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Developmental previewing: enhancing the adolescent's predictions of behavioral consequences.

The adolescent years are a time of significant biopsychosocial change. Adolescents develop a variety of cognitive skills that enable them to evaluate future consequences, weigh alternatives, and select behaviors. If these cognitive skills have not matured fully, however, the female adolescent may be predisposed to enact risk-taking behaviors, such as becoming pregnant. An intervention technique that encourage adolescents to predict the consequences of their actions may therefore be beneficial. One such technique, labeled previewing, promotes the cognitive skills necessary for averting future unplanned pregnancies and, in the event the adolescent has become a mother, for establishing a more adaptive relationship with the infant.

Adolescent↗

Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of brain 5-HT.

MDMA-induced 5-HT neurotoxicity has been proposed to involve oxidative stress due to increased formation of hydroxyl radicals. Recently, MDMA-induced 5-HT neurotoxicity has been shown to be accompanied by a suppression of behavioral and neurochemical responses to a subsequent injection of MDMA. The intent of the present study was to examine whether suppression of the MDMA-induced formation of hydroxyl radicals by an antioxidant, ascorbic acid, attenuates both the MDMA-induced depletion of 5-HT and the functional consequences associated with this depletion. Treatment of rats with ascorbic acid suppressed the generation of hydroxyl radicals, as evidenced by the production of 2,3-dihydroxybenzoic acid from salicylic acid, in the striatum during the administration of a neurotoxic regimen of MDMA. Ascorbic acid also attenuated the MDMA-induced depletion of striatal 5-HT content. In rats treated with a neurotoxic regimen of MDMA, the ability of a subsequent injection of MDMA to increase the extracellular concentration of 5-HT in the striatum, elicit the 5-HT behavioral syndrome, and produce hyperthermia was markedly reduced compared to the responses in control rats. The concomitant administration of ascorbic acid with the neurotoxic regimen of MDMA prevented the diminished neurochemical and behavioral responses to a subsequent injection of MDMA. Finally, a neurotoxic regimen of MDMA produced significant reductions in the concentrations of vitamin E and ascorbic acid in the striatum and hippocampus. Thus, the MDMA-induced depletion of brain 5-HT and the functional consequences thereof appear to involve the induction of oxidative stress resulting from an increased generation of free radicals and diminished antioxidant capacity of the brain.

Animals↗

Neonatal seizures: early-onset seizure syndromes and their consequences for development.

The determination of the developmental consequences of seizure syndromes in the neonate is based upon a number of factors which include: understanding of the clinical and electroencephalographic (EEG) features of neonatal seizures; current theories of the mechanisms by which neonatal seizures are generated; a current classification of neonatal seizures; potential etiologic and risk factors for seizures; and therapies. In addition, different seizure types, mechanisms of generation and etiologies of cerebral dysfunction may vary with conceptional age of the infant. There are a few distinct neonatal epileptic syndromes, which are rare, have been well described: benign neonatal convulsions; benign neonatal familial convulsions; early myoclonic encephalopathy and early infantile epileptic encephalopathy. The prognosis for the first two is relatively good while the outcome for the other two with encephalopathy is catastrophic. However, the majority of neonatal seizures occur as acute, reactive events in association with a wide range of etiologic factors. These etiologic factors, as well as those of the more traditionally defined syndromes, are the main determinants of eventual developmental outcome of neonates who experience seizures. Although experimental data suggests that some epileptic seizures eventually may have physiological, histological, metabolic, or behavioral consequences, there is yet direct evidence in humans to suggest that the occurrence of seizures themselves in the neonate is the main determinant of long-term outcome.

Acute Disease↗

The structural and functional consequences of chronic allergic inflammation of the airways.

Although asthma is generally considered a form of reversible airway obstruction, there is evidence that chronic allergic inflammation can lead to structural changes in the airway and a degree of progressive fixed airway obstruction. More importantly, these structural changes can lead to airway hyper-responsiveness. The structural consequences of chronic allergic inflammation are secondary to cellular proliferation and reorganization of the connective tissue constituents of the airway wall. Smooth muscle proliferation and hypertrophy may increase the potential for smooth muscle shortening against the elastic loads provided by lung parenchymal recoil and airway mucosal folding. Resident airway cells, as well as inflammatory cells, produce mediators, cytokines and growth factors that stimulate production of connective tissue proteins and proteoglycans that cause airway remodelling and altered mechanical function. Thickening of the airway wall internal to the smooth muscle layer can amplify the effect of smooth muscle shortening on airway calibre, and it could also stiffen the airway making it less distensible. Thickening of the airway wall external to the muscle can uncouple the airway from the distending force applied by the lung parenchyma. Early and aggressive anti-inflammatory medication may alter the natural history of asthma by preventing the structural changes that are a consequence of chronic allergic inflammation.

Airway Obstruction↗

Metabolic consequences of alcohol ingestion.

Many of the pathophysiological effects of alcohol ingestion relate to the pathways of ethanol metabolism. However, some of the acute and chronic effects of ethanol use are also attributable to the direct effects of ethanol, e.g. on membrane fluidity. Oxidation of ethanol to acetaldehyde is catalysed by alcohol dehydrogenase (ADH). There are at least six classes of ADH, some of which show inter-individual variation, i.e. genetic polymorphism, that influences the rate of ethanol oxidation. A consequence of ethanol oxidation is an increase in the NADH/NAD redox potential within the cytosol and mitochondria with subsequent alteration in several tissue metabolites. The popular hypothesis that most, if not all, of the consequences of chronic alcohol ingestion can be explained by these redox changes is still unproven. This should be considered in the context that most metabolic pathways of the liver are affected by alcohol, as are several endocrine axes in the whole body. In fact most, if not all, tissues and organs are deleteriously affected by chronic ingestion. Acetaldehyde, the product of ethanol oxidation, is chemically highly reactive, toxic and immunogenic. However, the concentrations achieved in vivo usually fall short of those used to produce these toxic effects in experimental situations. Oxidation of acetaldehyde is also coupled to redox changes, although primarily affecting the intra-mitochondrial redox. In addition, further oxidative pathways of ethanol metabolism can lead to the formation of fatty acid ethyl esters, hydroxyethyl free radicals and reactive oxygen species via the ethanol-specific cytochrome P450-2E1 system. There is no conclusive evidence that nutrient supplementation has beneficial effects on overall ethanol-mediated tissue damage.

Alcohol Drinking↗

Bioavailability, bioaccumulation and tolerance of chromium: consequences in the food chain of freshwater ecosystems.

Many abiotic and biotic factors can influence the partitioning equilibrium of heavy metals, thus influencing metal impact on aquatic environments. Unicellular algal species release soluble organic substances able to complex metals. In our laboratory a Cr-tolerant strain was selected and isolated from a wild type strain of Scenedesmus acutus. The exudates released by the two strains counteracted the growth inhibition caused by Cr(VI) and the exudates of the Cr-tolerant strain were more effective. On the contrary, the exudates did not reduce chromium toxicity to the cladoceran Daphnia magna. The reduction of chromium effect on algae seems the consequence of an algae-specific interaction among Cr(VI), exudates and algal cells. Chromium uptake resulted to be energy-dependent since bioaccumulation rate in subdued light condition was lower than at high light intensity. The effect of Cr(VI) on algae changed depending on metabolism of the cells and in particular it seemed to be related to the bioaccumulation rate. Tolerance in the selected strain could not be ascribed to a lower uptake of chromium. The difference in sensitivity to chromium between the two strains was exploited to evaluate if tolerance acquired by algae could have consequences for Daphnia. After treatment with Cr(VI), the two strains of S. acutus were used as food source for D. magna. The results indicate that chromium is accumulated by algae in a form not available for daphnids and that Cr tolerance acquired by the algae can be of some advantage to the consumer organism.

Animals↗

Population screening for cystic fibrosis: knowledge and emotional consequences 18 months later.

We assessed cystic fibrosis (CF) knowledge and emotional consequences of CF population testing 18 months after screening was offered. Questionnaires were sent to 593 individuals and 353 responded (59.5%). All respondents had sound knowledge of CF disease, although carriers were more likely to correctly state the pattern of CF inheritance and CF carrier rate in Australia. Eleven of 47 carriers falsely believed they were only very likely to be carriers, while nearly a third of test-negative individuals falsely believed they were definitely not carriers. Imprecise recall of the meaning of results may be due to memory loss over time, simplification of result meaning and minimization of risk. The Health Orientation Scale (HOS) was used to assess emotional consequences of CF carrier testing 18 months after testing. Both carriers and test-negative individuals thought most carriers would experience more negative feelings than most non-carriers. Carriers experienced less positive feelings about their test result compared to non-carriers. Interestingly, the carriers' own feelings about their result were more positive compared to how they thought most carriers would feel. These results suggest that carriers experience minimal adverse psychological effects, although a negative social stigma may be attached to carrying the CF gene mutation.

Adolescent↗

Mechanisms and consequences of paternally-transmitted chromosomal abnormalities.

Paternally-transmitted chromosomal damage has been associated with pregnancy loss, developmental and morphological defects, infant mortality, infertility, and genetic diseases in the offspring, including cancer. There is epidemiological evidence linking paternal exposure to occupational or environmental agents with an increased risk of abnormal reproductive outcomes. There is also a large body of literature on germ cell mutagenesis in rodents showing that treatment of male germ cells with mutagens has dramatic consequences on reproduction, producing effects such as those observed in human epidemiological studies. However, we know very little about the etiology, transmission, and early embryonic consequences of paternally-derived chromosomal abnormalities. The available evidence suggests that: 1) there are distinct patterns of germ cell-stage differences in the sensitivity of induction of transmissible genetic damage, with male postmeiotic cells being the most sensitive; 2) cytogenetic abnormalities at first metaphase after fertilization are critical intermediates between paternal exposure and abnormal reproductive outcomes; and 3) there are maternal susceptibility factors that may have profound effects on the amount of sperm DNA damage that is converted into chromosomal aberrations in the zygote and that directly affect the risk for abnormal reproductive outcomes.

Aneuploidy↗

Factors and consequences of conversion in laparoscopic sigmoidectomy for diverticular disease.

BACKGROUND: The disadvantages of laparoscopic elective sigmoidectomy for diverticular disease include the risk of conversion to open operation and longer operative time. The aim of this study was to analyse the causes and consequences of conversion in 168 consecutive patients who underwent a laparoscopically assisted colectomy between January 1994 and June 2001. METHODS: Data were collected prospectively to analyse the causes and consequences of conversion to open surgery in terms of postoperative morbidity and patient recovery. RESULTS: Postoperative mortality, morbidity, conversion and reoperation rates were zero, 21.4 per cent (n = 36), 14.3 per cent (n = 24) and 3.0 per cent (n = 5) respectively. The reasons for conversion were presence of intraperitoneal adhesions and/or inflammatory pseudotumour (n = 21), an intraoperative diagnosis of sigmoid cancer (n = 1), hypercapnia (n = 1) and abdominal bleeding (n = 1). Three preoperative factors were associated with a significant higher risk of conversion: surgical expertise, the presence of sigmoid stenosis or fistula, and the severity of diverticulitis on pathological examination. Morbidity was no different between laparoscopic sigmoidectomy (30 of 144; 20.8 per cent) and converted procedures (six of 24; 25.0 per cent). Open conversion was associated with a longer operative time and significantly delayed patient recovery and hospital discharge. CONCLUSION: Surgical experience and severe diverticular disease are predictive factors for conversion in laparoscopic elective sigmoidectomy. Even if necessary, conversion does not increase the morbidity rate.

Adult↗

Alterations in reference vessel diameter following intracoronary stent implantation: important consequences for restenosis based on percent diameter stenosis.

The scaffolding effect of stent implantation has the potential to alter vascular geometry and dimensions. The objective of this study was to determine the impact of intracoronary stent implantation on the reference vessel diameter and the consequences of this on the frequency of restenosis applying the binary definitions of restenosis based on percent diameter stenosis. Routine angiographic follow-up was performed in 79/80 consecutive patients who had a single elective Palmaz-Schatz stent implanted in denovo lesions in native coronary arteries 6.5 +/- 3.4 mo after the index procedure. Complete quantitative angiographic follow-up was available in 78 (98%). The mean reference vessel diameter was 2.9 +/- 0.6 mm preprocedure, increased to 3.1 +/- 0.5 mm immediately poststent implantation and was 2.6 +/- 0.6 mm at follow-up (F = 6.45, P = 0.0001, ANOVA for repeated measures). In view of the varying reference vessel diameter, percent diameter stenosis postangioplasty and at follow-up was determined by two methods: (1) automatically by the quantitative coronary angiographic analysis system and (2) by expressing the minimal luminal diameter postangioplasty and at follow-up as a function of the original preprocedural reference vessel diameter. The restenosis rate was significantly greater for all definitions of restenosis when the minimal luminal diameter was determined as a function of the original preprocedure reference vessel diameter (e.g., 34% vs. 18% for the > or = 50% criterion, P = 0.018). Stent implantation results in alterations in reference vessel diameter, which have important consequences for the frequency of restenosis presented as a binary variable based on percent diameter stenosis.

Aged↗

The pattern of breast cancer screening utilization and its consequences.

BACKGROUND: The objective of this study was to describe the pattern of screening utilization and its consequences in terms of tumor size and time of tumor appearance of invasive breast carcinoma among a population of women who were examined at a large service screening/diagnostic program over the last decade. METHODS: Utilization of mammography was assessed from a population of 59,899 women who received 196,891 mammograms at the Massachusetts General Hospital Breast Imaging Division from January 1, 1990 to March 1, 1999, among which 604 invasive breast tumors were found. Two hundred six invasive, clinically detected tumors also were seen during this period among women who had no record of a previous mammogram. Additional information was available on screening of women from March 1, 1999 to June 1, 2001. RESULTS: Fifty percent of the women who used screening did not begin until the age of 50 years, although 25% of the invasive breast tumors were found in women age < 50 years. Relatively few of the women who used screening returned promptly for their annual examinations; by 1.5 years, only 50% had returned. Approximately 25% of the invasive breast tumors were found in women for whom there was no record of a previous screening mammogram, and these tumors were larger (median, 15 mm) than the screen-detected tumors (median, 10 mm). Approximately 30% of the 604 invasive breast tumors in the screening population were found on nonmammographic grounds, and they also were larger (median, 15 mm) than the screen-detected tumors (median, 10 mm). However, only 3% of these 604 tumors were found by nonmammographic criteria within 6 months of the previous negative examination, and only 12% were found within 1 year. By back calculating the likely size of each of these tumors at the time of the negative mammogram, it could be seen that most tumors probably emerged as larger, palpable masses not because they were missed at the previous negative mammogram, because most were too small then to have been detected, but because too much time had been allowed to pass. CONCLUSIONS: Far too many women did not comply with the American Cancer Society recommendation of prompt annual screening from the age of 40 years. Consequently, almost 50% of the invasive tumors emerged as larger and, thus, potentially more lethal, palpable masses.

Breast Neoplasms↗

Individual housing during the play period results in changed responses to and consequences of a psychosocial stress situation in rats.

In the present study, the consequences of individual rearing during the play period on adult responses to aggression were investigated in a complex social setting. In a group of either socially or individually reared rats, an aggressor was repeatedly introduced. Separate control groups of individually and socially reared rats were not exposed to an aggressor. To allow an interpretation of the altered reactivity to aggression in terms of (in)efficient or (in)adequate behavior, not only the responses in the presence of the aggressor but also the consequences of the altered reactivity on subsequent behavior in the absence of the aggressor were observed. We demonstrated that a higher number of injuries, more agitation of the aggressor, and more ultrasonic distress vocalizations accompanied the altered responses of individually reared rats in the presence of the aggressor. In the absence of the aggressor, individually reared rats displayed less social stress-reducing behaviors (play and social grooming) than socially reared rats. It was concluded that individually reared rats display a less adequate response to aggression in this social context.

Aggression↗

Behavioral and immunological consequences of brief mother-infant separation: a species comparison.

The immediate behavioral and immunological consequences of a single 2-week maternal separation experience were studied in socially housed 7-month old bonnet and pigtail macaques. Maternal separation was associated with species dependent behavioral changes. Both species showed significant increases in ingestive behaviors associated with separation. Separated and matched controls showed an increase in disturbance behaviors (vocalization, startles, shaking, temper-tantrums) that subsided after 24-36 hours in control subjects, but continued, albeit with species-dependent patterns, in the separated monkeys. Allomaternal care of the separated bonnet infants but not the pigtail infants was associated with a progressive reduction of these disturbance behaviors during the separation period. Following a period of agitation, pigtail infants showed a depressive phase characterized by slouched, withdrawn postures and reduced motor activity. As a group, the separated infants of both species were not different from controls with respect to lymphocyte activation by mitogens, a measure of immunocompetence. However, when individual behavioral responses were considered, the change in lymphocyte activation during separation was significantly related to behavioral responses which reflected disturbance, such that the change in lymphocyte activation following in vitro stimulation with the mitogens phytohemagglutinin and Concanavalin A (markers of the immunocompetence of T lymphocytes) was related to levels of vocalization and time spent in slouched postures. The activation of B lymphocytes by pokeweed mitogen was not influenced by the separation experience nor was it associated with specific behavioral responses to separation. The importance of assessing the affective consequences of stressor is discussed.

Animals↗

Attenuation of the ethanol-induced hepatic redox change after chronic alcohol consumption in baboons: metabolic consequences in vivo and in vitro.

Acute ethanol administration results in increased hepatic NADH/NAD+ ratio and inhibition of galactose elimination, tricarboxylic acid cycle activity, and fatty acid oxidation. To determine how this redox change is affected by chronic alcohol consumption and to assess the resulting metabolic consequences, we studied baboons which were fed alcohol as 50% of their total calories. Redox changes were evaluated through measurement of galactose elimination in vivo and lactate/pyruvate ratios in liver slices in vitro. The metabolic consequences of these changes were assessed through measurement of CO2 production and fatty acid oxidation in liver slices and hepatic lipid accumulation. Chronic alcohol feeding resulted in attenuation of inhibition of galactose elimination, increase in the lactate/pyruvate ratio, and decrease in fatty acid oxidation which were caused by acute ethanol administration. These metabolic adaptations were associated with reduced accumulation of hepatic fat.

Alcohol Oxidoreductases↗

Phenotypic consequences of branch point substitutions.

The branch point sequence (BPS) is a conserved splicing signal important for spliceosome assembly and lariat intron formation. BPS mutations may result in aberrant pre-mRNA splicing and genetic disorders, but their phenotypic consequences have been difficult to predict, largely due to a highly degenerate nature of the BPS consensus. Here, we have examined the splicing pattern of nine reporter pre-mRNAs that have previously been shown to give rise to human hereditary diseases as a result of single-nucleotide substitutions in the predicted BPS. Increased exon skipping and intron retention observed in vivo were recapitulated for each mutated pre-mRNA, but the reproducibility of cryptic splice site activation was lower. BP mutations in reporter pre-mRNAs frequently induced aberrant 3' splice sites and also activated a cryptic 5' splice site. Systematic mutagenesis of BP adenosines showed that in most pre-mRNAs, the expression of canonical transcripts was lower for BP transitions than BP transversions. Differential splicing outcome for transitions vs. transversions was abrogated or reduced if introns were truncated to 200 nt or less, suggesting that the nature of the BP residue is less critical for interactions across very short introns. Together, these results improve prediction of phenotypic consequences of point mutations upstream of splice acceptor sites and suggest that the overrepresentation of disease-causing adenosine-to-guanosine BP substitutions observed in Mendelian disorders is due to more profound defects of gene expression at the level of pre-mRNA splicing.

Cell Line↗

Control and consequences of adrenergic activation of red blood cell Na+/H+ exchange on blood oxygen and carbon dioxide transport in fish.

The catecholamines, adrenaline and noradrenaline, are released into the circulation of fish during a variety of physical and environmental disturbances that share the common feature of a requirement for enhanced blood oxygen transport. Indeed, the dominant factor controlling the mobilization of catecholamines from chromaffin tissue is a depression of blood oxygen content usually coinciding with a reduction of hemoglobin-O2 (Hb-O2) binding to 50-60% saturation. The elevation of plasma catecholamine levels, under such conditions, activates a beta-adrenergic cyclic AMP-dependent Na+/H+ exchanger on the red blood cell (rbc) membrane. The adrenergic responsiveness AMP-dependent Na+/H+ exchanger on the red blood cell (rbc) membrane. The adrenergic responsiveness of the rbc Na+/H+ exchanger to catecholamines varies both within and between species. Such inter- and intra-specific differences may reflect, in part, the availability of cell surface beta-adrenoceptors that are functionally coupled to adenylate cyclase. The activation of rbc Na+/H+ exchange and the accompanying profound adjustments of intracellular and extracellular acid-base status, nucleoside triphosphate (NTP) levels, and cooperativity of Hb-O2 binding have important consequences on both O2 and CO2 transfer and transport in the blood that vary markedly at the sites of oxygenation (the gill) and deoxygenation (the tissues) thereby enabling simultaneous amelioration of O2 loading and unloading. At the gill, oxygen transfer is enhanced owing to increases in Hb-O2 affinity and capacity while at the tissues, oxygen delivery is facilitated by a reduction of Hb-O2 affinity. This reduction in affinity at the tissues is a consequence of the combined effects of increased cooperativity of Hb-O2 binding and a rise in venous PCO2 (PvCO2) caused by the titration of HCO3- by H+ extruded by the rbc Na+/H+ exchanger. This elevation of PvCO2 may contribute to the rise in arterial PCO2 (PaCO2) observed after adrenergic activation of rbc Na+/H+ exchange that is caused primarily by impairment of rbc CO2 excretion related to modification of the intracellular acid-base status.

Animals↗

Survival after retinoblastoma: long-term consequences and family history of cancer.

Retinoblastoma (Rb) is a rare childhood tumor of the eye. In the heritable form, tumors are often bilateral and survivors have a greatly increased risk both for a second malignancy and for having children with Rb. Familial patterns of both cancer and birth defects are poorly understood in families with a heritable cancer, and little is known of the ways that a heritable cancer affects the lives of long-term survivors. To find out more about these and other issues in the lives of long-term survivors of childhood and adolescent cancer, we interviewed 56 adult survivors of retinoblastoma (15 with the heritable form) and 84 brothers and sisters as controls, who formed part of a large retrospective cohort study. Rb survivors were interviewed between 1980 and 1983, when they were 30 years old on average. Types of employment and health problems did not differ between survivors and controls, regardless of sight, but the income of blind survivors was considerably less than that of partially sighted survivors. Despite similar marriage rates, fewer survivors than controls reported a pregnancy (RR = 0.45; 95% CI; 0.24-0.83 for both sexes combined). Parents of children with heritable Rb seemed more likely to have had cancer than parents in families with nonheritable Rb (P = 0.06), and mothers were more likely than fathers to be affected (P = 0.01). This small series suggests that having retinoblastoma may have many long-term consequences, reaching beyond genetic and physical effects to touch family life and income attainment and the health of other family members. Follow-up of more modern cohorts and the use of molecular tools will clarify the long-term consequences of more recent therapies, and patterns of familiar cancer.

Achievement↗

Permanent consequences in Langerhans cell histiocytosis patients: a pilot study from the Histiocyte Society-Late Effects Study Group.

BACKGROUND: Permanent consequences (PC) are often described among subjects with Langerhans cell histiocytosis (LCH) but data on the real incidence are scarce. Within the Histiocyte Society (HS), and in order to design a definitive late effects study, a retrospective survey was organized to describe the prevalence of PC among long-term survivors of LCH. METHODS: Nine institutions contributed with their LCH patients having a minimum follow-up of 3 years. Information was collected on their disease-history, and on type and date of onset of any PC. Because of the retrospective type of this study, it was accepted that each institution might have used different criteria to assess PC. RESULTS: One hundred eighty-two subjects were registered and in 95 (52%) at least 1 PC was reported. For some specific PC (e.g., anterior pituitary dysfunction) information was too scarce to provide reliable data. PC were more frequent among subjects with multisystem (MS) disease (71%), compared to those with single system (SS) disease (24%); P < 0.0001. The most frequently reported PC were diabetes insipidus (DI) (24%) orthopedic abnormalities (20%), hearing loss (13%), and neurological consequences (11.0%). Analysis of cumulative risk showed that some types of PC may become manifest more than 10 years from diagnosis. CONCLUSIONS: This survey on selected cases of LCH survivors has confirmed that late sequels are frequent, and that they are even more common among those with MS LCH. Our findings highlight the need for long-term and patient-oriented follow-up in children with LCH.

Adolescent↗