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Biomedical subjects

R M Fox

Publications and source records attributed to R M Fox.

At least 163 records · Page 9Linked to original sources

Fibre-optic bronchoscopy in small cell lung cancer: findings pre and post chemotherapy.

The aim of our study was to evaluate the role of fibre-optic bronchoscopy both in diagnosing patients with small cell lung cancer, and in assessing remission status following combination chemotherapy. Diagnostic bronchoscopic examination was performed in 40 patients and revealed that in all cases the lesion was located in the central bronchi. Following combination chemotherapy remission status in 18 patients was assessed by comparing the findings at repeat bronchoscopy with those of chest radiology. In ten patients there was no relationship between the findings at bronchoscopic examination and the chest radiograph (normal or abnormal). Adequate assessment of response of small cell lung cancer to therapy requires bronchoscopy in addition to chest radiology.

Bronchoscopy↗

Sensitivity of leukemic human null lymphocytes to deoxynucleosides.

The growth of cultured leukemic T-lymphocytes is readily inhibited by deoxynucleosides, particularly thymidine, deoxyguanosine, and deoxyadenosine. By contrast, Epstein-Barr virus-transformed B-lymphocytes are relatively resistant to deoxynucleosides. Growth inhibition correlates with the development of high deoxyribonucleoside triphosphate pools following exposure to deoxynucleosides. Leukemic T-lymphocytes are deficient in ecto-5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) activity, and it has been postulated that deficiency of this enzyme decreases the capacity of these cells to degrade deoxyribonucleotides, rendering them sensitive to deoxynucleosides. We find that the sensitivity of cultured null-type leukemic lymphocytes to growth inhibition of deoxynucleosides is similar to that of T-cells. However, the null cells contain normal levels of ecto-5'-nucleotidase. We infer that ecto-5'-nucleotidase deficiency does not have a central role in determining the deoxynucleoside sensitivity of leukemic lymphocytes.

B-Lymphocytes↗

Mechanism of deoxycytidine rescue of thymidine toxicity in human T-leukemic lymphocytes.

Cultured malignant human lymphocytes are highly sensitive to growth inhibition by thymidine (50% inhibitory dose congruent to 10(-5) M). Growth inhibition reflects sustained elevation of the deoxythymidine 5'-triphosphate pool associated with secondary elevation of the deoxyguanosine 5'-triphosphate pool and reduction in the deoxycytidine 5'-triphosphate (dCTP) pool. Deoxycytidine was capable of partially reversing thymidine growth inhibition at a concentration of 0.5 microM, and growth recovery was virtually complete at 8 microM. The dCTP pool remained depressed until growth inhibition reversal by deoxycytidine was complete, and at a higher concentration of deoxycytidine the dCTP rose above control levels, but the deoxythymidine 5'-triphosphate and deoxyguanosine 5'-triphosphate pools remained elevated. These results support the view that thymidine growth inhibition induces a critical deficiency of dCTP via allosteric inhibition of ribonucleotide reductase rather than inhibiting DNA replication directly by elevated deoxythymidine 5'-triphosphate or deoxyguanosine 5'-triphosphate pools.

Cell Division↗

Advanced male non-seminomatous germ-cell tumours. Combination chemotherapy with cis-platinum, vinblastine and bleomycin.

Nineteen men with advanced germ-cell tumours were treated with a combination of vinblastine, bleomycin and cis-diamminedichloroplatinum II (cis-platinum). One patient died nine days after starting chemotherapy. Seventeen patients responded to therapy (14 completely and three partially). Toxicity was very high, and three patients died of septicaemia during therapy. Eight patients remain in complete remission 36 to 80 weeks after starting chemotherapy.

Adolescent↗

Thymidine sensitivity of cultured leukaemic lymphocytes.

Cultured leukaemic lymphocytes from patients with T, null, or pre-B acute lymphoblastic leukaemia are shown to be highly sensitive to growth inhibition by thymidine. Thymidine sensitivity was correlated with reduced activity of the catabolic enzyme thymidine phosphorylase and sustained elevation of the deoxythymidine triphosphate pool after exposure to thymidine. It is suggested that thymidine may have a role in the management of certain acute lymphoblastic leukaemias of lymphomas.

B-Lymphocytes↗

Undifferentiated carcinoma in young men: the atypical teratoma syndrome.

In 5 young men with apparent undifferentiated carcinoma involving lung, mediastinum, and lymph-nodes subsequent response to treatment, tumour-marker analysis, and histology review suggested a diagnosis of embryonal-cell carcinoma. It is suggested that atypical presentation of extragonadal germ-cell tumours may be common. Because such tumours respond to chemotherapy, accurate diagnosis is essential.

Adolescent↗

Cis-dichlorodiammine platinum (II) in advanced ovarian carcinoma.

Twenty-seven patients with advanced ovarian cancer were treated with a total of 80 courses of cis-dichlorodiammine platinum (II) (cisplatin). The doses in three courses were less than 50 mg/m2, in 64 courses they were 50 mg/m2, and in eight courses they were 100 mg/m2. In addition, five courses of low-dose daily treatment (20 mg/m2 for five days) were administered. Twelve patients received cisplatin alone, 12 received cisplatin and cyclophosphamide (750 mg/m2), and three patients received cisplatin with other drugs. There were eight responders (33%) in the 24 evaluable patients. Renal toxicity occurred in four patients, ototoxicity in four, and leucopenia (which was life-threatening in one patient) occurred in 16 patients (white cell count less than 3.0 X 10(9)/L). There were two early drug-related deaths. The median survival of patients who responded to cisplatin treatment was longer than 30 weeks compared with nine weeks for non-responders.

Adolescent↗

Unknown primary adenocarcinoma: incidence of overinvestigation and natural history.

Out of 1300 patients referred to a medical oncology unit, there were 87 with metastatic cancer in whom a primary tumour site was not evident from the history and after physical examination and chest radiography had been carried out. An analysis of the investigations performed in these patients and their results showed that in only eight of the 87 patients did non-surgical investigations at presentation determine the primary site. In two patients it was identified by diagnostic laparotomy, and in a further 13 clinical follow-up led to recognition of the primary tumour site before death. Few investigations should be performed in patients in whom the primary site is known since they have a low yield, and in our population identifying the primary tumour did not improve the outcome or alter management. Treatable tumours should be excluded, and this may be done in most cases by simple blood tests, particularly those measuring acid phosphatase activity and other tumour markers.

Adenocarcinoma↗

Burkitt's lymphoma in Australia.

Three patients with Burkitt's lymphoma have been seen at Royal Prince Alfred Hospital during the past 18 months. Following treatment, two patients are in complete clinical remission.

Adolescent↗

Evidence for a new mechanism of cytotoxicity of 1-beta-D arabinofuranosylcytosine.

Inhibition of DNA synthesis by a pulse of 1-beta-D-arabinofuranosylcytosine (ara-C) results in reinitiation of DNA replication in DNA segments replicated earlier in that S phase and hence double replication of some DNA segments. Experiments were with tissue culture cell lines of human origin. DNA replicated early in S phase was labeled with a pulse of [3H]deoxycytidine with the cells pulsed later in S phase with ara-C. The DNA replicated after the time of the ara-C pulse was density labeled with 5-bromodeoxyuridine. Reinitiation of DNA replication in the already replicated [3H]DNA segments was demonstrated using CsCl density gradient analysis by an increase in the 3H label present in the light-heavy peak of semiconservatively replicated DNA. Also, in DNA of control cells, all of the 3H was in the same strand of the light-heavy DNA duplex as was the 5-bromodeoxyuridine, as shown by alkaline CsCl density gradient analysis of purified light-heavy DNA. However, after a pulse of ara-C, utilization of [3H]DNA strands as template strands was demonstrated by the presence of 3H label at the density of unsubstituted DNA chains in alkaline CsCl gradients of the purified light-heavy DNA. This double replication phenomenon can explain certain chromosomal abnormalities induced by ara-C.

Cell Cycle↗

Methotrexate nephrotoxicity.

The use of high dose methotrexate therapy in the treatment of malignant disease has been complicated by nephrotoxicity. Analysis of the basic physico-chemical properties of methotrexate has allowed the development of improved techniques of administering methotrexate, at high dose, which greatly reduces the incidence of nephrotoxicity.

Chemical Phenomena↗

Sequential pure red cell and megakaryocyte aplasia associated with chronic liver disease and ulcerative colitis.

The clinical course of a patient with chronic hepatitis and previous ulcerative colitis who subsequently developed pure red cell aplasia (PRCA) is described. The PRCA remitted initially with corticosteroid therapy. A subsequent relapse responded to cyclophosphamide therapy following splenectomy. This was followed by a fatal third episode of red cell aplasia associated with megakaryocyte aplasia.

Adolescent↗

Malignant haemangiopericytoma: case report and ultrastructural study.

A case of a rapidly fatal malignant haemangiopericytoma arising in the deep tissues of the face is recorded. The histology of the tumour was anaplastic but otherwise typical. Ultrastructural study confirmed the diagnosis by revealing tumour cells with delicate interdigitating cytoplasmic processes and basement membrane formation resembling pericytes. A feature of the tumour not previously recorded in haemangiopericytoma was ciliogenesis.

Basement Membrane↗