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PubMed2004

Development of light ion therapy at the Karolinska Hospital and Institute.

Recent developments in radiation therapy have made it possible to optimize the high dose region to cover almost any target volume and shape at the same time as the dose level to adjacent organs at risk is acceptable. Further implementations of IMRT (Intensity Modulated Radiation Therapy), and inverse treatment planning using already available technologies but also foreseeable improved design of therapy accelerators delivering electron- and photon beams, will bring these advances to the benefit of a broad population of cancer patients. Protons will therefore generally not be needed since in most situations the improvement will be insignificant or moderate due to the large lateral penumbra with deep proton therapy. A further step would be to use He-ions, which have only half the penumbra width of protons and still a fairly low-LET in the spread-out Bragg peak. There is however still a group of patients that cannot be helped by these advances as the tumor might be radioresistant for the presently utilized low ionization density beam qualities. The ultimate step in the therapy development process should therefore be to optimize the beam quality for each tumor-normal tissue situation. To facilitate beam quality optimization light ions are needed. It is argued that in many radioresistant tumors a dose-mean LET of 25-50 eV/nm in the target would be optimum as then tumor cells will be lost in the highest proportion through apoptotic cell kill and the superficial tissues will still be irradiated with a fairly low LET. Light ions using Li, Be, B, and C would then be the ideal choice. In this paper a light ion facility is outlined for the Karolinska University Hospital facilitating both dose distribution and beam quality optimization.

Humans↗
PubMed2002

Pathogenesis of bone erosions in rheumatoid arthritis.

Focal marginal joint erosions represent the radiographic hallmark of rheumatoid arthritis (RA). These bone changes are characteristically localized to the joint margins, but in addition, regions of focal bone resorption can be detected in the subchondral bone adjacent to the bone marrow space into which the synovial inflammatory tissues have extended. Because progressive destruction of the periarticular bone contributes significantly to joint dysfunction and disability in patients with RA, there is considerable interest in developing a better understanding of the pathologic mechanisms involved in this process and in developing therapies that can arrest these events. Previous analysis of joint tissues from patients with RA have provided morphologic evidence that osteoclasts are the cell types that mediate the focal bone resorption associated with the rheumatoid synovial lesion. Additional recent data from animal models have helped to further implicate these cells in the pathogenesis of focal bone erosions. Furthermore, analysis of RA synovium and joint tissues from animal models of inflammatory arthritis, as well as cell and tissues culture studies, have helped to define the cytokines and inflammatory mediators that are involved in the recruitment and activation of bone resorbing cells associated with focal bone erosions. These findings provide a rational framework for developing targeted therapies that can specifically inhibit or slow the progressive focal bone destruction associated with the rheumatoid synovial lesion.

Animals↗
PubMed2004

New developments in levodopa therapy.

More than 30 years after its development, levodopa is still the most effective treatment for the symptomatic control of Parkinson's disease (PD). Although a number of therapies have been developed in an attempt to improve PD management, such as dopaminergic agonists and inhibitors of COMT and MAO-B, most patients still depend on levodopa alone because of its superior ability to control PD symptoms. The issue of toxicity has been raised by in vitro studies suggesting that levodopa might be toxic to dopaminergic neurons, but this has since been answered by in vivo studies finding no evidence of toxicity and possibly even neurotrophic-like effects. A more pressing concern regarding levodopa is its association with the development of motor complications after long-term use. Pulsatile dopaminergic stimulation as a result of erratic absorption and the short half-life of levodopa have been central issues in attempts to explain this occurrence. Evidence suggests that altering the delivery of levodopa to provide a more continuous supply of this drug to the brain may result in improved control of PD symptoms.

Drug Administration Schedule↗
PubMed2001

The effects of repeated antenatal glucocorticoid therapy on the developing brain.

Antenatal glucocorticoid (GC) therapy improves infant outcome following preterm birth. As approximately 50% of women given a first course of antenatal GCs remain undelivered 7-14 d later, many clinicians administer further courses. GCs are known to be neurotoxic and there is concern that exposure during early development may have adverse effects on the immature brain. The aim of this investigation was to compare magnetic resonance (MR) indices of brain maturation in infants exposed to repeated antenatal GC therapy and born at or close to term, with non-GC exposed control infants. MR images were obtained during quiet sleep without sedation. T1 weighted volume images were obtained in the sagittal plane and T1, T2 weighted spin echo and inversion recovery images in the transverse plane. Brain volume and surface area were calculated from segmented image slices, and a measure of the complexity of cortical folding, the whole cortex convolution index (WCCI), from computerized analysis of a vector coded contour following algorithm. Analysis of covariance was used to compare the two groups after allowing for the effect of postmenstrual age. There were 10 infants in the GC group (range of antenatal GC exposure, 3-11 courses) and 6 controls. Each GC course comprised two 12-mg IM doses of betamethasone 24 h apart. GC exposed infants had a significantly lower WCCI (p = 0.001) and smaller surface area (p = 0.02), after allowing for postmenstrual age. There was no significant difference in brain volume (p = 0.5). Repeated antenatal GC exposure results in measurable differences in brain maturation when compared with gestational age matched non-GC exposed controls. The clinical relevance of these observations is not known.

Betamethasone↗
PubMed2002

Therapy planning for school-age children who stutter.

This article offers principles to consider in developing therapy plans for school-age children who stutter. Goals of speech therapy should be individualized, educationally relevant, and lead to functional outcomes that last. Skills and experiences gained through speech therapy should help children communicate effectively and develop positive attitudes about themselves as communicators. A variety of collaborative planning tools are presented to help IEP team members prioritize needs based on relative importance of behavioral, cognitive, and affective aspects of the stuttering problem from the perspective of the child, parents, and teachers. Strategies are included for overcoming some of the specific challenges inherent in therapy planning and goal setting for this population.

Child↗
PubMed1979

Systematic curricular development in physical therapy.

A three-year, federally funded competency-based education project has been completed at The Ohio State University, School of Allied Medical Professions. Six allied health divisions cooperated in the project: Physical Therapy, Medical Communications, Medical Dietetics, Medical Record Administration, Medical Technology, and Radiologic Technology. The purpose of the project was to have the six ongoing programs adapt an established, systematic process to plan for and develop curricular revisions. Professional roles and competencies were delineated as a basis for establishing performance criteria and instructional strategies. The materials that the Division of Physical Therapy developed and the processes that were used in conjunction with this project are described.

Competency-Based Education↗
PubMed1987

Influence of radiation therapy on oral Candida albicans colonization: a quantitative assessment.

An increase in quantity of oral Candida albicans was documented in patients receiving head and neck radiation therapy during and after therapy, as assessed by an oral-rinse culturing technique. The amount of the increase was greater in denture wearers and directly related to increasing radiation dose and increasing volume of parotid gland included in the radiation portal. A significant number of patients who did not carry C. albicans prior to radiation therapy developed positive cultures by 1 month after radiation therapy. The percentage of patients receiving head and neck radiation therapy who carried C. albicans prior to radiation therapy did not differ significantly from matched dental patient controls.

Candida albicans↗
PubMed2003

Predictors of long-term adherence to pelvic floor muscle exercise therapy among women with urinary incontinence.

This study assessed predictors of long-term adherence to pelvic floor muscle exercise (PFME) therapy including a health education programme among women with urinary incontinence. Sequential multiple regression analyses revealed several significant predictors that predicted 50% of variance in long-term adherence behavior. Short-term adherence significantly predicted long-term adherence. Further, women with frequent weekly wet episodes before and 1 year after therapy were more likely to have high adherence levels 1 year after therapy than women with fewer weekly losses. Thus, women seemed to adapt long-term adherence behavior to their symptoms. Adherence to PFME therapy was very high. The protocol checklist for the PFME therapy developed to standardize treatment among physiotherapists had structured therapy content, which may have optimized adherence behavior in this study. Implementation of this protocol checklist in clinical guidelines is suggested.

Aged↗
PubMed1987

Efficacy of teicoplanin in experimental group B streptococcal bacteremia and meningitis.

We evaluated the activity of teicoplanin against a type-III group B streptococcal strain in vitro and in vivo and compared the results with those of penicillin G. In vitro, the minimal inhibitory and minimal bactericidal concentrations of teicoplanin were 2- to 4-fold greater than those of penicillin G. In vivo studies were carried out with an experimental bacteremia and meningitis model in newborn rats. Eighty-one infected animals were randomized to receive teicoplanin 5, 10 or 20 mg/kg, twice daily, or penicillin G 50 or 200 mg/kg, twice daily, or saline (0.05 ml), twice daily. The mean serum levels of teicoplanin were maintained above 100 X the minimal bactericidal concentration for 7-8 h even with a dose of 5 mg/kg. The mean penetration of teicoplanin into the cerebrospinal fluid was estimated as 2.4-8.2% of those of concomitant levels in serum. The overall efficacy of teicoplanin was similar to that of penicillin G as judged by mortality rates. However, two bacteremic animals which were free of meningitis at the beginning of therapy developed this complication during 4 days of teicoplanin therapy, in contrast with none in the penicillin group. Further studies are needed to understand the reason(s) for these failures with teicoplanin therapy.

Animals↗
PubMedDate not supplied

Cerebral hemorrhage from a mycotic aneurysm developing during appropriate antibiotic therapy.

A patient with bacterial endocarditis had headaches, cerebrospinal fluid pleocytosis and normal cerebral angiograms. Fifteen days later, while on appropriate antibiotic therapy, he developed an intracerebral hematoma due to a mycotic aneurysm. Mycotic aneurysm is an infrequent but serious complication of bacterial endocarditis. An aneurysm should be considered whenever a patient with bacterial endocarditis has neurologic symptoms even when the patient is receiving antibiotics.

Adult↗
PubMedDate not supplied

Historical perspectives on women and mental illness and prevention of depression in women, using a feminist framework.

This article discusses Showalter's (1985) description of the historical perspectives of how women have been viewed in the culture and how these perspectives have influenced women's past treatment for mental illness. Using Caplan's (1974) level of prevention in health care and a feminist framework, suggestions are made for prevention or alleviation of depression in women in the contemporary culture. In The Female Malady, Showalter (1985) described three themes that were prevalent through three historical phases of English psychiatry: psychiatric Victorianism (1830-1870), psychiatric Darwinism (1870-1920), and psychiatric Modernism (1920-1980). Showalter described how the prevailing attitudes toward the mentally ill, and toward women in particular, were influenced by the social changes of each historical phase and how these attitudes affected the thinking and treatment used by the psychiatrists. The problems that these historical perspectives have caused for women are discussed. A feminist view of depression is given in which depression is equated with oppression. The guidelines for feminist therapy developed by the Task Force of the Feminist Therapy Collective, Inc., of Philadelphia and by feminist therapists in private practice in Philadelphia are discussed as an alternative to the traditional approach to therapy. Mental health promotion using Caplan's (1974) three levels of prevention in health care is discussed. Intervention strategies for each of these levels of prevention, following feminist guidelines and using techniques that have been found to be helpful for women, are described and discussed. The focus of these intervention strategies is to reduce effects of factors in the cultural environment that contribute to the oppression of women and, in turn, contribute to their becoming depressed.

Depressive Disorder↗
PubMed2002

Neurological rehabilitation: a science struggling to come of age.

Over the last few decades, there have been considerable improvements in the outcome of stroke patients both as regards mortality and disability. At least some of these improvements can be attributed to better organization of services and improved rehabilitation. Many patients, however, remain severely disabled and we will need to develop new strategies in which the focus will be on reversing impairments rather than simply helping patients to adapt to unaltered impairments. For this to happen, neurological rehabilitation research will have to develop therapies that have a clearly defined rationale and are rooted in neurosciences, are clinically described, are addressed to a well-characterized target population and are evaluated using appropriate outcome measures. Few studies at present meet all these criteria. The recent revolution in our understanding of the nervous system as being soft-wired, of the potential for recovery through reorganization and of the central role of afferent information associated with normal activity is ground for optimism and indicates the direction in which future therapies should be sought. The paper considers some approaches to providing appropriate afferent information, including inputs such as that from electrotherapy, novel approaches to assisted activity and constraint-induced therapy. We are on the verge of a revolution in neurological rehabilitation. If we exploit the new understanding of the nervous system arising from basic neurosciences in developing and evaluating therapies we should be able to build on the achievements of the last few decades so that fewer of our patients have to carry the burden of severe disability.

Humans↗
PubMed1991

[Current developments in systemic therapy of breast carcinoma].

New developments in hormone- and chemotherapy of metastasizing breast cancer comprise replacement of ovariectomy by LH-RH antagonists in premenopausal women, new antiestrogens with less residual estrogenic activity for use mainly in postmenopausal patients as well as new potent inhibitors of aromatase with fewer adverse effects also for postmenopausal women. These new drugs will possibly provide better efficacy with fewer side effects, but at higher cost. In chemotherapy the search for more potent regimes continues. Experiments are under way with high-dose chemotherapy plans in conjunction with autologous bone marrow transplantation and hemopoietic growth factors; however, the result of these latter studies are so far disappointing. It has become clear that in nonaggressive metastasizing cancer of the breast high rates of remission seem not to be the ultimate goal. At this stage of disease the natural course is very heterogeneous; therefore, chemotherapy has to be adapted to risk. The goal must be improvement of quality of life for the remaining life-span by palliation of symptomatic disease while inducing as few side effects of treatment as possible. New; more potent chemotherapeutic agents are not at sight. Research has recently produced derivatives of already known agents producing fewer adverse effects at equal efficacy. Decisive for the choice of primary chemotherapy are prognostic indicators of the disease. For most cases, tumor specific therapeutic modalities have to be optimized.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Topical therapy and the development of silver sulfadiazine.

Topical therapy is a selective approach to the prevention and treatment of infection in burns and other surgical wounds. Effective compounds possess certain chemical and physical properties. Prerequisites include low solubility, slow absorption, nonreactivity with wound exudates, proteins and ions and ability to achieve prolonged antimicrobial activity in the wound. These compounds yield much higher levels in the zone of infection than can be achieved by diffusion into the wound after systemic administration. The wide spectrum of antibacterial activity, the low toxicity, minimal tissue reaction, ease of application suggest that topical silver sulfadiazine therapy can safely be extended to other wound infections, wound covers and certain transplant materials.

Administration, Topical↗
PubMed1997

Toward cystic fibrosis gene therapy.

Cystic fibrosis (CF) is a common genetic disorder characterized by defective epithelial chloride transport and progressive lung disease. Although great strides have been made in the treatment of CF, it remains lethal, often by early adulthood. CF is one of the most extensively researched genetic diseases as a target for gene therapy development. It may also serve as an important model for gene therapy of other diseases. Preclinical and clinical research has lead to the rapid development of a variety of vectors designed to correct the basic defect in CF, including adenovirus, adeno-associated virus, and liposomes. Clinical studies have identified the host immune response and low vector efficiency as key impediments to effective CF gene therapy. Further research promises to refine vector technology and bring CF gene therapy to the bedside.

Adolescent↗
PubMed1998

Providing appropriate training and skills in developing countries.

This paper looks at the content, methods and evaluation of training in communication therapy developed in Vietnam over a two year period using a wider approach to treatment than a medical one. It argues that training to institution staff needs to combine the needs of a community and principles of community based rehabilitation with a more traditional medical model. It examines the need to develop training programmes for trainers based on a sharing of attitudes and awareness between institutions and communities as well as some more prescriptive and activity-based training. It examines the selection and role of trainees who attend such training courses and skills required by the trainers. It also relates these skills to possible approaches to service delivery in this country.

Community Health Services↗
PubMed1991

Bulbar and pseudobulbar palsy complicating therapy with high-dose cytosine arabinoside in children with leukemia.

Three of 38 children given high-dose cytosine arabinoside therapy developed a previously undescribed complication. Neurological problems are a frequent occurrence in patients given this therapy, particularly cerebellar ataxia, but the development of bulbar and pseudobulbar palsy has not been reported. In two of these cases, it was sufficiently marked for the course of treatment to be curtailed and occurred at a relatively low cumulative dose of the drug. Neurotoxicity can occur at any time using high-dose cytosine therapy.

Adolescent↗
PubMed1980

Optimal antibiotic therapy in bronchopulmonary infections.

Therapy of bronchopulmonary infections has evolved in the past 30 years. Only in the therapy of pneumococcal infections have, precise dosage programs been developed. Therapy of pneumococcal infection is optimal with penicillin G in low dosage. None of the newer agents has altered morbidity or mortality. The best agent for the treatment of pneumonia due to Staphylococcus aureus or members of the Enterobacteriaceae has not been established. Use of combination therapy consisting of an anti-Pseudomonas penicillin and an aminoglycoside has been shown to offer the greatest success in the treatment of Pseudomonas pulmonary infections. The optimal antibiotic and dosage program for the treatment of acute bacterial exacerbations of chronic bronchitis has yet to be defined. Further comparative studies of the chemotherapy of pulmonary infections are necessary.

Aminoglycosides↗