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Biomedical subjects

Louis M Aledort

Publications and source records attributed to Louis M Aledort.

At least 19 recordsLinked to original sources
PubMed2006

AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP.

BACKGROUND: Most current treatments for chronic immune thrombocytopenic purpura (ITP) act by decreasing platelet destruction. In a phase 1-2 study, we administered a thrombopoiesis-stimulating protein, AMG 531, to patients with ITP. METHODS: In phase 1, 24 patients who had received at least one treatment for ITP were assigned to escalating-dose cohorts of 4 patients each and given two identical doses of AMG 531 (0.2 to 10 microg per kilogram of body weight). In phase 2, 21 patients were randomly assigned to receive six weekly subcutaneous injections of AMG 531 (1, 3, or 6 microg per kilogram) or placebo. The primary objective was to assess the safety of AMG 531; the secondary objective was to evaluate platelet counts during and after treatment. RESULTS: No major adverse events that could be attributed directly to AMG 531 occurred during the treatment period; 4 of 41 patients had transient post-treatment worsening of thrombocytopenia. In phase 1, a platelet count that was within the targeted range (50,000 to 450,000 per cubic millimeter) and at least twice the baseline count was achieved in 4 of 12 patients given 3, 6, or 10 mug of AMG 531 per kilogram. Overall, a platelet count of at least 50,000 per cubic millimeter was achieved in 7 of 12 patients, including 3 with counts exceeding 450,000 per cubic millimeter. Increases in the platelet count were dose-dependent; mean peak counts were 163,000, 309,000, and 746,000 per cubic millimeter with 3, 6, and 10 microg of AMG 531 per kilogram [corrected], respectively. In phase 2, the targeted platelet range was achieved in 10 of 16 patients treated with 1 or 3 mug of AMG 531 per kilogram per week for 6 weeks. Mean peak counts were 135,000, 241,000, and 81,000 per cubic millimeter in the groups that received the 1-mug dose, the 3-mug dose, and placebo, respectively. CONCLUSIONS: AMG 531 caused no major adverse events and increased platelet counts in patients with ITP. (ClinicalTrials.gov number, NCT00111475 [ClinicalTrials.gov].).

Adrenal Cortex Hormones↗
PubMed2006

Echinocytosis--an unusual manifestation of hemangioma.

The case of a 21 year-old female with echinocytosis and a littoral cell hemangioma is reported. The patient had no significant past medical history and presented with abdominal pain and splenomegaly. A large percentage of echinocytes were noted on her peripheral smear in the absence of any known causes. A CT-recognized splenic mass led to splenectomy and a benign hemangioma was found. Red blood cell abnormalities resolved immediately after the surgery. This is the first case reported in the literature of echinocytosis as a consequence of a hemangioma.

Adult↗
PubMed2005

Therapeutic choices in the current millennium: hemophilia workshop highlights.

Many issues affect hemophilia care providers when managing bleeding episodes in individuals with hemophilia. A diverse group of hemophilia providers from the United States met at two workshops to discuss the issues influencing treatment choices in the current millennium and to learn about current advances in treatment of hemophilia. This paper provides a summary of the discussions at these workshops. Despite the progress made in the management of patients with hemophilia, the workshop highlighted the fact that there were still many unanswered questions.

Factor VIII↗
PubMed2005

United States' factor XI-deficiency patients need a safer treatment.

A replacement factor for Factor XI with is virally inactivated is not available in the U.S. Elsewhere an inactivated concentrate has been used. A review of the experience over 15 years suggests that this product is safe and effective and suggests its potential use in the U.S. The most serious complication of the factor was a slight increase in DIC and thrombotic events.

Blood Component Removal↗
PubMed2005

Thrombotic microangiopathy: differential diagnosis, pathophysiology and therapeutic strategies.

Several disease states manifest as thrombotic microangiopathies (TMA), most prominently thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). The recent discovery of the von Willebrand factor cleaving protease ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motif), found to be deficient in TTP, has helped separate these entities. In contrast, HUS is caused by direct endothelial damage by bacterial toxins, while in familial cases inappropriate complement activation through deficient factor H appears to be a major pathogenetic mechanism. Although enormous progress has been made towards understanding these syndromes, the diagnostic tools and therapies used have hardly changed in the last 20 years, with the standard of care remaining plasma exchange in most cases. In this review, we will cover the multiple etiologic factors for TMAs, with the resultant differential diagnoses, as well as provide insight into the latest pathophysiologic findings and possible implications for treatment.

Diagnosis, Differential↗
PubMed2004

Prospective screening of 205 patients with ITP, including diagnosis, serological markers, and the relationship between platelet counts, endogenous thrombopoietin, and circulating antithrombopoietin antibodies.

Immune thrombocytopenia purpura (ITP) is characterized by destruction of circulating platelets and the presence of antiplatelet antibodies. Many of the current immunomodulatory therapies act by reducing platelet destruction and usually do not have a lasting effect. This prospective, exploratory study characterized patients with ITP by identifying their demographic and comorbid clinical factors, use of treatments, serologic markers of autoimmunity, and possible relationships between platelet counts, concentrations of endogenous thrombopoietin (eTPO), and the presence of circulating anti-TPO antibodies. Data including medical history and laboratory evaluations were collected at a single patient visit on 205 patients (19 children, 186 adults). Reported histories revealed a 5% rate of thrombotic/ischemic events. Autoimmune markers including direct antiglobulin test and antinuclear antibodies were found more frequently than in the normal population; antiplatelet antibody testing was not done. eTPO concentrations were comparable to concentrations found in healthy volunteers. Our study confirmed that no significant inverse correlation occurred between circulating concentrations of eTPO and platelet counts in patients with ITP (Spearman r = -0.15). Two of the 205 patients tested (1%) had neutralizing activity of recombinant human TPO in a biological assay; however, this activity was confirmed to be anti-TPO antibody in only 1 patient.

Abortion, Spontaneous↗
PubMed2004

Factors affecting choice of hemostatic agent for the hemophilia patient with an inhibitor antibody.

Achieving adequate hemostasis in patients with hemophilia and high-titer inhibitor antibodies remains a challenge despite the development of plasma-derived and recombinant therapies to bypass the inhibitory effect. A group of hemophilia treaters met to examine the factors that influence physician choices among the very costly and cumbersome available therapies. Specific knowledge deficits in need of prospective research were identified with respect to the rational treatment of inhibitor patients.

Antibodies↗
PubMed2004

Advances in clotting factor treatment for congenital hemorrhagic disorders.

During the last 50 years, clotting factor replacement has evolved from the use of frozen plasma in the 1950s, through the serendipitous discovery of cryoprecipitate in the 1960s and the development of purified clotting factors in the 1970s and 1980s, to the era of recombinant clotting factors beginning in the 1990s. The dawn of the new millennium has seen the refinement of recombinant factor (rF) VIII with enhanced safety via the elimination of plasma-derived culture media or product stabilizers. During the last decade of the 20th century, a cure for hemophilia through gene therapy became a possibility. This was, in part, facilitated by availability of large (dogs) and small (mice) animal models for hemophilia A and B. Although this review will focus primarily on clotting factor replacement, the reader may refer to recent discourse on gene therapy for hemophilia.

Animals↗
PubMed2003

Orthopedic outcome studies and cost issues.

Standard therapy for years was on-demand therapy. Readers will learn of results of clinical experience in many different countries with a prophylactic approach to therapy as well as ongoing experimental designs to define optimal therapy. The costs of current prophylaxis regimens will be discussed.

Adolescent↗
PubMed2003

Why thrombin generation? From bench to bedside.

Intervention for clotting and bleeding disorders is costly, and clear-cut regimens undefined. The margin of safety between hemostasis and thrombosis is narrow and unpredictable. The use of a laboratory test to help define therapeutic regimens, dissect effects of these treatments, and to differentiate them are clearly needed. The current state of the art of thrombin generation is ready to do this.

Blood Coagulation Disorders↗
PubMed2002

End-stage liver disease in persons with hemophilia and transfusion-associated infections.

Many persons with hemophilia were infected with hepatitis C and B viruses (HCV, HBV) and HIV, but the consequences of these transfusion-acquired infections are poorly defined. We estimated the risk of HCV-related end-stage liver disease (ESLD) and the associations of age, HBV, and HIV with that risk. All 1816 HCV-seropositive hemophilic patients at 16 centers were followed for up to 16 years. Of these, 624 were HIV(-) and 1192 were HIV-coinfected; 135 had persistent HBV surface antigenemia, 1374 had resolved HBV infection, and 287 were HBV-uninfected. ESLD was defined as bleeding esophageal varices, hepatic encephalopathy, persistent ascites, or death excluding nonhepatic causes of these conditions. Competing risk models were used to estimate the annual hazard rate and cumulative incidence of ESLD. Proportional hazards models were used to estimate relative hazards of ESLD with covariates. ESLD developed in 127 of the HCV/HIV-coinfected participants, with an estimated 16-year cumulative incidence of 14.0% (95% confidence interval [CI], 11.6%-16.4%). Without HIV, 10 HCV-infected participants developed ESLD, for a significantly lower cumulative incidence of 2.6% (95% CI, 1.0%-4.3%, P <.0001). ESLD risk increased steeply with age in both groups. With HIV, ESLD risk was increased 8.1-fold (95% CI, 1.9-35.2) with HBV surface antigenemia, 2.1-fold (95% CI, 1.3-3.3) with fewer than 0.2 x 10(9)/L (200/microL) CD4(+) lymphocytes, and 1.04-fold (95% CI, 1.03-1.06) per year of age. Thus, HIV is associated with a markedly increased risk of HCV-related ESLD for persons with hemophilia, particularly with HBV infection, low CD4(+) lymphocytes, or older age.

Adolescent↗
PubMed2002

Kaposi's sarcoma-associated herpesvirus infection in elderly Jews and non-Jews from New York City.

BACKGROUND: Worldwide, Kaposi's sarcoma (KS) occurs in immunocompetent elderly adults, especially men. Elderly Jews have relatively high KS risk, but it is unclear whether this indicates heightened prevalence of KS-associated herpesvirus (KSHV), the KS agent. We studied Jewish and non-Jewish patients at a New York City geriatrics clinic. METHODS: We measured plasma antibodies against K8.1 (a KSHV glycoprotein) by enzyme immunoassay and against viral latency antigens by immunofluorescence assay. Individuals positive by either were considered KSHV-seropositive. Titres were performed for positive subjects. We used polymerase chain reaction to quantify circulating KSHV DNA. RESULTS: Of 467 subjects (median age 80 years), 40 were KSHV-seropositive (8.6%). Seroprevalence was 8.8% among Jews (18 of 204), similar to other religious groups, and did not differ by sex or region of birth. However, K8.1 antibody titres were higher in men than women (geometric mean titre 177 versus 35, P = 0.03) and increased with age (P = 0.02). The K8.1 titres were higher in three people from Central/Eastern Europe (1,280, 1,280, 320), all of whom were Jewish, than in others (geometric mean titre 39, P = 0.006). The single person with detectable circulating KSHV (457 copies/million cells) had the highest titre (5,120). CONCLUSIONS: The KSHV seroprevalence was not elevated among elderly Jews, despite their known high risk for KS. However, among KSHV-seropositive individuals, K8.1 titres were highest in subgroups at greatest risk for KS (men, older individuals, people from Central/Eastern Europe) and may identify individuals with poor immune control of KSHV replication during asymptomatic infection.

Age Distribution↗