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Significant increases in lymphocyte adenosine deaminase activity, T cell numbers and immune function have been achieved in the two children with SCID thus far treated with autologous T cells genetically-corrected by retroviral-mediated insertion of a normal ADA gene. Although the data obtained to date demonstrate that the use of ADA gene corrected peripheral T cells appears to be an effective treatment for ADA(-)SCID, it is theoretically preferable to try to develop a treatment for these children that will result in stem cell gene correction. The genetic correction of T cell progenitors with long-term immune reconstituting ability would be more desirable because repeated infusions of genetically altered cells should not be necessary and the generation of a more complete repertoire of T cell specificities might also be possible. Furthermore, the present treatment protocol involves indefinite continuation of enzyme replacement treatment with PEG-ADA. The demonstration of ADA gene expression in the progeny of transduced stem cells may simplify the decision concerning cessation of this very costly enzyme treatment (approximately $250,000/yr./patient). Recent evidence suggests that a small fraction of bone marrow or peripheral blood mononuclear cells bearing the CD34 antigen contains hematopoietic stem cells with both lymphoid and myeloid reconstituting ability. We propose in this amendment to supplement the infusion of human ADA gene-transduced autologous T cells in children with ADA(-)SCID with autologous peripheral blood CD34+ cells transduced with a second, readily distinguishable ADA vector.(ABSTRACT TRUNCATED AT 250 WORDS)
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A method is introduced, inferring the three-dimensional (3-D) location from the 2-D radiographic shadow of an opaque spherical reference body of known radius by considering its elliptical distortion, the 2-D shadow location and a known source-to-receptor distance. Three noncollinear spheres fixed to a rigid object constitute all possible degrees of freedom, i.e., the entire 3-D imaging geometry. The method may be used (a) to determine the 3-D imaging geometry from a single 2-D view and (b) to correct for foreshortening of object distances coplanar with the plane defined by the sphere triplet. Apart from the mathematical background the article describes a small feasibility experiment, performed with four different sphere diameters and a commercial dental ccd-receptor system (pixel length: 0.0195 mm). The mouse-cursor based image evaluation revealed an average underestimation of the critical depth- (x-) coordinate decreasing with increasing radius (-30.3% for r=0.5 mm to 2.8% for r=2.5 mm). Intraobserver reliability (the standard deviation between three single cursor-based assessments) ranged between 0% and 8% of the actual true depth. The main source of the input error is associated with the assessment of the amount of elliptical distortion, where subpixel accuracy is demanded. Consequently, software-based automated image evaluation is required using available methods for pattern recognition and point-spread correction. Provided sufficient accuracy, the method provides an important tool for foreshortening correction, depth assessment, motion analysis, and 3-D reconstruction from two or more 2-D views.
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The objectives of this study were to improve thrombolytic therapy in acute myocardial infarction by reducing the "door-to-needle" time in a 285-bed university hospital in Spain. A quality management approach was used involving all the relevant staff. Target standard was set at 35 minutes. Baseline data, intervention effect, and continuous monitoring were analyzed using x control charts. Analysis of baseline data showed a wide out-of-control variation and 72 minutes' average delay. Cause analysis revealed organizational and clinical problems that were subjected to intervention. Postintervention data showed a stable process, with an average of 30 minutes. Continuous monitoring showed further improvement in average time and predictable variation. The template of the current control chart has an average of 26 minutes. Quality management methods, particularly staff involvement in problem analysis and intervention design, and the use of control charts were useful to understand, solve, and continuously monitor an important clinical problem whose existence was evident only after it was measured.
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We propose the following guidelines for treatment of hypertension in the elderly. 1. Indications for Treatment. 1) Age: Lifestyle modification is recommended for patients aged 85 years and older. Antihypertensive therapy should be limited to patients in whom the merit of the treatment is obvious. 2) Blood pressure: Systolic BP > 160 mmHg, diastolic BP > 90 approximately 10 mmHg. Systolic BP < age + 100 mmHg for those aged 70 years and older. Patients with mild hypertension (140-160/ 90-95 mmHg) associated with cardiovascular disease should be considered for antihypertensive drug therapy. 2. Goal of Therapy for BP: The goal BP in elderly patients is higher than that in younger patients (BP reduction of 10-20 mmHg for systolic BP and 5-10 mmHg for diastolic BP). In general, 140-160/< 90 mmHg is recommended as the goal. However, lowering the BP below 150/85 should be done with caution. 3. Rate of Lowering BP: Start with half the usual dose, observe at the same dose for at least four weeks, and reach the target BP over two months. Increasing the dose of antihypertensive drugs should be done very slowly. 4. Lifestyle Modification: 1) Dietary modification: (1) Reduction of sodium intake is highly effective in elderly patients due to their high salt-sensitivity. NaCl intake of less than 10 g/day is recommended. Serum Na+ should be occasionally measured. (2) Potassium supplementation is recommended, but with caution in patients with renal insufficiency. (3) Sufficient intake of calcium and magnesium is recommended. (4) Reduce saturated fatty acids. Intake of fish is recommended. (2) Regular physical activity: Recommended exercise for patients aged 60 years and older: peak heart rate 110/minute, for 30-40 minutes a day, 3-5 days a week. (3) Weight reduction. (4) Moderation of alcohol intake, smoking cessation. 5. Pharmacologic Treatment: 1) Initial drug therapy. First choice: Long-acting (once or twice a day) Ca antagonists or ACE inhibitors. Second choice: Thiazide diuretics (combined with potassium-sparing diuretic). 2) Combination therapy. (1) For patients without complications, either of the following is recommended. i) Ca antagoinst + ACE inhibitor, ii) ACE inhibitor + Ca antagonist (or low-dose diuretics), iii) diuretic + Ca antagonist (or ACE inhibitor), iv) beta-blockers, alpha 1-blockers, alpha + beta blockers can be used according to the patho-physiological state of the patient. (2) For patients with complications. Drug(s) should be selected according to each complication. 3) Relatively contraindicated drugs. beta-Blockers and alpha 1-blockers are relatively contraindicated in elderly patients with hypertension in Japan. Centrally acting agents such as reserpine, methyldopa and clonidine are also relatively contraindicated beta-Blockers are contraindicated in patients with congestive heart failure, arteriosclerosis obliterans, chronic obstructive pulmonary disease, diabetes mellitus (or glucose intolerance), or bradycardia. These conditions are often present in elderly subjects. Elderly subjects are susceptible to alpha 1-blocker-induced orthostatic hypotension, since their baroreceptor reflex is diminished. Orthostatic hypotension may cause falls and bone fractures in the elderly.