Evaluation of mammographic image quality: pilot study comparing five methods.

A radiograph is considered of high quality when it allows a radiologist to identify abnormalities with high sensitivity and specificity. Although many methods for assessing image quality have been devised, it is not clear which is most meaningful or how well these methods correlate with one another. A pilot study was undertaken to compare five methods of evaluating mammographic image quality. Each of the methods was used to form separate rankings of 11 mammographic system configurations. In two of the methods, observers (three radiologists and three physicists) subjectively ranked the "image quality" of radiographs of phantoms obtained with each configuration. The third method ranked the systems according to contrast as measured densitometrically with an aluminum step wedge, and the fourth, in terms of lowest to highest mean glandular radiation doses to the breast. In the final method, observers based their rankings on mammograms of patients. The intra- and interobserver variabilities of each ranking method were assessed, as well as the correlations between methods, by using standard nonparametric statistical tests. Intraobserver consistency was high with any of the image quality ranking methods; however, image quality rankings based on either of the two phantoms provided better agreement among observers than did rankings based on images of patients. Surprisingly, no significant degree of correlation was found between any two image quality evaluation methods. Our work may have two implications for the American College of Radiology Mammography Accreditation Program: (1) small variations in phantom scores do not necessarily correlate with subjective variation in image quality in radiographs of patients, and (2) when small numbers of radiographs are used, the assessment of the quality of mammograms of patients may vary considerably among radiologists.     

The neuromuscular effects of sevoflurane and isoflurane alone and in combination with vecuronium or atracurium in the rat

Sevoflurane was compared to isoflurane anesthesia alone and in combination with atracurium or vecuronium in 84 rats using the sciatic nerve—anterior tibialis muscle preparation. Both bolus injection and infusion rate techniques were used to evaluate these drug interactions. The ED₅₀ (dose which produced a 50% depression of twitch tension) of atracurium was 311 ± 31 and 360 ± 32µg·kg^–1 during 1.25MAC sevoflurane and isoflurane anesthesia respectively. The ED₅₀ of vecuronium was 190 ± 27 and 149 ± 14µg·kg^–1 during 1.25MAC sevoflurane and isoflurane anesthesia respectively. The mean infusion rates of atracurium and vecuronium required to maintain a 50% depression of twitch tension were 5.04 ± 0.7 and 2.02 ± 0.3mg·kg^–1·hr^–1. These infusion rates were 5.04 ± 0.7 and 2.02 ± 0.3mg·kg^–1·hr^–1 during 1.25MAC sevoflurane and 3.73 ± 0.3 and 1.81 ± 0.4mg·kg^–1·hr^–1 during 1.25MAC isoflurane anesthesia respectively. With both atracurium and vecuronium, the infusion rate required to maintain a 50% depression twitch of tension was inversely related to the concentrations of isoflurane and sevoflurane. The authors conclude that sevoflurane is similar in potency to that of isoflurane in augmenting a vecuronium or atracurium induced neuromuscular blockade in a dose-dependent manner.(Shin YS, Miller RD, Caldwell JE, et al.: The neuromuscular effects of sevoflurane and isoflurane alone and in combination with vecuronium or atracurium in the rat. J Anesth 6: 1–8, 1992)     

The efficacy and safety of low-dose corticosteroids for rheumatoid arthritis

Low-dose corticosteroids (defined as less than or equal to 10 mg/d of prednisone or equivalent) are used increasingly for the management of rheumatoid arthritis. They are frequently substituted for nonsteroidal antiinflammatory drugs (NSAIDs), particularly in patients with gastrointestinal or other intolerance to NSAIDs, or as "bridge therapy" while patients await the benefits of delayed-acting, disease-modifying agents. Despite their clinical acceptance, published data concerning efficacy are meager. Adverse effects to low-dose corticosteroids are not so frequent nor so severe as those that occur with higher doses. Nevertheless, alterations in glucose metabolism, cutaneous atrophy, cataracts, and glaucoma are common. Osteoporosis, steroid-myopathy, a steroid-withdrawal syndrome, and dysfunction of the hypothalamic-pituitary-adrenal axis appear in some patients. Osteonecrosis, gastrointestinal, cardiovascular, infectious, or neurological complications probably do not occur. Fetal wastage, prematurity, or congenital malformations have not been proven with this dosage.     

Assessment of maternal nutrition.

A booklet, "Assessment of Maternal Nutrition," has been published by the American College of Obstetricians and Gynecologists in cooperation with The American Dietetic Association as a useful guide for physicians, nurses, dietitians, and nutritionists. Nutritional risks during pregnancy are clearly outlined. Clinical, dietary, and biochemical factors, as well as medical, obstetric, and social factors, are delineated as components of nutritional assessment. An A.D.A. Liaison Committee had major responsibility for the development of the "Eating Habits Questionnaire," a tool to screen dietary intake for major deficits and excesses, which is included in the booklet. It should be useful also as a starting point for nutrition education. Additional evaluation of the use and reliability of the screening tool is recommended.     

Entrapment of bioactive molecules in poly (alkylcyanoacrylate) nanoparticles

Poly (alkylcyanoacrylate) [PACA] nanoparticles have been studied since the early 1980s as possible colloidal drug delivery systems. Several excellent general reviews have since been published on this subject. This review focuses on the use of the two different methods (encapsulation and sorption) for the entrapment of drugs and model compounds in PACA nanoparticles. The term encapsulation is used when the drug or model compound is added at the same time or before the monomer to the polymerization template. The term sorption is used when the compound is added after the polymerization has taken place. High drug entrapment can be achieved with both methods and the method of entrapment (encapsulation or sorption) should be chosen depending on the type of drug to be entrapped and the method of particle preparation (interfacial polymerization of a coarse emulsion or a microemulsion or micellar polymerization). The type, chain length, and amount of monomer used for the polymerization as well as possible interactions of the compound with the monomer during polymerization should also be considered in the choice of entrapment method and these can also influence the extent of encapsulation.     

Publication rates of abstracts presented at annual scientific meetings: How does the Royal Australian and New Zealand College of Radiologists compare?

The abstract to publication ratio (APR) is a measure of the quality of scientific meetings. The aim of the present study was to determine the publication rate of abstracts presented at annual Royal Australian and New Zealand College of Radiologists (RANZCR) conferences, and to identify the publishing journals. All free paper research abstracts (oral or poster) presented by RANZCR radiologists, radiation oncologists and trainees at the four consecutive meetings between 1996 and 1999 were identified retrospectively from conference programmes. The PubMed database ( http:www.ncbi.nlm.nih.govPubMed ) was searched to determine whether or not the abstract had been published as a full paper. Of the 480 free paper research abstracts, 168 (35%) had been published as full articles. The overall abstract to publication ratio for radiology was 29% and for radiation oncology was 41%. Papers were published in a variety of journals but Australasian Radiology accounted for 27%. The mean time between presentation and publication was 16.5 months (median 17 months). These overall abstract to publication ratios are lower than those reported for overseas‐based meetings in each respective area. Guidelines to scientific committees could increase the APR by more rigorous selection of abstracts. Future research should look at barriers to the publication of research findings, and identify ways to assist the publication process.     

Rapid tracheal intubation with large-dose rocuronium: a probability-based approach

There are situations in anesthesia in which it may be desirable to achieve rapid tracheal intubation with perfect conditions, i.e., no coughing or straining. To determine the dose of rocuronium that gives a high probability of achieving perfect conditions for rapid (within 60 s) tracheal intubation, we administered a range of doses of rocuronium, some larger than used previously. Sixty adults, anesthetized with thiopental 4 mg/kg IV and alfentanil 10 microg/kg IV, received rocuronium 0.4 to 2.0 mg/kg IV. We used logistic regression to define the relationship of rocuronium dose to probability of achieving perfect intubation conditions. We estimated the doses giving 90% and 95% probability of achieving perfect intubation and used resampling to determine confidence limits for these estimates. Rocuronium 1.85 and 2.33 mg/kg gave, respectively, 90% and 95% probability of perfect intubation conditions. The confidence limits (5th and 95th percentile) for these estimates were 1.15 to 2.31 and 1.23 to 3.22 mg/kg, respectively. In conclusion, it is possible to achieve perfect intubation conditions with large doses of rocuronium, but the long duration of action and expense may limit the usefulness of the technique. IMPLICATIONS: We found that it is possible to have a 90% probability of achieving perfect conditions for rapid tracheal intubation with large (up to 2.0 mg/kg) doses of rocuronium. These large doses of rocuronium may be useful in, for instance, head trauma or open globe injuries if succinylcholine is contraindicated.     

Metabolic activation of fluoropyrrolidine dipeptidyl peptidase-IV inhibitors by rat liver microsomes.

The current study evaluated the potential for two dipeptidyl peptidase-IV (DPP-IV) inhibitor analogs (1S)-1-(trans-4-([(4-trifluoromethoxyphenyl)sulfonyl]amino)cyclohexyl)-2-[(3S)-3-fluoropyrrolidin-1-yl]-2-oxoethanaminium chloride and (1S)-1-(trans-4-([(2,4-difluorophenyl)sulfonyl]amino)cyclohexyl)-2-[(3S)-3-fluoropyrrolidin-1-yl]-2-oxoethanaminium chloride (MRL-A and MRL-B), containing a fluoropyrrolidine moiety in the structure, to undergo metabolic activation. The irreversible binding of these tritium-labeled compounds to rat liver microsomal protein was time- and NADPH-dependent and was attenuated by the addition of reduced glutathione (GSH) or N-acetylcysteine (NAC) to the incubation, indicating that chemically reactive intermediates were formed and trapped by these nucleophiles. Mass spectrometric analyses and further trapping experiments with semicarbazide indicated that the fluoropyrrolidine ring had undergone sequential oxidation and defluorination events resulting in the formation of GSH or NAC conjugates of the pyrrolidine moiety. The bioactivation of MRL-A was catalyzed primarily by rat recombinant CYP3A1 and CYP3A2. Pretreatment of rats with prototypic CYP3A1 and 3A2 inducers (pregnenolone-16alpha-carbonitrile and dexamethasone) enhanced the extent of bioactivation which, in turn, led to a higher degree of in vitro irreversible binding to microsomal proteins (5- and 9-fold increase, respectively). Herein, we describe studies that demonstrate that the fluoropyrrolidine ring is prone to metabolic activation and that GSH or NAC can trap the reactive intermediates to form adducts that provide insight into the mechanisms of bioactivation.