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Biomedical subjects

J J Shepherd

Publications and source records attributed to J J Shepherd.

At least 19 recordsLinked to original sources

Inactivation of retinoblastoma gene in malignant parathyroid growths: a candidate genetic trigger?

The molecular basis for parathyroid carcinoma remains undetermined. Parathyroid carcinoma potentially remains curable by early en bloc resection. This requires a reliable diagnostic tool as histological features alone are insufficient to distinguish parathyroid carcinoma from its benign counterpart, parathyroid adenoma. A variety of human cancers arise from the inactivation of the retinoblastoma (RB) gene, a tumour-suppressor gene on chromosome 13q14. We investigated the role of this gene in parathyroid growths by using a mouse monoclonal antibody to detect RB gene expression immunohistochemically. Two of the three parathyroid carcinomas in this study showed evidence of RB gene inactivation compared with one of 11 benign parathyroid entities. Three normal parathyroid glands stained showed strong evidence of RB gene expression in all three glands. The relationship between RB gene inactivation and parathyroid malignancy, however, was not statistically significant.

Animals

Hyperparathyroidism with normal albumin-corrected total calcium in patients with multiple endocrine neoplasia type 1.

In the largest reported family of patients with multiple endocrine neoplasia type 1 (MEN 1), hyperparathyroidism was expressed at first screening in 33 patients by elevation of ionized calcium (IC) (30 cases) or parathyroid hormone (three cases) without elevation of albumin-corrected total calcium (ACTC). Three of these 33 patients have shown a progressive rise in IC and later an elevation of ACTC. However, the age distribution suggests that in others the level of IC may remain stable at a minimally elevated level throughout life with ACTC remaining normal except for transient rises at the times of intercurrent illness or surgical operation. Even when ACTC is normal preoperatively, patients with an elevation of IC require radical subtotal parathyroidectomy or total parathyroidectomy and forearm implantation to restore IC to a normal level. Institutions that rely on ACTC as a screening test for hyperparathyroidism in MEN 1 will miss the diagnosis in nearly half of patients under the age of 30. The greatest deficiency in using ACTC occurs in the follow-up of patients who have undergone parathyroidectomy for MEN 1. Only three of 11 recurrences were evidenced by this measurement.

Adolescent

The natural history of multiple endocrine neoplasia type 1. Highly uncommon or highly unrecognized?

Among 2000 descendants of an English immigrant to Tasmania, Australia, the diagnosis of multiple endocrine neoplasia type 1 was found to be very highly probable or highly probable in 130 and moderately probable in 22. Another 242 children and siblings were 50% likely to have inherited this dominant gene. In all age groups, especially the elderly, the majority of affected members had symptoms of only one endocrine disorder or were asymptomatic. In teenagers, the most common presentation was pituitary lesions and the second most common presentation was insulinomas. Frequently, pituitary lesions or insulinomas developed before any parathyroid lesions could be detected. Elevation of gastrin levels, usually associated with hypercalcemia, was rarely seen in patients younger than 25 years. The classic presentation with symptoms of multiple endocrinopathy may represent only a small fraction of these patients in the community.

Adolescent

Relationship between methaemoglobin production and methylene blue plasma concentrations under general anaesthesia.

Recently, a family tree with a predisposition for the gene of multiple endocrine neoplasia Type 1 has been identified in Tasmania. As the surgical identification and localisation of parathyroid adenomas is facilitated by the administration of methylene blue, an opportunity has presented to measure the plasma concentration of methylene blue and methaemoglobin production. The study was undertaken to establish whether significant methaemoglobin concentrations were generated during the infusion and whether these concentrations could be related to the corresponding methylene blue concentrations. Mean peak methylene blue concentrations of 3.72 micrograms l-1, mean percentage methaemoglobin of 10.0 and a PaO2 within acceptable clinical ranges were found. No apparent relationship between methylene blue concentration and methaemoglobin production was found.

Adenoma

Latent familial multiple endocrine neoplasia in Tasmania.

The largest-known family tree of a kindred with multiple endocrine neoplasia type I, dating back to 1840, has been constructed in Tasmania. There are over 600 descendants of one English migrant and his spouse living today. Preliminary data suggests that overall, one-quarter of all family members, and one-half of those above the age of 40 manifest one or more endocrine tumours. In the majority of cases, the diagnosis was not suspected until the general practitioner was informed of the family history, as the symptoms are vague, sometimes bizarre, and overlap with those of common disorders.

Adult

Intraoperative and postoperative changes in peripheral white blood cell counts: the contribution of stress.

The effect of major surgery, blood loss and psychological stress on the peripheral white blood cell (WBC) populations of human patients and healthy volunteers was examined. During, and in the hours immediately after, major surgery, there was a highly significant fall in the numbers of circulating lymphocytes (mean congruent to 30%-60%) and a highly significant decrease in polymorphs (mean congruent to 160%-350%). Blood loss and psychological stress are not major factors contributing to this fall in peripheral blood lymphocytes in the human, as blood donors and invididuals under temporary stress (anxiety about an imminent dental procedure or an important examination) showed no change in their peripheral blood lymphocyte levels in the hours immediately after these experiences. Significant increases in circulating polymorph numbers, however, accompanied procedures involving even slight tissue trauma, e.g. following blood donation and tooth extraction, but did not occur after psychological stress alone, and were much smaller (congruent to 20%-55%) than those occurring after major surgery. Thus, apart from the complex question of anaesthesia, the nature of the surgical procedure, probably, that is, the degree of tissue trauma involved, is the most important trigger determining changes in the circulating WBC counts after operation.

Adolescent

A fifteen-year study of breast cancer in Tasmania.

Seven hundred and seventy-nine patients presenting with breast cancer in Tasmania between 1930 and 1975 have been studied. No comparisons of different treatment have been made, but overall survival has been assessed. Median survival in the group was only 3-3 years, but 30% of patients were still alive at ten years. Other factors assessed in relation to survival were axillary node involvement, site, size, age, parity, breast feeding and place of birth.

Adult