Registry of inherited bleeding disorders in Poland--current status and potential role of the HemoRec database.

We present data collected in HemoRec, an Internet-based platform implemented in 2006 in 15 haemophilia treatment centres in Poland and compare them with the national registry of inherited bleeding disorders established since 1991 at the Institute of Haematology and Blood Transfusion in Warsaw. We also analyse the current status of haemophilia treatment in Poland as well as future perspectives. Data on 1102 patients registered in HemoRec were analysed and compared with 4294 patients in the national registry (status as at 17.08.2009). The number of patients with severe haemophilia, mild/moderate haemophilia and von Willebrand in HemoRec is 530, 328 and 54 (respectively), compared with 1199, 1167 and 1128 in the national registry. The mean age of all haemophilic patients registered in HemoRec is 26.2 years, compared with 37.3 years in the general Polish male population in 2008. The number of haemophilic patients with inhibitor registered in HemoRec is 102 compared with 155 in the national registry (resulting in a prevalence of 14.9% of all severe haemophilia A and 1.6% of all severe haemophilia B patients). HemoRec includes data on a representative group of Polish haemophilic patients, mostly with haemophilia and haemophilia with inhibitor. von Willebrand's disease is largely under-registered in Poland. The survival of Polish haemophilic patients is shorter than that in the general population. The number of inhibitor patients in Poland is relatively large and should be decreased by wider availability of immunotolerance induction in 2010.

Single-dose (270 microg kg(-1)) recombinant activated factor VII for the treatment and prevention of bleeds in haemophilia A patients with inhibitors: experience from seven European haemophilia centres.

Several studies have suggested that recombinant factor VIIa (rFVIIa) is effective and safe at doses >90 microg kg(-1). In March 2007, the European Medicines Agency approved the use of single-dose rFVIIa 270 microg kg(-1) for the treatment of mild-to-moderate bleeds in haemophilia patients with inhibitors. The aim of this study was to describe the use of single-dose rFVIIa in a real-life setting. In November 2007, seven haemophilia specialists from five European countries convened to share and discuss their experiences with the single-dose rFVIIa regimen within haemophilia A. Case histories of eight patients were discussed in this retrospective study. Six adult and two paediatric patients (age range, 19 months-40 years) were treated with single-dose rFVIIa for a variety of target-joint bleeding, other bleeds and bleeding prevention. Treatment was successful in all the eight cases, with most patients requiring one dose to achieve bleeding resolution. No thrombotic or other safety concerns were raised by single-dose rFVIIa treatment. All patients and physicians preferred single-dose rFVIIa treatment to multiple injections; key benefits of single-dose rFVIIa treatment reported by patients and physicians included improved quality of life, greater convenience and ease of administration, improved compliance, faster control of bleeding, less injection-related pain and faster pain relief. In the patients reported here, single-dose rFVIIa 270 microg kg(-1) appears to be an effective and safe haemostatic treatment that improves the quality of life and convenience of treatment for patients. Such treatment might be of particular benefit for patients with difficult venous access or needle phobia.

Synthesis and biological evaluation of naphthalene-1,4-dione derivatives as potent antimycobacterial agents.

The recent increase in the incidence of tuberculosis with the emergence of multi-drug resistant (MDR) cases has lead to the search for new drugs that are effective against MDR strains of Mycobacterium tuberculosis (M. tb) and can augment the potential of existing drugs against tuberculosis. In the present study a series of naphthalene-1,4-dione derivatives were synthesized and evaluated for their in vitro antimycobacterial activity against M. tb H37Rv strain. Preliminary results indicated that most of the compounds demonstrated significant antimycobacterial activities. The most effective compounds of the series 7, 8 and 10 have MIC values of 3.13 microg/mL and growth inhibition of 99%. Compound 7 has an IC50 value of 0.49 microg/mL. Compounds 1, 3 and 18 with MIC values of 3.13 microg/mL also showed 96-98% growth inhibition. The objective of our study is to generate new leads through different mode of action and to optimize their structure to display the potent efficacy.

Addition of cladribine to induction/consolidation regimen does not impair peripheral blood stem cell mobilization and bone marrow harvest for autotransplantation in acute myeloid leukemia patients.

BACKGROUND: The previous study by the Polish Adult Leukemia Group has demonstrated that addition of cladribine to standard DNR+AraC induction potentiates the antileukemic activity. The goal of this study was to compare the efficacy of bone marrow or peripheral blood hematopoietic cell collection in patients who obtained remission after daunorubicine plus cytarabine induction with cladribine (DAC-7) or without addition of cladribine (DA-7) in preparation for autotransplantation. PATIENTS AND METHODS: Sixty-six patients aged 41 years (range, 17-58 years) were included in this study: 33 cases in the DAC-7 and 33 in the DA-7 arm. Hematopoietic cells were collected from the bone marrow (ABMT, n = 29) or from the peripheral blood (ABCT, n = 37) using cytopheresis after administration of AraC (2 x 2 g/m2) on days 1, 3, 5 and subsequent G-CSF (10 microg/kg) from day 7 as mobilization therapy. RESULTS: The numbers of harvested CD34+ cells were similar in the DAC-7 and DA-7 pretreated patients both after harvesting from peripheral blood (2.55 x 10(6)/kg vs 2.5 x 10(6)/kg) and from bone marrow (1.62 x 10(6)/kg vs 1.55 x 10(6)/kg), respectively. The proportion of patients with sufficient material for autologous bone marrow transplantation was higher in the DAC-7 compared with the DA-7 arm. All patients engrafted; hematopoietic recovery was similar in both subgroups. CONCLUSION: Addition of cladribine to a standard DA induction does not impair the harvesting of hematopoietic cells and their engraftment after autotransplantation.

Hemostatic Disorders in Hormonally Active Pituitary Tumors.

Endocrinopathies encompass heterogeneous diseases that can lead to hemostasis disorders at various stages over their clinical course. Normal hemostasis requires an equilibrium between the processes of coagulation and fibrinolysis, which depend on multiple activators and inhibitors. To date, the influence of various hormonal disorders on the hemostatic system has been assessed many times. The aim of this review was to analyze hemostasis abnormalities that occur in patients with hormonally active pituitary tumors: corticotropinoma, somatotropinoma, prolactinoma, gonadotropinoma and thyrotropinoma. Authors discuss studies that examined coagulation and hemostasis parameters among patients with these tumors, as well as analyze antithrombotic prophylaxis approach for endogenous hypercortisolemia subjects in particular.

Molecular characterisation of Duchenne muscular dystrophy and phenotypic correlation.

Dystrophin gene was analysed in 32 unrelated DMD families (46 subjects: 32 index cases and 14 sibs) for the presence of deletions by mPCR for 27 exons and cDNA probes for the entire gene. Deletions were identified in 32 patients (25 index cases and seven sibs) from 25 families. The concordance between the clinical phenotype and 'reading frame' hypothesis was observed in 24 (75%) cases. Of these, nine patients were wheelchair bound between 8-12 years of age, nine (age range 5-10 years) showed progressive difficulty in walking and six (age range 1.6-4 years) had onset of muscle weakness. One patient (CH), who was wheelchair bound at 12 years, the effect of mutation on the ORF could not be ascertained due to the presence of a junction fragment. Seven patients had inframe deletions of which four were wheelchair bound by the age of 13 years, and three (age range 5-7 years) although, ambulatory had difficulty in walking. There were eight patients who showed no deletion, of which four became wheelchair bound by the age of 12 years, four, though still ambulatory, were unable to run and tired easily. Correlation between phenotype and genotype of these DMD patients demonstrates that genetic studies of lymphocyte DNA may not always reflect the situation in the tissue involved in dystrophin, i.e. muscle. We describe a common dystrophin gene polymorphism in the Indian population with cDNA 11-14 that alters the Hind III restriction sites. Novel RFLPs were observed in 26 patients and their family members. Whether this is a polymorphism or, related to the diseased phenotype needs confirmation.

Human strengths and occupational safety.

This paper presents a review of relatively recent North American literature concerning human strengths. It briefly covers basic strength definitions, measurement and prediction of strengths, and the role of strengths in employee screening and job matching procedures. In addition to discussing variations in strength with body posture and duration of exertion, a brief reflection on torque exertion capabilities of individuals with common hand tools is also included.

Isokinetic pull-up strength profiles of men and women in different working posture.

This paper presents isokinetic (dynamic) strength profiles of males and females, engaged in infrequent force exertion, in 15 different working postures. The postures investigated ranged from kneeling to standing and involved both one-handed and two-handed exertions. The results indicated that both males and females exert maximum pull-up force with two hands in the stooped posture. Least force was exerted with the preferred hand at reach distance, in the sagittal plane (arm fully extended), in the sitting posture. As expected, large differences existed in the force exertion capability of males and females.

A biomechanical evaluation of staircase riser heights and tread depths during stair-climbing.

Several different staircase riser heights and tread depths were investigated in order to determine riser height and tread depth that minimized moments acting at the ankle, knee, and hipjoints while walking upstairs. The results indicated that joint moments were minimized when the riser height was 102 mm. For the tread depth, least moments were obtained when the depth was 305 mm.

Boundary line between the strength and endurance regions in manual lifting.

Previous work by Mital et al. showed that repetitive dynamic strength (RDS) of individuals is a better predictor of psychophysically acceptable weight (PAW) than either the maximal dynamic strength (MDS) or maximal static strengths (MSSs). It was also pointed out that somewhere between a frequency of one lift per minute and a frequency of three lifts per minute, the orientation of lifting tasks changes and muscular strengths no longer remain the limiting factor. This paper reports the results of a follow-up study conducted to pinpoint the lifting frequency just beyond which this transition takes place. The results indicated that a significant correlation existed between RDS and PAW for lifting frequencies up to 1·5 lifts per minute. Beyond 1·5 lifts per minute, no significant correlation between the two measures was found. We therefore concluded that lifting tasks performed every 40 seconds, or less frequently, are strength oriented. For those tasks which require lifting more frequently than once every 40 seconds, individual's strengths are not a limiting factor.

Reliability of repetitive dynamic strengths as a screening tool for manual lifting tasks.

Recent studies have shown that maximal dynamic strengths (MDSs) of individuals are superior and more reliable predictors of their maximum safe lifting capacity compared to maximal static strengths. The evidence, however, is based on studies that have investigated only infrequent lifting activities, i.e. lifting only a few times a day and with complete recovery from fatigue between successive lifts. It remains to be seen if MDSs are also as highly correlated to lifting capacity for frequent lifting tasks i.e. tasks that do not allow complete recovery from fatigue between successive lifts. The study reported here was conducted to determine the degree of affinity between MDSs and lifting capacities of individuals for frequent and infrequent lifting tasks. In addition, the hypothesis that lifting capacity for frequent manual lifting tasks will be more highly correlated to dynamic strength values which take into account the effect of repetition related fatigue, instead of MDSs, was tested. The results overwhelmingly supported the hypothesis. We therefore concluded that repetitive dynamic strength (RDS) is a more accurate measure of an individual's lifting capacity for frequently performed tasks, than maximal static or dynamic strengths, and deserves recognition as a reliable pre-employment screening tool for frequently performed manual lifting tasks. The experimental evidence also indicated that manual lifting tasks performed once every minute or less frequently are strength oriented while those per formed three times a minute or more frequently are not.

Cardiac rehabilitation: potential for ergonomic interventions with special reference to return to work and the Americans with Disabilities Act.

This paper briefly reviews the contemporary cardiac rehabilitation process and highlights its limitations. It argues that, in order to improve return-to-work chances, cardiac rehabilitation should focus on simulating actual work conditions. The role of ergonomics in the cardiac rehabilitation process is also outlined. Finally, the current impediments to early return to work are identified and corrective actions are suggested.

Accelerating the return to work (RTW) chances of coronary heart disease (CHD) patients: part 2--development and validation of a vocational rehabilitation programme.

PURPOSE: This paper, part 2 of the two-part paper, reviews return-to-work outcomes among individuals with coronary heart disease, who participated in an experimental field study reported in part 1 of the two-part paper. Study results reflected specific job stressors associated with physical and mental demands among various job tasks. Trends suggest that personality characteristics commonly associated with 'type a' personalities and cardiac disease risk factors may also serve as positive forces that influence return-to-work activity. METHODS/RESULTS: Relatively high levels of job satisfaction were reported among most experimental subjects. Despite having high return-to-work expectations, these patients lacked specific strategies and resources to facilitate a concrete return to work action plan. CONCLUSION: The researchers conclude that it is essential for cardiac rehabilitation staff, when creating a return to work transition for their cardiac patients, to explore the physical and psychosocial dimensions of jobs, the receptivity of the employer, and the accommodations needed to promote a safe and timely return to work.

Aerobic capacity of coronary heart disease (CHD) patients and its use in accommodating them in the workplace.

According to the American Heart Association, more than 1.5 million new Americans suffer from heart attacks and angina each year. Approximately one million of these victims survive, making coronary heart disease (CHD) the most pressing health problem in America. Worldwide, survivors of CHD number in millions. The sufferers of CHD create a very significant economic burden on the society (hospital services, medications, diagnostic tests, physician fees, lost work days and productivity, providing disability income to the victims, etc.). Besides the economic burden, pain and suffering, actual and perceived loss of physical capabilities, and grief to the family are other significant losses the victims suffer. The restoration of CHD patients to an active and productive role in society, therefore, has become a major goal of rehabilitation experts. This work provides aerobic capacity data on 111 male and 32 female CHD patients (myocardial infarction, angioplasty, and coronary artery bypass). The Bruce treadmill protocol was used for measuring aerobic capacity. The post-phase II cardiac rehab aerobic capacity for males range from 0.83 l/min to 5.41 l/min. For females the corresponding range was from 0.67 l/min to 4.04 l/min. These capacity data can be used by designers to design jobs that can be performed by CHD patients who have undergone phase II cardiac rehabilitation; successful accommodation of CHD patients, besides restoring their psychological outlook, could result in the savings of billions of dollars. In addition, a listing of jobs that can be performed by CHD patients is provided. The literature-based metabolic energy requirements for these jobs are also provided.

Accelerating the return to work (RTW) chances of coronary heart disease (CHD) patients: part 1--development and validation of a training programme.

PURPOSE: Conventional phase II cardiac rehabilitation (CR) programmes have not resulted in an improvement in returning coronary heart disease (CHD) patients to work in over 35 years. This 4 year field-initiated research, sponsored by the National Institute on Disability and Rehabilitation Research, compares conventional CR programmes with a low-intensity CR programme that simulates elements of work (job-simulated CR programme) in terms of return to work (RTW) and physiological conditioning. The effect of training on physical capabilities of patients participating in the job-simulated CR programme was also of equal interest. METHOD: Thirty patients (15 bypass and 15 angioplasty; 15 males and 15 females) participated in a conventional CR programme (control group). The job-simulated CR programme included 15 male and 2 female bypass and angioplasty patients (experimental group). Patients in the control group underwent regular aerobic exercise training (treadmill and bicycle). Experimental group patients participated in a series of low-intensity exercises such as progressive time exercises, flexibility exercises, and dexterity exercises. RESULTS: All patients participating in the low-intensity job-simulated CR programme returned to the same job they held at the onset of myocardial infarction (MI). In contrast, only 60% of the control group patients returned to work; at least one-third of these did not go back to the same job they held at the onset of M1. Patients in both groups achieved the same level of physiological conditioning. The physical functional capabilities of the experimental group patients improved significantly throughout training. CONCLUSION: The results of this field-study lead to the conclusion that a low-intensity phase II cardiac rehabilitation programme that simulates elements of work may be far superior to conventional endurance exercise-based cardiac rehabilitation programmes in terms of returning patients to work. Such a programme also strengthens patients, improving their physical capabilities, without compromising their physiological conditioning.

Deletion analysis of the dystrophin gene in Duchenne and Becker muscular dystrophy patients: use in carrier diagnosis.

The dystrophin gene was analyzed in 8 Duchenne muscular dystrophy (DMD) and 10 Becker muscular dystrophy (BMD) unrelated families (22 subjects: 18 index cases and 4 sibs) for the presence of deletions by multiplex polymerase chain reaction (mPCR; 27 exons) and Southern hybridization using 8 cDMD probes. Deletions were identified in 5 DMD and 7 BMD patients (6 index cases and 1 sib). The concordance between the clinical phenotype and "reading frame hypothesis" was observed in 11/12 patients (92%). The female relatives of DMD/BMD patients with identifiable deletions were examined by quantitative mPCR. Carriers were identified in 7 families. We also describe a variation in the HindIII pattern with cDNA probe 8 and 11-14. Molecular characterization of the dystrophin gene in this study has been helpful in advising the patients concerning the inheritance of the condition, and carrier diagnosis of female relatives, and should also prove useful for prenatal diagnosis.

Deficiency of the 50 kDa dystrophin-associated-glycoprotein (adhalin) in an Indian autosomal recessive limb girdle muscular dystrophy patient : immunochemical analysis and clinical aspects.

Abnormalities of dystrophin are a common cause of muscular dystrophy and testing for dystrophin gene or protein has become a part of routine diagnostic evaluation of patients who present with progressive proximal muscle weakness, high serum creatine kinase concentrations, and histopathological evidence of a dystrophic process. Patients who have no dystrophin abnormalities are assumed to have autosomal recessive muscular dystrophy. In a family consisting of 5 sibs, 2 mentally normal brothers presented with abnormal gait and protrusion of chest and hips. Muscle biopsy from one of them showed dystrophic changes and reduced patchy binding of dystrophin. No detectable deletion was observed in the patient's DNA and his brother with cDMD probes. Dystrophin associated proteins, beta-dystroglycan showed discontinuous immunostaining in the sarcolemma and alpha-sarcoglycan (adhalin) was totally absent, while beta-, gamma-, and delta-sarcoglycans were highly reduced. Immunoblot analysis showed dystrophin of normal molecular weight but of decreased quantity, beta-dystroglycan was reduced by about 37% while alpha-sarcoglycan was completely absent. This study is a first attempt for a systematic clinical, genetic and molecular investigation of the autosomal recessive LGMD in India.

Effect of body posture and common hand tools on peak torque exertion capabilities.

An experimental investigation was conducted to investigate the effects of body posture and of different types of common non-powered hand tools on maximum volitional torque exertion capabilities of males and females. Thirty-six males and 14 females applied peak torque in 21 different body postures while using nine different hand tools. The data analysis indicated that, for both males and females, the magnitude of volitional torque is strongly influenced by the type of tool used and the posture assumed. Between the two, however, the effect of hand tool is more profound. The correlation between the tool type and volitional torque was of the order of 0.71. No other variable was as strongly correlated with volitional torque. Maximum volitional torque profiles, as a function of posture and tool type, are provided for males and females.

Injuries due to handtools. Results of a questionnaire.

A questionnaire was mailed to various federal and state agencies in the United States to determine the frequency, severity and annual cost of handtool-related injuries in industry and to identify problem areas with regard to tool type, accident type, nature of injury, parts of body affected, type of industry and characteristics of the injured worker. The responses of various state and regional agencies were tabulated and analysed. This paper summarises the findings.

Subjective estimates of one-handed carrying tasks.

In this study, ten male and five female subjects, ranging between 21 and 23 years in age and in excellent physical health, voluntarily participated. Four different shapes of containers, 8.5 and 12.3 litres in capacity, were used to carry loads for distances of 100, 200, and 300 ft (30.48, 60.96, and 91.44 m, respectively). Individuals first subjectively estimated how much weight they could carry in a given type of container for the required distance and then verified it by actual carrying. The preferred (stronger) hand was used to hold the containers. In addition to the weight acceptable for comfortable carrying, pulse rate and ratings of perceived exertion (RPE) of the arm and whole body were also used as response measures. Results indicated that subjects could quite accurately estimate the amount of weight they could carry comfortably in one hand. RPE for one-handed carrying tasks was not one-tenth of the pulse rate as is the case for whole body tasks. The average pulse rate was 100 beats/min for the weights selected. Shape of the containers significantly influenced the amount of weight subjects were willing to carry in one hand. The acceptable amount of weight decreased with distance, but was found to increase with volume.