Biomedical subjects

M Manfredi

Publications and source records attributed to M Manfredi.

At least 19 recordsLinked to original sources

PubMed2006

Widespread neonatal brain damage following calcium channel blockade.

An abundance of evidence exists that shows calcium channel blockade promotes injury in cultured neurons. However, few studies have addressed the in vivo toxicity of such agents. We now show that the L-type calcium channel antagonist nimodipine promotes widespread and robust injury throughout the neonatal rat brain, in an age-dependent manner. Using both isolated neuronal as well as brain slice approaches, we address mechanisms behind such injury. These expanded studies show a consistent pattern of injury using a variety of agents that lower intracellular calcium. Collectively, these observations indicate that postnatal brain development represents a transitional period for still developing neurons, from being highly sensitive to reductions in intracellular calcium to being less vulnerable to such changes. These observations directly relate to current therapeutic strategies targeting neonatal brain injury.

Animals↗

PubMed2006

European Polistes venom allergy.

The American Polistes species venom mixture--that of P. annularis, P. fuscatus, P. metricus and P. exclamans--was the only commercially available mixture for diagnosis and therapy until 1996. However, these species of Polistes are not present in Europe, where P. dominulus and P. gallicus and to a lesser extent P. nimphus are widespread. The aim of this study was to assess the allergenic differences among the commercial American mix, P. dominulus and P. gallicus venom in European patients and therefore to verify if this mixture is suitable for diagnosis in these patients. We carried out skin tests, radioallergosorbent tests (RAST) and RAST inhibition in Italian patients with adverse reactions to Polistes stings. RAST inhibition results demonstrated that cross-reactivity between the American and European species is only partial and that P. dominulus and P. gallicus venoms have exclusive allergens. Skin tests and direct RAST confirmed these results and also showed that European Polistes venom is more suitable than the American mix in Italian patients. Moreover, we found a high rate of cross-reactivity between P. dominulus and P. gallicus. To conclude, P. dominulus and/or P. gallicus venoms are necessary for diagnosis and therefore in the therapy of European patients.

Adolescent↗

PubMed2006

In vitro antifungal susceptibility to six antifungal agents of 229 Candida isolates from patients with diabetes mellitus.

The most common antifungal drugs in current clinical use for the treatment of oral candidosis are polyenes and azoles, mainly used topically. Poor glycaemic control in association with other local factors, such as the presence of oral dental prostheses, salivary pH, salivary flow rate and tobacco habits, may lead to the development of oral candidosis. Topical antifungal agents are frequently used to prevent the development of candidal infections in patients with poor metabolic control, particularly in the elderly wearing dentures. The aim of this study was to assess the antifungal susceptibility of Candida isolates to six antifungal agents using a commercially available kit, Fungitest. The isolated were collected from patients affected by diabetes mellitus from two different geographic localities (London, UK, and Parma, Italy) and from a group of healthy non-diabetic subjects. No differences in antifungal susceptibility to the six agents tested were observed between Candida isolates from diabetic and non-diabetic subjects. However, differences were observed between the two geographically different diabetes mellitus populations. Oral yeast isolates from diabetes mellitus patients in the UK more often displayed resistance or intermediate resistance to fluconazole (P=0.02), miconazole (P<0.0001), and ketoconazole (P=0.01) than did isolates from diabetes mellitus patients in Italy. In addition, more C. albicans isolates were found in diabetic and non-diabetic subjects that were susceptible to fluconazole (P=0.0008 and P=0.01, respectively) than non-albicans isolates. The difference in the antifungal resistance of isolates from the two populations of diabetes mellitus patients may be related to differences in the therapeutic management of candidal infections between the two centres.

Antifungal Agents↗

PubMed2006

In vitro evaluation of virulence attributes of Candida spp. isolated from patients affected by diabetes mellitus.

BACKGROUND: Diabetes mellitus is a common disease found worldwide and it has been previously suggested that oral candidal infections may be more frequent or severe in patients with this disease. Systemic and local factors may influence the balance between the host and yeasts, and favour the transformation of Candida isolates from commensal to pathogenic microorganisms. Candida species have developed specific virulence mechanisms that confer the ability to colonise host surfaces, to invade deeper host tissue, or to evade host defences. Few studies have investigated the expression of the virulence attributes of oral Candida isolates in patients with diabetes mellitus. MATERIAL AND METHODS: The in vitro extracellular proteinase production and the in vitro ability to adhere to fibronectin of 229 Candida isolates of two geographic different groups of patients with diabetes mellitus and of healthy subjects were assessed. RESULTS: Candida isolates of patients with diabetes mellitus expressed a higher ability to adhere than those of healthy subjects. Higher levels of adhesion were also recorded in patients with a lower oral Candida colonisation. No differences were observed in the in vitro expression of extracellular proteinase of Candida isolates of patients with diabetes mellitus and those of non-diabetic subjects. Isolates of patients with type 2 diabetes mellitus expressed greater levels of proteinase than isolates of type 1 diabetes mellitus. CONCLUSIONS: Diabetes mellitus could be considered as an additional variable that may influence not only oral Candida carriage but also the ability of isolates to enhance the expression of virulence attributes.

Candida↗

PubMed2006

Analysis of the strain relatedness of oral Candida albicans in patients with diabetes mellitus using polymerase chain reaction-fingerprinting.

To increase our understanding of Candida pathogenicity, the identification of those strains most frequently associated with infections is of paramount importance. Polymerase chain reaction (PCR)-based methods are extremely effective in differentiating and determining reproducibility, they require minimum starting material and are rapid and simple to perform. In this study, the genetic relatedness of Candida albicans was assessed for two geographically different patient groups (London, UK and Parma, Italy) affected by diabetes mellitus. C. albicans samples from the oral cavities of non-diabetic healthy subjects were also examined by PCR fingerprinting to evaluate the possible genetic differences among endogenous strains in individuals with and without diabetes mellitus. PCR fingerprinting, with subsequent phylogenetic analysis of C. albicans isolates from the diabetic patients from London and Italy and from the non-diabetic subjects, revealed that there were significant differences (P < 0.0001) between C. albicans isolates indicative of the distinct ecological niches that occur in the oral cavities of these patient cohorts. The most diverse group comprised the isolates from the diabetic patients in the UK, possibly reflecting the antifungal treatment that these patients had received. Further studies that include isolates from patient cohorts with systemic diseases other than diabetes mellitus, and from more diverse geographic localities are required to explain the relatedness of C. albicans isolates in the mouth.

Candida albicans↗

PubMed2006

Use of levetiracetam in treating epilepsy associated with other medical conditions.

OBJECTIVE: This prospective, open-label study was conducted to evaluate the effectiveness, tolerability, and safety of levetiracetam in patients with epilepsy in whom unfavorable metabolism, complex drug interactions, or direct toxic effects of antiepileptic drugs (AEDs) had caused a worsening of comorbid conditions. METHODS: Study design included the introduction of levetiracetam, discontinuation of other AEDs, and a serial assessment comprising electroencephalograms and blood tests at baseline and 2, 6, and 12 months. Of 21 patients, 16 had partial and five generalized epilepsy. Concomitant pathologies were gastroenterological (six), vascular (four), endocrinological (four), or complex conditions including hematological (four) or dermatological (three) disease. A change of regimen was necessitated by drug-drug interactions in four patients, direct real or potential toxic effects of previous AEDs in 13, and a combination of interactions/toxic effects in four. RESULTS: After 12 months, 12 patients were seizure-free, nine had reductions in seizure frequency of 50-75%, and improvement in concomitant medical conditions was observed. No side effects were reported. CONCLUSION: Levetiracetam appears to be effective, well tolerated, and safe in patients with epilepsy and other medical conditions that are difficult to manage because of drug interactions or AED-related side effects.

Adolescent↗

PubMed2005

Rundown of GABA type A receptors is a dysfunction associated with human drug-resistant mesial temporal lobe epilepsy.

Pharmacotherapeutic strategies have been difficult to develop for several forms of temporal lobe epilepsy, which are consequently treated by surgical resection. To examine this problem, we have studied the properties of transmitter receptors of tissues removed during surgical treatment. We find that when cell membranes, isolated from the temporal neocortex of patients afflicted with drug-resistant mesial temporal lobe epilepsy (TLE), are injected into frog oocytes they acquire GABA type A receptors (GABA(A)-receptors) that display a marked rundown during repetitive applications of GABA. In contrast, GABA(A)-receptor function is stable in oocytes injected with cell membranes isolated from the temporal lobe of TLE patients afflicted with neoplastic, dysgenetic, traumatic, or ischemic temporal lesions (lesional TLE, LTLE). Use-dependent GABA(A)-receptor rundown is also found in the pyramidal neurons of TLE neocortical slices and is antagonized by BDNF. Pyramidal neurons in cortical slices of a traumatic LTLE patient did not show GABA(A)-receptor rundown. However, the apparent affinity of GABA(A)-receptor in oocytes microtransplanted with membranes from all of the epileptic patients studied was smaller than the affinity of receptors transplanted from the nonepileptic brain. We conclude that the use-dependent rundown of neocortical GABA(A)-receptor represents a TLE-specific dysfunction, whereas the reduced affinity may be a general feature of brains of both TLE and LTLE patients, and we speculate that our findings may help to develop new treatments for TLE and LTLE.

Adolescent↗

PubMed2005

BDNF modulates GABAA receptors microtransplanted from the human epileptic brain to Xenopus oocytes.

Cell membranes isolated from brain tissues, obtained surgically from six patients afflicted with drug-resistant temporal lobe epilepsy and from one nonepileptic patient afflicted with a cerebral oligodendroglioma, were injected into frog oocytes. By using this approach, the oocytes acquire human GABAA receptors, and we have shown previously that the "epileptic receptors" (receptors transplanted from epileptic brains) display a marked run-down during repetitive applications of GABA. It was found that exposure to the neurotrophin BDNF increased the amplitude of the "GABA currents" (currents elicited by GABA) generated by the epileptic receptors and decreased their run-down; both events being blocked by K252A, a neurotrophin tyrosine kinase receptor B inhibitor. These effects of BDNF were not mimicked by nerve growth factor. In contrast, the GABAA receptors transplanted from the nonepileptic human hippocampal uncus (obtained during surgical resection as part of the nontumoral tissue from the oligodendroglioma margins) or receptors expressed by injecting rat recombinant alpha1beta2gamma2 GABAA receptor subunit cDNAs generated GABA currents whose time-course and run-down were not altered by BDNF. Loading the oocytes with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate-acetoxymethyl ester (BAPTA-AM), or treating them with Rp-8-Br-cAMP, an inhibitor of the cAMP-dependent PKA, did not alter the GABA currents. However, staurosporine (a broad spectrum PK inhibitor), bisindolylmaleimide I (a PKC inhibitor), and U73122 (a phospholipase C inhibitor) blocked the BDNF-induced effects on the epileptic GABA currents. Our results indicate that BDNF potentiates the epileptic GABAA currents and antagonizes their use-dependent run-down, thus strengthening GABAergic inhibition, probably by means of activation of tyrosine kinase receptor B receptors and of both PLC and PKC.

Animals↗

PubMed2005

LGI1 gene mutation screening in sporadic partial epilepsy with auditory features.

Partial epilepsy with auditory features occasionally segregates in families as an autosomal dominant trait. In some families mutations in the leucine-rich glioma inactivated (LGI1) gene have been identified. Sporadic cases might harbour either denovo or low-penetrant LGI1 mutations, which will substantially alter the family risk for epilepsy. We selected sixteen sporadic patients with cryptogenic temporal lobe epilepsy and partial seizures with auditory features. We compared clinical features of these patients with those of published autosomal dominant family cases. We screened these patients for LGI1 mutations. Comparing the sporadic patients with the published familial cases no difference in either the primary auditory features or in the other associated epileptic manifestations was identified. Sequence analysis of the whole LGI1 gene coding regions in sporadic patients did not reveal changes in the LGI1 gene. The genetic analysis demonstrates that LGI1 is not a major gene for sporadic cases of partial epilepsy with auditory features at least in the Italian population. Screening of sporadic patients for LGI1 mutations appears not useful in genetic counselling of these patients.

Adult↗

PubMed2005

In vitro activity of a monoclonal killer anti-idiotypic antibody and a synthetic killer peptide against oral isolates of Candida spp. differently susceptible to conventional antifungals.

BACKGROUND/AIMS: A monoclonal killer anti-idiotypic antibody (mAbK10) and a synthetic killer peptide, acting as internal images of a microbicidal, wide-spectrum yeast killer toxin (KT) have been recently shown to express candidacidal in vitro and an in vivo therapeutic activity against experimental mucosal and systemic candidosis models caused by a reference strain of Candida albicans (10S). MATERIAL AND METHODS: The in vitro candidacidal activity of mAbK10 and synthetic killer peptide was compared using a colony forming unit assay against a large number of isolates of different Candida spp., obtained from oral saliva of adult diabetic (type 1 and 2) and nondiabetic subjects from Parma (Italy) and London (UK). RESULTS: Both the KT-mimics exerted a strong dose-dependent candidacidal activity, probably mediated by the interaction with beta-glucan KT receptors on target yeast cells, against all the tested strains, regardless of their species and pattern of resistance to conventional antifungal agents. CONCLUSIONS: These observations open new perspectives in the design and production of candidacidal compounds whose mechanism reflects that exerted in nature by killer yeasts.

Adult↗

PubMed2005

Jaw bone necrosis without previous dental extractions associated with the use of bisphosphonates (pamidronate and zoledronate): a four-case report.

Jaw bone necrosis is a clinical condition associated with defects in vascularization of the maxilla or the mandibular bone, usually present following head and neck radiotherapy and/or oral surgical interventions. Bisphosphonates are synthetic analogues of pyrophosphate used in the treatment of patients with hypercalcemia as a result of malignancy, bone metastasis and for the treatment of other disorders such as metabolic bone diseases, Paget's disease and osteoporosis. Over last 10 years, cases of jaw bone necrosis have been associated with the use of bisphosphonate therapy. In particular, Ruggiero et al. (J Oral Maxillofac Surg 2004; 62: 527-534) in 2004 described a large group of patients (63) with jaw bone necrosis probably related to the use of these drugs. It should be noted that all the patients in the group described either underwent head and neck radiotherapy or had a dental extraction while taking bisphosphonates. In the present study, we reported four cases of jawbone necrosis in patients taking pamidronate (Aredia) and zoledronate (Zometa) without having undergone any kind of radiotherapy or dental surgery. All the patients were females between the ages of 56 and 71 years; three were treated with bisphosphonates for bone metastasis and one for multiple myeloma. All the patients received surgical treatment with bone curettage, with partial and/or temporary improvement of the lesions. Although a treatment for bisphosphonate-induced bone lesions has not yet been established, we suggest careful evaluation of the patients' oral health before prescribing bisphosphonate treatment.

Aged↗

PubMed2005

Temporal lobe epilepsy surgery: different surgical strategies after a non-invasive diagnostic protocol.

AIM: To test a non-invasive presurgical protocol for temporal lobe epilepsy (TLE) based on "anatomo-electro-clinical correlations". METHODS: All consecutive patients with suspected TLE and seizure history <2 years were entered into the protocol, which included video-electroencephalographic (EEG) monitoring and magnetic resonance imaging (MRI). Three different TLE subsyndromes (mesial, lateral, mesiolateral) were identified by combined anatomical, electrical, and clinical criteria. "Tailored" surgery for each subsyndrome was offered. Patients with seizure history <2 years, MRI evidence of temporal mass lesion, and concordant interictal EEG and clinical data bypassed video-EEG monitoring and were directly scheduled for surgery. RESULTS: Lesionectomy was performed without video-EEG recording in 11 patients with tumorous TLE. Of 146 patients studied with video-EEG, 133 received a TLE diagnosis. Four were excluded for neuropsychological risks, eight refused surgery, and 121 underwent surgery. Of 132 consecutive patients who underwent surgery, 101 had at least one year of follow up. They were divided into a "hippocampal sclerosis/cryptogenic" group (n = 57) and a "tumours/cortical organisation disorders" group (n = 44). In the first group, extensive temporal lobectomy (ETL) was performed in 40 patients, anteromesial temporal lobectomy (AMTL) in 17 patients. At follow up, 47 patients were seizure free. In the second group, lesionectomy plus ETL was performed in 23 patients, lesionectomy plus AMTL in six patients, and lesionectomy alone in 15 patients. Thirty nine patients were seizure free. CONCLUSIONS: These findings suggest that different TLE subsyndromes can be identified accurately using non-invasive anatomo-electro-clinical data and can be treated effectively and safely with tailored surgery.

Adolescent↗

PubMed2005

Langerhans-cell histiocytosis: a clinical case without bone involvement.

BACKGROUND: Langerhans-cell histiocytosis (LCH) is a group of rare disorders histologically characterized by the proliferation of Langerhans cells. Multiple organs and systems may be involved by the disease. Typically, there is bone involvement and, less frequently, lesions may be found in the lungs, liver, lymph nodes, skin, and mucosae. Oral soft tissue lesions without bone involvement are rare. METHODS: We report a case of a 23-year-old man with LCH detected by oral soft tissue, cutaneous, and lung lesions. RESULTS: Due to the oral lesion diagnosis, important procedures were performed, which determined the staging of the disease. CONCLUSION: Gingival lesions could be one of the first manifestations of LCH. The periodontist should recognize and detect this important pathology with oral involvement.

Adult↗

PubMed2004

Brainstem reflex circuits revisited.

Our current understanding of brainstem reflex physiology comes chiefly from the classic anatomical-functional correlation studies that traced the central circuits underlying brainstem reflexes and establishing reflex abnormalities as markers for specific areas of lesion. These studies nevertheless had the disadvantage of deriving from post-mortem findings in only a few patients. We developed a voxel-based model of the human brainstem designed to import and normalize MRIs, select groups of patients with or without a given dysfunction, compare their MRIs statistically, and construct three-plane maps showing the statistical probability of lesion. Using this method, we studied 180 patients with focal brainstem infarction. All subjects underwent a dedicated MRI study of the brainstem and the whole series of brainstem tests currently used in clinical neurophysiology: early (R1) and late (R2) blink reflex, early (SP1) and late (SP2) masseter inhibitory reflex, and the jaw jerk to chin tapping. Significance levels were highest for R1, SP1 and R2 afferent abnormalities. Patients with abnormalities in all three reflexes had lesions involving the primary sensory neurons in the ventral pons, before the afferents directed to the respective reflex circuits diverge. Patients with an isolated abnormality of R1 and SP1 responses had lesions that involved the ipsilateral dorsal pons, near the fourth ventricle floor, and lay close to each other. The area with the highest probabilities of lesion for the R2-afferent abnormality was in the ipsilateral dorsal-lateral medulla at the inferior olive level. SP2 abnormalities reached a low level of significance, in the same region as R2. Only few patients had a crossed-type abnormality of SP1, SP2 or R2; that of SP1 reached significance in the median pontine tegmentum rostral to the main trigeminal nucleus. Although abnormal in 38 patients, the jaw jerk appeared to have no cluster location. Because our voxel-based model quantitatively compares lesions in patients with or without a given reflex abnormality, it minimizes the risk that the significant areas depict vascular territories rather than common spots within the territory housing the reflex circuit. By analysing statistical data for a large cohort of patients, it also identifies the most frequent lesion location for each response. The finding of multireflex abnormalities reflects damage of the primary afferent neurons; hence it provides no evidence of an intra-axial lesion. The jaw jerk, perhaps the brainstem reflex most widely used in clinical neurophysiology, had no apparent topodiagnostic value, probably because it depends strongly on peripheral variables, including dental occlusion.

Adult↗

PubMed2004

Nevoid basal cell carcinoma syndrome: a review of the literature.

The nevoid basal cell carcinoma syndrome (NBCCS) or Gorlin-Goltz Syndrome is an autosomal dominant disorder principally characterized by cutaneous basal cell carcinomas, multiple keratocysts, and skeletal anomalies. The present report reviews current knowledge of this disorder that has profound relevance to specialists in Oral and Maxillo-Facial Surgery, Oral Medicine and Radiology.

Basal Cell Nevus Syndrome↗

PubMed2004

Update on diabetes mellitus and related oral diseases.

Diabetes mellitus (DM) is a group of complex multisystem metabolic disorders characterized by a relative or absolute insufficiency of insulin secretion and/or concomitant resistance to the metabolic action of insulin on target tissues. The chronic hyperglycaemia of diabetes is associated with long-term systemic dysfunction. The present article summarizes current knowledge of DM and details the oral and dental implications of this common endocrine disorder.

Diabetes Complications↗

PubMed2003

Antiepileptic drugs and cortical excitability: a study with repetitive transcranial stimulation.

Repetitive transcranial magnetic stimulation (rTMS) delivered at various intensities and frequencies excites cortical motor areas. Trains of stimuli (at 5 Hz frequency, and suprathreshold intensity) progressively increase the size of muscle evoked potentials (MEPs) and the duration of the cortical silent period (CSP) in normal subjects. The aim of this study was to evaluate the effect of the antiepileptic drugs carbamazepine, gabapentin, and topiramate on cortical excitability variables tested with rTMS. We tested the changes in motor threshold, MEP size and CSP duration evoked by focal rTMS in 23 patients with neuropathic pain before and after a 1-week course of treatment with carbamazepine, gabapentin, topiramate and placebo. None of the three antiepileptic drugs changed the resting or active magnetic and electrical motor threshold. Antiepileptic treatment, but not placebo, abolished the normal rTMS-induced facilitation of MEPs, but left the progressive lengthening of the CSP during the rTMS train unchanged. Our results suggest that carbamazepine, gabapentin and topiramate modulate intracortical excitability by acting selectively on excitatory interneurons.

Analysis of Variance↗

PubMed2003

Unmyelinated trigeminal pathways as assessed by laser stimuli in humans.

Laser pulses excite superficial free nerve endings innervated by small-myelinated (Adelta) and unmyelinated (C) fibres. Whereas laser-evoked scalp potentials (LEPs) are now reliably used to assess function of the Adelta-fibre nociceptive pathways in patients with peripheral or central lesions, the selective activation of C-fibre receptors and recording of the related brain potentials remain difficult. To investigate trigeminal C-fibre function, we directed laser pulses to the facial skin and studied sensory perception and scalp evoked potentials related to Adelta- or C-fibre activation in healthy humans and patients--one having a bilateral facial palsy, two a trigeminal neuropathy, and two a Wallenberg syndrome. We also measured afferent conduction velocity and, with source analysis, studied the brain generators. Whereas laser pulses of low intensity and small irradiated area elicited pinprick sensations and standard Adelta-LEPs, laser pulses of very-low intensity and large irradiated area elicited warmth sensations and scalp potentials with a latency compatible with C-fibre conduction (negative wave 280 ms, positive wave 380 ms); the estimated conduction velocity was 1.2 m/s. The main waves of the scalp potentials originated from the anterior cingulate gyrus; they were preceded by activity in the opercular region and followed by activity in the insular region. The patient with bilateral facial palsy, who had absent trigeminal-facial reflexes, had normal Adelta- and C-related scalp potentials; the patients with trigeminal neuropathy, characterized by loss of myelinated and sparing of unmyelinated fibres, had absent Adelta- but normal C-related potentials; and the patients with Wallenberg syndrome had absent Adelta- and C-related potentials. We conclude that laser pulses with appropriate characteristics evoke brain potentials related to the selective activation of trigeminal nociceptive Adelta or thermal C fibres. The trigeminal territory yields rewarding LEP findings owing to the high density of thermal receptors and, because the short conduction distance, minimizes the problem of signal dispersion along slow-conducting unmyelinated afferents. The opercular-insular region and the cingulate gyrus are involved in the processing of C-fibre trigeminal inputs. The method we describe may prove useful in patients with lesions affecting the trigeminal thermal pain pathways.

Adult↗