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Biomedical subjects

N Garrison

Publications and source records attributed to N Garrison.

6 recordsLinked to original sources

Sparfloxacin for the treatment of acute bacterial maxillary sinusitis documented by sinus puncture.

PURPOSE: To evaluate the efficacy and safety of sparfloxacin in the treatment of patients with acute bacterial maxillary sinusitis, the microbiologic etiology of which was determined by maxillary sinus puncture. PATIENTS AND METHODS: Two hundred fifty-three patients enrolled in the open, noncomparative trial received sparfloxacin as a 400-mg loading dose followed by 200 mg once daily doses for a total of 10 days. One hundred ninety-eight patients were clinically evaluable and 82 were also bacteriologically evaluable. All treated patients were included in the safety analysis. Overall success was determined based on clinical success (resolution or reduction of signs and symptoms and sinus x-rays) and bacteriologic success (eradication and presumed eradication of baseline pathogens obtained by maxillary sinus puncture and aspiration). RESULTS: Overall success in the bacteriologically evaluable population at test-of-cure was 91.5% [75/82; 95% confidence interval (85.4%, 97.5%)]. For all pathogens, the eradication rate was 93.2% (109/117 baseline pathogens); individual pathogen eradication rates were 88.9% (16/18) for S. pneumoniae (including those strains exhibiting decreased susceptibility to penicillin); and 100% for H. influenzae (17/17), S. aureus (14/14), and M. catarrhalis (11/11). The majority of adverse events were of mild or moderate severity; the most frequently related adverse events were photosensitivity reaction, headache, nausea, and diarrhea. CONCLUSION: Sparfloxacin had an overall success rate of 91.5% for patients in this study and was generally well tolerated in the treatment of acute bacterial maxillary sinusitis.

Acute Disease↗

8-Bromo-cyclic AMP induces phosphorylation of two sites in SRC-1 that facilitate ligand-independent activation of the chicken progesterone receptor and are critical for functional cooperation between SRC-1 and CREB binding protein.

Elevation of intracellular 8-bromo-cyclic AMP (cAMP) can activate certain steroid receptors and enhance the ligand-dependent activation of most receptors. During ligand-independent activation of the chicken progesterone receptor (cPR(A)) with the protein kinase A (PKA) activator, 8-bromo-cAMP, we found no alteration in cPR(A) phosphorylation (W. Bai, B. G. Rowan, V. E. Allgood, B. W. O'Malley, and N. L. Weigel, J. Biol. Chem. 272:10457-10463, 1997). To determine if other receptor-associated cofactors were targets of cAMP-dependent signaling pathways, we examined the phosphorylation of steroid receptor coactivator 1 (SRC-1). We detected a 1.8-fold increase in SRC-1 phosphorylation in transfected COS-1 cells incubated with 8-bromo-cAMP. Phosphorylation was increased on two mitogen-activated protein kinase (MAPK) sites, threonine 1179 and serine 1185. PKA did not phosphorylate these sites in vitro. However, blockage of PKA activity in COS-1 cells with the PKA inhibitor (PKI) prevented the 8-bromo-cAMP-mediated phosphorylation of these sites. Incubation of COS-1 cells with 8-bromo-cAMP resulted in activation of the MAPK pathway, as determined by Western blotting with antibodies to the phosphorylated (active) form of Erk-1/2, suggesting an indirect pathway to SRC-1 phosphorylation. Mutation of threonine 1179 and serine 1185 to alanine in COS-1 cells coexpressing cPR(A) and the GRE(2)E1bCAT reporter resulted in up to a 50% decrease in coactivation during both ligand-independent activation and ligand-dependent activation. This was due, in part, to loss of functional cooperation between SRC-1 and CREB binding protein for coactivation of cPR(A). This is the first demonstration of cross talk between a signaling pathway and specific phosphorylation sites in a nuclear receptor coactivator that can regulate steroid receptor activation.

8-Bromo Cyclic Adenosine Monophosphate↗

Improving the request process to increase family consent for organ donation.

The greatest impediment to organ donation is refusal of family consent. This study examined the impact of 3 modifiable elements of the donation request on family consent rates: (1) decoupling (i.e., the family understands and accepts brain death before discussion of organ donation is begun); (2) the procurement coordinator participates in the request for consent; and (3) donation is requested in a quiet, private place. Data on the request process were collected prospectively for 707 medically suitable potential donors who had been referred to 3 organ procurement organizations. The average rate of consent for donation was 62.2%. Higher consent rates were independently associated with the 3 characteristics studied. These components were summarized in the Request Process Scale. Multivariate regression analyses indicated that consent rates can be as high as 74% when all 3 process elements are present. Hospitals and organ procurement organizations should incorporate these elements into their standard of practice when requesting organ donation.

Adolescent↗