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Biomedical subjects

G Giordano

Publications and source records attributed to G Giordano.

At least 19 recordsLinked to original sources

Neurotoxicity of domoic Acid in cerebellar granule neurons in a genetic model of glutathione deficiency.

This study investigated the role of cellular antioxidant defense mechanisms in modulating the neurotoxicity of domoic acid (DomA), by using cerebellar granule neurons (CGNs) from mice lacking the modifier subunit of glutamate-cysteine ligase (Gclm). Glutamate-cysteine ligase (Glc) catalyzes the first and rate-limiting step in glutathione (GSH) biosynthesis. CGNs from Gclm (-/-) mice have very low levels of GSH and are 10-fold more sensitive to DomA-induced toxicity than CGNs from Gclm (+/+) mice. GSH ethyl ester decreased, whereas the Gcl inhibitor buthionine sulfoximine increased DomA toxicity. Antagonists of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors and of N-methyl-D-aspartate (NMDA) receptors blocked DomA toxicity, and NMDA receptors were activated by DomA-induced l-glutamate release. The differential susceptibility of CGNs to DomA toxicity was not due to a differential expression of ionotropic glutamate receptors, as evidenced by similar calcium responses and L-glutamate release in the two genotypes. A calcium chelator and several antioxidants antagonized DomA-induced toxicity. DomA caused a rapid decrease in cellular GSH, which preceded toxicity, and the decrease was primarily due to DomA-induced GSH efflux. DomA also caused an increase in oxidative stress as indicated by increases in reactive oxygen species and lipid peroxidation, which was subsequent to GSH efflux. Astrocytes from both genotypes were resistant to DomA toxicity and presented a diminished calcium response to DomA and a lack of DomA-induced L-glutamate release. Because polymorphisms in the GCLM gene in humans are associated with low GSH levels, such individuals, as well as others with genetic conditions or environmental exposures that lead to GSH deficiency, may be more susceptible to DomA-induced neurotoxicity.

Animals↗

Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: a new effect for an old drug?

BACKGROUND: Polymorphonuclear leukocytes (PMN) from healthy subjects can produce and store tissue factor (TF), which is expressed on PMN surface upon in vitro stimulation with P-selectin. RESULTS: We report here that platelets and PMN from 12 patients with myeloproliferative disorders (MPD) (six with polycythemia vera, six with essential thrombocythemia) show up regulation of P-selectin and TF, respectively, in the absence of any in vitro challenge. The number of circulating mixed platelet-PMN aggregates was also increased. PMN TF expression as well as mixed platelet-PMN aggregates, but not platelet P-selectin, were significantly reduced in six MPD patients after treatment with hydroxyurea (HU). In vitro studies performed on PMN separated from healthy donors confirmed HU effects (0-1400 microm). HU prevented both P-selectin-induced TF expression and mixed cell aggregate formation. The inhibitory effect of HU was specific for P-selectin-induced PMN activation, as it did not affect formyl-methionyl-leucyl-phenylalanine-induced PMN TF expression. CONCLUSIONS: In MPD patients, platelet P-selectin-mediated TF expression on circulating PMN may play a role in thrombus formation and represents a novel target for the antithrombotic activity of HU.

Aged↗

Hypopituitarism findings in patients with primary brain tumors 1 year after neurosurgical treatment: preliminary report.

Hypopituitarism represents the consequence of many conditions, in both the adult and child population. It may occur after neurosurgical treatment of brain tumors arising near sella turcica. Much more attention has been focused on lesions far from the hypothalamic-pituitary region as possible causes of pituitary impairment, validating the concept of the particular fragility of these structures. The aim of this study was to evaluate pituitary function in particular GH deficiency (GHD) in patients submitted to neurosurgery for benign tumors of the central nervous system (CNS) not involving hypothalamic-pituitary region. We observed 37 patients with benign brain tumors [13 males, 24 females, age: 54.6+/-13.9 yr; body mass index (BMI): 25.1+/-4.0 kg/m2] performing a basic evaluation of the pituitary function and a dynamic test of the GH/IGF-I axis [GHRH (1 microg/kg iv)+arginine (0.5 g/kg iv) test] for 3 and 12 months after the neurosurgical treatment. Some degree of hypopituitarism was shown in 16 patients (43.2%) at the 3-months follow-up. Hypogonadism was present in 4 patients, hypoadrenalism in another 4 and hypothyroidism in 2. Two patients showed mild hyperprolactinemia and no patients had diabetes insipidus. Seven patients (18.9%) were GH deficient (peak GH <16.5 microg/dl). At 12 months retesting, some degree of hypopituitarism was confirmed in 8 patients, hypogonadism in 2 and hypothyroidism in one; no patients showed hypoadrenalism and GHD was present in 5. This data suggests that hypopituitarism of various degree may develop in patients who are submitted to neurosurgery for primary brain tumors, even far from hypothalamic-pituitary region.

Adult↗

3-Nitrotyrosine, a marker of nitrosative stress, is increased in breath condensate of allergic asthmatic children.

BACKGROUND: Asthmatic patients have high exhaled nitric oxide (NO) levels. NO-mediated inflammatory actions are mainly due to NO conversion into reactive nitrogen species, which can lead to nitrotyrosine formation. The aim of this study was to assess 3-nitrotyrosine (3-NT) levels in exhaled breath condensate (EBC) of asthmatic and healthy children and to investigate whether there is any relationship with exhaled NO (FE(NO)) and lung function. METHODS: The study included 20 asthmatic children (10 steroid-naive with intermittent asthma, 10 steroid-treated with unstable persistent asthma) and 18 healthy controls. They underwent FE(NO) measurement, EBC collection and spirometry. 3-NT was measured by a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in isotopic dilution. RESULTS: The median EBC concentration of 3-NT (expressed as nitrotyrosine/tyrosine ratio x 100) in asthmatic children was fivefold higher than in healthy subjects [0.23% (0.12-0.32) vs 0.04% (0.02-0.06), P < 0.001] with no difference between steroid-naive and unstable steroid-treated asthmatic patients. FE(NO) levels were higher in asthmatic [44.6 ppb (36.0-66.0)] than in healthy children [7.5 ppb (6.0-8.8), P < 0.001]. No correlation was found among 3-NT, FE(NO) and lung function parameters. CONCLUSION: Nitrotyrosine is high in EBC of asthmatic children and could be considered as a noninvasive marker of nitrosative events in the airways.

Adolescent↗

Hypopituitarism induced by traumatic brain injury in the transition phase.

Traumatic brain injury (TBI) has been associated with hypopituitarism in general and GH deficiency (GHD) in particular; the consequences of this on growth and development are likely to be critical in children and adolescents in the so-called "transition phase". In order to verify the consequences of TBI on pituitary function in the transition phase, we studied a population of adolescents and young adults 3 and 12 months after brain injury [no. = 23, 9 females, 14 males; age: 16-25 yr; body mass index (BMI): 21.9 +/- 0.6 kg/m2]. At 3 months, hypopituitarism was present in 34.6%. Total, multiple and isolated deficits were present in 8.6, 4.3 and 21.7%, respectively. Diabetes insipidus (DI) was present in 8.6% patients and mild hyperprolactinemia in 4.3%. At 12 months, hypopituitarism was present in 30.3%. Total, multiple and isolated deficits were present in 8.6, 4.3 and 17.4%, respectively. DI was present in 4.3% of patients and mild hyperprolactinemia in 4.3%. Total hypopituitarism was always confirmed at retesting. Multiple and isolated hypopituitarism were confirmed in 0/1 and 2/5, respectively. Two/23 patients showed isolated hypopituitarism at 12 months only; 1 patient with isolated at 3 months showed multiple hypopituitarism at retesting. GHD and secondary hypogonadism were the most common acquired pituitary deficits. These results show the high risk of TBI-induced hypopituitarism also in the transition age. Thus it is recommended that pediatric endocrinologists follow-up pituitary function of children and adolescents after brain injuries.

Adolescent↗

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Journal Article↗

Primary cutaneous plasmacytoma: a role for a triggering stimulus?

Primary cutaneous plasmacytoma is a rare type of cutaneous B-cell lymphoma, characterized by clonal proliferation of plasma cells, that primarily develops in the skin. Five cases have been described to date in which a local triggering stimulus may be involved in development of this skin tumour. We describe the case of a primary cutaneous plasmacytoma localized to the lower lip. This site had been affected for 15 years with recurrent herpes simplex virus-1 infection. Neoplastic plasma cells were found to be bcl-2-positive. We hypothesize that chronic stimulation of keratinocytes by herpes simplex virus-1, possibly through toll-like receptors, may have favoured the release of cytokines (e.g. interleukin-6) able to induce plasma cell proliferation, transformation and survival.

Aged↗

Surgical removal of a left lower third molar root after iatrogenic displacement in soft tissue. Case report.

Displacement of a tooth or a portion of it is an unusual but very serious event for the severe consequences it could have. Already Hill and Howe in the half of the past century understood and described the risks associated to this accident particularly frequent during impacted third lower molars avulsion. Displacements can be idiopathic or iatrogenic and the sites of displacements depend on the anatomy of the tooth and the surrounding region. After a complete review of the literature, the authors describe the surgical removal of a left lower third molar root displaced in the soft tissue after a first extraction of the entire tooth. The necessary precautions to limit the frequency of this accident are then discussed.

Adult↗

Long-term characterization, lagoon treatment and migration potential of landfill leachate: a case study in an active Italian landfill.

The elaboration of 10 years of monitoring of leachate quality and quantity, leachate treatment and degree of contamination of soil and surface waters at the Tre Monti site--an active, 4-million-m(3) landfill in Northern Italy--is presented in this study. A hydrological model of leachate production is applied, with a good match of the experimental data. The concentrations of all leachate components except sulfate are characterized by fluctuations over a constant or increasing value. Different ways of interpreting leachate quality data are discussed; the elaboration indicates that the pollutant load on the leachate treatment facility will remain basically constant as long as waste will be added to the landfill. The analysis of the data relative to 10 years of leachate pre-treatment in the adjoining, non-aerated lagoon system indicates that a significant removal is achieved for most leachate components; the operational conditions of the plant are described, and the removal mechanisms are discussed. Finally, the potential for contamination of soil and surface waters is examined by analyzing long-term quality trends of the sub-superficial waters sampled near the lagoons and by means of an analytical campaign conducted on clay cores sampled near and underneath the treatment ponds. The experimental values indicate that the clay layer located under the entire site offers an effective barrier to the migration of leachate contaminants.

Environmental Monitoring↗

Hypopituitarism and growth hormone deficiency (GHD) after traumatic brain injury (TBI).

In adults, hypopituitarism and growth hormone deficiency (GHD) should be suspected and diagnosed within an appropriate clinical context. It has been demonstrated that all patients with primary hypothalamic-pituitary diseases before and after any medical intervention (defined as neurosurgery, radiotherapy and medical therapy) are at obvious risk - more than just at high risk - for hypopituitarism (greater than 80% had severe GHD). The same obvious risk applies to patients diagnosed as having congenital or acquired GHD in childhood (between 30% and 50% of patients with severe GHD after retesting). Taking into account the fragility of the infundibular-hypothalamic structure, patients with other common pathological conditions of the central nervous system (CNS), such as traumatic brain injury (TBI), subarachnoid haemorrhage (SAH) or primary brain tumours (BT) with related medical intervention could be at risk for developing hypopituitarism, including GHD. GHD is the first and most common sign of pituitary impairment. Despite the risk of pituitary dysfunction and the results of some studies that these risks are greater than previously believed, neuroendocrine evaluations are still not routinely included as part of the clinical management plan for patients with TBI and SAH. Preliminary results of a multicenter study performed under the auspices of the Italian Society of Endocrinology underscore the high risk of hypopituitarism and GHD under these clinical conditions. Thus, careful screening of pituitary function should always be performed in patients following TBI and SAH.

Brain Injuries↗

Causes of sudden infant death syndrome from post-mortem examination.

Sudden infant death syndrome (SIDS) was first defined in the USA as: 'The sudden death of an infant under one year of age which remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history'. More recently, diverse studies have shown that some cases of SIDS can be explained, when an accurate post-mortem examination is performed. The primary objective of the present paper was to delineate possible causes of SIDS as derived from a review of autoptic studies reported in the literature.

Autopsy↗

A rare case of multiple congenital epulis.

We report a case in a female newborn infant of multiple congenital epulis, i.e. granular cell tumor, that was undetected during regular pregnancy ultrasound monitoring. At birth the neoplasms appeared as two voluminous lesions protruding from the newborn's mouth. The greater of them (5.5 cm x4 cm x3 cm) was pedunculated and attached to the external superior gingiva, shifting the alae nasi and making it difficult to enter the coanae. The second mass was somewhat smaller (3 cm x4 cm x2.5 cm), pedunculated and attached to the external inferior gum. A third smaller mass was less evident, unpedunculated and attached to the rim of the lower gingiva. Histologically the lesions were characterized by large cells, which had abundant pale acidophilic granular cytoplasm. A round-oval nucleus was located centrally. The cell membranes were distinct. Neither mitosis nor necrosis was found. Staining for cytoplasmic granules was intensely periodic acid-Schiff (PAS) positive and diastase resistant. Immunohistochemical negativity for S100 protein, positivity for lysozyme and numerous phagolysosomes in the cytoplasm of neoplastic elements, observed on ultrastructural examination, supported the hypothesis that the congenital type of granular cell tumor cannot have a Schwannian origin like that of the adult type, but is probably a mesenchymal lesion which, for unknown cause, regresses by a degenerative process.

Diagnosis, Differential↗

Coracoclavicular joints. Reflections upon incidence, pathophysiology and etiology of the different forms.

Since the first description of the coracoclavicular joint in 1861, many papers have been published reporting its occurrence, anatomical description, and geographical distribution. However, there are as yet no published articles with a convincing explanation for the rather variable forms of this variant. In this study, we investigated the occurrence of the coracoclavicular joint in the current and medieval population of Toulouse city and propose, through biometric measures, an explanation for the different forms of this anatomical variant. A total of 2192 chest X-rays taken for various conditions at a receiving hospital and 392 specimens (784 scapulae and an equal number of clavicles) of the L'Isle-Jourdain Series were examined with this aim. When present in the osteologic collection, the sizes of the articular conoid process as well as the height of the corresponding coracoid and acromial processes were noted. A coracoclavicular joint was noted in 0.82% and in 1.78% of the individuals examined in the radiological and osteologic series, respectively. The conoid process varied in size and correlated with the disposition of each correspondent coracoacromial arch. Osteoarthritis was noted in some of these joints when there was discordance between the conoid process size and the architecture of the correspondent coracoacromial arch, suggesting impingement. Our findings support a genetic origin for this variant, and suggest that its occurrence is also probably influenced by environmental factors. Osteoarthritis of this joint may be responsible for shoulder pain.

Acromioclavicular Joint↗

Increasing the bandwidth of resonant gravitational antennas: the case of explorer.

Resonant gravitational wave detectors with an observation bandwidth of tens of hertz are a reality: the antenna Explorer, operated at CERN by the ROG Collaboration, has been upgraded with a new readout. In this new configuration, it exhibits an unprecedented useful bandwidth: in over 55 Hz about its center operating frequency of 919 Hz the spectral sensitivity is better than 10(-20) Hz(-1/2). We describe the detector and its sensitivity and discuss the foreseeable upgrades to even larger bandwidths.

Journal Article↗

[Effect of alendronate on periprosthetic bone loss after cemented primary total hip arthroplasty: a prospective randomized study].

PURPOSE OF THE STUDY: Bone remodeling and osteolysis around total hip prostheses, with its inevitable corollary, prosthesis loosening, remains a difficult problem in orthopedic surgery. Alendronate (bisphosphonate) has proven its efficacy for the treatment of osteoporosis of the lumbar spine and femoral neck. A few in vitro studies have pointed out its inhibiting effect on particle-induced osteolysis. In vivo, one study has demonstrated its usefulness in preventing osteolysis around non-cemented total hip arthroplasties (THA). The purpose of this work was to study the efficacy of this agent for the prevention of changes in peri-prosthetic bone mineral density (BMD) after primary THA. MATERIAL AND METHODS: The study series included 38 patients with degenerative hip disease who underwent THA. The patients were randomized in double-blind fashion to two treatment arms: 10 alendronate and 600 mg calcium per day for 2 years (20 patients) or placebo and 600 mg calcium per day for 2 years (18 patients). Conventional x-rays and x-ray biphotonic absorptiometry (DPX) was performed on day four postop and at 3, 6, 12, and 24 months postop. The periprosthetic zones described by Grüen were used for analysis. RESULTS: DPX demonstrated a significant reduction in BMD in all patients included in the study. The bone loss was the same in both groups during the early postoperative period reaching maximum loss at 3 months. Differences were observed after this time. In the placebo group, bone loss reached a plateau at 6 months then BMD started to increase progressively, reaching 12.7% bone loss at 2 years follow-up (p<0.002). In the alendronate group, there was no plateau, BMD increased continuously starting from three months and reached 6.857% bone loss at 2 years (p<0.003). DISCUSSION: Administration of alendronate led to a significant reduction in peri-prosthetic bone loss at 2 years follow-up. These results are the first to our knowledge demonstrating the beneficial effect in vivo of alendronate on bone behavior around cemented THAs. CONCLUSION: This beneficial effect observed in vivo should be confirmed in further studies including a larger number of patients and longer follow-up. The action of alendronate could facilitate and even retard revision surgery by preserving bone stock.

Alendronate↗

Rare compound odontoma of the mandible in a 7-year-old child: case report.

BACKGROUND: A compound odontoma is a mixed tumor of odontogenic origin, in which both ectodermal and mesenchymal cells exhibit complete differentiation, resulting in the formation of tooth structures. It occurs with equal frequency in both sexes, and is often initially asymptomatic. CASE REPORT: A 7-year-old boy was recently examined in our Department for management of a compound odontoma. Surgical treatment was invasive because of the size of the lesion, but it was possible to use interceptive orthodontic treatment to restore the dental arch.

Child↗

Corticotrophin-releasing hormone inhibits insulin-like growth factor-I release from primary cultures of rat granulosa cells.

Corticotrophin-releasing hormone (CRH), a neuropeptide which modulates gonadal function during stress, is expressed by several cell types of the rat ovary and is able to suppress oestrogen release from rat granulosa cells. The mechanism of this effect is, however, not known. Since insulin-like growth factor (IGF)-I is produced by rat granulosa cells and exerts a synergistic role with FSH on granulosa cell steroidogenesis, we hypothesised that CRH may suppress oestrogen release from granulosa cells by inhibiting IGF-I release and/or stimulating the release of its binding protein (IGFBP-3). To test this hypothesis, granulosa cells were obtained from immature female Sprague-Dawley rats primed with diethylstilboestrol, and hormone concentrations were measured in the conditioned medium by radioimmunoassay. CRH suppressed oestrogen and IGF-I release stimulated by FSH used at a concentration of 1 IU/l, whereas it did not have any statistically significant effect on oestrogen and IGF-I release in basal conditions or in response to 5 IU/l FSH. The suppressive effects of CRH on oestrogen and IGF-I release were antagonised by a selective CRH receptor antagonist. CRH had no effects on IGFBP-3 release. CRH did not have any effect on oestrogen release stimulated by increasing concentrations of IGF-I and its suppressive effect on FSH-stimulated oestrogen release was overcome by the addition of low doses of exogenous IGF-I. In conclusion, CRH suppressed the release of oestrogen and IGF-I, but not of IGFBP-3. Thus, the inhibitory effects of CRH on oestrogen release could be mediated, partly, by a suppression of the autocrine/paracrine action of IGF-I.

Animals↗

Eversion versus conventional carotid endarterectomy for preventing stroke.

BACKGROUND: Carotid endarterectomy is conventionally undertaken by a longitudinal arteriotomy. Eversion carotid endarterectomy (CEA), which employs a transverse arteriotomy and reimplantation of the carotid artery, is reported to be associated with low perioperative stroke and restenosis rates but an increased risk of complications associated with a distal intimal flap. OBJECTIVES: The objective of this review was to determine whether eversion CEA was safe and more effective than conventional CEA. The null-hypothesis was that there was no difference between the eversion and the conventional CEA techniques (performed either with primary closure or patch angioplasty). SEARCH STRATEGY: The reviewers searched MEDLINE and the Cochrane Stroke Group Trials Register (last searched: December 1999), and hand searched eight surgical journals and conference proceedings. Researchers were contacted to identify additional published and unpublished studies. SELECTION CRITERIA: All randomised trials comparing eversion to conventional techniques in patients undergoing carotid endarterectomy were examined in this review. Outcomes were stroke and death, carotid restenosis/occlusion and local complications. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers to assess eligibility and describe trial characteristics, and by one reviewer for the meta-analyses. Discrepancies were resolved by discussion. When possible, unpublished data were obtained from investigators. MAIN RESULTS: Five trials were included for a total of 2465 patients and 2590 arteries. Three trials included bilateral carotid endarterectomies. In one trial, arteries rather than patients were randomised so that it was not clear how many patients had been randomised in each group, therefore, information on the risk of stroke and death from this study were considered in a separate analysis. There were no significant differences in the rate of perioperative stroke and/or death (1.7% vs 2.6%, odds ratio [OR] 0.44, 95% confidence interval [CI] 0.10-1.82) and stroke during follow-up (1.4% vs 1.7%, OR: 0.84, 95% CI: 0.43-1.64) between eversion and conventional CEA techniques. Eversion CEA was associated with a significantly lower rate of restenosis >50% during follow-up (2.5% vs 5.2%, OR: 0.48, 95% CI: 0.32 -0.72). However, there was no evidence that the eversion technique for CEA was associated with a lower rate of neurological events when compared to conventional CEA. There were no statistically significant differences in local complications between the eversion and conventional group. No data were available to define the cost-benefit of eversion CEA technique. REVIEWER'S CONCLUSIONS: Eversion CEA may be associated with low risk of arterial occlusion and restenosis. However, numbers are too small to definitively assess benefits or harms. Reduced restenosis rates did not appear to be associated with clinical benefit in terms of reduced stroke risk, either perioperatively or later. Until further evidence is available, the choice of the CEA technique should depend on the experience and familiarity of the individual surgeon.

Confidence Intervals↗