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Biomedical subjects

E De Carlo

Publications and source records attributed to E De Carlo.

At least 19 recordsLinked to original sources

Minimally invasive (99m)Tc-sestamibi radioguided surgery of parathyroid adenomas.

In the last 10 to 15 years surgery of primary hyperparathyroidism (PHPT) moved from the wide bilateral neck exploration to various types of limited neck exploration ranging from unilateral neck surgery to minimally invasive approaches as the minimally invasive radioguided parathyroidectomy. In contrast with the bilateral neck exploration, an accurate preoperative localizing imaging, which is mainly based on (99m)TC-sestamibi scintigraphy, is mandatory when planning a concise parathyroidectomy. Following imaging criteria, only a fraction of PHPT patients accounting for approximately 60% to 70% of all PHPT patients can be eligible for a minimally invasive parathyroidectomy. Only PHPT patients with a high probability to be affected by a solitary parathyroid adenoma showing a high (99m)TC-sestamibi uptake and with a normal thyroid gland should be offer a minimally invasive radioguided parathyroidectomy. The (99m)TC-sestamibi SPECT technique and the double-tracer 123-iodine or (99m)TC-pertecnetate/(99m)TC-sestamibi scintigraphic technique are the most sensitive and accurate preoperative imaging modalities and their utilization is recommended when considering a minimally invasive radioguided parathyroidectomy. Two main intraoperative procedures for the minimally invasive radioguided surgery have been described: the single-day protocol and the different-day protocol. In the single-day protocol a 740 MBq dose of (99m)TC-sestamibi is injected to the patient, scintigraphic imaging is obtained by dual-phase technique and then the patient is operated on within approximately 3 hours from radio-tracer injection. In the different-day protocol, a double-tracer parathyroid scintigraphy is obtained some days before surgery with the aim of better planning the type and extension of intervention. The day of intervention, for the purpose of radioguided surgery only, a low 37 MBq dose of (99m)TC-sestamibi is injected to the patient in the operating theatre a few minutes before the start of intervention. The main advantages of minimally invasive radioguided parathyroidectomy over the traditional wide bilateral neck exploration can be resumed as follows: a shortening in the operating and recovery time, possibility of local anesthesia, possibility of ambulatory surgery or same-day discharge, less postsurgical hypocalcemia, less postsurgical pain, favourable cosmetic results, benefits from a cost-analysis point of view.

Adenoma↗

Molecular characterisation of a field strain of bubaline herpesvirus isolated from buffaloes (Bubalus bubalis) after pharmacological reactivation.

Two healthy buffaloes (Bubalus bubalis) in a herd which had not been vaccinated against infectious bovine rhinotracheitis (IBR), were selected for their seropositivity for anti-bovine herpesvirus type 1 (BoHV-1) glycoprotein E antibodies, and injected intramuscularly daily with dexamethasone for five consecutive days (day 1 to day 5) to reactivate any latent herpesvirus. Blood samples and nasal and vaginal swabs were collected daily from day 5 to day 15 from each buffalo for virological examination. All the vaginal swabs and blood samples were negative, but 13 of the 22 nasal swabs were positive; a cytopathic effect was observed in primary cultures of bovine fetal lung cells, and the viral isolates were identified as a herpesvirus by PCR. The viral strains were characterised by the sequence analysis of the genes coding for glycoproteins D and B, and the gene sequences were then used for phylogenetic analysis. The isolates from both buffaloes appeared identical at the level of the two genes, and were more closely related to bovine herpesvirus type 5 than to BoHV-1.

Amino Acid Sequence↗

Graves' ophthalmopathy and atrophic thyroiditis: a case report.

Graves' ophthalmopathy (GO)--also known as thyroid-associated orbitopathy or ophthalmopathy--usually affects patients with Graves' disease. Antibodies stimulating the TSH receptor are thought to be involved in the pathogenesis of this important and disabling extra-thyroidal manifestation of Graves' disease. Less frequently, GO occurs in subjects who neither have nor have ever shown evidence of thyroid dysfunction ("euthyroid GO"), while the occurrence of GO in patients with autoimmune Hashimoto's thyroiditis is thought to be quite rare and has sporadically been reported. The late and abrupt occurrence of severe GO without hyperthyroidism in an 88-yr-old woman with primary myxedema due to atrophic thyroiditis must be considered as an exceptional event. In this patient, GO was combined with elevated titres of serum auto-antibodies directed against the TSH receptor, while serum levels of anti-thyroglobulin and thyroperoxidase antibodies were within the normal range or only occasionally slightly above the normal values.

Aged↗

The early diagnosis of multiple endocrine neoplasia type 1 (MEN 1): a case report.

We report the case of a patient presenting amenorrhea, hyperprolactinemia, headache and nuclear magnetic resonance (NMR) evidence of pituitary macroadenoma. The family history revealed that the patient's father had had a referred sporadic insulinoma, removed 25 yr before without evidence of other endocrine disorders. Physical examination evidenced a slight neck enlargement. Among biochemical and endocrinological assays performed, only hyperprolactinemia was observed. Neck ultrasonography (US) revealed a parathyroid enlargement and a 99mTcO4/MIBI scan showed two hyperplasic lesions. Considering the diagnostic suspect of multiple endocrine neoplasia (MEN1), we performed abdominal US and NMR studies, showing a pancreatic lesion compatible with neuroendocrine tumor. A total body 111In-DTPA-d-Phe1 -octreotide scan (Octreoscan) was also carried out, evidencing no pituitary tumor uptake but high uptake of the abdominal lesion. After surgery, the histological examination confirmed the two parathyroid adenomas and four non-functioning pancreatic neuroendocrine tumors. When the patient was admitted for studying the pituitary lesion and for planning the opportune therapy, an early and partially subclinical stage of MEN1 was identified, potentially already clear but otherwise undiagnosed, and the genetic state of the patient's relatives, as possible carriers of DNA mutation, was checked. The DNA study for germline mutations confirmed the clinical diagnosis of MEN1 syndrome in the patient and evidenced the same MEN1 mutation in her father and twin sister. In this case report, we would like to underline that, still today, a correct anamnesis and physical examination are the cornerstone of clinical approach to the patient. Furthermore, initial good practice approach is necessary to plan the diagnostic iter, enabling clinicians to decide upon the best orientation and interpretation of the results among several complicated and expensive exams.

Adolescent↗

Effects of a somatostatin analogue in occult gastrointestinal bleeding: a case report.

We describe the case of a patient with obscure gastrointestinal bleeding and anaemia, who required repeated transfusions for about 1 year. Because of the absence of a certain diagnosis and of a surgical approach indication, we established long-acting octreotide therapy, obtaining clinical stabilisation and interruption of the transfusional need. Withdrawal of long-acting somatostatin analogue therapy was associated with renewal of bleeding that was again successfully stopped by continuous i.v. somatostatin administration followed by re-establishment of the long-acting octreotide therapy. We suggested, in absence of surgical indications and when only palliative therapies are available, a therapeutic approach with long-term SMS analogues in patients with lower digestive bleeding of a known or unknown source.

Aged↗

Autoimmune diabetes mellitus, Hodgkin's disease and Graves' ophthalmopathy in a patient with 8.1 ancestral haplotype.

In this report, we describe the case of a 43-year-old woman affected by type 1 diabetes mellitus diagnosed 8 years before, who developed Graves' disease 2 years after chemotherapy and mantle radiotherapy treatment for Hodgkin's disease. Bilateral Graves' ophthalmopathy appeared four months before our observations. Intravenous methyl-prednisolone therapy was started, but was interrupted due to severe metabolic failure. Autoantibodies (anti-islet cells, anti-thyroid, thyroid-stimulating, non-organ-specific) were positive. Since the clinical picture suggested a genetic immunological ground predisposing to autoimmunity, we evaluated her HLA haplotype. Genomic typing of the patient permitted identification of the 8.1 ancestral haplotype, a Caucasoid haplotype unique in its association with many immunopathological diseases. Moreover, we also observed a haplotype unusual in Caucasians, trans DRB1*1101, DQA1*0103, DQB1*0603. To our knowledge, HLA-related genetic risk of developing thyroid autoimmunity after neck irradiation has never been studied. Although we cannot confirm a direct association between the 8.1 ancestral haplotype or DRB1*1101, DQA1*0103, DQB1*0603 and the diseases described, we suggest considering immunological parameters and HLA typing in candidate patients for mantle radiation therapy for Hodgkin's disease or other tumors. HLA haplotype determination could be useful in identifying the patients at raised risk of developing autoimmune diseases after irradiation, thus permitting a more appropriate follow-up schedule.

Adult↗

An in vivo OctreoScan-negative adrenal pheochromocytoma expresses somatostatin receptors and responds to somatostatin analogs treatment in vitro.

A 52-yr-old woman presented with hypertension, elevated urinary vanillylmandelic acid, metanephrines, normetanephrines, and plasma chromogranin A (CgA), but normal urinary catecholamine levels. Abdominal ultrasonography and subsequent MRI imaging showed a 3 cm nodular lesion of the right adrenal gland also visualized by 123I-meta-iodobenzylguanidine scintigraphy consistent with a pheochromocytoma (PC). Her OctreoScan was negative. The patient underwent right adrenalectomy and histological examination showed a PC. The adrenal medulla tissue was examined for somatostatin (SRIH) receptor subtypes 1 to 5 (SSTR1 to 5) expression by RT-PCR. Cultured tumor cells were treated with either SRIH, Lanreotide (Lan), or an SSTR2 (BIM-23 120) or SSTR5 (BIM-23 206) selective agonist. CgA secretion was measured in the medium by ELISA and catecholamine levels by HPLC after 6h. Cell viability was assessed after 48h. RT-PCR analysis showed that SSTR1, 2, 3 and 4 were expressed. CgA secretion was significantly reduced by SRIH (- 80 %), Lan (- 35 %), and the SSTR2 selective agonist (- 65 %). Norepinephrine secretion was reduced by SRIH (- 66 %), Lan (- 40 %), and BIM-23 120 (- 70 %). Epinephrine and dopamine secretion was also inhibited by treatment with SRIH (- 90 % and - 93 %, respectively) and BIM-23 120 (- 33 % and - 75 %, respectively) but not by Lan. Cell viability was also significantly reduced by SRIH (- 30 %), Lan (- 10 %), and the SSTR2 selective agonist (- 20 %). The SSTR5 selective agonist did not modify either CgA and catecholamine secretion or cell viability. Our data show that SSTRs may be present in a PC although OctreoScan is negative in vivo, and that SRIH and its analogs may reduce both differentiated and proliferative functions in chromaffin cells in vitro. These findings suggest that SRIH analogs with enhanced SSTR2 affinity might be useful in the medical therapy of PC, even when an OctreoScan is negative.

Adrenal Gland Neoplasms↗

Importance of radio-guided minimally invasive parathyroidectomy using hand-held gamma probe and low (99m)Tc-MIBI dose. Technical considerations and long-term clinical results.

AIM: (99m)Tc-MIBI radio-guided surgery results, obtained in a group of 141 patients with primary hyperparathyroidism (HPT), are reported. METHODS: All patients were preoperatively evaluated by a single day protocol based on double-tracer parathyroid scintigraphy and neck ultrasound, and then operated by the same surgical team. In 102 patients (72.3%) with a high scan/ultrasound probability of solitary parathyroid adenoma and normal thyroid gland, a minimally invasive radio-guided surgery was planned. In the other 39 patients (27.7%) with scan/ultrasound evidence of multi-glandular disease (n=8) or concomitant nodular goiter (n=31), the intraoperative gamma probe was used during a standard bilateral neck exploration. Intraoperative quick parathyroid hormone (PTH) levels were routinely measured. The minimally invasive radio-guided surgery technique we developed, consisted of: a) injection of a low 37 MBq (99m)Tc-MIBI dose in the operative theatre during anaesthesia induction, b) patient's neck scan with a hand-held gamma probe just before the surgical cut to localize the cutaneous projection of the parathyroid adenoma, c) intraoperative probe detection of the parathyroid adenoma and its removal through a small 2-2.5 cm skin incision. RESULTS: Minimally invasive radio-guided surgery was successfully performed in 99/102 patients (97.0%). The gamma probe was particularly useful in patients with an ectopic parathyroid adenoma in the upper mediastinum (n=11) or to the carotid bifurcation (n=1) or located deep in the neck (n=8). Minimally invasive radio-guided surgery was also obtained in 18/23 patients who had previously undergone thyroid/parathyroid surgery. The mean operative time for minimally invasive radio-guided surgery was 38 min. No major surgical complication was recorded. Conversion to bilateral neck exploration was required in only 3 cases because of intra-operative diagnosis of parathyroid carcinoma (n=2), and persistence of elevated quick PTH levels after removal of the preoperatively visualized parathyroid adenoma (n=1). Among patients treated by standard bilateral neck exploration, the gamma probe was useful in localizing a thymical enlarged parathyroid gland in 1 patient with multi-glandular disease, a parathyroid adenoma located deep in the neck in 4 patients with concomitant nodular goiter and an ectopic parathyroid adenoma to the carotid bifurcation in another. However, in some other patients with a parathyroid adenoma located near to the thyroid, it was difficult to intraoperatively distinguish the parathyroid adenoma from a MIBI avid thyroid nodule. CONCLUSION: It can be concluded that: (a) in primary HPT patients with high scan/ultrasound probability of solitary parathyroid adenoma and normal thyroid gland, the gamma probe appears to be an effective, rapid and safe technique to perform minimally invasive radio-guided surgery; b) a (99m)Tc-MIBI dose as low as 37 MBq appears to be adequate to successfully perform radio-guided surgery; c) the measurement of quick PTH is recommended during minimally invasive radio-guided surgery; d) minimally invasive radio-guided surgery can be performed also in HPT patients with previous parathyroid/thyroid surgery thus limiting surgical trauma; e) with the possible exception of parathyroid adenoma located in ectopic sites or deep in the neck, the gamma probe technique does not seem recommendable in HPT patients with concomitant nodular goiter.

Adult↗

[New perspectives in diagnosis and therapy of endocrine gastroenteropancreatic (GEP) tumors with somatostatin analogues].

In the last decade important progresses have been obtained in the diagnosis and therapy of endocrine gastroenteropancreatic (GEP) tumors, mainly derived from the somatostatin receptors characterization and the introduction of long acting somatostatin analogues. Receptorial scintigraphy with radio-labeled analogues (Octreoscan) is the first choice investigation for staging and follow-up of endocrine GEP tumors, thanks to the high sensitivity in revealing the primary tumor and metastases, and for its capability to reveal lesions that are not identified by other imaging methods. Moreover, somatostatin analogues uptake by tumors allow us to use radiopharmaceutical compounds for advanced disease treatment. Between the radio-labeled drugs until now studied, interesting results have been obtained by DOTA-lanreotide (MAURITIUS), DOTA0 Tyr3-octreotide (DOTATOC) and DOTA0 Tyr3-octreotate, bound to beta-emitting radio-isotope suitable for therapeutic use. In the field of the pharmacological therapy of GEP tumors, the clinical trials show that somatostatin analogues reduce the symptoms related to functionally active tumors and stabilize or slow tumor growth improving the patient quality of life. Although somatostatin analogues alone could not be able to cure GEP tumors, their early utilization in association with surgical debulking of primary tumor and metastases, embolization or chemoembolization, and interferon, chemotherapy and radio-metabolic therapy (mainly directed to the destruction of micrometastases), increases the possibility of a radical therapeutic intervention. The continuous evolution of pharmacological research provides always new analogues (octreotide LAR, lanreotide, vapreotide, BIM-23244, BN 81644, PTR-3173, BIM-23A387, SOM-230, etc.) with different pharmacokinetic and receptorial properties and acting with more effectiveness in the different individual clinical situations. In this context there have been recently introduced also the "chimeric" analogues. On the other hand, the widespread utilization of molecular biology and immunohistochemical methods can allow, in perspective, to better define the receptorial pattern of individual endocrine tumors, after their surgical removal. The necessity to integrate endocrinological, nuclear medicine, surgical, oncologic and laboratory competencies behaves a multidisciplinary approach based on the utilization of diagnostic-therapeutic protocols supplying comparable results. It does not appear unjustified to expect, in the future, a scenery of more "individual" and more effective therapies for patients affected by GEP tumours.

Biomarkers, Tumor↗

Endothelin-1 and endothelin-3 stimulate insulin release by isolated rat pancreatic islets.

Endothelins (ETs) are potent vasoconstrictive peptides released from the endothelium and other tissues, which act on target cells by receptorial calcium-mediated mechanisms. ET-1 levels are increased in diabetes, and observations suggest the involvement of ETs in the pathogenesis of diabetic angiopathy. However, it is not possible to exclude that ETs might also influence insulin secretion or function. In vivo infusion of ET-1 in rats induces hypoglycaemia and hyperinsulinemia and in vitro incubation with ET-1 stimulates insulin release by mouse islets. Therefore, ETs might be involved in a circulus vitiosus, resulting in hyperinsulinemia and diabetic angiopathy. The purpose of our study was to verify the effect of ET-1 on rat islets, in both the presence and absence of physiological glucose concentration. Moreover, we tested the effect of another isoform of endothelins, ET-3, and verified the involvement of extracellular calcium in such events. Islets were incubated with increasing ET-1 or ET-3, with or without glucose 5.6 mM. Other samples were prepared using calcium-free medium. Incubation in medium containing ET-1 and ET-3, in the presence of glucose and calcium, induced an increase in insulin release. When ET-1 and ET-3 were incubated without glucose and calcium, insulin release was not modified. Our studies demonstrate that: 1) ET-3, like ET-1, stimulates insulin release by rat isolated islets; 2) direct insulin stimulating effect on islets of both ET-1 and ET-3 is evident with physiological glucose concentrations and is calcium mediated. These results support the hypothesis of ET involvement in the regulation of insulin secretion.

Animals↗

Morphologic study of microcirculation in acromegaly by capillaroscopy.

Although wide range investigations on the heart and great vessels have been reported in acromegaly, the field of microcirculation is still largely vacant. The nailfold is a window through which we can observe in vivo the vascular bed. This study investigates through nailfold capillaroscopy the morphology of cutaneous microcirculation in acromegaly in relationship with the usual hormonal parameters of disease activity. Twenty-five acromegalic patients and 26 normal subjects, age and sex matched, were studied. A subgroup of acromegalics (8 patients) was considered in stable remission, and the remaining 17 had active disease. Capillaroscopy was performed in each subject by in vivo computer aided stereomicroscopy (magnification, x400). The following morphological parameters were calculated: the number of tortuous loops, meandering capillaries, and capillaries per millimeter; avascular areas; visibility of subpapillary plexus; the capillary length; and intercapillary distance. We were unable to perform the exam in 4 of 25 patients because visibility was poor. The capillary number and length were significantly reduced in acromegalics compared to controls [8.9 +/- 1.5 vs. 10.3 +/- 1.2 no./mm (P = 0.0010) and 174 +/- 49 vs. 255 +/- 24 microm (P < 0.0001)]. Moreover, in acromegalics, the numbers of tortuous loops and meandering capillaries were significantly increased [19 +/- 8 vs. 13 +/- 5 (P = 0.0027) and 10 +/- 12 vs. 0.7 +/- 1.1 (P < 0.0001)]. The capillaroscopic alterations were still observed in a smaller group of 8 nondiabetic and nonhypertensive acromegalics. We found branch-like capillaries in 4 acromegalic patients, but not in the control group. Finally, we observed a meaningful different and ameliorated capillaroscopic morphology in acromegalic patients in stable remission compared to active disease patients as far as the total number (density) and meandering capillaries were concerned. In conclusion, our study shows that in acromegaly, morphological alterations also affect the peripheral microcirculation, which seems to be influenced by the activity of the disease. We believe that nailfold capillaroscopy may represent an additional useful tool in the follow-up of acromegalic patients.

Acromegaly↗

Stimulatory effects of alpha-hANP on testosterone secretion in man.

Several recent observations suggest that atrial natriuretic peptides (ANP) can modulate steroidogenesis in isolated rat Leydig cells. At present, it is unknown whether ANP influence human testicular steroidogenesis. We therefore evaluated the effects of alpha-human ANP (hANP) administration on testosterone plasma levels in peripheral and internal spermatic venous blood of young men (catheterized for contrast study of varicocele). Six subjects were injected with 100 micrograms alpha-hANP in the cubital vein. Six different patients similarly received 50 micrograms LHRH. Three controls received 2 ml saline. Plasma LH, FSH, and testosterone were then determined 15 min before, at time of injection, and 15, 30, 45, and 60 min thereafter in spermatic vein and peripheral venous blood, as well as at 120 min in peripheral blood. LHRH--induced LH increase was followed by a marked increase of spermatic vein testosterone concentrations, but the peripheral testosterone concentration did not increase. Similarly, alpha-hANP administration did not affect peripheral testosterone and LH concentrations, but significantly increased spermatic vein testosterone levels (P less than 0.01). Our findings demonstrate that alpha-hANP exerts its stimulatory effect on testicular steroidogenesis in man without modifying gonadotropin secretion, suggesting that alpha-hANP may directly influence Leydig cell function.

Adolescent↗

Evidence for a dopaminergic involvement in the inhibitory effect of alpha human natriuretic peptide on prolactin in man.

Recently, it has been suggested that Atrial Natriuretic Peptides (ANP), as well as peripheral hormones, may have a role as central neurotransmitters or neuromodulators, and in humans it has been observed that alpha human ANP inhibits prolactin secretion. In this study, on 12 normal adult males, we evaluated the effects of ANP on the prolactin release induced by TRH and by the dopaminergic blocker sulpiride. Alpha-hANP administration was followed by a significant fall of prolactin plasma levels but did not influence TRH-induced prolactin response. Nevertheless, sulpiride-induced prolactin secretion was significantly lower after Alpha-hANP administration than after placebo pre-treatment (p values ranging between 0.01 and 0.001). Our results suggest that in man Alpha-hANP has no direct influence on lactotrope cells in inhibiting prolactin secretion, but seems to involve activation of the hypothalamic dopaminergic system.

Adult↗

Effect of prolonged physical exercise on muscular phospholipase A2 activity in rats.

Prolonged muscular exercise stimulates glucose uptake by the working muscles themselves. The mechanism of this phenomenon is at present unclear. It has been proposed that the kallikrein-kinin-prostaglandin system plays a role in the physiological regulation of muscular glucose metabolism during exercise. Since bradykinin can stimulate phospholipase A2, a key enzymatic step in prostaglandin synthesis, phospholipase A2 activity was assayed in rats at rest and in rats compelled to swim for 60 minutes. The physiological significance of an increase in muscular phospholipase A2 activity is not clear. Since bradykinin can stimulate both muscular glucose uptake and phospholipase A2 activity, it is possible that the increased activity of this enzyme is involved in the exercise-induced increase of muscular glucose uptake. Phospholipase A2 activity was strongly increased in the exercising rat muscles. A small but significant increase in phospholipase A2 activity was observed in the heart, whereas no variation in activity was demonstrated in either the kidney or the liver of exercising rats. These findings strongly indicate that prolonged exercise increases muscular phospholipase A2 activity only in the muscle and heart. This phenomenon appears to be strongly related to muscular contraction, since other stress situations such as cold exposure did not modify phospholipase A2 activity. Our data are in agreement with the hypothesis of a possible involvement of prostaglandins in the priming action of insulin on glucose uptake during muscular work.

Animals↗

Effect of exercise on plasma kallikrein and muscular phospholipase A2 activity in rats.

Many experimental observations show that prolonged physical exercise produces an increase of muscular glucose uptake. Recent findings suggest that the kallikrein-kinin-prostaglandin system may be related to this phenomenon, but so far, no direct evidence of quantitative alteration in this system has been observed during exercise. We measured plasma kallikrein and muscular phospholipase A2 activity, respectively the first and the last steps of reactions leading to prostaglandin synthesis. We demonstrated, for the first time, that during exercise plasma kallikrein activity increases in rats. We also observed an increase of muscular phospholipase A2 activity after exercise and a positive correlation between these parameters. Our findings demonstrate, under physiological conditions of enhanced muscular glucose uptake, a concomitant significant increase of plasma kallikrein and muscular phospholipase A2 activity, supporting the hypothesis that activation of the kallikrein-kinin-prostaglandin system may play some part in the enhanced muscular glucose uptake during physical activity.

Animals↗