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Biomedical subjects

G Longo

Publications and source records attributed to G Longo.

At least 37 records · Page 2Linked to original sources

Concentrations of insulin-like growth factor (IGF)-I and IGF binding protein-3 in the follicular fluid of women undergoing ovarian hyperstimulation with different gonadotropin preparations.

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) have an important regulatory role in follicular development and oocyte maturation. The aim of this prospective, randomized, double-blind study was to measure the concentrations of IGF-I and IGFBP-3 in follicular fluids collected from infertile women undergoing ovarian hyperstimulation using three different gonadotropin preparations. Twenty infertile women (mean age 33 years, range 28-40) undergoing in vitro fertilization (IVF) programs were recruited. After a written informed consent, each woman randomly underwent a long-protocol for ovarian hyperstimulation using gonadotropin-releasing hormone (GnRH)-analog and one of the following recombinant- and urinary-gonadotropins--alpha-follitropin, beta-follitropin or urofollitropin. Serum 17 beta-estradiol (E2) levels and follicle growth were assessed during the follicular phase. The concentrations of IGF-I and IGFBP-3 in the follicular fluid of aspirated dominant follicles were measured directly. Women treated with alpha-follitropin needed significantly lower doses of follicle-stimulating hormone (FSH) compared to those receiving beta-follitropin (p < 0.05). No other statistically significant differences were detected between groups. Serum E2 levels increased in the three groups from early to late follicular phase. Follicular fluid IGF-I and IGFBP-3 concentrations did not differ significantly in the three groups of women. A statistically significant relationship was observed between follicular fluid IGF-I and IGFBP-3 levels (r = 0.41, p = 0.001). Oocyte maturation correlated in a positive manner with IGF-I (r = 0.34, p = 0.01) and IGFBP-3 (r = 0.29, p = 0.03). These findings show that both recombinant- and urinary-gonadotropin preparations were equally effective in releasing IGF-I and IGFBP-3 in the follicular fluid of dominant follicles, and confirmed the role of these compounds on oocyte maturation.

Adult↗

Gastric permeability to sucrose is increased in portal hypertensive gastropathy.

BACKGROUND: Portal hypertensive gastropathy (PHG) is frequently found among patients with hepatic cirrhosis and at present the only way to detect and follow PHG is via endoscopy. OBJECTIVE: To assess gastric and intestinal permeability and investigate its relationship to endoscopic findings and indices of portal hypertension and hepatic function. DESIGN AND METHODS: Thirty-one non-diabetic patients with hepatic cirrhosis and PHG (PHG+) were studied and compared with 17 cirrhotic patients without PHG (PHG-). All patients underwent endoscopy for the assessment of PHG and Helicobacter pylori status, ultrasound determination of the diameters of spleen and portal vein, and, subsequently, an oral load of sucrose, lactulose, and mannitol. Sugar concentrations were determined in 6-h urine specimens and expressed as a percentage of the orally administered dose or as lactulose/mannitol ratio. RESULTS: The urinary sucrose excretion was significantly elevated in patients with PHG compared to those without (PHG+, 0.20% +/- 0.03; PHG-, 0.07% +/- 0.01; P< 0.001). No difference was found for the small intestinal probes lactulose and mannitol. Gastric sucrose permeability correlated positively with the endoscopic lesion score (P < 0.001), but not with other parameters of portal hypertension or hepatic function. H. pylori status did not influence gastric permeability. The sensitivity of this test reached 100% for PHG scores > 2. CONCLUSIONS: Gastric permeability to sucrose is increased in patients with PHG, independently of the presence of H. pylori. Sucrose permeability may be useful for the follow-up of patients with PHG.

Female↗

Management of fever in neutropenic patients with acute leukemia: current role of ceftazidime plus amikacin as empiric therapy.

To evaluate the current role of ceftazidime plus amikacin as empiric therapy in the management of fever in neutropenic patients with acute leukemia, we examined 172 febrile episodes in 106 patients enrolled during 1996-98. The overall success rate (survival of neutropenia, both with and without protocol modification) was 90%: 39% without modification and 51% with modification. We documented a significant difference in documented infections (DI) and fever of undetermined origin (FUO): success without modification was lower in DI and higher in FUO. Failure (death due to documented or presumed infection) was recorded in 10% of all episodes. Episodes with severe neutropenia were treated in 48% of cases without modification and in 41% with modification. No significant difference was observed in the status of underlying disease. 33% of gram-negative bacteria responsible for bloodstream infections were resistant to ceftazidime, of which 21% were multiresistant strains. We conclude that initial chemotherapy with ceftazidime plus amikacin remains a reasonable option for treating febrile and prolonged neutropenia, although patients with DI are likely to require additional or modified treatment. The emergence of resistant strains is an increasingly important issue.

Acute Disease↗

Amifostine in the treatment of low-risk myelodysplastic syndromes.

BACKGROUND AND OBJECTIVE: The phosphorylated aminothiol agent amifostine (Ethyol) protects bone marrow and other tissues from toxicity due to ionizing radiation and antineoplastic drugs, and stimulates progenitors from normal and myelodysplastic bone marrow. Contrasting results have been published so far on the effectiveness of amifostine in correcting cytopenia in patients with myelodysplastic syndromes (MDS). DESIGN AND METHODS: In a pilot phase II study we treated 26 patients with low risk MDS (13 RA, 2 RARS, 2 CMML, 9 RAEB with blasts < 10%) with amifostine (200 mg/m(2 )x 3/week for 4 weeks). RESULTS: Hemoglobin concentration, reticulocyte, neutrophil and platelet counts increased respectively in 6 (23%), 11 (42%), 13 (50%) and 9 (34%) of patients. Red cell transfusions were reduced (> 50%) in 4/26 patients and abolished in 1/26. Unexpectedly a significant decrease in soluble transferrin receptor level at week 4 of therapy, compared to the basal level (p<0.04), was observed in the whole population of patients. INTERPRETATION AND CONCLUSIONS: Amifostine can ameliorate cytopenia in some patients with MDS, with few and mild side effects. Neutropenia is more likely to be corrected than anemia or thrombocytopenia. Mechanisms underlying this biological effect remain to be clarified.

Aged↗

Mechanisms of methotrexate resistance in acute leukemia. Decreased transport and polyglutamylation.

Drug resistance limits the effectiveness of methotrexate (MTX) for the treatment of acute leukemia. An increased understanding of the pathways involved in folate metabolism has allowed investigations of the mechanisms of resistance observed in leukemic blasts obtained from patients. Acute lymphocytic leukemia (ALL) was studied for mechanisms of acquired MTX resistance. MTX transport in 27 patients with untreated ALL and 31 patients with relapsed ALL was measured using a previously described competitive displacement assay. Only 13% of the untreated patients were considered to have impaired MTX transport whereas over 70% of the relapsed patients had evidence of impaired MTX transport. Northern analyses and quantitative RT-PCR for the reduced folate carrier (RFC) were performed on the RNA available from the leukemic blasts of 24 patients in whom MTX transport had been measured. Six of 9 samples with impaired MTX transport had decreased RFC expression (one had no detectable RFC expression), while three had no decrease in RFC expression. Acute myelocytic leukemia (AML) was studied to determine the basis of the decreased MTX polyglutamylation. Enzyme kinetics of the enzyme folylpolyglutamate synthetase (FPGS) were studied, demonstrating FPGS in the myeloid cell lines and patient samples had a higher K(m) for MTX as a substrate than lymphoid cells. Measuring gamma-glutamyl hydrolase enzyme activity allowed a more accurate prediction of steady state levels of MTX polyglutamates. A knowledge of the mechanisms of MTX resistance that occur in leukemic blasts obtained from patients may allow the development of therapeutic strategies to circumvent resistance.

Antimetabolites, Antineoplastic↗

Orthotopic liver transplantation in a patient with severe haemophilia A and with advanced liver cirrhosis.

A patient with severe haemophilia A underwent orthotopic liver transplantation because of changes correlated to end-stage liver cirrhosis due to hepatitis B, C and D infection. Replacement therapy was carried out for 4 days and the clinical course was uneventful. At the time of reporting the patient has a normal working life. FVIII plasma concentration is normal. The indirect hyperbilirubinaemia may be related to the Gilbert's anomaly of the donor.

Activities of Daily Living↗

Intestinal permeability test as a predictor of clinical course in Crohn's disease.

OBJECTIVE: The clinical course of Crohn's disease is often unpredictable. The aim of this study was to select the most useful parameters able to predict clinical relapses. METHODS: One hundred-thirty Crohn's disease patients in clinical remission were followed every 4 months for 2 yr or until clinical relapse. Demographic and clinical data were recorded and intestinal permeability (lactulose/mannitol [L/M] test) and biochemical tests (white blood cell count, erythrocyte sedimentation rate, C-reactive protein, alpha1 acid glycoprotein, and serum iron) were performed at study entry. A subgroup of 54 patients had clinical follow-up and repeated tests every 4 months. RESULTS: Fifty-two patients (40%) relapsed during the 2-yr follow-up. A significant correlation was found between relapse and gender (p = 0.030) but not between relapse and age, extent and type of disease, previous surgery, or therapy. Increased L/M test (p = 0.0001) and decreased serum iron level (p = 0.0057) were associated with clinical relapse. Time-dependent analysis, performed on patients receiving serial evaluation, showed that L/M test alteration was the only variable that could predict a relapse (RR 8.84, 95% confidence interval [CI] 1.41-53.37; p < 0.05). CONCLUSIONS: The L/M test identifies Crohn's disease patients in apparent remission, but with a high risk of clinical relapse, better than clinical and biochemical indices. Different treatment strategies might be suggested for this subgroup of patients.

Adolescent↗

Zinc therapy increases duodenal concentrations of metallothionein and iron in Wilson's disease patients.

OBJECTIVE: Wilson's disease is effectively treated by zinc administration which, in vitro, increases metallothionein concentrations. To ascertain whether the latter also occurs in humans we measured metallothionein and trace element concentrations in the duodenal mucosa of 15 Wilson's disease patients: 12 treated with zinc sulphate, two treated with penicillamine, and one not yet on treatment. The control group consisted of 17 patients with dyspepsia, who underwent the same study protocol. METHODS: Metallothionein and trace element concentrations were measured in duodenal mucosa biopsies according to the silver-saturation hemolysate method and atomic absorption spectrophotometry. RESULTS: Metallothionein concentrations increased by 1500% after zinc and 150% after penicillamine in Wilson's disease patients, with respect to controls who had negative endoscopy and Wilson's disease patients who were not treated. A significant correlation was found between metallothionein and duodenal zinc concentrations. Mucosal iron concentration increased in Wilson's disease patients whether they were treated with zinc or penicillamine. Duodenum with duodenitis also had significantly increased iron levels compared with normal duodenum. CONCLUSIONS: Zinc administration increases intestinal metallothionein in Wilson's disease patients. The blockade of copper absorption and its elimination in the stools on desquamation of the intestinal cells probably explains one of the mechanisms underlying the effect of zinc treatment. Despite normal endoscopy, Wilson's disease patients present increased mucosal iron concentrations similar to those in controls with duodenitis. Metallothionein may therefore prevent oxidative damage caused by metal toxicity.

Adult↗

Clinical characteristics, treatment outcome and survival of 36 adult patients with primary anaplastic large cell lymphoma. Gruppo Italiano per lo Studio dei Linfomi (GISL).

BACKGROUND AND OBJECTIVE: Although in recent years anaplastic large-cell lymphoma (ALCL) has emerged as a distinct clinico-pathological entity, a gold standard for treatment has still not been defined. Goals of our histologic, phenotypic and clinical study were to present clinical findings, treatment outcome and survival rates of a small, but highly homogeneously treated, series of patients. DESIGN AND METHODS: From April 1991, 36 newly diagnosed adult patients with systemic ALCL CD30+, entered a prospective non-randomized trial in one of the institutions participating in a GISL (Gruppo Italiano per lo studio dei Linfomi) study and were treated with a MOPP/EBV/CAD hybrid scheme. Chemotherapy (CHT) was administered every 28 days, for a total of 6 cycles. After CHT, 19 patients received radiation therapy (RT) to the site of previously involved fields. Kaplan and Meier and log-rank tests were used for statistical analysis. RESULTS: The overall complete remission rate was 78%, the partial remission rate was 6%. The overall survival rate at 74 months was 69%. No statistically significant differences in response or survival rates were noted comparing ALCL-HL and -CT subgroups, T+ Null- and B- subtypes, or ALCL-HL and -CT, with different phenotypes. In the analysis of patients with T+ Null phenotype treated with CHT+RT in comparison with B-ALCL patients who had the same treatment, we observed statistically significant differences in the survival rate (p=0.048). No prognostic factors predictive of response or survival were identified. INTERPRETATION AND CONCLUSIONS: Our results show that using MOPP/ABV/CAD the results, in terms of remission rate and survival, are similar to those obtained with 3rd generation CHT regimens. The diagnosis of T and Null ALCL is the most important prognostic factor, because it is associated with a very good survival, even in patients with a high prognostic index. Finally, we believe that longer follow-ups are needed to evaluate long-term survival and toxicity with different treatments.

Adolescent↗

[Prenatal diagnosis of osteogenesis imperfecta. Report of a case].

Osteogenesis imperfecta is a heterogeneous group of connective tissue disorders; it is characterized by blue scleras, bone fragility and deformity secondary to recurring fractures. A case of osteogenesis imperfecta personally observed at the 21st week of gestation is presented.

Adult↗

Experimental colitis increases small intestine permeability in the rat.

Small intestine permeability is frequently altered in patients with Crohn's disease and is thought to play a pathogenic role. The aim of this study was to investigate the permeability and structure of small intestine tight junctions (TJ) in an animal model of chronic distal colitis. Seven days after colitis induction with trinitrobenzenesulfonic acid/ethanol, the duodenal and ileal TJ were studied by means of transmission electron microscopy using lanthanum nitrate, freeze fractures, and immunohistochemistry of occludin, ZO-1, and cingulin. Animals treated with intrarectal ethanol alone served as controls. In controls, 7.5% of duodenal and 9.6% of ileal TJ were permeable to lanthanum, whereas in colitis, permeability increased significantly (79.5% and 72.9%, respectively; p < 0.001, both segments compared with controls). In colitis, the percentage of "leaky" junctions in duodena as well as in terminal ilea correlated positively with the macroscopic colon damage score (p < 0.02 and p < 0.005, respectively). Freeze-fracture analysis and immunohistochemistry of cingulin and ZO-1 did not reveal any difference between control and treated animals, whereas the signal of the transmembrane protein occludin was found to be disrupted and irregular in both small intestine segments. Distal colitis induces an increase of TJ permeability throughout the entire small intestine, and the extent of alterations correlates with colonic damage. Alterations in the transmembrane protein occludin seem to be responsible for the observed changes. Further investigation is needed to elucidate the mechanism of TJ alterations by a remote focus of inflammation.

Animals↗