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Imaging in the new millennium.

The last few decades of the 20th century were marked by tremendous advances in diagnostic imaging and related therapeutic procedures. The new millennium holds great promise for more spectacular advances. Continuing evolution of computer technology coupled with existing and evolving digital imaging platforms will serve as a catalyst for significant developments in virtually all areas of imaging. This report surveys the potential of these advances in areas relevant to critical care.

Diagnostic Imaging↗

Basic principles of flow cytometry.

Although the basic principles of flow cytometry have changed little in the past quarter century, the applications of this technology have evolved substantially. As in the past, cytometers interrogate individual cells or particles in a stream with a laser as the cells move past a set of stationary detectors. Increasingly, more colors of fluorescence are being detected by cytometers, faster analysis and sorting rates are becoming possible, cytometers capable of multidirectional sorting are being marketed, and more reagents are becoming available for a wide variety of applications. Furthermore, flow cytometry has not stopped evolving. The development of narrow spectrum flourescent probes, the integration of molecular biologic techniques with flow cytometry, and the evaluation of cell-free markers such as cytokines will be key components in the continuing evolution of flow cytometry.

Analog-Digital Conversion↗

A randomized controlled trial of early surgery in Duchenne muscular dystrophy.

We performed a randomized controlled trial of early surgical treatment of contractures in 20 boys with Duchenne muscular dystrophy, age 4-6 yr. Surgery consisted of release of hip flexors, removal of iliotibial bands, and lengthening of tendo Achilles bilaterally. All patients were monitored for at least 12 months post-randomization, and assessed quantitatively for muscle strength and function. Surgery corrected the deformities, but had no beneficial effect on strength or function. Indeed, data in the second year showed more rapid deterioration of function in some of the operated boys. There appeared to be continued evolution of pathology following surgery, as assessed by sequential muscle ultrasound and muscle biopsy. We cannot recommend this type of surgery as a routine treatment.

Biopsy↗

Mimicking the way to autoimmunity: an evolving theory of sequence and structural homology.

Although the etiology of autoimmune diseases remains largely unknown, a prevailing theory concerns the infection-induced activation of self-reactive lymphocytes via the process of molecular mimicry. Here, we discuss the theory of molecular mimicry and its continued evolution from the initial basic considerations of sequence similarity to the current theories of structural homology. Such findings serve to further our understanding of T-cell receptor degeneracy and might one day provide a direct link between infection and autoimmune disease.

Amino Acid Sequence↗

[Characteristics and mechanisms of action of leukocyte depletion filters].

Since their creation, leukocyte depletion filters, used to prepare leukocyte-poor red cell or platelet concentrates, have been continuously evoluting: their volume has been reduced and their composition has been modified, polyester fibers have replaced cotton wool or cellulose acetate. In the same way, their capacity to remove leukocytes has increased. The mechanisms of cell separation are still unclear. Through published studies, different factors seem to be implicated, such as wetable surface of the filter, surface tension or charge density of fibers. It was also observed that removal of lymphocytes from red cell concentrates is rather based on trapping in the fiber network, and that removal of granulocytes, monocytes and platelets is partly due to activation and subsequent adhesion to the fibers. There have been few studies of the mechanism of leukocytes depletion from platelets concentrates.

Adsorption↗

The evolving role of information technology in the drug discovery process.

Information technologies for chemical structure prediction, heterogeneous database access, pattern discovery, and systems and molecular modeling have evolved to become core components of the modern drug discovery process. As this evolution continues, the balance between in silico modeling and 'wet' chemistry will continue to shift and it might eventually be possible to step through the discovery pipeline without the aid of traditional laboratory techniques. Rapid advances in the industrialization of gene sequencing combined with databases of protein sequence and structure have created a target-rich but lead-poor environment. During the next decade, newer information technologies that facilitate the molecular modeling of drug-target interactions are likely to shift this balance towards molecular-based personalized medicine -- the ultimate goal of the drug discovery process.

Animals↗

Hughes syndrome crosses boundaries.

Hughes (antiphospholipid) syndrome is a condition in continuous evolution. Since it was first described almost 20 years ago, significant advances in its diagnosis and management have been made. Recently, classification criteria for definite antiphospholipid syndrome have been proposed and validated. However, there is still controversy regarding issues such as the utility of new diagnostic tests (detecting antibodies to beta(2)-glycoprotein I, phospholipids other than cardiolipin or phospholipid mixtures), the role of antiphospholipid antibodies in neurological conditions such as demyelinating disease, cognitive impairment or migraine and the optimal management of thrombosis and obstetric manifestations. These are all briefly discussed in this review.

Abortion, Spontaneous↗

Orthoses and prostheses.

Orthoses and prostheses include a wide range of devices and strategies for correcting and alleviating dysfunction and disability. Features in these areas of technology include continuing evolution of new devices, further development of well-established approaches, a need for critical assessment, requirements for support from technical and health care workers, and the need to identify funding to achieve efficient programs.

Persons with Disabilities↗

Geminate recombination of diatomic ligands CO, O2, and NO with myoglobin.

The kinetics of geminate recombination of horse heart myoglobin with the diatomic ligands carbon monoxide, dioxygen, and nitric oxide have been reexamined. The new measurements are distinguished from previous studies by (1) consideration of the complete time range longer than 1 ps, (2) inclusion of the effect of temperature changes near ambient, (3) attention to the relation between recombination kinetics and the yield of dissociated partners on the millisecond time scale, and (4) use of singular value decomposition in the analysis. These picosecond results, together with earlier nanosecond data, for O2 prove that models incorporating one, two, or even three discrete intermediates are not sufficient to account for all features of geminate recombination kinetics. Instead, a continuous evolution of the geminate pair distribution is preferred.

Animals↗

Clinical and economic evaluation of surgical treatments for faecal incontinence.

BACKGROUND: Faecal incontinence affects 1-2 per cent of the adult population. While many patients can be managed successfully with conservative therapy, a small proportion require surgery. Improved imaging techniques and technological advances have led to the availability of a wide range of surgical treatments. Decision-makers increasingly require clinical and cost-effectiveness studies of surgical treatments for faecal incontinence. This review examines the practical aspects of undertaking such studies. METHODS: The practical issues related to different aetiologies, different types of treatment, defining outcomes, the hidden costs of the condition and its treatment, the rapid changes in technology and issues of patient choice were all considered. A Medline search was undertaken to identify relevant publications, and the reference lists of identified papers were scanned manually. RESULTS: There are few randomized controlled studies and those that have been performed have been limited in their scope. There has also been very limited health economic analysis undertaken. Strategies for conducting such studies, and the criteria they use, have been outlined. CONCLUSION: Randomized trials have a limited role in this setting because of variations in aetiology, difficulty in standardizing procedures, continuing evolution of devices, small patient numbers, concerns for patient choice and the need for long-term follow-up. Issues to be addressed when evaluating interventions for faecal incontinence include choosing appropriate measures of surgical outcome, using new continence scoring systems and tools for quality-of-life assessment, and choosing appropriate cost perspectives and time horizons for economic evaluation.

Colorectal Surgery↗

The state of ambulatory surgery and perianesthesia nursing.

The continued success of the ambulatory surgery environment of care has been achieved through patient, physician, and nursing staff satisfaction. The growth in this industry has been greatly influenced by advances in technology, as well as the development and administration of newer anesthetic agents. The implications delineated in this article provide an overview of what is in store for the specialty of perianesthesia nursing. Issues of competency, professional excellence, patient expectations, continuous quality improvement, research, and ethics have become part of the daily lexicon. Never before has the professional nurse been counted on for so much, and future expectations of the nurse continue to grow. To survive, the nurse needs to expand the boundaries of nursing practice as they have been defined. Nurses are the backbone of the delivery of patient care, nurses are on the front line guiding the patient through every care decision, and nurses are positioned to influence the continued evolution of ambulatory surgery and perianesthesia nursing care.

Ambulatory Surgical Procedures↗

One hundred cases of endoscopic brow lift.

The senior author's experience of using the endoscopic brow lift for rejuvenation of the upper third of the face is presented. One hundred patients underwent endoscopic brow elevation. In 98 cases this was done in combination with other aesthetic procedures. Patient follow-up ranged from 4 months to 53 months (mean: 17 months). No major complications were experienced, although a patient questionnaire identified a number of troublesome but transient minor complications. Levels of patient satisfaction were found to be high. The continuing evolution of this technique is reviewed, particularly relating to methods of brow fixation.

Adult↗

Psoriasis of early and late onset: a clinical and epidemiologic study from Spain.

BACKGROUND: The existence of 2 distinct forms of psoriasis related to age at onset has been postulated. However, precise data regarding the clinical and epidemiologic characteristics of psoriasis depending on the age at onset are still lacking. OBJECTIVE: The purpose of this study was to define the clinical and epidemiologic features of this disease in Spain and to compare patients with psoriasis of early and late onset. METHODS: An observational, analytic, cross-sectional, multicenter study was carried out. From January 1999 to November 1999, 179 participating dermatologists completed a questionnaire detailing the clinical and epidemiologic features of the first 10 consecutive patients with psoriasis seen in their clinical practice. The sample distribution was proportional to the Spanish population. Both statistical and descriptive analyses were performed. RESULTS: Available data were obtained from 1774 patients. The onset of the disease before 30 years of age was significantly associated with a higher incidence of family history of psoriasis, a more severe and extensive cutaneous involvement, and greater psychosocial impact. Guttate psoriasis, nail involvement, evidence of precipitating factors, and a recurrent clinical course were more frequent in this group of patients. Patients with psoriasis of late onset had a less severe clinical course and a more continuous evolution. Palmoplantar pustulosis was more frequent in this group of patients. No significant relationship was detected between the age at onset and development of joint involvement. CONCLUSION: Patients with early and late onset psoriasis often show different clinical and evolutionary features. From the analysis of our data, it seems that 2 different groups of patients with psoriasis related to age at onset can be defined.

Adolescent↗

Representing motion in a static image: constraints and parallels in art, science, and popular culture.

Representing motion in a picture is a challenge to artists, scientists, and all other imagemakers. Moreover, it presents a problem that will not go away with electronic and digital media, because often the pedagogical purpose of the representation of motion is more important than the motion itself. All satisfactory solutions evoke motion-for example, dynamic balance (or broken symmetry), stroboscopic sequences, affine shear (or forward lean), and photographic blur-but they also typically sacrifice the accuracy of the motion represented, a solution often unsuitable for science. Vector representations superimposed on static images allow for accuracy, but are not applicable to all situations. Workable solutions are almost certainly case specific and subject to continual evolution through exploration by imagemakers.

Art↗

Ten-year follow-up survey of clinical neuropsychologists: part I. Practices and beliefs.

A 21-item questionnaire previously used to survey practices and beliefs of clinical neuropsychologists (Sweet & Moberg, 1990; Sweet, Moberg, & Westergaard, 1996) was mailed in February 1999 to all ABPP Diplomates in clinical neuropsychology and a larger sample of randomly selected non-ABPP members of Division 40 (Clinical Neuropsychology) of the American Psychological Association. Results were compared with data previously collected in 1989 and 1994. Across 10 years there have been some persistent differences between neuropsychologists based on board certification status. These differences include degree of involvement in neuropsychological practice and forensic practice, involvement in research and teaching, frequency of subscribing to or regularly reading a variety of relevant journals, employment settings, use of assistants, and use of projective assessment. There are also a number of areas of shared belief and common practice. These important areas of agreement are unrelated to board certification status and are interpreted as signs of cohesiveness and maturity in the continuing evolution of the subspecialty. Shared beliefs and common practices include: appropriate field of training, type of degree, assessment philosophy, most types of information to be gathered in evaluations, and time spent per assessment. In general, the use of assistants is correlated significantly with the number of evaluations performed per month. Although sometimes viewed as exclusively providing assessment, the majority of neuropsychologists are also involved in treating patients with brain dysfunction. Survey data appear useful in characterizing and monitoring professional status and trends of clinical neuropsychology.

Adult↗

Cerebral malaria: clinical features, pathophysiology and treatment.

Herbert Gilles played an important role in the establishment of the Wellcome-Mahidol University, Oxford Tropical Medicine Research Programme in Thailand in 1979. The randomized, placebo-controlled trial of dexamethasone in cerebral malaria that was carried out in Chantaburi in 1980 yielded results which led to the abandonment of ancillary corticosteroid therapy in this disease and contributed to a rejection of the 'permeability hypothesis'. The clinical manifestations of strictly defined cerebral malaria have not been described both in non-immune adults in Thailand and Vietnam and in African children. Clinical and histopathological studies in human patients, together with laboratory studies of cyto-adherence, malaria 'toxin' and cytokine production have provided some evidence for both the 'mechanical' and 'toxin-cytokine' hypotheses to explain the pathophysiology of this condition. Chemotherapy is challenged by the continuing evolution of antimalarial resistance. Recently, the most powerful studies ever carried out with antimalarial drugs have demonstrated that artemether and quinine achieve similar case fatalities, in the range 11%-21%, and that both drugs have some advantages and disadvantages. Further studies are needed to define the efficacy and safety of prophylactic anticonvulsants and exchange transfusion in cerebral malaria. Cerebral malaria remains a major cause of mortality and, in African children, morbidity.

Adult↗

The age-associated decrease in the amount of amplifiable full-length mitochondrial DNA in human skeletal muscle.

There has been a continuous evolution in our concept [1] that mtDNA undergoes a range of mutations with age and that such alterations lead to a decline in mitochondrial bioenergy capacity. Here we report that a wide range of deletion mutations accumulate with age and the amount of full-length mtDNA (FLmtDNA) amplifiable by extra-long PCR (XL-PCR) markedly decreases with age. An analysis of single human quadriceps muscle fibres reveals a close correlation between the decrease in FLmtDNA and the decline in cytochrome c oxidase activity, an exemplifier of mitochondrial bioenergy. However, Southern blotting analysis of unamplified genomic DNA shows that there is little decrease in FLmtDNA in aged quadriceps. The results are interpreted to indicate that while there is little change in the total mtDNA with age, nonetheless a significant proportion of this mtDNA is extensively damaged such that it cannot be amplified by XL-PCR. The amplifiable FLmtDNA, which putatively represents the functional component of the mtDNA, decreases markedly with age.

Adolescent↗

Selection of multiresistant hepatitis B virus during sequential nucleoside-analogue therapy.

Hepatitis B virus (HBV) drug resistance to lamivudine is always accompanied by mutations in the viral polymerase gene at position 550, termed group 1 (M550V with L526M) or group 2 (M550I) mutations. The latter mutation has not been associated with famciclovir resistance. Thus, the addition of famciclovir to lamivudine therapy in persons with group 2 lamivudine resistance may lead to virus suppression. The effect of lamivudine/famciclovir combination therapy on HBV infection was monitored in 5 lamivudine-resistant patients by quantitative polymerase chain reaction and polymerase gene sequencing of serum virus. No patients treated with combination therapy had a decline in HBV load >1 log10. Continual evolution of the viral polymerase was detected in association with virologic resistance to both drugs. Cloning experiments identified the preexistence of these multidrug-resistant virus variants as minority species prior to addition of famciclovir therapy. HBV resistance to lamivudine monotherapy is associated with a complex mixture of variants that limit the efficacy of second-line nucleoside-analogue therapy. First-line potent combination therapy may reduce the emergence of HBV drug resistance.

2-Aminopurine↗