Background Patient beliefs, values, and preferences are crucial to decisions involving health care. In a large sample of persons at increased risk for stroke, we examined attitudes toward ...hypothetical major stroke.
Methods and Results Respondents were obtained from the Academic Medical Center Consortium (
n = 621), the Cardiovascular Health Study (
n = 321), and United Health Care (
n = 319). Preferences were primarily assessed by using the time trade off (TTO). Although major stroke is generally considered an undesirable event (mean TTO = 0.30), responses were varied: although 45% of respondents considered major stroke to be a worse outcome than death, 15% were willing to trade off little or no survival to avoid a major stroke.
Conclusions Providers should speak directly with patients about beliefs, values, and preferences. Stroke-related interventions, even those with a high price or less than dramatic clinical benefits, are likely to be cost-effective if they prevent an outcome (major stroke) that is so undesirable. (Am Heart J 1998;136:703-13.)
A novel isoquinuclidine containing selective melanocortin subtype-4 receptor small molecule agonist,
3 (RY764), is reported. Its in vivo characterization revealed mechanism-based food intake ...reduction and erectile activity augmentation in rodents.
A novel isoquinuclidine containing selective melanocortin subtype-4 receptor small molecule agonist,
3 (RY764), is reported. Its in vivo characterization revealed mechanism-based food intake reduction and erectile activity augmentation in rodents.
The public's attitude toward pharmacy Yellin, A K; Norwood, G J
Journal of the American Pharmaceutical Association (1961)
14, Številka:
2
Journal Article
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4-Amino-5,7-disubstituted pyridopyrimidines are potent, non-nucleoside inhibitors of adenosine kinase (AK). We recently identified a potent, orally efficacious analog, 4 containing a ...7-pyridylmorpholine substituted ring system as the key structural element of this template. In this report, we disclose the pharmacologic effects of five- and six-membered heterocyclic ring replacements for the pyridine ring in 4. These replacements were found to have interesting effects on in vivo efficacy and genotoxicity as well as in vitro potency. We discovered that the nitrogen in the heterocyclic ring at C(7) is important for the modulation of mutagenic side effects (Ames assay).
We have previously shown that appropriate modification of the benzocycloheptapyridine tricyclic ring system can provide potent farnesyl protein transferase (FPT) inhibitors with good cellular ...activity. Our laboratories have also established that incorporation of either pyridinylacetyl N-oxide or 4-N-carboxamidopiperidinylacetyl moieties results in pharmacokinetically stable inhibitors that are orally efficacious in nude mice. We now demonstrate that further elaboration of the tricyclic ring system by introducing a bromine atom at the 7- or the 10-position of the 3-bromo-8-chlorotricyclic ring system provides compounds that have superior potency and selectivity in FPT inhibition. These compounds have good serum levels and half-lives when given orally to rodents and primates. In vitro and in vivo evaluation of a panel of these inhibitors has led to identification of 15 (SCH 66336) as a highly potent (IC50 = 1.9 nM) antitumor agent that is currently undergoing human clinical trials.
The influence of dosing interval on the human antibody response to anthrax vaccine adsorbed (AVA) was evaluated in two retrospective serological studies. In both studies, the interval between the ...first two doses was 2, 3 or 4 weeks. In the first study, banked sera were selected from 89 at-risk individuals at a mean time of 13 days after the second dose of vaccine. In the second study, banked sera were selected from 51 at-risk individuals at a mean time of 48 days following the first dose of AVA. In both studies, the geometric mean anti-protective antigen IgG antibody titer increased significantly as the interval between the two doses increased from 2 to 4 weeks (
p=0.0005–0.029). In the first study, the seroconversion rate also increased as the interval between the first two doses increased (
p=0.0034). A prospective, randomized study has been completed and is being analyzed to confirm these findings.
The roles of selectins in the pulmonary margination and emigration of neutrophils were investigated by using mice genetically deficient in both E- and P-selectins (E/P mutants) and/or by intravenous ...injections of fucoidin (inhibiting both L- and P-selectins). E/P mutants were neutrophilic (14.7 +/- 4.9 x 10(6) vs. 0.8 +/- 0.1 x 10(6) neutrophils/ml). This neutrophilia was associated with increased margination of neutrophils within pulmonary capillaries (39.7 +/- 9.4 vs. 4.6 +/- 1.1 neutrophil profiles per 100 red blood cell profiles) but no change in margination within noncapillary pulmonary microvessels. After intratracheal instillation of Streptococcus pneumoniae, lungs of E/P mutants displayed increased neutrophil emigration (564 +/- 92 vs. 116 +/- 19 neutrophils per 100 alveolar profiles), edema (5.3 +/- 1.5 vs. 1.5 +/- 0.4 microliter/g body weight), and histologic evidence of lung injury compared with those in wild-type (WT). Fucoidin treatment did not affect neutrophil emigration during streptococcal pneumonia in WT or E/P mice. During pneumonia, the number of white blood cells (WBC) tethered to or spread upon the noncapillary vessel endothelium increased in both WT and E/P lungs. These are the first data demonstrating that neutrophil margination in uninfected pulmonary capillaries does not require E- and P-selectins; that streptococcal pneumonia induces an E- and P-selectin-independent increase in WBC interactions with noncapillary endothelium; and that migration of neutrophils to alveoli can occur despite deficiency or inhibition of all of the known selectins.
BACKGROUND:
With the general acceptance of lumpectomy, axillary staging, and radiotherapy as local treatment for infiltrating breast cancer, an appreciation is evolving for the spectrum of vascular ...lesions that occur in the mammary skin after this treatment. Most of these lesions develop within the prior radiation field after breast conservation treatment.
STUDY DESIGN:
A retrospective chart and slide review was conducted, consisting of five patients with cutaneous vascular lesions after breast conservation treatment for infiltrating breast cancer.
RESULTS:
The latent time interval from definitive treatment of breast cancer to the clinical recognition of vascular lesions ranged from 5 to 11 years. Two patients did not have either arm or breast edema, two patients had breast edema, and the fifth patient had arm edema. Lesions arising in the irradiated mammary skin included extensive lymphangiectasia (one), atypical vascular lesions (two), and cutaneous angiosarcoma (four).
CONCLUSIONS:
Atypical vascular lesions at the skin margins of mastectomy may be predictive of recurrence after resection of angiosarcoma. Excision of skin from the entire radiation field may be necessary to secure local control of the chest wall in patients with cutaneous angiosarcoma after therapeutic breast radiotherapy.
Despite considerable experience the reported frequency of misdiagnosis in patients undergoing appendectomy continues in the range of 20% to 40% in some populations.
We developed a clinical guideline ...that recommended abdominal computed tomography (CT) for all nonpregnant adults in whom the diagnosis of appendicitis was suspected unless the diagnosis could be ruled out clinically. The records of adult patients that underwent appendectomy from July 1998 through October 2001 were reviewed. The clinical guideline was developed in July 2000.
There were 194 appendectomies performed, 114 prior to the guideline and 80 after the development of the guideline. The rate of misdiagnosis decreased from 25% to 6% (P <0.05), the rate of CT use increased from 32% to 84% (P <0.05), and the perforation rate remained unchanged.
These results support the effectiveness of a clinical guideline that encourage the use of abdominal CT in decreasing the frequency of misdiagnosis in cases of suspected appendicitis.
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