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Biomedical subjects

K C Calman

Publications and source records attributed to K C Calman.

At least 73 records · Page 4Linked to original sources

Quality of life in cancer patients--an hypothesis.

Quality of life is a difficult concept to define and to measure. An hypothesis is proposed which suggests that the quality of life measures the difference, or the gap, at a particular period of time between the hopes and expectations of the individual and that individual's present experiences. Quality of life can only be described by the individual, and must take into account many aspects of life. The approach is goal-orientated, and one of task analysis. The hypothesis is developed in a diagramatic way, and several methods of testing the hypothesis suggested.

Goals↗

Consent, dissent, cement.

The patient-doctor relationship has two fundamental components. The first is the application of the skill and knowledge of the doctor in the care of the whole patient and family. The second is the right of the individual to have information about his or her illness or treatment, and to be involved in decision making. This relationship is built on trust and comes sharply into focus in the area of consent to take part in clinical trials. The argument is put forward that the use of written information should be seen as an extension of the communication between the doctor and the patient, and not as a legally restrictive device. The concept of an agreement, both on the part of the doctor and of the patient, to take part in a clinical trial is developed.

Clinical Trials as Topic↗

Effect of a subcutaneously growing Walker 256 carcinosarcoma on host tissue mitochondrial function and magnesium content.

Mitochondria were prepared from the liver, kidneys, and skeletal muscle of rats at 1, 6, 12, 18, and 26 days after inoculation with Walker 256 cells or sterile 0.9% NaCl solution and assessed for structural and functional integrity. Using polarography to measure respiration, it was found that all tissue mitochondria from both controls and tumor-bearing animals prepared 1 day after inoculations were damaged and had impaired respiratory function. This effect was believed to be caused by the presence of anesthetic molecules in the mitochondrial membranes rather than by tumor. On Day 6, all tissue mitochondria were respiring properly; no evidence of membrane disruption was apparent. From Day 12 onwards, mitochondria from the tumor-bearing animals would not consume oxygen unless magnesium ions were added to incubation media. Kidney required by far the greatest amount of magnesium, in one case, 10 mM MgCl2. The requirement of the liver never exceeded 3 mM MgCl2, and with the muscle no dependency developed. The quantity of magnesium ions necessary to restore normal kidney mitochondrial function increased with tumor size (r = 0.83). From Day 12 onwards, mitochondria prepared from the control animals respired normally, and all mitochondria from the controls and the tumor-bearing rats were structurally intact. When the magnesium content of the abnormal mitochondria prepared from the animals inoculated with tumor cells was measured by atomic absorption spectrophotometry, the mitochondria were found to be deficient by 18% for kidney (p less than 0.01) and 20% for liver (p less than 0.01) compared to controls (Student's t test).

Animals↗

Sequential methotrexate plus 5-FU in advanced breast and colorectal cancers: a phase II study.

Fifty-two patients with advanced breast or colorectal cancer have been treated with methotrexate (MTX) (50 mg/m2) followed 6 hours later by 5-FU (600 mg/m2). The mean serum MTX level immediately prior to 5-FU administration was 1.37 mumols/L (1.37 X 10(-6) M). Of 29 evaluable patients with breast cancer (six of whom had received prior chemotherapy), one achieved a complete response and five achieved a partial response (total response rate, 21%). Among 16 evaluable patients with colorectal cancer (three of whom had received prior chemotherapy), there were no objective responses. Although hematologic toxicity was generally mild, mucositis occurred in 20 patients (severe in three), and at least one early death was attributable to toxicity. These results indicate that at doses of MTX and 5-FU which are in general use in combination chemotherapy for breast cancer, sequential treatment does not have a therapeutic advantage. In colorectal cancer, the same combination is inactive.

Antineoplastic Combined Chemotherapy Protocols↗

Changes in anatomical distribution of tumour lesions induced by platelet-active drugs.

To examine the effect of platelet-active drugs on the spread of blood-borne tumour cells, two murine tumours, sarcoma 180 (S-180) and TLX-5 lymphoma, were selected. Following intravenous (IV) injection into CBA mice the former elicited thrombocytopenia and formed discrete pulmonary tumours, whereas the latter failed to elicit thrombocytopenia and formed discrete tumours in all visceral organs examined except the lungs. S-180 cells were injected IV into mice pre-treated with RA233 (known to prevent thrombocytopenia and thrombus formation) and TLX-5 cells were injected IV into mice pre-treated with Corynebacterium parvum (known to induce thrombocytopenia and thrombus formation). RA233 pre-treatment did not change survival time or incidence of S-180 pulmonary tumours but did result in a higher incidence of extrapulmonary tumours and a lower tumour cell burden immediately after injection. Pre-treatment with C. parvum resulted in a higher TLX-5 tumour cell burden but not discrete tumours in the lungs. On the basis of known drug activities it is proposed that thrombocytopenia induced in these experiments is in part a reflection of thrombus formation in the lungs which influences the speed of passage of tumour cells through capillaries. In some cases this may lead to a changed anatomical distribution of tumour lesions.

Animals↗

Effects of polysorbate 80 on the absorption and distribution of oral methotrexate (MTX) in mice.

This study is part of a programme of work aimed at improving the bioavailability of oral methotrexate (MTX). In preliminary experiments no significant effect of non-ionic surfactant polysorbate 80 (Tween 80) on absorption of 0.5 mg MTX X kg-1 in NMRI mice was observed except when the drug was given together with 6% polysorbate 80 in solution. Absorption from a higher dose of 3 mg MTX X kg-1 was increased when the drug was administered with 2% or 6% polysorbate 80. Plasma MTX measurements confirmed the significantly higher levels of MTX with 6% polysorbate 80 PO. In subsequent experiments, when Porton mice were used and 4 mg MTX X kg-1 was administered PO, higher plasma and brain levels of MTX were measured in animals given the drug with 6% polysorbate 80, suggesting the enhancement of MTX uptake by this non-ionic surfactant. Although the amount of MTX in the liver and kidney of mice given MTX with polysorbate 80 were not significantly different from the amounts in mice given MTX alone, the lower observed levels suggested that polysorbate 80 perhaps facilitates the elimination of the drug from these organs. The amount of plasma MTX in mice measured 1 h after oral administration of various MTX doses in the presence of 6% polysorbate 80 were significantly higher than the levels in mice given the drug without surfactant, but the significantly higher amounts of MTX in the brain were only observed following the doses of 2 and 6 mg MTX X kg-1.

Administration, Oral↗

A multicentre phase II trial of vindesine in malignant melanoma.

Fifty-three evaluable patients with advanced malignant melanoma have been treated with vindesine 3 mg/m2 i.v. weekly for a minimum of 6 weeks. An objective response rate of 26% was attained with 17% complete remissions, 78% of which were in stage II disease. The treatment was well tolerated, with alopecia the only clinically significant side-effect (43% of patients). Vindesine is superior to DTIC and should be considered as the best currently available drug for malignant melanoma.

Adolescent↗

The treatment of advanced carcinoma of the bladder with combination chemotherapy.

Thirty patients with advanced T4 transitional cell carcinoma of the bladder were treated in a prospective randomised trial with combination chemotherapy. Sixteen patients received cyclophosphamide, doxorubicin (Adriamycin) and 5-fluorouracil, whilst 14 patients received methotrexate, doxorubicin and 5-fluorouracil with folinic acid rescue. There were no complete or partial responses to either regime and there was progression in all patients. The 2 regimes were shown to be relatively non-toxic but failed to alter the natural course of the disease.

Antineoplastic Agents↗

Problems of the oncology outpatient: role of the liaison health visitor.

A survey by a liaison health visitor of outpatients attending an oncology department has identified and enumerated the principal problems with which she is confronted, and defined her role. The main medical symptoms of concern to the patient at home and needing attention by the liaison health visitor were anorexia, nausea, vomiting, and constipation: inadequate pain control due to poor drug compliance was also common. Other functions of the liaison health visitor include providing nursing aids and prostheses, support for bereaved relatives, and liaison with the community health care team.

Analgesia↗