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F Pacini

Publications and source records attributed to F Pacini.

At least 73 records · Page 4Linked to original sources
PubMed1996

A population-based study of inflammatory bowel disease in Florence over 15 years (1978-92).

BACKGROUND: In the group of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) are considered to be more frequent in Western countries and in areas with a high socioeconomic development but relatively infrequent in southern Europe. Sporadic reports have indicated a lower incidence and a milder course of the disease in Mediterranean countries. Although conclusive data on this point are still lacking, recent reports suggest an increase in both incidence and prevalence rates. METHODS: The incidence of UC and CD during the period January 1978 to December 1992 and their prevalence on 31 December 1992 were estimated in the 15-year-old population of the metropolitan area of Florence. Clinical, demographic, and follow-up information was collected for all identified IBD patients. RESULTS: A total of 796 residents (345 females and 454 males) were newly diagnosed as having IBD during the study period. Of these 593 had UC and 203 CD. The age-standardized incidence rates, calculated for each of five 3-year consecutive periods, rose from 3.8 (in 1978-80) to 9.6 per 100,000 person-years (in 1990-92) for UC and from 1.9 (in 1978-80) to 3.4 (in 1990-92) for CD. Both trends were statistically significant. The prevalence estimated on 31 December 1992 was 121.0 and 40.0 per 100,000 inhabitants for UC and CD, respectively. CONCLUSIONS: Our results confirm that IBD incidence rates and prevalence in this area of central Italy are currently comparable with those reported in northern Europe. These data are necessary for planning adequate health care services for IBD patients.

Adolescent↗
PubMed1996

Microvessel count: an indicator of poor outcome in medullary thyroid carcinoma but not in other types of thyroid carcinoma.

The growth of newly formed vessels (neoangiogenesis) represents an important step both in physiologic and pathologic situations. In particular, tumor growth and metastasis require angiogenesis. Microvessel count, which expresses a measure of tumor angiogenesis, has been associated with metastatic spread in cutaneous, mammary, prostatic, head, neck, and pulmonary cancer. In this study, the role of tumor angiogenesis as a prognostic indicator was examined in 157 primary thyroid cancers including 82 well-differentiated carcinomas, 52 medullary carcinomas, and 23 undifferentiated carcinomas. Microvessels were carefully counted by highlighting endothelial cells with anti-CD34 formalin-fixed tumor samples. The mean of microvessel count was 30.7 per field in papillary thyroid carcinomas, 39.4 per field in follicular thyroid carcinomas, 32.7 per field in undifferentiated carcinoma, and 41.8 per field in medullary carcinoma. We found that the number of newly formed vessels was significantly associated with poor prognosis only in medullary carcinoma. All of the dead patients with medullary carcinoma showed a microvessel count higher than 30, which resulted in a high statistical difference compared with alive patients (P = 0.00098). Multiple logistic regression analysis showed microvessel count, together with pTNM (P = 0.026). These results were also confirmed by Kaplan-Meir survival analysis (log-rank test; P = 0.04). By contrast, no differences in the number of microvessels was found between dead and living patients with well-differentiated carcinoma and undifferentiated carcinoma. In conclusion, microvessel count, as quantitation of tumor angiogenesis, plays an important prognostic role in medullary thyroid carcinomas.

Adolescent↗
PubMed1996

Human thyroglobulin reference material (CRM 457). 1st Part: Assessment of homogeneity, stability and immunoreactivity.

This paper describes the assessment of the homogeneity and stability of a purified and lyophilized human thyroglobulin (Tg), and characterizes its immunoreactivity. The purified and lyophilized Tg is intended to be used as a primary reference material to establish calibration of working serum based reference material. The programme involved the participation of 15 European laboratories and one laboratory from the United States. The homogeneity of the content of the ampoules was considered acceptable (< 9%). The stability was tested by accelerated temperature degradation showing predicted annual relative losses of 0.01% at -70 degrees C and 1.04% at -20 degrees C. The immunoreactivity of the Tg material as measured in different laboratories varied mostly according to the method used rather than the laboratory. The interlaboratory variability showed that the two commercial methods used in several laboratories (kit 1 and 2) had an interlaboratory variation (CV) of 15.9% (N = 5) and 7.1% (N = 3), respectively, whereas the total interlaboratory CV was 64.3% (N = 18). The immunoreactive Tg had dilution curves parallel with other Tg calibrators (those of the methods). Dilution curves of the Tg material after storage at various temperatures and time were parallel in both RIA and IRMA. In conclusion, we have prepared a Tg reference material which in extensive studies in several participating laboratories has demonstrated a sufficient homogeneity and stability as well as dilution curves parallel to the calibrators of all the immunoassays tested in the study. This reference material is considered the first step towards decreasing the interlaboratory variability between Tg immunoassays.

Drug Stability↗
PubMed1996

Human thyroglobulin reference material (CRM 457). 2nd Part: Physicochemical characterization and certification.

This report describes the characterization of a purified human thyroglobulin (Tg) reference material, and details the procedures used in its certification. The purified Tg is intended to be used as a primary reference material to establish calibration of working serum based reference material for immunoassay procedures. The programme involved the participation of 15 European laboratories and one laboratory from the United States. The physicochemical characterization showed by polyacrylamide gel electrophoresis and immunoblotting that the purified Tg had for the major part the expected molecular size of 660 kDa with traces of lower molecular forms. The amino acid composition was close to that demonstrated for the cDNA and the content of iodine was in keeping with a moderately to highly iodinated Tg. The mass concentration in reference material RM 457 is certified to be (0.324 +/- 0.018) g/L on the basis of protein determined by the Lowry method and supported by nitrogen determination, absorbance measurement, and amino acid analysis. This reference material is considered the first step towards decreasing the interlaboratory variability between Tg methods of measurement.

Amino Acids↗
PubMed1996

Expression of the Mr 67,000 laminin receptor is an adverse prognostic indicator in human thyroid cancer: an immunohistochemical study.

Increased expression of the Mr 67,000 laminin receptor (LR) is a consistent event which appears as cancer cells acquire an invasive and metastatic phenotype. The Mr 67,000 LR is one of the many laminin-binding proteins able to interact with the major glycoprotein of basement membranes, laminin. The recent development of a specific monoclonal antibody directed against the Mr 67,000 LR MLuC5 has allowed us to study large retrospective groups of human cancers with the aim of correlating the Mr 67,000 LR expression to the clinical, pathological, and survival data of the patients. A significant correlation has already been established between the increased expression of Mr 67,000 LR and survival of patients with breast, colon, ovary, lung, and endometrial cancers. In this study, we investigated the possibility that the detection of Mr 67,000 LR in thyroid human cancers could also be of prognostic value. We analyzed the expression of Mr 67,000 LR with immunohistochemistry using MLuC5 antibodies in paraffin sections of 40 benign and 170 malignant thyroid human tumors. We found that Mr 67,000 LR was not usually detectable in normal thyroid tissues adjacent to the lesion. Only 3 of the 40 thyroid adenomas examined (7.5%) presented cells positive for Mr 67,000 LR. For the malignant thyroid tumors examined, we found that 22.3% of papillary thyroid carcinomas, 38% of follicular thyroid carcinomas, 40% of poorly differentiated carcinomas, 25% of medullary carcinomas, and 58.3% of anaplastic carcinomas expressed a high level of Mr 67,000 LR. Although no correlation between the Mr 67,000 LR expression and survival was found in patients with follicular thyroid carcinomas, papillary thyroid carcinomas, anaplastic carcinomas, and medullary carcinomas, there was a significant correlation in primary thyroid cancers. Our data represent the first extensive study of the Mr 67,000 LR expression in human thyroid cancers and strongly suggest that its detection could be of prognostic value in the investigation of primary thyroid cancers.

Adult↗
PubMed1995

Early treatment of hereditary medullary thyroid carcinoma after attribution of multiple endocrine neoplasia type 2 gene carrier status by screening for ret gene mutations.

BACKGROUND: Germline missense point mutations of the ret proto-oncogene have been shown as causative in multiple endocrine neoplasia type 2 (MEN 2A and 2B) and in familial medullary thyroid carcinoma (FMTC). Most of the mutations are found in exon 10, 11, or 16 of the gene and are easily recognized by restriction analysis. METHODS: Using restriction analysis, we screened 58 subjects from nine kindreds. RESULTS: Family members (n = 16) already known to be affected with the disease carried the germline mutation. Among the 42 subjects apparently unaffected, 37 were not gene carriers and 5 were gene carriers. Basal and pentagastrin-stimulated serum calcitonin levels were normal in two patients and abnormal in three. All patients were treated with total thyroidectomy and central node dissection. In all cases multiple foci of MTC were shown at histologic examination. CONCLUSIONS: Our data indicate that genetic screening of MEN2 pedigrees allows the early identification of gene carriers. Because surgery of MTC in the preclinical phase has high probability of curing these patients, we suggest genetic screening soon after birth and total thyroidectomy in gene carriers as early as possible.

Base Sequence↗
PubMed1995

Assay of thyroglobulin in serum with thyroglobulin autoantibodies: an unobtainable goal?

Measurement of thyroglobulin (Tg) in serum with anti-Tg autoantibodies (TgAb) represents a difficult challenge. Immunoradiometric assays (IRMA) employing monoclonal anti-Tg antibodies not cross-reacting with endogenous TgAb have recently been developed and proposed for Tg assays in TgAb-positive sera. The aim of the present investigation was to assess the clinical reliability of this approach. Assays of serum Tg in patients with and without TgAb using one such monoclonal antibody IRMA (Thyroglobulin IRMA-Pasteur; IRMA-1) were compared with those obtained by a conventional IRMA employing polyclonal anti-Tg antibodies (HTGK-Sorin; IRMA-2). Preliminary studies for assessment of the interference of TgAb showed that the recovery of added Tg was significantly higher (P < 0.01) when determined by IRMA-1 (64.6 +/- 23%) than by IRMA-2 (49.5 +/- 20%). Study groups included 79 patients with differentiated thyroid carcinoma (DTC) treated by total thyroidectomy and radioiodine ablation; 24 had no metastases or residual thyroid tissue, 31 had a thyroid residue, and 24 had metastatic disease. Seventy-five patients with autoimmune thyroid disease (47 with Graves' and 28 with Hashimoto's disease) were also included. In TgAb-negative sera from DTC patients, similar Tg concentrations were found by both IRMA, i.e. undetectable in most patients with no residual thyroid or neoplastic tissue, low to moderately elevated in the majority of those with residual thyroid tissue, and markedly elevated in all patients with metastatic disease. Serum Tg was undetectable by both assays in several TgAb-positive sera from DTC patients with residual thyroid tissue or metastatic disease, respectively, in whom a detectable or even high serum Tg concentration was expected. Despite the lower in vitro interference of TgAb in IRMA-1, there was no difference between the two assays. In the group of patients with thyroid autoimmune disease, serum Tg concentrations were found to be high in TgAb-negative sera and much lower in TgAb-positive sera by both IRMAs. In conclusion, the present study demonstrates that the use of a monoclonal antibody IRMA for serum Tg, although less susceptible to in vitro TgAb interference, does not necessarily provide any substantial advantage with respect to a conventional polyclonal IRMA in detecting Tg in TgAb-positive sera. The finding of undetectable or lower than expected serum Tg by either method in TgAb-positive serum may well reflect a truly reduced serum Tg concentration. This might be due to an accelerated Tg metabolic clearance in the presence of TgAb.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

Identification of the Cys634-->Tyr mutation of the RET proto-oncogene in a pedigree with multiple endocrine neoplasia type 2A and localized cutaneous lichen amyloidosis.

Following the recent identification of specific germline mutations of the RET proto-oncogene in Multiple Endocrine Neoplasia type 2A (MEN2A) patients, we looked for mutations of this gene in a pedigree showing recurrence of MEN2A and localized Cutaneous Lichen Amyloidosis (CLA). Basal calcitonin and/or pentagastrin test performed in all the 10 available members of this pedigree confirmed the clinical diagnosis and allowed the presymptomatic identification of an additional carrier. A cys634-->tyr missense mutation, already reported as causative in MEN2A patients, was identified after SSCP analysis and direct sequencing of exon 11 of the RET protooncogene in one individual affected with both MEN2A and CLA, thus suggesting a common etiology for the two disorders. Taking advantage of the observation of an RsaI restriction site in the sequence surrounding the mutated codon, we could demonstrate that the same mutation is present in three other affected members, in the presymptomatic carrier and in one additional 25 years old healthy member who shows a mildly positive pentagastrin test.

Amyloidosis↗
PubMed1994

Serum soluble interleukin 2 (IL-2) receptor (sIL-2R) in differentiated thyroid carcinoma.

Increased concentrations of serum soluble interleukin-2 (IL-2) receptor (sIL-2R), a marker of T-lymphocyte activation, have been found in several metastatic solid tumors. To our knowledge, no information is available on serum sIL-2R in differentiated thyroid carcinoma (DTC). Aim of this study was to evaluate whether disease activity and/or thyroid status may affect circulating sIL-2R in DTC, since it is has recently been demonstrated that serum thyroid hormone concentration positively modulates circulating sIL-2R. DTC patients were divided into 3 groups: Group A: 48 patients without metastases or local recurrences; Group B: 16 patients with cervical lymph node metastases; Group C: 22 patients with distant metastases. All patients were evaluated after total thyroidectomy both off and on L-thyroxine (L-T4) therapy. Control group was composed by 20 healthy euthyroid subjects. sIL-2R was assayed by solid-phase ELISA. In the hypothyroid state, sIL-2R levels of Group A were significantly lower when compared to normal controls (256 +/- 130 vs. 461 +/- 186 U/ml, p < 0.001 by Student t test); Group B and Group C patients off L-T4 therapy had sIL-2R concentrations significantly higher (479 +/- 407 U/ml, Group B; 519 +/- 746 U/ml, Group C) when compared to hypothyroid patients of Group A (p < 0.01 and p < 0.05, respectively), but not significantly different from normal euthyroid controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma, Follicular↗
PubMed1994

Expression of p21 ras protein as a prognostic factor in papillary thyroid cancer.

We studied the expression of p21, the ras encoded protein, in primary tumour of 45 patients with papillary thyroid cancer (PTC). Patients were grouped according to outcome so that one group (31 patients) had a good outcome and the other (14 patients) a fatal outcome, after a follow-up of at least 5 years. The presence of p21 ras protein was assessed by immunohistochemistry with a specific monoclonal antibody (MAb Y-13259). The results were correlated with the outcome, with the expression of proliferating cell nuclear antigen (PCNA)/cyclin (as a marker of cell proliferation) and with other well established prognostic factors for PTC (age, grading, extension and tumour size; Endocrinol Metab Clin North Am 1990, 19, 545-576). p21 staining in tumours of living patients was negative in 15, weakly positive (1+) in 10 and strongly positive (2+ or more) in 6 patients. In tumours from deceased patients, p21 staining was negative in 1, weakly positive in 2 and strongly positive in the remaining 11 patients (P < 0.001, chi 2). PCNA immunostaining was increased in 63.6% (7/11) of the tumours from deceased patients compared to 17.8% (5/28) of the tumours of living patients, but no direct correlation was found between p21 and PCNA expression. Among the other prognostic factors studied, only age > or = 40 years was a significant predictor of poor outcome. The survival curve of patients with strongly positive p21 staining was similar to that of patients aged > or = 40 years at the time of diagnosis. The combination of p21 > or = 2+ and age > or = 40 was superior to age alone (P < 0.05) as a prognostic indicator of poor outcome. In conclusion, our results indicate that the p21 product of the ras (proto)oncogene is differently expressed in PTC, in relation to the degree of aggressiveness. Regardless of the pathogenetic role of the ras oncogene in thyroid tumorigenesis, our data indicate that the expression of the p21 ras protein may be regarded as a prognostic indicator in PTC. Furthermore, overexpression of p21 ras protein is associated with patients in the older age groups, and might contribute to the poor prognosis of elderly patients.

Adolescent↗
PubMed1994

Disappearance rate of serum calcitonin after total thyroidectomy for medullary thyroid carcinoma.

We studied the half-life of serum calcitonin (CT) in patients subjected to total thyroidectomy for medullary thyroid carcinoma (MTC). One patient showed a rapid serum CT component with a half-life of 3 hours and a slow component with a half-life of 30 hours; in another case only the 30-hour component was found. By chromatography of tumor extracts, we found that all the immunoreactive CT had a molecular weight of 3,600. After surgery, normalization of serum CT was achieved within 15 days in 4 patients, at 3 months and at 6 months in 2 other patients, while 1 patient never normalized. Normalization of serum CT after surgery is not an index of definitive cure in MTC, as demonstrated by one patient who relapsed 3 months after normalization of serum CT. However, as a general rule, patients who reach undetectable serum CT levels soon after surgery, are those having the best prognosis.

Adult↗
PubMed1994

Routine measurement of serum calcitonin in nodular thyroid diseases allows the preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma.

To assess whether routine measurement of serum calcitonin (CT) could improve the preoperative diagnosis of sporadic medullary thyroid carcinoma (MTC), 1385 consecutive patients presenting for nodular thyroid disease during the year 1991 were submitted to serum CT determination and fine needle aspiration cytology (FNAC). The clinical diagnosis was nontoxic nodular goiter in 1197 (86.4%) patients, toxic multinodular goiter in 65 (4.7%), autonomously functioning thyroid nodule (AFTN) in 64 (4.6%), and autoimmune thyroid disease (Graves' disease or Hashimoto's thyroiditis) with nodule(s) in 59 (4.3%). As controls, 177 patients with nonnodular thyroid disease and 32 normal subjects were also studied. Patients with FNAC suspicious of any kind of thyroid carcinoma and patients with elevated basal and pentagastrin-stimulated serum CT, regardless of the results of FNAC, were submitted to surgery. Eight (0.57%) patients (7 with nontoxic nodular goiter and 1 with AFTN) had elevated basal serum CT levels, ranging between 55-10,000 pg/mL. The pentagastrin test was abnormal in all of them. FNAC was suggestive of MTC in 2, thyroid carcinoma in 1, benign nodule in 3, and inadequate in 2. By histology, immunohistochemistry, and Northern blot analysis of total tumor RNAs, MTC was confirmed in all patients, including the 1 with AFTN, who had the association of microfollicular adenoma and a small MTC in the same lobe. After surgery, serum CT decreased to undetectable levels in 7 patients and remained undetectable in 6 of them during a mean follow-up of 22 months, although 1 of them had a positive response to pentagastrin. Forty-four patients in the group with normal serum CT levels had FNAC suspicious for differentiated thyroid carcinoma and were treated by surgery. Differentiated thyroid carcinoma, mostly papillary, was confirmed at histology in 43 subjects (3.1% of all thyroid nodules). In conclusion, the results of our study indicate that serum CT measurement is useful for the screening of sporadic MTC in patients with thyroid nodule(s). The prevalence of MTC, diagnosed by serum CT measurement in a 12-month period, among an unselected series of 1385 patients with nodular thyroid disease was surprisingly high: 0.57% of all thyroid nodules and 15.7% of all thyroid carcinomas. Serum CT measurement was superior to FNAC in suggesting the diagnosis of MTC and was devoid of falsely positive results. Increasing the diagnostic accuracy helped the surgeon to perform more radical treatment of MTC, thus achieving frequent normalization of postoperative serum CT levels. Whether this result indicates definitive cure remains to be established on the basis of longer follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗