Clinical effectiveness of biologics in clinical practice

TNF inhibitors are currently considered both effective and cost-effective in patients with active rheumatoid arthritis (RA), particularly in patients who have not responded fully to methotrexate. There is substantial doubt about the cost-effectiveness of TNF inhibitors as initial treatment for active RA. New data from the National Data Bank for Rheumatic Diseases now question the current consensus in methotrexate failures. The data suggest that in routine clinical practice TNF inhibitors provide only modest incremental benefits over best conventional therapy. If confirmed, these observational studies suggest that the economic argument underpinning the widespread use of TNF inhibitors in established RA is unsustainable.     

Modifications of the fertilized egg surface following the cortical reaction in Limulus polyphemus L. as viewed with the scanning electron microscope

In the development of the horseshoe crab, Limulus polyphemus, the fertilized egg undergoes a complicated cleavage (Stages 1–3) resulting in blastoderm formation (Stage 4). Stage 1 involves intralecithal cleavage and consists of nine discrete surface modifications (events) which have been briefly described with light microscopy by Brown and Barnum ('83). Since in Stage 1 the cortical reaction (events 1–4) has already been examined with ultrastructural methods, the objectives of the present study were to examine with scanning electron microscopy: (1) the first two of three intermittent granulations (events 5 and 7), and (2) the associated events characterized by smooth surfaces (events 4, 6, and 8). The first granulation occurs 2 1/2 to 3 hours after fertilization (22°C) and lasts approximately 1 1/2 hours. The second granulation appears approximately 5 hours after fertilization and lasts about 3 hours. The dynamic changes that occur during the two granulations involve the transformation of a smooth appearing embryonic surface, liberally coated with microvilli, into a granule-dominated surface on which microvilli are greatly reduced in number. Also of considerable interest are the numerous projections which begin to appear on the surface near the end of the second granulation (event 7) and dominate the surface of the following smooth step stage (event 8). Hypotheses on the significance of these dynamic changes and surface modifications involve relationships to the cell cycle, possible mechanisms for membrane storage, and secretory function.     

Effect of pharmacological agents on the activity of the circular and longitudinal smooth muscle layers of human fallopian tube ampullar segments

The in vitro determination of the effects of some pharmacological agents on the outer diameter and axial tension of human Fallopian tube ampullar segments showed that some drugs may act on the circular and longitudinal smooth muscle layers relatively separately. PGF2 alpha elicited an excitatory response in both muscle layers while norepinephrine and isoproterenol decreased the activity. Oxytocin and indomethacin had relatively limited effects on the spontaneous motility of the ampullar segments. The calcium antagonist verapamil inhibited the spontaneous periodic activity.