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Biomedical subjects

P Esposito

Publications and source records attributed to P Esposito.

At least 19 recordsLinked to original sources
PubMed2006

[Subthalamic stimulation in a patient with multiple system atrophy: a clinicopathological report].

INTRODUCTION: Efficacy of high frequency subthalamic nucleus (STN) stimulation has been demonstrated in idiopathic Parkinson's disease (IPD). However, since it may be difficult to differentiate IPD from multiple system atrophy with parkinsonian presentation (MSA-P), a few cases of MSA-P has been treated by deep brain stimulation (DBS) and showed no sustained improvement of clinical signs. We report a patient with a clinical misdiagnosed MSA-P, later confirmed by neuropathological study, who was improved by DBS for one year. CASE REPORT: A 63-year-old parkinsonian patient had been treated by levodopa for 6 years with a persistent good response. Over one year he progressively developed disabling fluctuations with severe axial syndrome and vegetative non motor symptoms in off periods. After checking usual contraindications, he was included in surgical procedure protocol (bilateral STN stimulation). During the first year after surgery, the clinical status improved with disappearance of non motor fluctuations, a 45 percent decrease of the OFF UPDRS III score, and a 39 percent reduction of the treatment. However after one year, axial symptoms reappeared with recurrent falls, as well as increasing dysarthry and swallowing difficulties which were only slightly improved by levodopa. He developed severe urinary disorders increased by a prostatic adenoma which led to surgical treatment. During the post operative period, 2 years after DBS, he died suddenly from an unexplained cause. A cerebral autopsy was performed and showed a good position of the two electrodes in the STN. Microscopic studies revealed severe neuronal depletion in the substantia nigra but no Lewy bodies. Immunohistochemical methods demonstrated numerous argyrophilic glial cytoplasmic inclusions positive for alpha-synuclein and ubiquitin in the STN, putamen, globus pallidus, pontine nuclei and cerebellar white matter, significant of MSA. CONCLUSION: This case shows that DBS can improve parkinsonian signs in MSA-P with persistent dopa sensitivity. However, probably because of striatal degeneration progression, this improvement is time limited and STN DBS cannot be recommended in MSA.

Adenoma↗
PubMed2005

[Systemic Candida albicans infection with neuromeningeal complication in a premature infant].

INTRODUCTION: Systemic maternal-fetal Candida albicans infections are uncommon diseases with a poor outcome. An associated cerebromeningeal infection increases morbidity. We present a case of neuromeningeal candidiasis following systemic neonatal infection in a premature infant. Management and therapeutic difficulties are outlined. OBSERVATION: The patient was a male infant born preterm at 30 weeks gestation. During his first week of life, he developed a systemic infection with an associated symptomatic hydrocephalus. Systemic candidaisis with neuromeningeal complication was diagnosed five weeks later. Despite treatment including cerebrospinal fluid (CSF) shunting and antimycotic medications (flucytosin and amphotericin B), the candidal infection did not resolve. Infectious and mechanical complications of the CSF drainage were treated by several surgical interventions during the following months. At 10 months of life, there was clinical and laboratory evidence of active persistent neuromeningeal candidaisis. Finally, candidal infection was eradicated with intravenous administration of fluconazole. After five year follow-up, the intellectual and psychological status of the patient was quite satisfactory, and no neurological deficits were found on clinical examination. DISCUSSION: Management of neuromeningeal candidaisis in premature infants is a challenging task particularly because of delayed diagnosis. Candida infection should routinely be suspected in cases of systemic infection with neurological impairment in premature infants. Fluconazole may constitute an efficient therapeutic option.

Amphotericin B↗
PubMed2005

Copper-zinc superoxide dismutase activity in healthy and inflamed human dental pulp.

AIM: To examine copper-zinc superoxide dismutase (Cu, Zn-SOD) activity in clinically healthy and symptomatic human dental pulps. METHODOLOGY: Twenty-five systemically healthy patients, 14 females and 11 males (age: 13.1-34.6 years; mean: 21.7 +/- 6.3), were the source of the pulp tissue. The condition of the pulps was assessed using clinical and radiographic evaluation. The pulp tissue was collected by longitudinally grooving and splitting the teeth (if extracted) or during endodontic treatment, and were age- and sex-matched between the healthy and the irreversible symptomatic pulpitis tissue groups. Cu, Zn-SOD activity was determined through spectrophotometric methods and a Mann-Whitney test assessed the significance of differences between the groups. RESULTS: The enzyme activities were 144.8 +/- 42.2 and 68.1 +/- 25.0 U mg(-1) in the healthy and irreversible symptomatic pulp tissue, respectively. The difference between the groups was statistically significant (P < 0.001). CONCLUSIONS: These results demonstrate a potential role for Cu, Zn-SOD during dental pulp inflammation in humans.

Adolescent↗
PubMed2005

Staphylococcus aureus septicemia in non-neutropenic adult patients hospitalized in internal medicine units.

PURPOSE: Staphylococcus aureus septicemia (SAS) is usually described in immunocompromised patients and during serious weakening diseases, associated with a neutropenic condition. Over the last recent years, clinic relevance of SAS has become more prominent owing to the progressive rise of methicillin-resistent strains in hospital-acquired infections and to its development in non-neutropenic patients. MATERIAL AND METHODS: The aim of our study was to evaluate the clinical features and outcome of non-neutropenic patients with positive blood culture for Staphylococcus aureus (SA) hospitalized in Internal Medicine Wards of our hospital during 1 year of observation. 24 patients with those characteristics were retrospectively recruited; five of them were then excluded from the analysis because of concomitant oncohematologic disease. The median age of the study group of patients (19 cases) was 56 years (range 18-87); 10 (52.6%) patients were male. RESULTS: Infection was hospital-acquired in 10 patients (52.6%). Predisposing factors were: central venous catheter (CVC) (47.4%), recent surgical intervention (21.0%), drug-addiction (15.8%). Main comorbidities were diabetes mellitus in 10 patients (52.6%), heart disease in 4 (21.0%), chronic renal failure in 3 (15.8%), cerebral vascular disease in 3 (15.8%). Fever >38 degrees C was found in all patients at the moment of SA isolation in blood culture. SA isolated-strains were methicillin-resistant in 7 patients (36.8%). Complications of bacteremia were: pneumonia in 4, endocarditis in 3, vertebral osteomyelytis in 2, septic splenic embolization in 1 and endophtalmitis in 1 patient. The septicemia-attributable mortality was 36.8% (7 patients). CONCLUSIONS: SAS in non-neutropenic patients observed in Internal Medicine Units are associated with significant morbidity and mortality, closer to that reported for neutropenic illnesses.

Adolescent↗
PubMed2004

Pharmacodynamic evaluation of a PEGylated analogue of human growth hormone releasing factor in rats and pigs.

The aim of this study was to assess the in vivo efficacy of monoPEGylated GRF(1-29)NH(2) having one PEG(5000) chains attached to either lysine 12 or 21 as compared to the GRF(1-29)NH(2) in rats and pigs. This analogue termed GRF-1PEG(5000) was tested after a single intravenous administration in rats and after a single intravenous or subcutaneous injection in pigs. After 1 h administration, GH concentrations returned to values close to controls in the group of rats injected with GRF(1-29)NH(2). In animals injected with the same dose of GRF-1PEG(5000), the AUC values corresponding to the whole period 0.5-48 h and particularly to the 0.5-8 h period were higher than in the placebo or in the GRF(1-29)NH(2) groups. Interestingly, two additional peaks were observed at about 6 and 8 h following administration. An increase in the response of the endogenous GH peaks was also observed in pigs administered GRF-1PEG(5000) by intravenous route. When GRF-1PEG(5000) was administered subcutaneously to pigs, a significant increase, as compared to placebo and GRF(1-29)NH(2,) in both GH and IGF-I levels was observed. This new analogue might find therapeutic application in paediatric growth hormone deficiency or in aging.

Animals↗
PubMed2004

Primary non-Hodgkin's lymphoma of the mandible. Report of a case.

A case of a 45-year-old white man admitted for an osteomyelitis and subsequently diagnosed affected by an IE stage, diffuse high grade large B cell non-Hodgkin's lymphoma of the mandible is reported. The patient presented a swelling in the right mandibular region with paraesthesia of the ipsilateral lower lip without nodal involvement of the neck. After an incisional biopsy, which showed a diffuse high grade large B-cell non-Hodgkin's lymphoma, the patient was staged and treated with CEOP protocol for six courses and subsequently external beam radiation therapy with complete remission of the lesion.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

PEGylation of growth hormone-releasing hormone (GRF) analogues.

Synthetically produced GRF1-29 (Sermorelin) has an amino acid composition identical to the N-terminal 29 amino acids sequence of the natural hypothalamic GHRH1-44 (Figure 1). It maintains bioactivity in vitro and is almost equally effective in eliciting secretion of endogenous growth hormone in vivo. The main drawbacks associated with the pharmaceutical use of hGRF1-29 relate to its short half-life in plasma, about 10-20 min in humans, which is caused mostly by renal ultrafiltration and enzymatic degradation at the N terminus. PEGylation has been considered as one valid approach to obtain more stable forms of the peptide, with a longer in vivo half-life and ultimately with increased pharmacodynamic response along the somatotropic axis (endogenous GH, IGF-1 levels). Different PEGylated GRF conjugates were obtained and their bioactivity was tested in vitro and in vivo by monitoring endogenous growth hormone (GH) serum levels after intravenous (i.v.) injection in rats, and intravenous and subcutaneous (s.c.) injection in pigs. It was found that GRF-PEG conjugates are able to bind and activate the human GRF receptor, although with different potency. The effect of PEG molecular weight, number of PEG chains bound and position of PEGylation site on GRF activity were investigated. Mono-PEGylated isomers with a PEG5000 polymer chain linked to Lys 12 or Lys 21 residues, showed high biological activity in vitro, which is similar to that of hGRF1-29, and a higher pharmacodynamic response as compared to unmodified GRF molecule.

Animals↗
PubMed2003

Lipid microparticles as sustained release system for a GnRH antagonist (Antide).

Lipid microparticles (LMs) as a sustained release system for a gonadotropin release hormone (GnRH) antagonist (Antide) were prepared and evaluated. Antide loaded microparticles (Antide-LMs) were obtained by a cryogenic micronization process starting from two different monoglycerides (glyceryl monobehenate and glyceryl monostearate) and using two different incorporation methods (co-melting and solvent evaporation). Antide-LMs, 2% (w/w) loading, were characterized for drug incorporation by RP-HPLC, particle size by laser diffractometry and surface morphology by scanning electron microscopy. In vitro peptide release and in vitro biological activity were also studied. Serum Antide and testosterone levels, as pharmacodynamic marker, were assessed following subcutaneous administration in rats. Antide-LMs showed a mean diameter of approximately 30 micro m and variable Antide release depending on lipid matrix and incorporation method. In vivo experiments demonstrated that detectable Antide plasma levels were present, in the case of Antide-LMs based on Compritol E ATO obtained by co-melting procedure, for at least 30 days after dosing. Testosterone levels were consistent with prolonged pharmacokinetic profiles. In vitro release of Antide from LMs correlated well with the in vivo release. In conclusion, LMs can sustain the release of Antide for at least 1 month. The levels of the initial 'burst' and the extent of the pharmacodynamic effect can be influenced by the lipid characteristics and by process conditions.

Animals↗
PubMed2003

Enalapril-induced acute recurrent pancreatitis.

Enalapril, an angiotensin-converting enzyme inhibitor, has several adverse effects, but acute pancreatitis is uncommon. The case of a patient with enalapril-induced pancreatitis is described. Development of severe, necrotizing pancreatitis after inadvertent rechallenge confirmed the causal relationship between enalapril and acute pancreatitis.

Acute Disease↗
PubMed2003

Catalase activity in human healthy and inflamed dental pulps.

AIM: To examine the catalase activity in clinically healthy and symptomatic human dental pulps to verify if an active defence system against oxidizing agents is present as a response to bacterial invasion. METHODOLOGY: Thirty-three systemically healthy patients, 18 females and 15 males (ages: 11.0-25.9 years; mean 18.8 +/- 3.6), were the source of the pulp tissue. The condition of the pulps was assessed using clinical and radiographic evaluations. The specimens were recovered by longitudinally grooving and splitting the teeth (if extracted) or during endodontic treatment, and were matched for age and sex between the healthy and inflamed specimen groups. Catalase activity was determined through spectrophotometric methods. RESULTS: Enzymatic activity was 1126 +/- 343 and 3074 +/- 698 mU mL(-1) x mg of total protein in the healthy and inflamed pulp tissue specimens, respectively. This difference was statistically significant (P<0.01). CONCLUSIONS: These results indicate a role for catalase during dental pulp inflammation in humans, and may represent an inherent biological defence system against reactive oxidants of this tissue.

Adolescent↗
PubMed2002

Set-up of large laboratory-scale chromatographic separations of poly(ethylene glycol) derivatives of the growth hormone-releasing factor 1-29 analogue.

In this paper we report the scale-up of the purification of poly(ethylene glycol) (PEG) derivatives of the growth hormone-releasing factor 1-29, from laboratory scale (100 mg of bulk starting material) to larger scale (3 g of bulk), through the use of a cation-exchange TSK-SP-5PW chromatographic column. A one-step purification process capable of purifying large amounts of mono-PEGylated GRF species from the crude reaction mixture was developed. A simple, straightforward stepwise gradient elution separation was developed at laboratory scale and then scaled up with a larger column packed with a chromatographic resin with the same chemistry which maintained the laboratory-scale separation profile. Active material recovery and material purity remained constant through the scale-up from the 13-microm stationary phase to the 25-microm larger column. Overall, the gram GRF equivalent/batch process scale showed to be quite reproducible, and could be considered as a good platform for scale up to production scale.

Cation Exchange Resins↗
PubMed2002

[Intracerebral radiation-induced cavernous angiomas].

We present four cases of cerebral cavernous angioma that developed after radiatherapy for brain tumor in three cases and for cavernous angioma in one case. The time interval between irradiation and the detection of the cavernous angioma varied from three to nine years and the doses from 24 to 60 Grays. Brain hemorrhage appeared in two cases. Explanation for the formation of cavernous malformations is unclear but is probably related to proliferation and dilatation of the vascular endothelium with formation of capillary telangiectasis with evolution to cavernous angiomas. The pediatric brain appears particularly vulnerable to radiation injury. The risk of hemorrhage appears higher than with spontaneous cavernous malformations.

Adolescent↗
PubMed2001

Acute stress increases permeability of the blood-brain-barrier through activation of brain mast cells.

Disruption of the blood-brain-barrier (BBB) is important in the pathophysiology of various inflammatory conditions of the central nervous system (CNS), such as multiple sclerosis (MS), in which breakdown of the BBB precedes any clinical or pathological findings. There is some evidence that relapsing-remitting MS attacks may be correlated with certain types of acute stressful episodes. Stress typically activates the hypothalamic-pituitary-adrenal (HPA) axis through the release of corticotropin releasing hormone (CRH), leading to production of glucocorticoids that down regulate immune responses. However, acute stress also has pro-inflammatory effects that appear to be mediated through activation of mast cells. Here we show that acute stress by immobilization increased permeability of rat BBB to intravenous 99Technetium gluceptate (99Tc). This effect was statistically significant in the diencephalon and the cerebellum, while it was absent in the cerebral cortex where there are not mast cells. Immobilization stress also induced activation of mast cells in diencephalon, the site where most mast cells are found in the rat brain. Both BBB permeability and mast cell activation were inhibited by the 'mast cell stabilizer' disodium cromoglycate (cromolyn). These results expand the pathophysiology of mast cells and implicate them in CNS disorders, that may possibly be induced or exacerbated by stress.

Acute Disease↗
PubMed2001

Non-invasive assessment of blood-brain barrier (BBB) permeability using a gamma camera to detect 99technetium-gluceptate extravasation in rat brain.

The blood-brain barrier (BBB) is a complex structure of endothelial cells, astroglia, pericytes, and perivascular macrophages enclosed by basal lamina. The BBB regulates the entry of blood-borne molecules and cells into the brain, but it is disrupted in various inflammatory conditions of the central nervous system (CNS). We previously showed that 30 min of immobilization stress increased 99technetium-gluceptate (99Tc) extravasation, measured by a gamma counter, in brain regions containing mast cells, an effect blocked by the mast cell stabilizer disodium cromoglycate [Brain Res. 888 (2001) 117]. Here we report the use of a gamma camera to assess BBB permeability by assessing 99Tc extravasation in the rat brain, during and following acute stress, without having to sacrifice the experimental animals. This method also allows for repeated experimentation on the same animal, since the half-life of 99Tc is only 6 h, and permits testing of potential inhibitors of BBB permeability.

Animals↗
PubMed2001

Peptic ulcer occurrence in follow-up of chronic gastritis in patients with treated and not eradicated CagA-positive Helicobacter pylori infection.

The aim of the present prospective investigation was to study 49 dyspeptic Helicobacter pylori (HP)-positive (HP+) or -negative (HP), CagA+ and CagA- patients with a normal pattern or pure chronic gastritis at initial histology as well as normal features or hyperemic gastropathy at initial endoscopy in a two-year follow up. All the HP+ patients were treated with omeprazole 20 mg twice a day plus amoxicillin 1 g twice a day for two weeks. No substantial change was seen in gastritis in CagA+ patients in whom the infection was not eradicated, and, in contrast, a progressive improvement in 13/14 successfully treated patients was found. At endoscopy, a progressive change to a normal picture was seen in 8 and no change in 6 of 14 patients whose HP infection was eradicated, in contrast a worsening in the 9 HP+ patients who were still infected was observed. In particular, peptic lesions arose in 6 of 21 CagA+ patients in whom the infection was not eradicated. In conclusions, the lack of change in chronic gastritis at histology and the progressive worsening of endoscopic hyperemic gastropathy (with peptic lesions arising in 28,6%) when HP+ CagA+ infection is not eradicated, unlike the progressive improvement of the anatomoclinical condition in the patients whose infection was eradicated, draws attention to the relevance of eradicating HP in CagA+ patients even when no peptic lesion is found at initial endoscopy.

Adult↗
PubMed2000

[Aspects of FLAIR sequences, 3D-CISS and diffusion-weight MR imaging of intracranial epidermoid cysts].

We propose to assess the usefulness of diffusion-weighted MR Imaging (DWI), fluid-attenuated inversion recovery (FLAIR) and constructive interference in steady state (CISS) sequences in depicting epidermoid cysts (EC). FLAIR, CISS and DWI were obtained in 7 patients among 22. All patients were studied with T1 and T2 sequences. On Spin Echo images, EC demonstrate signal similar to LCS, which may lead to difficult differentiation between EC and arachnoid cyst (AC), specially for inexperienced radiologists. EC appear with a heterogeneous signal on T1 images (32%), irregular limits (91%) and with extension through foramen of Pacchioni in 18% of cases. On FLAIR sequence, the tumors were heterogeneous, different from void signal of CSF in 86% of cases. On CISS sequence, the tumors appear heterogeneous, hyperintense but less than LCS and with irregular limits in all cases. Some more, CISS images allowed to appreciate exact tumor extension and their relations with nerves and vessels. On DWI images, signal is hyperintense in all cases. Our study exhibited the great usefulness of DWI, CISS and FLAIR sequences in diagnosis of EC and in differentiating EC from AC.

Brain Diseases↗