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Biomedical subjects

A Barrett

Publications and source records attributed to A Barrett.

At least 109 records · Page 6Linked to original sources
PubMed1983

Lung function after bone marrow grafting.

Results of a prospective lung function study are presented for 48 patients with acute myeloid leukemia (AML) treated with total body irradiation (TBI) and bone marrow transplantation (BMT) at the Royal Marsden Hospital between 1978 and 1980. Patients with active disease or who were in remission following cytoreductive chemotherapy had mildly impaired gas exchange prior to grafting. After TBI and BMT all patients studied developed progressive deterioration of lung function during the first 100 days, although these changes were subclinical. Infection and graft-versus-host disease (GvHD) were associated with further worsening of restrictive ventilatory defects and diffusing capacity (DLCO). Beyond 100 days, ventilatory ability returned to normal and gas transfer improved, although it failed to reach pre-transplant levels. There was no evidence of progressive pulmonary fibrosis during the first year after grafting.

Adolescent↗
PubMed1983

Interstitial pneumonitis following bone marrow transplantation after low dose rate total body irradiation.

Idiopathic and infective interstitial pneumonitis (IPn) is a common complication after bone marrow transplantation (BMT) in many centers and carries a high mortality. We report here a series of 107 patients with acute leukemia grafted at the Royal Marsden Hospital in which only 11 (10.3%) developed IPn and only 5 died (5%). Only one case of idiopathic IPn was seen. Factors which may account for this low incidence are discussed. Sixty of 107 patients were transplanted in first remission of acute myeloid leukemia (AML) and were therefore in good general condition. Lung radiation doses were carefully monitored and doses of 10.5 Gy were not exceeded except in a group of 16 patients in whom a study of escalating doses of TBI (up to 13 Gy) was undertaken. The dose rate used for total body irradiation (TBI) was lower than that used in other centers and as demonstrated elsewhere by ourselves and others, reduction of dose rate to less than 0.05 Gy/min may be expected to lead to substantial reduction in lung damage. Threshold doses of approximately 8 Gy for IPn have been reported, but within the dose range of 8 to 10.5 Gy we suggest that dose rate may significantly affect the incidence. Data so far available suggest a true improvement in therapeutic ratio for low dose rate single fraction TBI compared with high dose rate.

Acute Disease↗
PubMed1983

The treatment of metastatic germ-cell testicular tumours with bleomycin, etoposide and cis-platin (BEP).

Between July 1979 and December 1981, 43 patients with metastatic germ-cell tumours (36 testicular non-seminomas and 7 testicular seminomas) were treated with 2-6 cycles of bleomycin, etoposide and cis-platin (BEP). Forty (93%) are alive, 37 (86%) with no evidence of disease. Of 36 men with testicular non-seminoma 30 (83.3%) are alive and disease-free at 8-38 months (median 17.0 months). In the latter group 25/28 (89.3%) who had had no prior irradiation are alive and disease-free. Fourteen non-seminoma patients had small volume metastases and 13 are in complete remission, as are 12/14 patients with bulky disease. All 7 patients with advanced seminoma are alive and disease-free. It is concluded that BEP is a well tolerated and effective first line treatment for patients with metastatic germ-cell tumours.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Chemotherapy of primary (in situ) testicular tumours: response in advanced metastatic disease.

Five patients in whom primary testicular tumours were left in situ during chemotherapy for extensive metastatic disease are described. In four patients, the response of the primary and secondary tumour was comparable. In the fifth a small tumour in the testis became palpable during chemotherapy at the same time as metastases, and regressed on treatment. One possible explanation for the latter observation is protection from chemotherapy of a small, possibly partly intratubular primary, by the blood-testis barrier.

Abdomen↗
PubMed1983

Orchiectomy alone for Stage I testicular non-seminoma. A progress report on the Royal Marsden Hospital study.

Eighty-four patients with clinical Stage I non-seminomatous germ-cell testicular tumours were entered into a prospective study after orchiectomy to evaluate a policy of close surveillance without lymph node irradiation or node dissection; 16 (19%) have manifested evidence of metastatic disease and received chemotherapy. All patients in the study are alive, 3 of the 16 relapsing patients are receiving chemotherapy and the 13 who have completed it are in complete remission at 4 to 43 months (mean 21). Relapses were diagnosed at 2 to 8 months (mean 5.3 months) after orchiectomy and were not invariably associated with elevated serum markers. The relapse rate was significantly higher for malignant teratoma undifferentiated (MTU) primary tumours than malignant teratoma intermediate (MTI) (40.7 and 6.8% respectively) and preliminary data suggest that the association of MTU with vascular invasion places the patient at high risk of relapse. Pre-orchiectomy serum marker status was not a significant prognostic factor. Despite sub-optimal surgical management in 11/84 patients no example of scrotal recurrence has been encountered. It is concluded that a rigorously monitored policy of close surveillance after orchiectomy is a feasible and successful method of management in Stage I testicular non-seminoma. Further experience should allow patients requiring immediate post-orchiectomy chemotherapy to be identified.

Castration↗
PubMed1983

Semen analysis in testicular cancer and Hodgkin's disease: pre- and post-treatment findings and implications for cryopreservation.

Over a 7-year period, seminal analysis has been performed on 208 patients with testicular tumours, after orchiectomy, but before any other treatment. Only 22% of 54 patients with seminomas, and 29% of 154 patients with teratomas or mixed tumours, had sperm counts exceeding 10 million per ml. Very low sperm counts were observed in some patients who had previously fathered children. Post-treatment sperm counts were done in 117 patients, 80 of whom had received multiple drug chemotherapy: 42 of these men had pre- and post-treatment sperm counts. Overall, 24% of men receiving chemotherapy recovered sperm counts greater than 10 million per ml up to 3 years after therapy. Surprisingly, such recovery was seen in 35% of 23 men with initially poor sperm counts, but in only 26% of 19 with good initial counts. Only 27% of 49 patients with Hodgkin's disease had initial sperm counts of more than 10 million per ml; after chemotherapy only 1 of 29 patients recovered to this level. Only one quarter of these young men had semen which was adequate for cryopreservation. Artificial insemination with semen preserved in liquid nitrogen has been performed in 15 couples: 2 normal babies have been produced and a third pregnancy is progressing normally.

Dysgerminoma↗
PubMed1983

Effect of methylazoxymethanol acetate on rat liver nuclear and nucleolar RNA synthesis.

The effect of methylazoxymethanol acetate on rat liver nuclear and nucleolar RNA synthesis is investigated at various doses (5 to 50 mg/100 g body weight) and for various lengths of time (1 to 24 hr). The results show that this carcinogen is a potent inhibitor of both nuclear and nucleolar RNA synthesis. Like other carcinogens studied previously in this laboratory, e.g., N-hydroxy-2-acetylaminofluorene, aflatoxin B1, and actinomycin D, methylazoxymethanol acetate inhibits RNA synthesis at multiple sites. It impairs chromatin template function and selectively inhibits the activity of RNA polymerase II. Experimental evidence suggests the mechanism of inhibition of RNA polymerase II activity is due to a decrease in catalytic efficiency rather than in the total number of the enzyme. In addition, it is found that methylazoxymethanol acetate induces a dramatic condensation of nucleoplasmic chromatin.

Animals↗
PubMed1982

The management of metastatic seminoma testis.

Clinical details of 85 men presenting with previously untreated metastatic seminoma are presented. In Stage II disease relapse rate was related to the size of metastases. In IIA (32 patients) the relapse rate was 9.4%; IIB (11 patients), 18.2%; and IIC (23 patients), 39.1%. The continuous disease-free survival rate was significantly worse for IIC than IIA and IIB patients (P = 0.023). No instance of first relapse in supradiaphragmatic nodes was observed in 13 men with Stage II disease treated with irradiation limited to infradiaphragmatic nodes. In relapsing Stage IIC patients, extralymphatic metastasis was as frequent as abdominal relapse. On the basis of these observations, together with preliminary data in nine men receiving Cis-platinum-containing chemotherapy, all of whom are in complete remission, it is proposed that patients with Stage IIA and IIB disease should receive infradiaphragmatic irradiation with chemotherapy deferred until relapse. Stage IIC patients should receive chemotherapy initially, followed by irradiation. In Stage III and IV disease chemotherapy should be initial therapy with radiotherapy for bulky disease on an individualised basis. Moderate elevation of blood B-HCG levels is not inconsistent with a diagnosis of pure seminoma and does not appear to influence adversely the outcome of radiotherapy.

Antineoplastic Agents↗
PubMed1982

Orchidectomy alone in testicular stage I non-seminomatous germ-cell tumours.

53 patients with clinical stage I non-seminomatous germ-cell testicular tumours were entered into a prospective study to receive no treatment other than orchidectomy until unequivocal clinical evidence of metastases was established. Of this group, 9 men (17%) have relapsed, 8 within six months of orchidectomy. All 9 are alive and disease-free after chemotherapy. The relapse rate was higher in patients with malignant teratoma undifferentiated (embryonal carcinoma) primary tumours than in those with malignant teratoma intermediate (teratocarcinoma); 42.8 and 3.4%, respectively. The results were compared with those from 157 men treated by orchidectomy and radiotherapy for stage I disease. In this group, 49 patients (25.8%) relapsed and 85% of relapses occurred within one year of orchidectomy. The tempo relapse was identical for embryonal carcinoma and teratocarcinoma. Of 32 patients in whom serum markers were measured before orchidectomy, 24 (75%) had raised levels of alphafetoprotein and/or beta human chorionic gonadotropin. These preliminary results imply that routine lymphadenectomy or lymph node irradiation in clinical state I testicular non-seminoma may be unjustifiable.

Dysgerminoma↗
PubMed1982

Changes in serum amylase and its isoenzymes after whole body irradiation.

A study was carried out to assess the effect of total body irradiation on pancreatic and parotid isoenzymes of amylase in patients about to undergo bone-marrow transplantation who had received high-dose cyclophosphamide. Twelve patients were studied, enzyme activity being measured before and at various times after total body irradiation. Serum total amylase activity rose rapidly within 12 hours of irradiation to a maximum at 36 hours, returning to normal by six days; most of the increase was derived from salivary damage, with a much smaller pancreatic component. These results confirm that radiation produces acute changes in amylase activity, which may be of use in assessing radiation-induced damage.

Amylases↗
PubMed1982

Etoposide as a single agent in relapsed advanced lymphomas. A phase II study.

Twenty-three patients with relapsed lymphomas resistant to standard chemotherapy, 13 with Hodgkin's disease and 10 with non-Hodgkin's lymphomas, were treated with etoposide 120 mg/m2 i.v. daily for 5 days or orally for 7-10 days, repeated 3-weekly. This is a higher dose than has been used previously to treat these tumours. Objective responses were seen in eight of 13 (61%) patients with Hodgkin's disease (three CR, five PR) and in three of 10 (30%) patients with non-Hodgkin's lymphomas (three PR). The response rates for Hodgkin's disease are higher than those previously reported and are probably due to the greater dose of drug than has been previously employed. The dose-limiting toxicity was haematological, with gastro-intestinal toxicity occurring in the minority of patients only. It is concluded that etoposide has significant activity particularly in Hodgkin's disease. Its use in drug combinations should now be assessed.

Adult↗
PubMed1982

Evidence for the transcription os physiologically inactive rat-liver nucleolar chromatin by Escherichia coli RNA polymerase.

Rat-liver nucleoli (10-15 micrograms DNA) were digested with either 0.6 or 3 units of DNase I for various times (up to 1 h). RNA synthesis was then measured in the absence or presence of 3 units of Escherichia coli RNA polymerase. It was found that the nucleolar chromatin supporting the endogenous engaged RNA polymerase I transcription was completely destroyed in 3 min with either concentration of DNase I. The nucleolar chromatin template transcribed by E. coli RNA polymerase retained 50% of its original capacity even 60 min after 3 units of DNase I digestion. When hybridization experiments were conducted, it was found that the DNAs derived from both levels of DNase-I-digested nucleoli were incapable of forming hybrids with the labelled nucleolar RNA synthesized by the engaged RNA polymerase I from the untreated nucleoli. Since the engaged RNA polymerase I transcribes only the physiologically active genes of the nucleolar chromatin, and the RNA transcripts represent active gene product, these data suggest that DNase I digestion has completely destroyed the active genes of the nucleolar chromatin, and E. coli RNA polymerase is able to transcribe the inactive nucleolar chromatin template.

Animals↗
PubMed1982

Total body irradiation before bone marrow transplantation: a review.

An increasing number of centres are undertaking BMT and many different techniques are being evolved for TBI. The critical factors to be considered are total dose and dose rate. Conventional single treatments of 1000 cGy (rad) at low dose rates are effective and safe, but alternative fractionated regimes being explored. As few groups treat enough patients to be able to conduct a randomised study, careful and standardised recording of technique and doses given will be important in determining optimum ways of delivering TBI.

Adult↗
PubMed1982

Five years' experience with ChlVPP: effective low-toxicity combination chemotherapy for Hodgkin's disease.

Since 1975, 191 patients with Hodgkin's disease have been treated with a combination of chlorambucil, vinblastine, procarbazine and prednisolone (ChlVPP). Complete remission rates were 73% for previously untreated patients, 91% for patients previously treated with radiotherapy and 55% for patients previously treated with chemotherapy. In 59 patients with advanced disease who received no other treatment, a 5-year survival rate of 66% was comparable with that achieved by more toxic mustine-containing combinations. ChlVPP has few side effects, is easily given to outpatients, and can be combined with elective radiotherapy in selected patients.

Adolescent↗
PubMed1982

Dose-rate dependence of lung damage after total body irradiation in mice.

Idiopathic pneumonitis is a major cause of morbidity and mortality in patients with leukaemia undergoing total body irradiation (TBI) and bone marrow transplantation (BMT). The effect of variation in dose relate of TBI on the development of lethal and sublethal lung damage has been investigated in mice by measuring changes in carbon monoxide uptake. CBA mice were irradiated using a 60Co source at 0.02, 0.05, 0.1, 0.2, 0.5 and 1.0 Gy min -1 to a total dose of 15.5 Gy. A log-linear relationship between the severity of impairment of carbon monoxide uptake (Vco) and dose rate was found. Ventilatory requirement (ventilation rate/Vco) was raised 20 to 40 weeks after TBI at dose rates above 0.1 Gy min -1. Time of onset and extent of elevation of ventilatory requirement were also dose-rate dependent. The implications of these findings for clinical practice are discussed.

Animals↗
PubMed1982

Total body irradiation (TBI) before bone marrow transplantation in leukaemia: a co-operative study from the European Group for Bone Marrow Transplantation.

A survey was carried out of 15 centres in Europe giving total body irradiation before bone marrow transplantation to determine modalities of treatment. Linear accelerators and cobalt machines were used to deliver doses of 750 to 1050 cGy in single fractions at dose rates ranging from 2.5 to 35 cGy min-1. The incidence of interstitial pneumonitis was not affected by quality of radiation but for total lung doses of more than 800 cGy incidence correlated with dose rate. Many centres chose to limit lung doses to 800 cGy. Overall treatment time (including interruptions) was less important than the actual dose rate during treatment. Nausea and vomiting occurred when doses of 300 cGy had been delivered, so that time of onset varied with dose rate. Sedation appeared as successful as specific anti-emetics in controlling this.

Bone Marrow Transplantation↗