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Biomedical subjects

T W Lennard

Publications and source records attributed to T W Lennard.

At least 19 recordsLinked to original sources
PubMed2001

Germline SDHD mutation in familial phaeochromocytoma.

The genetic basis for familial phaeochromocytoma is unknown in many cases. Since the disorder has been reported in some cases of familial head and neck paraganglioma, which is caused by a mutation in the gene encoding succinate dehydrogenase complex subunit D (SDHD), we investigated this gene in kindreds with familial phaeochromocytoma. A germline SDHD frameshift mutation was identified in a two-generation family consisting of four children with phaeochromocytoma, but somatic mutations were not detected in 24 sporadic phaeochromocytoma tumours. Germline SDHD mutation analysis should be done in individuals with familial, multiple, or early-onset phaeochromocytomas even if a personal or family history of head and neck paraganglioma is absent.

Adolescent↗
PubMed2001

Management of a pregnant patient with Graves' disease complicated by thionamide-induced neutropenia in the first trimester.

A 31-year-old woman presented with neutropenia due to thionamide drug therapy for Graves' disease. She also reported 8 weeks of amenorrhoea and had a positive pregnancy test. Her drug therapy was discontinued and her neutropenia resolved uneventfully. The hyperthyroidism recurred a week later. After consideration of all treatment options, it was decided to observe until 14 weeks when an elective thyroidectomy was planned. Mother and fetus were monitored closely and both tolerated moderate hyperthyroidism well. At 14 weeks the patient underwent a total thyroidectomy after rendering her euthyroid with a short course of sodium ipodate. Labour was induced at 41 weeks. Delivery was complicated by fetal distress and precipitated a forceps delivery. A 3250 g male infant was born with poor Apgar score and required 2 h of ventilation. At 1 year, the child had reached all developmental milestones at appropriate times. Both mother and fetus may tolerate moderate thyrotoxicosis well in early pregnancy, an alternative that should be considered when thionamide drug therapy is contraindicated.

Adult↗
PubMed2001

Aggressive local treatment for screen-detected DCIS results in very low rates of recurrence.

AIMS: To review our institution's practice of treatment of a mammographically detected population of ductal carcinoma in situ (DCIS) patients and to determine the outcome. METHODS: Between April 1989 and March 1994, 304 women with median age 59 years (range 51-65) with DCIS detected on screening mammogram, were treated in the Newcastle General and Royal Victoria Infirmary Hospitals, Newcastle-upon-Tyne, UK. More than half of the women (n=176, 57.8%) decided to have mastectomy. Other treatment options were wide local excision (WLE) with radiotherapy (n=97, 32%) and WLE alone (n=31, 10.2%). All except five received adjuvant hormone treatment. RESULTS: Predominant DCIS was comedo in 122 (42%), followed by cribriform in 87 (30%) and micropapillary in 44 (15%) cases. Grade I was found to be commonest grade (54%) followed by grade II (27%) and grade III (11%). With a median follow-up of 88 months, there were six (2%) recurrences, all of which were in women who were given breast conservation treatment, WLE with radiotherapy (n=1, 1%) and without radiotherapy (n=5, 16.6%). Mastectomy in this series was not associated with any recurrence at all. In three cases the recurrence was invasive, one of who also had distant metastasis. CONCLUSIONS: The findings of this study suggest that in women with DCIS suitable for breast conservation, WLE when combined with radiotherapy is associated with a very low recurrence rate.

Antineoplastic Agents, Hormonal↗
PubMed2001

Adverse and beneficial effects of plant extracts on skin and skin disorders.

Plants are of relevance to dermatology for both their adverse and beneficial effects on skin and skin disorders respectively. Virtually all cultures worldwide have relied historically, or continue to rely on medicinal plants for primary health care. Approximately one-third of all traditional medicines are for treatment of wounds or skin disorders, compared to only 1-3% of modern drugs. The use of such medicinal plant extracts for the treatment of skin disorders arguably has been based largely on historical/anecdotal evidence, since there has been relatively little data available in the scientific literature, particularly with regard to the efficacy of plant extracts in controlled clinical trials. In this article therefore, adverse and beneficial aspects of medicinal plants relating to skin and skin disorders have been reviewed, based on recently available information from the peer-reviewed scientific literature. Beneficial aspects of medicinal plants on skin include: healing of wounds and burn injuries (especially Aloe vera); antifungal, antiviral, antibacterial and acaricidal activity against skin infections such as acne, herpes and scabies (especially tea tree (Melaleuca alternifolia) oil); activity against inflammatory/immune disorders affecting skin (e.g. psoriasis); and anti-tumour promoting activity against skin cancer (identified using chemically-induced two-stage carcinogenesis in mice). Adverse effects of plants on skin reviewed include: irritant contact dermatitis caused mechanically (spines, irritant hairs) or by irritant chemicals in plant sap (especially members of the Ranunculaceae, Euphorbiaceae and Compositae plant families); phytophotodermatitis resulting from skin contamination by plants containing furocoumarins, and subsequent exposure to UV light (notably members of the Umbelliferae and Rutaceae plant families); and immediate (type I) or delayed hypersensitivity contact reactions mediated by the immune system in individuals sensitized to plants or plant products (e.g. peanut allergy, poison ivy (Toxicodendron) poisoning).

Burns↗
PubMed2001

Adrenal masses: the investigation and management of adrenal incidentalomas.

Most general surgeons will face at sometime in their career an 'incidentaloma' of the adrenal gland. How should a surgeon approach an incidentaloma found during routine investigation for other unrelated disease processes? This paper discusses the investigation and management of adrenal incidentalomas and includes guidelines for the non-specialist.

Adrenal Gland Neoplasms↗
PubMed2000

Thyroid aspiration cytology in Newcastle: a six year cytology/histology correlation study.

BACKGROUND: Fine needle aspiration cytology (FNAC) is a well-established technique for pre-operative investigation of thyroid nodule(s). Thyroid FNAC was introduced in the teaching hospitals of Newcastle upon Tyne in 1981, initially with a small group of clinicians as aspirators. Audit results for 1981-1986 inclusive showed an unsatisfactory rate of 25.3% and prediction of malignancy with a sensitivity of 93.5%. FNAC has become more popular locally for the investigation of thyroid disease and the number of clinicians performing aspirates has increased. The results for recent years have, therefore, been audited. METHODS: Medical records were reviewed for 239 patients with a dominant thyroid nodule who had FNAC carried out in the 6 year period 1990-1995 and subsequent partial or complete thyroidectomy. RESULTS: Histology of thyroid specimens showed 60 follicular adenomas and 34 malignant lesions (including 19 papillary, 10 follicular and 3 medullary carcinomas, one lymphoma and one follicular neoplasm with indeterminate malignant potential). A total of 302 FNAC had been carried out on these 239 patients. On cytological grounds the unsatisfactory sample (AC0 and AC1) rate was 43.1% on initial aspiration which was reduced to 32.2% on repeated aspiration. FNAC predicted neoplasia (AC3, AC4 and AC5) with a sensitivity of 86.8%, a specificity of 67.0%, a negative predictive value of 87.5% and a positive predictive value of 65.5%. Malignancy was predicted by FNAC (AC3, AC4 and AC5) with a sensitivity of 88.9%. A FNAC report of AC5 had a positive predictive value for malignancy of 100%. CONCLUSIONS: FNAC is an invaluable and minimally invasive procedure for the pre-operative assessment of patients with a dominant thyroid nodule. It is, however, important that the number of aspirators and cytopathologists be kept small to maintain expertise and also that the results of FNAC be subjected to ongoing audit.

Adolescent↗
PubMed2000

Therapeutic applications of medicinal plants in the treatment of breast cancer: a review of their pharmacology, efficacy and tolerability.

Various active compounds (or their semi-synthetic derivatives) derived from medicinal plants have been assessed for their efficacy and tolerability in the treatment of breast cancer. Some of these plant species, including Taxus baccata (paclitaxel, docetaxel), Podophyllum peltatum (etoposide), Camptotheca acuminata (camptothecin) and Vinca rosea (vinblastine, vinorelbine) have well recognized antitumour activity in breast cancer, and have been evaluated in clinical trials. For example, results from recent Phase II/III trials have established docetaxel as the most active single agent in the treatment (first or second-line) of advanced metastatic breast cancer. For other plant species such as Panax ginseng and Allium sativum, antitumour activity has been evaluated in experimental studies using cultured cells and animal models, but the therapeutic potential in patients remains to be determined. Antitumour activity derived from medicinal plants may produce results via a number of mechanisms, including effects on cytoskeletal proteins which play a key role in mitosis (paclitaxel), inhibition of activity of topoisomerase enzymes I (camptothecin) or II (etoposide), stimulation of the immune system (Viscum album), or antiprotease-antioxidant activity. Medicinal plant-derived antineoplastic agents may be used in single agent or in combinational therapies, and have been used in first-line or second-line (including anthracycline-refractory patients) treatment of localized or metastatic breast cancer. Adverse effects resulting from the use of these agents include neutropenia and peripheral neuropathies.

Animals↗
PubMed1999

Prevalence of Ras mutations in thyroid neoplasia.

OBJECTIVE: Mutations at codons 12, 13 or 61 of ras which result in constitutive activation occur frequently in human malignancies. There have been varied reports on their prevalence and hence their likely significance in the pathogenesis of primary thyroid neoplasia. To address this, we have examined a large series of benign and malignant thyroid tumours for ras mutations. DESIGN: Genomic DNA was analysed for the presence of mutations at codons 12, 13 and 61 of H-ras, K-ras and N-ras by allele-specific oligonucleotide hybridization. Direct DNA sequencing was used to confirm the mutations. PATIENTS: A total of 90 samples with benign (66) and malignant (24) thyroid disease were investigated. RESULTS: A total of 14/90 (15.5%) samples had a ras mutation. All mutations were at codon 61 of either N-ras or K-ras. The positive cases were 1/25 (4%) nodular goitre, 7/38 (18%) follicular adenoma, 4/9 (44%) follicular carcinoma, 1/1 anaplastic carcinoma, 1/1 follicular variant of papillary carcinoma, and 1 metastatic follicular carcinoma in which the primary tumour had the same mutation. CONCLUSIONS: Our data demonstrate a relatively low overall prevalence of ras mutations in thyroid neoplasia, with a predominance in follicular neoplasms. Their presence in follicular adenomas suggests that they may have an early aetiological role in the development of thyroid neoplasia.

Adenocarcinoma, Follicular↗
PubMed1999

DNA ploidy and cell cycle distribution of breast cancer aspirate cells measured by image cytometry and analyzed by artificial neural networks for their prognostic significance.

Chromosomal abnormalities are commonly associated with cancer, and their importance in the pathogenesis of the disease has been well recognized. Also recognized in recent years is the possibility that, together with chromosomal abnormalities, DNA ploidy of breast cancer aspirate cells, measured by image cytometric techniques, may correlate with prognosis of the disease. Here, we have examined the use of an artificial neural network to predict: 1) subclinical metastatic disease in the regional lymph nodes and 2) histological assessment, through the analysis of data obtained by image cytometric techniques of fine needle aspirates of breast tumors. The cellular features considered were: 1) DNA ploidy measured in terms of nuclear DNA content as well as by cell cycle distribution; 2) size of the S-phase fraction; and 3) nuclear pleomorphism. A further objective of the study was to analyze individual markers in terms of impact significance on predicting outcome in both cases. DNA ploidy, indicated by cell cycle distribution, was found markedly to influence the prediction of nodal spread of breast cancer, and nuclear pleomorphism to a lesser degree. Furthermore, a comparison between histological assessment and artificial neural network prediction shows a closer correlation between the neural approach and the development of further metastases as indicated in subsequent follow-up, than does histological assessment. These data demonstrate that artificial neural networks are capable of providing powerful and reliable indicators of possible lymph node metastasis, using measurements of cellular features alone.

Breast Neoplasms↗
PubMed1997

New monoclonal antibodies to oestrogen and progesterone receptors effective for paraffin section immunohistochemistry.

Assessment of oestrogen and progesterone receptors (ER and PgR) in breast cancer is widely used for the prediction of response to endocrine therapy and as a prognostic marker. Cytosolic assays have been replaced in many centres by immunochemical techniques, which have many advantages including applicability to small samples, simplicity, and cost-effectiveness. This study describes the generation and characterisation of two novel murine monoclonal antibodies recognizing ER and PgR, designated NCL-ER-6F11 and NCL-PGR respectively, which are effective in heat-treated formalin-fixed, paraffin-embedded tissue. The antibodies have been characterized by Western blotting and by immunohistochemistry on normal and pathological breast and other tissues. NCL-ER-6F11 has been shown to compare favourably with a currently available ER antibody. These antibodies may prove of value in the assessment of hormone receptor status in human breast cancer.

Antibodies, Monoclonal↗
PubMed1997

Insulinoma: a review of current management.

Insulinomas are a relatively rare tumour which occur predominantly in the pancreas. The majority of the tumours are benign, but have profound effects upon the patient. The diagnosis of insulinoma is often elusive, and the management may involve demanding surgery with a significant morbidity. In this review article, all clinical aspects of insulinomas are examined. Particular emphasis is placed on the myriad modes of presentation, and the methods used to localise the tumour pre-operatively. Medical, as well as surgical treatments are discussed and their role in the management of both malignant and benign tumours. Despite potential difficulties encountered in managing patients with this tumour, a large majority may be either cured or achieve useful palliation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

A novel quantitative immunoassay system for p53 using antibodies selected for optimum designation of p53 status.

AIM: To develop a highly sensitive and specific enzyme linked immunosorbent assay (ELISA) system for analysis of p53 protein in cancer lysates. METHODS: The anti-p53 monoclonal antibodies DO7, 1801, BP53.12, and 421, and anti-p53 polyclonal antiserum CM1 were assessed by immunohistochemistry and western blot analysis to identify those most suitable for determining p53 status of cancer cells. Antibodies with desired characteristics were used to develop a non-competitive sandwich type ELISA system for analysis of p53 expression in cancer cytosols. Using the ELISA, p53 protein concentrations were measured in a small series of breast cancers, and the quantitative values compared with p53 immunohistochemical data of the same cancers. RESULTS: DO7 and 1801 gave the most specific and reliable results on immunohistochemistry and western blot analysis. Using these two antibodies, a non-competitive sandwich type ELISA system was developed to analyse p53 quantitatively. Analysis of the breast cancer series showed a good correlation between immunohistochemistry and the ELISA-tumours were generally positive using both techniques. Discrepancies were noted however: some cancers were immunohistochemically negative but ELISA positive. One explanation for this may be that the ELISA is more sensitive than immunohistochemistry. CONCLUSION: The p53 ELISA system is a non-competitive double monoclonal antibody sandwich method, using DO7 and 1801 which have been shown to be highly specific for p53 protein by immunohistochemistry and western blot analysis. The lower threshold of the assay is 0.1 ng/ml analyte in an enriched recombinant p53 preparation. As p53 is now regarded as a protein associated with prognosis in breast and other cancers, the assay may have clinical applications.

Antibodies, Monoclonal↗
PubMed1996

Insulin-like growth factor binding protein-3 in breast cyst fluid: relationships with insulin-like growth factors I and II and transforming growth factor-beta 1 and 2.

Women who have palpable breast cysts with intracystic Na/K > 3 may have a lower risk of developing breast cancer than those with intracystic Na/K < 3. In this study significantly higher concentrations of insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factors I and II (IGF-I, IGF-II) and transforming growth factor-beta 2 (TGF-beta2) were found in the Na/K > 3 sub-group. No difference was found in transforming-growth factor-beta 1 (TGF-beta1) levels between the two sub-groups of breast cysts. A positive correlation was obtained for IGFBP-3 and TGF-beta1 in the Na/ K > 3 sub-group consistent with reports that TGF-beta1 may regulate the production of IGFBP-3. Equimolar amounts of total IGFs and IGFBP-3 in breast cyst fluid imply that most, if not all, of these IGFs are protein-bound. The significantly higher concentrations of TGF-beta2 in the Na/K > 3 sub-group may partly explain the lower risk of breast cancer in this group of women.

Exudates and Transudates↗
PubMed1996

Prostate-specific antigen in breast cyst fluid: possible role of prostate-specific antigen in hormone-dependent breast cancer.

Prostate-specific antigen (PSA) is a 33 kDa serine protease which is produced by many different tissues in the body and has been shown to be present in low concentrations in breast milk and in about 30% of breast cancers. The presence of PSA in breast cancers is associated with the presence of steroid-hormone receptors and may be a favourable prognostic indicator. In this study, PSA immunoreactivity was measured in breast cyst fluid obtained from women with palpable breast cysts which is the most common benign breast disease. PSA was found to be present in very low concentrations in breast cyst fluid. In an attempt to understand the possible role of PSA in the breast, the effect of PSA on growth of the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 human breast cancer cell lines was studied. In addition, the effect of PSA on oestrone sulphatase activity and oestrogen 17-oxidoreductase activity in these cell lines was investigated. PSA, in low concentrations, was found to inhibit MCF-7 cell growth and to stimulate the conversion of oestradiol to the less potent oestrogen oestrone in this cell line. PSA had no effect on the MDA-MB-231 cell line. Our findings suggest that PSA may act as a negative growth regulator in hormone-dependent breast cancers.

17-Hydroxysteroid Dehydrogenases↗
PubMed1996

Retinoblastoma protein in human breast carcinoma: immunohistochemical study using a new monoclonal antibody effective on routinely processed tissues.

Cyclic phosphorylation/dephosphorylation of the retinoblastoma gene product (pRB) has been found to play a central role in the progression of the normal cell cycle, through modulation of the activity of the E2F family of transcription factors. Mutations of the retinoblastoma gene have been described in a wide variety of human malignancies including carcinomas of the breast. The present investigation reports the production and application of a new monoclonal antibody in an immunohistochemical study of pRB expression in 233 primary breast carcinomas, allowing an assessment of the contribution made by this tumour suppressor gene to tumour development and progression. Overall, there was loss of pRB expression in 21 per cent of breast tumours. Although high-grade tumours were found to lack detectable pRB more frequently than low-grade tumours, the difference did not prove statistically significant. In addition, pRB immunostaining was not related significantly to relapse or survival. No significant correlations were observed between apparent loss of pRB and tumour size, parity, patient lymph-node status, p53, c-erbB-2, c-jun, EGFR or steroid hormone receptor expression. Preliminary findings, however, did suggest a relationship between pRB expression and response to endocrine therapy.

Adult↗
PubMed1996

Inhibition of endothelial adhesion and invasion by breast carcinoma cells may contribute towards the anti-metastatic effects of tamoxifen.

The anti-metastatic actions of tamoxifen on the oestrogen receptor-(ER-) positive cell line, MCF-7 and Hs578T, which is ER-negative, were investigated by measuring changes in the tumour cell adherence to endothelium and invasion of Matrigel. The endothelial hybridoma EA.hy926 was grown to confluence on the bases of 96-well plates. Either tamoxifen, the pure ER antagonist ICI 182,780 or the control, phosphate-buffered saline (PBS), was added to each well in varying concentrations. Adhesion of tumour cells to the endothelium was then measured using an isotopic adhesion assay. Invasion was determined by measuring the number of cells passing across a Matrigel-coated filter with 8 microm diameter pores. After 24-h incubation, the number of cells which had invaded was determined by an XTT colorimetric assay. Tamoxifen and ICI 182,780 inhibited both adhesion to the model endothelium and Matrigel invasion of the ER-positive cell line at therapeutic concentrations (P<0.005). Neither compound, however, had an effect on the ER-negative cell line. This action of the ER antagonists may play a role in prolonging the disease-free survival seen in women with breast cancer who are treated with adjuvant tamoxifen.

Antineoplastic Agents↗
PubMed1996

Surgery for thyroid cancer.

What operation to perform in the case of a patient with thyroid cancer is a controversial issue, because there are few trials of treatments on which to base decisions. Small papillary tumours in young patients can be adequately treated by less than total thyroidectomy as can some variants of follicular carcinoma, but outwith these settings total thyroidectomy is recommended.

Adenocarcinoma, Follicular↗