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Biomedical subjects

M Pai

Publications and source records attributed to M Pai.

At least 19 recordsLinked to original sources
PubMed2006

Canadian multi-institutional survey of immune tolerance therapy (ITT) -- experience with the use of recombinant factor VIII for ITT.

Immune tolerance therapy (ITT) is currently the most effective approach to eradicate inhibitors in patients with haemophilia A. Limited evidence suggests that the use of plasma-derived factor VIII (pdFVIII) for ITT may be associated with a greater success rate than recombinant factor VIII (rFVIII). Analysis of ITT cases in Canada offered the opportunity to examine the success rate of using rFVIII for ITT, as rFVIII has been used almost exclusively for Canadian haemophilia A patients since 1994. The results of 32 patients from five haemophilia treatment centres were collated. Three patients continue on ITT. Of the 29 patients who completed ITT, 25 (86.2%) used rFVIII exclusively, and four used pdFVIII exclusively or pdFVIII followed by rFVIII. The initial FVIII dosing frequency was once per day in 72.4% of patients at an average dose of 98 U kg(-1) (range 50-200). Eight patients (25%) received one or more adjuvant therapies. The median duration of ITT was 1.1 years (mean 1.5 years, range 9 days to 6 years). The overall success rate of the 29 patients who completed ITT was 79.3% (23/29), which is comparable with the results of immune tolerance registries. Our results suggest that the success rate of ITT using rFVIII is not inferior to the results with pdFVIII.

Adjuvants, Immunologic↗
PubMed2006

Tailored prophylaxis in severe hemophilia A: interim results from the first 5 years of the Canadian Hemophilia Primary Prophylaxis Study.

BACKGROUND: Prophylactic treatment for severe hemophilia A is likely to be more effective than treatment when bleeding occurs, however, prophylaxis is costly. We studied an inception cohort of 25 boys using a tailored prophylaxis approach to see if clotting factor use could be reduced with acceptable outcomes. METHODS: Ten Canadian centers enrolled subjects in this 5-year study. Children were followed every 3 months at a comprehensive care hemophilia clinic. They were initially treated with once-weekly clotting factor; the frequency was escalated in a stepwise fashion if unacceptable bleeding occurred. Bleeding frequency, target joint development, physiotherapy and radiographic outcomes, as well as resource utilization, were determined prospectively. RESULTS: The median follow-up time was 4.1 years (total 96.9 person-years). The median time to escalate to twice-weekly therapy was 3.42 years (lower 95% confidence limit 2.05 years). Nine subjects developed target joints at a rate of 0.09 per person-year. There was an average of 1.2 joint bleeds per person-year. The cohort consumed on average 3656 IU kg(-1)year(-1) of factor (F) VIII. Ten subjects required central venous catheters (three while on study); no complications of these devices were seen. One subject developed a transient FVIII inhibitor. End-of-study joint examination scores--both clinically and radiographically--were normal or near-normal. CONCLUSIONS: Most boys with severe hemophilia A will probably have little bleeding and good joint function with tailored prophylaxis, while infusing less FVIII than usually required for traditional prophylaxis.

Canada↗
PubMed2006

Diagnosis of myocardial contusion after blunt chest trauma using 18F-FDG positron emission tomography.

Cardiac contusion is an infrequent complication of blunt chest trauma. The definite diagnosis of myocardial contusion is complex and needs a number of examinations such as electrocardiography, echocardiography, cardiac enzyme and radionuclide perfusion scan. We present a patient who had a blunt chest trauma from a car accident resulting in an acute myocardial infarction without injury to coronary arteries. The non-viable myocardium was diagnosed with (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) combined with (201)Tl perfusion single photon emission tomography (SPECT). This is the first report of FDG PET for the diagnosis of myocardial contusion in blunt myocardial trauma.

Accidents, Traffic↗
PubMed2006

False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria?

BACKGROUND: Despite certain drawbacks, the tuberculin skin test (TST) remains in widespread use. Important advantages of the TST are its low cost, simplicity and interpretation based on extensive published literature. However, TST specificity is reduced by bacille Calmette-Guérin (BCG) vaccination and exposure to non-tuberculous mycobacteria (NTM). METHODS: To estimate TST specificity, we reviewed the published literature since 1966 regarding the effect of BCG vaccination and NTM infection on TST. Studies selected included healthy subjects with documented BCG vaccination status, including age at vaccination. Studies of NTM effect had used standardised NTM antigens in healthy subjects. RESULTS: In 24 studies involving 240,203 subjects BCG-vaccinated as infants, 20,406 (8.5%) had a TST of 10+ mm attributable to BCG, but only 56/5639 (1%) were TST-positive if tested > or =10 years after BCG. In 12 studies of 12,728 subjects vaccinated after their first birthday, 5314 (41.8%) had a false-positive TST of 10+ mm, and 191/898 (21.2%) after 10 years. Type of tuberculin test did not modify these results. In 18 studies involving 1,169,105 subjects, the absolute prevalence of false-positive TST from NTM cross-reactivity ranged from 0.1% to 2.3% in different regions. CONCLUSIONS: The effect on TST of BCG received in infancy is minimal, especially > or =10 years after vaccination. BCG received after infancy produces more frequent, more persistent and larger TST reactions. NTM is not a clinically important cause of false-positive TST, except in populations with a high prevalence of NTM sensitisation and a very low prevalence of TB infection.

Adjuvants, Immunologic↗
PubMed2005

Inhibition of in-stent restenosis in rabbit iliac arteries with photodynamic therapy.

OBJECTIVES: Photodynamic therapy (PDT, the combination of light with a photosensitising drug in the presence of oxygen) inhibits restenosis after angioplasty without stenting. This study assesses the potential of PDT for prevention of in-stent re-stenosis. DESIGN AND METHODS: Normal rabbits were given the photosensitising agent 5-aminolaevulinic acid (ALA) 60 mg/kg, 3 h prior to endovascular illumination of the iliac artery (635 nm at 50 J/cm(2)) either immediately before or after deployment of an oversized (3 mm diameter) stent. PDT treated arteries were retrieved 3 or 28 days later and assessed for cell counts and vascular morphometry. Control arteries (stent but no PDT) were examined at 28 days. RESULTS: There were no adverse events and all vessels were patent at the end of the study. At 3 days there was almost complete medial cell ablation when light was delivered before stent deployment (17+/-1 cells/hpf), with little effect when illumination followed stent deployment (184+/-17 cells/hpf, p<0.0001). Twenty-eight days after PDT, the neointimal areas were 1.41+/-0.52 mm(2) (stent with no PDT), 1.24+/-0.54 mm(2) (light after stent) and 0.60+/-0.21 mm(2) (light before stent) (p=0.004). CONCLUSIONS: PDT before stent deployment caused almost complete medial cell ablation at 3 days with inhibition of in-stent restenosis at 28 days. PDT is worthy of further study as an adjuvant to percutaneous intervention in patients with vascular disease.

Aminolevulinic Acid↗
PubMed2005

Alternatives to the tuberculin skin test: interferon-gamma assays in the diagnosis of mycobacterium tuberculosis infection.

For nearly a century, there were no alternatives to the tuberculin skin test (TST) for diagnosing latent tuberculosis infection. Because of advances in immunology and genomics, for the first time, an alternative has emerged in the form of T cell based interferon-g (IFN-gamma) assays, a new generation of in vitro tests of cellular immunity. These assays measure cell mediated immune response by quantifying IFN-gamma released by T cells in response to stimulation by Mycobacterium tuberculosis antigens. Although early versions of IFN-gamma assays used purified protein derivative (PPD) as the stimulating antigen, newer versions use antigens that are significantly more specific to M. tuberculosis. These specific antigens include ESAT-6 and CFP-10. These proteins, encoded by genes located within the region of difference 1 (RD1) segment of the M. tuberculosis genome, are more specific to M. tuberculosis than PPD because they are not shared with any BCG substrains or several nontuberculous mycobacterial species. A review of current evidence on the performance of IFN-gamma assays and TST suggests that both the TST and IFN-gamma assays have advantages and limitations, and both tests appear to be useful at this time. The emergence of IFN-gamma assays is a much anticipated, welcome development that has, for the first time, increased the choice of tests available for diagnosing latent tuberculosis infection. Because both tests have their strengths and limitations, the decision to select one over the other will depend on the population, the goal of testing, and the resources available. To fully evaluate the utility of IFN-gamma assays in high burden countries such as India, long-term cohort studies are needed to determine the association between positive IFN-gamma results and the subsequent risk of active disease.

Antigens, Bacterial↗
PubMed2004

Comparing hand-held computers and paper diaries for haemophilia home therapy: a randomized trial.

Treatment of severe haemophilia with factor concentrates is by self-infusion in the home. Adherence to record keeping on paper diaries is poor. A randomized-controlled trial compared adherence with record keeping of paper diaries with hand-held computers. Forty-one individuals with severe haemophilia, were randomized to hand-held computers (n = 22) or paper diaries (n = 19) and followed for 6 months. About 86.2% (679 of 788) of infusions by patients in the computer group were in compliance with the data submission schedule compared with only 48.3% (358 of 741) of infusions by patients using paper diaries (P < 0.0001). The time intervals between infusions and the receipt of data were shorter in the computer group (median 0.25 vs. 25 days respectively, P < 0.0001). Reminder phone calls by the clinic were made less frequently to users of hand-held computers than to users of paper diaries (median one vs. five times, P < 0.0001). Accuracy of data was similar for both methods. Compliance with hand-held computers was superior to paper diaries. The clinic received data from hand-held computers mostly on the same day, and nurses could thereby provide clinical advice more effectively. Although hand-held computers did not result in increased accuracy, errors could be detected and corrected more rapidly. Electronic data can more easily be verified, analysed and summarized than that from paper diaries.

Adolescent↗
PubMed2002

Serum leptin in disabled and non-disabled children in an Indian slum population.

OBJECTIVE: To assess the concentration of serum leptin in a population of malnourished children and to compare the leptin levels of disabled and non-disabled children in this population. DESIGN: Case-control study. SUBJECTS: Eighty-one children, comprising 41 children with mixed disabilities and 40 non-disabled controls, were selected from 425 children involved in a case-control study assessing the nutritional status of children with disabilities in an Indian slum population. METHODS: Leptin was measured in the serum samples and was compared with anthropometry (weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ), weight-for-height Z-scores (WHZ), body mass index (BMI), mid-upper-arm circumference (MUAC), sub-scapular skinfold thickness and triceps skinfold thickness) and serum acute phase proteins. RESULTS: The children were very malnourished with WAZ=-2.07 (s.d. 1.15), HAZ=-2.15 (s.d. 1.85) and WHZ=-1.07 (s.d. 0.83). Leptin was extremely low in both the disabled (1.44 ng/ml; 95% confidence interval, CI, 1.23-1.69) and the non-disabled (1.19 ng/ml; 95% CI 1.04-1.35) children. There were no differences between the disabled and non-disabled groups as a whole but 15 children with neurological disabilities had significantly higher (P<0.05) serum leptin (1.65 ng/ml; 95% CI 1.29-2.06) than the non-disabled children. Girls (1.55 ng/ml; 95% CI 1.29-1.87) had significantly higher concentrations of leptin than boys (1.11 ng/ml; 95% CI 1.02-1.22; P=0.002). Leptin did not correlate with any biochemical or anthropometric measures. CONCLUSIONS: In this population, where malnutrition was common, serum leptin levels were very low and did not correlate with anthropometry. SPONSORSHIP: UK Department for International Development; Virgin Airways through the Great Ormond Street Hospital Trustees.

Acute-Phase Proteins↗
PubMed2002

Adequate vascular training opportunities can be provided without compromising patient care.

OBJECTIVES: to review the results of index operations in vascular surgery and to evaluate the impact of a specialist vascular training programme on patient outcome. METHODS: we undertook a 5-year (January 1995-December 1999) review of the weekly-collected mortality and morbidity data. The total number, 30-day mortality and stroke rate of all index operations i.e. AAA repairs (ruptured and elective), carotid operations and infra-inguinal bypasses (above and below knee, elective and emergency) was recorded. The number of operations performed by trainees under supervision was recorded. RESULTS: in the 5-year period 991 index operation were done of which 738 (74%) were done by trainees. Operations done by trainees were supervised by a consultant in 82% of cases with no significant effect on death or stroke rates. Overall vascular trainees performed 75% of the index operations of which 82% were supervised. CONCLUSIONS: trainees under supervision performed three out of four index operations. The mortality and morbidity of index operations in our unit compared well with accepted best mortality and morbidity figures. Our unit provides good training opportunities for vascular trainees whilst maintaining satisfactory standards of patient care.

Attitude of Health Personnel↗
PubMed2001

Platelets from patients with the Quebec platelet disorder contain and secrete abnormal amounts of urokinase-type plasminogen activator.

The Quebec platelet disorder (QPD) is an autosomal dominant platelet disorder associated with delayed bleeding and alpha-granule protein degradation. The degradation of alpha-granule, but not plasma, fibrinogen in patients with the QPD led to the investigation of their platelets for a protease defect. Unlike normal platelets, QPD platelets contained large amounts of fibrinolytic serine proteases that had properties of plasminogen activators. Western blot analysis, zymography, and immunodepletion experiments indicated this was because QPD platelets contained large amounts of urokinase-type plasminogen activator (u-PA) within a secretory compartment. u-PA antigen was not increased in all QPD plasmas, whereas it was increased more than 100-fold in QPD platelets (P <.00009), which contained increased u-PA messenger RNA. Although QPD platelets contained 2-fold more plasminogen activator inhibitor 1 (PAI-1) (P <.0008) and 100-fold greater u-PA-PAI-1 complexes (P <.0002) than normal platelets, they contained excess u-PA activity, predominantly in the form of two chain (tcu-PA), which required additional PAI-1 for full inhibition. There was associated proteolysis of plasminogen in QPD platelets, to forms that comigrated with plasmin. When similar amounts of tcu-PA were incubated with normal platelet secretory proteins, many alpha-granule proteins were proteolyzed to forms that resembled degraded QPD platelet proteins. These data implicate u-PA in the pathogenesis of alpha-granule protein degradation in the QPD. Although patients with the QPD have normal to increased u-PA levels in their plasma, without evidence of systemic fibrinogenolysis, their increased platelet u-PA could contribute to bleeding by accelerating fibrinolysis within the hemostatic plug. QPD is the only inherited bleeding disorder in humans known to be associated with increased u-PA.

Blood Platelet Disorders↗
PubMed2000

Imaging of malignant lymphomas with F-18 FDG coincidence detection positron emission tomography.

PURPOSE: The authors evaluated the utility of F-18 fluorodeoxyglucose (FDG) coincidence detection (CoDe) positron emission tomography (PET) for staging, post-treatment evaluation, and follow-up assessment of patients with malignant lymphomas. MATERIALS AND METHODS: Fifty-eight patients with histologically proved malignant lymphomas (4 Hodgkin's disease, 54 non-Hodgkin's lymphoma) underwent CoDe PET using F-18 FDG. CoDe PET was performed using a dual-head gamma camera equipped with coincidence detection circuitry. Of the 87 CoDe PET studies, 26 were performed for staging, 38 for post-treatment evaluation, and 23 for follow-up evaluation of recurrence. The entire trunk, from the cervical to the inguinal regions, or selected regions were scanned with the patient in the supine position. No attenuation correction was made and reconstruction was performed using filtered back-projection rather than iterative reconstruction. CoDe PET findings were compared with corresponding results of computed tomographic (CT) and magnetic resonance imaging (MRI), tissue biopsy, or clinical follow-up. RESULTS: For staging, 52 sites were positive on CoDe PET or CT-MRI. CoDe PET detected 49 sites (94%), and CT-MRI showed 47 sites (90%). CoDe PET detected five more lymphomatous lesions and missed three lesions. For post-treatment evaluation, CoDe PET showed a positive predictive value of 100% and a negative predictive value of 83%, but the validated cases numbered only 11. For follow-up for recurrence, CoDe PET had a negative predictive value of 90%, but frequent false-positive findings were noted in the head and neck region as a result of underlying inflammatory changes. CONCLUSIONS: For staging, FDG CoDe PET alone without attenuation correction is not sensitive enough to be used as an independent imaging method, especially for small abdominal lesions. However, it appears to be an accurate method for assessing residual disease and for patient follow-up.

Adolescent↗