Quantitative phenotypes correlated with a complex disorder offer increased power to detect linkage in comparison to affected-unaffected classifications. Asthma is a complex disorder characterized by ...periods of bronchial obstruction and increased bronchial hyper reactivity. In childhood and early adulthood, asthma is frequently associated also with quantitative measures of atopy. Genome wide quantitative multipoint linkage analysis was conducted for serum IgE levels and percentage of positive skin prick test (SPT(per)) using three large groups of families originally ascertained for asthma. In this report, 438 and 429 asthma families were informative for linkage using IgE and SPT(per) which represents 690 independent families. Suggestive linkage (LOD > or = 2) was found on chromosomes 1, 3, and 8q with maximum LODs of 2.34 (IgE), 2.03 (SPT(per)), and 2.25 (IgE) near markers D1S1653, D3S2322-D3S1764, and D8S2324, respectively. The results from chromosomes 1 and 3 replicate previous reports of linkage. We also replicate linkage to 5q with peak LODs of 1.96 (SPT(per)) and 1.77 (IgE) at or near marker D5S1480. Our results provide further evidence implicating chromosomes 1, 3, and 5q. The current report represents one of the biggest genome scans so far reported for asthma related phenotypes. This study also demonstrates the utility of increased sample sizes and quantitative phenotypes in linkage analysis of complex disorders.
We describe the structure of, and suggest an etiology for, the interatrial communication which can occur through the mouth of the coronary sinus. Based on the study of human embryos, we propose that ...the defect is best explained by dissolution of the wall of the coronary sinus adjacent to the left atrium, permitting shunting between the atriums through the right atrial orifice of the sinus.
An interatrial communication across the mouth of the coronary sinus defect was first described in 1965 by Raghib and colleagues, its existence being predicated on the basis of incomplete formation of the left "atriovenous fold". Their hypothesis implies that the coronary sinus never develops, and thus the atrial septum itself is incomplete.
We have studied the development of the coronary sinus in a series of human embryos. Based on this work, we present the anatomical findings in 6 specimens with varying degrees of dissolution of the walls of the coronary sinus, and ten specimens with isomerism of the right atrial appendages, in which the sinus has never been formed.
The coronary sinus defect is not a hole within the atrial septum, but a communication between the atriums through the mouth of the sinus. There was a range of defects in our series of specimens with usual atrial arrangement, extending from complete absence of the walls which normally separate the coronary sinus from the left atrium, to small fenestrations between this vessel and the left atrial cavity. In the hearts with isomerism of the right atrial appendages, however, we never observed an orifice of the coronary sinus. Thus, a coronary sinus defect cannot exist in this setting.
Our findings indicate that the defect requires initial formation of the walls of the coronary sinus, but with subsequent dissolution of the wall adjacent to the left atrium. This produces a communication between the atriums through the mouth of the sinus.
Defects in lateralization can be studied from the stance of populations, the individual, or the systems of organs within each individual. Unfortunately, and confusingly, the same terms are being ...applied to each of these situations, but inevitably with different meanings. Thus, there is presently no consensus on how we should use terms such as "heterotaxy" and "situs ambiguus". By far the least ambiguous use of these words is encountered when they are applied to the organs. In fact, each system of organs can accurately and simply be described in terms of its left-right morphology. All those organs which are paired then can be described, when interpreted on the basis of their intrinsic morphology, as being usually arranged, mirror-imaged, or as showing left or right isomerism. Within the heart, these changes are seen only in the atrial segment. The criterion for distinction of rightness or leftness within the atrial segment is the extent of the pectinate muscles relative to the atrioventricular junction. Application of this criterion permits unequivocal recognition of symmetry as opposed to lateralization. The same holds good for the other organs. Within any individual organ, therefore, the situation is neither ambiguous nor heterotaxic. Instead, it is lateralised or symmetrical. Within the individual, in contrast, there may well be discrepancies in the expected disposition of the systems of organs which produces potential ambiguity. To dispel this ambiguity, it is necessary to provide a full catalogue. For example, persons with otherwise normally arranged organs may have left bronchial isomerism. Other persons may have discordance between the thoracic organs, which are usually arranged, and the abdominal organs, which are mirror-imaged, but no evidence of isomerism. Within the population, however, we are unaware of any genetically or environmentally induced syndrome in which all individuals show evidence of mirror-imagery, or of isomerism, or of specific discordance between the systems. In fact, all known syndromes encompass all types of defective lateralization. When attempting to identify the genetic mechanisms for production of the syndromes, therefore, it could be positively misleading to attempt to separate isomerism from other perceived forms of"heterotaxy". Our preference is to consider any deviation from the usual arrangement as heterotaxy, and to specify the specific arrangement of the organs within each malformed individual.
The plate motion model NUVEL-1 predicts oblique convergence between the Pacific and Australian plates in the South Island of New Zealand. We used P and SH body waveform analysis to constrain the ...focal mechanisms of the 15 largest earthquakes (Ms > 5.8) that have occurred in this region since 1964, in order to see how the plate motion is accommodated. At the southern end of the Alpine Fault, convergence is achieved by oblique slip movement along a concentrated zone of deformation. In the southern offshore region one event may be related to thrusting of the Australian plate beneath the Pacific plate, and another strike-slip event probably demonstrates movement on an active strike-slip fault system parallel to, but offset from, the southern limit of the Alpine Fault. This geometry provides a possible mechanism for the rapid uplift of the Fiordland region. Deformation in the northern South Island is more distributed. In the south-west Marlborough region partitioning occurs between strike-slip faulting in the SE and reverse faulting farther NW in the Buller region. We suggest that the partitioning developed as a consequence of an increasing component of shortening that was accommodated by slip on reactivated pre-existing normal faults in the Buller region. Shortening in the Buller region may have deflected the NE end of the Alpine Fault towards the NW, forming the prominent bend. The Marlborough Fault System, with its youngest and most active faults to the SE, probably developed in an attempt to maintain a through-going strike-slip structure as each of the strike-slip faults was transported towards the north-west. Partitioning of the opposite polarity (with reverse faulting SE of the strike-slip faulting) occurs in north-east Marlborough. The boundary between the two different styles of partitioning in NE and SW Marlborough appears to coincide with a change in the nature of the downgoing slab and a change in strike of faults of the Marlborough Fault System. A normal faulting earthquake on the northern edge of the Chatham rise probably results from a complex interaction of the buoyant continental crust in that region with the subduction zone and the overlying Marlborough Fault System.
Executive summary: This report addresses the needs and problems of grown-up congenital heart (GUCH) patients and makes recommendations on organisation of national medical care, training of ...specialists, and education of the profession. The size of the national population of patients with grown-up congenital heart disease (GUCH) is uncertain, but since 80–85% of patients born with congenital heart disease now survive to adulthood (age 16 years), an annual increase of 2500 can be anticipated according to birth rate. Organisation of medical care is haphazard with only three of 18 cardiac surgical centres operating on over 30 cases per annum and only two established specialised units fully equipped and staffed. Not all grown-ups with congenital heart disease require the same level of expertise; 20–25% are complex, rare, etc, and require life long expert supervision and/or intervention; a further 35–40% require access to expert consultation. The rest, about 40%, have simple or cured diseases and need little or no specialist expertise. The size of the population needing expertise is small in comparison to coronary and hypertensive disease, aging, and increasing in complexity. It requires expert cardiac surgery and specialised medical cardiology, intensive care, electrophysiology, imaging and interventions, “at risk” pregnancy services, connection to transplant services familiar with their basic problem, clinical nurse specialist advisors, and trained nurses. An integrated national service is described with 4–6 specialist units established within adult cardiology, ideally in relation or proximity to university hospital/departments in appropriate geographic location, based in association with established paediatric cardiac surgical centres with designated inpatient and outpatient facilities for grown-up patients with congenital heart disease. Specialist units should accept responsibility for educating the profession, training the specialists, cooperative research, receiving patients “out of region”, sharing particular skills between each other, and they must liaise with other services and trusts in the health service, particularly specified outpatient clinics in district and regional centres. Not every regional cardiac centre requires a full GUCH specialised service since there are too few patients. Complex patients need to be concentrated for expertise, experience, and optimal management. Transition of care from paediatric to adult supervision should be routine, around age 16 years, flexibly managed, smooth, and explained to patient and family. Each patient should be entered into a local database and a national registry needs to be established. The Department of Health should accept responsibility of dissemination of information on special needs of such patients. The GUCH Patients’ Association is active in helping with lifestyle and social problems. Easy access to specialised care for those with complex heart disease is crucial if the nation accepts, as it should, continued medical responsibility to provide optimal medical care for GUCH patients.
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