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Biomedical subjects

S Blanche

Publications and source records attributed to S Blanche.

At least 109 records · Page 6Linked to original sources
PubMed1995

Hepatic toxicity associated with 2'-3' dideoxyinosine in children with AIDS.

Among 34 children with AIDS enrolled in a trial with 2'-3' dideoxyinosine (ddI), six (aged 1-6 years) developed liver abnormalities within 2-18 months after institution of ddI. Two children died of fulminant hepatic failure (one had also an adenovirus infection), and four had a striking elevation of alkaline phosphatases (AP: 1120-7000 IU/L). All of them received sulfa drugs and antifungic treatment with ketoconazole or fluconazole. Three had a serology positive for hepatitis C virus. The evolution of liver enzymes following withdrawal and rechallenge with ddI in the children with elevated AP was an indication of drug-induced toxicity in two patients. In both of the others, readministration of ddI did not cause any subsequent problems. Liver histology in the patients with fulminant hepatitis showed an extensive hepatic necrosis. Liver biopsy done in two other patients revealed a mild granulomatous hepatitis in one and nonspecific changes (i.e., steatosis and a mild inflammation) in the other. Hepatic toxicity has been described with ddI and other nucleoside analogs in adult patients. These six children had many potential causes of liver disease. It may be that ddI is not hepatotoxic per se but that it precipitates liver disease in predisposed patients. We recommend that liver functions be carefully monitored when using this drug.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Functional brain imaging in HIV-1-infected children born to seropositive mothers.

UNLABELLED: The aim of this work was to study cerebral function in vertically infected children with human immunodeficiency virus 1 (HIV-1). METHODS: PET with 18F-labeled fluorodeoxyglucose (FDG) was performed in eight children (2.5-5.5 yr): three with severe neurological symptoms and five without. Quantitative analysis was based on gray matter cortical and subcortical regions of interest for which glucose utilization was measured. RESULTS: Diffuse hypometabolism and subcortical hypermetabolism were found in the three children with severe neurological signs; the five other children had temporo-occipital cortical hypometabolism, mainly on the right side. CONCLUSION: Functional cerebral abnormalities seem to precede clinical symptoms in HIV-1infection of the brain in children.

AIDS Dementia Complex↗
PubMed1994

[Human immunodeficiency virus infection in children].

Four hundred to 600 pregnancies have now been carried to full-term by HIV seropositive women in France. The rate of transmission of the virus to the infant is around 20%, and there remains much uncertainty concerning the exact mechanism involved. Early diagnostic methods are based on isolating the virus in culture or PCR but the sensitivity of this test is only 50% at birth, although rising to nearly 100% by 6 months of age. In the infant, the main characteristic of the disease is the existence of a subgroup (comprising 15 to 20% of the patients) that develops AIDS early, in association with opportunistic infection and encephalopathy in the first months of life. Treatment choices remain very limited, with the hope of eventual prevention of maternal-fetal transmission. The gravity of the ensuing psychological and social problems calls for a multidisciplinary approach to the infant, family and relatives.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Relation of the course of HIV infection in children to the severity of the disease in their mothers at delivery.

BACKGROUND: Among infants with maternally transmitted human immunodeficiency virus (HIV) infection, there are two patterns of disease progression. In about a fifth of these infants there is a rapid progression to profound immunodeficiency, whereas in the majority the disease progresses much more slowly. METHODS: We studied the clinical and biologic characteristics of the mothers of infants infected with HIV type 1 (HIV-1) in the French Prospective Multicenter Cohort. Infection in the children was confirmed by serologic tests at the age of 18 months or by death from the acquired immunodeficiency syndrome at an earlier age. Only the 162 infected infants who could be followed for at least 18 months or until death were included in the analysis. RESULTS: The risk of opportunistic infections or encephalopathy in the first 18 months was 50 percent in the infants of mothers with class IV disease, according to the Centers for Disease Control and Prevention classification, and 14 percent in the infants of mothers with class II or III disease (relative risk, 3.6; 95 percent confidence interval, 1.8 to 7.3; P < 0.002). Forty-four percent of the former infants and 9 percent of the latter died before 18 months (relative risk, 4.7; 95 percent confidence interval, 2.1 to 10.4; P < 0.002). The risk of death correlated inversely with the mother's CD4+ cell count and directly with her HIV-1 p24 antigen level at delivery. There was also a direct correlation between the mother's CD4+ cell count and that of the infant at one, three, and nine months of age (correlation coefficient at nine months [n = 44], 0.48; P < 0.002). HIV-1 p24 antigen was detected more often in the infants whose mothers also had the antigen. CONCLUSIONS: In infants whose HIV infection is maternally acquired, the rate of disease progression varies directly with the severity of the disease in the mother at the time of delivery.

AIDS Dementia Complex↗
PubMed1994

Stroke and cerebral infarcts in children infected with human immunodeficiency virus.

OBJECTIVE: To study the causes of stroke and cerebral infarcts in children infected with the human immunodeficiency virus (HIV)-type 1. DESIGN: Case series. PATIENTS: Four of 380 HIV-infected children followed up in a 10-year period in our department who had a stroke with evidence of cerebral infarcts on radiological imaging. RESULTS: The four patients were severely immunodepressed, but their clinical status and outcome were different. Aneurysmal dilation of major cerebral arteries and thrombosis of these arteries or of small cortical vessels were discovered in two patients. Both patients had a history of frequent infections and had suffered repeated neurological events that resulted in severe clinical deterioration or death. An infectious causative agent was strongly suspected but was not detected. The other two patients had a more favorable outcome. An isolated cerebrovascular thrombosis was found in one patient, while in the other, HIV-1-related focal necrosis was suggested by the lack of permanent cerebrovascular abnormalities or thrombosis and by signs of necrosis in biopsy specimens of the brain. CONCLUSION: Stroke and cerebral infarcts in HIV-1 infected children have different causes and different prognoses.

Adolescent↗
PubMed1994

Long-term itraconazole prophylaxis against Aspergillus infections in thirty-two patients with chronic granulomatous disease.

We conducted a prospective, open study of oral itraconazole therapy (5 and then 10 mg/kg per day) to assess tolerance and potential efficacy in preventing fungal infections in patients with chronic granulomatous disease. Thirty-two patients were enrolled in one center between 1985 and 1991. Tolerance was excellent in all cases. Poor compliance was suspected in three cases. Two patients were excluded from efficacy analysis because itraconazole was used as part of therapy for pulmonary aspergillosis. Of 30 patients, 3 developed a fungal (Aspergillus) lung infection, an incidence 3.4/100 patient-years versus 11.5 in a historical control group that did not receive any prophylaxis (p = 0.13) and 9.55 in a historical group of patients who received daily ketoconazole prophylaxis (p = 0.19). The percentage of patients infected with Aspergillus was significantly different: 10% in the itraconazole group versus 34.4% in the untreated group (p = 0.013). These results require further evaluation through a comparative randomized trial to assess the possible benefit of itraconazole prophylaxis in patients with chronic granulomatous disease.

Administration, Oral↗
PubMed1994

Early impairment of gut mucosal immunity in HIV-1-infected children.

This study was performed in 27 HIV-1+ children to characterize the IgA hyperglobulinaemia observed in the serum during the course of HIV-1 infection. By contrast with serum IgG, which increased very early, IgA elevation was related to the decrease of CD4+ cell percentage. It was demonstrated that IgA1 subclass increased selectively. Secretory IgA (SIgA) and IgA and IgG activity to gliadin, bovine serum albumin (BSA) and at a lower level to casein could be detected in the serum at the early stages of HIV infection, but SIgA levels and IgA activity to gliadin further increased during the course of immunodeficiency. By contrast, IgA and IgG activity to tetanus toxoid did not change. These data demonstrate that the hyper IgA, closely related to the degree of immunodeficiency, could be due in part to a disturbance of the gut mucosal immune system. Moreover, impaired intestinal immunity seems to appear very early, and to progress during the course of paediatric HIV-1 infection.

CD4-Positive T-Lymphocytes↗
PubMed1994

Treatment of juvenile chronic myelomonocytic leukemia by allogeneic bone marrow transplantation.

Twelve of 15 patients with juvenile chronic myelomonocytic leukemia (JCMML) referred to our unit underwent allogeneic bone marrow transplantation (BMT) between 1982 and 1992. BMT was not performed in the remaining three cases because of poor overall condition in two and disease progression in one. Six patients received marrow from HLA-identical siblings after a chemotherapy conditioning regimen in five cases. BMT failed in one case. Long-term remission was achieved in three patients and two others are in remission 6 and 11 months after BMT. Remission was associated with autologous recovery in one patient and minimal mixed chimerism in another. In one patient, a first BMT procedure resulted in autologous recovery and relapse. A second transplant, with chemotherapy conditioning including TBI, was successful. BMT with marrow from a matched unrelated donor was also successful. IN contrast, BMT with marrow from mismatched related donors (five patients) failed because of graft failure and/or relapse. This single-center series indicates that HLA-identical BMT is an appropriate treatment for JCMML. However, on the basis of these results it cannot be ascertained whether chemotherapy or splenectomy are necessary prior to BMT. The best chemotherapy conditioning regimen remains to be defined, as regimens consisting exclusively of chemotherapy resulted either in long-term remission or in autologous recovery with relapse.

Antineoplastic Agents↗
PubMed1993

Treatment of familial hemophagocytic lymphohistiocytosis with antithymocyte globulins, steroids, and cyclosporin A.

Familial hemophagocytic lymphohistiocytosis (FHL) is a potentially fatal disease characterized by diffuse infiltration by histiocytes and T lymphocytes. Treatment with myelotoxic drugs, such as etoposide, brings about remission in most patients, but problems of toxicity remain, and the development of disease resistance can cause secondary relapses. We have used an alternative approach, based on the suggested primary role of T-cell activation in FHL, comprising combined treatment with steroids (2 to 5 mg/kg/d methylprednisolone intravenously, followed by progressive tapering) and rabbit antithymocyte globulins (10 mg/kg/d for 5 days), followed by maintenance therapy with cyclosporine A (CSA). In a pilot study of six patients (four with a family history of FHL), all showed systemic remission within 7 days, which was complete in five cases; despite treatment with intrathecal methotrexate, one patient died of severe brain involvement. Two patients received T-cell--depleted HLA--non-identical bone marrow transplants, which was successful in one case. The other three patients, who have been on CSA maintenance therapy for periods of 6 to 24 months, are in complete remission. We have observed no side-effects (there has been no persisting T-cell immunodeficiency). These results suggest that nonmyelotoxic treatments for FHL may be safe, effective, and worthy of further investigation; they also support the key role of T lymphocytes in the disease.

Antilymphocyte Serum↗
PubMed1993

Detection of HIV-specific cell-mediated cytotoxicity in the peripheral blood from infected children.

Cytotoxic T lymphocytes may play a significant role in containing the spread of HIV in infected individuals. Although HIV-infection is associated with immune suppression, a vigorous T lymphocyte response has been detected in infected adults. HIV can be transmitted from mother to child, either during pregnancy, when differentiation of the T lymphoid compartment is ongoing, or at birth when the neonate immune system is partially competent. The shorter asymptomatic period of pediatric infection could be related to differences in the host immune control of viral replication. HIV-specific cell-mediated cytotoxicity (CMC) from fresh and in vitro stimulated PBMC of HIV-infected children was measured. CD8+CD3+ T lymphocytes were found to be the major effector population. The vast majority of children examined had detectable HIV-specific CMC. A cross-sectional analysis of CMC responses as a function of clinical status revealed that 71% of asymptomatic children (CDC stage P1) recognized the Env protein, 14% the Gag protein, but none of them recognized the Pol protein. Cytolytic activities directed against these three proteins were detected in two thirds of paucisymptomatic children (P2A). In contrast, symptomatic children (P2B-F) did not show cytolytic activities toward the Gag and Pol proteins, and only 20% recognized the Env protein. In contrast in vitro generated secondary CTL were consistently detected at all stages of disease, even in children with low CD4+ cells counts.

Amino Acid Sequence↗
PubMed1993

Lack of selective V beta deletion in peripheral CD4+ T cells of human immunodeficiency virus-infected infants.

To investigate the possibility of super-antigen-mediated deletions of T cells expressing particular T cell receptor V beta (TcR V beta) gene segments during human immunodeficiency virus (HIV) infection, TcR V beta usage in CD4+ and CD8+ subsets was analyzed in a cohort of infants maternally infected by HIV and in a group of healthy neonates. We used a semi-quantitative anchored polymerase chain reaction technique together with cytofluorographic analysis with anti-V beta monoclonal antibodies. The representation of the 24 V beta families in CD4+ and CD8+ T cells from normal neonates was very similar to that in adults. Preferential expression of V beta 2 in the CD4+ subset was observed in both the neonates and in healthy adults. The representation of the 24 V beta families in peripheral CD4+ T cells from the HIV-infected infants showed no selective V beta deletion, even when the CD4+ subset was globally depleted. Moreover, the main characteristics of the control group (predominance of certain V beta families and V beta 2 skewing towards the CD4+ subset) were also present in all the HIV-infected infants.

Adult↗
PubMed1993

Severe combined immunodeficiency: a retrospective single-center study of clinical presentation and outcome in 117 patients.

We carried out a retrospective analysis of 117 patients with severe combined immunodeficiency who were examined in a single center between Jan. 1, 1970, and Jan. 1, 1992, for the purpose of evaluating disease onset, progression, and outcome. The frequency of case referral increased from 8 from 1970 to 1975 to 56 from 1986 to 1991. The most frequent phenotype was T-/B+ (absence of T lymphocytes and presence of B lymphocytes) (n = 51); there were 36 cases of alymphocytosis, 16 of adenosine deaminase deficiency, 13 of Omenn syndrome, and 1 of reticular dysgenesis. Protracted diarrhea and lung infections were the main infectious complications; infection with bacillus Calmette-Guérin occurred in 10 of 28 vaccinated patients, but none of the six recipients of oral polio vaccine subsequently had poliomyelitis. The presence of maternal T cells was suspected or proved in half the patients with alymphocytosis or T-B+ severe combined immunodeficiency but did not occur in the other forms of the disease. Of the 117 patients, 22 died before transplantation could be performed. Adenosine deaminase deficiency and Omenn syndrome were more frequently associated with death before hematopoietic stem cell transplantation was possible. Fetal liver transplantation was successful in 1 of 10 cases. The survival rate among the 30 recipients of bone marrow with identical human leukocyte antigens (HLA) was 80%, with a median follow-up of 129 months; 23 of 25 patients recovered full immune function. The survival rate among the 50 recipients of HLA-haploidentical T cell-depleted bone marrow was 56%, with a mean follow-up of 35 months. Of the latter patients, 10 (35%) still require immunoglobulin substitution. There has been a trend toward improvement in the survival rate of haploidentical bone marrow recipients, presumably because of more effective infection-control measures and better transplantation strategy.

Bone Marrow Transplantation↗
PubMed1993

Randomized study of two doses of didanosine in children infected with human immunodeficiency virus.

2'3'-Dideoxyinosine (didanosine) is a nucleoside analog active in vitro against human immunodeficiency virus. Few data are available regarding its use for the treatment of children. In a single-center, randomized, open-label trial, we compared two dosages of didanosine (120 vs 270 mg/m2 per day) for at least 6 months in 34 children infected with human immunodeficiency virus who had become resistant to or were intolerant of zidovudine. Serum levels of didanosine 1 hour after administration were significantly different in the two groups and remained stable with time. There was a significant reduction in human immunodeficiency virus-p24 antigenemia and quantitative cellular viremia with time but no difference between the two groups. The intensity of the biologic response, however, was significantly higher in the patients who had more than 50 CD4+ cells 10(6)/L at inclusion. No pancreatic or neurologic toxic effects were observed. In five children, liver function abnormalities developed that are unusual in this setting, and the death of one child from unexplained hepatocellular failure suggests that didanosine may be hepatotoxic. Three of these five children had preexisting liver disease. Although no definite conclusion can be made as to the optimal dose, there were no major differences between the two administration schedules in terms of biologic effects and tolerability.

Adolescent↗
PubMed1993

Timing of mother-to-child HIV-1 transmission depends on maternal status. The HIV Infection in Newborns French Collaborative Study Group.

OBJECTIVES: To estimate when mother-to-child transmission occurs and investigate the possible role of maternal factors. DESIGN: We studied virological data obtained in the first 3 months of life of 95 infected newborns born to HIV-1-seropositive mothers included in the French Prospective Cohort Study who did not breast-feed. METHODS: Comparative Western blot analysis of sequential blood specimens from neonates and mothers with incomplete antibody patterns enabled us to detect antibody production in some infants. The results of viral investigation of neonate specimens enabled us to describe the acute phase of infection in newborns. Because the process between infection and antibody production is irreversible, we chose a Markov modelling technique, which is well suited for staged clinical processes. RESULTS: About two-thirds (65%) of the infants were considered to have been contaminated during delivery. In the remaining infants, the contamination was estimated to have occurred in utero and 95% of them had been infected less than 59 days before delivery. The association between the mother's immunological and virological status and the time of transmission was examined. The greater the degree of maternal immunodeficiency at delivery (in terms of p24 antigen and Western blot pattern) the higher the risk of in utero transmission, showing that vertical transmission is dependent on the mother's immunological status. CONCLUSIONS: These estimates should be considered when designing strategies to prevent mother-to-child transmission.

Cohort Studies↗
PubMed1993

Bacillus Calmette-Guérin infection after vaccination of human immunodeficiency virus-infected children.

The use of Mycobacterium bovis/Bacillus Calmette-Guérin (BCG) to vaccinate against tuberculosis remains controversial. The development of tuberculosis in human immunodeficiency virus (HIV)-infected children demands specific evaluation of the risk/benefit ratio of BCG vaccination in this situation. In our institution 9 of 68 HIV-infected children vaccinated with BCG before the diagnosis of HIV infection was suspected developed vaccine-related complications: 7 of these children had a large satellite adenopathy with or without skin fistulae, whereas the other 2 had disseminated BCG infection beyond the satellite ganglion (involvement of the spleen and mesenteric and mediastinal lymph nodes in one case and the liver and lungs in the other). The children were vaccinated soon after birth; no particular problems were observed at that time, but complications appeared 3 to 35 months later. All but one of these children had a rapidly progressive form of HIV disease. The possibility of delayed local or disseminated BCG infection must be considered in analysis of the risk/benefit ratio of vaccination of HIV-infected children. The prognosis of HIV infection must be taken into account, even if the child is asymptomatic when vaccination is being considered.

BCG Vaccine↗