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Biomedical subjects

F Giordano

Publications and source records attributed to F Giordano.

At least 73 records · Page 4Linked to original sources

Experimental induction of epithelial-mesenchymal interconversions.

Under some in vitro conditions, such as exposure to collagen, growth factors and related molecules, and agents affecting DNA methylation, a cell phenotype shift can be observed from an epithelial to a mesenchymal state of differentiation. The reverse process, a mesenchymal-to-epithelial conversion can likewise be obtained by certain experimental manipulations. In some instances the change is fully reversible by removing the inducer substances, but in others the conversion appears to be stable and irreversible. Only a partial modulation of the cell phenotype is often seen, but sometimes a complete switch to a new phenotype occurs, and morphological, biochemical and functional characteristics of the parent cells can be abrogated. In some in vivo models development of sarcomatous tumours can be seen in animals transplanted with several types of carcinoma, and it is possible that in some of these experiments an epithelial-to-mesenchymal conversion has occurred too. In normal embryonic development as well as in pathological lesions including tissue repair, tumour invasion, and some malignant biphasic tumours, changes similar to the ones observed in experimental epithelial-mesenchymal interconversion seem to take place. Therefore, it is conceivable that experimentally-induced phenotype conversions reflect an inherent potential of cells, and that under some experimental circumstances normally silent genetic programs for epithelial or mesenchymal differentiation are activated, thus recapitulating a phenomenon that occurs in physiopathological circumstances in vivo.

Animals↗

Glomerular morphometry of twenty-three biopsied patients with IgA nephropathy.

The aim of the present study was the process of an easy method for quantitative evaluation of the alterations of the mesangial matrix, cellularity and urinary space in IgA glomerulonephritis (IgA-GN) by the image analysis technique. A Vidas (Kontron-Zeiss) image analyzer was employed for the morphometric study of renal biopsies from 23 patients with IgA-GN. The following parameters were assessed: mesangial matrix index, expressed as the ratio between mesangial area and total glomerular area x 100; mesangial cellularity index, considered as the ratio between the total number of nuclei contained in the glomerulus and the overall glomerular area in mm2 x 10(4); urinary space/glomerular area ratio. The morphometric results compared to the respective values observed in normal glomeruli indicate an increase in the overall area of glomeruli with IgA-GN and, conversely, a decrease in the total area occupied by the urinary space (p = 0.0001). It can therefore be concluded that the morphometric determination of the morphologic abnormalities occurring in the renal glomerulus with IgA-GN is an extremely useful method to describe the characteristics of this pathologic condition with a rapid and less laborious approach.

Adult↗

Renal transplantation from living donor parents in two brothers with Alport syndrome. Can asymptomatic female carriers of the Alport gene be accepted as kidney donors?

Renal transplantation from living donor parents was performed in two brothers with end-stage renal failure due to Alport syndrome (AS). Two years later, the patient receiving the kidney graft from the mother, obligate carrier of AS, presented persistent microhematuria and proteinuria with normal renal function. The histological study demonstrated ultrastructural glomerular lesions consistent with AS. The authors conclude that: (1) Alport patients should not be deprived of renal transplantation from living donors, since anti-GBM nephritis is a rare complication; (2) an oligosymptomatic female carrier of the Alport gene may be considered as living renal donor, although a longer follow-up is needed in order to draw definitive conclusions.

Adult↗

Impact of emergency medical helicopter service on mortality for trauma in north-east Italy. A regional prospective audit.

The hypothesis that high level on-the-field ATLS could influence mortality in severe trauma patients was tested by means of a prospective study. During a 7 month period, data of all the victims of severe involuntary trauma (road traffic accidents, work and sport accidents) in 3 Provinces of north-east Italy were entered in a database and analysed. The whole area is covered by a single emergency service which has direct control over all the ambulances and the Emergency Helicopter Service (EMHS). The area concerned by the study has a surface of 7,300 kmq with a population of 1 million inhabitants and is served by 12 first level hospitals and 4 second level institutions (trauma centres). All the patients who were still alive at the time of arrival of the first rescuers were considered, but only severe trauma patients with ISS > 15 were enclosed into the study. All the patients were followed up to their discharge from the ICUs (end point). There were three different rescue approaches: 82 Patients (GROUP A) were rescued by EMTs with BLS training, transported to the nearest level 1 hospital for stabilisation and subsequently transferred to a trauma center; 98 Patients (GROUP B) were rescued by EMTs and directly transported to a trauma centre which was the nearest institution; 42 Patients were rescued on the scene by the EMHS team including an anaesthesiologist with 10 years experience in trauma care and directly transported to a trauma centre after full on-the-field stabilisation (GROUP C) RESULTS: 222 severe trauma patients (ISS > 15) were considered. Mean ISS was 35.1 +/- 18.2 in group A, 33.4 +/- 19.6 in group B and 36.0 +/- 17.8 in group C. 67 patients died previous to ICU discharge (31%). 31 over the 82 pts in Group A (38%) died. 23 of them died even before reaching the trauma centre. The mean time elapsed between the first emergency call and the arrival at the trauma centre was 162 min (90'-300'). Mean ICU stay for patients who survived was 15 days. In Group B 31 over 98 patients (32%) died before ICU discharge. The mean time between the emergency call and hospital admission was 27'. Mean ICU stay for patients who were discharged, was 13 days. 5 over 42 patients rescued by the EMHS (Group C) died, none of them in the pre-hospital setting. Stabilisation included tracheal intubation in 34 cases (81%) and thoracic drainage in 6 (14%). All the patients arrived at the hospital with 2 i.v. line. The average amount of infused fluids were 600 mls of colloids and 810 mls of crystalloid. 13 patients with hypotension received and average of 1000 mls of colloids and 1200 mls of crystalloid. The average time elapsed between the emergency call and the final admission to the definitive care institution was 55'. Mean ICU stay was 11 days. Mortality rate in this group was 12%, significantly lower than in group A (p < 0.005) and group B (p < 0.05).

Air Ambulances↗

Epidemiological impact of prolonged systematic use of topical SDD on bacterial colonization of the tracheobronchial tree and antibiotic resistance. A three year study.

OBJECTIVE: to evaluate the effect of the prolonged systematic use of topical SDD (tobramycin 80 mg, polymyxin E 100 mg, amphotericin B 500 mg) on ICU ecology as expressed by changes in tracheal colonization and bacterial resistances. DESIGN: Prospective microbiological survey. SETTING: Polyvalent ICU of a 2000 beds general hospital. PATIENTS: Data concerning bacterial strains isolated from the tracheo-bronchial aspirates of all the patients admitted to a polyvalent ICU over 3 consecutive periods of 12 months ('88, '89, '90) were prospectively entered in a database and subsequently analyzed. During a 3-year period 502 patients required artificial ventilation for more than 72 h and 332 of them ('89 and '90) were treated with SDD. All samples collected within 72 h from ICU admission were excluded as well as duplicate samples from the same patients. INTERVENTION: All the patients admitted to the ICU in '89 and '90 and submitted to artificial ventilation for at least 24 h were routinely treated with topical SDD without i.v. antibiotic prophylaxis; in '88 SDD was not employed. MEASUREMENTS AND RESULTS: Criteria for collecting sputum samples and microbiological procedures remained unchanged throughout the study-time. Positive sputum were significantly less in '89 (80.8% versus 92.3% p < 0.001) and this was due to a very sharp decrease in the isolation of Gram-negative strains from 43-28% (-64% p < 0.0001) involving both: Enterobacteriaceae (-45%) and Pseudomonaceae (-77%). In 1990; however, a new increase in Gram negative was observed, although the overall amount of Gram-negative was still 49% lower in '90 if compared to '88 (p < 0.0001). A dramatic increase in Pseudomonas isolation was the only factor responsible for the "rebound" observed. An increasing percentage of Pseudomonas developed a resistance towards tobramycin and only 45% of Pseudomonas strains turned out to be sensible to tobramycin in '90 against 79% in '88. A similar trend was registered for all aminoglycosides with the exception of amikacin. Gram-positive colonizations tended to increase (+63%) (p < 0.0001) and this was mainly due to Coagulase negative Staphylococci (+290% p < 0.0001) and S. pneumoniae, whereas S. aureus isolations decreased (-18%) but not significantly. CONCLUSIONS: Our data suggest that the prolonged use of SDD is associated with dramatic changes in ICU ecology: the incidence of Gram negative colonization is significantly diminished by SDD whereas Gram positive tend to increase. Pseudomonas developed an increasing resistance towards tobramycin one of the components of the SDD formula we used.

Administration, Oral↗

Fabry's disease: heterozygous form of different expression in two monozygous twin sisters.

A 26-year-old woman presented widespread angiokeratomas predominantly in a swimsuit distribution pattern associated with acroparesthesia in all four limbs. The tentative diagnosis of Fabry's disease (FD) was confirmed by optical and electron-microscopic findings and by appropriate biochemical testing. The work-up showed ocular and renal manifestations of the disease. The monozygous twin sister of the patient was asymptomatic although she was shown to be heterozygous for the enzymatic defect. These 2 cases illustrate the concept of extreme lyonization which can explain observed phenotypic differences in heterozygous females with X-linked hereditary diseases. The father and mother of the patient were shown to be noncarriers of the trait, suggesting de novo mutation in the twin pregnancy. However, biochemical testing for the detection of FD heterozygous females cannot rule out the possibility of the mother being heterozygous with normal enzyme activity.

Adult↗

Conditions of cyclodextrin complexation.

In the past 20 years, cyclodextrin (CD) research has achieved considerable results, as indicated by the large number of publications and patents, the six international symposia on CDs, the new dosage forms of medicines prepared with CDs, etc. Sufficient data have accumulated to permit a survey of the most important conditions of CD complexation. Further, an account is presented of the success of precipitation of the complex involving furosemide and beta-CD.

Calorimetry, Differential Scanning↗

[Methylprednisolone versus prednisolone methylsulfobenzoate in pemphigoid: a comparative multicenter study].

Bullous pemphigoid is a bullous skin disease associated with basal membrane antibodies. At present, the first treatment of these lesions is with corticosteroids. In this randomized study we compared the clinical results obtained with methylprednisolone (MePr) in 28 patients and with prednisolone methylsulfobenzoate (MsPr) in 29 patients. Both drugs were administered orally in daily doses of 1 to 1.5 mg/kg bodyweight. Three clinical data were examined: the number of bullous lesions, the intensity of pruritus and the extent of erythema after 5 then 10 days of treatment. After 10 days, the number of bullous lesions had decreased by 83 p. 100 with MePr and by 78 p. 100 with MsPr, and the decrease of pruritus had been significantly more pronounced in the MePr group than in the Ms group (p < 0.05). There had been no difference between treatments in the regression of erythema. Altogether, good results were obtained in 22/28 patients under MsPr (78.6 p. 100) and 18/29 patients under MePr (62.1 p. 100). This raises the question of the value of pharmacokinetic studies not only with these two corticosteroids, but also with prednisone which seems to be better absorbed.

Administration, Oral↗

Structural characterization of terflavoxate.

Data are reported on the structural characterization of 3-methyl-4-oxo-2-phenyl-4H-1-benzopyran-8-carboxylic acid 1,1-dimethyl-2-(N-piperidinyl)ethyl ester hydrochloride (terflavoxate-HCl, Rec 15/2053, CAS 86433-39-8), a new antispasmodic for the lower urinary tract. UV, IR, NMR and MS spectra fully confirmed the structure. The X-ray crystal structure determination revealed that the molecular structure consists of a rigid platform, formed by the chromone system, with two arms, the phenyl group at C(2) and the ester chain at C(8). The ester chain conformation generates a small hollow where two oxygen atoms face.

Chemical Phenomena↗

Synthesis and antihistaminic activity of some thiazolidin-4-ones.

A new series of 2-(4- and 3-substituted phenyl)-3-[3-(N,N-dimethylamino) propyl]-1,3-thiazolidin-4-ones were synthesized, characterized, and evaluated for their ability to inhibit the contractions induced by histamine on guinea pig ileum. The measurement of pA2 values suggested that the reported compounds showed H1-antagonism. The more active compounds 5, 9, and 13 exhibited activity close to that of mepyramine.

Animals↗

Efficacy of intravenous propafenone in acute atrial fibrillation complicating open-heart surgery.

Early postoperative atrial fibrillation (AF) is a frequent complication of major cardiovascular surgery. To assess the effectiveness of intravenous propafenone in this setting, we studied 50 patients who developed AF within 48 hours after open-heart surgery. Intravenous propafenone (2 mg/kg in 10 minutes) was administered 15 minutes after the onset of the arrhythmia. Sinus rhythm was restored in 35 patients (70%) after a mean time of 22 +/- 6 minutes after the beginning of the infusion. The conversion was obtained in 28 of 32 patients (88%) who had a coronary artery bypass graft and in 7 of 18 patients (39%) who had valvular or septal surgery (p less than 0.01). In those whose arrhythmia did not convert to sinus rhythm, the ventricular rate was reduced from 142 +/- 14 beats/min to 108 +/- 9 beats/min (p less than 0.01). In patients whose arrhythmia was converted to sinus rhythm, mean cardiac index increased from a mean baseline value of 2.7 +/- 0.4 L/min/m2 to 3.4 +/- 0.1 L/min/m2 (p less than 0.05), while it remained virtually unchanged in those whose arrhythmia did not convert. No significant side effects were observed. We conclude that intravenous propafenone is effective in converting to sinus rhythm the majority of patients with AF complicating open-heart surgery. Heart rate was reduced in those who did not convert to sinus rhythm and no side effects nor hemodynamic deterioration were observed in any case.

Acute Disease↗

[Inotropic treatment in heart transplantation].

The safe conduct of anesthesia and intensive care for heart transplant recipient requires a sound understanding of the pathophysiology of advanced cardiac failure through knowledge of anesthetic and cardiovascular pharmacology and an appreciation of the altered physiologic and pharmacologic responses of acutely denervated and transplanted heart. The most serious dysfunction is acute distension and failure of the transplanted heart's right ventricle. Hemodynamic monitoring and TEE are useful in the management of inotropic support during heart transplantation.

Anesthesia↗

Carbon-13 nuclear magnetic resonance study of naproxen interaction with cyclodextrins in solution.

Changes in naproxen (NAP) 13C-chemical shifts were measured as a function of the concentration of alpha-, beta-, and gamma-cyclodextrin (alpha Cd, beta Cd, and gamma Cd, respectively) in aqueous solution in order to obtain details on the mechanism, geometry, and stoichiometry of the respective interactions. The probable structures of the inclusion compounds of NAP with natural cyclodextrins were constructed using a molecular graphics program. The higher stability of the beta Cd:NAP 1:1 (mol/mol) complex in comparison with alpha Cd:NAP 2:1 (mol/mol) and gamma Cd:NAP 1:1 or 1:2 (mol/mol) complexes was accounted for in terms of a deeper, more complete, and better fitting inclusion of the drug into the cavity of beta Cd. The inclusion behavior of NAP with some statistically substituted beta Cd derivatives [hydroxyethyl-beta Cd (HE beta Cd), hydroxypropyl-beta Cd (HP beta Cd), and methyl-beta Cd (M beta Cd)] was also investigated through 13C-NMR, UV, circular dichroism spectroscopy, and phase-solubility analysis. The stoichiometry of host:guest interactions was the same as with beta Cd, as were thermodynamics and basic complexation mechanisms. The binding between the host and guest molecules is thought to be mainly due to van der Waals, dipole-dipole, and hydrophobic interactions. The inclusion ability of the parent beta Cd was enhanced by the introduction of methyl, hydroxyethyl, and hydroxypropyl groups. The M beta Cd formed the most stable inclusion complex (apparent formation constant K(1:1) = 6892 L.mol-1 at 298 K); it was about three times more stable than those with HP beta Cd or HE beta Cd and four times more stable than that with beta Cd.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Isotopes↗