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PubMed1989

Practical considerations for electron therapy planning and preparation.

This Clinic recently commissioned its first electron beams for radiation therapy. Over the past twelve months at this institution, we have developed devices and techniques to obtain precise and reproducible electron therapy treatments. These devices and methods have been used in the treatment of irregularly shaped fields for areas of complex shape, or those adjacent to critical or radiosensitive tissues and areas where it has been cosmetically unsuitable for patients to carry treatment field markings. This paper describes the techniques used in six representative cases with due consideration to physics, dosimetry and practical aspects. Several recommendations result from our experiences here.

Electrons↗

PubMed1993

[Endophthalmitis. Importance of microbiologic studies for therapy and prognosis].

The fast and precise identification of infectious agents and their characterization is of upmost importance for the diagnosis and therapy of infectious endophthalmitis. A preliminary estimate of the most probable predominant agents may improve the choice of an adequate antimicrobial therapy prior to definitive microbiological analysis in culture media. A prospective study was performed in 46 patients with endophthalmitis. During surgery mostly undiluted samples were inoculated in 10 different culture media. Microscopic investigation and laboratory processing were performed within the next 10-120 min. A presumptive classification based on immediate direct microscopy and a preliminary recommendation on treatment were achieved in 25 cases. Culture yielded positive results in 38 cases (83%). In 8 cases the inoculates remained negative. Most of the positive cultures (92%) contained only gram-positive bacteria, including 10 cases of mixed gram-positive infections. In 2 samples bacteria and fungi were present, while 2 contained fungi only. Of 8 posttraumatic eyes, 4 were infected with Bacillus spp. The results show that specific therapeutic approaches are required. Direct inoculation of surgical culture media combined with immediate microscopic investigation permits a fast and precise microbiological diagnosis.

Adolescent↗

PubMedDate not supplied

A prototype beam delivery system for the proton medical accelerator at Loma Linda.

A variable energy proton accelerator was commissioned at Fermi National Accelerator Laboratory for use in cancer treatment at the Loma Linda University Medical Center. The advantages of precise dose localization by proton therapy, while sparing nearby healthy tissue, are well documented [R. R. Wilson, Radiology 47, 487 (1946); M. Wagner, Med. Phys. 9, 749 (1982); M. Goitein and F. Chen, Med. Phys. 10, 831 (1983)]. One of the components of the proton therapy facility is a beam delivery system capable of delivering precise dose distributions to the target volume in the patient. To this end, a prototype beam delivery system was tested during the accelerator's commissioning period. The beam delivery system consisted of a beam spreading device to produce a large, uniform field, a range modulator to generate a spread out Bragg peak (SOBP), and various beam detectors to measure intensity, beam centering, and dose distributions. The beam delivery system provided a uniform proton dose distribution in a cylindrical volume of 20-cm-diam area and 9-cm depth. The dose variations throughout the target volume were found to be less than +/- 5%. Modifications in the range modulator should reduce this considerably. The central axis dose rate in the region of the SOBP was found to be 0.4 cGy/spill with an incident beam intensity of 6.7 x 10(9) protons/spill. With an accelerator repetition rate of 30 spills/min and expected intensity of 2.5 x 10(10) protons/spill for patient treatment, this system can provide 50 cGy/min for a 20-cm-diam field and 9-cm range modulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Equipment Design↗

PubMed1999

Supplemental and complementary alternatives to hormone replacement therapy.

Tables 1 and 2 offer a summary of information currently available on the sources, dosages, and proposed health benefits of the supplemental and complementary nutritional therapies that can be suggested as alternatives to hormone replacement therapy. These therapies have the additional benefit of being broadly available to women of all socioeconomic strata, and should be acceptable to women of various ethnicities and cultures. Adequate intakes (AI) of vitamins are recommended based on observational or experimentally determined approximations of the average nutrient intake, by a defined population or group, that appears to sustain a defined nutritional state (Food and Nutrition Boar, Institute of Medicine, 1997). Reviewing the empirical evidence concerning the use of vitamin supplements leads to the conclusion that doses higher than AI or recommended daily requirements is not warranted. For those individuals who choose to supplement, counseling should be provided to caution about tolerable upper limits, those maximum levels of nutrient intake judged unlikely to pose a risk for adverse health effects (Food and Nutrition Boar, Institute of Medicine). Supplemental and complementary therapy directed at ameliorating symptoms or reducing the risk of menopause related illness (osteoporosis and CHD) becomes a decision balance of the woman's preferences, risk and health history, and personal and financial resources. There appears to be some protection of morbidity and mortality from CHD with antioxidant dietary intake. Osteoporosis appears to be delayed with calcium supplementation. Menopausal symptoms, CHD risk, and osteoporosis risk appears to be reduced with phytoestrogen supplementation, although doses have not been established. Research concerning the safety and efficacy of these therapies continues. Findings from current clinical trials, such as the Women's Health Initiative may render these and additional alternative therapies to HRT more precise in the near future.

Antioxidants↗

PubMed1996

[Recommendations for initial diagnosis and therapy in acute blood coagulation disorders].

Acute disturbances of blood coagulation during operations and intensive therapy require quick and precise action in order to avoid life-threatening situations. This paper reports on a simple system for the diagnosis and therapy of acute disturbances of blood coagulation. In the initial phase of bleeding, determination of fibrin monomers, d-dimers, reptilase time, number of platelets and AT III enables diagnosis of disseminated intravascular coagulation (DIC), hyperfibrinolysis and consumption coagulopathy. Particular attention is paid to local hyperfibrinolysis, a relatively rare complication but of high diagnostic importance. After some remarks on the recommended clinical test parameters, the principles of the treatment of various coagulation disturbances are described. AT III is of special importance for the treatment of DIC, where as different opinions exist regarding the application of heparin. Aprotinin has long proved successful in the specific treatment of hyperfibrinolysis. Using clinical examples, the practicability of the recommended diagnostic and therapeutic measures is demonstrated.

Acute Disease↗

PubMed1997

Fluid resuscitation in thermally injured pediatric patients.

More than two-thirds of critical burns in special burn units are children. The burned child continues to represent a special challenge, since resuscitation therapy must be more precise than that for an adult with a similar burn. Children have a limited physiologic reserve and the pediatric fluid replacement therapy is based on the principle of separate calculation of physiological and pathological losses. We have reviewed the most widely accepted pediatric isotonic fluid protocols. All these protocols calculate for replacement of pathological losses with a need of 2 ml/kg/% BSAB (body surface area burn) or 4 ml/kg/% BSAB. We choosed the formulas of two Shriner's Burns Institutes--the Cincinnati and the Galveston Unit as representatives, and calculated the fluid therapy for model burn children weights of 10 kg, 30 kg with 20, 40, 60, 80% BSAB. The results of calculations where compared with physiologic parameters of children. In conclusions we could show, that the 4 ml/kg/% BSAB formulas do replace all theoretically predicted pathophysiologic losses due to burns. However, the 2 ml/kg/% BSAB formulas are more practical as a guideline for resuscitation of pediatric patients because of greater therapeutical range and better clinical response of children threatened by burn shock. It is important to remember that all formulas are only guides to fluid therapy, they should be modified according to individual needs and clinical status of the patient. Only successful restoring and maintaining perfusion pressures leads to optimal oxygenation of injured and noninjured tissues, which promotes spontaneous healing, prevents wound conversion, minimise bacterial colonisation, and prepares the injured areas for early grafting.

Age of Onset↗

PubMed1988

Consequences of diagnostic errors in mastitis therapy trials.

The effect of errors that occur in the diagnosis of intramammary infectious mastitis on the precision of experiments measuring the efficacy of mastitis therapy has been investigated. Diagnostic errors within the range found by experienced workers can create large biases in the apparent cure rate of therapy particularly at cure rates of less than 0.5. Using confirmed methods of diagnosis rather than single samples and reducing the probabilities of false positive and false negative diagnoses to 0.01 and 0.05 respectively, the biases in the apparent cure rates are reduced to acceptable levels. A method is given for calculating the rates of occurrence of false positive and false negative diagnoses from the results of trials using confirmed diagnoses. These errors cannot be calculated from therapy trial data when diagnosis is based on single milk samples. Because the bias in the measurements of the cure rate is greatest at the lowest levels of elimination, estimates of spontaneous recovery in untreated quarters have the greatest error. For this reason experiments incorporating an untreated control group of infected quarters usually reduce the precision of the therapy trials. An experiment in which the efficacy of a test product is measured relative to a reference product has advantages. It minimizes the difficulties arising from scale of measurement, diagnostic errors and herd differences in response rate, and makes possible comparisons between trials. Further investigations are required on the importance of spontaneous recovery, particularly for studies of Escherichia coli therapy and dry period therapy. The results of this investigation have relevance to all types of mastitis investigation that measure the change in mastitis status of udder quarters, i.e. new infection rates.

Animals↗

PubMed2004

The management of neuropathic pain.

Although the definitive treatment for neuropathic pain remains elusive, scientific investigation continues to provide the field with better and better therapies. As our understanding of the neurophysiologic mechanisms of pain improves, pharmaceutic therapies have become more effective even as side effects are minimized. Surgical therapies have become more precise and less invasive. Advances in neurophysiology have given rise to new advances in the field of neuro-modulation. As this therapy continues to emerge, ablative procedures recede as therapies offering minimal invasiveness, reversible mechanisms, and long-standing relief emerge to the forefront of treatment for neuropathic pain.

Analgesics↗

PubMed2006

PET-based biological imaging for radiation therapy treatment planning.

Biologically conformal radiation therapy (BCRT), a convergence of intensity-modulated radiation therapy (IMRT) and positron emission tomography (PET)-based functional imaging, incorporates patient-specific, image-derived biological information. This approach may potentially lead to a paradigm shift in radiation therapyspatially varying dose prescriptions, or dose sculpting, for individualized and dosimetrically optimized treatment. This article reviews the current status of the technical, biological, and clinical aspects of PET-guided radiation therapy. It remains unclear, however, whether PET is currently capable of delineating the true extent of viable tumor with sufficient accuracy and precision to reliably guide therapy on a routine basis.

Humans↗

PubMed2002

[Transpupillary thermotherapy in occult subretinal neovascularization in age-related macular degeneration. Preliminary results].

PURPOSE: To determine the efficacy of transpupillary thermotherapy (TTT) to treat choroidal neovascularization (CNV) in patients with age-related macular degeneration (ARMD). PATIENTS AND METHODS: Eight patients (ten eyes) with occult CNV were treated by TTT. A 810 nm diode laser was used to perform TTT. The diode laser was delivered through a panfunduscopic contact lens. RESULTS: Three eyes showed a visual acuity improvement and a decrease in exudation on fluorescein angiography. Four eyes remained stable. Nevertheless, lesions worsened after treatment in three cases. One of these cases suffered an overtreatment. CONCLUSIONS: TTT may be a useful therapy in some cases of CNV in patients with age-related macular degeneration. Randomized and multicentric studies are necessary to stablish precise indications of this therapy.

Aged↗

PubMed1986

[Decision aids in determining therapy of breast cancer by preoperative staging using sonography and computerized tomography].

In a prospective study the preoperative ultrasonography of 54 cases of carcinoma of the breast was able to predict the pTNM staging precisely in 83.3% for tumor size and in 72.3% for lymphnode metastases. Multicentric-multifocal carcinomas were diagnosed by ultrasonography in 10 of 13 patients, better than by mammography (6 of 13). The CAT scan is indicated only in advanced tumor stages. The preoperative staging by ultrasonography enables with more precision planning and differentiated therapy of the carcinoma of the breast, especially in view of breast-preserving therapy.

Breast↗

PubMed2002

[Hadron therapy in carcinoma].

According to some statistics, in the developed countries of west Europe, one in three of population will have an encounter with cancer and, only one in eight of this will have treated by use a linear accelerator. Conventional accelerator-based treatments use photon or electron or proton beams collimated to the tumour place. However, some tumors are resistant on this therapy, while others have complex shapes or are located around vital radiosensitive organs. In those cases it is necessary higher radiobiological efficiency and higher precision. New generation of hadron therapy accelerators are arming with light ions. This therapy is characterized with high precision, in millimeter range over complex volumes. That is also good example how particle physics can benefit medical treatments.

Humans↗

PubMed1976

Fluid therapy in children.

Fluid therapy in children is based on biochemical and physiologic principles qualitatively and quantitiatively different from adults. The limitations imposed by body size requires greater precision in calculating fluid therapy for children. General methods of computing maintenance and deficit pediatric fluid therapy, and specific fluid therapy involved in treating acute problems associated with genitourinary disorders with be discussed.

Acute Kidney Injury↗

PubMed1986

[Fractures of the upper end of radius and ulna and recent dislocations of the elbow in children].

In this report concerned with luxation of the elbow and fractures of the upper end of two forearm bones in children emphasis is placed on the importance of the initial treatment, since sequelae are not corrected during growth. Correct therapy requires firstly a precise diagnosis, this depending on the obtaining of images of very good quality, if necessary taken during sleep if the child has to be anesthetized. Therapy should be as atraumatic as possible, particularly in the region of the head of radius, to avoid its subsequent necrosis.

Child↗

PubMed1995

Immediate changes in subcellular structures of transplanted tumors following photodynamic and laser hyperthermic therapy.

BACKGROUND AND OBJECTIVE: To further understand the precise process of the tumor cell degeneration after photodynamic therapy (PDT), laser hyperthermic therapy (LH), and combined treatments using an Nd:YAG laser. It is important to examine initial morphological alteration of tumor cells after these treatments. STUDY DESIGN/MATERIALS AND METHODS: In this study, nude mice bearing HeLa cell tumors were treated with PDT, LH, and combined treatments of the two. Tumor tissues obtained immediately after these treatments were analyzed using electron microscopy and morphometry. RESULTS: In the combined treatments, which produced more severe effects on tumor cells, morphological features of apoptosis such as cytoplasmic condensation, blebs, and apoptotic bodies appeared in the cells, although the typical alteration in the nuclear chromatin was not seen. CONCLUSION: Cytoplasmic alterations may proceed more rapidly than nuclear alterations in the cellular degeneration induced by the single or combined treatments of PDT and LH.

Animals↗

PubMed2002

Cyclosporine microemulsion (Neoral) absorption profiling and sparse-sample predictors during the first 3 months after renal transplantation.

UNLABELLED: Recent data suggest that optimal cyclosporine (CsA) exposure early post-transplant significantly reduces the risk of acute graft rejection. They indicate that trough level monitoring is inadequate for precise concentration-controlled therapy, and suggest that absorption profiling may offer a superior approach for guiding clinical immunosuppression with Neoral. An international, prospective, multicenter study examined the feasibility, accuracy, precision and clinical utility of cyclosporine microemulsion (Neoral) absorption profiling in de novo renal transplant recipients receiving basiliximab immunoprophylaxis and cyclosporine microemulsion maintenance immunosuppression. The nested pharmacokinetic study reported here was conducted in 4 study centers in which full (11-point) pharmacokinetic profiles were performed on days 3, 7, 14 and 84 post-transplant to examine absorption profile and absorption efficiency, and to determine optimal sparse-sampling pharmacokinetic methods to predict Neoral exposure. Twenty-four patients had complete 12-h pharmacokinetic (PK) data on all 4 sampling days. Area under the time-concentration curve (AUC) over the first 4 h of the 12-h dosage interval (AUC[0-4]) and AUC over the entire 12-h dosage interval (AUC[0-12]) reached 3803 +/- 1033 and 7462 +/- 2120 microg.h/L respectively, by day 3, remained stable throughout the first 2 weeks, and declined to 2310 +/- 698 and 4062 +/- 1158 microg.h/L by day 84 (p < 0.001). AUC[0-4], capturing the drug absorption phase, represented 52% of the AUC[0-12] values across the four PK study days (mean R2 > 0.90). Between-patient variability was highest for C0 and C1 (mean coefficient of variation [c.v.] 36-47%), and lower for C2 (mean c.v. 28%) and subsequent time-points during the dosing interval. Mean relative CsA absorption, measured by dose- and weight-adjusted AUC[0-4] and AUC[0-12], increased significantly over time. The dose- and weight-corrected AUC[0-4h] (DWC.AUC[0-4]) rose by over 100% (p < 0.001) from 753 +/- 202 at day 3 to 905 +/- 232 at day 7, 1080 +/- 330 at day 14 and 1521 +/- 316 by day 84, while the dose-and weight-corrected AUC[0-12h] (DWC.AUC[0-12]) rose by over 80% (p < 0.001) from 1477 +/- 390 microg.h/L/ mg/kg on day 3, to 1721 +/- 426 on day 7, 2086 +/- 478 on day 14 and 2690 +/- 602 on day 84 (p < 0.001). Relative CsA absorption varied over 5-fold between patients at day 3, but patients tended to remain within the same quartiles over time. Sparse-sample modeling identified optimum 3-point, 2-point and 1-point predictors for AUC[0-4] and AUC[0-12]. C2 was the most accurate and robust .1-point predictor for AUC[0-4] (mean R2: 0.80), while C3 was superior for AUC[0-12] (mean R2: 0.75). C0 was not a good predictor of either AUC[0-4] or AUC[0-12] (mean R2: 0.13 and 0.24, respectively). CONCLUSION: Absorption profiling defines the heterogeneity in CsA exposure and relative absorption post-transplant. A 2-h post-dose blood sample is the most consistent, accurate and robust single-point predictor of the absorption phase measured by AUC[0-4] and should replace trough level monitoring for accurate concentration-control of Neoral therapy in the clinical setting. The use of additional samples at 1 and 3h is more complex and costly, but increases prediction accuracy and may be valuable in selected patients with erratic absorption.

Area Under Curve↗

PubMed2002

What is the role of serial bone mineral density measurements in patient management?

The ability of dual X-ray absorptiometry (DXA) to monitor bone mineral density (BMD) has been well documented in epidemiologic and pharmaceutical trials. However, its application to monitoring of patients in clinical practice has been subject to recent controversies. Despite these controversies, most clinical centers rely on DXA for monitoring of patients, and therefore guidance is needed. In this article, we report the positions developed by an expert panel of the International Society for Clinical Densitometry on the use of densitometry for the serial measurement of bone mass for monitoring change in BMD. The panel found DXA to be a precise method of measuring change in BMD if used with an appropriate level of least significant change (LSC), at anatomic sites with good precision and response to therapy, and at 1- to 2-yr time intervals. Monitoring is acceptable for determining when therapy is indicated, and if an agent is not therapeutically effective (i.e., when bone loss occurs despite treatment). Each densitometry center should perform an in vivo precision study on individuals similar to the patient population at the center and determine LSC at a 95% confidence level. If such a precision study cannot be performed, benchmark precision might be used, although there was no agreement on what values should be used. The PA spine is the preferred anatomic site for monitoring. The total hip can be used when the spine study is technically invalid. We conclude with recommendations for further research.

Absorptiometry, Photon↗

PubMed2006

Cellular and molecular effects of protons: apoptosis induction and potential implications for cancer therapy.

Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols.

Apoptosis↗