Long term orexigenic effect of a novel melanocortin 4 receptor selective antagonist.

1. We designed and synthesized several novel cyclic MSH analogues and tested their affinities for cells expressing the MC1, MC3, MC4 and MC5 receptors. 2. One of the substances HS028 (cyclic [AcCys11, dichloro-D-phenylalanine14, Cys18, Asp-NH2(22)]-beta-MSH11-22) showed high affinity (Ki of 0.95nM) and high (80 fold) MC4 receptor selectivity over the MC3 receptor. HS028 thus shows both higher affinity and higher selectivity for the MC4 receptor compared to the earlier first described MC4 receptor selective substance HS014. 3. HS028 antagonised a alpha-MSH induced increase in cyclic AMP production in transfected cells expressing the MC3 and MC4 receptors, whereas it seemed to be a partial agonist for the MC1 and MC5 receptors. 4. Chronic intracerebroventricularly (i.c.v.) administration of HS028 by osmotic minipumps significantly increased both food intake and body weight in a dose dependent manner without tachyphylaxis for a period of 7 days. 5. This is the first report demonstrating that an MC4 receptor antagonist can increase food intake and body weight during chronic administration providing further evidence that the MC4 receptor is an important mediator of long term weight homeostasis.

Magnetic resonance imaging arthrography of the ankle.

Magnetic resonance imaging (MRI) arthrography of the ankle is a useful diagnostic modality in the detection and staging of lateral ankle ligament tears, particularly in patients who fail to respond to conservative management. MRI arthrography also may be helpful in determining the extent of ligamentous injury in professional athletes, for whom immediate surgical repair may be the initial treatment. Preoperative planning is optimized with MRI arthrography. Frequently, alternative diagnoses may be made for conditions that can simulate lateral ligamentous injury, thus obviating the need for diagnostic arthroscopy.

Detection of Epstein-Barr virus-specific antibodies by an automated enzyme immunoassay. Performance evaluation and cost analysis.

Detection of antibodies to specific antigens of Epstein-Barr virus (EBV) has been conventionally performed by an immunofluorescence assay (IFA). The procedure is labor intensive and expensive, and interpretation of results is subjective. We evaluated an automated enzyme immunoassay (EIA) (INC-STAR Corp., Stillwater, MN, USA) using 290 serum specimens submitted for the diagnosis of acute infection with EBV. Antibodies (IgG, IgM) to EBV capsid antigen and IgG class antibodies to the nuclear antigen of the virus were obtained using the LABOTECH Automated Microplate Analyzer (BioChem ImmunoSystems Inc., Allentown, PA, USA) and were compared to the antibody profile results obtained by IFA and Western blot as the "gold standard." For detection of acute infection with EBV (presence of IgM and IgG antibodies to the capsid antigen; absence of antibodies to the nuclear antigen), the EIA had 100% sensitivity (11 of 11) and 99% specificity (275 of 279) compared to IFA and Western blot results. A cost analysis of IFA and EIA procedures, based on an estimated annual volume of 12,000 procedures, indicated that $236,000 direct cost and 1,400 h technologist time could be saved with the automated compared with immunofluorescence procedure. The automated EIA for determination of antibodies provides cost-effective, accurate diagnosis of EBV infections in laboratories processing high numbers of specimens now processed by IFA.

MR arthrography of the ankle.

Injuries to the lateral ankle ligaments are extremely common. Many patients with acute injuries to the lateral ligament complex develop chronic ankle instability that requires surgical intervention. MR arthrography of the ankle plays a valuable role in identifying those patients who are most at risk for the development of chronic instability. MR arthrography of the ankle also aids in preoperative planning and in differentiating among other entities that can present as ankle instability.

Rheumatoid arthritis in an Icelandic textbook from 1782.

In 1782, Jón Pétursson, a district physician in Northern Iceland, published a textbook on arthritis and its remedies intended for common use. Working within a very simple diagnostic system, essentially comprising osteoarthritis (arthritis fixa) and inflammatory arthritis (arthritis vaga), he describes arthritis vaga as a common, chronic, symmetric, destructive, inflammatory polyarthritis, sometimes with systemic manifestations. It affected people of all ages with a peak incidence around forty, and had a female preponderance. The last observation is of particular interest as he knew he was contradicting all the available literature. Contemporary descriptions of Jón Pétursson suggest that he may have had rheumatoid arthritis himself which would explain his excellent description of this disease.