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Biomedical subjects

K Arthur

Publications and source records attributed to K Arthur.

At least 37 records · Page 2Linked to original sources
PubMed1994

Limb salvage surgery for widely infiltrating bony sarcomas.

OBJECTIVE: To determine whether neoadjuvant chemotherapy and radiotherapy for bony sarcomas extending into soft tissues would allow limb salvage yet maintain local disease control. DESIGN: A prospective cohort study. SETTING: A university-affiliated cancer centre in Alberta. PATIENTS: All patients with potentially curable, widely infiltrating bony sarcomas of the extremity without neurologic deficit, referred to the centre in the 6 years from January 1984 to December 1990. There were 11 patients; 1 did not complete the protocol. The mean follow-up was 24 months. INTERVENTIONS: Adriamycin (doxorubicin) was infused for 3 days at a rate of 30 mg/d. A few days later radiotherapy was given 5 days a week for 10 doses at a rate of 3.0 Gy per dose. Four to 5 weeks later the tumour was excised surgically, with placement of a bone allograft or prosthesis, allowing a 1-cm margin of healthy soft tissue and a 5-cm margin of healthy bone and marrow cavity whenever possible. MAIN OUTCOME MEASURES: Need for limb amputation, infectious complications, recurrence of local or regional disease. RESULTS: One patient underwent amputation after fracture through the tumour site. There were two postoperative infections, one acute and one chronic. All patients had full neurologic function of the distal limb. There was no local or regional recurrence of disease. CONCLUSION: Neoadjuvant chemotherapy followed by radiotherapy and tumour excision provides control of aggressive local bone sarcomas while maintaining limb integrity.

Bone Neoplasms↗
PubMed1992

Morphometry of gastric carcinoma: its association with patient survival, tumour stage, and DNA ploidy.

Morphometric image analysis of nuclear features was performed on tissue from 46 patients who had had curative resections for gastric cancer. Clinical, pathological, flow cytometric, and follow-up data were available for these patients, which were drawn from a larger, previously reported series. The morphometric data were compared with patient survival, clinico-pathological status, and DNA ploidy. Univariate survival analysis revealed that morphometric parameters were not significantly related to survival, but examination of clinico-pathological data showed lymph node involvement, involvement of the resection margin, and lymphatic invasion to be significantly associated (P < 0.01) with patient prognosis. Multivariate survival analysis using the Cox model found only lymph node and resection margin involvement to be independently related to survival. Comparison of morphometric results with the clinico-pathological parameters showed various features, relating to nuclear size, and its variation to be significantly associated (P < 0.01) with the presence of lymphatic invasion, resection margin involvement, and tumour pattern (intestinal/diffuse). A comparison of morphometry with flow cytometric analysis in these cases showed that nuclear size was not significantly related to either DNA aneuploidy or the DNA proliferative index.

Aged↗
PubMed1991

Tumor necrosis factor expression by human ovarian carcinoma in vivo.

Tumor necrosis factor (TNF) is a cytokine produced by monocytes and other cells with selective cytolytic activity against some but not all tumor cells. Cellular resistance to the cytolytic effects of TNF has been reported to be associated with autocrine production of TNF by the target cells. The purpose of this study was to determine whether or not human tumors produce tumor necrosis factor in vivo. Ovarian carcinoma tissue from 25 patients with ovarian carcinoma was examined for the presence of TNF. Four of 5 ascites fluid specimens and tissue sections of 16 of 20 patients were positive for TNF by immunoperoxidase staining. The source of the immunoreactive protein was further examined by in situ hybridization studies. TNF mRNA was detectable in each of the ascites specimens and 7 of 16 tissue sections that were positive by immunoperoxidase staining. These findings suggest that TNF is produced by some human tumors in vivo and that the association between TNF production and resistance to TNF antitumor action may be clinically relevant.

Ascites↗
PubMed1989

A comparison of chromosomal aberrations induced by in vivo radiotherapy in human sperm and lymphocytes.

Chromosomal aberrations in human sperm and lymphocytes were compared before and after in vivo radiation treatment of 13 cancer patients. The times of analyses after radiotherapy (RT) were 1, 3, 12, 24, 36, 48 and 60 months. The median total radiation dose was 30 Gy and the testicular dose varied from 0.4 to 5.0 Gy. Human sperm chromosome complements were analysed after fusion with golden hamster eggs. There were no abnormalities in sperm or lymphocytes before RT. Following RT there was an increase in the frequency of numerical and structural chromosomal abnormalities in both lymphocytes and sperm. For structural abnormalities there were more rejoined lesions (dicentrics, rings) in lymphocytes and more unrejoined lesions (chromosome breaks, fragments) in sperm. After RT there was a dramatic increase in the frequency of chromosomal abnormalities in lymphocytes: at 1 mo. the frequency was 42%, at 3 mo. 25%, at 12 mo. 14%, at 24 mo. 11%, at 36 mo. 9%, at 48 mo. 7% and at 6 mo. 4%. Since the majority of men were azoospermic after RT, there is little data on sperm chromosome complements before the analyses performed at 24 mo. post-RT. At 24 mo. the frequency of abnormalities was 13%, followed by 21% at 36 mo., 12% at 48 mo. and 22% at 60 mo. Thus it appears that the frequency of lymphocyte chromosomal abnormalities had an initial marked increase after RT followed by a gradual decrease with time whereas the frequency of sperm chromosomal abnormalities was elevated when sperm production recovered and remained elevated from 24 to 60 mo. post-RT. This difference in the effect of time makes it very difficult to compare abnormality rates in lymphocytes and sperm and to use analysis of induced damage in somatic cells as surrogates for germ cells since the ratio between sperm and lymphocytes varied from 1:1 (at 24 mo. post-RT) to 5:1 (at 60 mo. post-RT).

Adult↗
PubMed1989

Concomitant 5-fluorouracil infusion, mitomycin C and radical radiation therapy in esophageal squamous cell carcinoma.

This is a retrospective comparison of patients with unresected esophageal squamous cell carcinoma treated by radiation therapy and chemotherapy (21 patients) versus radiation therapy alone (34 patients). Pretreatment characteristics were comparable in both groups. In the combined modality group, treatment was given in split courses with concomitant radiation therapy (20 to 25 Gy in 10 fractions on days 1-12 and days 42-54) and chemotherapy (bolus Mitomycin C on day 1; 96 hr. of continuous 5 Fluorouracil infusion on days 1-4 and days 42-46). There was improvement in local disease control with the combined modality approach. Initial complete response was achieved in 86% of the radiation and chemotherapy group, versus 57% of the radiation alone group. The one-year local relapse-free rate was 67% versus 35%, and 2 year rate was 41% versus 28%. (p less than 0.05). The 1-year and 2-year survival was 64% and 32% respectively, for the radiation and chemotherapy group, versus 28% and 10% respectively for the radiation alone group (p less than 0.05). The majority of patients had disease relapsed, 81% of the combined modality group and 97% of the radiation alone group. However, the pattern of failure was different in the two groups. In the radiation and chemotherapy group, 29% had local failure alone, 53% had distant failure alone, and 18% had both local and distant failure. In the radiation alone group, 33% had local failure alone, 24% had distant failure alone, and 43% had both local and distant failure. Concomitant radiation therapy, 5 Fluorouracil infusion and bolus Mitomycin C is effective treatment for local control in esophageal squamous cell carcinoma, but not for distant hematogenous metastases. This combined modality treatment was well tolerated, with little additional hematological toxicity, esophagitis and stomatitis over radiation therapy alone.

Aged↗
PubMed1989

Neoadjuvant treatment in conservative surgery of peripheral sarcomas.

Twenty-five patients with soft-tissue and bony sarcomas of the head and neck and limbs were treated by local neoadjuvant therapy. It consisted of 90 mg of Adriamycin infused intra-arterially over 3 days into a vessel feeding the involved area and 30 Gy of radiotherapy given over 10 days; this was followed by a complete resection of the sarcoma 4 to 6 weeks later. All the tumors were associated with a high risk of local recurrence; eight were locally recurrent and the remainder were stage II to stage IV tumours. Serious local complications were seen in 4% of the patients. This rate compares well with other higher dose neoadjuvant regimens (35 Gy over 10 days), which are associated with a 35% local complication rate. Follow-up at a mean of 30 months demonstrated no local recurrence. All limbs were spared. Long-term morbidity was negligible. No effect on systemic control is suggested; only 63% of the patients were free of systemic disease. This report substantiates other similar experiences supporting neoadjuvant therapy followed by resection as the treatment of choice for local control of sarcomas.

Bone Neoplasms↗
PubMed1988

Tumor necrosis factor and endotoxin induce similar metabolic responses in human beings.

After injury, infection, or major operations a number of predictable metabolic responses occur. It has been proposed that the cytokine tumor necrosis factor (TNF)/cachectin is a primary mediator of these host responses. To test this hypothesis, we studied 16 tumor-bearing humans with normal renal and hepatic function, who received 24-hour continuous intravenous infusions of escalating doses of recombinant TNF (4 to 636/micrograms/m2/24 h). Serial measurements were made of vital signs and plasma concentrations of TNF, interleukin-1, adrenocorticotropic hormone, cortisol, iron, glucose, and C-reactive protein. Low doses of TNF had minimal metabolic effects, but infusions of greater than or equal to 545 micrograms/m2/24 hr (n = 8) resulted in fever, pituitary, and stress hormone release and acute phase changes. These alterations were compared with the changes that occurred in healthy humans (n = 13) receiving intravenous bolus injections of Escherichia coli endotoxin (4 ng/kg). TNF infusion in doses greater than or equal to 545 micrograms/m2/24 hr produced peak plasma TNF concentrations and metabolic responses that were similar to those after endotoxin injection. Interleukin-1 concentrations remained basal after TNF or endotoxin administration. TNF may represent the primary afferent signal that initiates many of the metabolic responses associated with sepsis and endotoxemia.

Acute-Phase Proteins↗
PubMed1988

Prolonged high dose ARA-C infusions in acute leukemia.

High doses of cytosine arabinoside (ara-C) were administered by continuous infusion to 24 patients with acute leukemia in relapse or blast phase of chronic myelogenous leukemia (CML). Ara-C was infused at a dose rate of 250 mg/M2/hr for 36 to 72 hr. The major toxicities were myelosuppression, diarrhea, and abdominal pain. Other toxicities included pulmonary edema, neurotoxicity, and liver function abnormalities. The gastrointestinal toxicity was dose-limiting and a phase II dose was established at 250 mg/M2/hr for 60-72 hr. Four patients treated with this dose schedule had objective responses. Two patients with CML in blast phase returned to chronic phase and have remained stable without maintenance therapy for 12 and 18 months. Two patients with acute myelogenous leukemia in relapse entered complete remissions which continued unmaintained for 4 and 6 months. Steady-state plasma ara-C levels ranged between 7 and 24 x 10(-6) M, while ara-U levels were as high as 4.5 x 10(-4) M. There was no detectable accumulation of ara-C or ara-U during the infusion period. These findings would suggest that the continuous infusion of high dose ara-C may be useful in the treatment of acute leukemia and CML in blast crisis.

Adult↗
PubMed1986

An increased frequency of human sperm chromosomal abnormalities after radiotherapy.

13 cancer patients were studied before radiotherapy (RT) and at regular intervals after RT to determine the effect of RT on chromosomal abnormalities in sperm. The men were 19-47 years old and received testicular radiation doses of 0.4-5.0 Gray. Human pronuclear sperm chromosomes were analysed after penetration of zona-pellucida-free hamster eggs. Unfortunately the hamster egg penetration rates were exceedingly low, both before and after RT and this limited the number of sperm chromosome complements which could be analysed. Before RT, the frequency of abnormal sperm chromosome complements was 0% (0/9). After RT, the majority of men were azoospermic for 24 months but complements could be analysed from 4 men. In the first 12 months the frequency of abnormalities was 13% (1/8) and at 24 months it was 13% (7/55). By 36 months after RT, most men had recovered sperm production and the frequency of abnormalities in 8 men was 21% (18/86), which is significantly higher than the rate in control donors (8.5%). For individual men the range was 6-67%, and there was a significant correlation between testicular radiation dose and the frequency of sperm chromosomal abnormalities. The frequencies of both numerical and structural abnormalities were significantly increased after RT. This is the first evidence that radiation may increase the frequency of chromosomal abnormalities in human gametes.

Adult↗
PubMed1985

A prospective serial study of the effects of radiotherapy on semen parameters, and hamster egg penetration rates.

Cancer patients were studied before radiotherapy (RT) and at regular intervals after treatment (1, 3, 12, 24, 36, 48 months) to determine the effect of radiotherapy on semen parameters and sperm function as assessed by the hamster egg penetration assay. The cancer patients received testicular radiation doses of 0.4 to 5.0 grays (40 to 500 rads). The pre-radiotherapy semen profile varied considerably but in general the profile was poor: 7/11 men had a sperm concentration less than 20 X 10(6)/ml and a total count of less than 50 X 10(6), while the hamster egg penetration rates were also very low with a mean of 5% (range 0% to 15%). This is the first study demonstrating that sperm function as well as sperm concentration is impaired in cancer patients pre-radiotherapy. At 3 and 12 months post-radiotherapy, 8/11 men were azoospermic. By 24 months 8/11 were producing sperm although only 2 had hamster egg penetration rates greater than 15%. All men studied at 36 months (4) and 48 months (3) post-radiotherapy had recovered spermatogenesis but hamster egg penetration rates were still poor. There was a highly significant inverse correlation between testicular radiation dose and subsequent sperm concentration and hamster egg penetration rates.

Adult↗
PubMed1977

Radiotheraphy in chemodectoma of the glomus jugulare.

Twenty-five patients treated for glomus jugulare tumours over a 13-year period are reviewed, the majority (20) receiving radiotherapy only. Only two patients developed tumour recurrence, one following inadequate-dose radiotherapy, the other after surgery. Both are doing well following radiotherapy for their recurrent disease. Two patients were lost to follow-up and five have died of unrelated disease, four with no tumour reactivation over a prolonged period. The remaining 16 patients have been maintained in continuous tumour control for periods ranging from 4 to 15 years. While these tumours are by nature slow growing and usually not malignant, they demand radical treatment due to the symptomatology they create. Radiotherapy would seem to offer excellent prospect of satisfactory tumour control.

Adult↗
PubMed1976

Radiotherapy in carcinoma of the middle ear and auditory canal.

In the decade 1961 to 1970, 89 patients with epidermoid carcinoma of the middle ear or auditory canal were seen. Seventy-eight were treated with 5-year survival figures of 22 per cent for middle ear, 42 per cent for auditory canal and 31 per cent for the total group. The majority of failures occurred within 18 months of diagnosis. The author suggests that radiotherapy and surgery must be combined to improve results. Eleven patients in the series developed second primary tumours.

Adolescent↗