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Biomedical subjects

Leigh Delbridge

Publications and source records attributed to Leigh Delbridge.

29 records · Page 2Linked to original sources

Independent genetic events associated with the development of multiple parathyroid tumors in patients with primary hyperparathyroidism.

Multiple parathyroid tumors, as opposed to hyperplasia, have been reported in a subset of patients with sporadic primary hyperparathyroidism (PHPT). It is not clear whether these multiple tumors are representative of a neoplastic process or whether they merely represent hyperplasia that has affected the parathyroid glands differentially and resulted in asynchronous growth. The molecular genetic techniques of comparative genomic hybridization (CGH), loss of heterozygosity (LOH), and MEN1 mutation analysis were performed on a series of five patients with multiglandular PHPT, each of which had two parathyroid tumors removed. Analysis of these multiple parathyroid tumors from patients with PHPT revealed that independent genetic events were associated with the development of a subset of these tumors. The DNA sequence copy number changes, identified by CGH analyses, either involved different chromosomal regions in the paired glands of a patient (two patients), or those regions implicated in one gland were not changed in a second gland from the same patient (two patients). Each of the three patients exhibiting LOH demonstrated different changes between the paired glands. Where LOH was detected in one gland from a patient, the other gland from the same patient either exhibited no allelic loss or the loss detected was in another region. Each of the three tumors exhibiting LOH at 11q13 was found to contain a somatic MEN1 mutation in the remaining allele, however these mutations were not present in the germline or in the paired gland from the same patient. Although it is possible that a separate series of genetic changes has arisen randomly in two separate glands within the same individual, it seems more likely that the development of these multiple tumors has arisen because of the involvement of other unknown factors. These factors may be genetic [such as the involvement of one or more germline mutations in an unknown low-penetrance gene(s), germline mosaicism or alterations in calcium-sensing receptor gene(s)], epigenetic, physiological, or environmental.

Cell Transformation, Neoplastic↗

Thyrothymic thyroid rests: incidence and relationship to the thyroid gland.

BACKGROUND: Rests of thyroid tissue within the thyrothymic area are relatively common and might be of clinical importance. The purpose of this study is to define the incidence and anatomy of thyroid tissue located in the line of the thyrothymic ligament, referred to here as "rests." STUDY DESIGN: Prospective descriptive intraoperative evaluation of 100 consecutive thyroid or parathyroid procedures was undertaken to identify the incidence and anatomical location of thyrothymic thyroid rests. Photographs and histologic confirmation of the thyroid remnants were obtained. RESULTS: One hundred eighty sides of the thyroid gland are examined in 100 consecutive patients. Thyroid rests in the thyrothymic area were found in 53 patients, or on 83 separate sides of the thyroid (46%). In patients who had rests identified, 30 (57%) had bilateral rests, with 16 (30%) only on the right, and 7 (13%) only on the left. Eighty percent of identified rests were still attached to the thyroid proper by a pedicle of thyroid tissue but 20% were entirely separate. Most rests were small, with 88% being less than 1 cm in diameter. CONCLUSION: Rests of thyroid tissue within the thyrothymic area, either as entirely separate nodules or as prolongations from the thyroid lobe, are relatively common and might be of clinical importance during thyroid or parathyroid surgery.

Adolescent↗

Short-term resolution of psoriasis after total thyroidectomy for euthyroid multinodular goitre.

A 36-year-old Chinese female with an 8-year history of chronic, generalized plaque psoriasis demonstrated a marked improvement of the disease after removal of an intercurrent euthyroid multinodular goitre. Thyroxine was commenced immediately postoperatively. No thyroid antibodies were detected and thyroid function and calcium levels remained within normal limits both pre- and postoperatively. Four weeks following surgery, narrow-band ultraviolet B (nbUVB) therapy was recommenced for recurrent psoriasis. The manifestations of psoriasis at this stage were less severe than before thyroidectomy and responded well to treatment, whereas before surgery the response to therapy had been poor. One year following total thyroidectomy, the patient received very effective psoriasis control with nbUVB therapy. The possible role of surgery and thyroid hormones in altering the pathogenesis of psoriasis in the acute setting is clearly of interest and warrants further research consideration.

Adult↗

Changing pattern of adrenalectomy at a tertiary referral centre 1970-2000.

BACKGROUND: In 1987, a report from this unit described the changing indications for open adrenalectomy over a 15-year period. The indications for adrenalectomy had switched from it being the principal therapeutic procedure used in advanced breast cancer in the early 1970s, to being predominately performed for Cushing's disease or incidental, asymptomatic, adrenal masses by the early 1980s. The aim of the present study was to evaluate the changes in the presentation and management of adrenal disease in the last 15 years and to compare these findings with our previously published results. METHODS: Information was gathered from a prospective database of all patients undergoing adrenalectomy in the University of Sydney Endocrine Surgical Unit at Royal North Shore Hospital from 1 January 1987 to 31 December 2000. Information was obtained on patient presentation, diagnostic investigations, indications for surgery, procedure performed and surgical outcomes. Prior to 1987, information was gathered by retrospective review of case notes of patients who had undergone adrenalectomy at Royal North Shore Hospital. During the period from 1 January 1970 to 31 December 2000, 236 patients underwent adrenalectomy. Excluding the 68 adrenalectomies performed for breast cancer, left 168 patients who underwent adrenalectomy for functional or non--functional masses. There were 97 (58%) women and 71 (42%) men, with a mean age of 48 years. RESULTS: Of the 168 patients, the principal indications for surgery were hyperaldosteronism (32%), phaeochromocytoma (20%), hypercortisolism (20%), incidentaloma (16%), carcinoma (6%) and other reasons (6%). Examination of the number of cases in each pathological group for the periods 1970-1986 and 1987-2000, revealed an 8-fold increase in the number of operations for hyper-aldosteronism, and a 3-fold increase in cases of phaeochromocytoma. The number of operations for the other pathological groups remained steady. The annual incidence of adrenalectomy in the hospital has steadily risen since 1990, with a linear increase in the adrenalectomy rate since the introduction of laparoscopic adrenalectomy in 1995. There were fewer complications in either the open or laparoscopic group since 1987 compared with the pre-1987 cohort. CONCLUSIONS: In the past 5 years, there has been a linear increase in the number of adrenalectomies performed in this unit for hyperaldosteronism and to a lesser extent phaeochromocytoma. This is a reflection of increased clinical awareness, improved diagnostic modalities and the advent of laparoscopic adrenalectomy.

Adrenal Gland Diseases↗

Comparative genomic hybridization analysis of adrenocortical tumors.

Comparative genomic hybridization (CGH) is a molecular cytogenetic technique that allows the entire genome of a tumor to be surveyed for gains and losses of DNA copy sequences. A limited number of studies reporting the use of this technique in adult adrenocortical tumors have yielded conflicting results. In this study we performed CGH analysis on 13 malignant, 18 benign, and 1 tumor of indeterminate malignant potential with the aim of identifying genetic loci consistently implicated in the development and progression of adrenocortical tumors. Tissue samples from 32 patients with histologically proven adrenocortical tumors were available for CGH analysis. CGH changes were seen in all cancers, 11 of 18 (61%) adenomas, and the 1 tumor of indeterminate malignant potential. Of the adrenal cancers, the most common gains were seen on chromosomes 5 (46%), 12 (38%), 19 (31%), and 4 (31%). Losses were most frequently seen at 1p (62%), 17p (54%), 22 (38%), 2q (31%), and 11q (31%). Of the benign adenomas, the most common change was gain of 4q (22%). Mann-Whitney analysis showed a highly significant difference between the cancer group (mean changes, 7.6) and the adenoma group (mean changes, 1.1) for the number of observed CGH changes (P < 0.01). Logistic regression analysis showed that the number of CGH changes was highly predictive of tumor type (P < 0.01). This study has identified several chromosomal loci implicated in adrenocortical tumorigenesis. Activation of a protooncogene(s) on chromosome 4 may be an early event, with progression from adenoma to carcinoma involving activation of oncogenes on chromosomes 5 and 12 and inactivation of tumor suppressor genes on chromosome arms 1p and 17p.

Adenoma↗

Using recombinant human thyroid-stimulating hormone for the diagnosis of recurrent thyroid cancer.

BACKGROUND: Recombinant human thyroid-stimulating hormone (rhTSH) has been suggested as a diagnostic agent in the diagnosis of recurrent thyroid cancer, instead of the current practice of thyroid hormone (THT) withdrawal. METHODS: An evidenced-based literature review was used as the basis for a cost-utility, decision-analytic model. Outcome measures were safety, efficacy (diagnostic performance and quality of life) and cost effectiveness of rhTSH. RESULTS: The literature search identified six comparative studies of rhTSH versus THT withdrawal. The most common adverse events associated with the use of rhTSH were headache (3.5-11.1%) and nausea (7.7-17%). When used as a diagnostic agent, the unadjusted sensitivity and specificity for rhTSH were 87% and 95%, respectively. Thus the use of rhTSH instead of THT withdrawal would result in a reduction in diagnostic accuracy, with 11% of patients' disease status being misclassified. Use of rhTSH resulted in a higher quality of life in the period prior to diagnostic testing than THT withdrawal (P < 0.001). When the impact of diagnostic performance, patient compliance to follow-up and modified quality of life were modelled over a 5 year time-frame, the incremental cost per QALY of rhTSH relative to THT withdrawal was $51 344.42. CONCLUSIONS: The use of rhTSH as a diagnostic agent appears to be safe but less diagnostically accurate and less cost-effective (on whole of healthcare cost basis) when used in the follow-up of patients with thyroid cancer who have had a previous negative radioiodine scan after thyroid hormone withdrawal.

Decision Support Techniques↗

23-hour care centre: changing the culture of care.

AIM: A 23-hour Care Centre was created at a principal referral hospital in Sydney in 2003. Its primary aim was to provide efficient and high quality care to patients requiring a brief stay in hospital for surgical or medical procedures, within one coordinated unit. DESIGN: The features underlying the 23-hour Care Centre as an innovative model of care were the clinical guideline driven approach and nurse-initiated discharge. All patients, emergency and elective as well as surgical and medical, who fitted the following criteria were admitted as '23-hour patients' to the Centre. The criteria were: absolute expectation of discharge within 24 hours; pre-admission screening by a nurse screener (if elective admission); agreed clinical guideline in place; and, agreement to protocol-based, nurse-initiated discharge. RESULTS: Following the first three months of the 23-hour Care Centre, 1601 patients utilised the 23-hour Care Centre as follows: 593 day only patients, 410 DOSA (day of surgery admission) patients and 598 23-hour patients. Excluding inappropriate admissions, overall discharge compliance was 83%. CONCLUSION: From the results generated throughout the trial it has become evident that the new clinical area offers a workable system of health care delivery for patients who require a brief stay in hospital, as it promotes an efficient use of hospital beds and services without compromising patient outcomes. However, further research is required to compare the efficiency and outcomes of care directly with that provided by the traditional inpatient hospital system.

Ambulatory Surgical Procedures↗