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Biomedical subjects

L Delbridge

Publications and source records attributed to L Delbridge.

At least 37 records · Page 2Linked to original sources
PubMed1998

A rapid method for DNA extraction from fine-needle aspiration biopsies of thyroid tumors, and subsequent RET mutation analysis.

The presence of germline and somatic mutations in the RET proto-oncogene (RET) in patients with hereditary and sporadic medullary thyroid carcinoma (MTC) may have important ramifications for patient management. It has been suggested that the presence of the mutation ATG-->ACG at codon 918 in sporadic MTC is associated with a worse prognosis, and hence the need for more aggressive surgical, or other, treatment. Since fine-needle aspiration biopsy (FNAB) is an important component of the preoperative management of patients with thyroid tumors, we developed a rapid (20-min) method that enables extraction of DNA from FNABs for RET mutation analysis. The method allows preoperative genetic analysis to aid in management of patients with MTC, and may be applied to other tumor types where a preoperative mutation analysis based on polymerase chain reaction amplification is desired.

Biopsy, Needle↗
PubMed1998

Re-operative surgery for recurrent or persistent primary hyperparathyroidism.

BACKGROUND: While initial surgery for primary hyperparathyroidism, in experienced hands, will result in a cure in 98% of cases, re-operative surgery remains a significant challenge. Because attitudes as to who should perform initial exploration for hyperparathyroidism are significantly different around the world, the approach to re-operative surgery may also vary. The aim of the present study was to examine a local experience of re-operative surgery for recurrent or persistent primary hyperparathyroidism. METHODS: Information on indications for surgery, the procedure performed, pathology and complications of all re-operative procedures for primary hyperparathyroidism in the period January 1962 to December 1996 were obtained from a prospective database. RESULTS: Sixteen patients with persistent (n = 12) or recurrent (n = 4) primary hyperparathyroidism were treated in the unit over the study period. Eight patients had their initial operation within the unit at Royal North Shore Hospital and eight were referred from elsewhere for re-operation. Nine of the 12 patients with persistent hyperparathyroidism were cured by re-operation with failures due to spillage at first operation (n = 1) or failure to find any additional pathology (n = 2). All four patients with recurrent hyperparathyroidism were cured. All the failures occurred early in the learning phase of the unit, with a 100% cure rate for re-operative procedures performed in the last 15 years. The most common finding in patients referred from elsewhere with a failed initial operation was a missed inferior adenoma in association with the thymus. Localization studies had a variable sensitivity, with sestamibi scintigraphy, selective venous sampling and ultrasonography providing the most reliable information. CONCLUSIONS: Re-operative surgery for persistent or recurrent hyperparathyroidism is an uncommon procedure in Australia when compared to major centres in the USA. Successful surgery depends upon experience and an accurate knowledge of the embryology and anatomy of the parathyroid glands.

Adenoma↗
PubMed1998

Expression of the parathyroid Ca(2+)-sensing receptor in cytotrophoblasts from human term placenta.

Fura-2-loaded human cytotrophoblasts responded to elevated extracellular Ca2+ concentration ([Ca2+]o) with monophasic or, in the case of large (> 20 microns) extravillous cells, biphasic elevations in intracellular free Ca2+ ion concentration ([Ca2+]i) that returned to baseline levels after restoration of control [Ca2+]o. Large extravillous cytotrophoblasts also responded to elevated [Mg2+]o with transient elevations in [Ca2+]i, consistent with the behaviour of the parathyroid Ca2(+)-sensing receptor. Expression of the parathyroid Ca2(+)-sensing receptor in placental cells was confirmed using Northern blot and reverse transcription (RT)-PCR analysis. However, the major transcript in human placental cells (6.2 kb) differed from that expressed by human parathyroid cells (5.6 kb). RT-PCR analysis and DNA sequencing of key PCR products also revealed the presence of a splice variant in placental and parathyroid cells that lacks exon 3.

Blotting, Northern↗
PubMed1997

Genetic testing for familial cancer. Consequences of RET proto-oncogene mutation analysis in multiple endocrine neoplasia, type 2.

OBJECTIVE: To assess clinician use and acceptance of RET proto-oncogene mutation testing in multiple endocrine neoplasia, type 2 (MEN 2) family members. DESIGN: A retrospective survey of clinicians managing 26 MEN 2 families with documented RET mutations to assess the effect of genetic screening on subsequent investigation and management of family members. SETTING: Tertiary referral center for RET mutation testing. MAIN OUTCOME MEASURES: The screening procedures used by clinicians and the altered incidence of C-cell hyperplasia vs medullary thyroid carcinoma in genetically as opposed to biochemically identified affected family members. RESULTS: Among RET mutation-positive patients, thyroidectomy performed for clinical or biochemical indication disclosed medullary thyroid carcinoma in 44 (98%) of 45 patients and precursor C-cell hyperplasia in only 1 (2%) patient. When prophylactic thyroidectomy was performed based on a positive genetic result, medullary thyroid carcinoma occurred in 3 (43%) of 7 patients and C-cell hyperplasia in 4 (57%) of 7 patients (P < .001). RET mutation-negative patients were not subjected to further biochemical testing, but 4 had already undergone thyroidectomy based on abnormal results of pentagastrin stimulation tests, including 2 patients who were known to be RET mutation-negative at the time of surgery. RET mutation testing was well accepted and resulted in additional family members consenting to screening in more than 85% of families. CONCLUSIONS: Genetic screening for RET proto-oncogene mutations in MEN 2 is a powerful diagnostic tool that enables prophylactic thyroidectomy to be performed in RET mutation-positive patients at an earlier stage of the disease process than does traditional biochemical screening.

Adolescent↗
PubMed1997

Teaching normal physical examination in a large-group interactive using artists' models.

BACKGROUND: The innovative use of artists' models within the context of a large-group interactive teaching session, at Royal North Shore Hospital is reviewed. METHODS: The models were used to teach normal physical examination skills to a group of junior medical students, during their surgical rotation. This same group of students were also exposed to traditional bedside tutorials. The students evaluated both teaching experiences. RESULTS: In the four areas of evaluation (interaction, explanation, presentation, and organization), the large-group interactive sessions were consistently rated higher than the bedside tutorial (P < 0.001). CONCLUSIONS: The teaching technique is presented as an effective way of delivering quality clinical training to a group of junior medical students in an environment where access to good teaching material is becoming increasingly difficult.

Anatomy↗
PubMed1996

Proton magnetic resonance and human thyroid neoplasia III. Ex vivo chemical-shift microimaging.

Magnetic-resonance chemical-shift microimaging, with a spatial resolution of 40 x 40 microns, is a modality which can detect alterations to cellular chemistry and hence markers of pathological processes in human tissue ex vivo. This technique was used as a chemical microscope to assess follicular thyroid neoplasms, lesions which are unsatisfactorily investigated using standard histopathological techniques or water-based magnetic-resonance imaging. The chemical-shift images at the methyl frequency (0.9 ppm) identify chemical heterogeneity in follicular tumors which are histologically homogeneous. The observed changes to cellular chemistry, detectable in foci of approximately 100 cells or less, support the existence of a preinvasive state hitherto unidentified by current pathological techniques.

Adenocarcinoma, Follicular↗
PubMed1996

Two-dimensional proton magnetic resonance spectroscopy for tissue characterization of thyroid neoplasms.

We have previously demonstrated that one dimensional (1D) proton (1H) magnetic resonance spectroscopy (MRS) can distinguish normal thyroid tissue from thyroid carcinoma using a spectral ratio of peak intensity at 1.7 ppm/0.9 ppm. Two dimensional (2D) 1H-MRS allows identification of specific molecules that have overlapping peaks in the 1D-MR spectrum. Specimens from 93 consecutive thyroid nodules were examined using 2D 1H-MRS on a Bruker AM-360 wide-bore spectrometer. There was a progressive increase in lipid cross peaks assigned to di-/triglycerides when comparing colloid/hyperplastic nodules to follicular adenoma, and adenoma to carcinoma. A specific cross peak attributable to cholesterol/cholesteryl esters was commonly seen in carcinomas. In contrast, two unassigned cross peaks unique to the thyroid were more prevalent in benign lesions. There was an overall increase in cross peaks attributable to cell surface fucosylation in carcinoma when compared to benign lesions, although the fucose spectral pattern was not specific for cancer. On this basis, a spectral ratio of peak intensity at 2.05 ppm/0.9 ppm more clearly distinguished benign follicular adenoma from carcinoma. 2D 1H-MRS thus identifies chemical changes that allow more specific tissue characterization of thyroid neoplasms.

Adenoma↗
PubMed1996

Recurrent substernal nodular goiter: incidence and management.

BACKGROUND: Surgery for recurrent multinodular goiter is associated with an increased risk of complications. When recurrence occurs in a substernal location, difficulties associated with surgical removal may be even more significant. METHODS: Information relating to indications for surgery, procedure performed, pathologic findings, and surgical complications was obtained from a prospective thyroid surgery database maintained in our unit for the past 39 years. RESULTS: During the study period 234 patients underwent operation for retrosternal recurrence of a nodular goiter. In the majority of cases (51%) the indication for surgery was the presence of compressive symptoms. In only four cases was a sternal split required to remove substernal recurrence. Complications occurred in 35 patients, including four permanent recurrent laryngeal nerve palsies. No patient had permanent hypoparathyroidism. CONCLUSIONS: Surgery for recurrent substernal goiter, although technically demanding, can be performed with a minimum of morbidity if appropriate attention is paid to anatomy and embryology. A sternal split is only rarely required.

Adult↗
PubMed1996

The identification of false positive responses to the pentagastrin stimulation test in RET mutation negative members of MEN 2A families.

OBJECTIVE: The pentagastrin stimulation test is the traditional test used for the identification of asymptomatic individuals in multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC). The identification of mutations in the RET proto-oncogene segregating with the disease phenotype in MEN 2A and FMTC families has made it possible to re-examine the validity of using this test for the identification of affected family members. DESIGN: Sequential and single pentagastrin stimulation test data were collected following the identification of RET mutation positive and RET mutation negative members of families with MEN 2A or FMTC. PATIENTS: RET mutations were identified in 16 Australian and New Zealand MEN 2A or FMTC families. An analysis of 39 individuals from these families was included in this study. Thirty-two individuals (14 males, 18 females) had previously been determined as RET mutation negative. Seven individuals (6 males, 1 female) had previously been determined as RET mutation positive. Two RET mutation negative males had thyroidectomy based on prior pentagastrin test results. MEASUREMENTS: Serum calcitonin levels in response to stimulation with pentagastrin were measured at 0, 1, 2, 5 and 10 minutes post injection. Mutation analysis of the RET proto-oncogene was performed in all individuals. In two RET mutation negative individuals from two MEN 2A families, thyroidectomy was performed and C-cells were quantitated in order to determine the diagnosis of C-cell hyperplasia. RESULTS: There was a statistically significant difference (P < 0.013) between RET mutation negative male and female mean peak calcitonin responses of 282 +/- 236 and 96 +/- 62 (mean +/- SD) ng/l respectively. False positive responses to pentagastrin stimulation were identified in seven individuals who were RET mutation negative in two of the 16 families. Histologic examination of the thyroid glands in the two RET mutation negative individuals who had thyroidectomy demonstrated C-cell hyperplasia in one but not in the other. CONCLUSIONS: There is considerable overlap between pentagastrin test results in individuals who are RET mutation positive and those who are RET mutation negative. These results indicate a need for routine performance of RET proto-oncogene analysis on all individuals at risk of developing MEN 2A or FMTC and a coupling of pentagastrin test results and RET proto-oncogene analysis in the decision to proceed with thyroidectomy.

Adolescent↗
PubMed1996

Somatic mutations in the RET proto-oncogene in sporadic medullary thyroid carcinoma.

OBJECTIVE: We have determined the frequency of specific mutations in the RET proto-oncogene in sporadic medullary thyroid carcinomas (MTCs) and correlated the presence or absence of a codon 918 mutation with the clinical characteristics of these tumours. DESIGN: Thirty paraffin-embedded sporadic MTCs and two frozen MTCs were collected for analysis of specific mutations in the RET proto-oncogene in codons 609, 611, 618 and 620 (exon 10); 630 and 634 (exon 11); 768 (exon 13); 883 (exon 15) and 918 (exon 16). A novel primer was designed which introduced a restriction site for Rsal in the presence of the specific codon 918 mutation (ATG-->ACG) in these tumour samples. A 'clinical-genetic' correlation was performed comparing the presence of absence of the codon 918 mutation with the following clinical characteristics: age at diagnosis, tumour size, presence or absence of metastases, MTC related morbidity, and base line calcitonin levels at diagnosis or most recent follow-up. PATIENTS: Patients were classified as having sporadic MTC if there was no family history of C-cell hyperplasia, MTC, phaeochromocytoma or parathyroid disease. Retrospective review of patient records enabled complete clinical data to be obtained in 28 of 32 patients. MEASUREMENTS: Base line calcitonin levels were measured by radioimmunoassay or calcitonin enzyme linked immunoassay. Cysteine codons in exons 10 and 11, specifically codons 609, 611, 618, 620, 630 and 634, were screened for the presence of mutations by sequence analysis. Specific mutations occurring at codons 768, 883 and 918 were screened for by restriction endonuclease digestion of PCR products. RESULTS: The mutation at codon 918ATG-->ACG was found in 21 of 32 (66%) MTCs and the mutation at codon 883GCT-->TTT was found in one of 32 MTCs. Where possible, the presence of 'germline-type' mutations in codons 609, 611, 618, 620, 630 and 634 were excluded. Ten MTCs did not have a mutation in codons 768, 883 or 918 of the RET proto-oncogene. The presence or absence of the somatic mutation at codon 918 did not correlate with any of the above clinical characteristics. CONCLUSION: Somatic mutations in the RET protooncogene occur frequently in sporadic MTCs.

Adult↗
PubMed1996

Primary hyperparathyroidism in childhood and adolescence.

OBJECTIVE: The aim of this study was to determine the nature of the presentation and pathology of primary hyperparathyroidism in children and adolescents and to compare these findings with adults. METHODOLOGY: Data were obtained from the Thyroid Surgery Database at Royal North Shore Hospital on all children and adolescents undergoing parathyroid surgery. These results were then compared to data obtained from the last 100 consecutive adult parathyroidectomies. RESULTS: A total of eight younger patients underwent parathyroidectomy including three children (0-12 years) and five adolescents (13-18 years). A common presentation in the younger age group was hypercalcaemic crisis (50%) with a serum calcium > 3.5 mmol/L and clinical signs of calcium intoxication. This compared to the adult age group where only 8% presented with crisis (P < 0.05). Eighty-eight per cent of the younger patients complained of abdominal symptoms compared to only 1% of adults. Seven of eight young patients had sporadic hyperparathyroidism. CONCLUSIONS: Primary hyperparathyroidism, although uncommon in the younger age group, is still most commonly associated with sporadic tumours. Familial syndromes do not constitute a large percentage of patients. Younger patients are more prone to present late with abdominal symptoms, toxicity and hypercalcaemic crisis, presumably due to delayed diagnosis of an uncommon condition in this age group.

Adenoma↗
PubMed1996

The aetiology, investigation and management of surgical disorders of the thyroid gland.

There have been many recent advances in our understanding of thyroid disease, including thyroid physiology, the molecular biology of thyroid neoplasms, guidelines for the management of surgical thyroid disease and the operative approach to thyroidectomy. The control of thyroid growth and function is better understood now that the thyroid stimulating hormone (TSH) receptor has been characterized as a G-protein coupled transmembrane receptor. The peripheral action of thyroid hormones is also better understood in terms of their interaction with nuclear thyroid hormone receptors. An adenoma-carcinoma sequence for the development of thyroid neoplasms has been proposed based on the characterization of a number of proto-oncogenes and tumour suppressor genes, and different pathways for the development of papillary and follicular thyroid carcinoma have been demonstrated. Fine needle biopsy has become, over the past few years, the principal diagnostic technique for evaluation of thyroid nodules, and has resulted in a significant reduction in the need for surgery for benign thyroid nodules. The approach to the management of thyroid carcinoma can now be based on comprehensive scoring systems for assigning patients to a particular risk group, the most recent of which is the MACIS system based on distant metastases (M), age (A), completeness of resection (C), invasion (I) and size (S). The capsular technique of thyroidectomy as described has now been shown to be the best method to preserve parathyroid blood supply, protect the recurrent laryngeal nerve and minimize the complications of thyroid surgery.

Drosophila Proteins↗
PubMed1995

Increasing incidence and changing presentation of thyroid cancer over a 30-year period.

During a 30-year period 8561 thyroidectomies were performed and 660 new patients presented with thyroid cancer. The number of thyroidectomies performed annually remained relatively constant for the past 20 years but the annual incidence of thyroid cancer increased from two patients in 1963 to 60 in 1992. Possible contributing factors include: altered referral patterns as a result of the introduction of fine-needle aspiration biopsy; an increase in the incidence of occult papillary cancer as a result of performing total thyroidectomy for multinodular goitre; and a background increase of thyroid cancer in the population. Data from the New South Wales State Cancer Registry implicate a background increase in the incidence of thyroid cancer in the population as a major contributing factor.

Humans↗
PubMed1995

Computerized consensus diagnosis: a classification strategy for the robust analysis of MR spectra. I. Application to 1H spectra of thyroid neoplasms.

We introduce and apply a new classification strategy we call computerized consensus diagnosis (CCD). Its purpose is to provide robust, reliable classification of biomedical data. The strategy involves the cross-validated training of several classifiers of diverse conceptual and methodological origin on the same data, and appropriately combining their outcomes. The strategy is tested on proton magnetic resonance spectra of human thyroid biopsies, which are successfully allocated to normal or carcinoma classes. We used Linear Discriminant Analysis, a Neural Net-based method, and Genetic Programming as independent classifiers on two spectral regions, and chose the median of the six classification outcomes as the consensus. This procedure yielded 100% specificity and 100% sensitivity on the training sets, and 100% specificity and 98% sensitivity on samples of known malignancy in the test sets. We discuss the necessary steps any classification approach must take to guarantee reliability, and stress the importance of fuzziness and undecidability in robust classification.

Adenocarcinoma, Follicular↗
PubMed1995

Papillary thyroid carcinoma arising in thyroglossal duct cysts: incidence and management.

The incidence and pathological features of papillary thyroid carcinoma arising in the thyroglossal duct cysts were reviewed and compared with papillary thyroid carcinoma arising elsewhere in the thyroid gland. In the 30 year period 1964 to 1993 there were 90 thyroglossal duct nodules or cysts treated surgically at the Endocrine Surgical Unit, Royal North Shore Hospital, Sydney, Australia. There were four cases of papillary thyroid carcinoma in this group (4.4%). In the same period 2814 cases presented with clinical single thyroid nodules which were treated surgically. There were 182 cancers in this group of which 121 were papillary thyroid carcinomas (4.3% of total cases). This is identical to the incidence seen in the thyroglossal duct. We conclude that the incidence of papillary thyroid carcinoma arising in the thyroglossal duct is no different to that arising elsewhere in the gland. The difference in number of carcinomas related only to the volume of follicular thyroid tissue present in the gland proper. That being the case, there is no reason to treat these cancers differently from papillary thyroid carcinoma elsewhere in the gland.

Adult↗
PubMed1995

Giant double parathyroid adenoma presenting as a hypercalcaemic crisis.

The largest documented case of a double parathyroid adenoma is reported. The patient presented in hypercalcaemic crisis with a large intrathoracic mass. After removal of a massive cystic parathyroid adenoma from the right superior mediastinum, a second very large parathyroid adenoma was found on the contralateral side adjacent to the left thyroid lobe. This case illustrates the importance of the cervical approach, as well as routine bilateral neck exploration, for all cases of primary hyperparathyroidism.

Adenoma↗