A haplotype and linkage disequilibrium analysis of the hereditary hemochromatosis gene region

Monoclonal antibodies were generated against serotonin (5-HT) and the C-terminal portion of the neuronal form of nitric oxide synthase (nNOS), the enzyme producing nitric oxide in neurons. These antibodies were used to compare the distribution of 5-HT- and nNOS-containing neurons in the raphe nuclei of four animal species (rat, mouse, guinea pig, and cat). It was found that the rat was the only species in which the raphe nuclei contain a substantial number of nNOS-immunoreactive (IR) cell bodies. In this species and as observed by other authors, all mesencephalic raphe nuclei contained nNOS-IR cells, the largest group being located in the nucleus raphe dorsalis. The coexistence of nNOS and 5-HT immunoreactivities in these nuclei was visualized by double labeling. In the medulla, the nuclei raphe magnus and obscurus displayed a rather low number of nNOS-IR neurons. In the other species, nNOS-IR cell bodies were found in very low numbers, whatever raphe nucleus was considered. The rostral pole of the nucleus raphe dorsalis and the nuclei raphe magnus and obscurus contained a few nNOS-IR neurons which did not show any coincidence with the 5-HT neurons. In addition, nNOS-IR axons were rare. It is concluded that in the mouse, guinea pig, and cat the involvement of nitric oxide in functions subserved by 5-HT within the raphe nuclei might be minimal.     

Safety and immunogenicity of a respiratory syncytial virus subunit vaccine (PFP-2) in ambulatory adults over age 60

The safety and immunogenicity of purified fusion protein (PFP-2) respiratory syncytial virus (RSV) vaccine was evaluated in a randomized placebo-controlled, double-blind study of 64 healthy adults over age 60. Vaccination was well tolerated with no significant acute side-effects. Twenty-nine of 33 vaccinees (87%) showed a greater than or equal to fourfold rise in serum IgG to the F protein of RSV at 8 weeks post vaccination. Twenty of 33 vaccine recipients (61%) had a greater than or equal to fourfold rise in serum neutralizing titer to group A and/or group B RSV. Response to vaccination was inversely correlated with pre-immunization serum neutralizing titers. Active surveillance throughout the ensuring winter identified three RSV infections in the placebo group and none in the vaccine group. Thus, PFP-2 was found to be safe and immunogenic in healthy older adults.     

In vitro laxity-testers for knee joints of mice

The knee joints of mice can be used as a model for studying the effects of interventions on knee laxity. The goal of this study was to quantify knee joint laxity in vitro. Three devices were developed: a positioning- and cementing device, an anterior-posterior (AP) laxity tester and a varus-valgus (VV) laxity tester. The positioning and cementing device was used to position the joint in a reproducible way and to attach clamping pins to the proximal femur and distal tibia using PM MA. The clamping pins were used to fix the joint to the AP- and VV-testers. In both testers the load was applied by means of a spindle-actuated spring while load and displacements were measured simultaneously. The load--displacement data were used to calculate displacement and compliance parameters. The performance of the testers was evaluated by testing 5 normal knee joints of 5 mice. Total AP-translation at + or - 0.8 N was 0.43 (+ or - 0.16 S.D.) mm with compliances of 0.14 (+ or - 0.05 S.D.) mm N(1) and 0.12 ( + or - 10.05 S.D.) mm N(-1) at 0.8 N posterior and anterior force, respectively. Total VV-rotation at + or - 4 Nmm was 17.2 (+ or - 2.6 S.D.) degrees with compliances of 0.9 degrees Nmm(-1) (+ or - 0.2 degrees Nmm(-1) S.D.) and 1.0 Nmm(-1) (+ or - 0.4 degrees Nmm(-1) S.D.) at 4 Nmm valgus and varus moment, respectively. The contributions of the deformations of the bones and the fixtures to the rotations were negligible in the VV-test. In the AP-test they account for approximately 0.07 ( + or - 0.03 S.D.)mm of the total AP-translation. This will not affect the utilization of the device for comparative analysis. It is concluded that in in vitro evaluation of AP- and VV-laxity in knees of mice is feasible with sufficient accuracy for evaluation of changes after ligament damage.     

Violent emergence from anesthesia: is it a pharmacological or psychological reaction?

A violent emergence from deep sedation is an uncommon reaction in the daily practice of anesthesia in the oral and maxillofacial surgery office. We present a case of a 22-yr-old male with a severe violent emergence from deep sedation that we attribute to a psychological rather than a pharmacological cause. A differential diagnosis is discussed, as are methods of treatment.     

Positive effects of allosteric modulators on the binding properties and the function of muscarinic acetylcholine receptors

Data are reviewed indicating that allosteric modulators can enhance the affinities of muscarinic receptors for their antagonists and agonists, that the enhancement of the affinity for agonists is relevant functionally, and that the allosterically induced conformational change also affects the interaction between the receptors and the G proteins.