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Biomedical subjects

L M Aledort

Publications and source records attributed to L M Aledort.

At least 73 records · Page 4Linked to original sources
PubMed1995

Human immunodeficiency virus (HIV) type 1 infection status and in vitro susceptibility to HIV infection among high-risk HIV-1-seronegative hemophiliacs.

Blood samples were obtained from 16 hemophiliacs who had a 50%-94% defined risk of human immunodeficiency virus (HIV) type 1 infection on the basis of treatment history and from 14 controls not at risk for HIV infection. HIV-1 was not detected in any of 12 patient samples by cocultivation nor in 14 patient samples by the polymerase chain reaction. Peripheral blood cells from 7 seronegative hemophiliacs at highest risk of seroconversion (94%) were less susceptible to HIV-1 infection in vitro than were cells from healthy controls (P < .025, one-tailed Wilcoxon rank sum test). In contrast, the susceptibility to HIV-1 infection of lymphocytes from 6 seronegative hemophiliacs at moderate risk (50%-56%) of seroconversion did not differ from that of cells from controls or from high-risk hemophiliacs. Therefore, prolonged periods of seronegative HIV-1 infection are not common in this high-risk population. In addition, among hemophiliacs there may exist heterogeneity in susceptibility to HIV-1 infection in vitro and in vivo.

Adult↗
PubMed1994

Risks of immunodeficiency, AIDS, and death related to purity of factor VIII concentrate. Multicenter Hemophilia Cohort Study.

In HIV-infected subjects with haemophilia, CD4 counts seem to fall more slowly in those on high-purity factor VIII (FVIII) than on intermediate-purity product. We evaluated whether risks for AIDS or death were associated with either product among 411 HIV-infected individuals. The relative hazard of AIDS was slightly elevated for both current (1.34) [corrected] and cumulative (1.01 per month) use of high-purity products (neither significant). The corresponding hazards for death were 1.49 and 1.03 (neither significant). Thus we found no evidence that high-purity FVIII concentrates retard the development of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Immune status of human immunodeficiency virus seropositive and seronegative hemophiliacs infused for 3.5 years with recombinant factor VIII. The Kogenate Study Group.

Recent studies suggest that treatment of hemophiliacs with highly purified factor VIII concentrates may preserve immune function. To test this hypothesis, we prospectively studied 51 hemophilic patients (21 human immunodeficiency virus [HIV] seropositive and 30 seronegative) who were on home therapy exclusively with recombinant factor VIII (Kogenate, Miles Laboratory, Berkeley, CA) for 3.5 years. Patients, all of whom had been previously treated with plasma-derived factor VIII concentrates, were monitored every 6 months with T-lymphocyte subsets and beta 2-microglobulin levels. Mean rate of change in absolute CD4 cell counts, calculated from regression slopes for individual patients, showed a small but statistically significant decrease over the 3.5-year study period for HIV seropositive hemophiliacs. No decrease in CD4 cell counts was seen in HIV seronegative hemophiliacs when the data for children under age 6 years were excluded from the analysis. beta 2-microglobulin levels and CD8 cell counts remained unchanged. These data show stability of immunologic parameters in HIV seronegative hemophiliacs, and a small decrease in CD4 cell counts in HIV seropositive hemophiliacs treated with recombinant factor VIII.

CD4-Positive T-Lymphocytes↗
PubMed1994

A longitudinal study of orthopaedic outcomes for severe factor-VIII-deficient haemophiliacs. The Orthopaedic Outcome Study Group.

OBJECTIVE: Arthropathy is the major cause of morbidity in haemophilia. In an attempt to establish optimal therapeutic regimens for persons with haemophilia, we hypothesized that no direct relationship exists between increasing factor dosage and orthopaedic outcomes over time. DESIGN: A longitudinal uncontrolled 6 year study was carried out. Ankles, knees and elbows of patients were studied using physical and X-ray examination scores. Bleeding episodes and treatment regimens were determined. The amount of time lost from work and school, as well as days in hospital, was also monitored. SETTING: Twenty-one international haemophilia centres were used to accrue and follow patients over the 6 year period. SUBJECT: Severe (< 1%) factor VIII deficient patients under the age of 25 without inhibitors were recruited into the study. INTERVENTION: The status of the six major joints of these patients were measured annually for mobility. X-ray evaluation of these joints was carried out at the beginning and end of the study. Using a World Federation of Haemophilia joint and X-ray score, stability, progression or regression of arthropathy was evaluated. RESULTS: Physical and X-ray examination scores increased significantly with age, and the number of joint bleeds were significant in determining the delta score. Approximately 10% of patients entered with all six joints normal. Of these, 50% remained so. Year-long prophylaxis significantly reduced the rate at which joints deteriorate both on physical (P = 0.02) and X-ray examination (P = < 0.001). Patients on prophylaxis had significantly fewer days lost from work or school, as well as fewer days spent in hospital (P = < 0.01). CONCLUSIONS: Higher doses of factor per se do not necessarily produce improved orthopaedic outcomes. However, full time prophylaxis is likely to produce the best orthopaedic outcome. The most critical factor for a good orthopaedic outcome is the reduction of joint bleeds.

Factor VIII↗
PubMed1994

Hepatitis A virus transmission by blood products in the United States. Transfusion Safety Study Group.

To address the question of HAV prevalence and seroconversion in relation to clotting factor concentrates, we assayed an early serum for 339 hemophiliacs followed every 6 months by the Transfusion Safety Study in the period from mid-1985 until mid-1992. We found 58.4% positive around entry, with an age-specific prevalence that did not vary with age. In comparison to rates for anti-HIV-negative blood donors, they were significantly higher. Based on testing of subsequent sera, 11 hemophiliacs (7.8% of 141 susceptibles) changed their anti-HAV status from negative to positive. In 9 instances, positivity immediately followed the first dose of intravenous immune globulin. A possible seroconversion followed treatment with blood components, and a possible seroconversion followed intermediate-purity, solvent/detergent(SD)-treated factor VIII concentrate. Neither of these 2 patients was anti-HAV IgM positive, so that passively transferred antibody is possible. The high prevalence among hemophiliacs at entry must be further investigated by determining the expected background rate in a US population similar to the hemophilia patients, and by comparing anti-HAV prevalence associated with SD-treated and heat-inactivated concentrates.

Adolescent↗
PubMed1994

HIV-1 infection incidence among persons with hemophilia in the United States and western Europe, 1978-1990. Multicenter Hemophilia Cohort Study.

We studied human immunodeficiency virus type 1 (HIV-1) infection incidence over time in a 16-center cohort of hemophiliacs in the United States and Europe and estimated the most likely date of seroconversion for all seropositive subjects. Five U.S. centers enrolled subjects independent of HIV-1 status, whereas 11 centers preferentially included seropositive subjects. We obtained unbiased estimates of HIV-1 infection incidence rates from the five centers and estimated dates of seroconversion from the distribution seen among seropositives from all centers. In the five-center cohort, infection incidence began in 1978, peaked in October 1982 at 22 infections per 100 person-years at risk, and declined to 4 per 100 person-years by July 1984. Few infections occurred after 1987, and by that time, 50% of the cohort had become infected. Median seroconversion dates for subgroups of all seropositives ranged from July 1980 to December 1983, depending on the dose and type of factor concentrate. Median dates in Europe ranged from September 1981 to March 1983 and reflected the use of products manufactured from American plasma. Infection incidence apparently peaked about the same time that public health interventions were introduced to reduce transmission. These interventions, including heat treatment of factor concentrates and deferral of high-risk donors, have prevented HIV-1 infection from becoming endemic among younger birth cohorts of persons with hemophilia.

Adolescent↗
PubMed1993

Three-year randomised study of high-purity or intermediate-purity factor VIII concentrates in symptom-free HIV-seropositive haemophiliacs: effects on immune status.

The availability of monoclonal-antibody-purified factor VIII (FVIII) concentrates allows us to test the hypothesis, based on in vitro observations, that their use in HIV seropositive haemophiliacs would result in a difference in the rate of deterioration of immune function. We designed a multicentre, prospective, randomised, controlled study of symptom-free HIV-infected patients with haemophilia A who were assigned to receive either an intermediate-purity or monoclonal-antibody-purified product. All had CD4 lymphocyte counts of 100-600/microL, were negative for hepatitis B surface antigen, had not received any antiretroviral or immunomodulating drugs before study entry, and had previously received replacement therapy with intermediate purity FVIII concentrates. Use of antiretroviral therapy was permitted. 60 patients were recruited and 30 were assigned to each group. 35 completed the 3 year study, 20 in the monoclonal arm and 15 in the intermediate-purity arm. Among those completing the study, there were no differences between the two groups in the occurrence of AIDS-defining diagnoses (1 in each group). There were, however, striking and significant differences in terms of changes in absolute CD4 counts. The group receiving monoclonal-antibody-purified concentrates had essentially stable counts while a significant drop was observed in the group receiving intermediate-purity FVIII. These differences were independent of the use of antiretroviral therapy. These observations support the use of high-purity concentrates in the treatment of symptom-free HIV-positive patients with haemophilia A, and they should be taken into account along with cost, by doctors making therapeutic decisions.

Adolescent↗
PubMed1993

Effect on lymphocyte subsets of clotting factor therapy in human immunodeficiency virus-1-negative congenital clotting disorders. The Transfusion Safety Study Group.

Patients with hemophilia A without human immunodeficiency virus type 1 (HIV-1) infection have lower CD4+ counts and CD4+/CD8+ ratios than controls. This is usually interpreted as a therapy-induced immunodeficiency. Our data re-examine the effect of therapy on peripheral blood mononuclear cell immunophenotypic subpopulations in all congenital clotting disorders. Since late 1985 we have prospectively observed HIV-1 uninfected persons with all types and severity of disorder. Controls were household members without clotting disorders or HIV-1 infection. Analyses of immunophenotype and treatment included a longitudinal random effects model. Compared with controls, age-adjusted CD4+ counts were significantly lower in treated patients (P < .0001) and in patients with all types of clotting disorders who were seldom or never treated (P = .0005). Significantly lower values among both treated and untreated clotting disorder subjects (P < .05) were likewise found for total lymphocytes, several other T-cell subsets, and the CD4+/CD8+ ratio. For most indexes, including the CD4+ count and CD4+/CD8+ ratio, the type of clotting deficiency was not a significant variable. Comparing persons who had no or minimal therapy with those having the most showed increases in CD8+ (P = .0017) and CD20+ CD21- counts (P = .0255), and a lower CD20+ CD21+/CD20+ ratio (P = .0106) in the latter. Controls and persons with clotting disorders differ in CD4+ count. Among those with clotting factor disorders, there is no difference attributable to type of clotting disorder or factor therapy. Large amounts of treatment increased CD8+ and CD20+ CD21- counts, but were not associated with a change in CD4+ count.

Antigens, CD↗
PubMed1993

Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphomas and other malignancies in patients with hemophilia.

Non-Hodgkin's lymphoma (NHL) is the most common human immunodeficiency virus (HIV)-associated malignancy in hemophiliacs. We studied the incidence and clinicopathologic features of NHL in 3,041 hemophiliacs followed at 18 US Hemophilia Centers between 1978 and 1989. Of the 1,295 (56.6%) who were HIV(+), 253 (19.5%) developed acquired immunodeficiency syndrome (AIDS), of whom 14 (5.5%) developed NHL. Three NHL occurred in HIV(-) hemophiliacs, for a 36.5-fold greater risk in HIV(+) than HIV(-) hemophiliacs (P < .001). The NHL incidence rate was 29-fold greater than in the US population by Surveillance, Epidemiology, and End Results (SEER) estimates (P < .001). Between 0 and 4 lymphomas have been observed per year between 1978 and 1989. At presentation 13 (92.9%) of the HIV(+) NHL were extranodal. Ten were stage IV, 1 stage II, and 3 stage IE. Ten (71.4%) were high-grade, 3 (21.4%) intermediate-grade, and 1 (7.1%) was a low-grade B-cell lymphoma. Epstein-Barr virus (EBV) DNA was detected in 36% by in situ hybridization, including one central nervous system (CNS) lymphoma. The mean CD4 cell count at NHL diagnosis was 64/mm3, the mean latency from initial HIV infection was estimated to be 59 months, and the median survival was 7 months. The incidence of basal cell carcinoma in HIV(+) hemophiliacs was 18.3-fold greater than in HIV(-) hemophiliacs (P < .001) and 11.4-fold greater than in the US population (P < .001). In conclusion, incidence rates of NHL and basal cell carcinoma in HIV(+) hemophiliacs are significantly increased over rates in HIV(-) hemophiliacs and over rates in the US population. Clinicopathologic presentation of NHL in HIV(+) hemophiliacs is similar to that in HIV(+) homosexual men.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Human immunodeficiency virus-related conditions in children and adults with hemophilia: rates, relationship to CD4 counts, and predictive value.

To further elucidate the natural history of human immunodeficiency virus (HIV) infection, we studied intermediate HIV-related conditions occurring before acquired immunodeficiency syndrome (AIDS) in a prospectively observed multicenter cohort of 738 HIV-infected persons with hemophilia. We analyzed the frequency in adults and children of common HIV-related conditions and the relative risk of AIDS after occurrence of these conditions, controlling for age at seroconversion and the percentage of CD4+ lymphocytes. Thrombocytopenia was the most frequently observed condition with cumulative incidences of 43% +/- 7% in adults and 27% +/- 6% in children and adolescents by 10 years after seroconversion. Oral candidiasis, fever, weight loss, and non-AIDS pneumonia were two to four times more common in adults than children, whereas herpes zoster risk was similar in the two age groups. HIV-related conditions were infrequent during the first 4 years of infection, particularly in children. With the exception of thrombocytopenia, mean CD4 counts were less than 350 cells/microL at the onset of the conditions. The relative hazard of AIDS after oral candidiasis was 18 in children and 3.8 in adults. Relative hazard in adults was also increased after persistent fever (10), weight loss (3.2), and non-AIDS pneumonia (2.2). Herpes zoster and thrombocytopenia were not significantly associated with AIDS in either age group. We conclude that intermediate HIV-related conditions occur more frequently in adults than in children with hemophilia. Persistent fever is the strongest predictor of AIDS in adults, whereas oral candidiasis is the strongest predictor in children. These findings should facilitate the design and conduct of clinical trials as well as the management of HIV-infected children and adults.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Consequences of chronic hepatitis C: a review article for the hematologist.

The hepatitis C virus (HCV) has been cloned, and assays capable of detecting antibody to HCV recombinant proteins (anti-HCV) have been developed. Concurrent with the cloning and development of the anti-HCV screening tests, trials with interferon alfa-2b have documented biochemical and histologic improvement in the indices of hepatitis C and non-A, non-B (NANB) in patients who were chronically infected. Subsequently, the anti-HCV assays and interferon alfa-2b have become clinically available. These new detection and treatment modalities can now be used in the management of hemophilics and other chronically transfused patients who bear great risk for blood-borne infections and manifest signs of chronic hepatitis.

Chronic Disease↗
PubMed1993

Congenital bleeding disorders. Rational treatment options.

There are rational, effective choices available for the treatment of common inherited bleeding disorders, according to assessment of safety, efficacy and cost. All currently available products for patients with haemophilia A (factor VIII deficiency) are comparable in terms of efficacy and viral safety. However, high purity products are recommended for those with coexisting human immunodeficiency virus (HIV) infection. Many patients with mild haemophilia A and most with von Willebrand's disease can be treated with desmopressin, which can be given as an intranasal spray in some countries. For the treatment of patients with factor XI deficiency, fresh frozen plasma remains the standard care, although solvent-detergent-treated fresh frozen plasma and factor XI concentrate are currently being investigated as alternatives. In the treatment of haemophilia B (factor IX deficiency), purified factor IX concentrates are particularly useful in clinical settings where large amounts of concentrate are to be used (e.g. surgical prophylaxis). Their usefulness in other contexts needs clarification. Treatment of inhibitors that may develop in response to administered coagulation factors is still limited to the use of prothrombin complex concentrates and porcine factor VIII. Active clinical trials are currently assessing the efficacy and safety of recombinant factor VIIa, Xa and tissue factor in this indication.

Autoimmune Diseases↗