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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.
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.
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.
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.
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.
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.
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.
There are a variety of publications advocating the ureteroscopic or the percutaneous approach for the treatment of transitional cell carcinoma of the renal pelvis. The diagnostic tool of choice for the upper urinary tract and collecting system is the flexible ureteroscope. One of the major concerns about ureteroscopic management of renal disease initially was the lack of flexibility of the instruments and therefore the inability to deal with demanding sites. The advent of new ureteroscopic techniques, as well as the continuous evolution of the technology, have paved the way for safe and effective access to the upper urinary tract. In the hands of an experienced urologist, such procedures can provide reliable treatment options for small upper urinary tract lesions. Coupling minimal morbidity with ever-improving optics and flexibility, the ureteroscope of today leaves no area of the urinary tract unseen. In patients with bulky tumors or in whom easy access and resection is not possible ureteroscopically, the percutaneous approach to the renal pelvis, although more invasive, provides a better working environment. Clearly, the most difficult aspect of ureteroscopic access to the lower pole is not just visibility but the loss of deflection caused by passage of various instruments through the working channel. Direct access via percutaneous approach with a large resectoscope avoids these problems.
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.
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.
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.
INTRODUCTION: The epidemiology of end-stage renal disease (ESRD) and renal replacement therapy (RRT) is under continuous evolution all over the world. Of particular interest is the development of RRT in the countries of the former Soviet bloc which underwent great political and socio-economical changes in the last decade. We report here the epidemiological analysis of ESRD and RRT in the three Baltic countries: Lithuania, Estonia, Latvia. Subjects and methods. This epidemiological report is based on data from centre questionnaires which were collected from 1996 onwards, with a response rate of 98-99%. RESULTS: The prevalence/incidence of RRT patients in 1999 were 213/99.5 p.m.p. in Lithuania, 186/45.5 p.m.p. in Estonia and 172/55.8 p.m.p. in Latvia. Haemodialysis (HD) was the most common RRT modality in Lithuania (60% of prevalent patients), but not in Estonia (29%), while in Latvia it was nearly as common as renal transplantation (45 and 46%, respectively). Home HD was not performed. The proportion treated by peritoneal dialysis (PD) was very low in Lithuania (4% of RRT patients), while the percentage was higher in Latvia (9%) and Estonia (20.4%). The percentage of patients on RRT treated by renal transplantation was high throughout, representing the main modality of treatment in Estonia (50.5% of RRT prevalent patients, 94 p.m.p.) and in Latvia (46%, 79 p.m.p.) and being high in Lithuania (36%, 77 p.m.p.). The main renal diseases leading to ESRD were glomerulonephritis, pyelonephritis and diabetes. CONCLUSION: The epidemiology of RRT in the Baltic countries is undergoing rapid changes. Transplantation has reached an impressive level. A high percentage of RRT patients live with a functioning graft.
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.
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.
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.
OBJECTIVE: To perform molecular analysis of the predominant viral populations and drug-resistance mutations from plasma and peripheral blood mononuclear cell (PBMC) compartments over time from an HIV infected patient, who experienced virological failure while on different HAART regimens. MATERIALS AND METHODS: In a longitudinal study proviral and plasma HIV-1 sequences were amplified in the pol, protease and env genes and were sequenced directly and analysed phylogenetically. Virus was recovered from time points corresponding to viral load peaks using co-culturing techniques. The periodic failure of different highly active antiretroviral therapy (HAART) regimens was analysed sequencing. RESULTS: Longitudinal follow-up studies revealed four inflection peaks of plasma viraemia associated with the recovery of culturable virus in vitro, which indicated failure of the concurrent HAART regimen. Molecular analysis of viral strains revealed evidence of continual evolution and compartmentalization of drug-resistance mutants/quasispecies between plasma and PBMC, with the widest spectrum of mutations isolated from plasma. Importantly, these data show the periodic appearance and clearance of drug-resistance mutants concomitant with the introduction and withdrawal of zidovudine over time. CONCLUSION: This report is unique in showing drug-induced compartmentalization of viral quasispecies under the control of different HAART regimens in both plasma and PBMC. Introduction and withdrawal of zidovudine from the HAART regimen had direct bearing on the appearance and disappearance of specific zidovudine drug-resistance mutations in plasma-derived virus. This data has important implications for the management of HIV-infected patients with poor compliance with certain HAART regimens, and also in predicting the late emergence of drug-resistance mutations via the latent integrated provirus.
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.
Specialty practice in general, and gastroenterology in particular, is undergoing significant transformation as we head into the new millennium. Gastroenterologists will need to adapt to the continued evolution and consolidation of managed care. Among other issues, gastroenterologists will need strategies for dealing with pricing pressures, changing technology, increased consumerism, a perceived specialist oversupply, and a rapidly aging population. These and other developments will drive a myriad of physician responses in an effort to confront changing practice realities.