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Biomedical subjects

A A Dawson

Publications and source records attributed to A A Dawson.

At least 19 recordsLinked to original sources
PubMed1996

Multiple myeloma in north east Scotland: a review of incidence and survival over three decades.

STUDY OBJECTIVE: (1) To review the pattern of published world age-standardised registration rates for myeloma (ICD8 and ICD9 203) for the five Scottish regional cancer registries between 1973-77 and 1983-87. (2) To review the patterns of world age-standardised incidence and survival for myeloma in Grampian region over the time period 1960-89. DESIGN: Retrospective analysis of cancer registration data and linked mortality data. SETTING: The five Scottish regional cancer registries (East, North, North East, South East and West Scotland). PATIENTS: Incidence: a total of 405 patients with myeloma resident in Grampian region (153 diagnosed between 1960-69, 252 diagnosed between 1980-89 inclusive). Survival: a total of 420 patients with myeloma treated in Grampian hospitals between 1968 and 1987 inclusive. MEASUREMENTS AND MAIN RESULTS: On average, the world age-standardised registration rates for the five regional registries increased from 2.8 to 3.1 cases per 100,000 in males and from 1.8 to 2.4 per 100,000 in females between 1973-77 and 1983-87. No clearcut pattern in the trends for individual registries was evident for males but, in general, an increasing trend in female rates was observed for the registries with the lowest rates initially, whilst those with the highest initial rates increased only slightly or even fell. After age and sex standardisation, the annual incidence of myeloma in NE Scotland has increased by 20 per cent between 1960-69 and 1980-89, from 2.4 to 2.9 cases per 100,000 population per year with a disproportionate increase in older patients. Between the two time periods female rates remained stable or increased over all age groups while male rates fell for ages under 69 years and rose for ages above this, a pattern which was reflected in changes in the male:female ratio. The five year survival rate for all ages (14%) has not improved since 1968-72 similar to overall Scottish figures. In NE Scotland, younger patients appear to fare better, and older patients worse, compared with the overall Scottish experience. CONCLUSIONS: The increase in myeloma incidence may be due to a combination of improved ascertainment, especially in the elderly and a possible true increase in incidence in females, suggestive of increased exposure to an aetiological agent in the past. A formal year birth cohort analysis is required to confirm this finding. The overall prognosis for myeloma remains poor, especially for elderly patients and efforts to elucidate the aetiology must continue.

Age Distribution↗
PubMed1995

p53 mutation and expression in lymphoma.

Mutation and abnormal expression of p53 was studied in 38 lymphomas [five Hodgkin's disease and 33 non-Hodgkin's lymphoma (NHL)]. CM1 polyclonal antibody was used to detect overexpression of p53. Three missense mutations were characterised in three cases of NHL after screening exons 5-8 of p53 of all the tumours with single-strand conformation polymorphism (SSCP) analysis. Only two out of three tumours with a missense mutation showed abnormal expression of p53 as measured by CM1. Conversely, seven out of nine tumours with positive CM1 staining had no point mutation demonstrated. Overexpression of p53 in the cases of NHL occurred in three out of twenty four low-grade tumours and five out of nine high-grade tumours (Kiel classification). The results suggest that abnormalities of p53 are commoner in high-grade than low-grade NHL, and that positive immunocytochemistry cannot be used to determine which tumours have mutations of p53.

Adult↗
PubMed1995

p53 mutation in the myelodysplastic syndromes.

We have studied point mutations in exons 5-8 of the p53 gene in the myelodysplastic syndromes (MDS) by using polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) analysis and direct nucleotide sequencing. The subtypes examined were: refractory anaemia (RA), refractory anaemia with ring sideroblasts (RARS), chronic myelomonocytic leukaemia (CMML), refractory anaemia with excess blasts (RAEB), refractory anaemia with excess blasts in transformation (RAEBt), and acute myeloid leukaemia (AML) which had evolved from MDS. 26 cases of MDS were studied. 12 of these were sequentially sampled but none changed its p53 status during the time of the study (18 months). Four mutations (one nonsense and three missense) were identified. Each case with a mutation was of an advanced MDS subtype, suggesting that p53 mutation in these diseases is a terminal genetic event in the process of leukaemogenesis. The nonsense mutation inserted a premature stop codon in a case of AML which had evolved from RAEB; this mutation has been reported before in both chronic myeloid leukaemia (CML) and Burkitt's lymphoma. The three missense mutations have not previously been reported in haematological malignancies.

Acute Disease↗
PubMed1995

Evidence for a seasonal variation in the presentation of Hodgkins disease.

An analysis by month of diagnosis was made of 1359 cases of Hodgkins disease (HD) on the Scotland and Newcastle Lymphoma Group (SNLG) registry 1979-1992 to look for evidence of seasonality. A March peak was evident when all cases were analysed (p < 0.01). The histological subtypes nodular sclerosing (NS) and mixed cellularity (MC) showed a similar pattern (p < 0.05) while lymphocyte depleted (LD) and lymphocyte predominant (LP) had no demonstrable seasonal variation. In a breakdown by age and sex there was evidence of seasonality in both sexes but only under the age of 40. This provides further evidence for the heterogeneity of HD and supports the hypothesis that different factors are involved in the aetiology of this condition in younger compared to older patients.

Adolescent↗
PubMed1995

Analysis of MDR1 and MDR3 multidrug resistance gene expression and amplification in consecutive samples in patients with acute leukaemias.

White blood cells from a total of 19 patients diagnosed as having acute lymphoblastic (ALL) or acute myeloid (AML) leukaemia were analysed (36 samples) for amplification and expression of the mdr1 and mdr3 genes. Nine of the patients had samples analysed at presentation and at subsequent stages of the disease (24 samples, including 4 at second relapse). Patients received standard MRC UK Trial remission-induction treatment protocols appropriate to disease and age. No amplification of either the mdr1 or mdr3 gene was found in any of the samples, and neither were mdr3 transcripts detected by dot-blot analysis using gene-specific probes. Transcripts of the mdr1 gene were found in only 2 ALL samples (of 10). However, mdr1 transcripts were detected in all AML patients and there was a significant increase in the transcript levels in these patients who went on to first and second relapse, compared with levels measured at presentation (P < 0.001). The results support the hypothesis that P-glycoprotein-mediated drug resistance may be a significant factor in tumour cell resistance to chemotherapy at relapse following initial induction-remission therapy for acute myeloid leukemia.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1994

Systemic hypertension--an unusual presentation of T-cell lymphoma.

Systemic hypertension is not commonly associated with lymphoid malignancy. We present two patients who had renal involvement with non-Hodgkins lymphoma (NHL) in which systemic hypertension was a major problem on presentation and resolved soon after appropriate chemotherapy.

Adult↗
PubMed1993

Outcome in colorectal adenocarcinoma: two seven-year studies of a population.

OBJECTIVE: To record every patient with proved colorectal adenocarcinoma presenting from a defined population over two years in 1968-9 and during 1980-2, and to compare treatment and outcome over seven years. DESIGN: Retrospective in 1968-9 and prospective in 1980-2. SETTING: Aberdeen general hospitals. SUBJECTS: Every patient presenting to the four general surgical units with histological proof of colorectal adenocarcinoma. MAIN FINDINGS: On average, one new patient presented each week per 100,000 population. The proportion of patients aged 65 and over rose from 67% to 71%. An operation was performed on 385 patients in 1968-9 and on 399 during 1980-2. At laparotomy the proportion of patients who seemed to be curable and had a radical operation rose slightly, from 56% to 61%, and operative mortality fell from 9% to 5%. In all there were 421 survivors of curative surgery, and seven years later three quarters were either alive (51%) or had died without recurrence (25%). In both studies some 40% of patients were considered incurable when they presented, but the number who had a palliative resection rose from 59% to 85%. CONCLUSIONS: The contribution of radical surgery to the treatment of colorectal adenocarcinoma is substantial, with three quarters of patients so treated showing no evidence of recurrence after seven years. Operative mortality in an elderly population is now low, and improvement in late outcome is more likely to come from developments in adjuvant therapy than in operative technique. A continuing problem is that 40% of patients are not curable when they present, although palliative resection can now be offered to over 80%.

Adenocarcinoma↗
PubMed1990

Non-Hodgkins lymphoma of the head and neck: experience in the Grampian area.

The records of 44 cases of non-Hodgkins lymphoma (NHL) presenting to the ear, nose and throat department in the Grampian area from 1980-1988 were examined in relation to site of occurrence, histology, age at presentation, clinical stage, treatment and survival. The median age was 67 years and there was a preponderance of high grade histology, especially in disease affecting the tonsil. Most deaths occurred in the first year; patients with high grade disease and those in stages three and four had a significantly poorer survival during the first year. The site of disease had no influence on survival.

Adolescent↗
PubMed1990

Obscure anaemia and hepatic dysfunction in Castleman's disease.

A case is reported illustrating a rare and puzzling cause of long standing anaemia and abnormal liver function tests. The diagnosis of Castleman's disease came to light only after an adrenal mass was noted during ultrasound examination. Removal of the mass led to a rapid reversal of all the abnormalities.

Adolescent↗
PubMed1989

The bleeding disorder in acute promyelocytic leukaemia: fibrinolysis due to u-PA rather than defibrination.

Three consecutive patients with acute promyelocytic leukaemia who presented with severe haemorrhagic syndromes were studied and the findings contrasted with those of two patients with classical defibrination after electroshock or complicated labour. The leukaemic patients showed no depletion of fibrinogen. There was no evidence of disordered thrombin generation by either intrinsic or extrinsic pathway sufficient to account for their haemorrhage. All, however, showed strikingly enhanced fibrinolytic activity, which could have accounted for bleeding. This fibrinolytic disorder was characterized by free u-PA in the plasma and differed from that seen after classical defibrination, where free t-PA was observed. U-PA was found also in malignant promyelocytes, which may be the source of u-PA activity in the patients' plasma. Bleeding in promyelocytic leukaemia may be primarily a fibrinolytic disorder.

Electrophoresis, Polyacrylamide Gel↗
PubMed1988

Accelerated increase in aortic diameter in patients treated for lymphoma.

Cytotoxic chemotherapeutic agents, particularly the anthracyclines, are known to be cardiotoxic, but toxic effects on the aorta have not previously been documented. In this study, diameters of ascending and descending thoracic aortae were measured by computerized tomography in 69 patients with lymphoma, before and after first-line treatment with one of 7 different regimes. Minor increases in aortic diameter over the study period due to the aging process were expected. These increases were greater than anticipated in both the ascending and the descending aortae after chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and CVP (cyclophosphamide, vincristine, and prednisolone) regimes. Smaller changes, or changes which were not statistically significant, were noted after MVPP (mustine, vinblastine, procarbazine, and prednisolone), ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisolone), ChlVP (chlorambucil, vincristine and prednisolone), mediastinal radiotherapy, and radiotherapy plus MVPP (MVPP/XRT). Cardiovascular damage associated with certain forms of cytotoxic therapy is not confined to the heart, but also affects the aorta.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

The effects of four drug regimens on sister chromatid exchange frequency in patients with lymphomas.

Patients undergoing first-line chemotherapy after diagnosis of lymphoma have considerable DNA damage in their peripheral blood lymphocytes, using sister chromatid exchange (SCE) frequency as a sensitive indicator. Different drug regimens produce different patterns of changes in SCE frequency. These may be related to their potential to induce second malignancies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Methylprednisolone, etoposide, vindesine, and chlorambucil (PEEC) alone or alternating with CHOP as initial or salvage therapy for non-Hodgkin's lymphoma.

A novel cytotoxic drug combination, PEEC, has been tested in the initial or salvage treatment of lymphomas. The PEEC combination alone is active in high grade or intermediate grade NHL with two complete and two partial remissions out of four patients so treated. When combined with standard CHOP therapy using an alternating regime, seven out of 11 patients obtained a complete remission and four partial remission. Ten patients were well, off treatment, beyond one year from presentation. The combination was less impressive, however, as salvage therapy with two partial responses in a heavily pre-treated group of nine patients.

Adult↗