The PTPN22 R620W polymorphism associates with RF positive rheumatoid arthritis in a dose-dependent manner but not with HLA-SE status

We have recently described the association between rheumatoid arthritis and a coding single-nucleotide polymorphism in the intracellular protein tyrosine phosphatase, PTPN22. The disease-associated polymorphism, 1858 C/T (rs2476601), encodes an amino-acid change (R620W) in one of four SH3 domain binding sites in the PTPN22 molecule. We have now extended our initial studies to address three questions: (1) Is the association with rheumatoid arthritis limited to rheumatoid factor (RF) positive disease? (2) Does homozygosity for PTPN22 R620W substantially increase disease susceptibility? (3) Is there an interaction between PTPN22 and the rheumatoid arthritis (RA)-associated HLA-DRB1 shared epitope alleles? A total of 1413 Caucasian rheumatoid arthritis patients and 1401 Caucasian controls were genotyped. The results support the view that PTPN22 was strongly and preferentially associated with RF positive disease (OR=1.75, 95% CI 1.46-2.10, P=1.3 x 10(-9)). The PTPN22 risk allele was not significantly associated with RF negative disease (OR=1.19, 95% CI 0.92-1.53, P=0.18), although a very weak association cannot be completely excluded. There was a strong dose effect on disease risk; two copies of the PTPN22 R620W allele more than doubles the risk for RF positive RA (OR=4.57, 95% CI 2.35-8.89). There was no evidence of a genetic association between PTPN22 and HLA susceptibility alleles.     

Adaptive modification of ingestive behavior in beach mice (Peromyscus polionotus).

The ability of an inland and beach race of the old-field mouse to use increasing concentrations of NaCl solutions was compared. Inland mice drank significantly more fluid at all concentrations than did beach mice. These differences became more pronounced as the salt concentration was increased. Food consumption was similar in both races while drinking water or a dilute salt solution, but beach mice ate significantly greater amounts when the concentration of salt was increased above 0.2 M. Weight losses on salt solutions were approximately equal in both races, although beach mice survived longer and tolerated the higher concentrations better. There was no difference in the ability of the races to concentrate urine or excrete Na⁺. When given a choice of distilled water or two salt solutions, beach mice consumed significantly more water (77%) than salt solutions (23%) whereas inland mice drank approximately equal amounts of water (54%) and salt solutions (46%). When deprived of anything to drink, beach mice almost stopped eating for the first two days while inland mice did not reduce their food consumption as quickly and died sooner. Thus, it appears that adaptive modifications of ingestive behavior are important for survival in habitats where salt accumlates and summer droughts may be a problem.     

Employing Empirically Supported Treatments: A Research-Informed Clinical Practitioner Perspective

Ruscio and Holohan (2006 ) offer many excellent ideas for improving research on empirically supported treatments (ESTs) applied to complex cases. They hope that, as more empirical findings are accumulated, clinical practitioners will be more willing to use ESTs in their clinical work with such patients. This commentary suggests additional research strategies that are necessary to acquire information more useful and relevant to clinical practitioners. These include (a) integrating information from research on empirically supported relationship factors with findings from EST outcome research, (b) studying longer term therapies attempting to address issues beyond the symptoms of diagnostic and statistical manual of mental disorders (DSM)-defined disorders, and (c) investigating the efficacy and effectiveness of integrative forms of psychotherapy. The author's successes and difficulties of incorporating ESTs in his integrative therapy for anxiety disorders are highlighted.     

Post-traumatic stress disorder: evidence for diagnostic validity and methods of psychological assessment

Post-traumatic stress disorder (PTSD) is a diagnosis that has been the subject of considerable criticism in the clinical literature. Of primary concern has been the question of whether PTSD is a disorder that can be discriminated reliably from already existing diagnoses, such as depression, dysthymia, or generalized anxiety disorder. This paper reviews the evidence that surrounds this controversy and employs the guidelines for validating a diagnosis established by Robins and Guze (1970) as the framework for the review. A second purpose of this paper is to present a multiaxial approach for the assessment of PTSD. This approach includes the use of structured interviews, psychometrics, and a psychophysiological assessment procedure. Studies that support the reliability and validity of the components of the multiaxial method are reviewed.     

The effects of prenatal alcohol exposure on radial arm maze performance in adult rats

The hippocampal formation is sensitive to the in utero exposure to ethanol. It is one brain area thought to play an important role in spatial memory. We examined radial arm maze performance in rats exposed to ethanol prenatally. Pregnant rats were placed into the following treatment groups: LC, 17% EDC (ethanol-derived calories), 35% EDC, PF 35% or PF 17%. The LC group was fed lab chow and water ad lib, the 17% EDC and 35% EDC groups were fed a liquid diet containing either 3.3% or 6.7% v/v ethanol, respectively. Pair-fed controls were fed the same volume of an isocaloric diet as was consumed by their respective ethanol-treated groups. At birth, litters were culled to six and cross fostered to untreated surrogate mothers. Testing was initiated at 60 days of age and continued until the test criterion was satisfied. One-half of the rats in the 35% EDC group did not reach criterion. The remainder of the 35% EDC group and the 17% EDC rats attained criterion but required twice as many trials as their respective pair-fed controls. These results suggest that in utero administration of ethanol affects spatial memory capacity in rat, an observation consistent with other deficits seen in hippocampus of rats prenatally exposed to ethanol.     

Laser induced thermal injury of rabbit cornea and treatment with anti-inflammatory agents

A moderately severe thermal injury of the central cornea of 48 Dutch-belted rabbit eyes was produced with a carbon (CO₂) laser. The lesions were photographed with a slit lamp (SL) camera immediately following the injury and at 1, 2, 4, 7, 14, 21, 30 and 60 days after the exposure. Lesion size, opaqueness, and depth were graded clinically by SL biomicroscopy at the same intervals. No significant differences were found (p 0.05) between groups of eyes treated with flurbiprofen (0.03%), prednisolone acetate (1%), and vehicle control four-times-a-day for three weeks following injury. Additionally, eyes were studied histopathologically at 3 and 60 days following injury by light and transmission electron microscopy, and clinically at 30 and 60 days by endothelial specular microscopy. Important clinical and histopathological findings included coagulative necrosis of the corneal epithelium, epithelial sloughing, fusion of stromal collagen, stromal edema and inflammatory cell infiltration, stromal scar formation, corneal thinning, endothelial hyperplasia and metaplasia, fibrinous anterior chamber reaction with hypopyon, and retrocorneal fibrous membrane formation.     

Fibrositis: symptom frequency and criteria for diagnosis. An evaluation of 291 rheumatic disease patients and 58 normal individuals

We administered a 17-item symptom questionnaire modified from Campbell to 155 patients with fibrositis diagnosed at 3 centers, each using different criteria sets. A high degree of agreement in symptom proportions was found among centers. "Fibrositic" symptoms were also common in 136 patients with a variety of rheumatic diseases but not in the 58 normal individuals studied. Symptoms distinguished fibrositis patients from normals easily, but had insufficient specificity to distinguish them from other rheumatic disease patients. The tender point count better separated fibrositic and nonfibrositic patients than historical criteria. No combination of questions and tender point count performed better than the tender point count alone.     

Efficacy and safety of hypromellose in ocular implant surgery

In order to assess the efficacy of hypromellose as a viscoelastic substance in cataract surgery with posterior chamber intraocular lens implantation, we studied a series of 88 cases who underwent surgery with either alternate use of a viscoelastic substance (hypromellose, 39 patients, or sodium hyaluronate, 5 patients) or air (44 patients) in the anterior chamber. Endothelial cell loss was least in the group in which air was used (18 +/- 3% cell loss, mean +/- SEM), compared with hypromellose (26 +/- 3%) and sodium hyaluronate (28 +/- 6%), but the difference in percentage cell loss between the groups did not reach statistical significance. Some operative difficulties were encountered in both groups. In both the air and hypromellose groups there were two patients with an early postoperative rise in intraocular pressure, but this was easily controlled, and in both groups there were two patients with postoperative corneal oedema which soon cleared. Visco-elastic substances used in this study were not shown to be superior to air in protecting the corneal endothelium. For this reason use of hypromellose should be confined to situations where its use is likely to confer some special advantage, as in the presence of a bound-down pupil in patient's with chronic glaucoma or perhaps to facilitate "in the bag" implantation.     

Leaf assemblages across the Cretaceous-Tertiary boundary in the Raton Basin, New Mexico and Colorado

Analyses of leaf megafossil and dispersed leaf cuticle assemblages indicate that major ecologic disruption and high rates of extinction occurred in plant communities at the Cretaceous-Tertiary boundary in the Raton Basin. In diversity increase, the early Paleocene vegetational sequence mimics normal short-term ecologic succession, but on a far longer time scale. No difference can be detected between latest Cretaceous and early Paleocene temperatures, but precipitation markedly increased at the boundary. Higher survival rate of deciduous versus evergreen taxa supports occurrence of a brief cold interval (<1 year), as predicted in models of an “impact winter.”     

Balloon embolization to occlude a Blalock-Taussig shunt

Balloon embolization was used to successfully occlude a large residual Blalock-Taussig shunt. The use of an "upstream" nondetachable balloon catheter to reduce flow and turbulence during final positioning of the detachable balloon may have made the technique safer and more precise.