Recurrent asthma exacerbations: co-existing asthma and common variable immunodeficiency.

Common variable immunodeficiency is characterized by impaired B-cell differentiation and defective immunoglobulin production manifesting as recurrent respiratory tract infections. While the condition can masquerade as asthma, late diagnosis of CVID in known asthmatic is rarely reported.We present the case of a 43-year-old lady with recurrent episodes of wheeze, cough, sinusitis and multiple lower respiratory tract infections. Transiently responsive to antibiotics and steroids. These episodes had been occurring for many years and she had a longstanding clinical diagnosis of asthma.As part of her work up for recurrent respiratory tract infections a CT thorax was performed and demonstrated bronchiectasis. Further tests including Immunoglobulin levels revealed critically low IgG, IgM, and IgA levels. Immunoglobulin replacement therapy was commenced with a reduction in exacerbation frequency and severity, and objective improvement of asthma control. Subsequent lung function tests demonstrated reversible airflow limitation (obstructive lung function with 13% reversibility in FEV1 post-bronchodilator) consistent with asthma.Our case illustrates the importance of searching for alternate and co-existent diagnoses in patients diagnosed with asthma who are unresponsive to conventional therapy. We believe that serum immunoglobulin measurement should form a component of such a workup.

Interactions between Plagiotremus spp., Labroides dimidiatus and their clients: evidence for behavioural niche partitioning.

This study employed community analysis and behavioural field observations to explore the inter-specific interactions between fangblenny species (Plagiotremus spp.), the cleaner wrasse Labroides dimidiatus and their target species and found that the presence of Plagiotremus spp. did not affect the total amount that L. dimidiatus cleaned but it did reduce the amount L. dimidiatus cleaned key prey species of the Plagiotremus spp. The behavioural interactions between adult L. dimidiatus and their clients changed in response to the presence of Plagiotremus spp., but the results suggested the potential cost of Plagiotremus spp. on L. dimidiatus may be offset by behavioural niche partitioning.

Comparison of cold knife cone biopsy and loop electrosurgical excision procedure in the management of cervical adenocarcinoma in situ: What is the gold standard?

OBJECTIVE: To compare the outcomes of patients with cervical adenocarcinoma in situ (ACIS) treated with cold knife cone (CKC) biopsy or loop electrosurgical excision procedure (LEEP) for the treatment of cervical adenocarcinoma in situ (ACIS). STUDY DESIGN: This is a retrospective, population-based cohort study of Western Australian patients with ACIS diagnosed between 2001 and 2012. Outcomes included pathological margin status and the incidence of persistent or recurrent endocervical neoplasia (ACIS and adenocarcinoma) during follow-up (<12 months) and surveillance (≥12 months) periods. RESULTS: The study group comprised 338 patients including 107 (32%) treated initially by LEEP and 231 (68%) treated by CKC biopsy. The mean age was 33.2 years (range 18 to 76 years) and median follow-up interval was 3.6 years (range <1 year to 11.8 years). Overall, 27 (8.0%) patients had ACIS persistence/recurrence while 9 (2.7%) were diagnosed with adenocarcinoma during the follow-up and surveillance periods. No patient died of cervical cancer within the study period. There were no significant differences in the incidence of persistent and/or recurrent endocervical neoplasia according to the type of excisional procedure. Patients with positive biopsy margins were 3.4 times more likely to have disease persistence or recurrence. CONCLUSION(S): LEEP and CKC biopsy appear equally effective in the treatment of ACIS for women wishing to preserve fertility. Patients undergoing conservative management for ACIS should be closely monitored, particularly if biopsy margins are positive in initial excision specimens. Patients and their clinicians should be aware of the potential risks of residual and recurrent disease.

A new approach for the automatic evaluation of the solidification structure in steel using orientational entropy filtering.

We present a new method for the automatic evaluation of the dendritic solidification structure in metallurgical micrographs of solidified steel. The evaluation of the microstructural parameters such as the primary dendrite arm spacing and the primary grain size are of high importance due to their direct relationship with the internal quality and mechanical properties of the cast product. Given the repeated geometric features in the micrographs and the regular pattern in colour intensity, we applied a filter mask to determine the local entropies within the masks in order to detect the centre coordinates of each individual dendrite. The orientation of the dendrites was determined by rotating the filter mask over each pixel to find the orientation which corresponds to the lowest entropy value. The segmentation of the microstructure was then performed via Delaunay tessellation and subsequent transformation of the triangular mesh into a rectangular grid, enabling the determination of the desired microstructural parameters.

Mesenteric vasculitis in adults with Henoch-Schonlein purpura: a not-so-benign condition.

INTRODUCTION: The gastrointestinal manifestations of Henoch-Schonlein purpura (HSP) are well characterised, but their recognition can be difficult when they occur in isolation. Furthermore, HSP can run a more serious course in adults, compared to children, in whom the disease usually occurs. MATERIALS AND METHODS: We describe two cases that illustrate the challenges of HSP with mesenteric vasculitis and the outcome in adults. CONCLUSION: Although self-limiting in most patients, the outcome of HSP in adults can be far from benign and even fatal.

The impact of single gene and chromosomal disorders on hospital admissions of children and adolescents: a population-based study.

BACKGROUND: It is well recognized that genetic disease makes a significant contribution to childhood illness. Here, we present recent population data describing the impact of single gene and chromosomal disorders on hospital admissions of children and adolescents. METHODS: Hospital admissions for patients aged 0-19 years between 2000 and 2006, with a single gene or chromosomal disorder, were extracted from the Western Australian Hospital Morbidity Data System using 296 diagnosis codes identified from the International Statistical Classification of Diseases, Tenth Revision, Australian Modification. Data extracted for each patient included the number, length and cost of all admissions. RESULTS: Between 2000 and 2006, 14,197 admissions were identified for 3,271 patients aged 0-19 years with single gene and chromosomal disorders, representing 2.6% of admissions and 4.3% of total hospital costs in this age group. Patients with genetic disorders had more admissions and stayed longer in hospital than patients admitted for any reason. Specific disorders associated with a high demand on hospital services included cystic fibrosis, Down syndrome, osteogenesis imperfecta, thalassemia, and von Willebrand's disease. CONCLUSIONS: Children and adolescents with single gene and chromosomal disorders placed higher demands on hospital services than other patients in their age group, but were responsible for a relatively small proportion of hospital admissions and costs. These data will enable informed planning of health care services for patients with single gene and chromosomal disorders in Western Australia.

Australian study on public knowledge of human genetics and health.

AIMS: This study was designed to obtain data on public understanding of genetic concepts in the adult population of Western Australia. It explored knowledge of genetic risk of disease, inheritance, biology, determinism, and factors that predict relatively higher genetic knowledge within the general population. METHOD: A cross-sectional telephone survey of 1,009 respondents. RESULTS: Most members of the Western Australian community are aware of basic genetic concepts and the link between genes, inheritance, and risk of disease. Significantly fewer understand the biological mechanisms underlying these concepts and there was some misconception around the meaning of 'increased genetic risk'. The odds of higher genetic knowledge (>19 out of 24 questions correct) were greater among those with 12 years or more education (OR = 3.0), those aged 18-44 years (OR = 2.3), women (OR = 2.0), those with annual household income of AUD 80,000 or more (OR = 1.8), and those who had talked with someone (OR = 1.7) or searched the internet (OR = 1.6) for information on genes and health. CONCLUSIONS: This study provides evidence of an association between social location and public knowledge of human genetic concepts related to health and disease. This is consistent with previous findings and raises questions about the acquisition of textbook genetics knowledge within socio-cultural contexts. The impact of misconceptions about genetic concepts on the uptake of preventive health behaviors requires further investigation, as does the level of genetics knowledge that is required to empower informed participation in individual and societal decisions about genetics and health.

Australia: public health genomics.

Australia has a multicultural society that has arisen from continuing migration. While the population is relatively small, just over 20.7 million, it is genetically diverse and is spread over a large land mass. The federal system of government is democratic, based on states and territories, and there is a socialized healthcare system, in which public and private models operate in parallel. Clinical genetics services are publicly funded by State Departments of Health, rather than by the Commonwealth Government, with the model of service provision varying from state to state. Each of these factors has important implications for the effective delivery of genetic screening programs and clinical genetic services that meet the needs of all Australians. Population genetic screening occurs throughout Australia predominantly as newborn screening programs and to identify pregnancies at risk of chromosomal and neural tube defects, while carrier screening programs are essentially ad hoc. Despite inevitable tensions between federal and state policies, there is increasing evidence of the development of national policy in a range of genetic issues, not least in newborn screening, genetic testing, and health professional education. However, further work is necessary to establish frameworks for the regulation and funding of new genetic tests across state/federal boundaries, which will be crucial to the establishment of a national approach to public health genomics policy.

Economic evaluation of the familial cancer programme in Western Australia: predictive genetic testing for familial adenomatous polyposis and hereditary non-polyposis colorectal carcinoma.

AIM: To evaluate costs and outcomes of genetic testing for familial colorectal cancer through services provided by Genetic Services of Western Australia (GSWA). METHODS: Costs and outcomes of predictive DNA-based testing for inherited colorectal cancers (CRC) were assessed, specifically for familial adenomatous polyposis (FAP) and hereditary non-polyposis CRC (HNPCC) using a decision-analysis model. Costs were assigned according to standards of care in Western Australia (WA). Cancer risks and the efficacy of surveillance on long-term outcomes were derived from the published literature. RESULTS: The cost-effectiveness of genetic testing was compared in first-degree relatives of known mutation carriers who have a 50% risk of carrying the mutated gene (intervention group) to individuals with the same risk but who do not undergo a genetic test (control subjects). Compared with control subjects undergoing the same high-level surveillance and surgery, the FAP and HNPCC intervention groups provided total savings of 13,390 US dollars and 14,783-15,460 per person (males-females), respectively. HPNCC mutation carriers also gained 1 CRC-free year. Compared to control subjects having only population surveillance, individuals in the FAP intervention group delayed the onset of CRC by 40 years for a net cost of 9,042 US dollars. Individuals in the HNPCC intervention group delayed the onset of CRC by 8 years at a net cost of 12,141 US dollars for males and 12,596 US dollars for females. CONCLUSIONS: Genetic testing for familial CRC in WA allows targeted surveillance for mutation carriers, which ensures the efficient use of resources and reduces cancer-related morbidity, if clinical recommendations for intervention are adopted.

Economic evaluation of neonatal screening for phenylketonuria and congenital hypothyroidism.

OBJECTIVE: To evaluate the costs and benefits of neonatal screening for phenylketonuria (PKU) and congenital hypothyroidism (CH). Neonatal screening for PKU and CH is common throughout the developed world. It represents a model of preventive care in that the screening procedure is simple and intellectual disability is otherwise irreversible. Changes in treatment and care, and in particular the advent of maternal PKU, require regular evaluation of a programme that also impacts on a large healthy population. METHOD: Costs of screening were based on the programme provided within Western Australia. Costs averted were derived using patterns of care currently adopted in Western Australia and applied according to historical patterns of intellectual disability for each condition. RESULTS: A net saving of dollar A2.9 million is attributable to the programme annually. The economic benefits derive from the prevention of intellectual disability which otherwise incurs costs throughout the life of the affected individual. Maternal PKU represented a minor proportion of overall costs. Sensitivity analysis showed that the cost savings were robust, given changes in the levels of intellectual disability, but varied according to the discount rate. The result of a net saving was evident under all assumptions. CONCLUSION: Neonatal screening for PKU and CH is a cost saving use of resources and the emergence of maternal PKU has not had a significant effect on the economic outcomes.

Predicting baseline laparoscopic surgery skills.

BACKGROUND: Laparoscopic surgery requires specialized dexterity even beyond that required for open surgery. Decreased tactile feedback, different eye-hand coordination, and translation of a two-dimensional video image into a three-dimensional working area are just some of the obstacles in the performance of laparoscopic surgery. Possession of certain nonsurgical skills may help in overcoming some of these obstacles. Prediction of baseline laparoscopic surgery skills may help further to refine the education of basic laparoscopic surgery skills. This investigation explores whether nonsurgical skills and demographic data can predict baseline laparoscopic surgery tasks. METHODS: First- and second-year students were given a survey regarding nonsurgical dexterity skills. The survey inquired about typing skills, play with computer games, ability to sew, skill with music instruments, use of chopsticks, and experience operating tools. Demographic data were requested as well. All the students underwent four tasks: placing a piece of bowel in a retrieval bag, placing a stapler on the bowel, measuring a piece of bowel, and performing a liver biopsy in a porcine animal model. Both objective (time and error) and subjective evaluation were assessed for all the tasks. Statistical analysis using analysis of variances (ANOVA) Kruskal-Wallis test with post hoc tests, two-tailed unpaired t-tests/Mann-Whitney test, and Fischer's exact tests/chi-square tests was performed when appropriate. RESULTS: There were 68 students in this investigation. Gender, medical student year, ethnicity, desire to enter a surgical field, and age were not associated with increased performance in any of the tasks. Chopstick use was associated with statistically significantly better mean time in placing a piece of bowel in a retrieval bag and measuring a piece of bowel (p < 0.04). The other nonsurgical dexterity skills did not statistically increase performance, as indicated by time, errors, or subjective scores, for the four tasks. CONCLUSIONS: It is difficult to predict baseline laparoscopic surgery skills.

Role of amiodarone in the treatment of fetal supraventricular tachyarrhythmias and hydrops fetalis.

We report three consecutive hydropic fetuses with fetal tachyarrhythmias treated with amiodarone-two in combination with digoxin and one with digoxin, procainamide, and propranolol. Sinus rhythm was achieved in one case and ventricular rate control was achieved in two cases. All fetuses treated with amiodarone gradually improved. Observed side effects of amiodarone were a maternal rash in one mother and transient neonatal hypothyroidism in one infant. We conclude that amiodarone might be effective and safe for fetal tachyarrhythmias and impending hydrops. The small number of patients suggests that a multicenter cooperative approach is required in order to determine if this is correct.

Subcutaneous glucose sensor values closely parallel blood glucose during insulin-induced hypoglycaemia.

AIMS: To assess the accuracy of the Minimed continuous glucose monitoring system (CGMS) in estimating blood glucose concentration during a controlled reduction in blood glucose. RESEARCH DESIGN AND METHODS: We studied nine adolescent diabetics (age 14 +/- 1.5 years) wearing the CGMS during hyperinsulinaemic hypoglycaemic clamp studies. The glucose values obtained by the CGMS were compared with the venous blood samples taken during the studies and measured at the bedside using a glucose oxidase technique. RESULTS: Blood glucose was lowered from euglycaemia to a mean of 2.8 mmol/l over 120 min and maintained at that level for a further 40 min. A total of 429 paired glucose measurements were available for analysis. Analysis using weighted Deming regression and t-tests revealed small differences between the methods, with blood glucose levels slightly higher than interstitial fluid levels. The mean difference across all values was 0.13 mmol/l. The observed difference was greatest at blood glucose values < 3.3 mmol/l. CONCLUSIONS: This study suggests that during a fall in systemic glucose the subcutaneous glucose sensor provides an accurate reflection of blood glucose. However, a small difference is apparent at blood glucose values < 3.3 mmol/l.

Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur.

Although skeletal pain plays a major role in reducing the quality of life in patients suffering from osteoarthritis, Paget's disease, sickle cell anemia and bone cancer, little is known about the mechanisms that generate and maintain this pain. To define the peripheral fibers involved in transmitting and modulating skeletal pain, we used immunohistochemistry with antigen retrieval, confocal microscopy and three-dimensional image reconstruction of the bone to examine the sensory and sympathetic innervation of mineralized bone, bone marrow and periosteum of the normal mouse femur. Thinly myelinated and unmyelinated peptidergic sensory fibers were labeled with antibodies raised against calcitonin gene-related peptide (CGRP) and the unmyelinated, non-peptidergic sensory fibers were labeled with the isolectin B4 (Bandeira simplicifolia). Myelinated sensory fibers were labeled with an antibody raised against 200-kDa neurofilament H (clone RT-97). Sympathetic fibers were labeled with an antibody raised against tyrosine hydroxylase. CGRP, RT-97, and tyrosine hydroxylase immunoreactive fibers, but not isolectin B4 positive fibers, were present throughout the bone marrow, mineralized bone and the periosteum. While the periosteum is the most densely innervated tissue, when the total volume of each tissue is considered, the bone marrow receives the greatest total number of sensory and sympathetic fibers followed by mineralized bone and then periosteum. Understanding the sensory and sympathetic innervation of bone should provide a better understanding of the mechanisms that drive bone pain and aid in developing therapeutic strategies for treating skeletal pain.

Intracardiac echocardiography in congenital heart disease: are we ready to begin the fantastic voyage?

Advances in and miniaturization of echocardiographic technology have led to many new methods of examining cardiovascular malformations. Intracardiac echocardiography (ICE) has reached a point where a real impact on clinical medicine can be anticipated. Use of ICE guidance during electrophysiologic and some interventional catheterization procedures will probably become standard clinical practice in the near future. Current results in adults and potential application to and limitations in the pediatric population are discussed.

Early fracture of the sacrum or pelvis: an unusual complication after multilevel instrumented lumbosacral fusion.

STUDY DESIGN: A retrospective review of a series of cases with a complication of instrumented lumbosacral fusion. OBJECTIVES: To present a previously undescribed complication, early sacral or pelvic stress fracture, after instrumented lumbosacral fusion and to identify the risk factors associated with this complication. BACKGROUND: There are a number of well-described complications of instrumented lumbosacral fusion, including delayed stress fracture of the pelvis. Early sacral or pelvic stress fracture after instrumented lumbosacral fusion has not been previously reported, to the authors' knowledge. METHODS: The authors present three cases of early stress fracture occurring at 2-4 weeks after surgery in patients who underwent instrumented multilevel lumbosacral fusions for degenerative lumbosacral disease. RESULTS: Two patients had sacral fracture, which to the authors' knowledge, has not been previously reported. Risk factors included lumbosacral instrumentation and fusion, osteoporosis in elderly women, and iliac crest bone graft procurement. All patients were treated conservatively, with restricted ambulation and gradual return to activity. CONCLUSION: This complication can cause significant morbidity and a delay in the patient's return to function. A better understanding of the related biomechanical forces and preoperative risk factors may identify patients at risk and may aid in surgical planning and in expectations of postoperative recovery.

Dynamic equilibria in the products of intramolecular Buchner additions of diazoketones to aryl rings bearing methoxy substituents.

Rhodium carboxylate catalyzed aromatic addition reactions of a range of diazoketones bearing methoxy-substituted aryl rings have been explored. While the existence of norcaradiene-cycloheptatriene equilibria in related compounds is well established, the aromatic addition products in this study display more complex dynamic equilibria due to conjugation with the methoxy group; the experimental evidence for this is discussed in detail. In the azulenone products 21-26 derived from p-methoxy-substituted diazoketones 14-16, the diastereomers interconvert via a spiro intermediate 39. A related mechanistic process in the azulenones 43-46 derived from the o-methoxy-substituted diazoketones 17, 18 interconverts regioisomers, explaining the conflicting reports for the regioselectivity of the cyclization of diazoketone 1. With the m-methoxy-substituted diazoketone 19, involvement of the methoxy group through a different pathway results in fragmentation of the azulenone to form the tetralone 47. With the azulenones 21-26 exclusive trapping of the norcaradiene associated with the less thermodynamically stable diastereomers in a cycloadduct with N-phenylmaleimide is observed. Due to the presence of the activating methoxy substituent on the aromatic ring, the aromatic addition reactions of the diazoketones studied were not very sensitive to the nature of the rhodium catalyst.

Decompressive surgery for typical lumbar spinal stenosis.

Between 1991 and 1992, 103 consecutive patients (average age, 65 years) underwent decompressive surgery for treatment of typical lumbar spinal stenosis. Clinical results at 1-year followup revealed that four patients had revision surgery. At 2- to 5-years followup, there were no additional revision surgeries. Two patients underwent revision surgery for a deep infection, and two underwent revision surgery for a superficial infection. Outcome results showed that 77 patients completed the questionnaire, 15 were lost to followup and 11 died. Postoperative results showed that 64 of 77 patients had no or mild pain, 72 of 77 patients stated that they were satisfied or somewhat satisfied with their overall results of surgery, and 73 of 77 were satisfied with pain relief. Younger patients had greater improvement in function and a greater reduction in severity scores. However, satisfaction was similar in both groups. Survivorship results (failure was revision surgery) showed at the end of 4 years, a patient had a 95% chance of not having revision surgery. Statistically, there was no association between outcome and cofactors such as scoliosis, spondylolisthesis, number of levels decompressed, discectomy, or smoking. Satisfaction rates for older patients were similar to patients younger than 65 years although physical function scores and severity scores were less.

Decompression, fusion, and instrumentation surgery for complex lumbar spinal stenosis.

Between 1990 and 1993, 54 consecutive patients were treated with decompression, fusion and instrumentation surgery for complex lumbar spinal stenosis. The mean age of the patients was 60 years. The average followup was 39 months. Clinically, there was one deep wound infection, and three mechanical failures. There were two staged operations. There were three revision surgeries performed for mechanical reasons. Of the 47 patients who completed the questionnaire, 96% of patients were very satisfied or somewhat satisfied with the operation, 98% were satisfied with relief of pain, 94% were satisfied with their ability to walk, 89% were satisfied with their strength, and 94% were satisfied with balance. Survivorship analysis (failure endpoint was revision surgery) revealed that at the end of 4 years, the patient had a 92% chance of not undergoing revision surgery for any reason (mechanical and infectious), and a 94% chance of not undergoing revision surgery for mechanical reasons. Lumbar decompression, fusion, and instrumentation surgery seems to be efficacious in patients with complex lumbar spinal stenosis (associated previous lumbar spine operations with evidence of radiographic instability, radiographic evidence of junctional stenosis after surgery, radiographic evidence of instability, degenerative spondylolisthesis greater than Grade I with instability, if present, and degenerative scoliosis with a curve greater than 20 degrees).

Distraction laminoplasty for decompression of lumbar spinal stenosis.

Distraction laminoplasty is a technical modification of routine laminectomy that allows decompression of the lumbar spinal canal with maximal bone preservation. The technique involves the application of a distraction force, in conjunction with an undercutting laminoplasty technique. It is safe, easily applied, and allows excellent canal visualization and decompression with minimal bone resection. The purpose of the current study is to describe the technical aspects of the technique.