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K Hoots

Publications and source records attributed to K Hoots.

14 recordsLinked to original sources
PubMed2004

Human immunodeficiency and hepatitis virus infections and their associated conditions and treatments among people with haemophilia.

Treatment with contaminated plasma products before 1990 resulted in extraordinary prevalence rates of human immunodeficiency virus (HIV) and hepatitis B and C viruses (HBV, HCV). In the Second Multicentre Haemophilia Cohort Study (MHCS-II) during 2001-03, 30% of HCV-seropositive survivors had HIV and 4.6% were HBV carriers. Highly active antiretroviral therapy (HAART) radically altered the consequences of HIV/HCV coinfection. Whereas opportunistic infections predominated previously, current major complications are liver failure and bleeding (exacerbated by decreased clotting factor synthesis, hypersplenic thrombocytopenia, and oesophageal varices). Most HIV-positives in MHCS-II were HIV RNA-negative and had > 200 CD4(+) cells microL(-1), but only 59% were on HAART. With HIV, especially after 41 years of age, liver disease was apparent (jaundice in 5%, ascites 7%, hepatomegaly 9%, splenomegaly 19%). HAART increases survival but may contribute to various comorbidities. Without HIV, sustained HCV clearance is obtained in > 50% with combined pegylated interferons plus ribavirin, but data in haemophilic populations, especially with HIV, are limited. In MHCS-II, HCV RNA negativity was 41% following standard interferon plus ribavirin; among interferon-naive participants (implying spontaneous HCV clearance), HCV RNA negativity was 12% with and 25% without HIV. Without HIV, spontaneous HCV clearance was much more likely with early age at infection and particularly with recent birth (late 1970s or early 1980s) but not with bleeding propensity or its treatment. Most (72%) participants had received no anti-HCV therapy. Hepatic and haematological conditions are likely to increase during the coming years unless most adult haemophiliacs are successfully treated for HIV, HCV or both.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS.

BACKGROUND: From studies of genetic polymorphisms and the rate of progression from human immunodeficiency virus type 1 (HIV-1) infection to the acquired immunodeficiency syndrome (AIDS), it appears that the strongest susceptibility is conferred by the major-histocompatibility-complex (MHC) class I type HLA-B*35,Cw*04 allele. However, cytotoxic T-lymphocyte responses have been observed against HIV-1 epitopes presented by HLA-B*3501, the most common HLA-B*35 subtype. We examined subtypes of HLA-B*35 in five cohorts and analyzed the relation of structural differences between HLA-B*35 subtypes to the risk of progression to AIDS. METHODS: Genotyping of HLA class I loci was performed for 850 patients who seroconverted and had known dates of HIV-1 infection. Survival analyses with respect to the rate of progression to AIDS were performed to identify the effects of closely related HLA-B*35 subtypes with different peptide-binding specificities. RESULTS: HLA-B*35 subtypes were divided into two groups according to peptide-binding specificity: the HLA-B*35-PY group, which consists primarily of HLA-B*3501 and binds epitopes with proline in position 2 and tyrosine in position 9; and the more broadly reactive HLA-B*35-Px group, which also binds epitopes with proline in position 2 but can bind several different amino acids (not including tyrosine) in position 9. The influence of HLA-B*35 in accelerating progression to AIDS was completely attributable to HLA-B*35-Px alleles, some of which differ from HLA-B*35-PY alleles by only one amino acid residue. CONCLUSIONS: This analysis shows that, in patients with HIV-1 infection, a single amino acid change in HLA molecules has a substantial effect on the rate of progression to AIDS. The different consequences of HLA-B*35-PY and HLA-B*35-Px in terms of disease progression highlight the importance of the epitope specificities of closely related class I molecules in the immune defense against HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Therapeutic choices for patients with hemophilia and high-titer inhibitors.

Effective treatment of bleeding episodes in hemophilia with high titer inhibitors (HTI) remains a challenge, despite the fact that the therapeutic armamentarium has expanded considerably over the past few years. Treatment safety has improved with the availability of porcine factor VIII (FVIII) and bypassing products such as recombinant factor VIIa (rFVIIa), and plasma-derived activated Prothrombin Complex Concentrates (aPCCs) that are virally inactivated. The major drawbacks of rFVIIa and aPCCs are their unpredictable hemostatic effect, lack of laboratory assays to monitor efficacy and dosing frequency, and the risk of thrombosis. The proceedings of a one-day workshop of physicians who specialized in treating patients with hemophilia held in Vienna on May 13, 2000 have been summarized. In making a decision regarding the choice of product, physicians often consider the type of bleeding episode (life or limb threatening), age of the patient, volume of the reconstituted product, previous exposure to plasma derived products, cost, efficacy, and safety. For plasma naïve patients, to achieve rapid hemostasis a majority of the panelists used porcine FVIII (for patients who lack porcine inhibitory antibodies) or rFVIIa. For patients previously treated with plasma derived factors, in addition to the above concentrates, aPCCs were recommended. Although no data exists regarding safety and efficacy, switching products was routinely practiced either because of availability or cost. Furthermore, the panelists were uncertain about the efficacy of bypassing agents in the prevention of joint disease in inhibitor patients. The workshop participants felt that future research offers the best solution to resolve some of the dilemmas faced by clinicians and may help individualise treatment in a hemophilia patient with a high titer inhibitor.

Animals↗
PubMed2000

Sucrose formulated recombinant human antihemophilic factor VIII is safe and efficacious for treatment of hemophilia A in home therapy--International Kogenate-FS Study Group.

To add an increased level of safety to antihemophilic factor replacement therapy, a full-length, recombinant Factor VIII (rFVIII) product has been developed without human-derived plasma proteins during purification and formulation and using an additional solvent/detergent viral inactivation step. This first clinical trial of a sucrose-formulated full-length rFVIII (rFVIII-FS) was conducted in previously treated patients (> or = 100 prior exposure days) with severe (<2% FVIII) hemophilia A in North America (NA) and Europe (EU). Pharmacokinetic profiles for rFVIII-FS were compared with those of currently licensed rFVIII product (Kogenate) in 35 patients. Safety and efficacy during home therapy were evaluated in 71 patients. The new formulation displayed a pharmacokinetic profile similar to that of rFVIII. Patients on home therapy received a cumulative total of 11,867 exposure days, 12,546 infusions, and 22,443,694 IU of rFVIII-FS. Of 2585 bleeds, 93.5% were treated with 1-2 infusions and 80.5% of responses were rated as excellent or good. No evidence of de novo inhibitor formation was observed. Only 0.27% of infusions were associated with any drug-related adverse event. Except for an episode of intermittent chest pain with palpitations which ceased after treatment with analgesics, associated adverse events were mild or moderate. Overall, rFVIII-FS provided excellent hemostatic control, was well-tolerated, and caused no significant adverse effects, thus demonstrating safety and efficacy for treatment of bleeds in patients with hemophilia A.

Adolescent↗
PubMed1999

Effects of plasma HIV RNA, CD4+ T lymphocytes, and the chemokine receptors CCR5 and CCR2b on HIV disease progression in hemophiliacs. Hemophilia Growth and Development Study.

We have investigated the effects of plasma HIV RNA, CD4+ T lymphocytes and chemokine receptors CCR5 and CCR2b on HIV disease progression in hemophiliacs. We prospectively observed during follow-up 207 HIV-infected hemophiliacs in the Hemophilia Growth and Development Study. Plasma HIV RNA was measured on cryopreserved plasma from enrollment using the Chiron Corporation bDNA (version 2.0) assay. Genoytpe variants CCR2b-641 and CCR5-delta32 were detected using standard molecular techniques. Those with the mutant allele for CCR2b, and to a lesser extent CCR5, had lower plasma HIV RNA, and higher CD4+ T lymphocytes than did those without these genetic variants. After controlling for the effects of plasma HIV RNA and CD4+ T lymphocytes, those with the CCR2b mutant allele compared with those wild-type, had a trend toward a lower risk of progression to AIDS, adjusted relative hazard of 1.94 (95% confidence interval [CI], 0.9-4.18; p = .092), and AIDS-related death, relative hazard 1.97 (95% CI, 0.98-4.00; p = .059). We conclude that plasma HIV RNA, CD4+ T lymphocytes, and CCR genotypes are correlated, and the protective affect of CCR2b against HIV disease progression is not completely explained by plasma HIV RNA or CD4+ T-lymphocyte number.

Acquired Immunodeficiency Syndrome↗
PubMed1999

HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage.

A selective advantage against infectious disease associated with increased heterozygosity at the human major histocompatibility complex [human leukocyte antigen (HLA) class I and class II] is believed to play a major role in maintaining the extraordinary allelic diversity of these genes. Maximum HLA heterozygosity of class I loci (A, B, and C) delayed acquired immunodeficiency syndrome (AIDS) onset among patients infected with human immunodeficiency virus-type 1 (HIV-1), whereas individuals who were homozygous for one or more loci progressed rapidly to AIDS and death. The HLA class I alleles B*35 and Cw*04 were consistently associated with rapid development of AIDS-defining conditions in Caucasians. The extended survival of 28 to 40 percent of HIV-1-infected Caucasian patients who avoided AIDS for ten or more years can be attributed to their being fully heterozygous at HLA class I loci, to their lacking the AIDS-associated alleles B*35 and Cw*04, or to both.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Clotting factor concentrates and immune function in haemophilic patients.

Patients with haemophilia often exhibit a variety of disturbances in immune function. Although infections with HIV, hepatitis and other viruses no doubt contribute to these abnormalities, chronic exposure to extraneous proteins in clotting factor concentrates (CFCs) may also play a role. Numerous in vitro and ex vivo studies show that protein contaminants--such as immunoglobulins, fibrinogen and fibronectin--can depress various immune function indicators. Generally, such studies show that intermediate-purity CFCs are more inhibitory than very high-purity (e.g. monoclonal-purified) CFCs. In many, but not all, studies, the degree of immunosuppression correlates with the amount of intermediate-purity CFC administered over time. Among various indicators of immune function, CD4+ lymphocyte number is a marker for the progression of HIV infection, and maintenance of CD4+ number is associated with delayed progression. A number of studies suggest that, compared with intermediate-purity CFCs, use of very high-purity CFCs is associated with longer preservation of this class of lymphocytes. However, it remains to be seen whether this translates to improved long-term clinical outcomes. Further research is needed on the impact of CFCs on the immune system. For the time being, however, evidence to date favours the use of very high-purity products because they appear to preserve immune function and reduce the risk of infection with hepatitis and other viruses.

Blood Coagulation Factors↗
PubMed1997

Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study.

The critical role of chemokine receptors (CCR5 and CXCR4) in human immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a search for polymorphisms in other chemokine receptor genes that mediate HIV-1 disease progression. A mutation (CCR2-64I) within the first transmembrane region of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an allele frequency of 10 to 15 percent among Caucasians and African Americans. Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts (3003 patients) revealed that although CCR2-64I exerts no influence on the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2-64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele. Because CCR2-64I occurs invariably on a CCR5-+-bearing chromosomal haplotype, the independent effects of CCR5-Delta32 (which also delays AIDS onset) and CCR2-64I were determined. An estimated 38 to 45 percent of AIDS patients whose disease progresses rapidly (less than 3 years until onset of AIDS symptoms after HIV-1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+ genotype, whereas the survival of 28 to 29 percent of long-term survivors, who avoid AIDS for 16 years or more, can be explained by a mutant genotype for CCR2 or CCR5.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The incidence and significance of hemostatic abnormalities in patients with head injuries.

Abnormal coagulation and fibrinolysis is a frequent complication in patients with head injury. This complication can be severe enough to lead to hemorrhage or thrombosis. A study was undertaken to determine if the hemostatic abnormalities are reliable indicators of outcome. Hemostasis in 269 patients with head injuries alone was screened using platelet count (PC), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin clotting time (TCT), fibrinogen assay (FIB), level of fibrin-fibrinogen degradation products (FDP), and disseminated intravascular coagulation (DIC) score in the first 24 hours after injury. Test results were compared with the outcome (discharged or dead) in the entire group and in subgroups divided on the basis of the severity of injury as determined by the Glasgow coma score (GCS). Increased consumptive coagulopathy at admission, as reflected in the DIC score, predicts the outcome of head-injured patients with a high degree of accuracy. The degree of increase of the initial FDP level and prolongation of TCT also correlated positively with the outcome. Prolongation of the APTT correlated strongly with unfavorable outcome in a large group of patients, and in a small group, markedly accelerated APTT also predicted death. Stepwise logistic regression analysis demonstrated that GCS, FDP level, and DIC score predicted outcome. Other tests did not provide additional predictive value. Abnormal hemostasis frequently complicates the course of patients with head injuries. This study demonstrates that hemostasis tests are predictors of outcome in these patients.

Adolescent↗
PubMed1983

Mediastinal masses.

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Anesthesia, General↗