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Biomedical subjects

W M Gregory

Publications and source records attributed to W M Gregory.

At least 73 records · Page 4Linked to original sources
PubMed1988

Who should measure quality of life, the doctor or the patient?

The extent to which a doctor or health professional can make a valid assessment of a patient's quality of life, anxiety and depression was investigated in a series of cancer patients. Doctors and patients filled out the same forms, viz. the Karnofsky, Spitzer, Linear Analogue Self Assessment Scales and a series of simple scales designed for this study, at the same time. Correlations between the two sets of scores were poor, suggesting that the doctors could not accurately determine what the patients felt. A further study examining the reproducibility of these scales demonstrated considerable variability in results between different doctors. It is concluded that if a reliable and consistent method of measuring quality of life in cancer patients is required, it must come from the patients themselves and not from their doctors and nurses.

Anxiety Disorders↗
PubMed1988

Prognostic factors for survival in stage IIIB and IV Hodgkin's disease: a multivariate analysis comparing two specialist treatment centres.

A multivariate analysis of prognostic factors was carried out on 301 patients with clinical or pathological stage III/IV Hodgkin's disease treated using the same combination chemotherapy (MVPP) at two centres (Christie Hospital, Manchester, 151 patients, St. Bartholomew's Hospital, London, 150 patients). There were no significant difference in CR or relapse free and overall survival at 5 and 10 years between the two groups. Cox analysis of the Christie data alone produced four significant factors for survival - age, sex, lymphocyte count and stage. The latter three factors showed the same trend for the St. Bartholomew's Hospital patients but failed to reach statistical significance. Analysis of the combined data showed all four factors to be of importance in predicting survival. Three different prognostic groups were identified which separated patients with good, intermediate or poor prognosis in both centres. The good prognostic group included patients aged less than 45 years, lymphocyte count greater than 0.75 x 10(9) l-1 and female patients with stage IIIB disease (5 year survival 85%). The rest were of poorer prognosis with male stage IV patients faring particularly badly (5 year survival 40%). Problems associated with the use of multivariate analysis to produce useful prognostic groupings in patients from different centres, are discussed.

Age Factors↗
PubMed1988

Short-term therapy for acute myelogenous leukemia.

Since 1978, 187 patients (age range, 15 to 59, median 44 years) have received short-term chemotherapy as part of three sequential open studies (B-IX, X, Xb) or a randomized clinical trial (B-XI). An intended six cycles of Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), cytarabine (ara-C), and thioguanine (TG) were administered with as short an intercycle time as possible. No further therapy was administered. Complete remission (CR) was achieved in 118 of 187 patients (63%). On univariate and multivariate analyses achievement of CR correlated adversely with a low serum albumin at presentation and an antecedent marrow disorder. Forty-five patients continue in first remission between 15 months and 8 1/2 years, no relapses being seen after 3 1/2 years (median follow-up, 3 1/2 years). The median duration of remission was 1 year. M3 morphology, a blast count less than 100 x 10(9)/L, and absence of hepatosplenomegaly correlated favorably with remission duration. There was no difference in duration of remission between patients receiving 3, 4, 5, or 6 cycles. The best results overall were achieved in patients under the age of 40, with 43% projected to remain free of disease at 5 years. Fifty patients remain alive between 17 months and 9 years, the predicted actuarial survival being 25% at 5 years.

Actuarial Analysis↗
PubMed1988

A mathematical model of drug resistance applied to treatment for small-cell lung cancer.

A mathematical model has been applied to patients with small-cell lung cancer (SCLC) in order to estimate the proportions of resistant and sensitive tumor at presentation, and the efficacy of the treatment, measured in terms of proportions of tumor killed with each cycle of therapy. The model uses estimates of tumor volume obtained from computed tomographic (CT) scans of the chest before each course of chemotherapy. Application of the model to a trial using single-agent high-dose cyclophosphamide (HDC) showed that HDC killed approximately 94% of the sensitive tumor on each application, but that the proportion of tumor resistant to HDC rose from an average of 1% to an average of 15% after the first cycle, assuming a 30-day tumor doubling time. These estimates proved fairly insensitive to different assumptions about tumor doubling time and inaccuracies in volume measurement and may thus provide a useful additional evaluation technique for some clinical trials.

Carcinoma, Small Cell↗
PubMed1988

In-vivo measurement of spin lattice relaxation time (T1) of bone marrow in healthy volunteers: the effects of age and sex.

Magnetic resonance images of the spine, sternum, femoral heads and upper femoral shafts were obtained from 90 healthy volunteers to determine the normal ranges of spin lattice relaxation time (T1) for different regions of the bone marrow. The influence of age, sex and oral contraceptive usage on bone marrow T1 was assessed. Differences observed between the T1 of the various regions of the bone marrow examined were consistent with the expected distribution of erythropoietic cells and fatty marrow. Bone marrow T1 was found to decrease with age, significantly lower mean T1 values being observed in subjects over 40 years of age than for those in the 20-40 years age group. The mean bone marrow T1 of females in the 20-40 years age group was significantly higher than that for males of comparable age. For subjects over 40 years of age, the difference in bone marrow T1 observed between males and females was not significant. Oral contraceptive usage had no effect on bone marrow T1.

Adult↗
PubMed1988

In-vivo measurement of spin lattice relaxation time (T1) of liver in healthy volunteers: the effects of age, sex and oral contraceptive usage.

Magnetic resonance imaging of 81 healthy adult volunteers has been undertaken to establish the normal range of liver spin lattice relaxation time (T1) at 0.08 tesla. The influence of age, sex and oral contraceptive usage has been assessed. Liver T1 decreased with age. The mean liver T1 of subjects under 40 years of age was significantly longer than that of older subjects. A wider range of T1 values was observed in the younger age group. No difference in T1 was found between males and females who were not oral contraceptive users. The mean liver T1 of females who were taking the pill was significantly longer than that of females of similar age who were not oral contraceptive users. Serial examinations of eight oral contraceptive users showed that mean liver T1 values were significantly longer in the 3 weeks during which they were taking the pill than during the week off the pill.

Adult↗
PubMed1987

The relationship between chronic lymphocytic leukaemia and prolymphocytic leukaemia. IV. Analysis of survival and prognostic features.

The prognostic value of biological, clinical and laboratory features was analysed in a series of 265 patients with chronic lymphocytic leukaemia (CLL) and prolymphocytic leukaemia (PLL). On univariate analysis seven features were shown to influence significantly the survival of the whole group of patients: absolute prolymphocyte count (ABS PROL), percentage of prolymphocytes (%PROL), WBC, spleen size, age, intensity of surface-membrane immunoglobulin (SmIg) and mouse (M) rosettes. Multivariate regression analysis of these features showed that only ABS PROL and spleen size had independent prognostic significance. The survival in PLL (38 cases) was significantly shorter than in CLL (227 cases) (median survival = 3 and 8 years, respectively). Patients with CLL with an increased %PROL (11-55%), defined as CLL/PL, could be divided into two groups: those with ABS PROL less than or equal to 15 X 10(9)/l (26 cases) fell within the 'standard-prognostic risk' for typical CLL (i.e. less than or equal to 10% PROL), whereas the survival outlook for the cases with ABS PROL greater than 15 X 10(9)/l (40 cases) was as bad as for PLL. A scoring system was generated with the four features that showed high prognostic significance: ABS PROL, spleen size, SmIg and M-rosettes. The score proved to be superior to any single feature as a predictor of survival, being especially useful in the analysis of the CLL/PL group: cases with high scores (greater than 2) had a median survival of 2.5 years, while the median has not been reached for those with low scores (less than or equal to 2). We suggest that this scoring system may help to identify the cases of CLL/PL that behave as PLL, and as such may benefit from different treatment.

Humans↗
PubMed1987

Reproducibility of spin lattice relaxation time (T1) measurement using an 0.08 tesla MD 800 magnetic resonance imager.

The reproducibility of T1 measurements using an MD 800 magnetic resonance imager operating at 0.08 T (3.4 MHz) has been assessed by repeated imaging over a 15-week period of a phantom containing six copper-sulphate solutions of different dilutions. The standard pulse sequence of this scanner with an inversion time of 200 ms and a repetition time of 1 s was used. Reproducibility was excellent for the lower T1 range (less than 350 ms), but greater variability was observed at higher T1 values (greater than 490 ms). A linear relationship between T1 and temperature has been demonstrated and a method for standardising T1 values obtained at different temperatures is described.

Magnetic Resonance Spectroscopy↗
PubMed1987

Cross-reactive variable-region associated epitopes of human IgG1 lambda paraprotein detected by a monoclonal antibody panel.

This paper describes the production and characterization of a panel of 15 mouse monoclonal antibodies selected for putative activity against V-region related or allotypic determinants of a single IgG1 lambda paraprotein obtained from a patient with malignant lymphoplasmacytoid lymphoma. The specificity of each reagent for epitopes on the heavy (H) or light (L) chain or for conformational determinants (CD) of the immunogen was determined and the ability of one reagent to compete with another for these sites investigated. The fine specificity of the antibodies was assessed by screening on a large series of normal and paraprotein-containing sera. One monoclonal showed specificity for the Glm(f) allotype. The 14 other reagents identified a minimum of nine different epitopes in the V region of the immunogen, with four antibodies detecting private conformationally determined idiotypic specificities. Eight determinants were V-region markers also expressed on other paraproteins. A total of 30 out of 159 different paraproteins cross-reacted with one or more of the antibodies. Four of the shared epitopes were lambda-chain associated, three were H-chain associated and one was a conformational determinant. Homologies of lambda chain were identified more frequently among other paraproteins than those of H chain. The relationship between epitope expression and H-chain class of paraprotein was not random. The frequency of expression of cross-reactivities in association with IgG1 proteins was always exceeded by higher frequency of epitope expression in association with other classes of H-chain isotype. The potential therapeutic value of such panels of characterized monoclonal reagents is discussed.

Antibodies, Monoclonal↗
PubMed1986

Adult acute lymphoblastic leukaemia: a study of prognostic features and response to treatment over a ten year period.

Between 1974 and 1984 69 adults with acute lymphoblastic leukaemia (ALL) were treated with two different protocols. Fifty-four (78%) of the patients entered complete remission (CR); 27 of these then received a consolidation protocol consisting of daunorubicin, cytosine arabinoside and 6-thioguanine, followed by two courses of intravenous methotrexate 500 mg m-2 with folinic acid rescue. All patients received intrathecal methotrexate and cranial irradiation (24 Gy) followed by maintenance therapy with 6-mercaptopurine and methotrexate for at least 2 years. The median survival for all patients was 23 months from the time of presentation with an actuarial 5-year survival of 21%. The actuarial chance of surviving 5 years in CR for patients receiving the consolidation protocol was 38% compared to 19% for patients receiving no consolidation (P = NS). Only patient age and white cell count at presentation were found to influence the chance of achieving CR and the chance of overall survival. The presence or absence of c-ALL antigen did not influence prognosis. Patients younger than 35 years with low white cell counts at presentation (less than 10 X 10(9)1(-1] had a particularly good prognosis but no patient with T-ALL and no patient older than 50 years old at diagnosis survived more than 18 months.

Adolescent↗
PubMed1986

Treatment of acute lymphoblastic leukaemia in adults.

Between 1972 and 1982, 112 consecutive previously untreated adults (aged 15-69 years, median 26) commenced therapy for acute lymphoblastic leukaemia (ALL) at St Bartholomew's Hospital. The first 63 patients entered into the study received initial treatment which comprised four cycles of adriamycin and vincristine, prednisolone and L-asparaginase with the first cycle (OPAL). In 1978, six cycles were given, with escalating doses of adriamycin and cyclophosphamide from cycle 3 (HEAV'D). Central nervous system (CNS) prophylaxis incorporated intrathecal methotrexate and cytosine arabinoside with cranial irradiation. Maintenance chemotherapy consisted of 6-mercaptopurine, cyclophosphamide and methotrexate for 3 years. Results obtained with the OPAL and HEAV'D regimens were not significantly different. The overall complete remission (CR) rate was 66% (73/111), factors correlating unfavourably with achievement of CR being advanced age (P less than 0.001) and L3 morphology/B-ALL immunophenotype (P less than 0.01). Fifty-three patients have relapsed, the bone marrow being the primary site in 43. Extramedullary relapse alone occurred in 10 (seven CNS, two testicular and one skin). Only three of the 64 patients who had complete CNS prophylaxis subsequently relapsed in the CNS as an isolated site. One patient died in CR, 19 remain in continuous CR between 2.5 and 10.5 years. The median duration of remission of the 73 patients who achieved CR was 18.5 months, factors correlating favourably with duration of CR being low blast cell count at presentation (P less than 0.002) and common ALL immunophenotype (P less than 0.04). Twenty-four patients remain alive, with a median survival of all patients of 18 months. Long-term survival is possible for approximately 20% of adults with ALL treated relatively intensively.

Acute Disease↗
PubMed1986

Follicular lymphoma: prognostic factors for response and survival.

One hundred forty-eight patients with newly diagnosed follicular lymphoma were treated over a 12-year period. Twenty-two patients received radiotherapy for stage I and II disease, followed by adjuvant chemotherapy in 14 patients. One hundred thirteen were treated at presentation with short courses of chemotherapy, most often with single-agent chlorambucil for bulky stage II and stages III and IV disease. Thirteen patients were managed expectantly until there was evidence of disease progression. The median survival was 9 years. Patients treated with radiotherapy for stage I and II disease had an 83% relapse-free survival, but those with bulky stage II or stages III and IV disease treated with chemotherapy pursued a remitting and relapsing course with a 70% response rate at initial and subsequent retreatments, but a median duration of remission of 4 years in stage III and 1 year in stage IV disease (P = .041). Patients were observed in relapse and retreatment was administered as appropriate, once every 33 months on average. Poor prognosis patients could be identified by a combination of the presentation characteristics: B symptoms, hepatosplenomegaly, anemia, and abnormal liver function. These factors predicted a poor response to treatment and correlated with a short survival. Histologic subgroups were not associated with differences in survival, but transformation to a diffuse high-grade lymphoma was observed in 23 of the 72 patients (32%) at risk, with a median follow-up of 6 years and 6 months, and was associated with a very poor prognosis. The present treatment strategy has proved successful for most patients with localized disease and those older patients with indolent small volume disseminated follicular lymphoma. New approaches are being investigated for the younger poor prognosis patients.

Adult↗
PubMed1985

The biological and clinical significance of HCG-containing cells in seminoma.

The morphological appearance, incidence and prognostic significance of human chorionic gonadotrophin (HCG)-containing cells in seminomas were examined in a retrospective series of 228 orchidectomy specimens, obtained between 1958 and 1972. Sections from each tumour were stained with haematoxylin and eosin (H & E) and immunocytochemically for HCG. In 33 (14.5%) of the tumours HCG-containing cells were observed, but in only 12 were these recognised in an initial study of the H & E stained sections. HCG staining was seen predominantly in syncytiotrophoblastic giant cells and rarely in "mulberry" cells and mononuclear seminoma cells. Of the patients whose tumours included HCG-containing cells 23% died of their disease within 2 years of orchidectomy, compared with only 8% of the patients whose tumours lacked this feature. It is concluded that immunocytochemical staining for HCG should form part of the routine histological assessment of seminomas, and that the presence of HCG-containing cells indicates a more aggressive disease.

Adult↗
PubMed1985

High-dose cyclophosphamide in small-cell carcinoma of the lung.

Eighteen patients with untreated small-cell cancer of the lung have been treated with cyclophosphamide 200 mg/kg on two occasions at an interval of four weeks. An additional eight patients received etoposide in addition to cyclophosphamide. Measurements of tumor volume were made by thoracic computed tomographic (CT) scan before and after each cycle. When compared with our previous study in which only one cycle of cyclophosphamide was given, the double procedure did not increase response rate, decrease the incidence of local relapse, or prolong the relapse-free interval. Survival after relapse was shorter with two cycles of chemotherapy mainly due to greater difficulty in administering further chemotherapy. The CT scans showed a decrease in tumor volume from 99.2 cc to 21 cc after the first cycle, but a smaller decrease to 14.1 cc after the second. These results show that the rapid emergence of drug resistance imposes limitations on the use of very high-dose cytotoxic chemotherapy.

Adult↗
PubMed1982

Application of Jackson, Aspden Acute Myeloid Leukaemia model.

The comparison of a series of small clinical trials into the treatment of Acute Myelogenous Leukaemia at St Bartholomew's Hospital, London, is described using a previously published mathematical model. The work demonstrates the value of a coherent presentation and analysis of available information in assisting clinicians in their decision-making.

Clinical Trials as Topic↗
PubMedDate not supplied

Second primary malignant neoplasms in patients treated for Hodgkin's disease at St Bartholomew's Hospital.

The incidence of second malignant neoplasms (SMN's) was investigated in a group of 529 patients with Hodgkin's Disease (HD) treated at St Bartholomew's Hospital (SBH). SMN's were seen in 27 of these patients giving an incidence rate three and a half times that expected in an age and sex matched normal population (p = much less than 0.001). The incidence rate was higher in those receiving multiple chemotherapy and radiotherapy for relapsed HD compared with those receiving primary radiotherapy, chemotherapy or chemotherapy with adjuvant radiotherapy (p = 0.02). However, the increased incidence rate in those patients treated with chemotherapy on relapse, may reflect in part a delayed effect of their primary therapy, since the incidence rate in the primary treatment group only becomes significantly raised after six years. When allowance was made for this delay the difference between the two groups was no longer significant. The incidence rates for Non-Hodgkin's Lymphoma (NHL) and myelogenous leukaemia were 32 and 57 times those expected, compared with only two and a half times the expected rate for non-haematological SMN's (p = much less than 0.001). The four acute myeloid leukaemias (AML) all occurred within five years of treatment compared to wide-ranging intervals between treatment and occurrence of SMN in the other groups. The increased incidence of NHL may be an alternative expression of lymphoid abnormality rather than a treatment-related occurrence. Multiple SMN's were diagnosed in three patients. This represented a highly significant (p = much less than 0.001) increase over the expected incidence of multiple neoplasia in the general population. Several factors may contribute to the development of SMN's in HD, including an inherent disposition of HD itself. The time-dependent incidence pattern of SMN's with a delay followed by an increased incidence rate, suggests that treatment plays a key role. It is not yet clear whether more intensive, or multiple treatments add to the risk accrued for the initial treatment.

Adult↗