First-generation offspring of male mice exposed to 239Pu-citrate show no evidence of leukaemia or life shortening

The aim was to test whether male mice injected with ²³⁹Pu citrate transmit induced mutations that lead to specific causes of death, decrease longevity or both. Male CBA/Ca mice injected with ²³⁹Pu citrate solutions at nominal activities of 6 and 60 Bq g^?–?1 were mated to females (same strain) 54?–?68 days later. Absorbed doses to the testes were estimated to be approximately 0.3 and 4.0?cGy. Control males were injected with carrier only. Longevity was evaluated. All 1807 progeny were given detailed necropsies. Haematological analysis was used in an attempt to identify leukaemia. Male progeny from both treated groups lived significantly longer than those from the control, and there was no difference in longevity between the two treatments. No evidence was found of the induction of leukaemia or of any of the numerous probable causes of death. Although numerous significant differences were found in the many comparisons made between the three groups, there was no clear indication that any harmful effects were associated with paternal preconceptional plutonium exposure. This was in spite of the initial body burden (higher dose) being approximately 2800 times the maximum body burden allowed for workers when this study was initiated.     

The filaggrin null genotypes R501X and 2282del4 seem not to be associated with psoriasis: results from general population study and meta‐analysis

Background Psoriasis vulgaris could be associated with the filaggrin null genotype since certain known susceptibility loci for psoriasis are shared with susceptibility loci for atopic dermatitis. Furthermore, filaggrin expression is lowered in psoriatic skin lesions but normally expressed in uninvolved skin. So far five relatively small patient‐based case‐control studies have rejected a possible association between psoriasis and the two most prevalent filaggrin null mutations, 2282del4 and R501X. Objectives To reinvestigate a possible association between psoriasis and filaggrin null mutation status by using cross‐sectional general population questionnaire data. Also, to perform a meta‐analysis including published studies that investigated the relation between filaggrin gene mutations R501X and 2282del4, respectively, and psoriasis vulgaris. Methods Between June 2006 and May 2008, a cross‐sectional study was performed in the general population in Copenhagen. A random sample of 7931 subjects aged 18–69 years was invited to participate in a general health examination including a questionnaire and 3471 (43.7%) participated. A total of 3335 (96.1%) individuals were filaggrin genotyped for the 2282del4 and R501X mutations. A meta‐analysis was undertaken to investigate the relation between filaggrin gene mutations and psoriasis vulgaris. Results The prevalence of self‐reported psoriasis was 6.7% among the 3240 respondents. The prevalence of the R501X and 2282del4 filaggrin null genotypes was 9.3% in subjects who reported psoriasis and 8.0% in subjects who did not report psoriasis (OR = 1.28; 95% CI = 0.74–1.89; P = 0.78). The meta‐analysis found no association between the filaggrin null genotypes R501X and 2282del4 and psoriasis (OR = 1.04; 95% CI = 0.81–1.35). Conclusions Psoriasis was not associated with the R501X and 2282del4 filaggrin null genotypes in a general population study and in a meta‐analysis on published studies.     

Contemporary management of aortic branch compromise resulting from acute aortic dissection

PURPOSE: In an earlier report, we documented the incidence and impact of aortic branch compromise complicating acute aortic dissection (AD) over a 21-year interval (1965-1986). In the current study, management of peripheral vascular complications (PVCs) of AD over the past decade was reviewed. METHODS: Medical records of patients treated for AD over the interval January 1, 1990, to December 31, 1999, were reviewed. Patients with branch compromise confirmed with radiography or operation and patients with spinal cord ischemia that was based on results of a physical examination defined the study group. Comparisons between subgroups with and without PVC over a 30-year interval were analyzed with the chi(2) test. RESULTS: A total of 187 patients (101 proximal and 86 distal) were treated for AD over the study interval. A total of 53 (28%) of these patients had clinical evidence of organ or limb malperfusion (7 cerebral, 3 upper extremity, 5 spinal cord, 11 mesenteric, 12 renal, and 24 lower extremity [sites inclusive]), and one of three (17 patients) of these underwent specific peripheral vascular intervention. The remaining 65% (36) of the PVC group had complete or partial malperfusion resolution after central aortic therapy (medical or surgical) alone. Open techniques for treating PVC included aortic fenestration (9), femorofemoral grafting (2), and aortofemoral grafting (1). All had favorable outcomes with no mortality. Endovascular procedures in five patients included abdominal aortic fenestration (3) or stenting of the renal (2), mesenteric (2), and iliac (1) arteries with clinical success in three patients and two deaths. The in-hospital mortality rate for the entire group of 187 patients was 18% (15% for proximal aortic operation, 8% in medically treated patients). The presence of aortic branch compromise was not a statistically significant predictor of the patient mortality rate (23% with and 16% without; P =.26). Overall mortality rate in the current study (18% vs 37%; P =.000006) and the mortality rate with PVC (23% vs 51%; P =.001), in particular with mesenteric ischemia (36% vs 87%; P =.026), decreased significantly when compared with prior experience. CONCLUSIONS: The overall mortality rate from AD during the past decade has decreased significantly. Similar trends were noted in patients with PVCs, a previously identified high-risk subgroup. Increased awareness and prompt, specific management of PVCs, in particular when visceral ischemia is present, have contributed to improved outcomes in patients with AD.