Is ABO blood group truly a risk factor for thrombosis and adverse outcomes?

ABO blood type is one of the most readily available laboratory test, and serves as a vital determinant in blood transfusion and organ transplantation. The ABO antigens are expressed not only on red blood cell membranes, determining the compatibility of transfusion, but also on the surface of other human cells, including epithelium, platelet and vascular endothelium, therefore extending the research into other involvements of cardiovascular disease and postoperative outcomes. ABO blood group has been recognized as a risk factor of venous thrombosis embolism since the 1960's, effects now understood to be related to ABO dependent variations are procoagulant factor Ⅷ(FⅧ) and von Willebrand factor(vWF) levels. Levels of vWF, mostly genetically determined, are strongly associated with venous thromboembolism(VTE). It mediates platelet adhesion aggregation and stabilizes FⅧ in plasma. Moreover, many studies have tried to identify the relationship between ABO blood types and ischemic heart disease. Unlike the clear and convincing associations between VTE and ABO blood type, the link between ABO blood type and ischemic heart disease is less consistent and may be confusing. Other than genetic factors, ischemic heart disease is strongly related to diet, race, lipid metabolism and economic status. In this review, we'll summarize the data relating race and genetics, including ABO blood type, to VTE, ischemic heart disease and postoperative bleeding after cardiac surgery.     

Does blood group affect survival following pancreatoduodenectomy for periampullary malignancy?

Background

Blood group is reported to have an effect upon survival following pancreatoduodenectomy for pancreatic ductal adenocarcinoma. The effect of blood group is not known, however, among patients with other periampullary cancers. This study sought to review this.

The ratio of α-galactosidase to β-glucuronidase activities in dried blood for the identification of female Fabry disease patients

Summary Female heterozygous patients with Fabry disease are difficult to identify because of the relatively high residual activity of α-galactosidase. We systematically evaluated the activities of various lysosomal enzymes in dried blood samples from Fabry patients and found that the β-glucuronidase activity was frequently elevated. The ratio of α-galactosidase to β-glucuronidase proved to be a helpful tool for the diagnosis of female Fabry disease patients.     

LIMP-2 expression is critical for β-glucocerebrosidase activity and α-synuclein clearance

Mutations within the lysosomal enzyme β-glucocerebrosidase (GC) result in Gaucher disease and represent a major risk factor for developing Parkinson disease (PD). Loss of GC activity leads to accumulation of its substrate glucosylceramide and α-synuclein. Since lysosomal activity of GC is tightly linked to expression of its trafficking receptor, the lysosomal integral membrane protein type-2 (LIMP-2), we studied α-synuclein metabolism in LIMP-2–deficient mice. These mice showed an α-synuclein dosage-dependent phenotype, including severe neurological impairments and premature death. In LIMP-2–deficient brains a significant reduction in GC activity led to lipid storage, disturbed autophagic/lysosomal function, and α-synuclein accumulation mediating neurotoxicity of dopaminergic (DA) neurons, apoptotic cell death, and inflammation. Heterologous expression of LIMP-2 accelerated clearance of overexpressed α-synuclein, possibly through increasing lysosomal GC activity. In surviving DA neurons of human PD midbrain, LIMP-2 levels were increased, probably to compensate for lysosomal GC deficiency. Therefore, we suggest that manipulating LIMP-2 expression to increase lysosomal GC activity is a promising strategy for the treatment of synucleinopathies.The lysosomal integral membrane protein type-2 (LIMP-2) is the receptor for lysosomal transport of the acid hydrolase β-glucocerebrosidase (GC) (1) catalyzing the intralysosomal degradation of the sphingolipid glucosylceramide (GluCer). Mutations within the gene encoding LIMP-2 (SCARB2, scavenger receptor B2) cause action myoclonus renal failure syndrome (AMRF) (2, 3), a progressive myoclonic epilepsy (PME) associated with renal failure, ataxia, the presence of undefined storage material in the brain, and premature death. LIMP-2–deficient (LIMP-2^−/−) mice (4) are a valid disease model for AMRF. To date, several SCARB2 mutations have been identified in AMRF, as well as in some PME cases (5, 6). AMRF/PME mutants mislocalize to the endoplasmic reticulum (ER) and fail to transport GC to lysosomes (7, 8). The crystal structure of the ectodomain of LIMP-2 highlights a helical bundle in LIMP-2 as the GC binding site (9).Mutations in GBA1, the gene encoding GC, lead to Gaucher disease (GD), a lysosomal storage disorder that has been linked to Parkinson disease (PD) (10). LIMP-2 has been identified as a modifier for the neurological presentation of GD (11). The neuropathological hallmark of PD and other synucleinopathies is Lewy bodies (LBs) that contain aggregated α-synuclein (α-syn). LBs can also be found in brains of patients with GD (12), who have about a 20-fold increased risk of developing PD. In transgenic and pharmacological [conduritol β-epoxide (CBE)] induced GD mice, a reduction in GC activity leads to accumulation of different soluble and insoluble α-syn species (13–15), whereas adenoviral overexpressed GC lowered α-syn levels in transgenic mouse models of GD and PD (16). Moreover, recent data suggest that accumulated α-syn disrupts ER/Golgi trafficking of GC, resulting in a positive feedback loop that amplifies the pathological effects of α-syn (14). Because trafficking of GC requires LIMP-2 (1) and genetic variations within the LIMP-2 locus have been linked to PD and dementia with LBs (17–19), we were prompted to examine the role of LIMP-2 in α-syn aggregation.     

Methodology matters: what type of research is suitable for evaluating community treatment supporters for HIV and tuberculosis treatment?

The choice of research method relevant to the evaluation of delivery of a health intervention is not always straightforward. We use the evaluation of HIV and tuberculosis community treatment supporters in promoting adherence to treatment in Africa as a case study to illustrate the pros and cons of operational research and randomised controlled trials. The choice of this intervention for the case study reflects the importance of maximising the benefits of unprecedented efforts to scale-up treatments of these two epidemics. International policy supporting the role of community treatment supporters in tuberculosis is largely based on the findings of operational research studies. This reflects the advantages that operational research is less costly than randomised controlled trials, provides more rapid answers to policy questions, enables standard evaluation of the intervention in 'real life' conditions in several diverse settings and has in-built potential to influence policy and practice, because the research is conducted within health programmes. Recent evidence on the role of community treatment supporters in HIV is largely based on randomised trials. This reflects the advantages that randomised trials compared to operational research are more rigorous and generate a more convincing result. Operational research and randomised trials may be viewed as providing complementary findings to inform new policies and practice aimed at improving programme performance and patient outcomes. However, in practice, insufficient funds are likely to be made available for randomised trials to answer all the current research questions on delivery of programme interventions. In deciding on the type of research to evaluate a particular health intervention, dialogue is necessary with policy-makers to weigh up explicitly the trade-offs between research rigour and other factors such as cost, speed of implementation of research and speed of policy uptake and of change in programme practice.     

Lack of evidence for an association between α-adducin and blood pressure regulation in Asian populations

Recent studies have found the tryptophan allele of a glycine to tryptophan polymorphism at position 460 (G460W) of the α-adducin protein to be associated with essential hypertension in European populations. We examined whether the tryptophan allele is associated with hypertension in a different population, comprised of subjects of Chinese origin from Taiwan, and Chinese and Japanese origin from the San Francisco Bay area and Hawaii. We adapted the 5′ allelic discrimination assay or TaqMan to type individuals for the G460W polymorphism, and using this method we typed more than 1000 individuals. The frequency of the W allele was slightly increased in the treated subjects in the Chinese population (0.458 v 0.423) but not the Japanese population (0.549 v 0.558). We considered dominant, recessive, and additive models in our analysis. There was a significant result for a recessive model for systolic blood pressure in the Chinese population (χ² 6.84, df = 2, P < .05), but only suggestive evidence for diastolic blood pressure (χ² 3.30). In contrast, in the Japanese population, there was no evidence for a positive association under any model. For the combined Chinese and Japanese samples, the evidence for association with α-adducin was not significant.     

Helicobacter pylori “test-and-treat” strategy is not suitable for the management of patients with uninvestigated dyspepsia in Shanghai

Objective. The safety of Helicobacter pylori “test-and-treat” and “test-and-endoscopy” strategies for the management of young patients with uninvestigated dyspepsia has not been evaluated in Shanghai. Material and methods. A total of 14,101 consecutive patients with dyspepsia receiving endoscopy in our hospital from October 2002 to December 2003 were retrospectively studied. The detection rates of esophageal or gastroduodenal malignancies and alarm symptoms were investigated, and H. pylori status was assessed. Results. A total of 202 (1.4%) gastrointestinal (GI) malignancies were found, including 162 cases (1.15%) of gastric cancer, 4 of gastric lymphoma, 35 (0.25%) of esophageal cancer and 1 case of duodenal cancer. Among those patients with GI malignancies, 99 (49.0%) were infected with H. pylori and 108 (53.5%) presented with alarm symptoms. Eighteen patients (0.46%, 18/3952) under 45 years of age were diagnosed as having gastric cancer. Of these patients, 5 (27.8%) presented with alarm symptoms and 13 (72.2%) were infected with H. pylori. If the H. pylori “test-and-treat” strategy were used in dyspeptic patients under the age of 45 years without alarm symptoms in the Shanghai region, then 13 cases (72.2%) of gastric cancer would be missed. If the H. pylori “test-and-endoscopy” strategy were applied, then 3 cases (16.7%) of gastric cancer would be missed. Conclusions.H. pylori “test-and-treat” and “test-and-endoscopy” strategies are both not suitable for the management of patients with uninvestigated dyspepsia in Shanghai. For most Shanghai dyspeptic patients, prompt endoscopy should be recommended as the first-line initial management option.     

Association between blood group antigens and rheumatic valve involvement and severity ın endemic areas

BackgroundRheumatic valve disease is an important public health problem in developing countries. We sought to evaluate the possible role of blood antigens as a risk factor for severe rheumatic valve disease.MethodsTwo hundred and fifty-four patients with severe rheumatic mitral and/or aortic valve disease with the surgical indication were enrolled to the study. Control group was composed of age and gender matched 2668 healthy volunteers.ResultsThere were 216 patients with aortic valve involvement and 249 patients with mitral valve involvement. One hundred and seventy-five patients had mitral stenosis, 96 patients had severe mitral regurgitation and 61 patients had severe aortic regurgitation. The distribution of blood groups among patients was as follows: Group A=42.9%, Group B=19.2%, Group AB=8.6%, and Group O=29.1%. The distribution of blood groups in the control group was Group A=40.8%, Group B=16.4%, Group AB=7.6%, and Group O=35.1%. There was no significant difference between blood groups of patients and controls (p=0.141).ConclusionBlood group does not seem to be a risk factor for rheumatic valve involvement or severity of the disease.     

Which patients with sexual dysfunction are suitable for testosterone replacement therapy?

According to all the consensus and statements of the major societies, hypogonadism should be considered a medical problem, termed late onset hypogonadism (LOH) or testosterone deficiency syndrome (TDS), only when symptoms are present. One of the most common symptoms of LOH/TDS is sexual dysfunction (SD). The main purpose of this review is to discuss the role of testosterone (T) in men's sexual function, including epidemiology, pathophysiology, diagnostic procedures, and treatment efficacy in patients affected by erectile dysfunction (ED). The prevalence of hypogonadism in men with ED ranges from 1.7% to 35%. In ED patients, hypogonadism is often associated with reduced sexual desire and nocturnal penile erections, while association with sex-induced erection is less evident. This is because T regulates not only cyclic guanosine monophosphate (cGMP) formation, through nitric oxide synthase (NOS) stimulation, but also its catabolism, through phosphodiesterase-5 (PDE5) activity. The androgen-dependent PDE5 expression could explain the reduced effectiveness of PDE5 inhibitors (PDE5i) in the treatment of erectile dysfunction in hypogonadal patients. Accordingly, T substitution in these subjects restores responsiveness to PDE5i. Recognising hypogonadism in patients with ED is essential in order to appropriately treat the disease. However, suspecting LOH/TDS in SD patients is not an easy task. Recently published structured inventories, such as ANDROTEST, might help physicians to recognize hypogonadism and to further pursue its appropriate diagnosis and treatment.     

New-onset type 2 diabetes mellitus – A high-risk group suitable for the screening of pancreatic cancer?

BackgroundType 2 diabetes mellitus is widely considered to be associated with pancreatic cancer.ObjectiveTo determine the incidence of pancreatic cancer in new-onset type 2 diabetic patients by measuring the serum level of CA 19-9 and performing abdominal ultrasonography (US).Patients and methodsConsecutive type 2 diabetic patients in whom diabetes was diagnosed within 36 months were included in this prospective study. Serum CA 19-9 measurement and US were performed in all patients. If any of two was positive, abdominal computer tomography (CT) was carried out. Endoscopic ultrasound-guided fine needle aspiration or direct surgical referral was performed on patients with CT-identified lesions.ResultsA total of 115 patients were enrolled. CA 19-9 was elevated in 10 patients but pancreatic cancer diagnosed in neither of them. Pancreatic cancer was revealed by morphological means in three patients without elevated CA 19-9 level. The sensitivity, specificity, positive-, negative predictive values and validity were 0%, 90.4%, 0%, 97.9% and 87.9% for CA 19-9, 66.7%, 100%, 100%, 99% and 99% for US, respectively. The value of the Standardized Incidence Ratio for pancreatic cancer in new-onset type-2 diabetic patients was 198.6 (95% CI = 6.25–46.9).ConclusionsThe prevalence of pancreatic cancer in patients with new-onset type-2 diabetes is significantly higher than that in the general population and screening is beneficial for detecting PaC in this patient population. CA 19-9 and US is not reliable screening modality for pancreatic cancer screening in this population.     

Child mortality associated with reasons for non-breastfeeding and weaning: is breastfeeding best for HIV-positive mothers?

OBJECTIVE: To estimate child mortality associated with reasons for the non-initiation of breastfeeding and weaning caused by preceding morbidity, compared with voluntary weaning as a result of maternal choice. METHODS: Demographic and Health Surveys were analysed from 14 developing countries. Women reported whether they initiated lactation or weaned, and if so, their reasons for non-initiation or stopping breastfeeding were classified as voluntary choice or as a result of preceding maternal/infant illness. Rates of child mortality and survival analyses were estimated, by reasons for non-breastfeeding or weaning. RESULTS: Mortality was highest among never-breastfed children. Child mortality among women who never initiated breastfeeding was significantly higher than among women who weaned. Preceding maternal/infant morbidity was the most common reason for not breastfeeding (63.9%), and the mortality of children never breastfed because of preceding morbidity was higher than in children not breastfed as a result of maternal choice; 326.8 per 1000 versus 34.8 per 1000, respectively. Mortality among breastfed children who were weaned because of preceding morbidity was higher than among those weaned voluntarily; 19.2 per 1000 versus 9.3 per 1000, respectively. Failure to initiate lactation was significantly more frequent among women reporting complications of delivery and with low birthweight infants. CONCLUSION: Child mortality as a result of the voluntary non-initiation of breastfeeding or voluntary weaning was lower than previously estimated, and this should be used as a benchmark when counselling HIV-positive mothers on the risks of non-breastfeeding or weaning to prevent mother-to-child transmission of HIV.