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Biomedical subjects

C Fisher

Publications and source records attributed to C Fisher.

At least 415 records · Page 23Linked to original sources

Ifosfamide plus mesna with and without adriamycin in soft tissue sarcoma.

Early results with ifosfamide plus mesna in soft tissue sarcoma showed an initial response rate of 38% in 42 patients. All these patients treated at The Royal Marsden Hospital plus 30 more (total 67) have now been analysed. Single doses of 5 or 8 g/m2 ifosfamide were given over 24 h by infusion in dextrose saline together with 400 mg/m2 or 600 mg/m2, respectively, of mesnum every 4 h to give a total of 9 doses. A diuresis of 200 ml/hour was maintained during therapy. Treatment was repeated 3-weekly. CR was seen in 6 and PR in 10 patients. More recently doxorubicin was added to ifosfamide therapy in an attempt to improve on these results. At first only 20 mg/m2 doxorubicin was given but this was escalated to 40 mg/m2 and 60 mg/m2. Mesna has been given in higher dosage (5 g/m2 over 24 h), but otherwise the schedule is as above. In all 60 patients have been treated and most are now evaluable for response. Encephalopathy has been seen with both regimens. The incidence and patient characteristics are reported.

Adolescent↗

Plasma prolactin and estradiol during sleep in impotent men and normal controls.

There are no investigations of sleep-related changes in circulating prolactin and estradiol in impotent men without known organic pathology. This study compares plasma levels of both hormones during sleep in 17 physically healthy patients with erectile impotence and 11 normal controls. Five men had never been able to achieve intercourse (primary impotent group) and 12 suffered from a lifelong history of intermittent erectile failure (secondary impotent group). The subjects, aged 23 to 36, were studied in a sleep laboratory from 3 to 6 nights with the last two devoted to sequential blood sampling every 20 min. Samples were pooled during consecutive 2-hr periods from 11 PM to 7 AM for hormonal assessment. There were no statistical differences in sleep measures among groups. Mean prolactin and estradiol values for all subjects were within the normal range. Both impotent groups showed a significant nocturnal increase in prolactin concentration and no time-related changes in plasma estradiol. There were no statistical differences in the plasma concentration of both hormones among groups or between study nights. The results suggest that severe and long-lasting erectile failure may occur in physically healthy individuals without associated abnormalities in circulating prolactin and estradiol.

Adult↗

Synovial sarcoma: ultrastructural and immunohistochemical features of epithelial differentiation in monophasic and biphasic tumors.

Nineteen synovial sarcomas, six biphasic and 13 monophasic tumors, were examined by light and electron microscopy and immunohistochemically for the presence of the epithelial markers keratin and epithelial membrane antigen (EMA). Ultrastructurally, intercellular spaces with processes are present to varying degrees in the spindle cell component of all synovial sarcomas, and junctional specializations occur in most cases. Tumors of the two types differ in their content of external (basal) lamina, which encloses the epithelial component of all biphasic tumors and is detectable in the spindle cell component of two thirds of them, but is absent from the majority of monophasic tumors. Keratin and EMA were demonstrated in both components of all six biphasic tumors. Of the 13 monophasic tumors, keratin was present in nine, EMA in eight, and at least one epithelial marker in ten. Synovial sarcoma is regarded as a distinctive soft tissue tumor with variable epithelial-like differentiation. The use of electron microscopy can increase the specificity of immunohistochemical studies of soft tissue sarcomas and allow more accurate differentiation of monophasic synovial sarcoma from other spindle cell tumors, particularly those that do not express markers.

Epithelium↗

Measurement of lipogenesis in isolated preputial gland cells of the rat and the effect of oestrogen.

Lipogenesis was measured in isolated preputial gland cells of female rats after ovariectomy and after the administration of oestradiol benzoate. Ovariectomy decreased preputial gland cell lipogenesis and also altered the pattern of lipid synthesis, producing a relative decrease in the proportion of polar lipids and an increase in the proportion of 'triglycerides'. Although daily administration of 2 or 10 micrograms oestradiol benzoate for 7 days produced slight increases in preputial gland cell lipogenesis in ovariectomized rats, the effects were not significant. A single injection of 10 micrograms oestradiol benzoate, however, produced significant increases in preputial gland cell lipogenesis of ovariectomized rats at both 2 and 24 h and, moreover, at 24 h the pattern of polar lipid and triglyceride labelling was restored to normal. Prior administration of actinomycin D reduced the lipogenic effect of oestradiol benzoate. Oestradiol benzoate had little or no effect on preputial gland cell lipogenesis in male rats. These results confirm that oestrogen is able to stimulate preputial lipogenesis in female rats. Whether this action of oestrogen is related to its pheromone-producing effect on the preputial glands is not yet known.

Animals↗

Evidence for increased epidermal growth factor receptors in human sarcomas.

The results of an immunocytochemical study of the epidermal growth factor receptor (EGFR) in 35 human soft-tissue sarcomas, using a murine monoclonal antibody (MAb) EGF-R1, are reported. In many of the tumours staining was stronger than in the adjacent stroma, suggesting increased levels of receptor. Particularly strong staining was seen in one epithelioid sarcoma and in the spindle-cell component of a synovial sarcoma. Binding studies carried out on an epithelioid sarcoma cell line established from one of the specimens, using radiolabelled EGF, showed that approximately 8% of the receptors were of high affinity with a dissociation constant (KD) of approximately 10(-10)M, while the remainder were of lower affinity with a KD of 10(-9)M. The cells expressed a total of 1.7 X 10(6) receptors/cell which is equivalent to that found in some epidermoid tumours where gene amplification has been demonstrated. These data suggest that, as with other tumours recently reported, increased levels of epidermal growth factor receptor may be related to transformation.

Antibodies, Monoclonal↗

Nocturnal penile tumescent evaluation of erectile function in insulin-dependent diabetic men.

This study compared nocturnal penile erections in four age-matched groups of young subjects: diabetic patients with and without erectile problems, psychogenically impotent men and healthy control subjects. All men were assessed under similar conditions during three nights, each for a total of 156 study nights. Diabetic impotent men exhibited a significantly decreased number of erectile episodes (p less than 0.05) and episodes of maximum tumescence per night (p less than 0.01). They also spent significantly less time in tumescence (p less than 0.005) and in simultaneous rapid eye movement sleep and tumescence (p less than 0.005). Diabetic men without sexual problems, psychogenically impotent men, and normal control subjects did not differ. Diabetic men in both groups spent less sleep time in rapid eye movement sleep and had longer latencies to onset of rapid eye movement. The decreased time in erection noted in impotent diabetic patients was no longer significant when adjusted for differences in duration of rapid eye movement sleep. In comparison to healthy control subjects and psychogenically impotent men, non-impotent diabetic men did show significantly diminished circumferential increases during erections, similar in degree to impotent diabetic patients (p less than 0.05).

Adult↗

Modification of the United States' diet to effect changes in blood lipids and lipoprotein distribution.

Twenty men, 19 premenopausal and 14 postmenopausal women consumed a diet for 13 weeks that supplied 35% of the calories from fat, 50% from carbohydrate, and 15% from protein. The diet was low in cholesterol, saturated fat, and salt, and high in complex carbohydrate and fiber. The 7-day menu was composed of common well-accepted foods prepared in a simple attractive manner. Plasma total cholesterol, LDL cholesterol, and VLDL cholesterol were reduced, but triglyceride levels were not different than after self-selected diets. When 20% of the complex carbohydrate was replaced by simple carbohydrate and other diet components remained optimal, triglyceride and VLDL cholesterol levels increased in men and premenopausal women and total cholesterol increased in premenopausal women. These results suggest that beneficial effects on the blood lipids and lipoprotein distribution of men and women may be obtained by minimal modification of a typical U.S. diet.

Adult↗

Lupus-like nephritis heralding the definitive manifestation of systemic lupus erythematosus.

Four patients presented with the nephrotic syndrome. The histological appearances on renal biopsy were in three characteristic and in one suggestive of lupus nephritis. These patients did not initially have other clinical features of SLE, but three had a positive ANA and one a raised DNA titre. Remission occurred in two patients, in one spontaneously and in another following corticosteroid therapy, but two developed renal failure. During follow-up all developed elevated DNA binding levels and arthralgia or lymphopenia. The ARA classification criteria for lupus were only fulfilled at this late stage.

Adult↗

An assessment of the value of electron microscopy in tumour diagnosis.

The contribution of electron microscopy to the diagnosis of tumours in a general hospital has been investigated. During a three year period 235 cases were examined, of which 66 (28%) were diagnostic problems by light microscopy. In 42 (64%) of the problem cases a contribution towards diagnosis was made by ultrastructural examination, which was most useful for anaplastic polygonal cell tumours, of some value for spindle cell neoplasms, and least helpful in the further categorisation of metastatic carcinoma.

Humans↗

The measurement and characterisation by high pressure liquid chromatography of immunoreactive alpha-melanocyte stimulating hormone in human plasma.

Immunoreactive alpha-MSH was found in human plasma and in normal subjects ranged from less than 10-45 pg/ml. Plasma alpha-MSH concentrations were within the normal range in 13 out of 15 subjects during the last trimester of normal pregnancy and only just outside the normal range in the remaining two. Elevated plasma alpha-MSH concentrations were found in 6 of the 11 patients with Nelson's syndrome and in 10 of the 11 patients with pituitary dependent Cushing's disease. Separation on high pressure liquid chromatography (HPLC) revealed two major peaks of immunoreactivity. These peaks, which were identified as des-acetyl alpha-MSH and alpha-MSH were similar in size in normal subjects and Cushing's disease. In Nelson's syndrome, on the other hand, there was a greater proportion of des-acetyl alpha-MSH and it is possible that this peptide is secreted from tumour cells of anterior lobe origin. Although there was no correlation between the circulating alpha-MSH and the degree of pigmentation the high concentrations of plasma immunoreactive alpha-MSH in Cushing's disease and the HPLC profiles in Nelson's syndrome could provide useful information as to the localization of the defects in these particular disorders.

Adolescent↗

Granular cell tumour of the breast.

Four cases of granular cell tumour of the breast reflecting the lifetime experience of one surgeon are presented. Recent advances in the pathology of this condition suggest that the customary term 'myoblastoma' is inappropriate, and that 'granular cell tumour' is preferable. The clinical and pathological features are reviewed and the differential diagnoses discussed, with emphasis on the distinction from carcinoma which may be mimicked both clinically and on frozen examination. The diagnosis may be made by pre-operative aspiration cytology, and a conservative surgical approach is recommended.

Adult↗

Abnormal skin development in pupoid foetus (pf/pf) mutant mice.

At 13 days of development the epidermis of mice homozygous for the pupoid foetus (pf/pf) mutation varies in thickness between one and ten cell layers. By 16 days of development cells from the dermis have invaded the epidermis and may be found throughout the epidermis and on its surface. Among these cells are nerve fibres and Schwann cells as well as other unidentified cells. Antibodies directed against fibronectin bind to these abnormal groups of cells in the mutant epidermis and on its surface. A basal lamina, as determined by ultrastructure and by the immunofluorescent localization of laminin, was always found at the interface of the mutant epidermis and the invading cell population. By 19 days of development the mutant epidermis is thickened and is permeated by a network of cells including nerve fibres, Schwann cells, blood vessels, and collagen and fibronectin-secreting cells. A basal lamina always separates these groups of invading cells from the epidermal cell population.

Animals↗

Clear-cell sarcoma of tendons and aponeuroses: a clinicopathologic study. Presentation of six additional cases with review of the literature.

Clear-cell sarcoma of tendons and aponeuroses is a rare and slowly growing soft tissue sarcoma, affecting mainly young adults. During the last 15 years, approximately 60 cases have been reported in the literature. In this report, six additional cases followed in the Sarcoma Unit at The Royal Marsden Hospital are presented, representing approximately 1% of the total number of sarcomas treated in our unit between 1972 and 1982. A review of the literature has also been included.

Adolescent↗