Factor X deficiency is a rare haemorrhagic condition, normally inherited as an autosomal recessive trait, in which a variable clinical presentation correlates poorly with laboratory phenotype. The factor X (F10) genes of 14 unrelated individuals with factor X deficiency (12 familial and two sporadic cases) were sequenced yielding a total of 13 novel mutations. Family studies were performed in order to distinguish the contributions of individual mutant F10 alleles to the clinical and laboratory phenotypes. Missense mutations were studied by means of molecular modelling, whereas single basepair substitutions in splice sites and the 5' flanking region were examined by in vitro splicing assay and luciferase reporter gene assay respectively. The deletion allele of a novel hexanucleotide insertion/deletion polymorphism in the F10 gene promoter region was shown by reporter gene assay, to reduce promoter activity by approximately 20%. One family manifesting an autosomal dominant pattern of inheritance possessed three clinically affected members who were heterozygous for a splice-site mutation that was predicted to lead to the production of a truncated protein product. A model which accounts for the dominant negative effect of this lesion is presented. Variation in the antigen level of heterozygous relatives of probands was found to be significantly higher between families than within families, consistent with the view that the nature of the F10 lesion(s) segregating in a given family is a prime determinant of the laboratory phenotype. By contrast, no such relationship could be discerned between laboratory phenotype and polymorphism genotype.

Clonal analysis of lymphocytes from patients with myelodysplastic syndrome (MDS) has been carried out using X-chromosome inactivation patterns detected by the probe M27 beta, and by polymerase chain reaction amplification of the immunoglobulin heavy chain gene hypervariable region, CDR3. Of 32 female patients heterozygous for M27 beta only seven (22%) demonstrate monoclonality of peripheral blood lymphocytes. 12 (37%) give unequivocal polyclonal results and the remaining cases give patterns of X-inactivation which cannot be interpreted either way. A study of 68 MDS patients showed five (7%) with a population of B-cells with a monoclonal rearrangement of CDR3 compared with none out of 60 normal individuals, none out of 15 with B-non Hodgkin lymphoma (B-NHL) in remission and 19 out of 25 (75%) of cases of B-chronic lymphocytic leukaemia (B-CLL). Monoclonal lymphocytes were found by both techniques in only two females with MDS. We conclude that the presence of polyclonal lymphocytes is a common finding in patients with MDS.

The histology, immunophenotype and clinical presentation of 43 cases of T-cell lymphoma are described. Cases were classified into nine types; T-lymphocytic lymphoma (three), mycosis fungoides (six), Sézary syndrome (two), T-zone lymphoma (13), angioimmunoblastic lymphadenopathy (AIL)-like T-cell lymphoma (five), pleomorphic medium cell (one), large cell immunoblastic (four), large cell polylobated (five) and lymphoblastic (four). The patients comprised 26 males and 17 females aged between 15 and 86 years. The majority showed disseminated disease at the time of diagnosis (18 stage IV, nine stage III, five stage II, eight stage I and three cases not staged). Thirty-one patients showed lymph node involvement. Cutaneous involvement was a common finding (18 cases, 10 cases excluding mycosis fungoides and Sézary syndrome). Details of therapy and clinical follow-up were obtained in 37 cases. With simple chemotherapy only one complete response (7%, 1/16) was obtained. With aggressive therapy 48% (13/27) of patients showed complete responses. Twenty patients died during the follow-up period. Life table analysis showed a 58% probability of surviving 1 year and 36% probability of surviving 3 years. There was a significant difference in survival probability between low/intermediate-grade (lymphocytic, Sézary syndrome, mycosis fungoides and T-zone lymphoma including AIL-type) lymphomas and high-grade (large cell immunoblastic and polylobated and lymphoblastic) lymphomas (P less than 0.025). However, when survival of T-zone and AIL-like T-cell lymphoma was compared with survival of large cell immunoblastic and polylobated lymphomas no significant difference was detected. Age (less than 50 years) and stage I or II disease were associated with significantly better survival (P less than 0.005 and P less than 0.05).

Background: Remote and Rural pre-hospital care practitioners manage serious illness and injury on an unplanned basis, necessitating technical and non-technical skills (NTS). However, no behaviour rating systems currently address NTS within these settings. Informed by health psychology theory, a NTS-specific behaviour rating system was developed for use within pre-hospital care training for remote and rural practitioners.Method: The Immediate Medical Care Behaviour Rating System (IMCBRS), was informed by literature, expert advice and review and observation of an Immediate Medical Care (IMC) course. Once developed, the usability and appropriateness of the rating system was tested through observation of candidates' behaviour at IMC courses during simulated scenarios and rating their use of NTS using the IMCBRS.Results and Conclusion: Observation of training confirmed rating system items were demonstrated in 28-62% of scenarios, depending on context. The IMCBRS may thus be a useful addition to training for rural and remote practitioners. Highlights A patient safety behaviour rating system for rural/remote settings was developed.  Testing of the system suggests that its content may be appropriate and observable.  Some elements were more observable, which may affect future work using this system. BackgroundRural/remote practitioners manage serious illness and injury on an infrequent, unplanned basis. Within rural/remote settings the first person at the scene of a medical emergency is often a general practitioner (GP) or practice nurse. Compared to urban or hospital-based settings, those attending an emergency in these settings may be doing so single-handedly or with limited assistance, for considerable time within potentially harsh conditions, prior to an ambulance providing transport to definitive care. Quite often, working in such settings requires decisions to be made based on the distance to hospital and the patient's likelihood of survival. Effective pre-hospital care thus necessitates a high level of non-technical skills (NTS), such as communication and decision-making (1). The importance of NTS within these settings is evident within research which suggests the factors involved in the likelihood of surviving out of hospital cardiac arrest include a witnessed cardiac arrest, provision of bystander CPR, shockable cardiac rhythm and return of spontaneous circulation (ROSC) within the field (2). The tasks involved in this example necessitate communication skills involved in the provision of CPR (e.g. communicating planned actions to others) and decision-making skills (e.g. who should do what) about how to respond to the situation. In order for optimal care to be provided both technical (e.g. providing CPR) and non-technical (e.g. co-ordinating people at the scene of an emergency) skills need to be employed. Consequently, approaches to improving patient safety and clinical outcomes from emergency care should focus not only on clinical skills and operational and service factors, such as ensuring equipment ...