Biomedical subjects

F Passarelli

Publications and source records attributed to F Passarelli.

At least 19 recordsLinked to original sources

PubMed2006

Sentinel lymph node biopsy for high risk cutaneous squamous cell carcinoma: case series and review of the literature.

AIMS: Cutaneous squamous cell carcinoma (SCC) is the second most common skin cancer. The metastatic potential is generally low. However, there are subgroups of patients at higher risk, for whom sentinel lymph node biopsy (SLNB) might be useful. SLNB might allow the timely inclusion of high risk patients in more aggressive treatment protocols, sparing at the same time node-negative patients the morbidity of potentially unnecessary therapy. Our aim was to introduce the concept of SLNB for patients with high risk cutaneous SCC. PATIENTS AND METHODS: We examined a consecutive series of high risk cutaneous SCC patients undergoing SLNB at our large dermatological hospital, and performed a literature review and pooled analysis of all published cases of SLNB for cutaneous SCC. RESULTS: Among the 22 clinically node-negative patients undergoing SLNB at our hospital, one patient (4.5%) showed a histologically positive sentinel node and developed recurrences during follow-up. Sentinel node-negative patients showed no metastases at a median follow-up of 17 months (range: 6-64). The incidence of positive sentinel nodes in previous reports ranged between 12.5% and 44.4%. Pooling together patients from the present and previous studies (total 83 patients), we calculated an Odds Ratio of 2.76 (95% CI 1.2-6.5; p=0.02) of finding positive sentinel nodes for an increase in tumor size from <2 cm to 2.1-3 cm to >3 cm. CONCLUSIONS: Our case series and the pooled analysis support the concept that SLNB can be performed for high risk cutaneous SCC. Prospective multicenter studies are needed to examine the role, utility and cost-effectiveness of SLNB for this population.

Adult↗

PubMed2006

Dacryocystostenting: technical and long-term results.

PURPOSE: We describe our experience in treating epiphora caused by chronic inflammation and obstruction of the nasolacrimal system by endonasal placement of a polyurethane stent in the nasolacrimal duct, with long-term assessment of patency (4 years). MATERIAL AND METHODS: Between July 1998 and May 2001, 57 stents were inserted using Song's technique. All procedures were carried out in the radiology suite following mild sedation and local anaesthesia of the conjunctival and nasal mucosa. The follow-up investigation concerns 23 stents assessed 24-48 months after placement. RESULTS: At follow-up after 4 years, 20 stents (86.9%) were obstructed. Fifteen of the stents removed underwent histological analysis that showed occlusion of the stent with granulation tissue (eight cases), necrotic material (four cases) and fibrosis (three cases). CONCLUSIONS: Although encouraging in terms of safety, simplicity and reproducibility, the results obtained with the polyurethane stent demonstrate poor long-term efficacy and stimulate the search for new strategies such as programmed stent removal or the development of a more biocompatible material.

Adolescent↗

PubMed2003

An increased expression of the mGlu5 receptor protein following LTP induction at the perforant path-dentate gyrus synapse in freely moving rats.

The involvement of metabotropic glutamate (mGlu) receptors in the induction of long-term potentiation (LTP) in vivo has been consistently documented. We have investigated whether LTP induction in the dentate gyrus of rats leads to changes in expression of mGlu2/3 or -5 receptor subtypes in the hippocampus. LTP was induced at the medial perforant path-dentate gyrus synapses, and mGlu receptor expression was examined by Western blot or in situ hybridization. An up-regulation of mGlu5 receptors was observed in the hippocampus both 24 and 48 h following LTP induction. This effect was restricted to the dentate gyrus and CA1 region, whereas no changes in mGlu5 receptor protein (but an increase in mRNA levels) were observed in the CA3 region. The increased expression of mGlu5 receptors was directly related to the induction of LTP, because it was not observed when tetanic stimulation was carried out in animals treated with the NMDA receptor antagonist, 2-amino-5-phosphonopentanoate (AP5). Western blot analysis also showed a reduced expression of mGlu2/3 receptors in the whole hippocampus 24 h after LTP induction, indicating that the increased expression of mGlu5 receptors was specific. These data suggest that an up-regulation of mGlu5 receptors is a component of the plastic changes that follow the induction of LTP at the perforant path-dentate gyrus synapse.

2-Amino-5-phosphonovalerate↗

PubMed2003

DNA repair enzymes and cytotoxic effects of temozolomide: comparative studies between tumor cells and normal cells of the immune system.

O6-alkylguanine-DNA alkyltransferase (OGAT) and the mismatch repair system (MRS) play a crucial role in the susceptibility of tumor cells to the cytotoxic effects of agents that generate O6-methylguanine in DNA, including the triazene compound temozolomide (TMZ). Studies performed with peripheral blood mononuclear cells (MNC) showed that TMZ was scarcely active on lymphocyte functions not dependent on cell proliferation (e.g. NK activity and cytokine-mediated induction of CD1b molecule in adherent MNC). In contrast, TMZ depressed proliferation and lymphokine activated killer (LAK) cell generation in response to IL-2. In this case, a reasonably good inverse relationship was found between OGAT levels of MNC and their susceptibility to TMZ. This study also analyzed the ratio of the toxic effect of TMZ on MNC and on tumor cells (i.e. "Tumor-Immune Function Toxicity Index", TIFTI). A particularly favorable TIFTI can be obtained when OGAT levels are extremely high in MNC and markedly low in tumor cells. This holds true for MRS-proficient neoplastic cells, but not for MRS-deficient tumors. In conclusion, strategies aimed at modulating OGAT and MRS may improve the clinical response to TMZ. However, the use of OGAT inhibitors to potentiate the antitumor activity of TMZ might result in a concomitant increase of the immunosuppressive effects of the drug, thus reducing the relative TIFTI.

Antineoplastic Agents, Alkylating↗

PubMed2003

Postpartum cerebral ischaemia after accidental dural puncture and epidural blood patch.

Puerperal women are reported to have a rate of cerebral infarction 13 times greater than non-pregnant females. We report a case of cerebral ischaemia in a 30-yr-old healthy parturient after epidural analgesia for labour, complicated by dural puncture treated with two epidural blood patches. Investigations showed the development of cerebral ischaemia on postpartum day 14. A transcranial Doppler ultrasonography showed vasospasm of the left middle cerebral artery still present at 3-month follow-up. At 1-yr follow-up, the patient had homonymous hemianopsia. We discuss the possible causative mechanism of the cerebral ischaemia in relation to the dural puncture and epidural blood patch.

Adult↗

PubMed2001

The mammalian homologue of the novel peptide Bv8 is expressed in the central nervous system and supports neuronal survival by activating the MAP kinase/PI-3-kinase pathways.

Previous studies have identified the mammalian homologue of Bv8 (mBv8), a small protein originally isolated from skin secretions of the frog, Bombina variegata. In situ hybridization showed that mBv8 RNA was widely expressed in the rodent CNS, with high levels being detected in layer II of the cerebral cortex, limbic regions, cerebellar Purkinje cells, and dorsal and ventral horns of the spinal cord. A similar pattern of distribution was found by examining the presence of mBv8 protein by immunocytochemistry. Addition of frog Bv8 to cultured cerebellar granule cells reduced the extent of apoptotic death induced by switching the growing medium from 25 to 5 mM K+. Bv8 could also protect cultured cortical neurons against excitotoxic death. Both effects were prevented by PD98059 and LY294002, which inhibit the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI-3-K) pathways, respectively. In cultured cerebellar granule cells, Bv8 stimulated both the MAPK and the PI-3-K pathways, as revealed by Western blot analysis of phosphorylated p44/p42 MAPKs and phosphorylated Akt, respectively. We conclude that mBv8 acts as an endogenous neurotrophic factor and supports neuronal survival through the activation of the MAPK/PI-3-K pathways.

Amphibian Proteins↗

PubMed2001

Effect of collateral blood flow and cerebral vasomotor reactivity on the outcome of carotid artery occlusion.

BACKGROUND AND PURPOSE: Evidence suggests that an alteration in cerebral hemodynamics plays a relevant role in the occurrence of stroke in patients with carotid occlusion. The purpose of the present study was to evaluate the relationships among baseline characteristics, type and number of collateral pathways, cerebral vasomotor reactivity (VMR), and outcome of patients with carotid occlusion. METHODS: One hundred four patients with symptomatic or asymptomatic internal carotid artery occlusion were followed up prospectively for a median period of 24 months. Cerebral VMR to apnea was calculated with transcranial Doppler ultrasonography by means of the breath-holding index (BHI) in the middle cerebral arteries. The patency of the 3 major intracranial collateral vessels was also evaluated. RESULTS: During the follow-up period, 18 patients experienced an ischemic stroke ipsilateral to internal carotid artery occlusion. Among factors considered, only older age, number of collateral pathways, and BHI values in the middle cerebral artery ipsilateral to the occluded side were significantly associated with the risk of ipsilateral stroke (P<0.001, P=0.008, and P<0.001, respectively; multiple Cox regression analysis). A normal VMR and favorable prognosis characterized patients with full collateral development; in this group, no patient experienced an ischemic event. On the other hand, an impaired VMR and increased probability of experiencing a stroke were found in patients without collateral pathways; the annual risk of ipsilateral stroke in this group was 32.7%. Patients with 1 or 2 collateral pathways showed a different VMR ranging from normal to strongly reduced BHI values. The ipsilateral stroke event risk was 17.5% in patients with 1 collateral vessel and 2.7% in patients with 2 collateral pathways. In this case, the risk of cerebrovascular events occurring during the follow-up period was significantly related to VMR. CONCLUSIONS: These data suggest that cerebral hemodynamic status in patients with carotid occlusive disease is influenced by both individual anatomic and functional characteristics. The planning of strategies to define the risk profile and any attempt to influence patients' outcome should be based on the evaluation of the intracranial hemodynamic adaptive status, with particular attention to the number of collateral vessels and the related VMR.

Aged↗

PubMed2001

Becker's nevus syndrome.

Becker's nevus (BN) is a unilateral hyperpigmented, often hairy, cutaneous hamartoma, with geographic borders. It is usually localized on the shoulder, anterior chest, scapula, or upper arm, but there have been reports of BN in other areas (eg, lower extremities, face). In most cases, the lesion appears in late childhood or adolescence, and both congenital and familial cases have been described.

Adolescent↗

PubMed2000

Impaired cerebral vasoreactivity and risk of stroke in patients with asymptomatic carotid artery stenosis.

CONTEXT: Standards for treating patients with asymptomatic carotid artery stenosis have been difficult to establish because of the lack of evidence for factors influencing these patients' prognoses. However, preliminary evidence suggests that an alteration in cerebral hemodynamic function may play a relevant role in the occurrence of stroke in patients with carotid artery disease. OBJECTIVE: To investigate the relationship between cerebrovascular reactivity to hypercapnia and cerebrovascular events in patients with severe unilateral asymptomatic carotid artery stenosis. DESIGN AND SETTING: Prospective, blinded longitudinal study conducted in an outpatient neurovascular department in Italy between June 1996 and April 1998, with a median follow-up of 28.5 months. PATIENTS: Ninety-four patients with asymptomatic carotid artery stenosis of at least 70% (74 men; mean age, 71 years). MAIN OUTCOME MEASURES: Subsequent occurrence of cerebral ischemic events (transient ischemic attack or stroke) or death, analyzed by cerebrovascular reactivity to hypercapnia (measured by transcranial Doppler ultrasonography and calculated by the breath-holding index values in the middle cerebral arteries). RESULTS: The overall annual rate for all ischemic events was 7.9%. Seventeen patients (18%) had ischemic events, all but 1 of which were ipsilateral to the carotid artery stenosis. Among factors considered, only lower breath-holding index values in the middle cerebral artery ipsilateral to carotid artery stenosis were significantly associated with the risk of an event (hazard ratio, 0.09; 95% confidence interval, 0.02-0.38; P=.001, by multivariate analysis). Based on data from previously studied healthy subjects, the cutoff of the breath-holding index for distinguishing between impaired and normal cerebrovascular reactivity was determined to be 0.69. Using this cutoff, the annual ipsilateral ischemic event risk was 4.1% in patients with normal and 13.9% in those with impaired breath-holding index values. CONCLUSIONS: These results suggest a link between impaired cerebrovascular reactivity and the risk of ischemic events ipsilateral to severe asymptomatic carotid stenosis.

Aged↗

PubMed1999

Effects of haloperidol on the expression of lymphocyte dopamine receptor mRNAs in the rat.

1. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate the effects of haloperidol treatment (1 mg/kg/day for 2, 7 or 21 consecutive days) on the expression of D1B and D3 dopamine receptor mRNAs in the rat lymphocytes. 2. The expression of D1B receptor mRNA was significantly decreased after 2 days of treatment and progressively returned toward basal values at the end of treatment. Conversely, haloperidol failed to modify the expression of lymphocyte D3 receptor mRNA. 3. These results indicate short-lasting dynamic changes of expression of lymphocyte D1B dopamine receptor mRNA by haloperidol and suggest that the effects of dopamine and dopaminergic drugs on the immune system might be mediated, at least in part, by direct interaction of these substances with dopamine receptors on lymphocyte membrane.

Animals↗

PubMed1999

Opioid-dopamine interaction in planaria: a behavioral study.

The behavioral response of planaria to the exposure to selective opioid agonists was studied. The mu agonist [d-ala2, N-methyl-Phe4,Gly5-ol]enkephalin (DAMGO) and the 6 agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) failed to alter motor activity at all doses tested. Low doses of the selective kappa agonist (+/-)-trans-U-50-trans-3,4-dichloro-N-methyl-N[2-(1-pyrrodinyl)-cyclohexyl]benzene acetamide methasulphonate (U50, 488) and bremazocine-HCl increased motor activity leading to C-like position (CLP) and screw-like hyperkinesia (SLH). These changes were identical to those seen previously with the exposure to D2 or D1 dopamine receptor agonists, respectively. Higher doses of kappa agonists produced the enhancement of CLP and SLH together with robust snake-like movements (SLM). This latter response, that was typical of stimulation of kappa opioid receptors, was blocked by co-exposure to naloxone or the selective kappa antagonist Nor-binaltorphimine (Nor-BNI). Finally, co-exposure to sulpiride or SH-23390 respectively blocked the CLP or SLH response produced by U50,488 or bremazocine. Our data indicate the presence of kappa opioid receptors in planaria and suggest the functional interaction between the opioid and dopamine system in this simple animal model.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1999

Cerebrovascular reactivity in carotid artery occlusion: possible implications for surgical management of selected groups of patients.

OBJECTIVES: The aim of this study was to use transcranial Doppler ultrasonography to investigate cerebrovascular reactivity to hypercapnia in the middle cerebral arteries of patients with carotid occlusion with different outcomes. PATIENTS AND METHODS: Cerebrovascular reactivity to hypercapnia was calculated with the breath-holding index (BHI). Patients with unilateral carotid occlusion were divided as follows: asymptomatic (20 patients), transient ischemic attack (TIA) (20 patients), minor (20 patients) and major stroke (14 patients). Values of BHI homolateral to the carotid occlusion were compared with those of 25 healthy subjects and 34 stroke patients without significant carotid stenosis. RESULTS: BHI values were comparable in healthy controls, non stenotic stroke patients and asymptomatic occluded patients. BHI values of patients with symptomatic occlusion were significantly lower than those of the above-mentioned groups (P<0.0001). Moreover, the reduction of BHI was significantly associated with the extent of the neurological impairment. In fact, BHI values were significantly higher in TIA than in minor and major stroke (P<0.0001) and in minor than in major stroke patients (P<0.02). Finally, we found that a BHI value homolateral to carotid occlusion of 0.69 can be considered the cut-point for distinguishing between symptomatic and asymptomatic patients. CONCLUSION: Prospective studies are needed to demonstrate if the presence of this threshold value may help in selecting a subset of patients with asymptomatic carotid occlusion or with transient or mild neurological deficit with the highest probability of benefiting from surgical therapy.

Analysis of Variance↗

PubMed1999

Near infrared spectroscopy and transcranial Doppler in monohemispheric stroke.

We simultaneously performed near infrared spectroscopy (NIRS) and transcranial Doppler (TCD) to evaluate the effects of hypercapnia as well as of scalp ischemia on the blood flow at two different depth levels within the brain and of the scalp vessels. A decrease in the backscattered light intensity, meaning an increment of blood volume, was detected at the end of hypercapnia in all healthy subjects. This decrement was partly masked by ischemia in the cutaneous vessels. In 2 patients with a monohemispheric lesion in the middle cerebral artery (MCA) territory, an increase in NIRS response was found in the healthy hemisphere, while in the stroke side the CO2-induced changes were negligible. TCD data showed a similar increment of blood flow velocity to the hypercapnia in both hemispheres, with no differences between the affected and normal side in 1 patient, whereas in the second one, no increment was observed on the affected side, probably due to internal carotid artery stenosis. The two methods nicely integrate: TCD mainly tests subcortical changes in the MCA flow, while NIRS is exquisitely sensitive to cortical arterioles and capillary blood flow modifications.

Blood Flow Velocity↗

PubMed1999

Outcome of carotid artery occlusion is predicted by cerebrovascular reactivity.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the possibility of obtaining prognostic indications in patients with internal carotid occlusion on the basis of intracranial hemodynamic status, presence of previous symptoms of cerebrovascular failure, and baseline characteristics. METHODS: Cerebral hemodynamics were studied with transcranial Doppler ultrasonography. Cerebrovascular reactivity to apnea was calculated by means of the breath-holding index (BHI) in the middle cerebral arteries. Sixty-five patients with internal carotid artery occlusion were followed-up prospectively (median, 24 months), 23 patients were asymptomatic and 42 symptomatic (20 with transient ischemic attack and 22 with stroke). RESULTS: During the follow-up period, 11 symptomatic patients and 1 asymptomatic patient had another ischemic event ipsilateral to carotid occlusion. Among factors considered, only lower BHI values in the middle cerebral arteries ipsilateral to carotid occlusion and older age were significantly associated with the risk of developing symptoms (P=0.002 and P=0.003, respectively; Cox regression multivariate analysis). Based on our data, a cut point of the BHI value for distinguishing between pathological and normal cerebrovascular reactivity was determined to be 0.69. All patients except one, who developed TIA or stroke during the follow-up period, had BHI values ipsilateral to carotid occlusion of <0.69. CONCLUSIONS: These data suggest that impaired cerebrovascular reactivity is predictive for cerebral ischemic events in patients with carotid occlusion.

Aged↗

PubMed1998

Functional correlates of nicotine administration: similarity with drugs of abuse.

Changes in the local utilization of cerebral glucose resulting from administered drugs acting on the central nervous system can be evaluated quantitatively by the [14C]2-deoxyglucose method. We report the findings obtained by the [14C]2-deoxyglucose method that contribute to understanding the cerebral functional effects of drugs of abuse and discuss in particular the similarities between nicotine and other addictive drugs. A common consequence of the intravenous administration of psychomotor stimulants and opioids in the rat is the increase in glucose utilization in the shell of nucleus accumbens. This functional change is accompanied by increased local extracellular concentrations of dopamine. Altered functional activity and dopamine neurotransmission in the shell of the nucleus accumbens thus represent distinctive neurobiological markers of the addictive properties of several drugs, independently of the specific neurochemical mechanisms of action. It has recently been shown that the intravenous administration of a pulse of nicotine, at single-unit doses corresponding to those that maintain self-administration in the rat, produces neurochemical and metabolic changes in the shell of the nucleus accumbens that closely resemble those of psychomotor stimulants and opioids. The latter results demonstrate that nicotine shares with highly addictive drugs a distinct neurochemical and functional consequence. They therefore contribute to the neurochemical definition of the addictive nature of nicotine. These neurochemical and functional changes may contribute to the changes in expression of intracellular second messengers and neurotransmitter/receptor systems observed particularly in the shell following the administration of drugs of abuse.

Animals↗

PubMed1998

Dopamine receptor mRNAs in the rat lymphocytes.

It has been suggested that dopamine might play a role in the regulation of the immune system. In this study, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate the expression of mRNA for the different subtypes of dopamine receptors in the rat lymphocytes. D1, D3 and D5 receptor mRNAs were identified. These results provide further evidence for the interaction of dopamine systems and the immune system, and suggest to further investigate whether the immunosuppressive actions of dopamine and dopaminergic drugs might depend on a direct interaction with dopamine receptors on the lymphocyte membrane. Moreover, they suggest the suitability of this animal species to further investigate the correlation between changes in the expression of central and peripheral dopamine receptors produced by manipulations of the dopamine systems.

Animals↗

PubMed1997

Dopamine release in striatal slices of rats previously submitted to electroconvulsive shock.

The effects of single and repeated electroconvulsive shock (ECS) on the release of dopamine from rat striatal slices were investigated using the fractional release technique. Experiments were performed 24 h after the single or the last of seven ECS sessions. Repeated, but not single, ECS was associated with reduced dopamine release in response to chemical stimulation. These results suggest that repeated ECS affects the regulation of striatal dopamine presynaptic receptors.

Animals↗

PubMed1997

Functional correlates of heroin sensitization in the rat brain.

The aim of the study was to measure the changes in cerebral energy metabolism and c-fos mRNA expression following challenge with heroin in drug-naive rats and in animals previously sensitized to the drug. Acute heroin administration to drug naive-rats produced a generalized metabolic depression. In contrast, challenge with heroin in drug-sensitized rats produced selective metabolic increases in structures belonging to the basal ganglia. These changes were accompanied by increased c-fos mRNA expression in the caudate-putamen nucleus. These results demonstrate that the process of sensitization to heroin is coupled to functional changes that are confined to the subcortical motor circuits of the basal ganglia.

Animals↗