Use of lablab (Lablab purpureus (L.) Sweet) for bio-control by native arthropods and its effect on yield of pumpkins.

Silverleaf whitefly (SLW, Bemisia tabaci MEAM1) and aphids are sap-sucking insects, which pose a serious threat to Australian cucurbit crops and the horticulture industry. Traditional chemical control for these insect pests is becoming less effective, and there is a need to search for alternative or supplementary methods. This study aimed to manipulate the habitat of pumpkin crops in a tropical setting (Queensland, Australia), by growing pumpkins (var. Japanese pumpkin) alone and between lablab (Lablab purpureus L. Sweet). It was hypothesized that the presence of lablab will increase the populations of natural enemies, and through their control of insect pests such as SLW and aphids, will affect pumpkin yield. The population of arthropods (natural enemies and pests of pumpkin), with a focus on SLW and aphids, were sampled weekly on both lablab and pumpkin crop for a total of 21 weeks. Results showed that lablab hosted more enemies of SLW per plant than pumpkin in either treatment. In addition, adult SLW numbers were significantly higher in the pumpkin-only crop compared with the pumpkin grown between lablab, while pumpkin in the mixed plantings had significantly more ladybirds and lacewing larvae (P < 0.05). While there was no significant difference in the average fruit weight between treatments, the total weight (kg) and number of marketable pumpkins per hectare was greater (P < 0.05) for the pumpkin/lablab treatment than the pumpkin-only treatment. This study shows that growing lablab alongside a pumpkin crop may enhance natural enemies of SLW and could significantly increase the yield.

Mesenchymal stem cell technology in the treatment of degenerative disc disease.

AIM: Low back pain is the leading cause of disability and a major health problem around the world. As of today, symptomatic relief is the best option offered to patients, with mixed results. This study will review the use of mesenchymal stem cell (MSC) technology in the conservative and surgical treatments of degenerative disc disease (DDD). METHODS: A series of PubMed-National Library of Medicine searches were performed. Only articles in English journals or with published with English language translations were included. Level of evidence of the selected articles was assessed. RESULTS: There are multiple in-vitro and animal studies describing successful intervertebral disc (IVD) repair/regeneration with the use of live MSC therapy. Only 3 human studies (22 patients) with inconsistent results have been performed using bone marrow MSCs injected into diseased IVDs in patients with DDD. There exist multiple in-vitro and animal studies describing successful bony fusion with the use of MSC-containing bone graft substitutes. Only 3 retrospective human studies (115 patients) using CBM in spinal fusion have been performed with successful fusion rates ranging from 90.2%-92.3%. However, these studies lacked power and had significant conflicts of interest. There are multiple challenges with the use of MSC technology in humans. CONCLUSION: MSCs may be a promising therapy in the treatment of DDD. However, their lack of success in human models leaves room for further research and focus in this field. Currently, there is no clinical evidence to support the use of this technology in the conservative or surgical management of patients with DDD.

Device closure of secundum atrial septal defect's and the risk of cardiac erosion.

Cardiac erosion related to transcatheter atrial septal defect closure devices is of increasing concern. Erosion is reported to have occurred with most of currently available occluder devices. Perhaps due to the very large number of implants worldwide, the Amplatzer (St Jude) occluder is associated with the majority of cardiac erosion events reported in the literature. Best current estimates of the incidence of erosion with the St Jude device are between one and three cases per 1000 implants. Most events occur early after implantation and it is rare, although not unheard of, for events to occur after a year following device insertion. It is important that those involved with closure programmes are vigilant for the problem, because device-related erosion is associated with a significant mortality risk. Despite considerable debate, the risk factors (either patient or device) for erosion remain unclear and require further investigation. Currently available data sets have focussed largely on erosion cohorts and are unable to place these cases in appropriate context with non-erosion closure cases. What is certain is that programmes implanting these devices must take care to implant appropriately sized devices and have in place plans to ensure that patients are both well informed and can access help and advice in the event of developing symptoms.

C5 nerve root palsy following decompression of the cervical spine: a systematic evaluation of the literature.

C5 nerve root palsy is a rare and potentially debilitating complication of cervical spine surgery. Currently, however, there are no guidelines to help surgeons to prevent or treat this complication. We carried out a systematic review of the literature to identify the causes of this complication and options for its prevention and treatment. Searches of PubMed, Embase and Medline yielded 60 articles for inclusion, most of which addressed C5 palsy as a complication of surgery. Although many possible causes were given, most authors supported posterior migration of the spinal cord with tethering of the nerve root as being the most likely. Early detection and prevention of a C5 nerve root palsy using neurophysiological monitoring and variations in surgical technique show promise by allowing surgeons to minimise or prevent the incidence of C5 palsy. Conservative treatment is the current treatment of choice; most patients make a full recovery within two years.

Correlation of echocardiographic and angiographic measurements of the pulmonary valve annulus in pulmonary stenosis.

OBJECTIVES: The pulmonary valve (PV) annulus is routinely measured angiographically in PV stenosis prior to balloon dilation. We sought to establish whether this radiation exposure is justified, or whether echocardiographic measurements prior to the procedure are sufficient to guide balloon selection. BACKGROUND: Previous studies have found a strong correlation between echocardiographic and angiographic measurements of the PV annulus. However, error of measurement and its implication for procedural practice has not been explored. METHODS: A total of 90 procedures in 84 patients were analyzed, at a median age 7.6 months (range 1 day to 14.2 years). The contemporaneous echocardiographic and angiographic measurements were recorded, and the original echocardiograms were re-measured in the 72 available cases by two independent reviewers. RESULTS: There was a good correlation between the two measurement methods (R(2) = 0.87). However, the echocardiographic PV measurements were smaller on average, with a significant variation in that discrepancy (mean ratio 0.941 (±0.16)). There was no significant reduction in error if extreme measurements (PV annulus z-score <-3) were excluded (P = 0.09), or if the reviewed echocardiographic measurements were used (P = 0.58). CONCLUSIONS: There is an unacceptable discrepancy between the measurement techniques: 95% of patients are predicted to have an echocardiographic measurement error between -37% and +26%. Therefore, there is no correction factor that could be employed to allow safe selection of balloon size, and balloon pulmonary valvoplasty without angiographic PV measurement cannot be advocated.

Chronic treatment with a glucagon receptor antagonist lowers glucose and moderately raises circulating glucagon and glucagon-like peptide 1 without severe alpha cell hypertrophy in diet-induced obese mice.

AIMS/HYPOTHESIS: Antagonism of the glucagon receptor (GCGR) represents a potential approach for treating diabetes. Cpd-A, a potent and selective GCGR antagonist (GRA) was studied in preclinical models to assess its effects on alpha cells. METHODS: Studies were conducted with Cpd-A to examine the effects on glucose-lowering efficacy, its effects in combination with a dipeptidyl peptidase-4 (DPP-4) inhibitor, and the extent and reversibility of alpha cell hypertrophy associated with GCGR antagonism in mouse models. RESULTS: Chronic treatment with Cpd-A resulted in effective and sustained glucose lowering in mouse models in which endogenous murine Gcgr was replaced with human GCGR (hGCGR). Treatment with Cpd-A also led to stable, moderate elevations in both glucagon and glucagon-like peptide 1 (GLP-1) levels, which were completely reversible and not associated with a hyperglycaemic overshoot following termination of treatment. When combined with a DPP-4 inhibitor, Cpd-A led to additional improvement of glycaemic control correlated with elevated active GLP-1 levels after glucose challenge. In contrast to Gcgr-knockout mice in which alpha cell hypertrophy was detected, chronic treatment with Cpd-A in obese hGCGR mice did not result in gross morphological changes in pancreatic tissue. CONCLUSIONS/INTERPRETATION: A GRA lowered glucose effectively in diabetic models without significant alpha cell hypertrophy during or following chronic treatment. Treatment with a GRA may represent an effective approach for glycaemic control in patients with type 2 diabetes, which could be further enhanced when combined with DPP-4 inhibitors.

Identification of immunogenic regions within the alternative reading frame protein of hepatitis C virus (genotype 3).

Hepatitis C virus (HCV) encodes ten classic proteins as well as a newly discovered alternative reading frame protein (ARFP) whose synthesis originates from the core region by a +1 frameshift. ARFP is produced by all HCV genotypes, but its function remains unknown. Although the immunogenicity of genotype 1- and 2-derived ARFP in infected hosts has been reported, no information is available for genotype 3-encoded ARFP. HCV genotype 3 core/ARFP region was PCR amplified, cloned, and sequenced. Recombinant ARFP and peptides were employed in ELISAs with patient serum samples. The effect of peptides on peripheral blood mononucleocytes (PBMCs) was also studied. DNA cloning and sequencing of HCV genotype 3 strain (PKHCV3) revealed it to encode 160 aa ARFP, which harbors a C-terminal extension of 36 aa. Serum from 74 of 88 patients (84%) contained rARFP-reactive antibodies. Peptide ELISAs showed that all regions of rARFP were immunogenic, with peptide F7 (DSLSPRRAGAKAGPGLSPGT) being the most immunodominant. When incubated with PBMCs from HCV-infected individuals, F7 stimulated the production of TNFα and IL10. PKHCV3-derived ARFP encodes a 160 aa protein and antibodies against its entire length are found in 84% of all genotype 3-infected subjects. Peptide ELISAs revealed F7 to be highly immunogenic and capable of eliciting impressive T-cell responses.

Diagnosis of Alagille syndrome-25 years of experience at King's College Hospital.

OBJECTIVE: The aim of the study was to study the clinical and histological features of Alagille syndrome (AGS) at presentation comparing the value of the various modalities before the implementation of genetic diagnosis. PATIENTS AND METHODS: We performed a retrospective analysis of the records of 117 children diagnosed as having AGS after referral to King's College Hospital between 1980 and 2005. RESULTS: Cholestasis was seen in 104 of 117 (89%), characteristic facies in 91 of 117 (77%), posterior embryotoxon in 72 of 117 (61%), butterfly vertebrae in 44 of 117 (39%), heart disease (most often peripheral pulmonary stenosis) in 107 of 117 (91%), and renal disease in 27 of 117 (23%). Serum cholesterol levels of >5 mmol/L were seen in 52 of 86 (60.4%). Liver biopsy showed characteristic features of paucity of interlobular bile ducts in 59 of 77 (76.6%) children younger than 16 weeks of age, in 10 of 14 (71.4%) between 16 weeks and 1 year of age, and in 8 of 12 (66.66%) older than 1 year of age. Other biopsy findings were those of nonspecific hepatitis and biliary features. Iminodiacetic acid scans showed no excretion of isotope into the bowel after 24 hours in 21 of 35 (60%), and small/no gallbladder on ultrasound was seen in 29 of 104 (27.8%). Eleven of 117 (9.4%) had a diagnostic laparotomy and operative cholangiography, 2 proceeding to Kasai portoenterostomy before referral to our unit. CONCLUSIONS: Clinical features of AGS are not as consistently informative as suggested in the literature. Hypercholesterolaemia is nonspecific but may be a helpful pointer. Histology is not characteristic in 25%; hepatobiliary iminodiacetic acid scan and ultrasound may suggest a false diagnosis of biliary atresia in 60% and 28%, respectively, supporting the concept that infants with liver disease warrant early referral to a specialist centre. The advent of genetic diagnosis will redefine the syndrome with likely effects on the prognosis of the defined group.

RNAi-mediated germline knockdown of FABP4 increases body weight but does not improve the deranged nutrient metabolism of diet-induced obese mice.

OBJECTIVE: To investigate the impact of reduced adipocyte fatty acid-binding protein 4 (FABP4) in control of body weight, glucose and lipid homeostasis in diet-induced obese (DIO) mice. METHODS: We applied RNA interference (RNAi) technology to generate FABP4 germline knockdown mice to investigate their metabolic phenotype. RESULTS: RNAi-mediated knockdown reduced FABP4 mRNA expression and protein levels by almost 90% in adipocytes of standard chow-fed mice. In adipocytes of DIO mice, RNAi reduced FABP4 expression and protein levels by 70 and 80%, respectively. There was no increase in adipocyte FABP5 expression in FABP4 knockdown mice. The knockdown of FABP4 significantly increased body weight and fat mass in DIO mice. However, FABP4 knockdown did not affect plasma glucose and lipid homeostasis in DIO mice; nor did it improve their insulin sensitivity. CONCLUSION: Our data indicate that robust knockdown of FABP4 increases body weight and fat mass without improving glucose and lipid homeostasis in DIO mice.

A comparison of alternative plant mixes for conservation bio-control by native beneficial arthropods in vegetable cropping systems in Queensland Australia.

Cucurbit crops host a range of serious sap-sucking insect pests, including silverleaf whitefly (SLW) and aphids, which potentially represent considerable risk to the Australian horticulture industry. These pests are extremely polyphagous with a wide host range. Chemical control is made difficult due to resistance and pollution, and other side-effects are associated with insecticide use. Consequently, there is much interest in maximising the role of biological control in the management of these sap-sucking insect pests. This study aimed to evaluate companion cropping alongside cucurbit crops in a tropical setting as a means to increase the populations of beneficial insects and spiders so as to control the major sap-sucking insect pests. The population of beneficial and harmful insects, with a focus on SLW and aphids, and other invertebrates were sampled weekly on four different crops which could be used for habitat manipulation: Goodbug Mix (GBM; a proprietary seed mixture including self-sowing annual and perennial herbaceous flower species); lablab (Lablab purpureus L. Sweet); lucerne (Medicago sativa L.); and niger (Guizotia abyssinica (L.f.) Cass.). Lablab hosted the highest numbers of beneficial insects (larvae and adults of lacewing (Mallada signata (Schneider)), ladybird beetles (Coccinella transversalis Fabricius) and spiders) while GBM hosted the highest numbers of European bees (Apis mellifera Linnaeus) and spiders. Lucerne and niger showed little promise in hosting beneficial insects, but lucerne hosted significantly more spiders (double the numbers) than niger. Lucerne hosted sig-nificantly more of the harmful insect species of aphids (Aphis gossypii (Glover)) and Myzus persicae (Sulzer)) and heliothis (Heliothis armigera Hübner). Niger hosted significantly more vegetable weevils (Listroderes difficillis (Germar)) than the other three species. Therefore, lablab and GBM appear to be viable options to grow within cucurbits or as field boundary crops to attract and increase beneficial insects and spiders for the control of sap-sucking insect pests. Use of these bio-control strategies affords the opportunity to minimise pesticide usage and the risks associated with pollution.

Interventions complementing surgery as part of multistage treatment for hypoplastic left heart syndrome: one center's experience.

BACKGROUND: Interventional procedures often are used as part of multistage treatment for hypoplastic left heart syndrome (HLHS). This study aimed to evaluate the efficacy of interventions in multistage treatment of HLHS. METHODS AND RESULTS: Between 1999 and 2007, 78 interventions were performed for 58 children with HLHS at different stages of surgical treatment. Group 1, involving 30 interventions for 22 patients with postoperative pulmonary arterial stenosis, showed reduced pulmonary artery pressure and increased vessel diameter. Group 2, involving 15 interventions after the Norwood operation for 12 patients with aortic arch obstruction, showed success for 11 patients. Group 3, involving eight balloon angioplasties of narrowed Glenn anastomosis for seven patients, showed abolition of the pressure gradient between the superior vena cava and the right pulmonary artery. Group 4, involving eight interventional closures of a fenestration for eight patients after a Fontan operation, showed increased oxygen saturation for all eight patients. Group 5, involving seven interventions for six patients in whom venovenous collaterals were closed percutaneously, showed improved oxygen saturation. For Group 6, uncommon miscellaneous interventions were used to stabilize the patients' condition before the next surgical treatment. CONCLUSIONS: Interventional procedures play an important role during multistage treatment of HLHS. They allow for a reduction in the number of operations or stabilization of the patients' condition before the next surgical treatment.

A crescent-shaped spindle for improved dissolution testing.

Current practices of drug dissolution testing require that the experimental conditions, such as medium and its volume and apparatus and its associated stirrer rotation speed, be established for each test product to achieve certain 'expected' dissolution characteristics or results. In reality, however, the purpose of dissolution testing should be to determine potentially unknown dissolution results reflective of a test product based on its formulation and/or manufacturing attributes. For appropriate testing, in particular for comparative purposes, the experimental conditions must be the same or consistent from product to product i.e. product independent. This article describes a newly developed spindle, known as crescent-shaped, which can easily be installed in the vessel-based dissolution apparatuses (basket and paddle) to provide a product-independent dissolution testing approach for improved drug dissolution assessments. The new spindle provides an improved stirring and mixing environment, leading to better characterization of pharmaceutical products. The use of the crescent-shaped spindles offers additional significant advantages over the current practices, such as: (1) allows analyses using a single method, compared to hundreds as currently required, for both immediate and extended-released products having the same or different active ingredients; (2) provides improved dissolution characteristics of products by avoiding false slow release properties for fast release type products; (3) simplifies testing by avoiding the necessity of developing separate QC and bio-relevant dissolution methods; (4) provides a rugged testing environment free from common sensitivities, in particular to de-aeration and vibration effects. Considering that the new design provides significant advantages, the spindle may be considered for inclusion in the Ph. Eur., as an option, in the general chapter on dissolution testing.

Use of the Amplatzer muscular ventricular septal defect occluder for closure of perimembranous ventricular septal defects.

BACKGROUND: Transcatheter closure of a perimembranous ventricular septal defect (PmVSD) is usually performed with an asymmetric Amplatzer occluder, which is not an ideal device. Experience with the use of the Amplatzer muscular ventricular septal defect occluder (MVSO) to close selected PmVSDs is presented. SETTING: Two tertiary referral centres for paediatric cardiology in two countries. OBJECTIVE: To look at the safety and efficacy of the application of the MVSO in patients with appropriate PmVSD anatomy. PATIENTS AND INTERVENTION: The procedure was performed in 10 patients aged 3.2-40 (mean 12.5) years. All had a PmVSD with a mean diameter of 5.4 (range 4-11) mm, with an extension towards the muscular septum. The mean distance of the defect from the aortic valve was 5.4 (range 4-6) mm. In all but one patient, the MVSO was introduced in routine antegrade transvenous fashion (4-mm device in one patient, 6-mm device in five, 8 mm in two, 10 mm in one, and 12 mm in one). In one patient, the device was deployed by retrograde implantation. RESULTS: All procedures except one were performed without complications, and complete closure of the VSD was achieved. One patient with a residual shunt developed haemolysis, which resolved over 10 days. In three patients, trivial, non-progressive tricuspid regurgitation appeared after the procedure. No other complications were observed over 1.7 (range 0.2-3.5) years of follow-up. CONCLUSION: Application of the MVSO for closure of selected PmVSDs seems to be a safe and effective treatment option.

Managed Care Network for the assessment of cardiac problems in children in a district general hospital: a working model.

AIM: To assess a model for cardiology assessments in children with suspected heart disease by a general paediatrician with special expertise in paediatric cardiology (PsePC) in a district general hospital. METHODS: A new monthly "screening" clinic was established in May 2004 by the PsePC to reduce the burden of new referrals on outreach tertiary paediatric cardiology services. All patients were to have echocardiograms as part of their referral for cardiac assessment. Over a one year period (May 2004-April 2005), through audit, details of referrers, indications for referral, echocardiography assessments, and subsequent management were recorded. This was compared with the pattern of patients seen in the joint paediatric cardiology outreach clinics over a two year period (May 2003-April 2005). RESULTS: In the "screening" clinic, there were 75 appointments for 65 patients seen in 12 months. Fifty five of these patients had normal echocardiographic studies. Of the 47 referrals with heart murmurs in asymptomatic children, four had structurally abnormal hearts on echocardiographic assessment. Between May-October 2003 and November 2003-April 2004, the number of new patients with normal echocardiographic studies seen in the paediatric cardiology outreach clinic was 33/106 (31%) and 28/110 (25.4%) respectively. Following the introduction of the "screening" clinic, the number decreased to 21/99 (21%) during May-October 2004, and 10/102 (9.8%) during November 2004-April 2005. CONCLUSION: This model can work effectively in order to identify pathology requiring input of a paediatric cardiologist more appropriately. Paediatricians with specific training in paediatric cardiology are potentially well equipped to provide this basic screening service.

Complications of transcatheter closure of atrial septal defects.

Transcatheter device closure of atrial septal defects has proved to be remarkably successful, and is usually preferred by both patients and parents. But how does it compare with the gold standard of surgical closure?

Rapid evolution of right ventricular cardiomyopathy after surgical closure of a secundum atrial septal defect.

Rapidly developing diffuse right ventricular cardiomyopathy presenting with right heart failure in a 9-year-old boy within 2 months after surgical closure of a secundum atrial septal defect is reported. The child was treated by palliative surgery with partial exclusion of the right ventricle by bidirectional Glenn shunt.

Three- and four-dimensional reconstruction of intra-cardiac anatomy from two-dimensional magnetic resonance images.

The present study was designed to evaluate the feasibility and clinical usefulness of three-dimensional (3D) reconstruction of intra-cardiac anatomy from a series of two-dimensional (2D) MR images using commercially available software. Sixteen patients (eight with structurally normal hearts but due to have catheter radio-frequency ablation of atrial tachyarrhythmias and eight with atrial septal defects (ASD) due for trans-catheter closure) and two volunteers were imaged at 1T. For each patient, a series of ECG-triggered images (5 mm thick slices, 2-3 mm apart) were acquired during breath holding. Depending on image quality, T1- or T2-weighted spin-echo images or gradient-echo cine images were used. The 3D reconstruction was performed off-line: the blood pools within cardiac chambers and great vessels were semi-automatically segmented, their outer surface was extracted using a marching cube algorithm and rendered. Intra- and inter-observer variability, effect of breath-hold position and differences between pulse sequences were assessed by imaging a volunteer. The 3D reconstructions were assessed by three cardiologists and compared with the 2D MR images and with 2D and 3D trans-esophagal and intra-cardiac echocardiography obtained during interventions. In every case, an anatomically detailed 3D volume was obtained. In the two patients where a 3 mm interval between slices was used, the resolution was not as good but it was still possible to visualize all the major anatomical structures. Spin-echo images lead to reconstructions more detailed than those obtained from gradient-echo images. However, gradient-echo images are easier to segment due to their greater contrast. Furthermore, because images were acquired at least at ten points in the cardiac cycles for every slice it was possible to reconstruct a cine loop and, for example, to visualize the evolution of the size and margins of the ASD during the cardiac cycle. 3D reconstruction proved to be an effective way to assess the relationship between the different parts of the cardiac anatomy. The technique was useful in planning interventions in these patients.

The efficacy and safety of stent redilatation in congenital heart disease.

OBJECTIVES: To assess the extent of neointimal proliferation and the safety and efficacy of stent redilatation in patients with stents implanted for aortic coarctation or branch pulmonary artery stenosis. DESIGN: Retrospective observational study. SETTING: Tertiary referral centre. PATIENTS AND INTERVENTIONS: Of 60 patients with Palmaz stents, 12 with coarctation and 12 with branch pulmonary artery stenosis (with 21 stented sites) underwent recatheterisation and stent redilatation. RESULTS: Neointimal thickening > 1 mm was detected in six of the 12 coarctation stents and at nine of the 21 stented sites in branch pulmonary arteries (five of which had been overdilated at implantation). Eight of the coarctation stents were electively underdilated at implantation. Coarctation stent redilatation increased median (range) lumen diameter from 9.2 (6.3-11.1) mm to 11.7 (9.8-14.1) mm (p = 0.002), decreased gradient from 10.5 (0-20) mm Hg to 0.5 (0-15) mm Hg (p = 0.008), and increased the ratio of stent diameter to descending aorta diameter from 0.66 (0.38-1.02) to 0.85 (0.52-1.2) (p = 0.008). Pulmonary artery stent redilatation increased lumen diameter from 6.9 (3.8-13.5) mm to 8.8 (4.8-14.1) mm (p < 0.001), decreased gradient from 24 (2-62) mm Hg to 12 (0-29) mm Hg (p < 0.001), and increased the ratio of stent diameter to diameter of distal pulmonary artery from 0.66 (0.44-1.5) to 0.86 (0.48-1.88) (p = 0.001). Dilatation of one peripheral pulmonary artery stent resulted in rupture of the vessel distal to the stent. CONCLUSIONS: Neointimal proliferation is precipitated by overdilating stents at implantation. Redilatation using balloons matched to distal vessel diameter increases stent lumen size, but may not optimise vessel diameter. Redilatation is effective whether the indication for redilatation is a resistant stenosis at implantation, underexpansion at implantation, neointimal proliferation, or relative stenosis caused by growth.

Closure of aortopulmonary window with amplatzer duct occluder device.

Aortopulmonary window is a relatively uncommon congenital heart defect. We report on a patient with a small aortopulmonary window, who presented with an asymptomatic murmur and in whom catheter closure was successfully performed with an Amplatzer Duct Occluder.