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PubMed1990

Teratogenicity of steady-state concentrations of etretinate and metabolite acitretin maintained in maternal plasma and embryo by intragastric infusion during organogenesis in the mouse: a possible model for the extended elimination phase in human therapy.

Etretinate (Tegison, Tigason), a retinoid used for the treatment of skin disorders such as psoriasis, was shown to teratogenic in the human. Because of the long terminal half-life of this drug (100 days), considerable plasma levels of etretinate and its main metabolite, etretin (acitretin), were observed for up to 2 years following discontinuation of therapy. We have therefore investigated, in a newly developed animal model, the potential teratogenic risk of such persisting levels of these aromatic retinoids. Etretinate was administered by intragastric infusion throughout organogenesis in the mouse (day 8-15) via subcutaneously implanted osmotic minipumps connected to external reservoirs containing oily solutions of the drug. Dose-dependent developmental effects were found, the fetal weight decreased and the resorption rate and incidence of major malformation increased. A dose of 0.84 mg/kg/day resulted in retinoid-specific defects, in particular shortening of the limbs and cleft palate. This low dose infused resulted in mean etretinate concentrations of 6.5 ng/ml maternal plasma and 12.5 ng/g embryo (measured on days 10 and 12 of gestation). The corresponding concentrations of the metabolite etretin were 38 ng/ml plasma and 95 ng/g embryo. Our results emphasize the high teratogenic risk of relatively low, persisting concentrations of etretinate and etretin such as those observed after discontinuation of human therapy, because the area of the concentration-time curve is likely to be the decisive parameter in regard to teratogenesis.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Do adjusted clinical groups eliminate incentives for HMOs to avoid substance abusers? Evidence from the Maryland Medicaid HealthChoice program.

The adequacy of risk adjustment to eliminate incentives for managed care organizations (MCOs) to avoid enrolling costly patients had been questioned. This study explored systematic differences in expenditures between beneficiaries with and without substance disorders assigned to the same capitation rate group under the Maryland Medicaid HealthChoice program. The investigators used fiscal year (FY) 1995 to 1997 Medicaid data to assign beneficiaries to rate cells based on FY 1995 diagnoses and compared the distribution of expenditures for beneficiaries with and without substance disorders, defined using FY 1997 and FY 1995 diagnoses. Results showed that differences in FY 1997 expenditures between beneficiaries with and without FY 1995 substance disorders were negligible. However, MCOs could expect greater average losses and lower average profits on beneficiaries with FY 1997 substance disorders. Thus, the adjusted clinical groups methodology used to adjust capitation payments in the HealthChoice program attenuated, but did not eliminate, financial incentives for MCOs to avoid substance abusers.

Adolescent↗
PubMed2004

Pathophysiology, diagnosis and treatment of food protein-induced gastrointestinal diseases.

PURPOSE OF REVIEW: Although our general understanding of food hypersensitivity has improved in recent years, gastrointestinal food protein-induced diseases still pose diagnostic and therapeutic dilemmas. RECENT FINDINGS: Food allergy in children and adults may involve any part of the gastrointestinal tract. Clinical presentations include protein-induced enterocolitis syndrome, enteropathy and proctocolitis, as well as eosinophilic gastroenteritis and related disorders. For many of these conditions, our understanding of the pathophysiology is incomplete. Manifestations are mostly non-IgE mediated, and skin prick testing and measurement of food-specific IgE antibody levels are of limited diagnostic value. Atopy patch testing may be of benefit in identifying food items associated with late-onset gastrointestinal reactions. A definitive diagnosis of gastrointestinal food allergy, however, still relies on formal food challenges. Depending on the clinical presentation, gastrointestinal biopsies may be required. In infancy, hypoallergenic formula or maternal elimination diets have been shown to effectively control the gastrointestinal manifestations of food allergies. Growth parameters and micronutrient levels need to be carefully monitored while on elimination diets for prolonged periods. In older children and adults with eosinophilic gastrointestinal disorders, the response to dietary restriction is variable. Corticosteroids may be required to control symptoms in those who failed to respond to hypoallergenic diets. In eosinophilic esophagitis, steroids can be administered topically in the form of swallowed aerosols. Leukotriene receptor antagonists and other novel therapies may be useful as steroid-sparing agents. SUMMARY: Early diagnosis and treatment of food protein-induced gastrointestinal diseases may prevent significant nutritional complications. Further research is needed to develop diagnostic tools for these mainly cell-mediated disorders.

Digestive System↗
PubMed1999

Discriminant analysis of event-related potential curves using smoothed principal components.

Principal component analysis enhanced by the use of smoothing is used in conjunction with discriminant analysis techniques to devise a statistical classification method for the analysis of event-related potential data. A training set of premedication potentials collected from adolescents with attention-deficit hyperactive disorder (ADHD) is used to predict whether adolescents from an independent subject group will respond to long-term medication. Comparison of outcome prediction rates demonstrates that this method, which uses information from the whole ERP curve, is superior to the classification technique currently used by clinicians, which is based on a single ERP curve feature. The need to administer an initial dose of medication to classify patients is also eliminated.

Adolescent↗
PubMed1979

A solid phase, sandwich-type radioimmunoassay for antithyroglobulin: elimination of false positive results and semiquantitative measurement of antithyroglobulin in the presence of elevated thyroglobulin.

Thyroid disorders can be associated with elevated concentrations of serum antithyroglobulin antibodies (anti-Tg) and/or thyroglobulin (Tg), but none of the available anti-Tg assays deals with anti-Tg measurements in the presence of abnormally high Tg levels. The competitive binding radioassay produces falsely elevated values for anti-Tg if serum Tg is elevated and either falsely elevated or depressed values if both Tg and anti-Tg are abnormally high. The falsely elevated anti-Tg values can be identified by measuring the formation of Tg[125I]anti-Tg complexes in the supernatant of the anti-Tg assay (supernatant assay). For screening purposes, we modified the original anti-Tg RIA into a solid phase, sandwich-type RIA. Anti-Tg in serum or standard is first bound to plastic cups coated with Tg and then quantitated by binding of [125I]Tg. This assay has a detection limit of 2 U/ml serum, intra- and interassay coefficients of variation of 9--15%, and a normal range of less than 2 U/ml. When sera with normal Tg concentrations were analyzed, the results for anti-Tg obtained by the competitive binding RIA and the new sandwich RIA were comparable as far as positives and negatives were concerned, and the numerical values for positive sera correlated moderately well (r = 0.79); the sandwich assay, in general, gave lower values for anti-Tg. The major advantages of the sandwich anti-Tg RIA are the elimination of false positive results and its applicability to sera containing high levels of both Tg and anti-Tg. In the latter case, the results indicate the level of free anti-Tg present, as opposed to antibody present in the form of Tg-anti-Tg complexes.

Antibodies↗
PubMed1991

Structural basis for the inactivation of the P54 mutant of beta-lactamase from Staphylococcus aureus PC1.

The crystal structure of a mutant protein of a class A beta-lactamase from Staphylococcus aureus PC1, in which Asp179 is replaced by an asparagine (P54), has been determined and refined at 2.3-A resolution (1 A = 0.1 nm). The resulting crystallographic R factor [formula: see text] are the observed and calculated structure factor amplitudes) is 0.181 for 12289 reflections with I greater than or equal to sigma (I) within the 6.0-2.3-A resolution range. The mutated residue is located at the C-terminus of an extensive loop (the omega-loop), remote from the active site, and results in a drastically reduced activity. Examination of the native and P54 structures reveals that the overall fold is similar, except that there is substantial disorder of the omega-loop of P54. This is a consequence of the elimination of a salt bridge between Asp179 and Arg164 that links the two ends of the omega-loop in native beta-lactamase. It is associated with a difference in side-chain conformation between Asn179 in P54 and Asp179 in the native structure. An alternate interaction occurs in P54 between Asn179 and Ala69, adjacent to the catalytic Ser70. This disorder affects catalysis since some of the disordered residues, in particular Glu166, form part of the active site.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonium Sulfate↗
PubMed2004

Reflecting on imagery: a clinical perspective and overview of the special issue of memory on mental imagery and memory in psychopathology.

The authors provide an overview of the papers in the special issue of Memory on mental imagery and memory in psychopathology. The papers address emotional, intrusive mental imagery across a range of psychological disorders including post-traumatic stress disorder (PTSD), agoraphobia, body dysmorphic disorder, mood disorders, and psychosis. They include work on information processing issues including modelling cravings, conditioning, and aversions, as well as imagery qualities such as vividness and emotionality. The overview aims to place the articles in a broader context and draw out some exciting implications of this novel work. It provides a clinical context to the recent growth in this area from a cognitive behavioural therapy (CBT) perspective. We begin with PTSD, and consider links to imagery in other disorders. The clinical implications stemming from this empirical work and from autobiographical memory theory are discussed. These include consideration of a variety of techniques for eliminating troublesome imagery, and creating healthy, realistic alternatives.

Anxiety Disorders↗
PubMed2006

[The personality change in epilepsy patients].

UNLABELLED: Personality disorders in epilepsy patients are frequent, and cause behaviour that is quite often troublesome for social environment of patients. The peculiarity of the clinical picture and mechanism of disorder formation has caused great interest. The term 'characteropathy in epilepsia patient', with characteristic viscosity as its important basic symptom, was eliminated from present medical terminology. Current worldwide international disease classification systems (DSM-IV and ICD-10) do not distinguish the separate form of personality disorders related to epilepsy. THE AIM: of the work is to analyse personality change in epilepsy patients on the basis of information from the patients and their relatives by means of the Adjective Check List (ACL) by Gough and Heilbrun, with taking into consideration the incidence of depression and the phenomenon of 'out-of-body experience'. MATERIAL AND METHODS: 40 patients with idiopathic generalized epilepsy with tonic - clonic seizures in age 19-55 years (mean 28 years) and 30 persons of age - matched control groups were examined. Each examined person and relative filled in ACL form two times in order to answer a question about the features of actual and premorbid patient's personality. The change of personality was evaluated according to ACL criteria and the psychoterapeutic criteria. In analysis were also taken into account the incidence of depression and the phenomenon of 'out-of-body experience'. RESULTS: The personality change in epilepsy patients was more frequent than in the control group and more frequent concerned need scales of ACL (endurance, deference, self- and others understanding, and aggression scale). In the grave epilepsy group considerable behavioral and interpersonal relationships change (more subordination tendency), features of dementia, and often phenomenon 'out-of-body experience' were observed. The range of personality change in the mild epilepsy group, like in control group, included the adaptation of family functioning principles to the patients' needs, the change of patients' emotional reaction and the meaning of life. In this group depression was often, but the phenomenon 'out-of-body experience' hardly ever appeared. CONCLUSIONS: The personality change in epilepsy patients was found in more than 80% of patients and concerned need scales of ACL (endurance, deference, self- and others understanding and aggression scale), and thematic scales (self ideal, self-control, and self-confidence scale). In the grave epilepsy group considerable behavioral changes, features of dementia, and often the phenomenon 'out-of-body experience' were observed. In the mild epilepsy group the changes were limited to alter of conviction and emotional response, often depression appeared, but hardly ever the phenomenon 'out-of-body experience' was observed.

Adult↗
PubMed1999

The psychotic patient.

Psychotic disorders are relatively rare in the primary care setting, compared with depressive and anxiety disorders, but patient suffering is significantly higher for patients with psychotic symptoms. Primary care physicians are assuming more responsibility for the area of these patients in today's managed care environment. The practitioner needs to eliminate medical, substance, and mood origins of the psychotic symptoms before assuming a patient has a psychotic disorder (e.g., schizophrenia). This article outlines a diagnostic and treatment approach for patients with psychotic symptoms who are managed in the primary care setting.

Algorithms↗
PubMed2004

Comparative pharmacodynamics and plasma concentrations of d-threo-methylphenidate hydrochloride after single doses of d-threo-methylphenidate hydrochloride and d,l-threo-methylphenidate hydrochloride in a double-blind, placebo-controlled, crossover laboratory school study in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: Methylphenidate has four optical isomers due to two asymmetries (erythro-threo and dextro-levo). The initial commercial formulation eliminated the erythro isomer, but the dextro-levo asymmetry was racemic, with equal amounts of d and l-threo isomers (d,l-MPH). Previous work has suggested that the d-threo isomer methylphenidate (d-MPH) rather than the l-threo isomer (l-MPH) is responsible for the clinical effects in children with attention-deficit/hyperactivity disorder (ADHD). This study compared the efficacy of acute equimolar doses of d-MPH and dl-MPH in reducing ADHD symptoms over an 8-hour period in a laboratory school setting and investigated the relationship of efficacy to plasma levels of MPH. METHOD: Thirty-two children with ADHD enrolled in this double-blind, placebo-controlled, crossover study, and 31 completed the study. On seven separate occasions separated by at least 6 days, the children received a single morning dose of d-MPH (2.5, 5, or 10 mg), d,l-MPH (5, 10, or 20 mg), or placebo and then were observed in a laboratory classroom setting for 8 hours. At specified intervals, blinded observers rated behavior, and the children performed a computerized math test. The plasma levels of MPH were related to the response to study medication. The safety profiles of the two formulations were compared. RESULTS: For both formulations, the responses to both MPH preparations were dose related, the plasma concentrations of l-MPH were negligible and of d-MPH were indistinguishable, and clinical efficacy was highly correlated with plasma concentrations of d-MPH. The efficacy of the d-isomer was equivalent to the racemic preparation in reducing ADHD symptoms and increasing academic productivity. CONCLUSIONS: The efficacy of MPH resides in the d-isomer. The elimination of the l-isomer does not diminish the efficacy of an acute dose of methylphenidate.

Administration, Oral↗
PubMedDate not supplied

Effects of thyroid dysfunction on prednisolone and prednisone interconversion and disposition in the rat.

The effects of thyroid dysfunction on the reversible metabolism and disposition of prednisolone and prednisone were examined in male Wistar rats. Hyperthyroid rats were produced by daily ip injections of 20 micrograms of I-triiodothyronine/100 g body weight for 6 days. Hypothyroid rats were obtained by providing 0.05% 6-propyl-2-thiouracil in drinking water ad libitum for 21 days. Rats were given 10 mg/kg of prednisolone or prednisone iv, blood samples were collected, and the steroids in plasma were assayed by HPLC. A recently developed pharmacokinetic model encompassing interconversion kinetics was applied. Unexpectedly, the hyperthyroid state increased the AUC (by 163%) of prednisolone (unlike in man) via reduced (66%) prednisolone elimination clearance (CL10), but also caused enhanced (101%) prednisone elimination clearance (CL20). The hypothyroid state increased the AUC (by 117%) of prednisolone via a 56% reduction in CL10 and a reduction in CL20. Prednisone formation of prednisolone (CL21) was about 13-fold greater than the reverse process (CL12), and both interconversion clearances were increased 20-40% by thyroid dysfunction. Experimental thyroid disorders thus alter prednisolone/prednisone pharmacokinetics in rats primarily by selective and sometimes unusual changes in elimination clearance rather than affecting the relative rates of steroid interconversion. Reversible metabolism is much less important in rats compared to man.

Animals↗
PubMed1992

Cerebrospinal-fluid neuropeptides: a biochemical subgrouping approach.

Cerebrospinal-fluid (CSF) corticotropin-releasing hormone, somatostatin, and thyrotropin-releasing hormone were measured by specific radioimmunoassays in 257 hospitalized psychiatry patients suffering from dementia disorders (n = 85), schizophrenia (n = 104), and mood and anxiety disorders (n = 39). Neurological controls (n = 29) were also investigated. Since there were large overlaps of the peptide levels across the nosological groups we subjected the dataset to a three-dimensional normal mixture distribution analysis. We obtained four biochemically separable clusters. Dementia disorders, but not the others, were heterogeneously distributed in these clusters but after eliminating the effects of age and illness duration this difference disappeared. No single clinical, psychological, or background variable emerged as a prominent correlate of the neuropeptide clusters. It is concluded that although CSF neuropeptide concentrations in psychiatric patient populations appear to be separable into distinct, normally distributed subgroups this distinction does not coincide with present nosological classifications.

Adolescent↗
PubMed2002

Apheresis of immune diseases and apheresis using immunological specificity.

It has been clearly shown that autoimmune diseases can be treated by apheresis by eliminating immune complexes, however, the effects of therapeutic apheresis are not limited to immune disorders. Almost all diseases are associated with immune systems. Immune systems can be regulated by advanced techniques of apheresis, including immunoadsorption and immunocytapheresis, removing immune effector molecules and various immune-associated cells selectively. Therefore, apheresis can be used as a nondrug treatment for many diseases. In addition, disease-associated proteins that cause disease or are produced in the course of diseases and accumulate in the body could be eliminated selectively by apheresis using the extremely powerful ability of the immune system to recognize polypeptide structures specifically and distinguish miniscale differences among molecules. In this article, we discuss the current status of treatment of immune diseases by apheresis and possible treatment approach of a variety of diseases by apheresis based on immune reactions.

Autoimmune Diseases↗
PubMed2005

[The fate of patients with very severe and chronic mental disorders when there is no psychiatric hospital: a case study].

The Eastern Townships (Estrie) is an area of Québec which has never had a psychiatric hospital and is thus an extreme example of deinstitutionalization. How can people with the most severe mental illnesses be cared for? Does this system have harmful consequences? The authors present a case study with both qualitative and quantitative data to elucidate their questions. They found 36 patients with very severe mental illness (prevalence 12,4/100 000). This region does not send its most severely ill patients outside and generally succeeds in providing them with care and services in a network of small and medium size residential facilities. On the other hand, the authors have also been able to identify a certain drift of patients towards the correctional system ; cases with double or triple diagnosis do not easily have access to care ; through lack of an alternative, patients with potentially chronic violence often are stuck in a hospital in short stay beds (prevalence 1,6/100 000). It thus appears possible to eliminate the use of a psychiatric hospital for patients with very severe mental disorders as long as they are provided with supervised and long term care facilities (need : 10-20 places/100 000).

Adolescent↗
PubMed1997

Synaptic elimination, neurodevelopment, and the mechanism of hallucinated "voices" in schizophrenia.

OBJECTIVE: After peaking during childhood, synaptic density in the human frontal cortex declines by 30%-40% during adolescence because of progressive elimination of synaptic connections. The characteristic age at onset of schizophrenia--late adolescence and early adulthood--suggests that the disorder could arise from irregularities involving this neurodevelopmental process. METHOD: A computer simulation of a speech perception neural network was developed. Connections within the working memory component of the network were eliminated on the basis of a "Darwinian rule" in order to model loss of synapses. As a comparison, neuronal cell death, also postulated as being linked to both neurodevelopment and schizophrenia, was simulated. The authors determined whether these alterations at low levels could enhance perceptual capacity and at high levels produce spontaneous speech percepts that simulate hallucinated speech or "voices." RESULTS: Eliminating up to 65% of working memory connections improved perceptual ability; beyond that point, network performance declined and speech hallucinations emerged. Simulating excitotoxic neuronal loss at low levels also improved network performance, but in excess it did not produce hallucinations. CONCLUSIONS: The model demonstrates perceptual advantages of selective synaptic elimination as well as selective neuronal loss, suggesting a functional explanation for these aspects of neurodevelopment. The model predicts that psychosis arises from a pathological extension of one of these neurodevelopmental trends, namely, synaptic elimination.

Auditory Perception↗
PubMed1998

[Incidence and elimination of false-negative results of ferritin determination].

Introduction of turbidimetric homogeneous immunoassays made the determination of plasma ferritin concentration wide-ranging available. However, high-dose hook effect or prozone effect occurring at samples with high ferritin concentration can lead to false-negative results. According to the authors, this phenomenon has considerable clinical significance, in patients with iron-overload disorders false-negative laboratory values may result in inaccurate diagnosis. The prozone effect can be eliminated by reaction kinetic analysis of measurements. The authors developed a neural network classification procedure based on artificial intelligence technology for the recognition of the reactions with differing kinetic flow, and made a computer software for helping the application of the classification system. False-negative results can be filtered using this new technology following the laboratory determination, thus sensitivity of plasma ferritin determination may become safe enough even in case of high concentration samples.

False Negative Reactions↗
PubMed1994

Effects of postural change on aspiration in head and neck surgical patients.

This study was designed to define the effects of postural change on liquid aspiration during videofluorographic examination of oropharyngeal swallow in head and neck surgical patients. Thirty-two patients were given two swallows of five different amounts of liquid barium as tolerated. When aspiration occurred, the patient's head and/or body position was changed, new posture being determined by the swallowing disorder identified as the cause of the aspiration. Postural techniques were successful in eliminating aspiration on at least one volume of liquid in 81% of these patients. Patients in all surgical groups were able to use postures with equal success. A variety of positions were used in each type of surgical patient, indicating that these patients exhibited a variety of swallowing problems. Results emphasize the importance of introducing postural techniques during the radiographic study of oropharyngeal swallow to facilitate safe oral intake of liquids.

Adult↗