Relative contribution of Ki-ras gene analysis and brush cytology during ERCP for the diagnosis of biliary and pancreatic diseases

Background: Ki-ras mutation analysis from material collected during ERCP has been claimed to improve the diagnosis of pancreatic and bile duct carcinomas as compared with conventional cytology. Our aim was to study the relative contribution of both Ki-ras analysis and brush cytology in patients with a significant stricture at ERCP. Methods: Brushings were collected in duplicate for both analyses in 142 patients in whom a definitive diagnosis was obtained by histology or a minimal follow-up of 6 months. Results: For pancreatic strictures, sensitivity, specificity, and accuracy of Ki-ras analysis vs. cytology in detecting malignancy were 81% vs. 66%, 72% vs. 100%, and 70% vs. 74%, respectively. For biliary strictures, they were 25% vs. 42%, 100% vs. 100%, and 35% vs. 43%, respectively. The combination of the two methods only marginally increased their sensitivity and accuracy in both types of strictures. Conclusion: Ki-ras analysis is a sensitive method for diagnosing pancreatic but not biliary carcinoma. However, its specificity is lowered by a high frequency of Ki-ras mutations in patients with chronic pancreatitis (25%) who did not manifest cancer development within a 6-month follow-up period. In pancreatic duct strictures, brush cytology appears to be more specific in detecting malignancy; specificity for Ki-ras and cytology are equivalent for the diagnosis of malignant bile duct strictures. Therefore, making a clinical decision on the sole basis of Ki-ras analysis is probably not justified in the majority of the cases. (Gastrointest Endosc 1998;47:479-85.)     

De Novo Mutations in the Motor Domain of KIF1A Cause Cognitive Impairment,Spastic Paraparesis,Axonal Neuropathy,and Cerebellar Atrophy

KIF1A is a neuron‐specific motor protein that plays important roles in cargo transport along neurites. Recessive mutations in KIF1A were previously described in families with spastic paraparesis or sensory and autonomic neuropathy type‐2. Here, we report 11 heterozygous de novo missense mutations (p.S58L, p.T99M, p.G102D, p.V144F, p.R167C, p.A202P, p.S215R, p.R216P, p.L249Q, p.E253K, and p.R316W) in KIF1A in 14 individuals, including two monozygotic twins. Two mutations (p.T99M and p.E253K) were recurrent, each being found in unrelated cases. All these de novo mutations are located in the motor domain (MD) of KIF1A. Structural modeling revealed that they alter conserved residues that are critical for the structure and function of the MD. Transfection studies suggested that at least five of these mutations affect the transport of the MD along axons. Individuals with de novo mutations in KIF1A display a phenotype characterized by cognitive impairment and variable presence of cerebellar atrophy, spastic paraparesis, optic nerve atrophy, peripheral neuropathy, and epilepsy. Our findings thus indicate that de novo missense mutations in the MD of KIF1A cause a phenotype that overlaps with, while being more severe, than that associated with recessive mutations in the same gene.     

What do people appreciate in physicians' communication? An international study with focus groups using videotaped medical consultations

Background

The literature shows that the quality of communication is usually determined from a professional perspective. Patients or lay people are seldom involved in the development of quality indicators or communication.

Objective

To give voice to the lay people perspective on what constitutes ‘good communication’ by evoking their reactions to variations in physician communication.

Design

Lay people from four different countries watched the same videotaped standardized medical encounters and discussed their preferences in gender‐specific focus groups who were balanced in age groups.

Setting and participants

Two hundred and fifty‐nine lay people (64 NL, 72 IT, 75 UK and 48 BE) distributed over 35 focus groups of 6–8 persons each.

Main variables studied

Comments on doctors'' behaviours were classified by the GULiVer framework in terms of contents and preferences.

Results

Participants prevalently discussed ‘task‐oriented expressions’ (39%: competency, self‐confident, providing solutions), ‘affective oriented/emotional expressions'' (25%: empathy, listening, reassuring) and ‘process‐oriented expressions'' (23%: flexibility, summarizing, verifying). ‘Showing an affective attitude’ was most appreciated (positive percentage within category: 93%, particularly facilitations and inviting attitude), followed by ‘providing solution’ (85%). Among disfavoured behaviour, repetitions (88%), ‘writing and reading’ (54%) and asking permission (42%) were found.

Conclusions

Although an affective attitude is appreciated by nearly everybody, people may vary widely in their communication needs and preferences: what is ‘good communication’ for one person may be disliked or even a source of irritation for another. A physician should be flexible and capable of adapting the consultation to the different needs of different patients. This challenges the idea of general communication guidelines.     

Rearrangements of the RAR-α gene in acute promyelocytic leukaemia:

We have used genomic probes which specifically recognize DNA rearrangements of the RAR-alpha locus on chromosome 17q21 in patients with acute promyelocytic leukaemia (APL) and acute myeloid leukaemia (AML) subtypes. Molecular data were examined in comparison with morphological and immunophenotypic characterization at diagnosis in 20 hypergranular FAB M3 cases, five microgranular APL (M3v), 51 non-M3 AML and 12 myeloid CML blast crises. Rearrangements of the RAR-alpha locus were only detected in 23/25 APL cases and in none of the other FAB subtypes analysed. Surface marker characterization showed a consistent immunophenotypic profile--HLADR negative, CD9 and CD13/33 positive--in all M3 and M3v cases. Neither HLADR negativity nor CD9 positivity were associated with RAR-alpha rearrangements in non M3 AML. Our data indicate that RAR-alpha gene rearrangements are relevant diagnostic features of both M3 and M3v, and may prove useful molecular marker for follow-up analysis in APL patients.     

Seasonal changes in melatonin concentrations in female Iberian red deer (Cervus elaphus hispanicus)

In deer, most of the earlier investigations on pineal function examined the effects of artificial photoperiods or the administration of melatonin to manipulate reproduction. However, endogenous melatonin rhythms have not been studied in red deer. Thus, we monitored seasonal changes in plasma melatonin concentrations in 16 adult female Iberian red deer living in outdoor enclosures. Blood was sampled on the day of each seasonal change every 3-4 hr overnight and 1 hr before and after sunset and sunrise. In addition, in six of the previous hinds, blood sampling during the hour prior and after sunset and sunrise was collected every 20 min. Significant differences were found both in amplitude and duration of the nocturnal plasma melatonin profiles in the four seasonal changes (P < 0.01). The nocturnal mean level of melatonin, the duration of nocturnal secretion levels and maximal concentrations were significantly higher at the winter solstice than in summer solstice or equinoxes (P < 0.05). Moreover, the mean overnight concentrations were significantly higher at the spring equinox and winter solstice than during the summer solstice and autumn equinox (P < 0.05). A pronounced elevation from low levels was recorded 1 hr after sunset, remained elevated during the hours of darkness and declined to low levels 1 hr after dawn. Concentrations close to sunrise were higher than those near sunset at all changes of season (P < 0.05). These results show for the first time in red deer that the pineal gland of the adult female is highly responsive to both daily and seasonal changes in natural environmental illumination, although overnight levels lasted longer than the photoperiodic night is all cases, particularly at the winter solstice.     

Design of a Master of Science Sustainable Chemistry

Chemistry is the central science for value creation by physical products in the socio-economic system. Unsustainable processes over many decades have led to pressure on the planet and an urgent need for prioritizing sustainable development on a global level. Due to the central role of chemistry, the chemistry profession is an important stakeholder group to shape the transformation towards sustainable development. In order to provide relevant skills, higher education in chemistry requires a view of chemistry in the context of the framework of sustainability and the uptake of new content that is not covered in conventional teaching of chemistry. Such content includes environmental chemistry and toxicology, benign design of chemicals (teaching of chemistry), but also a broader context such as alternative business models and overarching knowledge of international policies and strategies to implement change with respect to chemical industry, chemical products and business (teaching about chemistry) in favor of sustainable development. In this paper, we describe a first of its kind program following this approach: An M.Sc. Sustainable Chemistry. It addresses the above mentioned topics and aims for international professionals of the chemical sector.     

Positive selection of protective variants for type 2 diabetes from the Neolithic onward: a case study in Central Asia

The high prevalence of type 2 diabetes and its uneven distribution among human populations is both a major public health concern and a puzzle in evolutionary biology. Why is this deleterious disease so common, while the associated genetic variants should be removed by natural selection? The ‘thrifty genotype'' hypothesis proposed that the causal genetic variants were advantageous and selected for during the majority of human evolution. It remains, however, unclear whether genetic data support this scenario. In this study, we characterized patterns of selection at 10 variants associated with type 2 diabetes, contrasting one herder and one farmer population from Central Asia. We aimed at identifying which alleles (risk or protective) are under selection, dating the timing of selective events, and investigating the effect of lifestyle on selective patterns. We did not find any evidence of selection on risk variants, as predicted by the thrifty genotype hypothesis. Instead, we identified clear signatures of selection on protective variants, in both populations, dating from the beginning of the Neolithic, which suggests that this major transition was accompanied by a selective advantage for non-thrifty variants. Combining our results with worldwide data further suggests that East Asia was particularly prone to such recent selection of protective haplotypes. As much effort has been devoted so far to searching for thrifty variants, we argue that more attention should be paid to the evolution of non-thrifty variants.