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Biomedical subjects

G J Morgan

Publications and source records attributed to G J Morgan.

At least 127 records · Page 7Linked to original sources

Detection of the hybrid BCR/ABL messenger RNA in single CFU-GM colonies using the polymerase chain reaction.

In order to study which hemopoietic precursor cells express the hybrid BCR/ABL fusion mRNA we have developed a technique based on the polymerase chain reaction (PCR) for the examination of single hemopoietic colonies grown on semi-solid agar. The technique was developed by examining single CFU-GM colonies grown from newly diagnosed patients with chronic myeloid leukaemia (CML). RNA was isolated from individual 14 day colonies and reverse transcribed to a complementary DNA (cDNA) copy which formed the substrate for a PCR. We have studied 3 cases of CML using this method and have found that 5 out of 5, 9 out of 10 and 20 out of 23 colonies examined were positive. Thus we describe a simple and useful technique for the study of gene expression in a limited number of hemopoietic precursor cells.

Bone Marrow↗

Molecular analysis of a CML patient with a long duration of chronic phase before and after lymphoid blast crisis.

A patient who was diagnosed with chronic myeloid leukemia remained in chronic phase for 14 years before progressing into a lymphoid blast crisis in 1983. The acute phase was successfully treated, and the patient has remained in an indolent chronic phase to date. Cytogenetic and molecular analysis during this second chronic phase confirm the presence of the Philadelphia chromosome and its transcribed BCR-ABL mRNA. The breakpoint within M-bcr occurred in the 3' portion of the region and expressed a hybrid joining the b3 exon of BCR to the a2 exon of ABL.

Blast Crisis↗

Polymerase chain reaction for detection of residual leukaemia.

The occasional finding of cells positive for the Philadelphia (Ph) chromosome months or years after bone-marrow transplantation for chronic myeloid leukaemia raises the possibility that the Ph-positive clone may never be eradicated. The polymerase chain reaction with probes able to detect the transcript of the bcr/abl hybrid gene at very low levels was used to study marrow cells from seven patients in continuing haematological and cytogenetic remission 5-7 years after allogeneic bone-marrow transplantation for chronic myeloid leukaemia. No evidence of the leukaemic mRNA was found. Thus, it seems that all leukaemic cells were eradicated in these patients and that they are truly cured.

Adolescent↗

Molecular biology of the Philadelphia positive leukaemias.

The Philadelphia (Ph) chromosome is a small chromosome 22, which results from a reciprocal translocation between the long arms of chromosome 9 and 22, designated t (9;22) (q34;q11). It was first described in association with chronic myeloid leukaemia (CML), where 90% of cases examined are Ph-positive. A similar cytogenetic abnormality has also been identified in the acute leukaemias but in a much lower percentage. The ubiquitous nature of the translocation in CML suggested that it was causally implicated in the pathogenesis of the disease. Recent work at the molecular level has corroborated this idea. As a consequence of the translocation, the Abelson protooncogene (ABL), located on chromosome 9 is moved to chromosome 22 where it is joined to a truncated gene, known as BCR. The result of this genomic reorganisation is a hybrid gene encoding a novel chimaeric protein product with enhanced protein tyrosine kinase activity. It is thought that it is this activity which is necessary for the generation of the leukaemic phenotype. The t(9;22) has provided a model to illustrate how cellular proto-oncogenes can be activated by chromosomal translocation and has stimulated interest in investigating other chromosomal translocations in human malignancies.

Chromosomes, Human, Pair 22↗

The total cost of care and the use of pharmaceuticals in the management of rheumatoid arthritis: the Medi-Cal program.

Medicaid claims data were analyzed to investigate the prevalence and cost of rheumatoid arthritis (RA) in the Medi-Cal program. It was estimated that approximately 24,000 Medi-Cal recipients receive treatment for RA each year. The sample of Medi-Cal RAs studied averaged more than $2500 annually in total direct health care expenditures. The total cost of RA to Medi-Cal is projected to be $19.26 million (+/- $0.90 million) annually. Inclusion of possible gastrointestinal side effects of drug therapy increases the total cost to $20.49 million (+/- $0.91 million). While only 6.5% of the sample of RAs were hospitalized and 4.9% received nursing home care annually, these services are estimated to account for nearly 70% of RA-related expenditures. Less than 7% of Medi-Cal RAs receive disease modifying antirheumatic drugs (DMARDs). More than 75% of Medi-Cal RAs received aspirin or NSAIDs. These relieve pain and inflammation, but have not been demonstrated to halt the process of joint destruction.

Anti-Inflammatory Agents↗

A cluster of three cases of aplastic anaemia in children.

During a 2-week period three unrelated children presented with severe aplastic anaemia at a general hospital serving a population of 25,000 children aged 0-15 years. The probability of this occurring by chance alone was 0.00009 (exact probability cluster analysis). Serology for common viral infections including hepatitis A & B and infectious mononucleosis was negative. It was not possible to demonstrate IgM antibodies to human parvovirus (HPV) by radioimmunoprecipitation or HPV virions by DNA hybridization in the patients or any members of their families. Epidemiological investigation failed to demonstrate a common environmental toxin. It did reveal, however, that all three patients had spent time, within the preceding 3 months in a swimming pool and its surrounding area in a region of Cardiff where none of them resided. Pool maintenance was satisfactory and water analysis showed no abnormality. The possibility must remain that the cluster was caused by an undisclosed environmental toxin.

Anemia, Aplastic↗

Hypothenar hammer syndrome: an occupational cause of Raynaud's phenomenon.

Hypothenar hammer syndrome is an uncommonly recognized, occupationally associated cause of Raynaud's phenomenon, induced by traumatic compromise of the vascular supply to the hand. Two patients are presented, one with preexisting Raynaud's phenomenon who sought attention after the development of cutaneous ulcers. The features of the syndrome are reviewed, and the importance of its recognition in the appropriate occupational setting as a potentially curable form of Raynaud's phenomenon is emphasized.

Adult↗

Quality of life in patients receiving auranofin therapy: confirmation of efficacy using nontraditional health status measures.

Traditionally, assessment of therapeutic efficacy in patients with rheumatoid arthritis (RA) has been based on objective measurement of disease parameters, such as the number of tender and swollen joints, 10-cm analogue pain scale, or grip strength. More recently, however, it has been realized that these parameters may not provide a true reflection of the impact of disease or therapy on the patient's overall emotional state and ability to function--the "quality of life." Nontraditional measurements of health status have been used by several researchers in order to provide comprehensive data about the benefits of drug therapy. Most recently the Auranofin Cooperating Group conducted a prospective, 6-month, randomized, double-blind, multicenter study that compared auranofin (AF) oral gold with placebo in the treatment of RA. The study was unique in that it assessed the efficacy of AF using a battery of nontraditional health status measures ("quality-of-life" measures) in addition to the traditional parameters used to chart rheumatic disease activity. Composite scores were calculated for 4 distinct dimensions of RA: physical, functional, pain, and global. Pairwise correlations between composite scores ranged from 0.45 to 0.67, indicating that the scores represented different dimensions of the impact of RA. Results indicated that AF effectively improves several dimensions of RA. In addition, it was apparent that several health status measures are sensitive to changes in clinical status. These measures may be useful in future clinical trials of RA, perhaps indicating when DMARD therapy should be initiated. They should also prove useful in drug trials for other diseases.

Arthritis, Rheumatoid↗

Hereditary motor and sensory neuropathy of neuronal type with onset in early childhood.

Eleven cases of a severe neuropathy with onset in early childhood are described. The condition commences with distal weakness and wasting of the lower limbs and subsequently involves the hands, causing severe paralysis of the hands and feet towards the end of the second decade. Sensory changes are common but are usually only mild. The peripheral nerves are not enlarged. Claw hand, scoliosis and other orthopaedic deformities are seen in the later stages. CSF protein is not elevated and there is only mild slowing of motor conduction velocities. The pathological changes in sural nerve biopsies are those of axonal degeneration affecting myelinated and unmyelinated fibres. Family studies suggested autosomal recessive inheritance in two kindreds and dominant inheritance in another. Five cases were sporadic. The condition is clinically more severe and of earlier onset than hereditary motor and sensory neuropathy (HMSN) type II and differs electrophysiologically and pathologically from Déjerine-Sottas disease.

Adolescent↗

Non-giant cell temporal arteritis. Three cases and a review of the literature.

We report two cases of polyarteritis and some of hypersensitivity angiitis diagnosed by temporal artery biopsy. Autopsies showed no evidence of giant cell arteritis. A review of the English literature provides seven further autopsy cases of necrotizing vasculitis diagnosed by temporal artery biopsy. The term temporal arteritis includes many types of vasculitis, giant cell arteritis being one of them.

Diagnosis, Differential↗

Penicillamine-induced myositis in rheumatoid arthritis.

A patient with rheumatoid arthritis who developed multiple mononeuropathies multiplex was shown to have vasculitis in nerve biopsy, but no evidence of inflammatory muscle disease in muscle biopsy. Treatment with penicillamine caused the rare complication of polymyositis, documented clinically, electrophysiologically, and by light and electron microscopy in a second muscle biopsy. The evidence presented supports the concept that penicillamine may induce polymyositis or aggravate a pre-existing low-grade myositis.

Arthritis, Rheumatoid↗

The effect of aerobic exercise on serum creatine kinase activities.

Aerobic exercise is now a common form of recreational exercise among young women. In a previous study, more than a third of a group of young mothers volunteering blood samples to establish a creatine kinase (CK) reference range for Duchenne muscular dystrophy (DMD) carrier detection regularly participated in aerobic exercise programs. Aerobic exercise programs include eccentric exercises. As eccentric exercise is known to produce a delayed CK peak, this study was carried out to determine the effect of aerobic exercise on serum CK activities. The postexercise serum CK activity peak was monitored in 15 young women (age range 20-23 years) following aerobic exercise classes (45 minutes on 3 consecutive days). Peak values at 24-48 hours following the last class ranged from 90 to 3473 U/liter, or 1.55 to 34.71 times resting values. It is concluded that aerobic exercise programs should be excluded in order to obtain accurate resting serum CK values for muscle disease diagnosis.

Creatine Kinase↗