High prevalence of papillary thyroid carcinoma in nodular Hashimoto's thyroiditis at the first diagnosis and during the follow-up.

BACKGROUND: The association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) remains to be elucidated. MATERIALS AND METHODS: A total of 484 HT patients were retrospectively subdivided into two groups: 243 without thyroid nodules, TNs (HTN-) and 241 with TNs (HTN+). Fine-needle aspiration cytology was available in 152 HTN+ patients. This group was compared to a group of 161 patients with nodular goiter (NG) without HT. Finally, 70 HTN+ and 37 NG patients underwent surgery. RESULTS: A very high prevalence of suspicious/malignant cytology (Thy 4-5) at the first diagnosis (38/124; 31%) and during the follow-up (6/28; 22%) was found in HTN+ group. In HTN- group, 22/130 (17%) patients developed TN, but none showed malignant features during the follow-up. HTN+ patients had higher prevalence of Thy 4-5 (44/152 = 28.9%) compared to NG patients (12/161 = 7.4%, p < 0.0001). Increased independent odds ratio (OR) for malignancy was conferred by serum TSH > 1.0 µUI/ml, [OR 1.93, 95% confidence interval (CI) 1.41-2.64, p < 0.0001], male sex (OR 3.44, CI 1.48-8.02, p = 0.004) and HT (OR 3.14; CI 1.08-9.31, p < 0.05). Malignant histology (mostly PTC) was confirmed higher in HTN+ (48/70, 68.6%) compared to NG (15/37, 40.5%; p < 0.05). Higher prevalence of extrathyroidal infiltration (24/48, 50%) and vascular invasion (25/48, 52%) was found in HTN+ vs NG (2/15, 1.3% p < 0.01), (3/16, 1.8% p < 0.05), respectively. CONCLUSIONS: This study confirms higher prevalence of suspicious/malignant cytology and PTC at histology in nodular HT compared to NG, without evidence of malignancy in non-nodular HT patients during the follow-up.

Primary thyroid leiomyosarcoma: a case report and review of the literature.

Primary thyroid leiomyosarcoma (LMS) is an extremely rare tumor. We report a case of a 47-year-old male with a rapidly growing neck mass and disfagia. Preoperative investigations were diagnostic of anaplastic carcinoma. Total thyroidectomy with partial esophagectomy and dissection of right infrahyoid muscles was performed. Through histolological and immunohistochemical evaluations a primary thyroid high-grade LMS was diagnosed. At 2 months of follow-up a local recurrence was detected and consequently the patient was submitted to chemotherapy with partial response. He is still alive 9 months after surgery. Diagnosis of primary thyroid LMS is difficult due to its similarity to other more common thyroid tumors. To date, there is no standard therapy and prognosis is poor.

Both thyroid autoimmunity and increased serum TSH are independent risk factors for malignancy in patients with thyroid nodules.

AIM: To assess the relevance of thyroid autoimmunity and TSH as risk factors for malignancy in thyroid nodules (TN). SUBJECTS AND METHODS: Retrospective analysis on 2053 patients with single/prevalent TN submitted to fine needle aspiration cytology (FNAC). Anti-thyroid autoantibodies (ATA) [anti-thyroperoxidase (TPOAb), anti-thyroglobulin (TgAb)] and TSH were measured. Cytology was classified as benign (class II), indeterminate (class III), and suspicious or malignant (class IV). Histology was available in 301 patients. Associations of malignancy with independent variables were determined by multivariate logistic regression analysis. RESULTS: Higher prevalence of class IV (14.2% vs 6.8%: p<0.001) and class III (23.5% vs 17.1%: p<0.001) were found in ATA+ vs ATA- TN. Histology confirmed increased prevalence of cancer in ATA+ (p<0.05) TN and in those with diffuse lymphocytic thyroid infiltration (p<0.05). Interestingly, the prevalence of malignancies observed in operated class III nodules was strikingly lower in ATA+ (1/20, 5%), than in ATA- patients (34/67, 50.7%; p<0.001). Increased independent odds ratio (OR) for malignancy was conferred by any ATA [OR 2.21; 95% confidence interval (CI)=1.49-3.29, p<0.0001]; TPOAb (OR 2.15; CI=1.42-3.25, p<0.0001) and TgAb (OR 1.67; CI=1.05-2.67, p<0.05), by serum TSH>1.0 µUI/ml (OR 1.95; CI=1.01-3.76, p<0.05), and by young age (10-29 yr: OR 2.09; CI=1.02-4.26, p<0.05). A formula was calculated to assess the relative contribution of ATA, TSH, and age to the risk of TN malignancy. CONCLUSIONS: Both thyroid autoimmunity and increased TSH represent independent risk factors for TN malignancy.

A novel mutation of the DSRAD gene in a Chinese family with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant cutaneous disorder, characterized by a mixture of hyperpigmented and hypopigmented macules mostly on the dorsal portions of the extremities. Pathogenic mutations have been identified in the double-stranded RNA-specific adenosine deaminase (DSRAD) gene. We studied a Chinese family that included four affected individuals with DSH phenotypes. PCR and direct sequencing were carried out to detect the entire coding region and exon-intron boundaries of the DSRAD gene. A novel nucleotide c.3002G>T missense mutation in the exon 11 of the DSRAD gene was detected in the proband and his father. This information expands the database on DSRAD gene mutations associated with DSH.

Establishing a 'Physician's Spiritual Well-being Scale' and testing its reliability and validity.

The purpose of this study was to develop a Physician's Spiritual Well-Being Scale (PSpWBS). The significance of a physician's spiritual well-being was explored through in-depth interviews with and qualitative data collection from focus groups. Based on the results of qualitative analysis and related literature, the PSpWBS consisting of 25 questions was established. Reliability and validity tests were performed on 177 subjects. Four domains of the PSpWBS were devised: physician's characteristics; medical practice challenges; response to changes; and overall well-being. The explainable total variance was 65.65%. Cronbach α was 0.864 when the internal consistency of the whole scale was calculated. Factor analysis showed that the internal consistency Cronbach α value for each factor was between 0.625 and 0.794 and the split-half reliability was 0.865. The scale has satisfactory reliability and validity and could serve as the basis for assessment of the spiritual well-being of a physician.

Plasma cells in the carotid plaque: occurrence and significance.

OBJECTIVE: Atherosclerosis is one of the leading causes of disability and mortality worldwide. Inflammation, including monocytes, T and B cells, plays a key role in its pathogenesis. Our purpose was to evaluate plasma cells' presence in a large series of carotid artery plaques and the clinical association. PATIENTS AND METHODS: Forty-eight consecutive patients treated with carotid endarterectomy were retrospectively analyzed to assess plasma cells' presence inside the plaque. A semiquantitative grading score was applied, ranging from absence, scattered, clusters of 5-10, and sheets of >10 plasma cells. Plasma cell's location, as intraplaque, subendothelial or peri-adventitial, was also defined. RESULTS: In 75% of plaques analyzed, plasma cells were detected: scattered in 63.9%, in clusters in 22.2%, and in sheets in 13.9% of cases. In all cases, plasma cells were observed only inside the plaque. In 13.9% and in 11.1% of cases, plasma cells showed, respectively, a concomitant subendothelial or peri-adventitial distribution. In 5.6% of plaques, there was a simultaneous distribution in subendothelial, peri-adventitial layer, and intraplaque. Association between the presence of symptoms and plasma cells infiltrate was found. CONCLUSIONS: Our results suggest that plasma cells could be a key parameter linked to plaque instability. Some types of configurations are significantly associated with the occurrence of cerebrovascular symptoms.

Fetal programming of atherosclerosis: may the barker hypothesis explain the susceptibility of a subset of patients to develop stroke or cardiac infarct?

The risk stratification of young adults between subjects who will develop a mild form of atherosclerosis and subjects who will undergo a severe disease remains inaccurate. In the eighties of the previous century, David JP Barker has demonstrated the relationship between fetal conditions and occurrence of pathologies in adulthood. In this paper, the multiple evidence that might explain the increased susceptibility to severe forms of atherosclerosis, including stroke and cardiac infarct, in subjects who underwent intrauterine growth restriction (IUGR) will be analyzed. Specifically, we will review those inter-connected data indicating an association between a low weight at birth and an adult phenotype which might favor a severe outcome of atherosclerosis. Young and adult subjects born too small (IUGR) or too early (pre-terms) might represent a subgroup of "at risk subjects", more susceptible toward severe forms of atherosclerosis. Given that low birth weight (LBW) may be considered a surrogate of IUGR, this phenotypic feature could be considered among those indispensable clinical data collected in every patient presenting with atherosclerosis, irrespectively of age. According to the hypothesis that structural arterial changes might represent the link between LBW and susceptibility to atherosclerosis later in life, we suggest that the prevention of atherosclerosis should begin at birth. Regenerative and physiological substances such as thymosin Beta-4 could be challenged for a new "arterial regenerative medicine" in the perinatal period. The goal of this new approach should be the reinforcement of the structure of the arterial wall, allowing LBW newborns to avoid the most severe complications of atherosclerosis later in life: a dream that our research could contribute to bringing to life.

The diagnostic value for differentiated thyroid carcinoma metastases of thyroglobulin (Tg) measurement in washout fluid from fine-needle aspiration biopsy of neck lymph nodes is maintained in the presence of circulating anti-Tg antibodies.

OBJECTIVE: Serum thyroglobulin (Tg) is the marker of differentiated thyroid carcinoma (DTC) after total thyroidectomy, but its value is limited by the interference of anti-Tg antibodies (TgAb). Detection of Tg in fine-needle aspiration biopsy (Tg-FNAB) washout fluid is used to identify neck DTC recurrences/metastases, but the interference of serum TgAb in this procedure is unknown. PATIENTS AND METHODS: Seventy-three patients (41 after surgery for thyroid cancer and 32 with thyroid nodules) evaluated for suspicious cervical lymph nodes were retrospectively reviewed. Tg was assayed by immunoradiometric assay or chemiluminescent assay in ultrasound-guided FNAB used for cytology. Serum TgAb were detected by passive agglutination or chemiluminescent assay. On the basis of preliminary data obtained in lymphadenitis, Tg-FNAB more than 36 ng/ml and more than 1.7 ng/ml (in the presence or absence of thyroid gland, respectively) was considered as indicative of metastasis. RESULTS: In 51 TgAb-negative patients, Tg-FNAB was positive in 15 (12 with malignant and three with nondiagnostic cytology), all with histologically confirmed DTC metastases. Of the remaining 36 patients with negative Tg-FNAB, 30 had nonsuspicious and six had suspicious cytology. Histology of the latter showed four undifferentiated thyroid cancer metastases and two lymphadenitis. In 22 TgAb-positive patients, Tg-FNAB was positive in 14 (12 with malignant and two with nondiagnostic cytology), all with histologically confirmed DTC metastases. CONCLUSIONS: Clinical performance of Tg-FNAB appears to be not substantially affected by TgAb, and this procedure remains superior to cytology in the identification of DTC neck metastases. However, cytology should always be performed because, irrespective of TgAb, Tg is undetectable in FNAB from undifferentiated metastases.

High prevalence of suspicious cytology in thyroid nodules associated with positive thyroid autoantibodies.

OBJECTIVE: We assessed the association between thyroid autoimmunity and thyroid cancer in a retrospective series of unselected thyroid nodules submitted to fine-needle aspiration cytology (FNAC) to avoid the selection bias of surgical series. SUBJECTS AND METHODS: Ultrasound (US)-guided FNACs were obtained from 590 unselected consecutive patients with single thyroid nodules and positive (ATA + , n = 197) or negative (ATA - , n = 393) serum anti-thyroid antibody (ATA). Cytological results were classified in three classes of increased risk of malignancy: low risk or benign (class II); indeterminate risk (class III); and suspect or malignant (class IV). RESULTS: A higher prevalence of class III (28.9% vs 21.4%, P < 0.05) and class IV (18.8% vs 9.2%, P < 0.001) and lower prevalence of class II (52.3% vs 69.5%, P < 0.001) were found in ATA + vs ATA - nodules respectively. By multivariate logistic regression analysis ATA + conferred a significant risk (odds ratio (OR): 2.29 (95% confidence interval (CI): 1.39-3.76)) for class IV cytology independently from age and sex. In 106 patients where thyroidectomy was carried out, thyroid cancer was found in 54/61 (88.5%) patients with class IV nodules (with similar positive predictive value for cancer in ATA + (96.4%) and ATA- (81.8%) nodules), in 6/31 (19.3%) of class III nodules (all ATA - ) and in none of 14 class II nodules. Non-specific cytological atypias from hyperplastic nodules in lymphocytic thyroiditis probably accounted for the different prevalence of cancer in class III ATA + and ATA - nodules. Histologically proven thyroid cancer (mostly papillary) was then observed in a higher proportion (27/197 = 13.7%) of ATA + , when compared with ATA - nodules (33/393 = 8.4%, P = 0.044), but the significance of this finding is limited by the low number of class II nodules operated on. CONCLUSIONS: The presence of ATA + confers an increased risk of suspicious or malignant cytology in unselected thyroid nodules. Since ATA + is not responsible for increased false-positive class IV FNAC, our study provides indirect evidence supporting a significant association between thyroid carcinoma and thyroid autoimmunity, although further studies with a different design are needed for a definitive histological proof.

Expression of ATP7B in normal human liver.

ATP7B is a copper transporting P-type ATPase, also known as Wilson disease protein, which plays a key role in copper distribution inside cells. Recent experimental data in cell culture have shown that ATP7B putatively serves a dual function in hepatocytes: when localized to the Golgi apparatus, it has a biosynthetic role, delivering copper atoms to apoceruloplasmin; when the hepatocytes are under copper stress, ATP7B translocates to the biliary pole to transport excess copper out of the cell and into the bile canaliculus for subsequent excretion from the body via the bile. The above data on ATP7B localization have been mainly obtained in tumor cell systems in vitro. The aim of the present work was to assess the presence and localization of the Wilson disease protein in the human liver. We tested immunoreactivity for ATP7B in 10 human liver biopsies, in which no significant pathological lesion was found using a polyclonal antiserum specific for ATP7B. In the normal liver, immunoreactivity for ATP7B was observed in hepatocytes and in biliary cells. In the hepatocytes, immunoreactivity for ATP7B was observed close to the plasma membrane, both at the sinusoidal and at the biliary pole. In the biliary cells, ATP7B was localized close to the cell membrane, mainly concentrated at the basal pole of the cells. The data suggest that, in human liver, ATP7B is localized to the plasma membrane of both hepatocytes and biliary epithelial cells.

Pharmacokinetics of metoprolol enantiomers in Chinese subjects of major CYP2D6 genotypes.

OBJECTIVE: CYP2D6 mediates both alpha-hydroxylation and O-demethylation of metoprolol. In Chinese subjects, CYP2D6*1 (the wild-type) alleles are relatively uncommon. Subjects with P34S (C188-->T188) and S486T (G4268-->C4268) mutations (CYP2D6J or CYP2D6*10A) are more frequently seen. Recently, the CYP2D6*2 (CYP2D6L) genotype that results in R296C (C2938-->T2938) and S486T mutations was also found important. In this study, metoprolol pharmacokinetics was investigated in subjects of these 3 major genotypes. METHODS: Allele-specific polymerase chain reaction was used to differentiate CYP2D6*1 and CYP2D6*2 alleles from the common CYP2D6*10A allele in Chinese. Subjects with both CYP2D6*1 and CYP2D6*2 have homozygous C188 in the exon 1, whereas subjects with CYP2D6*10A have T188. Metoprolol pharmacokinetics was compared in 16 C188 subjects (6 homozygous CYP2D6*1 subjects and 10 heterozygous CYP2D6*1/CYP2D6*2 subjects), 12 heterozygous C/T188 subjects, and 12 homozygous T188 subjects. RESULTS: No significant difference in plasma concentration profile or urinary alpha-hydroxymetoprolol excretion could be found among subjects with R296C polymorphism (CYP2D6*1/CYP2D6*2). Therefore data from subjects with CYP2D6*1 and CYP2D6*2 were pooled to compare with data from subjects with CTP2D6*10A. The area under plasma concentration curves (AUC) of S-metoprolol was 1411+/-116 (mean +/- SEM, n = 16), 1899+/-120 (n = 12), and 3588+/-435 (n = 12) nmol x hr/L for homozygous C188, heterozygous C/T188, and homozygous T188 subjects, respectively. The urinary recovery of all 4 alpha-hydroxymetoprolol diastereomers was significantly lower in T188 subjects than in C188 subjects. CONCLUSION: The P34S polymorphism but not the R296C polymorphism resulted in higher metoprolol plasma concentrations and lower urinary metoprolol metabolite levels in Chinese subjects. This finding suggests that a lower dose of metoprolol may be used in subjects with T188 mutation (CYP2D6*10A allele).

Molecular basis of genetic variation in debrisoquin hydroxylation in Chinese subjects: polymorphism in RFLP and DNA sequence of CYP2D6.

Debrisoquin hydroxylation phenotype was determined in 124 Chinese persons living in Taiwan, and two poor metabolizers were identified with a urinary metabolic ratio (MR) greater than 12.6. The other subjects, extensive metabolizers, showed a normal frequency distribution of log(MR). Most subjects (50%) showed a 44/29 kb pattern in restriction fragment length polymorphism (RFLP) analysis with use of Xba I, and 30% and 15% of the subjects exhibited a homozygous 29/29 kb and 44/44 kb pattern, respectively. Among extensive metabolizers, subjects with the 44/44 kb pattern had a significant higher log(MR) than those with the 44/29 pattern, and the log(MR) of the subjects with the 44/29 kb pattern was significantly higher than that of the subjects with 29/29 kb pattern. All nine exons and intron 3 of C gamma P2D6 were amplified with polymerase chain reaction (PCR) and sequenced for four extensive metabolizers. Two major polymorphisms were found: one at position 188 of exon 1 and the other at position 4268 in exon 9. With PCR and endonuclease digestion, polymorphisms at exon 1, intron 3, and exon 9 were investigated. Only two of 254 alleles showed a heterozygous guanine at 1934 base pairs (G1934) to adenine (A) mutation, commonly found in white poor metabolizers. Approximately 70% of alleles showed thymine at 188 base pairs (T188), and 76% showed cytosine at 4268 base pairs (C4268) instead of C188 and G4268, as is found in most white subjects. Subjects with T188 or C4268 showed a significant higher log(MR) than subjects with homozygous C188 and G4268. The C/T188, G/A1934, G/C4268, and RFLP polymorphisms may explain the interracial variations between Chinese and white subjects, as well as the genetic variations among Chinese subjects.

Formation of morphine from codeine in Chinese subjects of different CYP2D6 genotypes.

Codeine and morphine pharmacokinetics among different CYP2D6 genotypes was compared in this study. Polymerase chain reaction tests were used to determine CYP2D6 genotypes in leukocyte deoxyribonucleic acid in 32 unrelated volunteers. Based on the genotypes, subjects were categorized into three groups: homozygous C/C188 (n = 8), heterozygous C/T188 (n = 12), and homozygous T/T188 (n = 12). Each subject was given a single oral dose of 30 mg codeine phosphate tablet after overnight fasting. Plasma concentration of codeine and 24-hour urinary morphine recovery were measured with HPLC. All three genotypes of subjects showed almost identical time profiles of plasma codeine. Urinary morphine glucuronide was hydrolyzed with beta-glucuronidase. The total recovered amount of morphine and glucuronides was 4349 +/- 646, 2564 +/- 242, and 1127 +/- 164 nmol (mean +/- SEM), respectively, for C/C188, C/T188, and T/T188 subjects (p < 0.05). The significant lower amount of urinary morphine but identical codeine plasma concentration suggested a lower partial clearance of the formation of morphine from codeine in T/T188 subjects. The results suggest a future study to assess the analgesic effect of codeine in different genotypes of CYP2D6 extensive metabolizers.

Propranolol disposition in Chinese subjects of different CYP2D6 genotypes.

Propranolol pharmacokinetics among different genotypes of CYP2D6 was compared in this study. The Chinese (Han) population consisted of 44 healthy unrelated individuals living in southern Taiwan. Endonuclease tests based on polymerase chain reaction were used to determine C/T188 genotypes of CYP2D6 in leukocyte deoxyribonucleic acid. Based on codon 188 genotypes, subjects were categorized into three groups: homozygous C/C188 (n = 13), heterozygous C/T188 (n = 14); and homozygous T/T188 (n = 17). Each subject was given a 40 mg propranolol tablet. Blood samples were drawn before and 12 hours after propranolol administration to measure propranolol and 4-hydroxypropranolol. Three genotypes showed distinct time profiles of plasma propranolol and 4-hydroxypropranolol. The area under plasma concentration curve values (mean +/- SEM), were 322.0 +/- 40.8, 481.6 +/- 77.5, and 766.1 +/- 92.8 nmol.hr/L, respectively, for C/C188, C/T188, and T/T188 subjects (p < 0.05). The 48-hour excreted amount of 4-hydroxy-S-propranolol-O-glucuronide, but not 4-hydroxy-R-propranolol-O-glucuronide, was significantly higher for C/C188 than for T/T188 subjects (p < 0.05). This study shows a different propranolol disposition in Chinese subjects of different CYP2D6 genotypes.

Effects of fish oil supplementation on acute ischemic brain injury in the rat.

We studied the effects of long-term fish oil (FO) dietary supplementation on brain edema, polymorphonuclear neutrophil (PMN) infiltration, and infarct size in a rat stroke model. Rats were given regular rat chow with or without FO supplement (20% of total calories) for 7 weeks. Body weight did not differ between the two groups. In the FO group, an increase in eicosapentaenoic acid and a decrease in arachidonic acid content in hepatic phospholipids were significant in the phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine but not in the phosphoinositol fraction. Platelet activity reflected by serum thromboxane B2 levels was reduced in the FO group. Postischemic brain edema and PMN infiltration were not different between the two groups. The infarct volume was significantly greater in the FO group (controls: 96 +/- 7 mm3, n = 49; FO group: 124 +/- 6 mm3, n = 53; p = 0.0036). The greater ischemic brain injury in the FO-supplemented animals is probably related to the intraischemic hyperglycemia, which was worse in the FO group than in the control group (controls: 265 +/- 19 mg/dl, n = 14; FO group: 340 +/- 18 mg/dl, n = 16; p = 0.0079).

Functional mutation in the promoter region of thrombomodulin gene in relation to carotid atherosclerosis.

Thrombomodulin is an important endothelial anticoagulant protein that decreases thrombin activity and activates protein C. Our recent study has shown that the G-33A promoter mutation of thrombomodulin gene is associated with coronary artery disease. This study was conducted to determine whether the G-33A mutation in the promoter region of thrombomodulin gene is a genetic risk factor for ischemic stroke or carotid atherosclerosis. The functional significance of this mutation was also evaluated. We recruited 333 patients (mean age 64 years, 59% male) with ischemic stroke and 257 age- and sex-matched controls. In all study participants, carotid atherosclerosis was assessed by Duplex scanning, and thrombomodulin G-33A promoter mutation was detected by single-strand conformation polymorphism. Luciferase reporter gene assay was used to assess the influence of this mutation on thrombomodulin promoter activity. There was no significant difference in the thrombomodulin G-33A mutation frequency (GA+AA genotypes) between the stroke and the control groups (18.3 vs. 24. 1%, P=0.105). The G-33A mutation frequency was also similar between the study participants with and without carotid atherosclerosis (22.2 vs. 19.8%, P=0.550). When only younger subjects (age

Increased microsomal irreversible binding of phenytoin by valproic acid.

Phenytoin is known to be metabolized to form p-hydroxyphenyl-phenyl-hydantoin, possibly via the arene oxide intermediate. The reactive arene oxide may bind to macromolecules irreversibly and cause toxicity. In this study, valproic acid was found to increase the irreversible binding of phenytoin to rat liver microsomes at high concentrations. The effect was similar to that of TCPO and could be reversed by adding glutathione. Valproic acid may increase the hepatotoxicity of phenytoin.

The usefulness of 99mTc-SestaMIBI scan in the diagnostic evaluation of thyroid nodules with oncocytic cytology.

OBJECTIVE: To assess the relevance of (99m)Tc-SestaMIBI (MIBI) scan in the diagnostic evaluation of thyroid nodules with oncocytic cytology. SUBJECTS AND METHODS: Twenty-four patients with a single (or prevalent) 'cold' solid nodule with Hurthle cells (HC) at fine needle aspiration cytology (FNAC) were studied. Cytological diagnosis of oncocytic metaplasia (OM) or HC tumor (HCT) was made when HC on the smear were comprised 10-75%, or >75%. Nodules concentrating MIBI at early and late (2 h after washout) stages were considered MIBI-positive. In all cases histological findings were obtained after total thyroidectomy. RESULTS: FNAC was malignant or suspect for malignancy in 16 cases (six HCT and 10 OM) and not suspect in eight (two HCT and six OM). Histological examination revealed 14 malignant tumors (11 HCT and three OM), and 10 benign thyroid lesions (three HCT and seven OM). Sensitivity of FNAC for malignancy was 92.8% and specificity was 70.0%; HCT were identified by FNAC in only 35.7% and OM in 70.0% of cases. No significant difference in MIBI positivity was found between malignant and benign thyroid nodules. The highest percentage of MIBI positivity was found in HCT (78.5%), but MIBI-positive nodules were also observed in thyroid lesions with HC metaplasia (40.0%). CONCLUSIONS: MIBI scintiscan has no value in differentiating malignant from benign HC thyroid neoplasias. Most HCT are MIBI-positive, but this scan is not sufficiently specific to differentiate true HC neoplasias from other thyroid lesions showing HC at FNAC, although an MIBI-negative scan strongly supports the absence of true HCT.

Calcitonin gene-related peptide in the human trigeminal sensory system at developmental and adult life stages: immunohistochemistry, neuronal morphometry and coexistence with substance P.

The distribution of calcitonin gene-related peptide (CGRP) has been examined by the indirect immunofluorescence technique in the Gasserian ganglion and spinal nucleus of the human trigeminal nerve. In the ganglion CGRP is present in almost 50% of primary sensory neurons, in varicose and non-varicose nerve fibres and in pericellular basket-like plexuses around non-immunoreactive ganglionic perikarya. Morphometric analysis reveals that the CGRP-positive neuronal population is heterogeneous in cell size. Observation of specimens from subjects at fetal, perinatal and adult life stages reveals that the percentage of CGRP-immunoreactive cells reaches a maximum at perinatal stages and then remains constant, declining only in old age. Pericellular basket-like nerve fibres are detectable only in fetal and pre-term and full-term newborn tissue. Coexistence between CGRP and substance P (SP) occurs, SP being present in about one quarter of the CGRP-immunoreactive neurons and CGRP being localized in a little more than half of the SP-immunoreactive neurons. However, perikarya, nerve fibres and pericellular fibres containing only one or other peptide are also present. Bundles of immunoreactive fibres and dot-like nerve terminals occur in the spinal tract and superficial and deep regions of the spinal trigeminal nucleus. A particularly dense plexus is present in the peripheral nuclear layers. Double immunostaining shows a similar regional distribution for SP. However, in inner substantia gelatinosa the density of CGRP-immunoreactive fibres is much higher than that of SP-immunoreactive ones. The results obtained add information to our knowledge of the organization of neurochemically identified neurons in the human trigeminal sensory system.

GAP-43 persists in adulthood and coexists with SP and CGRP in human trigeminal sensory neurones.

Immunohistochemistry was used to examine the occurrence and colocalization of the growth-associated protein GAP-43 with substance P (SP) and calcitonin gene-related peptide (CGRP) in the human trigeminal ganglion and sensory nucleus at perinatal and adult life stages. The results obtained show that: GAP-43-like immunoreactive (LI) material persists in trigeminal primary sensory neurones of the normal adult; the GAP-43-LI ganglionic population partially overlaps with those immunoreactive to SP and CGRP; the distribution pattern of the protein in the spinal nucleus varies with age; in the adult subnucleus caudalis GAP-43 is co-distributed with SP and CGRP. It is suggested that the trigeminal GAP-43-LI neuronal system may retain the capacity for structural and functional plasticity in adult life.