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At least 145 records · Page 8Linked to original sources

Codon reassignment in Candida species: an evolutionary conundrum.

A number of Candida species translate the standard leucine CUG codon as serine rather than as leucine. Such codon reassignment in nuclear-encoded mRNAs is unusual and raises a number of important questions about the origin of the genetic code and its continuing evolution. In particular we must establish how a codon can come to be reassigned without extinction of the species and what, if any, selective pressure drives such potentially catastrophic changes. Recent studies on the structure and identity of the novel CUG-decoding tRNA(Ser) from several different Candida species have begun to shed light on possible evolutionary mechanisms which could have facilitated such changes to the genetic code. These findings are reviewed here and a possible molecular mechanism proposed for how the standard leucine CUG codon could have become reassigned as a serine codon.

Base Sequence↗

Advances in ultrasound biomicroscopy.

The visualisation of living tissues at microscopic resolution is attracting attention in several fields. In medicine, the goals are to image healthy and diseased tissue with the aim of providing information previously only available from biopsy samples. In basic biology, the goal may be to image biological models of human disease or to conduct longitudinal studies of small-animal development. High-frequency ultrasonic imaging (ultrasound biomicroscopy) offers unique advantages for these applications. In this paper, the development of ultrasound biomicroscopy is reviewed. Aspects of transducer development, systems design and tissue properties are presented to provide a foundation for medical and biological applications. The majority of applications appear to be developing in the 40-60-MHz frequency range, where resolution on the order of 50 microm can be achieved. Doppler processing in this frequency range is beginning to emerge and some examples of current achievements will be highlighted. The current state of the art is reviewed for medical applications in ophthalmology, intravascular ultrasound, dermatology, and cartilage imaging. Ultrasound biomicroscopic studies of mouse embryonic development and tumour biology are presented. Speculation on the continuing evolution of ultrasound biomicroscopy will be discussed.

Animals↗

Medicaid managed care and the emergency department: the first one hundred days.

Spurred by concerns over increasing costs and variable quality, public and private third-party payors are moving their subscribers into managed care plans. A central feature of many of these plans is coordination of patient care through a primary care provider (PCP). In exchange for easy access to the PCP, patients are expected to limit their use of emergency services for episodic, primary, and urgent care problems. The State of Connecticut has begun a transition from a fee-for-service Medicaid plan into a managed care product. Because many Medicaid patients had freely used emergency services under the fee-for-service arrangement, urban teaching hospital emergency departments rapidly became a focus of efforts to control cost and change care-seeking behavior. The Hartford Hospital Emergency Department (ED) began screening, education, and referral of managed Medicaid patients in the fall of 1995 and recorded experiences with patients, administrators, and health care providers involved in the implementation of the managed care program. The first 3 mo following plan implementation were chaotic and frustrating for all parties, with many difficulties due to an unprepared infrastructure. Changes in ED operations and maturation of the payor and health care provider network eventually resulted in a reasonably smooth system accompanied by reductions in ED visit volumes of at least 15%. Continual evolution of role and goals will be necessary if EDs are to maintain an active presence in a health care system dominated by managed care plans.

Aid to Families with Dependent Children↗

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↗

[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↗

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↗

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↗

Laparoscopically implantable nerve-stimulating electrode (LINSE): application to the cavernous nerve in acute and chronic canine models.

Using a new laparoscopic procedure, we investigated stimulation of the cavernous nerves to achieve erection in a canine model. The technique was developed during acute experiments in four dogs, following which, chronic studies (4- to 6-weeks survival after surgery) were undertaken in three dogs. A monopolar cuff electrode was inserted laparoscopically by a transperitoneal approach and placed around the cavernous nerve. The leads were brought out to the subcutaneous space, where they were attached to stimulation receivers that could be activated by an external radiofrequency transmitter. An intracavernous pressure elevation indicative of successful stimulation was obtained acutely in five of eight cavernous nerves in the four acute-study dogs and in four of six nerves in the three chronic-study dogs. The implanted equipment associated with four of six cavernous nerves failed mechanically in the chronic-study animals, such that only two receiver-electrode sites were intact at the time of sacrifice 4 to 6 weeks later. Transmitter-driven stimulation of one of these two sets produced an intracavernous pressure rise above 100 cm H2O. We present this technique as part of the continuing evolution of laparoscopy as both a research and a clinical tool. The present use of the laparoscopically implantable nerve-stimulating electrode is a new animal research tool and a potential first step in the human application of the technology.

Animals↗

Laparoscopic common bile duct exploration: a review.

The use of laparoscopic methods to explore the common bile duct is now well-established, although they continue to undergo continuous evolution and improvement. In experienced hands laparoscopic management of choledocholithiasis may be undertaken with morbidity and mortality at least as good as that of open surgery. The use of diagnostic endoscopic retrograde cholangiopancreatography (ERCP) with or without sphincterotomy before or after laparoscopic intervention must be evaluated. The degree of acceptance that laparoscopic techniques for common bile duct exploration (CBDE) will achieve within the surgical community remains to be determined, but will likely increase as more practicing surgeons familiarize themselves with them.

Cholangiography↗

Prevalence of the type I and type II DHFR genes in trimethoprim-resistant urinary isolates of Escherichia coli from Greece.

Trimethoprim resistance in 64 Escherichia coli urinary isolates from five hospitals in Greece was studied. Of the 40 isolates exhibiting transferable high-level resistance (MIC > 1024 mg/L), 21 hybridized with a specific probe for dihydrofolate reductase (DHFR) I, 13 with a probe for DHFR II, and one with a probe for DHFR V. Eleven isolates hybridized with a probe for transposon Tn7. Among the 17 isolates with non-transferable high-level resistance, seven hybridized with the probe for DHFR I, three with the probe for DHFR II, and eight were Tn7-positive. None of the seven isolates with low-level resistance (MIC 4-1024 mg/L) reacted with the probes used. Of the 28 isolates positive for DHFR I, 12 (43%) failed to hybridize with the Tn7 probe. Conversely, three isolates hybridized with the Tn7 probe, but not with the probe for DHFR I. Colony hybridization experiments showed that all but three transconjugants reacted similarly to their respective parent strains. The plasmids coding for trimethoprim-resistant DHFRs were found to differ on the basis of restriction enzyme analysis. These findings suggest that trimethoprim resistance among E. coli urinary isolates in Greece is mediated predominantly by heterogeneous transferable plasmids encoding either DHFR I or DHFR II. The dissociation between DHFR I and Tn7, together with the high incidence of trimethoprim-resistant isolates which did not hybridize with the probes for the common DHFR I or II types, indicates the continued evolution of trimethoprim resistance determinants.

Bacteriuria↗

Combined therapy as an alternative to exenteration for locally advanced vulvovaginal cancer. II. Results, complications, and dosimetric and surgical considerations.

We have introduced a therapeutic alternative to exenteration for locally advanced vulvovaginal cancer using surgery for the vulvar (external genital) phase of this disease presentation, combined with radiotherapy for the internal genital phase (with adequate overlap of fields to protect surgical margins). The rationale is that this approach treats the cancer and its dual regional spread patterns, while at the same time preserving the bladder and/or rectum, and should be associated with less morbidity and mortality than exenterative surgery. This report updates our experience with a total of 48 treated cases (37 primary cases and 11 cases of recurrent disease). Of the 37 primary cases, 20 were FIGO stage III, 4 were FIGO stage IV, and 3 other cases represented "field" cancers involving vulva and/or cervix and/or vagina. Utilizing a Life Table analysis, the 5-year survival for the primary cases was 75.6%. Published FIGO survival for stage III is 32% and for stage IV 10.5%. Life Table analysis projects a 62.6% survival for recurrent cases and an overall 72% 5-year survival for all 48 cases treated. With 48 patients treated, 48 bladders and 48 rectums were at risk for surgical removal had exenteration been employed. One patient had a total pelvic exenteration for local failure, and one had a posterior exenteration for local failure. One bladder and one rectum were lost to permanent diversion because of radiation injury. Thus, 5 of these major viscera were lost of the 96 total, and 91 (94.8%) were retained. Radiation therapy and surgical details have been reviewed relevant to local control and local failure and complications. The continuing evolution of treatment modifications of all modalities will be discussed. The apparent advantages of this combined therapeutic approach over exenterative surgery include high probability of bladder and/or rectal preservation, low primary mortality, low treatment morbidity, and very good results in cancer control.

Brachytherapy↗

Medical technology and academic medicine: the doctor-producers' dilemma.

Diagnostic technologies differ from therapeutic technologies in several ways. Use of a diagnostic technologies is increasing faster than overall medical care. New diagnostic technologies tend to be additive and often have multiple uses. In evaluating their benefits, one should assess marginal, not absolute, utilities and measure clinical as well as financial costs. Although the use of therapeutic technologies is more circumscribed, these technologies tend to be in continuous evolution, especially when new. Comparative evaluations of therapeutic technologies are expensive and time-consuming. Pro-technology reimbursement biases may be the most important of the many factors promoting technology use. Academic medical centers, which have become increasingly clinically specialized, must now compete with their own graduates for specialty patients. At the same time they are urged to respond to contradictory national health policies that favor production of more generalists under a pro-specialty reimbursement system. Suggestions for more appropriate technology use should cover multiple approaches, including the changing of current financial incentives and the use of technology assessment to improve quality of care and education.

Academic Medical Centers↗

"A world of knowledge at your fingertips": the promise, reality, and future directions of on-line information retrieval.

Medical knowledge resources are increasingly available in electronic form, particularly on the World Wide Web. The promise of this medium is that it offers a vast "world of knowledge at your fingertips." The reality, however, is somewhat different, as information systems are not well integrated into clinical practice, prove difficult to find specific information in, and contain content of varying quality. The continued evolution of the medium in the future should, however, be beneficial, as synthesized evidence-based resources become available and these resources are integrated into electronic medical record systems.

Education, Medical↗

Characterization of middle cerebral artery occlusion infarct development in the rat using fast nuclear magnetic resonance proton spectroscopic imaging and diffusion-weighted imaging.

A nuclear magnetic resonance study of the middle cerebral artery occlusion in the rat is presented. Experiments were performed on seven animals before and after occlusion, which occurred in situ. The emphasis in this study was on evaluating rapid proton spectroscopic imaging. Data were acquired with experimental durations of between 4 and 15 minutes for a 32 by 32 spatial matrix, with 64 spectroscopic data points per spatial element. The spectroscopic data were interleaved with diffusion-weighted nuclear magnetic resonance water images of the same slice. The study was terminated at about 6 hours after occlusion. The brains were then frozen in liquid nitrogen for biochemical imaging. The results showed that the signal from N-acetyl aspartate decreased and that of lactate increased within the infarcted region. The temporal course of these intensity changes varied between animals. Nineteen cortical spreading depressions (CSD) were observed by electrophysiologic monitoring during the experiments. Of these, 11 could be unambiguously detected in the lactate images, and a further 3 were on the threshold of detectability. As only a single slice could be examined, it is possible that the centers of depression for the remaining 6 CSD were outside the slice. To the authors' knowledge, this is the first report of the measurement of CSD using proton spectroscopic imaging. Thus, it is shown that this method is valuable not only in following the continuous evolution of proton metabolites with a good spatial and temporal resolution, but also in observing transient phenomena which are believed to play an important role in the expansion of the infarcted territory.

Animals↗