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Biomedical subjects

V Parisi

Publications and source records attributed to V Parisi.

At least 37 records · Page 2Linked to original sources

Detection of circulating tumor cells in carcinoma patients by a novel epidermal growth factor receptor reverse transcription-PCR assay.

The epidermal growth factor receptor (EGFR) is overexpressed in 50-70% of human primary breast, lung, and colon carcinomas, whereas it is not usually expressed in hematopoietic cells. We developed a novel reverse transcription-PCR (RT-PCR)-Southern blot assay for the detection of circulating, EGFR mRNA-expressing tumor cells in carcinoma patients. The assay was set up by increasing the amount of cDNA step by step in the PCR reaction. The highest sensitivity and specificity were found when using 800 ng of cDNA in the PCR reaction. Peripheral blood samples from 91 patients with either colon (38), lung (30), or breast (23) carcinomas and from 38 healthy volunteers were analyzed. EGFR transcripts were found in 44 of 75 (59%) patients with metastatic carcinoma and in 4 of 38 (10.5%) healthy donors (P < 0.001; chi2 test). The expression of EGFR, cytokeratin 19, and carcinoembryonic antigen mRNA in blood samples from patients with metastatic colon carcinoma was compared. EGFR, cytokeratin 19, and carcinoembryonic antigen transcripts were found in 8 of 11 (73%), 3 of 11 (27%), and 5 of 11 (45%) patients, respectively. Furthermore, two of seven (29%) Dukes' B and five of nine (55%) Dukes' C colon carcinoma patients were found to express EGFR mRNA in the peripheral blood. All patients that expressed EGFR transcripts in the peripheral blood were found to express the EGFR protein in the corresponding primary carcinoma, as assessed by immunohistochemistry. These data suggest that the EGFR assay that we developed is a highly specific and sensitive technique to detect circulating tumor cells in patients affected by different carcinoma types.

Breast Neoplasms↗

A novel parameter to estimate the minimum number of bound ligands needed to activate an ion channel.

We consider the Hill coefficient obtained from concentration-response curves and we stress the differences between the use of binding and the use of current for the response. We first show that in order to estimate the cooperativity of binding sites one must use the coefficient obtained from the binding curves and not that obtained from the current curves. For what concerns the estimation of the minimum number of bound ligands needed to activate the channel, while the coefficient obtained from the binding is simply not applicable, we show that the coefficient obtained from the current is not appropriate. We finally introduce a novel parameter that predicts the number of ligand molecules required to open the channel from current measurements at very low ligand concentration. The above considerations are exemplified by a few theoretical models.

Animals↗

Effects of nicergoline on the retinal and cortical electrophysiological responses in glaucoma patients: a preliminary open study.

PURPOSE: The retinal dysfunction and the delayed visual cortex responses shown by patients affected by glaucoma can be objectively assessed by Pattern Electroretinogram (PERG) and Visual Evoked Potentials (VEP) recordings. The present study aims to evaluate the effects of nicergoline on the retinal function and on the visual cortical responses in glaucoma patients. METHODS: Sixty patients (mean age 44.6+/-3.7) with open angle glaucoma were enrolled. The patients were divided into two groups: NG Group, where 30 patients were treated with nicergoline (Cebran((R)), 2 cps day) for 30 days; and CG Group, where 30 patients were not treated. Simultaneous recordings of PERG and VEP were performed in NG patients at the baseline, at 30 days after treatment with nicergoline (day 30), and at 45 days from the end of the treatment (day 75). PERG and VEP were recorded in CG patients at the baseline and after 30 and 75 days. The visual stimulus for recording PERGs and VEPs was a checkerboard whose elements subtended a visual arc of 60' and 15' with a 70% contrast, and alternated at a frequency of 2 Hz. RESULTS: At the baseline none of the electrophysiological parameters observed in NG Group patients differed (P>0.05) from those of CG Group patients. At days 30 and 75, in CG Group patients the values of the PERG and VEP parameters were unmodified (P>0.05) with respect to the baseline. In NG Group patients, the 30-day treatment period with nicergoline induced a significant (P<0.01) improvement of the PERG and VEP parameters. At day 75 all the electrophysiological parameters of NG Group did not differ significantly (P>0.05) from those at the baseline. CONCLUSION: Treatment with nicergoline induces an improvement of the retinal function and of the visual cortical responses in patients affected by glaucoma. This effect disappears within 45 days after the suspension of the treatment.

Adrenergic alpha-Antagonists↗

Cytidine-5'-diphosphocholine (citicoline) improves retinal and cortical responses in patients with glaucoma.

PURPOSE: To evaluate the effects of cytidine-5'-diphosphocholine (citicoline) on retinal function and on cortical responses in patients with glaucoma. DESIGN: Randomized clinical trial. PARTICIPANTS: Forty patients with open-angle glaucoma were randomly divided into two age-matched groups: citicoline group ([GC] n = 25) and placebo group ([GP] n = 15). METHODS: The GC patients were treated with Neuroton (citicoline, 1000 mg/day intramuscularly) for 60 days; GP patients were treated with placebo (physiologic solution with additives) for 60 days. After 120 days of washout (day 180), the GC patients were divided into two age-matched groups: in 10 patients (GC1 group) the washout was prolonged for a further 120 days; in 15 patients (GC2 group) a second 60-day period of citicoline treatment was followed by a second 120-day period of washout. At day 180, the washout was extended for another 180 days in GP patients. In all subjects, retinal and cortical responses were evaluated by simultaneous recordings of visual evoked potentials (VEPs) and pattern-electroretinograms (PERGs) at baseline, after 60 days, and after 180 days. At day 300, VEPs and PERGs were also evaluated in GC1 patients, and at 240 and 360 days in GC2 and GP patients. MAIN OUTCOME MEASURES: Visual evoked potential parameters (P100 latency and N75-P100 amplitude); PERG parameters (P50 latency and P50-N95 amplitude); and intraocular pressure. RESULTS: The GP patients displayed similar VEP and PERG parameters in all examinations performed. In GC patients, the treatment with citicoline induced a significant (P < 0.01) improvement of VEP and PERG parameters, and their values were significantly different (P < 0.01) with respect to those of GP patients (P < 0.01). Visual evoked potentials and PERGs, recorded in GC patients after washout, revealed that although there was a worsening trend, the electrophysiologic improvement was still maintained. After a second period of washout, GC1 patients had VEP and PERG parameters similar (P > 0.05) to baseline ones and to those of GP patients. In GC2 patients, a second period of citicoline treatment induced a further (P < 0.01) improvement of VEP and PERG parameters CONCLUSION: Citicoline may induce an improvement of the retinal and of the visual pathway function in patients with glaucoma.

Cytidine Diphosphate Choline↗

Major surgery for a gastric cancer in a haemophilic with high inhibitor titre successfully performed by the use of recombinant FVIIa.

A total gastrectomy with omentectomy and resection of the distal oesophagus in a 69-year-old haemophilia A patient with high inhibitor of 128 Bethesda units is described. Surgery was successfully performed after infusion of 112 microg kg-1 bw of recombinant FVIIa. Ninety-two microg kg-1 were given thereafter at time intervals of 2 h until 12 h, then every 3 h until 24 h, and every 4 h until 48 h after surgery. Doses were gradually reduced in the following days and finally discontinued on day 28 after surgery. The complete treatment schedule required the administration of a total of 708 mg of recombinant FVIIa. Using this approach, we observed normal haemostasis, and there were no signs of excessive postoperative bleeding or wound haematoma. No clinical side-effects or evidence of systemic activation of coagulation occurred during the treatment. As judged from the clinical course of this major surgery, recombinant FVIIa appears to be highly efficacious and safe and should be used as first line treatment in high titre inhibitor patients with cross-reactivity to porcine factor VIII, undergoing surgery.

Aged↗

Visual function correlates with nerve fiber layer thickness in eyes affected by ocular hypertension.

PURPOSE: To test whether the high variability observed when measuring pattern electroretinogram (PERG), visual evoked potentials (VEP), and spatial contrast sensitivity (SCS) in eyes with ocular hypertension is associated with variation in nerve fiber layer thickness, as measured by optical coherence tomography (OCT). METHODS: The study involved 32 untreated eyes (32 patients; age range, 29-64 years) showing a normal whiteon-white 24/2 Humphrey (San Leandro, CA) perimetry, IOP between 23 and 28 mm Hg, best corrected acuity of 20/20 or better, and none of the following papillary signs on conventional color stereo slides: rim notch(es), peripapillary splinter hemorrhages, or increased vertical-to-horizontal cup-to-disc ratio. On recruitment, each eye underwent SCS testing, OCT, PERG, and VEP recordings. Linear regression (Pearson's test) or Spearman's rank regression was adopted for the analysis of the data. RESULTS: The 95% confidence limits of the electrophysiological data were: PERG P50 latency, 59.3 to 63 msec; PERG P50 to N95 amplitude, 0.74 to 1.15 cmV; VEP P100 latency, 113 to 118 msec; VEP N75 to P100 amplitude, 3.81 to 4.90 micromV. The 360 degrees nerve fiber layer thickness overall (NFLO) ranged between 113 and 169 microm (145+/-16 microm; mean+/-SD) and significantly correlated with PERG P50 to N95 amplitude (r: 0.518; P = 0.002), PERG P50 latency (r: -0.470; P = 0.007), VEP N75 to P100 amplitude (r: 0.460; P = 0.008), VEP P100 latency (r = -0.422; P = 0.016) and SCS at 3 cyc/deg (r: -0.358; P = 0.044). CONCLUSIONS: The variability of PERG, VEP, and SCS testing observed in eyes with ocular hypertension is associated with differences in NFL thickness (the thinner the layer, the worse the visual function).

Adult↗

Correlation between morphological and functional retinal impairment in multiple sclerosis patients.

PURPOSE: To assess whether a correlation exists between optic nerve fiber layer (NFL) thickness and the retinal or visual pathway function in multiple sclerosis (MS) patients previously affected by optic neuritis. METHODS: Fourteen patients with a diagnosis of definite MS were examined. All had been affected by optic neuritis (MSON) with complete recovery of visual acuity (14 eyes included in study). These were compared with 14 eyes from 14 age-matched control subjects. NFL thickness was measured by optical coherence tomography (OCT). Three different measurements in each quadrant (superior, inferior, nasal, and temporal) were taken and averaged. The data in all quadrants (12 values averaged) were identified as NFL Overall, whereas the data obtained in the temporal quadrant only (3 values averaged) were identified as NFL Temporal. Retinal and visual pathway function was assessed by simultaneously recording pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) using high-contrast (80%) checkerboard stimuli subtending 15 minutes and 60 minutes of the visual arc (min arc) and reversed at the rate of two reversals per second. RESULTS: In MSON eyes there was a significant (P < 0.01) reduction in NFL thickness in both NFL Overall and NFL Temporal evaluations compared with the values observed in control eyes. PERG, (15-min arc checks) and VEP (15-min arc and 60-min arc checks), showed a significant (P < 0.01) delay in latency and reduction in amplitude. NFL Overall and NFL Temporal values were significantly correlated (P < 0.01) to the PERG P50 latency and P50 to N95 amplitude recorded with 15-min arc checks. No correlations (P > 0.01) between NFL values and the other electrophysiological data (PERG recorded with 60-min arc checks and VEP recorded with 15-min arc and 60-min arc checks) were found. CONCLUSIONS: There is a correlation between PERG changes and NFL thickness in MS patients previously affected by optic neuritis, but there is no correlation between VEP changes and NFL thickness.

Adult↗

Are only repeated triplets guilty?

It is well known that in some places of the human genome one finds a variable number of tandem repeats of trinucleotides; it is now commonly acknowledged that in many cases an excessive expansion of such a number is the cause of nervous system diseases. Moreover there exist cases of genetic disorders linked with loci where a variable number of tandem repeats of sequences longer than three bases has been found. The abnormal number of these repeats in few cases has been associated with the onset of the disease. Considering the above facts, we have performed an extensive study of published sequences of genes connected with various diseases. We have examined, inside or near those genes, all possible tandem repeats. The analysis has led to the detection of a large number of repeats of both triplets and longer sequences, many of which, as far as we know, had not been pointed out before. The results of our analysis lead us to put forward the hypothesis that in more cases than those till now established, a variable number of tandem repeats of generic sequences, not only of triplets, could be associated with disease onset. Finally we suggest to allocate experimental researches for all the possible tandem repeats and their possible correlation with the neurodegenerative disorders and with other kinds of syndromes.

Base Sequence↗

Impaired VEP after photostress response in multiple sclerosis patients previously affected by optic neuritis.

The aim of our work was to evaluate if an optic nerve involvement (multiple sclerosis patients previously affected by optic neuritis) may induce any change in visual evoked potential (VEP) after photostress response. VEP in basal conditions and after photostress were assessed in 10 patients with defined multiple sclerosis without a history of optic neuritis (MSWO); in 14 patients with defined multiple sclerosis previously affected by optic neuritis but with complete recovery of the visual acuity (MSON) and in 14 age-matched controls. In order to complete the investigation of the retinal function, Transient Pattern electroretinogram (PERG) and steady-state focal-ERG (counterphased gratings presented at 8 Hz in the macular region) were performed in MSON patients only. In MSWO eyes VEP parameters in basal condition and after photostress did not undergo significant changes compared to controls (ANOVA; P > 0.05). In MSON eyes we observed basal VEP with delayed P100 peak latency and reduced N75-P100 amplitude when compared with the control ones (P < 0.01). In MSON eyes the parameters of VEP after photostress underwent large changes and longer recovery time (RT) than in control and MSWO eyes (P < 0.01). In addition; in MSON eyes we found increased transient PERG P50 latency (P < 0.01) and reduced P50-N95 amplitude (P < 0.01); Focal-ERG (that displays a major component at 16 Hz; 2nd harmonic:2P) with reduced 2P amplitudes and delayed 2P phases (P < 0.01). Our results indicate that patients previously affected by optic neuritis present an abnormal VEP after photostress response and this may be ascribed predominantly to an involvement of the inner retinal layers as indicated by the concomitant impairment of PERG and focal-ERG responses.

Adult↗

Neural conduction in visual pathways in newly-diagnosed IDDM patients.

OBJECTIVES: Visual evoked potentials (VEPs) show abnormal responses in newly-diagnosed insulin-dependent diabetic (IDDM) patients. Electrophysiological methods allow one to dissect and explore different structures contributing to neural conduction in the visual pathways. The aim of our work was to assess whether the VEP abnormalities are due to impaired function of the retinal layers and/or a delayed conduction in the postretinal visual pathways. METHODS: Simultaneous recordings of VEP and pattern-electroretinogram (PERG) were performed at two intervals (at entry of the study and after 3 months) in 14 newly-diagnosed IDDM patients (age: 24.8+/-6.8 years; duration of disease: 3+/-1.5 months), and in 14 age-matched control subjects. RESULTS: In comparison with control subjects, IDDM patients showed: VEP P100 latencies significantly delayed (P < 0.01), a significant impairment of all PERG parameters (P < 0.01) and retinocortical time (RCT, difference between VEP P100 and PERG P50 latencies) and latency window (LW, difference between VEP N75 and PERG P50 latencies) also significantly increased (P < 0.01). All electrophysiological parameters were not significantly changed when retested after 3 months. No correlations were found between VEP P100 latency, RCT, LW and PERG parameters. CONCLUSIONS: Impaired PERG indicates an involvement of the innermost retinal layers; increased values of RCT and LW represent an index of delayed neural conduction in the postretinal visual pathways. Therefore two sources, one retinal (impaired PERG) and one postretinal (delayed RCT and LW), may independently contribute in to the abnormal responses of VEP observed in newly-diagnosed IDDM patients. Three months of relatively-stable metabolic control have not normalized the VEP and PERG impairment.

Adolescent↗

Outcome of 67 patients with hepatocellular cancer detected during screening of 1125 patients with chronic hepatitis.

OBJECTIVE: We performed this prospective screening trial in chronic hepatitis virus-infected patients to determine the incidence of hepatocellular cancer (HCC) and the resectability and long-term survival rates of these HCC patients. SUMMARY BACKGROUND DATA: Chronic hepatitis B or C virus infection is a major etiologic factor in human HCC. It is not clear if routine screening of chronic viral hepatitis patients improves the survival of patients who develop HCC. METHODS: Screening for HCC was offered to patients chronically seropositive (>5 years) for hepatitis B or C infection. All patients underwent percutaneous core liver biopsy to assess the histologic severity of chronic liver injury. Patients were screened initially and every 3 months thereafter with serum alpha-fetoprotein and transabdominal ultrasound evaluations; HCC was confirmed by needle biopsy of liver tumors. RESULTS: Screening was performed on 1125 hepatitis-positive patients (804 with hepatitis C, 290 with hepatitis B, 31 with both). On liver biopsy, 800 patients had mild chronic active hepatitis and 325 had severe chronic active hepatitis, cirrhosis, or both. Initial screening detected HCC in 61 patients. HCC was detected in six more patients during follow-up; thus, the incidence of HCC was 5.9% (67/1125). However, 66 of the 67 HCC cases (98.5%) arose in the 325 patients with severe chronic active hepatitis or cirrhosis (66/325 [20.3%] vs. 1/800 [0.1%], p < 0.0001 [Wilcoxon signed rank]). Median follow-up of the 67 HCC patients was 24 months. Locally advanced or metastatic, unresectable HCC occurred in 43 patients (64.2%); 24 patients (35.8%), including the 6 patients detected during follow-up screening, underwent margin-negative resection. The median survival for the 24 resected patients was 26 months, compared to 6 months for the 43 patients with unresectable cancer (p < 0.0001, Wilcoxon signed rank). CONCLUSIONS: HCC was found to arise in 20.3% of patients with chronic hepatitis B or C infection and severe liver injury. Initial screening detected resectable lesions in less than half the HCC patients. Routine screening of chronic hepatitis B or C virus-infected patients with ultrasound and alpha-fetoprotein determination should be reserved for patients with severe chronic active hepatitis, cirrhosis, or both.

Adult↗

Electrophysiological evaluation of the macular cone system: focal electroretinography and visual evoked potentials after photostress.

In this article, the methodologies and clinical applications of two electrophysiological tests, the focal electroretinogram (FERG) and the visual evoked potentials (VEPs) after photostress, are described. These techniques provide somewhat complementary results about macular function because they tap the activity of different neural substrates along the pathway of the cone system and allow evaluation of the macular function under steady-state (ie, the FERG) or dynamic (ie, the VEPs after photostress) conditions. The results obtained in patients with different macular pathologies indicate that while the FERG provides direct information about the extent and sites of macular dysfunction, the VEPs after photostress represent an objective, although not specific, index of the dynamic properties of macular performance after exposure to intense light stimulation. The combined use of both techniques appears to be promising for gaining further insights into the diagnosis and pathophysiology of macular diseases.

Electroretinography↗

A study of oligonucleotide occurrence distributions in DNA coding segments.

In this paper we present a general strategy designed to study the occurrence frequency distributions of oligonucleotides in DNA coding segments and to deal with the problem of detecting possible patterns of genomic compositional inhomogeneities and disuniformities. Identifying specific tendencies or peculiar deviations in the distributions of the effective occurrence frequencies of oligonucleotides, with respect to what can be a priori expected, is of the greatest importance in biology. Differences between expected and actual distributions may in fact suggest or confirm the existence of specific biological mechanisms related to them. Similarly, a marked deviation in the occurrence frequency of an oligonucleotide may suggest that it belongs to the class of so-called "DNA signal (target) sequences". The approach we have elaborated is innovative in various aspects. Firstly, the analysis of the genomic data is carried out in the light of the observation that the distribution of the four nucleotides along the coding regions of the genoma is biased by the existence of a well-defined "reading frame". Secondly, the "experimental" numbers found by counting the occurrences of the various oligonucleotide sequences are appropriately corrected for the many kinds of mistakes and redundancies present in the available genetic Data Bases. A methodologically significant further improvement of our approach over the existing searching strategies is represented by the fact that, in order to decide whether or not the (corrected) "experimental" value of the occurrence frequency of a given oligonucleotide is within statistical expectations, a measure of the strength of the selective pressure, having acted on it in the course of the evolution, is assigned to the sequence, in a way that takes into account both the value of the "experimental" occurrence frequency of the sequence and the magnitude of the probability that this number might be the result of statistical fluctuations. If the strength of the selective pressure evaluated in this fashion turns out to be sufficiently large, the corresponding sequence will be considered to have an occurrence frequency beyond expectations and, hence, to be statistically and biologically interesting.

Algorithms↗

Neural conduction in the visual pathways in ocular hypertension and glaucoma.

BACKGROUND: The aim of our work was to evaluate neural conduction in visual pathways in subjects with ocular hypertension and glaucoma. METHODS: We assessed simultaneous recordings of pattern electroretinograms (PERG) and visual evoked potentials (VEP) in 16 subjects with ocular hypertension (OHT), in 16 subjects with primary open-angle glaucoma (POAG) and in 15 age-matched controls. The visual stimuli were checkerboard patterns (the check edges subtend 15 min of visual arc; contrast 70%) reversed at the rate of 2 reversals/s. RESULTS: In OHT and POAG patients we found PERG and VEP latencies significantly longer than in controls. The P50-N95 PERG amplitudes were significantly reduced in OHT and POAG eyes. VEP amplitudes were significantly reduced in POAG eyes, while in OHT they were similar to controls. The retinocortical time (RCT; difference between VEP P100 latency and PERG P50 latency) was longer in POAG patients than in controls; no differences between patients with OHT and controls were observed. Moreover, we observed that in POAG the longer RCT was inversely related to the PERG amplitude. CONCLUSION: Our results suggest that involvement of the innermost retinal layers in POAG is accompanied by slowed neural conduction in the visual pathways.

Electroretinography↗

Electrophysiological assessment of visual function in IDDM patients.

Various electrophysiological tests have been employed to reveal functional abnormalities at different levels of the visual system in insulin-dependent diabetic (IDDM) patients. The aim of our work was to assess, with a comprehensive neurophysiological protocol evaluating the retinal, macular and visual pathways functions, whether and when such electrophysiological abnormalities do appear in IDDM patients free of any fluorangiographic sign of retinopathy with various disease duration. Flash-electroretinogram (ERG), oscillatory potentials (OPs), pattern-electroretinogram (PERG), and visual evoked potentials (VEPs) in basal condition and after photostress were assessed in 12 control subjects (C) and 42 aged-matched IDDM patients without clinical retinopathy (DR-) divided, on the basis of the disease duration, into 4 groups (1-5, 6-10, 11-15, 16-20 years). In addition another age-matched group of IDDM patients with a background retinopathy (DR+; n = 12; duration of disease 18 +/- 49 years) was evaluated. In all IDDM DR-patients PERG and VEP were significantly impaired. In addition, groups 11-15 and 16-20 years displayed impaired OPs. All electrophysiological parameters were further impaired in DR+ patients. In conclusion, retinal, macular and visual pathways functions are differently impaired in IDDM (DR-) patients with different disease duration. Electrophysiological impairment starts in the nervous conduction of the visual pathways with an early involvement, goes on in the innermost retinal layers and in the macula and ends in the middle and outer retinal layers.

Adult↗

A discriminant function for preeclampsia: case-control study of minor hemoglobins, red cell enzymes, and clinical laboratory values.

A case-control study was performed in eight pairs of women to determine whether preeclamptic women developed abnormalities in minor hemoglobins, glycolytic enzymes, or other blood components that might provide insight into the pathophysiology of preeclampsia, or that in combination might be used as a marker for the condition. These variables and standard clinical tests were analyzed as discriminators between preeclamptic and control women. The subjects were matched for age, ethnicity, parity, and gestational age. Blood samples were taken at the time of diagnosis of preeclampsia and at comparable gestational ages for matched normal controls. Variables differing significantly between groups included increases in uric acid (UA), low-density lipoproteins (LDL), phosphoglycerate kinase (PGK), and mean platelet volume (MPV), and decreases in glyceraldehyde phosphate dehydrogenase (G3PD) in preeclamptic women compared to normal controls. Discriminant analysis revealed the following function to separate the groups: 0.7764 (UA) + 0.8086 (PGK) -0.7032 (G3PD) + 0.1399 (LDL) -0.2386 (MPV). A discriminant score of > or = 275 indicated a > or = 90% probability of preeclampsia. The results are consistent with perturbations in red cell glycolysis in preeclampsia. Further prospective studies are warranted to test the efficacy of this discriminant function in predicting preeclampsia.

Adult↗