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Treatment of acute hyponatremia: ensuring the excretion of a predictable amount of electrolyte-free water.

BACKGROUND: Hypertonic saline is the recommended therapy to shrink swollen brain cells in patients with acute hyponatremia accompanied by seizures. OBJECTIVES: In the absence of hypertonic saline, hypertonic mannitol will shrink the cell volume. Because mannitol is excreted rapidly, our aim was to ensure that it would be excreted with electrolyte-free water (EFW) and to evaluate the renal mechanisms responsible for EFW excretion. DESIGN: A randomized, prospective, placebo-controlled study in rats was carried out in a research laboratory. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: The control group of rats (n = 6) was administered hypotonic saline, a loop diuretic, vasopressin, and glucose by the intraperitoneal route; in the experimental group (n = 6), glucose was replaced with mannitol. Plasma electrolytes were measured at 0 and 210 mins, and balances for water, sodium, and potassium were obtained from 0 to 90 mins and from 90 to 210 mins. MEASUREMENTS AND MAIN RESULTS: Virtually 100% of the administered mannitol was excreted within 210 mins, and half was excreted in the first 90 mins. The urine contained EFW only in the mannitol group because of a larger volume in the first 90 mins (EFW, 3.7 mL) and to a lower excretion of NaCl in the next 120 mins (EFW, 3.5 mL). CONCLUSIONS: The combined use of mannitol and a loop diuretic caused the excretion of a predictable volume of EFW because the urine was iso-osmotic to plasma and contained all the administered mannitol. The calculated decrease in intracellular fluid volume was equivalent when mannitol was retained or excreted.

Acute Disease↗

Attentional impairment in persons with multiple sclerosis.

Multiple sclerosis (MS) entails various cognitive and psychological changes. The capacity to direct attention (CDA) is the ability to inhibit competing and distracting stimuli while processing information from the environment. A strong CDA is essential for effective functioning in daily life. The CDA may be reduced by MS lesions and by excessive attention-draining demands imposed by the disease. The purpose of this study was to assess CDA using a one-group descriptive correlational design. The sample consisted of 33 outpatients in symptom remission with relapsing-remitting MS who had virtually no physical disability. As theorized, the MS group presented with attentional deficits of varying severity, despite the presence of few physical symptoms. These deficits were unrelated to depressive symptoms. Findings indicate that nurses need to consider attentional problems even in the most early disease states. Further research is needed to better understand the impact of attentional deficits on daily life functioning and to develop nursing interventions for conservation or restoration of CDA in individuals with relapsing-remitting MS.

Activities of Daily Living↗

Virtual reality: a new prosthesis for brain injury rehabilitation.

Virtual Reality (VR) technology is a relatively new application to rehabilitation medicine, yet it offers considerable potential to achieve significant successes in assessment, treatment and improved outcome, thereby increasing our knowledge of neuroplasticity. The capabilities of VR are especially evident in neurological rehabilitation, where cognitive and behavioural problems often interact with physical impairments to reduce the overall level of functioning and interaction. The need for effective interventions in neurological rehabilitation demands communication and collaboration between disciplines. This paper presents some of the current areas of the clinical applications of VR, emphasising the link between experimental evidence on recovery after brain damage and the clinical problems encountered in a ward setting.

Brain Injuries↗

Novel compounds in preclinical/early clinical development for the treatment of HIV infections.

Virtually all the compounds that are currently used, or under advanced clinical trial, for the treatment of HIV infections, belong to one of the following classes: (i) nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), (ii) non-nucleoside reverse transcriptase inhibitors (NNRTIs) and (iii) protease inhibitors (PIs). In addition to the reverse transcriptase and protease step, various other events in the HIV replicative cycle are potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120 (polysulphates, polysulphonates, polyoxometalates, zintevir, negatively charged albumins); (ii) viral entry, through blockade of the viral coreceptors CXCR4 and CCR5 [bicyclams (AMD3100), polyphemusins (T22), TAK-779]; (iii) virus-cell fusion, through binding to the viral glycoprotein gp41 [T-20 (DP-178), siamycins, betulinic acid derivatives]; (iv) viral assembly and disassembly, through NCp7 zinc finger-targeted agents [2,2'-dithiobisbenzamides (DIBAs), azadicarbonamide (ADA)]; (v) proviral DNA integration, through integrase inhibitors such as L-chicoric acid; (vi) viral mRNA transcription, through inhibitors of the transcription (transactivation) process (peptoid CGP64222, fluoroquinolone K-12, Streptomyces product EM2487). Also, in recent years new NRTIs, NNRTIs and PIs have been developed that possess, respectively, improved metabolic characteristics (i.e. phosphoramidate and cyclosaligenyl pronucleotides of d4T), or increased activity against NNRTI-resistant HIV strains, or, in the case of PIs, a different, non-peptidic scaffold. Given the multitude of molecular targets with which anti-HIV agents can interact, one should be cautious in extrapolating from cell-free enzymatic assays to the mode of action of these agents in intact cells. A number of compounds (i.e. zintevir and L-chicoric acid, on the one hand; and CGP64222 on the other hand) have recently been found to interact with virus-cell binding and viral entry in contrast to their proposed modes of action targeted at the integrase and transactivation process, respectively.

Amino Acid Sequence↗

Clinical impact of transesophageal echocardiography in the diagnosis and management of infective endocarditis.

Transesophageal echocardiography (TEE) has assumed a prominent role in the diagnosis and management of infective endocarditis (IE). The impact of negative TEE findings on the management of patients suspected of having IE is not clear. To better understand how a negative TEE examination would influence patient management, the medical records of 93 consecutive patients undergoing TEE to evaluate for IE were examined. The influence of TEE was assessed based on changes in diagnosis, antibiotic therapy, or the need for surgical intervention during hospitalization. The negative predictive value of TEE was found to be 100% in native valves and 90% in prosthetic valves. The overall impact of negative TEE findings was significant in terms of final diagnosis and duration of antibiotic therapy (a negative TEE resulted in 60% reduction in antibiotic duration, p = 0.0001). These findings suggest that in patients with native heart valves, a negative TEE examination virtually excludes IE. In patients with prosthetic valves, a negative TEE significantly decreases the likelihood of IE but does not completely exclude the diagnosis; therefore, in this setting, a negative finding should be closely correlated with the clinical course.

Adult↗

ApoAI deficiency results in marked reductions in plasma cholesterol but no alterations in amyloid-beta pathology in a mouse model of Alzheimer's disease-like cerebral amyloidosis.

Epidemiological studies suggest links between cholesterol metabolism and Alzheimer's disease (AD), with hypercholesterolemia associated with increased AD risk, and use of cholesterol-lowering drugs associated with decreased risk. Animal models using cholesterol-modifying dietary or pharmacological interventions demonstrate similar findings. Proposed mechanisms include effects of cholesterol on the metabolism of amyloid-beta (Abeta), the protein that deposits in AD brain. To investigate the effect of genetic alterations in plasma cholesterol on Abeta pathology, we crossed the PDAPP transgenic mouse model of AD-like cerebral amyloidosis to apolipoprotein AI-null mice that have markedly reduced plasma cholesterol levels due to a virtual absence of high density lipoproteins, the primary lipoprotein in mice. Interestingly and in contrast to models using non-physiological high fat diets or cholesterol-lowering drugs to modify plasma cholesterol, we observed no differences in Abeta pathology in PDAPP mice of the various apoAI genotypes despite robust differences in plasma cholesterol levels between the groups. Absence of apoAI also resulted in reductions in brain but not cerebrospinal fluid cholesterol, but had no effect on brain apolipoprotein E levels. These and other data suggest that it is perhaps the level of brain apolipoprotein E, not cholesterol per se, that plays a primary role in brain Abeta metabolism.

Alzheimer Disease↗

Preventing vertical HIV transmission in the year 2000: progress and prospects--a review.

In the USA, progress in the ability to eliminate vertical HIV-1 transmission that was unthinkable just a few years ago has been virtually achieved with fewer than 200 new cases of infant HIV infection reported in 1999. Nevertheless, critical research questions as well as public health challenges remain. New infant HIV infections continue to occur among women who did not obtain prenatal care or who were not offered HIV testing during pregnancy and innovative approaches are needed to address these barriers. The CDC-funded Mother-Infant Rapid Intervention At Delivery (MIRIAD) Study in five US metropolitan areas is one such approach that will test the feasibility of offering rapid testing to women presenting late in pregnancy or at delivery with undocumented HIV status. In addition, further research addressing the role of the placenta in preventing or enhancing in utero HIV transmission is needed. Internationally, new clinical trial findings provide hope that a short course of antiretrovirals can substantially reduce vertical HIV-1 transmission in resource-poor settings in the developing world where most paediatric HIV infections occur. Future research will focus on the role of post-perinatal exposure prophylaxis with antiretrovirals administered to the infant and on the prevention of postnatal transmission of HIV-1 through breast milk while maintaining adequate nutrition. A major challenge is to translate trial results into a coordinated public health implementation plan in order to maximally reduce mother-to-child HIV-1 transmission worldwide.

Adult↗

Treatment and control of severe infections caused by multiresistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the leading causes of nosocomial infections. Severe infections, such as pneumonia or bacteraemia, are associated with high mortality rates and are often difficult to treat, as the repertoire of useful anti-pseudomonal agents is limited (some beta-lactams, fluoroquinolones and aminoglycosides, and the polymyxins as last-resort drugs); moreover, P. aeruginosa exhibits remarkable ability to acquire resistance to these agents. Acquired resistance arises by mutation or acquisition of exogenous resistance determinants and can be mediated by several mechanisms (degrading enzymes, reduced permeability, active efflux and target modification). Overall, resistance rates are on the increase, and may be different in different settings, so that surveillance of P. aeruginosa susceptibility is essential for the definition of empirical regimens. Multidrug resistance is frequent, and clinical isolates resistant to virtually all anti-pseudomonal agents are increasingly being reported. Monotherapy is usually recommended for uncomplicated urinary tract infections, while combination therapy is normally recommended for severe infections, such as bacteraemia and pneumonia, although, at least in some cases, the advantage of combination therapy remains a matter of debate. Antimicrobial use is a risk factor for P. aeruginosa resistance, especially with some agents (fluoroquinolones and carbapenems), and interventions based on antimicrobial rotation and restriction of certain agents can be useful to control the spread of resistance. Similar measures, together with the prudent use of antibiotics and compliance with infection control measures, are essential to preserve the efficacy of the currently available anti-pseudomonal agents, in view of the dearth, in the near future, of new options against multidrug-resistant P. aeruginosa strains.

Anti-Bacterial Agents↗

[Mapping of superficial veins for vascular replacement using duplex ultrasound].

With regard to surgical vascular reconstruction, we evaluated the saphenous veins of 110 patients as potential substitute vessels by duplex ultrasound. The technique is analogous to the one used for diagnosis of varicose veins. Finally 74 patients underwent a surgical intervention with exploration or removal of veins. The comparison between the 74 operative findings available for analysis and the results of duplex ultrasound showed agreement in 93%. The duplex technique informs not only about the permeability and morphology of the veins but also by direct skin marking about their precise position. In comparison with phlebography, it is in experienced hands at least as reliable, without morbidity and virtually without inconvenience to the patient. In our opinion, the non-invasive duplex ultrasound method is quite adequate for the preoperative judgement of veins destined for vessel replacement.

Aged↗

Computer-assisted neurosurgery system: Wayne State University hardware and software configuration.

Computer-assisted neurosurgery uses the latest technological advancements in imaging, computers, mechanics, and electronics to improve the accuracy and reduce the invasiveness and risk of neurosurgical procedures. We describe the Wayne State University, Detroit, Michigan, computer-assisted neurosurgical system with the emphasis on software and discuss the theory guiding the development of this system and its application in real-time position tracking systems. Our system consists of the Neurological Surgery Planning System (NSPS) software which we developed at our medical center and three types of position tracking systems: the Zamorano-Dujovny (Z-D) are digitizer for frame-based procedures, an articulated arm, and an infrared-based digitizer for frameless procedures. The NSPS software is designed to offer neurosurgeons a safe and accurate method to approach intracranial lesions by preoperatively planning a surgical trajectory. Software consisting of the most advanced technologies in computer vision, computer imaging/graphics, and stereotactic numeric analysis forms the core of the system. Capabilities for correlating data from imaging studies to facilitate image reconstruction, image mapping, and three-dimensional (3D) visualization of target volumes enable the neurosurgeon to simulate surgical procedures into a preoperative protocol to be used during surgery, both to follow the preplanned trajectory and to track the position of surgical instruments in real-time on the computer monitor. The tracking systems position and orient the surgical instruments relative to the patient's head. With these devices, the display of the surgical instruments together with the virtual images create an excellent intraoperative tool.

Algorithms↗

Advances in ultrasound: from microscanning to telerobotics.

This paper is in memory of W V Mayneord (1902-1988). Experiments conducted in Mayneord's laboratory were amongst the first to show that ultrasound had diagnostic potential. Now, one in every four imaging studies uses ultrasound. Amongst numerous contemporary advances, microscanning is concerned with imaging subcentimetre size volumes of tissue in three dimensions with 10-100 microns resolution. The traditional approach is by pulse echo imaging, with a focused ultrasonic beam in the frequency range 20-100 MHz. This approach may be complemented by ultrasonic CT (to correct for attenuation and speed variations), reflex transmission imaging (to provide attenuation data) and synthetic aperture scanning (to decrease imaging time). Harmonic microscanning may reduce artefacts, and elasticity imaging may also be possible. Microscanning is likely to have applications in pathology and in the operating room, for trackless microintervention, in molecular biology and drug studies, and in experimental imaging of small mammals including, in particular, the mouse. Robotics is the engineering science concerned with devices that are able to execute tasks usually performed by humans. Two procedures, ultrasonically guided biopsy and ultrasonic laparoscopy, are being used to demonstrate the feasibility of telerobotics. The approach is that of telepresence, as distinct from supervisory control or virtual reality. Problems associated with image compression and communications latency are identified. Although incremental developments in medical ultrasound have resulted from clinical pull, major advances have, in general, been due to technical push.

England↗

Advances in control of cancer pain.

The wide variety of techniques and rapidly developing complex technologies currently available for managing pain, as well as the multidimensional nature of cancer pain, require that a multidisciplinary approach to treatment be used in virtually all health care settings. Members of each health care discipline have unique and very important contributions to make to the care of patients with cancer pain. This critical fact has only recently been recognized and incorporated into the management of persons with pain in inpatient, outpatient, and home settings. The development and refinement of multidisciplinary teams, coupled with the use of the most current and effective therapeutic interventions available, should result in better care of and quality of life for patients with cancer pain.

Administration, Oral↗

Environmental modifiers in carcinogenesis.

The natural history of neoplastic development can be divided into at least three distinct stages - initiation, promotion and progression. These stages can be defined by biological experimentation and by histopathological characterization of the lesions involved in the various stages. It is now possible, both in human beings and in experimental animals, to distinguish by morphological techniques all stages from very early 'precursor' lesions to the final malignant state. Although the final stage - progression - of the neoplastic process can be altered by therapeutic intervention, the principal site at which the natural history of neoplastic development can be actually and potentially regulated is that of promotion. Promoting agents that are relatively selective for carcinogenesis in several different tissue types have now been identified both in experimental systems and in human beings. In at least two experimental systems - those of epidermal carcinogenesis and hepatocarcinogenesis - the general characteristics of both initiation and promotion are virtually identical. Such studies have demonstrated that the activity of promoting agents exhibits a threshold level as well as a maximal level and that the action of promoting agents is reversible; the identification of promoting agents in our environment is therefore of considerable importance in understanding the nature of and preventing the development of human cancer. In addition, the interpretation of whole-animal bioassays for carcinogenic agents in the environment must take into account the existence of promoting agents and recognize that their action is distinct from that of complete and incomplete carcinogens, in order rationally to extrapolate to situations of human risk.

Carcinoma, Hepatocellular↗

Virtual three-dimensional blackboard: three-dimensional finger tracking with a single camera.

We present a method for three-dimensional (3D) tracking of a human finger from a monocular sequence of images. To recover the third dimension from the two-dimensional images, we use the fact that the motion of the human arm is highly constrained owing to the dependencies between elbow and forearm and the physical constraints on joint angles. We use these anthropometric constraints to derive a 3D trajectory of a gesticulating arm. The system is fully automated and does not require human intervention. The system presented can be used as a visualization tool, as a user-input interface, or as part of some gesture-analysis system in which 3D information is important.

Journal Article↗

Health education: special issues for older adults.

The older adult population in the United States has grown substantially since the turn of the century. With extended longevity and the relatively good functional status of most older adults, prevention programs that identify and intervene on risk factors in older adults may be an effective means to dealy ill health. The availability of data to guide both the selection and evaluation of prevention services for older adults, however, is strikingly limited in virtually all areas. Until recently, all persons over the age of 65 were treated as a single category of older adults although the older population is very heterogeneous. Most agree that prevention and education for this age group should focus on the prevention of disease, maintenance of existing abilities, and on prevention of deterioration of impairments that result in dysfunction or handicap. The most effective methods for developing behavioral intervention strategies may result from an integration of the behavioral diagnostic framework and current value expectancy and social learning theories. Health education interventions based on these strategies can be very effective in older age groups in terms of both improving adherence behavior with therapeutic and prevention intervention, and potentially in reducing morbidity and excess mortality.

Aged↗

An improved treatment procedure for testicular biopsy specimens offers more efficient sperm recovery: case series.

OBJECTIVE: To report an improved sperm recovery procedure from testicular biopsy specimens for intracytoplasmic sperm injection (ICSI). DESIGN: Case series and controlled study. SETTING: Procedures were performed in a tertiary IVF center. PATIENT(S): Nonobstructive azoospermic cases (15 patients) and obstructive azoospermic cases (5 patients). INTERVENTION(S): Intracytoplasmic sperm injection was carried out using testicular sperm isolated from a testicular biopsy specimen either with or without erythrocyte lysing buffer treatment. MAIN OUTCOME MEASURE(S): The time required to collect spermatozoa and the intactness and fertilization and developmental rates of oocytes. RESULT(S): In 7 of the 15 nonobstructive cases, it was possible to perform ICSI when, after shredding of the testicular tissue, no (or virtually no) sperm were present. There was no difference in the fertilization rates (83% and 68%) and developmental rates (87% and 89%) of the 54 sibling oocytes from another 5 patients in whom ICSI was carried out with sperm either treated or not treated with erythrocyte lysing buffer. CONCLUSION(S): Erythrocyte lysing buffer treatment of testicular biopsy specimens enhances the efficiency of sperm collection in those cycles in which spermatozoa are present and does not affect fertilization and embryo development.

Ammonium Chloride↗

[Arterial pressure and race. A study in pauper children attending schools in an urban strip in Lisbon].

OBJECTIVE: To determine whether race is a factor of blood pressure levels in school-age children of similar social status, and to investigate other potential determinants of the levels of blood pressure. DESIGN: Inquiry in schools of the suburbs of Lisbon. SETTING: Three schools, four medical observers (general practitioners with school-health functions). SUBJECTS: Three hundred ninety seven children, aged 6-14 years, both sexes, 296 being white and 101 non-white. INTERVENTIONS: Inquiry to the following individual characteristics--sex, age, race, birthplace, type of housing, house availability of water, electricity and waste water, type of transportation to school, number of cohabitans, family income, school marks. Individual determination of systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), weight and height. MEASUREMENTS AND MAIN RESULTS: Blood pressure values were cross-analyzed with all the determined variables, and the virtual correlations were checked. Main results as follows: Race does not influence either SBP or DBP. In this age group, sex does not influence blood pressure values. The used markers of socioeconomical status have equally no influence on blood pressure. Age has only a significant repercussion on SBP. No significant correlation was found between height and blood pressure. Body weight, however, influence either SBP or DBP. SBP was found to be lower in the second of two successive measurements, and the difference increases with age. CONCLUSIONS: In this school-aged biracial population, body weight seems to be the major factor of blood pressure levels, in the sense-bigger weight, higher SBP and DBP.

Adolescent↗

[Coronary angiography and intravascular ultrasound examination of a 60-year-old patient with familial HDL deficiency (Tangier disease)].

A 60-year-old homozygous patient with familial high density lipoprotein deficiency (Tangier disease) was examined by coronary angiography and intravascular ultrasound because of typical angina pectoris. We found a normal left ventricular function, moderately diffuse coronary sclerosis without stenosis, and no critical stenosis of peripheral arteries. Intravascular ultrasound revealed normal thickness and the three-layer appearance of the arterial intima, media, and adventitia within the peripheral arteries, and showed a single, discrete arteriosclerotic lesion in one iliac artery segment. The lack of severe atherosclerosis was remarkable insofar as massive foam cell formation in reticuloendothelial tissues and the virtually complete absence of circulating HDL is characteristic of Tangier disease and had been previously demonstrated in this patient.

Arteriosclerosis↗