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Biomedical subjects

C Fisher

Publications and source records attributed to C Fisher.

At least 361 records · Page 20Linked to original sources

Role of compartmental resection for soft tissue sarcoma of the limb and limb girdle.

A total of 143 consecutive operations for soft tissue sarcoma of the extremity, performed by one surgeon over a 5-year period, was studied to determine the place of compartmental excision. The surgical aim was to achieve the nearest to radical surgery compatible with preservation of a functional limb. Of the operations, 73 were for previously untreated primary tumour and 70 for local recurrence. Two tumours arose in areas previously irradiated for other malignancies and 35 recurrences had occurred despite prior radiotherapy; of the 106 remaining cases, adjuvant radiotherapy was used for 79. Adjuvant chemotherapy was used only occasionally and was more often regional than systemic. For the majority of tumours, compartmentectomy was inappropriate or inadequate: 49 were extracompartmental in origin and 48 extended beyond their compartment of origin at the time of surgery. The remaining 46 were confined to one compartment; in only 21 of these 46 operations was a radical compartmental excision performed. Compartmental excision was more likely to be performed when the tumour was centrally located within a compartment, was so large that it replaced most of the muscle group, or was high grade or recurrent (particularly when adjuvant radiotherapy had already been used). The general preference was to combine less-than-radical surgery with adjuvant radiotherapy rather than sacrifice entire muscle groups or adjacent, functionally important, structures such as artery or nerve. This reflects the proven efficacy of radiotherapy in controlling microscopic disease. Overall, compartmental excision was considered appropriate in only 15 per cent of operations.

Adolescent↗

Diagnosis of soft tissue tumours by Tru-Cut biopsy.

Tru-Cut biopsies were obtained from 52 consecutive patients referred with soft tissue tumours. Forty-five patients had soft tissue sarcomas; seven had benign soft tissue tumours. Of the biopsies 96 per cent provided adequate material for diagnosis. The histological diagnosis made from the Tru-Cut biopsy was compared with that made from the resected specimen. There were no false positive diagnoses of malignancy. The accuracy of Tru-Cut biopsy was 98 per cent for the diagnosis of malignancy and 94 per cent for the diagnosis of sarcoma. Tumour subtype was correctly specified in 85 per cent of sarcomas and tumour grade in 88 per cent. Tru-Cut biopsy should replace open biopsy as the primary means of diagnosis of soft tissue tumours unless a satisfactory tissue sample cannot be obtained.

Adolescent↗

Preoperative cytology and mammography in patients with single-duct nipple discharge treated by surgery.

Microdochectomy has been the routine management for single-duct nipple discharge. Our review of 176 consecutive patients surgically treated between 1975 and 1988 revealed eight patients with in situ carcinomas and seven with infiltrative carcinomas. Seventeen patients had multiple papillomas, two had atypical hyperplasia and two had atypical epitheliosis. Case selection for surgery has recently been advocated. In our study, nipple discharge cytology was helpful in 67 per cent of cases with underlying malignant pathology. Mammography was found to be unreliable, alerting suspicion in only two of 15 cases.

Adolescent↗

The region of the HPV E7 oncoprotein homologous to adenovirus E1a and Sv40 large T antigen contains separate domains for Rb binding and casein kinase II phosphorylation.

Some genital human papillomavirus (HPV) types, such as 16 and 18, are highly associated with malignant cervical tumors while others, such as HPV 6, are only rarely found in these malignancies. The E7 oncoproteins of HPV 6, 16 and 18 each have a 17 amino acid region with striking homology to adenovirus E1a and SV40 LT. E1a, LT and the E7 oncoprotein of HPV16 all bind the cellular Rb protein in vitro, and for E1a and LT this region of homology contains sequences essential for interaction with Rb. We have now found that in HPV 16 E7 this region (amino acids 21-37) contains two separate biochemical activities, each of which contributes to E7-mediated transformation. Rb binding was localized to the N terminus of this region, while the C terminus was shown to serve as a substrate for casein kinase (CK) II, which phosphorylated serine-31 and serine-32. Replacement of the two serines by non-phosphorylatable amino acids led to a reduction in transforming activity and abolished phosphorylation but did not affect Rb binding. Rb binding and CK II phosphorylation were also examined for the E7 proteins of HPV 6 and HPV 18. HPV 16 and 18 E7 bound similar amounts of Rb, but HPV 6 E7 consistently bound less. Phosphorylation rates also varied, with HPV 18 E7 being 2-fold faster than HPV 16 E7, which in turn was 2-fold faster than HPV 6 E7. We conclude that Rb binding and phosphorylation of E7 by CKII are independent activities which are required for efficient transformation by E7 and that these activities correlate directly with the relative oncogenic potential of these viruses.

Adenovirus Early Proteins↗

Endometrial stromal sarcomas.

The case histories of 15 patients with endometrial stromal sarcoma attending the Royal Marsden Hospital between 1973 and 1987 were reviewed. Eight patients were classified as having low-grade and seven as high-grade tumors using specific histological criteria. Those patients with low-grade tumors had a long relapse-free and overall survival in the absence of receiving specific therapy after initial surgery. Five are alive and disease free, one has shown a partial response to hormonal manipulation, and one is alive with disease on no therapy. Only one patient has died and this occurred 111 months postdiagnosis. Conversely, all seven patients with high-grade tumors relapsed with local disease and three have died. Thus, after surgical resection patients with low-grade tumors probably do not require treatment until relapse, whereas adjuvant radiotherapy should be given to those patients with high-grade tumors. On relapse, hormone therapy should be the treatment of first choice for patients with low-grade tumors, whereas chemotherapy is more appropriate for patients with high-grade tumors.

Adult↗

Treatment of extremity soft tissue sarcomas with surgery and radiotherapy.

The results of treatment with a combination of surgery and radiotherapy of 102 patients with nonmetastatic extremity soft tissue sarcoma are reported. Seventy-nine patients were previously untreated and 23 had locally recurrent disease. Sixty-six tumours were situated in the lower limb and 16 in the limb girdles. Fifty-nine were high grade lesions, and 64 were over 5 cm in length. Surgical clearance was "good" (wide or radical) in only 34 cases. Sixty-eight patients received post-operative irradiation, 23 pre-operative irradiation and 11 both pre- and post-operative radiotherapy. Seventeen patients subsequently developed local recurrence and 9 of these remain disease-free after further surgery. Actuarial 5 year local control and disease-free survival rates for new cases were 87 and 65.4%; and for previously recurrent cases these figures fell to 75 and 54.8%. Following a univariate analysis of patient, tumour, surgical and radiotherapeutic factors only previous local recurrence (p less than 0.1 greater than 0.05) was found to significantly increase the risk of further local relapse. Multivariate analysis found high tumour grade [relative risk (RR) 8.4], tumour size greater than 15 cm (RR 3.66), previous local recurrence (RR 6.47) and proximal site (RR 12.7) to be independent poor risk factors for survival.

Actuarial Analysis↗

Solitary choroidal metastasis in bronchial carcinoma.

Choroidal metastases, although uncommon, are a well-recognized complication of malignant disease and their development is usually associated with other soft tissue metastases and a poor prognosis. About one-third of choroidal metastases arise from carcinoma of the bronchus. They are rarely solitary. Histologically confirmed solitary choroidal metastasis from squamous carcinoma of the bronchus has not been previously reported in the literature. We describe such a case.

Aged↗

Radical radiotherapy for carcinoma of the anal canal.

The treatment of squamous cell carcinoma of the anal canal remains controversial, and recent reports have recommended combined chemotherapy and radiotherapy rather than radiotherapy alone as primary treatment. In order to define the role for more aggressive local therapy we have performed a retrospective analysis on patients with squamous cell carcinoma of the anal canal treated at the Royal Marsden Hospital between 1958 and 1986. Among 42 patients who received radical radiotherapy (RRT) the overall 5-year caused specific survival (CSS) was 52%. Tumour stage and node involvement were the most important prognostic factors. The 5 year CSS were T1 100%, T2 59%, T3 40% and T4 0% (P less than 0.05). The 5-year CSS for node-negative patients was 64% compared to 23% for node-positive patients (P less than 0.095). A minimum tumour dose of 60 Gy in 30 fractions over 6 weeks was essential to achieve local control and was associated with minimal late morbidity and with the retention of anal continence in all patients locally controlled.

Adult↗

Nutritional effects on the growth and fatness of broilers.

1. Broiler chickens given diets high in protein, or choice-fed on a high protein balancer, had much lower abdominal fat contents than those reported in many recent experiments. The values for males were 10.8 g/kg liveweight at 56 d at 2.43 kg liveweight in one experiment in Scotland and 16.0 g/kg liveweight at 42 d at 1.93 kg liveweight in another in South Africa. For females the values were 18.8 g/kg liveweight at 56 d at 2.15 kg liveweight in Scotland and 15.7 g/kg liveweight at 42 d at 1.60 kg in South Africa. 2. The content of abdominal fat was, in general, increased by reducing the protein content of the diet or by dilution of the food with oil or starch. It was, in general, reduced by diluting the food with dietary fibre which also reduced liveweight gain. 3. The results are consistent with the idea that chickens attempt to control their food intake so that they achieve a particular fatness. This level of fatness differs between the sexes and between degrees of maturity.

Abdomen↗

Time-dependent inhibition of growth of human keratinocytes and fibroblasts by cyclosporin A: effect on keratinocytes at therapeutic blood levels.

The effect of cyclosporin A (CyA) on the growth of cultured normal human keratinocytes and fibroblasts was studied. Tritiated thymidine incorporation per DNA content was used for short-term studies (1-2 days) and cell counting for longer term studies (up to 14 days). CyA caused a dose- and time-dependent inhibition of growth of both cell types. Keratinocytes (serum free, 70 microM Ca2+) were more sensitive to CyA than fibroblasts (10% serum). For keratinocytes, at 2 days growth was 61% and 6% of controls with 3 and 10 micrograms/ml CyA, respectively, at 4 days growth was 51% with 1 microgram/ml with complete inhibition at 10 micrograms/ml, and at 11 days growth was 58 and 39% with 0.1 and 1 micrograms/ml. For fibroblasts, at 4 days growth was 72 and 58% of controls with 10 and 30 micrograms/ml CyA, respectively, at 10 days growth was 76, 43 and 10% with 3, 10 and 30 micrograms/ml, and at 14 days growth was 41 and 11% with 3 and 10 micrograms/ml with complete inhibition with 30 micrograms/ml. For keratinocytes the effect of 24 h of CyA on growth was reversible. Growth of keratinocytes was inhibited by 10% delipidized serum, and 1% serum had a small stimulatory effect, but the action of CyA was unaltered. We conclude that increasing the duration of exposure to CyA increases the concentration-dependent growth inhibition. At therapeutic blood levels of CyA the growth of cultured keratinocytes but not fibroblasts is inhibited. The benefit of CyA in reducing the hyperproliferation of psoriasis may include a direct effect on keratinocytes.

Cell Count↗

The value of electronmicroscopy and immunohistochemistry in the diagnosis of soft tissue sarcomas: a study of 200 cases.

Two hundred soft tissue sarcomas, accrued consecutively over a 4-year period, were examined by light and electronmicroscopy and by routine immunohistochemistry. The commonest tumour type was malignant fibrous histiocytoma. Fibrosarcoma, composed only of fibroblasts, was diagnosed in only one case; three others, composed also of myofibroblasts, could be regarded as fibrosarcomas or myofibrosarcomas. Immunohistochemistry was of most value in the diagnosis of rhabdomyosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumour of Schwann cell type and epithelioid sarcoma. Electronmicroscopy was of most use for the diagnosis of malignant peripheral nerve sheath tumour of perineurial cell type and marker-negative monophasic synovial sarcoma, and for confirming malignant fibrous histiocytoma. Fifteen of 19 marker-negative spindle cell tumours (79%) were diagnosable by electronmicroscopy. A combination of techniques resulted in a specific diagnosis in 193 cases (96.5%). The routine use of electronmicroscopy in sarcoma diagnosis can improve accuracy of diagnosis, establish the true frequency of marker-positivity for each ultrastructurally confirmed tumour type and minimise the number of unclassifiable cases.

Biomarkers, Tumor↗

Persistent carcinoma in situ of the testis after chemotherapy for advanced testicular germ cell tumours.

The chemosensitivity of testicular carcinoma in situ (CIS) was analysed in 25 testes excised 10 weeks to 4.5 years following platinum-based chemotherapy. CIS was present in 8 of the 23 evaluable cases (35%), in 5 of which the lesion coexisted with invasive germ cell tumour. It is concluded that CIS may persist or recur after chemotherapy. This has implications for occult presentation of metastatic germ cell tumours and also for the management of the contralateral testis in patients with testicular germ cell tumours.

Adolescent↗

Decrease in xenon clearance during response to cold, dry air: problems of interpretation.

In order to increase our understanding of the nasal response to cold, dry air (CDA), we studied changes in xenon clearance as an indicator of nasal blood flow. Eight individuals previously shown to respond to CDA had measurements of xenon clearance made in the left inferior turbinate before, during, and after a 15-minute exposure to either CDA (-7 degrees C to 0 degrees C, less than 10% relative humidity) or room air. The half-life in seconds for xenon clearance on the day when CDA was inhaled was 56 +/- 6, 41 +/- 5, and 110 +/- 31, before, during, and 10 minutes after challenge, respectively. On the control day, with subjects breathing room air, the equivalent measurements of half-life in seconds were 54 +/- 8, 41 +/- 6, and 42 +/- 4, respectively. Xenon clearance was prolonged significantly (p less than .01) after exposure to CDA during the clinical response. The interpretation of the change in xenon clearance as an indicator of nasal blood flow is discussed.

Air↗

A midwife's view of the history of modern breastfeeding practices.

The author finds that three things make breastfeeding successful: the mother's desire; correct positioning of the baby; and the baby's control of time at the breast. Restrictions of feeding time originated early in this century. Combined with descriptions of babies sucking from the nipple instead of the breast, misinformation has spread about breastfeeding in spite of correct knowledge being available. A review of textbooks and articles should be undertaken.

Breast Feeding↗