Phase I Trial of Methotrexate-Albumin in a Weekly Intravenous Bolus Regimen in Cancer Patients

The scale was easy to apply and proved to be useful in comparing the effectiveness of different modes of treatment in two clinical trials. Follow-up data were available for 176 patients at one year and for 106 patients at two years. The mean (+/- SE) activity-index score (possible range, 74 to 172) decreased in one year from 108 +/- 3 to 87 +/- 2 in the group receiving continuous medical therapy, from 107 +/- 3 to 88 +/- 2 in the group receiving medical therapy for symptoms only, and from 109 +/- 3 to 78 +/- 2 in the surgical-therapy group (P less than 0.0001 for the change from base line, for all comparisons).

The evaluation of the success of therapy for gastroesophageal reflux disease (GERD) has thus far been primarily on the basis of the endoscopic evaluation of the ability of drugs to heal esophageal mucosal breaks and to a lesser extent on their ability to decrease the diverse symptoms of acid reflux. However, because most patients with GERD have no visible esophageal lesions using conventional endoscopic methods, this paradigm requires serious reconsideration. As patients with nonerosive reflux disease (NERD) are just as symptomatic as patients with erosions and are no easier to treat the use of endoscopic end points alone, as criteria for determining healing and efficacy of therapy requires reassessment. In addition, the symptoms of GERD are now appreciated to be broad-based, including many extraesophageal symptoms that contribute to the marked reduction in quality of life for GERD patients. For this reason, and because endoscopic criteria cannot be applied to evaluating therapy in NERD, the success of GERD therapy should be judged primarily in terms of diminishment of GERD-related symptoms–a return to the traditional way that patients judge therapeutic success.

MRI is considered the gold standard for imaging of synovitis, and MRI bone marrow oedema has been shown to be the strongest independent predictor of radiographic progression in RA.6 7 However, broader usage of MRI in clinical routine settings may be restricted by workflow considerations, cost and limited availability. MTX-HSA every 2-4 weeks, achieving plasma concentrations between 10 and 20 μmol/liter, proved to be safe and effective, based on observation of the three responding patients. All 17 patients were evaluable for DLT within the first two consecutive courses; 13 patients received at least three courses, 12 patients received at least seven courses, and 8 patients received more than seven consecutive courses. One patient withdrew informed consent after two courses, and treatment was discontinued in two patients because of tumor-induced health deterioration after the second or third injection. Indocyanine green (ICG)-enhanced fluorescence optical imaging (FOI) is an established technology for imaging of inflammation in animal models.

Ultrasonography (US) in greyscale mode (GSUS) and US in power Doppler mode (PDUS) have been demonstrated as valid tools for the assessment of synovitis and scoring of clinical activity in RA.8, -, 10 In daily clinical practice, PDUS is more available than MRI and often used for fast and dynamic assessment of joint inflammation.11 However, apart from clinical studies, the examination procedure is usually limited to a reduced number of joints12 due to time constraints. With recent advances in the management of rheumatic diseases, imaging plays a major role in early diagnosis, estimation of prognosis and evaluation of therapeutic outcome. In rheumatoid arthritis (RA), treat-to-target strategies1 and the adequate use of disease-modifying drugs1 2 require sensitive instruments that allow a valid detection of affected joints. This study was supported by BMBF project “ArthroMark”, subproject no. 7 “Clinical study on Biomarkers and Imaging”. One of the technical devices (FOI) was provided via an unrestricted educational grant by Pfizer Company, Berlin, Germany.

Subclinical inflammation

Thus, findings in these phases seem to be of special interest. The highest sensitivity was seen in P2 and is comparable to the sensitivity of US with MRI as reference reported from other studies.30 32 While the meaning of the phases is still unclear, an adequate interpretation of an FOI exam requires a specific reading of all the phases. In the control group, FOI was normal in 97.8% joints.

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Details about GERD BAHNER German Conductor rare signed photo, 1976

We conducted a long-term, randomized trial of medical therapy (lifestyle modifications and up to four medications) and surgical therapy (Nissen fundoplication) in 247 patients (243 men and 4 women) with peptic esophageal ulcer, stricture, erosive esophagitis, or Barrett’s esophagus. They received by random assignment either continuous medical therapy, medical therapy for symptoms only, or surgical therapy. Symptoms were assessed quarterly with a disease-activity index; esophagoscopy was performed at base line and each year for two years. The outcomes evaluated at one and two years included the activity index, and the endoscopic grade of esophagitis.

Poststudy treatment is ongoing, with no signs of a tumor relapse in this patient at the time of completing this article (December 1998; tumor response time, 31 months, ongoing). dose level), which resolved under ongoing treatment. In some patients, grade 2 or grade 3 transaminitis and hyperbilirubinemia were associated with a rapid progression of liver metastases.

The mean activity-index score and the grade of esophagitis were significantly better in the surgical-therapy group than in either medical-therapy group during the two years of follow-up (P less than 0.003). Conventional medical treatment for gastroesophageal reflux disease involves life-style modifications and combination drug therapy, but few studies have included these features in their protocols. Antireflux surgery has seldom been studied prospectively, and there have been no trials comparing modern medical and surgical treatments for reflux disease.

Fat-saturated coronal proton-density (FS-PD-TSE), non-enhanced and enhanced T1-TSE with subtraction, coronal and axial fat-saturated postintravenous gadolinium (Dotarem, 0.2 ml/kg/body weight) (FS-T1-TSE) sequences of the clinically dominant hand were performed in 25 patients (1.5 T MRI; Siemens Magnetom Symphony, Erlangen, Germany). MRI findings (MCP 1-5, interphalangeal joint finger 1 (IP), PIP 2-5, DIP 5 and wrist as a whole) were scored according to the OMERACT (Outcome Measures in Rheumatoid Arthritis Clinical Trials) criteria.19, -, 21 The RAMRI score was calculated. We report the results of the first comparative study of this commercially available FOI system with CE, US and contrast-enhanced MRI in two major cohorts of patients with arthritis and allied conditions and controls. Careful clinical examination (CE) is a prerequisite but may miss subclinical inflammation in early disease as well as in clinical remission under treatment.3, -, 5 Conventional radiography is commonly used as an indicator of prognosis and represents the standard outcome measure of disease progression in clinical studies but is displaying the result of previous inflammatory processes rather than presenting current disease activity.

Of several symptoms thought to be related to gastrooesophageal reflux disease (GORD), only heartburn (68% vs 48%) and acid regurgitation (60% vs 48%) occurred in more of the patients with GORD (as determined by pH monitoring) than of those with normal pH monitoring. When heartburn or acid regurgitation clearly dominated the patient’s complaints, they had very high specificity (89% and 95%, respectively) but low sensitivity (38% and 6%) for GORD. A third of the patients reported such inconclusive symptomatology at history-taking that no preliminary diagnosis about the presence or absence of GORD could be made.

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