Effective use of TNF antagonists

Tumor necrosis factor (TNF) antagonists are biologic response modifiers that have significantly improved functional outcomes in patients with rheumatoid arthritis (RA). RA is a progressive disease in which structural joint damage can continue to develop even in the face of symptomatic relief. Before the introduction of biologic agents, the management of RA involved the use of disease-modifying antirheumatic drugs (DMARDs) early in the course of disease. This focus on early treatment, combined with the availability of the anti-TNF agents, has contributed to a shift in treatment paradigms favoring the early and timely use of DMARDs with biologic therapies. Improvement in symptom control does not always equate to a reduction in disease progression or disability. With the emergence of structure-related outcome measures as the primary means for assessing the effectiveness of antirheumatic agents, the regular use of X-rays is recommended for the continued monitoring and evaluation of patients. In addition to the control of symptoms and improvement in physical function, a reduction in erosions and joint-space narrowing should be considered among the goals of therapy, leading to a better quality of life. Adherence to therapy is an important element in optimizing outcomes. Durability of therapy with anti-TNF agents as reported from clinical trials can also be achieved in the clinical setting. Concomitant methotrexate therapy might be important in maintaining TNF antagonist therapy in the long term. Overall, the TNF antagonists have led to improvements in clinical and radiographic outcomes in patients with RA, especially those who have failed to show a complete response to methotrexate.     

Effective use of regional intensive therapy units.

OBJECTIVE--To determine the effectiveness of regional intensive therapy units. DESIGN--Retrospective and prospective study of patients transferred to a regional intensive therapy unit over four years. SETTING--Glasgow regional intensive therapy unit. MAIN OUTCOME MEASURES--Severity of illness was assessed at the time of referral to the unit with the acute physiological and chronic health evaluation (APACHE) scoring system. Mortality was calculated. RESULTS--A significant association was found between increasing duration of illness before transfer and mortality, which was independent of the severity of illness. Mortality also varied depending on the referring hospital. CONCLUSIONS--When transfer of critically ill patients is required this should be done as early as possible to make best use of the services available. The mortality of patients transferred after 10 days casts doubt on whether further aggressive intensive therapy is appropriate.     

Effective use of a joystick by an infant monkey

The acquisition of the ability to use a joystick to maintain contact between a cursor and moving target is described for an infant bonnet macaque (Macaca radiata). The infant was first exposed to a very elementary joystick task while living in a social group at the age of 3.5 months. With task difficulty increased in small increments over a total of only 9 weeks of access to the tasks, the infant was able to maintain contact with a small moving target for over 2.5 sec by the age of 7.5 months. © 1994 Wiley-Liss, Inc.     

Long-tailed macaques use human hair as dental floss

Long-tailed macaques in Lopburi, Thailand, use human hair as if it were dental floss. This eccentric behavior is seen mainly in a large group of macaques that live at the old Buddhist shrine of Prang Sam Yot. Many monkeys of this group take hair and sort a few pieces to make a string and then brush their teeth by pulling it tightly with right and left hands alternatively between their teeth. This habit is not seen in the other localities near Lopburi and is rare even in the surrounding groups. Monkeys in the Prang Sam Yot shrine are worshipped as servants of God and people respect them, even when they ride on their heads. This behavior could be considered a newly occurring cultural behavior, which has become established under very specialized circumstances.     

Effective use of a Limited Antiviral Stockpile for Pandemic Influenza

Just allocation of resources for control of infectious diseases can be profoundly influenced by the dynamics of those diseases. In this paper we discuss the use of antiviral drugs for treatment of pandemic influenza. While the primary effect of such drugs is to alleviate and shorten the duration of symptoms for treated individuals, they can have a secondary effect of reducing transmission in the community. However, existing stockpiles may be insufficient for all clinical cases. Here we use simple mathematical models to present scenarios where the optimum policies to minimise morbidity and mortality, with a limited drug stockpile, are not always the most intuitively obvious and may conflict with theories of justice. We discuss ethical implications of these findings.     

Physician assistants and bioterrorism preparedness

Despite the resources dedicated since 2001 to training health providers in emergency and bioterrorism preparedness and response, the literature on the participation of physician assistants (PAs) is very limited. The purpose of this pilot study was to explore the training level and experiences of PAs in the diagnosis and treatment of chemical, biological, radiological, nuclear, and explosive agents that could be used in a bioterrorism attack. The study population consisted of licensed PAs in 37 northern Texas counties. Data were collected through mailed and web-based surveys. Response rate was 36%. More than half of the respondents (58.6%) had not participated in bioterrorism preparedness and response training. Results also indicated that the level of training has not increased since September 11, 2001. However, most respondents were receptive to the idea of participating in both preparedness training and response efforts. It is recommended that state agencies increase training opportunities for PAs in bioterrorism preparedness and response.     

Effective use of nitrocellulose-blotted antigens for phage display monoclonal antibody selection

The combinatorial phage display library approach to antibody repertoire cloning offers a powerful tool for the isolation of specific antibodies to defined target antigens. Panning strategy is often a very critical point for selecting antibody displayed on the surface of bacteriophages. Most selection strategies described to date have relied on the availability of purified and often recombinant antigen, providing the possibility to perform selections on a well defined antigen source. However, when the antigen is difficult to purify by means of laborious and time-consuming chromatography procedures, panning of phage antibody libraries has to be performed on complex antigen sources such as cell surfaces or tissue sections, or even by in vivo selection methods. This provides a series of technical and experimental complications. In the present work, we successfully generated a mouse monoclonal antibody fragment from a phage display library directed against protein E7 of HPV18 avoiding antigen purification as for immunizing mice as for antibody library selection. Our work demonstrates the feasibility of phage antibody selections on antigens transferred to a nitrocellulose membrane as solid support, using one-dimensional polyacrylamide gel electrophoresis system as the only practice to separate a given antigen present in bacterial crude cell lysate.     

Effective use of preparative chiral HPLC in a preclinical drug synthesis

Access to a key 3-aryl-delta-lactone intermediate in enantiopure form using preparative chiral chromatography allowed expedited preparation of an important drug discovery target. A preclinical drug discovery strategy that combines rapid route discovery with effective use of preparative chiral chromatography can result in significant savings of both time and labor.     

Effective use of sequence correlation and conservation in fold recognition.

Protein families are a rich source of information; sequence conservation and sequence correlation are two of the main properties that can be derived from the analysis of multiple sequence alignments. Sequence conservation is related to the direct evolutionary pressure to retain the chemical characteristics of some positions in order to maintain a given function. Sequence correlation is attributed to the small sequence adjustments needed to maintain protein stability against constant mutational drift. Here, we showed that sequence conservation and correlation were each frequently informative enough to detect incorrectly folded proteins. Furthermore, combining conservation, correlation, and polarity, we achieved an almost perfect discrimination between native and incorrectly folded proteins. Thus, we made use of this information for threading by evaluating the models suggested by a threading method according to the degree of proximity of the corresponding correlated, conserved, and apolar residues. The results showed that the fold recognition capacity of a given threading approach could be improved almost fourfold by selecting the alignments that score best under the three different sequence-based approaches.     

Effective use of renal cortical slices in transport and metabolic studies

The uptake and metabolism of two water-soluble vitamins were measured in rat renal cortical slices, isolated tubules, and vesicles of the brush-border and basolateral cell membranes to determine (a) whether it is possible to produce slices that have open tubules and, (b) whether slices and tubules metabolize vitamins similarly. Transport of ascorbic acid is sodium-dependent in slices and in brush-border vesicles but is sodium-independent in basolateral vesicles, suggesting that the brush-border membrane of slices is accessible to components of the bathing solution. Nicotinic acid was metabolized similarly (97-98%) in both slices and isolated tubules. Oxygen consumption by slices maintained in a closed chamber was constant as pO2 decreased from 88% to 58%. Slices are concluded to be a suitable model for transport and metabolic studies providing that care is taken in their preparation and use.