Foreign body in tracheobronchial tree

Inhalation of foreign body into the tracheobronchial tree is a medical emergency sometimes resulting into sudden death. The current mortality rate due to foreign body inhalation ranges from 0% to 1.8%. Children with or without positive history of aspiration were examined and diagnosis was made on the basis of history, clinical findings, radiological evaluation and strong index of suspicion. A review of 30 cases of suspected foreign body aspiration revealed, children between 6 months were found to be very vulnerable to aspiration. Majority of children were boys. 80% of the patients had positive history of inhalation. Only 50% of the patients presented immediately i.e. within 24 hours after aspiration. Common symptoms were cough and respiratory distress. Decreased air entry was the significant clinical sign (50%). Obstructive emphysema and mediastinal shift were found in the majority of cases (50%). Rigid bronchoscopy under general anaesthesia and patient ventilating using a jet ventilator is a very safe and effective technique.     

The role of coronary angioplasty and stenting in acute myocardial infarction

Despite the improvements in the pharmacological treatment of acute myocardial infarction, it is recognised that thrombolysis fails to reproduce reperfusion in a significant proportion of patients. Coronary interventional techniques have been shown to offer an alternative reperfusion strategy. There is increasing evidence that mechanical reperfusion may offer significant advantages over established thrombolytic therapy.     

Structural requirements for novel willardiine derivatives acting as AMPA and kainate receptor antagonists

1. The natural product willardiine is an AMPA receptor agonist. We have examined the structural changes required to convert willardiine into an antagonist at AMPA and kainate receptors. Structure-activity analysis has been carried out to discover the structural features required to increase the potency and/or selectivity of the antagonists at AMPA or kainate receptors. 2. Reduction of the fast component of the dorsal root-evoked ventral root potential (fDR-VRP) has been used to investigate AMPA receptor antagonist activity. To examine antagonist activity at kainate receptors, the ability of compounds to depress kainate-induced depolarisations of dorsal root fibres was assessed. 3. Blocking ionisation of the uracil ring by adding a methyl group to the N(3) position was not sufficient to convert willardiine into an antagonist. However, willardiine derivatives with a side-chain bearing a carboxylic acid group at the N(3)-position of the uracil ring could antagonise AMPA and kainate receptors. 4. S stereochemistry was optimal for antagonism. When compounds with differing interacidic group chain lengths were compared, a group chain length of two methylene groups was preferable for AMPA receptor antagonism in the series of compounds bearing a carboxyalkyl side chain (UBP275, UBP277 and UBP279 reduced the fDR-VRP with IC(50) values of 287+/-41, 23.8+/-3.9 and 136+/-17 micro M, respectively). For kainate receptor antagonism, two or three methylene groups were almost equally acceptable (UBP277 and UBP279 reduced dorsal root kainate responses with apparent K(D) values of 73.1+/-4.5 and 60.5+/-4.1 micro M, respectively). 5. Adding an iodo group to the 5-position of UBP277 and UBP282 enhanced activity at kainate receptors (UBP291 and UBP301 antagonised kainate responses on the dorsal root with apparent K(D) values of 9.83+/-1.62 and 5.94+/-0.63 micro M, respectively). 6. The most useful antagonist identified in this study was UBP301, which was a potent and approximately 30-fold selective kainate receptor antagonist. UBP282 may also be of use in isolating a non-GluR5-mediated kainate response.     

Multiple melanomas after treatment for Hodgkin lymphoma in a non-Dutch p16-Leiden mutation carrier with 2 MC1R high-risk variants

BACKGROUND: A 19-base pair germline deletion in exon 2 of the CDKN2A (cyclin-dependent kinase inhibitor 2A) gene (Leiden mutation) has been detected in Dutch families with familial melanomas. The penetrance of CDKN2A mutations varies widely and is influenced by environmental and unrelated genetic factors such as variants in the MC1R gene. OBSERVATIONS: We describe a 25-year-old German woman who developed 8 invasive melanomas and 6 in situ melanomas after radiation therapy and polychemotherapy for Hodgkin lymphoma. Genetic testing revealed a constitutional CDKN2A Leiden mutation in the proband and her sister, mother, and mother's sister. The proband also carried high-risk MC1R variant alleles R151C and R160W, which she had inherited from her father and her mother, respectively. The less affected mutation carrier sister did not have high-risk MC1R variant alleles. Analysis of DNA from paraffin-embedded tissues showed loss of heterozygosity at CDKN2A loci in all 3 melanomas studied but not in Hodgkin lymphoma. The pedigree revealed several types of cancers on both sides of the family, but no Dutch ancestors were found. No mutations in the CDK4, B-raf, and N-ras genes were detected either in the germline or in tumors from the patient. CONCLUSION: This study shows the variability of the penetrance of the CDKN2A Leiden mutation within the same family, which could be due to genetic or exogenous factors.     

Retrograde non trans‐septal balloon mitral valvotomy in mitral stenosis with interrupted inferior vena cava,left superior vena cava,and hugely dilated coronary sinus

A 22‐year‐old woman with severe mitral stenosis was referred to us for further evaluation and management. She was found to have severe mitral stenosis, severe tricuspid regurgitation with dilated right atrium and right ventricle with persistent left superior vena cava and hugely dilated coronary sinus. Valve was suitable for balloon mitral valvotomy. Cardiac catheterization showed interrupted inferior vena cava with azygos continuation to right atrium and large left superior vena cava draining to coronary sinus which was very much dilated. Right trans‐jugular approach was tried for balloon mitral valvotomy, but was unsuccessful due to a very large right atrium and coronary sinus. Retrograde non trans‐septal approach was used and balloon valvotomy was done successfully using a 24 mm × 40 mm TYSHAK balloon without any major complication. Reduction in the transmitral pressure gradient on cardiac catheterization data and transthoracic echocardiography confirmed successful procedure. Balloon mitral valvotomy can be done successfully in patients with the above unusual cardiac anatomy with no major procedural complications. © 2015 Wiley Periodicals, Inc.     

Effect of patent ductus arteriosus on the heart in preterm infants

There continues to be controversy on the long‐term effects of a patent ductus arteriosus (PDA) and its management. However, the hemodynamic effects of a large PDA in a preterm infant are well known. This article aims to provide insight into the adaptive changes and remodeling effects of a PDA on the myocardium in preterm infants.     

How is the risk of being diagnosed with referable diabetic retinopathy affected by failure to attend diabetes eye screening appointments?

Background/AimsThis study examines the anecdotal impression that in diabetes eye screening there is a relationship between number of consecutive missed screening appointments and the incidence of referable retinopathy at the next screening appointment that is attended.MethodsA retrospective observational audit was conducted of data from 62,067 people who were due for annual diabetes eye screening in the North East London Diabetes Eye Screening Programme between January 2010 and January 2017, and who had missed at least one screening appointment within that time.ResultsMissing 5 consecutive screening appointments increased the incidence of referable retinopathy from a programme average of 4% up to 15%. The incidence of referable retinopathy in people missing 10 or more consecutive appointments was ~20%. There was an association between younger age, male gender, type I disease, and being of African ethnicity with increasing number of missed appointments.ConclusionsThere was a strong association between the number of missed appointments and the proportion of patients showing referable retinopathy at the next visit. Approaches to reduce the number of missed appointments may help to reduce the incidence of referable retinopathy. These may be targeted at those showing the greatest non-attendance behaviour in the current study.Subject terms: Diabetes complications, Health services     

Melanocortin receptor 1 variants and melanoma risk: A study of 2 European populations

Variation within the melanocortin receptor 1 (MC1R) gene, that influences phenotypic traits and susceptibility to melanoma, is abundant across the populations. We assessed and compared the risk of melanoma in 2 European populations, German and Spanish, by genotyping MC1R variants through direct DNA sequencing from 1,185 melanoma cases and 1,582 controls. The presence of any variant in both populations was associated with a significantly increased risk of melanoma (odds ratio OR = 1.67, 95% confidence interval CI 1.40–1.99). The population attributable fractions (PAF) associated with the MC1R variants in both populations was over 25%. However, the results showed a statistically significant (p < 0.0001) higher frequency of MC1R variants in the German (70%) than in the Spanish population (60%). The red‐hair colour (RHC) variants, though associated with increased risk in both populations, were more common in the German than in the Spanish population (p < 0.0001). Interestingly, non‐RHC variants increased the disease risk in the Spanish (OR = 1.60, 95% CI 1.20–2.14) but not in the German population (OR = 1.07, 95% CI 0.80–1.44). Although RHC variants explained a major proportion of the observed PAF in the German population, in the Spanish population the major contributor to the PAF was the non‐RHC V60L variant. We also observed reduced historic linkage disequilibrium between the variants V92M and T314T in the gene in German melanoma cases. In conclusion, our data underscored the unambiguous importance of the MC1R variants towards the population burden of melanoma. However, the variants that are associated with the disease differ between the investigated populations. © 2009 UICC     

Data quality and clinical audit

Clinical audit has an increasingly important role in the quality of care being offered to patients. Only good-quality data can enable valid conclusions to be drawn, which in turn enable changes to be made for the better. More and more patient data are held on NHS computer systems, and increasingly these data are being used to facilitate the audit process. The quality of any such data needs to meet the highest standards. This article briefly defines the audit cycle and goes on to consider a typical data model. The various elements of the data model are defined, the understanding of which should enable individuals to avoid pitfalls in data collection and ensure that the data they collect for clinical audit are of the highest quality.     

Anti-thrombotic therapy for non-rheumatic atrial fibrillation

Recent randomized trials of antithrombotic therapy in non-rheumatic atrial fibrillation have helped to clarify the benefits of warfarin and aspirin. Low-risk patients (normotensives aged &lt;60 with normal left ventricular function) have a small risk of thromboembolic events and are unlikely to benefit significantly from anticoagulants, but may benefit from aspirin with little increase in risk of bleeding. High-risk patients (&gt;75 years, impaired left ventricular function, previous thromboembolism and/or associated conditions such as hypertension and diabetes mellitus) have an increased risk of thromboembolism, and benefit from long-term anticoagulant therapy to a greater degree than with aspirin, although at a risk of increased bleeding complications.