Abstract: Rapid and cost effective diagnosis of p53 mutations of a sample of patients is achieved by employing a selected plurality of diagnostic tools, in a hierarchy of increasing accuracy and cost per tool, in which each tool detects essentially no false positives. Diagnostic tests that may be included among the plurality of tests selected include, in order of increasing accuracy and cost:(a) immunoassays,(b) analysis of DNA from a patient sample by quantitative amplification of p53 exons using amplification primers complementary to intron regions flanking each exon and examination of the length or quantity of each amplified fragment for nucleotide insertions or deletions relative to the normal p53 gene.

Abstract: Reliable and cost effective testing for mutations in the RB1 gene can be accomplished by quantitatively amplifying exons of the sample RB1 gene using primers complementary to intron regions flanking each exon; and then determining the lengths and/or quantities of the amplification products for each exon and comparing that length or quantity to the length or quantity of amplification products obtained when a wild-type RB1 gene is amplified using the same primers. Differences in length between an amplified sample exon and the corresponding amplified wild-type exon reflect the occurrence of an insertion or deletion mutation in the sample RB1 gene. Differences in quantity reflect the complete absence of an exon, or heterozygosity for a mutant exon. Next, the nucleic acid sequence of each exon found to contain an insertion or deletion mutation is determined, or of all exons in the event no insertion or deletion mutations are identified.

Abstract: A hierarchy of at least two assay techniques is utilized in testing for disease-associated mutations. The first assay in the hierarchy is selected to provide a highly specific test for the existence of the disease-associated mutation, although the accuracy of the test need not be high. The final assay in the hierarchy is selected to provide a highly accurate and highly specific test for the existence of the disease associated mutation. Intermediate tests of progressively greater accuracy may also be included in the hierarchy. Once the hierarchy has been selected for a given mutation-associated disease, a patient sample is analyzed the patient sample using the first, lowest accuracy assay in the hierarchy. If the result of the first assay is negative for the presence of a disease-associated mutation, then the next assay in the hierarchy is performed.

Abstract: A constant release rate indomethacin formulation in tablet unit dosage form, said tablet comprising an intimate admixture of from 50 to 200 mg of indomethacin, from about 1.7 to 3.7 weight percent of a slow-dissolving, water-insoluble cellulose derivative, from about 1.5 to 5.0 weight percent of a tabletting disintegrant, and from about 40 to 80 weight percent of a pharmaceutically acceptable bulking agent or diluent.

Abstract: A constant order release rate solid oral dosage formulation of propranolol or a pharmaceutically acceptable salt thereof, said formulation comprising: a therapeutically effective amount of propranolol or a pharmaceutically acceptable salt; from about 0.5 to 6.0 weight percent of an acid-retardant or hydrophobic cellulose derivative; from about 2.5 to 35 weight percent of a hydrogenated vegetable oil: from about 1 to 20 weight percent of an acrylic acid polymer; from about 0.5 to 4.0 weight percent of fumed silicon dioxide and from about 0.4 to 3.0 percent of a lubricant.

Abstract: A constant order release rate solid oral dosage formulation of quinidine or a pharmaceutically acceptable salt thereof, said formulation comprising: a therapeutically effective amount of quinidine or a pharmaceutically acceptable salt; from about 0.5 to 6.0 weight percent of an acid-retardant or hydrophobic cellulose derivative; from about 2.5 to 35 weight percent of a hydrogenated vegetable oil: from about 1 to 20 weight percent of an acrylic acid polymer; from about 0.5 to 4.0 weight percent of fumed silicon dioxide and from about 0.4 to 3.0 percent of a lubricant.

Abstract: A constant order release rate solid oral dosage formulation of hydralazine or a pharmaceutically acceptable salt thereof, said formulation comprising: a therapeutically effective amount of hydralazine or a pharmaceutically acceptable salt; from about 0.5 to 6.0 weight percent of an acid-retardant or hydrophobic cellulose derivative; from about 2.5 to 35 weight percent of a hydrogenated vegetable oil: from about 1 to 20 weight percent of an acrylic acid polymer; from about 0.5 to 4.0 weight percent of fumed silicon dioxide and from about 0.4 to 3.0 percent of a lubricant.

Abstract: A constant release aspirin tablet comprising from 85-95 weight percent of aspirin, from 1.5-5 weight percent of microcrystalline cellulose, from 1-10 weight percent of cellulose acetate phthalate, from 0.75-4 weight percent of a plasticizer, from 0.75-5 weight percent of corn starch, and from 0.5 to 2 percent of a lubricant.

Abstract: A constant order release rate solid oral dosage formulation of verapamil or a pharmaceutically acceptable salt thereof, said formulation comprising: a therapeutically effective amount of verapamil; from about 0.5 to 6.0 weight percent of an acid-retardant or hydrophobic cellulose derivative; from about 2.5 to 35 weight percent of a hydrogenated vegetable oil: from about 1 to 20 weight percent of an acrylic acid polymer; from about 0.5 to 4.0 weight percent of fumed silicon dioxide and from about 0.4 to 3.0 percent of a lubricant.

Abstract: A constant order release aspirin tablet comprising aspirin, from 0.5 to 10 weight percent of a hydrogenated vegetable oil and from 0.5 to 7 weight percent of a saccharide selected from the group consisting of lactose, sucrose, dextrose fructose and maltose. The aspirin tablet is administered once or twice a day for the chronic treatment of arthritis, and has substantially lessened gastrointestinal side effects.

Abstract: An improved tablet formulation is provided comprising an effective amount of an active therapeutic agent, especially an acidic therapeutic agent such as aspirin, a release-controlling agent, and an erosion-promoting agent in relative amounts to provide a criticality factor of less than 450, and in proportions of release-controlling and erosion-promoting agent, respectively, between 0.8-1.6 and 1.0-7.5 weight percent per tablet. The tablets of this invention exhibit zero order release in vitro and closely approximate zero order absorption in vivo. The aspirin tablets of the invention produce minimal epigastric distress and can be administered twice-a-day to provide the desired therapeutic effect. The preferred release-controlling agent is cellulose acetate phthalate and the preferred erosion-promoting agent is corn starch.

Abstract: A method for lowering serum uric acid is disclosed which comprises administering to a human for its uricosuric activity a pharmaceutical composition comprising 7-chloro-2-methyl-3,3a-dihydro-2H,9H-isoxazolo (3,2-b) (1,3)-benzoxazin-9-one.7-chloro-2-methyl-3,3a-dihydro-2H,9H-isoxazolo (3,2-b) (1,3) benzoxazin-9-one is a useful compound having valuable pharmacological properties, for example, it is a valuable anti-inflammatory agent, as evidenced by its ability to inhibit the local edema formation characteristic of inflammatory states when administered systemically to warm-blooded animals.