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PubMed2006

Long-term behavioral and developmental consequences of pre- and perinatal nicotine.

Research has shown that cigarette use during pregnancy can result in increased fetal mortality, sudden infant death syndrome, and behavioral and attentional disorders during childhood. Neurochemical and behavioral consequences of prenatal nicotine exposure have been well documented although few studies have examined long-term behavioral consequences that persist into adulthood. In this study, fifty-eight male and female Long-Evans rats were exposed to chronic nicotine prenatally and postnatally via subcutaneous infusions (0.96 mg/kg/day) in the dam. Nicotine exposure continued in the pups via maternal milk until the dams' osmotic mini-pumps became exhausted at approximately postnatal day (P) 11. At weaning, animals were group housed until behavioral testing at P60 to assess spatial learning and memory in the Morris water maze (MWM). Mild deficits in spatial learning were observed in nicotine-exposed females. These behavioral differences were accompanied by significant reduction in weight gain of nicotine-exposed females beginning at puberty, suggesting a hormonal interaction. Long-term effects of nicotine exposure were less striking in males. Nicotine-exposed males had significantly slower swim speeds than controls, but latency to reach the hidden platform was equal between groups by the conclusion of testing. Weight gain in males did not differ between groups as a result of prenatal nicotine exposure.

Animals↗
PubMed2006

Social consequences of HIV-positive women's participation in prevention of mother-to-child transmission programmes.

Approximately two-third of the worlds HIV/AIDS cases are found in sub-Saharan Africa. The rate of mother-to-child-transmission (MTCT) has been found to lie between 15 and 40%. The aim of this study was to explore the social consequences affecting the experience HIV-positive women have when taking part in a prevention of mother-to-child-transmission programme (PMTCT). Few studies have investigated this earlier. A cross section of 52 participating women enrolled into a PMTCT programme were randomly selected and interviewed, using a structured questionnaire. There were three main findings. The most important consequence of participating was the difficulty associated with the breast-feeding issue. For the women who because of a wish to prevent MTCT are employing formula feeding, this causes suspicion and prejudice amongst people in the local community. Few people influence a woman's decision to take part, as they tend to keep their HIV status to themselves. More information to the general public about HIV and PMTCT programmes will enhance acceptance to HIV, and generate an environment conducive towards participation in PMTCT programmes.

Adult↗
PubMed2005

Drugs and alcohol: treating and preventing abuse, addiction and their medical consequences.

Recent advances in the fields of genetics, molecular biology, behavioral neuropharmacology, and brain imaging have dramatically changed our understanding of the addictive process and why relapse occurs even in the face of catastrophic consequences. Addiction is now recognized as a chronic brain disease that involves complex interactions between repeated exposure to drugs, biological (i.e., genetic and developmental), and environmental (i.e., drug availability, social, and economic variables) factors. Its treatment, therefore, requires, in general, not only a long-term intervention but also a multipronged approach that addresses the psychiatric, medical, legal, and social consequences of addiction. Also, because addiction usually starts in adolescence or early adulthood and is frequently comorbid with mental illness, we need to expand our treatment interventions in this age group both for substance abuse and psychiatric disorders.

Alcoholism↗
PubMed2006

Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences.

Reactive oxygen species (ROS) are generated as by-products of cellular metabolism, primarily in the mitochondria. Although ROS are essential participants in cell signaling and regulation, when their cellular production overwhelms the intrinsic antioxidant capacity, damage to cellular macromolecules such as DNA, proteins, and lipids ensues. Such a state of "oxidative stress" is thought to contribute to the pathogenesis of a number of neurodegenerative diseases. Growing evidence supports the involvement of oxidative stress as a common component of glaucomatous neurodegeneration in different subcellular compartments of retinal ganglion cells (RGCs). Besides the evidence of direct cytotoxic consequences leading to RGC death, it also seems highly possible that ROS are involved in signaling RGC death by acting as a second messenger and/or modulating protein function by redox modifications of downstream effectors through enzymatic oxidation of specific amino acid residues. Different studies provide cumulating evidence, which supports the association of ROS with different aspects of the neurodegenerative process. Oxidative protein modifications during glaucomatous neurodegeneration increase neuronal susceptibility to damage and also lead to glial dysfunction. Oxidative stress-induced dysfunction of glial cells may contribute to spreading neuronal damage by secondary degeneration. Oxidative stress also promotes the accumulation of advanced glycation end products in glaucomatous tissues. In addition, oxidative stress takes part in the activation of immune response during glaucomatous neurodegeneration, as ROS stimulate the antigen presenting ability of glial cells and also function as co-stimulatory molecules during antigen presentation. By discussing current evidence, this review provides a broad perspective on cellular mechanisms and potential consequences of oxidative stress in glaucoma.

Animals↗
PubMed2005

Intimate partner violence: forms, consequences and preparedness to act as perceived by healthcare staff and district and community leaders in a rural district in northern Vietnam.

OBJECTIVES: A qualitative study was conducted among healthcare staff and district and community leaders in May and June 2002 to describe their perceptions of violence occurring between intimate partners. It focused on male violence towards females, and its forms, consequences and preparedness to act in a rural setting in Vietnam. METHODS: Twenty men and 20 women were strategically selected for focus group discussions and a phenomenographic approach was employed. FINDINGS: Violence was described not only as physical but also, primarily, as affecting women's mental health status. Mental violence was exemplified as verbally offending, ignoring or humiliating a woman. Sexual abuse was mentioned less frequently. IPV was considered to be a private matter, occurring in the home away from relatives, neighbours and the local community. Only very serious cases would seek health care. Divorce and deteriorating family finances were reported as serious consequences, not least for the children. Local reconciliation groups, comprised of trusted community members, played a role in mediating, while health professionals were found to be uninformed about prevalence rates and reluctant to intervene. CONCLUSIONS: Gender-based violence needs to receive attention from policy makers, and effective advocacy programmes are needed at all levels. In Vietnam, partner violence against women seems to be recognized at Government level. At community level, Women's Union staff and local reconciliation groups are prepared to act. However, the subject is surrounded by silence. We found that healthcare workers exhibited a lack of understanding of violence against women as a health problem in their own working environment.

Attitude↗
PubMed2005

Orchid diversity: an evolutionary consequence of deception?

The Orchidaceae are one of the most species-rich plant families and their floral diversity and pollination biology have long intrigued evolutionary biologists. About one-third of the estimated 18,500 species are thought to be pollinated by deceit. To date, the focus has been on how such pollination evolved, how the different types of deception work, and how it is maintained, but little progress has been made in understanding its evolutionary consequences. To address this issue, we discuss here how deception affects orchid mating systems, the evolution of reproductive isolation, speciation processes and neutral genetic divergence among species. We argue that pollination by deceit is one of the keys to orchid floral and species diversity. A better understanding of its evolutionary consequences could help evolutionary biologists to unravel the reasons for the evolutionary success of orchids.

Journal Article↗
PubMed2006

The flash-lag effect is reduced when the flash is perceived as a sensory consequence of our action.

The flash-lag effect (FLE) is defined as an error in localization that consists of perceiving a flashed object to lag behind a moving one when both are presented in physical alignment. Previous studies have addressed the question if it is the predictability of the flash, or the moving object, that modulates the amount of the error. However, the case when the flash is self-generated, and hence can be internally predicted, has not yet been addressed. In Experiment 1, we compare four conditions: flash unpredictable, flash externally predicted by a beep, flash internally generated (and predicted) by pressing a key, and flash triggered by a key press but temporally unpredictable. The FLE was significantly reduced only when the flash was internally predictable. In Experiment 2, we rule out the possibility that the reduction of the FLE was due to the use of the key press as a temporal marker. We conclude that when the flash is perceived as a sensory consequence of our own action, its detection can be speeded up, thereby resulting in a reduction of the FLE. A third experiment supports this interpretation. The mechanism by virtue of which the detection is accelerated could be related to efferent signals from motor areas predicting the sensory consequences of our actions.

Attention↗
PubMed2005

Rating the severity of the medical consequences of drug-induced liver injury.

Risk analysis in drug development aims to allow for clear decisions showing whether or not the benefit of an intervention outweighs the risk. One of the difficulties in doing this in a repeatable and clear way is the problem of comparing different adverse events, as seriousness is often subjective. Using drug-induced liver injury as our model, we show that clinical, laboratory, and histological manifestations of liver reactions can be ranked by experienced hepatologists and these rankings can be used to rank the consequences of drug-induced side effects as a continuum. This risk ranked information could be transformed to standardized scores (z score) and the risks displayed by standard techniques; adverse events can then be compared with effects from other drugs and possibly with the consequences due to untreated disease or natural occurrences. As a risk is a function of both the seriousness of the event and the probability of its occurrence, risk can therefore be displayed in terms of probability and hazard to further ease communication. We propose that risk management of drugs in development would be improved, especially in terms of risk communication, if the hazard were ranked by means of a common scale and displayed in graphic form against the likelihood of occurrence.

Chemical and Drug Induced Liver Injury↗
PubMed2001

A nationwide survey of self-reported red light running: measuring prevalence, predictors, and perceived consequences.

A United States probability sample of 880 licensed drivers participated in a telephone survey of red light running perceptions and behaviors. Despite most drivers believing red light running was problematic and dangerous, approximately one in five respondents reported running one or more red lights when entering the last ten signalized intersections. Among several demographic and attitude variables, only age group predicted recent red light running. Specifically, younger respondents were more likely to be violators. Drivers also reported being more likely to run red lights when alone, and were typically in a hurry when speeding up to be beat red lights. Contrary to expectations, frustration was not as important for predicting red light running as it was for other driving behaviors, such as speeding, tailgating, weaving, and gesturing angrily at others. Additionally, drivers perceived and received few consequences for running red lights. Less than 6% had received a traffic ticket for red light running and most believed that police would catch less than 20% of violators. Slightly more than one in ten had been involved in a red light running crash. Respondents most commonly suggested legal initiatives to reduce red light running. Accordingly, we recommend traffic safety experts pursue interventions that apply immediate and consistent negative consequences to violators to change the public's red light running perceptions and behavior.

Accidents, Traffic↗
PubMed2003

Economic consequences of injury and resulting family coping strategies in Ghana.

The toll of human suffering from illness and injury is usually measured by mortality and disability rates. Economic consequences, such as treatment costs and lost productivity, are often considered as well. Lately, increasing attention has been paid to the economic effects of illness on a household level. In this study, we sought to assess the economic consequences of injuries in Ghana by looking at the effects on households and the coping mechanisms these households employed. Using cluster sampling and household interviews, we surveyed 21,105 persons living in 431 urban and rural sites. We sought information on any injury that occurred to a household member during the prior year and that resulted in one or more days of disability time.A total of 1609 injuries were reported for the prior year. Treatment costs and disability days were higher in the urban area than in the rural. Coping strategies were different between the two areas. Rural households were more likely to utilize intra-family labor reallocation (90%) than were urban households (75%). Rural households were also more likely to borrow money (24%) than were urban (19%). Households in both areas were equally likely to sell belongings, although the nature of the belongings sold were different. Although injuries in the urban area had more severe primary effects (treatment cost and disability time), the ultimate effect on rural households appeared more severe. A greater percentage of rural households (28%) reported a decline in food consumption than did urban households (19%). These findings result in several policy implications, including measures that could be used to assist family coping strategies and measures directed toward injuries themselves.

Absenteeism↗
PubMed2003

[Consequences of the bilateral vagus nerve section at a cervical level].

We present the consequences corresponding to a bilateral section of the main trunk of vagus nerve at cervical level in a patient with an oropharyngeal carcinoma with bilateral neck nodes. As a consequence of the bilateral resection of both vagus nerves during neck dissections, as well as motor and sensitive damage of the larynx and pharynx, we could observe affection of the normal tone of the oesophagus, stomach and duodenum which forced to enteral nutrition by direct jejunal access, and a disorder of the cardiac rhythm due to loss of the parasympathetic innervation appeared.

Bradycardia↗
PubMed2003

The epidemiology and consequences of maternal malaria: a review of immunological basis.

Millions of women who become pregnant in malaria-endemic areas are at increased risk of contracting malaria infection that jeopardises the outcome of pregnancy. The complication of this infection for mother and baby are considerable. In absence of any other reason, it was thought that the increased risk of infection during pregnancy was related to suppression of pre-existing malaria immunity. Although this concept is plausible, the significantly higher risk of maternal malaria and consequences in primigravidae compared with multigravidae suggests that there are more to mere immunosuppression in pregnancy. The mechanisms underlying some of the striking epidemiological and clinical features of malaria in pregnancy could be related to differences in the strains of parasite populations infecting pregnant women occasioned by the cyto-adherent properties of human placenta, presence or absence of anti-adhesion antibodies acquired from previous pregnancies or the elevated production of some pro-inflammatory cytokines in response to parasitisation of human placenta. Malaria infection of placenta causes a shift from Th2 to Th1 cytokine profile that may be detrimental to pregnancy. The increased susceptibility in the first pregnancy can be explained by the absence of anti-adhesion antibody in the primigravida that is being exposed for the first time to a different strain of malaria parasite sub-population that adhere exclusively to chondroitin sulphate A and hyaluronic acid (HA) in the placenta. In reviewing the epidemiology and consequences of maternal malaria, we have highlighted possible immunological and molecular basis that could account for the higher impact of malaria in pregnancy especially among primigravidae. These factors could be the basis for future research and vaccine formulation.

Adult↗
PubMed1991

The biologic and social consequences of perinatal cocaine use in an inner-city population: results of an anonymous cross-sectional study.

Cocaine use among pregnant women and reports of its adverse perinatal consequences have increased substantially over the past 10 years. However, most researchers have studied patients registered at drug treatment centers or have relied on voluntary participation by patients, either of which introduces the possibility of selection bias. To determine the frequency and consequences of prenatal cocaine use among an unselected inner-city obstetric population, we collected urine samples from parturient women at a municipal hospital and anonymously tested these specimens for metabolites of cocaine, marijuana, opiates, and methadone. Urine specimens, with linked obstetric data sheets, were available from a study population of 1111 patients, and pediatric data sheets were available for 846 mother-infant pairs. Cocaine metabolites were found in 11.5% of the urine samples collected, whereas metabolites of marijuana, opiates, and methadone, respectively, were present in 1.1%, 1.2%, and 0.3% of the specimens. Cocaine users were more likely than nonusers to have had no prenatal care (51% vs 8.8%; p less than 0.0001), to be American-born rather than Caribbean-born (71% vs 33%; p less than 0.001), and to have a higher parity (1.83 vs 1.14; p less than 0.0001). Infants of cocaine users had a lower mean gestational age (-0.93 weeks; p less than 0.01), a lower mean birth weight (2560 +/- 788 vs 3151 +/- 699 gm; p less than 0.001), and an increased probability of having an Apgar score of less than 7 at 5 minutes (12.5% vs 3.2%; p less than 0.0001). Multiple linear regression analysis that isolated confounding variables such as the presence or absence of prenatal care, maternal age and parity, and the use of cigarettes and alcohol did not substantially affect the differences described above. The effect of cigarette smoking on reducing fetal size was cumulative. In conclusion, cocaine is the most commonly used illicit drug among parturients in this community and is strongly associated with underutilization of prenatal care services. Infants of cocaine users are more likely to be preterm and depressed at birth and to have a low birth weight. Cocaine use, through the above-noted effects, increases the need for prenatal care while simultaneously decreasing the likelihood that it will be obtained.

Adult↗
PubMed1998

Ketoconazole inhibition of triazolam and alprazolam clearance: differential kinetic and dynamic consequences.

BACKGROUND: Kinetic and dynamic consequences of metabolic inhibition were evaluated in a study of the interaction of ketoconazole, a P4503A inhibitor, with alprazolam and triazolam, two 3A substrate drugs with different kinetic profiles. METHODS: In a double-blind, 5-way crossover study, healthy volunteers received (A) ketoconazole placebo plus 1.0 mg alprazolam orally, (B) 200 mg ketoconazole twice a day plus 1.0 mg alprazolam, (C) ketoconazole placebo plus 0.25 mg triazolam orally, (D) 200 mg ketoconazole twice a day plus 0.25 mg triazolam, and (E) 200 mg ketoconazole twice a day plus benzodiazepine placebo. Plasma concentrations and pharmacodynamic parameters were measured after each dose. RESULTS: For trial B versus trial A, alprazolam clearance was reduced (27 versus 86 mL/min; P < .002) and apparent elimination half-life (t1/2) prolonged (59 versus 15 hours; P < .03), whereas peak plasma concentration (Cmax) was only slightly increased (16.1 versus 14.7 ng/mL). The 8-hour pharmacodynamic effect areas for electroencephalographic (EEG) beta activity were increased by a factor of 1.35, and those for digit-symbol substitution test (DSST) decrement were increased by 2.29 for trial B versus trial A. For trial D versus trial C, triazolam clearance was reduced (40 versus 444 mL/min; P < .002), t1/2 was prolonged (18.3 versus 3.0 hours; P < .01), and Cmax was increased (2.6 versus 5.4 ng/mL; P < .001). The 8-hour effect area for EEG was increased by a factor of 2.51, and that for DSST decrement was increased by 4.33. Observed in vivo clearance decrements due to ketoconazole were consistent with those anticipated on the basis of an in vitro model, together with in vivo plasma concentrations of ketoconazole. CONCLUSION: For triazolam, an intermediate-extraction compound, impaired clearance by ketoconazole has more profound clinical consequences than those for alprazolam, a low extraction compound.

Administration, Oral↗
PubMed1998

Inhibition of triazolam clearance by macrolide antimicrobial agents: in vitro correlates and dynamic consequences.

BACKGROUND: Macrolide antimicrobial agents may impair hepatic clearance of drugs metabolized by cytochrome P4503A isoforms. Potential interactions of triazolam, a substrate metabolized almost entirely by cytochrome P4503A in humans, with 3 commonly prescribed macrolides were identified using an in vitro metabolic model. The actual interactions, and their pharmacodynamic consequences, were verified in a controlled clinical study. METHODS: In an in vitro model using human liver microsomes, 250 mumol/L triazolam was incubated with ascending concentrations (0 to 250 mumol/L of troleandomycin, azithromycin, erythromycin, and clarithromycin. In a randomized, double-blind, 5-trial clinical pharmacokinetic-pharmacodynamic study, 12 volunteers received 0.125 mg triazolam orally, together with placebo, azithromycin, erythromycin, or clarithromycin. In a fifth trial they received placebo plus placebo. RESULTS: Mean 50% inhibitory concentrations versus 4-hydroxytriazolam formation in vitro were as follows: 3.3 mumol/L troleandomycin, 27.3 mumol/L erythromycin, 25.2 mumol/L clarithromycin, and greater than 250 mumol/L azithromycin. Apparent oral clearance of triazolam when given with placebo or azithromycin was nearly identical (413 and 416 mL/min), as were peak plasma concentrations (1.25 and 1.32 ng/mL) and elimination half-life (2.7 and 2.6 hours). Apparent oral clearance was significantly reduced (P < .05) during erythromycin and clarithromycin trials (146 and 95 mL/min). Peak plasma concentration was correspondingly increased, and elimination half-life was prolonged. The effects of triazolam on dynamic measures were nearly identical when triazolam was given with placebo or azithromycin, but benzodiazepine agonist effects were enhanced during erythromycin and clarithromycin trials. CONCLUSION: The in vitro model identifies macrolides that may impair triazolam clearance. Anticipated interactions, and their pharmacodynamic consequences in volunteer subjects, were verified in vivo.

Administration, Oral↗
PubMed2001

Functional consequences of the autosomal dominant G272A mutation in the human GLUT1 gene.

The first autosomal dominant missense mutation (G272A) reported within the human GLUT1 gene and shared by three affected family members was investigated in respect to functional consequences. Substitution of glycine-91 by site-directed mutagenesis with either aspartate or alanine resulted in a significant decrease in transport activity of GLUT1 expressed in Xenopus oocytes. Expression of mutant transporters was confirmed by immunoblot, 2-deoxy-glucose uptake and confocal laser microscopy. The data agree with 3-O-methyl-glucose uptake into patient erythrocytes and indicate that the loss of glycine rather than a hydrophilic side chain (Gly91Asp) defines the functional consequences of this mutation.

Alanine↗
PubMed2003

Consequences of road traffic accidents for different types of road user.

The study aimed to describe the immediate and later physical, social and psychological consequences of a road traffic accident for vehicle occupants, motorcyclists, cyclists and pedestrians amongst consecutive hospital attenders at an Accident and Emergency Department. Physical and accident details were collated from hospital records. Subjects completed questionnaires at hospital attendance, 3 months, 1 and 3 years. There were 1148 respondents from 1441 consecutive attenders over a 1-year period. The main outcome measures were self-report physical status, standard measures of post-traumatic stress disorder, mood, travel anxiety and health status at 3 months, 1 and 3 years. There were marked differences in injury pattern and immediate reaction between road user groups. Pedestrians and motorcyclists suffer the most severe injuries and report more continuing medical problems and greater resource use, especially in the first 3 months. There were few differences in psychological or social outcomes at any stage of follow-up. Despite differences between the road user groups in their injuries, immediate reactions and treatment, there were few longer-term differences. A third of all groups described chronic adverse consequences which were principally psychological, social and legal.

Absenteeism↗
PubMed1998

Long-term physical, psychological and social consequences of a fracture of the ankle.

The long-term physical, psychological and social outcomes of 68 patients with an ankle fracture were investigated by using a postal questionnaire 6 years after injury. Patients were treated at a level I Trauma Centre between January 1989 and December 1989. Where applicable, the outcomes were compared with the outcomes of severely injured patients who were investigated previously. Physically, the patients were suffering from problems in the extremities and the spine. Surprisingly, half of them (52 per cent) had psychological complaints due to the initial injury. Eighty-nine per cent of the patients returned to work. This result seems to be only slightly better than the return to work in severely injured patients (74 per cent). Those with an ankle fracture needed less time to return to work (3 months versus 13 months in the severely injured patients). Further social changes (marital status, leisure activities) were mostly found in the severely injured patients. Patients with an ankle fracture as well as severely injured patients are affected by long-term consequences. The differences between the two groups are not as pronounced as is generally assumed. Probably, the consequences of lesser injuries are frequently disregarded, whereas severely injured patients are doing better than expected.

Adolescent↗