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Biomedical subjects

M Clementi

Publications and source records attributed to M Clementi.

At least 109 records · Page 6Linked to original sources
PubMed1997

Quantitative analysis of hepatitis C virus activity in vivo in different groups of untreated patients.

Highly sensitive competitive PCR (cPCR) and competitive reverse transcription PCR (cRT-PCR) methodologies were recently developed and applied for quantifying viral DNA and RNA species (including HCV RNA) present in clinical samples at low concentration. In this study, we used cRT-PCR to compare the viral load of 118 untreated patients with HCV infection and different clinical conditions (80 patients with chronic hepatitis, 18 infected subjects with persistently normal ALT levels and various degrees of liver injury, 10 HCV infected subjects that tested positive for anti-LKM1 antibodies, and 10 patients with HCV infection and cryoglobulinemia). The results indicate that while great individual variability of HCV viremia is detectable even among patients with similar clinical conditions, the mean HCV RNA copy number in samples from patients with different clinical conditions was similar in all groups with the single exception of patients that tested positive for anti-liver-kidney microsomal auto-antibodies type 1 (anti-LKM1); interestingly, lower HCV viremia levels were revealed in these anti-LKM1-positive cases with liver disease of uncertain pathogenesis.

Gene Dosage↗
PubMed1997

Quantitative liver parameters of HCV infection: relation to HCV genotypes, viremia and response to interferon treatment.

BACKGROUND/AIMS: This study aimed to evaluate the relation between the number of hepatocytes positive for HCV antigens and the amount of HCV RNA in the liver and to evaluate the relationship between the above parameters and viremia levels, HCV genotype and response to interferon treatment. METHODS: This was a retrospective study on 31 consecutive patients with chronic HCV-related liver disease, selected on the basis of the availability of frozen liver tissue for both liver HCV antigens detection and liver HCV RNA quantitation. HCV antigens (immunohistochemistry), liver and plasma HCV RNA (competitive RT-PCR), and HCV genotype (commercial kit) were studied. RESULTS: A significant correlation (p=0.0005) was found between the amount of liver HCV RNA (log 10 copy/microg of extracted RNA) and the number of HCV-infected hepatocytes (scored from 0 to 3). These parameters were not significantly correlated with viremia levels. The highest liver HCV RNA levels and HCV antigen scores were found in patients infected with genotype 1b. Liver HCV RNA (median 541 x 10(3) vs 118 x 10(3) copy number/microg, p=0.031) and liver HCV antigens (mean score 2.3 vs 1.3, p=0.018) but not plasma HCV RNA (median 14956 x 10(3) vs 2885 [correction of 2.885] x 10(3) copy number/ml, ns) were significantly higher in patients not responding to interferon treatment compared to responders. CONCLUSIONS: The tissue parameters tested in this study were significantly correlated, shared the same clinical implications and predicted short-term response to interferon treatment better than viremia levels. We suggest that these tests should be included in the study protocol of patients under evaluation for interferon treatment, basing the choice on local facilities.

Adult↗
PubMed1997

Clinical implications of GBV-C/HGV infection in patients with "HCV-related" chronic hepatitis.

BACKGROUND/AIMS: To evaluate the clinical, biochemical and histological implications of a concomitant HGV infection in "HCV-related" chronic liver disease. METHODS: Eighty-three HCV-RNA positive patients with chronic liver disease were tested for GBV-C/HGV coinfection by heminested PCR. RESULTS: Twenty-two (26.5%) patients were found to be positive for GBV-C/HGV RNA. GBV-C/HGV+ patients differed significantly from GBV-C/HGV- ones for younger age, higher frequency of history of drug addiction, which in turn might favor coinfection with interferon-sensitive HCV genotypes (3a), and increased probability of long-term response to interferon. GBV-C/HGV infection appears to have no responsibility for specific aspects of HCV infection such as biochemical or histological cholestatic features, lymphoid follicles, symptomatic cryoglobulinemia or presence of serum autoantibodies, including LKM1. It does not worsen the HCV-related disease (ALT levels and histological activity) and does not significantly interfere with HCV infection, as explored by the number of hepatocytes positive for HCV antigens. The amount of steatosis (mean score) was shown to be higher in GBV-C/HGV+ patients. A virological follow up was performed in 17 interferon-treated GBV-C/HGV+ patients On the whole, GBV-C/HGV seems to be as sensitive to IFN treatment as HCV, but recurrence after withdrawal is more frequent. In spite of this, ALT levels often remain normal after treatment withdrawal. CONCLUSIONS: The present data suggest that GBV-C/HGV infection, apart from more marked liver steatosis, does not modify the overall picture of chronic hepatitis due to HCV infection.

Adolescent↗
PubMed1997

Dynamic features of human immunodeficiency virus type 1 (HIV-1) viremia: kinetics of cell-free HIV-1 RNA after therapeutic plasma exchange.

To gain insight into the variables that influence the dynamics of human immunodeficiency virus type 1 (HIV-1) viremia levels, HIV-1 RNA molecules were quantified in plasma from an infected patient undergoing therapeutic plasma exchange (TPEx). After each TPEx procedure (2000 mL of fluid exchanged per session), HIV-1 genome molecule levels dropped to 58%-63% of the basal level but rapidly reverted to pre-TPEx values (doubling time = 3.50-4.04 h). Of interest, mobilization of extravascular cell-free virions (on average, 5.15 x 10(4) viral genome molecules/h) had already occurred during TPEx. After three daily TPEx procedures, HIV-1 viremia rebounded to basal values, while HIV-1 proviruses and viral transcripts in peripheral blood lymphocytes constantly tested at stable levels. Overall, this study extends previous analyses of the rate of HIV-1 turnover, using an alternative approach to the use of antiretroviral drugs, and it provides, albeit indirectly, insights into the amount and dynamic features of extravascular cell-free virus.

Cell-Free System↗
PubMed1997

Homozygous delta 32 deletion of the CCR-5 chemokine receptor gene in an HIV-1-infected patient.

BACKGROUND: Recent research has found that entry of non-syncytium-inducing (NSI), monocyte-macrophage-tropic HIV-1 isolates requires binding to both CD4 and CCR5 receptors, and that delta 32/delta 32 homozygous individuals are protected against infection. OBJECTIVE: To analyse the polymorphism of CCR-5 gene in HIV-1-infected and uninfected subjects. DESIGN AND METHODS: CCR-5 sequences were amplified by polymerase chain reaction (PCR) from DNA of peripheral blood mononuclear cells. Samples from 152 HIV-1-infected subjects and 122 uninfected controls were tested for the detection of the 32 base-pair deletion. HIV-1 phenotype was determined by viral isolation and MT-2 evaluation. RESULTS: The wild-type/delta 32 heterozygous and delta 32/delta 32 homozygous conditions were represented in 10.7 and 0.8% of healthy controls and in 9.8 and 0.7% of HIV-1-infected subjects, respectively. Of note, the delta 32/delta 32 deletion of the CCR-5 gene was detected by PCR and sequencing confirmed in a patient with progressive infection harbouring a clade B virus with SI phenotype. CONCLUSIONS: delta 32/delta 32 homozygosity for the CCR-5 gene does not confer absolute protection against HIV-1 infection, suggesting that either macrophage-tropic viral strains could use coreceptors other than CCR-5 or infect independently of the presence of a functional CCR-5 coreceptor. Alternatively, primary infection sustained by T-cell-tropic isolates, although exceptional, may occur.

Adult↗
PubMed1997

Reductions in viral load and increases in T lymphocyte numbers in treatment-naive patients with advanced HIV-1 infection treated with ritonavir, zidovudine and zalcitabine triple therapy.

In order to test the hypothesis that a combination of protease inhibitors with nucleoside analogues-agents known to inhibit different steps of the human immunodeficiency virus (HIV) life cycle--is likely to prove more effective in reducing viral loads than either of those modalities alone, we performed a 60 week, open-label trial in 32 HIV-positive patients with depressed CD4 T lymphocyte cell counts but no active AIDS-defining illnesses. For the first 2 weeks, patients received 600 mg twice daily of liquid ritonavir, a protease inhibitor; then zidovudine 200 mg three times daily and zalcitabine 0.75 mg three times daily were added to the treatment regimen. Mononuclear blood cell fractions were analysed for infected cell levels, using a co-culture system. HIV-1 RNA in plasma was measured both by reverse transcriptase-polymerase chain reaction (RT-PCR) and reverse transcriptase quantitative PCR (QcRT-PCR); lymphocyte counts were determined by standard laboratory methods. In the 2 weeks of ritonavir therapy, both the mean count of infectious blood cells and plasma HIV RNA levels decreased dramatically. Mean CD4 cell counts increased from 173 cells/mm3 at baseline to 286 cells/mm3; CD8 cell counts rose from 951 cells/mm3 to 1,141 cells/mm3. With the introduction of the nucleoside analogues, infectious cell counts and plasma virus dropped another log unit to a nadir at 8 weeks, while CD4 T lymphocyte counts continued to rise slowly. By week 28, 12 patients had withdrawn due to adverse events, none of which were life-threatening. At week 36, infectious material could not be detected in the cells of 10 of the 17 remaining patients; by week 60, four of the seven patients with residual viraemia at week 24 had undergone viral relapse. After the introduction of a more palatable capsule formulation of ritonavir at week 52, infectious cells and plasma virus were undetectable in 50-60% of patients. The combination of protease inhibitors and nucleoside analogues significantly reduces HIV load, and in some patients may suppress viral activity for sustained periods.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Carcinoma of the duodenum: management and survival in 14 cases.

AIMS: The aim of this study is to evaluate the role of surgery in the treatment of adenocarcinoma of the duodenum. METHODS: From 1955 to 1994, 14 patients with primary adenocarcinoma of the duodenum underwent surgical treatment in our department. Presenting signs and symptoms were mainly related to obstruction and bleeding. Upper gastrointestinal contrast study, Computed Tomography (CT) and duodenoscopy were the primary diagnostic procedure modalities. All diagnoses were confirmed histologically. The tumors were staged pathologically according to the new TNM classification (UICC, 1992). Eight patients received palliative treatment or exploratory laparotomy. The remaining 6 patients were resectable for cure. RESULT: Operative mortality was 35.7%. The 5-year survival rate for patients who underwent curative resection was 33.3%. None of the patients who underwent palliative procedures or exploratory laparotomy survived for more than 11 months. CONCLUSIONS: In the management of resectable adenocarcinomas of the duodenum surgical radicality including lymphadenectomy should be pursued. Unresectable adenocarcinomas treated with palliative procedure had a very poor prognosis.

Adenocarcinoma↗
PubMed1997

Rhodococcus equi pneumonia in a patient with occult HIV infection: successful therapy.

We report a case of Rhodococcus equi cavitary pneumonia in a 37-year-old patient with occult HIV infection. Because of his good immune status, the patient was given oral erythromycin and rifampin which rapidly resolved the infection. This modality of treatment may be sufficient in HIV-positive selected patients fur the resolution of Rhodococcus equi pneumonia.

Actinomycetales Infections↗
PubMed1997

Differential effect of stress on gastric somatostatin, prostaglandin E and gastrin release in the rat.

BACKGROUND: The relationship between gastric mucosal damage induced by stress, peptides present in the gastric mucosa and is not clear. Aim of this study was to determine whether cold-restraint stress affected the release of gastric somatostatin, gastrin and in the isolated perfused stomach preparation. METHODS: Male Sprague-Dawley rats were used, 12 cold-restraint stressed and 12 unstressed controls. 4 additional unstressed rats were treated with aspirin (100 mg/kg p.o.). After 30 minutes, isolated stomachs were perfused for 50 minutes with Krebs-Ringer buffer added with isoproterenol or carbamylcholine plus somatostatin-14 or carbamylcholine alone, somatostatin, gastrin and prostaglandin E2 release in the portal vein effluent were measured by radioimmuno-assay. Histology of the gastric mucosa was obtained from a further 4 stressed and 4 unstressed rats. RESULTS: In the stomach from stressed animals, the somatostatin response to isoproterenol and the prostaglandin E2 response to carbamylcholine plus somatostatin were significantly lower than in the controls, whereas gastrin response to carbamylcholine was enhanced by stress. Treatment with aspirin abolished the prostaglandin E2 response to stimulation. Gastric mucosa histology from stressed and unstressed animals showed no significant lesions. CONCLUSIONS: The inhibition of gastric somatostatin and prostaglandins release coupled to an enhanced acid stimulatory influence appear to antidate gastric mucosal injury and should play a role in the stress ulcer genesis.

Analysis of Variance↗
PubMed1996

Familial congenital bicuspid aortic valve: a disorder of uncertain inheritance.

Congenital bicuspid aortic valve (BAV) is one of the most frequent heart defects detected by echocardiographic investigation and necropsy (0.9-1% of the general population), but only 16 families with familial congenital BAV have been described up to now. We report on a family in which 4 members of two generations (2 brothers, 1 sister, and her son) are affected with BAV. The BAV mode of inheritance is discussed.

Adult↗
PubMed1996

Anesthesiologic problems in Williams syndrome: the CACNL2A locus is not involved.

We present the case of a patient affected with Williams syndrome (WS), who developed a suspected malignant hyperthermia (MH) reaction to general anesthesia. The proximity to the WS region of the gene encoding the L-type voltage-gated calcium channel alpha 2/delta-subunit (CACNL2A) on 7q11.23-q21.1, previously shown to be closely linked to some forms of MH susceptibility, prompted us to investigate whether this gene is deleted in WS. Linkage studies and fluorescence in situ hybridization analysis demonstrated that the CACNL2A locus is localized outside the WS deleted region.

Adolescent↗
PubMed1996

Low hepatitis C viremia levels in patients with anti-liver/kidney microsomal antibody type 1 positive chronic hepatitis.

BACKGROUND/AIMS: The majority of adult patients positive for anti-liver-kidney microsomal antibody are also positive for anti-hepatitis C virus and serum HCV RNA. In these patients the role played by hepatitis C virus infection in the progression of liver damage and its relationship with anti-liver-kidney microsomal antibody are, however, still a matter of debate. METHODS: To clarify this point we have compared hepatitis C viremia in sera from 31 hepatitis C virus-related chronic hepatitis patients positive for anti-liver-kidney microsomal antibody with that of 31 patients with hepatitis C virus-related chronic hepatitis without autoantibodies using a newly developed competitive reverse transcription-polymerase chain reaction technique. Reverse transcription-polymerase chain reaction was performed using a synthetic competitor of a length similar to that of wild template (71 bp vs 86 bp). RESULTS: The results obtained have been related to hepatitis C virus genotypes. Anti-liver-kidney microsomal antibody/anti-HCV positive patients show a median value of hepatitis C virus genome molecules (626829/ml, range 9780-25651424), significantly lower than anti-liver-kidney microsomal antibody negative/anti-HCV positive patients (10158314/ml, range 101822-67429974) (p < 0.001). No hepatitis C virus genotype was significantly associated with anti-liver-kidney microsomal antibody, although a predominance of genotype 1 (subtypes a and b) has been observed in these patients. CONCLUSIONS: Since a low hepatitis C viremia has been observed in anti-liver-kidney microsomal antibody positive patients with disease severity comparable to that of patients without autoantibodies, it is conceivable that in them autoimmune mechanisms may cooperate with viral infection in sustaining disease activity.

Adolescent↗
PubMed1996

Differential humoral immune response against hepatitis C virus antigenic synthetic peptides in infected patients with and without mixed cryoglobulinaemia.

In this study we have evaluated the prevalence of antibodies against core region peptides (residues 1-28, 21-38 and 51-68), the envelope 1, the non-structural (NS) 4 and 5 proteins of hepatitis C virus (HCV) in sera from 65 chronically HCV-infected patients, 47 with mixed cryoglobulinaemia (MC+) and 18 without (MC-). The major binding sites were located within the core region. Regions 1-28 and 51-68 were recognized by a similar proportion of MC+ and MC- patients, while peptide 21-38 was less frequently detected by samples from MC+ patients (65.5% versus 100%, P = 0.011). The patterns of the reactions showed a minimum of three binding sites: one, located within region 51-68, was shared by both groups; a second determinant was identified at residues 1-21 for MC+ patients and at residues 28-38 for MC- patients; a third, not exactly localized, lay between residues 1 and 38. Recognition of NS5 peptides was not significantly different between MC+ and MC- patients, but while the former mostly reacted either with peptide 1 (residues 2294-2309) (five of 15 sera) or with peptide 2 (residues 2304-2319) (nine of 15 sera), the latter group showed a more scattered reaction. Antibodies to HCV peptides prevalently belonged to IgGl subclass. However, whereas IgGl antibodies against peptide 21-38 and peptide 1 of NS5 were more frequently found in MC- rather than in MC+ patients (100% versus 63.8%, P = 0.003, and 22.2% versus 4.2%, P = 0.025, respectively), IgG3 antibodies against region 1-28 were more frequent in MC+ patients (53.19% versus 16.6%, P = 0.0078). Overall, the data suggest that a differential humoral immune response to HCV antigens occurs in patients with and without cryoglobulinaemia.

Adult↗
PubMed1996

Headache in patients with neurofibromatosis type 1.

A study of headache in a homogeneously ascertained population of 181 subjects suffering from neurofibromatosis type 1 is described. All subjects underwent a diagnostic protocol including imaging studies (for subjects over 5 years old up until 1992). Headache data were collected by means of a questionnaire. Headache was present in 55 of 181 subjects (25 males). Overall headache frequency was 30%, which is not significantly different from the frequency of headache reported in the general population. Headache was primary in 52 cases (5 migraine and 47 tension-type) and secondary to obstructive hydrocephalus with brain tumor-induced intracranial hypertension in 3 with a tension-type pattern. It was concluded that headache is not a specific feature of neurofibromatosis type 1, it is not significantly related to central nervous system abnormalities, and in itself, it is not an indication for neuroradiological examination.

Adolescent↗
PubMed1996

Analysis of HIV-1 load in blood, semen and saliva: evidence for different viral compartments in a cross-sectional and longitudinal study.

OBJECTIVES: To quantify the HIV-1 load (measured as copies of viral RNA/ml using competitive reverse transcription-polymerase chain reaction) in blood, semen and saliva and to look for relationships between the viral burden, the clinical and immunological status and antiretroviral therapy. METHODS: Peripheral blood, semen and whole saliva samples were collected from 26 anti-HIV-1-seropositive patients selected for a cross-sectional study. Nine of the 26 patients provided samples of the three biological fluids for a longitudinal study. RESULTS: HIV-1 RNA was detected in 26 out of 26 samples of plasma, in 25 out of 26 samples of semen and in 24 out of 25 samples of saliva. The median number of HIV-1 copies in plasma was 14 817/ml (range: 167-254 880), in semen was 515/ml (range: 0-196 050) and in saliva was 162/ml (range: 0-72 080). The viral load in semen and in saliva was significantly lower than in plasma (P < 0.0001). The HIV-1 RNA levels in plasma and in saliva were correlated (P < 0.05), but levels in semen were not correlated with either plasma or saliva levels. The HIV-1 copy number in plasma was significantly higher in symptomatic patients than in asymptomatic subjects (P < 0.05). Plasma and saliva HIV-1 RNA levels were higher in subjects with a CD4+ cell count < 200 x 10(6)/l than in subjects with a CD4+ cell count > 200 x 10(6)/l (P < 0.05). The HIV-1 RNA load in either plasma, semen or saliva is not related to antiretroviral therapy. CONCLUSIONS: The absence of a correlation between plasma and semen loads suggests that semen and blood are distinct viral compartments. Viral load in semen is not related to the clinical stage of HIV infection or to the CD4+ lymphocyte count. Consequently, HIV-1-infected subjects are potentially infectious at all stages of immuno-deficiency and adequate precautions must always be taken to prevent the sexual transmission of HIV.

Adult↗