Factor concentrates for haemophilia in the developing world

A total of 191 patients were evaluated at our department for azoospermia, and 11 were found to have azoospermia due to ejaculatory duct obstruction as proved by normal serum hormones, normal testicular biopsy, low ejaculate volume and absence of fructose in semen. Also transrectal ultrasound was performed, revealing distended seminal vesicles and dilated ejaculatory ducts. All these criteria together suggested ejaculatory duct obstruction as a cause of azoospermia. All patients underwent endoscopic management for treatment of their ejaculatory duct obstruction in the form of resection and/or incision of the ejaculatory duct ostium inside the urethra and patency was checked intraoperatively by injection of sterile methylene blue in the vas and visualizing the efflux of the blue dye endoscopically. Intraoperative patency was documented in 10 patients and postoperative patency by follow-up semen analysis in 7 patients (70% patency rate) of which 2 (20% pregnancy rate) were able to conceive within 2 years of endoscopic treatment. Postoperative complications included acute urinary retention in 1 patient, haematuria in 5 and recurrent epididymitis in 2 patients.     

Intestinal geohelminthiasis in the developing world

AIM: The applicability of ultrasound for diagnosing mediastinal diseases is limited by the surrounding thorax containing air and bone, permitting only restricted echo windows. Transoesophageal endoscopic ultrasound circumvents this problem and provides good visualisation of nearly all parts of the mediastinum. We evaluated the value of endoscopic ultrasonography for mediastinal staging of Hodgkin's and non-Hodgkin lymphoma patients. PATIENTS AND METHODS: From August 1994 to July 1995 36 Hodgkin's and non-Hodgkin lymphoma patients underwent clinical staging and were endosonographically examined for mediastinal involvement. CT in the spiral technique was used as the reference. RESULTS: In assessing mediastinal involvement, endoscopic ultrasound revealed a sensitivity of 96% and a specificity of 75%. There were limitations in the right paratracheal region and the area lateral to the aortic arch. CONCLUSION: Endoscopic ultrasound is a highly valuable imaging procedure for diagnosing mediastinal spread of malignant lymphomas and has interesting potentials in assessing the clinical course during therapy.     

Management of haemophilia in Sweden

The incidence of living haemophiliacs in Sweden (total population 8.1 millions) is about 1:15,000 males and about 1:30,000 of the entire population. The number of haemophiliacs born in Sweden in 5-year periods between 1931-1975 (June) has remained almost unchanged. The total number of haemophilia families in Sweden is 284 (77% haemophilia A, 23% haemophila B) with altogether 557 (436 with A and 121 with B) living haemophiliacs. Of the haemophilia A patients 40% have severe, 18% moderate, and 42% mild, haemophilia. The distribution of the haemophilia B patients is about the same. Inhibitors have been demonstrated in 8% of the patients with severe haemophilia A and in 10% of those with severe haemophilia B. There are 2 main Haemophilia Centres (Stockholm, Malm?) to which haemophiliacs from the whole of Sweden are admitted for diagnosis, follow-up and treatment for severe bleedings, joint defects and surgery. Minor bleedings are treated at local hospitals in cooperation with the Haemophilia Centres. The concentrates available for treatment in haemophilia A are human fraction I-0 (AHF-Kabi), cryoprecipitate, Antihaemophilic Factor (Hyland 4) and Kryobulin (Immuno, Wien). AHF-Kabi is the most commonly used preparation. The concentrates available for treatment in haemophilia B are Preconativ (Kabi) and Prothromplex (Immuno). Suffcient amounts of concentrates are available. In Sweden 3.2 million units of factor VIII and 1.0 millino units of factor IX are given per year. Treatment is free of charge. Only 5 patients receive domiciliary treatment, but since 1958 we in Sweden have practised prophylactic treatment of boys (4-18 years old) with severe haemophilia A. At about 5-10 days interval they receive AHF in amounts sufficient to raise the AHF level to 40-50%. This regimen has reduced severe haemophilia to moderate. The joint score is identical with that found in moderate haemophilia in the same age groups. For treatment of patients with haemophilia A and haemophilia B complicated by inhibitors we have used a large dose of antigen (factor VIII or factor IX) combined with cyclophosphamide. In most cases this treatment produced satisfactory haemostasis for 5 to 30 days and prevented the secondary antibody rise.     

Management of haemophilia in Greece

A short review is given on several aspects of the management of haemophilia in Greece. A total number of 429 patients with congenital haemorrhagic disorders has been registered. The incidence of F. VIII deficiency is 85.9% and that of F. IX 12.9%. Information concerning distribution throughout the country, age, social standard, financial position and education is given too. Haemophiliacs are systematically treated by Athens specialized Haemophilia Treatment Centres. The most widely therapeutic material still used, is fresh frozen plasma. Lyophilized cryoprecipitate and F. IX (prothrombincomplex) concentrate are also prepared but they are not for every day use. Imported concentrates are used only for very serious cases. Home therapy is attempted in limited scale and it is largely discussed. Consultation, out-patients treatment and hospitalization, if needed, are free of charge for haemophiliacs regardless of their financial position or their national insurance.     

Australia's role in HIV prevention in the developing world

A scientist with the National Centre in HIV Epidemiology and Clinical Research at the University of New South Wales in Sydney, Australia, addresses the fact that Australians working in the area of HIV infection have been very successful in prevention, treatment, and care. In the early 1980s, a bipartisan political decision was made to foster an effective partnership between HIV-infected communities, health care providers, and governments. HIV-infected communities included sex workers, prisoners, Aboriginal people, and high profile gay community activists. These three different groups succeeded in forming such a partnership, as reflected in the fact that the annual number of new HIV cases is down to 500 from a peak of 3000 in 1984. A key method used to contain HIV infection was needle-and-syringe exchange programs and continuing access to needles to prevent HIV transmission in the injecting drug community. Even though Australia has all this experience and success, it had a backseat role in ushering in the UNAIDS program because Australia did not contribute a significant share of the agency's relatively small budget (US$100 million/year). If Australia were to give just 10%, it would acquire a front row seat along with the Netherlands, Sweden, Belgium, France, and the UK. These nations have the greatest say as to where UNAIDS funds go. The Australian international aid organization has recently received an increase in funds, $110 million for 4 years to spend on four areas, one of which is HIV/AIDS. Australia has just allocated $25 million for a 5-year program for HIV/STD (sexually transmitted disease) prevention in Indonesia. This money would have been able to buy Australia a leading role in UNAIDS. Australians need to reassess their priorities. Australians can help their neighbors in the Asia-Pacific region move away from their denial of HIV to HIV prevention and care. They can conduct clinical trials of shorter and more user-friendly regimens of antiviral drugs that may lead to reduced perinatal transmission and research on microbicides. They can prevent tuberculosis and introduce manageable methods of securing safe blood supplies and mass screening.     

Health research in the developing world: a gastroenterological view from Bangladesh

OBJECTIVES: To identify knowledge levels of academic surgeons about Food and Drug Administration (FDA) and Institutional Review Board (IRB) regulations for clinical research and to determine whether being a member in an IRB, conducting or participating in clinical trials, or being a member in surgical societies affected knowledge levels. DESIGN: Survey of surgical department faculty members in 20 universities. RESULTS: Sixty-five responses were received from 14 sites. Overall mean (+/- SEM) correct score was 6.7 +/- 0.2 of a possible 20 points. The best predictor of overall score was being a primary investigator of a clinical trial (P < .001), followed by being or having been a member of an IRB (P < or = .02). The total mean score of members of the Surgical Infection Society (8.2 +/- 0.5) was significantly higher (P < .001) than that of nonmembers (6.1 +/- 0.2), a phenomenon not observed with other surgical societies. In certain hypothetical clinical scenarios, all respondents were mistakenly willing to conduct clinical trials without obtaining appropriate approval from the FDA. Four (22%) of 18 IRB member respondents and 16 (25%) of the 65 respondents were willing to conduct human research without appropriate approval from patients, the IRB, or both. CONCLUSIONS: Knowledge deficits exist in the academic surgical community about the role and requirements of the FDA and local IRBs for conducting clinical research. Further study is required to determine the reasons for this deficit and to identify appropriate interventions.     

Rheumatic heart disease in the developing world: prevalence, prevention, and control

Rheumatic heart disease (RHD) continues to be a common health problem in the developing world, causing morbidity and mortality among both children and adults. Although little longitudinal data are available, evidence suggests that there has been little if any decline in the occurrence of RHD over the past few decades. Recent reports from the developing world have documented rheumatic fever (RF) incidence rates as high as 206/100,000 and RHD prevalence rates as high as 18.6/1000. The high frequency of RHD in the developing world necessitates aggressive prevention and control measures. The major interventions for prevention and control include: (1) reduction of exposure to group A streptococci, (2) primary prophylaxis to prevent initial episodes of RF, and (3) secondary prophylaxis to prevent recurrent episodes of RF. Because recurrent episodes of RF cause increasingly severe cardiac complications, secondary prophylaxis is the most crucial feature of an effective RHD programme. For some impoverished countries, secondary prophylaxis may be the only intervention that can realistically be implemented. In addition to this intervention, however, financial and human resources must be committed, and all of these elements must be integrated into existing primary health care systems. Because RHD continues to be a common health problem in the developing world, greater emphasis needs to be placed on the simple and cost-effective prevention and control measures that are currently available to combat this disabling disease.     

Control of the synovium in haemophilia

The method of administration of alteplase has evolved since its introduction to clinical practice in the late 1980s. The initial dosage regimen of a graded administration of 100 mg was replaced by the front-loaded weight adjusted regimen, the efficacy of which was demonstrated in the GUSTO 1 trial. Double bolus administration was shown to achieve superior TIMI 3 patency of the infarct related artery in a small angiographic study, but the COBALT trial failed to show equivalence and indeed showed a slightly higher mortality and incidence of stroke, so cannot be recommended. Reteplase, a deletion mutant of alteplase, also showed superior efficacy in achieving coronary patency but no clinical superiority in outcomes in the 15,000 patient GUSTO 3 trial. The case of administration of reteplase, however, has some attraction as an alternative to alteplase. Trials of newer agents based on further modifications of alteplase are ongoing, but at present the front-loaded alteplase regimen remains the standard for clinical practice.     

Our new fragile world doesn't consist of developed and developing countries only

Health conditions have improved worldwide; therefore, the division into developed and developing countries no longer holds true. International organizations tend to divide countries into three groups. An increasing number of people are born in middle income countries where health conditions continue to improve. However, in a number of the least developed countries, mortality is on the rise in a spiral of economic stagnation, environmental problems, social misery, and ethnic/civil conflicts. This requires the medical assistance of international agencies from abroad. Since the 1960s there has been a drastic decline of child mortality in developing countries, especially in Asia. 1 billion people live in countries with child mortality under 20/1000, almost 3 billion live in countries with child mortality ranging 20-100/1000, and over 1 billion live in the least developed countries with child mortality over 100/1000. Unicef divides countries into developed, developing, and least developed countries, while the World Bank groups them as high-, medium-, and low-income countries. Thailand's child mortality is the same as that of Russia, while Cuba has a lower rate than Washington, D.C. On the other hand, Singapore is a developed high-income country with one of the world's healthiest populations. Stagnation and conflicts in the former socialist countries mean that many Asian and Latin American countries have better health status than some parts of Europe. Despite Africa's high mortality, its population growth is the highest in the world: in 20 years its population has doubled. Economic stagnation and the debt burden in many of these countries has resulted in ethnic conflicts and the collapse of social institutions: Somalia, southern Sudan, Rwanda, Liberia, Angola, perhaps Zaire, and Mozambique. The organization Physicians Beyond Borders is an example of extending humanitarian help and combatting social collapse in the least developed countries.     

Assessing and developing versatility: Executive survival skill for the brave new world.

Explores reasons for the crisis in leadership among top executives and argues that the solution lies in a better understanding of the full spectrum of competencies required for success in a constantly changing and increasingly competitive global marketplace, as well as more powerful, integrated, and accessible tools for helping line managers select and develop leadership talent for the future. The focus is particularly on assessing and developing the increasingly essential survival skill of executive versatility, the ability to adapt to and perform effectively across a wide range of new challenges and changing contexts. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Proprioceptive training in haemophilia

Joint and muscle injury associated with direct damage to the tissues and muscle atrophy may ensue following immobility. Rehabilitation of the injury is linked with the return to normal functional values such as range of motion, muscle strength, and muscle tone. It is, however, likely that subtle changes or differences still exist in the site of injury or haemarthrosis. In particular proprioception may be distorted due to the direct injury of sensory receptors and to feedback systems. The implications of such damage are important, where proprioception plays an important part in the control, timing and organisation of coordinated bodily actions.     

Mutations in haemophilia A

In the present study DNA from 281 unrelated haemophilia A patients including 15 inhibitor patients has been analysed by Southern blotting technique. Using various restriction enzymes, cloned factor VIII cDNA probes and genomic fragments we have identified 14 mutations. Six of the mutations are novel partial factor VIII gene deletions. One deletion affects exon 1, two deletions concern exon 6, another deletion, of which breakpoints are sequenced, takes part of exon 16 and two deletions affect exon 26. Besides the deletions, eight point mutations have been found at the TaqI restriction sites of exons 18, 24 and 26. Five C-->T mutations resulted in nonsense mutations, one in exon 18, one in exon 26 and three in exon 24. Two G-->A mutations caused a missense mutation in exon 24 leading to an arginine/glutamine exchange. Although two patients showed this mutation, their clinical phenotypes were different, possibly due to an additional unidentified sequence polymorphism. A G-->T mutation in exon 26 substituted the arginine with leucine. All deletions and seven of the point mutations are associated with severe disease with a detectable inhibitor in the patient with the TaqI-point mutation in exon 18. One of the G-->A mutations is associated with mild haemophilia but the patient also has developed an inhibitor. Amongst these mutations the origin of the mutation could be determined in four kindred, one of which showed maternal mosaicism.     

Progression of HIV in haemophilia

A series of permeability thresholds to Ca2+ metabolites and macromolecules, occurring at different times when cells are attacked by complement, has been established by imaging HeLa cells transiently expressing a recombinant cytosolic fusion protein of firefly luciferase and aequorin (luciferase-aequorin) to measure changes in ATP and cytosolic free Ca2+. Nuclear fluorescence of propidium was used as a measure of permeability to small molecules, and luciferase activity imaged to assess lysis. The rise in cytosolic free Ca2+ observed after C9 attack preceded by at least 60 s both the increase in propidium fluorescence, measured in single cells, and the decrease in ATP monitored by luciferase light emission. These effects were dependent on the concentration of C9. At concentrations of C9 up to 4 micrograms/ml no loss of luciferase-aequorin protein was detected at the end of the experiment. Thus the membrane integrity of the cells remained intact, even though the cells were permeable to propidium. These results confirmed our earlier observations that propidium permeability in cells attacked by complement was not a reliable measure of cell death. They also show that it is vital to take account of cellular heterogeneity if the mechanisms by which cells respond to membrane pore former attack are to be correctly interpreted.     

Obstructed labor injury complex: obstetric fistula formation and the multifaceted morbidity of maternal birth trauma in the developing world

Prolonged obstructed labor may produce injuries to multiple organ systems. The best known, and most common, of these injuries is obstetric fistula formation. When obstructed labor is unrelieved, the presenting fetal part is impacted against the soft tissues of the pelvis and a widespread ischemic vascular injury develops that results in tissue necrosis and subsequent fistula formation. Unlike the postsurgical vesicovaginal fistula, however, which is usually the result of focal trauma to otherwise healthy tissues, the obstetric fistula is the result of a "field injury" to a broad area. The field injury that is produced by prolonged obstructed labor may result in multiple birth-related injuries in addition to (or instead of) a vesicovaginal fistula. Focusing simply on the "hole" between the bladder and the vagina ignores the multifaceted nature of the injury that many of these patients have sustained. These injuries may include total urethral loss, stress incontinence, hydroureteronephrosis, renal failure, rectovaginal fistula formation, rectal atresia, anal sphincter incompetence, cervical destruction, amenorrhea, pelvic inflammatory disease, secondary infertility, vaginal stenosis, osteitis pubis, and foot-drop. In addition to their physical injuries, women who have experienced prolonged obstructed labor often develop serious social problems, including divorce, exclusion from religious activities, separation from their families, worsening poverty, malnutrition, and almost unendurable suffering. Isolated almost exclusively to the developing world, particularly Africa, this problem has not received the international attention that it deserves, from either a medical or a social standpoint.     

Management of trauma to primary and developing teeth

Traumatic dental injuries to the young child can present both diagnostic and therapeutic challenges. Luxation injuries to the primary dentition are the most common injuries. Yet, they are the most controversial with regard to definitive treatment, prognosis, and sequelae. Damage to the developing teeth subsequent to primary tooth injury is often unavoidable and has permanent effects on the dentition. Diagnostic criteria, treatment options, and outcomes are presented in this article; however, treatment decisions are often based on patient behavior.