Search PubMed⌕ Search

Biomedical subjects

M Colombo

Publications and source records attributed to M Colombo.

At least 73 records · Page 4Linked to original sources
PubMed1998

Production and characterization of a bicistronic Moloney-based retroviral vector expressing human interleukin 2 and herpes simplex virus thymidine kinase for gene therapy of cancer.

Gene-based therapeutic strategies for cancer mainly include augmentation of immunotherapeutic and chemotherapeutic approaches. In this study we report the design and functional assay of a novel bicistronic Moloney-based retroviral vector expressing human interleukin-2 (IL-2) and herpesvirus thymidine kinase (tk) through a cap-dependent translation and an internal ribosome entry site (IRES)-regulated translation, respectively. This construct has the potential for allowing combination of cytokine and suicide gene therapy, especially in areas such as the brain, composed of post-mitotic cells refractory to transduction by type C retroviral vectors. Accordingly, human glioma cells were used as targets for gene transfer after selecting a packaging cell clone that produced a reasonable titer of recombinant virus and expressed high levels of IL-2 and tk transcripts. Although transduction efficiency was reduced in glioma cells as compared with murine NIH 3T3 cells, transgene expression was effectively achieved. Transduced glioma cells were sensitive to ganciclovir and secreted around 1000 U/ml IL-2 in the culture supernatants. Simultaneous production of IL-2 and tk in vivo by genetically treated tumor cells would hopefully potentiate the effect of gangiclovir-induced metabolic suicide, possibly by boosting the immune response associated with tumor debulking or by amplifying the bystander response.

Antimetabolites↗
PubMed1998

Degradation of 2,4,6-trichlorophenol by a specialized organism and by indigenous soil microflora: bioaugmentation and self-remediability for soil restoration.

A selected mixed culture and a strain of Alcaligenes eutrophus TCP were able to totally degrade 2,4,6,-TCP with stoichiometric release of Cl-. In cultures of Alc. eutrophus TCP, a dioxygenated dichlorinated metabolite was detected after 48 h of incubation. Experiments conducted with soil microcosms gave evidence that: the degradative process had a biotic nature and was accompanied by microbial growth; the soil used presented an intrinsic degradative capacity versus 2,4,6-TCP; the specialized organism used as inoculum was effective in degrading 2,4,6-TCP in a short time. These results could be utilized for the adoption of appropriate remediation techniques for contaminated soil.

Alcaligenes↗
PubMed1998

Transmission of hepatitis G virus in patients with angioedema treated with steam-heated plasma concentrates of C1 inhibitor.

BACKGROUND: Hepatitis G virus (HGV) is a blood-borne flavivirus that may cause acute and chronic transfusion-transmitted infections. Patients with complement component 1 (C1) inhibitor (C1-INH) deficiency may acquire blood-borne infections through infusion of plasma concentrates. STUDY DESIGN AND METHODS: Serum samples from 84 patients with C1-INH deficiency (19 who received unmodified C1-INH concentrates, 23 who received steam-heated concentrates, and 42 untreated patients) were tested for HGV RNA and hepatitis C virus (HCV) RNA by a nested polymerase chain reaction (PCR). The samples were also tested for antibodies to the E2 envelope protein of HGV (anti-HGV) and to HCV with enzyme-linked immunosorbent assays. RESULTS: Nine (11%) patients had serum HGV RNA; that is, 7 (17%) of 42 patients previously treated with C1-INH concentrates and 2 of 42 previously untreated patients. HGV RNA was as common in the 19 patients treated with unmodified concentrates as in the 23 given steam-heated concentrates (16 vs. 17%, p = 0.60). Anti-HGV was more common among the recipients of unmodified concentrates than among those given steam-heated concentrates (26 vs. 0%, p = 0.014). HCV RNA was more frequently detected in treated patients than in untreated patients (33 vs. 7%, p = 0.005) and in the 19 recipients of unmodified concentrates than in the 23 treated with steam-heated concentrates (58 vs. 16%, p = 0.003). Only one HGV RNA-seropositive patient had elevated serum aminotransferase activity, compared to 11 with HCV RNA. CONCLUSION: HGV was transmitted by both unmodified and steam-heated concentrates, but it caused persistent viremia in a minority of the cases and was rarely associated with liver disease.

Adult↗
PubMed1998

Effect of zinc or zinc plus arginine supplementation on antibody titre and lymphocyte subsets after influenza vaccination in elderly subjects: a randomized controlled trial.

OBJECTIVE: to evaluate whether oral supplementation with zinc or zinc/arginine increases the antibody response to influenza vaccine or modulates the lymphocyte phenotype in elderly subjects. DESIGN: a randomized controlled trial with two supplemented groups and one control group. SETTING: a community nursing home. PARTICIPANTS: 384 subjects aged 64-100 (mean age 82 years) examined in three separate studies. INTERVENTION: oral supplementation with zinc (400 mg/day) or zinc plus arginine (4 g/day) for 60 days starting 15 days before influenza vaccination. The control groups received vaccine only. MEASUREMENTS: haematological and nutritional indices, antibody titre against influenza viral antigens, lymphocyte phenotype. RESULTS: supplementation with zinc or zinc plus arginine increased zinc plasma concentrations restoring the age-related impairment in zinc concentrations to values found in younger people. The antibody titre against influenza viral antigens was not increased in zinc or zinc/arginine supplemented groups in comparison with subjects receiving vaccine alone. The number of CD3, CD4 or CD8 lymphocytes was not affected by zinc or zinc/arginine supplementation. CONCLUSION: prolonged supplementation with zinc or zinc/arginine restores zinc plasma concentrations but is ineffective in inducing or ameliorating the antibody response after influenza vaccination in elderly subjects.

Aged↗
PubMed1998

Functional differentiation along the anterior-posterior axis of the hippocampus in monkeys.

We tested whether the primate hippocampus was functionally heterogenous along its anterior-posterior axis. Two monkeys were trained on both a spatial and nonspatial memory task and the incidence of spatial and nonspatial delay activity in the anterior, middle, and posterior hippocampus was noted. Spatial delay activity (activity in the delay period after the sample stimulus on the spatial memory task) was more common in the posterior than the anterior hippocampus, whereas nonspatial delay activity (activity in the delay period after the sample stimulus on the nonspatial memory task) was evenly distributed throughout the hippocampus. Furthermore, delay neurons in the anterior hippocampus exhibited scalloping delay activity, whereas those in the middle and posterior hippocampus did not. These findings suggest that the hippocampus is functionally heterogeneous and that the posterior regions may be more important for processing spatial information, whereas the anterior regions may be more important for directing or coding movements to points in space.

Acoustic Stimulation↗
PubMed1998

Dissociation between muscle and skin sympathetic nerve activity in essential hypertension, obesity, and congestive heart failure.

Essential hypertension, obesity, and congestive heart failure are characterized by an increase in muscle sympathetic nerve activity. Whether in these conditions skin sympathetic nerve activity is also increased has never been systematically examined, however. In 10 untreated mild essential hypertensive, 12 untreated normotensive obese, 10 mild (New York Heart Association class II) heart failure, and 10 normotensive lean healthy control subjects, we measured beat-to-beat arterial blood pressure (Finapres technique), body mass index, and postganglionic sympathetic nerve activity in skeletal muscle and skin areas (microneurographic technique, peroneal nerve). The muscle and skin nerve measurements were made in a randomized sequence. All data were obtained with the subject supine in a quiet, semidark environment at constant temperature over two periods of 30 minutes each, separated by a 20- to 30-minute interval. Blood pressure was increased only in hypertensive and body mass index only in obese subjects. Muscle sympathetic nerve activity quantified as bursts/min was markedly and significantly (P<.01) greater in essential hypertensive (33.3+/-1.7), obese (42.2+/-2.8), and congestive heart failure subjects (55.8+/-4.3) in comparison with control subjects (23.9+/-1.6). This was the case also for muscle sympathetic nerve activity, quantified as bursts per 100 heart beats. In contrast, skin sympathetic nerve activity (bursts per minute) was superimposable in hypertensive, obese, heart failure, and control subjects, its ability to increase being documented in all four groups by the marked response to an acoustic stimulus. Thus, in various diseases, muscle but not skin sympathetic activity is increased, with the sympathetic activation not being uniformly distributed over the whole cardiovascular system.

Adult↗
PubMed1998

Treatment of obstetric and gynecologic infections with meropenem: comparison with imipenem/cilastatin.

The aim of this study was to compare the clinical and bacteriologic efficacy of meropenem with imipenem/cilastatin in the treatment of obstetric and gynecologic infections. This was a controlled, multicenter, randomized study with two parallel groups and a follow-up period of up to 4 weeks. A total of 105 hospital in-patients requiring antibacterial parenteral therapy were enrolled, 52 in the meropenem group and 53 in the imipenem/cilastatin group. Both drugs were administered at 0.5 g every 8 hours, by slow intravenous infusion over 20-30 minutes; for meropenem the administration by intravenous bolus injection (over approximately 5 minutes) was allowed. The mean duration of therapy was 5 days for both treatments. At the end of treatment, all 46 evaluable patients in the meropenem treatment group had a satisfactory clinical response, while in the imipenem/cilastatin group 5/49 patients were clinical failures. The difference between the treatment groups in clinical response was statistically significant (100% vs 89.8%; p=.026). A similar result was seen in the intention-to-treat analysis (98% vs 84.6%; p=0.017). Both treatments were well tolerated, but fewer meropenem patients experienced treatment-related adverse events in comparison with imipenem/cilastatin (11.5% vs 15.1%).

Adolescent↗
PubMed1998

The natural history of hepatocellular carcinoma in Western countries.

Hepatocellular carcinoma (HCC) often has a long-lasting subclinical incubation period during which it may grow as a solitary mass. This does not mean that, in some patients, the tumor may be found as more than one nodule when it is first detected. The so-called expanding, encapsulated type of tumor seems to prevail among Oriental, Italian and French patients, rather than the more aggressive, spreading form of tumor. However, many patients with apparently single encapsulated HCC nodes may have ancillary tumors detectable only with highly sensitive imaging techniques or during surgery. There are important variations in the growth rate of this tumor, even in a single patient with multiple nodes. These differences in the growth patterns of HCC have made a clear understanding of the natural history of this tumor and prediction of patient survival difficulty. Thus, survival times are better correlated with the severity of liver impairment than with the number or size of tumors. Hepatic failure and gastrointestinal bleeding are the leading causes of death in both Oriental and Caucasian patients, accordingly. There are still many aspects of the natural history of HCC to be investigated, including whether or not all HCCs originate from one clone of transformed liver cells or more, as well as identifying which tumor and/or patient characteristics may predict individual tumor growth rates.

Carcinoma, Hepatocellular↗
PubMed1998

High prevalence but low pathogenicity of hepatitis G virus infection in Italian patients with genetic haemochromatosis.

BACKGROUND: Various environmental factors have been shown to hasten cirrhosis and hepatocellular carcinoma in patients with genetic haemochromatosis. AIM: To assess the prevalence and the role of the recently identified hepatitis G virus in 70 patients with genetic haemochromatosis in comparison with 40 patients with cryptogenic chronic hepatitis and 200 regular blood donors. PATIENTS: Six patients with genetic haemochromatosis (9%) had serum hepatitis B surface antigen, 14 (20%) had serum hepatitis C virus RNA. A liver biopsy was available in 66 patients with genetic haemochromatosis (43 with cirrhosis) and 40 with cryptogenic hepatitis (4 with cirrhosis). METHODS: Serum HGV-RNA was detected by a reverse transcriptase polymerase chain reaction using primers derived from the 5'-non-coding and non-structural-5A regions of the viral genome. Serum IgG antibodies against HGV were detected by enzyme-linked immunosorbent assay using a recombinant E2 protein of the virus envelope. RESULTS: The prevalence of serum HGV-RNA was higher in patients with cryptogenic hepatitis (n = 6, 15%) and genetic haemochromatosis (n = 6, 9%) than in donors (n = 3, 1.5%) (p = 0.0008 and p = 0.01, respectively). The corresponding figures for serum anti-HGV were 4 (10%), 16 (23%) and 10 (5%). The six haemochromatotic patients with serum HGV-RNA more often had parenteral exposure to blood (50% vs 5%, p < 0.001), and persistently elevated serum aminotransferases (100% vs 31%, p < 0.001) than the 64 non-viraemic patients. The six HGV-RNA seropositive patients with cryptogenic hepatitis were older than the 34 non-viraemic patients (56 vs 34 years, p < 0.05). CONCLUSIONS: The prevalence of serum markers of HGV infection in patients with genetic haemochromatosis is higher than in blood donors, but similar to that of patients with cryptogenic chronic hepatitis. However, HGV is not a cofactor of morbidity in patients with genetic haemochromatosis.

Adult↗
PubMed1997

High rates of hepatitis G virus infection in multitransfused patients with hemophilia.

The parallel measurement of serum antibodies to the hepatitis G virus (anti-HGV) and of viremia (HGV-RNA) should improve our understanding of HGV transmission by coagulation factor concentrates. The aim of this study was to assess the relationship between HGV, the type of concentrate infused, and liver disease in multitransfused hemophiliacs. To this end, anti-HGV and HGV-RNA were evaluated by an enzyme-linked immunosorbent assay and a nested-polymerase chain reaction assay in patients treated lifelong with nonvirus-inactivated plasma-derived concentrates (n = 128), virus-inactivated concentrates (n = 33), or recombinant factors (n = 7), and in 200 regular blood donors. The prevalence of serum HGV-RNA and anti-HGV was higher in the recipients of nonvirus-inactivated factors than in blood donors (HGV-RNA: 9% v 1.5%, P = .002; anti-HGV: 32% v 5%, P < .0001). In the recipients of virus-inactivated concentrates the prevalences of these markers were similar to those in blood donors (HGV-RNA: 3% v 1.5%; anti-HGV: 15% v 5%). The prevalence of either marker in the recipients of nonvirus-inactivated concentrates was higher than in the recipients of virus-inactivated factors (39% v 18%, P = .04). The former group had serum hepatitis C virus (HCV) RNA or anti-HCV more frequently than the latter group (HCV-RNA: 86% v 15%, P < .0001; anti-HCV: 96% v 18%, P < .0001). Serum alanine aminotransferase was persistently high in 83 (81%) patients with HCV-RNA alone, in 8 (89%) with HCV/HGV coinfection, and in none of the three patients with HGV-RNA only. Thus, HGV infection in hemophiliacs is more common than previous studies of HGV-RNA prevalence have suggested, but it resolved in most cases and caused chronic viremia only in a small number of patients, without biochemical evidence of persistent liver damage.

Adolescent↗
PubMed1997

A multicenter controlled, randomized, open trial of interferon alpha2b treatment of anti-human immunodeficiency virus-negative hemophilic patients with chronic hepatitis C. Hepatitis Study Group of the Association of Italian Hemophilia Centers.

There is limited information about the long-term efficacy of prolonged therapy (more than 6 months) with interferon alpha in hemophilic patients with chronic hepatitis C who are not coinfected with the human immunodeficiency virus (HIV-1). One hundred and seven hemophiliacs were randomly assigned to 3 million U of interferon alpha2b three times weekly for 12 months or no therapy. The patients were followed up for at least 12 months posttreatment. Response was assessed by both serial alanine aminotransferase (ALT) levels and hepatitis C virus (HCV)-RNA measured by reverse transcribed polymerase chain reaction (RT-PCR) method. Before treatment, serum levels of HCV-RNA were measured quantitatively by second-generation branched-DNA assay and the HCV genotype was determined by RT-PCR. Serum HGV-RNA, a marker of infection with the hepatitis G virus, was also measured by RT-PCR. Normalization of ALT was sustained and serum HCV-RNA was cleared in 6 of 45 treated patients, compared with none of the 50 untreated controls (13% v 0% P < .01). Low pretreatment viremia was the only feature that was associated with an increased likelihood of sustained response (P < .01). This study shows that multitransfused hemophiliacs with chronic hepatitis C not coinfected with HIV-1 respond at low rates to prolonged interferon therapy.

Adolescent↗
PubMed1997

The incidence and risk factors of community-acquired hepatitis C in a cohort of Italian blood donors.

To assess the incidence and source of community-acquired hepatitis C virus (HCV) infection among subjects at low risk for blood-borne diseases, we prospectively studied a cohort of 16,515 repeat blood donors over a mean follow-up time of 36 months. Second- and third-generation methods were used for hepatitis C virus antibody (anti-HCV) testing. HCV RNA was determined in the serum of anti-HCV-positive donors by reverse-transcription polymerase chain reaction. Liver biopsy was performed in the viremic subjects. Risk factors for HCV infection were identified by a psychosocial questionnaire in the whole cohort. During follow-up, 5 donors became infected with HCV. The incidence was 1 per 10,000 person-years (95% confidence interval, 0.3-2.4 per 10,000). During the 6 months before seroconversion, four subjects (80%) underwent medical or surgical percutaneous procedures, compared with 26.5% in the entire donor cohort (difference between frequencies, 53.5%; CI: 18.9-89.1). One seroconverting donor had sexual intercourse with an infected subject. Only 1 infected donor developed clinically evident acute hepatitis. HCV RNA remained detectable in 4 of 5 subjects for 8 to 36 months after seroconversion, and liver biopsy showed chronic hepatitis in all cases. Thus, new cases of hepatitis C occur among individuals without a history of known risk factors, some of which may be caused by nosocomial exposure.

Adult↗
PubMed1997

A randomized, controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis B e antigen in serum.

Short-term interferon treatment of serum hepatitis B e antigen (HBeAg)-negative carriers with serum hepatitis B virus (HBV) DNA and histological features of chronic hepatitis B has been largely unsuccessful. In a pilot study of long-term treatment, 42 such patients were randomly assigned to 6 million units of interferon alfa 2b (IFN-alpha2b) three times per week for 24 consecutive months (n = 21, 4 with cirrhosis) or to no therapy (n = 21, 3 with cirrhosis). Five patients (24%) discontinued therapy because of treatment-related adverse reactions. Serum levels of alanine transaminase (ALT) became persistently normal and HBV DNA undetectable by dot-blot assay in 8 patients receiving interferon and in 2 untreated controls (38% vs. 10%; P = .03). Hepatitis flare-ups disappeared in 17 patients during therapy compared with 6 controls (81% vs. 29%; P < .001). During a median period of 22 months after interferon was stopped, 2 treated patients (10%) lost serum hepatitis B surface antigen (HBsAg) and seroconverted to antibodies to hepatitis B surface antigen (anti-HBs). Serum ALT remained persistently normal and HBV DNA undetectable by dot-blot assay in 6 initial responders and 1 initial nonresponder, compared with none of the 21 untreated controls (sustained response: 33% vs. 0; P < .001). Comparative analysis of pre- and posttreatment liver biopsies showed that mean Knodell scores dropped in the treated group (10.3 to 5.3; P = .01), but not in the untreated group (9.3 to 9.8; not significant). In conclusion, a 24-month course of treatment with 6 MU IFN-alpha2b was well tolerated by most patients, led to sustained suppression of HBV in one third, and attenuated hepatitis in 81% of patients.

Adult↗
PubMed1997

Surgery for genitourinary prolapse and stress incontinence: a randomized trial of posterior pubourethral ligament plication and Pereyra suspension.

OBJECTIVE: Our purpose was to compare two antiincontinence procedures in patients with severe genitourinary prolapse and coexisting clinical or potential stress incontinence. STUDY DESIGN: In addition to cystopexy, 109 patients with a urethrocystocele of grade 2 or more and a positive stress test result with prolapse reduction received posterior pubourethral ligament plication or Pereyra suspension. RESULTS: Of 55 patients undergoing posterior pubourethral ligament plication, 15 were clinically and 40 potentially incontinent; the same figures were 21 and 33, respectively, among 54 patients undergoing the Pereyra procedure. Follow-up was for 3 to 9 years. Subjective (60% vs 71%, p = 0.72) and objective (27% vs 57%, p = 0.14) cure rates were not statistically different among patients who were clinically incontinent (posterior pubourethral ligament plication vs Pereyra suspension). Among potentially incontinent patients, subjective (85% vs 100%, p = 0.03) and objective (50% vs 76%, p = 0.04) continence rates were higher after the Pereyra procedure. Overall, the cotton swab test had negative results (maximum straining angle < or = 30 degrees) after successful surgery in 79% and 96%, respectively, of patients (p = 0.03). Four subjects (7%) underwent removal of one Pereyra suture because of urinary retention or suprapubic wound infection. CONCLUSION: Cystopexy with Pereyra suspension is recommended, particularly for patients with prolapse and potential stress incontinence.

Female↗