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PubMed2001

Imaging erythrocytes under physiological conditions by atomic force microscopy.

Since its invention in the mid 1980s atomic force microscopy has revolutionised the way in which surfaces can be imaged. Close to atomic resolution has been achieved for some materials and numerous images of molecules on surfaces have been recorded. Atomic force microscopy has also been of benefit to biology where protein molecules on surfaces have been studied and even whole cells have been investigated. Here we report a study of red blood cells which have been imaged in a physiological medium. At high resolution, the underlying cytoskeleton of the blood cell has been resolved and flaws in the cytoskeleton structure may be observed. Comparison of the normal 'doughnut' shaped cells with swollen cells has been undertaken. Differences in both the global properties of the cells and in the local features in cytoskeleton structure have been observed.

Animals↗
PubMed2001

Atomic force microscopy as a novel pharmacological tool.

With the advent of the atomic force microscope (AFM), the study of biological samples has become more realistic because, in most cases, samples are not covered or fixed, which makes it possible to observe them while the cells are alive. This advantage of the AFM allowed the advent of a new invention: nanobiosensors using the cantilever (probe) of the AFM and, in this case, it is possible to observe the entering or exiting of specific molecules (including medications) from living cells. This is the smallest biosensor in the world, measuring about 100 microm long (about the width of a hair). Beyond sensing the area of interest with this biosensor, it is also possible to see the area and exactly what is occurring on it, in real time. This new tool will be very useful for several areas: molecular pharmacology, enzymology, physiology, molecular biology, biotechnology, biophysics, physical chemistry, analytical chemistry, and organic chemistry. This article discusses, mainly, the applications of this new technique to the field of pharmacology.

Biosensing Techniques↗
PubMed1999

Tapping-mode atomic force microscopy produces faithful high-resolution images of protein surfaces.

Compared to contact-mode atomic force microscopy (CMAFM), tapping-mode atomic force microscopy (TMAFM) has the advantage of allowing imaging surfaces of macromolecules, even when they are only weakly attached to the support. In this study, TMAFM is applied to two different regular protein layers whose structures are known to great detail, the purple membrane from Halobacterium salinarum and the hexagonally packed intermediate (HPI) layer from Deinococcus radiodurans, to assess the faithfulness of high-resolution TMAFM images. Topographs exhibited a lateral resolution between 1.1 and 1. 5 nm and a vertical resolution of approximately 0.1 nm. For all protein surfaces, TMAFM and CMAFM topographs were in excellent agreement. TMAFM was capable of imaging the fragile polypeptide loop connecting the transmembrane alpha-helices E and F of bacteriorhodopsin in its native extended conformation. The standard deviation (SD) of averages calculated from TMAFM topographs exhibited an enhanced minimum (between 0.1 and 0.9 nm) that can be assigned to the higher noise of the raw data. However, the SD difference, indicating the flexibility of protein subunits, exhibited an excellent agreement between the two imaging modes. This demonstrates that the recently invented imaging-mode TMAFM has the ability to faithfully record high-resolution images and has sufficient sensitivity to contour individual peptide loops without detectable deformations.

Bacterial Proteins↗
PubMed1999

International approaches to the concept of integrated control of nematode parasites of livestock.

Livestock production systems throughout the world are under severe and sustained pressures. These are diverse and multi-factorial, ranging from the need to redress the oversupply of livestock commodities from the protected industries of the industrialised world, meeting animal welfare expectations, attempts to ease animal-induced land degradation and pollution, and competition with alternative products. As a consequence, funding for research to the ruminant livestock industries has been contracting universally. This applies particularly to research on those diseases of grazing livestock that are not zoonotic, threats to trade, or major "killer" diseases. Gastrointestinal helminths fall outside these priorities. The last decade has witnessed a major contraction throughout the world in the number of research centres and staff involved in applied veterinary parasitology research. This coincides with a time when these livestock industries need the most help. Resistance to anthelmintic drugs amongst the major nematode parasites of sheep and goats has now reached alarming proportions throughout the world and threatens the future viability of continued small ruminant production in many countries. Anthelmintic resistance is also increasing in the important nematode parasites of cattle. Also, this time coincides with the apparent reduction in the discovery and development of entirely new anthelmintic products by the pharmaceutical industry. As a consequence, those remaining researchers and extension personnel who have the responsibility of providing support to the ruminant livestock industry, are showing innovation and lateral thinking in ways to combat the perennial problem of internal parasites in grazing livestock. There are a number of excellent examples of parasite-control schemes, which do not rely entirely on anthelmintic treatment. These are now being supplemented with some exciting novel approaches to dealing with particularly pressing parasite problems. Also there is a move towards the development of true integrated approaches in the control of nematode parasites of livestock, which employ several of these methods when appropriate. This proves that as far as worm control in livestock is concerned, the old adage "necessity is the mother of invention", holds true.

Animal Husbandry↗
PubMed2001

Preparative enantioseparation by simulated moving bed chromatography.

Simulated moving bed (SMB) chromatography was invented in the 1960s in the petrochemical industry and has since then been widely used to produce petrochemicals and sugars at the multi-ton scale. In the early 1990s its principle could be successfully adapted to chromatographic enantioseparation, due to developments in system design, chiral stationary phase synthesis and improvements in modelling and simulation of non-linear chromatographic behaviour. Since then a lot of separation systems have been brought into production, which are reviewed. In addition new developments are outlined in the field of system design and stationary phase development.

Chromatography, Liquid↗
PubMed2003

Evolution of ion-exchange: from Moses to the Manhattan Project to modern times.

This article explores the history of ion-exchange from records of desalination in the Old Testament and the writings of Aristotle, to the identification of the phenomenon of ion-exchange by two English agricultural chemists, to the invention of suppressed conductivity by Small et al. [Anal. Chem. 54 (1975) 462]. It then focuses on the characteristics of the gradual and continuous evolution of ion chromatography with suppressed conductivity to its current state, with an emphasis on those discoveries that punctuated or revolutionized this evolution.

Chromatography, Ion Exchange↗
PubMed2002

Emergent literacy skills and training time uniquely predict variability in responses to phonemic awareness training in disadvantaged kindergartners.

The factors that predicted variability in responses to phonemic awareness training were investigated in kindergartners who live in poverty. Treatment children (n=42) received both analytic and synthetic phonemic awareness computer-assisted instruction, while controls (n=34) received no special training. Mean age of participants was approximately 5 years 7 months. Pretests included initial phonemic awareness, letter knowledge, word-level reading, invented spelling, vocabulary knowledge, and print concepts. Spelling skills emerged as the best consistent predictor of variability in phonemic awareness in response to instruction. We propose that relations between phonemic awareness and spelling skills are bidirectional: Spelling influenced growth in phonemic awareness and phonemic awareness contributed to growth in spelling skills. The amount of exposure that children had to the treatment intervention contributed uniquely to individual differences in posttest levels of phonemic awareness and spelling.

Analysis of Variance↗
PubMed1987

Harmony and beauty in medical research.

We too often report the results of biomedical research as if there were no people involved in producing those results. However, without physicians and PhD's there would be no medical research. Moreover, reference to the history of medicine and science reveals that very often the men and women who have created the most important medical breakthroughs and perceived the most significant facts of medicine have also been unusually talented in other disciplines as well: music, the arts, poetry and literature. I do not believe that this correlation of talents is an accident. Rather, I argue that the kind of medicine and science that a person accomplishes is a reflection of the personality and skills that the person brings to his or her work. Thus, those doctors who have been most sensitive to their culture, and most inventive in their everyday lives, have also been the most insightful and original in their work. Music, the arts, poetry, and literature actually contribute in essential ways to the training of eminent doctors, and influence the way in which they perceive medicine. I therefore argue that it is not enough that we do our utmost to push back the veils of ignorance in our clinics and laboratories: we must also begin to push back the veils of ignorance that surrounds the questions of who does the best biomedical research and why. We must recognize the intricate ways in which the who, the how, and the what of research are inextricably entwined.

Art↗
PubMed1996

The outcome for children with blunt trauma is best at a pediatric trauma center.

PURPOSE: The mortality rate for pediatric trauma patients cared for in adult trauma centers has been shown, by means of TRISS methodology, not to differ significantly from that of the Major Trauma Outcome Study (MTOS). The question remains, however, whether the outcome of injured children is better in a designated pediatric trauma center (DPTC). The authors' hypothesis is that outcome is better at a DPTC. METHODS: The records of 1,797 children (0 to 15 years of age) admitted to a DPTC between 1987 and 1993 were reviewed. TRISS methodology was used to calculate probability of survival for outcome comparison with the MTOS. The data also was compared with outcome in relation to the admitting Glasgow Coma Score (GCS) reported in the National Pediatric Trauma Registry (NPTR). RESULTS: The outcome of all children at this DPTC had a Z score of +1.4199 (P > .1). The Z score of children admitted because of penetrating trauma (PT, n = 460) did not differ significantly from that of the MTOS. However, the children admitted because of blunt trauma (BT, n = 1,337) had a Z score of +3.3501 (M score = .90), which is significantly better than that of the MTOS (P < .001). The BT population with an ISS of > or = 9 (n = 149) had a Z score of +2.8686 (P < .005) (M = .95). By GCS comparison, the BT group had a outcome similar to that reported in the NPTR. Head injury was the cause of death for 26 (84%) of the 31 PT deaths and 20 (83%) of the 24 BT deaths (three of the remaining four had associated severe head injury). Only 1 of 24 (4%) BT liver injuries and 5 (21%) of 24 BT splenic injuries required surgical intervention. This low incidence of liver and splenic surgical invention is similar to that reported by other DPTCs, but for children treated at adult centers the rates are 37% to 58% and 43% to 53% for liver & splenic surgical intervention, respectively. CONCLUSION: Children with BT have a significantly better outcome at a DPTC; the outcome for children with PT does not differ. Successful nonoperative treatment of blunt abdominal injuries is more likely to occur at a DPTC than at adult trauma centers "with pediatric committment." Thus, children with blunt injuries should be taken to a DPTC, when available.

Adolescent↗
PubMed1997

High-frequency intratracheal pulmonary ventilation: improved gas exchange at lower airway pressures.

PURPOSE: Conventional ventilation in the neonatal intensive care unit causes iatrogenic injury to fragile newborn lungs, especially those with preexisting pathology or prematurity. Intratracheal pulmonary ventilation (ITPV), developed by Dr Theodor Kolobow and associates at the National Institutes of Health (NIH), incorporates a continuous flow of humidified gas through a reverse thrust catheter positioned at the distal end of the endotracheal tube. In animal studies ITPV was shown to facilitate gas exchange at low peak pressures by reducing physiological dead space, facilitating exhalation, and enhancing CO2 elimination. The specific aims of this project were (1) to invent a new ITPV-specific ventilator; (2) to optimize gas exchange in a newborn animal model at low airway pressures using higher frequency ITPV; and (3) to demonstrate efficacy and improved ventilation at lower airway pressures in a prematurity model. METHODS: (1) A new ventilator had to be constructed. The first prototype is microprocessor driven, incorporating controls for flow, pressures, and concentrations of gases. The ventilator has the capability to vary Fio2, respiratory rate (0 to 15 Hz), and inspiratory-expiratory I:E ratio. (2) Prototype testing was performed. Newborn lambs (n = 3, 6 to 7 kg) underwent tracheotomy and placement of arterial and venous lines. Lambs were initially supported on conventional mechanical ventilation (CMV). Animals were allowed to achieve steady state with measurements of baseline vital signs, arterial blood gases, and ventilatory settings. ITPV was instituted at a rate of 100 breaths per minute and flow adjusted to achieve lower peak carinal pressures than obtainable on conventional ventilation. In a stepwise fashion, respiratory rate, I:E ratio, and ITPV flows were varied while initially maintaining Paco2 constant, and then allowing improvement. (3) These experiments were repeated in preterm lambs (n = 6, 1.8 to 3.6 kg). RESULTS: At the time of transition from CMV to ITPV (rate, 100, I:E, 1:3), gas exchange was maintained despite a documented drop in average peak carinal pressure for the newborn lambs from 28.3 cm H2O on CMV to 10.3 cm H2O on ITPV (P = .028). The average peak carinal pressure fell even further at higher ITPV rates with adjustments in I:E ratio. For the premature lambs, peak carinal pressures also fell significantly on ITPV (44 to 32 cm H2O, P = .002) with corresponding significant improvement in ventilation (Paco2 from 52.2 to 31.9 mm Hg, P = .029). CONCLUSIONS: (1) Our new ITPV ventilator operates at rates and I:E ratios previously unobtainable. (2) In newborn and premature lambs ITPV functions most effectively at higher rates with higher gas flow rates and with longer exhalation, providing significantly improved gas exchange at significantly lower peak carinal pressures. (3) ITPV may prove beneficial in achieving gas exchange in newborns while avoiding barotrauma. Based on these data, we have initiated human clinical studies of ITPV in newborns with congenital diaphragmatic hernia or prematurity to improve gas exchange and reduce barotrauma in the neonatal intensive care unit.

Animals↗
PubMed1990

Suffocation, recurrent apnea, and sudden infant death.

We reviewed the cases of 27 young children from 27 different families who were suffocated by their mothers. The certainty, or near certainty, of suffocation was based on reliable observation or recording of the suffocation, maternal confession, or successful prosecution in a criminal court. Eighteen of the children are alive, although one has severe brain damage; nine are dead. Twenty-four were reported to have had previous episodes of apnea, cyanosis, or seizure, and 11 had had 10 or more such episodes that were either invented or caused by the mother. Repetitive suffocation usually began between the ages of 1 and 3 months and continued until it was discovered, or the child died, 6 to 12 months later. The 27 children had 15 live elder siblings and 18 who had died suddenly and unexpectedly in early life; 13 of the dead siblings had had recurrent apnea, cyanosis, or seizures, and, although most of them at the time of death were certified as having sudden infant death syndrome, it is probable that some were suffocated. Repetitive suffocation has a characteristic clinical presentation that should allow identification before brain damage or death occurs. The characteristics should also allow the cause of death of some cases of sudden infant death to be established more accurately.

Adult↗
PubMed1991

Prebiotic co-evolution of self-replication and translation or RNA world?

A prebiotic scenario is proposed, based on the recent "domain hypothesis" model (Lahav, 1989, J. molec. Evol. 29, 475-479), suggested for domain propagation of RNA-like molecules in a fluctuating environment. The same system is suggested now not only for the evolution of ribozymes, but also for the evolution of directed peptide synthesis, as follows: Short, self-structured strands (termed prebioectons), each possessing a templatable domain which is chargeable by an amino acid, are the predecessors of tRNA (proto-tRNA). Complementary domains are formed on these prebioectons during an environmental cycle such as wetting-drying, followed by their dissociation from their template domain and ligation, to form the predecessor of mRNA (proto-mRNA). The evolution of directed peptide synthesis is suggested to be based on the ability of the charged prebioectons to attach preferentially to their complementary domains on the proto-mRNA. Two stages of this process are envisioned, namely: (a) Template-directed, random peptide synthesis taking place when non-specifically-charged prebioectons are sequentially attached each to its complementary domain on the proto-mRNA, followed by peptide bond formation. (b) Template-and-sequence-directed peptide synthesis, which can be realized after the "invention" of a catalytic molecule capable of specifically charging a proto-tRNA by an amino acid; this is the crucial evolutionary stage, where a crude genetic code becomes functional. Gradually, catalytic peptides and ribozymes are selected for their functions and evolve, while being encoded in the primitive "memory" of the emerging system. Thus, rather than the RNA monopoly postulated by the RNA World hypothesis, an early co-evolution of primitive enzymes and ribozymes is suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

An introduction to the STEM.

It is particularly appropriate for this Journal to devote one of its issues to the subject of the scanning transmission electron microscope (STEM) and its uses because the initial stimulus for its invention was precisely the problem of discerning ultrastructural details in biological material. To a large extent the capabilities of the instrument have been shown to offer the potential of solving many such problems and what is most needed today is to put such instruments in the hands of biologists together with the information on how and when to use them. This issue should go a long way in satisfying this latter need. The purpose of this article is to try to provide a setting for the more detailed expositions which follow. In order to do this we must necessarily give a very general treatment and avoid detail. In addition, we will concentrate on those aspects of the STEM which apply to biological uses, and we will therefore ignore the more esoteric applications, such as convergent beam diffraction patterns.

Microscopy, Electron, Scanning↗
PubMed1997

Prey dominance in discrete predator-prey systems with a prey refuge.

The effects of a prey refuge in a multiprey discrete system with predation is studied. We demonstrate the stable coexistence of species that would otherwise exclude each other without a prey refuge. With a prey refuge, we show that an endangered prey not only recovers from the brink of extinction, but also dominates the system. We invent notions of dominance that guarantee the extinction of all the dominated prey in the system. With the extermination of most of its prey, the predator either coexists with the dominant prey or is driven to extinction. By using a precise mathematical definition, we obtain that a prey with a sufficiently high carrying capacity persists in a predator-prey system with a prey refuge.

Animals↗
PubMed1989

Psychological features of obesity.

The study of obesity from a variety of psychological perspectives has been exciting and inventive, although we still do not understand fully the role of psychological variables in the etiology of obesity. Many of the factors thought to be of etiologic significance--field dependence, lack of impulse control, inability to delay gratification, or a maladaptive eating style--have not been supported by experimental evidence. Other factors once thought to be of importance as causes of obesity, depression and dysphoria, for example, appear, instead, to be consequences of being obese and may serve to maintain and intensify weight-related problems. Dieting behavior in response to weight concerns appears, perversely, to be implicated in increasing overweight and adiposity. Finally, arousability in response to food cues in the environment may play a causal role in some obesities.

Eating↗
PubMed1999

Motor and perceptual factors in pseudoneglect.

An important variant of the traditional line bisection task has involved a mechanical device invented by Bisiach and his colleagues (Bisiach et al. Perceptual and premotor factors of unilateral neglect. Neurology 1990;40:1278-81 [3]). This tool was devised to dissociate motor from perceptual factors in hemi-spatial neglect, by means of a mid-line indicator which moved 'congruently' or 'non-congruently' with the direction of hand movement. In the non-congruent condition, Bisiach was able to demonstrate a reduction, or reversal, of the direction of bisection error in a number of patients with neglect. These errors were interpreted as instances of 'motor' neglect. Bisiach et al. [3] also tested 10 normal subjects, who did not differ on the two conditions of the task. However, the original experiment [3] required the use of the right hand only, and it has since become clear that bisection errors in normal subjects (i.e. pseudoneglect) are more substantial when dextral subjects use their left hands. By using a modified version of the Bisiach Tool we show that there is an effect of the motor versus perceptual condition on this task, but only when subjects use their non-dominant (left) hand.

Adult↗
PubMed2000

Laparoscopic lumbar interbody spinal fusion.

Laparoscopic ALIF is an evolving technique requiring the participation of a laparoscopic surgeon experienced in advanced laparoscopic techniques and knowledgeable in anterior lumbar spinal exposures. Initial enthusiasm for this technique was fostered by the development of interbody fusion devices and a method of exposing the anterior lumbar spine, which takes advantage of the ability of minimally invasive surgeries to improve exposure and visualization while minimizing collateral tissue damage and injury to healthy tissue. Preliminary studies have demonstrated laparoscopic ALIF feasibility. These same studies have been able to prove only minor advantages with the laparoscopic versus open technique using the current implants and bone grafting techniques for single-level disc disease. General acceptance of laparoscopic ALIF awaits further investigation. Reasons for a lack of general acceptance include the expense of the interbody fusion devices and laparoscopic equipment, the unfamiliarity of this advanced laparoscopic technique to spine and general surgeons, and the steep learning curve of the procedure. Intraoperative complications that arise are often severe, such as vascular injuries. Many skeptics appropriately believe that initial enthusiasm and zealousness must be tempered with scientific effort that provides data from long-term follow-up. For laparoscopic ALIF to gain general acceptance, randomized comparisons of laparoscopic ALIF to open ALIF and posterior lumbar spinal fusion and controlled studies with long-term follow-up documenting symptomatic outcome variables and spinal fusion rates must be completed. As new modalities are developed, minimally invasive techniques may facilitate their utility. The indications, procedures, and surgical principles of ALIF are unchanged, and physicians must not invent indications to justify the technique; however, eventually we may be able to redefine the indications to take full advantage of the endoscopic techniques and biological advances.

Humans↗
PubMed1991

Quality assurance in the surgical intensive care unit. Where it came from and where it's going.

The early history of QA is one of stunning achievements. Men and women led by a vision of what hospital health care should be brought about fundamental changes in the structure of hospitals and medical schools. These successes required lifetimes of work and enormous capital (Flexner's war chest would have amounted to billions of 1990 dollars). A second wave of reform included the creation of credentialing committees, tissue committees, and infection control efforts. Although less dramatic in their impact, these efforts have had measurable influence on the outcome of health care and, under the joint administration of local hospitals and the JCAHO, continue to guarantee excellence in health care. The most recent attempts at quality assurance, driven at least in part by a federal mandate to control costs, have been much more modest in their success. Committed groups working within a sound theoretical framework have had great difficulty monitoring and evaluating centrally a process as decentralized as health care. The regularity with which new fashions in QA have appeared underscores the frustration felt with this approach. If the quality of health care is to be monitored centrally, reliable measures of quality will be required. No one knows if such measures actually exist. The absence of objective evidence that quality has been improved by these efforts suggests that little has been accomplished, perhaps because all easily attainable improvements had already been implemented. The basic concept of a centrally monitored hospital structure within which provision is made for ongoing observation and innovation by those actually involved in the care of patients retains the advantages of central monitoring and local invention. It is a model that will be hard to improve on. We should persist in our efforts, but fundamental advances are unlikely. In the end, quality is only doing everything the best it can be done. The best quality assurance requires an excellent hospital in which a well-trained and committed staff has a central mandate and local purview to do the best possible job. Two thousand years after Hammurabi's minions busied themselves determining the appropriate punishment for various medical misadventures, the Greek Hippocrates advocated a less complex approach to the same problem. He suggested that the quality of health care could be best guaranteed by administering an oath to physicians, exhorting them simply to do what was best for their fellow men. This approach has seen us through two millennia and, however variable its results, may not be easily improved on.

Cost-Benefit Analysis↗