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Biomedical subjects

D Crowther

Publications and source records attributed to D Crowther.

At least 127 records · Page 7Linked to original sources
PubMed1988

The significance of residual mediastinal abnormality on the chest radiograph following treatment for Hodgkin's disease.

The chest radiographs (CXRs) of 110 patients with mediastinal Hodgkin's disease (HD) were reviewed to determine the incidence, degree, and significance of mediastinal abnormalities following treatment. Residual mediastinal abnormalities were defined as either minimal or measurable, and occurred in 64% of all patients at the completion of treatment, but were more common in those with bulky mediastinal disease at presentation (40 of 48, 83%). Fifty-one patients with a mediastinal abnormality at the end of treatment had follow-up films available. Partial or complete regression of the abnormality occurred by 1 year in 30 of these patients (59%). Over a median follow-up of 80.5 months, there were more relapses (13 of 70, 19%) in patients with residual abnormalities following treatment than in those where the mediastinum was considered normal (four of 40, 10%). Measurable abnormality was associated with a higher relapse rate (six of 25, 24%) than minimal abnormality (seven of 45, 16%), but none of these differences were statistically significant. the subsequent relapse rate for patients with persisting abnormality at 1 year was 14%, compared with 17% for patients in whom regression had occurred and 14% in whom the mediastinum had always been considered normal. Considering the whole group, the presence of a mediastinal abnormality following treatment did not predict for relapse, but for the 34 patients treated by chemotherapy (CTR) alone, a residual abnormality was associated with a significantly higher relapse rate (P = .029). We conclude that following mediastinal radiotherapy (XRT) administered either alone or combined with CTR, residual mediastinal abnormalities do not indicate the need for further treatment. However, following CTR alone, such abnormalities may signify persisting disease and we recommend that XRT be considered for these patients.

Adolescent↗
PubMed1988

Phase I/II study of recombinant human granulocyte colony-stimulating factor in patients receiving intensive chemotherapy for small cell lung cancer.

Twelve patients with advanced small cell carcinoma of the bronchus were treated by continuous infusion of recombinant human granulocyte colony-stimulating factor (rh G-CSF) at the following dose levels: 1 microgram, 5 micrograms, 10 micrograms, 20 micrograms and 40 micrograms/kg/day for 5 days. No toxicities resulted from the treatment and in all 12 patients the number of peripheral neutrophils increased rapidly to a maximum of 100 x 10(9)/l in one patient at 10 micrograms/kg/day. The neutrophils were shown to be functionally normal in tests of their mobility and bactericidal activity. During the Phase II part of the patients were treated using a combination of i.v. Adriamycin, Ifosfamide and Etoposide. The chemotherapy was repeated every 3 weeks. rh G-CSF was given to each patient for 14 days on alternate cycles of chemotherapy and reduced the period of absolute neutropenia considerably (median of 80%), with a return to normal, or above normal, neutrophil counts within 2 weeks after day 1 of chemotherapy. Ten severe infective episodes were observed during the 20 cycles of chemotherapy which did not include rh G-CSF, while only one infective episode occurred in 20 courses when treated with rh G-CSF. These results demonstrate the utility of rh G-CSF in restoring functional neutrophils to patients undergoing intensive chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Phase I study of recombinant DNA granulocyte macrophage colony stimulating factor.

In this Phase I study of rh GM-CSF three patients have been entered at each of the following dose levels--0.3, 1, 3, 10 and 30 micrograms/kg/day. The mean total white cell count (x 10(9)/l) over the first ten days of rh GM-CSF rose from 11 to 14 at 3 micrograms/kg, 8 to 23 at 10 micrograms/kg and 7 to 27 at 30 micrograms/kg. Side effects included transient pyrexias after the first two infusions of rh GM-CSF and bone pains which were severe and required analgesia in two patients receiving 30 micrograms/kg and one receiving 10 micrograms/kg. No neutralizing antibodies to rh GM-CSF have been detected in the six patients tested to date. Patients are now being studied at 60 micrograms/kg/day.

Colony-Stimulating Factors↗
PubMed1988

The behavior of autologous indium-114m-labeled lymphocytes in patients with lymphoid cell malignancy.

It has been shown that radioactive material can be localized to lymphocyte traffic areas using radiolabeled autologous lymphocytes and that 114mIn deposited in such a way in rats produces a lymphopoenia by establishing a selective internal irradiation of circulating lymphocytes. The study reported here was undertaken to investigate the feasibility of using this technique in patients with lymphoid cell malignancy. Up to 22.7 MBq was administered to seven patients with active non-Hodgkin's lymphoma involving the spleen and the behavior of the radioactive material was followed over subsequent months. Estimates of the activity in peripheral blood, bone marrow, excreta samples, and of the variation in the whole-body distribution were obtained. The administered radioactive material cleared rapidly from the blood, 85% being removed within the first 30 min. There was an almost immediate uptake of most of this by the spleen and liver with less than 5% of administered activity accumulating in the bone marrow. After 48 hr, the whole-body distribution changed only slowly and there was a regular decrease of the activity in the spleen. Excretion of radioactive material occurred via both the urine and feces and amounted to less than 1% of administered activity per day. This pharmacokinetic data was used to calculate radiation absorbed doses to various organs for a standard man. It is concluded that this represents a feasible technique for the targeting of radioactive material for the treatment of lymphoid malignancy.

Adult↗
PubMed1987

Psychological problems associated with diagnosis and treatment of lymphomas. I: Retrospective study.

Patients treated for Hodgkin's disease and non-Hodgkin's lymphoma have a better prognosis than other patients with cancer so may have a lower prevalence of psychological and social morbidity. Trained interviewers used standardised methods to assess 90 patients at a mean of 32 months after the diagnosis of Hodgkin's disease or non-Hodgkin's lymphoma. Chemotherapy and radiotherapy had commonly caused adverse effects including hair loss, vomiting, nausea, and loss of appetite. Although most patients were free of disease and not receiving treatment at follow up, some still suffered from a lack of energy (31 patients), loss of libido (19), irritability (22), and tiredness (19); 30 patients complained of continued impairment of thinking or disturbance of short term memory. After diagnosis 21 patients had suffered from an anxiety state or depressive illness, or both, while 27 had experienced borderline anxiety or depression, or both. Mood disturbance was positively correlated with adverse effects of treatment, particularly those affecting the gastrointestinal tract. Social adjustment was less affected, but failure to return to work, or a long delay in returning to work, and a persistent lack of interest in leisure activities gave cause for concern. These findings of substantial psychiatric and social morbidity in patients with Hodgkin's disease and non-Hodgkin's lymphoma prompted a prospective study of these patients to determine their nature and duration.

Adolescent↗
PubMed1987

Psychological problems associated with diagnosis and treatment of lymphomas. II: Prospective study.

A prospective study of 120 patients newly diagnosed as having Hodgkin's disease and non-Hodgkin's lymphoma was conducted to determine the nature, extent, and timing of the psychiatric and social morbidity associated with the diagnosis and treatment. Patients were interviewed at diagnosis and two, six, and 12 months later by trained interviewers using standardised questionnaires. Psychiatric morbidity was greatest in the three months before treatment, but new episodes of anxiety and depression developed throughout the year of follow up. Altogether 39 patients suffered a depressive illness or anxiety state, or both, and a further 37 experienced borderline anxiety or depression, or both, during the 15 months of assessment. The most common adverse effects of treatment were hair loss, nausea, vomiting, sore mouth, and changes in perception of taste. Toxicity of treatment was associated with psychiatric morbidity. Conditioned responses to chemotherapy were experienced by 32 patients. Social morbidity was low, although difficulties in returning to work and to previous levels of leisure activity were noted. Although most patients were no longer receiving treatment and were free of disease at the one year follow up, 51 patients continued to complain of loss of energy, 24 of loss of libido, 38 of tiredness, 23 of irritability, 18 of poor concentration, and 23 of memory impairment. These results confirm our retrospective study and suggest that a high price is paid for long term survival by a substantial proportion of patients receiving treatment for Hodgkin's disease and non-Hodgkin's lymphoma.

Adult↗
PubMed1987

A phase I study of recombinant interferon gamma administered by s.c. injection three times per week in patients with solid tumours.

Human recombinant DNA interferon gamma (IFN-G), with a specific activity of 2 X 10(6) IU/mg protein, was administered s.c. 3 days per week for 2 months to patients with solid tumors. The maximum tolerated dose (MTD) was 10 X 10(6) IU/m2 (5.0 mg/m2) per injection, and six patients were treated at the MTD. Two of these ceased treatment because of severe subjective toxicity (headache, rigors and pyrexia) and three patients developed WHO grade 3 leucopenia. Subjective toxicity varied considerably between patients and some patients at low dose levels experienced severe constitutional symptoms whilst others treated at the MTD had few side effects. These differences were unrelated to pharmacokinetic parameters. Bioavailability of this IFN-G administered s.c. was very variable from one patient to another at the same dose level. We therefore counsel caution in using this IFN-G preparation s.c. in phase II studies.

Adult↗
PubMed1987

A randomized trial of two types of adjuvant chemotherapy in radiotherapy-treated patients with clinical stages I and II high-grade non-Hodgkin's lymphoma.

This paper reports the 8-year results of comparing the use of two types of adjuvant chemotherapy following involved field radiotherapy for clinical stages I and II high-grade non-Hodgkin's lymphoma. Twenty-four patients received 6 weeks of VAP plus 2 years of oral maintenance chemotherapy, and 30 had six cycles of CMOPP. Four patients were not in complete remission at completion of i.v. chemotherapy (CR rate 91%). Ten patients (18.5%) have relapsed (VAP/M = 5; CMOPP = 5), with only two of these remaining alive, both of them being disease free. There have been three deaths from intercurrent causes, one from malignant melanoma and the other two from myocardial infarction. The relapse-free survivals at 2, 5 and 8 years were 80%, 76% & 76% respectively. The overall survivals at the same time points were 86%, 72% & 68%. There were no significant differences in either relapse-free or overall survival for either of the two treatment groups. The shorter period of weekly intravenous chemotherapy (VAP/M) was better tolerated than 36 weeks of CMOPP, and the former appears to produce equivalent results.

Adolescent↗
PubMed1987

Failure to preserve fertility in patients with Hodgkin's disease.

The hypothesis that the "down-regulated" gonad is less vulnerable to the effects of cytotoxic chemotherapy for advanced Hodgkin's disease has been investigated. Thirty men and eighteen women were randomly allocated to receive an agonist analogue of gonadotrophin-releasing hormone prior to, and for the duration of, cytotoxic chemotherapy. Buserelin (d-Ser-[TBU]6 LHRH ethylamide) was prescribed in two different dosage schedules to twenty men, and in a single dosage schedule to eight women. A standard gonadotrophin-releasing hormone test (GnRH 100 micrograms) was performed 1 week prior to and on day 1 of each cycle of chemotherapy. In all patients peak luteinizing hormone responses to GnRH were suppressed throughout treatment. The higher of the two dosage schedules used in the men caused more effective suppression of luteinizing hormone, and both regimens led to an initial suppression of peak follicle-stimulating hormone responses to GnRH, which was not maintained. At follow-up assessment up to 3 years from the completion of treatment, all men treated with buserelin were profoundly oligospermic and four of the eight women were amenorrhoeic. All ten male controls were profoundly oligospermic, and six of nine female controls were amenorrhoeic. In the dosages and schedules investigated, buserelin was ineffective in conserving fertility.

Amenorrhea↗
PubMed1987

Phase I/II study of recombinant human granulocyte colony-stimulating factor in patients receiving intensive chemotherapy for small cell lung cancer.

Twelve patients with advanced small cell carcinoma of the bronchus were treated by continuous infusion of recombinant human granulocyte colony-stimulating factor (rhG-CSF) at the following dose levels: 1 microgram, 5 micrograms, 10 micrograms, 20 micrograms and 40 micrograms kg-1 day-1 for 5 days. No toxicities resulted from the treatment and in all 12 patients the number of peripheral neutrophils increased rapidly to a maximum of 100 x 10(9) l-1 at 10 micrograms kg-1 day-1. The neutrophils were shown to be functionally normal in tests of their mobility and bactericidal activity. During the phase II part of the study the patients were treated by a combination of intravenous adriamycin 50 mg m-2, ifosfamide 5 g m-2 by i.v. infusion with mesna 8 g m-2 on day 1, and etoposide 120 mg m-2 on days 1, 2 and 3 also intravenously. The chemotherapy regime was repeated every 3 weeks. RhG-CSF was given to each patient for 14 days on alternate cycles of chemotherapy and reduced the period of absolute neutropenia considerably (median of 80%), with a return to normal, or above normal, neutrophil counts within 2 weeks after day 1 of chemotherapy. Six severe infective episodes were observed during the cycles of chemotherapy which did not include rhG-CSF, while no infective episodes occurred when patients were treated with rhG-CSF. These results demonstrate the utility of rhG-CSF in restoring functional neutrophils to patients undergoing intensive chemotherapy.

Aged↗
PubMed1987

Migration of leukaemic lymphocytes (chronic lymphocytic leukaemia) through a 3-D collagen gel: a possible prognostic factor.

Migratory properties of malignant lymphocytes in 27 patients with chronic lymphocytic leukaemia (CLL) were investigated using 3-D collagen gel. There was significant impairment of migration in malignant lymphocytes as compared with normal lymphocytes. Moreover there was an inverse correlation between Rai's staging and the migration index. Patients with progression of disease also showed a decrease in migration index. There was no correlation between kappa and lambda type in terms of migration index. The prognostic significance of the migratory properties of malignant lymphocytes is also discussed.

B-Lymphocytes↗
PubMed1987

Hypothesis: persistent expression of fetal phenotypic characteristics by fibroblasts is associated with an increased susceptibility to neoplastic disease.

Published data from our own and other laboratories have indicated that fibroblasts obtained from patients with different types of epithelial cancers commonly display aberrant (i.e. fetal-like or transformed) phenotypic characteristics. Previous interpretations of these results have tended to regard the study of fibroblasts as a convenient means to demonstrate genetic abnormalities also expressed in the target epithelial cell population and did not ascribe a particular causative role to fibroblast abnormalities in the genesis of neoplastic lesions. In this communication we present an alternative, but not mutually exclusive, hypothesis suggesting that aberrations expressed solely by fibroblasts may lead to the development of an epithelial tumour by virtue of a dysfunction in normal epithelial-mesenchymal interactions.

Disease Susceptibility↗
PubMed1987

Phase I clinical trial of methylene dimethane sulfonate.

Methylene dimethane sulfonate is the first member of the homologous series of straight-chain diol sulfonates. It was selected for phase I testing because of high activity in the rat Yoshida sarcoma system and a possible novel site of alkylation due to its small molecular size. Methylene dimethane sulfonate was administered as a rapid iv bolus infusion to 39 patients at doses ranging from 14 to 225 mg/m2. Nausea and vomiting were not severe but total alopecia occurred in the majority of patients at doses greater than 100 mg/m2. The dose-limiting toxic effect was thrombocytopenia, which was cumulative with lower, more prolonged nadirs following successive courses. The median time to platelet count nadir was 21 days, with recovery by 35 days. A minor response was seen in one patient with an adenocarcinoma of the lung. The recommended dose for phase II studies is 125 mg/m2 for patients who have received prior chemotherapy and 150 mg/m2 for those who have not, in an every 35-day schedule.

Adult↗
PubMed1986

Occurrence of a fetal fibroblast phenotype in familial breast cancer.

We have previously shown that fetal and adult human skin fibroblasts display distinctive migratory phenotypes when cultured on 3-dimensional collagen gels in vitro. In the present study, we have used this information to assess the migratory behavior of fibroblasts obtained from patients with either benign or malignant breast disease, and correlated this with the presence of a family history of breast cancer. We have observed that fibroblasts from 17/34 patients with no previous family history of breast cancer displayed fetal-type behavior in our assay system; in contrast, fibroblasts from 15/16 patients with a positive family history of breast cancer behaved abnormally. This apparently increased probability of expressing a fetal-type migratory phenotype in the patients with a family history is statistically significant (p less than 0.008). Skin fibroblasts obtained from 2 healthy and unaffected first-degree relatives (one male and one female) of patients with a family history of breast cancer also exhibited a fetal-type migratory phenotype.

Breast Diseases↗
PubMed1986

A phase II study of human rDNA alpha-2 interferon in patients with low grade non-Hodgkin's lymphoma.

Thirty-five patients with a diagnosis of non-Hodgkin's lymphoma of low histological grade were treated with 2 X 10(6)/m2 of human rDNA alpha 2 IFN-a2 by subcutaneous injection. Treatment was continued until progressive disease was documented or one year of therapy had been given. None of the patients had to stop treatment because of toxicity and no treatment delays or suspensions of therapy were necessary as a consequence of myelosuppression. Thirty four patients were evaluable and seventeen (50%) obtained an objective response (2 CR, 15 PR) with a median duration of eleven months. Sixteen patients were untreated prior to receiving interferon but were felt to need some form of therapy rather than be suitable for a watch policy. Eleven of these patients responded (69%) with 95% confidence limits lying between 41% and 89%. No other pretreatment factors appeared to affect the likelihood of response. Single agent IFN-alpha 2 has significant activity in the low grade non-Hodgkin's lymphomata and warrants further investigation in this disease.

Aged↗
PubMed1985

In vivo distribution studies of radioactively labelled platinum complexes; cis-dichlorodiammine platinum(II), cis-trans-dichlorodihydroxy-bis-(isopropylamine) platinum(IV), cis-dichloro-bis-cyclopropylamine platinum(II), and cis-diammine 1,1-cyclobutanedicarboxylate platinum(II) in patients with malignant disease, using a gamma camera.

The in vivo distribution in man of the four platinum derivatives cis-dichlorodiammine platinum(II) (DDP), cis-trans-dichlorodihydroxy-bis-(isopropylamine) platinum (IV) (CHIP), cis-dichloro-bis-cyclopropylamine platinum(II) (CP), and cis-diammine 1, 1-cyclobutanedicarboxylate platinum(II) (CBDCA) has been observed. The availability of these compounds labelled with the radioactive isotope of platinum, platinum-191, has made serial in vivo imaging of their distribution possible. Injection of 17-35 MBq (5-28 mg) of the labelled compound IV was followed by imaging, using a gamma camera, with particular reference to the kidneys, liver, and tumour site. Hepatic and renal clearances were observed in all nine patients, but no unequivocal evidence of tumour uptake was found. The left kidney uptake was estimated at times up to 7 days after injection. Mathematical analysis of some of the uptake curves failed to show any significant difference between the clearance times observed. However, the two patients who received CBDCA did show a higher initial renal uptake, falling within the 1st day to levels comparable with those of the other compounds, and the three patients who received DDP showed consistently liver uptake.

Adult↗