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At least 127 records · Page 7Linked to original sources

The clinical use of oral sulfonylureas in the management of non-insulin dependent diabetes mellitus (NIDDM).

Eighty percent of Americans afflicted with diabetes mellitus have Type II or non-insulin dependent diabetes mellitus (NIDDM). Impaired or defective insulin secretion and insulin resistance are universal pathophysiologic findings. Management involves attention to diet, exercise, and commonly the use of insulin and/or oral sulfonylureas. Currently there are six marketed first and second generation agents available for use in the United States. Although the newer agents are more potent, they all share a similar mechanism of action. These agents can only be effective if the patient has retained beta cell secretory function. Pharmacokinetic and pharmacodynamic differences may make the newer agents, glyburide and glipizide, preferred in the management of Type II diabetes mellitus. The combined use of insulin and oral sulfonylureas may be useful for the patient exhibiting persistent fasting hyperglycemia despite maximal oral drug therapy. The precise role for combination therapy and optimal patient characteristics awaits further study.

Administration, Oral↗

Details of hyperplastic polyps of the stomach shrinking after anti-Helicobacter pylori therapy.

The precise etiology of hyperplastic polyps of the stomach is unknown, but recent studies suggest that they arise as a consequence of inflammation occurring in intimate association with Helicobacter pylori infection. The process of polyp regression after anti-H. pylori therapy, however, is unclear. Here we report a patient with large hyperplastic polyps of the stomach that regressed markedly after anti-H. pylori therapy. Histological examination of the regressed polyps revealed a decrease in the height of the hyperplastic foveolar epithelium and a decrease in the amount of inflammatory cell infiltration in the stroma. In addition, the percentage of Ki-67-positive hyperplastic epithelial cells markedly decreased after anti-H. pylori therapy, indicating that the epithelial cell proliferation rate had markedly decreased after treatment. At the same time, the degree of cyclooxygenase-2 expression in epithelial cells in the polyps decreased after treatment. Because cyclooxygenase-2 is expressed at sites of inflammation or neoplasm, these findings are consistent with a decrease in inflammatory cell infiltration, and represent resolving inflammation.

Anti-Bacterial Agents↗

A computational study into the use of polyacrylamide gel and A-150 plastic as brain tissue substitutes for boron neutron capture therapy.

A precise evaluation of the dosimetric performance of epithermal neutron beams designed for boron neutron capture theory of brain tumours requires the use of a phantom material that closely matches brain tissue. The aim of this study was to investigate how well polyacrylamide gel (or PAG) and A- 150 plastic performed as substitutes for brain tissue compared with standard phantom materials such as water and polymethyl-methacrylate (or PMMA). Thermal neutron fluence, photon dose and epithermal neutron dose distributions were calculated for the epithermal neutron beam available at the University of Birmingham. The results presented in this paper show that the PAG provides a good simulation of radiation transport in the brain with differences from the real brain of +9.4%, - 10.8% and +5.1% at a depth of 50 mm for thermal neutron fluence, gamma dose and epithermal neutron dose distributions respectively. The polyacrylamide gel presented is therefore a promising substitute for brain tissue that can, as a dosimeter, provide a three-dimensional map of the absorbed dose delivered by the epithermal neutron beam. However, this study does not investigate the agreement between doses derived from magnetic resonance and physical doses for such gels. A- 150 plastic was shown to be a better substitute for brain tissue than PMMA, with differences from brain of -1.9%, -12.4% and - 13.2% at a depth of 50 mm for thermal neutron fluence, gamma dose and epithermal neutron dose distributions respectively, against +21.1%, -16.2% and +19.2% for PMMA. A-150 plastic should therefore be the material of choice for solid phantoms.

Acrylic Resins↗

125I interstitial implant, precision high-dose external beam therapy, and 5-FU for unresectable adenocarcinoma of pancreas and extrahepatic biliary tree.

Twelve patients with adenocarcinoma of the pancreas and two patients with carcinoma of the extrahepatic biliary tree received combined therapy with 125I implant, precision high-dose (PHD) photon external beam therapy, and systemic 5-fluorouracil (5-FU). The 125I implant delivered 120 to 210 Gy (median 140 Gy). PHD external beam therapy was given with high-energy photons (10, 15 or 45 meVp) and was initiated 4 to 6 weeks postimplant. A dose of 48.6 to 63 Gy was delivered over 5.5 to 7 weeks in 1.8 Gy increments. Six patients received 5-FU, 500 mg/m2 via weekly intravenous bolus injection. No patient was lost to follow-up (range, 3.5-57 months). Acute postoperative morbidity included pancreatic fistula in two patients and gastrointestinal tract bleeding, pulmonary embolism, and cholangitis in one patient each. No patient died of radiation complications. Median survival of the patients with pancrease cancer was 15 months. One patient is alive at 41 months with hepatic metastasis. Satisfactory palliation was observed in patients with pancreas cancer treated with 125I interstitial implant followed by PHD external beam photon therapy and 5-FU. Patient survival did not seem superior to that of patients treated with PHD external beam therapy +/- chemotherapy, a less morbid procedure. Two cases of bile duct cancer treated in similar fashion are presented.

Adenocarcinoma↗

[More precise indications for fluid therapy during transportation to hospital are required].

Although early intravenous fluid therapy for haemorrhage and shock is usually given before arrival at the hospital, its value is unclear and more precise indications are needed. The indications will take into account such factors as transport time, volume and type of bleeding, and the presence or absence of concomitant head injury. Fluid resuscitation can be omitted if transport time is less than 30 min, but may be beneficial if it is more than 30 min. Choice of infusion rate should be guided by the estimated risk of re-bleeding when haemorrhage is uncontrolled, and by cerebral perfusion where severe head injury is present.

Ambulances↗

Evaluation and medical therapy of acute gastrointestinal bleeding.

Gastrointestinal bleeding is a major reason for hospitalization and an important cause of morbidity and mortality. Diagnosis and treatment of this common clinical problem has changed markedly over the past 40 years. The initial approach to patients with gastrointestinal bleeding should be both therapeutic and diagnostic, with close attention to cardiovascular status and clotting parameters. Once the patient is stabilized, clinical history, physical examination, gastric aspirate, and laboratory data should be assessed to determine if the bleeding site is in the upper or lower gastrointestinal tract. Once that is determined, a more specific diagnosis should be made if possible, as therapy often will depend upon a precise diagnosis. Therapy includes angiographic and pharmacologic techniques, as well as tamponade in the case of esophageal varices. The use of antacids in acute upper gastrointestinal bleeding is well established, while the role of cimetidine is less clear. Newer modalities of treatment, such as the use of laser coagulation, are currently being evaluated.

Angiography↗

[Intensity Modulated Radiation Therapy (IMRT)].

Radiotherapy plays an important role in the management of cancer patients, and half of the patients with malignant tumors are treated with radiotherapy in the United States. In Japan, the necessity of radiation therapy has come to be widely acknowledged in cancer treatment, and more and more cancer patients are being treated with radiation. External beam radiation is the most-used radiotherapy at the present time. The advantage is that this treatment modality can be used in a short time, although the problem is that not only the cancer lesion but also the surrounding normal tissue is irradiated,causing an adverse effect on normal tissue. In order to solve this problem,treatments such as 3D-Conformal Radiation Therapy (3D-CRT), Intensity Modulated Radiation Therapy (IMRT), Stereotactic Radiation Surgery (SRS) and Stereotactic Radiation Therapy (SRT) are clinically used as an extremely precise radiotherapy, thanks to the advances in computer technology in recent years. Therefore, the purpose of these extremely precise radiation therapies is to administer a high dose to the tumor intensively, and to suppress quantities of magnetism to normal tissues. IMRT treatment results for prostate cancer patients and head and neck cancer patients are reportedly better than with other irradiation methods. In this chapter,we explain the external irradiation method with the focus on IMRT and the extremely precise radiotherapy preformed in the Tokyo Women's Medical University Hospital.

Head and Neck Neoplasms↗

Dosimetric precision requirements in radiation therapy.

Based on simple radiobiologic models the effect of the true distribution of absorbed dose in therapy beams on the response of uniform tumor volumes are investigated. Under assumption that the dose variation in the beam is small it is shown that the response of the tumor to radiation is determined by the mean dose to the tumor volume. Quantitative expressions are also given for the loss in tumor control probability as a function of the degree of dose variations around the mean dose level. When the dose variations are large the minimum tumor dose is best related to tumor control. It is finally shown that high tumor control rates can only be achieved with a very high accuracy in dose delivery. If the normalized dose response gradient is higher than 3, as is frequently the case, the relative standard deviation of mean dose in the target volume should be less than 3 per cent to achieve an absolute standard deviation in tumor control probability of less than 10 per cent.

Cell Survival↗

"Distributed proton radiation therapy"--a new concept for advanced competence support.

The increased interest in high precision radiation therapy is to a large extent driven by the potential of modern imaging technology. The aim of this project was to analyse how an expensive proton facility best could support a multi-centre health care system. We have developed a model for distributed expert collaboration where all clinical experts will work close to their patients in regional centres. Patients who are candidates for proton therapy will be examined and dose-planned at their regional clinic, discussed in a fully information supported video conference and digitally made available at the proton treatment facility. The proton facility itself will be placed near a communication centre easily reached by all patients where they will be treated under full responsibility of their own physician at the home clinic. This concept has been analysed in detail both with respect to the overall functionality and with respect to possible weaknesses. It was found that the concept of distributed radiation therapy, as proposed here, will offer a stable clinical solution for advanced radiation therapy. It will support the spread of knowledge, serve as a fully developed backup system and the concept will further serve as an efficient base for clinical research.

Ambulatory Care Facilities↗

Dose broadening due to target position variability during fractionated breath-held radiation therapy.

Recent advances in Stereotactic Radiosurgery/Conformal Radiotherapy have made it possible to deliver surgically precise radiation therapy to small lesions while preserving the surrounding tissue. However, because of physiologic motion, the application of conformal radiotherapy to extra-cranial tumors is, at present, geared toward slowing the progression of disease rather than obtaining a cure. At the University of Rochester, we are investigating the use of patient breath-holding to reduce respiratory-derived motion in fractional radiotherapy. The primary targeting problem then becomes the small variation in tumor location over repeated breath-holds. This paper describes the effects of residual target position uncertainty on the dose distribution observed by small extra-cranial tumors and their neighboring tissues during fractional radiation treatment using breath holding. We employ two computational methods to study these effects: numerical analysis via Monte Carlo simulation and analytical computation using three-dimensional convolution. These methods are demonstrated on a 2-arc, 10-fraction treatment plan used to treat a representative lung tumor in a human subject. In the same human subject, the variability in position of a representative lung tumor was measured over repeated end-expiration breath-holds using volumetric imaging. For the 7 x 7 x 10 mm margin used to treat this 12 mm diameter tumor and the measured target position variability, we demonstrated that the entire tumor volume was irradiated to at least 48 Gy-well above the tumoricidal threshold. The advantages, in terms of minimizing the volume of surrounding lung tissue that is radiated to high dose during treatment, of using end-expiration breath holding compared with end-inspiration breath-holding are demonstrated using representative tumor size and position variability parameters. It is hoped that these results will ultimately lead to improved, if not curative, treatment for small (5-20 mm diameter) lung, liver, and other extra-cranial lesions.

Dose Fractionation, Radiation↗

Just-in-time tomography (JiTT): a new concept for image-guided radiation therapy.

Soft-tissue target motion is one of the main concerns in high-precision radiation therapy. Cone beam computed tomography (CBCT) has been developed recently to image soft-tissue targets in the treatment room and guide the radiation therapy treatment. However, due to its relatively long image acquisition time the CBCT approach cannot provide images of the target at the instant of the treatment and thus it is not adequate for imaging targets with intrafraction motion. In this note, a new approach for image-guided radiation therapy-just-in-time tomography (JiTT)-is proposed. Differing from CBCT, JiTT takes much less time to generate the needed tomographical, beam's-eye-view images of the treatment target at the right moment to guide the radiation therapy treatment.

Algorithms↗

Tumor cell apoptosis present at diagnosis may predict treatment outcome for patients with medulloblastoma.

PURPOSE: To determine if the degree of tumor cell apoptosis at diagnosis predicts outcome, tissue sections of medulloblastoma were examined and the amount of apoptosis and progression-free survival were correlated. PATIENTS AND METHODS: The study cohort consisted of 43 children in whom medulloblastoma was diagnosed between 1984 and 1995: 29 patients at high risk (HR) treated with radiation and chemotherapy, and 14 children at low risk (LR) treated with radiation alone. A terminal deoxynucleotidyl transferase (TdT) end-labeling assay was used to detect apoptosis in paraffin-embedded tissue sections prepared at diagnosis. RESULTS: Progression-free survival was examined in cohorts of children whose tumors were divided into quartiles based on the apoptotic index (AI) of their pretreatment tumor specimens. A comparison of these four groups of children revealed an association between AI and outcome (p = 0.03); patients with tumors in the highest AI quartile had substantially improved outcome compared to all other patients combined (p = 0.02). In this cohort of patients treated with different therapies, assignment at the time of diagnosis to LR and HR groups based on widely-accepted clinical criteria was not closely associated with outcome (p = 0.47). CONCLUSION: AI is a strong indicator of treatment outcome for children with medulloblastoma after treatment with cytotoxic therapy, independent of risk group. Because HR and LR patients included in this study received different modalities of cytotoxic therapy, it is possible that AI predicts outcome independent of the precise antineoplastic therapy a patient receives.

Adolescent↗

Radiation-recall skin disorders associated with the use of antineoplastic drugs. Pathogenesis, prevalence, and management.

Radiation-recall dermatitis is the occurrence, with subsequent administration of cytotoxic chemotherapy, of an acute inflammatory toxicity in a previously quiescent radiation field. It may occur from days to weeks, and sometimes years, after the radiation therapy. The precise mechanism is unknown. One hypothesis suggests that the initial radiation therapy leads to a depletion of tissue stem cells within the irradiated field and that subsequent cytotoxic chemotherapy exposure causes a 'remembered' reaction among the remaining surviving cells. An alternative proposition suggests that radiation induces heritable mutations within surviving cells, which then produce a subgroup of defective stem cells that are unable to tolerate the second insult of chemotherapy. Recently, ataxia telangiectasia gene mutation and protein kinase deficiency have been associated with patients who have increased susceptibility to severe radiation-induced skin toxicity. Most of the lesions will heal with supportive treatment. Although some reports have noted that radiation-recall dermatitis recurred with subsequent continued administration of the same chemotherapeutic agent, such experience is not universal. At present, a decision as to whether the same chemotherapeutic agent can be continued will usually be determined by the severity of the initial reaction, the chemoresponsiveness of the tumor to this particular agent, the individual patient's wishes, and a clinical judgment that takes into account the availability of alternative therapy.

Antineoplastic Agents↗

The impact of automated blood pressure devices on the efficiency of clinical trials.

By reducing measurement error, automated blood pressure (BP) devices should enhance the precision of BP estimation and thereby decrease sample size requirements in clinical trials of BP-lowering therapy. Enhanced precision would be particularly relevant to clinical trials assessing the efficacy of nonpharmacological therapies. In the present investigation, resting (clinic) BPs by the Dinamap 8100 (a stationary device) and the Accutracker II (an ambulatory device) were as precise as manual BPs given an equal number of observations by each method. However, both the Dinamap and Accutracker devices underestimated resting diastolic BP in comparison to the manual observers. Estimates of average daytime and 24-hour ambulatory BP, based on large numbers of observations over an extended period of time, were extremely precise. These findings suggest that the use of automated devices to measure resting BP may not reduce samples sizes, whereas use of ambulatory BP devices should reduce samples sizes considerably.

Bias↗