The mechanism of action of phenobarbital on the metabolism of 131J-B.S.P. in cholestasis induced by ANIT in isolated and perfused rat liver (author's transl)

In order to establish whether the increased B.S.P. secretion in the bile following phenobarbital administration is the consequence of change in the bile output or represents a consequence of the enzymatic induction, the dynamics of the elimination of 131J-B.S.P. was studied in animals treated with ANIT and Phenobarbital in the conditions of isolated perfused liver. At the same time the levels of the conjugation enzyme of B.S.P. were also determined. It was noted that after Phenobarbital the biliary elimination of 131J-B.S.P. is in correlation with the important increase of the output; in the animals treated with ANIT, on the other hand, the biliary excretion of B.S.P. is minimal. The biliary elimination is directly proportional to the increased of the bile output and reflects the changes found in the perfusate. Our findings allow us to assume that the increased of the bile output and in a smaller extent the result of the stimulation B.S.P. conjugation with Gluthation.     

Second primary malignancies in thyroid cancer patients

The late health effects associated with radioiodine ((131)I) given as treatment for thyroid cancer are difficult to assess since the number of thyroid cancer patients treated at each centre is limited. The risk of second primary malignancies (SPMs) was evaluated in a European cohort of thyroid cancer patients. A common database was obtained by pooling the 2-year survivors of the three major Swedish, Italian, and French cohorts of papillary and follicular thyroid cancer patients. A time-dependent analysis using external comparison was performed. The study concerned 6841 thyroid cancer patients, diagnosed during the period 1934-1995, at a mean age of 44 years. In all, 17% were treated with external radiotherapy and 62% received (131)I. In total, 576 patients were diagnosed with a SPM. Compared to the general population of each of the three countries, an overall significantly increased risk of SPM of 27% (95% CI: 15-40) was seen in the European cohort. An increased risk of both solid tumours and leukaemias was found with increasing cumulative activity of (131)I administered, with an excess absolute risk of 14.4 solid cancers and of 0.8 leukaemias per GBq of (131)I and 10(5) person-years of follow-up. A relationship was found between (131)I administration and occurrence of bone and soft tissue, colorectal, and salivary gland cancers. These results strongly highlight the necessity to delineate the indications of (131)I treatment in thyroid cancer patients in order to restrict its use to patients in whom clinical benefits are expected.     

Murine dorsal hair type is genetically determined by polymorphisms in candidate genes that influence BMP and WNT signalling

Mouse dorsal coat hair types, guard, awl, auchene and zigzag, develop in three consecutive waves. To date, it is unclear if these hair types are determined genetically through expression of specific factors or can change based on their mesenchymal environment. We undertook a novel approach to this question by studying individual hair type in 67 Collaborative Cross (CC) mouse lines and found significant variation in the proportion of each type between strains. Variation in the proportion of zigzag, awl and auchene, but not guard hair, was largely due to germline genetic variation. We utilised this variation to map a quantitative trait locus (QTL) on chromosome 12 that appears to influence a decision point switch controlling the propensity for either second (awl and auchene) or third wave (zigzag) hairs to develop. This locus contains two strong candidates, Sostdc1 and Twist1, each of which carry several ENCODE regulatory variants, specific to the causal allele, that can influence gene expression, are expressed in the developing hair follicle, and have been previously reported to be involved in regulating human and murine hair behaviour, but not hair subtype determination. Both of these genes are likely to play a part in hair type determination via regulation of BMP and/or WNT signalling.     

Micropapillary carcinoma: Description and rise in incidence in the French Marne-Ardennes thyroid cancer registry

ContextYearly incidence of thyroid cancer has nearly tripled in the past four decades, due to improvements in and better use of diagnostic procedures, enabling detection of smaller tumors, and notably micropapillary carcinoma (MPC: ≤ 10 mm).ObjectivesThe aim of our study was to confirm increasing incidence, to describe the characteristics and circumstances of discovery, and to examine the reasons for this rise in incidence of MPCs, based on the French Marne-Ardennes registry for 1975–2014.DesignThis was a retrospective observational cohort study.ResultsTwo thousand six hundred and seventy-one patients with thyroid cancer were included for the period 1975–2014, with 966 (36.2%) MPCs. The percentage increased from 18.9% for 1975–1984 to 45.1% for 2005–2014. Standardized incidence per 100,000 patient-years increased from 0.86 for 1975–1984 to 6.20 for 2005–2014. Incidence increase was higher in women (ranging from 1.15 to 8.91) than in men (from 0.20 to 2.54). Incidence increased more in ≥ 50 year-olds (from 0.41 to 4.21) than in < 50 year-olds (from 0.45 to 1.99). Most MPCs (84.6%) were discovered incidentally on histology, and were mainly unifocal (79.4%). Incidental MPCs were smaller, affected older patients and were less multifocal than those suspected before surgery. MPCs were associated with excellent survival and low morbidity, with < 1.9% progression.ConclusionThe present study confirmed the large rise in incidence of MPCs reported elsewhere. Most MPCs were discovered incidentally on histological examination in the context of surgery for benign pathology. Changes in access to health care and in physicians’ and pathologists’ practices are likely explanations for our findings.