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.

Erythrophagocytosis by neutrophils--a rare morphological phenomenon resulting in acquired haemolytic anaemia?

Erythrophagocytosis by neutrophils is a rare morphological phenomenon described in patients with clonal malignancies of haematopoiesis with myelodysplasia and in some haemolytic conditions including paroxysmal cold haemoglobinuria, haemolysis caused by snake-bite, sickle cell anaemia and other defects of red cells. We describe a female patient who presented with acquired haemolytic anaemia. Erythrophagocytosis was found in around 35% of neutrophils of the peripheral blood. A similar picture was seen in the bone marrow, but with additional erythrophagocytosis by macrophages. These two processes were considered as the main causes of anaemia, but the first one seemed to be predominant. Malignancies, autoimmunisation disorders and infections were excluded. Immunosuppressive therapy with corticosteroids was implemented, but had to be stopped because of side effects. Long-term normalization of peripheral blood morphology was achieved after splenectomy. Splenectomy may be considered a therapeutic option for patients with diagnosed neutrophil erythrophagocytic hyperactivity. Therapy with corticosteroids is also possible, but the long-term effects remain unknown.

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.

Predictive value of depression and social support with respect to alcohol abstinence.

CONTEXT: Two co-morbid conditions which have been found in high proportions among treatment-seeking alcohol-dependent subjects are depression and low social support. AIM: We attempted to study both the factors simultaneously in the setting of Alcoholics Anonymous centers in Mumbai. The study intends to understand (1) if pre-existing depression affected the probability of a person abstaining from alcohol and (2) if social support affected the probability of a person abstaining from alcohol. A thorough review of the existing literature was done before initiating the study. MATERIALS AND METHODS: A single-observer, cross-sectional study was conducted. Subjects with a history of alcohol dependence were included. However, those with other substances abuse and those with a history of anti-depressant usage were excluded. Questionnaires were administered. The Hamilton Depression Scale assessed depression. Similarly, social support was assessed by Social Provisions Scale by Weiss. RESULTS: According to this study depression does not affect alcohol abstinence as the χ(2) test shows an insignificant result. Social support also showed a negative correlation with alcohol abstinence. CONCLUSION: This result is consistent with the findings of other studies such as Davidson et al. (1998). However it is not consistent with the results of the studies having a longer follow-up period. The study had some limitations primarily due to time constraints, the main one being that this study would reveal more significant results if done as a longitudinal study as opposed to a cross-sectional study. Also while interacting with subjects in a group like Alcoholics Anonymous it is important to gain the confidence of the group before obtaining confidence of the individual.

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.

Changing trends in US injury profiles: revisiting non-fatal occupational injury statistics.

The purpose of this paper is to review the current trends in non-fatal injury profiles of workers in the United States. It is generally accepted that occupational injury and illness rates are affected by many factors, such as the amount and quality of training, employee turnover rates, work experience, extent of mechanization and automation, job-related parameters, and worker gender. In the last decade, not only have the technologies used in the workplace changed significantly, there has been a greater awareness among employers and employees as to the importance of containing work injuries. Additionally, the extent of outsourcing for labor-intensive jobs has increased dramatically owing to cheaper labor costs in places such as China and Mexico. These changes have affected the manufacturing sector of US industry more than any other sector. How these changes have influenced the injury and illness profiles of the American worker is of considerable interest given the increased attention paid to work-workplace design, injury hazard control, and ergonomics in general. In this paper, we compare the injury and illness profiles of US workers separated by nearly a decade. The trends from early 1990s are compared to those from early 2000s. Data from the Bureau of Labor Statistics were used to compile the injury statistics. The results of our comparison show that while the absolute numbers of work-related injuries and illnesses have declined over the last 10 years, the basic trends associated with different factors remain almost unchanged. The reasons for this decline are discussed in this paper.

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.

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.

Design guidelines for accommodating amputees in the workplace.

Rehabilitation experts have been addressing the problem of accommodating disabled workers in the workplace for many years. When these disabled workers return to work, accomplishing the tasks they performed prior to their disability can present a serious challenge. Meeting this challenge successfully requires that employers provide accommodations at the workplace so that the disabled workers can continue to contribute efficiently to the operation of the enterprise. Disabilities that are caused by amputations are quite critical. The severity of the injury in terms of loss of a limb and the costs associated with accommodations make this type of disability extremely significant. This paper deals with accommodating "permanent partial" and "permanent total disabilities" due to amputations. The paper is divided into two main parts. The first part focuses on the causes of amputations, types, and difficulties that an amputee faces in the work environment. In this part, an understanding of the amputee physiology has been developed. The second part of the paper addresses the various measures that employers may take in accommodating the amputees at the workplace. Design guidelines are provided to make the workplace suitable for the amputees.

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.

Performance reduction in finger amputees when reaching and operating common control devices: a pilot experimental investigation using a simulated finger disability.

This paper reports results of an experimental laboratory investigation to determine if finger amputations (most pervasive upper extremity injury in the United States) result in significant work performance deterioration in tasks requiring operation of common control devices found in industrial settings. Ten male student volunteers from the University of Cincinnati participated in this study. The finger disability simulated was of an extreme nature, and was defined as the loss of four fingers in the preferred hand and the thumb in the nonpreferred hand. While being seated, participants activated 5 types of industrial control devices (a rotary dial, a push button, a toggle switch, a castor wheel, and a rocker switch). The controls were assembled on a device attached to a cylindrical pole, such that the control assembly could move up and down the cylindrical pole. The vertical height of control location (15, 20, and 30 in. from the seat reference point) and angle of control location in vertical plane (0 degree, 45 degrees, 90 degrees, and 135 degrees) were varied in the experiment. Participants also had their torso restrained or unrestrained while reaching and activating controls, in addition to the presence or absence of the simulated disability in each participant. Functional reaches and arm reaches from the wall were measured for participants in the sample to determine the distances at which to place the control pole assembly. If a participant was able to reach the control, the time taken to activate and operate the control was recorded. Overall results indicate that participants took significantly longer (p < 0.05) to activate controls in the presence of the simulated disability. Physical restraint did not significantly alter performance provided the participant was able to reach the control. The type of control and the height of location of the control also significantly affected work performance.

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.

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.

Human acid ceramidase gene: novel mutations in Farber disease.

Farber disease is an autosomal recessive disorder caused by lysosomal acid ceramidase (AC) deficiency. It commonly manifests during the first few months after birth with a unique triad of painful and progressive deformed joints, subcutaneous nodules, and progressive hoarseness. In order to understand the molecular mechanism(s) of pathogenesis of Farber disease, we isolated and characterized a full-length human AC gene, mapped its chromosomal location, determined the tissue-specific expression, and analyzed mutations in Farber disease patients. We also studied the AC-mRNA expression in gastrointestinal tumors and adjoining normal tissues. In addition, we determined the pattern of tissue-specific AC-mRNA expression in the adult mouse and during fetal development. Our results show that human AC gene consists of 14 exons and 13 introns spanning approximately 26.5 kb of genomic DNA. It is mapped to human chromosome 8p22-21.2, a region often disrupted in several cancers. The AC-mRNA is expressed in the mouse fetus from the seventh day of gestation. Interestingly, while the AC-mRNA is expressed in all segments of the normal gastrointestinal tract, none of the gastrointestinal tumor tissues had any AC-mRNA expression. We also uncovered four novel mutations in Farber disease patients that were not previously reported. Taken together, our results not only attest to the physiological importance of AC but also uncover several new mutations in Farber disease that may advance our knowledge towards establishing a genotype-phenotype correlation in this disease.

Analysis of multiple activity manual materials handling tasks using A Guide to Manual Materials Handling.

Manual handling of materials continues to be a hazardous activity, leading to a very significant number of severe overexertion injuries. Designing jobs that are within the physical capabilities of workers is one approach ergonomists have adopted to redress this problem. As a result, several job design procedures have been developed over the years. However, these procedures are limited to designing or evaluating only pure lifting jobs or only the lifting aspect of a materials handling job. This paper describes a general procedure that may be used to design or analyse materials handling jobs that involve several different kinds of activities (e.g. lifting, lowering, carrying, pushing, etc). The job design/analysis procedure utilizes an elemental approach (breaking the job into elements) and relies on databases provided in A Guide to Manual Materials Handling to compute associated risk factors. The use of the procedure is demonstrated with the help of two case studies.

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.

Reach profiles of men and women 65 to 89 years of age.

Reach and anthropometric data were collected on a heterogeneous group of subjects 65 to 89 years of age. The purpose of this pilot study was to determine whether the process of aging has an effect on the ability to reach. Analysis of the data collected showed that age-related changes had an effect on reaching in the vertical plane, especially for the male subjects. The vertical reach fingertip and grip (VRT and VRG) measurements for men 85 to 89 years old were significantly lower than those for all other age groups, indicating that reaching abilities decrease between the ages of 80 and 85 years. The results for women were not as conclusive, but additional analysis showed a decline in VRT and VRG in terms of stature. Horizontal reach measurements showed no age-related effect in the analysis. An attempt was made to compare reach data collected here with those collected in previous studies. However, comparisons of the reach data were limited as a result of differences in reaching activities and measuring techniques in other studies. Anthropometric measurements of this older cohort were compared with those of a younger population. It was noted that older subjects had smaller anthropometric measurements than their younger cohorts. Differences in body size and reach, whether statistically significant or not, need to be considered when designing living environments and appliances for the aged.

Effectiveness of noise barriers on an interstate highway: a subjective and objective evaluation.

The objective of this study was to determine the actual and perceived effectiveness of noise barriers along interstate highways. Using a 5-mile section of Interstate 71 in the greater Cincinnati area as the study area, traffic noise readings and opinions of residents living along the sections of the highway were recorded. Noise readings were taken before and after the noise barriers were erected. A questionnaire was designed to elicit noise-related annoyance of the residents in the areas adjoining the highway. The results indicated that, in general, noise barriers were effective as indicated by a reduction in noise levels by as much as 11 dBA. The barriers, however, failed to bring noise levels for locations closer to the highway within the levels desired by the government (67 dBA). Most residents living right next to the highway were very satisfied with the installation of noise barriers. In general, these individuals felt that the quality of life improved with the noise barrier installation. The same, however, was not true of residents living a few blocks away from the highway--they felt the noise barriers were a waste of money. There was no significant difference in traffic noise pattern during the weekdays or weekends. Noise readings taken in two different locations were observed to be similar.