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PubMed1996

Biomedical three-dimensional holographic microimaging at visible, ultraviolet and X-ray wavelengths.

A new imaging technology is under advanced development that has several key advantages over conventional forms of microimaging performed with standard light microscopes, confocal light microscopes, and electron microscopes. The image created by this microscope possesses several unique features: It is intrinsically three-dimensional; it can be formed with very high contrast, a characteristic of the phase-sensitive nature of the recording; the information contained in the image is obtained in a single exposure of the specimen, a feature that eliminates the accumulation of damage to living systems that can occur with techniques utilizing multiple exposures; the method of image construction is fundamentally free from aberration (distortion), thereby obviating the need to employ complex procedures for correction; the exact focal plane of any optical section is digitally determined through computation and is not based on any mechanical adjustments; and the principles of operation, including the computational processes and modalities of image presentation, are uniform over the full range of spectral coverage spanning from the visible (approximately 500 nm) to the X-ray (approximately 0.3 nm) regions. The application of this new technology is expected to open new cost-effective avenues to the understanding, prevention and treatment of broad areas of human disease.

Animals↗
PubMed2002

Patella inversion method for exposure in revision total knee arthroplasty.

Satisfactory performance of revision total knee arthroplasty (TKA) requires adequate exposure. This article shows the patella inversion method of exposure in a large consecutive series of revision TKAs.Between 1987 and 1999, 420 revision TKAs were performed. Exposure was facilitated by the patella inversion method. No attempt was made to evert the patella. This technique of exposure was used in 95% (397 of 420) of patients. There were no episodes of patellar tendon avulsion in this series. Multiple exposure options are available in revision TKA. Extensile techniques violate the extensor mechanism. For most patients, these methods were unnecessary. The patella inversion method afforded adequate exposure in most patients without violating the extensor mechanism.

Arthroplasty, Replacement, Knee↗
PubMed1989

Animal model for ultraviolet radiation-induced melanoma: platyfish-swordtail hybrid.

Sunlight exposure is strongly indicated as one of the important etiologic agents in human cutaneous malignant melanoma. However, because of the absence of good animal models, it has not been possible to estimate the wavelengths or wavelength regions involved. We have developed a useful animal model from crosses and backcrosses of platyfish (Xiphophorus maculatus) and swordtails (Xiphophorus helleri). Two strains of these fish are susceptible to invasive melanoma induction by exposure to filtered radiation from sunlamps in the wavelength ranges lambda greater than 290 nm and lambda greater than 304 nm. Multiple exposures on 5-20 consecutive days beginning on day 5 after birth or a single exposure of approximately 200 J/(m2.day) of lambda greater than 304 nm result in a tumor prevalence of 20% to 40% at 4 months of age compared with a background rate of 12% in one strain and 2% in another. Exposure of the fish to visible light after UV exposure reduces the prevalence to background. The melanomas are similar in many respects to mammalian melanomas, as judged by light and electron microscopy. The genetics of the crosses determined by others and the high sensitivity of the hybrids to melanoma induction indicate that the UV radiation probably inactivates the one tumor repressor gene (or a small number of tumor repressor genes) in the hybrid fish. The small size of the animals and their high susceptibility to melanoma induction make them ideal for action spectroscopy.

Animals↗
PubMed1989

Mosquito salivary gland antigens identified by circulating human antibodies.

Salivary glands were removed from female mosquitoes of laboratory-reared strains of species common to southern Florida. Protein antigens were isolated from homogenates of these glands by denaturing electrophoresis and transferred to nitrocellulose for immunoblotting with serum samples obtained from human volunteers. A spectrum of antigens with a wide range of molecular weights (14 to 126 kilodaltons) were identified by antibodies in human serum for each species. Both species-unique and species-shared antigens were present. The results of these studies indicate that the humoral response to mosquito bite is complex, with a multitude of antigens provoking antibody responses. Since each individual has his or her own unique exposure history to mosquitoes, it seems unlikely that desensitization to a specific immunogen will confer protection in clinical situations in which multiple exposures to a variety of mosquito species occur.

Animals↗
PubMed2004

Capillaria hepatica-induced hepatic fibrosis in rats: paradoxical effect of repeated infections.

Multiple exposures to parasitic agents are considered an important factor in the genesis of the most severe forms of the diseases they cause. Capillaria hepatica-induced septal fibrosis of the liver in rats usually runs without signs of portal hypertension or hepatic failure. After determining the hepatic profile of 15 animals during the course of a single infection, we submitted 20 rats to multiple Capillaria hepatica infections to determine whether repeated exposures would augment fibrosis production, transforming septal hepatic fibrosis into a true cirrhosis. Ten single-infection rats served as controls. A total of 5 exposures, with 45-day intervals, were made. Histological changes were followed by means of surgical liver biopsies, collected prior to infection and to each re-infection. Functional changes were minimal and transient. Although a slight recrudescence of fibrosis was observed after the first two re-infections and when the single-infected control group was re-infected at the end of the experiment, subsequent re-infections failed to increase the amount of fibrosis. On the contrary, there occurred quantitative and qualitative evidence of collagen degradation and suppression of parasite development. These paradoxical results are in keeping with the hypothesis that a complex immunological modulation participates in the mechanism of hepatic fibrosis induced by Capillaria hepatica infection in rats.

Animals↗
PubMed1984

The present status of biological effects of toxic metals in the environment: lead, cadmium, and manganese.

The number of reports concerning the chemical toxicology of metals which are released in the environment by natural as well as anthropogenic sources, have been increasing constantly. Lead, cadmium, and manganese have found a variety of uses in industry, craft, and agriculture owing to their physical and chemical properties. The environmental burden of heavy metals has been rising substantially by smelter emission in air and waste sewage in water. Further, organic compounds of lead and manganese used as antiknock substances in gasoline are emitted into the atmosphere by automobile exhaustion. Such environmental contamination of air, water, soil, and food is a serious threat to all living kinds. Although these metals are known to produce their toxic effects on a variety of body systems, much emphasis has been placed on their effects on the nervous system owing to apparent association of relatively low or "subclinical" levels of metallic exposure with behavioral and psychological disorders. Clinical and animal data on environmental exposure show that while lead and manganese are most toxic to the nervous system, cadmium exerts profound adverse effects on kidney and the male reproductive system. It appears that the consequences of exposure to lead in adults are less severe than the types of exposure associated with hyperactivity in neonates. Except for a few reports, hyperactivity has indeed been observed in animals exposed to either of these three metals. Experimental work has also shown that these metals produce behavioral changes by altering the metabolism of brain neurotransmitters, especially catecholamines. Recently, it is hypothesized that these metals exert their toxic effect by damaging biological defences which exist in the body to serve as protective mechanisms against exogenous toxins. A voluminous publication list with diverse opinions on the biological effects of metals is available and there is an urgent need to compile assessment of the existing literature to identify the future theme of research work. The problem of metal toxicity becomes even more complex owing to simultaneous or successive exposure of the general population to different physical, chemical, biological, and psychological factors in the environment. The net toxic manifestations produced by multiple exposure should, therefore, be different from those produced by a single factor as the result of their additive, synergistic or antagonistic action. Even though a metal may not exist in sufficient amounts to cause any disability, the toxicity could result when a second factor is also present.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1994

Geographic analysis of pathogen exposure in bighorn sheep (Ovis canadensis).

Antibody responses were examined among 998 bighorn sheep (Ovis canadensis) in California (USA) to determine spatial patterns of pathogen exposure. Using a shifting frame analysis, a specific geographic region was delineated that contained bighorn sheep with higher (P < 0.05) levels of multiple exposure (antibodies detected against > or = two pathogens), as well as higher prevalence values for eight of ten individual pathogens. This region in southwestern California encompassed all of the peninsular populations of bighorn sheep recently proposed for listing as endangered by the U.S. Fish and Wildlife Service.

Animals↗
PubMedDate not supplied

[Cardiopathy caused by physical or chemical agents].

BACKGROUND: Occupational cardiovascular diseases do not possess any specific clinical and physiopathogenetic features. OBJECTIVES: The paper summarizes the results of the most recent studies on chemical and physical cardiovascular risks, and assesses the current degree of risk for occupational cardiovascular disease. METHODS: Scientific literature and medline databases on this topic were carefully considered. RESULTS AND CONCLUSION: The scientific literature often provides interesting information on the cardiotoxicity of chemical and physical agents in workplaces; however, a large amount of data refers to high-dose exposures. On the contrary, nowadays exposure conditions have progressively improved and toxic concentrations in air in most cases are below the environmental threshold limit values. In workplaces multiple exposures to different cardiovascular risks, both occupational and non-occupational, are often present simultaneously and these cardiovascular diseases have not been adequately studied in comparison to other occupational organic and systemic diseases. Moreover, possible interferences between occupational cardiotoxic substances and cardiological therapy are still poorly investigated, even though such situations frequently occur.

Air Pollutants, Occupational↗
PubMedDate not supplied

[The evaluation of occupational exposure to carcinogenic substances: limit values and risk assessments].

Considering that nowadays there is no unanimity about the possibility of adopting environmental and/or biological limit values in occupational exposure to carcinogens, some aspects are discussed about the mechanism of action of carcinogens, their metabolism and problems deriving from the possible multiple exposures, interactions and speciation of the different compounds. After the analysis of the results obtained by means of two different approaches by the American Conference of Governmental Industrial Hygienist and the Environmental Protection Agency of the United States, the authors examine some aspects of the qualitative and as far as possible quantitative comparison for the 16 substances included in both lists and they discuss how the mathematical models are used in the process of carcinogenic risk evaluation. Finally, it is considered the possible application even in occupational carcinogenesis of a model such as the one of the EPA.

Carcinogens↗
PubMed1983

Pharmacokinetics of nicotine in rats after multiple-cigarette smoke exposure.

The pharmacokinetics of nicotine and its major metabolites was evaluated in male rats after multiple-cigarette smoke exposure. A smoke-exposure apparatus was used to deliver cigarette smoke to the exposure chamber. The rats were exposed to smoke from a single cigarette every 8 hr for 14 days and to the smoke of a cigarette spiked with radiolabeled nicotine on the 15th day. Blood and urine samples were collected at timed intervals during the 10-min smoke-exposure period of the last cigarette and up to 48 hr thereafter. Nicotine, cotinine, and other polar metabolites were separated by thin-layer chromatography and quantified by liquid scintillation counting. The data were analyzed by computer fitting, and the derived pharmacokinetic parameters were compared to those observed after a single iv injection of nicotine and after a single-cigarette smoke exposure. The results indicated that the amount of nicotine absorbed from multiple-cigarette smoke was approximately 10-fold greater than that absorbed from a single cigarette. Also, unlike the single-cigarette smoke exposure experiment, nicotine plasma levels did not decay monotonically but increased after the 5th hr, and high plasma concentrations persisted for 30 hr. The rate and extent of the formation of cotinine, the major metabolite of nicotine, were decreased as compared with their values following a single-cigarette smoke exposure. It was concluded that nicotine or a constituent of tobacco smoke inhibits the formation of cotinine and may affect the biotransformation of other metabolites. Urinary excretion tended to support the conclusions that the pharmacokinetic parameters of nicotine and its metabolites were altered upon multiple as compared to single dose exposure.

Absorption↗
PubMed2002

Coagulopathy as a result of factor V inhibitor after exposure to bovine topical thrombin.

We describe a case of severe coagulopathy after mesenteric revascularization. Laboratory investigation results revealed the presence of plasma inhibitors of factor V believed to result from exposure to bovine thrombin used for intraoperative hemostasis. Vascular and cardiothoracic surgeons commonly use topical thrombin for surgical hemostasis, and many patients undergo multiple exposure. More patients likely have factor V inhibitors develop than has previously been realized, and this may account for some otherwise unexplained postoperative coagulation disorders. This report may alert surgeons to coagulation disturbances that can result from exposure to bovine thrombin and provide guidelines for diagnosis and management.

Administration, Topical↗
PubMed1990

Characterization of N-nitrosourea-induced tumors of the nervous system; their prospective value for studies of neurocarcinogenesis and brain tumor therapy.

Two decades of research with resorptive neurocarcinogens firmly established the high potency of methyl and ethylnitrosourea (MNU and ENU) as neurocarcinogens, particularly in rats. There are significant differences in susceptibility to these agents among species. There are also differences among age groups. Fetuses are between 50 to 100 times more susceptible than adult rats. One single iv inoculation of 20-50 mg/kg ENU into pregnant rats may produce neurogenic tumors in 100% of the offspring. The tumors produced by these compounds have been well characterized morphologically, biologically, biochemically and histochemically. Tumors produced by both compounds are mostly gliomas and neurinomas (Schwannomas), however, clear differences exist between ENU and MNU produced neoplasms. Transplacental exposure to ENU generally results in a high number of anaplastic neurinomas and mostly differentiated gliomas (astrocytomas, oligodendrogliomas or mixed gliomas). In contrast, multiple exposures of adult rats to MNU result in a moderate number of mostly differentiated neurinomas and a high number of anaplastic gliomas. Tumors usually start out as well differentiated oligodendrogliomas or astrocytomas. As they grow larger, they become more mixed and anaplastic. In contrast to spontaneous gliomas in old rats, MNU and ENU-induced astrocytomas can be readily identified with well established biomarkers such as the S100 protein and particularly GFAP (glial fibrillary acidic protein). Neurinomas are also strongly positive for S100 protein. No reliable markers exist for oligodendrogliomas. Neurogenic tumors induced by MNU or ENU, as well as derived cell lines and clones from such tumors, have been successfully used as models for neurocarcinogenesis and therapeutic screening.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

[Approach to epidemiological cohort designs].

In neurological cohort studies participants are those who are "at risk" of developing the outcome (i.e., stroke, dementia, parkinsonism) and should be free of such event when their follow-up is begun. They are classified and controlled at the outset by their risk or "exposition" factors. There are several alternatives of selecting the study population, although the most known are those of the large population bases (for example, Framingham Heart Study, the Rochester MN, etc.). There should be standardized procedures of classification and follow-up and the investigator who makes the diagnosis should be blinded to the exposure status, when it is possible. In cohort studies, we will consider several frequency measures, such as incidence and risk, and the most frequent association measures, such as relative risk, risk difference, and rate ratio. The advantages of a cohort study in neurology are: a) the exposure is known to occur prior to the onset of the outcome and is measured prior to the occurrence of the outcome, b) multiple exposures and outcomes (end-points) can be studied simultaneously, and they usually have good control, c) it is good for rare exposures (if there was adequate sampling), and it is good for common outcomes. The disadvantages of a cohort studies are: a) they are expensive and time-consuming; b) possibility of change in investigators for very long studies, or attrition of participants; c) not good for rare outcomes; d) exposures can change, exposures are not independent of other potential causes and prognostic factors, and e) knowledge of exposure may alter surveillance for the disease or alter the likelihood that a particular diagnostic label will be applied. It is useful for the clinical neurologist to know and to understand these terminology and concepts.

Cohort Studies↗
PubMed1989

Carcinogenic risk assessment of complex mixtures.

Although procedures for assessing the carcinogenic risks associated with exposure to individual chemicals are relatively well developed, risk assessment methods for mixtures of chemicals are still in the developmental stage. In this paper, we examine the difficulties in assessing the risks of exposure to complex mixtures, with special reference to the potential for synergistic effects among the components of the mixture. Statistical models for describing the joint action of multiple exposures are reviewed, and their implications for low-dose risk assessment are examined. The potential use of pharmacokinetic models to describe the metabolism of mixtures is also considered. Application of these results in regulating mixtures of carcinogenic substances is illustrated using examples involving multiple contaminants in drinking water and polycyclic aromatic hydrocarbons produced from combustion sources.

Carcinogenicity Tests↗
PubMed1991

An estimating equation approach for the analysis of case-control studies with exposure measured at several levels.

Liang gave an extension of the Mantel-Haenszel estimating procedure for a common odds ratio to logistic regression models. It is applicable to case-control studies with multiple exposure levels, which yield K 2 x J tables. This paper provides variance and covariance estimators, which are consistent in both sparse-data and large-strata, for Liang's estimating functions in the K 2 x J tables case, and proposes an approximate confidence interval method for the common odds ratios.

Analysis of Variance↗
PubMedDate not supplied

Sperm motility analysis using multi-exposure photography (MEP) before and after in vitro-treatment of the semen.

Different methods and culture media were used on the same semen samples. Ejaculated and treated samples were evaluated by means of multiple exposure photography (MEP) in order to study changes in sperm motility. A statistical analysis of the normal sperm population distribution curve was done with two objectives: (1) evaluating semen improvement after treatment; and (2) finding out whether the post-treatment sample differed from the original one. When variables were analysed in the individual subject, a significant percentage improvement of mean velocity was observed. Only two methods improved the percentage of motile sperm. The influence of treatment and of culture media on sperm responses was also tested and a significant influence of the media was found (Ham F10 showed the best responses). No significant differences between the ejaculated and treated samples were found when mean velocity, percentage of motile sperm, variance population, and kurtosis were analysed, as grouped treatment variables.

Culture Media↗
PubMed1987

Morphological evidence for increased protein synthesis in CNS neurons after soman exposure.

Fine structural changes in neurons of the dorsal hippocampus, caudate nucleus, supraoptic nucleus (SON), and ventral horn of the spinal cord of adult male or spayed female cats were studied after single and multiple doses (dose range 1.0-20.0 micrograms/kg sc) of the organophosphonate, pinacolyl methylphosphonofluoridate (soman). Increases in amounts of rough endoplasmic reticulum (rER) and polyribosomes, proliferation of Golgi complexes, as well as indentations of nuclear membranes occur after single and multiple exposures. The degree of change is dependent on dose, duration of exposure, and time of survival after exposure. The cell organelles affected are essential for protein synthesis and changes in their quantities are morphological indicators for changes in protein synthesis. The data presented in this study suggest an initial increase in protein synthesis after soman exposure, followed by early signs of degeneration. Soman (10 micrograms/kg iv) inhibition of cholinesterases of whole blood, spinal cord, and caudate nucleus of control and cats from which electrophysiological recordings of Renshaw cell field potentials were taken show significant differences. Moreover, while blood values are unmeasurable, spinal cord and caudate nucleus values are 42.21 and 53.6% those of controls at 30 min after injection and 63.41 and 50.75% those of controls after 240 min, respectively. No differences are noted between Renshaw cell field potentials after treatment and controls. Similarly, no changes in gross behavior are noted after 10 micrograms/kg sc. Yet, morphological signs of increases in protein synthesis are present. It is concluded that soman induces increased protein synthesis in many areas studied and that this increase is not dependent on inhibition of cholinesterase to a degree that affects gross behavior of evoked potentials from a CNS cholinergic-transmitting synapse--the motoneuron axon collateral and Renshaw cell (J. C. Eccles, P. Fatt, and K. Koketsu (1954), J. Physiol, 126, 524-562).

Animals↗
PubMed1994

Subchronic inhalation toxicity studies with hydrochlorofluorocarbon 123 (HCFC 123).

Hydrochlorofluorocarbon 123 (HCFC 123) is one of the chemicals being considered as a replacement for the chlorofluorocarbons. Four subchronic inhalation toxicity studies from 1 to 3 months in duration have been conducted with HCFC 123. One study utilized rats and dogs, while the others were limited to rats only. The exposure levels have ranged from 300 ppm up to 20,000 ppm. Although the studies were conducted over a 14-year period, the results were consistent. In all studies, increases in liver weights were seen at 1000 ppm and above; additionally, one showed this effect at 500 ppm. Histopathological findings were minimal, consisting primarily of focal necrosis in the liver of the dogs at 10,000 ppm. Induction of peroxisomal activity, lowering of serum cholesterol and triglyceride levels, and an increase in urinary fluoride levels were also seen. The 4-hr LC50 in the rat has been reported as 35,000 ppm. At 20,000 ppm for 6 hr, the total daily dose on a concentration times time basis is almost equal to the LC50, yet, in the 4-week study, with 20 exposures at this level, there was no mortality or even marked signs of toxicity. There appeared to be no evidence for cumulative toxicity from multiple exposures in these studies. Overall, HCFC 123 appears to have a low level of toxicity by the inhalation route.

Administration, Inhalation↗