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The state of the art of dysmorphology.

The art of dysmorphology is simply a more detailed historical and clinical evaluation of a potentially dysmorphic individual. It requires precise observation and collating of all physical features, followed by interpretation, categorization, and diagnosis. It also requires an understanding of morphogenesis combined with an appreciation of form. Clinicians who practice dysmorphology well have certain personality traits that aid them in their pursuit of a diagnosis. Dysmorphology is at its apex of clinical maturation, but scientific discoveries and technology have begun to explain how and why malformations arise and why syndromes vary. Nevertheless, expertise in dysmorphology remains a clinical skill attainable by all who desire it. This visual diagnostic modality is inexpensive and often quick. Continued emphasis in training of dysmorphology in genetic fellowship programs will be critical to producing well-balanced clinical geneticists.

Child, Preschool↗

State-of-the-art challenges for mental health services research.

BACKGROUND: Research-based, state-of-the-art services for people with serious mental disorders would consist of demonstrably effective treatments, organized synergistically, and financed in ways that create incentives to provide such treatment. While research exists in these domains of treatment, organization and financing, this research base contains significant gaps, and what is known frequently neither informs policy making nor enters practice. REVIEW: The NIMH services-research portfolio has identified successful patient-level and system-level interventions for people with serious mental disorders, but much of this research has yet to make its way into practice. Similarly, while we have made progress in asking "what is good care?", we have much less information about the answers to "what constitutes an adequate try?". Writing a prescription for an efficacious medication does not constitute an adequate trial of that medication. Similarly, offering people boring psychosocial rehabilitation programs does not constitute an adequate try of promoting recovery via rehabilitation services, but what does? Defining what constitutes an adequate try can be a way of allocating scarce resources or it can be a polite way of defining when a system gets to give up on someone. As state governments move to contract with managed care entities for services for Medicaid beneficiaries, one of the great contracting challenges is defining and monitoring the provision of what constitutes an adequate try. DISCUSSION: To obtain better value for our health care expenditures, we need to find ways to get what we know works into practice, whether we are contracting for services or deciding which clinical therapies to pursue. For example, problem-oriented family therapy has been shown to improve clinical outcomes for people with schizophrenia, yet such interventions are rare in practice. We also need to pay more attention to the quality of the clinical care actually being delivered - not what was prescribed, nor what the clinician was trained in, nor what the job description was, but what actually is occurring. Figuring out how to contract for and disseminate efficacious treatments so that they occur and are effective in real-world settings is critically important yet is a largely unexplored area of services research. We need to answer both "what is good care?" and "how do we get it to happen?".

Journal Article↗

State of the art in comparative cancer clinical trials.

In order to investigate the current state of the art in clinical cancer research, a survey of comparative cancer clinical trials was conducted using a MEDLINE literature search of the 6-month interval from July to December of 1985. Data were obtained primarily from the published abstracts. The major observations from the study are as follows. First, trials in cancer research are published in an extraordinarily wide range of journals covering most of the major medical specialties in addition to the many cancer specialty journals. Second, randomization is now used quite extensively. It is the predominant method of control in chemotherapy trials and in trials reported in cancer journals. However, its use is much less common in other specialties, especially surgery, so efforts to popularize randomization in these specialties would be beneficial. Third, sample sizes are highly variable, and the median sample size (96 patients) is too small to reliably detect and evaluate moderate treatment advances. Finally, our survey reveals that published trials show an inordinately large proportion of breakthroughs in treatment compared with the generally accepted view that only slow progress is being made in developing effective cancer treatments. Our view is that this result reflects the strong tendency to publish only studies with positive results. This hypothesis is supported by the fact that in nonrandom trials there tend to be more positive conclusions and an absence of a strong association between conclusions and sample size.

Clinical Trials as Topic↗

DNA 2000: International Symposium on the State-of-the-Art in Genetic Analysis, June 1-3, 2000, Boston, U.S.A.

DNA 2000, an international symposium on state-of-the-art genetic analysis, was held at the Back Bay Hilton in Boston, Massachusetts, on 1-3 June, 2000. Meeting highlights are described. The meeting was organized and sponsored by the California Separation Science Society (CaSSS; www.casss.org) and other co-sponsors including the Human Genome Organisation (HUGO). DNA 2000 brought together a group of specialists in DNA detection and analysis methods from around the world in a venue presenting not only new technologies but also their applications in candidate gene studies, molecular diagnosis, analysis of complex diseases, and even studying the origin and evolution of humans.

DNA↗

Inflammatory markers in nasal lavage fluid from Industrial Arts teachers.

Exposure to wood dust can cause allergic and nonallergic rhinitis. Inflammatory markers [cells, albumin, tryptase, and eosinophil cationic protein (ECP)] were examined in nasal lavage fluid (NAL) sampled from 24 Industrial Arts (IA) teachers exposed to wood dust and other irritants and from 24 control subjects. The IA teachers had more nasal complaints but they did not differ significantly from the controls regarding ECP concentration (median 4.1 and 4.7 micrograms/L, respectively), albumin concentration (median 30.7 and 20.7 g/L), and percentage of neutrophils (median 56 and 34) in NAL. Tryptase was not detected. No marked inflammation was thus found, but the albumin concentration was higher in subjects reporting nasal stuffiness. In the IA teachers, a relationship between the percentage of neutrophils and the number of classes during the working week was found (Spearman's rank correlation coefficient 0.53, p < 0.01) indicating a possibility of wood-dust-related inflammatory effects on the nasal mucosa.

Albumins↗

The art of medicine: seminars for practicing physicians.

Using a needs assessment based on a consumer opinion study, a series of seminars on "The Art of Medicine" was set up for medical staff in a large health maintenance organization. Taught by fifteen staff physicians who underwent a facilitator training program, the seminars focused on physician-patient relationships, with participants encouraged to reflect on successful interactions, particularly focusing on their own behavior. A syllabus included eleven observations for successful medical encounters, literature abstracts, and sample case studies. Qualitative evaluation indicated a positive response to the seminars, and further offerings on similar topics are planned.

Education, Medical, Continuing↗

State-of-the-art of the production of retroviral vectors.

Retroviral vectors are still the vectors that are used in the majority of gene therapy trials for treatment of acquired or inherited diseases. In this review, the present state-of-the-art of the production of retroviral vectors and the most important parameters, such as the choice of the producer cell line, stability issues, medium additives, serum, type of bioreactor, that influence production issues is presented and discussed in light of an optimal vector production. The available literature data clearly indicate that, on one hand, the choice of the producer cell line is of utmost importance for obtaining a high level producer cell line, and that, on the other hand, the optimization of the medium, e.g. the replacement of glucose by fructose, has a potential for improving vector production rates and titers. Finally, the use of high-density perfusion culture systems for adherent as well as for suspension cells presents the best choice for a production system, because high cell densities imply high reactor specific production rates, which must be associated with a rapid harvest of the produced vector, thus avoiding vector inactivation due to an extended residence time. The overall optimization of the cultivation and production parameters will have a significant impact on the use of retroviral vectors for gene therapy purposes.

Animals↗

Focal nodular hyperplasia: lesion characteristics on state-of-the-art MRI including dynamic gadolinium-enhanced and superparamagnetic iron-oxide-uptake sequences in a prospective study.

PURPOSE: To image a cohort of patients with pathology-proven focal nodular hyperplasia (FNH) to assess which characteristics of state-of-the-art magnetic resonance imaging (MRI) of the liver are the most useful for improving the detection and characterization of FNH. MATERIALS AND METHODS: In 14 patients, pathology-proven FNH (N=33) were prospectively examined using gadolinium (Gd) and superparamagnetic iron-oxide (SPIO) contrast media. All lesions were evaluated for signal intensity (SI), fatty infiltration, central scar, mode of enhancement with Gd, and uptake of SPIO. The percentage of dynamic contrast enhancement in the arterial, portal, and delayed phases was assessed. The contrast-to-noise ratio (CNR) before and after administration of SPIO contrast was calculated. RESULTS: The SI of the lesions was low to isointense on T1-weighted (T1W) images, and intermediate to isointense on T2W images. Fatty infiltration of the lesions was present in 6%. The percentages of enhancement in the liver and lesion were 110%, 115%, and 95%, and 151%, 182%, and 160%, respectively (P<0.0001). All lesions showed uptake of SPIO with improved conspicuity of the central scar and septa. The CNR values precontrast and post-Gd/SPIO were significantly different for T1 in- and opposed-phase and black-blood echo-planar imaging (BBEPI). CONCLUSION: Combining dynamic Gd-enhanced imaging with T1W and T2W sequences after administration of SPIO facilitates comprehensive evaluation of FNH.

Adult↗

Identification of indigoid dyes in natural organic pigments used in historical art objects by high-performance liquid chromatography coupled to electrospray ionization mass spectrometry.

Pigments are among the most important components of historical paintings and textiles and their nature provides the unique character of color. They can be divided into two main groups: inorganic and organic, extracted from plants or animals. Their identification is a necessary stage in the conservation of art objects. Reversed-phase liquid chromatography with electrospray ionization mass spectrometry (ESI-MS) and UV/visible spectrophotometric methods were elaborated for the identification of indigoid (indigo, indirubin, isoindigo, isoindirubin) color components of natural dyestuffs and their natural or synthetic precursors (indican, isatin, indoxyl, 2-indolinone). ES-MS offers detection limits in the range 0.03-5.00 microg ml(-1) for the color compounds examined. The method developed made it possible to identify indigo and its isomers in genuine Indian indigo, indigo from woad and Tyrian Purple. It was applied to the identification of natural dyes on fiber from a 19th century Japanese tapestry, 'Cranes in the landscape'. A procedure based on freezing and grinding of a sample before the extraction of dyes from the textile was developed. The components of the extract obtained were identified after acidic hydrolysis as indigotin and methylene blue.

Chromatography, High Pressure Liquid↗

State of the Art and Future Needs in Cytogenetic/Molecular Genetics/Arrays in childhood lymphoma: summary report of workshop at the First International Symposium on childhood and adolescent non-Hodgkin lymphoma, April 9, 2003, New York City, NY.

BACKGROUND: A significant number of studies describe the cytogenetics and molecular genetics of adult non-Hodgkin lymphoma (NHL); however, similar knowledge is lacking regarding pediatric NHL. METHODS: A workshop to discuss the "State of the Art and Future Needs in Cytogenetic/Molecular Genetics/Arrays" in pediatric NHL was held in conjunction with the First International Symposium on Childhood and Adolescent Non-Hodgkin Lymphoma on April 9, 2003 in New York City. RESULTS: Cytogenetic characteristics of pediatric NHL include 14q11.2 rearrangements in T-cell lymphoblastic leukemia/lymphomas (LBL), ALK rearrangements in anaplastic large cell lymphomas (ALCL), and CMYC translocations in both Burkitt and Burkitt-like lymphomas (BL/BLL). Pediatric diffuse large B-cell lymphoma (DLBCL) is cytogenetically different from DLBCL in adults, suggesting a different disease in children. Microarray studies demonstrate three types of T-cell leukemia, the leukemic counterpart of LBL, that block T-cell differentiation at different stages of T-cell development, corresponding to LYL, TAL1, and HOX-expressing leukemias. ALCL cell lines have a unique expression profile compared to normal T-cells. Germinal centers of BL have CMYC expression signatures, indicating that CMYC expression is ectopic and does not reflect the physiology of the normal cell counterpart. CONCLUSIONS: Additional cytogenetic, molecular and microarray investigations of NHL in children are vital to better understand these diseases, their etiology, and differences from adult NHL. A greater understanding of pediatric NHL will lead to disease-specific and patient-individualized therapies of these diseases.

Adolescent↗

Direct infusion mass spectrometry as a fingerprint of protein-binding media used in works of art.

A direct infusion mass spectrometry method for the characterization of proteinaceous glues from binding media used in pictorial works of art prior to conservation or restoration treatment is proposed. Amino acids are released by acid hydrolysis and dissolved in a mixture of acidic water and ethanol. This mixture is directly infused into a mass spectrometer without any derivatization. The mass spectrometer is operated in positive ion electrospray mode (ESI-MS) to yield [M+H](+) ions for the amino acids. Relative amounts of each amino acid are calculated for each protein (beef and porcine gelatines, albumin, casein and egg). The analyzed proteins were satisfactorily distinguished. The method is easy and fast, and shows good sensitivity and resolution. The proposed method has been successfully applied to artistic samples from items of the cultural heritage of Valencia (Spain).

Adhesives↗

Multiple chemical sensitivity: state of the art symposium. The role of chemical allergens.

Multiple chemical sensitivity (MCS) has been defined as "an acquired disorder of recurrent symptoms, referable to multiple organ systems, occurring in response to chemically unrelated compounds at doses far below those established in the general population to cause harmful effects" [Cullen, State Art Rev. Occup. Med. 2, 655 (1987)]. The pathophysiologic basis for the MCS syndrome has not been clearly defined. However, allergic reactions to specific chemicals encountered in the environment are much better understood.

Allergens↗

Antifungal therapy--state of the art at the beginning of the 21st century.

The most relevant information on the present state of the art of antifungal chemotherapy is reviewed in this chapter. For dermatomycoses a variety of topical antifungals are available, and safe and efficacious systemic treatment, especially with the fungicidal drug terbinafine, is possible. The duration of treatment can be drastically reduced. Substantial progress in the armamentarium of drugs for invasive fungal infections has been made, and a new class of antifungals, echinocandins, is now in clinical use. The following drugs in oral and/or intravenous formulations are available: the broad spectrum polyene amphotericin B with its new "clothes"; the sterol biosynthesis inhibitors fluconazole, itraconazole, and voriconazole; the glucan synthase inhibitor caspofungin; and the combination partner flucytosine. New therapy schedules have been studied; combination therapy has found a significant place in the treatment of severely compromised patients, and the field of prevention and empiric therapy is fast moving. Guidelines exist nowadays for the treatment of various fungal diseases and maintenance therapy. New approaches interfering with host defenses or pathogenicity of fungal cells are being investigated, and molecular biologists are looking for new targets studying the genomics of pathogenic fungi.

Animals↗

Performance comparison of a state-of-the-art neuro-SPET scanner and a dedicated neuro-PET scanner.

The physical performances of two current state-of-the-art scanners dedicated to functional imaging of the brain, one a single-photon emission tomography (SPET) scanner and the other a positron emission tomography (PET) scanner, have been compared under identical conditions. The aim of the study was to compare the capabilities of the devices under conditions resembling the routine clinical environment, as well as to consider other issues such as radiation burden for some common investigations. Both systems have slightly less than 11-cm axial fields of view. The PET system can be operated in a septa-less (3D) mode as well as conventionally with septa (2D). The spatial resolution of both devices was less than 8 mm in all dimensions in scattering media. On average, the PET scanner's resolution was approximately 10%-15% better than the SPET system. Energy resolution on the SPET system was superior due the scintillator used [NaI(Tl)]. Sensitivity in air with a line source on the PET system was found to be approximately 150 times greater in 3D and approximately 25 times greater in 2D than with the SPET system. A normal subject was studied on each system in an attempt to obtain the highest quality data possible for a subjective comparison. It is clear that, while PET retains the advantages of more desirable radiopharmaceuticals and higher sensitivity, the quality obtainable from SPET devices has improved markedly. SPET may prove as useful for many clinical investigations.

Brain↗

Work-related respiratory problems in industrial arts teachers.

Because of reports of respiratory complaints in Swedish industrial arts (IA) teachers, a cross-sectional study was performed on 130 IA teachers in Stockholm to study the relationship between the work environment and health, and especially the aforementioned complaints. One hundred and twelve other school employees served as control subjects. Sex, age, and smoking habit distribution were similar in the two groups. All subjects answered a questionnaire about their health problems, and the IA teachers answered questions about their work environment. The work environment consisted of many old and neglected workshops (hereafter called shops). Compared to the control subjects, the IA teachers had more complaints in respect of the skin, eyes, nose, throat, and lower airways--including chronic bronchitis (OR 12.4, 95% confidence interval 2.95-110.5). A higher occurrence of symptoms existed in shops with bad ventilation and dust-spreading machines and in shops where dust-spreading cleanup methods were used. A suspected interaction between smoking and work environment was noted for some symptoms, especially impaired smell and chronic bronchitis. In conclusion, several factors in the work environment were identified as risk factors for health. Identification of these risk factors should result in a program to reduce the health problems in the work environment.

Adult↗

The legitimacy of clinical knowledge: towards a medical epistemology embracing the art of medicine.

The traditional medical epistemology, resting on a biomedical paradigmatic monopoly, fails to display an adequate representation of medical knowledge. Clinical knowledge, including the complexities of human interaction, is not available for inquiry by means of biomedical approaches, and consequently is denied legitimacy within a scientific context. A gap results between medical research and clinical practice. Theories of knowledge, especially the concept of tacit knowing, seem suitable for description and discussion of clinical knowledge, commonly denoted "the art of medicine." A metaposition allows for inquiry of clinical knowledge, inviting an expansion of the traditional medical epistemology, provided that relevant criteria for scientific knowledge within this field are developed and applied. The consequences of such approaches are discussed.

Decision Making↗

The force module for the bending art system. Preliminary results.

The force module for the bending art system (BAS) is used to calculate the initial forces and moments expected to act on a tooth after changing arch wires. The present study analyses the accuracy of the force module on the basis of 10 patients treated with the BAS (with an average observation period of 10 months). An average of 6 arch wires (0.16" x 0.016" steel) were used on each jaw. The approximate pressure in the periodontium was determined and statistically evaluated from the force module readings. The resulting average pressure values for the molars ranged between 0.26 N/cm2 and 0.54 N/cm2. The value in the area of the incisors, cuspids and bicuspids ranged between 1.03 N/cm2 and 2.83 N/cm2. Maximum pressure was 8.02 N/cm2. The results are discussed from a clinical point of view on a case-to-case basis. They are plausible in and for themselves. The more severe the initial state of misalignment, the higher the pressure values. These forces can be reduced by increasing the number of arch wires or by altering the form of the archwire correspondingly. The computer-generated values should be confirmed by taking a direct measurement on the tooth. The force module is just the first step in providing a reproducible estimation of the forces acting on a tooth. Even if the calculated absolute values should still be judged with reservation, they are nevertheless suitable for providing a comparative evaluation of various treatment concepts with reference to the forces acting on the periodontium and can serve clinicians as a rapidly available decision-making aid.

Adolescent↗

Bending and torquing accuracy of the bending art system (BAS).

With the bending art system (BAS) the computerized production of individual arch wires has become possible. The BAS consists of an intraoral camera, a computer program and a bending machine producing the archwire by consecutive bending and twisting procedures. This study examines the accuracy of the bending machine when using 0.016" x 0.016" and 0.016" x 0.022" steel wire of rectangular cross-section. Bending angles ranging from 6 degrees to 54 degrees, and torsion angles ranging from 2 degrees to 35 degrees were tested; also the minimum distance between these individual operations was determined. The bent pieces of wire were analysed in a 3D-coordinate gauging system. The 0.016" x 0.016" steel wire showed a mean measuring error of 0.62 degree in bending procedures and of 0.72 degree in torsion procedures, whereas the 0.016" x 0.022" steel wire showed an error of 0.87 degree with edgewise bendings and of 0.86 degree with torsions. To ensure this accuracy a minimum distance of 0.5 mm to 0.7 mm, depending on which kind of bending combination is used, between bending and torsion is required. The error could be reduced even further if a more constant wire material and a more accurate calibration of the bending machine were used. All in all the precision of the bending machine meets the clinical requirements.

Computer-Aided Design↗