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A Picone

Publications and source records attributed to A Picone.

At least 19 recordsLinked to original sources

Limits and drawbacks of video-assisted parathyroidectomy.

BACKGROUND: Minimally invasive video-assisted parathyroidectomy (MIVAP) is a novel minimally invasive approach to primary hyperparathyroidism (PHPT). It is a gasless operation characterized by a single central incision and external retraction. This paper describes the drawbacks and limitations of this procedure based on a 5-year experience and 260 operations. METHODS: Of 364 patients with PHTP, 260 were selected for MIVAP. In most patients a unilateral minimally invasive exploration was performed. RESULTS: MIVAP was carried out successfully in 239 patients with a mean operating time of 40 (range 20-180) min. Conversion to cervicotomy was required in 21 patients (8.1 per cent). Complications included recurrent nerve palsy in two patients (0.8 per cent), haemorrhage that required reoperation 6 h after parathyroidectomy in one patient (0.4 per cent) and transient hypoparathyroidism in six patients (2.5 per cent). In five patients (2.1 per cent) persistent PHPT developed shortly after surgery. CONCLUSION: After 5 years of experience, MIVAP appears to be feasible, safe and applicable to the majority of patients with PHPT.

Adenoma↗

MEN1 gene alterations do not correlate with the phenotype of sporadic primary hyperparathyroidism.

Loss of heterozygosity (LOH) in the MEN1 region on chromosome 11q13 and MEN1 gene mutations have been found in a subset of sporadic parathyroid tumors. The question of whether these genetic abnormalities in the parathyroid tumors might influence the clinical and biochemical characteristics of primary hyperparathyroidism (PHPT) remains to be elucidated. The aim of the present study was to correlate the presence of MEN1 gene alterations in PHPT tumors with the clinical phenotype. Using microsatellite analysis for LOH at 11q13 and DNA sequencing of the coding exons, the MEN1 gene was studied in 38 parathyroid tumors of patients with sporadic PHPT. Fourteen tumors showed LOH at 11q13, and mutations of MEN1 gene were detected in 7 cases. The clinical and biochemical characteristics of patients were unrelated to the presence or absence of LOH and/or MEN1 gene mutations. In conclusion, MEN1 gene alterations are rather common in sporadic PHPT and their presence does not correlate with the clinical manifestations of the disease.

Adenoma↗

A quick intraoperative parathyroid hormone assay in the surgical management of patients with primary hyperparathyroidism: a study of 206 consecutive cases.

OBJECTIVE: The traditional surgical approach for patients with primary hyperparathyroidism (PHPT) consists of the identification of at least four glands and in the removal of all hyperfunctioning parathyroid tissue. DESIGN: To evaluate whether intraoperative parathyroid hormone (PTH) monitoring will allow a more limited surgical procedure by confirming complete removal of all hyperfunctioning tissue. METHODS: Plasma samples were obtained from 206 consecutive patients with sporadic PHPT before skin incision, during manipulation of a suspected adenoma, and 5 min (T-5) and 10 min after removal of abnormal parathyroid tissue. PTH was measured by a quick immunochemiluminescent assay (QPTH). The operative success was defined by a decrease of PTH greater than 50% of the highest pre-excision value. RESULTS: A >50% decrease of PTH occurred in 203 patients and was evident at T-5 in the majority of cases. All but three had normal serum calcium the day after surgery and afterwards. PTH concentration did not show a >50% decrease in the remaining three cases after completion of surgery. One patients had negative neck exploration and remained hypercalcemic; the other two had normal serum calcium at follow-up. Thus, the intraoperative QPTH correctly predicted the outcome of surgery in 201 patients (97.5%) (200 true positive and 1 true negative), and provided three false positive and two false negative results. CONCLUSIONS: The intraoperative QPTH measurement represents a useful tool to assist the surgeon during parathyroidectomy. It indicates whether all hyperfunctioning parathyroid tissue has been removed, limiting the procedure to a unilateral neck exploration in most cases.

Adult↗

Evidence of increased matrix metalloproteinase-9 concentration in patients following cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response, which can result in acute lung injury known as "postperfusion syndrome." Neutrophil activation with concomitant serine protease release has been implicated in the pathogenesis of "postperfusion syndrome." Increased plasma levels of neutrophil elastase (NE) have been demonstrated in patients undergoing CPB, and it is well documented that both NE and matrix metalloproteinase-9 (MMP-9) have a synergistic role in pulmonary injury. We, therefore, hypothesized that plasma levels of MMP-9 would be elevated in patients after CPB. Human plasma was obtained after informed consent from eight patients undergoing CPB. Plasma was collected at the start of CPB, 5 minutes after the initiation of CPB, and at the termination of CPB (156 +/- 17 min). All samples were analyzed by both standard enzyme-linked immunosorbent assay (ELISA) and gelatin zymography for MMP-9 (free and total enzyme) concentration. Data were expressed as means +/-SE and assessed by analysis of variance (ANOVA). Plasma MMP-9 concentration was significantly increased at the end of CPB (191 +/- 30.4 ng/mL; p <.05) as compared to both the start of CPB (28.3 +/- 13.2 ng/mL) and 5 minutes after the initiation of CPB (44.3 +/- 15.4 ng/mL). Patients undergoing CPB show an increase in serum MMP-9 levels. Prior studies utilizing an animal model of "postperfusion syndrome" have shown that inhibition of MMP-9 and NE prevented pulmonary injury following CPB. The results of the current study suggest that such an approach may also have merit in the clinical setting of cardiopulmonary bypass.

Adult↗

Six novel MEN1 gene mutations in sporadic parathyroid tumors.

We report nine mutations of the multiple endocrine neoplasia type 1 (MEN1) gene in sporadic parathyroid adenomas. Six of them have not previously been described: E60X, P32R, 261delA, 934+2T-->G, S443P, and 1593insC. The tissue samples were initially submitted to LOH analysis at 11q13 followed by SSCP screening of LOH-positive samples. Mutations were identified by direct sequencing and subcloning. Three (E60X, P32R, and 261delA) were in exon 2, one (934+2bp) in the splice junction of exon 5, one (S443P) in exon 9, and one (1593insC) in exon 10. The 3 mutations in exon 2 were associated with loss and/or creation of a restriction site. The corresponding germline sequence of the MEN1 gene was normal. Most mutations would likely result in a nonfunctional menin protein, and therefore in the loss of a tumor suppressor protein.

Adenoma↗

Parathyroid expression of calcium-sensing receptor protein and in vivo parathyroid hormone-Ca(2+) set-point in patients with primary hyperparathyroidism.

A reduced expression of calcium-sensing receptor (CaR) messenger ribonucleic acid and protein accompanied by abnormalities in parathyroid cell proliferation and PTH secretion are present in primary hyperparathyroidism. We studied the expression of CaR protein by immunohistochemistry in 36 sporadic parathyroid adenomas and investigated the relationship between CaR expression and several preoperative clinical parameters, including the set-point of Ca(2+)-regulated PTH secretion (measured in vivo). The adenomas were classified in 4 categories according to the intensity of immunohistochemical staining: 5 (14%) showed a CaR staining intensity similar to that of normal parathyroid ( ), 10 (27%) showed moderate staining (++), 16 (45%) showed weak staining (+), and 5 (14%) were negative (-). The intensity of CaR staining was not related to preoperative serum Ca(2+), PTH levels or adenoma volume. Twenty-nine patients underwent preoperatively the calcium infusion test to evaluate the PTH-Ca(2+) set-point. Individual values of PTH-Ca(2+) set-point ranged from 1.38-1.93 mmol/L and were significantly correlated with basal Ca(2+) levels (r = 0.96; P: = 0. 0001) and adenoma volume (r = 0.5; P: = 0.01). The mean PTH-Ca(2+) set-point values were significantly different in the 4 groups of patients classified according to immunohistochemical staining intensity of their adenoma (P: = 0.025; F = 3.78); the mean PTH-Ca(2+) set-point was significantly higher in the groups classified as negative than in those classified as weak or moderate. No correlation was observed between the PTH-Ca(2+) set-point and basal PTH levels or between the percent maximal PTH inhibition and adenoma volume and basal PTH or Ca(2+) levels. In summary, our data suggest that there is a relationship between apparent CaR protein expression and PTH-Ca(2+) set-point abnormality, suggesting that a reduced receptor content might have an important role in the pathogenesis of primary hyperparathyroidism.

Adenoma↗

Multicenter study on hepatitis C virus infection in patients with dilated cardiomyopathy. North Italy Transplant Program (NITP).

Preliminary epidemiological and histological studies from Japan suggested that hepatitis C virus (HCV) infection has a role in the development of dilated cardiomyopathy (DCM). This multicenter study was conducted to verify this hypothesis on a large cohort of Italian patients with end-stage heart failure. Antibodies to HCV were determined in the 752 consecutive patients (608 males and 144 females; age, 53 +/- 13 years) who entered the waiting list for cardiac transplantation from 1995 to 1997 at the six cardiac surgery centers participating in the North Italy Transplant program. Three hundred and nine patients (41%) had dilated, 9 (1%) restrictive, and 4 (0.5%) hypertrophic cardiomyopathy; 284 patients (38%) had ischemic, 65 (9%) valvular, and 22 (3%) congenital heart disease; 5 patients (0.5%) had primary pulmonary hypertension; 54 patients (7%) had other or nonspecified heart disease. Overall, 41 of 752 patients (5.4%) resulted anti-HCV-reactive. Serological evidence of HCV infection was found in 12 of 309 patients with DCM (3.9%; 95% CI, 1.7-6.0), and in 29 of 443 without DCM (6.5%; 95% CI, 4.2-8.8), without statistical difference (difference of prevalence rate: 2.6%; 95% CI, -4.9 to 5.8). In conclusion, HCV does not seem to have a primary role in the pathogenesis of DCM. However, since our findings are in disagreement with those obtained in smaller series of patients of other ethnicity, large studies from different countries should be conducted.

Aged↗

[Video-assisted parathyroidectomy: a series of 85 cases].

AIM OF THE STUDY: To verify the feasibility of video-assisted parathyroidectomy, set up the indications and report the results in a series of 85 patients. MATERIAL AND METHODS: From 1997 to 1999, 85 patients affected by primary hyperparathyroidism due to single gland disease, with an adenoma smaller than 35 mm as demonstrated by preoperative imaging, were referred for video-assisted parathyroidectomy. There were 62 females and 23 males. Mean age was 53 years, (range 23-82). Video-assisted parathyroidectomy was associated with intra-operative PTH quick-assay. Calcium testing was controlled before leaving the hospital, 1 month and 3 months later, and postoperative laryngoscopy was performed in all patients. RESULTS: There were five conversions to open cervicotomy: three due to a contra-lateral second adenoma, two because of an intrathyroidal adenoma. The mean operative time for video-assisted procedure was 59 minutes (range: 25-180). Circulating PTH levels 10 minutes after the removal of the affected gland(s) always dropped significantly, and pathological report confirmed the parathyroid nature of the specimens (mean diameter 13 mm, range 7-35). Morbidity consisted of five cases of transient hypocalcemia and one permanent laryngeal nerve paralysis. We registered no persistent or recurrent disease (mean follow-up 12.8 months, range 1-28). CONCLUSIONS: Video-assisted parathyroidectomy is feasible, and its results are similar to those of traditional procedure, while it seems superior as regards postoperative course and aesthetic results. It also allows different strategical decisions even during operation (i.e. bilateral exploration or thyroid lobectomy) by the same approach.

Adenoma↗

No evidence for mutations in the calcium-sensing receptor gene in sporadic parathyroid adenomas.

Inactivating mutations of the calcium-sensing receptor gene (CaR) might explain abnormalities in the regulation of both parathyroid cell proliferation and parathyroid hormone secretion. In a previous study, using RNAse A protection assay, no mutations were identified in a series of parathyroid specimens from patients with primary and secondary hyperparathyroidism, but the analysis was incomplete, since part of exon 6 could not be analyzed. In the present study, we examined the presence of mutations in the CaR gene in 20 parathyroid adenomas using direct sequencing. The entire coding region of the CaR gene was successfully amplified by polymerase chain reaction and directly sequenced. This analysis did not identify CaR gene mutations in any tumors studied. A polymorphism that encoded a single amino acid change (Ala826Thr) was identified in 4 parathyroid adenomas and in 8 of 50 normal unrelated subjects. Loss of heterozygosity studies were also performed on adenomas using markers for the locus of the CaR gene on chromosome 3q. No allelic loss was demonstrated. In conclusion, our results extend previous observation and suggest that clonal somatic mutations of the CaR gene and allelic loss at the CaR locus on chromosome 3q do not play a major role in the pathogenesis of sporadic parathyroid tumors.

Adenoma↗

A new mutation of the MEN1 gene in an italian kindred with multiple endocrine neoplasia type 1.

OBJECTIVE: To report a new mutation of the multiple endocrine neoplasia type 1 (MEN1) gene in an Italian kindred. DESIGN: The study included the female proband, aged 50 years, affected by primary hyperparathyroidism, insulinoma and prolactinoma, and ten relatives. Blood samples were obtained for biochemical and genetic analyses. Clinical screening tests included serum glucose, ionized calcium, intact parathyroid hormone, GH, insulin and prolactin. The coding sequence, including nine coding exons and 16 splice sites, was amplified by PCR and directly sequenced. RESULTS: Two additional cases of primary hyperparathyroidism were identified among the paternal family members. The sequence analysis showed a heterozygous T to C transition at codon 444 in exon 9, resulting in a leucine to proline substitution (L444P) in the patient and in the two paternal family members with primary hyperparathyroidism. The L444P amino acid change was absent in 50 normal subjects. The mutation determined the loss of a BlnI restriction site of the wild-type sequence and the creation of a new restriction EcoRII site. The patient, but not her paternal affected relatives, also had a common heterozygous polymorphism (D418D) in exon 9. CONCLUSIONS: A new MEN1 mutation (L444P) in exon 9 has been identified; this substitution caused the loss of a BlnI restriction site and the creation of a new EcoRII site.

Antisense Elements (Genetics)↗

Investigations into the sterility of manually assembled extracorporeal circuits with vented reservoirs.

This study was designed to investigate the ability of an extracorporeal circuit (ECC) with a vented hard shell reservoir to remain sterile for a period of 72 h under dry conditions. The study was conducted in three phases. In Phase One: Two previously published methods for detecting contamination of the ECC were compared. A group of positive controls was collected by contaminating identical circuits with a known level of Enterobacter cloacae (ATTC: 13047) before initiating a regimen of "sample-dilute-sample" culturing. Negative controls for this phase were conducted by randomly sampling 1 L per manufacturer's lot of lactated ringers with each detection method. Culture results suggest that large volume filtration, but not small aliquot sampling, is sensitive to extremely low levels of contamination. No growth was detected in any negative control samples. In Phase Two: 19 ECC consisting of a membrane oxygenator, vented hardshell reservoir, arterial filter, and PVC tubing were removed from their sterile packages, assembled, and left unprotected in the moderate traffic environment of a research laboratory. The circuits were then primed with Lactated Ringer's solution. The prime solution was sampled for aerobic contamination by large volume filtration. None of the 19 samples detected contamination. In Phase Three: 43 ECC identical to the Phase Two circuits were assembled and left unprotected in the substerile pump room. The circuits were then primed, circulated, and cultured as in Phase Two. One of the 43 samples was discarded because of a recognized break in aseptic technique during sample collection. None of the remaining samples detected contamination. Mathematical calculations of binomial probabilities suggest that the chance of an open ECC developing a detectable level of contamination within 72 h of its dry assembly is insignificant.

Enterobacter cloacae↗

Systemic inflammation induced by cardiopulmonary bypass: a review of pathogenesis and treatment.

The acute respiratory distress syndrome (ARDS) is a severe alteration in lung structure and function that develops secondary to a traumatic stimulus. When ARDS develops following cardiopulmonary bypass (CPB) it is know as postpump syndrome (PPS). ARDS can be caused by a single massive insult ("hit"); however, sequential minor insults ("hits") are more common clinically. The concept of multiple sequential insults causing ARDS has been termed the "two-hit" model of ARDS. The purpose of this article is to summarize our studies testing the hypothesis that PPS is caused by multiple sequential insults. To confirm our hypothesis, we developed a porcine model of "two-hit" PPS. Our model was composed of sequential benign insults, with CPB as the "first hit" and low dose of endotoxin as the "second-hit." It is our hypothesis that the mechanism of PPS is CPB-induced priming of polymorphonuclear leukocytes (PMNs) ("first-hit") with subsequent PMN activation by a second insult ("second-hit") such as endotoxin. Our model confirms this clinically relevant postulate, and we provide strategies to disrupt the inflammatory cascade leading to PPS.

Cardiopulmonary Bypass↗

A multicenter prospective study on the risk of acquiring liver disease in anti-hepatitis C virus negative patients affected from homozygous beta-thalassemia.

Although the risk of transfusion-transmitted hepatitis has been recently reduced, transfusion-dependent beta-thalassemia patients may still develop liver disease due to viral infection or iron overload. We assessed the frequency and causes of liver dysfunction in a cohort of anti-hepatitis C virus (HCV) negative thalassemics. Of 1,481 thalassemics enrolled in 31 centers, 219 (14.8%) tested anti-HCV- by second-generation assays; 181 completed a 3-year follow-up program consisting of alanine-aminotransferase (ALT) measurement at each transfusion and anti-HCV determination by third-generation enzyme-immunoassay (EIA-3) at the end of study. Serum ferritin levels were determined at baseline and at the end of follow-up. Ten patients were anti-HCV+ by EIA-3 at the end of follow-up. Of them, seven were already positive in 1992 to 1993 when the initial sera were retested by EIA-3, one tested indeterminate by confirmatory assay, and two had true seroconversion (incidence, 4. 27/1,000 person years; risk of infection, 1/7,100 blood units, 95% confidence interval [CI], 1 in 2,000-1 in 71,000 units). At baseline, 67 of 174 thalassemics had abnormal ALT. Of those with normal ALT, seven subsequently developed at least one episode of moderate ALT increase (incidence, 24.6/1,000 person-years). All of the 20 patients with ferritin values >/=3,000 ng/mL had clinically relevant ALT abnormalities, as compared with 53 of 151 with <3,000 ng/mL (P < .005). Hepatic dysfunction is still frequent in thalassemics. Although it is mainly attributable to siderosis and primary HCV infection, the role of undiscovered transmissible agents cannot be excluded.

Adolescent↗

Exogenous surfactant and positive end-expiratory pressure in the treatment of endotoxin-induced lung injury.

OBJECTIVE: To evaluate the efficacy of treating endotoxin-induced lung injury with single dose exogenous surfactant and positive end-expiratory pressure (PEEP). DESIGN: Prospective trial. SETTING: Laboratory at a university medical center. SUBJECTS: Nineteen certified healthy pigs, weighing 15 to 20 kg. INTERVENTIONS: Pigs were anesthetized and surgically prepared for hemodynamic and lung function measurements. Animals were randomized into four groups: a) Control pigs (n = 4) received an intravenous infusion of saline without Escherichia colilipopolysaccharide (LPS); b) the LPS group (n = 5) received an intravenous infusion of saline containing LPS (100 microg/kg); c) the PEEP plus saline group (n = 5) received an intravenous infusion of saline containing LPS. Two hours after LPS infusion, saline was instilled into the lung as a control for surfactant instillation, and the animals were placed on 7.5 cm H2O of PEEP; d) the PEEP plus surfactant group (n = 5) received an intravenous infusion of saline containing LPS. Two hours following LPS infusion, surfactant (50 mg/kg) was instilled into the lung and the animals were placed on 7.5 cm H2O of PEEP. PEEP was applied first and surfactant or saline was instilled into the lung while maintaining positive pressure ventilation. All groups were studied for 6 hrs after the start of LPS injection. At necropsy, bronchoalveolar lavage was performed and the right middle lung lobe was fixed for histologic analysis. MEASUREMENTS AND MAIN RESULTS: Compared with LPS without treatment, PEEP plus surfactant significantly increased PaO2 (PEEP plus surfactant = 156.6 +/- 18.6 [SEM] torr [20.8 +/- 2.5 kPa]; LPS = 79.2 +/- 21.9 torr [10.5 +/- 2.9 kPa]; p<.05), and decreased venous admixture (PEEP plus surfactant = 12.5 +/- 2.0%; LPS = 46.9 +/- 14.2%; p< .05) 5 hrs after LPS infusion. These changes were not significant 6 hrs after LPS infusion. PEEP plus surfactant did not alter ventilatory efficiency index (VEI = 3800/[peak airway pressure - PEEP] x respiratory rate x PacO2), or static compliance as compared with LPS without treatment at any time point. Cytologic analysis of bronchoalveolar lavage fluid showed that surfactant treatment significantly increased the percentage of alveolar neutrophils as compared with LPS without treatment (PEEP plus surfactant = 39.1 +/- 5.5%; LPS = 17.4 +/- 6.6%; p< .05). Histologic analysis showed that LPS caused edema accumulation around the airways and pulmonary vessels, and a significant increase in the number of sequestered leukocytes (LPS group = 3.4 +/- 0.2 cells/6400 micro2; control group = 1.3 +/- 0.1 cells/6400 micro2; p < .05). PEEP plus saline and PEEP plus surfactant significantly increased the total number of sequestered leukocytes in the pulmonary parenchyma (PEEP plus surfactant = 8.2 +/- 0.7 cells/6400 micro2; PEEP plus saline = 3.9 +/- 0.2 cells/6400 micro2; p <.05) compared with the control and LPS groups. CONCLUSIONS: We conclude that PEEP plus surfactant treatment of endotoxin-induced lung injury transiently improves oxygenation, but is unable to maintain this salutary effect indefinitely. Thus, repeat bolus dosing of surfactant or bolus treatment followed by continuous aerosol delivery may be necessary for a continuous beneficial effect.

Animals↗

Aerosolized surfactant improves pulmonary function in endotoxin-induced lung injury.

Surfactant dysfunction is a primary pathophysiologic component in patients with adult respiratory distress syndrome (ARDS). In this study we tested the efficacy of aerosolized surfactant (Sf ) replacement in a severe lung injury model of endotoxin-induced ARDS. Twenty-one certified healthy pigs were anesthetized, surgically prepared for measurement of hemodynamic and lung function, then randomized into one of four groups: (1) control (n = 5), surgical instrumentation only; (2) lipopolysaccharide (LPS) (n = 6), infused with Escherichia coli LPS (100 microgram/kg) without positive end- expiratory pressure (PEEP) and ventilated with a nonhumidified gas mixture of 50% N2O and 50% O2; (3) LPS + PEEP (n = 4), infused with LPS, placed on PEEP (7.5 cm H2O), and ventilated with a humidified gas mixture; and (4) LPS + PEEP + Sf (n = 6), infused with LPS, placed on PEEP, and ventilated with aerosolized Sf (Infasurf, ONY, Inc.). All animals were studied for 6 h. Arterial PO2 significantly decreased in both the LPS and LPS + PEEP groups (LPS + PEEP = 74 +/- 19 mm Hg; LPS = 74 +/- 19 mm Hg, p < 0.05) while venous admixture (Q S/Q T) increased in these groups (LPS + PEEP = 43.3 +/- 3.9%; LPS = 47.7 +/- 11%, p < 0.05) as compared with the control group. PEEP + Sf reduced the fall in PO2 (142 +/- 20 mm Hg) and rise in Q S/Q T (15.1 +/- 3.6%) caused by LPS. Delayed induction of PEEP (2 h following LPS) did not significantly improve any parameter over the LPS group without PEEP in this ARDS model. LPS without PEEP (3.4 +/- 0.2 cells/6,400 micrometer2) caused a marked increase in the total number of sequestered leukocytes in the pulmonary parenchyma as compared with the control group (1.3 +/- 0.1 cells/6,400 micrometer2). LPS + PEEP + Sf (2.3 +/- 0.2 cells/6,400 micrometer2) significantly decreased while LPS + PEEP significantly increased (4.0 +/- 0.2 cells/6,400 micrometer2) the total number of sequestered leukocytes as compared with the LPS without PEEP group. In summary, aerosolized surfactant replacement decreased leukocyte sequestration and improved oxygenation in our porcine model of endotoxin-induced lung injury.

Aerosols↗

Preoperative localization of suspicious parathyroid adenomas by assay of parathyroid hormone in needle aspirates.

OBJECTIVE: To determine the usefulness of parathyroid hormone (PTH) measurement in needle aspirates of a suspicious neck mass to confirm its parathyroid nature in patients with primary hyperparathyroidism. METHODS: Thirty-three patients with surgically proved primary hyperparathyroidism were submitted to neck ultrasound (US), parathyroid scintigraphy, and assay of PTH in the aspirate (PTHa) of the suspicious cervical mass. RESULTS: Based on the results of neck US and parathyroid scintigraphy, patients were divided into two groups. Group 1: 16 patients (seven with nodular goiter) with concordant positive US and scintigraphic results. In all but one patient, PTHa was detectable and often markedly elevated (> 1000 pg in 12 patients, between 292 pg and 803 pg in three patients and 53 pg in one patient). The patient with undetectable PTHa had a small lower left parathyroid adenoma (8x8x10 mm). Group 2: 17 patients (12 with nodular goiter) with discordant US and scintigraphic results. PTHa established the parathyroid nature of the mass in 13 cases (> 1000 pg in 8 patients, between 501 pg and 953 pg in three patients and 90 and 79 pg in two patients): 11 of these had a suspected lesion by US examination but the scintigraphy results were negative; two had a mass that gave positive scintigraphy results but was of uncertain origin according to US: in both cases an intrathyroidal parathyroid adenoma was found. PTHa was undetectable in four cases (three with nodular goiter): all of these had equivocal US results, and three had positive scans and one a negative scan. CONCLUSIONS: Assay of PTHa is a simple method and should be useful for confirming the parathyroid nature of a cervical mass in patients with discordant or non-diagnostic US and scintigraphic results.

Adenoma↗

Development of thyroid papillary carcinomas secondary to tissue-specific expression of the RET/PTC1 oncogene in transgenic mice.

Gene rearrangements activating the RET proto-oncogene are frequently associated with human thyroid carcinomas belonging to the papillary subtype. These arrangements cause the fusion of the tyrosine-kinase domain of RET to the 5'-terminal region of different genes creating the RET/PTC chimeric oncogenes. Here we report the generation of transgenic mice lines expressing the RET/PTC1 oncogene under the control of the thyroid-specific rat thyroglobulin promoter. RET/PTC1-transgenic mice developed thyroid tumors displaying the histological aspect of papillary carcinomas. These tumors were slowly progressive and did not cause premature death of the animals. Two additional mice developed areas of thyroid hyperplasia. Immunohistochemical and reverse-transcriptase polymerase chain reaction analyses confirmed the thyroid-specific expression of the transgene. Given the frequency of activating rearrangements of RET in human papillary thyroid carcinomas we conclude that this animal system could be a good model for studying the neoplastic progression of thyroid carcinomas.

Animals↗