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Biomedical subjects

G Montini

Publications and source records attributed to G Montini.

At least 37 records · Page 2Linked to original sources
PubMed1996

Extracorporeal photochemotherapy for the treatment of graft-versus-host disease.

Photopheresis is an extracorporeal photochemotherapy (ECP) used for the treatment of oncological and autoimmune diseases. Lymphocytes are drawn from the patients by leukapheresis, treated with 8-methoxypsoralen (8-MOP) and ultraviolet light A (UVA) in an extracorporeal system; then, reinfused to the host. Because skin exposure to 8-MOP and UVA (PUVA) has been shown to improve cutaneous GVHD, we evaluated in a pilot study, if ECP might be beneficial for patients with GVHD unresponsive to conventional protocols. In this study, we enrolled 9 children or young adults, with acute (no = 1) or chronic extensive GVHD (no. = 8). A significant improvement was observed in three of the 5 patients with scleroderma-like lesions and in one patient with severe liver involvement. Karnofsky performance score improved from 30-50% to 90% in the 4 responders. The better control of GVHD in these patients allowed a reduction of the immunosuppressive therapy that was, finally, discontinued in two. No significant side effects were observed during ECP. Our results suggest that ECP is a nonaggressive treatment that may benefit patients with c-GVHD unresponsive to standard immunosuppressive therapies.

Adolescent↗
PubMed1995

Determination of inulin in plasma and urine by reversed-phase high-performance liquid chromatography.

We report a new HPLC procedure for measuring inulin in plasma and urine. Samples after dilution are boiled in mild acidic conditions and then analyzed on a C18 column. Solvent system A is 3.2 mM HCl, pH 2.5, and B is acetonitrile-3.2 mM HCl (60:40, v/v), pH 2.5. The separation is carried out in 8 min with a flow-rate of 1.0 ml/min and the absorbance monitored at 280 nm. The relationship between inulin and the recorded peak area is linear from 0.2 to 3.2 mg/ml with a correlation coefficient of 0.999 for plasma and 0.999 for urine. Within-run precision, measured at three inulin concentrations, ranged from 0.9 to 1.7% in plasma and from 0.8 to 1.2% in urine. Between-run precision varied in plasma from 2.7 to 3.2% and in urine from 3.0 to 3.3%. Analytical recovery ranged from 102 to 107% in plasma and from 101 to 105% in urine, respectively. The method is sensitive, selective and only 30-microliters samples are required. Therefore, it could be used to evaluate the glomerular filtration rate even in small babies and to perform studies in animals.

Adult↗
PubMed1995

Extracorporeal photochemotherapy as adjuvant treatment of heart transplant recipients with recurrent rejection.

Recurrent rejection is an uncommon, severe complication after heart transplantation that is associated with a poor long-term prognosis. Photopheresis (ECP), a new form of extracorporeal photo-chemotherapy used for the treatment of cutaneous T cell lymphoma and several autoimmune diseases, has also been used for prevention and treatment of acute rejection in heart transplant recipients. It seems to induce specific suppression of both cellular and humoral rejection. In this study, we evaluated whether ECP added to standard therapies allowed better control of rejection and reduction of conventional immunosuppressive drugs in patients with repeated rejection episodes. Eight heart transplant recipients (6 men and 2 women, mean age 48 yr), with recurrent rejection were treated with ECP for 6 months. Endomyocardial biopsies (EMB) were performed monthly. As a result of treatment, 7 patients on ECP experienced a reduction of the number and severity of rejection episodes. The fraction of EMB negative for rejection increased from 13 to 41%, whereas the fraction of specimens with multifocal and/or diffuse moderate lymphocytes infiltration (grades 3A and 3B) decreased from 41 to 21%. ECP allowed reductions of daily immunosuppressive therapy: prednisone by 44% (16.9 vs. 9.4 mg), cyclosporine by 21% (366 vs. 291 mg), and azathioprine by 29% (137 vs. 97 mg). No major side effects were observed. We conclude that, although the number of patients is small, the use of ECP was safe and associated with improved control of recurrent rejection. This allowed tapering of immunosuppressive drugs, which was particularly useful in two patients with insulin-dependent diabetes and one with sternal wound osteomyelitis.

Adult↗
PubMed1994

A community outbreak of haemolytic-uraemic syndrome in children occurring in a large area of northern Italy over a period of several months.

From March to October 1993, 15 cases of haemolytic-uraemic syndrome (HUS) in children were detected in a large area of northern Italy, where only 8 cases had occurred in the previous 5 years. Analysis of stool and serum specimens obtained from 14 cases showed evidence of Verotoxin-producing Escherichia coli (VTEC) infection in 13. Serum antibodies to the E. coli O157 lipopolysaccharide (LPS) were found in 8 patients and to the O111 LPS in 2. An O86 VTEC was isolated from another patient. Fourteen children needed dialysis, and 1 died. No obvious epidemiologic link was observed among cases, most of whom lived in small townships. A case-control study did not show an association between HUS and food or exposure to cattle, but suggested an association with contact with chicken coops (OR = 6.5, 95% C.I. 1.2-34.9). However, VTEC were not isolated from stool samples obtained from the chicken coops involved. The risk factors for VTEC infection related to living in rural settlements, including the exposure to live poultry, should be considered in outbreak investigations.

Animals↗
PubMed1994

Immunohistochemical distribution of endothelin in biopsies of pediatric nephrotic syndrome.

In a retrospective, double-blind study, we analyzed, utilizing an immunohistochemical technique, the distribution of Endothelin (Et) in 20 renal biopsies of 17 children with nephrotic syndrome (NS): 9 cases of steroid-responsive and 8 of steroid-resistant minimal-change disease (MCD) and 3 cases of focal segmental glomerulosclerosis (FSGS). Thirteen out of 20 biopsies (9/9 steroid-responsive MCD and 4/8 steroid-resistant MCD) showed a weak positivity of the vascular endothelial cells, as the normal renal tissue samples obtained from tumor nephrectomies. Seven out of 20 biopsies, all steroid-resistant NS, showed a marked positivity of the vascular endothelium and of the tubules and/or interstitial cells. In 4 of these 7 cases (1 MCD, 3 FSGS) a positivity of glomeruli was also revealed. The positivity of vascular endothelium seems to confirm its central role in Et production. The marked immunoreactivity detected in the endothelial cells and other renal components reveals a local increase in Et in some steroid-resistant MCD and, particularly, in FSGS. These preliminary observations suggest that Et may participate (cause or epiphenomenon) in the mechanisms underlying the development of glomerulosclerosis and the progression of renal damage.

Biopsy↗
PubMed1994

Erythropoietin stimulates testosterone production in man.

Human recombinant erythropoietin (rHuEPO) treatment improves sexual function in end-stage renal failure patients with a still-debated mechanism. Experimental data suggested that rHuEPO was able to stimulate rat Leydig steroidogenesis; therefore, it has been suggested that rHuEPO may induce its effects in humans by acting on gonadal steroid production. Thirteen young adult males (age range, 16-28 yr) catheterized at peripheral and left internal spermatic venous levels during a contrast study for varicocele, were studied. In five subjects, rHuEPO (60 IU/kg, up to a maximum of 4000 IU total) was injected over 1 min in the cubital vein. Similarly, in other five patients, 50 micrograms GnRH were infused. In three subjects, 2 mL saline were injected, as controls. Plasma LH, FSH, and testosterone (T) levels were then determined at -15, 0, 15, 30, 45, 60, 90, and 120 min simultaneously in peripheral and spermatic venous blood. rHuEPO infusion did not have any effect on plasma LH and FSH levels in peripheral or spermatic veins. Similarly, rHuEPO infusion did not affect peripheral T concentration, but increased (approximately 400% vs. controls; P < 0.05) spermatic T levels. GnRH infusion induced an increase in plasma LH and FSH levels in both peripheral and spermatic veins. After GnRH infusion, an increase of approximately 12-fold (P = 0.05-0.001) in T was observed only at the spermatic venous level, without any peripheral T variation. These findings show that rHuEPO was able to influence testicular steroidogenesis by stimulating T production in man, whereas the absence of any effect on gonadotropin secretion suggests that rHuEPO might act directly on human Leydig cell function.

Adolescent↗
PubMed1994

Continuous peritoneal dialysis in newborns.

OBJECTIVES: To report the complications and outcome of 10 newborns affected by acute renal failure (ARF), treated by continuous peritoneal dialysis (CPD). DESIGN: All newborns admitted for tertiary treatment to the Neonatal Intensive Care Unit of the University of Padova, who underwent CPD between February 1986 and December 1990, were analyzed retrospectively. PATIENTS: Ten newborns (mean weight 2077 g, range 540-4930 g) received CPD, 6 of whom were preterm. All the survivors completed the study. INTERVENTIONS: A number 9, 5 French Tenckhoff catheter was used, and a closed circuit was created by means of a modified continuous ambulatory peritoneal dialysis (CAPD) technique. The mean duration of dialytic therapy was 7 days. RESULTS: At the end of the dialytic period, 7 of the 10 patients had normal serum potassium and sodium values. CPD produced two different types of complications: leakage of the dialytic fluid in very low weight newborns and one episode of peritonitis during a chronic dialysis treatment. Six died of severe respiratory failure (in no case, however, was this attributable to ARF or CPD procedure). All but one of the survivors regained normal renal function. The only exception necessitated a kidney transplant. CONCLUSION: We believe that this technique, although invasive, improves the outcome of both preterm and low birth weight newborns affected by ARF.

Acute Kidney Injury↗
PubMed1993

Pharmacokinetics and hematologic response to subcutaneous administration of recombinant human erythropoietin in children undergoing long-term peritoneal dialysis: a multicenter study.

For a study of the pharmacokinetics and hematologic response of subcutaneously administered recombinant human erythropoietin (rHuEPO), 24 children (mean age, 10 years 3 months; range, 3 months to 18 years) maintained by peritoneal dialysis and with anemia caused by end-stage renal failure (mean hemoglobin level, 6.5 gm/dl; range, 4.7 to 7.9) were treated with rHuEPO administered subcutaneously at an initial dose of 25 IU/kg twice per week. After a 4-week interval, in the case of no response (hemoglobin increase < or = 1 to 1.5 gm/dl per month) the rHuEPO dosage was increased every 4 weeks according to the following schedule: 50, 75, 100, and 150 IU/kg twice per week. The administration of rHuEPO produced a rapid increase in serum concentration with a mean peak level of 59.8 mU/ml after 9 hours. Mean area under the curve to 72 hours was 2020 mU/ml per hour (range, 568 to 6609); mean elimination half-life and mean residence time were, respectively, 25.2 hours (range, 6.2 to 58.7) and 42.0 hours (range, 10.9 to 96). Of 24 children entered in the study, six had the drug suspended early because of renal transplantation (n = 1), lack of compliance (n = 4), or severe worsening of hypertension (n = 1). Eighteen patients had increased hemoglobin levels (to 9.4 +/- 1.7 gm/dl after 24 weeks of treatment). No correlation was found between the increase in hemoglobin concentration and any of the pharmacokinetic data or the peak erythropoietin level reached during the kinetic profile. Eight children required an increase of antihypertensive medications to maintain satisfactory blood pressure values. We conclude that low doses of subcutaneously administered rHuEPO slowly release the drug into the blood and satisfactorily increase hemoglobin levels with very few side effects.

Adolescent↗
PubMed1993

Applications of extracorporeal photochemotherapy in "non-oncological" diseases.

Photopheresis (ECP) is a new therapy for oncological and autoimmune diseases consisting in the reinfusion of 3-9 x 10(9) leukocytes, taken from the patient by leukapheresis, and treated in an extracorporeal system with 8-methoxypsoralen and ultraviolet light A. Nine patients affected by T cell immunomediated diseases (2 scleroderma, 1 chronic GVHD, 1 polyarteritis, 1 rheumatoid arthritis and 4 heart transplant patients with numerous episodes of acute rejection) were treated with ECP. Photopheresis was performed on 2 consecutive days every 3-4 weeks. All patients affected by autoimmune diseases experienced an improvement during treatment with ECP. In 2 of the 4 patients with heart transplant, rejection was reversed by photopheresis. No major side effects were observed during the treatment. In conclusion ECP is a safe and well tolerated therapy. Although the number of patients is small, ECP seems to be an effective modality in many diseases.

Adolescent↗
PubMed1993

Cardiovascular function in a chronic peritoneal dialysis pediatric population on recombinant human erythropoietin treatment.

Anemia, through a hyperkinetic state, is an important contributor to myocardial function impairment. To determine the cardiovascular effects of recombinant human erythropoietin (rHuEPO) therapy, 10 chronic peritoneal dialysis (CPD)-treated anemic children were studied before and during 18 months of treatment. The following parameters were recorded: hemoglobin (Hb) [percent of target level (TL) = x-2 standard deviations of normal Hb values for age and sex], heart rate (HR, beats/minute), mean arterial pressure (MAP, mmHg), end-diastolic left ventricular diameter (EDLVD, mm/sm BSA), shortening fraction (SF, percent), and interventricular septal thickness (IVS, mm/sm BSA). Student's t-test for paired data showed (vs time before treatment, T0) a progressive increase in Hb, a progressive decrease in HR, and a progressive increase in MAP. EDLVD progressively decreased, while SF and IVS remained unchanged throughout the study. Regression analysis showed a close correlation between anemia correction and decrease of HR (p < 0.01), while no correlation was found between Hb and EDLVD or SF, IVS, or MAP. Our data indicate that anemia correction in these patients is mainly associated with a decrease in hyperkinetic state (HR reduction with SF unvaried), while left ventricular function and dimensions remain normal, despite an increase in MAP.

Anemia↗
PubMed1992

Effect of high doses of human recombinant erythropoietin on the need for blood transfusions in preterm infants.

To determine whether prophylactic treatment with recombinant human erythropoietin (rHuEPO) and iron would reduce the need for blood transfusions, we randomly assigned 22 premature infants with gestational ages less than or equal to 32 weeks and birth weights less than or equal to 1.75 kg to receive rHuEPO, 400 IU/kg three times a week, plus iron, 20 mg/wk intravenously, from the second day of life (11 infants), or no rHuEPO and no iron (11 infants). The two groups had similar birth weights and clinical variables. The treated infants required fewer blood transfusions (0.8 +/- 1.5 vs 3.1 +/- 2.1; p = 0.01) and less volume of packed erythrocytes (14.2 +/- 25.9 vs 48.4 +/- 34.0 ml/kg; p = 0.02). The amounts of blood sampled were not different (19.5 +/- 21.1 vs 27.8 +/- 19.1 ml/kg; p = 0.35). Reticulocyte and hematocrit values were higher in the treated group (4.46% +/- 0.8% vs 1.49% +/- 1.1% (p = 0.0001) and 48.1% +/- 7.3% vs 43.8% +/- 4.7% (p = 0.004), respectively). No side effects of either rHuEPO or intravenously administered iron were noted. These data indicate that rHuEPO, in combination with iron supplementation, is effective in reducing the need for blood transfusions in the premature infant. More information is needed on dosage, timing, and iron and vitamin supplementation.

Birth Weight↗
PubMed1992

Evidence for specific binding and stimulatory effects of recombinant human erythropoietin on isolated adult rat Leydig cells.

The presence of specific binding of recombinant human erythropoietin and its effect on testosterone production were evaluated in isolated intact adult rat Leydig cells. Maximal specific binding was observed after 135 min incubation at 34 degrees C. Scatchard analysis of the binding data revealed two distinct classes of binding sites for [125I]-recombinant human erythropoietin with dissociation constant of (Kd1) 1.9 x 10(-10) mol/l and (Kd2) 1.37 x 10(-8) mol/l respectively and binding capacity of (Bmax1) 12.3 fmol/10(6) cells and (Bmax2) 42.8 fmol/10(6) cells, respectively. GnRH, hCG, IGF-I and EGF did not induce any modification of recombinant human erythropoietin-specific binding. Recombinant human erythropoietin added to isolated adult rat Leydig cells exerted a stimulatory effect on testosterone production reaching its maximal effect at the dose of 10(-10) mol/l (testosterone production from 14.9 +/- 1.7 to 45.1 +/- 6.2 pmol/10(6) cells/3 h). Addition of anti-recombinant human erythropoietin serum completely blocked the recombinant human erythropoietin-stimulated testosterone production. These results show that purified adult rat Leydig cells possess recombinant human erythropoietin specific binding, and suggest that this glycoprotein directly influences rat Leydig steroidogenesis.

Animals↗
PubMed1992

Evoked potentials before and after anemia correction with recombinant human erythropoietin in end-stage renal disease.

Subclinical involvement of the nervous system in uremic adults has been detected by modern neurophysiological techniques. Chronic anemia is one of the possible factors responsible for neural dysfunction in uremia. We evaluated neurophysiological (brainstem auditory and somatosensory evoked potential) abnormalities and their possible modification following anemia correction with recombinant human erythropoietin in 14 children with end-stage renal disease maintained by hemodialysis. Only peripheral and 8th cranial nerve electrophysiological data are significantly abnormal in our patients, and they are not acutely modified by anemia correction. These data confirm the importance of electrophysiological testing of uremic children for detecting nervous system involvement at an early stage and for monitoring the efficacy of its management.

Adolescent↗
PubMed1991

Effect of human recombinant erythropoietin on bleeding time, platelet number and function in children with end-stage renal disease maintained by haemodialysis.

We studied platelet number and function in nine anaemic children with end-stage renal disease during a clinical trial with recombinant human erythropoietin (rHu-EPO). All the children showed a correction in both haematocrit and haemoglobin levels which was followed by a significant reduction in bleeding time. We also observed a significant increase in platelet count after both 6 and 12 weeks of therapy; at the same time mean platelet volume decreased and a normal platelet mass was maintained. The mean baseline platelet aggregation response to ADP was normal, but was decreased to collagen (P less than 0.05 vs normal control). Platelet production of thromboxane B2 in serum was also lower than normal controls. After correction of anaemia with rHu-EPO, platelet aggregation improved in patients with a decreased baseline response, and mean levels of thromboxane B2 became normal. In conclusion, the treatment with rHu-EPO improved haemostatic balance not only by correcting anaemia, but also by increasing platelet count and function.

Adolescent↗
PubMed1991

Somatosensory pathway dysfunction in uremic children.

Neurophysiological studies have shown defects in peripheral conduction in up to 75% of adults with end-stage renal disease (ESRD), though abnormalities of central conduction seem more variable. There are no comparable pediatric data. We therefore measured median nerve somatosensory evoked potentials (SEPs) in 10 children with ESRD, maintained by hemodialysis, who had no neurological signs or symptoms, and compared the results with those for age-matched controls. The latencies of N9, P14, N20 and P22, and interpeak latencies, N9-N20, N9-P14 and P14-N20, were not significantly different between the two groups (Student's t test). However, the children with ESRD were significantly retarded in growth and when arm length was taken into account, a significant difference in peripheral conduction was revealed. There was no correlation with other indexes of disease severity (parathormone, aluminium, Hb, Na, K, Cl, BUN and creatinine). SEPs appear to reflect subclinical changes in peripheral conduction in sensory pathways in children with ESRD which are not correlated with other measures of disease severity.

Adolescent↗