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PubMed2004

Hepatocellular carcinoma and liver tumors in South African children: a case for increased prevalence.

BACKGROUND: The high regional incidence of hepatocellular carcinoma (HCC) in South Africa also may be present in children of the region, although the link to hepatitis B (HBV) appears less clear. The objective of this study was to assess the incidence and probable causes of HCC in South African children. METHODS: Data were obtained from seven participating pediatric oncology units and from the tumor registry to review hepatic tumors in children in South Africa. RESULTS: One hundred ninety-four children (ages 0-14 years) presented with malignant primary hepatic tumors (1988-2003). One hundred twelve tumors (57%) were hepatoblastoma (HB), 68 tumors (35%) were hepatocellular carcinoma (HCC) (including 9 patients with the fibrolamellar variant, 6 of which occurred in black children), 10 tumors (5%) were sarcoma of the liver, and 4 tumors were lymphoma. The ratio of HB to HCC (1.67) was markedly lower compared with other reports, suggesting a greater prevalence of HCC. Correlation with population statistics indicated an incidence of 1.066 malignant liver tumors per year per 10(6) children age < 14 years (HB, 0.61 per 10(6) children; HCC, 0.39 per 10(6)). Two-thirds of patients with HCC were positive for HBV surface antigen (HBsAg), and HCC occurred mostly in black African patients (93%). The mean age of onset was 1.47 years for HB and 10.48 years for HCC. A preponderance of males (3.5:1.0) was noted in the HBsAg-positive group that was not reflected elsewhere. Serum alpha-fetoprotein (AFP) levels were raised both in patients with HB (100%; most AFP levels were very high) and in patients with HCC (69%), although 15% of patients with HCC had low or normal AFP levels. CONCLUSIONS: It appeared from the current results that HCC is more prevalent among children in South Africa compared with the children in more developed countries, although their rates were lower that the rates noted in adults. A collaborative approach will be required to improve their diagnosis and management.

Adolescent↗
PubMed2003

Quantitative fluorescence of 5-FU-treated fetal rat limbs using confocal laser scanning microscopy and Lysotracker Red.

BACKGROUND: LysoTracker Red (LT) is a paraformaldehyde fixable probe that concentrates into acidic compartments of cells and tissues. After cell death, a high level of lysosomal activity (acidic enzyme) is expressed in tissues resulting from phagocytosis of apoptotic bodies by neighboring cells. LT was shown previously to be an indicator of cell death in a manner similar to other standard assays (Annexin, terminal dUTP nick end labeling, Nile blue sulfate, neutral red, and acridine orange). METHODS: LT fluorescence in fetal rat hindlimbs at gestational day 14 was measured 8 h after administration of the teratogen, 5-fluorouracil (5-FU), with the use of confocal laser scanning microscopy (CLSM). Four dose levels of 5-FU (0, 20, 30, and 40 mg/kg) were studied. The preparation technique involved staining with LT, paraformaldehyde fixation, methanol dehydration, and clearance with benzyl alcohol and benzyl benzoate. After this treatment, the limb was nearly transparent and ready for CLSM analysis. RESULTS: LT staining was observed in specific regions undergoing apoptosis in normal (control) hindlimbs. After 5-FU treatment, highly fluorescent regions appeared in the progress zone (PZ) of the limb. A dose-dependent response to 5-FU treatment was observed. Compared with controls, hindlimbs treated with 20, 30, and 40 mg/kg of 5-FU exhibited more fluorescence within the highly proliferative PZ. These results showed a dose-response relation between 5-FU exposure and LT uptake. CONCLUSIONS: We found that three-dimensional volumetric regions indicating a high level of fluorescence in the embryonic limb bud can be quantified with three different computer analysis programs. The combination of a sample preparation procedure that clears tissue, a CLSM technique that addresses the equipment variables, and an application of statistical population analysis procedures enabled the visualization and quantification of fluorescence in entire fetal rat hindlimbs that were approximately 500 microm in thickness.

Animals↗
PubMed1995

Does levodopa therapy delay death in Parkinson's disease? A review of the evidence.

Studies examining the mortality from Parkinson's disease have been reviewed to assess the impact of levodopa therapy. These include national mortality data taken from death certificate returns, cohort studies comparing the deaths observed in a group of patients with those expected from population statistics, and case-control studies comparing deaths in patients with those in a matched control group. It is concluded that the decrease in crude mortality rate in the early 1970s in several western countries was mirrored by a decrease in observed to expected mortality rates in cohort studies over the same period. The rise in crude mortality in the late 1970s and early 1980s paralleled an increase in observed to expected mortality in cohort studies. These trends are compatible with the hypothesis that levodopa delayed the death of a cohort of frail elderly parkinsonian patients who succumbed approximately 5 years later, leading to an apparent "catch-up" increment in national mortality data. Whilst crude mortality in England and Wales does not appear to be increasing as fast as before the introduction of levodopa, recent cohort and case-control studies report mortality ratios comparable to those seen in the prelevodopa era. Further case-control studies are required to determine the position with current treatment regimens.

Aged↗
PubMed2006

Bayesian evidence synthesis to extrapolate survival estimates in cost-effectiveness studies.

This paper is concerned with survival extrapolation that represents an integral part of cost-effectiveness analysis. In the absence of long-term survival estimates from randomized clinical trials or meta-analysis we show how age-sex matched U.K. population data can additionally be used to estimate survival patterns. We adopt a Bayesian approach and we synthesize evidence from different sources such as patient registries, U.K. population statistics and meta-analyses. We also present methodology for Bayesian analysis of the additive hazards model and we show how to apply the techniques using freely available software. The methods are illustrated using data from a cohort of cardiac arrhythmia patients.

Aged↗
PubMed1991

Basic determinants for FM responses in the inferior colliculus of rats.

The response of 835 click-sensitive neurons in the inferior colliculus (IC) to ramp frequency modulated (FM) tones was studied in the anaesthetized rat. More than 70% of the cells were sensitive to the FM sound, and over 25% were "FM specialized". Systematic variations of the stimulus parameters showed that sweep velocity, sweep range, and intensity of the FM signal were the 3 basic determinants for the unit response. For an "FM specialized" cell, the response pattern to each of the parameters was either monotonic or bell-shaped. The population statistics of response patterns to the FM parameters, including the tuning factors, were generated. A stimulus domain was proposed to represent the "receptive space" of the FM cells.

Acoustic Stimulation↗
PubMed1993

Bronchial carcinoma mortality in the German chromate-producing industry: the effects of process modification.

This study updates a 1982 report on mortality at two German chromate-producing factories. The main objective of the study was to establish whether the change-over to a production process using lime-free conversion of chromite ore, thus eliminating the formation of calcium chromate, had resulted in a distinct reduction in bronchial carcinoma mortality among workers exposed for the first time after the change-over (completed in 1958 in Leverkusen and 1964 in Uerdingen). A total of 1417 workers with at least 1 year of exposure were enrolled in the study. The observation period ended on 31 December 1988. The expected number of deaths was calculated using population statistics for North Rhine-Westphalia. The risk was determined in the form of a standardised mortality ratio (SMR), i.e. the ratio of observed deaths to expected deaths. In the group of 739 workers exposed before the process change-over was completed, 432 died during the observation period, 66 of them from bronchial carcinoma. This significant excess produced an SMR of 2.27 (95% confidence interval: 1.78-2.85). Where the cause of death was unknown, cases were allocated to a cause of death on the basis of the percentage occurrence of various causes of death in the specific subcohort. The cohort of 678 workers first exposed after the process modification had been completed had a slightly increased SMR for lung cancer of 1.26 (95% confidence interval: 0.58-2.38) based on nine cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2000

Method availability and the prevention of suicide--a re-analysis of secular trends in England and Wales 1950-1975.

BACKGROUND: In England and Wales in the 1960s there were marked declines in suicide rates. These reductions were partly attributable to the detoxification of the domestic gas supplies; however, their extent varied by age and gender, with the most striking effects seen in older men. The objective of this study was to investigate method-specific trends in suicide between 1950 and 1975 to elucidate possible explanations for the patterns seen in different demographic groups. METHODS: An analysis of age-standardised method-specific suicide rates for England and Wales between 1950 and 1975 was carried out using routinely available mortality and population statistics. RESULTS: As has previously been shown, there were marked reductions in suicides by gassing in men and women of all ages between 1960 and 1975. In women and younger men, the effects of these reductions on overall suicide rates were partially offset by rises in drug overdose deaths (method substitution), but there were no immediate increases in the use of other suicide methods. In contrast, in older men, reductions in suicide by gassing were accompanied by only a slight increase in overdose suicides as well as reductions in rates of suicide using all other methods. The modest rise in overdose fatalities in older men occurred despite the fact that they were more often prescribed barbiturates and tricyclic antidepressants than younger men. CONCLUSIONS: Accessibility to and the lethality of particular methods of suicide may have profound effects on overall suicide rates. Such effects appear to depend upon the popularity of the method and the extent to which alternative methods that are acceptable to the individual are available. Social and psychological interpretations of fluctuations in suicide rates should only be made after assessing the possible contribution to these of changes in method availability and lethality.

Adolescent↗
PubMed2005

Effect of Thunbergia laurifolia, a Thai natural product used to treat drug addiction, on cerebral activity detected by functional magnetic resonance imaging in the rat.

RATIONALE: Thunbergia laurifolia Linn. (TL) is an herbal medicine used to treat alcohol and drug addiction in Thai traditional medicine. A previous study demonstrated that an extract of TL increases rat striatal dopamine release in vitro. OBJECTIVES: This study determined whether a methanol extract of TL altered rat brain region activity using in vivo functional nuclear magnetic resonance imaging (fMRI) in a manner consistent with the observed effects in vitro on dopamine release. METHODS: fMRI was performed on a 2.35-T Bruker MR system. MR images were acquired from rat brain using the rapid acquisition relaxation enhanced sequence (field of view 50 mm). The imaging parameters used for the anatomical scan yielded an in-plane spatial resolution of 0.2x0.2 mm. Consecutive single-slice functional imaging over the rat brain investigated the changes in signal intensity in various parts of the brains induced by TL (200 mg/kg, i.p.) or vehicle administration. RESULTS: These demonstrate that TL increased signal intensity in various brain areas such as nucleus accumbens, globus pallidus, amygdala, frontal cortex, caudate putamen and hippocampus. These are similar to those reported previously to show effects after either cocaine or amphetamine administration. Physiological variables were not affected by the injection of TL (200 mg/kg, i.p.), but there was a small decrease in arterial blood pressure. CONCLUSIONS: The results indicate that TL increases significant neuronal activity in specific brain regions responsible for reward and locomotor behaviour (fixed-effect analysis); however, there is no significant difference between TL and vehicle-treated groups with random-effect analysis (population statistic). The active compound(s) in TL responsible for the pharmacological effects of TL remain to be identified.

Acanthaceae↗
PubMed2002

MRI-based blood oxygen saturation measurements in infants and children with congenital heart disease.

BACKGROUND: Vessel oxygen saturation can be determined with MR oximetry using an in vivo measurement of signal decay (T2) and the calibration curve relating T2 to blood oxygen saturation (%HbO(2)), where: 1/T2=1/T2O+K (1-%HbO(2)/100)(2) and K is a constant parameter which correlates with measured fibrinogen levels. The ability to noninvasively measure %HbO(2) in cardiac chambers and vessels has enormous potential in children with congenital heart disease (CHD). OBJECTIVE: The purpose of the study was to prospectively characterize the T2-%HbO(2) relationship in infants where T2-%HbO(2) is the relationship between T2 and %HbO(2) (blood oxygen saturation) expressed by the equation given above, and to determine whether adult values for K and T2O (where T2O is the T2 of fully oxygenated blood) can be extrapolated to pediatric patients with CHD. A second objective was to apply this method to calculate the %HbO(2) in vivo using MR imaging in infants with CHD. MATERIALS AND METHODS: Fifteen patients with CHD undergoing cardiac catheterization (9 male; 6 female), median age 8 months, were recruited for the calibration study. T2O and K were measured directly from blood samples, compared with the values estimated from adult population statistics, and plotted against hematocrit and fibrinogen, respectively. In four studies of infants with CHD, T2 measurements were converted to %HbO(2) using the calibration curve. RESULTS: The T2-%HbO(2) relationship in infants correlated with the adult calibration statistics (1/T2O vs. hematocrit, r=0.77; K vs. fibrinogen, r=0.61). Our initial in vivo studies demonstrated that the MR oximetry reflected the expected oxygen saturations. CONCLUSION: Adult values for T2-%HbO(2) calibration can be used to measure blood oxygen saturation in vivo in children with CHD.

Blood Gas Analysis↗
PubMed1998

Statistical model of the hippocampal CA3 region. I. The single-cell module: bursting model of the pyramidal cell.

A model with intermediate complexity is introduced to reproduce the basic firing modes of the CA3 pyramidal cell. Our model consists of a single compartment, has two variables (membrane potential and internal calcium concentration), and involves two separate stages for interspike mechanisms and firing. Interspike dynamics is governed by voltage- and calcium-dependent ionic channels but no channel kinetics are provided. This model is suitable to be included in our statistical population model (Part II, following paper). Bifurcation analysis reveals that interspike dynamics rather than sodium firing has the dominant role in the control of bursting/nonbursting behavior.

Action Potentials↗
PubMed1999

[Facial cleft birth rate in former East Germany before and after the reactor accident in Chernobyl].

Cleft lip palates (CLP) are caused by a variety of factors. Ionizing radiation is only one of these factors. The meltdown of the nuclear reactor at Chernobyl on April 26, 1986, and the subsequent radioactive fallout did not cause any acute radiation sickness in Germany. Nevertheless, in West Berlin a significant increase of trisomy-21 cases was reported in births 9 months after the Chernobyl reactor accident. In our study we analyzed the influence of the radioactive fallout after the Chernobyl disaster on the rate and regional distribution of CLP newborns in the former German Democratic Republic (GDR). In contrast to the Federal Republic of Germany an ongoing malformation register for CLP newborns had existed in the former GDR since 4 July 1967. Environmental data were collected from national and international environmental authorities and atomic energy agencies. Population statistics were taken from the statistical year-book of the former GDR. During a 10-year period from 1980 to 1989, the average number of CLP newborns in the GDR was 1.88 per 1,000 live births. A significant prevalence increase was recorded in 1983, 1987 und 1988. In comparison to the mean rate in the period from 1980 until 1986, 1987 demonstrated an increase of 9.4%. Regional prevalence increases were seen in the three northern districts of Schwerin, Rostock and Neubrandenburg, where the radioactivity measurements in general showed higher levels of the radionuclides caesium-137 und strontium-90 than in other districts. Owing to the comprehensive malformation register for CLP patients in the GDR, this is the first study for Germany, analyzing the CLP rate before and after the fallout in Chernobyl. The results support the allegation of the influence of radiation-induced increase of CLP newborns after the Chernobyl reactor accident.

Abnormalities, Radiation-Induced↗
PubMed2004

Obesity and colorectal cancer.

BACKGROUND: To correlate obesity and colorectal cancer for Greek living conditions. PATIENTS AND METHODS: We studied 97 patients, who over the last 5 years were diagnosed histopathologically with colorectal cancer. 75.3% of the patients were either overweight or centrally obese; secondly, 21.6% patients had diabetes, percentages higher than those in the population (statistically significant). Hyperinsulinaemia and resistance to insulin have been implicated in colorectal carcinogenesis. CONCLUSIONS: As our sample was small, no statistically significant evidence correlating diet and/or physical activity to colorectal cancer has emerged.

Adult↗
PubMed1994

Discharge frequencies and intervals between pulses: are they always the same?

Neuronal discharge recorded as action potentials with intervening interpulse intervals can be converted to a frequency format. The ease of this interconversion masks two important problems in this process. For the same data set, the dynamics of change with the measured variable will be different for each of these two methods of characterizing discharge and each of these forms of rate indexing will have a different mean value. In all neuronal discharge studies, it may be initially necessary to determine whether normal population statistics apply to the primary data expressed in the IPI-mode or in the Hz-mode.

Action Potentials↗
PubMed1985

The demography of maternal mortality--seven Swedish parishes in the 19th century.

Complications of childbirth is a leading death cause for women of reproductive ages in the developing countries today. The unique Swedish population statistics from the 19th century permit comparable historical studies. In seven Swedish parishes 170 maternal deaths were observed - 595 per 100,000 live births. Eclampsia, obstructed labor and hemorrhage were responsible for 92 deaths, and puerperal sepsis for only 15 deaths. Indirect obstetrical deaths, like pneumonia, tuberculosis, dysentery and heart diseases, accounted for 30.8% (41/133) of the specified death causes. With a time limit of 1 year instead of 42 days following delivery, maternal mortality was increased by 17%. Out of 14 married women 1 died from childbirth. Maternal deaths accounted for 40-50% of all deaths in the central ages of reproduction, leaving the motherless children with a highly increased death risk. Of the live born, 3% survived 5 years after the mothers' death. Of children aged 1-5 only 13% survived 5 years after the mothers death.

Demography↗
PubMed1986

Humoral immunodeficiency.

Humoral (or antibody) immunodeficiency syndromes may occur as apparent congenital or acquired abnormalities, with deficiencies in all or in only some classes of immunoglobulins. Most patients are recognized because of recurrent infections with high-grade extracellular encapsulated bacterial pathogens, but some with selective IgA deficiency or with transient hypogammaglobulinemia of infancy may have few or no infections. Although general population statistics are not available, most defects are thought to be rare; humoral immunodeficiency is more prevalent than cellular immunodeficiency, possibly due to early death from the latter defects. Disorders affecting B-cell function may be inherited as X-linked recessive or as autosomal traits. Although considerable information exists about such defects at a functional and cellular level, the primary biologic errors are as yet unknown for all of them. Apparent abnormalities of B-cell maturation and/or intrinsic B-cell malfunction are seen in a majority of these defects. The heterogeneity of B-cell morphology and function in large pedigrees of patients with X-linked agammaglobulinemia makes it unlikely that the defect is due to a distinct gene rearrangement abnormality at a specific stage of B-cell maturation. Early recognition of B-cell deficiency and institution of adequate immunoglobulin replacement therapy can prevent extensive damage to the lungs and other life-threatening problems from infection and allow a relatively normal childhood and adult life.

Agammaglobulinemia↗
PubMedDate not supplied

Practical design criteria for a dynamic ratio imaging system.

Problems encountered and solutions devised during the construction of a productive Ca2(+)-imaging system are discussed. Many of these relate to the rapid and interactive nature of experiments on cytosolic Ca2+. The emphasis on accurate photometric quantitation of dynamically changing images contrasts with that of most image-processing software packages, which concentrate either on leisurely massage of static images or on descriptions of lateral motions of objects without concern for their brightnesses. Particularly important goals for Ca2(+)-imaging include real-time ratioing, psychophysically effective display formats, ease of experiment annotation, mass storage of image sequences, automated extraction of time courses and population statistics, aids to presenting images for seminars and publications, and program modifiability.

Calcium↗
PubMed1994

Neurogenesis of spinothalamic and spinocerebellar tract neurons in the lumbar spinal cord of the rat.

The temporal and spatial neurogenic patterns of spinothalamic and spinocerebellar neurons were determined in spinal cord segment L1 of the rat. Neurogenic patterns were demonstrated with [3H]thymidine administered to fetal rats during the period when neurons with supraspinal projections are known to be generated, i.e. on one of embryonic (E) days E13, E14, or E15. The animals were allowed to survive 50 to 100 days postpartum, then neurons with spinothalamic and spinocerebellar projections were retrogradely filled with fluorescent axonal tracers, Fluoro-Gold or True blue, which were pressure injected into the dorsal thalamus and cerebellum in various combinations in the same and in separate animals. Neurons labeled with each retrograde tracer and [3H]thymidine and neurons labeled with retrograde tracers alone were counted in spinal cord segment L1 in each of the animals. Spinothalamic and spinocerebellar neurons were found to be separate and distinct populations. Statistical analysis of the data showed that spinothalamic and spinocerebellar neurons also have distinctly different patterns of neurogenesis which suggest early determination in each cell line. The temporal neurogenic pattern followed a projection-distance gradient, such that spinothalamic neurons, which have longer axons than spinocerebellar neurons, completed neurogenesis prior to spinocerebellar neurons in each region of the spinal gray.

Animals↗
PubMed1985

Inhibition of lectin-induced lymphocyte activation by 2-cyclohexene-1-one: analysis of DNA synthesis in individual cells by BUdR quenching of Hoechst 33258.

A novel technique utilizing the quenching of fluorescence Hoechst 32258 by bromodeoxyuridine (BUdR) was used to investigate the effect of depressed glutathione (GSH) on the activation of human peripheral blood lymphocytes by phytohemagglutinin (PHA) or concanavalin A (con A). This technique allows the quantification of DNA synthesis in individual cells. Lymphocytes were purified by Ficoll-Hypaque density gradient centrifugation and treated with 5 X 10(-5) M to 1 X 10(-6) M 2-cyclohexene-1-one (2-CHX-1), a reagent which specifically depletes intracellular GSH, and/or interferes with GSH-protein interactions, and 25 micrograms/ml BUdR in the presence or absence of PHA or con A. At 72 h lymphocyte smears were stained with Hoechst 33258 and examined using a computer controlled microscope photometer. When DNA synthesis was assayed using BUdR quenching two populations of lymphocytes were noted; a population which incorporated little or no BUdR (unactivated) and a population which incorporated BUdR sufficient to quench 33258 fluorescence by approximately 35%. Cells treated with graded doses of 2-CHX-1 which reduced glutathione levels by 10-90%, showed a progressive loss of cells from the activated population and the appearance of these cells in the inactivated population. Statistical analysis of the frequency histograms demonstrated that there were no cells which incorporated an intermediate amount of BUdR. This data demonstrates that depressed intracellular GSH or inhibition of GSH-protein interactions inhibits an early step in the biochemical sequence of events leading to DNA synthesis but does not inhibit the DNA synthetic process per se.

Benzimidazoles↗