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PubMed1999

A model of prebiotic replication: survival of the fittest versus extinction of the unfittest.

A model of prebiotic replication discussed by Szathmary and Maynard Smith (1997) is refined in accordance with Lifson's (1997) theory on the crucial stages in the origin of animate matter. The refined model accounts for two processes associated with replication: (1) Replicators always decompose at some rate. (2) Replicators deplete their reactants at a rate equal to the rate of their own replication. Consequently, replicators and their reactants are linked by a non-linear feedback process that keeps them within limits and leads them toward a steady state. The model suggests that: (a) All competing replicators, including those which replicate at sub-exponential "parabolic" and super-exponential "hyperbolic" rates, are subject to natural selection. (b) Survival/extinction is determined by positive/negative net-replication irrespective of the mechanism of replication. (c) Being fit/unfit is the consequence of survival/extinction rather than its cause. In other words, natural selection and survival of the fit is the outcome of continual extinction of the unfit.

Animals↗

PubMed1986

Environmental specificity of tolerance to morphine-induced analgesia in a terrestrial snail: generalization of the behavioral model of tolerance.

Terrestrial snails, Cepaea nemoralis, develop tolerance to morphine-induced analgesia, such that after 7-9 days of treatment with morphine (10 mg/kg) their response latencies to an aversive thermal stimuli (38.5 degrees C) are not significantly different from those of untreated control animals. In Experiment A snails were rendered tolerant to morphine using either of two pre-injection cues (light and dark background brightness or color) and then assessed for morphine-induced alterations in thermal nociceptive responses in both environments. In Experiment B snails were made tolerant to morphine in the presence of one of two different thermal cues (a stressful temperature of 35 degrees C that is normally avoided or an ambient temperature of 22 degrees C) and then tested for morphine-induced alterations in nociceptive responses in both environments. In the two experiments tolerance to morphine-induced analgesia was displayed when snails were exposed to the pre-injection environmental cue normally associated with the administration of morphine, but not when exposed to the alternative pre-injection cue. These results demonstrate that various environmental factors (background colors or brightness as well as temperature cues and potentially thermal stress), can function as environmental specific cues for the development of tolerance to morphine-induced analgesia in molluscs, in a manner consistent with a behavioral mechanism of tolerance. Thus, these results suggest that environmental specificity of tolerance involving either classical (Pavlovian) conditioning or habituation may be a general phenomenon having an early evolutionary development and broad phylogenetic continuity.

Analgesia↗

PubMed2005

pfcrt is more than the Plasmodium falciparum chloroquine resistance gene: a functional and evolutionary perspective.

Genetic, physiological and pharmacological studies are gradually revealing the molecular basis of chloroquine resistance (CQR) in the malaria parasite, Plasmodium falciparum. Recent highlights include the discovery of a key gene associated with resistance, pfcrt (Plasmodium falciparum chloroquine resistance transporter; PfCRT), encoding a novel transporter, and the characterization of global selective sweeps of haplotypes containing a K76T amino acid change within this protein. Little is known about the cellular mechanism by which resistant parasites escape the effects of chloroquine (CQ), one of the most promising drugs ever deployed, due in part to an unresolved mechanism of action. The worldwide spread of CQR argues that investigations into these mechanisms are of little value. We propose, to the contrary, that the reconstruction of the evolutionary and molecular events underlying CQR is important at many levels, including: (i) its potential to assist in the development of rational approaches to thwart future drug resistances; (ii) the stimulation of the use of CQ-like compounds in drug combinations for new therapeutic approaches; and (iii) the consideration of how the CQ-selected genome will function as the context in which current and future drugs will act, particularly in light of the many reports of multidrug resistance. The purpose of this review is to highlight, discuss and in some cases challenge the interpretations of recent findings on CQR. We consider the natural function of the PfCRT protein, the role of multiple genes and "genetic background" in the CQR mechanism, and the evolution of CQR in parasite populations. Genetic transformation techniques are improving in P. falciparum and continue to provide important insight into CQR. Here, we also discuss more subtle, yet important pharmacological approaches that may have been overlooked in a traditional "gene for drug resistance" way of thinking.

Animals↗

PubMed1998

Joint care admissions to a psychiatric unit: a prospective analysis.

Despite developments in general hospital liaison psychiatry over the past 20 years, joint care still remains underdeveloped in Europe. Psychiatry continues to move from the mental hospital to the general hospital unit without the parallel evolution of combined medical and psychiatric. An inpatient unit that provides both medical and psychiatric care may provide an essential integration of care that can benefit a select group of patients. The aims of this study were to prospectively evaluate the profile, treatment, and follow-up of patients admitted to the joint-care unit, and to examine the difficulties associated with the treatment of these patients on a joint unit. Eighty-nine patients were admitted to the joint care unit over a 6-month period. Their median length of stay was 2 days (range 1-52 days). Fifty-six (50%) were female. The majority (68) (76%) of the group were admitted following acts of deliberate self-harm. The overall predominant psychiatric diagnosis was depression (41) (46%). During admission, 23 (26%) patients were found to have behavioral and psychiatric problems that were difficult to manage on the ward. Eleven patients caused difficulties for staff relating to the management of their physical illness. Thirty-six (33%) patients were referred for further psychiatric inpatient care from the joint-care unit. The extra burden of these patients' care was felt to fall on the staff working on the psychiatric unit. The joint care unit provided a combined psychiatric and medical service. It was used predominantly by patients following acts of deliberate self-harm. Joint care allowed a comprehensive assessment and initiation of treatment of this patient group as well as a learning experience for medical and nursing staff. The inclusion of such a unit is a worthwhile consideration in any general hospital psychiatric service, with advanced planning easing staff workload.

Acute Disease↗

PubMed2002

The origins of Michael Conrad's research programs (1964-1979).

This paper summarizes Michael Conrad's academic and professional career from the time he began his Ph.D. studies in 1964 to his appointment at Wayne State University in 1979. It describes the origins of several of his major research interests and presents a personal evaluation of how this early work continues to be of fundamental importance.

Biological Evolution↗

PubMed2004

High-speed chromosome sorting.

Structural and genetic characterization of chromosomes is necessary to understand both normal and pathologic physiology in any species. Flow cytometry and cell sorting technologies provide a means for precise measurement of chromosomal makeup as well as for the isolation of specific chromosomes for further study. Advancements in molecular biology protocols and pressures from large-scale sequencing endeavors placed increased demand on the developers of these instruments for enhanced throughput and quality of results. The ensuing improvements in sorting performance led to the development of a new generation of cytometers known as high-speed cell sorters. These machines provide superior results in less time and are cheaper and simpler to operate than their predecessors. Robust chromosome sorting can now be performed in the laboratories of individual investigators for a variety of gene- and sequence-specific studies. Resolution of the flow karyotype with increased refinement, and the development of new applications for this technology will assure that cell sorting continues to play an important role in cytogenetics, our understanding of molecular processes such as evolution and disease etiology, and ultimately serve as a launching point for predictive medicine.

Animals↗

PubMed2000

Morphological castes in a vertebrate.

Morphological specialization for a specific role has, until now, been assumed to be restricted to social invertebrates. Herein we show that complete physical dimorphism has evolved between reproductives and helpers in the eusocial naked mole-rat. Dimorphism is a consequence of the lumbar vertebrae lengthening after the onset of reproduction in females. This is the only known example of morphological castes in a vertebrate and is distinct from continuous size variation between breeders and helpers in other species of cooperatively breeding vertebrates. The evolution of castes in a mammal and insects represents a striking example of convergent evolution for enhanced fecundity in societies characterized by high reproductive skew. Similarities in the selective environment between naked mole-rats and eusocial insect species highlight the selective conditions under which queen/worker castes are predicted to evolve in animal societies.

Analysis of Variance↗

PubMed1990

Associative agnosias and the functions of the left hemisphere.

Associative agnosias are traditionally regarded as perceptual, and ideational apraxia as motor, deficits, but they can be understood as amnesias for generic knowledge, caused by bilateral or unilateral left-hemispheric cortical lesions. Current theories of hemispheric specialization explain these syndromes' mandatory link with left-hemispheric damage, and are validated by this link. This link reflects the multiple nature of generic, categorical representational systems, not all reducible to natural language, and the left hemisphere's principal role as their substrate, regardless of their dependence on language. The distinction between processing novel information, and processing based on well-established, routinized representations, captures a fundamental difference between the functions of the right and left hemispheres. The complementary link of apperceptive agnosias with right-and associative agnosias with left-hemisphere lesions is an expression of this general principle in the posterior cortex. Future studies of the neuroanatomy of agnosias in animals may offer insights into the evolutionary continuities of hemispheric specialization.

Agnosia↗

PubMed2000

Teicoplanin Chemistry and Microbiology.

The chemistry, microbiology and mode of action of teicoplanin, as well as the mechanism, control and epidemiology of glycopeptide resistance, are discussed in detail. The antibacterial activity of teicoplanin against Gram-positive bacteria, including those expressing resistance to unrelated compounds, is similar to that of vancomycin but with increased potency, particularly against Streptococcus spp and Enterococcus spp. Some strains of coagulase-negative Staphylococcus spp, particularly S. haemolytieus, are less susceptible to teicoplanin than to vancomycin. Teicoplanin is active against vancomycin resistance caused by VanB and VanC, but is not active against VanA resistant strains. The epidemiology of GISA and VISA strains of S. aureus is, as yet, poorly understood with more work necessary to elucidate the sequence of events leading to their evolution. Despite the increasing importance of glycopeptide resistance, teicoplanin has proved its clinical worth and continues to have important potential in the treatment of life-threatening Gram-positive sepsis.

Anti-Bacterial Agents↗

PubMed2004

A canine model of laparoscopic segmental liver resection.

Laparoscopic hepatectomy has been recently proposed for the treatment of liver tumors, however there is a lack of experimental models to study surgical technique and the metabolic reactions after this procedure. The dog is an important animal for research but the laparoscopic hepatectomy model is not well established in this animal. We describe the surgical laparoscopic technique of left liver segmentectomy in the dog and the preliminary results of this procedure. Female dogs weighting more then 15 kg were used. Four transversal abdominal incisions (two of 1 cm and two of 0.5 cm) were made for the introduction of the video camera and the other laparoscopic instruments. The liver was inspected and the left lobe was mobilized through incision of the left triangular hepatic ligament. The vascular pedicle corresponding to the left medial lobe (corresponding to segment II) was identified, dissected, and clamped, delimiting a correspondent ischemic area. The hepatic parenchyma was divided according to the previous delimitation with minimum bleeding. The segment of the liver was then removed through an enlarged abdominal incision. The incisions were closed by continuous suture. The mean time of the procedure was forty minutes. We observed normal clinical evolution without any sign of complications due to the hepatic resection, and normal augmentation of body weight on follow-up of more than 3 months. Left hepatectomy in the dog is a viable procedure and may serve for surgical training and development of research projects in this field.

Animals↗

PubMed1999

Circular epidemiology.

Circular epidemiology can be defined as the continuation of specific types of epidemiologic studies beyond the point of reasonable doubt of the true existence of an important association or the absence of such an association. Circular epidemiology is an extreme example of studies of the consistency of associations. A basic problem for epidemiology is the lack of a systematic approach to acquiring new knowledge to reach a goal of improving public health and preventive medicine. For epidemiologists, research support unfortunately is biased toward the continued study of already proven hypotheses. Circular epidemiology, however, freezes at one point in the evolution of epidemiologic studies, failing to move from descriptive to analytical case-control and longitudinal studies, for example, to experimental, clinical trials. Good epidemiology journals are filled with very well-conducted epidemiologic studies that primarily repeat the obvious or are variations on the theme.

Bias↗

PubMed1994

Clinical features of systemic lupus erythematosus.

Case reports, case series, and analytical clinical research studies continue to define and refine our understanding of the clinical presentation of lupus and its evolution over time. Major areas of interest in the past year have included malignancies, osteoporosis, neonatal lupus, central nervous system lupus, pregnancy, and renal disease. New emphasis has been placed on the importance of gynecologic malignancies in systemic lupus erythematosus. Osteoporosis, especially the role of corticosteroid therapy in the development of osteoporosis, remains a controversial area, particularly in premenopausal women. The poor outcome of many infants with neonatal lupus has been documented in several reports. A more sensitive brain imaging test for central nervous system lupus--brain single photon emission computed tomography--has been introduced. The effect of pregnancy on disease activity and the appropriate use of second-line agents in pregnancy have been reviewed. The importance of hypertension and other clinical variables in predicting renal outcome (as opposed to reliance on renal biopsy findings) was emphasized in two studies.

Female↗

PubMed1988

Planetary environments and the conditions of life.

Life arose on Earth within a billion years (1 Ga) after planetary accretion and core formation. The geological record, which begins 3.8 Ga BP, indicates environmental conditions much like today's, except for the absence of oxygen. By 3.5 Ga BP microbial ecosystems were already colonizing shallow marine hydrothermal environments along shorelines of volcanic islands. Although similar environments could have existed more than 3.8 Ga BP, they may not have been the spawning grounds of life. Geophysical models of the first 600 Ma of Earth history following accretion and core formation point to a period of great environmental disequilibrium. In such an environment the passage of energy from Earth's interior and from the Sun through gas-liquid-solid domains and their boundaries with each other generated a dynamically interacting, complex hierarchy of self-organized structures, ranging from bubbles at the sea-air interface to tectonic plates. Nested within this hierarchy were the precursors of living systems. The ability of a planet to produce such a hierarchy is speculated to be a prerequisite for the origin and sustenance of life. Application of this criterion to Mars, which apparently experienced no plate tectonism, argues against the origin of martian life. Because only further geological and biogeochemical exploration of the planet can place these qualitative speculations on firm ground, the search for evidence of extinct life on Mars continues to be of highest scientific priority.

Biological Evolution↗

PubMed2006

Onset of a Boson mode at the superconducting critical point of underdoped YBa2Cu3Oy.

The thermal conductivity kappa of underdoped YBa2Cu3Oy was measured in the T-->0 limit as a function of hole concentration p across the superconducting critical point at pSC identical with 5.0%. The evolution of bosonic and fermionic contributions to kappa was tracked as the doping level evolved continuously in each of our samples. For p< or =pSC, we observe a T3 component in kappa which we attribute to the boson excitations of a phase with long-range spin or charge order. Fermionic transport, observed as a T-linear term in kappa which persists unaltered through pSC, violates the Wiedemann-Franz law, since the electrical resistivity varies as log(1/T) and grows with decreasing p.

Journal Article↗

PubMed2006

Chronic bilateral stimulation of the anterior thalamus of kainate-treated rats increases seizure frequency.

PURPOSE: Electrical stimulation of the anterior nucleus of the thalamus (ANT) is receiving increased attention as a novel means of controlling intractable epilepsy, and has entered human clinical trial. Animal data supporting the anticonvulsant benefit of ANT stimulation, however, has been obtained from acute chemoconvulsant models of epilepsy rather than models of chronic epilepsy with spontaneous seizures. It is unknown whether ANT stimulation is effective in models of chronic epilepsy. METHODS: Bilateral ANT stimulation was evaluated in rats with chronic epilepsy following acute status epilepticus (SE) produced by systemic kainic acid (KA) administration. The evolution of epilepsy following KA SE and the effects of ANT stimulation were monitored by continuous video-EEG. RESULTS: Following KA SE, most rats have 2-8 seizures per day, and the average seizure rate increases over time, doubling over the course of 14 weeks. Behavioral seizure severity, after the initial development of epilepsy, remains stable. Seizure frequency during ANT stimulation was 2.5 times the baseline seizure frequency. In some cases stimulation triggered seizures were observed. The effects of stimulation were specific to the ANT. Stimulation applied to electrodes placed outside the ANT did not significantly worsen seizure frequency. CONCLUSIONS: ANT stimulation exacerbated seizure frequency in rats with chronic epilepsy following kainate status epilepticus.

Acute Disease↗

PubMed1977

Persistent themes: a naturalistic study of personality development in the family.

This pilot longitudinal study of normal children and their families examines the associations noted between behaviors appearing in early childhood and concerns expressed by the same youngster fifteen years later. These concerns were seen to be related to continuing transactions around a particular issue within the family system. A case description of the evolution of the particular patterns of one of the family systems studied and the details of their recurring negotiations includes an examination of two subsystems of the family unit: the mother-infant pair and the parenting couple. The impact of this family system's struggle upon the developing youngster and her personality as a late adolescent is discussed.

Adolescent↗

PubMed2006

Impact of cyclosporine reduction with MMF: a randomized trial in chronic allograft dysfunction. The 'reference' study.

Long-term use of calcineurine inhibitors (CNIs) may contribute to the development of chronic allograft dysfunction (CAD). We investigate the impact of the introduction of MMF combined with cyclosporine (CsA) 50% dose reduction. An open, randomized, controlled, multicenter, prospective study was conducted in 103 patients, receiving a CsA-based therapy with a serum creatinine between 1.7-3.4 mg/dL, more than 1 year after transplantation. They were randomized to receive MMF with half dose of CsA (MMF group) or to continue their maintenance CsA dose (control group). A total of 96 weeks after randomization, the evolution of renal function assessed by regression line analysis of 1/SeCr improved in the MMF group (positive slope) vs. the control group (negative slope), 4.2 x 10(-4) vs. -3.0 x 10(-4), respectively (p < 0.001). Concurrently, the absolute renal function improved significantly in the MMF group. No episode of biopsy-proven acute rejection occurred. One patient in each group lost his graft because of biopsy-proven chronic allograft nephropathy. There was a significant decrease of triglycerides level in the MMF group. Anemia and diarrhea were statistically more frequent in the MMF group. In CAD, the reduction of CsA in the presence of MMF results in significant improvement in renal function during a 2-year follow-up.

Adult↗

PubMed1995

Harmonisation of specialist training in Europe: is it a mirage?

For the past 18 years there has been a proliferation of European committees, boards, associations, colleges, and working groups set up to promote the harmonisation of specialist training in Europe. It has been taken as read that this objective is desirable. The fact that these bodies have achieved remarkably little is telling, and it is time to question their activity. There are good practical reasons behind the evolution of Europe's disparate training schemes, and the arguments for retaining diversity rather than continuing to strive for homogeneity are persuasive.

Education, Medical↗

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