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At least 595 records · Page 33Linked to original sources
PubMed2000

Micronuclei and gene mutations in transgenic big Blue((R)) mouse and rat fibroblasts after exposure to the epoxide metabolites of 1, 3-butadiene.

1,3-Butadiene (BD) is a commodity compound and by-product in the manufacture of synthetic rubber that elicits a differential carcinogenic response in rodents after chronic exposure. Mice are up to approximately 1000-fold more sensitive to the tumorigenicity of inhaled BD than rats, thereby confounding human risk assessment analyses. Rodent transgenic in vivo and in vitro models have been recently utilized for generating genetic toxicology data in support of risk assessment studies. However, studies have not been extended to investigate multiple endpoints of genetic damage using in vitro transgenic models. The goal of this study was to evaluate possible differences in the production of genetic damage in transgenic Big Blue((R)) mouse (BBM1) and rat (BBR1) fibroblasts exposed to three predominant epoxide metabolites of BD. Analyses of cytotoxicity, micronucleus (MN) formation, cII mutant frequency (MF) and apoptosis were assessed after in vitro exposure of BBM1 and BBR1 cells exposed to various concentrations of butadiene monoepoxide (BMO), diepoxybutane (DEB) and butadiene diolepoxide (BDE). Both BMO and DEB reduced cell survival in BBM1 and BBR1 cells. However, BDE decreased cell survival only in BBM1 cells at the concentrations evaluated. Concentration-dependent increases in the formation of MN was observed in both BBM1 and BBR1 cells, with DEB being the most potent followed by BDE and then BMO. The dose-response for mutations induced at the cII locus was essentially equal after DEB exposure of BBM1 and BBR1 fibroblasts. In contrast, the cII MF was significantly increased only in BBM1 cells after exposure to either BMO or BDE. These data demonstrate a differential genetic response for gene mutations but not for MN formation in transgenic BBM1 and BBR1 fibroblasts and suggest a rodent species-specific difference in the persistence of DNA damage that results in gene mutations. In addition, apoptosis was observed in BBR1 cells but not in BBM1 cells when treated with any of the three BD epoxide metabolites. This response may partially explain the differential response to mutations induced by BMO and BDE. These data offer insight into specific differences in mouse and rat cells with respect to their response to BD epoxide metabolites. Such data may help to explain the different tumorigenicity results observed in rodent BD carcinogenicity studies.

Analysis of Variance↗
PubMed2005

Trends in solubility of polymorphs.

Polymorphism of drug substances has been the subject of intense investigation in the pharmaceutical field for over 40 years. Considering the multitude of reports on solubility or dissolution of polymorphs in the literature, an attempt is made in this study to answer the question: How big is the impact of polymorphism on solubility? A large number of literature reports on solubility or dissolution of polymorphs were reviewed and the data were analyzed for trends in solubility ratio of polymorphs. The general trend reveals that the ratio of polymorph solubility is typically less than 2, although occasionally higher ratios can be observed. A similar trend is also observed for anhydrate/hydrate solubility ratios, although anhydrate/hydrate solubility ratios appear to be more spread out and higher than the typical ratio for nonsolvated polymorphs. An attempt is also made in this commentary to estimate the ratio of solubilities of polymorphs from thermal data. The trend in estimated solubility ratio shows good agreement with the one observed with experimentally determined solubility values.

Algorithms↗
PubMed1999

A quantitative three-dimensional model of the Drosophila optic lobes.

A big step in the neurobiology of Drosophila would be to establish a standard for brain anatomy to which to relate morphological, developmental and genetic data. We propose that only an average brain and its variance would be a biologically meaningful reference and have developed an averaging procedure. Here, we present a brief outline of this method and apply it to the optic lobes of Drosophila melanogaster wild-type Canton S. Whole adult brains are stained with a fluorescent neuropil marker and scanned with the confocal microscope. The resulting three-dimensional data sets are automatically aligned into a common coordinate system and intensity averages calculated. We use effect-size maps for the fast detection of differences between averages. For morphometric analysis, neuropil structures are labelled and superimposed to give a three-dimensional probabilistic map. In the present study, the method was applied to 66 optic lobes. We found their size, shape and position to be highly conserved between animals. Similarity was even higher between left and right optic lobes of the same animal. Sex differences were more pronounced. Female optic lobes were 6% larger than those of males. This value corresponds well with the higher number of ommatidia in females. As females have their additional ommatidia dorsally and ventrally, the additional neuropil in the medulla, lobula and lobula plate, accordingly, was found preferentially at these locations. For males, additional neuropil was found only at the posterior margin of the lobula. This finding supports the notion of male-specific neural processing in the lobula as described for muscid and calliphorid flies.

Animals↗
PubMedDate not supplied

Bone scan as a screening tool in children and adolescents with back pain.

Retrospective review of 142 patients from 2 teaching hospitals, investigated for persistent backache. The inclusion criteria were to be up to 18 years, to have no known associated diseases, and to have had a bone scan as a part of their work up. Other tests were also used to reach the final diagnosis. The utility of the bone scan to detect underlying pathology was assessed. On the whole, 75 patients were found to have pathology while only 52 children had a positive bone scan. We also looked for associated findings that could indicate the presence of pathology. The age of the patients, the duration of symptoms, and the presence of night pain seemed to be irrelevant on predicting underlying pathology. The sensitivity of the bone scan was low, 0.613 (95% CI: 0.549-0.654), although it proved to be highly specific, 0.91 (95% CI: 0.83-0.95). A careful analysis of the data and the different diagnosis suggests that Technetium bone scan still holds a place in the study of these patients; however, there is a big concern by the fact that some primary malignancies went undetected on the scan.

Adolescent↗
PubMed2003

The spine in fibrodysplasia ossificans progressiva: a case report.

STUDY DESIGN: A case report of fibrodysplasia ossificans progressiva (FOP). OBJECTIVES: To report a very rare cause of back pain. SUMMARY OF BACKGROUND DATA: FOP is an autosomal dominant disorder with overexpression of bone morphogenetic protein 4 and negative HLA B27. Pathognomonic are congenital malformations of the big toes. METHODS: The authors report on a patient with FOP who presented with back pain at their outpatient clinic. RESULTS: On physical examination, several indurated masses were visible and palpable close to the left and right scapula and the thoracic spine. These were not tender or painful, nor warmed or inflamed. A significantly decreased range of motion of all levels of the spine and the shoulder were found. On the radiographs, segmentation defects of the cervical and lumbar spine as well as synostoses of the spinal processes were seen. The cervical vertebral bodies were small and unusually high. Heterotopic ossifications could be discerned in the lumbar postural muscles and the facet joints of the spine were ankylosed. Additionally to these findings, on the thoracic radiographs ossifications of the muscles of the shoulder girdle could be seen. The pathognomonic shortening of the first metatarsal bone and the proximal phalanx was bilaterally present. The surface shaded 3D-reconstruction of the computed tomography of the trunk showed multiple bulky and confluating ossifications of the shoulder girdle. The spinal processes of the thoracic spine were anklyosed by massive ossifications of the postural muscles. CONCLUSIONS: In FOP, diagnosis can be made by the typical clinical and radiological features.

Adolescent↗
PubMed2004

Oral health in Iran.

The health network in the Islamic Republic (I.R.) of Iran is an integrated public health system with a four-level Dental Health Care System integrated into it by 1997. The first level is one of primary prevention at 'health houses', at the next, oral hygienists and dentists in health centres perform basic oral health care services such as fillings, scaling and extractions. At the third level, dentists manage and treat oral diseases in 'urban health centres, while the last level is for advanced treatment by specialists in university health centres in the big cities. There are about 13,000 dentists nationwide (1 dentist: 5,500 population) and nearly 1,200 specialists in universities and private practices. Data from surveys in the past two decades, show a marked decline in dental caries from DMFT of 4 to 1.5 in 12-year-old children. However, the general level of oral health is still not satisfactory, particularly among children. The percentage of caries-free children (deciduous and permanent teeth) among 6- and 9-year-olds is 13.8 and 11.5 respectively and more than 50% of 12-year-old children have caries experience, with the decayed component being the greatest component. The main objective would be to cope with the dental caries problem in primary teeth and, in this respect, the national oral health plan should be aimed at developing oral hygiene skills, reducing the frequency of sugar intake, instituting water fluoridation, improving access to fissure sealants and regular dental care, and finally promoting dental health services toward minimum treatment intervention and effective preventive strategies and health promotion.

Academic Medical Centers↗
PubMed2007

Split dose recovery studies using homologous recombination deficient gene knockout chicken B lymphocyte cells.

To understand the role of proteins involved in DSB repair modulating SLD recovery, chicken B lymphoma (DT 40) cell lines either proficient or deficient in RAD52, XRCC2, XRCC3, RAD51C and RAD51D were subjected to fractionated irradiation and their survival curves charted. Survival curves of both WT DT40 and RAD52 (-/-) cells had a big shoulder while all the other cells exhibited small shoulders. However, at the higher doses of radiation, RAD51C(-/-) cells displayed hypersensitivity comparable to the data obtained for the homologous recombination deficient RAD54(-/-) cells. Repair of SLD was measured as an increase in survival after a split dose irradiation with an interval of incubation between the radiation doses. All the cell lines (parental DT40 and genetic knockout cell lines viz., RAD52(-/-), XRCC2(-/-), XRCC3(-/-) RAD51C(-/-) and RAD51D(-/-)) used in this study demonstrated a typical split-dose recovery capacity with a specific peak, which varied depending on the cell type. The maximum survival of WT DT40 and RAD52(-/-) was reached at about 1-2 hours after the first dose of radiation and then decreased to a minimum thereafter (5h). The increase in the survival peaked once again by about 8 hours. The survival trends observed in XRCC2 (-/-), XRCC3(-/-), RAD51C (-/-) and RAD51D(-/-) knockout cells were also similar, except for the difference in the initial delay of a peak survival for RAD51D(-/-) and lower survival ratios. The second phase of increase in the survival in these cell lines was much slower in XRCC2(-/-) , XRCC3(-/-), RAD51C(-/-) and RAD51D(-/-) and further delayed when compared with that of RAD52(-/-) and parental DT40 cells suggesting a dependence on their cell cycle kinetics. This study demonstrates that the participation of RAD52, XRCC2, XRCC3, RAD51C and RAD51D in the DSB repair via homologous recombination is of less importance in comparison to RAD54, as RAD54 deficient cells demonstrated complete absence of SLD recovery.

Animals↗
PubMed2003

Frequent misdiagnosis and mismanagement of hyperprolactinemic patients before the introduction of macroprolactin screening: application of a new strict laboratory definition of macroprolactinemia.

BACKGROUND: Macroprolactin (big big prolactin) has reduced bioactivity and is measured by immunoassays for prolactin when it accumulates in the plasma of some individuals. We applied normative data for serum prolactin after treatment of sera to remove macroprolactin to elucidate the contribution of macroprolactin to misleading diagnoses, inappropriate investigations, and unnecessary treatment. METHODS: We reviewed records of women attending a tertiary referral center who had prolactin >1000 mIU/L. Application of a reference interval to polyethylene glycol (PEG)-treated hyperprolactinemic sera identified 21 patients in whom hyperprolactinemia was accounted for entirely by the presence of macroprolactin. Presenting clinical features, diagnoses, and treatment were compared in these patients and 42 age-matched true hyperprolactinemic patients. RESULTS: Prolactin concentrations in sera of 110 healthy individuals ranged from 78 to 564 mIU/L. The range of values for the sera after PEG treatment was 70-403 mIU/L. For macroprolactinemic samples, PEG treatment decreased mean (SD) prolactin from 1524 (202) mIU/L to 202 (27) mIU/L but decreased it only from 2096 (233) mIU/L to 1705 (190) mIU/L in true hyperprolactinemic patients (P <0.01 between groups). Oligomenorrhea or amenorrhea and galactorrhea were the most common clinical features in both groups, although they occurred more frequently in true hyperprolactinemic patients (P <0.05). Serum estradiol and luteinizing hormone concentrations were significantly higher in participants with macroprolactinemia than in those with true hyperprolactinemia (P <0.05). Among participants with retrospectively identified macroprolactinemia, pituitary imaging was performed in 93% and treatment with dopamine agonist was prescribed in 87%. CONCLUSIONS: Macroprolactin is a significant cause of misdiagnosis, unnecessary investigation, and inappropriate treatment. The use of an appropriate reference interval for the PEG immunoprecipitation procedure may be of particular importance in those patients who have an excess of both macroprolactin and monomeric prolactin.

Adult↗
PubMed1996

Eustrongylidiasis--a parasitic infection acquired by eating live minnows.

The objective of this study was to heighten physician awareness of eustrongylidiasis by investigating the epidemiology of this parasitic infection. The nematode Eustrongylides ignotus was recovered surgically from our patient, in whom eustrongylidiasis simulated acute appendicitis. The patient had consumed two live minnows obtained from Big Timber Creek of Belmawr, NJ. The authors determined the E ignotus infestation rate of free-living minnows at this creek. With this data, they approximate the probability of human infection with E ignotus after eating live minnows and attempt to evaluate the hypothesis that eating live minnows may lead to eustrongylidiasis.

Abdomen, Acute↗
PubMed2002

From pharmacovigilance to pharmacoperformance.

The pharmaceutical industry is going through a period of enormous upheaval, as new sciences, technologies and commercial pressures reshape the way in which it performs research and development. PwC Consulting estimates that the top 20 companies will each need to launch between four and six times the number of drugs they currently produce, as well as improving the quality of those drugs, merely to maintain shareholder returns. This has huge implications for pharmacovigilance departments. More drugs means more trials, more patients and -- of course -- more safety reports for evaluation. The pharmacovigilance teams in most big companies are ill prepared for this transition being already stretched to the limit. But as demand for patients to participate in clinical trials increases -- with shorter development times, higher success rates in discovery and greater productivity -- so companies with a poor reputation for safety will suffer. What is it then that companies should be doing to remain compliant and be seen to be safe in the eyes of the consumer? Can pharmacoepidemiology support both molecules in the marketplace as well as those in research and development and what is really needed to enable this? Key to success will be the ability to capture, analyse and evaluate data (from disparate sources) in real time and to make rapid decisions on the appropriate course of action. Putting better structures, processes and technological platforms in place to cope with a big increase in throughput is only a short-term solution yet is it enough to fulfil the objective in the long-term of ensuring compliance and patient safety?

Adverse Drug Reaction Reporting Systems↗
PubMed1994

Separating description and evaluation in the structure of personality attributes.

Personality attributes typically combine descriptive and evaluative aspects, as do most personality constructs and the factors in the Big Five taxonomy. However, an auxiliary representation, in which the descriptive and evaluative aspects are clearly separated, has technological utility in some areas of research and assessment. D. Peabody and H. G. Gough independently developed structural models of this type, each with 3 dimensions. Studies used a multiple-method, multiple-replication approach, with data sets involving a large, representative set of familiar personality adjectives, to uncover a structure with 5 orthogonal dimensions, 4 descriptive and 1 highly evaluative, easily measurable with adjective scales. These dimensions demonstrated a complex relation to previous Peabody factors and to the Big Five, and they may be useful in integrating some venerable constructs into the structure of personality attributes.

Adolescent↗
PubMedDate not supplied

[Correlation between survival time and severity of injuries in fatal injuries in traffic accidents].

INTRODUCTION: In forensic pathology, only trauma systems based on disintegration of anatomic structure of organs and tissues, could be used for objectivization, comparison and establishing of severity of injuries. Trauma systems based on pathophysiological values are useless. The Abbreviated Injury Scale (AIS) and its derivate Injury Severity Score (ISS) are the most common. AIS coded injuries are divided into six body regions and injuries are assigned a six-digit score in relation to their severity. ISS results the sum of the squares of the highest AIS values from the three most severely injured body regions. In this way, the ISS values are discontinued and vary from 0 (absence of injuries) to 75 (incompatible-with-life injury). PURPOSE: The purpose of this paper is to establish the correlation degree between outliving period and trauma severity in persons fatally injured in traffic accidents, and according to this finding to point out the ISS value of critical injury. MATERIAL AND METHOD: A retrospective autopsy study was performed; it included the material of the Institute of Forensic Medicine in Belgrade of 1998. The autopsy reports and accessible clinical medical data were analyzed for persons over the age of 18, fatally injured in traffic accidents who survived trauma less than 15 days. The sample was statistically prepared (chi 2-test, t-test, correlation coefficient, regression line). RESULTS AND DISCUSSION: The sample included 272 persons: 193 males and 79 females. The proportion of men was more significant (chi 2 = 4.76; 0.01 < p < 0.05). Average age was 51.08 years (SD = 18.08): males 49.84 +/- 17.41 and females 54.09 +/- 19.38. The most frequently injured persons in our sample were pedestrians (134). The authors combined the autopsy and accessible clinical data in order to obtain the ISS value for each case. They considered that all persons found dead on the spot or died ante portam did not outlive trauma. The sample distribution by ISS values showed three peaks: for ISS--75, 41-50 and 26-35. Peaks indicated the number of the injured body regions and trauma severity in these persons. In 87 persons who did not survive, the ISS value was 75. There were 73 persons without outliving period with ISS values less than 75: their mean ISS value was 31.87 (SD = 11.30). In 112 cases the mean outliving period was 4.79 days (SD = 3.77) and their mean ISS value was 18.05 (SD = 15.33), which was a statistically significant lower ISS value than in previous group (t = 7.015; p < 0.001). A weak negative correlation between outliving period and ISS values in our sample was noted (coefficient of linear correlation r = -0.452). Our sample is representative (t = 8.37). Coefficient of a determination (r2 = 0.20), pointed to the fact that direct correlation outliving period-trauma severity was only about 20% and the rest of correlation i.e. 80% depended on other factors (e.g. effective emergency medical system and triage, prompt and correct diagnosis, adequate medical treatment and care, etc.). The calculated linear regression was as follows: outliving period approximately 52-3 ISS. This regression pointed out that critical and potentially fatal injury, in our sample, was injury with ISS of 17. There were 22 persons with ISS < or = 7. Six of them died on the spot as car passengers; they died due to mechanical asphyxia (thoracoabdominal pressure) or respiratory and/or circulation failure due to critical chest injury (flail chest, contusions and rupture of the lungs with consequent haemopneumothorax). The rest of 16 persons survived trauma in an average of 8.56 days (SD = 3.88), and the causes of death were pneumonia, thrombus and fat embolism, sepsis, etc. CONCLUSION: By anaylzing our sample of fatally injured persons in traffic accidents (unpenetrated blunt trauma), there was a negative weak correlation between the outliving period and severity of injury based on ISS. This correlation was partly direct but mostly depended on other factors (e.g. effective emergency medical system and triage, prompt and correct diagnosis, adequate medical treatment and care, etc.). Establishment of these factors could be possible through state medical projects in big medical trauma centres. Prospect registration, evaluation and scoring of all injuries in hospitals and dissecting rooms, and comparison of the obtained results, can give valid data on mortality of injured people, bad diagnosis, and appropriate medical treatment. The autopsy of injured persons dead on the spot can point out what kind of injuries are incompatible with life, as well as with their severity. The autopsy of injured persons who survived trauma can point to the most frequent injury complications, clinical diagnosis and preventable deaths. According to this paper, the critical injury by ISS is 17. In such cases, the forensic pathologist must answer the following questions: whether the death was due to trauma; whether the precipitated cause of death was the consequence or complication of injury; what were the mechanism and mode of dying; whether the death was preventable; if there were possible malpractice and negligence, etc.

Accidents, Traffic↗
PubMed2005

Shortchanged? An assessment of chronic disease programming in major US city health departments.

A self-administered survey was distributed to members of The Big Cities Health Coalition, a group of Health Officers/Commissioners from 17 of the largest US metropolitan health departments. The survey asked participants about their chronic disease priorities, data sources, budgets, and funding sources as well as examples of successful chronic disease interventions. Members of the Coalition discussed the survey results in a scheduled conference call. Chronic diseases account for 70% of all deaths nationwide on average, yet the health departments surveyed allocated an average of 1.85% of their budgets to chronic disease. Average chronic disease spending per inhabitant was 2.33 dollars, with a median of 1.56 dollars. Among the group's top chronic disease priorities were asthma, diabetes, tobacco, cancer, and cardiovascular disease (CVD). Nearly half of the group's chronic disease spending was on tobacco. Chronic disease funding sources varied across localities, but direct federal funding was minimal. In 14 cities serving a combined 37 million people (13% of the US population), direct federal chronic disease funding totaled 8.7 million dollars, an average of 0.24 dollars per capita. The group described successful chronic disease interventions, particularly related to tobacco and asthma.

Budgets↗
PubMed1993

Big brother.

Both purchasers and providers will need to change the way they hold patient records on computer, or they could find themselves in breach of the law. Michael Cross examines a report by the Data Protection Registrar.

Computer Security↗