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Biomedical subjects

H J Shaw

Publications and source records attributed to H J Shaw.

At least 19 recordsLinked to original sources

Effects of oestradiol-17 beta on FSH-stimulated steroidogenesis in cultured marmoset granulosa cells.

A role for oestradiol in ovarian follicular development is well recognized. However, a number of disparate effects have been reported for the action of oestradiol in the primate ovary. To investigate this further, we have examined the effects of oestradiol on the differentiation of granulosa cells isolated from small (0.5-1 mm) antral follicles obtained from the ovaries of prepubertal marmoset monkeys (Callithrix jacchus). Granulosa cells were co-cultured with oestradiol and human FSH (hFSH) for 48 h, or were pretreated with oestradiol for 48 h before addition of gonadotrophin for a further 48 h. Oestradiol (0.01-100 nmol/l) had no effect on basal or hFSH-stimulated progesterone accumulation and aromatase activity when the hormones were added concurrently. Furthermore, oestradiol did not influence the ability of hFSH to induce LH/human chorionic gonadotrophin (hCG) responsiveness in immature granulosa cells. The absence of synergism between oestradiol and hFSH in the induction of marmoset granulosa cell differentiation was independent of the presence of phenol red in culture medium. However, gonadotrophin-stimulated steroidogenesis was attenuated when cells were cultured in the presence of phenol red compared with in its absence; this effect was more pronounced for gonadotrophin-stimulated aromatase activity but was evident for LH/hCG-stimulated progesterone accumulation at higher doses of hCG (10 and 100 ng/ml). An effect of phenol red on basal steroidogenesis was less obvious.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Role of partial laryngectomy after irradiation in the treatment of laryngeal cancer: a view from the United Kingdom.

This retrospective study evaluates the use of conservation surgical salvage techniques in cases of early (T1 and T2) laryngeal cancer after full-dose external irradiation. Fifty patients in one London hospital and 68 patients in another were studied for the period 1963 to 1988. Treatment policy directed that the majority of limited glottic and supraglottic tumors should be treated initially by external irradiation. The small number of glottic treatment failures had a good chance of salvage by vertical partial laryngectomy if recurrence or a new primary was detected early. Recurrence of supraglottic cancer was salvaged occasionally by horizontal partial laryngectomy if strict indications were observed. Total laryngectomy remained the final minority salvage option.

Cobalt Radioisotopes

Fine needle aspiration cytology in the head and neck region.

Although needle aspiration diagnosis was described over 50 years ago, many patients with neck swellings are still subjected to hazardous and unnecessary open diagnostic surgical biopsy. In a six-month period, over 200 fine needle aspirates were performed on tumours from the head and neck region, 44% of which were positive for cancer. The technique of aspiration, its advantage for the patient, clinician and cytopathologist, and the results of the study will be discussed. Close cooperation between the clinician and the cytopathologist is essential.

Adolescent

Developmental changes in luteinizing hormone/human chorionic gonadotropin steroidogenic responsiveness in marmoset granulosa cells: effects of follicle-stimulating hormone and androgens.

Factors regulating LH/hCG responsiveness in primate granulosa cells were examined in the marmoset monkey (Callithrix jacchus). Granulosa cells were isolated and pooled from small antral (0.5-1.0 mm) and large preovulatory (greater than or equal to 2 mm) follicles from mid- to late follicular phase ovaries of cyclic marmosets. The cells from small and large follicles were cultured in serum-free medium for 48 h in the absence or presence of increasing concentrations of hCG (0.1-100 ng/ml) with or without 0.1 microM androgen [testosterone or 5 alpha-dihydrotestosterone (DHT]). Granulosa cells from small follicles were also cultured in the absence or presence of a constant concentration of human FSH (30 ng/ml) with or without androgen for 48 h before exposure to hCG for an additional 48 h. Steroidogenic responsiveness was assessed by measuring progesterone accumulation in culture medium and aromatase activity in washed monolayers. Granulosa cells from large follicles showed dose-dependent increases in both progesterone accumulation and aromatase activity in response to treatment with hCG. In contrast, granulosa cells from small follicles were unresponsive to hCG. However, pretreatment of granulosa cells from small follicles for 48 h with FSH stimulated hCG responsiveness. The effects of both testosterone and DHT on hCG-stimulated aromatase activity and progesterone accumulation by granulosa cells from large preovulatory follicles were inhibitory. Testosterone and DHT also suppressed basal (no hCG) progesterone accumulation in these cells, but had no effect on basal aromatase activity. The effects of androgens on FSH-induced hCG responsiveness in immature granulosa cells were variable. The results show a development-related increase in marmoset granulosa cell responsiveness to LH/hCG and provide evidence that FSH and androgens interact to regulate the onset and expression of this critical event during preovulatory follicular development in the primate ovary.

Androgens

Surgical salvage for squamous cancer involving the supraglottic larynx.

Anatomically the supraglottic larynx has been shown to be self contained as regards its boundaries and lymphatic compartments which tend to limit the spread of cancer arising within the region until it reaches the margins of the supraglottis (Pressman and Simon, 1961). These may be called Type A tumours. Advanced glottic tumours secondarily involving the supraglottis may be considered a sub-group within the larynx (transglottic).

Carcinoma, Squamous Cell

A modification of the MacFee incisions for neck dissection.

The dissection of cervical lymphatics for cancer after radiotherapy imposes a special need to ensure good healing of skin flaps with good access and acceptable aesthetic results. Adaptability of incisions for extended surgery is also desirable. Although it is felt that the adoption of the basic MacFee incision pattern fulfils these criteria, the author has for years employed curved modifications of the two horizontal incision lines. This develops a waisted skin bridge which is freely mobile and gives better access to the deep structures. The technique is contrasted with other approaches and described in detail. It complies with the safe principle of join-free linear incisions and is practical for regular use.

Humans

Induction cytotoxic chemotherapy: the significance of apparent complete clinical regression after using the Price Hill Schedule A protocol for squamous carcinoma of the head and neck.

A small group of 46 previously untreated patients out of about 260 in all who have received Price Hill Schedule A cytotoxic chemotherapy, achieved apparent complete clinical regression (ACCR) of their disease before local treatment. Forty patients were classified T3 or T4, over half having clinically positive nodes at the start of treatment. A determinate survival rate of 70 per cent disease free at three years was obtained and 74 per cent achieved quality relief of all symptoms. Two patients declined local treatment and survived three years disease free after chemotherapy alone. No recurrence has occurred to date in seven patients achieving apparent complete histological regression (ACHR) in their surgical specimens. Although ACCR does not automatically improve prognosis it is likely that it does enhance the complete remission rate, especially for those also achieving ACHR. Benefits to patients obtaining ACCR with this minimally toxic chemotherapy schedule are listed.

Adult

Cellular aspects of pre-ovulatory folliculogenesis in primate ovaries.

According to current concepts of pre-ovulatory folliculogenesis in primate ovaries, each growing follicle has a 'threshold' requirement for stimulation by FSH which must be met if it is to enter the oestrogen-secretory phase of pre-ovulatory development. Until recently, our understanding of the intra-follicular mechanisms underlying FSH action on granulosa cells was based largely on information from non-primate laboratory animals, mainly polyovulators such as rats. The present paper describes studies on FSH-regulated granulosa cell function in relation to pre-ovulatory development in vivo and in vitro using a laboratory primate, the common marmoset (Callithrix jacchus). Measurement of aromatase activity is used as an index of granulosa cell cytodifferentiation to verify three major tenets of the 'threshold' hypothesis: (i) that granulosa cells acquire increased responsiveness to FSH and LH during pre-ovulatory growth; (ii) that these developmentally related changes are directly induced by FSH; and (iii) that intrafollicular steroids modify FSH action and thereby contribute to the establishment of follicular FSH thresholds. The results obtained highlight the value of this experimental animal model for studies of cellular and molecular aspects of pre-ovulatory folliculogenesis which are relevant to human ovaries.

Animals

Factors influencing follicle-stimulating hormone-responsive steroidogenesis in marmoset granulosa cells: effects of androgens and the stage of follicular maturity.

Preovulatory changes in the steroidogenic function of primate granulosa cells were studied using the cyclic marmoset (Callithrix jacchus) as a model. Antral follicles (greater than or equal to 0.5 mm diameter) were dissected from mid-late follicular phase ovaries (7 days after prostaglandin-induced luteolysis) and classified by diameter as small (0.5-1.0 mm), medium (1.1-1.9 mm) or large (greater than or equal to 2.0 mm). Granulosa cells from follicles in each size category were isolated and pooled to assess steroid biosynthesis. The aromatase activity of freshly isolated granulosa cells from large follicles was 200 times greater than that of small follicles, confirming their relatively advanced preovulatory status. Granulosa cells were cultured for 48 h in the presence and absence of human (h) FSH (0.1 ng/ml), with and without 0.1 microM androgen (testosterone or 5 alpha-dihydrotestosterone), to assess basal and hormone-responsive steroidogenesis (progesterone accumulation in culture medium and aromatase activity in washed granulosa cell monolayers). Basal granulosa cell steroidogenesis increased with follicular size, and there was a development-related pattern of response to hFSH and androgen. hFSH responsiveness (maximum fold-stimulation induced by hFSH) declined with follicular size, being 2-6 times greater for granulosa cells from small vs. large follicles. On the other hand, hFSH sensitivity increased with follicular size; the dose of hFSH giving 50% of the maximum response (ED50) for cells from large follicles being 10-20 times less than that of cells from small follicles. For granulosa cells from small follicles, treatment with 0.1 microM androgen in the presence of hFSH led to dramatic (up to 16-fold) enhancement of steroidogenic responses to hFSH. In contrast, for granulosa cells from large follicles, the presence of androgen substantially inhibited aromatase activity stimulated by hFSH and had weak inhibitory effects on progesterone accumulation. These results show that granulosa cell steroidogenesis becomes increasingly sensitive to hFSH during preovulatory follicular development in marmosets. The marked ability of androgen to directly augment hFSH-responsive steroidogenesis in vitro is lost during preovulatory development, such that androgen acts in mature granulosa cells to suppress hFSH-stimulated aromatase activity. These observations are evidence of development-dependent changes in granulosa cell responses to FSH and androgens which may contribute to the control of preovulatory follicular development in primates.

Androgens

Total glossectomy.

Total glossectomy is a procedure based on sound oncologic principles, and its usefulness may not be fully appreciated. Given the dimensions of the tongue and the need to obtain a wide margin of resection, this procedure may be indicated in selected T3 lesions and recurrences after irradiation. The procedure offers excellent palliation of pain, and form and function may be preserved by rim mandibulectomy when indicated. New reconstructive techniques allow for speedier recovery. Aspiration need not be a complication of total glossectomy if care is taken to preserve the superior laryngeal nerve. Speech rehabilitation plays an important role in returning these patients to their normal environment. Overall 1 and 3 year disease-free survival rates have been encouraging.

Adolescent

A view of partial laryngectomy in the treatment of laryngeal cancer.

Attention is drawn to the problems of surgical resection by partial laryngectomy after full therapeutic dosage of telecobalt irradiation. Material is presented from two treatment centres to indicate trends in surgical treatment and the complications experienced. Results will be given which confirm a reasonable expectation of cure and functional conservation by vertical partial laryngectomy for recurrence of glottic cancer after irradiation. The results of treatment of recurrent supraglottic cancer by horizontal partial laryngectomy gave more cause for concern in terms of complications and survival. In conclusion an attempt is made, based on the quoted experience, to define the position of conservation surgery in two centres for laryngeal cancer in the United Kingdom.

Combined Modality Therapy

Advanced laryngeal cancer: a management perspective.

A retrospective study of 197 T3 and T4 squamous cell carcinomas of the larynx presenting between 1969 and 1978 has been undertaken. These patients have in the main been treated by primary radiotherapy with back-up salvage surgery. The aim of the study was to examine survival, and to try to identify reasons for failure of control. Various prognostic factors have been analysed and are discussed. Overall 5-year survival was 53 per cent but patients with nodal disease responded poorly. Subglottic tumours have a better survival than usually reported. Failure to pick up recurrence was the main problem, and in particular a persistently fixed cord carried a very poor prognosis if laryngectomy was delayed.

Aged

Relationships between luteinizing hormone, follicle-stimulating hormone and prolactin secretion and ovarian follicular development in the weaned sow.

Folliculogenesis was studied by assessing development of the largest 10 follicles obtained from 10 sows 48 h after weaning and by analyzing changes in plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) for 24 h before weaning until 48 h after weaning. Follicular diameter, follicular fluid volume, and concentrations of estradiol and testosterone and granulosa cell numbers were determined in all follicles, and 125I-hCG binding to theca and granulosa and maximal aromatase activity in vitro was determined in five follicles/sow. Overall, a significant rise in LH, but not in FSH, occurred at weaning, although in individual sows an increase in LH was not necessarily related to subsequent estrogenic activity of follicles. In 9/10 sows, PRL fell precipitously after weaning. In lactation, LH was negatively, and after weaning, positively, correlated with FSH and PRL. Marked variability in follicular development existed within and between sows. Overall, most follicular characteristics were positively correlated to follicular diameter; however, in larger follicles the number of granulosa cells was variable and unrelated to estrogenic activity, which--together with theca and granulosa binding of hCG--increased abruptly at particular stages of follicular development. Differences in maturation of similarly sized follicles from different sows were related to estrogenic activity of the dominant follicles but not to consistent differences in LH, FSH or PRL secretion. Both the dynamics and the control of folliculogenesis in the sow, therefore, appear to be complex.

Animals

The use of free tissue transfer in reconstruction following head and neck tumour resection.

Experience in the use of free vascularised tissue flaps in reconstruction following major head and neck resections for malignant disease has been described. The benefits of the use of free flaps are improved function and cosmesis with more rapid rehabilitation and reduced in-patient stay in a group of patients, many of whom had a limited life expectancy. The disadvantages of this technique are the need for special equipment and for medical and nursing staff trained and experienced in this type of work.

Adult

Uncommon malignant tumours of the larynx. A 35 year review.

Sixty-five primary malignant laryngeal tumours, other than simple squamous cell carcinomas, treated at the Royal Marsden Hospital between 1949 and 1984 are presented. Of the 11 histological types pseudosarcomas (24 cases), verrucous carcinomas (9 cases) and lymphoreticular tumours (9 cases) predominated. Determinate three-year follow-up data were available in 50 cases. Sixteen patients (32 per cent) died of their neoplasms but survival was strongly related to histology. Only one death occurred among 24 determinate cases of pseudosarcoma and verrucous carcinoma. Radiotherapy was effective treatment for these two tumour types and for reticuloendothelial tumours. However, combined therapy yielded poor results with the other histological types.

Combined Modality Therapy