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Biomedical subjects

Michael Makris

Publications and source records attributed to Michael Makris.

15 recordsLinked to original sources
PubMed2007

Progression to end-stage liver disease in patients with inherited bleeding disorders and hepatitis C: an international, multicenter cohort study.

Prior to 1990, many patients with inherited bleeding disorders were infected with hepatitis C virus (HCV). This study assessed the risk of end-stage liver disease (ESLD) in patients with hemophilia with chronic hepatitis C. Patients were infected between 1961 and 1990 and were followed up to August 2005. Of 847 anti-HCV(+) patients, 160 (19%) spontaneously cleared HCV and 687 (81%) developed chronic hepatitis C. Coinfection with HIV was present in 210 patients. After 35 years of infection the cumulative incidence of ESLD was 11.5% (95% CI, 8.2%-14.8%) in HIV(-) patients and 35.1% (95% CI, 29.2%-41.0%; P < .001) in patients coinfected with HIV. Independent risk factors of ESLD were HIV coinfection (hazard ratio 13.8; 95% CI, 7.5-25.3), older age at infection (hazard ratio 2.3 per 10 years; 95% CI, 2.0-2.8), alcohol abuse (hazard ratio 4.9; 95% CI, 2.5-9.6), and presence of HCV genotype 1 (hazard ratio 2.2; 95% CI, 1.1-4.2). With longer duration of HCV infection, the risk of developing ESLD is emerging in patients with inherited bleeding disorders. Risk factors for rapid progression to ESLD are alcohol abuse, coinfection with HIV, older age at infection, and presence of HCV genotype 1.

Adolescent↗
PubMed2006

Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation.

Acquired hemophilia A is a severe bleeding disorder caused by an autoantibody to factor VIII. Previous reports have focused on referral center patients and it is unclear whether these findings are generally applicable. To improve understanding of the disease, a 2-year observational study was established to identify and characterize the presenting features and outcome of all patients with acquired hemophilia A in the United Kingdom. This allowed a consecutive cohort of patients, unbiased by referral or reporting practice, to be studied. A total of 172 patients with a median age of 78 years were identified, an incidence of 1.48/million/y. The cohort was significantly older than previously reported series, but bleeding manifestations and underlying diseases were similar. Bleeding was the cause of death in 9% of the cohort and remained a risk until the inhibitor had been eradicated. There was no difference in inhibitor eradication or mortality between patients treated with steroids alone and a combination of steroids and cytotoxic agents. Relapse of the inhibitor was observed in 20% of the patients who had attained first complete remission. The data provide the most complete description of acquired hemophilia A available and are applicable to patients presenting to all centers.

Adolescent↗
PubMed2006

Cognitive appraisals and psychological distress following venous thromboembolic disease: an application of the theory of cognitive adaptation.

Venous thrombosis is a common and life-threatening disease that has received little attention in health psychology. The present study applied the theory of cognitive adaptation (TCA) to examine patients' reactions to venous thrombosis. Patients (N = 123) aged 16-84 recruited from anticoagulation units in the north of England completed measures of TCA constructs (meaning, mastery, self-esteem and optimism) and various outcome variables (anxiety, depression, thrombosis worries and quality of life) within 1 month of their thrombosis. The TCA explained large and significant amounts of variance in the outcome variables. In line with expectations, mastery, self-esteem and optimism were associated with positive adjustment. However, meaning was associated with elevated levels of distress. The results are discussed in relation to the search for meaning and the use of different control strategies in the early phases of adaptation to thrombosis.

Adaptation, Psychological↗
PubMed2006

Gastrointestinal bleeding in von Willebrand disease.

Gastrointestinal bleeding due to colonic angiodysplasia is a well-recognised complication of von Willebrand disease (vWD), occurring almost exclusively in subtypes of the disease associated with a reduction in high-molecular-weight (HMW) multimers of von Willebrand factor (vWF). A deficiency of vWF HMW multimers also provides the link between aortic stenosis and gastrointestinal (GI) bleeding in Heyde's syndrome. The diagnosis and treatment of the angiodysplastic bleeding in vWD can be very difficult and the role of vWF containing concentrates in treatment and prophylaxis remains to be established.

Angiodysplasia↗
PubMed2006

Theophylline as 'add-on' therapy to cetirizine in patients with chronic idiopathic urticaria. A randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: Chronic urticaria is a prevalent condition associated with substantial disability. Its pathogenesis is not clearly understood and is divided into autoimmune and chronic idiopathic urticaria (CIU). We investigated if the non-specific phosphodiesterase inhibitor theophylline could provide additional benefit to the histamine-1 receptor (H-1R) antagonist cetirizine in CIU. METHODS: This was a double-blind, placebo-controlled, parallel study. Patients were randomized to receive either cetirizine and theophylline (200 mg twice daily; group A, 67 subjects) or cetirizine and placebo for 6 months (group B, 67 subjects). Group A patients took theophylline for 6 more months. Response was assessed by visual analog scale (VAS) and treatment effectiveness score (TES). Blood theophylline levels were also determined at visit t=1 and t=7. RESULTS: The study was completed by 54 of the 67 patients (80.6%) in group A and 51 of the 67 patients (76.1%) in group B. The physician VAS values for group A were lower after t=3, while the patient VAS values were decreased after t=2. The physician and patient TES values in group A were statistically higher (p<0.05) at all time points except for t=1. At least 1 month of theophylline addition was necessary to obtain statistically significant benefit over cetirizine, and reducing theophylline by 50% during phase 2 did not alter this benefit. Pruritus values were reduced, but not statistically significant. CONCLUSIONS: Addition of theophylline to conventional H-1R antagonists was well tolerated without any adverse effects and provided considerable additional benefit in the management of CIU.

Adolescent↗
PubMed2004

The impact of HIV on mortality rates in the complete UK haemophilia population.

OBJECTIVE: To estimate the effect of HIV-1 infection on subsequent mortality in a complete population. DESIGN: Prospective cohort study. SUBJECTS: A total of 7250 haemophilic males were registered in the UK Haemophilia Centre Doctors' Organisation database, 1977-1998. Most were infected with hepatitis C virus. In the early 1980s, 1246 were infected with HIV-1 from contaminated clotting factor concentrate. The main outcome measure was the date of death. RESULTS: During 1977-1984 annual mortality in severely haemophilic males was 0.9%. For those with HIV, annual mortality increased progressively from 1985 reaching over 10% during 1993-1996 before falling to 5% in 1997-1999, whereas without HIV it remained approximately 0.9% throughout 1985-1999. For moderately/mildly haemophilic males the annual mortality was 0.4% during 1977-1984. Without HIV it remained approximately 0.4% throughout 1985-1999, but with HIV it was similar to that in severe haemophilia with HIV. Survival was strongly related to age at HIV infection. The large temporal changes in mortality with HIV were largely accounted for by HIV-related conditions. Without HIV annual liver disease mortality remained below 0.2% throughout 1985-1999, but with HIV it was 0.2% during 1985-1990, 0.8% during 1991-1996, and 0.8% during 1997-1999. CONCLUSION: These data provide a direct estimate of the effect of HIV-1 infection on subsequent mortality in a population with a high prevalence of hepatitis C. From approximately 3 years after HIV infection, large, progressive increases in mortality were seen. From 1997, after the introduction of effective treatment, substantial reductions occurred, although mortality from liver disease remained high.

Adolescent↗
PubMed2004

Systematic review of the management of patients with haemophilia A and inhibitors.

The London Directorate of Health and Social Care Research and Development Group recently commissioned the School of Health and Related Research at the University of Sheffield to perform a systematic review of the management of patients with haemophilia A and inhibitors. The main areas of the review were the epidemiology of inhibitors, the role and effectiveness of immune tolerance induction, and the control of acute bleeding. In addition, an economic model of the different treatment strategies was constructed. Among the findings was that the overall prevalence of inhibitors in unselected haemophilic populations is 5-7%, with the cumulative inhibitor risk varying from 0% to 39%. The prevalence of inhibitors was inversely related to the size of the reported population. Immune tolerance induction was considered desirable, with evidence suggesting that the Bonn protocol may be more effective than either the Malmo or low-dose protocols. Immunosuppressive drug regimens on their own were ineffective. Activated prothrombin complex concentrates (aPCC) were more effective than non-aPCC. Recombinant activated factor VII was also effective, but there were no randomized trials comparing this agent with aPCC. Porcine factor VIII was highly effective in both treating acute bleeding episodes and preventing bleeding after surgery.

Disease Management↗
PubMed2004

Acquired Glanzmann's thrombasthenia without thrombocytopenia: a severe acquired autoimmune bleeding disorder.

Acquired Glanzmann's thrombasthenia (GT) is an uncommon accompaniment to immune thrombocytopenic purpura. Rarely, GT may present as an acquired autoimmune disorder of platelet function, with rapid onset of a moderate-to-severe bleeding tendency, a prolonged bleeding time, but with a normal platelet count and normal platelet glycoprotein (GP) expression. This is caused by an autoantibody with specificity for platelet GP IIb/IIIa or an epitope close to that of the GP, resulting in partial or complete refractoriness of the patient's platelets to ADP, collagen and arachidonic acid. We describe two patients with acquired GT and a normal platelet count, who presented with severe bleeding. The first patient responded gradually to immunosuppressive treatment but eventually developed non-Hodgkin's lymphoma. The second patient had no other underlying conditions and remitted spontaneously within 2 years.

Aged↗
PubMed2003

Enzymatically catalyzed disulfide exchange is required for platelet adhesion to collagen via integrin alpha2beta1.

Integrin alpha2beta1 is the principal adhesive receptor for collagen but platelets also adhere through glycoprotein VI (GPVI). Integrin alphaIIbbeta3 may augment platelet adhesion. We have shown that disulfide exchange is necessary for platelet adhesion to fibrinogen, fibronectin, and collagen. However 2 questions remained: (1) Can activated alphaIIbbeta3 explain the observed role of disulfide exchange in adhesion to collagen, or is this role common to other integrins? (2) Is disulfide dependence specific to the integrin receptors or shared with GPVI? To discriminate adhesive functions of alpha2beta1 from those of alphaIIbbeta3 we used Glanzmann platelets and alphaIIbbeta3-specific antibodies applied to normal platelets. To resolve adhesive events mediated by alpha2beta1 from those of GPVI we used synthetic peptides specific to each receptor. We addressed direct integrin ligation using purified alpha2beta1 and recombinant I domain. We observed the following: adhesion to the alpha2beta1-specific peptide was disulfide-exchange dependent and protein disulfide isomerase (PDI) mediated; membrane-impermeant thiol blockers inhibited alpha2beta1, but not GPVI mediated, adhesion; direct blockade of PDI revealed that it is involved in adhesion through alpha2beta1 but not GPVI; and purified alpha2beta1, but not recombinant I domain, depended on free thiols for ligation. These data suggest that the enzymatically catalyzed adhesion-associated reorganization of disulfide bonds is common to members of the integrin family and specific to this family.

4-Chloromercuribenzenesulfonate↗
PubMed2003

Management of excessive anticoagulation or bleeding.

The number of patients anticoagulated with warfarin has rapidly increased over the last decade. Approximately 1% of these patients experience serious bleeding and 0.5% die annually from bleeding. The management of hemorrhage in the overanticoagulated patient is complex and is based on balancing the risks and benefits of each therapeutic intervention. For life-threatening bleeding, the use of clotting factor concentrates is essential for immediate anticoagulation reversal, whereas for less severe bleeding intravenous vitamin K is the treatment of choice. Vitamin K (by the intravenous or oral route) should also be used in overanticoagulated patients who are not actively bleeding but who are at high risk of doing so if their anticoagulation is not, at least partially, corrected.

Anticoagulants↗
PubMed2003

Evaluation of the Roche LightCycler: a simple and rapid method for direct detection of factor V Leiden and prothrombin G20210A genotypes from blood samples without the need for DNA extraction.

The Roche LightCycler is a micro-volume thermocycler that combines extremely rapid polymerase chain reaction with fluorescence resonance energy transfer analysis of amplified products. We have evaluated the use of minimally processed blood samples for detection of two point mutations known to increase the risk of venous thromboembolism. Results from the LightCycler using the supernatant of diluted heated blood were compared with those gained by traditional methods based on polymerase chain reaction and restriction enzyme digestion. For factor V Leiden mutation, there was complete agreement between both methods in detection of wild-type (n = 82), heterozygous (n = 100) and homozygous (n = 18) genotypes. Similarly, the prothrombin G20210A mutation showed complete agreement for wild-type (n = 135), heterozygous (n = 63) and homozygous (n = 2) subjects.

3' Untranslated Regions↗
PubMedDate not supplied

IgE-mediated sensitization in seafood processing workers.

Occupational-related allergic sensitization has been reported in fishery workers. The aim of this study was to investigate the prevalence, work-related symptoms, and possible risk factors in this occupationally exposed population in Greece. Sixty-four fish and seafood processing workers were compared with 60 controls regarding sensitization to seafood allergens. All participants underwent skin-prick tests (SPTs) with cod, sardines, shrimp, spiny lobster, crabs, salmon, mussels, and trout plus negative and positive control. The level of specific IgE (radioallergosorbent test) was evaluated in subjects with positive SPTs. Sensitization criteria were both SPTs and the corresponding positive radioallergosorbent test. Atopic status was tested with SPTs to seven common inhalant allergens. Potential risk factors for IgE sensitization were investigated using logistic regression analysis. Twenty-three of 64 workers (35.9%) were sensitive to at least one of the seafood allergens tested, and the prevalence in the control group was 10% (6/60; odds ratio, 5.049; 95% CI, 1.884-13.533). The prevalence of sensitization in allergen species tested in the fishery workers group was shrimp, 12.5%; spiny lobster, 10.9%; mussels, 7.8%; crabs 3.1%; cod, 3.1%; sardines, 1.6%; salmon, 1.6%; and trout, 1.6%. Presence of atopy (p = 0.02), intensity (p = 0.03), and duration of exposure (p = 0.03) was found as potential risk factors for IgE sensitization. Four of 64 (6.25%) workers reported work-related symptoms. Occupational exposure to fish and seafood significantly increases the likelihood of sensitization in seafood allergens and atopy, duration, and intensity of exposure may represent potential risk factors in seafood processing workers.

Adult↗
PubMedDate not supplied

Pattern of sensitization to honeybee venom in beekeepers: a 5-year prospective study.

Beekeepers are at increased risk for honeybee (Hb) venom allergy and they represent a unique population for Hymenoptera venom studies. The aim of this was to prospectively examine the pattern of Hb venom sensitization over a 5-year period in new beekeepers and define possible predisposing factors. Thirty-five beekeepers were tested every 6 months for 5 years with in vivo and in vitro methods to detect the possible development of sensitization to Hb and common wasp (Cw) venom. Inclusion criteria included the lack of previous beekeeping activity and absence of sensitization or reported reaction to Hymenoptera stings. Subjects with both in vivo and in vitro tests that were definitely positive or with one definitely positive and the other doubtful were considered sensitized. Ten of 35 new beekeepers (28.6%) and 3 of 36 controls (8.3%) developed sensitivity to Hb venom during the 5-year period. The risk ratio in incidence studies was calculated at 3.43 (SE of log risk ratio = 0.61; 95% CI of risk ratio = 1.03-11.42). All sensitized beekeepers were detected within the first 18 months of occupational exposure; 8 of 10 (80%) beekeepers were detected during the initial 12 months and the 2 remaining beekeepers were detected between 12 and 18 months. One of 35 (2.9%) beekeepers and 1 of 36 controls (2.8%) were sensitized to Cw venom. The number of stings per year and atopy had no effect on sensitization rate. Although predisposing factors to sensitization or anaphylaxis could not be identified, beekeepers developed sensitization to bee venom in <18 months.

Adult↗