Plasmonic support-mediated activation of 1 nm platinum clusters for catalysis.

Nanometer-sized metal clusters are prime candidates for photoactivated catalysis, based on their unique tunable optical and electronic properties, combined with a large surface-to-volume ratio. Due to the very small optical cross sections of such nanoclusters, support-mediated plasmonic activation could potentially make activation more efficient. Our support is a semi-transparent gold film, optimized to work in a back-illumination geometry. It has a surface plasmon resonance excitable in the 510-540 nm wavelength range. Ptn clusters (size distribution peaked at n = 46 atoms) have been deposited onto this support and investigated for photoactivated catalytic performance in the oxidative decomposition of methylene blue. The Pt cluster catalytic activity under illumination exceeds that of the gold support by more than an order of magnitude per active surface area. To further investigate the underlying mechanism of plasmon-induced catalysis, the clusters have been imaged with optically-assisted scanning tunneling microscopy under illumination. The photoactivation of the Pt clusters via plasmonic excitation of the support and subsequential electronic excitation of the clusters can be imaged with nanometer resolution. The light-induced tunneling current on the clusters is enhanced relative to the gold film support.

Effects of serotonergic agents on survival and hemolymph composition of the larval mosquito Aedes aegypti (Diptera: Culicidae, L.) in vivo: does serotonin regulate hemolymph acid-base homeostasis?

The role of serotonin in the regulation of larval Aedes aegypti hemolymph composition was investigated in vivo using two reuptake inhibitors (SSRIs), alaproclate HCl and 6-nitroquipazine maleate, and the receptor antagonist methiothepin mesylate. Larvae were placed in media differing in pH and salinity in the presence and absence of serotonergic agents. The toxicity of each agent was strongly influenced by ambient pH. For each agent, toxicity was negligible in acidic media, intermediate in neutral media and greatest in alkaline media. By contrast, toxicity of all agents was independent of salinity. No effects on mass-specific body water or hemolymph volume were observed whereas hemolymph osmotic pressure, Na(+) concentrations and pH differed significantly among treatments. 6-nitroquipazine caused a decrease in Na(+) from 115+/-1.7 to 103+/-0.9 mmol l(-1), and alaproclate caused alkalosis of the hemolymph from pH 7.55+/-0.026 to pH 7.72+/-0.044. Methiothepin decreased hemolymph osmotic pressure from 329+/-9.9 to 304+/-8.8 and showed the greatest overall toxicity. Control larvae excreted net base in pH 4 media (1.4 micromol g(-1) h(-1)) and net acid in pH 7 (1.2 micromol g(-1) h(-1)) and pH 11 (5.1 micromol g(-1) h(-1)) media. In pH 4 media, alaproclate and methiothepin caused a shift to net H(+) excretion (1.1 and 1.5 micromol g(-1) h(1), respectively) whereas these agents did not influence acid excretion rates in pH 7 or pH 11 media. The hypothesis that serotonin is involved in hemolymph acid-base balance is discussed.

Malignant thymic carcinoid is not prevented by transcervical thymectomy in multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant tumour syndrome. It is characterized by primary hyperparathyroidism, pituitary neoplasia and foregut lineage neuroendocrine neoplasia. Malignant thymic carcinoid tumours are an uncommon but important manifestation of MEN 1. Transcervical thymectomy is often advocated as prophylaxis against thymic carcinoids, although there is a paucity of evidence to support the efficacy of this procedure. This is the first report of a malignant thymic carcinoid occurring in an MEN 1 patient following prior parathyroidectomy and transcervical thymectomy. It is concluded that transcervical thymectomy does not reliably provide prophylaxis against thymic carcinoid.

Phenotype and phenocopy: the relationship between genotype and clinical phenotype in a single large family with multiple endocrine neoplasia type 1 (MEN 1).

BACKGROUND: The majority of reports describing the natural history and prognosis of multiple endocrine neoplasia type 1 (MEN 1) utilize phenotypic rather than molecular genetic criteria to establish a diagnosis of MEN 1. OBJECTIVES AND PATIENTS: We sought to determine the spectrum of endocrine abnormality amongst 152 members (64 gene carriers and 88 noncarriers) of a large MEN 1 family in whom a determination of MEN 1 status had previously been made by phenotype screening. The predictive utility of both clinical and molecular screening techniques are described. RESULTS: A novel IVS2-3 (C-G) MEN1 mutation was identified in affected members of this family. Seven (10%) of 71 individuals satisfying clinical diagnostic criteria for MEN 1 were found to be genetically negative (excluded by mutation analysis and haplotyping) for MEN 1. These cases of MEN 1 phenocopy comprised four cases of primary hyperparathyroidism, two 'nonsecretory' pituitary adenoma and one case of coincident prolactinoma and hyperparathyroidism. Three of the patients with hyperparathyroidism had previously required parathyroidectomy and each had achieved normocalcaemia following parathyroid resection. Predictive genetic testing prospectively identified three children with the MEN 1 genotype. Serum calcium was normal at the time of their initial molecular genetic diagnosis. In each case hyperparathyroidism subsequently developed during adolescence. CONCLUSION: Multiple endocrine neoplasia type 1 phenocopy is an important differential diagnosis in patients exhibiting an multiple endocrine neoplasia type 1 phenotype. This is a relevant consideration, particularly when the diagnosis of multiple endocrine neoplasia type 1 is made using sensitive, but nonspecific, criteria such as mild hyperparathyroidism, pituitary micoadenoma, and hyperprolactinaemia. Confirmatory genetic testing should be undertaken to confirm clinical diagnoses of multiple endocrine neoplasia type 1.

Preoperative sestamibi scanning and surgical findings at bilateral, unilateral, or minimal reoperation for recurrent hyperparathyroidism after subtotal parathyroidectomy in patients with multiple endocrine neoplasia type 1.

HYPOTHESES: Preoperative parathyroid radioisotope scanning is of little or no value in patients with multiple endocrine neoplasia type 1 when 4 or more hypertrophied glands are present. Scanning using technetium Tc 99m sestamibi and single photon emission computed tomography will achieve a high level of sensitivity and specificity after 3 or more glands have previously been removed, justifying limited surgical reexploration. DESIGN: In a prospective study, the preoperative documented report of the predicted site of residual parathyroid was compared with the surgical findings in 13 patients having 19 scans and 17 reoperations. SETTING: All patients belonged to one family, previously described as Tasman family 1, and were confirmed by genetic testing as having multiple endocrine neoplasia type 1. In 10 of 13 patients, reexploration was being undertaken more than 10 years after the first operation. MAIN OUTCOME MEASURES: Scanning was regarded as successful when the documented preoperative report correctly predicted the side and quadrant in which a gland was found at surgery. Surgery was regarded as successful when calcium levels decreased to or below normal levels and were maintained. RESULTS: All 13 scans before first reexploration were successful in identifying the location of a residual parathyroid. From a statistical viewpoint, this equates to 100% sensitivity and 92% specificity. However, despite accurate localization of 1 residual gland in every patient, 7 supernumerary glands in 4 patients and 1 parathyroid remnant in a fifth patient were not localized so that sensitivity in locating all glands in every patient was only 61%. Scans performed for persistent hypercalcemia 48 to 72 hours after reexploration in 2 patients were unsuccessful in demonstrating any residual parathyroid. Scans performed 3 months after surgery in the same 2 patients and a third patient were successful, with sensitivity and specificity of 100%. Apart from patient 11, who awaits reexploration, normocalcemia was eventually achieved in every patient, with 11 of 12 having an initial period of hypocalcemia. CONCLUSIONS: Three months after reexploration and trimming or resection with transplant of half a gland left at first operation, sestamibi scanning achieved sensitivity and specificity of 100% in locating supernumerary parathyroids in patients with multiple endocrine neoplasia type 1 and persistent hypercalcemia. Before first reexploration, however, scans rarely provided new information, predominantly showing only the hypertrophied half-gland remnant.

Octreotide improves biochemical, radiologic, and symptomatic indices of gastroenteropancreatic neoplasia in patients with multiple endocrine neoplasia type 1 (MEN-1). Implications for an integrated model of MEN-1 tumorigenesis.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant tumor syndrome associated with parathyroid, gastroenteropancreatic (GEP), and pituitary neoplasia. Gastrinoma and GEP malignancy are common life-threatening endocrine complications of MEN-1. An effective management strategy for these disorders remains to be determined. The authors attempted to determine the role of the somatostatin analogue, octreotide, in ameliorating features of hypergastrinemic GEP neoplasia associated with MEN-1. METHODS: Five MEN-1 patients with hypergastrinemia and either symptoms of GEP neoplasia or hepatic metastases received a trial of octreotide, 100 microg subcutaneously, three times daily for 3 months. RESULTS: Treatment with octreotide was associated with a rapid symptomatic and biochemical response. In all patients serum gastrin fell to < 25% of the pretreatment value. The serum glycoprotein-alphasubunit (a marker of enterochromaffin-like [ECL] cell hyperplasia, gastric carcinoidosis, and disseminated enteropancreatic malignancy) was elevated at baseline in three patients. In each case the serum glycoprotein-alphasubunit normalized after treatment with octreotide. Hepatic metastases were present in two patients at baseline. The size of the metastases diminished by up to 15% during the period of octreotide treatment. Four patients reported symptoms prior to treatment: lethargy, easy fatigability, and generalized musculoskeletal discomfort. A marked symptomatic improvement occurred in each case. No patient experienced side effects related to octreotide therapy and all elected to remain on treatment after completion of the trial. CONCLUSIONS: Octreotide is a safe and effective adjunct to surgical strategies for the management of GEP neoplasia in hypergastrinemic MEN-1 patients.

Osteoporosis in multiple endocrine neoplasia type 1: severity, clinical significance, relationship to primary hyperparathyroidism, and response to parathyroidectomy.

BACKGROUND: Sporadic primary hyperparathyroidism (PHPT) occurs most frequently in postmenopausal women. Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal-dominant disease in which mild to moderate PHPT develops in most gene carriers by 20 years of age. Primary hyperparathyroidism associated with MEN 1 is typically recurrent, despite initially successful subtotal parathyroidectomy. Osteoporosis is considered a complication of sporadic PHPT and an indication for parathyroidectomy. In the setting of MEN 1, however, the relationship of bone mass to PHPT, fracture risk, and parathyroidectomy is unknown. HYPOTHESIS: Parathyroidectomy improves bone mineral density for patients with primary hyperparathyroidism in the setting of MEN 1. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Twenty-nine women with MEN 1 belonging to a single family with a history of MEN 1. INTERVENTIONS: Parathyroidectomy. MAIN OUTCOME MEASURES: Bone mineral density (BMD) and history of skeletal fracture. RESULTS: Osteopenia and osteoporosis were diagnosed in 41% and 45% of patients, respectively. Forty-four percent of patients with uncontrolled PHPT had severe osteopenia (T score, <-2.0) by 35 years of age. Reduction in BMD was greatest at the femoral neck. Reduced BMD was associated with an increased likelihood of skeletal fracture (P = .05). Patients with uncontrolled PHPT had lower femoral neck and lumbar spine BMDs than those in whom PHPT was controlled by parathyroidectomy (P = .005 and .02, respectively). Successful parathyroidectomy improved femoral neck and lumbar spine BMDs by a mean +/- SEM of 5.2% +/- 2.5% and 3.2% +/- 2.9%, respectively. CONCLUSIONS: Osteoporosis is a frequent and early complication of PHPT in MEN 1. Despite difficulty in achieving a cure of PHPT in MEN 1, parathyroidectomy has an important role in the optimization of BMD for patients with MEN 1.

Enteropancreatic malignancy associated with multiple endocrine neoplasia type 1: risk factors and pathogenesis.

BACKGROUND: Enteropancreatic malignancy is an important cause of morbidity and mortality associated with multiple endocrine neoplasia type 1 (MEN 1). However, the risk factors and mechanisms of the tumorigenesis of this malignancy are poorly understood. METHODS: The authors conducted a retrospective study of factors associated with the development of malignant enteropancreatic tumor in 69 patients with MEN 1 belonging to a single family. RESULTS: Metastatic enteropancreatic tumor and gastrinoma were identified in 20% and 36% of patients, respectively. Compared with MEN 1 patients who did not have an immediate family history of enteropancreatic malignancy, MEN 1 patients with a first-degree relative affected by enteropancreatic malignancy had an increased risk of developing disseminated tumor (odds ratio, 3.7; P < 0.05). In addition, hypergastrinemia and advanced age were both associated with a significant increase in the risk of enteropancreatic malignancy. Elevated serum glycoprotein alpha subunit levels were associated with enterochromaffin-like cell hyperplasia, gastric carcinoid formation, and disseminated enteropancreatic tumor in hypergastrinemic patients (P < 0.05). CONCLUSIONS: Disease modifier factors act in concert with the MEN 1 gene to modulate the development of enteropancreatic neoplasia. It is possible to identify MEN 1 patients at high risk for developing aggressive enteropancreatic tumors. Heritable disease modifier factor(s) affecting enteropancreatic malignancy appear to reside at loci distinct from that of the MEN 1 gene.

Expression of the MEN-1 gene in a large kindred with multiple endocrine neoplasia type 1.

In 1983 a large family with MEN-1 (designated Tasman 1) was identified in Tasmania. Kindred screening and case follow-up over the subsequent 15 years has yielded data on over 160 MEN-1-affected patients. Hyperparathyroidism is present in over 60% of gene carriers by age 20 years and 95% by age 30 years. Hyperplasia is the characteristic pathological finding. Kaplan-Meier analysis indicates hyperparathyroidism recurs in the majority of patients despite near-total parathyroidectomy. Gastrinoma, 'nonfunctioning' pancreatic adenoma and insulinoma occur in up to 60, 50 and 10% of patients, respectively. Metastatic gastroenteropancreatic (GEP) tumours develop in up to 35% of family members, being frequent in some branches of Tasman 1, whilst rare in others. Pituitary disease developed in 19% of patients. Prolactinoma and 'nonfunctioning' adenoma account for 76 and 24%, respectively, of pituitary abnormalities. Prolactinomas exhibit clustering within branches of the Tasman 1 kindred. Adrenal adenomas occur in 36% of patients. The majority of adrenal lesions are benign and nonsecretory and develop in association with pancreatic neoplasia. Carcinoid tumours are uncommon but important malignancies. Malignant thymic carcinoid occurs in male patients, whereas bronchial carcinoid occurs predominantly in women. Prior to recognition of MEN-1 in Tasman 1, complications of hyperparathyroidism and malignancy accounted for the majority of patient mortality. Since commencement of prospective screening, malignant GEP tumours and cardiovascular disease have become the most prevalent causes of death amongst MEN-1-affected patients.

The outcome of subtotal parathyroidectomy for the treatment of hyperparathyroidism in multiple endocrine neoplasia type 1.

BACKGROUND: The efficacy of subtotal parathyroidectomy for the treatment of hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN 1) is unclear. The long-term outcome and optimal timing of operation remain controversial. OBJECTIVE: To determine the long-term outcome of parathyroidectomy for primary hyperparathyroidism in the presence of MEN 1. DESIGN: Case series and retrospective analysis. SETTING: Tertiary referral center. PATIENTS: Patients with MEN 1 from 2 families. INTERVENTIONS: Subtotal parathyroidectomy, ie, resection of 3 1/2 parathyroid glands from each patient. MAIN OUTCOME MEASURES: Recurrence of hyperparathyroidism. RESULTS: Thirty-seven patients underwent subtotal parathyroidectomy. Overall, persistent postoperative hypoparathyroidism developed in 24%, normocalcemia was maintained in 46%, and hyperparathyroidism recurred in 30%. However, after adjustment for the duration of follow-up (by using the Kaplan-Meier method), the cumulative recurrence rates for hyperparathyroidism were 15% at 2 years, 23% at 4 years, 55% at 8 years, and 67% after 8 years. Early recurrence of hyperparathyroidism (within 5 years of operation) was less likely to develop in patients in whom ionized calcium levels of 1.00 mmol/L (4.00 mg/dL) or less were achieved during the perioperative period than in patients in whom this degree of hypocalcemia failed to develop (P=.01). CONCLUSIONS: While relatively long periods of disease remission are possible after subtotal parathyroidectomy, our results indicate that recurrent hyperparathyroidism eventually develops in most patients with MEN 1.

Adrenal lesions in a large kindred with multiple endocrine neoplasia type 1.

OBJECTIVE: To review the prevalence and natural history of adrenal lesions occurring in patients from a single kindred with multiple endocrine neoplasia type 1 (MEN-1). DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Medical records of 33 patients from the Tasman 1 MEN-1 kindred who had undergone abdominal computed tomographic (CT) scanning were reviewed. In 30 patients, the results of abdominal ultrasonographic examinations were available for correlation with CT scan. Computed tomographic and ultrasound scans of 18 patients were reviewed by a radiologist blinded to the patients' clinical details. Three patients underwent adrenalectomy, and the histopathologic material was reviewed. MAIN OUTCOME MEASURES: Computed tomographic and ultrasound scans. RESULTS: Adrenal lesions were detected in 12 patients (36%) by CT scan examination. Ultrasound imaged 58% of these lesions. Pancreatic lesions were present in all cases of adrenal disease. Follow-up was available for 8 patients with adrenal disease. Over 5.5 years, 6 patients (75%) had stable disease, 1 patient had an adrenal lesion that enlarged by 5 mm, and 1 patient had a lesion that enlarged by 50 mm. Adrenal histopathologic material was available in 3 patients. Macronodular cortical hyperplasia was present in 2 patients and a cortical adenoma present in 1 patient. Another kindred had bilateral macronodular cortical hyperplasia at autopsy. CONCLUSIONS: Adrenal lesions are common in MEN-1 and occur in association with pancreatic disease. Abdominal CT scan is more sensitive than ultrasonographic examination in detecting adrenal disease. Primary hypersecretory syndromes of the adrenal glands appear to be rare, and the majority of lesions follow an indolent clinical course.

Spectrum of pituitary disease in multiple endocrine neoplasia type 1 (MEN 1): clinical, biochemical, and radiological features of pituitary disease in a large MEN 1 kindred.

Prolactinomas and somatotropinomas are reported to be the pituitary lesions most frequently associated with multiple endocrine neoplasia type 1 (MEN 1). However, few reports have documented the full spectrum of pituitary disease in this condition. We report herein the clinical, biochemical (PRL, alpha-subunit, insulin-like growth factor-I, cortisol, and thyroid function), and radiological (magnetic resonance imaging and computerized tomography scan) characteristics of pituitary disease occurring in a single MEN 1 pedigree containing 165 MEN 1-affected members. Pituitary lesions were detected in 30 (18%) of 165 patients overall. In the subgroup of MEN 1 patients (n = 131) living after recognition of MEN 1 in the kindred, pituitary lesions were detected in 25 (19%). In 76% of patients with pituitary lesions, the diagnosis was made by prospective screening; the remainder sought medical attention for symptomatic pituitary disease. Prolactinomas accounted for 76%, and nonfunctioning adenomas accounted for the remaining 24%. alpha-Subunit elevation was observed in 29% of 41 patients tested, and an aggressive alpha-subunit secreting macroadenoma developed in 1 subject with a previously documented prolactinoma. Progression of pituitary disease occurred in 47% of patients with prolactinoma. There were no cases of Cushing's disease, thyrotropinoma, or somatotropinoma. We conclude that 1) in addition to prolactinomas, nonfunctioning pituitary tumors are common in MEN 1; 2) alpha-subunit hypersecretion is frequent in MEN 1; 3) comprehensive screening may identify many clinically significant but asymptomatic pituitary lesions; and 4) prolactinomas occurring in MEN 1 may behave more aggressively than sporadic prolactinomas.

Prolactinomas in a large kindred with multiple endocrine neoplasia type 1: clinical features and inheritance pattern.

Multiple endocrine neoplasia type 1 (MEN 1) is associated with neoplasia and hyperfunction of the parathyroid and pituitary glands, pancreatic islet cells, and neuroendocrine cells of the gut. The inheritance pattern is autosomal dominant, and the underlying genetic defect is situated at chromosome 11q13. The MEN 1 gene behaves as a defective copy of a normally constitutive tumor suppressor gene. Development of the MEN 1 phenotype, however, is a multistep and multifactorial process. The Tasman 1 genealogy is the largest MEN 1 pedigree detected to date. Thus far, 90 related members with MEN 1 have been screened for evidence of prolactinoma. Prolactinomas were found in 18 patients (20%). Prolactinomas were not evenly distributed in the genealogy; in 2 branches of the overall genealogy prolactinomas were present in 50% or more of MEN 1-affected members. The familial distribution of prolactinomas in these branches was consistent with an autosomal dominant mode of inheritance. In the remainder of the pedigree, prolactinomas were uncommon and did not display this inheritance pattern. This pedigree represents one of the largest published MEN 1 genealogies in which the risk of developing prolactinoma follows an autosomal dominant pattern of transmission. It is the first to demonstrate an inheritance pattern for prolactinomas acting in addition to, yet distinct from, the inheritance of the underlying MEN 1 gene defect. These findings are consistent with the existence of an undefined second genetic defect involved in the pathogenesis of prolactinoma in MEN 1.

Somatotrophinomas in multiple endocrine neoplasia type 1: a review of clinical phenotype and insulin-like growth factor-1 levels in a large multiple endocrine neoplasia type 1 kindred.

PURPOSE: Within the spectrum of pituitary disease in multiple endocrine neoplasia type 1 (MEN-1), widely disparate prevalence rates for somatotrophinomas have been described. Studies that combine multiple, small MEN-1 kindreds report pituitary disease in 60% to 65% of patients, somatotrophinomas accounting for 27% to 37% of total pituitary lesions. However, reports based on large MEN-1 family screening programs have produced lower prevalence rates for pituitary adenomas (9% to 40%), of which somatotrophinomas comprise up to 14%. We sought to determine the prevalence of both biochemical and clinically overt growth hormone (GH) hypersecretion in the largest reported MEN-1 genealogy, the Tasman 1 kindred. PATIENTS AND METHODS: The Tasman 1 MEN-1 kindred contains 165 members with established MEN-1. We reviewed the records of 124 MEN-1 patients for evidence of acromegaly or gigantism. To determine if clinical criteria underestimate the occurrence of biochemical GH hypersecretion, a subset of 33 patients was assessed for elevated levels of serum insulin-like growth factor-1 (IGF-1). RESULTS: No cases of acromegaly or gigantism were detected in the 124 patients reviewed. Of the 33 patients screened with IGF-1, 13 had previously diagnosed pituitary lesions--11 prolactinomas and 2 nonsecretory lesions. The IGF-1 levels were normal in all patients studied. There were no significant differences in mean IGF-1 values between patients with and without pituitary lesions. CONCLUSIONS: This report represents the largest study of growth hormone secretion patterns thus far described in MEN-1. The apparent absence of somatotrophinomas in a kindred of this size is unexpected. These results support the existence of kindred-specific MEN-1 phenotypes. We conclude that the pathogenesis of GH-secreting adenomas in MEN-1 is influenced by secondary factors acting in synergy with the well-documented primary MEN-1 gene defect on chromosome 11q13.

P53 tumour suppressor gene expression in hyperparathyroidism.

BACKGROUND: Mutations of the p53 tumour suppressor gene lead to the loss of control of normal cellular proliferation and differentiation and have been shown to be associated with the development of malignancy. METHOD: Archival paraffin resection specimens from 86 cases of hyperparathyroidism treated surgically using the rabbit polyclonal CMI antibody were investigated to detect p53 immunoreactivity in these sections. RESULTS: Eighteen of the 86 sections examined (21%) showed nuclear immunoreactivity. No correlation was detected between tumour histology and p53 immunoreactivity (P = 0.45), nor was there any correlation between tumour clonality and immunoreactivity (P = 0.54). Multiple endocrine neoplasia type 1 (MEN 1) status did not correlate with p53 immunoreactivity. A significant correlation between p53 immunoreactivity and preparathyroidectomy calcium levels of > 1.5 mmol/L was detected (P < 0.005) although no correlation was noted between p53 immunoreactivity and higher levels of preparathyroidectomy intact parathyroid hormone (PTH) levels. CONCLUSION: A relationship is postulated between abnormal serum calcium regulation and p53 mutation in hypercalcaemic states associated with hyperparathyroidism.

The prevalence of MEN-1 in Tasmania.

BACKGROUND: An extensive programme was undertaken to trace and screen four known families in Tasmania with multiple endocrine neoplasia type 1 (MEN-1). METHODS: Written and personal contact was made with family members over the age of 20 years recommending a review by family practitioners for the purpose of recording their medical history and collecting a blood sample. Those suspected of MEN-1 were referred to our Department for further investigation. RESULTS: In January 1993, the total number of individuals alive and known to be affected by MEN-1 was 107, giving a prevalence of MEN-1 disease in Tasmania of 23/100 000. The estimated prevalence of MEN-1 trait in Tasmania (including affected cases and those considered at 50% risk of possessing the trait) is 45/100 000. CONCLUSION: The prevalence of MEN-1 has never previously been determined accurately. The prevalence of MEN-1 in Tasmania is at the upper end of the possible range and would justify the allocation of resources for screening programmes equal to those available for the detection of several less prevalent genetic diseases.

Hyperparathyroidism presenting as pancreatitis or complicated by postoperative pancreatitis.

BACKGROUND: The association of hyperparathyroidism with acute pancreatitis either pre-operatively or postoperatively has been questioned in recent overseas literature. METHODS: A review of medical records and histology reports in the Royal Hobart Hospital from 1971 to 1993 was carried out to identify all cases of acute pancreatitis associated with primary hyperparathyroidism. RESULTS: Seven cases are presented, six with histological confirmation, of hyperparathyroidism associated with pancreatitis in a period when 137 confirmed cases of primary hyperparathyroidism were treated. None of these patients had gallstones. In two, alcohol abuse may have been the aetiological factor. Five patients had successful neck exploration and none of them have experienced any further attacks including a 25 year old who had four hospitalizations and one laparotomy for pancreatitis in the year before parathyroidectomy 12 years ago. Two patients died from acute pancreatitis, one without exploration and the other with a mediastinal parathyroid adenoma that was not located at surgery. CONCLUSIONS: Most parathyroid surgeons would proceed to mediastinotomy, if necessary, at initial exploration in a patient with previous hypercalcaemic crisis. This should also be considered in patients with a history of acute pancreatitis.

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.