A novel mutation in the last exon of ATRX in a patient with α-thalassemia myelodysplastic syndrome

Abstract:  We describe a patient with acquired alpha-thalassemia myelodysplastic syndrome (ATMDS). A previously healthy 66-year-old man presented with hemoglobin of 9.3 g/dL, mean corpuscular volume 59 fL, and a bone marrow aspirate with increased erythroid precursors and hypolobulated megakaryocytes. Hemoglobin H inclusions were seen in most red cells after 1% brilliant cresyl blue supravital stain of the peripheral blood. At the molecular level, we identified of a novel mutation in the most 3' exon of the ATRX gene ( C GA→ T GA substitution in codon 2407) resulting in a premature termination codon (p.R2407X). This case provides further evidence for a link between ATRX mutations and ATMDS, and suggests a possible role for the conserved Q-box element in ATRX function.     

The importance of self-examination in the earliest diagnosis of multiple primary cutaneous melanomas: a report of 47 cases

BACKGROUND: Development of more than one primary melanoma in a patient is a relatively uncommon but well-recognized phenomenon. Its frequency has ranged from 1.2% to 8.2% in several series. This subgroup of patients with multiple primary lesions has not been characterized sufficiently. We report the experience of the Melanoma Unit of University Hospital Spedali Civili of Brescia, Italy. METHOD: Study subjects were drawn from 1240 patients with histologically confirmed melanoma, including melanoma in situ. From this group, multiple melanomas developed in 47 patients (3.79%). Every one of our patients has been taught to perform self-examination of the skin to detect suspicious pigmented lesions. RESULTS: Of the 47 patients described in this study, 38 had two primary melanomas, 7 had three melanomas and 2 had 5 and 10 melanomas, respectively. Mean age at first diagnosis was 46.2 years. The majority of subsequent melanomas (74.5%) were removed within 5 years of the initial operation. Synchronous lesions were found in 10 patients. In male patients, the lesion appeared most frequently on the trunk; in female patients, melanoma appeared mostly on the lower extremities. The second primary melanomas developed in the same anatomic region from the first in 53.2% of our patients. The proportion of in situ to invasive melanomas was greater for the second melanomas compared with the first melanomas. Regarding invasive melanomas, the mean thickness of the first melanomas was 1.31 mm compared with 0.66 mm for the second ones. Dividing patients into two groups, of more and less than 50, it is highlighted that in older patients synchronous lesions appear more frequently (36.4% vs. 8.0%); the median time interval between sequential melanomas is longer (84 vs. 63.7 months); and the ratio between the primary and secondary melanoma mean thickness is lower (1.21 : 1.08 vs. 1.43 : 0.63 mm). CONCLUSIONS: The study confirms that second primary melanoma is usually thinner than the first lesion, and it is more common in the same region of the body as the initial melanoma. The highest risk for a second melanoma is during the first 5 years, but a much longer time interval of 28 years is possible. Continued medical follow-up with complete skin examinations seems prudent, but it is very important to promote self-skin evaluation in patients to detect not only metastases but also subsequent primary melanomas in their earliest phases.     

Critical ovarian hyperstimulation syndrome in a coasted in-vitro fertilization patient

We report an instance of critical ovarian hyperstimulation syndrome in a highly responsive in-vitro fertilization patient despite the preventive measure of a 4 day 'coast' interval during which no gonadotrophins were administered while gonadotrophin-releasing hormone agonist therapy continued until serum oestradiol concentrations fell below 3000 pg/ml.      

Comparison of failure characteristics of a range of cancellous bone-bone cement composites

Over the past decade, orthopedic surgery has embraced an increase in the depth of cement penetration into the adjacent cancellous bone structure. The resultant interdigitation transforms this zone into a thick layer of continuous interpenetrating composite material. The failure behavior of the composite formed with a number of potential bone cements with different bonding ability was investigated. The cancellous bone-cement composites exhibit considerable resistance to crack extension, and in situ optical observation indicates that the contribution of the cancellous bone is analogous to that of a typical fiber bridging process. The critical stress intensity factor and the work of fracture have been used to quantify the failure characteristics of the cancellous bone-cement composites. The nature of the crack propagation through these cement-bone composites was also captured via optical microscopy, and scanning electron microscopic images were taken of the failure surfaces. The R-curve behavior, or crack extension characteristic, of the cancellous bone-cement composite was also determined. The interesting outcome is that the cancellous bone-PMMA (poly-methylmethacrylate) composite, despite the absence of chemical bonding with bone, required the highest energy to fracture. In addition, the dimensional stability of the cement has a great effect on the interface.     

PAF-acether in chronic arthritis

Platelet activating factor (PAF-acether) is a potent pro-inflammatory mediator. The possible involvement of this molecule in the pathogenesis of chronic erosive arthritis has been investigated using an animal model, antigen-induced arthritis in the rabbit, which closely resembles rheumatoid arthritis. The arthritic joint fluids from rabbits with antigen-induced arthritis contained low levels of PAF-acether in the acute stages of the disease. However, PAF-acether was not detectable in the chronic stages of the lesion. The biologically inactive precursor/metabolite of PAF-acether, lyso-PAF-acether, was detectable in both control and arthritic joint washes. However, the levels of lyso-PAF-acether in the arthritic joint fluids were significantly elevated above those of control in the acute stages of the disease, but not in the chronic stages. Intra-articular injection of PAF-acether at doses up to 100 times the levels detected in the acute stages of this model did not induce joint swelling or leucocyte accumulation in normal rabbits. This study suggests that PAF-acether may contribute to the acute phase of antigeninduced arthritis but is less likely to be involved in the chronic processes.