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Limited predictive value of inducible sustained ventricular tachycardia for future occurrence of spontaneous ventricular tachycardia in patients with coronary artery disease and relatively preserved cardiac function.

To evaluate the significance of inducible sustained ventricular tachycardia (VT) in patients with coronary artery disease and relatively preserved cardiac function, 33 patients who met the following criteria were studied; documented nonsustained VT but no history of life-threatening arrhythmia, inducible sustained VT at electrophysiologic study, and implantation of a cardioverter-defibrillator. Eighteen patients developed clinical sustained VT within 2 years. By univariate analysis, left ventricular ejection fraction (EF) and the cycle length of induced VT were associated with clinical VT occurrence. By multivariate analysis, however, EF was the only independent predictor. Among 23 patients with EF 40% (P <.01). In coronary artery disease patients with relatively preserved EF, the incidence of clinical VT is considerably low even though sustained VT is inducible. Inducible VT is therefore not appropriate for risk stratification in this patient population.

Aged↗

Protein kinase C translocation in intact vascular smooth muscle strips.

Using intact muscle strips from the bovine carotid artery, the time course of translocation of protein kinase C (PKC) from the cytosol to the membrane fraction was measured in response to various agonists that induce contractile responses. PKC activity was assessed by Ca2+/phospholipid-dependent phosphorylation of histone. Exposure of the muscle strips to phorbol ester (12-deoxyphorbol 13-isobutyrate) induced a rapid and sustained translocation of PKC from the cytosol to the membrane fraction, and a slowly developing but sustained contractile response. Histamine induced a comparable initial translocation of PKC to the membrane which then decreased somewhat to a stable plateau significantly above basal values. Histamine also led to a rapid and sustained increase in tension. Angiotensin I, which caused a rapid but transient contraction, induced a rapid initial translocation of PKC to the membrane. The membrane-associated PKC then declined to a stable plateau significantly lower than that seen after a histamine-induced response, and only slightly above the basal value. Endothelin, which induced a sustained contraction, caused a sustained translocation of PKC from the cytosol to the membrane. In contrast, although exposure to 35 mM-KCl induced a rapid and sustained contraction, it caused only a transient translocation of PKC; the membrane-associated PKC returned to its basal value within 20 min. These results demonstrate that PKC in intact smooth muscle can be rapidly translocated to the membrane and remains membrane-bound during sustained phorbol ester- or agonist-induced contractions, but that such a sustained translocation of PKC does not occur during prolonged stimulation with KCl.

Angiotensin II↗

Attenuation of psychosocial stress-induced hypertension by gamma-linolenic acid (GLA) administration in rats.

This study investigated a model of psychosocial stress-induced hypertension in the rat, and examined effects of the prostaglandin E precursor, gamma-linolenic acid (GLA) on the development of hypertension during psychosocial stress. In the first study, male rats were housed four/cage for an acclimation period of 21 days, followed by a 14-day control period. An experimental group (N = 12) was then placed in isolation cages for 14 days, then regrouped for a 7-day recovery period. Controls (N = 12) remained group-housed. Eight animals per group were sacrificed after the experimental period, and four per group after recovery for organ weight analysis. Mean systolic blood pressure (BP) was similar between groups during the control period (126 +/- 2 and 125 +/- 2 mm Hg), but increased during isolation, reaching 140 +/- 2 mm Hg (P less than 0.001) by Day 14. During recovery BP returned to control levels. No changes in heart rate, heart weight/body weight or adrenal weight were seen. The second study utilized a protocol similar to that of the experimental group of the first study, minus the recovery period. On Day 1 of the control period 28-day osmotic pumps were implanted ip, releasing olive oil or GLA in olive oil. Four groups of rats (N = 8/group) received either (i) olive oil (controls), (ii) 0.018 mg GLA/hr, (iii) 0.040 mg GLA/hr, or (iv) 0.040 mg GLA/hr with no stress. Organ weights were obtained following stress in groups 1-3. Controls developed a sustained elevation in BP within 24 hr of isolation. Animals receiving 0.018 mg GLA/hr developed elevated BP upon isolation, but the BP was less than that of controls on Days 1 (P less than 0.05) and 14 (P less than 0.001) of isolation. Animals receiving 0.040 mg GLA/hr demonstrated a greatly attenuated rise in BP vs controls (P less than 0.001) on all isolation days. GLA in unstressed rats had no effect on BP. Heart rate, heart weight/body weight, and adrenal weight were unchanged in all groups. These data suggest that (i) isolation is a useful tool for investigating reversible psychosocial stress-induced hypertension, and (ii) GLA, while not affecting BP in unstressed animals, produces a dose-dependent attenuation of the BP response to chronic stress.

Adrenal Glands↗

Perspectives in agrobiotechnology.

This review surveys the most important and promising contributions of agricultural biotechnology to the development of sustainable, environment-friendly agriculture. It deals with the recent achievements of genetic technology for the development of new transgenic microbial, plant and animal products. It also deals with the newest developments and perspectives of microbial intervention in agricultural practices, such as biofertilizers, biocontrol agents, and various microbiological products used in modern agriculture. The review surveys the outlook for a waste-free, environment-friendly sustainable agricultural practice, including waste management, recycling and bioremediation technologies. The review lists the most important marketable agrobiotechnological products, and their present and projected sales volume.

Agriculture↗

Qualitative research to make practical sense of sustainability in primary health care projects implemented by non-governmental organizations.

Sustainability continues to be a serious concern for Primary Health Care (PHC) interventions targeting the death of millions of children in developing countries each year. Our work with over 30 Non-Governmental Organizations (NGOs) implementing USAID's Child Survival and Health Grants Program (CSHGP)-funded projects revealed the need for a study to develop a framework for sustainability assessment in these projects. We surveyed NGO informants and project managers through semi-structured interviews and questionnaires. This paper summarizes our study findings. The NGOs share key values about sustainability, but are skeptical about approaches perceived as disconnected from field reality. In their experience, sustainable achievements occur through the interaction of capable local stakeholders and communities. This depends strongly on enabling conditions, which NGO projects should advance. Sustainability assessment is multidimensional, value-based and embeds health within a larger sustainable development perspective. It reduces, but does not eliminate, the unpredictability of long-term outcomes. It should start with the consideration of the 'local systems' which need to develop a common purpose. Our ability to address the complexity inherent to sustainability thinking rests with the validity of the models used to design interventions. A participant, qualitative research approach helped us make sense of sustainability in NGO field practice.

Child↗

Strategies in engineering sustainable biochemical synthesis through microbial systems.

Growing environmental concerns and the urgency to address climate change have increased demand for the development of sustainable alternatives to fossil-derived fuels and chemicals. Microbial systems, possessing inherent biosynthetic capabilities, present a promising approach for achieving this goal. This review discusses the coupling of systems and synthetic biology to enable the elucidation and manipulation of microbial phenotypes for the production of chemicals that can substitute for petroleum-derived counterparts and contribute to advancing green biotechnology. The integration of artificial intelligence with metabolic engineering to facilitate precise and data-driven design of biosynthetic pathways is also discussed, along with the identification of current limitations and proposition of strategies for optimizing biosystems, thereby propelling the field of chemical biology towards sustainable chemical production.

Metabolic Engineering↗

Supraspinal factors in human muscle fatigue: evidence for suboptimal output from the motor cortex.

1. Voluntary activation of elbow flexor muscles can be optimal during brief maximal voluntary contractions (MVCs), although central fatigue, a progressive decline in the ability to drive the muscle maximally, develops during sustained or repeated efforts. We stimulated the motor cortex and motor point in human subjects to investigate motor output during fatigue. 2. The increment in force (relative to the voluntary force) produced by stimulation of the motor point of biceps brachii increased during sustained isometric MVCs of the elbow flexors. Motoneuronal output became suboptimal during the contraction, i.e. central fatigue developed and accounted for a small but significant loss of maximal voluntary force. During 3 min MVCs, voluntary activation of biceps fell to an average of 90.7% from an average of > 99%. 3. The increment in force (relative to the voluntary force) produced by magnetic cortical stimulation was initially small (1.0%) but also increased during sustained MVCs to 9.8% (with a 2 min MVC). Thus, cortical output was not optimal at the time of stimulation nor were sites distal to the motor cortex already acting maximally. 4. A sphygmomanometer cuff around the upper arm blocked blood supply to brachioradialis near the end of a sustained MVC and throughout subsequent brief MVCs. Neither maximal voluntary force nor voluntary activation recovered during ischaemia after the sustained MVC. However, fatigue-induced changes in EMG responses to magnetic cortical stimulation recovered rapidly despite maintained ischaemia. 5. In conclusion, during sustained MVCs, voluntary activation becomes less than optimal so that force can be increased by stimulation of the motor cortex or the motor nerve. Complex changes in excitability of the motor cortex also occur with fatigue, but can be dissociated from the impairment of voluntary activation. We argue that inadequate neural drive effectively 'upstream' of the motor cortex must be one site involved in the genesis of central fatigue.

Adult↗

Use of in vitro and in vivo data in the design, development, and quality control of sustained-release decongestant dosage forms.

STUDY OBJECTIVES: To investigate the use of in vitro and in vivo data in the development of a sustained-release, carbomer-based dosage form (Entex LA tablets); and to compare the in vitro dissolution of pseudoephedrine from a sustained-release, hydroxypropylcellulose-based dosage form (Entex PSE tablets) and four branded competitors with different sustained-release matrixes. DESIGN: Entex LA: In vitro testing by rotating bottle method and in vivo testing as double-blind, randomized, crossover, 24-hour study. Entex PSE and four competitors: in vitro testing by paddle method. SETTING: A pharmaceutical research and development facility. PATIENTS: Fifteen health, adult, volunteer Caucasian men between ages 18 and 40 years. MAIN RESULTS: Three formulations of Entex LA, varying in carbomer content by 3-5%, were studied. As carbomer content increased, in vitro dissolution rate directionally decreased. Plasma concentrations of active ingredients guaifenesin and phenylpropanolamine were also slightly although directionally decreased. The in vitro method was sensitive to small changes in carbomer content. Larger changes in carbomer content would be required to establish an in vitro-in vivo correlation. The in vitro comparison of Entex PSE and four similar branded products showed important differences in dissolution profiles. The mean cumulative release of pseudoephedrine from Entex PSE was 39% at 1.5 hours, 62% at 4.0 hours, and 80% at 8.0 hours. The other products released pseudoephedrine more rapidly, with the two fastest-dissolving products releasing 61-62% in the first 1.5 hours. CONCLUSIONS: Sustained-release, polymer-based dosage forms such as Entex LA and Entex PSE can be complex and pose special challenges in design, development, and reformulation. For Entex LA, changes in polymer concentration and dye system influenced the in vitro (dissolution) performance. In vivo (plasma) data helped establish a defined range in which carbomer concentration could be varied to achieve the best manufacturing performance without affecting product performance. For Entex PSE and four branded competitor products, the cumulative in vitro release (dissolution) of pseudoephedrine varied widely. Release from Entex PSE was more consistent and more gradual than that from some of the comparison products. Because the absorption rate of the active ingredients pseudoephedrine and gauifenesin is governed by the dissolution rate, the observed differences suggest that the products tested may differ in biologic performance. Although in vitro dissolution data may not necessarily correlate with in vivo differences in clinical safety or efficacy, the potential for unexpected product performance may be signaled by inconsistent in vitro dissolution characteristics, especially for sustained-release dosage forms.

Adolescent↗

Practice and professional development plans (PPDPs): results of a feasibility study.

BACKGROUND: Dissatisfaction with uniprofessional education structures as a means of improving the quality of healthcare has led to proposals to develop ways of integrating professional learning and organisational development. AIMS: Test the feasibility of introducing practice and professional development plans using a centrally sponsored project in Wales. DESIGN: Qualitative observational study. STUDY SAMPLE: All 541 practices in Wales were alerted to the project and invited to apply. A selection process was suggested to Health Authorities but not always efficiently conducted: 23 practices were selected and 18 participated in the process. METHOD: Central funding was made available to health authorities. The project framework was designed by an educational department and conceptualised as the development of personal portfolios linked to one key organisation change in each practice, facilitated by external consultants who would typically hold workshops or other events. An independent researcher using non-participant observation techniques at workshops and practices undertook documentary analysis and fieldwork in four health authorities. RESULTS: Difficulties were encountered with the process of implementing the project: marketing and practice selection inconsistencies delayed the work and it was difficult to recruit practices into the project. The lack of experienced individuals to do the work and practitioner suspicion about perceived 'management' agendas were significant problems. After initial hesitancies most practices appreciated the value of developing wider ownership and commitment to proposed practice changes. Organisations found it difficult to support individual completion of the personal portfolio component of the plans. The ability to develop systems for clinical services was dependent on having already established a culture of effective teamwork in the organisation. CONCLUSIONS: This work supports the view that organisational development has considerable potential for bringing about effective change, and individual contributions could form a valuable component of personal portfolios. We believe that the existing structures in education and management in the health service are not yet able to support these processes. Evidence from the fields of risk management and quality improvement all point to the need to develop effective organisational systems and the results of this feasibility study indicate that alternative models of sustaining organisational development need careful evaluation.

Education, Medical, Continuing↗