Hemochromatosis gene in leukemia and lymphoma

The gene causing hereditary hemochromatosis (HH), HFE is an HLA class I-like gene with no known immunological function but indirectly related to the immune functions because of its role in iron transport. It is located 6.5 Mb telomeric to HLA-A. The most common mutation of HFE, C282Y, has a Celtic origin and most patients with HH are homozygous for it in Northern European populations. While there is an enormously increased risk for hepatocellular cancer in hemochromatosis that is attributed to the toxic effects of iron, the risk for extra-hepatic cancers is also increased slightly. Recent studies have found genetic associations between several cancers and C282Y but only in the presence of a particular allele of the transferrin receptor gene. This suggests that the increased cancer risk is more likely due to the effects of iron. In childhood acute lymphoblastic leukemia (ALL), however, there is a strong association of C282Y with a gender effect in two different Celtic populations. This association does not require homozygosity for C282Y or an interaction with the transferrin receptor gene, and is male-specific. The other HFE mutation H63D does not confer increased risk to childhood ALL. Acute myeloblastic leukemia and Hodgkin's disease in adults do not have an association with HFE. Its male-specificity, occurrence in childhood and the lack of a gene-dosage effect suggest that the C282Y association in childhood ALL may reflect the involvement of another HLA-linked gene in leukemia susceptibility.     

Aquatic antagonists: Catalaphyllia jardinei sting

Catalaphyllia jardinei is a blue-green soft coral whose red-violet tipped tentacles have made it a very colorful, popular animal prized by amateur aquarists (Figure 1). Its normal habitat is the Indo-Pacific area from Seychelles through Vanuatu and from Northern Australia to Southern Japan. It is regarded as mildly venomous. However, to our knowledge, no reports exist on its sting's effects on man.     

Globalization, migration and health

The term 'globalization' describes the integration of economic systems through improved communication, but it also represents increased insecurity for those with few resources--particularly refugees. This article examines why people migrate, their numbers, constraints on their movement and their particular health care needs. Immigrants have much to contribute to their recipient countries, but at some loss to their homelands. Both economically and morally, more liberal immigration policies would be beneficial. Policies towards asylum seekers should not be more restrictive in the aftermath of 11 September 2001 and detention should be the exception rather than the rule. Globalization should be managed so as to improve people's lives throughout the world.     

Hemodialysis vascular access dysfunction from basic biology to clinical intervention

Hemodialysis vascular access dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population at a cost of over 1 billion dollars per annum. Venous stenosis and thrombosis as a result of venous neointimal hyperplasia are the major causes of hemodialysis vascular access dysfunction. Despite the magnitude of the clinical problem, there are currently no effective therapies for this condition. We believe that this could be because of an inadequate understanding of the pathogenesis of this condition. At a histological level, venous neointimal hyperplasia (both in human specimens and in a pig model) is characterized by the presence of smooth muscle cells/myofibroblasts, microvessel formation (angiogenesis), and the accumulation of extracellular matrix components, all of which could be potential targets for therapeutic intervention. In particular, polytetrafluoroethylene dialysis access grafts could be the ideal clinical model for testing out novel local therapies to block neointimal hyperplasia. The current review describes the lesion of venous neointimal hyperplasia in human samples and in a pig model and suggests possible future directions for the development of effective local therapies for this condition.     

Availability of Diagnostic and Treatment Services for Acute Stroke in Frontier Counties in Montana and Northern Wyoming

CONTEXT: Rapid diagnosis and treatment of ischemic stroke can lead to improved patient outcomes. Hospitals in rural and frontier counties, however, face unique challenges in providing diagnostic and treatment services for acute stroke. PURPOSE: The aim of this study was to assess the availability of key diagnostic technology and programs for acute stroke evaluation and treatment in Montana and northern Wyoming. METHODS: In 2004, hospital medical directors or their designees were mailed a survey about the availability of diagnostic technology, programs, and personnel for acute stroke care. FINDINGS: Fifty-eight of 67 (87%) hospitals responded to the survey. Seventy-nine percent (46/58) of responding hospitals were located in frontier counties, with an average bed size of 18 (11 SD). Of the hospitals in frontier counties, 44% reported emergency medical services prehospital stroke identification programs, 39% had 24-hour computed tomography capability, 44% had an emergency department stroke protocol, and 61% had a recombinant tissue plasminogen activator protocol. Thirty percent of hospitals in frontier counties reported that they met 6-10 of the criteria established by the Brain Attack Coalition to improve acute stroke care compared to 67% of hospitals in the nonfrontier counties. CONCLUSION: A stroke network model could enhance care and improve outcomes for stroke victims in frontier counties.     

Measuring psychological adjustment to HIV infection

AIMS: A modified version of the Mental Adjustment to Cancer Scale (The Mental Adjustment to HIV Scale--MAHIVS) was used to evaluate patterns of psychological adjustment in response to HIV infection. METHODS: A sample of 164 HIV positive homosexual/bisexual men were recruited across three Australian centers (79 asymptomatic (CDC II/III) and 85 symptomatic HIV infection (CDC IV)). Factor analysis of the MAHIVS was conducted and the predictive validity of the MAHIVS was investigated using the General Health Questionnaire, while The Diagnostic Interview Schedule was used to assess current and lifetime psychiatric disorder. Other measures of adjustment/coping were used to investigate the construct validity of the MAHIVS (neuroticism, locus of control, defense style). RESULTS: Factor analysis of the MAHIVS detected four factors: Hopelessness, Fighting Spirit/Self Efficacy, Personal Control, and Minimization. Hopelessness and Fighting Spirit factors exhibited acceptable levels of internal consistency and validity, with significant correlations detected with psychological symptoms and significant association with other measures of psychological adjustment and personality. Fighting Spirit emerged as a potential indicator of psychological resilience, whereas Hopelessness was significantly associated with psychological symptoms and current major depression (but not past depression). CONCLUSIONS: The findings indicate the validity of the MAHIVS and support the presence of common themes in the psychological adaptation to life-threatening illness that can be detected across disease categories and groups.     

Vasopeptidase Inhibition Prevents Endothelial Dysfunction of Resistance Arteries in Salt-Sensitive Hypertension in Comparison With Single ACE Inhibition

-To determine whether natriuretic peptides in addition to the renin-angiotensin system are involved in functional and structural vascular changes in salt-sensitive hypertension, we compared equipotent hypotensive treatment with the dual neutral endopeptidase/ACE inhibitor omapatrilat (35 mg. kg(-1). d(-1)) or the ACE inhibitor captopril (100 mg. kg(-1). d(-1)). The reactivity and geometry of mesenteric resistance arteries from Dahl salt-sensitive rats were studied in vitro under perfused and pressurized conditions. Chronic salt administration increased systolic blood pressure by 57+/-4 mm Hg, whereas concentrations of atrial natriuretic peptide were reduced in heart and in plasma (P:<0.05). In addition, the medial cross-sectional area of small mesenteric arteries was increased and endothelium-dependent relaxation in response to acetylcholine and contraction in response to endothelin-1 were impaired in the mesenteric arteries of salt-sensitive rats on a high-salt diet (P:<0.05). Concomitant treatment with either omapatrilat or captopril reduced the increase in systolic blood pressure and hypertrophic remodeling to a similar degree (P:<0.05) but affected plasma and cardiac atrial natriuretic peptide levels differently (P:<0.05). In addition, omapatrilat normalized endothelium-dependent relaxations to a greater extent than captopril (P:<0.05). Furthermore, vasopeptidase inhibition increased cGMP levels compared with captopril (P:<0.05). Contractions to endothelin-1 were normalized by either antihypertensive drug. These results suggest that in the Dahl rat, with similar reductions in systolic blood pressure, omapatrilat is superior to captopril in preventing impaired endothelial function in small resistance arteries. Thus, vasopeptidase inhibition may have therapeutic advantages of the prevention of changes in vascular function and structure in salt-sensitive forms of hypertension.