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[The immunostimulating action of suramin in infection with the infectious rhinotracheitis virus].

The immunostimulating antiviral preparation suramin has a favourable effect on the process and outcome of an experimental infection with the virus of infectious rhinotracheitis (bovine herpes virus type 1, BHV1), thus reducing the gravity of the clinical course and increasing the survival rate. The therapeutic protective effect of the preparation is expressed in the prevention of virus-induced immunosuppression which is markedly strong during the acute phase of the infection process. Suramin restored the number, viability, relative share in the bronchial lavage population, phagocytic and microbicidal capacity of the alveolar macrophages--a major factor of the local defence mechanisms of the lung. In a similar way suramin influenced some parameters of the systemic immunity (number and differential count of polymorphonuclear phagocytes, plaque- and rosette-forming cells). The application of suramin in doses lower than those used for virus inhibition and its considerable action on different mechanisms of the immune system suggested that the preparation's therapeutic effect could be related mainly to its immunostimulating properties.

Adjuvants, Immunologic↗

Medicinal protection with Chinese herb-compound against radiation damage.

Experiments were carried out on mice and the subjects irradiated for cancer therapy to evaluate the protective efficacy of a Chinese medicinal herb-compound (CMHC). The lethality and the degree of leucopenia caused by radiation in mice medicated with CMHC were significantly less in comparison with control mice (p less than 0.01 and p less than 0.001, respectively). CMHC significantly improved the WBC and the thrombocytes in irradiated workers (p less than 0.01 and p less than 0.001, respectively). The WBC count of 40 patients under radiotherapy while treated with CMHC recovered from 3450 +/- 77/c.mm to 5425 +/- 264/c.mm (p less than 0.001); whereas, in the control group, without any medication, the WBC count dropped significantly (p less than 0.001). Our results revealed the applicabilities of CMHC in protection against radiation damage in spaceflight and in other fields.

Animals↗

[Luminescence, induced by UV-irradiation, of intact human skin].

UV-C induced chemiluminescence of human skin was investigated in vivo by means of an image-producing system using photon-counting camera and computer PERICOLOR-1000. Luminescence after UV-C application is shown to decline nonexponentially, the parameters of the decline depending on irradiation dose, skin specimen and previous irradiations. If the same skin specimen is irradiated second time 3-36 hours after the first irradiation, the luminescence decline time increases from one-two minutes to more than half an hour. During the time when the decline is slow the images produced by irradiation through the diaphragm do not sustain distinct contours due to the luminescence of nonirradiated skin. The luminescence is shown to be under the organisms' control and to diminish significantly after the application of acetylsalicylic acid.

Aspirin↗

Chlorhexidine, fluoride varnish, and xylitol chewing gum: underutilized preventive therapies?

The successful implementation of a preventive dentistry program depends, to a large extent, on the compliance of the patient. The scheduled program would include: recall appointments, all instructions relative to oral hygiene, use of nightly fluoride rinses, and control of diet. To ensure that high-risk patients who have cariogenic bacteria are adequately treated, chlorhexidine rinses may be required on a periodic basis. The patient's level of risk must determine all treatment decisions. For low-risk patients, the times between recall appointments can be extended when evidence of caries arrest and remineralization can be documented. High-risk patients should be recalled at least every three months, until evidence of lesion arrest and/or remineralization has been documented. For patients with extremely low saliva flow rates, the combined chlorhexidine and fluoride method may be required. If the caries risk is still judged to be high according to bacteria counts and/or evidence of further lesion development or progression, more frequent applications of chlorhexidine may be required. Because fluoride varnish is generally more effective on smooth surfaces than on fissure sites, moderate caries-risk patients should receive fluoride varnish on smooth surfaces, and sealants, when indicated, on fissure sites. As the caries risk of the patient is reduced to a low-risk level, less frequent use of fluoride-containing or fluoride releasing products is indicated, and there can be longer periods between recall examinations. Three applications of fluoride varnish, applied to a single week, appear to provide greater caries protection than two applications per year. Attempts should be made to ensure that the varnish is applied immediately after cleaning the teeth and protected as long as possible after the varnish has been applied (preferably at least 10 hours). Fluoride varnish appears to be as effective as topical fluoride gel and may be safer. Thus, a greater frequently of application is permitted without a significant risk of fluorosis. Prevention is more cost effective as the patient shifts from a high-risk level to a low-risk level. Recall appointments can subsequently be extended and more conservative prevention treatments are warranted. Over an extended treatment period, the cost for the preservative dentistry option should be comparable to and perhaps less than the cost of placing and replacing dental restorations.

Chewing Gum↗

Adenine nucleotide metabolism and cell fate after oxidant exposure of rat cortical neurons: effects of inhibition of poly(ADP-ribose) polymerase.

We exposed cultured neurons prelabeled with 14C-adenine to H2O2 with or without the poly(ADP-ribose) polymerase (PARP) inhibitor 3,4-Dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ) to quantify its effects on acute ATP depletion, later ATP synthesis, cellular and nuclear morphology, extent of DNA fragmentation, and PARP cleavage. According to the extent of the acute ATP depletion, the exposures were classified as 'mild' (50 microM H2O2), 'moderate' (100-250 microM H2O2), or 'severe' (500 microM-1 mM H2O2) insults. Mild exposure had no significant effects on the parameters studied. In the 'moderately' exposed neurons, ATP depletion to 59+/-6% of control was associated with a decrease in the cell counts, apoptotic morphology, and cleavage of PARP. In this group, DPQ prevented the acute ATP (to 95+/-15% of control), preserved cell morphology, and improved cell survival. In the 'severe' group, ATP depletion to 18+/-4% was associated with necrosis and intact PARP. DPQ elevated ATP levels (to 44+/-12% of control) and post-insult ATP synthesis, improved cell counts, and altered cell morphology towards apoptosis rather than necrosis. Post-insult application of DPQ was less effective. Our results show that the extent of oxidant-induced ATP depletion and cell fate can be modified by PARP inhibition, to some extent also after the insult.

Adenosine Diphosphate↗

Phase I clinical trial with HIV-1 gp160 plasmid vaccine in HIV-1-infected asymptomatic subjects.

The aim of the study was to investigate the safety of an HIV-1 gp160 plasmid vaccine. Four asymptomatic HIV-1-infected subjects with CD4+ lymphocyte counts >500/microl were injected with four times 400 microg of HIV-1 modified gp160 env and rev coding DNA vaccine at 0, 4, 10 and 28 weeks. Safety parameters, including autoimmune antibodies as well as CD4+/CD8+ cell counts and HIV-1 plasma concentrations, were monitored for 52 weeks after the first vaccine application. Follow-up data for more than 3 years are now available. The DNA vaccine proved to be safe and, specifically, did not induce anti-DNA autoimmune antibodies. Vaccination had no long-term effects on the CD4+/CD8+ lymphocyte counts, plasma HIV-1 RNA concentrations or disease progression. The present data supplement published data from Philadelphia, USA, where a dose-escalating study (30-300 microg) with the same HIV-1 DNA vaccine was performed.

AIDS Vaccines↗

Are poor responses to praziquantel for the treatment of Schistosoma mansoni infections in Senegal due to resistance? An overview of the evidence.

This paper summarizes and concludes in-depth field investigations on suspected resistance of Schistosoma mansoni to praziquantel in northern Senegal. Praziquantel at 40 mg/kg usually cures 70-90% of S. mansoni infections. In an initial trial in an epidemic S. mansoni focus in northern Senegal, only 18% of the cases became parasitologically negative 12 weeks after treatment, although the reduction in mean egg counts was within normal ranges (86%). Among other hypotheses to explain the observed low cure rate in this focus, the possibility of drug resistance or tolerance had to be considered. Subsequent field trials with a shorter follow-up period (6-8 weeks) yielded cure rates of 31-36%. Increasing the dose to 2 x 30 mg/kg did not significantly improve cure rates, whereas treatment with oxamniquine at 20 mg/kg resulted in a normal cure rate of 79%. The efficacy of praziquantel in this focus could be related to age and pre-treatment intensity but not to other host factors, including immune profiles and water contact patterns. Treatment with praziquantel of individuals from the area residing temporarily in an urban region with no transmission, and re-treatment after 3 weeks of non-cured individuals within the area resulted in normal cure rates (78-88%). The application of an epidemiological model taking into account the relation between egg counts and actual worm numbers indicated that the low cure rates in this Senegalese focus could be explained by assuming a 90% worm reduction after treatment with praziquantel; in average endemic situations, such a drug efficacy would result in normal cure rates. Laboratory studies by others on the presence or absence of praziquantel resistance in Senegalese schistosome strains have so far been inconclusive. We conclude that there is no convincing evidence for praziquantel-resistant S. mansoni in Senegal, and that the low cure rates can be attributed to high initial worm loads and intense transmission in this area.

Animals↗

A laboratory evaluation of Compur M 1000 Miniphotometer and the Compur M 11OO minicentrifuge.

The Compur Miniphotometer and Minicentrifuge are portable instruments designed for rapid estimation of haemoglobin, red cell count and haematocrit on capillary blood. Haemoglobin and haematocrit results correlate well with reference methods. Accurate red cell counts are only obtained when the sample MCV is within the range 83--103 fl, thus restricting the application of this method. The Compur M 1000 Miniphotometer and Compur M 1100 Minicentrifuge have been designed as portable instruments to permit rapid estimations of haemoglobin concentration, red cell count and haematocrit by the non-laboratory worker.

Centrifugation↗

Improvement of pneumonia and arthritis in Felty's syndrome by treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF).

A 63-year old man with Felty's syndrome and pneumonia of unknown origin was treated with GM-CSF. Granulocyte counts increased and arthritis-related symptoms improved under GM-CSF. Pneumonia was treated effectively with antibiotics only during or after GM-CSF application. This suggests, that antibiotic-resistant infections can be treated effectively in patients with Felty's syndrome when granulocyte counts are raised by GM-CSF.

Felty Syndrome↗

Multivariate statistical modeling: alternative approach to test evaluation, applied to counting reticulocytes by flow cytometry.

We present a statistical path analysis model for the evaluation of two tests in the absence of a "gold standard" method. This model is applied to the evaluation of flow-cytometric and visual reticulocyte counting by using as the comparison method a combination of three hematological measurements: hemoglobin concentration (HGB), mean cellular volume (MCV), and erythrocyte density width (EDW). We assumed that, in general, a higher reticulocyte count is associated with a lower HGB value and with greater values for MCV and EDW. Applying this assumption and the statistical model, we demonstrated that flow cytometry was superior to visual reticulocyte counting in the low-value range studied. The path analysis model is potentially applicable in other cases where two tests are to be compared, and when no gold standard is available.

Erythrocyte Count↗

Detecting human CD34+ and CD34- hematopoietic stem and progenitor cells using a Sysmex automated hematology analyzer.

In clinical medicine, particularly in the newly developing stem cell therapies required to support the practice of regenerative medicine, the measurement of both CD34+ and CD34- hematopoietic stem cells (HSC)/hematopoietic progenitor cells (HPC) is important in obtaining more accurate information about the total HSC/HPC content in various stem/progenitor cell sources. We report the results of an investigation into methods of detecting CD34+ and CD34- HSC/HPC using the immature information (IMI) channel incorporated into the Sysmex XE-2100 and SE-9000 automated hematology analyzers. In this study, CD34+ and CD34- HSC/HPC were separated by immunologic methods and quantified by flow cytometry (FACScan) and IMI channel analysis. In addition, CD34-/CD133+ HSC were prepared by a sequential antibody-based positive selection strategy. These cells appeared in the same area as CD34+ cells in the IMI channel of the automated hematology analyzer. These findings confirmed that an automated hematology analyzer can be used to measure both CD34+ and CD34- HSC. These results may explain the difference in HSC/HPC counts sometimes observed between the automated hematology analyzer and flow cytometric methods for CD34+ measurement. The results of this study demonstrated the potential of automated cell counting methods for measuring HSC content in cellular products for both research and clinical applications.

AC133 Antigen↗

Fluorescent retrograde neuronal tracers that label the rat facial nucleus: a comparison of Fast Blue, Fluoro-ruby, Fluoro-emerald, Fluoro-Gold and DiI.

Many fluorescent retrograde tracers are commercially available for neuroanatomical studies. They have been used with varying success in different models and can be very effective in the study of the facial nerve and nucleus. We compare the tracers Fast Blue (FB), Fluoro-ruby, Fluoro-emerald, Fluoro-Gold (FG), and DiI in the rat facial nucleus after application to the buccal division of the nerve. There were no significant differences between counts of cells on the left and right sides of the brain stem with any of the tracers. FB produced a lower sample variation than the other tracers, and together with DiI, demonstrated greater axonal labelling when applied to the surface of the epineurium. FB and FG resulted in strong retrograde labelling of the facial nucleus after only 2 days from injection. All the tracers produced adequate cell labelling after 1 week from nerve application. This labelling persisted for up to 8 weeks for most tracers except FG, which did not produce satisfactory labelling at 8 weeks.

Amidines↗

[A 13-week dermal toxicity study of prednisolone farnesylate (PNF) gel in rats with a recovery period of 5 weeks].

The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF gel was administered dermally to the rats at doses of 0.25, 1, 4 and 16 mg/kg/day for 13 weeks, then the drug was withdrawn for 5 weeks to evaluate the reversibility. In addition, 10 mg/kg/day prednisolone gel (PN gel), which is approximate to 16 mg/kg/day PNF gel in prednisolone molarity, was also administered to the rats for comparison. The results are summarized as follows: 1. In the PNF gel 16 mg/kg/day group, temporary erythema at the application site, retarded body weight gains, a decrease in the white blood cell count and lymphocyte ratio with an increase in the segmented neutrophil ratio, an elevation of serum AIP activity were observed. The pathological examinations revealed atrophy of the adrenal glands, lymphatic organs and skin. In addition, histopathological lesions were also found in the liver, pancreatic islets, bone, bone marrow and mammary glands. 2. In the PNF gel 4 mg/kg/day group, retarded body weight gains were observed, and histopathological lesions were noted in the adrenal glands, lymphatic organs, skin at the application site, liver and bone marrows. 3. In the groups that received less than 1 mg/kg/day of PNF gel, there were no toxic signs induced by the drug. 4. In the PN gel 10 mg/kg/day group, drug-related changes were almost similar to those of the PNF gel group, but the severity of the lesions was stronger than in the PNF gel group. 5. After the 5-week recovery period, the above changes almost completely disappeared and so it was demonstrated that the changes were reversible. 6. Based on these results, it was concluded that the overt toxic dose of PNF gel was 4 mg/kg/day and the non-toxic dose was 1 mg/kg/day in the present study.

Administration, Cutaneous↗

[Developments of automated cell counter and its clinical laboratory application].

A rapid development has taken place in recent years in the field of automatic cell counting and automatic differential machine for miscellaneous blood cells. In the present paper we concisely summarized the history on the development of these machines, then reported the results obtained using STKS-VCS (automatic blood cell counter and cell analyzer based on flow system). 1. The precision of the STKS was established as follows using the coefficient of variation, 0.39-3.96% for 5 CBC parameters. WBC differentials; under 1% for neutrophils and lymphocytes, 6 to 9% for monocytes and eosinophils, approximately 18% for basophils. 2. Time profile of CBC and WBC differential data by same machine, was almost unchanged until 24 hours from blood taking using both glass and plastic vials. 3. Good correlation was obtained as for white cell differential between data from VCS and by manual ones with 4 skilled technicians according to NCCLS method. 4. Predictive value of tests applied to normal and abnormal population, high true positive and negative ratio and low false positive and negative ratio, which results helped us, to share more times to observe abnormal samples more carefully. 5. So called "flags" which predicts presence of abnormal cells (e.g. immature granulocytes, atypical lymphocytes) was useful to screen abnormal cell population in VCS system.

Blood Cell Count↗

Multimodal management, including precisely targeted irradiation, in a severe refractory case of Evans syndrome.

A challenging case of acute autoimmune thrombocytopenia (ITP) which evolved into a chronic refractory case of Evans syndrome over a period of more than 23 years is presented and may illustrate current therapeutic dilemmas now perplexing patients and clinicians. Newer modalities are being developed and their eventual role in the scheme of clinical management remains to be established. While this development unfolds, highly targeted radiotherapy was applied in this case to reduce platelet uptake by a refractory recurrent splenule with the goal of stabilizing the platelet count until promising investigational thrombopoietic agents or other newer, less toxic therapies might become available for wider application.

Adult↗

Total amount of ECP per eosinophil as indicator for the activity state of eosinophils.

Eosinophil cationic protein (ECP) serum concentrations yield additional information regarding the activity of allergic diseases because ECP serum concentrations correlate very well with blood eosinophil counts. We established spontaneous serum ECP release per eosinophil during in vitro coagulation amounting to 0.03-0.5 pg per eosinophil. When comparing the ECP per eosinophil ratio with the eosinophil concentration, a decreasing trend of released ECP in serum was observed towards higher eosinophil counts. The total amount of extractable ECP in eosinophilic granulocytes is determined by means of extraction with application of a 0.5% Cetyl-trimethyl-ammonium-bromide solution. The total amount of extractable ECP in eosinophils amounts to 0.4-17 pg/eosinophil. Results showed a slight tendency to decrease with higher eosinophil counts. Irrespective of their concentration in blood, eosinophils were demonstrated to release 2-4% of their total ECP amount. It is concluded from experiments in this study that release during in vitro clotting or measuring the total amount of extractable ECP does not yield any additional diagnostic value in detecting the degree of activation in eosinophils.

Adolescent↗

Quantification of cutaneous mast cells using morphometric point counting and a conjugated avidin stain.

Mast cells in normal human skin and in lesional cutaneous tissue from two patients with mastocytosis were quantified with the use of a morphometric point counting technic in combination with the mast cell-specific stain, conjugated avidin. Mast cells in normal human flank skin occupied a relatively small percentage of the dermal volume, with a mean value of 0.40% (+/- 0.14 SD), while a marked increase in mast cell content was demonstrated in cutaneous lesional tissue from two patients with the macular and nodular forms of mastocytosis (2.5% and 64.3%, respectively). In a comparative study with the use of morphometric analysis, conjugated avidin proved objectively to be as good as toluidine blue, and subjectively superior to this stain for mast cell identification in both human and murine skin. The combination of morphometric point counting and the conjugated avidin stain provides a useful tool for establishing the diagnosis of mastocytosis and is applicable to a variety of experimental systems.

Adolescent↗

Differential effects of transdermal nicotine on microstructured analyses of tics in Tourette's syndrome: an open study.

BACKGROUND: The treatment of Tourette's syndrome (TS) is often unsatisfactory. However, there is some evidence that transdermal nicotine patch (TNP) application may improve tics of nonsmoking TS patients who are refractory to haloperidol treatment. METHODS: In this open study we applied two 10 mg TNP for 2 consecutive days to four TS patients whose symptoms were not controlled by haloperidol and to a never-medicated TS patient, all of whom are non-smokers. The Yale Global Tic Severity Scale (YGTSS) and a quantified video-taped micro-structured analysis of tics (head-shake tics, eye-blinks, vocal tics, facial grimace and other body tics) were both carried out to assess the change after the application of TNP. RESULTS: TNP application significantly reduced the YGTSS by an average of 50%, with no reported side-effects, for up to 4 weeks but not 16 weeks, as compared with TNP-free period. Consistent with these results, the total counts of tics also showed a significant decrease for up to 4 weeks after the TNP application. CONCLUSION: TNP application differentially affected individually quantified tics, which may suggest a differential role of nicotinic receptors in the generation of different tics.

Administration, Cutaneous↗