A reconsideration of the evidence for Escherichia coli STa (heat stable) enterotoxin-driven fluid secretion: a new view of STa action and a new paradigm for fluid absorption

1. Summary, 7
2. Introduction, 8
3. Existing model of net fluid transport, 8
4. A new model for net fluid absorption, 10
5. Evidence for the new model for net fluid absorption, 12
5.1 Evidence from altering ambient carbon dioxide levels, 13
5.2 The role of carbonic anhydrase in net fluid absorption, 14
5.3 Evidence from perfusion with antibiotics, 14
5.4 Evidence from chronic animal models of diarrhoeal disease and resection studies, 14
5.5 Evidence from oral rehydration solution studies, 15
5.6 Evidence from numerical calculations, 16
5.7 Evidence from gene product deletion studies, 17
6. Lack of evidence for the present model of Sta-driven intestinal secretion, 17
6.1 Changes in short circuit current in Ussing chamber studies, 17
6.2 Evidence from T 84 cell studies, 17
6.3 Proxy in vivo systems, 18
6.4 Short duration perfused in vivo loops, 18
6.5 Notional bicarbonate secretion in vivo and in vitro , 19
7. Reconciliation of the new model for fluid absorption with STa action, 21
7.1 Experimentally based evidence, 21
7.2 Clinical evidence from enzyme deletion, 22
8. Acknowledgements, 23
9. References, 23     

Models of vegetation dynamics in semi-arid vegetation: Application to lowland Central Otago, New Zealand

Predictions from three conceptual models of the dynamics of semi-arid vegetation (Clementsian succession, alternative stable states and annuation/pulse phenomena) are used to review the available evidence on changes in the vegetation of semi- arid lowland Central Otago, New Zealand. Evidence is presented from Central Otago that corresponds with Clementsian succession and with annuation/pulse phenomena, although there is so far no formal evidence of alternative stable states. A declining- productivity model, which combines aspects of the other models, is also shown to fit the process of vegetation change in vegetation dynamics in Central Otago are insufficient for the employment of management frameworks such as degradation gradient assessment and the state-and-transition model.     

An evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter pylori

OBJECTIVES: To provide Canadian primary care physicians with an evidence-based clinical management tool, including diagnostic and treatment recommendations, for patients who present with uninvestigated dyspepsia. RECOMMENDATIONS: The management tool has 5 key decision steps addressing the following: (1) evidence that symptoms originate in the upper gastrointestinal tract, (2) presence of alarm features, (3) use of nonsteroidal anti-inflammatory drugs (NSAIDs), (4) dominant reflux symptoms and (5) evidence of Helicobacter pylori infection. All patients over 50 years of age who present with new-onset dyspepsia and patients who present with alarm features should receive prompt investigation, preferably by endoscopy. The management options for patients with uninvestigated dyspepsia who use NSAIDs regularly are: (1) to stop NSAID therapy and assess symptomatic response, (2) to treat with NSAID prophylaxis if NSAID therapy cannot be stopped or (3) to refer for investigation. Gastroesophageal reflux disease can be diagnosed clinically if the patient''s dominant symptoms are heartburn or acid regurgitation, or both; these patients should be treated with acid suppressive therapy. The remaining patients should be tested for H. pylori infection, and those with a positive result should be treated with H. pylori-eradication therapy. Those with a negative result should have their symptoms treated with optimal antisecretory therapy or a prokinetic agent. VALIDATION AND EVIDENCE: Evidence for resolution of the dyspepsia symptoms was the main outcome measure. Supporting evidence for the 5 steps in the management tool and the recommendations for treatment were graded according to the strength of the evidence and were endorsed by consensus of committee members. If no randomized controlled clinical trials were available, the recommendations were based on the best available evidence. LITERATURE REVIEW: Evidence was obtained from MEDLINE searches for pertinent articles published from 1966 to October 1999. The searches focused on dyspepsia, diagnosis and treatment. Additional articles were retrieved through a manual search of bibliographies and abstracts from international gastroenterology conferences.     

Mixed function oxidases and herbivore polyphagy: the devil's advocate position

Abstract. 1. Evidence used to support the theory that mixed function oxidases (MFOs) are important in the survival of polyphagous herbivores is briefly reviewed. This evidence includes data on patterns of variation in MFO activity among species and among developmental stages within species. It also includes data on induction of MFO activity by plant compounds and metabolism of plant cornpounds by MFOs.
2. It is argued that the evidence presently available does not offer strong support of the theory because key pieces of information are lacking. Evidence which tends to refute the theory is reviewed and discussed.
3. Experiments are proposed which could more rigorously test the theory.     

Sexual strategies of female Japanese macaques (Macaca fuscata)

Evidence is reviewed that female Japanese macaques have multiple male mating partners when they are available and show a preference for mating with sexually unfamiliar males. Several lines of evidence suggest that this aspect of female sexual behavior results in the offspring of an individual female being sired by more than one male thereby maintaining the genetic diversity of the troop. Evidence is presented in this paper that a decrease in the number of adult troop males and a lack of extra-troop migrant males in the Arashiyama West troop of Japanese macaques following transplantation to a ranch in south Texas had consequences for the sexual behavior of the females.     

Gezamenlijke besluitvorming zorgt voor een betere toepassing van evidence-based medicine in de geriatrische patiënt

Evidence based medicine (EBM) is the integration of the best research evidence, clinical expertise and patient values in the decision making process for patient care. However, elderly people are often excluded from participating in scientific studies and they often have multiple morbidities, which complicates the application of EBM. Shared decision making (SDM), a process where clinicians and patients share the best available evidence when faced with the task of making decisions, and where patients are supported to consider options, to achieve appropriate treatment can help to shape EBM for this group of patients.In this article, we provide tools for finding relevant literature for the geriatric patient population and for shaping the SDM process to achieve personalized care.     

Drug resistance plasmids in Lactobacillus acidophilus and Lactobacillus reuteri.

Sixteen strains of Lactobacillus reuteri and 20 strains of Lactobacillus acidophilus were tested for resistance to 22 antibiotics by using commercially available sensitivity disks. Evidence suggesting linkage of these resistances to plasmids was obtained by "curing" experiments with acridine dyes and high growth temperatures. Examination of plasmid patterns of agarose gel electrophoresis provided further evidence of loss in plasmid DNA under curing conditions in some of the strains examined.     

Prostaglandin E as the neural mediator of the febrile response

The evidence favoring a role for prostaglandin E (PGE) as the neural mediator of the febrile response is reviewed and considered under five different essential criteria which would need to be satisfied, if such a role is to be accepted. These criteria are: the ability of intracerebrally microinjected exogenous PGE to cause fever; the detection of increased levels of endogenous PGE in the brain during the normal production of fever; the ability of substances that inhibit the production and release of PGE to block normal fevers; the ability of substances that are specific PGE antagonists to inhibit normal fevers; and the identification of a specific site and cell type for the release of PGE in response to the action of pyrogens. Evidence from the literature that supports these criteria is reviewed and presented in this format, and the conclusion is drawn that the evidence available is more than sufficient to support the initial hypothesis.     

Amphibian Limb Regeneration and its Relation to Nerves

Much circumstantial evidence points to a neurotrophic influencein amphibian limb regeneration. Although fine-structural observationsof nerves in regenerating limbs have indicated the possibilitythat neurosecretory vesicles accumulate distally in these axons,there is no clear-cut demonstration available that these organellesare neurotropic. Evidence is accumulating that the neural influencein newt limb regeneration is transneuronal. There is also evidencethat trophic substances other than those found in the nerveitself may be involved in the supporting limb regeneration.The characterization of the neurotrophic substance is considereda central task for students of regeneration in the future.     

Analysis of somatic mutation and class switching in naive and memory B cells generating adoptive primary and secondary responses

Clonal progeny of naive B cells (producing a primary antibody response) and of memory B cells (producing a secondary response) were identified in a cell transfer system. Primary response clones are typically derived from IgM precursors and express unmutated V regions. Multiple isotype switches occur in these clones. Secondary response clones derive from IgG1 precursors and express highly mutated V regions. Additional switches do not occur. With one exception, there was no evidence for somatic mutation during clonal expansion. The generation of mutated memory cells may thus represent a distinct differentiation pathway. Evidence is presented that, in this pathway, mutants that have lost antigen binding specificity but that remain available for stimulation by a different antigen arise upon antigenic stimulation.     

Multidrug resistance ABC transporters

Clinical multidrug resistance is caused by a group of integral membrane proteins that transport hydrophobic drugs and lipids across the cell membrane. One class of these permeases, known as multidrug resistance ATP binding cassette (ABC) transporters, translocate these molecules by coupling drug/lipid efflux with energy derived from the hydrolysis of ATP. In this review, we examine both the structures and conformational changes of multidrug resistance ABC transporters. Together with the available biochemical and structural evidence, we propose a general mechanism for hydrophobic substrate transport coupled to ATP hydrolysis.     

When do epileptic patients need treatment? Starting and stopping medication.

Decisions about when to start and stop antiepileptic treatment have important implications for patients with epilepsy. Clinical practice varies and is determined more by dogmatic teaching than by knowledge of either the clinical course of epilepsy or the influence of the drugs. A review of the available evidence shows the need for further studies on the effects of starting and withdrawing treatment on the clinical course and prognosis of epilepsy.     

Squeezing the most out of existing literature: a systematic re‐analysis of published evidence on ecological responses to altered flows

相似文献   

Rapid induction of vitamin A deficiency in rabbits

Clinical and biochemical evidence of vitamin A deficiency was produced in rabbits as early as 4-5 weeks after weaning to a vitamin A deficient diet from dams maintained during lactation on the deficient diet. Mean serum retinol levels at the time of weaning for the deficient dams were 25 +/- 6 micrograms/dl compared with 74 +/- 8 micrograms/dl for the controls. Five weeks after weaning, 25% of pups fed the vitamin A deficient diet had ocular lesions characterized by the accumulation of sloughed epithelium on the cornea. At this time, mean serum values of the pups were 10 +/- 4 micrograms/dl for the deficient group and 73 +/- 8 micrograms/dl for the controls. Evidence of critically depleted liver stores was documented in the deficient rabbits by an elevated relative dose response test (54 +/- 18%) that did not occur in the control group (6 +/- 5%). Although food consumption was similar, weight gain was lower in the deficient group when compared to the control group.     

Gluconate Metabolism in Escherichia coli

On the basis of information available in the literature, gluconate dissimilation in Escherichia coli is thought to occur via the hexose monophosphate pathway. Evidence is presented in this study that gluconate is catabolized in this organism via an inducible Entner-Doudoroff pathway. This evidence is based on chromatographic examination of end products produced from (14)C-labeled gluconate or glucose, distribution of (14)C in the carbon atoms of pyruvate formed from specifically labeled (14)C-glucose and (14)C-gluconate, and the ability of cell-free extracts to produce pyruvate from 6-phosphogluconate. Degradation of gluconate by an Entner-Doudoroff pathway occurred simultaneously with a glycolytic cleavage of glucose. A relationship between gluconate-induced, Entner-Doudoroff pathway activity and catabolism of glucose in Escherichia coli and other bacterial species is discussed.     

An evidence-based approach to prescribing NSAIDs in musculoskeletal disease: a Canadian consensus. Canadian NSAID Consensus Participants.

OBJECTIVE. To make recommendations for the long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) in primary care practice, particularly for patients at high risk for NSAID-induced complications. OPTIONS. The use of misoprostol to prevent gastrointestinal ulceration and other unwanted NSAIDs effects was considered. The role of cyclooxygenase-2 (COX-2) versus COX-1 inhibiting agents was also examined. OUTCOMES. Reduction of complications associated with long-term use of NSAIDs. EVIDENCE. Evidence was gathered in late 1995 from published research studies and reviews. Position papers were prepared by faculty and advisory board members and discussed at the Canadian NSAID Consensus Symposium in Cambridge, Ont., Jan. 26 and 27, 1996. VALUES. Recommendations were based on randomized, placebo-controlled clinical trials (level I evidence) and case-control studies (level II evidence) involving NSAID use when such evidence was available. When the scientific literature was incomplete or inconsistent in a particular area, recommendations reflect the consensus of the participants at the symposium (level III evidence). Physicians were recruited from across Canada for their expertise in rheumatology, gastroenterology, epidemiology, gerontology, family practice, and clinical and basic scientific research. BENEFITS, HARMS AND COSTS. Although a reduction in complications due to inappropriate NSAID use should reduce costs of additional investigations, admissions to hospital and time lost from work, definitive cost analysis studies are not yet available. RECOMMENDATIONS. Currently, no NSAID is available that lacks potential for serious toxicity; therefore, long-term use of NSAIDs should be avoided whenever possible, particularly in high-risk patients (e.g., those who are elderly, suffer from hypertension, congestive heart failure, renal or hepatic impairment or volume depletion, take certain concomitant medications or have a history of peptic ulcer disease) (level I evidence). If NSAIDs are to be used in patients with gastric or nephrotoxic risk factors, the lowest effective dose of NSAID should be used (level III evidence); NSAIDs that are weak COX-1 inhibitors may be preferred (level II evidence). In addition, concomitant administration of misoprostol is recommended in patients at increased risk for upper gastrointestinal complications (level I evidence). However, the clinical judgement of the practising clinician must always be part of any therapeutic decision. VALIDATION. These recommendations are based on the consensus of Canadian experts in rheumatology, gastroenterology and epidemiology, and have been subjected to external peer review.     

Enhanced replication of HIV-1 in vivo in pigtailed macaques (Macaca nemestrina)

Non-human primate models for acquired immunodeficiency syndrome (AIDS) are important for studies of prevention and intervention strategies. Ideally, such models would make use of human immunodeficiency virus type 1 (HIV-1) and animals that are readily available for research. HIV-1 was obtained from an infected macaque, and passaged sequentially in three groups of two Macaca nemestrina neonates each. Evidence for enhanced viral replication was first found in one of the group 2 animals, and in both group 3 animals. Observations that underlie this conclusion are sustained viral recovery from peripheral blood mononuclear cells (PBMCs), increased and accelerated production of antiviral antibodies, and the ability to detect plasma viral ribonucleic acid (RNA) months after infection. There was no evidence of CD4 depletion in any of the animals during the follow-up period. These data suggest that a useful non-human primate model for AIDS can be attained in pigtailed macaques ( M. nemestrina ).     

Enhanced replication of HIV-1 in vivo in pigtailed macaques (Macaca nemestrina)

Non-human primate models for acquired immunodeficiency syndrome (AIDS) are important for studies of prevention and intervention strategies. Ideally, such models would make use of human immunodeficiency virus type 1 (HIV-1) and animals that are readily available for research. HIV-1 was obtained from an infected macaque, and passaged sequentially in three groups of two Macaca nemestrina neonates each. Evidence for enhanced viral replication was first found in one of the group 2 animals, and in both group 3 animals. Observations that underlie this conclusion are sustained viral recovery from peripheral blood mononuclear cells (PBMCs), increased and accelerated production of antiviral antibodies, and the ability to detect plasma viral ribonucleic acid (RNA) months after infection. There was no evidence of CD4 depletion in any of the animals during the follow-up period. These data suggest that a useful non-human primate model for AIDS can be attained in pigtailed macaques (M. nemestrina).     

Evidence for the activation of 6-phosphofructo-1-kinase by cAMP-dependent protein kinase in Aspergillus niger

Abstract The change from pentose phosphate pathway to glycolysis plays a significant role in the physiology of Aspergillus niger during the induction of citric acid accumulation. Evidence is shown for the importance of 6-phophofructo-1-kinase in this process since it is activated by phosphorylation. By incubating a purified active form of enzyme together with commercially available alkaline phosphatase, 6-phosphofructo-1-kinase activity was lost after a certain time suggesting that the enzyme was dephosphorylated. Inactive 6-phosphofructo-1-kinase could be isolated from the cells in the early stage of growth in a high citric acid yielding medium. The enzyme was 'in vitro' activated by isolated protein kinase in the presence of cAMP, ATP and Mg²⁺ ions. Additional evidence for covalent phosphorylation of inactive 6-phosphofructo-1-kinase was obtained by incubating both enzymes together with labelled [ γ −³²P]ATP. The activating enzyme was partially purified from A. niger mycelium.