Whole body MR imaging in ankylosing spondylitis: a descriptive pilot study in patients with suspected early and active confirmed ankylosing spondylitis

Background  

Ankylosing spondylitis is a chronic inflammatory rheumatic disorder which usually begins in early adulthood. The diagnosis is often delayed by many years. MR imaging has become the preferred imaging method for detection of early inflammation of the axial skeleton in ankylosing spondylitis.     

Comparison of airway diameter measurements from an anthropomorphic airway tree phantom using hyperpolarized 3He MRI and high-resolution computed tomography.

An anthropomorphic airway tree phantom was imaged with both hyperpolarized (HP) 3He MRI using a dynamic projection scan and computed tomography (CT). Airway diameter measurements from the HP 3He MR images obtained using a newly developed model-based algorithm were compared against their corresponding CT values quantified with a well-established method. Of the 45 airway segments that could be evaluated with CT, only 14 airway segments (31%) could be evaluated using HP 3He MRI. No airway segments smaller than approximately 4 mm in diameter and distal to the fourth generation were adequate for analysis in MRI. For the 14 airway segments measured, only two airway segments yielded a non-equivalent comparison between the two imaging modalities, while eight more had inconclusive comparison results, leaving only four airway segments (29%) that satisfied the designed equivalence criteria. Some of the potential problems in airway diameter quantification described in the formulation of the model-based algorithm were observed in this study. These results suggest that dynamic projection HP 3He MRI may have limited utility for measuring airway segment diameters, particularly those of the central airways.     

Interleukin-1 (IL-1) production in a mouse tissue chamber model of inflammation. II. Identification of (tissue) macrophages as the IL-1 producing cells and the effect of anti-inflammatory drugs

We have used our newly described mouse tissue chamber model [1], to investigate the process of IL-1 production in more detail. The inflammatory reaction in the tissue surrounding the implanted chambers was investigated histologically and by using the polymerase chain reaction (PCR). The inflammatory response included influx of leucocytes into the granuloma surrounding the tissue chamber, expression of IL-1 on macrophages present in the inflamed tissue and an increase in the mRNA coding for IL-1 and IL-6 proteins in the granuloma. The effects of three anti-inflammatory or immunosuppressive drugs, prednisolone, indomethacin and cyclosporin A, on IL-1 and PGE₂ production in zymosan andBordetella-pertussis-vaccine (BPV)-challenged tissue chambers were also examined. Oral treatment with prednisolone and cyclosporin A of zymosan-challenged animals showed a dose-dependent reduction of IL-1 concentrations, but no effect of indomethacin. Both prednisolone and indomethacin dose-dependently reduced PGE₂ concentrations to control levels, while cyclosporin A was effective only at the highest dose tested (100 mg/kg/day p.o.). In drug-treated BPV-challenged animals, prednisolone and cyclosporin A also showed a dose-dependent reduction of IL-1, while indomethacin was again ineffective. Prednisolone and indomethacin also dose-dependently reduced the PGE₂ concentrations to control levels, whereas cyclosporin A was effective only at the highest dose tested (100 mg/kg/day p.o.).This model will be useful for investigating the mechanisms controlling the production of IL-1 from the mRNA level to the secretion of mature biologically active protein [1], and in the search for new drugs which could selectively interfere with this process.     

Genetic and cytological characterization of the RecA-homologous proteins Rad51 and Dmc1 of Schizosaccharomyces pombe

The Schizosaccharomyces pombe rad51⁺ and dmc1⁺ genes code for homologues of the Escherichia coli recombination protein RecA. Deletion of rad51⁺ causes slow growth, retardation of cell division and a decrease in viability. rad51 cells have a defect in mating-type switching. The DNA modification at the mating-type locus required for mating-type switching contributes to slow growth in the rad51 mutant. Cell mating is reduced in crosses homozygous for rad51. Ectopic expression of the dmc1⁺ gene allowed us to demonstrate that the reduction in meiotic recombination in dmc1 mutants is not caused by a disturbance of rad24 expression from the dmc1-rad24 bicistronic RNA. We describe the functional defects of terminally epitope-tagged Dmc1 and Rad51 and discuss it in terms of protein interaction. Presumptive Rad51 and Dmc1 foci were detected on spreads of meiotic chromatin.     

Cidea is associated with lipid droplets and insulin sensitivity in humans

Storage of energy as triglyceride in large adipose-specific lipid droplets is a fundamental need in all mammals. Efficient sequestration of fat in adipocytes also prevents fatty acid overload in skeletal muscle and liver, which can impair insulin signaling. Here we report that the Cide domain-containing protein Cidea, previously thought to be a mitochondrial protein, colocalizes around lipid droplets with perilipin, a regulator of lipolysis. Cidea-GFP greatly enhances lipid droplet size when ectopically expressed in preadipocytes or COS cells. These results explain previous findings showing that depletion of Cidea with RNAi markedly elevates lipolysis in human adipocytes. Like perilipin, Cidea and the related lipid droplet protein Cidec/FSP27 are controlled by peroxisome proliferator-activated receptor gamma (PPARgamma). Treatment of lean or obese mice with the PPARgamma agonist rosiglitazone markedly up-regulates Cidea expression in white adipose tissue (WAT), increasing lipid deposition. Strikingly, in both omental and s.c. WAT from BMI-matched obese humans, expression of Cidea, Cidec/FSP27, and perilipin correlates positively with insulin sensitivity (HOMA-IR index). Thus, Cidea and other lipid droplet proteins define a novel, highly regulated pathway of triglyceride deposition in human WAT. The data support a model whereby failure of this pathway results in ectopic lipid accumulation, insulin resistance, and its associated comorbidities in humans.     

Quality of emergency room triage of medical inpatients to an acute care clinic or chronic health care facilities

OBJECTIVE: To evaluate the accuracy of emergency room triage by general internists assigning medical patients to four different health care settings. DESIGN: Prospective trial. SETTING: Medical emergency room of a university hospital providing primary and referral care. PATIENTS: 974 consecutive patients admitted for acute medical care, excluding patients admitted to intensive care units. INTERVENTION AND MEASUREMENTS: After primary evaluation patients were assigned to one of four groups: A) acutely ill requiring acute care in a general medical ward (n = 598); B) acutely ill requiring acute care limited to two to three days (n = 201); C) chronically ill with realistic chances for rehabilitation (n = 77); and D) chronically ill requiring definite referral to skilled nursing home care (n = 98). Nine months later, outcome and placement after index hospitalization were evaluated in surviving patients. MAIN RESULTS: 159 (16%) patients died; three (1%) were lost to follow-up. Evolution confirmed the appropriateness of the initial triage of 90% of the remaining 812 patients (83%). Allocations were correct in 96%, 95%, and 91% of cases in groups A, B, and C, respectively. In group D, only 44% were definitely transferred to nursing homes; 56% were rehabilitated and returned to their previous social settings or entered homes for the aged. CONCLUSIONS: Clinical judgment of general internists in an emergency room adequately identifies patients requiring acute care of regular or short duration and chronically ill patients with realistic prospects for rehabilitation. But the need for nursing home placement is overestimated. To avoid patient misplacement the authors propose direct access to a specialized geriatric assessment facility.