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Barbara A Konkle

Publications and source records attributed to Barbara A Konkle.

10 recordsLinked to original sources
PubMed2024

Genetics of Latin American Diversity Project: Insights into population genetics and association studies in admixed groups in the Americas.

Latin Americans are underrepresented in genetic studies, increasing disparities in personalized genomic medicine. Despite available genetic data from thousands of Latin Americans, accessing and navigating the bureaucratic hurdles for consent or access remains challenging. To address this, we introduce the Genetics of Latin American Diversity (GLAD) Project, compiling genome-wide information from 53,738 Latin Americans across 39 studies representing 46 geographical regions. Through GLAD, we identified heterogeneous ancestry composition and recent gene flow across the Americas. Additionally, we developed GLAD-match, a simulated annealing-based algorithm, to match the genetic background of external samples to our database, sharing summary statistics (i.e., allele and haplotype frequencies) without transferring individual-level genotypes. Finally, we demonstrate the potential of GLAD as a critical resource for evaluating statistical genetic software in the presence of admixture. By providing this resource, we promote genomic research in Latin Americans and contribute to the promises of personalized medicine to more people.

Humans↗
PubMed2005

Correlates of spontaneous clearance of hepatitis C virus among people with hemophilia.

People with hemophilia were formerly at very high risk of infection with hepatitis C virus (HCV). Approximately 20% of HCV-infected patients spontaneously clear the virus. To identify correlates of spontaneous clearance of HCV, we studied a cohort of HCV-infected hemophilic subjects without human immunodeficiency virus infection who had never been treated with interferon. Plasma HCV RNA was persistently undetectable in 192 (27.0%) of 712 HCV-seropositive subjects. In multivariate analyses, HCV clearance was more likely in subjects infected with HCV at younger age, especially with infection before age 2 years (40.1%) compared with after age 15 years (14.9%, P(trend) < .0001), and with relatively recent infection, especially after 1983 (42.8%) compared with before 1969 (18.2%, P(trend) < .0001). HCV clearance was marginally reduced with African ancestry (19%) and greatly increased with chronic hepatitis B virus (HBV) infection (59.1%, P = .001). Resolved HBV infection, coagulopathy types and severity, types of clotting factor treatment, and sex were not associated with HCV clearance. In conclusion, hemophilic subjects coinfected with chronic HBV and those infected with HCV before age 2 years or after 1983 were significantly more likely to spontaneously clear HCV viremia. These data highlight and clarify the importance of nongenetic determinants in spontaneous recovery from HCV infection.

Adolescent↗
PubMed2005

Phase I study of the novel taxane CT-2103 in patients with advanced solid tumors.

BACKGROUND: CT-2103 (Cell Therapeutics, Seattle, Wash.) is a water-soluble macromolecular conjugate of paclitaxel to a polyglutamate backbone, designed to enhance tumor permeability and to improve intratumoral delivery of paclitaxel. Preclinical studies indicate that CT-2103 has substantial antitumor efficacy in xenograft tumor models. METHODS: We performed a phase I trial in patients with advanced solid tumors to determine the maximum tolerated doses (MTD) of CT-2103 when administered as short intravenous infusion every 3 weeks. RESULTS: Seven patients received a total of 16 cycles (range 1-3) of CT-2103 at doses of 235 and 270 mg/m(2). Two of five patients treated at 235 mg/m(2) and one of two patients treated at 270 mg/m(2) experienced grade 3/4 neutropenia. Four patients experienced a marked increase in PTT within 30 min of the start of infusion. Neuropathy was more severe than expected. Two patients developed grade 3 neuropathy that prompted a 50% dose reduction of CT-2103 and persisted for 8 months in one, and over a year in the other. Three patients experienced grade 1 or 2 neuropathy. Neurotoxicity was cumulative and prevented patients from receiving prolonged administration of CT-2103. CONCLUSIONS: The unexpectedly high rate of cumulative toxicity observed in our study needs to be taken into consideration in future trials of CT-2103. Prior taxane use may not be a predictor of severe neurotoxicity.

Dose-Response Relationship, Drug↗
PubMed2005

Fresh frozen plasma prepared with amotosalen HCl (S-59) photochemical pathogen inactivation: transfusion of patients with congenital coagulation factor deficiencies.

BACKGROUND: Photochemical treatment (PCT) with amotosalen HCl (S-59) was developed to inactivate pathogens and white blood cells in plasma (PCT-FFP) used for transfusion support. STUDY DESIGN AND METHODS: An open-label, multicenter trial was conducted in patients with congenital coagulation factor deficiencies (factors [F]I, FII, FV, FVII, FX, FXI, and FXIII and protein C) to measure the kinetics of specific coagulation factors, hemostatic efficacy, and safety of PCT-FFP. Posttransfusion prothrombin time (PT), partial thromboplastin time (PTT), and clinical hemostasis were evaluated before and after PCT-FFP transfusions. RESULTS: Thirty-four patients received 107 transfusions of PCT-FFP for kinetic studies or therapeutic indications (mean dose, 12.8 +/- 8.5 mL/kg). Incremental factor recoveries ranged from 0.9 to 2.4 IU per dL per IU per kg (FII, FV, FVII, FX, FXI, and protein C). Mean pretransfusion PT (20.7 +/- 22.2 sec) corrected after PCT-FFP (13.8 +/- 2.4 sec, p < 0.001). Mean pretransfusion PTT (51.2 +/- 29.3 sec) corrected after PCT-FFP (32.0 +/- 5.1 sec, p < 0.001). Thirteen patients required 77 transfusions for therapeutic indications. PCT-FFP provided effective hemostasis and was well tolerated. CONCLUSIONS: Replacement coagulation factors in PCT-FFP exhibited kinetics and therapeutic efficacy consistent with conventional FFP.

Adolescent↗
PubMed2003

Role of splenectomy in patients with refractory or relapsed thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) was once uniformly fatal. Therapeutic plasma exchange in combination with immunosuppressive and anti-platelet agents, however, have resulted in improved survival rates of greater than 80% for patients with TTP. In spite of aggressive plasma exchange and adjuvant therapy, a number of TTP patients are refractory to treatment. In addition, up to 40% of TTP patients who initially respond to therapy eventually relapse. Alternative therapies such as splenectomy have been used with varying degrees of success in refractory and relapsing TTP patients. The usefulness of splenectomy in preventing relapse of TTP or treating those patients who are refractory to plasma exchange remains controversial. We present a single institution's experience with 14 patients who underwent splenectomy for refractory (six patients) or relapsed (eight patients) TTP since 1984. In both patient groups, splenectomy induced stable long-term remissions. Six of six (100%) patients who were refractory to plasma exchange, survived to be discharged from the hospital, apparently free of disease. Four of eight patients (50%) who had a splenectomy for relapsing TTP went into a complete remission and had no further relapses of their disease. Moreover, in relapsing patients who failed to experience long-term remission, the relapse rate after splenectomy was 0.3 events per patient year compared to 1.0 events per patient year prior to splenectomy. We conclude that splenectomy is a reasonable treatment option for TTP patients refractory to standard plasma exchange therapy or who have experienced multiple and/or complicated relapses. We believe this is the first series that demonstrates efficacy of splenectomy in plasma exchange-refractory TTP.

Adult↗
PubMed2003

Use of recombinant human antithrombin in patients with congenital antithrombin deficiency undergoing surgical procedures.

BACKGROUND: Hereditary antithrombin (AT) deficiency is associated with a significant risk of venous thromboembolism. Patients with this disorder frequently require long-term anticoagulation. Discontinuation of anticoagulation for childbirth or surgery may carry a substantial thrombotic risk. For this reason, replacement with AT concentrate has been used when anticoagulation is interrupted. A new recombinant human AT concentrate, produced using transgenic technology, has recently been developed. STUDY DESIGN AND METHODS: Human recombinant AT (rhAT) was provided by GTC Biotherapeutics, Inc. on a compassionate-use basis for five patients with hereditary AT deficiency who underwent six surgical procedures. Patients were treated perioperatively. Dosing was determined individually by the investigators with a goal of maintaining an AT activity of 80 to 150 percent. RESULTS: There was no clinical evidence of thrombosis or bleeding. Four of the five patients had postoperative duplex ultrasound studies of the lower extremities, which showed no evidence of acute thrombosis. Four patients were tested for antirecombinant rhAT antibodies postoperatively and were negative. CONCLUSION: These case reports indicate that rhAT can provide effective support for AT-deficient patients who undergo surgery. Further study of this product is needed to define optimal dosing and further assess clinical response.

Adult↗
PubMed2003

Thrombotic disorders: diagnosis and treatment.

Hematologists are increasingly involved in the diagnosis and management of patients with venous and arterial thromboembolic disorders. There have been major advances in recent years in our understanding of the central role of hypercoagulability in the pathogenesis of thrombosis. This has led to new approaches to the diagnosis of patients at risk for thrombosis and the development of more rational antithrombotic strategies. In Section I, Dr. Andrew Schafer reviews current concepts of acquired and inherited hypercoagulable states. It is now recognized that most, if not all, patients with venous thromboembolism have a genetic basis for the disorder ("thrombophilia"). The level of lifelong, baseline hypercoagulability in any individual may be determined by the type(s) and number of thrombophilia(s) that are inherited. Clinical episodes of thrombosis are precipitated by acquired thrombogenic triggers, which may be overt (e.g., pregnancy) or subclinical. In Section II, Dr. Mark Levine discusses the complex problem of thrombosis in patients with cancer. The goals of treating acute venous thromboembolism in cancer patients are to prevent recurrence, minimize the risk of anticoagulant-induced bleeding, and improve quality of life. New developments have improved treatment of venous thromboembolism in these patients, including outpatient therapy and secondary prevention with low-molecular-weight heparin. In Section III, Dr. Barbara Konkle reviews the diagnosis and management of thrombotic complications associated with pregnancy and hormonal therapy. Patient management is discussed based on data on thrombotic risks associated with hormonal treatment of infertility, pregnancy and the post-partum period in women with and without underlying thrombophilic risk factors. In Section IV, Dr. Clive Kearon discusses the management of anticoagulation before and after elective surgery. In the past, there has been no consensus on the perioperative management of anticoagulation for patients who require long-term warfarin therapy. This review considers the expected risks and benefits of different approaches to anticoagulation in patients who require warfarin because of atrial fibrillation, a mechanical heart valve, or a history of venous thromboembolism.

Anticoagulants↗