropenem arm and 49 (52%) in the ceftazidime arm had acute leukaemia. 56 (61%) and 52 (55%) patients respectively had a neutrophil count of < 0.1 x 10(9)/l at randomization and the median duration of neutropenia was 6.5 and 8 d, respectively. Thirty-one (34%) and 28 (29%) patients had a microbiologically defined infection, 14 (15%) and 17 (18%) a clinically defined infection and the remaining 47 (51%) and 50 (53%) had unexplained fever. After 72 h of treatment, 46 (50%) patients in the meropenem arm and 53 (56%) patients in the ceftazidime arm were alive on unmodified monotherapy. 42 (46%) and 47 (49%) of these completed the study on monotherapy alone. Only 2 patients (2%) in each arm had to stop treatment owing to allergic reactions. None of the observed differences were statistically significant and we therefore conclude that meropenem was an effective and safe alternative to ceftazidime for empiric treatment of fever during neutropenia.

A case of severe pancytopenia caused by ibuprofen.

We here present the case of a patient with severe neutropenia, haemolytic anaemia and thrombocytopenia associated with long-term use of ibuprofen. The blood parameters rapidly normalized when the drug was discontinued, and no further treatment, except for a short course of antibiotics, was required.

Single-dose intravenous melphalan in advanced multiple myeloma.

Eight patients with progressive multiple myeloma were given an intermediate intravenous dose of melphalan (30 mg/m2). A response lasting 2-18 months was observed in 7 patients. The bone marrow toxicity was well acceptable and most courses could be given on an outpatient basis. Intermediate-dose intravenous melphalan may be considered an alternative for treatment of relapsing or progressive multiple myeloma, even if the patient has previously received oral melphalan.

Diagnostically usable skin lesions in Candida septicaemia.

We present three patients with hematological malignancies, all neutropenic and febrile despite broadspectrum antibiotics. They all developed a sparse rash with purpuric maculopapules with a violaceous hue centrally. These skin lesions were associated with systemic Candida infections and responded well to antifungal treatment. They appeared to be a short-cut to the diagnosis of systemic Candida infections for both the hematologist and the dermatologist.

Emergency department screening for unsuspected carbon monoxide exposure.

Carbon monoxide (CO) is the leading toxic cause of death in the United States today. Unsuspected exposure to this gas will sometimes result in clinically significant, but undiagnosed, toxicity. A high incidence of such unsuspected exposures would make screening for these worthwhile among high-risk populations. We conducted a two-part study to determine the value of screening for unsuspected CO exposure in a population of patients presenting to an emergency department. The first part of our study involved the prospective screening of ED patients using CO breath analysis, regardless of their chief complaint. In the second part, COHGB levels of all patients who underwent arterial blood gas analysis during the study period were reviewed retrospectively. Of 1,038 patients screened by this combined approach, only 29 (2.8%) had abnormal CO breath readings and/or COHGB levels. Of a condensed subgroup of 152 patients defined retrospectively by chief complaint, eight (5.3%) had abnormal values. We conclude that routine screening of ED patients for unsuspected CO exposure is not practical. Although yield increases when patients are screened in a more selective manner on the basis of chief complaint, such an increase still does not appear to justify the screening process.

Pneumococcal vaccination in splenectomized patients with hematological disorders.

Seventy splenectomized patients were vaccinated with Pneumovax, a pneumococcal polysaccharide vaccine. Twenty-four of the patients had a malignant and 30 a nonmalignant hematological disorder. The remaining 16 were patients with no known hematological disorder, seven with intra-abdominal carcinomas and nine with non-malignant reasons for splenectomy. About 90% of the patients with non-malignant hematological disorders responded to vaccination with a rise in antibody titres, which was significantly higher than in the other two groups studied. Malignant hematological disorders lowered the response rate to 61-67%. Patients with no known hematological disorder but with intra-abdominal carcinomas also responded less frequently, while those in this group with other surgical reasons for splenectomy had a response rate comparable to healthy individuals. No serious side-effects were reported and we therefore conclude that all splenectomized patients should be vaccinated with a pneumococcal vaccine. However, it must always be born in mind that one third of the patients with malignant disease did not respond to vaccination.

The effect of cyclosporin A on the course of murine infection by Schistosoma mansoni.

The effect of the immunomodulating substance cyclosporin A (CyA) has been evaluated in mice infected with Schistosoma mansoni. Administration of CyA at the time of infection or during the schistosomulum stage resulted in failure of the larvae to develop into adult worms. However, a serological response was noted. Administration of CyA during the establishment of the adult worm stage resulted in a reduction of the worm burden as compared to non-treated mice. The established worm pairs, however, seemed to be sterile since no eggs were demonstrated in the liver. Infection of mice with cercariae which had been exposed to CyA in vitro resulted in only a slight reduction of the worm burden for the highest concentration of CyA tested (100 micrograms/ml). The results of the study show that administration of CyA in vivo affects the host-parasite relationship in favour of the host.

A review of the concerned parent movement in the United States of America.

Parent groups of various sizes, structures and emphases, whose common goal is to prevent drug use among young people, have grown rapidly in recent years throughout the United States of America. There are now more than 4,000 formal parent organizations striving to achieve a drug-free life for young people. The parent groups have unified into a nationwide parent movement, which has become the most influential force for the prevention of drug abuse in the country, affecting public laws, policies and attitudes. The parent groups are undertaking various activities within such areas as prevention, treatment and drug law enforcement to deal with problems of drug abuse. The leaders of the movement are predominantly volunteers, representing a variety of backgrounds. Such leadership has been able to ensure co-operation with social and public health services, and other agencies concerned. The parent movement has proved successful in formulating policies that are conducive to the prevention and reduction of drug abuse, and the recent decline in drug abuse has, to a certain extent, been attributed to the movement.

Self-concept of white, middle socioeconomic status addicts: a controlled study.

Commonalities in the developmental patterns of both narcotic addiction and negative self-attitudes motivated this controlled study of 70 White, middle socioeconomic status (WMSES) addicts and 70 WMSES nonaddicts. The hypothesis that measures of self-attitudes would distinguish addicts from nonaddicts was confirmed with highly significant differences. The hypothesis that antecedent conditions purported to result in positive self-attitudes would distinguish addicts from controls was also supported. Developmental conditions posited as indices of early self-attitudes further discriminated the two groups. A self-reported profile of the WMSES addict was compiled describing drug-use patterns and childhood situations.