Search PubMed⌕ Search

Biomedical subjects

M H Cullen

Publications and source records attributed to M H Cullen.

At least 73 records · Page 4Linked to original sources

Chemotherapy for poor risk germ cell tumours. An independent evaluation of the POMB/ACE regime.

We have evaluated the 7-drug, alternating, high-dose cisplatin regime for germ cell tumours, designated POMB/ACE, in 55 patients with advanced malignant teratomas and 5 patients with bulky metastatic seminomas. All of the latter and 5 of the teratoma patients had relapsed following radiotherapy, chemotherapy or both. The previously untreated teratoma patients included 13 whose tumours were extragonadal. The primary testicular tumour patients comprised 16 with large and 21 with very large volume metastases according to the Medical Research Council criteria. POMB/ACE is effective therapy for poor risk patients with germ cell tumours (including those with the most advanced disease, i.e. hepatic and cerebral metastases) and prolonged treatment after marker normality seems unnecessary. It is a complex regime with significant toxicity and cannot be recommended for the treatment of patients with germ cell tumours who have an excellent prognosis with simpler, shorter and less toxic treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Testing new drugs in untreated small cell lung cancer may prejudice the results of standard treatment: a phase II study of oral idarubicin in extensive disease.

We have evaluated the orally active anthracycline idarubicin at a dose of 40 mg/m2 in divided doses over 24 hours in 21 previously untreated patients with extensive-stage small cell carcinoma of the lung (SCCL). Subsequent iv therapy was cyclophosphamide (1000 mg/m2), vincristine (1 mg/m2), and etoposide (120 mg/m2 iv on Day 1 and 250 mg/m2 orally in divided doses on Day 2; CVE) in patients who failed to respond to idarubicin and in relapsed patients. Three (14%) of 21 patients treated with idarubicin responded, with two complete responses (CR). Patients failing to respond promptly and those who relapsed were treated with CVE. Seven patients did not receive CVE for the following reasons: early death, four patients; early CNS disease, two; and refusal, one. Fourteen patients received CVE. Of 12 patients failing to respond to idarubicin, eight progressed on CVE, three achieved partial response (PR), and one achieved CR. Two idarubicin responders who received CVE achieved PR and CR. The median survival of all 21 patients was 6 months. For those with World Health Organization performance scores of 0 or 1 the median survival was 6.2 months and for the rest it was 2.6 months. Although CVE chemotherapy was instituted promptly in patients not responding to idarubicin, these results seem inferior to those previously seen in our center with standard treatment from the start. We believe that patients with extensive SCCL often require a rapid and more guaranteed response to their first treatment.

Aged↗

Cisplatin, etoposide, and radiotherapy in regional inoperable squamous cell carcinoma of the bronchus.

Thirty-three ambulatory patients with limited stage, inoperable, squamous cell carcinoma of the bronchus were administered cisplatin (60 mg/m2 IV on day 1) and etoposide (VP-16) (400 mg/m2 orally in divided doses over days 3, 4, and 5). This regimen was repeated every 28 days for a maximum of six courses. Radiotherapy was given to patients who did not respond to chemotherapy for urgent relief of local symptoms, or as adjuvant to chemotherapy in responding patients. Response to chemotherapy was assessable in 28 patients. Patients experiencing early death were included in the evaluation. Ten patients (36%) had progressive disease and nine (32%) had stable disease during chemotherapy. Eight patients achieved radiologically verified partial response (PR) and one, a complete response (CR) verified bronchoscopically, yielding an overall response rate of 32%. Of responding patients who proceeded to radiotherapy, one patient showing PR was converted to a CR; another patient with PR improved, although not to CR. The median survival of 33 patients was 49 weeks. There were two deaths among nine responding patients (at 38 and 48 weeks), and nine deaths among 19 nonresponders (six before the 27th week). The principle toxic reactions were nausea and vomiting, which were serious (greater than grade 2) in 29 of 33 patients. All patients receiving more than one course of chemotherapy suffered total alopecia. Cisplatin/etoposide is an effective combination in some patients with regional, squamous cell lung cancer, but randomized trials comparing it to radiotherapy alone are required to establish real survival benefit.

Adult↗

Combined granulocyte and platelet transfusions: inter-relationship between granulocyte and platelet recoveries in the presence and absence of complicating factors.

191 combined collections of granulocytes (PMN) and platelets (PLT) obtained by discontinuous cytapheresis were given to 23 patients with acute myeloid leukaemia (AML). The circulation in recipients of the concomitantly transfused cells was compared by measuring the % recovery of PMN at 1 h, and of PLT at 1 and 20 h. The recovery of both cells was greatly reduced in transfusions accompanied by a transfusion reaction. Fever in recipients had no effect on the recovery of either cell, but PMN recovery was significantly higher in patients receiving oral prednisolone. Alloimmunization to PLT, defined as recovery levels less than 15% at 1 h and/or less than 10% at 20 h, was recorded in 42 transfusions, and PMN recovery was significantly reduced in this group. In transfusions where PMN recovery was 'low' (less than 5%); the recovery of the coincidentally transfused PLT was significantly reduced only in transfusions accompanied by a reaction. These results emphasize the deleterious effects of transfusion reactions and suggest that donor PMN frequently circulate less well in recipients alloimmunized to PLT from the same donor.

Blood Group Incompatibility↗

Chemotherapy and immunotherapy for acute myelogenous leukemia.

Eighty-six consecutive untreated adults with acute myelogenous leukemia were treated with a combination of Adriamycin, vincristine, prednisolone, Cytosine Arabinoside, and BCG. Complete remission was achieved in 39 (45%) patients; these patients were then allocated on an alternate basis to receive BCG and monthly chemotherapy with or without weekly irradiated allogeneic blast cells. The median duration of remission was eight months and was the same for both groups. The median survival of those achieving complete remission was 19 months compared with two months for those not achieving complete remission. Nine patients are still alive without relapse and five of these patients have been disease free for more than three years.

Adolescent↗

Prevention of effects of alcohol intoxication by naloxone.

In a double-blind, cross-over study of twenty male volunteers intravenous injection of 0.4 mg naloxone prevented the impairment of psychomotor performance induced by low levels of blood alcohol. The possibility that alcohol produces intoxication by stimulating the release of endogenous opioid peptides should be investigated.

Adult↗

Histological transformation of non-Hodgkin's lymphoma: a prospective study.

Forty-three lymph node biopsies were performed prior to retreatment in 30 unselected patients who had relapsed following chemotherapy for advanced non-Hodgkin's lymphoma of low grade histological type. Eight patients (27%) showed unequivocal evidence of transformation to a high grade variety of lymphoma. These included 4 out of 21 cases originally having had follicular lymphoma and 4 out of 9 cases having had diffuse lymphoma. In 2 further patients with follicular lymphoma, relapse was diagnosed following examination of the bone marrow and in one the tumor had clearly transformed. In 5 of the transformed lymphomas the cell type was predominantly centroblastic, in 2 immunoblastic and in the remaining 2 centrocytic (anaplastic). Five of the 9 cases developing high grade lymphoma have died after a median interval of 5 months from transformation, whereas only 3 of 23 cases showing no change are dead. In 4 patients low grade lymphoma persisted in the bone marrow at the time of nodal transformation. The clinical circumstances at the time of rebiopsy were unhelpful in predicting transformation.

Bone Marrow↗

The effect of nitrous oxide on the cell cycle in human bone marrow.

The effect of 24 h exposure to nitrous oxide on the cell division cycle in human bone marrow has been studied in vivo using the technique of DNA flow microfluorimetry. All patients who received nitrous oxide showed a significant increase in the proportion of early S-phase cells with a decrease in late S, G2 and mitotic cells. These changes resemble those seen following the use of S-phase-specific cytotoxic drugs. Control patients showed no such effect. Parallel studies have suggested that interference with the function of vitamin B12 underlies this response. Nitrous oxide may provide a convenient method for studying the cell kinetic aspects of acute B12 deficiency and the possibility of using it to increase the therapeutic index of antitumour drugs is discussed.

Bone Marrow↗

Haematological features of angioimmunoblastic lymphadenopathy with dysproteinaemia.

A study of seven patients with AILD has confirmed previously reported cytological and immunological changes in the peripheral blood. In themselves these changes should not be considered as specific. Histological examination of the bone marrow may show more characteristic lesions which involve haemopoietic, lymphoid, and stromal cells. Three patients had bone marrow features similar to myelofibrosis, which are considered to be diagnostic of AILD.

Aged↗