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Biomedical subjects

F Monaco

Publications and source records attributed to F Monaco.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Evaluation of lung function as a prognostic index before and after surgical resection due to NSCLC].

BACKGROUND: Although there were several studies on survival, death and morbidity rates after lung resection, considering both limited and extended resections, lung exercise capacity has been quite seldom taken into account as an index for prognosis. The aim of this study compare the consequences of three kinds of lung resections (pneumonectomy, lobectomy and wedge resection), to test pre- and post-surgery exercise capacity for patients affected by NSCLC in order to obtain more detailed prognostic indices. METHODS: All the patients were studied by means of thorough lung static function and hemogas analytical tests before and after surgical resection, from 15 days to 12 twelve months' time past surgery. RESULTS: In fact, in relation to lung resection due to neoplasms, several studies pointed out that zone-limited resections show an obvious anatomical benefit in terms of parenchyma spair compared to lobectomy; however, it is underlined that the functional benefits of small resections don't really prevail over post-lobectomy anatomical advantages. Furthermore local relapses are more common after small resections rather than after lobectomy. CONCLUSIONS: Neither limited lung resection nor lobectomy alone, therefore, in accordance with nearly all the recent and still ongoing studies in this huge research field, has a significant effect on exercise capacity. Only pneumonectomy is associated with impaired exercise performance, and, nevertheless, quite below our expectations.

Carbon Dioxide↗
PubMed2002

Chronic alcohol use and first symptomatic epileptic seizures.

OBJECTIVE: To establish whether chronic alcoholism and alcohol consumption are risk factors for developing a first symptomatic epileptic seizure. METHODS: Multicentre case-control study of 293 patients (160 men, 133 women) with a first seizure symptomatic (either acute or remote) of head trauma, stroke, or brain tumour, matched to 444 hospital controls for centre, sex, age (+/-5 years), and underlying pathology. RESULTS: The risk of first seizure in alcoholics was no higher than in non-alcoholics for men (odds ratio 1.2, 95% confidence interval 0.4 to 3.2) or women (1.5, 0.1 to 54.4). The odds ratio (both sexes) was 1.2 (0.8 to 1.7) for an average intake of absolute alcohol of 1-25 g/day, 0.9 (0.5 to 1.5) for 26-50 g/day, 1.6 (0.8 to 3.0) for 51-100 g/day, and 1.4 (0.5 to 3.5) for >100 g/day. CONCLUSIONS: We found no evidence of an association between alcohol use or alcoholism and a first symptomatic seizure.

Adult↗
PubMed2001

Diagnosis of psychogenic paralysis: the role of motor evoked potentials.

BACKGROUND: In the nineties, there has been evidence that motor evoked potential (MEP) studies might improve the diagnosis of psychogenic paralysis. OBJECTIVE: To review a series of patients (1986-1999) who finally had a diagnosis of psychogenic paralysis at our Institutions. To detect if, over that period, the time taken to make the diagnosis had changed, and, if so, this had any relationship to the diagnostic tests used or to other variables. METHODS: We selected a patient sample (n=21) seen by the same team of neurologists, whose diagnostic criteria were homogeneously based on the DSM IV, and who were studied with MEPs. We analysed their clinical features, the type and timing of the investigations done, and the time taken to make the diagnosis. These variables acted as the dependent factors in a Multivariate Analysis of Variance (MANOVA) model, in which the year of observation was the fixed factor. RESULTS: The diagnosis was 50% earlier in the period 1993 to 1999 (10 patients) than in the period 1986-1992 (11 patients) (F = 28.3, p < 0.0001). The only associated change was an earlier MEP study (F=18.4, p < 0.0001), which invariably showed normal findings. CONCLUSION: MEP studies contributed to speed up the diagnosis of psychogenic paralysis. Possibly, normal MEPs rendered the neurologist confident about the physiological integrity of motor fibers in the corticospinal tract, anterior roots and plexuses. Such integrity, if nerve trunks and muscles are intact, and in the appropriate diagnostic context, implies a psychogenic cause for paralysis.

Adolescent↗
PubMed2001

Mood and behavioural disorders following traumatic brain injury: clinical evaluation and pharmacological management.

In order to investigate phamacotherapeutic responsiveness of major depression and other behavioural disturbances associated with traumatic brain injury (TBI), 20 post-TBI patients were diagnosed as being depressed by two independent neuropsychiatrist observers, out of 37 consecutive TBI subjects sent to psychiatric counselling for poor compliance during rehabilitation programmes or psychiatric/behavioural disturbances after return to society. They were subsequently divided into two subgroups, depending on time elapsed from trauma (A: within 6 months; B: at 24-36 months post-trauma) and were enrolled in an open informed pharmachological study. Rating at baseline included Glasgow Coma Score on hospital admission, length of coma, length of hospitalization, Functional Independence Measure (FIM), Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression scale (CGI). BPRS and CGI were repeated after 12 weeks of oral administration of citalopram (20 mg a day) and carbamazepine (600 mg a day). At baseline, psychiatric symptoms in group B were worse than in group A (particularly somatic overconcern, anxiety, depressed mood, psychomotor slowness, inappropriate and labile affect). At T1, the global (group A and B combined) CGI and BPRS scores showed a statistically significant improvement when compared with T0, even if group B scores remained higher than group A. The results of this study suggest that: (a) citalopram combined with carbamazepine is effective in reducing depression and behavioural disorders following TBI, and (b) these disturbances should be addressed as soon as possible during the acute rehabilitation period.

Adult↗
PubMed2001

Different respiratory syncytial virus and Quillaja saponin formulations induce murine peritoneal cells to express different proinflammatory cytokine profiles.

The recognition of a pathogen or a vaccine antigen formulation by cells in the innate immune system leads to production of proinflammatory cytokines, which will determine the ensuing acquired immune response quantitatively and qualitatively. Tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 and IL-6 are the first set of cytokines produced upon such an encounter, which have roles both in protective immunity and immunopathogenesis evident with respiratory syncytial virus (RSV). RSV antigens in different physical adjuvant-vaccine formulations were analysed for their capacity to provoke cultured murine peritoneal cells to produce these three proinflammatory cytokines. RSV immunostimulating complex (ISCOM), i.e. both antigen and adjuvant are incorporated in the same particle, induced high levels of IL-1alpha being of the same magnitude or higher than those of live RSV and lipopolysaccharide (LPS). Live virus and LPS induced higher levels of IL-6 and TNF-alpha than ISCOM and so did non-adjuvanted UV-inactivated RSV but only at high doses. ISCOM-Matrix, i.e. ISCOM without antigens, admixed as a separate entity to inactivated RSV, downregulated or blocked the cytokine response to the inactivated RSV in contrast to ISCOM. Kinetic studies showed that ISCOM induced cytokine production first detected at hours 1, 2, 4 for TNF-alpha, IL-6 and IL-1alpha respectively, which was earlier than for the other antigen formulations containing corresponding doses of antigen and/or Quillaja adjuvant. Peak values for production of TNF-alpha and IL-6 were at 8 h and for IL-1alpha at 72 h following stimulation with ISCOM. The delayed appearance of IL-1alpha may reflect the cell-bound nature of this cytokine.

Adjuvants, Immunologic↗
PubMed2001

Cortical excitability and sleep deprivation: a transcranial magnetic stimulation study.

The objective was to assess the changes in cortical excitability after sleep deprivation in normal subjects. Sleep deprivation activates EEG epileptiform activity in an unknown way. Transcranial magnetic stimulation (TMS) can inform on the excitability of the primary motor cortex. Eight healthy subjects (four men and four women) were studied. Transcranial magnetic stimulation (single and paired) was performed by a focal coil over the primary motor cortex, at the "hot spot" for the right first dorsal interosseous muscle. The following motor evoked potential features were measured: (a) active and resting threshold to stimulation; (b) duration of the silent period; (c) amount of intracortical inhibition on paired TMS at the interstimulus intervals of 2 and 3 ms and amount of facilitation at interstimulus intervals of 14 and 16 ms. The whole TMS session was repeated after a sleep deprivation of at least 24 hours. After the sleep deprivation, the threshold to stimulation (in the active and resting muscle), as well as the silent period, did not change significantly. By contrast, the paired stimulus study showed a significant (p<0.05) reduction in both intracortical inhibition and facilitation. Thus, TMS showed that sleep deprivation is associated with changes in inhibition-facilitation balance in the primary motor cortex of normal subjects. These changes might have a link with the background factors of the "activating" effects of sleep deprivation.

Adult↗
PubMed2001

Gemcitabine, paclitaxel, and trastuzumab in metastatic breast cancer.

A phase II trial evaluated the effectiveness and toxicity of combination paclitaxel (Taxol), gemcitabine (Gemzar), and trastuzumab (Herceptin) as first-line therapy for patients with newly diagnosed HER2-overexpressing metastatic breast cancer. To date, 27 patients have received paclitaxel at 175 mg/m2 over 3 hours on day 1, plus gemcitabine at 1,200 mg/m2 on days 1 and 8, plus trastuzumab at a 4-mg/kg loading dose on day 1, followed by 2 mg/kg weekly. Treatment cycles were repeated every 21 days. Responding or stable patients who had received six cycles of combination therapy continued single-agent trastuzumab weekly until disease progression. Treatment was generally well tolerated with grade 4 toxicity limited to myelosuppression. In all, 12 patients have achieved a partial remission and 1 patient had progressive disease; 14 patients continue treatment and have not yet been evaluated for response. Combination treatment with paclitaxel, gemcitabine, and trastuzumab is well tolerated and appears to be highly active. Accrual will continue to a total enrollment of 46 patients.

Adult↗
PubMed2000

Defective T cell fas function in patients with multiple sclerosis.

BACKGROUND: Fas (CD95) triggers programmed cell death and is involved in shutting off the immune response. Inherited deleterious mutations hitting Fas or its signaling pathway cause autoimmune/lymphoproliferative syndrome (ALPS). OBJECTIVE: To assess the possibility that decreased Fas function plays a role in development of MS. METHODS: The authors evaluated Fas function in long-term T cell lines (21 days of culture) from 32 patients with relapsing-remitting MS (RRMS), 15 with secondary progressive MS (SPMS), and 15 with primary progressive MS (PPMS) by assessing cell survival upon Fas triggering by monoclonal antibodies (Mab). RESULTS: Fas-induced cell death was significantly lower in all patient groups than in controls, and lower in SPMS than in RRMS. Moreover, 8/15 patients with PPMS, 10/15 with SPMS, and 8/32 with RRMS were frankly resistant to Fas. Frequency of resistance to Fas-induced cell death was significantly higher in all patient groups than in controls (2/75), and higher in SPMS than in RRMS. The findings that the parents of two Fas-resistant patients were Fas-resistant and that fusion of T cells from two Fas-resistant patients with Fas-sensitive HUT78 cells gave rise to Fas-resistant hybrid lines suggest that Fas-resistance is due to inherited alterations of the Fas signaling pathway, with production of molecules exerting a dominant negative effect on a normal Fas system. CONCLUSIONS: Defects of the immune response shutting-off system may be involved in the pathogenesis of MS, particularly in its progressive evolution.

Adult↗
PubMed2000

Thymosin-alpha1 regulates MHC class I expression in FRTL-5 cells at transcriptional level.

In this study we examined the effect of the synthetic peptide thymosin-alpha1 (T(alpha)1) on MHC class I expression in FRTL-5 cells. Treatment with T(alpha)1 increased expression of MHC class I surface molecules and mRNA, which reached its peak (153 +/- 8 % of the control value) after 12 h. Chloramphenicol acetyltransferase (CAT) analysis, following transfection with a plasmid containing the regulatory sequence of MHC class I (or its deletion derivatives) with the CAT reporter gene, and electrophoretic mobility shift assay experiments demonstrated that the action of T(alpha)1 was at the transcriptional level, and its mechanism of action is likely due to increased binding between the complex p50/fra-2 and the enhancer A sequence of the 5' flanking region of a swine class I gene (PD1). An increase in the expression of MHC class I surface molecules was also observed by flow cytometry in murine and human tumor cell lines and in primary cultures of human macrophages. This study shows for the first time an effect of Talpha1 on the regulation of gene expression at the molecular level, and may further contribute to explaining the results obtained using Talpha1 in the control of infectious diseases and tumor growth.

Animals↗
PubMed2000

A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study Group in Epilepsy.

PURPOSE: To assess the clinical impact of monitoring serum concentrations of antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy. METHODS: One-hundred eighty patients with partial or idiopathic generalized nonabsence epilepsy, aged 6 to 65 years, requiring initiation of treatment with carbamazepine (CBZ), valproate (VPA), phenytoin (PHT), phenobarbital (PB), or primidone (PRM) were randomly allocated to two groups according to an open, prospective parallel-group design. In one group, dosage was adjusted to achieve serum AED concentration within a target range (10-20 microg/ml for PHT, 15-40 microg/ml for PB, 4-11 microg/ml for CBZ, and 40-100 microg/ml for VPA), whereas in the other group, dosage was adjusted on clinical grounds. Patients were followed up for 24 months or until a change in therapeutic strategy was clinically indicated. RESULTS: Baseline characteristics did not differ between the two groups. Most patients with partial epilepsy were treated with CBZ, whereas generalized epilepsies were most commonly managed with PB or VPA. PHT was used only in a small minority of patients. A total of 116 patients completed 2-year follow-up, and there were no differences in exit rate from any cause between the monitored group and the control group. The proportion of assessable patients with mean serum drug levels outside the target range (mostly below range) during the first 6 months of the study was 8% in the monitored group compared with 25% in the control group (p < 0.01). There were no significant differences between the monitored group and the control group with respect to patients achieving 12-month remission (60% vs. 61%), patients remaining seizure free since initiation of treatment (38% vs. 41%), and time to first seizure or 12-month remission. Frequency of adverse effects was almost identical in the two groups. CONCLUSIONS: Only a small minority of patients were treated with PHT, the drug for which serum concentration measurements are most likely to be useful. With the AEDs most commonly used in this study, early implementation of serum AED level monitoring did not improve overall therapeutic outcome. and the majority of patients could be satisfactorily treated by adjusting dose on clinical grounds. Monitoring the serum levels of these drugs in selected patients and in special situations is likely to be more rewarding than routine measurements in a large clinic population.

Adolescent↗
PubMed2000

Cortical excitability in cryptogenic localization-related epilepsy: interictal transcranial magnetic stimulation studies.

PURPOSE: To assess whether single-and paired-pulse transcranial magnetic stimulation (TMS) can measure the interictal brain excitability of medicated patients with cryptogenic localization related epilepsy (CLE). Changes in the balance between excitation and inhibition are the core phenomena in focal epileptogenesis. TMS can assess this balance in the primary motor cortex. METHODS: We selected 18 patients with CLE and similar clinical features in whom we located the epileptogenic area reliably, with 11 age-and sex-matched healthy controls. For both motor cortices, we determined the threshold to TMS, the duration of the cortical silent period, and the corticocortical inhibition and facilitation curve. RESULTS: TMS was safe. The more antiepileptic drugs (AEDs) taken by the patients, the higher their threshold to TMS. The silent period duration failed to show significant changes. On paired TMS, a cluster analysis identified a homogeneous subgroup of patients (n = 7) who showed a significantly defective corticocortical inhibition and excess facilitation. With respect to the epileptogenic area, the phenomenon was bilateral in four of these patients, ipsilateral in two, and contralateral in one. The phenomenon was independent of AEDs and many other clinical variables. However, this patient group had a higher seizure frequency and a higher proportion of electroencephalograms (EEGs) showing interictal generalized epileptic discharges than the rest of the patients. CONCLUSION: Paired TMS provided a valuable pathophysiologic insight into the interictal excitatory state of the cortex in CLE. This method can potentially supply useful prognostic clinical information.

Adolescent↗
PubMed2000

Transforming growth factor-beta1 down-regulation of major histocompatibility complex class I in thyrocytes: coordinate regulation of two separate elements by thyroid-specific as well as ubiquitous transcription factors.

Transforming growth factor (TGF)-beta1-decreased major histocompatibility complex (MHC) class I gene expression in thyrocytes is transcriptional; it involves trans factors and cis elements important for hormone- as well as iodide-regulated thyroid growth and function. Thus, in rat FRTL-5 thyrocytes, TGF-beta1 regulates two elements within -203 bp of the transcription start site of the MHC class I 5'-flanking region: Enhancer A, -180 to -170 bp, and a downstream regulatory element (DRE), -127 to -90 bp, that contains a cAMP response element (CRE)-like sequence. TGF-beta1 reduces the interaction of a NF-kappaB p50/fra-2 heterodimer (MOD-1) with Enhancer A while increasing its interaction with a NF-kappaB p50/p65 heterodimer. Both reduced MOD-1 and increased p50/p65 suppresses class I expression. Decreased MOD-1 and increased p50/p65 have been separately associated with the ability of autoregulatory (high) concentrations of iodide to suppress thyrocyte growth and function, as well as MHC class I expression. TGF-beta1 has two effects on the downstream regulatory element (DRE). It increases DRE binding of a ubiquitously expressed Y-box protein, termed TSEP-1 (TSHR suppressor element binding protein-1) in rat thyroid cells; TSEP-1 has been shown separately to be an important suppressor of the TSH receptor (TSHR) in addition to MHC class I and class II expression. It also decreases the binding of a thyroid-specific trans factor, thyroid transcription factor-1 (TTF-1), to the DRE, reflecting the ability of TGF-beta1 to decrease TTF-1 RNA levels. TGF-beta1-decreased TTF-1 expression accounts in part for TGF-beta1-decreased thyroid growth and function, since decreased TTF-1 has been shown to decrease thyroglobulin, thyroperoxidase, sodium iodide symporter, and TSHR gene expression, coincident with decreased MHC class I. Finally, we show that TGF-beta1 increases c-jun RNA levels and induces the formation of new complexes involving c-jun, fra-2, ATF-1, and c-fos, which react with Enhancer A and the DRE. TGF-beta1 effects on c-jun may be a pivotal fulcrum in the hitherto unrecognized coordinate regulation of Enhancer A and the DRE.

Animals↗
PubMed2000

[Elective and emergency minimally invasive surgery in pleural diseases].

In the last years the video-assisted thoracic surgery (V.A.T.S.) assumed an important order for the diagnosis and treatment of the pleural disease. In this particular field, the procedure allows obtaining almost the same outcomes of traditional surgery and is very safety. V.A.T.S. reduces hospital time and trauma with a fast return to the working life. The Authors describe their experience and outline the diagnostic and therapeutic indications for the treatment of choice and emergency.

Elective Surgical Procedures↗
PubMed1999

Zinc sulfate supplementation improves thyroid function in hypozincemic Down children.

In subjects affected by trisomy 21 (Down syndrome), hypothyroidism is the most common endocrinological deficit. Plasma zinc levels, which are commonly detected below the normal range in Down patients, are related to some endocrinological and immunological functions; in fact, zinc deficiency has been shown to impair immune response and growth rate. Aims of this study were to evaluate (1) the role of zinc deficiency in subclinical hypothyroidism and (2) thyroid function changes in Down children cyclically supplemented with zinc sulfate. Inverse correlations have been observed between age and triiodotironine (T3) and between zinc and thyroid-stimulating hormone (TSH); higher TSH levels have been found in hypozincemic patients at the beginning of the study. After 6 mo of supplementation, an improvement of thyroid function (TSH levels: 3.96 +/- 1.84 vs 2.64 +/- 1.33 mUI/mL basally and after 6 mo, respectively) was observed in hypozincemic patients. In the second cycle of supplementation, a similar trend of TSH was observed. At the end of the study, TSH significantly decreased in treated hypozincemic subjects (4.48 +/- 1.93 vs 2.96 +/- 1.20 mUI/mL) and it was no longer different in comparison to normozincemic patients. We suggest zinc supplementation to the diet in hypozincemic Down children as a simple and useful therapeutic tool.

Adolescent↗
PubMed1999

Interactions between anticonvulsant and psychoactive drugs.

This review considers the relevance of pharmacokinetic interactions between antiepileptic drugs (AEDs) and psychoactive drugs in the treatment of mood disorders in patients with epilepsy. The determination of plasma levels of some of these drugs (mainly the AEDs) has enabled clinicians to evaluate the kinetic modifications during the course of such combined therapies and to adjusting the dosages in cases of subtherapeutic or toxic levels. In general, phenobarbital, phenytoin, and carbamazepine stimulate the catabolic degradation of tricyclic antidepressants (TCAs), and TCAs have an inhibitory effect on the elimination of AEDs. The newer antidepressants that selectively inhibit the reuptake of serotonin (SSRIs), although in different fashions for the different substances (fluoxetine, fluvoxamine, paroxetine) may cause an increase of plasma AED levels through inhibition of the isoenzyme P450 2D6. Similarly, antipsychotics (APs) are more rapidly metabolized when AEDs are co-administered, whereas AED metabolism is scarcely influenced by AP. Finally, plasma levels of tranquilizers are lowered by AED co-therapy. As the concomitant administration of AED and psychoactive drugs becomes increasingly used for treatment of mood disorders in patients with or without epilepsy, therapeutic drug monitoring may be useful in designing correct and rational therapy.

Anticonvulsants↗
PubMed1999

Combination versus sequential doxorubicin and docetaxel as primary chemotherapy for breast cancer: A randomized pilot trial of the Hoosier Oncology Group.

PURPOSE: To evaluate the efficacy and toxicity of combination and sequential dose-dense chemotherapy with doxorubicin and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) as primary chemotherapy of breast cancer. PATIENTS AND METHODS: Patients with newly diagnosed stage II or noninflammatory stage III breast cancer were randomly assigned to receive the same total doses of doxorubicin and docetaxel over a 12-week period before definitive surgery. Patients in arm A received sequential therapy with doxorubicin 75 mg/m(2) every 2 weeks for three cycles followed by docetaxel 100 mg/m(2) every 2 weeks for three cycles. Patients in arm B received combination therapy with doxorubicin 56 mg/m(2) plus docetaxel 75 mg/m(2) every 3 weeks for four cycles. Granulocyte colony-stimulating factor was administered on days 2 to 12 of each cycle in both groups. RESULTS: Forty patients were entered onto the trial. Pretreatment tumor size averaged 5.7 cm with clinically positive axillary lymph nodes in 23 patients (57%). As expected, myelosuppression was severe in both groups; however, >/= 80% of planned dose-intensity was delivered. Hand-foot syndrome was more common after sequential therapy. Clinical responses were similar in both groups, with an overall response rate of 87%, including 20% clinical complete remissions. Pathologic complete remission or residual in situ disease only was confirmed in five patients (12.8%). Patients who received sequential therapy had fewer positive lymph nodes (mean, 2.17 v 4.81; P <.037) at definitive surgery. CONCLUSION: Primary chemotherapy with doxorubicin and docetaxel is well tolerated and highly active. A sequential treatment schedule increases toxicity but may result in more substantial lymph node clearance than combination therapy.

Adult↗