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Biomedical subjects

M De Luca

Publications and source records attributed to M De Luca.

At least 19 recordsLinked to original sources

Cardiac protection by volatile anaesthetics: a multicentre randomized controlled study in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

BACKGROUND AND OBJECTIVES: To evaluate the effects of total intravenous anaesthesia vs. volatile anaesthesia on cardiac troponin release in coronary artery bypass grafting with cardiopulmonary bypass, we performed a multicentre randomized controlled study to compare postoperative cardiac troponin release in patients receiving two different anaesthesia plans. METHODS: We randomly assigned 75 patients to propofol (intravenous anaesthetic) and 75 patients to desflurane (volatile anaesthetic) in addition to an opiate-based anaesthesia for coronary artery bypass grafting. Peak postoperative troponin I release was measured as a marker of myocardial necrosis. RESULTS: There was a significant (P < 0.001) difference in the postoperative median (25th-75th percentiles) peak of troponin I in patients receiving propofol 5,5 (2,3-9,5) ng dL(-1) when compared to patients receiving desflurane 2,5 (1,1-5,3) ng dL(-1). The median (interquartile) troponin I area under the curve analysis confirmed the results: 68 (30.5-104.8) vs. 36.3 (17.9-86.6) h ng dL(-1) (P = 0.002). Patients receiving volatile anaesthetics had reduced need for postoperative inotropic support (24/75, 32.0% vs. 31/75, 41.3%, P = 0.04), and tends toward a reduction in number of Q-wave myocardial infarction, time on mechanical ventilation, intensive care unit and overall hospital stay. CONCLUSIONS: Myocardial damage measured by cardiac troponin release could be reduced by volatile anaesthetics in coronary artery bypass surgery.

Aged↗

Patient re-training in peritoneal dialysis: why and when it is needed.

The aim of this multicenter, quantitative, observational study was to analyze compliance and re-training needs of patients on peritoneal dialysis (PD) through the assessment of patient knowledge (with a Patient Questionnaire; phase 1) and patient behavior (home visit with a Score Card; phase 2). A total of 353 patients from 11 Italian centers participated in the first phase and 191 patients from nine centers in the second phase. Overall, 66% of questions on the Patient Questionnaire were answered correctly. Correct answers were more frequent in females than males, in patients under 55 years of age, and in those with higher education. The lowest rate of correct answers involved questions related to diet and physical activity (67% and 51%, respectively). Data collected during the home visit showed that 25% of patients were partially compliant with their drug therapy. Twenty-three percent of patients were non-compliant with the exchange protocol procedures, with a significant association between compliance and the incidence of peritonitis, and 11% were non-compliant with the exit-site protocol procedures without a statistically significant correlation to peritonitis. By combining the two evaluations, we found that approximately one-third (29%) of patients needed reinforcement of knowledge and ability to correctly perform PD as related to infection control and 27% for the correct use of drugs. Looking at the combined evaluation of infection control and drug use, results showed that 47% of patients needed re-training. This need for re-training was greater for younger patients (less than 55 years old), patients with lower education degree and patients in the early or late phase of PD therapy (less than 18 months or more than 36 months). Gender and degree of autonomy had no effect on the need for re-training.

Aged↗

fMRI resting state networks define distinct modes of long-distance interactions in the human brain.

Functional magnetic resonance imaging (fMRI) studies of the human brain have suggested that low-frequency fluctuations in resting fMRI data collected using blood oxygen level dependent (BOLD) contrast correspond to functionally relevant resting state networks (RSNs). Whether the fluctuations of resting fMRI signal in RSNs are a direct consequence of neocortical neuronal activity or are low-frequency artifacts due to other physiological processes (e.g., autonomically driven fluctuations in cerebral blood flow) is uncertain. In order to investigate further these fluctuations, we have characterized their spatial and temporal properties using probabilistic independent component analysis (PICA), a robust approach to RSN identification. Here, we provide evidence that: i. RSNs are not caused by signal artifacts due to low sampling rate (aliasing); ii. they are localized primarily to the cerebral cortex; iii. similar RSNs also can be identified in perfusion fMRI data; and iv. at least 5 distinct RSN patterns are reproducible across different subjects. The RSNs appear to reflect "default" interactions related to functional networks related to those recruited by specific types of cognitive processes. RSNs are a major source of non-modeled signal in BOLD fMRI data, so a full understanding of their dynamics will improve the interpretation of functional brain imaging studies more generally. Because RSNs reflect interactions in cognitively relevant functional networks, they offer a new approach to the characterization of state changes with pathology and the effects of drugs.

Adult↗

Epidural block does not worsen oxygenation during one-lung ventilation for lung resections under isoflurane/nitrous oxide anaesthesia.

BACKGROUND AND OBJECTIVES: The aim of this prospective, randomized, controlled clinical study was to evaluate the effects of thoracic epidural anaesthesia combined with isoflurane/nitrous oxide anaesthesia on intraoperative oxygenation during one-lung ventilation for lung resections. METHODS: Forty patients were randomly allocated to receive general anaesthesia maintained with isoflurane/nitrous oxide (group General, n = 20) or the same anaesthetic combined with thoracic epidural anaesthesia (group Integrated, n = 20). All patients were mechanically ventilated with the same settings (FiO2 = 0.5; VT = 9 mL kg(-1); inspiratory: expiratory time = 1:1; inspiratory pause = 10%). Effects on oxygenation were evaluated by determining the changes in PaO2/FiO2 ratio at 10, 30, 45 and 60 min of one-lung ventilation as compared to values obtained after induction of anaesthesia (supine, two-lung ventilation). RESULTS: The PaO2/FiO2 ratio was decreased in both groups during one-lung ventilation until the end of surgery. No differences were found at any observation time between the groups. Ventilation with 100% oxygen because of SpO2 decrease <92% was required in nine patients of group General (45%) and in eight patients of group Integrated (40%) (P = 0.64). Manual re-inflation of the operated lung was required in one patient of group General only (P = 0.99). Heart rate was lower in group Integrated than in group General throughout the study. No differences between the two groups in mean arterial pressure were observed. CONCLUSIONS: Adding a thoracic epidural block to isoflurane/nitrous oxide anaesthesia during one-lung ventilation for lung resections does not result in clinically relevant detrimental effects on intraoperative oxygenation.

Anesthesia, Epidural↗

Hypertension in headache patients? A clinical study.

OBJECTIVES: The aim of the present study was to assess the prevalence of hypertension in patients with headache, coming to the observation of an Headache Center. MATERIALS AND METHODS: A total of 1486 consecutive outpatients were examined, and blood pressure was determined in all patients. RESULTS: Migraine without aura (MO) was the most common diagnosis, followed by migraine associated with tension-type headache, migraine with aura (MA), episodic tension-type headache (ETTH), chronic tension-type headache (CTTH), cluster headache (CH), and medication-overuse headache (MOH). Hypertension was present in 28% of the patients, and it was particularly common in MOH (60.6%), CTTH (55.3%), CH (35%), ETTH (31.4%), less common in MO (23%) and MA (16.9%). In all headache groups, the prevalence of hypertension was higher than in the general population, within all age groups. After adjustment for age and gender, hypertension was found to be more common in tension-type, and especially in CTTH, than in migraine. These findings could be affected by 'Berkson's bias': and should not be extrapolated to the general population, but apply only to the subpopulation of patients who come to the observation of an Headache Center, and who may have more disabling symptoms. CONCLUSION: Hypertension could be one of the factors leading to exacerbation of the frequency and severity of attacks, both in migraine and tension-type headache. Hypertension has important therapeutic implications and should be actively sought in headache patients, and more thoroughly investigated, with ad-hoc surveys in the general population.

Adult↗

[Spontaneous splenic rupture in a patient with cytomegalovirus infection].

The Authors report a case of spontaneous splenic rupture in a patient with Cytomegalovirus infection, stress the main characteristics of this infection and describe the mechanism that, during the viral infection, causes morphological and functional alterations of the spleen. The hypersplenism secondary to hyperfunctioning, the formation of immunocomplexes with secondary infarction, mainly of the white pulp, and the disseminated intravascular coagulation are responsible, as in the observed case, of the rupture of splenic capsula. The Authors conclude that the wide diffusion of Cytomegalovirus infection needs the knowledge of all the pathologic signs of this infection to make a timely diagnosis and treatment.

Adult↗

Bone regeneration after removal of a mandibular cyst and following prosthetic rehabilitation with implants. Case report.

This study shows the spontaneous bone regeneration after a Partch II surgical operation without using filling materials. The following functional and esthetic rehabilitation was made with overdenture on implants even in the recovery zone. A male patient, 59 years old, with a cystic lesion of 3.5 mm diameter in the mandibular bone was submitted to surgical enucleation of this neoformation. Postoperative radiological examinations, orthopantomography and TC DentaScan were performed to value the bone regeneration. Four implants of 10 mm diameter and 4.1 mm length were subsequently fixed in the mandibular bone and also in the regeneration area. Then, the rehabilitation of the patient with an overdenture on implants was possible. Radiographic controls after cystic enucleation showed a good recovery of the region occupied by the neoformation. The implants fixed proved to be solid and it was possible to carry out an overdenture on them. The cystectomy alone, performed with conservative technique, without subsequent filling of the remaining cavity with biointegrative materials, permitted bone regeneration also in a large remaining cavity. This regeneration was sufficient to guarantee the success of the subsequent overdenture on implants, and very good functional and esthetic results in a patient totally edentulous in the mandibular bone.

Bone Regeneration↗

Permanent repigmentation of piebaldism by erbium:YAG laser and autologous cultured epidermis.

BACKGROUND: Several surgical techniques have been proposed for the treatment of piebaldism. These procedures, however, are poorly suited for the treatment of large leucodermal lesions, can cause scars and require multiple donor sites. Recently, it has been reported that autologous cultured epidermis induces scarless repigmentation of large vitiligo lesions, using a single small donor site. OBJECTIVES: To induce permanent repigmentation of large achromic lesions in patients suffering from piebaldism by means of autologous cultured epidermal grafts using a rapid, simple and non-invasive surgical procedure. METHODS: Six patients with piebaldism were enrolled in this study. Achromic epidermis was removed by means of appropriately set erbium:YAG laser and autologous cultured epidermal grafts were applied on to the recipient bed. Melanocyte content was evaluated by 3,4-dihydroxyphenylalanine reaction. The percentage of repigmentation was calculated using a semiautomatic image analysis system. RESULTS: Autologous cultured epidermis, bearing a controlled number of melanocytes, induced repigmentation of all piebald lesions. The mean percentage repigmentation was 95.45% (2791.5 cm2 repigmented/2924.2 cm2 transplanted). CONCLUSIONS: Autologous cultured epidermal grafts induce permanent and complete repigmentation of piebald lesions, in the absence of scars. Erbium:YAG laser surgery is a rapid and precise tool for disepithelialization, hence allowing treatment of large piebald lesions during a single surgical operation.

Adolescent↗

Novel mutations in the CHST6 gene causing macular corneal dystrophy.

Macular corneal dystrophy (MCD) is an autosomal recessive disease characterized by corneal opacities and caused by mutations in a carbohydrate sulfotransferase gene, known as CHST6. MCD type I patients show missense mutations in the CHST6-coding region, and MCD type II patients show a large deletion and replacement in the upstream region of CHST6. The objective of this study was to identify the genetic defect in CHST6 gene causing MCD in Italian families. We investigated MCD genotype by using polymerase chain reaction followed by direct sequencing, and results were confirmed by restriction analysis. An enzyme-linked immunosorbent assay was performed to assess the presence of sulfated keratan sulfate in the serum of MCD patients. Biochemical analysis revealed a MCD type I phenotype in two families and a type II phenotype in another family. Two novel missense mutations and a polymorphism in the coding region of CHST6 gene were identified in patients with MCD type I. In one MCD II family, a homozygous deletion in the upstream region of CHST6 gene was found.

Corneal Dystrophies, Hereditary↗

Long term follow-up of patients affected by temporomandibular joint dysfunction treated with orthodontic and/or prosthetic occlusal therapy.

AIM: Clinical evidences about therapeutic effectiveness of splint therapy and modern concept concerning the etiopathogenesis of temporomandibular disorders (TMD) lead to a review of the therapeutic approach accepted until the middle 90s for the solution of this derangement of the stomathognatic system. Aim of this study is to produce a long term follow-up of a sample of TMD patients, to estimate the validity and utility of the present therapeutic procedures. METHODS: After diagnostical classification of the patients observed, they have been included in a therapeutic protocol. The outcomes obtained (46 patients at the 1st control in 1994 and 38 patients at the last control in 2001) are re-examined with an average follow-up of 10 years. RESULTS: The results obtained showed the efficacy of the therapeutic procedures carried out (36 healed, 9 improved and 1 worsened at the 1994 check-up: on the whole, a successful result in 98% of cases; 17 healed, 21 improved and 8 lost at the 2001 check-up: on the whole, a successful result in 100% of cases), but at present their application has to be reviewed according to a more conservative and careful therapeutic approach, based on the evaluation of some fundamental parameters. CONCLUSION: The rehabilitative occlusal therapy, in its various aspects, is successful in the long term treatment of TDMs, as long as it is used only when it is possible to determine a correct indication.

Adult↗

Evidence of early cortical atrophy in MS: relevance to white matter changes and disability.

OBJECTIVE: To assess cortical gray matter (GM) changes in MS and establish their relevance to clinical disability and to inflammatory changes of white matter (WM) in patients with the relapsing-remitting (RR) and primary progressive (PP) forms of the disease. METHODS: Conventional MRI examinations were obtained in patients with definite MS who had either the RR or the PP form of the disease. An automated analysis tool was used with conventional T1-weighted MR images to obtain total and cortical brain volumes normalized for head size. Total brain lesion load was estimated on conventional proton density and T2-weighted MR images. The relationship between volumetric MR measures and scores of clinical disability was assessed. RESULTS: Normalized cortical volumes (NCV) were lower for both RR and PP MS patients than for normal control subjects (p < 0.001) but were similar between the two patient groups (p > 0.5). NCV decreases in both patients groups were detected even in those patients with short disease duration (<5 years; p < 0.001 in RR MS and p < 0.05 in PP MS) and minimal brain lesion volume (<5 mL; p < 0.0001 in RR MS and p < 0.005 in PP MS). Measures of NCV in individual patients were negatively correlated with T2-weighted lesion volume (r = -0.47, p < 0.001) and disease duration (r = -0.25, p < 0.05) only in the patients with RR MS. NCV correlated with Expanded Disability Status Scale scores across all of the patients, but the strength of the correlation was stronger (p < 0.05) for PP (r = -0.64, p < 0.0001) than for RR (r = -0.27, p = 0.04) MS patients. CONCLUSIONS: These data confirm substantial neocortical volume loss in MS patients and suggest that neocortical GM pathology may occur early in the course of the disease in both RR and PP MS patients and contribute significantly to neurologic impairment. Although a proportion of this neocortical pathology may be secondary to WM inflammation, the extent of the changes suggests that, especially in patients with PP MS, an independent neurodegenerative process also is active.

Adolescent↗

New arylpiperazine derivatives with high affinity for alpha1A, D2 and 5-HT2A receptors.

A series of novel long-chain arylpiperazines bearing a coumarin fragment was synthesized and the compounds were evaluated for their affinity at alpha(1), D(2 )and 5-HT(2A) receptors. Most of the new compounds showed high affinity for the three types of receptors alpha(1A), D(2) and 5-HT(2A) which depends, fundamentally, on the substitution of the N(4) of the piperazine ring. From the series emerged compound 6, which had an haloperidol-like profile at D(2) and 5HT(2A) receptors (pK(i) values of 7.93 and 6.76 respectively). The higher alpha(1A) receptor affinity (pA(2)=9.07) of this compound could contribute to a more atypical antipsychotic profile than the haloperidol.

Algorithms↗

Laparoscopic banding: selection and technique in 830 patients.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) with the Lap-Band has been our first choice operation for morbid obesity since September 1993. Results in terms of complications and weight loss are analyzed. METHODS: 830 consecutive patients (F 77.9%) underwent LAGB. Initial body weight was 127.9 +/- SD 23.9 kg, and body mass index (BMI) was 46.4 +/- 7.2 kg/m2. Mean age was 37.9 (15-65). Steps in LAGB were: 1) establishment of reference points for dissection (equator of the balloon inflated with 25 cc air and left crus); 2) creation of a retrogastric tunnel above the bursa omentalis; 3) creation of "virtual" pouch; 4) embedding the band. RESULTS: Mortality was 0, conversion 2.7%, and follow-up 97%. Major complications requiring reoperation developed in 3.9% (36 patients). Early complications were 1 gastric perforation (requiring band removal) and 1 gastric slippage (requiring repositioning). Late complications included 17 stomach slippages (treated by band repositioning in 12 and band removal in 5), 9 malpositions (all treated by band repositioning), 4 gastric erosions by the band (all treated by band removal), 3 psychological intolerance (requiring band removal), and 1 HIV positive (band removed). A minor complication requiring reoperation in 91 patients (11%) was reservoir leakage. 20% of patients who had % excess weight loss < 30 had lost compliance to dietetic, psychological and surgical advice. BMI declined significantly from the initial 46.4 +/- 7.2 to 37.3 +/- 6.8 at 1 year, 36.4 +/- 6.9 at 2 years, 36.8 +/- 7.0 at 3 years, and 36.4 +/- 7.8 at 5 years. CONCLUSION: LAGB is a relatively safe and effective procedure.

Adolescent↗

Autologous fibrin-cultured limbal stem cells permanently restore the corneal surface of patients with total limbal stem cell deficiency.

BACKGROUND: Ocular burns cause depletion of limbal stem cells, which leads to corneal opacification and visual loss. Autologous cultured epithelial cells can restore damaged corneas, but this technology is still developing. We sought to establish a culture system that allows preservation of limbal stem cells and preparation of manageable epithelial sheets and to investigate whether such cultures can permanently restore total limbal stem cell deficiency. METHODS: We selected a homogeneous group of patients whose limbal cell deficiency was evaluated by scoring the gravity of the clinical picture and the keratin expression pattern. Stem cells, obtained from the limbus of the contralateral eye, were cultivated onto a fibrin substrate and their preservation was evaluated by clonal analysis. Fibrin cultures were grafted onto damaged corneas. RESULTS: Fibrin-cultured limbal stem cells were successful in 14 of 18 patients. Re-epithelialization occurred within the first week. Inflammation and vascularization regressed within the first 3-4 weeks. By the first month, the corneal surface was covered by a transparent, normal-looking epithelium. At 12-27 months follow-up, corneal surfaces were clinically and cytologically stable. Three patients had a penetrating keratoplasty approximately 1 year after restoration of their corneal surface. Their visual acuity improved from light perception or counting fingers to 0.8-1.0. CONCLUSIONS: Preservation of limbal stem cells in culture gives new perspectives on the treatment of ocular disorders characterized by complete limbal stem cell deficiency. The multicenter nature of this study and the handiness and ease of long-distance transportation of the fibrin-cultured epithelial sheets suggest that this technology can now be widely applied.

3T3 Cells↗

Regulation of P-selectin binding to the neutrophil P-selectin counter-receptor P-selectin glycoprotein ligand-1 by neutrophil elastase and cathepsin G.

In the inflammatory response, leukocyte rolling before adhesion and transmigration through the blood vessel wall is mediated by specific cell surface adhesion receptors. Neutrophil rolling involves the interaction of P-selectin expressed on activated endothelium and its counter-receptor on neutrophils, P-selectin glycoprotein ligand-1 (PSGL-1). Here, it is reported that P-selectin binding to neutrophils is lost under conditions that cause the release of proteinases from neutrophil primary granules. Treatment of neutrophils with the purified neutrophil granule proteinases, cathepsin G and elastase, rapidly abolished their capacity to bind P-selectin. This inactivation corresponded to loss of the N-terminal domain of PSGL-1, as assessed by Western blot analysis. A loss of intact PSGL-1 protein from the surfaces of neutrophils after the induction of degranulation was also detected by Western blot analysis. Cathepsin G initially cleaved near the PSGL-1 N-terminus, whereas neutrophil elastase predominantly cleaved at a more C-terminal site within the protein mucin core. Consistent with this, cathepsin G cleaved a synthetic peptide based on the PSGL-1 N-terminus between Tyr-7/Leu-8. Under conditions producing neutrophil degranulation in incubations containing mixtures of platelets and neutrophils, the loss of PSGL-1, but not P-selectin, from platelet-neutrophil lysates was detected. Cathepsin G- or neutrophil elastase-mediated PSGL-1 proteolysis may constitute a potential autocrine mechanism for down-regulation of neutrophil adhesion to P-selectin.

Amino Acid Sequence↗

Gene correction of integrin beta4-dependent pyloric atresia-junctional epidermolysis bullosa keratinocytes establishes a role for beta4 tyrosines 1422 and 1440 in hemidesmosome assembly.

The cytoplasmic domain of beta4 integrin contains two pairs of fibronectin-like repeats separated by a connecting segment. The connecting segment harbors a putative tyrosine activation motif in which tyrosines 1422 and 1440 are phosphorylated in response to alpha6beta4 binding to laminin-5. Primary beta4-null keratinocytes, obtained from a newborn suffering from lethal junctional epidermolysis bullosa, were stably transduced with retroviruses carrying a full-length beta4 cDNA or a beta4 cDNA with phenylalanine substitutions at Tyr-1422 and Tyr-1440. Hemidesmosome assembly was evaluated on organotypic skin cultures. beta4-corrected keratinocytes were indistinguishable from normal cells in terms of alpha6beta4 expression, the localization of hemidesmosome components, and hemidesmosome structure and density, suggesting full genetic and functional correction of beta4-null keratinocytes. In cultures generated from beta4(Y1422F/Y1440F) keratinocytes, beta4 mutants as well as alpha6 integrin, HD1/plectin, and BP180 were not concentrated at the dermal-epidermal junction. Furthermore, the number of hemidesmosomes was strikingly reduced as compared with beta4-corrected keratinocytes. The rare hemidesmosomes detected in beta4(Y1422F/Y1440F) cells were devoid of sub-basal dense plates and of inner cytoplasmic plaques with keratin filament insertion. Collectively, our data demonstrate that the beta4 tyrosine activation motif is not required for the localization of alpha6beta4 at the keratinocyte plasma membrane but is essential for optimal assembly of bona fide hemidesmosomes.

3T3 Cells↗

p63 identifies keratinocyte stem cells.

The proliferative compartment of stratified squamous epithelia consists of stem and transient amplifying (TA) keratinocytes. Some polypeptides are more abundant in putative epidermal stem cells than in TA cells, but no polypeptide confined to the stem cells has yet been identified. Here we show that the p63 transcription factor, a p53 homologue essential for regenerative proliferation in epithelial development, distinguishes human keratinocyte stem cells from their TA progeny. Within the cornea, nuclear p63 is expressed by the basal cells of the limbal epithelium, but not by TA cells covering the corneal surface. Human keratinocyte stem and TA cells when isolated in culture give rise to holoclones and paraclones, respectively. We show by clonal analysis that p63 is abundantly expressed by epidermal and limbal holoclones, but is undetectable in paraclones. TA keratinocytes, immediately after their withdrawal from the stem cell compartment (meroclones), have greatly reduced p63, even though they possess very appreciable proliferative capacity. Clonal evolution (i.e., generation of TA cells from precursor stem cells) is promoted by the sigma isoform of the 14-3-3 family of proteins. Keratinocytes whose 14-3-3final sigma has been down-regulated remain in the stem cell compartment and maintain p63 during serial cultivation. The identification of p63 as a keratinocyte stem cell marker will be of practical importance for the clinical application of epithelial cultures in cell therapy as well as for studies on epithelial tumorigenesis.

3T3 Cells↗