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Biomedical subjects

R Grosso

Publications and source records attributed to R Grosso.

11 recordsLinked to original sources
PubMed2000

A comparison of stavudine plus lamivudine versus zidovudine plus lamivudine in combination with indinavir in antiretroviral naive individuals with HIV infection: selection of thymidine analog regimen therapy (START I).

BACKGROUND: No clinical trial results directly comparing two nucleoside analog pairs in a drug regimen for HIV that includes a protease inhibitor are available. OBJECTIVE: To compare the safety and efficacy of stavudine (d4T) + lamivudine (3TC) with zidovudine (ZDV) + 3TC, each in combination with indinavir (IDV). DESIGN: Randomized, open-label, multi-center. SETTING: Fifteen HIV clinical research centers. PATIENTS: Two-hundred and four antiretroviral-naive HIV-1-infected-patients with CD4 cell counts > or = 200 x 10(6)/l and HIV-1 RNA > or = 10,000 copies/ml (bDNA assay), modified to 5000 copies/ml. INTERVENTION: d4T 40 mg twice a day, 3TC 150 mg twice a day plus IDV 800 mg every 8 h compared with ZDV 200 mg every 8 h (modified to 300 mg every 12 h) plus 3TC and IDV. MEASUREMENTS: Primary endpoint: plasma HIV-1 RNA < 500 copies/ml. Additional endpoints: HIV-1 RNA < or = 50 copies/ml; change from baseline in HIV-1 RNA and CD4 cell counts; safety and adverse events. RESULTS: For HIV-1 RNA, 62% of patients on d4T + 3TC + IDV and 54% of patients on ZDV + 3TC + IDV had < 500 copies/ml HIV RNA at weeks 40 through 48 [90% confidence interval, -0.204 to 0.036; P= 0.213], with 49% and 47% respectively achieving < or = 50 copies/ml at 48 weeks (90% CI, -0.134 to 0.096; P = 0.834). Median change in CD4 cell counts at 48 weeks was +227 x 10(6)/l and +198 x 10(6)/l for the d4T- and ZDV-containing arms, respectively. The median time-weighted average change from baseline in CD4 cell counts was significantly greater at 48 weeks in the d4T-containing arm (142 x 10(6)/l versus 110 x 10(6)/l; P = 0.033). Serious adverse events were not significantly different between treatment arms, but there were significant differences for frequency of adverse events of all severity with increased nausea and vomiting in the ZDV-containing arm, and increased diarrhea and rash in the d4T-containing arm. CONCLUSIONS: These results support the choice of d4T + 3TC as a nucleoside analog pair in combination with a protease inhibitor in an initial HIV treatment regimen.

Anti-HIV Agents↗
PubMed2000

A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: selection of thymidine analog regimen therapy (START II).

OBJECTIVE: Comparison of stavudine (d4T), didanosine (ddI) and indinavir (IDV) with zidovudine (ZDV), lamivudine (3TC) and IDV in HIV-1 infected patients. DESIGN: Randomized, open-label. SETTING: Fourteen HIV Clinical Research Centers. PATIENTS: Two-hundred and five patients with less than 4 weeks antiretroviral treatment, naive to 3TC and protease inhibitors and with CD4 cell counts > or = 200 x 10(6)/l and plasma HIV-1 RNA levels > or = 10,000 copies/ml. INTERVENTIONS: Stavudine 40 mg and ddI 200 mg twice daily plus IDV 800 mg every 8 h compared with ZDV 200 mg every 8 h or 300 mg twice daily, 3TC 150 mg twice daily plus IDV. MAIN OUTCOME MEASURES: The proportion of patients with plasma HIV-1 RNA levels < 500 copies/ml and < or = 50 copies/ml and changes in CD4 cell counts were compared. RESULTS: In an analysis of the primary endpoint, 61% of patients on d4T + ddI + IDV and 45% of patients on ZDV + 3TC + IDV had all HIV-1 RNA values obtained between weeks 40 and 48 < 500 copies/ml [95% confidence interval (CI) for the difference between proportions, 1.7-30.3%; P = 0.038]. In an intent-to-treat analysis, the percentage of all patients randomized with all HIV-1 RNA levels < 500 copies/ml between 40 and 48 weeks were 53% for the d4T + ddI + IDV arm and 41% for the ZDV + 3TC + IDV arm (95% CI, -1.4% to 25.7%; P = 0.068). At 48 weeks 41% and 35% were < or = 50 copies/ml for the stavudine- and ZDV-containing arms respectively (P > 0.2). The median time-weighted average increases in CD4 cells count over 48 weeks were 150 x 10(6)/l cells for the d4T arm and 106 x 10(6)/l cells for the ZDV arm (P= 0.001). The occurrence of serious adverse events was not significantly different between arms. CONCLUSION: The combination of stavudine, ddl and IDV resulted in potent antiretroviral effects over a 48-week period, comparable or superior to zidovudine, 3TC and IDV supporting the use of stavudine, ddI and a protease inhibitor as an initial antiretroviral treatment.

Adolescent↗
PubMed1999

p27/kip1 expression in oligodendrogliomas and its possible prognostic role.

p27/kip1 regulates the G1-S transition of the cell cycle by inhibiting cyclinD-CDK4, cyclinE-CDK2 and cyclinA-CDK2 complexes. Regulation of p27 levels occurs mainly post-translationally by ubiquitin-mediated proteasomal proteolysis. Although genetic changes of p27/kip1 are extremely rare, in many human carcinomas p27 levels are reduced, correlate with histological malignancy, and are associated with poor prognosis. In astrocytic gliomas, p27 decreases with anaplasia and is almost absent in glioblastomas. p27/kip1 was immunohistochemically studied in 37 oligodendrogliomas, categorized according to WHO classification. In this series, the immunohistochemical reaction for p27 was confined to nuclei. p27 score showed a tendency to decrease with malignancy. When the p27 score was considered as high versus low expression (cut-off of p27 labeling index, LI, at 25%), it represented an independent prognostic factor in univariate (P = 0.02) and in multivariate analysis (P = 0.04). The risk ratio suggested that the p27 low expression group had a threefold increased possibility to show a reduced survival. Moreover, p27 levels did not correlate with MIB-1 LI, suggesting that p27 is not merely associated with the control of proliferation.

Brain Neoplasms↗
PubMed1998

Prognostic significance of telomerase in brain tumors

Telomeres help to maintain chromosomal stability and integrity. They are progressively lost, conditioning aging and mortality. Telomerase enzyme activation stabilizes the telomere length, permitting the proliferation of cancer cells. Four papers are reviewed dealing with increased expression of telomerase associated with increased labelling index of MIB-1 (Ki-67) and malignancy in astrocytomas, ependymomas, and oligodendrogliomas. Telomerase expression can be utilized for differentiating malignant from benign tumors with histological resemblance. The significance of telomerase in tumor progression is discussed within the field of brain neoplasias.

Journal Article↗
PubMed1998

Cyclin D1 expression in gliomas.

Cyclin D1 (cycD1) expression was defined immunohistochemically using monoclonal antibody DCS-6 and polyclonal antiserum H-295 in 50 glioma biopsies. The number of positive nuclei was higher for H-295 than for DCS-6, with a ratio of 3:1. The labelling index (LI) was compared to the grade of histological malignancy and to Ki-67 MIB-1 LI. The LI for cycD1 increased with histological malignancy, in parallel with the increase in MIB-1 LI. In most tumours, the maximum LI for cycD1 and MIB-1 were found in the same areas. The mean MIB-1 LI: mean cycD1 LI ratio does not vary in the three grades of astrocytic tumours. However, in this study the correlation between the two LIs was not statistically significant. Staining for cycD1 antigen does not necessarily imply that the gene is overexpressed since other molecular mechanisms can also be responsible for cell cycle deregulation. In invasive areas, the cycD1 LI is frequently higher than in solid tumour, either because more tumour cells are positive or because reactive astrocytes and activated microglia express cycD1. The relative contribution of neoplastic and reactive cells remains to be defined.

Astrocytes↗
PubMed1998

CDKN2/p16 inactivation and p16 immunohistochemistry in astrocytic gliomas.

CDKN2/p16 inactivation is the most frequent alteration in the molecular regulation of G1-S transition. CDKN2/p16 homozygous deletions was studied in paraffin-embedded sections of 45 astrocytic tumours by multiplex PCR. Immunohistochemistry for p16 and proliferation marker Ki-67 MIB-1 was performed in adjacent sections; their labelling index (LI) have been calculated. CDKN2/p16 gene was not deleted in astrocytomas, while homozygous deletion was found in 26.7% anaplastic astrocytomas, and in 55.0% of glioblastomas. Analysis of CDKN2/p16 homozygous deletion in discrete areas of the same tumour, showed that the deletion occurred independently of the phenotypic aspect of the areas. Nevertheless a genotypic and phenotypic heterogeneity is present in few cases. p16 immunohistochemistry mostly corresponds to the genotypic pattern. No correlation was found between CDKN2/p16 homozygous deletion and MIB-1 LI.

Astrocytoma↗
PubMed1994

[Plasma levels of the serum antioxidants (uric acid, ceruloplasmin, transferrin) in term and preterm neonates in the first week of life].

Development of serum antioxidants (ceruloplasmin, transferrin, uric acid and bilirubin) an the 1st, 4th, 7th days of life has been evaluated in 50 healthy NGA newborns (25 preterm with 35 +/- 0.6 week of gestational age and 2270 +/- 150 g of weight, 25 a term with 39 +/- 0.8 week of gestational age and 3480 +/- 220 g of weight) and in apparent absence of oxidant stress. The ceruloplasmin values increase from the 1st to 7th days of life and change significantly at the 4th day between a term and preterm newborns (p < 0.01); the transferrin values reduce significantly an the 1st (p < 0.01) and 7th days of life (p < 0.05); the uric acid values reduce in the two groups an the 1st day (p < 0.01). Our results show in the newborn a prevalent antioxidant activity of the studied substances. The plasma levels of uric acid may be compared, in the first week of life, to the hypoxanthine levels as acute ipoxia gauges.

Age Factors↗
PubMed1989

[Glycerol erythrocyte lysis test in the 1st month of life in neonates at term and premature infants].

Foetal erythrocytes have an enhanced resistance to osmotic haemolysis that they retain for the first 5 days after birth, particularly in premature newborns. The erythrocyte fragility test was used to study the increased resistance to osmotic haemolysis in 155 healthy newborns (50 NGA born to term, 55 NGA premature and 50 SGA born to term) as well as 31 newborns (20 born to term and 11 premature) with aspecific hyperbilirubinaemia. The drug used was glycerol which is specific in its reaction to alterations in erythrocyte membrane stability and made it possible to assess changes arising in the first month after birth, both naturally and in response to phototherapy. The results show a much higher resistance in neonatal than adult erythrocytes that gradually decrease during the first month after birth without, however, falling to adult levels. No changes in resistance attributable to the phototherapy adopted in newborns with hyperbilirubinaemia were encountered. The glycerol test proved extremely sensitive in the diagnosis of neonatal haemolytic anaemias easy to use so that congenital spherocytosis can be identified earlier than is otherwise possible.

Anemia, Neonatal↗
PubMedDate not supplied

[Chronic gallbladder disease & its surgical therapy, personal experience].

The chronic alitiasic cholecystopathy represents an unusual trmorphological disease not well defined in literature; it is characterized by a chronic alteration of gallbladder without gallstones. The authors present a retrospective study on a group of 21 patients having undergone cholecistectomy from January 1992 to January 1995. The choice for the surgical treatment was made on the basis of blind gallbladder after i.v. cholangiography, and cholecystography and/or tickning of the gallbladder wall performed through ultrasonography, in patients with hystory of biliary pains not responding to the pharmacological therapy. The removed gallbladder has been histologically examined, observing the absence of gallstone and the presence of chronic inflammation of the gallbladder wall. The c.a.c. is a pathology whose etiopatogenesis is yet discussed, some authors assert in fact that on its basis there are functional symptoms. Although in the past these kinds of disease were considered functional disorders this study revealed that in some cases there are organic problems and that the surgical treatment is necessary.

Adolescent↗