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At least 325 records · Page 18Linked to original sources
PubMed1985

Proton therapy at Harvard.

Fractionated precision high-dose proton radiotherapy has been carried out at the Harvard Cyclotron Laboratory (HCL) since 1973, in a collaborative effort with the Radiation Medicine Department of Massachusetts General Hospital (MGH) and the Retina Service of the Massachusetts Eye and Ear Infirmary (MEEI). This paper will discuss proton treatment in general, treatment planning procedures, and results to date in major patient categories. 846 patients have been treated with fractionated proton therapy at the Harvard Cyclotron, with normal tissue and tumor responses consistent with an RBE of 1.1 for the proton beam. Proton beam therapy is the treatment of choice for patients with uveal melanomas, and chordomas and chondrosarcomas involving the skull base and cervical spine. Improved dose distribution possible with protons have allowed greater doses than are given conventionally to be delivered to patients with prostatic carcinoma, head and neck malignancies, ano-rectal cancers, and retroperitoneal tumors. Doses employed have been usually 10 to 20% greater than normally would be delivered in our department to such tumors. Generally, local control rates have been good.

Animals↗
PubMed1984

LOCATE: an application of computed tomography in radiation therapy treatment planning with emphasis on tumor localization.

Computed tomography can provide precise information for radiation therapy treatment planning. However, inaccuracies in radiation field design may occur when the radiation oncologist attempts to transfer information about tumor location from the transverse plane of the CT scan to the longitudinal plane of the simulation film. This report describes a new computer program, LOCATE, which addresses this problem. The program uses operator generated information from the cross sectional CT images to draw an outline of tumor on AP and lateral longitudinal scanned projection radiographs. The resultant images are useful because they are in the same plane as radiographs obtained on a therapy simulator. The impact of LOCATE on radiation treatment planning for 26 patients is discussed along with several cases in which LOCATE was particularly helpful.

Adult↗
PubMed1987

Microcomputer-assisted data management for multiinstitutional pediatric clinical cancer trials.

Microcomputer assisted data management techniques, utilized in the oversight of two multiinstitutional trials for children with previously untreated acute lymphoblastic leukemia and unfavorable prognostic features, are presented. In the first study, such oversight hastened identification of unexpectedly prolonged delays, so that treatment could be successfully modified. In the second study, inferiority of one therapy was rapidly demonstrated, and after careful review that therapy was halted. Performance monitoring is discussed in terms of consideration of the overall quality of a clinical trial, namely, how complete are the data submitted and how precisely was protocol therapy administered; measurement of the quality of institutional participation, and identification of deficiencies in reporting or performance in the records of individual patients.

Acute Disease↗
PubMed1992

Therapy of alopecia areata with diphencyprone.

The properties of diphencyprone (DPC), its possible mechanism of action in the therapy of alopecia areata (AA), and its side-effects are summarized. The results of our own study of treatment in 45 patients with AA, with a mean treatment duration of 72 (15-146) weeks, are presented, and compared with the results of previous studies. We suggest that, in future, therapy protocols should define entry criteria and therapy results more precisely, and include follow-up assessments to establish the length of remission. In view of the low response rates and short lengths of remission, the indications for DPC therapy should be set more rigorously.

Adolescent↗
PubMed2004

In face of the increasing efficacy of lipid-lowering therapy, is there still a place for LDL-apheresis?

Based on a large body of evidence, high LDL-cholesterol concentrations in blood is a key factor of coronary heart disease (CHD). Overall, the observational studies show a curvilinear relationship between blood cholesterol level and coronary heart disease risk. Even more relevant are the randomised trials, firmly establishing that within just a few years a cholesterol-lowering therapy confers a dramatic effect on cardiovascular morbidity and mortality. More recent studies indicate that there is a greater risk reduction in those subjects achieving lower low-density lipoprotein cholesterol (LDL-C) levels--i.e. lower is better. While this favours aggressive therapy, it is nevertheless imperative to precise patients selection for every therapy that entails a major commitment for the patient and medical community. Therefore, well-defined criteria for use of LDL-apheresis have yet to be established in the light of the expanding therapeutic armamentarium. Based on the current knowledge of the impact of statin therapy and anticipating that new options will further optimize the management of dyslipidemia in high-risk patients, we propose a reliable assessment of the effects of LDL-apheresis.

Anticholesteremic Agents↗
PubMed1995

Transesophageal echocardiography in diagnosing cardioembolic stroke.

Stroke is a disease with high morbidity and mortality that afflicts older people. The most common type of stroke is ischemic, and 15-20% of these strokes are cardioembolic. Because clinical features are not very specific for the type of stroke, diagnostic aides are needed to identify the mechanism of stroke so that appropriate therapy can be initiated. Numerous studies have shown that transesophageal echocardiography (TEE) is a more sensitive tool for diagnosing cardioembolic stroke than transthoracic echocardiography (TTE). However TTE and TEE are still considered complementary as they both provide unique information. The many abnormalities that can be identified by TEE and their therapy are discussed in this review, along with indications and complications of TEE. TEE has demonstrated that cardioembolic causes of stroke are much more common than previously thought. With a more precise diagnosis, appropriate therapy can be provided to help prevent cardiogenic stroke.

Cerebrovascular Disorders↗
PubMed2004

Fiducial markers implanted during prostate brachytherapy for guiding conformal external beam radiation therapy.

Prostate movement imposes limits on safe dose-escalation with external beam radiation therapy. If the precise daily location of the prostate is known, dose escalation becomes more feasible. We have developed an approach to dose escalation using a combination of prostate brachytherapy followed by external beam radiation therapy in which fiducial markers are placed along with (125)I seeds during transperineal interstitial permanent prostate brachytherapy. These markers serve to verify daily prostate location during the subsequent external beam radiotherapy. Prior to implementing this approach, preliminary studies were performed to test visibility of the markers. Three different (125)I seed models, as well as gold and silver marker seeds were placed within tissue-equivalent phantoms. Images were obtained with conventional x-rays (75-85 kV) and 6 MV photons from a linear accelerator. All (125)I seed models were clearly visible on conventional x-rays but none were seen with 6 MV photons. The gold markers were visible with both energies. The silver markers were visible with conventional x-rays and 6 MV x-rays, but not as clearly as the gold seeds at 6 MV. Subsequently, conventional x-rays, CT scans, and 6 MV port films were obtained in 29 patients in whom fiducial gold marker seeds were implanted into the prostate during (125)I prostate brachytherapy. To address the possibility of "seed migration" within the prostate, CT scans were repeated 5 weeks apart in 14 patients and relative positions of the gold seeds were evaluated. The repeated CT scans showed no change in intraprostatic gold marker location, suggesting minimal migration. The gold seeds were visible with conventional x-rays, CT, and 6 MV port films in all patients. During the course of external beam radiation therapy, the gold markers were visible on routine 6 MV port films and were seen in different locations from film to film suggesting prostate motion. Mean daily displacement was 4-5 mm in the anterior-posterior, and 4-5 mm in superior-inferior dimensions. Left-right displacement appeared less, averaging 2-3 mm. We conclude that implantation of gold marker seeds during prostate brachytherapy represents an easily implemented and practical means of prostate localization during subsequent image-guided external beam radiotherapy. With such markers, conformality of the external beam component can be confidently improved without expensive new equipment.

Brachytherapy↗
PubMed2025

Phage therapy for Klebsiella pneumoniae: Understanding bacteria-phage interactions for therapeutic innovations.

Klebsiella pneumoniae (KP) is a Gram-negative bacterium that commonly resides in the human gastrointestinal tract and can also act as an opportunistic pathogen and cause extra-intestinal infections. KP poses a global health threat because it causes both hospital- and community-acquired infections in immune-competent and immunocompromised hosts. These infections can be multidrug-resistant and/or hypervirulent, making KP infections difficult to treat and deadly. In the absence of effective treatments for recalcitrant KP infections, bacteriophage (phage) therapy is gaining attention as a promising alternative. In this review, we evaluate KP epidemiology and epitope diversity, discuss interactions between KP-targeting phages and their bacterial hosts from an eco-evolutionary perspective, and summarize recent efforts in phage therapy for treating KP infections. We also discuss novel approaches, including genetic engineering and machine learning, as initial steps toward developing KP-targeting phage therapy as a precision medicine approach for an emerging and dangerous pathogen.

Phage Therapy↗
PubMed1994

[Quantitative measurement of inflammation in HLA-B27 acute anterior uveitis using the Kowa FC-100 laser flare-cell meter].

PURPOSE: LFP represents a major gain of sensitivity over slit-lamp evaluation of aqueous flare, allowing to detect subclinical changes of flare both in low grade and high grade flare situations. It is now possible to exactly quantify anterior chamber inflammation and determine inflammatory patterns. The purpose of this study was to determine the mean initial and evolutionary flare in AAU and the mean duration of an AAU episode. PATIENTS AND METHODS: Since 1990 routine LFP follow-up of inflammation in uveitis patients is performed by the same technician with a Kowa FC-1000 laser flare-cell meter. The standard treatment for AAU was to begin with hourly topical 1% prednisolone acetate drops during the day and ointment at night and mydriatic drops. In case of a flare rise or persistence of the initial high flare after 48 hours a periocular injection of betamethasone (4 mg) was added to the topical therapy. End of an episode was defined as a flare under 8 photons/ms. RESULTS: Mean initial flare was 160.7 +/- 22 ph/ms (n = 61). Mean duration of an AAU episode was 18.5 +/- 15 days and evolution of mean flare showed that 50% flare reduction occurred on day 2 of therapy and 90% reduction on day 8. With our treatment protocol 14% of non complicated AAU needed an additional periocular steroid injection. CONCLUSION: LFP represents a major improvement in the management of AAU patients by allowing precise adjustment of therapy and favors good patient compliance because of the numbered evidence of disease recovery.

Acute Disease↗
PubMed2006

Emerging therapeutic options for atopic dermatitis: beyond TIMs.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that significantly impacts both patients and their families. Although current therapies provide relief of symptoms for most but not all patients, they do not prevent or eradicate the disease. In this new era of biological therapy, medications that precisely target the molecular mediators of inflammation are being developed at a rapid pace. These biologic agents have proven useful for treating many inflammatory illnesses, as well as providing insight into disease pathogenesis. In atopic dermatitis, these new therapies may prove highly useful to both treat and prevent the disease. In this review article, we briefly review the pathogenesis of AD to discuss current therapies and to introduce potential new treatments.

Anti-Inflammatory Agents↗
PubMed1987

[Determination of the ovulation date in stimulated cycles with Clostilbegyt].

Modern sterility therapy presupposes a precise ovulation timing in stimulated cycles. The different contribution and importance clinical hormono-analytical and ultrasonographic methods to and for the determination of the ovulation date were tested in 137 cycles of 84 women with a Clostilbegyt therapy as well as in a control group of 27 spontaneous cycles. It was stated that the results ascertained by ultrasonography are of special importance. Nevertheless the determination of 17 beta-estradiol and the LH estimation must not be neglected as functional criteria. In order to supervise the corpus luteum phase determinations of progesterone, 17 beta-estradiol and prolactin during the second part of the cycle are to be included into a control program.

Adult↗
PubMed2000

Short term in vivo precision of proximal femoral finite element modeling.

As more therapies are introduced to treat osteoporosis, precise in vivo methods are needed to monitor response to therapy and to estimate the gains in bone strength that result from treatment. A method for evaluating the strength of the proximal femur was developed and its short term reproducibility, or precision, was determined in vivo. Ten volunteer subjects aged 51-62 years (mean 55.6 years), eight women and two men, were examined using a quantitative computed tomography (QCT) protocol. They were positioned, scanned, repositioned and re-scanned. The QCT images were registered in three-dimensional space, and finite element (FE) models were generated and processed to simulate a stance phase load configuration. Stiffness was computed from each FE model, and strength was computed using a regression equation between FE stiffness and fracture load for a small set (n = 6) of experimental specimens. The coefficients of variation (COV) and repeatability (COR= 2.23* 42*COV) were determined. The COV for the FE fracture load computed was 1.85%, and the detectable limit (coefficient of repeatability) for serial measurements was 5.85%. That is, if a change of 5.85% or more in computed FE fracture load is observed, it will be too large to be consistent with measurement variation, but instead can be interpreted as a real change in the strength of the bone. The detectable limit of this method makes it suitable for serial research studies on changes in femoral bone strength in vivo.

Biomechanical Phenomena↗
PubMed1997

Target volume definition in radiation therapy.

Target volume definition in radiation therapy is a broad field of interdisciplinary research. We give a brief history of clinical research in this field and outline some remarkable steps which led to the well-defined target volume concepts. The challenges in target volume definition for high-precision conformal radiation therapy are discussed, and possibilities of improving target volume definition, such as the integration of modern imaging modalities and the use of computer-based systems to support the radiation oncologist are indicated, as well as novel techniques for increasing the accuracy of patient positioning. All these tools should be evaluated with regard to their potential for increasing the therapeutic ratio and, as appropriate, should be implemented in clinical practice. However, target volume definition is a complex process influenced by many factors, currently under investigation. While questions remain in this field, and the impact of the influencing factors is not defined, the process of target volume definition should remain the subject of clinical research.

Humans↗
PubMed2005

[Triple oral therapy in type 2 diabetes].

Type 2 diabetes has a complex pathophysiology, combining a defect of insulin secretion by the pancreas, an increased glucose production by the liver and a reduced insulin-mediated glucose uptake by the skeletal muscle. Each of these abnormalities can be partially reversed by a specific drug, an agent promoting insulin secretion (sulphonylurea or glinide), metformin and a thiazolidinedione (glitazone), respectively. Therefore, a triple oral therapy, targeting simultaneously the three main metabolic abnormalities of type 2 diabetes, deserves special attention. Recent clinical trials have shown both the efficacy and safety of this triple oral therapy. However, its precise place remains to be better specified in the overall management of type 2 diabetes.

Administration, Oral↗
PubMed2026

Cost-Effectiveness and the Economics of Genomic Testing and Molecularly Matched Therapies.

Cost-effectiveness analysis of precision oncology can help guide value-driven care. Next-generation sequencing is increasingly cost-efficient over single gene testing because diagnostic algorithms require multiple individual gene tests to determine biomarker status. Matched targeted therapy is often not cost-effective due to the high cost associated with drug treatment. However, genomic profiling can promote cost-effective care by identifying patients who are unlikely to benefit from therapy. Additional applications of genomic profiling such as universal testing for hereditary cancer syndromes and germline testing in patients with cancer may represent cost-effective approaches compared with traditional history-based diagnostic methods.

Humans↗
PubMed2002

Immunosuppressive therapy for paediatric transplant patients: pharmacokinetic considerations.

Immunosuppressive therapy in paediatric transplant recipients is changing as a consequence of the increasing number of available immunosuppressive agents. Generic and other new formulations are now emerging onto the market, clinical experience is growing, and it is expected that clinicians should tailor immunosuppressive protocols to individual patients by optimising dosages and drugs according to the maturation and clinical status of the child. Most information about the clinical pharmacokinetics of immunosuppressive drugs in paediatrics is centred on cyclosporin, tacrolimus and mycophenolate mofetil in renal and liver transplant recipients; data regarding other immunosuppressants and transplant types are limited. Although the clinical pharmacokinetics of these drugs in paediatric transplant recipients are still under investigation, it is evident that the pharmacokinetic parameters observed in adults may not be applicable to children, especially in younger age groups. In general, patients younger than 5 years old show higher clearance rates irrespective of the organ transplanted or drug used. Another important factor that frequently affects clearance in this patient population is the post-transplant time. In accordance with these findings, and in contrast with the usual under-dosage in children, the need for higher dosages in younger recipients and during the early post-transplant period seems evident. To achieve the best compromise between prevention of rejection and toxicity, dosage individualisation is required and this can be achieved through therapeutic drug monitoring (TDM). This approach is particularly useful to ensure the cost-effective management of paediatric transplant recipients in whom the pharmacokinetic behaviour, target concentrations for clinical use and optimal dosage strategies of a particular drug may not yet be well defined. Although TDM may be a tool for improving immunosuppressive therapy, there is little information concerning its positive contribution to clinical events, including outcomes, for paediatric patients. Substantial information to support the use of TDM exists for cyclosporin and, to a lesser extent, for tacrolimus, but a diversity of options affects their implementation in the clinical setting. The role of TDM in therapy with mycophenolate mofetil and sirolimus has yet to be defined regarding both methods and clinical indications. Pharmacodynamic monitoring appears more suited to other immunosuppressants such as azathioprine, corticosteroids and monoclonal or polyclonal antibodies. If coupled with pharmacokinetic measurements, such monitoring would allow earlier and more precise optimisation of therapy. Very few population pharmacokinetic studies have been carried out in paediatric transplant patients. This type of study is needed so that techniques such as Bayesian forecasting can be applied to optimise immunosuppressive therapy in paediatric transplant patients.

Area Under Curve↗