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PubMed2002

Treatment of community-acquired lower respiratory tract infections in adults.

Community-acquired lower respiratory tract infection (LRTI) is a common cause of acute illness in adults. The spectrum of disease ranges from a mild mucosal colonisation or infection, acute bronchitis or acute exacerbation of chronic bronchitis/chronic obstructive pulmonary disease (AE-CB/COPD), to an overwhelming parenchymal infection with the patient presenting with severe community-acquired pneumonia (CAP). Although the great majority of LRTIs are self-limiting viral infections, CAP is most often a bacterial disease with a substantial mortality. Thus, antibiotic treatment is rarely indicated for acute bronchitis and is only indicated for the more severe cases of AE-CB/COPD, but it is nearly always indicated for CAP, for which a delay in treatment may increase the risk of a fatal outcome. It may be difficult to differentiate between a viral and a bacterial LRTI, or between bronchitis/AE-CB/COPD and CAP. This may be one reason why antibiotics are prescribed to more than two-thirds of patients with LRTIs in Europe and the USA. Considering the worldwide development of antibiotic resistance, this is not an acceptable situation. Since an empirical approach is nearly always necessary in the management of LRTI, greater emphasis must be placed on the decision of whether or not to prescribe an antibiotic at all. This decision should be based on an assessment of the severity of the disease, including underlying risk factors, and on markers for bacterial/parenchymal/ invasive LRTI. The choice of empirical therapy must be based on the same data together with epidemiological information. The choice of antibiotic must always cover Streptococcus pneumoniae, which remains the main pathogen of morbidity and mortality in CAP. In hospital, attempts should be made to obtain an aetiological diagnosis in order to be able to switch to a specific treatment or to evaluate a failure of empirical therapy. Several guidelines for the management of community-acquired pneumonia have been published during the last 10 yrs. Some reports indicate that the implementation of such guidelines has resulted in lowered costs, length of stay in hospital and mortality. However, the results from these studies are not consistent and the evidence is still weak.

Adult↗

PubMed2001

Lack of heritability of circulating leptin concentration in humans after adjustment for body size and adiposity using a physiological approach.

OBJECTIVE: To construct a simple physiological model of leptin kinetics, based on measures of body size and composition, which is suitable for investigating the influence of genetic and other influences on circulating leptin levels in humans. METHODS: Consideration of the kinetics of the secretion and clearance of leptin led to a predicted linear relationship between ln(leptin), ln(fat mass), and a function of non-fat body compartments. Results obtained from this model were compared with those from two published empirical models based on adjustment for fat mass alone or for body mass index. Overnight fasted leptin levels, body composition data (dual-energy X-ray absorptiometry) and questionnaire responses were obtained from 527 twin pairs (127 monozygotic, 400 dizygotic; 37 male (age 18-68 y, BMI 18-32 kg/m2), 489 female (age 18-71, BMI 17-44) drawn from the St Thomas' UK Adult Twin Registry. RESULTS: In a partial correlation analysis ln(fat mass) and ln(height) (r=0.80, P<0.0001) and r=-0.22, P<0.0001 respectively) were independent predictors of ln(leptin) in females but ln(lean mass) was not (r=-0.01). A regression model incorporating ln(fat mass), ln(height) and a second order polynomial in age provided an adequate fit of the ln(leptin) data in females (r2=71%). ln(Leptin) values adjusted for body size and composition using the model were not significantly heritable (P=0.11), were significantly related to gender (r2=2.3%) and to ln(insulin) (r2=5.7%), but not to menopausal status (r2=0.7%), hormone replacement therapy (r2=0.4%), past or current smoking (r2=1.1%), or percentage trunk fat (r2=0.5%). Both empirical models found significant heritability (h2=36-42%), overestimated the effect of gender in the data (r2=14-16%), and produced significant relationships between adjusted ln(leptin) and percentage trunk fat (r2=4-12%). CONCLUSIONS: We conclude that our physiologically based model provides an adequate description of the relationship between leptin and body composition and provides a more reliable framework than current empirical approaches for the investigation of other influences on circulating leptin levels. Heritable variations in the control of leptin secretion are unlikely to contribute significantly to variations in leptin levels at the population level.

Absorptiometry, Photon↗

PubMed2006

Ab initio calculations of dispersion coefficients for nucleic acid base pairs.

The results of ab initio calculations of two- and three-body dispersion coefficients for the four most important nucleic acid bases are reported. The isotropic as well as anisotropic coefficients were found by using the time-dependent Hartree-Fock approach and the aug-cc-pVDZ basis set. Single and double excitation coupled-cluster theory with noniterative treatment of triple excitations [CCSD(T)] was used to find the values of static polarizabilities which were subsequently used to estimate the values of the CCSD(T) dispersion coefficients. A comparison of these estimated CCSD(T) dispersion coefficients with coefficients found by using empirical approaches based on atomic contributions revealed that the latter are not reliable.

Anisotropy↗

PubMed1998

[Innovative new approaches in pharmacology].

After a brief recall of the molecular bases of the pharmacological actions, the two main ways of discovery of new drugs are described. On the one hand, the "deductive" approach starts with the elucidation of the pathogenic mechanisms and leads to selective drug designs for the appropriate receptors. The recent contributions of the molecular biology in this way are illustrated by some examples: "knock out" mice for the study of gene functions, discovery of new antibiotics thanks to genomic sequencing of bacteria, new pathogenic concepts about inflammation... On the other hand, the empirical approach is now grounded on two performant methods: High Throughput Screening and Combinatorial Chemistry which together have already given practical results. It is obvious that these two approaches are not opposite, but complementary.

Animals↗

PubMed2006

[Dignity in the care of terminal ill and dying patients. Definitions and supportive interventions in palliative care].

Most patients, family members, health care professional as well as volunteers would agree that dignified care and being allowed to die with dignity are superior and unquestionable goals of palliative care. Although the majority of people have a more or less vague concept of dignity and despite its significance for palliative care, only a few empirical approaches to describe the sense of dignity from patients' and health care professionals' perspectives have been undertaken. However, individual descriptions of the dignity concept and definitions can serve as an impetus to improve the current palliative care practice by the development and evaluation of psychotherapeutic interventions for patients near the end of life and the allocation of resources. This article considers an internationally developed empirical-based model of dignity in severe and terminal ill patients by Chochinov et al. Furthermore, it illustrates the understanding of dignity as well as self-perceived exertions of influence on a patient's dignity from the perspective of health care professionals and volunteers. Psychotherapeutic interventions and strategies are introduced that can help conserve the sense of dignity of patients during palliative care.

Attitude to Death↗

PubMed1988

Stability over time in the distribution of population forecast errors.

A number of studies in recent years have investigated empirical approaches to the production of confidence intervals for population projections. The critical assumption underlying these approaches is that the distribution of forecast errors remains stable over time. In this article, we evaluate this assumption by making population projections for states for a number of time periods during the 20th century, comparing these projections with census enumerations to determine forecast errors, and analyzing the stability of the resulting error distributions over time. These data are then used to construct and test empirical confidence limits. We find that in this sample the distribution of absolute percentage errors remained relatively stable over time and data on past forecast errors provided very useful predictions of future forecast errors.

Demography↗

PubMed2004

Habitat selection and population regulation in temporally fluctuating environments.

Understanding and predicting the distribution of organisms in heterogeneous environments lies at the heart of ecology, and the theory of density-dependent habitat selection (DDHS) provides ecologists with an inferential framework linking evolution and population dynamics. Current theory does not allow for temporal variation in habitat quality, a serious limitation when confronted with real ecological systems. We develop both a stochastic equivalent of the ideal free distribution to study how spatial patterns of habitat use depend on the magnitude and spatial correlation of environmental stochasticity and also a stochastic habitat selection rule. The emerging patterns are confronted with deterministic predictions based on isodar analysis, an established empirical approach to the analysis of habitat selection patterns. Our simulations highlight some consistent patterns of habitat use, indicating that it is possible to make inferences about the habitat selection process based on observed patterns of habitat use. However, isodar analysis gives results that are contingent on the magnitude and spatial correlation of environmental stochasticity. Hence, DDHS is better revealed by a measure of habitat selectivity than by empirical isodars. The detection of DDHS is but a small component of isodar theory, which remains an important conceptual framework for linking evolutionary strategies in behavior and population dynamics.

Animals↗

PubMed1995

Long timestep dynamics of peptides by the dynamics driver approach.

Previous experience with the Langevin/implicit-Euler scheme for dynamics ("LI") on model systems (butane, water) has shown that LI is numerically stable for timesteps in the 5-20 fs range but quenches high-frequency modes. To explore applications to polypeptides, we apply LI to model systems (several dipeptides, a tetrapeptide, and a 13-residue oligoalanine) and also develop a new dynamics driver approach ("DA"). The DA scheme, based on LI, addresses the important issue of proper sampling, which is unlikely to be solved by small-timestep integration methods or implicit methods with intrinsic damping at room temperature, such as LI. Equilibrium averages, time-dependent molecular properties, and sampling trends at room temperature are reported for both LI and DA dynamics simulations, which are then compared to those generated by a standard explicit discretization of the Langevin equation with a 1 fs timestep. We find that LI's quenching effects are severe on both the fast and slow (due to vibrational coupling) frequency modes of all-atom polypeptides and lead to more restricted dynamics at moderate timesteps (40 fs). The DA approach empirically counteracts these damping effects by adding random atomic perturbations to the coordinates at each step (before the minimization of a dynamics function). By restricting the energetic fluctuations and controlling the kinetic energy, we are able with a 60 fs timestep to generate continuous trajectories that sample more of the relevant conformational space and also reproduce reasonably Boltzmann statistics. Although the timescale for transition may be accelerated by the DA approach, the transitional information obtained for the alanine dipeptide and the tetrapeptide is consistent with that obtained by several other theoretical approaches that focus specifically on the determination of pathways. While the trajectory for oligoalanine by the explicit scheme over the nanosecond timeframe remains in the vicinity of the full alpha R-helix starting structure, and a high-temperature (600 degrees K) MD trajectory departs slowly from the alpha helical structure, the DA-generated trajectory for the same CPU time exhibits unfolding and refolding and reveals a range of conformations with an intermediate helix content. Significantly, this range of states is more consistent with spectroscopic experiments on small peptides, as well as the cooperative two-state model for helix-coil transition. The good, near-Boltzmann statistics reported for the smaller systems above, in combination with the interesting oligoalanine results, suggest that DA is a promising tool for efficiently exploring conformational spaces of biomolecules and exploring folding/unfolding processes of polypeptides.

Alanine↗

PubMed1990

Identification of calmodulin-binding proteins.

We have outlined and partially characterized a series of biotinylated calmodulin derivatives that may be useful in the study of calmodulin-binding protein expression, physical points of calmodulin-target interaction, and proteolytic mapping of related calmodulin-binding proteins. Biotinylated calmodulins offer several advantages as probes of protein-protein interactions. First, biotinylation can be directed to different amino acid residues. Second, biotinylation can be carried out under mild, near-physiological conditions, reducing the likelihood that conditions of protein modification would destroy biological function. Third, biotinylated proteins are stable, and reagents needed for their preparation and detection are relatively inexpensive. Fourth, the sensitivity of avidin-chromogenic enzyme systems is approaching that of radioactivity, with the added advantage that chromogens can be visualized in a relatively short time with respect to autoradiography. However, as with any protein modification procedure, one must be cautious when interpreting the results obtained with biotinylated proteins. For calmodulin-binding proteins, some interactions are impaired by modification of specific lysyl residues. On the other hand, interaction of biotinylated calmodulin with phosphodiesterase occurs, but this interaction may obscure recognition of the biotin residue by avidin. One approach to circumvent this problem is to have a series of site-directed biotinylated proteins available for use as outlined in this chapter. The choice of which agent to use is determined by the primary sequence of the protein of interest and whether any information is available concerning the effects of chemical modification on structure (i.e., acetylation experiments, modification of free sulfhydryls). In the absence of such information, an empirical approach can be taken. Photobiotin affords an easy means for biotinylation of proteins; however, the sites of modification are not always predictable. NHS-biotin derivatives are readily available and are relatively easy to use. Finally, one may wish to biotinylate the protein while liganded to its normal interacting molecule, in the case of calmodulin, calcium ion is the obvious choice. However, calmodulin could also be biotinylated while bound to a specific binding protein such as calcineurin. The latter method may be of use in determination of changes in reactivities of specific amino acid residues subsequent to binding. Finally, it may prove advantageous to biotinylate genetically engineered calmodulin, yeast calmodulin, or plant calmodulin to further define calmodulin-target protein interactions. Thus, the use of biotinylated calmodulin derivatives may offer insights into a range of structural and functional questions relevant to regulation of specific calmodulin-binding proteins.

Alkaline Phosphatase↗

PubMed1991

Approaches to minimizing interference by cross-reacting molecules in immunoassays.

Here we review techniques useful in eliminating or reducing interferences caused by molecules that cross-react in immunoassays. The biochemical rationale for using these techniques is discussed. Examples are taken from recent studies aimed at reducing interferences caused by endogenous molecules such as digoxin-like immunoreactive factors or steroid hormones. In this context the role of protein-binding of cross-reacting molecules is also considered. Immunoassay ligand selectivity can be inherently limited by the heterogeneity of the antigenic response or by the structural similarity of epitopes on multiple ligands. Certain empirical approaches have proved useful in maximizing the analytical specificity of immunoassays. These approaches include isolating the relevant ligands before immunoassay, adjusting the kinetic or equilibrium conditions used during the assays, and developing more specific antisera. The physicochemical properties of the cross-reacting molecule best dictate which technique(s) to use. The approaches discussed here are general and apply to minimizing interference caused by a wide variety of both endogenous and exogenous cross-reacting molecules.

Antibody Specificity↗

PubMed1980

[Inhibitors of folic acid metabolism (author's transl)].

In contrast to antibiotic research, the study of folic acid metabolism and folic acid antagonists is conducted in the classical tradition of chemotherapy established by Paul Ehrlich. The elucidation of the mechanism of action of sulphonamides created an important prerequisite for the understanding of the biosynthesis of folic acid. The synthesis of inhibitors of dihydrofolate-reductase was guided on the one hand by the structure of dihydrofolate itself, and on the other hand by the fact that this substnce is essential for the growth of certain bacteria. Both approaches led to the synthesis of compounds which were effective and could be used therapeutically. The mechanism of selectivity of folic acid antagonists is described. A short account of the biochemical and genetic basis of resistance to folic acid antagonists is also given. The study of folic acid metabolism and folic acid antagonists provides a good example of the successful interaction of mechanistically inspired biochemical and chemical methods on the one hand, and an empirical approach characterised by the study of more complex biological phenomena on the other hand.

Folic Acid↗

PubMed1994

Pulmonary infiltrations in febrile patients with neutropenia. Risk factors and outcome under empirical antimicrobial therapy in a randomized multicenter study.

BACKGROUND: Different empirical approaches to antimicrobial treatment of lung infiltrates in patients with neutropenia were studied within a prospective, randomized multicenter trial. METHODS: Patients with neutropenia with hematologic malignancies and fever of 38.5 degrees C or higher associated with newly diagnosed lung infiltrates were randomized for an initial therapy with acylaminopenicillin plus aminoglycoside (Group A), third-generation cephalosporin plus aminoglycoside (Group B), or the double beta-lactam combination (Group C), each in combination with rifampin. Nonresponders were given empirical amphotericin B plus 5-fluorocytosine beginning on day 4, day 5, or day 6 under study. RESULTS: Of 295 patients entered, 91.2% were evaluable. Complete response was obtained in 61.3% with no significant difference between treatment groups. The addition of rifampin did not improve treatment results. Only 27.1% of patients achieved a complete response by antibiotic therapy without additional antifungal therapy. Fungi dominated in cases of microbiologically documented infections and were associated with a poorer outcome compared with bacterial pneumonias. The trend of leukocyte counts under study had a highly significant effect on the outcome of infection. CONCLUSIONS: Lung infiltrates in febrile patients with neutropenia represent a high risk of treatment failure. Persistent neutropenia has a significantly adverse effect on the outcome of infection. Incorporation of systemic antifungal agents into first-line therapy, particularly in selected high-risk subgroups, might improve future treatment results. The quality of diagnostic techniques to establish the etiology of pulmonary infiltrates needs to be improved.

Adolescent↗

PubMed1990

Biopsychosocial elements of empathy: a multidimensional model.

Empathy is a topic of growing concern in a variety of disciplines. Although considerable empathy research is reported, often single dimensions of a multidimensional and multiphasic construct are actually being studied. Empathy is a unitary construct involving biopsychosocial components and is particularly well suited for nursing study because of its theoretical congruence with nursing philosophy and concerns. Empathy's importance goes beyond the usual emphasis on helper empathy. Although commonly associated with prosocial behavior, empathy involves underlying processes which may be used for either positive or negative social purposes. Recent technological improvements in research methodology, concerns regarding social violence, and conceptual shifts have led to greatly increased interest in the phenomenon of empathy and an expanded research thrust. One major recent change in empathy research is the tendency to view the phenomenon as multidimensional and consequently to include a variety of measures to capture different elements of the construct. This paper reviews the major approaches to measurement of empathy and classifies these approaches according to the dimensions of empathy that they measure. Physiological change in association with empathy is less frequently measured, but because empathy is commonly assumed to include an emotional response to another, concomitant physiological changes should accompany the emotional aspect of empathy and indicators of physiological response may be appropriate measures to include in nursing studies of empathy. A conceptualization of empathy is presented that considers empathy to be a multidimensional phenomenon, with emotional, cognitive, communicative, and relational components. Because empirical approaches can only examine the most easily measured aspects of empathy, phenomenological approaches are also needed to begin to capture the total construct.

Cognition↗

PubMedDate not supplied

Quitting smoking.

Four factors which influence smoking treatment outcome are identified: environmental variables, client characteristics, process variables, and specific treatment approaches. Important environmental factors are stress and social support. Of client characteristics, sex is the best predictor of treatment success. Men are more likely to quit and maintain abstinence than women. However, the majority of women alter their smoking habits during pregnancy. Low-income persons and ethnic minorities are underrepresented among subjects in treatment studies and have larger percentages of smokers in the population at large. Extraverted smokers are more likely to begin to smoke and have difficulty quitting. Also, the more anxious, poorly adjusted smoker has more trouble quitting than the less troubled smoker. The higher the client's sense of self-efficacy, the better the chance of that person entering treatment and doing well. Furthermore, smokers who take in lower levels of nicotine are more successful at quitting. Many process questions are suggested. Few have been approached empirically. The effectiveness of ex-smokers as therapists in smoking cessation programs has not been systematically investigated, even though the smoking history of therapists is a question frequently asked by clients. We suggest that the skill and empathy of group leaders is more important than smoking history. Smoking therapists should be aware of nonspecific treatment factors such as positive expectations, social reinforcement, and self-disclosure which may have a powerful influence on the efficacy of smoking treatment. Specific treatment approaches were classified into three categories: low-contact approaches, including educational, self-help, and minimal treatment approaches; psychological treatments; and pharmacological treatment. Education, self-help, and minimal treatment approaches are thought to be accretively effective when the large size of the audience is considered. Also, innovative treatments which address the influence of social support systems and physiological addition are promising treatments for individuals requiring a structured or intensive method of quitting.

Black or African American↗

PubMed2001

Pain in nursing home residents: management strategies.

Pain is prevalent and undertreated in nursing home residents, despite the existing wide array of effective pharmacological and nonpharmacological treatment modalities. In order to improve the quality of life of these vulnerable individuals, practitioners require education about the correct approach to assessment and management. Assessment should be comprehensive, taking into account the basic underlying pathology (e.g. osteoarthritis, osteoporosis, peripheral neuropathy, fibromyalgia, cancer) as well as other contributory pathology (e.g. muscle spasm, myofascial pain) and modifying comorbidities (e.g. depression, anxiety, fear, sleep disturbance). Pharmacological management should be guided by a stepped-care approach, modelled after that recommended by the World Health Organization for treatment of cancer pain. Nonopioid and opioid analgesics are the cornerstone of pharmacological pain management. Tricyclic antidepressants and anticonvulsants can be very effective for the treatment of certain types of neuropathic pain. In addition to treating the pain per se, attention should be given to prevention of disease progression and exacerbation, as maintaining function is of prime importance. Nursing home residents with severe dementia challenge the practitioner's pain assessment skills; an empirical approach to treatment may sometimes be warranted. The success of treatment should be measured by improvement in pain intensity as well as physical, psychosocial and cognitive function. Effective pain management may impact any or all of these functional domains and, therefore, substantially improve the nursing home resident's quality of life.

Aged↗

PubMed2005

Microbial metabolomics: replacing trial-and-error by the unbiased selection and ranking of targets.

Microbial production strains are currently improved using a combination of random and targeted approaches. In the case of a targeted approach, potential bottlenecks, feed-back inhibition, and side-routes are removed, and other processes of interest are targeted by overexpressing or knocking-out the gene(s) of interest. To date, the selection of these targets has been based at its best on expert knowledge, but to a large extent also on 'educated guesses' and 'gut feeling'. Therefore, time and thus money is wasted on targets that later prove to be irrelevant or only result in a very minor improvement. Moreover, in current approaches, biological processes that are not known to be involved in the formation of a specific product are overlooked and it is impossible to rank the relative importance of the different targets postulated. Metabolomics, a technology that involves the non-targeted, holistic analysis of the changes in the complete set of metabolites in the cell in response to environmental or cellular changes, in combination with multivariate data analysis (MVDA) tools like principal component discriminant analysis and partial least squares, allow the replacement of current empirical approaches by a scientific approach towards the selection and ranking of targets. In this review, we describe the technological challenges in setting up the novel metabolomics technology and the principle of MVDA algorithms in analyzing biomolecular data sets. In addition to strain improvement, the combined metabolomics and MVDA approach can also be applied to growth medium optimization, predicting the effect of quality differences of different batches of complex media on productivity, the identification of bioactives in complex mixtures, the characterization of mutant strains, the exploration of the production potential of strains, the assignment of functions to orphan genes, the identification of metabolite-dependent regulatory interactions, and many more microbiological issues.

Bacteria↗

PubMed1999

Molecular design versus empirical discovery in peptide-based vaccines. Coming to terms with fuzzy recognition sites and ill-defined structure-function relationships in immunology.

In view of our increased understanding of the molecular basis of immunological recognition, it is commonly believed that it should be possible to apply molecular design strategies to the development of peptide-based vaccines. The stated aim is to transform the development of a vaccine from a trial and error empirical operation into a so-called rational, structure-based process. In the present review, it is argued that it is misleading to oppose rational and empirical approaches in vaccine research since both are needed in the practice of experimental science. Many reasons are given for the view that the molecular design of synthetic vaccines is not a realistic scientific enterprise. The capacity of a peptide to induce a protective immune response depends on many extrinsic factors and regulatory mechanisms of the recipient host which are not amenable to molecular design of the peptide immunogen. It seems safe to predict that the development of peptide-based vaccines will continue to be driven by empirical discovery rather than by so-called rational design.

Antigen-Antibody Reactions↗

PubMedDate not supplied

[West syndrome--new therapeutic approach].

West syndrome (WS) is an age dependent epileptic syndrome caused by various brain disorders. WS has been frequently classified in two groups, cryptogenic and symptomatic. As symptomatic WS consists of patients with numerous types of brain lesions, the prognosis and evolutional changes may be different among the types of brain lesions. WS is resistant to treatment to most conventional antiepileptic drugs, and only valproic acid, benzodiazepines, adrenocorticotropic hormone (ACTH), corticosteroids and vigabatrin have been found efficacious. Benzodiazepine, notably nitrazepam, and less clonazepam had been effective in bringing spasms under control but emerging tolerance and significant side effects (hypotonia and drowsiness) precluded its wider use. ACTH has been the treatment of choice for infantile spasms ever since Sorel and Dusaucy-Bouloye described its effectiveness in 1958. Despite the empirical approach steroids were capable of controlling the spasms and normalizing EEG in about 60% of cases. Corticotropin (ACTH) was used in doses from 5 to 180 I.U. daily, prednizolone 2-10 mg/kg daily, hydrocortisone 5-10 mg/kg daily and dexamethason 0.3-0.5 mg/kg. However, poor consensus was defined regarding the best steroid molecule to use, the dosage, and the duration of treatment. Also frequent and sometimes serious side effects have occurred during ACTH therapy, notably serious infections and hypertension that promoted continuous search for alternative and safer drugs tolerated outpatient treatment, good tolerance and minor side effects. Recently a specific visual field loss has been reported in treated adults that raised concern about safety of vigabatrin. New reports in children claim that vigabatrin treatment of children and adolescents has a lower risk for visual field defect than in adults, because of reported reversibility. Vigabatrin paediatric advisory group recommend the trial of vigabatrin for 12-14 days as first treatment for WS and in the case of good clinical response continuation of therapy for six months. Other new antiepileptic drugs (lamotrigine, topiramate, felbamate and zonisamide) have shown significant efficacy in the treatment of resistant WS to previous medication. The current task is to determine risk/benefit ratios of these two drugs (vigabatine, ACTH) and to delineate the group of patients with WS where their use would be optimal.

Humans↗