|
| ||
|
|
||
Careful Assessment (careful + assessment)
Selected AbstractsIs This Atrial Fibrillation?ANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2009Amir S. Jadidi M.D. A 19-year-old girl was referred to our cardiology department for catheter ablation (isolation of the pulmonary veins) of paroxysmal atrial fibrillation (AF). The diagnosis was made upon a 12-lead ECG of the arrhythmia documented in the emergency room. The ECG showed an irregular tachycardia without wide QRS complexes. Careful assessment revealed the irregularity of the rhythm was a sweep artifact due to a mechanic failure of the ECG-machine to advance the article smoothly. During EP study a concealed anteroseptal accessory pathway causing an orthodromic AV reentrant tachycardia was eliminated by radio-frequency ablation. This example emphasizes the need for careful assessment of an ECG tracing, including printed legends and technical data. [source] Establishing pragmatic estimated glomerular filtration rate thresholds to guide metformin prescribing: careful assessment of risks and benefits is requiredDIABETIC MEDICINE, Issue 5 2008J. T. George No abstract is available for this article. [source] Long-term landscape evolution: linking tectonics and surface processesEARTH SURFACE PROCESSES AND LANDFORMS, Issue 3 2007Paul Bishop Abstract Research in landscape evolution over millions to tens of millions of years slowed considerably in the mid-20th century, when Davisian and other approaches to geomorphology were replaced by functional, morphometric and ultimately process-based approaches. Hack's scheme of dynamic equilibrium in landscape evolution was perhaps the major theoretical contribution to long-term landscape evolution between the 1950s and about 1990, but it essentially ,looked back' to Davis for its springboard to a viewpoint contrary to that of Davis, as did less widely known schemes, such as Crickmay's hypothesis of unequal activity. Since about 1990, the field of long-term landscape evolution has blossomed again, stimulated by the plate tectonics revolution and its re-forging of the link between tectonics and topography, and by the development of numerical models that explore the links between tectonic processes and surface processes. This numerical modelling of landscape evolution has been built around formulation of bedrock river processes and slope processes, and has mostly focused on high-elevation passive continental margins and convergent zones; these models now routinely include flexural and denudational isostasy. Major breakthroughs in analytical and geochronological techniques have been of profound relevance to all of the above. Low-temperature thermochronology, and in particular apatite fission track analysis and (U,Th)/He analysis in apatite, have enabled rates of rock uplift and denudational exhumation from relatively shallow crustal depths (up to about 4 km) to be determined directly from, in effect, rock hand specimens. In a few situations, (U,Th)/He analysis has been used to determine the antiquity of major, long-wavelength topography. Cosmogenic isotope analysis has enabled the determination of the ,ages' of bedrock and sedimentary surfaces, and/or the rates of denudation of these surfaces. These latter advances represent in some ways a ,holy grail' in geomorphology in that they enable determination of ,dates and rates' of geomorphological processes directly from rock surfaces. The increasing availability of analytical techniques such as cosmogenic isotope analysis should mean that much larger data sets become possible and lead to more sophisticated analyses, such as probability density functions (PDFs) of cosmogenic ages and even of cosmogenic isotope concentrations (CICs). PDFs of isotope concentrations must be a function of catchment area geomorphology (including tectonics) and it is at least theoretically possible to infer aspects of source area geomorphology and geomorphological processes from PDFs of CICs in sediments (,detrital CICs'). Thus it may be possible to use PDFs of detrital CICs in basin sediments as a tool to infer aspects of the sediments' source area geomorphology and tectonics, complementing the standard sedimentological textural and compositional approaches to such issues. One of the most stimulating of recent conceptual advances has followed the considerations of the relationships between tectonics, climate and surface processes and especially the recognition of the importance of denudational isostasy in driving rock uplift (i.e. in driving tectonics and crustal processes). Attention has been focused very directly on surface processes and on the ways in which they may ,drive' rock uplift and thus even influence sub-surface crustal conditions, such as pressure and temperature. Consequently, the broader geoscience communities are looking to geomorphologists to provide more detailed information on rates and processes of bedrock channel incision, as well as on catchment responses to such bedrock channel processes. More sophisticated numerical models of processes in bedrock channels and on their flanking hillslopes are required. In current numerical models of long-term evolution of hillslopes and interfluves, for example, the simple dependency on slope of both the fluvial and hillslope components of these models means that a Davisian-type of landscape evolution characterized by slope lowering is inevitably ,confirmed' by the models. In numerical modelling, the next advances will require better parameterized algorithms for hillslope processes, and more sophisticated formulations of bedrock channel incision processes, incorporating, for example, the effects of sediment shielding of the bed. Such increasing sophistication must be matched by careful assessment and testing of model outputs using pre-established criteria and tests. Confirmation by these more sophisticated Davisian-type numerical models of slope lowering under conditions of tectonic stability (no active rock uplift), and of constant slope angle and steady-state landscape under conditions of ongoing rock uplift, will indicate that the Davis and Hack models are not mutually exclusive. A Hack-type model (or a variant of it, incorporating slope adjustment to rock strength rather than to regolith strength) will apply to active settings where there is sufficient stream power and/or sediment flux for channels to incise at the rate of rock uplift. Post-orogenic settings of decreased (or zero) active rock uplift would be characterized by a Davisian scheme of declining slope angles and non-steady-state (or transient) landscapes. Such post-orogenic landscapes deserve much more attention than they have received of late, not least because the intriguing questions they pose about the preservation of ancient landscapes were hinted at in passing in the 1960s and have recently re-surfaced. As we begin to ask again some of the grand questions that lay at the heart of geomorphology in its earliest days, large-scale geomorphology is on the threshold of another ,golden' era to match that of the first half of the 20th century, when cyclical approaches underpinned virtually all geomorphological work. Copyright © 2007 John Wiley & Sons, Ltd. [source] The promise and the potential consequences of the global transport of mycorrhizal fungal inoculumECOLOGY LETTERS, Issue 5 2006Mark W. Schwartz Abstract Advances in ecology during the past decade have led to a much more detailed understanding of the potential negative consequences of species' introductions. Moreover, recent studies of mycorrhizal symbionts have led to an increased knowledge of the potential utility of fungal inoculations in agricultural, horticultural and ecological management. The intentional movement of mycorrhizal fungal species is growing, but the concomitant potential for negative ecological consequences of invasions by mycorrhizal fungi is poorly understood. We assess the degree to which introductions of mycorrhizal fungi may lead to unintended negative, and potentially costly, consequences. Our purpose is to make recommendations regarding appropriate management guidelines and highlight top priority research needs. Given the difficulty in discerning invasive species problems associated with mycorrhizal inoculations, we recommend the following. First, careful assessment documenting the need for inoculation, and the likelihood of success, should be conducted prior to inoculation because inoculations are not universally beneficial. Second, invasive species problems are costly and often impossible to control by the time they are recognized. We recommend using local inoculum sources whenever possible. Third, non-sterile cultures of inoculum can result in the movement of saprobes and pathogens as well as mutualists. We recommend using material that has been produced through sterile culture when local inoculum is not available. Finally, life-history characteristics of inoculated fungi may provide general guidelines relative to the likelihood of establishment and spread. We recommend that, when using non-local fungi, managers choose fungal taxa that carry life-history traits that may minimize the likelihood of deleterious invasive species problems. Additional research is needed on the potential of mycorrhizal fungi to spread to non-target areas and cause ecological damage. [source] Experimental and Clinical Evidence for Loss of Effect (Tolerance) during Prolonged Treatment with Antiepileptic DrugsEPILEPSIA, Issue 8 2006Wolfgang Löscher Summary:, Development of tolerance (i.e., the reduction in response to a drug after repeated administration) is an adaptive response of the body to prolonged exposure to the drug, and tolerance to antiepileptic drugs (AEDs) is no exception. Tolerance develops to some drug effects much more rapidly than to others. The extent of tolerance depends on the drug and individual (genetic?) factors. Tolerance may lead to attenuation of side effects but also to loss of efficacy of AEDs and is reversible after discontinuation of drug treatment. Different experimental approaches are used to study tolerance in laboratory animals. Development of tolerance depends on the experimental model, drug, drug dosage, and duration of treatment, so that a battery of experimental protocols is needed to evaluate fully whether tolerance to effect occurs. Two major types of tolerance are known. Pharmacokinetic (metabolic) tolerance, due to induction of AED-metabolizing enzymes has been shown for most first-generation AEDs, and is easy to overcome by increasing dosage. Pharmacodynamic (functional) tolerance is due to "adaptation" of AED targets (e.g., by loss of receptor sensitivity) and has been shown experimentally for all AEDs that lose activity during prolonged treatment. Functional tolerance may lead to complete loss of AED activity and cross-tolerance to other AEDs. Convincing experimental evidence indicates that almost all first-, second-, and third-generation AEDs lose their antiepileptic activity during prolonged treatment, although to a different extent. Because of diverse confounding factors, detecting tolerance in patients with epilepsy is more difficult but can be done with careful assessment of decline during long-term individual patient response. After excluding confounding factors, tolerance to antiepileptic effect for most modern and old AEDs can be shown in small subgroups of responders by assessing individual or group response. Development of tolerance to the antiepileptic activity of an AED may be an important reason for failure of drug treatment. Knowledge of tolerance to AED effects as a mechanism of drug resistance in previous responders is important for patients, physicians, and scientists. [source] Complications of central venous catheters in patients with haemophilia and inhibitorsHAEMOPHILIA, Issue 6 2001M. Morado We report our clinical experience with central venous catheters (CVCs) in 15 patients with haemophilia who, in total, had 34 catheters inserted. Eighteen devices were Hickman, six were Port-A-Cath and 10 were nontunnelled catheters (one Quinton, seven antecubital, one jugular and one subclavian vein access). All patients had factor VIII/IX inhibitors at the time of insertion. The mean age at operation was 8.8 years (range 16 months,39 years). Eight of the 15 patients (26/34 implanted catheters, 76%) presented some kind of complication. Pericatheter bleeding during the postoperative period affected a total of seven CVCs (7/34, 20%) in six patients, which required substitutive treatment for several days. Infection was reported in 15 of the CVCs (15/34, 44%), and four of these (4/15, 26%) had more than one episode, with a mean of 1.4 infection episodes per catheter (21/15). The infection rate was 0.2 infections per 1000 patient days or 0.1 per 1000 catheter days. Despite the usefulness of CVCs in haemophilic patients, the high incidence of complications requires careful assessment of the type of device as well as continuous surveillance. [source] Are Migraine and Coronary Heart Disease Associated?HEADACHE, Issue 2004An Epidemiologic Review In evaluating the cardiovascular risks of triptans (5-HT1B/1D agonists) for the treatment of migraine, the possible relationship between migraine and cardiovascular disease warrants careful assessment. The vascular nature of migraine is compatible with the possibility that migraine is a manifestation of cardiovascular disease or is linked to cardiovascular disease via a common mechanism. If so, then migraine itself,independent of the use of triptans,may be associated with an increased risk of cardiac events. This article considers the epidemiologic literature pertinent to evaluating the association of migraine with coronary heart disease. The research reviewed herein fails to support an association between migraine and coronary heart disease. First, data from several large cohort studies show that the presence of migraine does not increase risk of coronary heart disease. Furthermore, although migraineurs are generally more likely than nonmigraineurs to report chest pain, the presence of chest pain in most studies did not predict serious cardiac events such as myocardial infarction. That the gender- and age-specific prevalence of migraine does not overlap with that of coronary heart disease is also consistent with a lack of association between migraine and atherosclerotic cardiovascular disease. While migraine appears not to be associated with coronary heart disease, preliminary evidence suggests a possible link of migraine with vasospastic disorders such as variant angina and Raynaud's phenomenon. These results warrant further investigation in large prospective studies. [source] Internet use by patients in an inflammatory bowel disease specialty clinicINFLAMMATORY BOWEL DISEASES, Issue 10 2007Robert R. Cima MD Abstract Background: Patient education is known to improve satisfaction in and participation with treatment. A careful assessment of internet use by inflammatory bowel disease (IBD) patients to gather information has not been reported. Our aim was to evaluate internet use to gather general health- and disease-specific information in patients presenting to an IBD clinic. Methods: A cross-sectional anonymous survey using a convenience sample of patients (N = 175) at a tertiary-care institution's IBD clinic was performed. Results: In all, 169 surveys (97%) were returned for analysis. The median age was 46 (17,84), 83 men and 81 women (5 missing). In known IBD patients (87%), 85 (50%) had Crohn's disease and 62 (37%) ulcerative colitis; 81% of patients had home internet access. The most common information sources were: gastroenterologists (59%), internet (54%), and primary-care physicians (54%). Ninety-two patients (54%) used the internet to gather IBD-specific information. Age-specific use (<40, 40,65, >65) was 73%, 48%, 37.5%, respectively. There was a significant positive association between level of education and internet use (P < 0.0001), but not with income. Internet sites most commonly visited were organization- or institution-specific. Factors that most influenced a user's choice of an internet site were noncommercial status (59%) and ease of use (53%). The majority of patients (57%) rated internet information "trustworthy" to "very trustworthy." Conclusions: Over half of patients in an IBD clinic used the internet to gather IBD-specific information. Use was inversely associated with age and positively correlated with education level. There was no income association. These findings suggest web-based IBD information may become increasingly important in the future. (Inflamm Bowel Dis 2007) [source] Extubation score in the operating room after liver transplantationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2010S. SKURZAK Background: Early extubation after liver transplantation (LT) is an increasingly applied safe practice. The aim of the present study was to provide a simple extubation rule for accelerated weaning in the operating room (OR). Methods: Data of 597 patients transplanted at the LT center of Turin (Italy) were retrospectively analyzed. Fifty-two nonextubated patients (excluding those with a scheduled early reoperation) were compared with 545 successfully extubated patients (not in need of reintubation within the first 48 h). Significant variables at univariate analysis were entered into a logistic regression model and the regression coefficients of independent predictors were used to yield a prognostic score called the safe operating room extubation after liver transplantation (SORELT) score. Results: Two major and three minor criteria were found. The major ones were blood transfusions (higher than/or equal to 7 U of packed red blood cells) and end of surgery lactate (higher than/or equal to 3.4 mmol/l). The minor ones were status before LT (home vs. hospitalized patient), duration of surgery (longer than/or equal to 5 h), vasoactive drugs at the end of surgery (dopamine higher than 5 ,g/kg/min or norepinephrine higher than 0.05 ,g/kg/min). Patients who fulfill the SORELT score-derived criteria (fewer than two major/one major plus two minor/three minor criteria) can be considered for OR extubation. Conclusion: Early extubation after LT requires a very careful assessment of the pre-operative, intraoperative, graft and post-operative care data available. The SORELT score helps as a simple and objective aid in considering such a decision. [source] Researching Internet-Based Populations: Advantages and Disadvantages of Online Survey Research, Online Questionnaire Authoring Software Packages, and Web Survey ServicesJOURNAL OF COMPUTER-MEDIATED COMMUNICATION, Issue 3 2005Kevin B. Wright This article examines some advantages and disadvantages of conducting online survey research. It explores current features, issues, pricing, and limitations associated with products and services, such as online questionnaire features and services to facilitate the online survey process, such as those offered by web survey businesses. The review shows that current online survey products and services can vary considerably in terms of available features, consumer costs, and limitations. It is concluded that online survey researchers should conduct a careful assessment of their research goals, research timeline, and financial situation before choosing a specific product or service. [source] Alveolar Macrophage Graded Hemosiderin Score from Bronchoalveolar Lavage in Horses with Exercise-Induced Pulmonary Hemorrhage and ControlsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2002Michele Y. Doucet The objective of this study was to determine if a quantitative scoring system for evaluation of hemosiderin content of alveolar macrophages obtained by bronchoalevolar lavage provides a more sensitive test for the detection of exercise-induced pulmonary hemorrhage (EIPH) in horses than does endoscopy of the lower airways. A sample population composed of 74 Standardbred racehorses aged 2,5 years was used. Horses were grouped as either control (EIPH-negative) or EIPH-positive based on history and repeated postexertional endoscopic evaluation of the bronchial airways. Bronchoalveolar lavage was performed and cytocen-trifuge slides were stained with Perl's Prussian blue. Alveolar macrophages were scored for hemosiderin content by a method described by Golde and associates to obtain the total hemosiderin score (THS). Test performance criteria were determined with a contingency table. All subjects had some degree of hemosiderin in the alveolar macrophages, regardless of group. The distribution of cells among the different grades followed a significantly different pattern for the control group versus horses with EIPH (P < .05). When using a THS of 75 as a cutoff point, the THS test was found to have a sensitivity of 94% and a specificity of 88%. The level of agreement beyond chance, between the EIPH status and the THS test result was very good (Cohen's kappa = 74%). The conclusion was made that careful assessment and scoring of alveolar macrophages for hemosiderin by means of the Golde scoring system shows promise as a more sensitive approach than repeated postexertional endoscopy alone to detect EIPH. [source] Pediatric Anogenital Warts: A 7-Year Review of Children Referred to a Tertiary-Care Hospital in Montreal, CanadaPEDIATRIC DERMATOLOGY, Issue 3 2006Danielle Marcoux M.D. Over a 7-year period, 72 patients under the age of 12 years were seen at our dermatology clinic for anogenital warts, corresponding to a prevalence of 1.7/1000 in our patient population. Sixty-four percent (46/72) were girls. Congenital, prenatal, ascending infections occurred in two subjects. The onset of anogenital warts occurred before age 2 in 28% and between 2 and 6 years of age in 62% of children and tended to be younger in boys. We identified unusual cutaneomucosal serotypes human papillomavirus 7 and 57 (three and eight instances, respectively). The modes of transmission of anogenital warts in children cannot be identified either by the clinical appearance of the lesions or by human papillomavirus typing. We conclude that the best way to identify possible sexual abuse is still by history taking, careful assessment of the socio-clinical context, and physical examination. [source] Risk Factors for Suicide Attempts in Methamphetamine-Dependent PatientsTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2008Suzette Glasner-Edwards PhD The purpose of this study was to identify risk factors for suicide attempts (SA) in methamphetamine (MA)-dependent patients. MA-dependent adults (N = 526) who participated in the Methamphetamine Treatment Project were interviewed before and three years after treatment. Baseline psychiatric, medical, demographic, and substance use characteristics were assessed using the Addiction Severity Index and the Beck Depression Inventory (BDI). Lifetime history of SA was assessed at follow-up. Risk factors for SA included gender, intravenous MA use, BDI > 20 at baseline, and clinically significant psychiatric history. Psychiatric characteristics of MA users are strongly associated with SA, warranting careful assessment of psychiatric history. [source] Videofluoroscopic Swallow Studies in Unilateral Cricopharyngeal Dysfunction,THE LARYNGOSCOPE, Issue 6 2003Stacey L. Halum MD Abstract Objectives/Hypothesis Although the cricopharyngeus muscle is a ring-like structure, unilateral cricopharyngeal dysfunction can produce significant dysphagia. This entity has not been well described in the literature. The aims of the study were to identify the characteristic findings on videofluoroscopic swallow studies in patients with dysphagia secondary to unilateral cricopharyngeal dysfunction, to note the associated vagal nerve injury, and to evaluate patient outcomes following ipsilateral cricopharyngeal myotomy. Study Design Retrospective clinical investigation. Methods The clinic charts, electromyographic tests, videostroboscopic examinations, and videofluoroscopic swallow studies were reviewed from a series of patients who presented to our institution from 1993 to 2001 with dysphagia and findings on videofluoroscopic swallow studies suggestive of unilateral cricopharyngeal dysfunction on posterior,anterior view. In patients treated with ipsilateral cricopharyngeal myotomy, postoperative findings on swallow studies and patient outcomes were also reviewed. Results Eighteen patients demonstrated findings characteristic of unilateral cricopharyngeal muscle dysfunction on videofluoroscopic swallow study. The common feature was a unilateral shelf-like barrier at the cricopharyngeus on the posterior,anterior view with pooling of liquid bolus in the ipsilateral pyriform sinus and episodic shunting to the contralateral side. Eight patients did not have evidence of cricopharyngeal dysfunction (ie, cricopharyngeal bar) on lateral films. Of the 18 patients, 14 had histories consistent with vagal injury secondary to trauma (n = 2), neoplastic involvement (n = 7), iatrogenic injury (n = 2), or central nervous system disease (n = 3). Results of videostroboscopic examinations demonstrated vocal fold motion impairment in 14 patients, and electromyographic test results confirmed unilateral vagal injuries in those who underwent electromyographic testing (n = 6). In the remaining 4 of 18 patients, videostroboscopic examinations demonstrated normal vocal fold abduction but impaired lengthening with a posterior glottic gap, and electromyographic test results (n = 4) indicated unilateral superior laryngeal nerve involvement. Of the 15 patients treated with ipsilateral cricopharyngeal myotomy, 1 patient required postoperative esophageal dilations for an esophageal stricture distal to the cricopharyngeus, whereas the remaining 14 patients had functional resolution of their dysphagia. Conclusion In patients presenting with dysphagia and evidence of unilateral vagal injury, careful assessment of posterior,anterior view on videofluoroscopic swallow study should be included to evaluate for unilateral cricopharyngeal dysfunction. [source] De Novo Donor-Specific Antibody at the Time of Kidney Transplant Biopsy Associates with Microvascular Pathology and Late Graft FailureAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009L. G. Hidalgo We studied whether de novo donor-specific antibodies (DSA) in sera from patients undergoing kidney transplant biopsies associate with specific histologic lesions in the biopsy and prognosis. DSA were assessed in 145 patients at the time of biopsy between 7 days to 31 years posttransplant. DSA was detected in 54 patients (37%), of which 32 represented de novo DSA. De novo DSA was more frequent in patients having late biopsies (34%) versus early biopsies (4%), and was usually either against class II alone or class I and II but rarely against class I alone. Microcirculation inflammation (glomerulitis, capillaritis) and damage (glomuerulopathy, capillary basement membrane multilayering), and C4d staining were associated with de novo DSA. However, the degree of scarring, arterial fibrosis and tubulo-interstitial inflammation did not correlate with the presence of de novo DSA. De novo DSA correlated with reduced graft survival after the biopsy. Thus, de novo DSA at the time of a late biopsy for clinical indication is primarily against class II, and associates with microcirculation changes in the biopsy and subsequent graft failure. We propose careful assessment of de novo DSA, particularly against class II, be performed in all late kidney transplant biopsies. [source] Is This Atrial Fibrillation?ANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2009Amir S. Jadidi M.D. A 19-year-old girl was referred to our cardiology department for catheter ablation (isolation of the pulmonary veins) of paroxysmal atrial fibrillation (AF). The diagnosis was made upon a 12-lead ECG of the arrhythmia documented in the emergency room. The ECG showed an irregular tachycardia without wide QRS complexes. Careful assessment revealed the irregularity of the rhythm was a sweep artifact due to a mechanic failure of the ECG-machine to advance the article smoothly. During EP study a concealed anteroseptal accessory pathway causing an orthodromic AV reentrant tachycardia was eliminated by radio-frequency ablation. This example emphasizes the need for careful assessment of an ECG tracing, including printed legends and technical data. [source] Assessment of Emotions: Anxiety, Anger, Depression, and CuriosityAPPLIED PSYCHOLOGY: HEALTH AND WELL-BEING, Issue 3 2009Charles D. Spielberger Anxiety, anger, depression, and curiosity are major indicators of psychological distress and well-being that require careful assessment. Measuring these psychological vital signs is of critical importance in diagnosis, and can facilitate treatment by directly linking intense emotions to the events that give rise to them. The historical background regarding theory and research on anxiety, anger, depression, and curiosity is briefly reviewed, and the nature and assessment of these emotional states and personality traits are examined. The construction and development of the State-Trait Anxiety Inventory (STAI), the State-Trait Anger EXpression Inventory (STAXI-2), and the State-Trait Personality Inventory (STPI) to assess anxiety, anger, depression, and curiosity, and the major components of these emotional states and personality traits, are described in detail. Findings demonstrating the diverse utility and efficacy of these measures are also reported, along with guidelines for their interpretation and utilisation in research and clinical practice. Research with the STAI, STAXI and STPI over the last 40 years has contributed to understanding vitally important measurement concepts that are especially applicable to the assessment of emotions. These concepts included the state,trait distinction, item intensity specificity, and the importance of items that describe the presence or absence of emotions. [source] Percutaneous permeation of enantiomers and racemates of chiral drugs and prediction of their flux ratios using thermal data: A pharmaceutical perspectiveCHIRALITY, Issue 5 2003Mohsen I. Afouna Abstract Albeit pharmacological, pharmacokinetic, and toxicological differences between enantiomeric pairs or between the pure enantiomers and racemate of chiral drugs are known to exist for decades, we are just beginning to realize that there are apparent differences between these species with respect to their percutaneous permeation as well. Such differences in permeation are likely to be enhanced when chiral drugs are formulated with chiral excipients, necessitating a careful assessment of the effect of formulation excipients on the permeation as well as the overall therapeutic outcomes. The in vitro transport data from the preclinical investigations, using laboratory animal models and/or in vitro cell culture systems, must be carefully validated in vivo as there are differences between these models and the human skin. Mathematical models such as MTMT that utilize the interdependence of certain physicochemical characteristics and percutaneous permeability have a predictive value in assessing the flux behavior of enantiomers and racemates. Chirality 15:456,465, 2003. © 2003 Wiley-Liss, Inc. [source] | |||||||||||||