Severe Disease Conditions Research Articles

Controlling diabetes by chromium complexes: The role of the ligands

Diabetes, particularly type II diabetes, is a severe disease condition which affects human health worldwide, with a dramatically increasing trend in Asian countries including China. Currently, no efficient drugs other than those with observable side effects are available. Chromium complexes, with the most known representative chromium picolinate, have been listed as one of most attractive health supplements to attenuate this disease condition in western countries. Recent efforts have been made to develop new chromium complexes with novel ligands. Although fair amounts of reviews have been published to emphasize the biological activity, preclinical and clinical information of chromium picolinate, this mini-review is trying to cover the entire picture of updated research efforts on various chromium complexes highlighting the role of ligands. Chromium phenylalanine sensitizes insulin cell signaling pathway via the activation of phosphorylation of Akt (protein kinase B (PKB)) and/or AMPK (AMP-activated protein kinase). The biological activities, toxicity, pharmacological features and clinical implications, including the effect of anti-oxidative capacities, protective effect on obese-induced heart dysfunction, and efficacy and safety of chromium supplementation in diabetes are discussed as well.

The Basic Documentation for Psycho-Oncology Short Form (PO-Bado SF)--an expert rating scale for distress screening: development and psychometric properties.

The aim of this study is to validate the Basic Documentation for Psycho-Oncology Short Form (PO-Bado SF), a six item interview-based expert rating scale for distress screening in cancer patients. Using a heterogeneous multicenter study sample (n = 1551), we examined validity, reliability, and dimensionality of the PO-Bado SF. The Hospital Anxiety and Depression Scale (HADS), the Distress Thermometer, the Questionnaire on Stress in Cancer, and the Patient Health Questionnaire were used to investigate convergent validity. Confirmatory factor analysis was applied to address unidimensionality. An optimal cutoff point was determined by ROC analysis and the maximum of Youden's index. An additional study with n = 41 audio recorded PO-Bado SF interviews was carried out to assess inter-rater reliability. Mean age of the study sample was 64.0 (SD = 12.0), 42% were women. About 24% of the patients suffered from metastases. The one-factor solution was confirmed; internal consistency of the PO-Bado SF was high (α = 0.84). The PO-Bado SF total score correlated significantly with all psychosocial measures, the highest correlation was with the HADS total score (r = 0.64). Patients with severe disease conditions (metastases, psychological/psychiatric treatment in the past, low performance status) received higher distress ratings (p < 0.001). Using HADS total score (>13) as external criterion, an optimal PO-Bado SF cutoff score of >9 emerged (sensitivity 0.75; specificity 0.82). Inter-rater reliability was satisfactory for each of the six items (intra class correlation of 0.75 to 0.85). The PO-Bado SF is a short, reliable and valid expert rating scale to identify distressed cancer patients.

Village doctor-assisted case management of rural patients with schizophrenia: protocol for a cluster randomized control trial

BackgroundStrict compliance with prescribed medication is the key to reducing relapses in schizophrenia. As villagers in China lack regular access to psychiatrists to supervise compliance, we propose to train village ‘doctors’ (i.e., villagers with basic medical training and currently operating in villages across China delivering basic clinical and preventive care) to manage rural patients with schizophrenia with respect to compliance and monitoring symptoms. We hypothesize that with the necessary training and proper oversight, village doctors can significantly improve drug compliance of villagers with schizophrenia.Methods/designWe will conduct a cluster randomized controlled trial in 40 villages in Liuyang, Hunan Province, China, home to approximately 400 patients with schizophrenia. Half of the villages will be randomized into the treatment group (village doctor, or VD model) wherein village doctors who have received training in a schizophrenia case management protocol will manage case records, supervise drug taking, educate patients and families on schizophrenia and its treatment, and monitor patients for signs of relapse in order to arrange prompt referral. The other 20 villages will be assigned to the control group (case as usual, or CAU model) wherein patients will be visited by psychiatrists every two months and receive free antipsychotic medications under an on-going government program, Project 686. These control patients will receive no other management or follow up from health workers. A baseline survey will be conducted before the intervention to gather data on patient’s socio-economic status, drug compliance history, and clinical and health outcome measures. Data will be re-collected 6 and 12 months into the intervention. A difference-in-difference regression model will be used to detect the program effect on drug compliance and other outcome measures. A cost-effectiveness analysis will also be conducted to compare the value of the VD model to that of the CAU group.Discussion/implicationsLack of specialists is a common problem in resource-scarce areas in China and other developing countries. The results of this experiment will provide high level evidence on the role of health workers with relatively limited medical training in managing severe psychiatric disease and other chronic conditions in developing countries.Trial registrationChiCTR-TRC-13003263.

Trajectories of functional limitation in early rheumatoid arthritis and their association with mortality

This study aimed to identify subgroups with distinct trajectories of functional (HAQ) progression over 10 years following diagnosis of RA and identify baseline characteristics associated with the trajectories and their prognostic value for mortality. Between 1986 and 1998, 1460 patients with RA symptoms <2 years and prior to disease-modifying treatment (DMARDs) were recruited to an inception cohort (Early RA Study). Standard clinical, functional and laboratory assessments were performed at presentation and annually. Deaths were tracked by the National Health Service Central Register. Growth mixture modelling was used to identify distinct trajectories of HAQ score progression and survival analysis employed to compare all-cause mortality across the trajectory classes. Four HAQ score progression classes were identified: moderate increasing (46%), low stable (6%), moderate stable (28%) and high stable (20%). Only the moderate-increasing class exhibited an accelerated decline in function over normal ageing. Compared with the moderate-increasing class, individuals with high-stable HAQ scores were more likely to be female, have more severe disease and other coexistent conditions. Low-stable class patients were more likely to be male and report less pain. The high-stable class had increased risk of mortality compared with the moderate-increasing class after adjusting for potential confounding factors, whereas low-stable and moderate-stable classes were at reduced mortality risk. The effect of RA on function is set within the first few years and is affected by comorbidity. Identifying distinct groups of patients may help to target those at greater risk of poor functional outcome and mortality.

Tracheobronchial lesions in eosinophilic pneumonia

Eosinophilic pneumonia (EP) is characterized by eosinophil infiltration in the lung parenchyma. However, tracheobronchial lesions associated with the disease have been poorly described. To clarify the frequency and characteristics of cases with tracheobronchial lesions in EP, we performed a retrospective review of EP patients. We included 36 EP cases seen from January 2004 to December 2007 at the Kinki-Chuo Chest Medical Center. The incidence of tracheobronchial nodules and associated clinical features were analyzed. Of these 36 patients, 29 had chronic eosinophilic pneumonia (CEP); 1, acute EP; 3, drug-induced EP; 2, allergic bronchopulmonary aspergillosis; and 1, parasite-related EP. Only 2 of the 29 CEP cases had tracheobronchial lesions. For both of these cases, bronchoscopy revealed multiple whitish nodules on the tracheobronchial mucosa. The associated histopathological findings revealed squamous metaplasia and eosinophil infiltration in the subepithelial region. In both cases, the nodules disappeared after steroid therapy. The prevalence of tracheobronchial lesions was 6.9% in CEP patients and 5.6% in EP patients overall. EP patients were divided into 3 groups: CEP with nodules (n=2), CEP without nodules (n=27), and other EP (n=7). We found that the CEP with nodules group showed a relatively higher incidence of respiratory symptoms, higher white blood cell (WBC) count, and higher levels of peripheral and bronchoalveolar eosinophilia than the other groups. Tracheobronchial nodules represent rare observations within the EP population, which are likely to reflect a severe disease condition.

Prediction of early allograft dysfunction using serum phosphorus level in living donor liver transplantation

Serum phosphorus is greatly affected by liver surgeries, but its change after liver transplantation has not yet been clarified. We investigated the predictive role of serum phosphorus for early allograft dysfunction (EAD) after living donor liver transplantation (LDLT). Perioperative factors, including serum phosphorus level, of 304 patients who underwent LDLT were retrospectively studied and compared between patients with and without EAD after LDLT. Potentially significant factors (P<0.15) in univariate comparisons were subjected to multivariate logistic regression analysis to develop a prediction model for EAD. A total of 48 patients (15.8%) met the EAD criteria. Patients with EAD experienced more severe preoperative disease conditions, higher one-month mortality and more elevated serum phosphorus concentrations during the first week after surgery compared with patients without EAD (P=0.016). Multivariate analysis showed that a serum phosphorus level ≥4.5mg/dl on postoperative day 2 was an independent predictor of EAD occurrence after LDLT (relative risk: 2.36, 95% confidence interval [1.18-4.31], P=0.017), together with a history of past abdominal surgery, emergency transplantation and preoperative continuous veno-venous haemodiafiltration. These data indicate that hyperphosphataemia during the immediate postoperative days could be utilized as a predictor of EAD after LDLT.

Evaluation on Effect of Resistance Improvement of Bacterial Leaf Blight and Brown Planthopper for Three Dominant Indica Restorer Lines

A novel bacterial blight (BB) resistance gene, Xa23, and brown planthopper (BPH) resistance gene, Bph18(t) were introgressed into three popular restorer lines (Minghui 86, Shuhui 527, and Zhehui 7954) for wild abortive cytoplasmic male sterility by marker-assisted backcross and pyramiding breeding approaches in combination with artificial inoculation and stringent phenotypic selections. The four derived BB resistant restorer lines [Minghui 86-Xa23, Shuhui 527-Xa23, Zhehui 7954-Xa23, and Zheshu-Xa23-Bph18(t)] and their derived hybrid combinations with Ⅱ-32A and Huhan11A demonstrated similar BB resistance spectrum as the donor parent, IRBB23. The three derived BPH resistant restorer lines [Shu 527-Bph18(t), Zhehui 7954-Bph18(t), and Zheshu-Xa23-Bph18(t)] showed resistant or moderate resistant to BPH. The newly developed BB and BPH resistant restorers and their derived hybrids were identical to their respective original versions for agronomic traits especially under disease free condition. However, under severe disease condition, the four BB resistant restorer lines exhibited significantly higher grain weight and spikelet fertility as compared to the respective original restorer lines thus further resulting in BB resistant hybrids with significantly higher grain yields than their respective original hybrids. The results indicated that the Xa23 gene could completely express its dominant resistance in different backgrounds of both restorer and male sterile lines across different growth stages,suggesting its immense breeding value in BB resistance improvement for hybrid rice. However, effect of resistant improvement of Bph18(t) for BPH depends on genetic background. Improvement of resistance of BB and BPH for restorer lines by molecular marker-assisted backcross and pyramiding was deeply discussed.

Developing Restorer Lines Pyramiding Different Resistant Genes to Blast and Bacterial Leaf Blight by Marker-assisted Selection in Rice

The novel blast resistance genes, Pi-GD-1(t), Pi-GD-2(t), and GLP8-6(t) from rice variety Sanhuangzhan 2 (here abbreviated them as G1, G2, and G8, respectively) and bacterial blight (BB) resistance gene, Xa23, were introgressed into three elite restorer lines (Minghui 86, Shuhui 527, and Zhehui 7954) by marker-assisted pyramiding breeding approaches in combination with artificial inoculation and stringent phenotypic selections. The five derived blast and bacterial blight resistance restorer lines, Minghui 86-G1-G2-Xa23, Shuhui 527-G2-Xa23, Mingzhe-G2-G8-Xa23-1, Mingzhe-G2-G8-Xa23-2, and Mingzhe-G1-G2-G8Xa23, demonstrated similar or wider blast resistance spectrum as compared with the donor parent, Sanhuangzhan 2. The five derived BB resistant restorer lines and their derived hybrid combinations with II-32A demonstrated similar BB resistance spectrum to the donor parent, IRBB23. The newly developed BB resistant restorers and their derived hybrids were identical to their respective original versions for agronomic traits especially under disease free condition. However, under severe disease condition, the five BB resistant restorer lines exhibited significantly higher grain weight, spikelet fertility, and grain yield as compared with the respective original restorer lines, thus further resulting in significantly higher grain yields in BB resistant hybrids than in their 第 9期 潘晓飚等: 分子标记辅助选育水稻抗白叶枯病和稻瘟病多基因聚合恢复系 1583 respective original hybrids.

1,5-Anhydroglucitol in diabetes mellitus

The measure of glycated hemoglobin (HbA1c) concentration is the gold standard of glycemic control index in diabetes management and is well known as a marker for diabetes complications. However, HbA1c level neither accurately reflect glucose fluctuations, nor does it provide a clear indication of glycemic control in recent days or weeks. HbA1c concentration measurement can be confounded in patients with anemia, hemoglobinopathy, liver disease, or renal impairment. 1,5-Anhydroglucitol (1,5-AG) structurally resembles glucose. It can be influenced by diet or medication, gender and race, especially severe renal disease and various pathological conditions. Most notably, 1,5-AG level is reflective of short-term glucose status, postprandial hyperglycemia, and glycemic variability which are not captured by HbA1c assay. 1,5-AG may suggest an alternative index of subtypes of diabetes and a warning sign of diabetes complications. This review provides an overview of our current understanding of the role of 1,5-AG marker in diabetes. However, further investigations on the associations between this glycemic marker and diabetes complications are needed.

A prospective cohort study of endodontic treatments of 1,369 root canals: results after 5 years

The purpose of this prospective study was: 1) to follow-up a large number of endodontic treatments performed by a single operator, periodically checked over a 5-year period; and 2) to correlate outcome to a number of clinical variables. This prospective study included all consecutive cases during the selected time period. All cases were followed regularly for a 5-year period. At the 5-year end point of the study, 470 patients with 816 treated teeth and with 1,369 treated root canals were available for evaluation. The overall rate of success among the 816 teeth/1,369 root canals available for evaluation was 88.6%/90.3%. The success rate for 435 teeth/793 root canals undergoing vital pulp therapy was 91.5%/93.1%. Teeth/root canals with necrotic pulp but without detectable periapical bone lesion were successfully treated in 89.5%/92.3%. If the pulp necrosis was complicated by apical periodontitis, the success rate fell to 82.7% for the teeth and 84.1% for the root canals (P = .037). Teeth with periapical lesion <5 mm had a success rate of 86.6%, and in cases where the lesion was ≥ 5 mm the rate of success was 78.2%. More severe disease conditions negatively affects outcome. An optimal working length was identified. Excess of root canal filling material decreases success. Infected pulp space should be treated with an effective intracanal dressing. The quality of the coronal restoration or the placement of intracanal post retentions does not affect treatment outcome.

Growth differentiation factor-15, a novel biomarker related with disease severity in patients with hypertrophic cardiomyopathy

BackgroundThe growth differentiation factor 15 (GDF-15) has been shown up-regulated in stress conditions and to have regulatory actions in myocyte hypertrophy. We hypothesized that GDF-15 could be related to disease severity and functional status in patients with hypertrophic cardiomyopathy (HCM). Methods and resultsWe performed a study which includes 102 consecutive outpatient HCM subjects, 73% males, aged 47.1±14.6years. A complete history and clinical examination was performed, including 12-lead electrocardiogram, echocardiography, symptom-limited treadmill exercise, 24-hour ECG-Holter monitoring, and magnetic resonance with Gadolinium. Several biomarkers, associated with myocardial remodeling and damage, were compared to GDF-15 levels. The assays were performed with commercial ELISAs or standardized methods when available. There was a significant association between GDF-15 levels and comorbidities, being higher in hypertension (p=0.001), diabetes (p=0.030), atrial fibrillation (p=0.012), dyspnea (p=0.020) and NYHA≥II functional class (p=0.037). GDF-15 levels were positively correlated with clinical variables (age, worse exercise capacity and mild renal dysfunction) and biomarkers of interstitial remodeling, such as metalloproteinase-2 (r: 0.40; p=0.009), N-terminal pro-B-type natriuretic peptide (r: 0.28; p=0.049), high-sensitivity troponin T (r: 0.30; p=0.003) and von Willebrand factor (r: 0.33; p=0.001). Multivariate analysis was assessed to estimate the involvement of these different factors in the GDF-15 levels, confirming the independent implication of severe dyspnea and functional status. ConclusionsThe present results show that higher levels of GDF-15 are associated to conditions of severe disease in HCM. Hence, GDF-15 is suggested as a novel marker related to the severity and could represent a further useful tool in monitoring functional capacity of HCM patients.

Role of Rifampin-Based Combination Therapy for Severe Community-Acquired Legionella pneumophila Pneumonia

To review the literature concerning the role of rifampin in the combination treatment of Legionella pneumophila pneumonia. A search of MEDLINE and Ovid databases was conducted (January 1970-May 2011) using the search terms Legionella pneumophila, pneumonia, Legionnaires' disease, rifampin or rifampicin, macrolide, fluoroquinolone, erythromycin, clarithromycin, levofloxacin, ciprofloxacin, and moxifloxacin In vivo studies published in English that compared antimicrobial therapies including rifampin for the treatment of Legionella pneumonia, as well as in vitro studies including an assessment of rifampin bioactivity, were included. Macrolides and fluoroquinolones have been effective as monotherapy in the treatment of L. pneumophila pneumonia. This review includes evidence summaries from 4 bioactivity evaluations, 6 clinical studies, and 6 reported cases of combination rifampin use. Combined with supporting evidence, the role of combination rifampin therapy is further delineated. Interpretation of the data is limited by the potential for selection bias and lack of consistent comparators. Rifampin therapy should be considered only for patients with severe disease or significant comorbid conditions (eg, uncontrolled diabetes, smoking, or obstructive lung disease) including immunocompromised hosts and those refractory to conventional monotherapy regimens. Caution for significant adverse drug events and drug-drug interactions should be taken with the addition of rifampin.

Improvement of bacterial blight resistance of hybrid rice in China using the Xa23 gene derived from wild rice ( Oryza rufipogon)

A novel bacterial blight (BB) resistance gene, Xa23, identified from Oryza rufipogon was introgressed into three popular restorer lines (Minghui63, YR293 and Y1671) for wild abortive cytoplasmic male sterility by marker-assisted backcross breeding approach in combination with artificial inoculation and stringent phenotypic selections. The three derived BB resistant restorer lines (Minghui63– Xa23, YR293– Xa23 and Y1671– Xa23) and their hybrid combinations with Zhenshan97A (Shanyou63– Xa23), NongfengA (Fengyou293– Xa23) and Zhong9A (Zhongyou1671– Xa23) demonstrated similar BB resistance spectrum as the donor parent, CBB23 (B). The newly developed BB resistant restorers and their derived hybrids were identical to their respective original versions for agronomic traits especially under disease free condition. However, under severe disease condition, the three BB resistant restorer lines exhibited significantly higher grain weight and spikelet fertility as compared to the respective original restorer lines thus further resulting in BB resistant hybrids with significantly higher grain yields than their respective popular original hybrids. The results indicated that the Xa23 gene could completely express its dominant broad spectrum resistance in different backgrounds of both restorer and male sterile lines across different growth stages, suggesting its immense breeding value in BB resistance improvement for hybrid rice. Moreover, a reasonable utilization and deployment of Xa23 gene for efficient control of BB disease in hybrid rice production was recommended.

Chitosan microspheres in novel drug delivery systems.

The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems.

Could antibodies against Serum Amyloid A function as physiological regulators in humans?

The natural structuring of the immune system is responsible for the functional physiological state of the body. The development of natural autoantibodies involved in homeostasis relies on the ability to distinguish between exposed/masked and altered/non-altered self antigens. The objectives of this article were to address the relationships between antigen and autoantibodies against serum amyloid A (SAA), define SAA protein concentrations in 219 blood donor (BD) sera and determine their autoantibody levels and search for possible clinical associations with autoimmune and thrombotic diseases. Just recently, an increasing number of reports have indicated significantly decreased levels of autoantibodies against pro-inflammatory molecules, such as anti-TNF-alpha, anti-IL-6, or anti-CRP found in diseased conditions, as compared to healthy donors, or even to less severe disease conditions. In accord with this line of thought, our data indicate a predominant presence of anti-SAA autoantibodies in healthy BDs (above 95% as tested by the immunoblot analysis, n = 41). Using ELISA, high levels of anti-SAA antibodies were confirmed with a median OD = 0.996 for the BD group (n = 219). This suggests that anti-SAA antibodies might have a physiological role in homeostasis and/or the innate immune system and could actually be a part of the natural antibody repertoire. Significantly, lower median levels were found in patients with arterial thrombosis. Based on 219 BD sera, we could establish a new median value of 20 μg/ml for SAA antigen and a cut-off value of 114.7 μg/ml (97.5th percentile). Significantly, higher concentrations of SAA were observed for antiphospholipid syndrome, rheumatoid arthritic, and SLE patients.

EUREGIO MRSA-net Twente/Münsterland: Search &amp; Follow durch euregionale Netzwerkbildung

Staphylococcus aureus causes the majority of healthcare-associated infections worldwide. Particularly critical are infections caused by methicillin-resistant Staphylococcus aureus (MRSA), for which there are few possibilities of antibiotic therapy. It is known that the occurrence of MRSA is directly associated with increased morbidity and mortality. There is also evidence for an increased lethality in hospital-acquired MRSA infections and MRSA bacteraemia in comparison to methicillin-sensitive S. aureus. Besides prolonged and severe disease conditions, the occurrence of MRSA results is extremely laborious and has for the hospitals very expensive consequences, in extreme cases the closure of an entire ward. Nosocomial infections due to MRSA lead to a significantly prolonged length of stay of the patient and leads therefore to extra costs due to recommended hygiene measures (e. g. isolation in a single room). The long-term treatment options can have side effects and are often limited to expensive antibiotics. The growing number of patients treated with severe underlying diseases and the increasing number of expensive medical treatments leads to a further exacerbation of this situation. In times of limited financial resources, this might lead to irresolvable conflicts between the patient safety required and the health funding available.

A Novel Method of Distal End-Tidal CO2 Capnography in Intubated Infants: Comparison With Arterial CO2 and With Proximal Mainstream End-Tidal CO2

The objective of this study was to evaluate a novel method of distal end-tidal CO2 capnography by comparison with PaCO2 and with the more standard method that measures mainstream proximal end-tidal CO2 in intubated infants. Included in the study were all infants who were ventilated with conventional mechanical ventilation and intubated with a double-lumen endotracheal tube in our NICU during the study period. Data were collected prospectively from 2 capnographs simultaneously and compared with PaCO2. Sidestream distal end-tidal CO2 was measured by a Microstream capnograph via the extra port of a double-lumen endotracheal tube. Mainstream proximal end-tidal CO2 was measured via capnograph connected to the endotracheal tube. Twenty-seven infants (median [range] birth-weight: 1835 [490-4790] g; gestational age: 32.5 [24.8-40.8] weeks) participated in the study. We used for analysis 222 and 212 measurements of distal end-tidal CO2 and proximal end-tidal CO2, respectively. Distal compared with proximal end-tidal CO2 had a better correlation with PaCO2 and a better agreement with PaCO2. The accuracy of distal end-tidal CO2 decreased, but it remained a useful measure of PaCO2 in the high range of PaCO2 (>or=60 mmHg) or in conditions of severe lung disease. A subanalysis for infants who weighed<1500 g (13 infants, 84 observations) revealed a good correlation and agreement between distal end-tidal CO2 and PaCO2 and poor correlation and agreement for proximal end-tidal CO2. Distal end-tidal CO2 measured via a double-lumen endotracheal tube was found to have good correlation and agreement with PaCO2, remained reliable in conditions of severe lung disease, and was more accurate than the standard mainstream proximal end-tidal CO2.

Phylogenetic analysis of Shiga toxin 1 and Shiga toxin 2 genes associated with disease outbreaks

BackgroundShiga toxins 1 and 2 (Stx1 and Stx2) are bacteriophage-encoded proteins that have been associated with hemorrhagic colitis, hemolytic uremic syndrome and other severe disease conditions. Stx1 and Stx2 are genetically and immunologically distinct but share the same compound toxin structure, method of entry and enzymatic function.ResultsPhylogenetic analysis was performed using Stx1 and Stx2 amino acid and nucleotide sequences from 41 strains of Escherichia coli, along with known stx sequences available from GenBank. The analysis confirmed the Stx1 and Stx2 divergence, and showed that there is generally more sequence variation among stx2 genes than stx1. The phylograms showed generally flat topologies among our strains' stx1 and stx2 genes. In the stx2 gene, 39.5% of the amino acid sites display very low nonsynonymous to synonymous substitution ratios.ConclusionThe stx1 and stx2 genes used in this phylogenetic study show sequence conservation with no significant divergence with respect to place or time. These data could indicate that Shiga toxins are experiencing purifying selection.

Blood pressure reduction in pregnancy by sodium chloride

Volume expansion in the presence of elevated aldosterone availability is a hallmark of normal pregnancy. Intravascular volume depletion characterizes severe pregnancy-associated disease conditions such as intra-uterine growth retardation, chronic hypertension or pre-eclampsia [1]. Two hypotheses have been forwarded to explain volume depletion in pregnancy: the first hypothesis charges inappropriate sensing of vascular ‘overfilling’, resulting in an increased transendothelial loss of fluid to the extravascular compartment. In contrast, the second hypothesis focuses on vascular ‘underfilling’ due to inappropriately low aldosterone levels. The second hypothesis is based on the assumption that a compensatory increase in the circulating fluid volume is required in normal pregnancy to support fetal substrate delivery. According to the second concept, maternal blood pressure increases due to counter-regulatory mechanisms when placental blood supply is reduced [2]. In support of the ‘underfilling’ hypothesis are observations that a compromised volume status before pregnancy or a reduced ability to retain sodium by pregnant women predicts a complicated pregnancy outcome. The relevance of intravascular volume expansion during normal pregnancy is also supported by the clinical observation that further reduction of fluids by prescribing either diuretics or salt restriction does not prevent or improve the course of the disease [3]. On the contrary, acute volume expansion in overt pre-eclampsia has been observed to transiently decrease blood pressure [4]. Assuming low aldosterone availability to be the cause rather than the consequence of pre-eclampsia [5], we recently observed an association between a reduced 18-methyl oxidase, the rate limiting enzymatic step of aldosterone synthase (CYP11B2), an increased frequency of polymorphisms in the gene of the same enzyme and pre-eclampsia [6]. Likewise, patients with inborn corticosterone methyl oxidase deficiency are known to decompensate at times of sodium deprivation. Here, we demonstrate for the first time the utility of prescribing supplemental NaCl for a woman with neither the increase in aldosterone production nor the blood pressure drop expected during pregnancy.

NATURAL AND EXPERIMENTAL WEST NILE VIRUS INFECTION IN FIVE RAPTOR SPECIES

We studied the effects of natural and/or experimental infections of West Nile virus (WNV) in five raptor species from July 2002 to March 2004, including American kestrels (Falco sparverius), golden eagles (Aquila chrysaetos), red-tailed hawks (Buteo jamaicensis), barn owls (Tyto alba), and great horned owls (Bubo virginianus). Birds were infected per mosquito bite, per os, or percutaneously by needle. Many experimentally infected birds developed mosquito-infectious levels of viremia (>10(5) WNV plaque forming units per ml serum) within 5 days postinoculation (DPI), and/ or shed virus per os or per cloaca. Infection of organs 15-27 days postinoculation was infrequently detected by virus isolation from spleen, kidney, skin, heart, brain, and eye in convalescent birds. Histopathologic findings varied among species and by method of infection. The most common histopathologic lesions were subacute myocarditis and encephalitis. Several birds had a more acute, severe disease condition represented by arteritis and associated with tissue degeneration and necrosis. This study demonstrates that raptor species vary in their response to WNV infection and that several modes of exposure (e.g., oral) may result in infection. Wildlife managers should recognize that, although many WNV infections are sublethal to raptors, subacute lesions could potentially reduce viability of populations. We recommend that raptor handlers consider raptors as a potential source of WNV contamination due to oral and cloacal shedding.