Mutation detection rate and spectrum in familial hypercholesterolaemia patients in the UK pilot cascade project.

Cascade testing using DNA-mutation information is now recommended in the UK for patients with familial hypercholesterolaemia (FH). We compared the detection rate and mutation spectrum in FH patients with a clinical diagnosis of definite (DFH) and possible (PFH) FH. Six hundred and thirty-five probands from six UK centres were tested for 18 low-density lipoprotein receptor gene (LDLR) mutations, APOB p.Arg3527Gln and PCSK9 p.Asp374Tyr using a commercial amplification refractory mutation system (ARMS) kit. Samples with no mutation detected were screened in all exons by single strand conformation polymorphism analysis (SSCP)/denaturing high performance liquid chromatography electrophoresis (dHPLC)/direct-sequencing, followed by multiplex ligation-dependent probe amplification (MLPA) to detect deletions and duplications in LDLR.The detection rate was significantly higher in the 190 DFH patients compared to the 394 PFH patients (56.3% and 28.4%, p > 0.00001). Fifty-one patients had inadequate information to determine PFH/DFH status, and in this group the detection rate was similar to the PFH group (25.5%, p = 0.63 vs PFH). Overall, 232 patients had detected mutations (107 different; 6.9% not previously reported). The ARMS kit detected 100 (44%) and the MLPA kit 11 (4.7%). Twenty-eight (12%) of the patients had the APOB p.Arg3527Gln and four (1.7%) had the PCSK9 p.Asp374Tyr mutation. Of the 296 relatives tested from 100 families, a mutation was identified in 56.1%. In 31 patients of Indian/Asian origin 10 mutations (two previously unreported) were identified. The utility of the ARMS kit was confirmed, but sequencing is still required in a comprehensive diagnostic service for FH. Even in subjects with a low clinical suspicion of FH, and in those of Indian origin, mutation testing has an acceptable detection rate.

Audit of maternal serum screening: strategies to augment counselling in response to women's views.

Women's opinion on the maternal serum screening programme offered at one maternity unit in East Northumberland (1991-1992) was evaluated. The responses from 1,774/2,633 women showed a general acceptance of the test but 722/1,774 (40%) wanted more information and a third, more explanation. Recommendations, which included a 'gold standard' protocol, a video to complement revised patient information literature and a coordinator to facilitate interdisciplinary communication and training with support for midwives, were introduced. The audit cycle was completed by a repeat questionnaire survey of 2,489 women from the postnatal ward (1992-1994) with a 67.3% response. An overall improvement in levels of satisfaction with reduction in, but not eradication of, the need for more information and explanation had occurred. These findings have relevance to the current controversy surrounding the counselling implications of maternal serum screening and have led to the formation of a network of professionals to develop the programme in our region.

SEM analysis of incinerated teeth as an aid to positive identification.

Tooth crown and root fragments from a crime scene in which the remains were purposefully cremated, crushed and scattered were analyzed using a scanning electron microscope (SEM) in order to aid the identification process. The SEM was used to confirm the presence of parallel striations in tooth enamel and dentine as a means of determining past dental restoration. In the case presented, incinerated tooth fragments of determined type and position were subjected to SEM analysis, and ascertained to have had previous dental work that matched antemortem dental records of a missing person.

Size of the sella turcica and its relation to iron deficiency anemia: a prehistoric example.

This paper examines the usefulness of volume and area assessments of the sella turcica from radiographs in order to aid in the differential diagnosis of iron deficiency anemia in past populations. Lateral and posterior-anterior radiographs were taken of each cranium in the sample. The length, depth, and width of the sella turcica were then measured directly from the appropriate view, and subsequently the volume and area were calculated for each. The 20-25 year-old cohort was found to yield the most promising results; however, a statistical difference was not found to exist using the volume or area. The width dimension was found to be of far more use than any other in this study. In no instance was any feature of typical porotic hyperostosis, visually or radiographically, found to be statistically correlated with any difference in the dimensions of the sella turcica. A discussion of how the various dimensions of the sella turcica react to changes in size of the hypophysis cerebri is presented.

A radiographic technique of interest to physical anthropologists.

A radiographic technique for processing a large number of human crania was developed to aid in the diagnosis of porotic hyperostosis in a large skeletal population. These images are made directly onto photographic paper, thereby reducing costs and increasing the rate of processing. The technique is especially well suited for radiographing human skeletal material and gives excellent diagnostic image quality.

Cribra orbitalia in two temporally disjunct population samples from the Dakhleh Oasis, Egypt.

Cribra orbitalia (CO), an osseous sign of anemic stress, occurs in 67% (n = 296) of the pre-Roman (n = 153) and Roman (n = 143) period crania from the Dakhleh Oasis, Egypt. CO is primarily a childhood condition in these samples, and its prevalence is significantly higher in virtually all cohorts in the pre-Roman group, including among females, who display higher rates of active lesions. This temporal trend suggests that the underlying causative factors (i.e., synergism between disease and nutrition) were less pervasive in the Roman period. In both population samples, anemic stress develops in some perinates prior to the expected minimum age for the development of iron deficiency anemia. This suggests additional causes of anemic stress in the Dakhleh population. A strong candidate is folic acid deficiency and its concomitant, megaloblastic anemia, which results from weaning of infants on goat's milk, a known practice in ancient Egypt. The putative incorporation of other food items in the weanling diet, particularly honey, a confirmed source of C. botulinum, represents yet another retrospective data source to help understand the epidemiological profile of cribra orbitalia in this population. Comparative data from other Egyptian populations, though limited, show similar patterns, however, they display a lower prevalence than the data from Dakhleh.

Maternal serum screening for Down's syndrome: a survey of midwives' views.

The lack of consensus regarding the implementation of maternal serum screening, has led to a widespread variation in practice. The importance of the role of midwives within the service has been recognised. All maternity units in the Northern region now have a designated 'co-ordinator' in an attempt to improve service delivery, professional liaison and training. This study was designed to obtain midwives' views about maternal serum screening in principle and to assess whether any changes had occurred since the introduction of co-ordinators. Semi-structured, postal questionnaires were sent to all midwives in one health authority for them to complete and return. Within this authority, one maternity unit offered universal screening whereas the other maintained a selective policy. Responses were obtained from 90 out of 133 (67.7%). There was almost unanimous support for the principle of screening 86 out of 90 (95.5%) and most midwives considered the offer of screening should be an NHS service, independent of age 78 out of 90 (86.7%). Half of the respondents 46 out of 90 (51.2%) reported that the introduction of a co-ordinator had been successful in improving staff education but requests for further training and updating were made by 69 out of 90 (76.6%) despite having had this organized training input: although those midwives who were regularly involved with screening made significantly fewer requests 27 out of 45 (60%). These findings confirmed our previous recommendation that ongoing responsibility for such provision would be required. The results of the study provided a useful contribution towards the review of screening policy undertaken by the health authority, as well as evidence upon which to base further development of the role of the co-ordinators in their support of midwives.

Infant feeding and weaning practices in Roman Egypt.

Current knowledge of infant feeding and weaning practices during the Roman period in Egypt is limited to scanty documentary and iconographic evidence. Stable nitrogen and carbon isotope analysis provides another avenue to explore this question. A sample of 49 infant and juvenile human skeletal remains from the Kellis 2 cemetery in the Dakhleh Oasis, Egypt, was used to determine patterns of infant feeding and weaning. delta(15)N values indicate that supplementary foods were introduced at around 6 months of age, and that weaning was complete by 3 years of age. By 6 months of age, delta(13)C values become increasingly enriched over adult values, and reach peak enrichment at approximately 1.5 years of age. Beyond this age, delta(13)C gradually declines to approach adult values. This enrichment in infant delta(13)C values is indicative of consumption of (13)C-enriched supplementary foods. Based on isotopic study of faunal and botanical remains from the ancient village of Kellis, we conclude that at approximately 6 months of age, infants were fed milk of goat and/or cow.