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Biomedical subjects

J J Shepherd

Publications and source records attributed to J J Shepherd.

At least 37 records · Page 2Linked to original sources
PubMed1993

Cause of death in multiple endocrine neoplasia type 1.

OBJECTIVE: Little data are available on the natural history of untreated multiple endocrine neoplasia type 1 (MEN-1). These data are essential in deciding treatment that may carry significant morbidity. We determined the causes of death in a large MEN-1 kindred with data available over a period of 130 years. Most cases were unrecognized as MEN-1 at the time of patient's death. DESIGN: Retrospective study of recorded medical data from 1861 to 1991. PATIENTS: One hundred fifty-nine deaths occurred, of which 46 were in individuals classified as "highly probable" of having MEN-1. RESULTS: Of 46 deaths in those classified as "highly probable" of having MEN-1, 20 (43.5%) died of a recognized complication of MEN-1 (12 of malignant neoplasms, six of renal calculi, and two of peptic ulcer). If accidental deaths are excluded, 50% of the deaths in patients with MEN-1 were the result of MEN-1, and the mean age of death (50.9 years)was significantly younger than that of other family members. CONCLUSIONS: It is concluded that MEN-1 leads to premature death, and that neoplasia rather than peptic ulcer disease is the main cause of death. Deaths from pituitary tumor or malignant endocrine tumors within the thorax were just as common or more common than deaths from pancreatic malignant neoplasms.

Adult↗
PubMed1993

Multiple endocrine neoplasm, type 1. Gastrinomas, pancreatic neoplasms, microcarcinoids, the Zollinger-Ellison syndrome, lymph nodes, and hepatic metastases.

OBJECTIVE: We reviewed the age of presentation, malignant potential, and outcome of gastrinomas and pancreatic tumors in patients with multiple endocrine neoplasm, type 1. DESIGN: Screening of one very large and one smaller, possibly related family on an island, including serum gastrin estimations and, when indicated, pancreatic ultrasound. SETTING AND PATIENTS: Over 2000 family members and their family physicians were advised on screening procedures. INTERVENTION: Data were collected and reviewed retrospectively and prospectively for all medical records, investigations, surgical procedures, and available tissue samples. OUTCOME MEASUREMENTS: Criteria for diagnosis were established for radiological, biochemical, and histological studies. RESULTS: Sixty-two patients had evidence of gastrinoma or pancreatic neoplasm. In 19 patients the diagnosis was based on demonstration of a tumor. In 21 patients the diagnosis was based on elevated serum gastrin concentration in the absence of demonstrable tumor. None of these patients required gastric surgery if they first underwent parathyroidectomy. In 18 patients the diagnosis was based on the combination of demonstrated pancreatic tumor plus elevated glucagon (two patients), gastrin (11 patients), or insulin (five patients) concentration. Peptic ulcer was difficult to control in seven of the 11 patients with elevated gastrin concentrations plus demonstrated tumor. Four patients had liver metastases that appeared to be secondary to the pancreatic gastrinoma. In patients with insulinomas, the first symptoms occurred before age 20 years. Elevated serum gastrin concentrations were not seen before age 24 years and were observed to occur for the first time in two patients after age 50 years.

Adolescent↗
PubMed1993

Peptide alpha-amidation activity in human plasma: relationship to gastrin processing.

OBJECTIVE AND DESIGN: C-terminal amidation is an essential processing step towards bioactivation of many peptides including gastrin. This reaction is catalysed by peptidylglycine alpha-amidating mono-oxygenase (PAM, EC 1.14.17.3) which converts the glycine extended precursors on their carboxyl termini to the des-glycine amidated peptide products. In the case of gastrin, most of the amidation is thought to occur in the antrum. However substantial quantities of glycine extended gastrin and PAM are present in plasma. It is unclear whether circulating PAM reflects the secretory activity of the gastrin secreting cell or whether PAM is involved in the postsecretory processing of gastrin. The aim of the present study was to relate the circulating amidation activity to the plasma concentrations of glycine extended and amidated gastrins. PATIENTS AND MEASUREMENTS: Plasma PAM, gastrin-amide and gastrin-gly were measured in subjects with different gastrin secretory status: healthy subjects basally and following a meal, members of families with multiple endocrine neoplasia type 1 (MEN-1) with normal and high plasma gastrin, and patients with hypergastrinaemic atrophic gastritis. RESULTS: Patients with MEN-1 and hypergastrinaemia tended to have a higher plasma PAM activity than MEN-1 subjects with normal circulating G-NH2 indicating a cosecretion of hormone and PAM. However in contradistinction to patients with medullary thyroid carcinoma, PAM activity does not appear to be a useful tumour marker of gastrinoma. Hypergastrinaemia from a non-tumour source (hypergastrinaemic non-atrophic gastritis) was associated with a lower plasma PAM activity than in normal subjects and may reflect the secretion of a greater proportion of already amidated gastrin. In general, there was no relationship between plasma PAM activity and the ratio of amidated to non-amidated gastrin suggesting that circulating PAM was not involved in the amidation of gastrin. Feeding increased circulating gastrin but had no effect on plasma PAM activity. CONCLUSION: The results support the view that gastrin is amidated at the site of its synthesis and that hypergastrinaemia is associated with elevated plasma amidating enzyme activity only when the gastrin originates from tumour sources.

Anemia, Pernicious↗
PubMed1993

Ultrasonography of the pancreas in patients with multiple endocrine neoplasia type I.

Fifty-seven patients with the multiple endocrine neoplasia type I (MEN-1) syndrome underwent sonographic examinations, and focal pancreatic lesions were demonstrated in 18 (33%). Size ranged from 5 to 65 mm in diameter, and multiple lesions were seen in five patients. Eight patients with pancreatic lesions less than 20 mm have been followed over a period of 1 to 6 years. Of these eight patients, only one had a lesion that increased in size. Ultrasonography was able to detect asymptomatic pancreatic tumors in a higher proportion of MEN-1 patients than previously. Sonography is a useful method of detecting islet cell tumors greater than 5 mm in diameter and is able to follow up these lesions to assess increase in lesion size and number.

Adenoma, Islet Cell↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1986

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↗
PubMed1985

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↗