Biomedical subjects
P Larson
Publications and source records attributed to P Larson.
Single dose pharmacokinetics, safety and tolerability of MK-0476, a new leukotriene D4-receptor antagonist, in healthy volunteers.
MK-4076 or sodium 1-(1(R)-(3-(2-(7-chloro-2-quinolinyl)-(E)- ethenyl)phenyl) 3-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl) cycloproprane) acetate is a novel, potent, and specific LTD4-receptor antagonist. The safety, tolerability and plasma drug profiles of single oral doses of MK-0476 (capsules) were evaluated in 18 healthy male volunteers assigned to one of the two parallel 9-subject panels. Under fasting conditions, increasing single doses of 20 to 800 mg were administered in a first part of the study and in a second part, 200 mg MK-0476 was given either as a solution, under fasting conditions, or as capsules, after a standard breakfast. All volunteers completed the study. Side effects, reported by the investigator to be related to study drug, were mild and transient. No laboratory abnormalities were noted. In the evaluated dose range of MK-0476 (20 to 800 mg) the median value of tmax ranged from 2 to 4 h, while the apparent t1/2 value averaged 4 to 5 h. The median tmax value of the 200 mg capsule dose was not significantly different from the median tmax of the 200 mg oral solution dose indicating that neither disintegration nor dissolution is a rate-limiting step for the absorption of MK-0476 from capsules. There was a statistically significant increase in the AUC (geometric mean ratio of fed/fast was 2.52 with 95% confidence interval of 1.25, 5.06) and in Cmax (geometric mean ratio of fed/fast was 1.36 with 95% confidence interval of 0.60, 3.04) when MK-0476 was given together with a breakfast, suggesting an increase in bioavailability.(ABSTRACT TRUNCATED AT 250 WORDS)
Iron-initiated tissue oxidation: lipid peroxidation, vitamin E destruction and protein thiol oxidation. Inhibition by a novel antioxidant, U-78517F.
Oxidative injury was initiated by addition of ferrous ammonium sulfate (FAS) to a suspension of whole rat brain homogenate in Krebs buffer. After FAS addition, tissue vitamin E dropped sharply over a 30-sec interval and then recovered marginally for 5 min. After 5 min, vitamin E levels dropped to a low and constant level. Also after 5 min, TBARS (thiobarbituric acid reactive substances, a color test for lipid peroxidation) showed a statistically significant (P < or = 0.05) increase that continued through the remainder of the 30-min experiment. Reduced protein thiols decreased significantly (P < or = 0.05) at 15 min post FAS addition. This suggests that, in this model of iron-initiated lipid peroxidation (LP), the endogenous antioxidant vitamin E is first depleted before membrane lipids and membrane bound proteins show evidence of oxidative injury. A novel antioxidant, U-78517F, inhibited the destruction of vitamin E, LP and protein thiol oxidation in this model. The efficacy of the compound after different times of addition is described.
The nature and course of olfactory deficits in Alzheimer's disease.
OBJECTIVE: The aim of this study was to determine the specific nature and course of olfactory deficits in Alzheimer's disease. Previous studies had noted impaired odor identification, but there was no unanimity about the presence of odor detection deficits. METHOD: Odor identification was tested in 55 patients with Alzheimer's disease and 57 elderly control subjects by using the University of Pennsylvania Smell Identification Test. Odor detection was assessed in 46 subjects with Alzheimer's disease and 40 control subjects by using a forced-choice threshold test with geraniol as the odorant. RESULTS: Significant deficits in olfactory identification were present in subjects who were in the earliest stages of cognitive impairment, and these deficits increased as Alzheimer's disease progressed. There was some overlap in individual smell identification test scores between cognitively impaired patients and normal elderly subjects. On the other hand, odor detection deficits did not appear until Alzheimer's disease was relatively advanced. Smell identification test scores were correlated with Mini-Mental State scores, but geraniol detection was not. CONCLUSIONS: Odor identification is impaired early in Alzheimer's disease and may be more influenced by cognitive status than is acuity of odor detection, which is not altered until later in the disorder. The pattern of hyposmia in Alzheimer's disease suggests that the disorder may not "begin in the nose," as has been theorized previously. Further refinement of olfactory testing may be useful in the diagnostic evaluation of early dementia.
Lateral chest roentgenograms in debilitated nursing home residents.
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Selective effect of cefoxitin prophylaxis on post-cesarean-section microbial flora.
A double-blind study was done to test the efficacy of cefoxitin in the prevention of post-cesarean-section infection. The antibiotic was given in three 2-g doses; the initial dose was given immediately after the cord was clamped, and subsequent doses were given four and eight hours later. Cefoxitin prophylaxis significantly reduced morbidity serious enough to require therapeutic antibiotics or to prolong the hospital stay and led to an overall reduction in the anaerobic microbial flora of the endocervix. However, the antibiotic was selective for the overgrowth of enterococci, which were present in nearly half the postoperative cultures of patients who had received the drug. Enterococcal sepsis occurred in one patient, and three other patients had significant bacteriuria and/or urinary tract infections from enterococci. No cefoxitin-resistant strains of Enterobacteriaceae, among species normally sensitive to the drug, were isolated from the stool samples after prophylaxis. The risk of enterococcal colonization and superinfection must be weighted against the benefits of reduction of the infection risk when deciding upon routine antibiotic prophylaxis for cesarean section.
Red cell antibody problems in 1000 liver transplants.
Liver transplant patients frequently require large amounts of blood. The frequency and nature of their red cell (RBC) antibody problems were examined. Records were reviewed in 496 adults and 286 children undergoing 1000 consecutive transplants. Twenty-two percent of adults and 14 percent of children had RBC alloantibodies. Antibodies of potential clinical significance were found before transplant in 6.3 percent of adults and 1.0 percent of children; despite immunosuppression, they appeared 1 to 5 weeks after transplant in an additional 7.5 and 5.2 percent respectively. These antibodies probably represented secondary immune responses. Of 58 transplant patients with prior potentially significant antibodies, 8 required 7 to 110 units of antigen-untyped blood after 8 to 28 units of antigen-negative blood; of these patients, one had subsequent hemolysis. Positive direct antiglobulin tests in 24 percent of adults and 10 percent of children were most often thought to be due to nonspecific adsorption of IgG. Anti-recipient ABO antibodies developed in 22 of 60 (37%) evaluable ABO-unmatched grafts; 13 cases had associated hemolysis. In all, 36 percent of adults and 20 percent of children had diverse RBC antibody problems. Resolution of these problems is an important part of the laboratory support necessary for a liver transplantation program.
Mohs micrographic surgery for melanoma.
The results of multiple investigators have confirmed the value of Mohs surgery in the treatment of melanoma. In addition, these studies have contributed to our understanding of the biologic behavior of melanoma. The success of Mohs surgery confirms that melanoma grows in a contiguous fashion before it spreads systemically. It is known that once tumor breaks away from the main mass, trying to improve survival by increasing the extent of conventional surgery is often fruitless. Therefore, the goal of surgery is to remove all of the tumor, including the silent contiguous foci. If melanoma did not grow in a contiguous fashion before metastasis, the results of Mohs surgery would be inferior to wide excision, and higher local recurrences would be expected. Instead, the excellent results support the concept of contiguous tumor growth. Satellites and in-transit metastases that appear later may be removed with the fixed-tissue technique. We have also learned that melanoma sends out silent contiguous extensions, necessitating excision of some normal-appearing skin. The width of those extensions is unrelated to the depth of the melanoma. The value of Mohs surgery is the ability to identify these extensions microscopically and to excise tumor-bearing tissue while sparing normal skin. In fact, Mohs surgery often spares a diameter of 1.8 cm or more when compared with standard surgery, a distinct advantage to patients whose melanomas are on the head, neck, hands, feet, or genitalia or in patients whose melanoma has indistinct clinical margins and would require an even wider margin of normal skin when using standard surgical techniques. We now have long-term results from large numbers of patients--confirmed by multiple investigators and data--to support the concept of Mohs surgery for melanoma. This information emphasizes the important role that Mohs micrographic surgery plays in the treatment of melanoma.
Micrographic surgery for the microscopically controlled excision of carcinoma of the external ear.
Micrographic surgery is particularly valuable for treating carcinomas of the external ear because the total microscopic control of excision afforded by this method permits selective removal of the clinically unpredictable cancerous outgrowths. The maximum conservation of normal tissues, including the cartilaginous framework that gives shape to the ear, is a benefit next in importance to the unusually high 5-year cure rates (97.1% in a series of 1213 cases of basal cell carcinoma and 92.3% in a series of 871 cases of squamous cell carcinoma). The fresh-tissue technique for removing most auricular carcinomas usually permits the excision of the successive layers in 1 day, and repair, if needed, can be done immediately. The fixed-tissue technique is still used by the authors for some extensive, bone-invading carcinomas.
The Lewis blood group system in liver transplantation.
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Psychological services offered to female veterans.
Questionnaires were sent to 153 chiefs of Veterans Administration psychology services to request information on service provision to women veterans; 91 responses were received. Services were classified according to four categories: (a) individual women served in response to requests; (b) individual programs designed to meet specific needs; (c) educational programs offered to female clients; and (d) staff training programs. Correlations between each of the four categories and the following factors were calculated: (a) size of the city as determined by population in which each Veterans Administration Medical Center is located; (b) state population of female veterans; (c) number of female staff psychologists; (d) annual percentage of female clients served; (e) income of female clients; (f) total number of psychologists on the staff; and (g) total annual number of clients. Significant correlations were found between number of services offered routinely in response to requests and each of the following factors: (a) state population of female veterans; (b) income of female veteran clients; (c) total number of psychologists on the staff; and (d) annual number of clients.
Hemoglobin SC disease causing ischemic necrosis.
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Advances in fused-silica column technology for the analysis of underivatized drugs.
The chemical durability of a cross-linked 5% phenyl methylsilicone stationary phase is investigated for the analysis of underivatized drugs. Column performance is tested with respect to quantitative reproducibility, solvent extractability, selectivity for various drug families, and capacity for the polar solute. Data are presented showing the effects of a polar solvent and a serum extract on column lifetime with splitless and cool on-column injection. Examples of a human drug screen and the forensic analysis of street heroin are provided.
Caution advised when managing diabetic retinopathy by continuous subcutaneous insulin infusion.
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In vitro assay for predicting protein efficiency ratio as measured by rat bioassay: collaborative study.
Seven laboratories collaborated in testing the calculated protein efficiency ratio (C-PER and DC-PER). The collaborative study required each laboratory to analyze 6 foods and a control protein (ANRC casein) for in vitro apparent protein digestibility, amino acid composition, and PER via rat bioassay. The 6 foods or food ingredients tested were nonfat dry milk, cooked chicken muscle, protein-fortified dry breakfast cereal, textured soy protein, oat-based dry breakfast cereal, and durum wheat flour. Data obtained from the study were analyzed statistically for the intralaboratory variation for each method of analysis (i.e., amino acid analysis, PER, etc.). The ability of the C-PER to rapidly predict rat PER was also measured. The C-PER and DC-PER methods were adopted official first action.
Nurses' and physicians' performance on clinical simulation test: hypertension.
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Psychopathology in self-identified female-to-male transsexuals, homosexuals, and heterosexuals.
The comparative self-esteem and psychological well-being of female-to-male transsexuals, homosexuals, and heterosexuals (patient and nonpatient) were studied. Results indicated that individual candidates for sex-change surgery varied appreciably in self-concept and adjustment, and as a group were indistinguishable from psychiatric controls. Nonpatient homosexuals and heterosexuals demonstrated the most positive self-esteem and level of adjustment.