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Biomedical subjects

P J Hallam

Publications and source records attributed to P J Hallam.

7 recordsLinked to original sources
PubMed2003

Analysis of the referral pattern to a supraregional bone and soft tissue tumour service.

AIM: To investigate the sources of delay in diagnosis and determine if there was a similar diagnostic error rate as found by the Musculoskeletal Tumour Society, which subsequently altered patients' management and affected outcome. PATIENTS AND METHODS: A prospective review of 100 consecutive patients referred to our institution analysed causes for delay in referral and whether prior investigations or procedures had complicated further management. RESULTS: Patients were symptomatic for 14.8 months (range, 0-26 months) prior to consultation with their GP. A further 13.5 months (range, 0.5-120 months) elapsed before referral by the local hospital (94) or GP (6) to the bone and soft tissue service. A significant delay in referral of more than a month occurred in 72 patients. Those patients with malignant disease were symptomatic for 7.6 months (range, 0.5-11 months) prior to seeking medical advice with a further 7.5 months (range, 0-13 months) elapsing prior to onward referral at their local hospital. From the study group, 63 patients were subjected to complex imaging studies (bone scan, CT, MRI) prior to referral; 34 biopsies or surgery were performed in 34 cases by referring teams, 16 of which complicated subsequent management. CONCLUSIONS: If a high suspicion of a soft tissue or bone tumour is suspected from the history, examination and plain radiograph, then early referral to a specialist centre is recommended where relevant, high-quality investigations can be arranged in a short time leading to a planned biopsy, confirmation of diagnosis and definitive treatment at an earlier stage.

Adult↗
PubMed1998

Three novel PROC gene lesions causing protein C deficiency.

Missense mutations, three of them novel (Asn210-->Val, Asn248-->Ile, Ala355-->Val), were found in the protein C (PROC) genes of 7 patients with inherited protein C deficiency associated with venous thrombosis. Comparison with the phenotypic effects of mutations in the analogous residues of factor IX causing haemophilia B and the use of molecular modelling has provided explanations as to how these lesions might alter either the structure, function or secretion of the protein C molecules encoded.

DNA Mutational Analysis↗
PubMed1996

Severe perinatal thrombosis in double and triple heterozygous offspring of a family segregating two independent protein S mutations and a protein C mutation.

Molecular genetic and phenotypic analyses were performed in a highly unusual case of combined protein S and protein C deficiency manifesting in a family in which a child had died perinatally from renal vein thrombosis. Antenatal diagnosis in a second pregnancy was initially performed by indirect restriction fragment length polymorphism (RFLP) tracking using a neutral dimorphism within the PROS gene and served to exclude severe protein S deficiency. Am umbilical vein blood sample at 22 weeks gestation showed isolated protein C deficiency. This pregnancy proceeded to a full-term delivery without thrombotic complications. Molecular genetic analysis of the PROC and PROS gene segregating in the family then yielded one PROC gene lesion in the father and two PROS gene lesions, one in each parent. These lesions were shown to segregate with the respective deficiency states through the family pedigree. Analysis of DNA from paraffin-embedded liver tissue taken from the deceased child showed the presence of both PROS mutations, as well as the PROC mutation. Genotypic analysis of the second child showed a PROC mutation, but neither PROS mutation consistent with its possession of normal protein S levels and a low/borderline protein C level. Antenatal diagnosis was then performed in a third pregnancy by direct mutation detection. However, although the fetus carried only the paternal PROS and PROC gene lesions, the child developed renal thrombosis in utero. It may be that a further genetic lesion at a third locus still remains to be defined. Alternatively, the intrauterine development of thrombosis in this infant could have been caused, at least in part by a transplacental thrombotic stimulus arising in the protein S-deficient maternal circulation. This analysis may, therefore, serve as a warning against extrapolating too readily from genotype to phenotype in families with a complex thrombotic disorder.

Female↗
PubMed1995

Population differences in the frequency of the factor V Leiden variant among people with clinically symptomatic protein C deficiency.

The factor V Leiden variant, responsible for the phenomenon of activated protein C resistance, was found to be less frequent among British (0.06) and Swedish/Danish (0.15) protein C deficiency patients than previously reported in a Dutch study (0.19). In the Swedish population, a significantly increased frequency of the factor V Leiden allele was apparent in protein C deficiency patients as compared to healthy controls. However, this was not found in the British population. Coinheritance of the factor V Leiden variant is therefore unlikely to be the sole determinant of whether a person with protein C deficiency will come to clinical attention. Nevertheless, when patient data were analysed by type of protein C deficiency, it was noted that the frequency of the factor V Leiden variant was 2.8-fold higher in type II patients compared to type I patients. A possible explanation of this disparity is discussed.

Alleles↗
PubMed1992

Duplication of part of chromosome 17 is commonly associated with hereditary motor and sensory neuropathy type I (Charcot-Marie-Tooth disease type 1).

Hereditary motor and sensory neuropathy type I (HMSNI), also known as Charcot-Marie-Tooth disease type 1 (CMT1), has been shown to be genetically heterogeneous. A major gene maps to chromosome 17 (CMT1A). A set of loci, D17S122, D17S125, and D17S124, show tight linkage to the CMT1A locus, and a duplication of D17S122 has been detected in some families. We show that the locus D17S122 is duplicated in affected individuals from 7 informative families with HMSNI. The duplication was demonstrated either by differences in hybridization densities between two bands of a restriction fragment length polymorphism or by the presence of all three alleles. No normal individual had the duplication. A single recombinant exists between the MspI polymorphism of D17S122 and the duplicated band, suggesting that the duplication is of considerable size. Patients with HMSN type II do not show the duplication. These findings will have considerable impact on the diagnosis of chronic demyelinating neuropathies, in patients with or without similarly affected relatives.

Charcot-Marie-Tooth Disease↗