A real-time (PCR) for a real life…? Quantitative evaluation of BCL2/IGH in follicular lymphoma and its implications for clinical practice

Follicular lymphoma (FL) is highly associated with the molecular rearrangement BCL2/IGH. Although BCL2/IGH has been studied many times in follicular lymphoma, its real clinical value remains controversial. In this study, we performed quantitative testing by real-time polymerase chain reaction in 56 FL patients with median follow-up of 44 months (range, 9-102 months); chemotherapy was administered in 52 of 56 cases. Pretreatment numbers of BCL2/IGH varied in wide ranges, with a median of 2947 (range, 0-1,261,013) copies/10(6) cellular equivalent in peripheral blood (PB) and 4650 copies/10(6) cellular equivalent (range, 1-1,056,813) in bone marrow (BM), the difference between PB and BM was significant (p?= 0.006). Pretreatment of BCL2/IGH quantities were correlated to clinical parameters (e.g., age, stage, sex, lactate dehydrogenase, B symptoms, grade, bulky disease, chemotherapy regimen) and to progression free-survival. Advanced clinical stage (III and IV) and microscopic BM involvement were significantly associated with higher numbers of BCL2/IGH in PB (p < 0.05) and in BM (p = 0.05), regardless all or newly diagnosed patients were evaluated. High pretreatment burden of BCL2/IGH was associated with significantly shorter progression-free survival; p = 0.003 and p = 0.047 for PB and BM, respectively. In conclusion, pretreatment quantity of BCL2/IGH in PB or BM seems to mirror the extent of disease and can provide an auxiliary prognostic parameter in FL. Our results also support evidence of the negative prognostic value of microscopic BM involvement in FL.     

Age-related neoplastic risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germ line RET Cys634Trp (TGC>TGG) mutation

RET testing in multiple endocrine neoplasia type 2 for molecular diagnosis is the paradigm for the practice of clinical cancer genetics. However, precise data for distinct mutation-based risk profiles are not available. Here, we survey the clinical profile for one specific genotype as a model, TGC to TGG in codon 634 (C634W). By international efforts, we ascertained all available carriers of the RET C634W mutation. Age at diagnosis, penetrance, and clinical complications were analyzed for medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism (HPT), as well as overall survival. Our series comprises 92 carriers from 20 unrelated families worldwide. Sixty-eight subjects had MTC diagnosed at age 3-72 years (mean 29). Lymph node metastases were observed in 16 subjects aged 20-72 and distant metastases in 4 subjects aged 28-69. Forty-one subjects had pheochromocytoma detected at age 18-67 (mean 36). Amongst the 28 subjects with MTC and pheochromocytoma, six developed pheochromocytoma before MTC. Six subjects had HPT diagnosed at age 26-52 (mean 39). Eighteen subjects died; of the 16 with known causes of death, 8 died of pheochromocytoma and 4 of MTC. Penetrance for MTC is 52% by age 30 and 83% by age 50, for pheochromocytoma penetrance is 20% by age 30 and 67% by age 50, and for HPT penetrance is 3% by age 30 and 21% by age 50. These data provide, for the first time, RET C634W-specific neoplastic risk and age-related penetrance profiles. The data may facilitate risk assessment and genetic counseling.     

Denture tooth selection: an analysis of the natural maxillary central incisor compared to the length and width of the face. Part I.

A project was devised by the removable prosthodontic faculty to determine clinically if there is a correlation between the length and width of the maxillary central incisor on a cast and the length and width of the face. A millimeter gauge was used to measure the lengths and widths of the maxillary incisor on a cast. The Trubyte tooth indicator was selected to measure the length and width of the face. This tooth indicator is designed for calibration of the 16 to 1 ratio between facial dimension and maxillary central incisors.     

Modulatory Effect of the Euro-Lupus Low-Dose Intravenous Cyclophosphamide Regimen on Circulating Immune Cells in Systemic Lupus Erythematosus

Archivum Immunologiae et Therapiae Experimentalis - A Euro-Lupus regimen of low-dose intravenous cyclophosphamide (CFA) is commonly used to treat severe organ manifestations of systemic lupus...     

Ribosomal protein S17 gene (RPS17) is mutated in Diamond-Blackfan anemia

Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia characterized as a normochromic macrocytic anemia with a selective deficiency in red blood cell precursors in otherwise normocellular bone marrow. In 40% of DBA patients, various physical anomalies are also present. Currently two genes are associated with the DBA phenotype--the ribosomal protein (RP) S19 mutated in 25% of DBA patients and RPS24 mutated in approximately 1.4% of DBA patients. Here we report the identification of a mutation in yet another ribosomal protein, RPS17. The mutation affects the translation initiation start codon, changing T to G (c.2T>G), thus eliminating the natural start of RPS17 protein biosynthesis. RNA analysis revealed that the mutated allele was expressed, and the next downstream start codon located at position +158 should give rise to a short peptide of only four amino acids (Met-Ser-Arg-Ile). The mutation arose de novo, since all healthy family members carry the wild-type alleles. The identification of a mutation in the third RP of the small ribosomal subunit in DBA patients further supports the theory that impaired translation may be the main cause of DBA pathogenesis.     

Temporal trends in maternal mortality in Canada I: estimates based on vital statistics data

ObjectivesVital Statistics and World Health Organization reports show a recent increase in maternal mortality in Canada. We carried out a study of temporal trends, regional variations, and causes of death in Canadian maternal mortality using Vital Statistics data.MethodsWe used Vital Statistics death registrations to ascertain maternal deaths between 1981 and 2007. Maternal mortality rates, risk ratios, and 95% confidence intervals were estimated, and the Cochran-Armitage test was used to evaluate temporal trends. We used hospitalization data from the Canadian Institute for Health Information from 1996 to 2007 to confirm maternal mortality trends observed in the Vital Statistics data.ResultsMaternal mortality rates increased significantly from 4.5 (95% CI 3.3 to 5.8) in 1981 to 1983 to 4.7 (95% CI 3.5 to 6.2) in 1996 to 1998 and to 7.2 (95% CI 5.7 to 9.0) per 100 000 live births in 2005 to 2007 (P value for trend < 0.001). The most common causes of maternal death were diseases of the circulatory system, obstetric embolism (venous thromboembolism and amniotic fluid embolism), and hypertension. Deaths due to diseases of the circulatory system and puerperal infection increased significantly from 1981 to 2007. Maternal mortality rates in the hospitalization data were higher and did not show an increase over time. Provincial and territorial maternal mortality rates from Vital Statistics data showed varying degrees of under-ascertainment (12% to 70%) compared with hospitalization data.ConclusionTemporal increases in maternal mortality in Canada observed in Vital Statistics data do not correspond with stable temporal trends observed in hospitalization data, and appear to be an artefact of changes in the coding and ascertainment of maternal deaths.     

Antihypertensive action of soluble epoxide hydrolase inhibition in Ren‐2 transgenic rats is mediated by suppression of the intrarenal renin–angiotensin system

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