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PubMed2002

Use and fate of pesticides in the Amazon State, Brazil: risk to human health and the environment.

During the last 30 years, the increase of the human population in the Amazon introduced the need for additional food production and caused the state government to implement programs to increase and improve agricultural production. The production of nontraditional crops introduced several problems unknown to traditional farmers, since they are not well adapted to tropical conditions. Their susceptibility to insects, fungi and other plagues, and the competition with native vegetation forced farmers to use pesticides intensively. Amazonian farmers were not adequately prepared for the use of this new technology; they ignored the risk of pesticides to human health and the environment. Using the region of the state capital Manaus as an example, the characteristics of the pesticide use are described (e.g. the increased use and the lack of personal protective equipment, as well as the legal situation). In detail, the registration status of pesticides used in the State of Amazonas and the state of their registration in the European Union is compared. Finally, it is concluded that the use and the fate of pesticides in the Amazon region has to be monitored. Data of the effects on humans and on the environment have to be collected from the literature or have to be produced in standardized tests, so that an environmental risk assessment becomes possible. Training and information programs are urgently needed in order to build up environmentally sustainable agriculture. Finally, the enforcement of Brazilian laws concerning pesticide registration has to be improved.

Agriculture↗
PubMed2003

Effects of education, self-care instruction and physical exercise on patients with chronic heart failure.

BACKGROUND: Evidence is now evolving of the importance of team management for patients with chronic heart failure. This includes education, patient self-care and physical exercise training. How such programs should be implemented is still under discussion. AIM: To assess the efficacy of an in-hospital rehabilitation clinic-based program, we studied its influence on cardiopulmonary parameters and quality of life in an outpatient setting. METHODS AND RESULTS: 75 patients (62 male, 13 female, mean age 65+/-8 years) underwent an exercise program including education, bicycle ergometer, muscle strength training and the 6-min walk test as a training unit for 4 weeks. Patients were studied at baseline (T1), before discharge (T2) and after a follow-up period of 29.9+/-5.5 weeks (T3). Baseline data (T1): left ventricular ejection fraction (LVEF): 33.8+/-7.6%, left ventricular end-diastolic volume (LVEDV): 130+/-51 ml, peak VO(2): 12.3+/-4.3 ml/kg, maximum work load (Watt max): 71+/-27 W. At discharge (T2) and follow-up (T3) LVEF increased to 36.8+/-8% and 41.8+/-9.2%, LVEDV decreased to 127+/-43 ml and 114+/-40 ml, peak VO(2) increased to 14.1+/-5.1 ml/kg and 15.2+/-5 ml/kg, and Watt max increased to 84+/-28 Wand 98+/-42 W (all p<0.01). Quality of life improved significantly at discharge and follow-up in nearly all domains and in the summary score for physical health. There were no significant changes for anxiety and depression at T2 and T3. CONCLUSION: A specialized in hospital rehabilitation program including education, patient self management and training has a sustained positive effect on cardiopulmonary parameters and physical well-being.

Aged↗
PubMed1992

Efficacy and electrophysiologic effects of oral sotalol in patients with sustained ventricular tachycardia caused by coronary artery disease.

The efficacy of oral sotalol in preventing sustained ventricular tachycardia induction by invasive electrophysiological testing was assessed in 22 patients (60 +/- 9 years) with prior myocardial infarction. Programmed stimulation consisted of two basic drives followed by up to three extrastimuli at two right ventricular sites. At baseline, sustained monomorphic ventricular tachycardia was inducible in all patients. With sotalol (360 +/- 172 mg/day), it was no longer inducible in 10 patients; in 12 others, it remained inducible and its cycle length was only minimally prolonged (322 +/- 42 to 345 +/- 44 msec, p less than 0.05). Sotalol markedly prolonged sinus cycle length, uncorrected QT interval, and right ventricular effective and functional refractory periods, but had little effect on ventricular conduction time either in sinus rhythm or with right ventricular pacing. There was no significant difference in drug dose or in electrophysiologic effect of drug that related to efficacy, nor was there any correlation between drug-induced prolongation of ventricular tachycardia cycle length and its effects. Six patients received oral sotalol over the long term without spontaneous recurrence of ventricular tachycardia (follow-up: 23 +/- 18 months). These results demonstrate that sotalol is effective (45%) against sustained ventricular tachycardia induction at moderate doses and is well tolerated over a long term in the setting of remote myocardial infarction. However, its electrophysiologic effects as measured at invasive testing are not predictive of efficacy against ventricular tachycardia induction.

Administration, Oral↗
PubMed2005

Exploiting genotypic variation in plant nutrient accumulation to alleviate micronutrient deficiency in populations.

More than 2 billion people consume diets that are less diverse than 30 years ago, leading to deficiencies in micronutrients, especially iron (Fe), zinc (Zn), selenium (Se), iodine (I), and also vitamin A. A strategy that exploits genetic variability to breed staple crops with enhanced ability to fortify themselves with micronutrients (genetic biofortification) offers a sustainable, cost-effective alternative to conventional supplementation and fortification programs. This is more likely to reach those most in need, has the added advantages of requiring no change in current consumer behaviour to be effective, and is transportable to a range of countries. Research by our group, along with studies elsewhere, has demonstrated conclusively that substantial genotypic variation exists in nutrient (e.g. Fe, Zn) and nutrient promotor (e.g. inulin) concentrations in wheat and other staple foods. A rapid screening technique has been developed for lutein content of wheat and triticale, and also for pro-vitamin A carotenoids in bread wheat. This will allow cost-effective screening of a wider range of genotypes that may reveal greater genotypic variation in these traits. Moreover, deeper understanding of genetic control mechanisms and development of molecular markers will facilitate breeding programs. We suggest that a combined strategy utilising plant breeding for higher micronutrient density; maximising the effects of nutritional promoters (e.g. inulin, vitamin C) by promoting favourable dietary combinations, as well as by plant breeding; and agronomic biofortification (e.g. adding iodide or iodate as fertiliser; applying selenate to cereal crops by spraying or adding to fertiliser) is likely to be the most effective way to improve the nutrition of populations. Furthermore, the importance of detecting and exploiting beneficial interactions is illustrated by our discovery that in Fe-deficient chickens, circulating Fe concentrations can be restored to normal levels by lutein supplementation. Further bioavailability/bioefficacy trials with animals and humans are needed, using varying dietary concentrations of Fe, Zn, carotenoids, inulin, Se and I to elucidate other important interactions in order to optimise delivery in biofortification programs.

Carotenoids↗
PubMed1984

Atrial conduction: effects of extrastimuli with and without atrial dysrhythmias.

The effects of cycle length and stimulation site on intraatrial conduction and refractoriness were evaluated in patients with and without atrial flutter (AFI) or fibrillation (AF) using the extrastimulus technique. Nineteen patients with spontaneous sustained AFI or AF were compared with 19 control patients. Programmed stimulation was performed at the right atrium and coronary sinus at drive cycle lengths of 600 and 450 ms. The atrial effective refractory period was similar in the patients with atrial dysrhythmias and the control group. The right atrial effective refractory period at a drive cycle length of 600 ms was significantly shorter in patients with AF (211 ms) than in patients with AFI (235 ms, p = 0.05). The conduction time of late (coupling intervals more than 50% of the drive cycle length) premature impulses was similar in the patients with atrial dysrhythmias and the control group. However, early extrastimuli (coupling intervals less than 50% of the drive cycle length) at a drive cycle length of 600 ms produced significantly more intraatrial conduction delay in the patients with atrial dysrhythmias than in the control patients. At a drive cycle length of 450 ms, similar delays in intraatrial conduction occurred in the patients with and without atrial dysrhythmias because of an increase in the maximal-observed intraatrial conduction delay in the control patients. This study shows that delay in conduction of early premature atrial stimuli at a drive cycle length of 600 ms is a marker of patients with spontaneous AFI and AF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

Sports ability in young men and the incidence of cardiovascular disease.

PURPOSE: For physical activity to reduce the risk of cardiovascular disease, it must be sustained throughout life. We sought to determine the relation between the ability of young adults in different sports and their continued physical activity in midlife, and subsequent cardiovascular disease. SUBJECTS AND METHODS: Baseline self-reported ability in tennis, golf, football, baseball, and basketball was assessed in a cohort study involving 1019 male medical students (median age, 22 years). Physical activity and sports participation were assessed 22 years later. The incidence of cardiovascular disease was assessed during a median follow-up of 40 years, using annual questionnaires, medical records, and death certificates. RESULTS: Subjects with high ability in tennis as young adults had the highest participation in the sport in midlife (median age, 48 years). In the midlife questionnaire administered in 1978, 33% reported playing tennis within the past week and 51% within the past year. Tennis was the only sport in which a higher ability during medical school was associated with a lower risk of cardiovascular disease. After adjustment for father's occupation, parental incidence of cardiovascular disease, serum cholesterol level, cigarette smoking, body mass index, and hypertension during follow-up, the relative hazard of developing cardiovascular disease was 0.56 (95% confidence interval [CI]: 0.35 to 0.89) in the high-ability group and 0.67 (95% CI: 0.47 to 0.96) in the low-ability group, compared with the no-ability group. CONCLUSION: Our results support the association between sustained activity in aerobic sports and a lower risk of cardiovascular disease. Sustainability of activity should be considered when developing physical education programs for young adults.

Adult↗
PubMed1999

Ventricular assist device programs: design and function.

Ventricular assist device programs can be structured in a variety of models and can make use of personnel derived from a broad spectrum of clinical and hospital-based practice. When aggressively and proactively negotiated with payers, these programs can be cost-effective and thoroughly self-sustaining.

Animals↗
PubMed2002

Factors influencing private health providers' technical quality of care for acute respiratory infections among under-five children in rural West Bengal, India.

In many developing countries, private health practitioners provide a significant portion of curative care for diseases which are of public health importance. Currently, health sector reform efforts in these countries are fostering increased participation of private providers in the delivery of health services, including those of public health importance. Guaranteeing good technical quality of care is critical to the process. However, little is known about private providers' technical quality of care (disease management practices) and the factors influencing these services. The purpose of this study was to contribute information on this topic. The study was conducted among private providers in rural West Bengal, India and focused on providers' disease management practices for acute respiratory infections (ARI) among under-five children. World Health Organization (WHO) guidelines for ARI case management were used as the expected standard of care. Observations of patient-provider encounters and interviews with the providers and mothers were the main sources of data. The study found that private health providers in rural West Bengal have inadequate technical quality of care. The problem was related both to low levels of performance (limited potential) and inconsistency in performance (within-provider variation). Limited potential for good technical quality for ARI among the providers was related to lack of knowledge (technical incompetence). One of the important factors influencing within-provider variation was patient load. Since rural private providers operate on a fee-for-service payment system, there are incentives related to seeing many patients. The study concluded that to bring about sustainable improvements in private providers' ARI disease management practices, training programs and interventions that improved compliance were necessary.

Acute Disease↗
PubMed1997

Do we now understand the control of the fetal circulation?

Physiological research has now given us a reasonably complete picture of fetal cardiovascular control in late gestation, especially with respect to the responses to acute hypoxaemia. Reflex, endocrine and auto/paracrine mechanisms all play a part. This review questions how complete our knowledge is when we address the clinically important issues of the influence of gestational age, sustained hypoxia and the effects of nutrition in altering the programming of cardiovascular development.

Animals↗
PubMed2025

Integrated epigenetic and genetic programming of primary human T cells.

Targeted epigenetic engineering of gene expression in cell therapies would allow programming of desirable phenotypes without many of the challenges and safety risks associated with double-strand break-based genetic editing approaches. Here, we develop an all-RNA platform for efficient, durable and multiplexed epigenetic programming in primary human T cells, stably turning endogenous genes off or on using CRISPRoff and CRISPRon epigenetic editors. We achieve epigenetic programming of diverse targeted genomic elements without the need for sustained expression of CRISPR systems. CRISPRoff-mediated gene silencing is maintained through numerous cell divisions, T cell stimulations and in vivo adoptive transfer, avoiding cytotoxicity or chromosomal abnormalities inherent to multiplexed Cas9-mediated genome editing. Lastly, we successfully combined genetic and epigenetic engineering using orthogonal CRISPR Cas12a-dCas9 systems for targeted chimeric antigen receptor (CAR) knock-in and CRISPRoff silencing of therapeutically relevant genes to improve preclinical CAR-T cell-mediated in vivo tumor control and survival.

Humans↗
PubMed1990

NK cell-induced cytotoxicity is dependent on a Ca2+ increase in the target.

In previous work we showed that programmed cell death (PCD) in thymocytes is mediated by a sustained increase in cytosolic Ca2+ concentration, resulting in the activation of an endogenous endonuclease, DNA fragmentation, and cell death. In this study we investigated the roles of Ca2+ and DNA fragmentation in target cell killing by natural killer (NK) cells. The effector cells induced a rapid, sustained increase in cytosolic Ca2+ concentration in Jurkat target cells. Buffering the target cell cytosolic Ca2+ with the Ca2(+)-selective dye, quin-2, prevented target cell killing. Extensive DNA fragmentation was associated with killing in every target tested, and this response was also blocked by quin-2. The endonuclease inhibitor, aurintricarboxylic acid, inhibited both DNA fragmentation and killing without influencing the Ca2+ increase in target cells. Thus, it is concluded that NK cell killing depends on a Ca2+ increase and appears to involve endogenous endonuclease activation in target cells.

Aminoquinolines↗
PubMed1999

Venous air embolism from central venous catheterization: a need for increased physician awareness.

OBJECTIVES: To report a series of patients with clinically diagnosed venous air embolism (VAE) and major sequelae as a complication of the use of central venous catheters (CVCs), to survey health care professionals' practices regarding CVCs, and to implement an educational intervention for optimizing approaches to CVC insertion and removal. SETTING: Tertiary care, university-based 806-bed medical center. INTERVENTIONS: We surveyed 140 physicians and 53 critical care nurses to appraise their awareness of the proper management and complications of CVCs. We then designed, delivered, and measured the effects of a multidisciplinary educational intervention given to 106 incoming house officers. MEASUREMENTS AND MAIN RESULTS: Although most physicians (127, 91%) chose the Trendelenburg position for CVC insertion, only 42 physicians (30%) reported concern for VAE. On CVC removal, only 36 physicians (26%) cited concern for VAE. Some physicians (13, 9%) reported elevating the head of the bed during CVC removal, possibly increasing the risk of VAE. Awareness of VAE or its prevention did not correlate with the level of physician training, experience, or specialty. After the educational intervention, concern for and awareness of proper methods of prevention of VAE improved (p < .001). At 6-month follow-up, reported use of the Trendelenburg position continued, but concern cited for VAE had returned to baseline. CONCLUSIONS: There is inadequate awareness of VAE as a complication of CVC use. Focused instruction can improve appreciation of this potentially fatal complication and knowledge of its prevention, but the effect declines rapidly. To achieve a more sustained improvement, a more intensive, hands-on, periodic educational program will likely be necessary, as well as reinforcement through enhanced supervision of CVC insertion and removal practices.

Academic Medical Centers↗
PubMedDate not supplied

Electrophysiologic actions of lidocaine in a canine model of chronic myocardial ischemic damage--arrhythmogenic actions of lidocaine.

Lidocaine facilitated the induction of ventricular arrhythmias by programmed electrical stimulation in 16 dogs, 5 to 14 days after a temporary (90-min) occlusion of the left anterior descending coronary artery. In these 16 animals, programmed stimulation failed to produce ventricular tachyarrhythmias in any animal before lidocaine administration (3 mg/kg), while after lidocaine administration, programmed stimulation produced nonsustained ventricular tachycardia in four animals (25%), sustained ventricular tachycardia in nine animals (56%), and ventricular fibrillation in one animal (6%). Delayed electrical activity in ischemically injured ventricular myocardium produced by premature ventricular stimuli (mean +/- SD = 179 +/- 34 ms) was delayed further by the administration of lidocaine (237 +/- 42 ms, p less than 0.01), resulting in continuous local electrical activity between the final premature ventricular stimulus and the initial beat of the resultant ventricular tachycardia. Lidocaine administration did not alter myocardial refractoriness in normal ventricular tissue, but it prolonged refractoriness in ischemically injured ventricular myocardium. These results show that lidocaine can have arrhythmogenic actions when administered in the presence of existing ischemic injury, possibly the result of increased delay in activation of ischemically injured ventricular myocardium with localized reentry of myocardial electrical activity.

Animals↗
PubMed1991

In vivo effect of bradykinin during ischemia and reperfusion: improved electrical stability two weeks after myocardial infarction in the pig.

In this study, the effect of bradykinin or saline infusion during ischemia and reperfusion on electrical stability, 2 weeks after myocardial infarction, was assessed. Acute myocardial infarction was induced in 21 pigs by a transluminal occlusion of the left coronary artery with a catheter balloon, inflated for 45 min. Bradykinin was administered by a 30-min infusion that started after 30 min of coronary occlusion and was continued until 15 min after reperfusion. Although creatine kinase levels in bradykinin-treated animals were significantly lower (p less than 0.001), 2 week survival was not different between groups. In survivors, the filtered QRS (ventricular deflection) duration (detected using signal-averaged electrocardiography) was significantly prolonged in saline-treated pigs, whereas in bradykinin-treated pigs this prolongation was prevented. The terminal voltage of the QRS complex was significantly lower in saline-treated pigs than in bradykinin-treated pigs. These two parameters signify an improved electrical stability after bradykinin treatment. Refractory periods in saline-treated hearts were longer than in bradykinin-treated hearts (106 +/- 10% vs. 95 +/- 13%, p less than 0.05). Also, current thresholds in the infarct border zones showed a greater variance in saline-treated hearts (p less than 0.001), pointing toward more tissue heterogeneity of the infarct border zone. Programmed electrical stimulation showed a trend toward reduced inducibility of sustained ventricular tachycardia in bradykinin-treated hearts. Therefore, bradykinin improves electrical stability weeks after experimental myocardial infarction.

Animals↗
PubMed1997

Control-relevant intervention in the treatment of minor and major depression in a long-term care facility.

The authors assessed the effect of a control-relevant psychosocial intervention in 31 nursing home residents with either major depressive episode or minor depression. An initial group of 22 residents were randomized to either active treatment or waiting list. Four of 11 residents randomized to active treatment were deemed Responders, compared with 0 of 11 on the waiting list (P < 0.05). Of the total of 31 residents who participated in the intervention, 14 (45%) were deemed Responders during the intervention period. For these Responders, the Hamilton Rating Scale for Depression (Ham-D) and Geriatric Depression Scale scores improved significantly during the intervention. The improvement in the Ham-D was not sustained 2 months after intervention was terminated. These findings suggest that a psychosocial intervention enhancing socialization according to each resident's choice had a positive therapeutic impact on almost half of the nursing home residents with major or minor depression. However this effect could not be sustained by the residents without the support of the structured program.

Aged↗
PubMed2006

Hospital services for children in the Solomon Islands: rebuilding after the civil conflict.

AIMS: The Solomon Islands health service, infrastructure and economy were severely affected by the civil conflict that occurred between 1998 and 2003. In 2002 plans to rebuild health services for children, especially those provided in provincial hospitals, were developed by paediatricians, in collaboration with the World Health Organization. We aimed to inform this process by an assessment of the strengths and weaknesses of the child health service, particularly in provincial hospitals. METHODS: A systematic assessment of the quality of hospital care for children in Solomon Islands was conducted in November 2003. The study used a WHO assessment tool, modified for use in the Asia-Pacific region. RESULTS: The assessment highlighted several problems in clinical care, human resources, health financing, referral systems, and training, and has been used as a basis for several interventions for improving the quality of paediatric care. CONCLUSION: This study and the initiatives that have followed it demonstrate the link between such assessments, child health policy and quality improvement activities. Such programs can be implemented even where resources are very limited. Sustaining initiatives based on this assessment will be important for the Solomon Islands if it is to achieve the Millennium Development Goals for child survival by 2015.

Child↗
PubMed2004

The tooty fruity vegie project: changing knowledge and attitudes about fruits and vegetables.

OBJECTIVES: The Tooty Fruity Vegie (TFV) project was a multi-strategic, school-based intervention aimed at preventing the large decline in fruit and vegetable intake that typically starts during primary school. METHODS: During 1999 and 2000, TFV was implemented in 10 volunteer primary schools across the Northern Rivers region of New South Wales. Surveys were conducted, in late 2000, with children, parents, teachers and principals across nine intervention and three matched control schools. Intervention schools' management teams also completed strategy implementation indexes indicating how often, how well and with how many people each major strategy was implemented. RESULTS: Completed surveys from 613 parents (59%), 392 older children (65%), 50 teachers (81%) and all 10 intervention principals and school management teams showed the project was well implemented, achieved high reach and was very positively received. The project enhanced the quality, diversity and frequency of classroom fruit and vegetable-promoting activities, substantially increasing children's involvement and enjoyment levels. It significantly improved children's fruit and vegetable knowledge, attitudes, access and preparation skills; parents' knowledge and involvement in fruit and vegetable-promoting activities in schools and beyond; and teachers' perceived support for doing fruit and vegetable promotions. CONCLUSION: Despite some methodological limitations, which may limit confidence in our findings, survey results across all target groups consistently indicated that primary schools can be supported to establish, implement and sustain highly acceptable and effective fruit and vegetable-promoting programs.

Child↗
PubMedDate not supplied

Hoxd13 expression in the developing limbs of the short-tailed fruit bat, Carollia perspicillata.

Bat forelimbs are highly specialized for sustained flight, providing a unique model to explore the genetic programs that regulate vertebrate limb diversity. Hoxd9-13 genes are important regulators of stylopodium, zeugopodium, and autopodium development and thus evolutionary changes in their expression profiles and biochemical activities may contribute to divergent limb morphologies in vertebrates. We have isolated the genomic region that includes Hoxd12 and Hoxd13 from Carollia perspicillata, the short-tailed fruit bat. The bat Hoxd13 gene encodes a protein that shares 95% identity with human and mouse HOXD13. The expression pattern of bat Hoxd13 mRNA during limb development was compared with that of mouse. In bat and mouse hindlimbs, the expression patterns of Hoxd13 are relatively similar. However, although the forelimb Hoxd13 expression patterns in both organisms during early limb bud stages are similar, at later stages they diverge; the anterior expression boundary of bat Hoxd13 is posterior-shifted relative to the mouse. These findings, compared with the Hoxd13 expression profiles of other vertebrates, suggest that divergent Hoxd13 expression patterns may contribute to limb morphological variation.

Animals↗