Overt hypothyroidism in pregnancy and language development in offspring: is there an association?

PURPOSE: Overt hypothyroidism during pregnancy is linked to various obstetric complications, such as premature birth and fetal death. While some studies have shown that maternal hypothyroidism can impact a child's Intelligence Quotient (IQ) and language development, findings are controversial. The aim of this study was to explore the connection between treated maternal hypothyroidism during pregnancy and offspring neurodevelopment, focusing on learning and language and examining related maternal obstetric complications. METHODS: Group 1 included 31 hypothyroid women with elevated thyroid stimulating hormone (TSH) (> 10 mU/L, > 10 µIU/mL) during pregnancy, and Group 2 had 21 euthyroid women with normal TSH levels (0.5-2.5 mU/L, 0.5-2.5 µIU/mL). Children underwent neuropsycological assessments using the Griffiths-II scale. RESULTS: Pregnancy outcome showed an average gestational age at delivery of 38.2 weeks for hypothyroid women, compared to 40 weeks for controls, and average birth weight of 2855.6 g versus 3285 g for controls, with hypothyroid women having children with higher intrauterine growth restriction (IUGR) prevalence and more caesarean sections. The 1-min APGAR score was lower for the hypothyroid group's children, at 8.85 versus 9.52. Neuropsychological outcomes showed children of hypothyroid mothers scored lower in neurocognitive development, particularly in the learning and language subscale (subscale C), with a notable correlation between higher maternal TSH levels and lower subscale scores. CONCLUSION: Fetuses born to hypothyroid mothers appeared to be at higher risk of IUGR and reduced APGAR score at birth. Neurocognitive development seemed to affect language performance more than the developmental quotient. This alteration appeared to correlate with the severity of hypothyroidism and its duration.

Localization of mesenchymal stromal cells dictates their immune or proinflammatory effects in kidney transplantation.

Multipotent mesenchymal stromal cells (MSC) have recently emerged as promising candidates for cell-based immunotherapy in solid-organ transplantation. However, optimal conditions and settings for fully harnessing MSC tolerogenic properties need to be defined. We recently reported that autologous MSC given posttransplant in kidney transplant patients was associated with transient renal insufficiency associated with intragraft recruitment of neutrophils and complement C3 deposition. Here, we moved back to a murine kidney transplant model with the aim to define the best timing of MSC infusion capable of promoting immune tolerance without negative effects on early graft function. We also investigated the mechanisms of the immunomodulatory and/or proinflammatory activities of MSC according to whether cells were given before or after transplant. Posttransplant MSC infusion in mice caused premature graft dysfunction and failed to prolong graft survival. In this setting, infused MSC localized mainly into the graft and associated with neutrophils and complement C3 deposition. By contrast, pretransplant MSC infusion induced a significant prolongation of kidney graft survival by a Treg-dependent mechanism. MSC-infused pretransplant localized into lymphoid organs where they promoted early expansion of Tregs. Thus, pretransplant MSC infusion may be a useful approach to fully exploit their immunomodulatory properties in kidney transplantation.

The treatment of neuroendocrine tumors with long-acting somatostatin analogs: a single center experience with lanreotide autogel.

The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lanreotide autogel given to metastatic well-differentiated (WD) neuroendocrine tumors (NET) patients observed in our Institute between 2005 and 2008. Patients with metastatic NET referred to our tertiary referral center were given lanreotide autogel 120 mg/month by deep sc injection for a period of at least 24 months. The efficacy was evaluated by the relief of disease symptoms, behavior of tumor markers and response rate in terms of time to tumor progression. Safety and tolerability were evaluated by assessing the onset of adverse events and treatment feasibility. Twenty-three patients (13 males), median age 62 yr (range 32-87) were considered for the study. All patients were affected by WD metastatic NET and had tumor progression in the last 6 months before the enrolment in the study. Median duration of response was 28 months (range 6-50 months). Fourteen patients (60.9%) showed flushing and diarrhea which improved by 85.7% and 55.6%, respectively, bronchoconstrinction and abdominal pain also ameliorated. A complete, partial or no-changed response in the tumor markers behavior was observed, respectively, in 42.9%, 22.9%, and 17.1% of cases. According to RECIST (Response Evaluation Criteria In Solid Tumors) criteria (version 1.1), there were 2 partial regression (8.7%) and 15 stable disease (65.3%); 6 patients (26.0%) progressed. No patient complained from any severe adverse reaction. The results of our study suggest that lanreotide autogel is effective in the symptoms, biochemical markers, and tumor progression control of WD metastatic NET and confirm that the treatment is well tolerated.

Levothyroxine therapy in preventing nodular recurrence after hemithyroidectomy: a retrospective study.

AIM: To determine the effect of levothyroxine (L-T4) therapy on the recurrence rate of nodular disease in patients previously treated with lobectomy for benign nodular goiter. METHODS: Two hundred and thirty-tree patients (38 males, 195 females; age 49.9+/-13.1 yr) with no post-surgical evidence of nodular disease in the remnant, were followed- up yearly with serum TSH and ultrasound (US). Nodular recurrence was defined as a lesion of at least 5 mm at US. Patients were divided in 2 groups based on whether or not they had been treated with L-T4 after surgery: Group 1 (45 patients) who did not receive any L-T4, and Group 2 (188 patients) treated with L-T4. Group 2 was further subdivided in Group 2a (123 patients) receiving L-T4 substitutive therapy (TSH>or=0.5 and

Bone marrow-derived mesenchymal stem cells improve islet graft function in diabetic rats.

Type 1 diabetes is associated with a progressive loss of beta cells and pancreatic islet transplantation could represent a cure for this disease. Herein we explored whether transplantation of bone marrow-derived mesenchymal stem cells (MSCs) allowed a reduced number of pancreatic islets to improve glycemic control in diabetic rats, by promoting islet vascularization. We transplanted 2000 syngenic islets alone or in combination with MSCs (10(6) cells) under the kidney capsules of diabetic Lewis rats. Animals transplanted with 2000 islets never reached normoglycemia. In contrast, rats transplanted with 2000 islets plus MSCs, showed a gradual fall in glycemia after transplantation, with normoglycemia maintained until killing. Comparable glycemic control was obtained with transplantation of 3000 islets alone. The MSC preparation used for in vivo experiments expressed high levels of vascular endothelial growth factor (VEGF(165)) and, at less extent, VEGF(189), as evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). In transplanted animals, vascularization was quantified by morphometric analysis of islet grafts with anti-RECA and anti-insulin antibodies. MSCs were stained with PKH-26. Mean capillary density was 1002 +/- 55 capillaries/mm(2) in islets transplanted alone. Co-infusion of MSCs with islets significantly increased the number of capillaries to 1459 +/- 66 capillaries/mm(2). In conclusion, our study indicated that co-transplantation of MSCs with pancreatic islets improved islet graft function by promoting graft vascularization.

Influence of agricultural practices on the contamination of maize by fumonisin mycotoxins.

The objective of the present work was to investigate the effect of different agricultural practices on the contamination of maize by fumonisin mycotoxins. Corn samples were collected from 16 maize fields located in Aragón (northeastern Spain) during the 2007 crop year. Corn samples were collected from each field five times at different maturation stages: F1, day 0 (milky corn); F2, day 15; F3, day 30 (yellow corn); F4, day 45; and F5, ripe corn at harvest. The agricultural practices evaluated were type of seed (conventional and transgenic), planting method (dry and wet planting), tillage system (plowing and minimum tillage), type of irrigation (flood and sprinkler), residue management of preceding crop (removal and burial), nitrogen fertilization level (kg N per ha), and harvest date. Mycotoxin analysis was carried out with the ROSA Fumonisin test, which measures both fumonisin B1 and B2 by lateral flow immunoassay. No fumonisins were detected in milky corn (F1 and F2 stages). Only one field had fumonisins in F3 yellow corn (1,037 microg/kg); this field was part of the only farm affected by borer insects. One-third of fields had fumonisins at the F4 stage (363 microg/kg), and 62.5% of the fields were positive for fumonisins at the F5 harvest stage (520 microg/kg). Wet planting and the removal of debris from the previous crop significantly lowered the risk of fumonisin in corn. The use of insect-resistant maize seeds tended to reduce fumonisin levels. However, higher levels of nitrogen fertilizer had a tendency to increase fumonisin levels in corn. Tillage system, type of irrigation, and harvest date had no clear effect on fumonisin levels.

Protection from Staphylococcus aureus mastitis associated with poly-N-acetyl beta-1,6 glucosamine specific antibody production using biofilm-embedded bacteria.

Staphylococcus aureus vaccines based on bacterins surrounded by slime, surface polysaccharides coupled to protein carriers and polysaccharides embedded in liposomes administered together with non-biofilm bacterins confer protection against mastitis. However, it remains unknown whether protective antibodies are directed to slime-associated known exopolysaccharides and could be produced in the absence of bacterin immunizations. Here, a sheep mastitis vaccination study was carried out using bacterins, crude bacterial extracts or a purified exopolysaccharide from biofilm bacteria delivered in different vehicles. This polysaccharide reacted specifically with antibodies to poly-N-acetyl-beta-1,6-glucosamine (PNAG) and not with antibodies to other capsular antigens or bacterial components. Following intra-mammary challenge with biofilm-producing bacteria, antibody production against the polysaccharide, milk bacterial counts and mastitis lesions were determined. Bacterins from strong biofilm-producing bacteria triggered the highest production of antibodies to PNAG and conferred the highest protection against infection and mastitis, compared with weak biofilm-producing bacteria and non-cellular inocula. Thus, bacterins from strong biofilm bacteria, rather than purified polysaccharide, are proposed as a cost-efficient vaccination against S. aureus ruminant mastitis.

Antibacterial efficiency of Spanish Satureja montana essential oil against Listeria monocytogenes among natural flora in minced pork.

The purpose of this study was to examine the effectiveness of winter savory (Satureja montana) essential oil (EO) for control of growth and survival of experimentally inoculated Listeria monocytogenes serovar 4b (10(4) CFU/g) among natural flora in minced pork. EOs of French thyme (Thymus vulgaris F) and rosemary (Rosmarinus officinalis) cultivated in the same region of Aragon (northeastern Spain) were used as reference ingredients. The EOs obtained by hydrodistillation were added at concentrations of 0.25, 0.5, 1, and 2.5 microl/g (vol/wt), and the samples were kept at 4 degrees C in air for up to 7 days. The populations of L. monocytogenes and total viable bacteria were determined in the control and treated samples at 0, 1, 3, 5, and 7 days. Moderate activity of S. montana EO against L. monocytogenes was observed (at 2.5 microl/g, reductions of 0.27 log CFU/g by day 3 and 0.61 log CFU/g by day 7), with higher activity against aerobic flora. The greatest reduction in aerobic flora was on day 3 (at 2.5 microl/g) from 1.10 to 1.45 log CFU/g. S. montana EO was comparable to T. vulgaris F EO in listericidal activity, but R. officinalis EO was ineffective against the L. monocytogenes and aerobic flora in the minced meat model. The approximately 3-log reduction in aerobic flora with T. vulgaris F EO at 0.25 to 2.5 microl/g after 5 days of storage was the most significant reduction. Depending on sensory considerations, the addition of active EOs in combination with other preservation techniques for synergistic effects may provide alternatives to synthetic chemical preservatives. Suggestions on relationships between chemical composition and biological activities of EOs are outlined.

Morphometric study of the interproximal unit in the esthetic region to correlate anatomic variables affecting the aspect of soft tissue embrasure space.

BACKGROUND: The presence of a normal papilla is crucial to avoid the unpleasant esthetic defects that are of major concern to periodontists, restorative dentists, and patients. During the course of progressive periodontitis and following periodontal treatment, it is not uncommon to have a partial loss of the interdental papilla. This loss can lead to an unesthetic gingival appearance. This study evaluated different anatomic variables in an effort to determine their role in the papillary appearance of maxillary incisors. METHODS: A total of 178 interdental embrasures in 58 patients were selected randomly for examination. For each patient, a digital photograph and a modified periapical radiograph of the interdental embrasure of the four maxillary incisors were taken by using a special metric device fixed to a centrator as a reference marker. Clinical and radiographic data were obtained for the distance from the contact point to the alveolar crest and for the interradicular distance. We used a classification system with regard to peri-implant soft tissue based on esthetic assessments related to the space between reference lines through the highest gingival curvature of the crown-tooth margin and the contact point. RESULTS: In the group of interdental sites with an interradicular distance of less than approximately 2.4 mm, an increase in the distance between the contact point and the bone crest corresponded to a marked increase in the interdental black triangle's dimensions and, therefore, a less esthetic smile. In particular, when the interradicular distance was >2.4 mm, we statistically estimated that the other anatomic variable considered, the distance from the contact point to the alveolar crest, lost its influence on whether the interdental papilla would be present or absent. CONCLUSION: The interradicular distance and the distance between the contact point and the alveolar crest have independent and combined effects on the presence or absence of the interdental papilla.

[Perinatal prognosis of pregnancies complicated by placental chronic intervillitis]. / Pronostic périnatal des grossesses compliquées d'intervillites chroniques placentaires.

UNLABELLED: SUBJECT. Massive Chronic Intervillositis is an infrequent inflammation lesion of the placenta, characterized by lymphohistiocytic intervillous infiltration, associated with fibrinoid deposition. The purpose of this study was to evaluate the perinatal outcome of pregnancies complicated by such lesions. MATERIAL AND METHODS: We conducted a descriptive retrospective multicentric analysis of a series of pregnancies for which placenta or products of abortion were analyzed between January 1995 and September 2005, at the University Hospital of Bordeaux. After re-examining the histology slides, we performed a semi-quantitative graduation of the cell infiltration and fibrinoid deposition. RESULTS: Twenty-five women were included (one twin-pregnancy and two histologic recurrences). We found three spontaneous abortions before 22 weeks, four intrauterine fetal deaths and three neonatals deaths. Seven of eight elective inductions pregnancies, were performed for intrauterine growth restriction less than 2.5 percentile. The rate of pregnancy loss was 55% and the perinatal mortality was 29%. 77% of fetuses are small for gestational age. Three mothers were pre-eclamptic. 21% of the fetuses had a congenital malformation. Only 32% of the fetuses were alive one week after birth. Histologically, 25% were associated with lesions of Villitis of Unknown Etiology. 77% of the cell infiltration was grade 3 and seemed to be correlated with severe growth restriction. We describe 3 cases of antenatal diagnosis of Chronic Intervillositis, realised after immunofixation on chorionic villous sampling. CONCLUSION: Massive Chronic Intervillositis is a recurrent lesion with a poor prognosis complicated by spontaneous abortion, intrauterine growth restriction and perinatal fetal death. Currently, there is no treatment. Chorionic villous sampling in severe growth restriction might be useful in order to obtain at the same time the fetal karyotype and an histological probe of the placenta.

Bioinformatic analysis of expressed sequence tags derived from a compatible Alternaria brassicicola-Brassica oleracea interaction.

SUMMARY Alternaria brassicicola is a necrotrophic fungal pathogen that causes black spot disease on members of the Brassicaceae plant family. In order to identify candidate fungal pathogenicity genes and characterize a compatible host response, a suppression subtractive hybridization (SSH) cDNA library enriched for A. brassicicola and Brassica oleracea genes expressed during the interaction was created, along with a fungal cDNA library representing genes expressed during nitrogen starvation (NS). A total of 3749 and 2352 expressed sequence tags (ESTs) were assembled into 2834 and 1264 unisequence sets for the SSH and NS libraries, respectively. We compared two methods to identify the origins (plant vs. fungal) of ESTs in the SSH library using different classification procedures, with and without the availability of a database representing the A. brassicicola whole genome sequence and Brassicaceae-specific genes. BLASTX analyses of the 2834 unisequence set using the GenBank non-redundant database identified 114 fungal genes. Further BLASTN analyses of the genes with unidentifiable origin using a database consisting of the 1264 fungal unisequence set from the nitrogen-starved library identified 94 additional fungal genes. By contrast, BLASTN analyses of the same SSH unisequence set using a partially assembled A. brassicicola whole genome draft sequence identified a total of 310 unisequenes of fungal origin. Our results indicated that even a small number of organism-specific EST sequences can be very helpful to identify pathogen genes in a library derived from infected tissue, partially overcoming the limitation of the public databases for little studied organisms. However, using the whole genome draft sequence of A. brassicicola we were able to identify approximately 30% more fungal genes in the SSH library than without utilizing this resource. The putative role of specific fungal and plant genes identified in this study in a compatible interaction is discussed.

Antimicrobial resistance of Salmonella spp. from pigs at slaughter in Spain in 1993 and 2001.

AIM: To compare the incidence of antimicrobial resistance among Salmonella serotypes isolated in a pig slaughterhouse in Zaragoza (Spain) during 1993 and 2001. METHODS AND RESULTS: A total of 168 isolates representing 10 serotypes were examined by disc diffusion method using 17 antibiotics. Data showed that the majority of the strains were resistant to streptomycin (97%), sulfadiazine (93.4%) and tetracycline (83.3%). A large proportion of the collection was multidrug resistant (MDR, resistance to four or more antibiotics) with a greater incidence in 2001. The findings imply an increasing incidence of MDR amongst S. Typhimurium, and all S. Typhimurium-definitive phage type (DT) 104 isolates were resistant to ampicillin, chloramphenicol, streptomycin, sulphonamide and tetracycline (R-ACSSuT). This resistance phenotype had spread among other phage and serotypes. Salmonella Ohio was also a MDR serotype and this is not a serotype normally associated with drug resistance. CONCLUSIONS: A large proportion of the strains were MDR and this showed that pork products could be a potential vehicle of MDR Salmonella food-borne infections. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings may have significant public health consequences and could contribute to the development of useful practices aimed at limiting the transmission of MDR Salmonella serotypes through the food chain.

Group 3 chromosome bin maps of wheat and their relationship to rice chromosome 1.

The focus of this study was to analyze the content, distribution, and comparative genome relationships of 996 chromosome bin-mapped expressed sequence tags (ESTs) accounting for 2266 restriction fragments (loci) on the homoeologous group 3 chromosomes of hexaploid wheat (Triticum aestivum L.). Of these loci, 634, 884, and 748 were mapped on chromosomes 3A, 3B, and 3D, respectively. The individual chromosome bin maps revealed bins with a high density of mapped ESTs in the distal region and bins of low density in the proximal region of the chromosome arms, with the exception of 3DS and 3DL. These distributions were more localized on the higher-resolution group 3 consensus map with intermediate regions of high-mapped-EST density on both chromosome arms. Gene ontology (GO) classification of mapped ESTs was not significantly different for homoeologous group 3 chromosomes compared to the other groups. A combined analysis of the individual bin maps using 537 of the mapped ESTs revealed rearrangements between the group 3 chromosomes. Approximately 232 (44%) of the consensus mapped ESTs matched sequences on rice chromosome 1 and revealed large- and small-scale differences in gene order. Of the group 3 mapped EST unigenes approximately 21 and 32% matched the Arabidopsis coding regions and proteins, respectively, but no chromosome-level gene order conservation was detected.

A 2500-locus bin map of wheat homoeologous group 5 provides insights on gene distribution and colinearity with rice.

We constructed high-density deletion bin maps of wheat chromosomes 5A, 5B, and 5D, including 2338 loci mapped with 1052 EST probes and 217 previously mapped loci (total 2555 loci). This information was combined to construct a consensus chromosome bin map of group 5 including 24 bins. A relatively higher number of loci were mapped on chromosome 5B (38%) compared to 5A (34%) and 5D (28%). Differences in the levels of polymorphism among the three chromosomes were partially responsible for these differences. A higher number of duplicated loci was found on chromosome 5B (42%). Three times more loci were mapped on the long arms than on the short arms, and a significantly higher number of probes, loci, and duplicated loci were mapped on the distal halves than on the proximal halves of the chromosome arms. Good overall colinearity was observed among the three homoeologous group 5 chromosomes, except for the previously known 5AL/4AL translocation and a putative small pericentric inversion in chromosome 5A. Statistically significant colinearity was observed between low-copy-number ESTs from wheat homoeologous group 5 and rice chromosomes 12 (88 ESTs), 9 (72 ESTs), and 3 (84 ESTs).

A chromosome bin map of 16,000 expressed sequence tag loci and distribution of genes among the three genomes of polyploid wheat.

Because of the huge size of the common wheat (Triticum aestivum L., 2n = 6x = 42, AABBDD) genome of 17,300 Mb, sequencing and mapping of the expressed portion is a logical first step for gene discovery. Here we report mapping of 7104 expressed sequence tag (EST) unigenes by Southern hybridization into a chromosome bin map using a set of wheat aneuploids and deletion stocks. Each EST detected a mean of 4.8 restriction fragments and 2.8 loci. More loci were mapped in the B genome (5774) than in the A (5173) or D (5146) genomes. The EST density was significantly higher for the D genome than for the A or B. In general, EST density increased relative to the physical distance from the centromere. The majority of EST-dense regions are in the distal parts of chromosomes. Most of the agronomically important genes are located in EST-dense regions. The chromosome bin map of ESTs is a unique resource for SNP analysis, comparative mapping, structural and functional analysis, and polyploid evolution, as well as providing a framework for constructing a sequence-ready, BAC-contig map of the wheat genome.

In vitro antimicrobial activity of essential oils from aromatic plants against selected foodborne pathogens.

The purpose of this study was to examine the effectiveness of selected essential oils for the control of growth and survival of pathogenic microorganisms of significant importance in food hygiene and to determine whether the antimicrobial effect was due to the major compounds of the oils. MIC and MBC were determined by the tube dilution method. Essential oils from Thymus vulgaris from Spain and France, Salvia sclarea, Salvia officinalis, Salvia lavandulifolia, Lavandula latifolia, Lavandula angustifolia, three hybrids of Lavandula latifolia x Lavandula angustifolia (Lavandin 'Super', Lavandin 'Abrialis', and Lavandin 'Grosso'), Rosmarinus officinalis, Hissopus officinalis, and Satureja montana were evaluated. Inhibition ranged from the strong activity of Satureja montana and Thymus vulgaris (France) to no inhibition with Salvia sclarea and Hissopus officinalis for each of the test strains: Salmonella Enteritidis, Salmonella Typhimurium, Escherichia coli O157:H7, Yersinia enterocolitica, Shigella flexneri, Listeria monocytogenes serovar 4b, and Staphylococcus aureus. Because some of the essential oils were highly inhibitory in small quantities to selected pathogenic microorganisms, they may provide alternatives to conventional antimicrobial additives in foods.

Effect of enamel matrix derivative on human periodontal fibroblasts: proliferation, morphology and root surface colonization. An in vitro study.

BACKGROUND: Several clinical trials have shown the effectiveness of Emdogain(R) (EMD) in promoting tissue regeneration, even though the underlining biological mechanism is still poorly known. OBJECTIVES: The aim of the present study was to verify the effect of EMD on the proliferation of human periodontal ligament (PDL) fibroblasts and on their colonization and differentiation following contact with the root surface of extracted teeth in vitro. METHODS AND RESULTS: Fibroblasts from PDL were seeded on Petri dishes and cell growth was evaluated by cell counting in the presence and absence of EMD, after 1, 3 and 8 d of culture. A significant effect of EMD upon cellular proliferation at d 3 and 8 was detected. When PDL cells were grown for 12 d with EMD on etched human root surface, a change in cell morphology was observed. Scanning electron microscopy revealed that cells grown on root EMD-treated surface present a body with a flattened surface closely adherent to the substrate and an outer smooth surface rounded in shape. From the flattened surface some thin and elongated cellular processes connecting with the substrate were also observable. PDL cells grown on EMD-treated surface showed lack of alkaline phosphatase activity, as some authors noticed in cementoblasts in vitro. CONCLUSIONS: In conclusion, our data indicate that EMD enhances human PDL fibroblast proliferation. Furthermore, the cells in the presence of EMD show morphological changes that make them more similar to cementoblasts than to fibroblasts, suggesting a process of cellular differentiation that could play an important role in periodontal tissue repair.

Parameter estimation in a model for multidimensional recording of neuronal data: a Gibbsian approximation approach.

This article proposes improved numerical procedures for estimating parameters in a spatiotemporal lattice model introduced for the analysis of cortical activities monitored from arrays of diodes. The numerical algorithms are based on approximations inspired by statistical physics. Both Gibbsian and mean-field approximations are used; they allow for computing local conditional probabilities inside the lattice. The statistical procedures rely on the computation of pseudomaximum-likelihood estimators. The estimators are evaluated on the basis of Monte Carlo simulations. These simulations show that mean-field approximations are useful for reducing the variance of estimators when the data are recorded from arrays of 144 diodes (which are in accordance with standard practice). In light of these improved methods, we give new interpretations for a data set obtained from optical recording of a Guinea pig's auditory cortex in response to pure tone stimulations.

Giant prolactinomas in men: efficacy of cabergoline treatment.

OBJECTIVE: The term 'giant prolactinoma' can be used for tumours larger than 4 cm in diameter and/or with massive extrasellar extension. Cabergoline (CAB), a long-lasting dopamine agonist (DA), safe and well tolerated, is effective in normalizing PRL levels and inducing tumour shrinkage in micro- and macroprolactinomas. The purpose of this prospective study was to evaluate the efficacy and safety of CAB also for giant prolactinomas. PATIENTS AND METHODS: Ten men with giant prolactinomas with a median age of 44.8 years were treated with CAB. Before CAB, four patients had previously undergone transsphenoidal surgery without modifying the parasellar extension of the tumour or their visual defects. Pretreatment serum prolactin (PRL) levels ranged between 1230 and 22 916 micro g/l (mean +/- SEM: 5794 +/- 1996) and tumour volume was between 21.8 and 105.5 cm3 (mean +/- SEM: 50.7 +/- 8.8). CAB was administered at an initial low dose of 0.5 mg three times a week and, in five patients who did not achieve serum PRL normalization, the dose was progressively increased up to 10.5 mg/week. The duration of treatment was 13-68 months (mean 38.9). PRL levels and pituitary target organ hormones were assayed before, after 30 days and then every 3 months after the beginning of CAB treatment. Magnetic resonance imaging (MRI) was carried out before, after 1-3 months, after 6 months and then every 10-12 months to evaluate tumour shrinkage. RESULTS: In every patient, a significant PRL decrease (P = 0.0086) of at least 96% of the pretreatment values occurred (from 5794 +/- 1996 to 77 +/- 38, mean +/- SEM); a persistent normalization of PRL levels was achieved in five out of 10 patients (50%) beginning from the first 3-6 months of CAB treatment (only one patient needed 12 months of therapy). A significant tumour shrinkage (P = 0.0003) was achieved after 12 months of therapy in nine out of 10 patients (90%), with a volume reduction greater than 95% in three, of 50% in four and 25% in two patients. Tumour volume decreased from 50.7 +/- 8.8 to 28.6 +/- 9.4 and then to 22.3 +/- 8.8 cm3 (mean +/- SEM) after 6 and 12 months of CAB treatment, respectively. An improvement of visual field defects (VFD) was obtained in six of the seven patients presenting visual impairment before CAB treatment. Among the eight patients presenting libido and potency (L-P) failure, five normalized their PRL levels. In two of these a complete restoration of libido and potency was observed. Three patients with secondary hypoadrenalism and a patient with secondary hypothyroidism were treated with substitutive therapy during all the study time. The drug was well tolerated by all patients and no one discontinued the therapy. CONCLUSIONS: These data suggest that, in giant, aggressive prolactinomas, CAB represents a first-line therapy effective in reducing PRL levels and determining tumour shrinkage.