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Biomedical subjects

E Benedetti

Publications and source records attributed to E Benedetti.

At least 91 records · Page 5Linked to original sources
PubMed1998

Alfa-interferon in the treatment of essential thrombocythemia: clinical results and evaluation of its biological effects on the hematopoietic neoplastic clone. Italian Cooperative Group on ET.

The efficacy of alfa-interferon (alfa-IFN) in essential thrombocythemia (ET) patients has been reported by several authors. The aim of this study is to assess the magnitude of the effect of alfa-IFN on the neoplastic clone. As of December 1993, 11 ET patients received alfa-IFN at a dose of 3-6 MU/s.c./day for 6 months. Ten of 11 obtained complete hematological remission (CHR) and one achieved partial hematological remission. Megakaryocyte concentration was reduced in six cases. The spleen,which was enlarged in four patients, decreased in size in two patients. Seven of eight patients who were symptomatic at diagnosis obtained resolution of symptoms. In order to obtain indications about the structural modifications induced by alfa-IFN in ET megakaryocytes (Mks), Fourier-transform infra-red microspectroscopy analysis performed on 10 single Mks of each patient, was done in seven of 11 patients; the analysis showed a reduction of A1/A2 ratios (A1 integrated area of the band at 1080 cm(-1) due to the nucleic acids absorption; A2 integrated area of the band at 1540 cm(-1) due to proteic components absorption) in five cases, and in three of these five patients A1/A2 ratios achieved normal values. After alfa-IFN treatment we did not observe any change in the methylation pattern of DNA from the granulocyte fraction. Our results confirm the efficacy of alfa-IFN in ET patients, and the decrease of A1/A2 ratios in several patients is a demonstration of the depth of the effect of alfa-IFN on the neoplastic clone. The results of clonality studies showed the persistence of clonal hematopoiesis. Whether higher alfa-IFN dose and/or more prolonged alfa-IFN therapy may allow a restoration of polyclonal hematopoiesis remains to be determined and should be explored in future clinical trials.

Adolescent↗
PubMed1998

Kidney transplantation in recipients with mental retardation: clinical results in a single-center experience.

Mental retardation has been a controversial relative contraindication to organ transplantation. Currently, there are few data available in the literature that describe the outcome of kidney transplantation in mentally retarded patients. In a series of 1,271 kidney transplantations performed between January 1968 and March 1996, we identified eight patients (0.6%) with significant mental retardation (IQ < 70). Only cooperative patients supervised by a reliable long-term caregiver, with long life expectancy, and able to take medication under supervision, were accepted as candidates, independent of the IQ level. At a mean follow-up of 7.3 years, seven patients are alive with functioning grafts, and one lost the kidney to chronic rejection 10 years after transplantation and died of sepsis after resuming dialysis. The 1- and 5-year patient and graft survival are thus 100%. Compliance with immunosuppressive treatment and clinical follow-up was excellent in all of the recipients. The patient quality of life and health were judged by the support persons as highly improved after transplantation in comparison to dialysis. We conclude that kidney transplantation in properly selected patients with mental retardation provides excellent patient and graft survival rates and improves quality of life. In such patients, the presence of mental retardation should not be considered a contraindication to kidney transplantation.

Adolescent↗
PubMed1998

Structure of cyclic peptides: the crystal and solution conformation of cyclo(Phe-Phe-Aib-Leu-Pro).

A solid-state and solution conformation analyses of the cyclopentapeptide cyclo(Phe-Phe-Aib-Leu-Pro) has been carried out by X-ray diffraction and nuclear magnetic resonance techniques. The structure of the hexagonal crystals, grown from a methanol solution [a = b = 16.530(4) A, c = 21.356(9) A, space group P6(5), Z = 6], shows the presence of one intramolecular N-H ..O=C hydrogen bond with the formation of a gamma-turn (C7). The Aib3 residue, at the center of the gamma-turn, presents unexpected values of the torsion angles [phi = 70.5 degrees and psi = -73.8 degrees], which have been observed only once before for this helicogenic residue. A cis peptide bond occurs between Leu4 and Pro5; all other peptide bonds are trans. The overall conformation for the cyclopentapeptide with one cis-peptide bond on one side and an intramolecular gamma-turn on the opposite side results in an equatorial topology of the side-chains of the Phe1, Phe2 and Leu4 residues. Indeed, the Calpha-Cbeta and Cbeta-Cgamma bonds of these residues lie approximately in the mean plane of the cyclic ring system. The structure is compared with data in the literature on cyclic pentapeptides. In addition the Pro-Phe-Phe moiety shows a conformation similar to that observed in other larger cyclic bioactive peptides, which indicates a reduced number of conformations for this sequence. The solution study was carried out in three different solvent systems: chloroform, acetonitrile and methanol in the temperature interval 220-300 K. In all three solvents the room temperature spectra show that the peptide is conformationally nonhomogeneous. In acetonitrile at low temperatures it is possible to reduce the conformational equilibrium to two predominant conformers which differ for the cis-trans isomerism of the Leu4-Pro5 peptide bond.

Magnetic Resonance Spectroscopy↗
PubMed1998

An approach to the study of primitive thrombocythemia (PT) megakaryocytes by means of Fourier transform infrared microspectroscopy (FT-IR-M).

Chronic myeloid leukemia (CML), polycythemia vera (PV), idiopathic myelofibrosis (IM) and primary thrombocythemia (PT) are myeloproliferative diseases of clonal origin. Megakaryocyte series are commonly involved in these disorders. In a previous paper of us, megakaryocytes (MKs) from PV and PT patients were shown to be more pathological with respect to the MKs from CML. This paper describes a Fourier transform infrared microspectroscopy (FT-IR-M) study analyzing the cytoplasm and nucleus areas of MKs from thrombocythemic patients which exhibited numerous giant cells (from 100 to 190 microm in diameter). The size of these cells makes it possible to analyze the cell parts using FT-IR-M technique. The infrared determinations on 10 single MKs for each case examined in these two different cell regions revealed spectral differences with a high degree of reproducibility. Finally, the spectra of whole MKs from normal donors and from thrombocythemic patients were also compared.

Humans↗
PubMed1998

Omental transfer for salvage of the moribund lower extremity.

Use of omental flaps is well documented in soft tissue reconstruction of the head and neck, chest wall, and abdomen. Three cases of omental transfer for soft tissue reconstruction of the lower extremities are presented. In two patients, free vascularized omental flaps were used to cover deep soft tissue defects over the lower leg and in one patient, a pedicle flap was used to cover a deep groin defect extending into the hip joint. In all patients, use of an omental graft allowed revascularization and subsequent wound healing with good cosmetic results.

Aged↗
PubMed1998

A prospective study of the predictive value of polymerase chain reaction assay for cytomegalovirus in asymptomatic kidney transplant recipients.

Cytomegalovirus (CMV) infection carries the potential for high morbidity in transplant recipients. The institution of pre-emptive therapy prior to the onset of clinical disease on the basis of CMV-polymerase chain reaction (PCR) is very attractive. We prospectively studied 52 asymptomatic kidney transplant recipients to test the hypothesis that serial CMV-PCR assays during the first 3 months post-transplant would identify patients at risk for CMV disease. Twenty-three patients (44.2%) had positive CMV-PCR tests at least once; 2 (8.6%) developed CMV. None of the 29 patients continuously negative for CMV-PCR developed CMV disease. CMV-PCR status did not influence patient and graft survival or the incidence of acute rejection. We conclude that while a substantial number of kidney transplant recipients become positive for CMV-PCR in the early post-transplant period, only a minority will develop CMV disease. Negative CMV-PCR assay is an accurate negative predictor for CMV disease but the value of CMV-PCR as a guide for pre-emptive anti-CMV therapy in kidney transplant recipients appears limited.

Adult↗
PubMed1998

What makes a coronary myocardial bridge symptomatic?

The clinical significance of coronary myocardial bridging has been debated and different interventional strategies proposed. We discuss the case of a patient who presented with the recent onset of symptoms of exertional chest pain, diaphoresis, and electrocardiographic signs of acute anterior myocardial wall ischemia. Cardiac catheterization demonstrated a segmental high-grade narrowing of the mid left anterior descending coronary artery during systole consistent with bridging. Intravenous fluid resuscitation and calcium channel blockade resulted in normalization of his electrocardiogram and complete resolution of his anginal symptoms and coronary angiographic systolic narrowing.

Administration, Oral↗
PubMed1997

Intrasplenic hepatocyte allotransplantation in dalmation dogs with and without cyclosporine immunosuppression.

Hepatocyte allotransplantation has been performed successfully in several small animal models for the amelioration of inborn metabolic errors. Before a human clinical trial of hepatocyte allotransplantation can be attempted, preliminary experience in a large animal model is needed. We transplanted isolated mongrel hepatocytes into the spleen of dalmatians in the attempt to cure their inborn error of uric acid metabolism. Of 10 dalmatian recipients, two that received 9-10 x 10(9) mongrel hepatocytes died early after surgery of acute portal hypertension and hemorrhage. The eight long-term survivors received 5-6 x 10(9) hepatocytes and were randomized either to no treatment or to oral cyclosporine (CsA). Levels of CsA were adjusted to maintain trough levels between 400 and 800 ng/ml. In the four nonimmunosuppressed dalmatians, a reproducible average reduction in urinary uric acid excretion (UUAEx) of 23.7% was achieved; values returned to baseline within 14 days. In the CsA-immunosuppressed dalmatians, the average decline in UUAEx was 30%. The partial correction of the metabolic defect persisted for an average of 25 days in three immunosuppressed dogs, whereas in one dog, the partial correction lasted for over 90 days. No change in UUAEx was observed in two dalmatians that underwent sham laparotomy and intrasplenic injection of saline solution; CsA given alone to dalmatians did not modify UUAEx. We conclude that the dalmatian dog is a valuable large animal model for studies of the role of hepatocyte transplantation in the cure of inborn hepatic metabolic errors.

Animals↗
PubMed1997

Determination of secondary structure of normal fibrin from human peripheral blood.

The secondary structure of human fibrin from normal donors and from bovine and suilline plasma was studied by Fourier transform ir spectroscopy and a quantitative analysis of its secondary structure was suggested. For this purpose, a previously experimented spectrum deconvolution procedure based on the use of the Conjugate Gradient Minimisation Algorithm with the addition of suitable constraints was applied to the analysis of conformation-sensitive amide bands. This procedure was applied to amide I and III analysis of bovine and suilline fibrin, obtained industrially, and to amide III analysis of human fibrin clots. The analysis of both amide I and III in the first case was useful in order to test the reliability of the method. We found bovine, suilline, and human fibrin to contain about 30% alpha-helix (amide I and III components at 1653 cm-1, and 1312 and 1284 cm-1, respectively), 40% beta-sheets (amide I and III components at 1625 and 1231 cm-1, respectively) and 30% turns (amide I and III components at 1696, 1680, 1675 cm-1, and 1249 cm-1, respectively). The precision of the quantitative determination depends on the amount of these structures in the protein. Particularly, the coefficient of variation is < 10% for percentage values of amide I and III components > 15 and 5%, respectively. The good agreement of our quantitative data, obtained separately by amide I and amide III analysis, and consistent with a previous fibrinogen (from commercial sources) study that reports only information about fibrin beta-sheet content obtained by factor analysis, leads us to believe that the amounts of secondary structures found (alpha-helix, beta-sheets, and turns) are accurate.

Algorithms↗
PubMed1997

Recipient preconditioning and donor-specific bone marrow infusion in a pig model of total bowel transplantation.

BACKGROUND: In an outbred pig model of total bowel transplantation, we previously showed that simultaneous donor-specific bone marrow infusion (DSBMI), rather than promoting engraftment, sensitizes recipients and causes rejection; it also aggravates the risk of generalized graft-versus-host disease (GVHD) and infection, and tends to reduce recipient and graft survival. Small and large animal models of bone marrow-induced transplant tolerance suggest that some form of recipient preconditioning (RPC) may facilitate engraftment of co-transplanted bone marrow cells and fully expose their tolerogenic potential. METHODS: In a preclinical model, we prospectively studied the effect of RPC on simultaneous DSBMI and total (i.e., small and large) bowel transplantation. RPC consisted of whole body irradiation with 400 R (day 0); some recipients additionally received horse anti-pig antithymocyte globulin (days -2, -1, and 0). We studied six groups of outbred pigs, all of which underwent at least a total bowel transplant: group 1, nonimmunosuppressed control pigs (n=5); group 2, nonimmunosuppressed DSBMI pigs (n=13); group 3, tacrolimus pigs (n=7); group 4, DSBMI+tacrolimus pigs (n=15); group 5, RPC+nonimmunosuppressed DSBMI pigs (n=11); and group 6, RPC+DSBMI+tacrolimus pigs (n=14). RESULTS: RPC did not prolong overall survival at 7, 14, 21, and 28 days after transplant. Survival rates were 100%, 100%, 86%, and 71% in group 3; 71%, 43%, 29%, and 29% in group 6; 55%, 9%, 0%, and 0% in group 5; and 60%, 0%, 0%, and 0% in Group 1. Moreover, RPC (groups 5 and 6) increased the incidence of death from rejection, GVHD, and infection when compared with group 3. Survival was significantly higher for RPC+DSBMI+tacrolimus pigs (group 6), compared with RPC+nonimmunosuppressed DSBMI pigs (group 5). Survival greater than 28 days was noted only in pigs that received tacrolimus after transplant: 71% in group 3 versus 29% in group 6. With both RPC and DSBMI (groups 5 and 6), rejection, GVHD, and infection were not mutually exclusive events. In groups 5 and 6, at autopsy, the incidence of rejection and GVHD was 17%; rejection and infection, 17%; and GVHD and infection, 45%. A combination of all three immunologic events was noted in 14%. CONCLUSIONS: RPC, combined with DSBMI, and with or without posttransplant immunosuppression, does not prolong survival after total bowel transplantation. Rather, it increases the incidence of death from rejection, GVHD, infection, or a combination of these three immunologic events. According to this preclinical study, RPC and unmodified DSBMI do not improve patient and graft outcome after total bowel transplantation and need to be refined before being applied clinically.

Animals↗
PubMed1997

Combined liver-total bowel transplantation has no immunologic advantage over total bowel transplantation alone. A prospective study in a porcine model.

BACKGROUND: Rejection remains a major obstacle to successful bowel transplantation in humans. It has been suggested that a simultaneous liver transplant would shield the bowel graft from immunologic attack, but the liver shortage would be aggravated. In a preclinical model, we studied the influence of simultaneous liver grafting by comparing the incidence of early bowel rejection after combined liver-total (small- and large-) bowel transplants vs total bowel transplants alone. METHODS: We assessed the incidence of early post-transplant rejection, graft-vs-host disease, and infection after combined liver-total bowel transplants (group 1, n = 10) and total bowel transplants alone (group 2, n = 9) in outbred Yorkshire Landrace pigs. Liver and bowel grafts were transplanted orthotopically with portal vein drainage after recipient hepatectomy (group 1) and total enterectomy (groups 1 and 2). Posttransplant immunosuppression was performed with intravenous tacrolimus (whole blood levels, 15 to 30 ng/mL) and prednisolone. In groups 1 and 2, bowel biopsy specimens from the ileostomy were obtained daily. In group 1, liver biopsy specimens were obtained weekly. Rejection was graded according to a 4-point scoring system (none, mild, moderate, and severe). RESULTS: Overall graft survival at days 7, 14, and 21 was 89%, 44%, and 11%, respectively, in group 1 vs 100%, 100%, and 86%, respectively, in group 2 (P < .001). Death rates owing to (irreversible) rejection at days 7, 14, and 21 were 0% in groups 1 and 2 (P = .48). Grading of bowel rejection episodes, based on the results of daily biopsy specimens, was not significantly different between the groups whether on individual days or overall. In group 1, the incidence of liver rejection episodes was as high as 66% (day 14 and at autopsy). At autopsy, generalized graft-vs-host disease (skin, native intestine, and native liver) was noted in 55% of group 1 and 43% of group 2 pigs (P = .55). Graft-vs-host disease was noted concurrently with rejection episodes of the liver or bowel grafts. CONCLUSIONS: Simultaneous liver grafting did not further reduce the incidence of early bowel rejection or graft-vs-host disease when compared with total bowel transplants alone. Based on the results of this preclinical study, simultaneous liver grafting is not indicated for patients with short-bowel syndrome and normal liver function.

Animals↗
PubMed1997

Qualitative and quantitative analysis of the secondary structure of cytochrome C Langmuir-Blodgett films.

A qualitative and quantitative analysis of the conformation of Langmuir-Blodgett (LB) dried films of cytochrome C on silicon wafers was performed by Fourier transform ir (FTIR) spectroscopy. A deconvolution procedure was applied to the amide I band analysis, in order to determine the percentage of the different secondary structures. Qualitative analysis was performed by examining difference spectra. Films obtained by spreading protein solutions at pH 7.4 and 1, dried at 25 and 100 degrees C, on silicon wafers were also examined in order to detect spectral components associated with denatured protein domains, and to compare them with cytochrome C LB films. FTIR spectroscopy showed that the following important changes characterise LB film spectra: (a) the alpha-helix component is higher (its percentage is 57 and 54%) than the one estimated in dried film obtained by spreading the solutions at pH 7.4 on a silicon substrate (43%), (b) there is an increase in the intensity of bands attributed to protonated carboxy group bands, involved and not involved in the formation of hydrogen bonds, and a decrease in those attributed to deprotonated carboxy groups, (c) the intensity of several bands attributed to aromatic amino acids and aliphatic chains increases, and (d) bands due to O-H stretching vibrations of crystallization water are present. These conformational changes could be induced by protein-protein interaction caused by the close packing of molecules that occurs during LB film formation; it cannot be excluded that they may be accompanied by partial changes in the tertiary structure of the protein. A preferential orientation of protein molecules in LB films is also a possibility.

Animals↗
PubMed1997

Pulmonary artery pseudoaneurysm after tube thoracostomy.

Pulmonary artery pseudoaneurysm has been described as a complication of Swan-Ganz catheterization and right heart catheterization. Isolated cases of this condition occurring in blunt and penetrating chest trauma have been reported. In this communication, we describe the case of a patient with intracranial hemorrhage who required positive-pressure ventilation and in whom subsequent pneumothorax developed, necessitating tube thoracostomy. A persistent opacification of the lung field resulted in evaluation with computed chest tomography and color-flow Doppler ultrasonography. A pseudoaneurysm of the lingular segmental artery was identified and successfully obliterated by Gelfoam coil embolization.

Aneurysm, False↗