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At least 703 records · Page 39Linked to original sources
PubMed1981

Multiple-pulse laser retinal damage thresholds.

The additivity from multiple exposures of the retina to laser light sources is investigated with regard to empirical and theoretical models. Prior data indicate additivity consistent with a total-on-time formulation in the case of point source conditions but not for extended source conditions. Thermal model calculations agree with the extended source results, but only agree with point-source data when the pulse repetition rate is higher than 10 Hz. The anomaly at low pulse repetition rates can still be interpreted in terms of a thermal damage mechanism if spatial variations are considered.

Lasers↗
PubMed1963

In vitro studies of mammalian somatic cell variation. II. Isoimmune cytotoxicity with a cultured mouse lymphoma and selection of resistant variants.

When long term cultures of mouse lymphoma cells, known to possess the isoantigenic phenotype determined by the H-2(d) allele, are incubated with anti H-2d isoantibody and guinea pig complement, slightly more than 99 per cent of cells are killed under optimal conditions. Growth in mass culture and colony formation by single cells after incubation with isoantibody and complement are employed to assess the cytotoxic effect. The cytotoxic action of isoantibody is complement-dependent, for viability of cells exposed to antibody alone is unaltered. When excess isoantibody and optimum concentrations of complement are used, killing begins as soon as these reagents are mixed with the cells, and no further killing occurs after 5 to 15 minutes at 37 degrees C. About 80 per cent of cells are killed with an isoantiserum containing antibody to two isoantigenic components of the H-2d complex. That the cytotoxic action is mediated through the H-2 isoantigen is shown by (a) isoantiserum containing only anti H-2d antibody produces maximal cell killing, and (b) isoantiserum from which anti H-2d antibody has been removed by absorption loses all cytotoxic activity. Variant cells resistant to the cytotoxic action of anti H-2d isoantibody were isolated from lymphoma cell populations surviving multiple exposures to isoantibody and complement. These variants can be distinguished morphologically from the isoantibody-sensitive parent cell line. Although variants are resistant to anti H-2d isoantibody, these cells possess H-2d isoantigen but in a lower concentration than found in cells of the parent line. The basis for resistance to cytotoxic isoantibody is discussed.

Animals↗
PubMed2000

Synthetic malaria peptide vaccine elicits high levels of antibodies in vaccinees of defined HLA genotypes.

A multiple antigen peptide (MAP) malaria vaccine containing minimal Plasmodium falciparum circumsporozoite protein repeat epitopes was assessed for safety and immunogenicity in volunteers of known class II genotypes. The MAP/alum/QS-21 vaccine formulation elicited high levels of parasite-specific antibodies in 10 of 12 volunteers expressing DQB1*0603, DRB1*0401, or DRB1*1101 class II molecules. In contrast, volunteers of other HLA genotypes were low responders or nonresponders. A second study of 7 volunteers confirmed the correlation of class II genotype and high responder phenotype. This is the first demonstration in humans that a peptide vaccine containing minimal T and B cell epitopes composed of only 5 amino acids (N, A, V, D, and P) can elicit antibody titers comparable to multiple exposures to irradiated P. falciparum-infected mosquitoes. Moreover, the high-responder phenotypes were predicted by analysis of peptide/HLA interactions in vitro, thus facilitating the rational design of epitope-based peptide vaccines for malaria, as well as for other pathogens.

Adult↗
PubMed2001

Antibodies to glycans dominate the host response to schistosome larvae and eggs: is their role protective or subversive?

Multiple exposures of chimpanzees to the radiation-attenuated schistosome vaccine provoked a strong parasite-specific cellular and humoral immune response. Specific IgM and IgG were directed mainly against glycans on antigens released by cercariae; these were also cross-reactive with soluble antigens from larvae, adult worms, and eggs. Egg deposition was the major antigenic stimulus after challenge of vaccinated and control chimpanzees with normal parasites, eliciting strong antiglycan responses to egg secretions. Glycan epitopes recognized included LacdiNAc, fucosylated LacdiNAc, Lewis(X) (weakly), and those on keyhole limpet hemocyanin. Antibodies to peptide epitopes became prominent only during the chronic phase of infection, as glycan-specific IgM and IgG decreased. Because of their intensity and cross-reactivity, the antiglycan responses resulting from infection could be a smoke screen to subvert the immune system away from more vulnerable larval peptide epitopes. Their occurrence in humans might explain the long time required for antischistosome immunity to build up after infection.

Animals↗
PubMed2006

Dynamics of T cells subsets and lymphoproliferative responses during structured treatment interruption cycles and after definitive interruption of HAART in early chronic HIV type-1-infected patients.

Little is known about the consequences of short cycles of structured treatment interruption or definitive interruption of HAART for both T cell subset dynamics and T lymphoproliferative responses (LPR). Immunological follow-up was performed in 45 early chronical HIV-1-infected patients during short STI cycles during the first 12 weeks after the definitive interruption of HAART (DTI) and, thereafter, until VL reached a plateau. During STI cycles, CD8(+), CD8(+), CD28(+), activation markers and naive CD4(+) T cells increased significantly (p < 0.0001), while both naive CD8(+) and memory CD4(+) T cells decreased. During DTI, CD8(+) CD28(+) T cells fell and CD4(+) naive T cells stabilized and the rest of the T cell subsets presented changes similar to those during STI cycles. Despite a transient increase in LPR to recall antigens and HIV proteins during STI cycles, LPR to polyclonal stimuli and pathogens decreased over the study. Differences in T cell subset dynamics and LPR observed throughout the study suggest that multiple exposures to low levels of antigen could improve the immune system, mainly by driving T cell maturation. Conversely, higher and longer viral replication after cessation of HAART overwhelms the immune system. These data may help to guide future immune-based therapies.

Adult↗
PubMed2006

Comprehensive integration of nutrition into medical training.

Nutrition must be integrated into the medical school curriculum to train physicians who can effectively provide nutrition care for the prevention and management of chronic diseases. This article describes the comprehensive nutrition curriculum developed at the University of Colorado School of Medicine. Two fundamental principles have guided the school's approach to medical nutrition education: 1) nutrition content must be broad in nature and be vertically integrated across the preclinical and clinical years and continued through postgraduate training, and 2) active adult learning (eg, "learning by doing") should be practiced whenever possible. From our experience, we have identified several key elements important for the successful integration of nutrition into the curriculum. First, identifying a core group of committed faculty to advocate for nutrition and serve as role models and having a physician nutrition specialist at the helm provides constant momentum for the advancement of nutrition education. Second, establishing a network of linkages with other elements of the existing curriculum creates the opportunity to add nutrition content without necessarily adding time. The third key element is an emphasis on incorporating nutrition in clinical training. Students must be routinely exposed to physicians practicing nutrition for nutrition to become part of standard patient care. This can be accomplished through multiple exposures to nutrition throughout the curriculum (ie, vertical integration). Finally, a coordinator is needed to monitor the many "fronts" of the integrated nutrition curriculum and to continue networking and program implementation.

Colorado↗
PubMed1987

Dangers of anaesthesia in Munchausen's syndrome.

Patients with Munchausen's syndrome often undergo multiple surgical operations under general anaesthesia. They tend to have multiple exposures to routinely used anaesthetic agents. A patient with Munchausen's syndrome who developed an anaphylactoid reaction to thiopentone is described and the importance of obtaining previous case notes is stressed.

Anaphylaxis↗
PubMed1985

Tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced chromosome aberrations in mouse keratinocyte cell lines: a possible genetic mechanism of tumor promotion.

The effect of the tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the induction of numerical and structural chromosomal aberrations, double minute chromosomes (DM) and homogeneously staining regions (HSR) was investigated in two mouse keratinocyte cell lines (HEL-30 and HEL-37) using G- and C-banded chromosomal preparations. The frequency of polyploid metaphases and of structural aberrations increased several fold during the first two cell cycles. The increase of gaps, chromatid and isochromatid breaks was accompanied by inter- and intrachromosomal exchanges, which were virtually absent in control cultures. The induction of chromosomal aberrations was similarly expressed in both cell lines at different passage levels and was largely independent of the TPA dose applied (10(-9) - 10(-6) M). The non-promoting phorbolester 4-O-methyl-TPA (10(-6) M) did not produce any chromosomal aberrations above the control level. Effects were already visible within one cell cycle (24 h) after treatment and increased with longer and multiple exposure. Moreover, the TPA-induced chromosomal aberrations persisted for several days after elimination of the promoter and further cultivation of cells in fresh medium. Structural alterations were not randomly distributed but chromosomes 1 and 2 were preferentially involved in breaks, while chromosomes 1-3 and 9-13 were mainly involved in chromosomal exchanges. Chromosomes 7 and 14, which are numerically underrepresented in HEL cells, were least involved in breaks. Most interesting, the frequency of metaphases carrying DMs increased 2- to 3-fold after TPA treatment, and the alterations were partially reversible after removal of TPA. These early effects of TPA at the chromosomal level could play an essential role in the mechanism of tumor promotion and may be responsible for the observed persistence of alterations induced during the first stage of tumor promotion.

Animals↗
PubMed1975

Tumor induction by carcinogenic agents in aquarium fish.

The effects of nine carcinogens on 1,220 guppies [Poecilea reticulata (Lebistes reticulatus)] and 40 zebra fish (Danio rerio) were studied. Multiple exposure techniques included skin application, im and ip injections, feeding, implantation in pellets, and dissolving of the compound in the aquarium water. 7-12-Dimethylbenz[a]anthracene, 3-methylcholanthrene, and benzidine produced no tumors in the fish. N-2-Fluorenylacetamide, omicron-aminoazotoluene, 4-dimethylaminoazobenzene, diethylnitrosamine, and dimethylnitrosamine induced tumors in the livers of some of the fish. These neoplasms included cholangiomas, hepatoadenomas, cholangiocarcinomas, and hepatocellular cancers. Nitrosomorpholine caused not only hepatic tumors in guppies and zebra fish but also intestinal adenocarcinomas and poorly differentiated connective-tissue lesions in the abdominal cavities of zebra fish. Experimental induction of tumors in aquarium fish offers wide possibilities for comparative cancer research. Fish are a suitable model for the testing of compounds for carcinogenic activity and for the screening of environmental carcinogens.

2-Acetylaminofluorene↗
PubMed1978

Effect of reovirus infection on pulmonary tumor response to urethan in strain A mice.

The effect of reovirus type 3 infection on the pulmonary adenoma response to urethan in strain A mice was examined. Urethan carcinogenesis in this system was suppressed from 30 to 60% when mice were exposed to reovirus either 6 days before, on the same day as, or 14 days after urethan administration. These findings suggested that reovirus infection interfered with the progression of urethan-induced pulmonary adenoma rather than the induction of lung tumors by urethan. When mice received multiple exposures to reovirus, the lung tumor response was enhanced. These findings indicated that reovirus infection in particular and virus infection in general may play an important role in the carcinogenic response to environmental chemicals.

Adenoma↗
PubMed2002

Respiratory illness in agricultural workers.

Respiratory diseases have long been recognized in association with work in farming. Overall, only a small proportion of the population is employed in agriculture, so respiratory disease in farmers is not a major public health issue. However, farmers are known to have high morbidity and mortality from certain respiratory diseases, as shown by routinely collected statistics. Despite this, knowledge of the frequency, nature and risk factors for some respiratory disorders in agricultural workers is incomplete. Multiple exposures are common and some exposures can give rise to more than one specific disease. Moreover, the most common respiratory symptoms reported by farm workers (wheeze, dyspnoea and cough) are relatively non-specific and can be associated with several occupational respiratory disorders. This review describes the main occupational respiratory illnesses in farming and summarizes the current literature about epidemiology and prevention. The most important diseases are rhinitis and asthma, which, although common, are not usually fatal. Some non-allergic conditions, e.g. asthma-like syndrome and organic toxic dust syndrome, are not yet fully understood, but appear to be common among farm workers. The most serious respiratory diseases are hypersensitivity pneumonitis and respiratory infections, but these are rare. Most importantly, respiratory diseases are preventable by controlling harmful exposures to organic dust, toxic gases and chemicals on farms through improvements in animal rearing techniques, ventilation of animal accommodation, careful drying and storage of animal feed-stuffs, crops and other products, and use of personal protective equipment.

Agricultural Workers' Diseases↗
PubMed1991

Regression methods for estimating attributable risk in population-based case-control studies: a comparison of additive and multiplicative models.

A regression method that utilizes an additive model is proposed for the estimation of attributable risk in case-control studies carried out in defined populations. In contrast to previous multivariate procedures for the estimation of attributable risk, which have utilized logistic regression techniques to adjust for confounding factors, the model assumes an additive relation between the covariates included in the regression equation. As an empirical example, additive and logistic models were fitted to matched case-control data from a population-based study of childhood astrocytoma brain tumors. Although both models fitted the data well, the additive model provided a more satisfactory estimate of the risk attributable to multiple exposures, in the absence of significant additive interaction. In contrast to the results from the logistic model, the adjusted estimates of the risk attributable to each factor included in the additive model summed to the overall estimate for all of the factors considered jointly. Thus, the additive approach provides a useful alternative to existing procedures for the multivariate estimation of attributable risk when the additive model is determined to be appropriate on the basis of goodness-of-fit.

Astrocytoma↗
PubMed1988

Semi-automated analysis of manually reconstructed tracks of progressively motile human spermatozoa.

Several alternative algorithms for computer-assisted derivation of measurements of movement characteristics from manually reconstructed tracks of progressively motile human spermatozoa were compared. Fifty tracks were reconstructed at 30 Hz from video recordings and analysed using traditional manual methods and by four combinations of computer algorithms. The best algorithm set was identified ('Videomot.mdpt') and the values for the curvilinear, average path and linear velocities (VCVL, VAVE and VLIN respectively), the amplitude of lateral displacement of the sperm head about the axis of progression (AH) and the number of times the sperm head crossed the average path (the 'beat/cross frequency', BXF) obtained using it were compared to those obtained by manual analysis. There was a considerable time saving when the computer-assisted method was used and the values it gave for the various movement characteristics showed good correspondence with those obtained manually. In addition, repeated data entry and analysis was found to be highly reproducible. When the tracks were re-plotted at 6 Hz (as used by the multiple-exposure photomicrography method for sperm motility analysis) insufficient information remained in the tracks for reliable determination of anything other than VLIN. We conclude that the Videomot.mdpt program provides reliable values for the movement characteristics of progressively motile human spermatozoa, and believe it will be of great value in the validation of commercial systems providing automated sperm movement analysis and in laboratories which do not have access to such costly equipment.

Algorithms↗
PubMed1998

Control strategies for Marek's disease: a perspective for the future.

Marek's disease virus is an evolving pathogen, acquiring virulence in response to increasingly effective vaccines. Although vaccine efficacy is generally good, industry has placed a high priority on more effective products. The search for better vaccines has been conducted mainly in the arena of molecular biology, and has been thus far disappointing. Various conditions prevail that currently limit the potential to develop suitable long-term solutions. A new paradigm based on reduction of early exposure, multiple levels of host resistance, and improved cooperation among stakeholders is proposed for consideration.

Animals↗
PubMed1975

Effect of training on the use of weight-bearing orthoses.

Weight-bearing orthoses have been disigned with the primary goal of reducing or eliminating weight bearing in skeletal structures. In evaluating various designs and adjustments of these orthoses, we found that the training of the subject in the use of his orthosis was one of the most significant factors in controlling weight bearing. Subjects fitted with instrumented ischial weight-bearing and patellar-tendon-bearing orthoses walked over a force plate which measured forces imparted to the floor. The force data from the orthoses and force plate were computer-processed with single frame, multiple exposure photographic data to provide plots of axial loading in the orthosis and total axial loading imparted to the floor during the duration of the stance phase. The difference between these two forces represents the load carried by the skeletal system. Measurements were made first with subjects who had no specific instructions about the use of their orthoses. The subjects were then instructed how to use their orthoses more efficiently. In all cases, the effect of training produced a 30 to 50 percent increase in loading borne through the orthosis.

Biomechanical Phenomena↗
PubMed2006

An assessment of digital stereotaxis in the National Health Service Breast Screening Programme.

A woman may be invited back for further assessment if an abnormality is found on her mammogram. A stereotactic attachment is used to determine where to place the biopsy device. Digital equipment has the advantage of providing images almost instantaneously and utilising software to determine the location of the sampling device. These devices should make the procedure quicker and hence less traumatic for the women. However, digital devices have poorer spatial and contrast resolution, which could adversely affect the accuracy of sampling device placement. Although the dose received during a normal screening mammogram is well known, the dose for the stereo procedure is unknown, partly because only a small part of the breast is directly irradiated. However, the lady may undergo multiple exposures. For a prospective survey of doses and technique arm of the study a proforma was completed for 134 women. The dose women received during a stereotactic procedure was estimated.

Aged↗
PubMed2005

Incorporation of therapeutic interventions in physiologically based pharmacokinetic modeling of human clinical case reports of accidental or intentional overdosing with ethylene glycol.

Although occupational uses of the high production volume (HPV) chemical ethylene glycol (EG) have not been associated with adverse effects, there are case reports where humans have either intentionally or accidentally ingested large quantities of EG, primarily from antifreeze. The acute toxicity of EG can proceed through three stages, each associated with a different metabolite: central nervous system depression (ethylene glycol), cardiopulmonary effects associated with metabolic acidosis (glycolic acid), and ultimately renal toxicity (oxalic acid), depending on the total amounts consumed and the effectiveness of therapeutic interventions. A physiologically based pharmacokinetic (PBPK) model developed in a companion paper (Corley et al., 2005). Development of a physiologically based pharmacokinetic model for ethylene glycol and its metabolite, glycolic acid, in rats and humans. Toxicol. Sci., in press 2005) was refined in this study to include clinically relevant treatment regimens for EG poisoning such as hemodialysis or metabolic inhibition with either ethanol or fomepizole. Such modifications enabled the model to describe data from several human case reports, confirming the ability of the previous model to describe the pharmacokinetics of EG and its metabolite, glycolic acid, in humans across a broad range of doses and multiple exposure routes. By integrating the case report data sets with controlled studies in this PBPK model, it was demonstrated that fomepizole, if administered early enough in a clinical situation, can be more effective than ethanol or hemodialysis in preventing the metabolism of EG to more toxic metabolites. Hemodialysis remains an important option, however, if treatment is instituted after a significant amount of EG is metabolized or if renal toxicity has occurred.

Antidotes↗
PubMed1998

The response to repeated nitric oxide inhalation is inconsistent in patients with acute respiratory distress syndrome.

BACKGROUND: Nitric oxide (NO) is administered frequently in patients with acute respiratory distress syndrome (ARDS) and pulmonary hypertension. The efficacy of this therapy over several days is not well known. The authors first determined the consistency of the response to repeated administration of NO and then the baseline variables that were associated with improvement in patients with severe ARDS. METHODS: In a prospective trial, 32 mechanically ventilated patients with severe ARDS received 10 parts per million NO by inhalation. In 22 of these patients, its effect was tested repeatedly (up to four times) in several days. Improvement was defined as an increase >10% in the ratio of pressure of oxygen in arterial blood (P(aO2)) to the inspiratory pressure of oxygen (FIO2) from baseline. Patients showing such an improvement were maintained on NO inhalation. RESULTS: Twelve of the 22 patients (54%) showed a clinically significant and reproducible increase in the P(aO2)/FIO2 ratio with NO, from 74 +/- 30 mmHg (mean +/- SD) to 95 +/- 41 mmHg (P < 0.001). In three patients (14%), P(aO2) did not improve, even with multiple exposures. In seven patients (32%), an inconsistent response was seen on different days. Mean pulmonary artery pressure decreased for the entire group from 34 +/- 10 mmHg to 29 +/- 9 mmHg (P < 0.01), but this decrease did not correlate with the increase in P(aO2) in individual patients. The baseline P(aO2)/FIO2 ratio and mixed venous oxygenation (P(vO2)) were significantly lower, and the venous admixture was greater in patients showing beneficial effects of NO inhalation on P(aO2). CONCLUSIONS: Repeated NO inhalation caused a consistent improvement in P(aO2) in about one half of these patients with severe ARDS; no significant benefit or inconsistent effects on pulmonary gas exchange were noted in the others. These findings could be related to the complexity of the mechanisms regulating the vasomotor changes in this syndrome. Severe baseline hypoxemia may be associated with a more favorable effect of NO on P(aO2).

Acute Disease↗