Showing papers by "Royal Devon and Exeter Hospital published in 2008"

Human CHN1 Mutations Hyperactivate α2-Chimaerin and Cause Duane's Retraction Syndrome

Abstract: Duane9s retraction syndrome (DRS) is a complex congenital eye movement disorder caused by aberrant innervation of the extraocular muscles by axons of brainstem motor neurons. Studying families with a variant form of the disorder (DURS2-DRS), we have identified causative heterozygous missense mutations in CHN1, a gene on chromosome 2q31 that encodes α2-chimaerin, a Rac guanosine triphosphatase–activating protein (RacGAP) signaling protein previously implicated in the pathfinding of corticospinal axons in mice. We found that these are gain-of-function mutations that increase α2-chimaerin RacGAP activity in vitro. Several of the mutations appeared to enhance α2-chimaerin translocation to the cell membrane or enhance its ability to self-associate. Expression of mutant α2-chimaerin constructs in chick embryos resulted in failure of oculomotor axons to innervate their target extraocular muscles. We conclude that α2-chimaerin has a critical developmental function in ocular motor axon pathfinding.

A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine.

Abstract: Introduction: Genetic factors influence circulating thyroid hormone levels, but the common gene variants involved have not been conclusively identified. The genes encoding the iodothyronine deiodinases are good candidates because they alter the balance of thyroid hormones. We aimed to thoroughly examine the role of common variation across the three deiodinase genes in relation to thyroid hormones. Methods: We used HapMap data to select single-nucleotide polymorphisms (SNPs) that captured a large proportion of the common genetic variation across the three deiodinase genes. We analyzed these initially in a cohort of 552 people on T4 replacement. Suggestive findings were taken forward into three additional studies in people not on T4 (total n = 2513) and metaanalyzed for confirmation. Results: A SNP in the DIO1 gene, rs2235544, was associated with the free T3 to free T4 ratio with genome-wide levels of significance (P = 3.6 × 10−13). The C-allele of this SNP was associated with increased deiodinase 1 (D1) function with resulting increase in free T3/T4 ratio and free T3 and decrease in free T4 and rT3. There was no effect on serum TSH levels. None of the SNPs in the genes coding for D2 or D3 had any influence on hormone levels. Conclusions: This study provides convincing evidence that common genetic variation in DIO1 alters deiodinase function, resulting in an alteration in the balance of circulating free T3 to free T4. This should prove a valuable tool to assess the relative effects of circulating free T3 vs. free T4 on a wide range of biological parameters.

Management of hypothyroidism in adults

Abstract: Hypothyroidism is one of the commonest chronic disorders in Western populations. In the United Kingdom, the annual incidence of primary hypothyroidism in women is 3.5 per 1000 and in men 0.6 per 1000.1 During 2006 12 million prescriptions for levothyroxine (50 μg or 100 μg tablets) were dispensed in England, equivalent to about 1.6 million people taking long term thyroid replacement therapy, about 3% of the population.2 The management of hypothyroidism is generally considered straightforward and is mostly carried out in primary care in the UK. Cross sectional surveys of patients taking levothyroxine have, however, shown that between 40% and 48% are either over-treated or under-treated.3 4 Furthermore, a small but significant proportion of patients continue to feel unwell despite taking levothyroxine.5 This review discusses current approaches in the management of hypothyroidism in adults. #### Sources and selection criteria We searched PubMed and the Cochrane Library databases for the keywords hypothyroidism and thyroxine. We identified further references from the original articles and recent review articles. We studied articles only in the English language, and gave priority to those published in the past 10 years and those reporting randomised controlled trials. #### Summary points

Evaluation of patients with a painful total knee replacement

Abstract: Evaluation of patients with painful total knee replacement requires a thorough clinical examination and relevant investigations in order to reach a diagnosis. Awareness of the common and uncommon problems leading to painful total knee replacement is useful in the diagnostic approach. This review article aims to act as a guide to the evaluation of patients with painful total knee replacement.

Performance of oxygen delivery devices when the breathing pattern of respiratory failure is simulated

Abstract: Oxygen is the commonest drug prescribed in hospitals The inhaled concentration is altered by the administered oxygen flow rate, the characteristics of the delivery device and the patient's respiratory pattern Using healthy volunteers we measured the inspired oxygen concentration achieved with different devices both at rest and when the breathing pattern of respiratory failure was simulated by binding the subjects' chests until the forced expiratory volume in 1 s was reduced by > 50% and the respiratory rate was > 25 breathsmin(-1) With this respiratory pattern, there was a statistically significant fall in F(I)o(2) while administering oxygen via a Hudson mask at 4 lmin(-1) (238% (95% CI 174-303%) reduction), 12 lmin(-1), humidified (178% (95% CI 88-267%) reduction) and 24 lmin(-1), humidified (122% (95% CI 50-193%) reduction) There was no statistically significant change with a nonrebreathing (reservoir) mask at 15 and 110 lmin(-1) or with a Vapotherm 2000i at 40 lmin(-1), humidified, via nasal prongs We conclude that the F(I)o(2) delivered by high flow devices is unaffected when the breathing pattern of respiratory failure is simulated The F(I)o(2) achieved at rest by a nonrebreathing mask (068) is less than that often quoted in the literature

The management of bone loss in revision total knee replacement

Abstract: The management of bone loss in revision replacement of the knee remains a challenge despite an array of options available to the surgeon. Bone loss may occur as a result of the original disease, the design of the prosthesis, the mechanism of failure or technical error at initial surgery. The aim of revision surgery is to relieve pain and improve function while addressing the mechanism of failure in order to reconstruct a stable platform with transfer of load to the host bone. Methods of reconstruction include the use of cement, modular metal augmentation of prostheses, custom-made, tumour-type or hinged implants and bone grafting. The published results of the surgical techniques are summarised and a guide for the management of bone defects in revision surgery of the knee is presented.

The detection of full thickness rotator cuff tears using ultrasound

Abstract: We have examined the accuracy of 143 consecutive ultrasound scans of patients who subsequently underwent shoulder arthroscopy for rotator-cuff disease All the scans and subsequent surgery were performed by an orthopaedic surgeon using a portable ultrasound scanner in a one-stop clinic There were 78 full thickness tears which we confirmed by surgery or MRI Three moderate-size tears were assessed as partial-thickness at ultrasound scan (false negative) giving a sensitivity of 962% One partially torn and two intact cuffs were over-diagnosed as small full-thickness tears by ultrasound scan (false positive) giving a specificity of 954% This gave a positive predictive value of 962% and a negative predictive value of 954% Estimation of tear size was more accurate for large and massive tears at 965% than for moderate (888%) and small tears (916%) These results are equivalent to those obtained by several studies undertaken by experienced radiologists We conclude that ultrasound imaging of the shoulder performed by a sufficiently-trained orthopaedic surgeon is a reliable time-saving practice to identify rotator-cuff integrity

Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome.

Abstract: Spondylothoracic dysostosis (STD), also known as Jarcho-Levin syndrome (JLS), is an autosomal-recessive disorder characterized by abnormal vertebral segmentation and defects affecting spine formation, with complete bilateral fusion of the ribs at the costovertebral junction producing a "crab-like" configuration of the thorax. The shortened spine and trunk can severely affect respiratory function during early childhood. The condition is prevalent in the Puerto Rican population, although it is a panethnic disorder. By sequencing a set of candidate genes involved in mouse segmentation, we identified a recessive E103X nonsense mutation in the mesoderm posterior 2 homolog (MESP2) gene in a patient, of Puerto Rican origin and from the Boston area, who had been diagnosed with STD/JLS. We then analyzed 12 Puerto Rican families with STD probands for the MESP2 E103X mutation. Ten patients were homozygous for the E103X mutation, three patients were compound heterozygous for a second nonsense mutation, E230X, or a missense mutation, L125V, which affects a conserved leucine residue within the bHLH region. Thus, all affected probands harbored the E103X mutation. Our findings suggest a founder-effect mutation in the MESP2 gene as a major cause of the classical Puerto Rican form of STD/JLS.

Dropped head syndrome: a case series and literature review.

Abstract: Study design Case series and literature review. Objective To describe Dropped Head Syndrome (DHS) to the orthopedic community and examine the management of this condition including the role of surgery. Summary of background data DHS is characterized by severe neck extensor weakness, resulting in chin-on-chest deformity in the standing or sitting position, which is correctable by passive neck extension. The syndrome is familiar to neurologists but is little known in the orthopedic community and literature. DHS patients may present to the spinal surgeon to consider surgical management. Methods We summarize the case histories of 7 patients who presented to the Exeter Spinal Unit with this disabling condition. Investigation, management, and the few publications on surgical management of DHS are discussed. One of the patients in our series underwent surgical management, and we discuss the possibilities for surgical management, along with the outcome of surgery in this case. Results Seven cases of DHS presented to our unit, 4 with acute presentation and 3 with gradual onset. Six patients were treated conservatively. One patient was treated surgically but was unhappy with the outcome. Conclusion We conclude that the option of surgical management must be carefully considered in each case, especially with respect to the potential disadvantages in elderly patients.

Radioiodine treatment for benign thyroid disorders : results of a nationwide survey of UK endocrinologists

Abstract: Background A survey of physicians' practice relating to radioiodine administration for hyperthyroidism was carried out in the UK over 15 years ago and showed wide variations in patient management. This led to the development of national guidelines for the use of radioiodine in hyperthyroidism. As there have been significant advances in the field since that survey, we carried out another survey to study the prevalent practices relating to radioiodine therapy for benign thyroid disorders across the UK. Subjects and methods We mailed 698 UK consultant endocrinologists a questionnaire on radioiodine treatment based on three patient scenarios: hyperthyroid Graves' disease, subclinical hyperthyroidism and nontoxic goitre. Results The response rate was 40%. For the scenario of an initial presentation of Graves' disease, 80%, 19% and 0.4% of respondents preferred thionamide, radioiodine or thyroidectomy, respectively. There were inconsistencies in respondents' recommendations on radioiodine dose, the use of pre- and post-radioiodine supplementary treatments, timing of a repeat dose, and the use of radioiodine in thyroid eye disease. For the case of subclinical hyperthyroidism, one-third of respondents would generally initiate treatment. The majority were more likely to treat subclinical hyperthyroidism in the presence of paroxysmal atrial fibrillation or osteoporosis. If a decision were made to treat subclinical hyperthyroidism, 63%, 35%, 1% and 0.4% would recommend radioiodine, thionamide, beta-blocker and thyroidectomy, respectively. For the scenario of nontoxic goitre, 62%, 21%, 13% and 5% favoured observation, thyroidectomy, radioiodine and thyroxine, respectively. Conclusions There remain significant differences in several aspects of clinical practice relating to the use of radioiodine treatment for benign thyroid disorders in the UK.

Salivary duct carcinoma in situ of the parotid gland.

Abstract: Aims: To describe three cases of purely in situ salivary duct carcinoma, so as better to define the entity. Methods and results: Three primary tumours of the parotid gland are presented, in each case composed of cysts and ducts and lined by high nuclear grade epithelial cells. All parts of each tumour were surrounded by a myoepithelial cell rim and there was no evidence of invasion. The tumour cells expressed immunohistochemical markers seen in invasive salivary duct carcinoma of usual (high-grade) type. In two cases the androgen receptor (AR) reaction was strong, but there was no immunohistochemical expression of HER2 protein or gene amplification by in situ hybridization. In the remaining case, fewer nuclei stained for AR, but both HER2 protein and gene amplification were demonstrated. Conclusions: Salivary duct carcinoma in situ is morphologically similar to breast ductal carcinoma in situ and, although our cases are few, salivary duct carcinoma in situ can possibly be subdivided into luminal and non-luminal cell types, as can analogous mammary neoplasms. The present study cannot determine whether low-grade cribriform cystadenocarcinoma, architecturally similar but immunohistochemically different, is part of the spectrum of salivary duct carcinoma in situ, or whether it represents a separate entity.

The safety and efficacy of bilateral simultaneous total hip replacement: an analysis of 2063 cases.

Abstract: Comparison of the safety and efficacy of bilateral simultaneous total hip replacement (THR) and that of staged bilateral THR and unilateral THR was conducted using DerSimonian-Laird heterogeneity meta-analysis. A review of the English-language literature identified 23 citations eligible for inclusion. A total of 2063 bilateral simultaneous THR patients were identified. Meta-analysis of homogeneous data revealed no statistically significant differences in the rates of thromboembolic events (p = 0.268 and p = 0.365) and dislocation (p = 0.877) when comparing staged or unilateral with bilateral simultaneous THR procedures. A systematic analysis of heterogeneous data demonstrated that the mean length of hospital stay was shorter after bilateral simultaneous THR. Higher blood transfusion requirements were expected following bilateral simultaneous THR than staged or unilateral THR, and surgical time was not different between groups. This procedure was also found to be economically and functionally efficacious when performed by experienced surgeons in specialist centres.

ABCD of the phosphodiesterase family: interaction and differential activity in COPD

Abstract: Phosphodiesterases (PDEs) are important enzymes that hydrolyze the cyclic nucleotides adenosine 3′5′-cyclic monophosphate (cAMP) and guanosine 3′5′-cyclic mono-phosphate (cGMP) to their inactive 5′ monophosphates. They are highly conserved across species and as well as their role in signal termination, they also have a vital role in intracellular localization of cyclic nucleotide signaling and integration of the cyclic nucleotide pathways with other signaling pathways. Because of their pivotal role in intracellular signaling, they are now of considerable interest as therapeutic targets in a wide variety diseases, including COPD where PDE inhibitors may have bronchodilator, anti-inflammatory and pulmonary vasodilator actions. This review examines the diversity and cellular localization of the isoforms of PDE, the known and speculative relevance of this to the treatment of COPD, and the range of PDE inhibitors in development together with a discussion of their possible role in treating COPD.

Autochthonous hepatitis E in Southwest England: a comparison with hepatitis A.

Abstract: The incidence of hepatitis A is falling. In contrast, autochthonous hepatitis E is an emerging infection in developed countries. The objective of this study was to compare both laboratory-confirmed cases of hepatitis A and autochthonous hepatitis E over a 2-year period in Cornwall and Devon and anti-hepatitis A virus (HAV) IgG and anti-hepatitis E virus (HEV) IgG seroprevalence in blood donors. The databases of microbiology laboratories in Cornwall and Devon were searched for the number of diagnostic HEV and HAV assays performed during 2005–2006 and the number of confirmed cases of acute hepatitis A and hepatitis E detected. Patients were followed up until recovery or death. Sera from 500 blood donors from the regional centre were tested for HEV and HAV IgG. In total, 28 cases of autochthonous hepatitis E were identified from 838 assays, and 20 cases of hepatitis A were identified from 4503 assays. Compared to hepatitis A cases, patients with hepatitis E were older (mean age 61 vs. 45 years, P = 0.003), less likely to present in winter (P = 0.028) and had more complications (five vs. one). The IgG seroprevalence rates in blood donors were 45% for HAV and 16% for HEV. There was no relationship between HAV and HEV IgG seropositivity. Autochthonous hepatitis E may be more common than hepatitis A, affects older patients, is less likely to occur in winter and may be associated with more complications. Patients with acute hepatitis, whatever their age or travel history, should be tested for HEV.

The Use of Long Cemented Stems for Femoral Impaction Grafting in Revision Total Hip Arthroplasty

Abstract: Background: Following revision total hip arthroplasty involving femoral impaction grafting, fractures usually have occurred distal to a standard-length stem in an area of weakened bone that was left inadequately supported. The purpose of the present study was to determine whether the use of a long stem decreases the rate of femoral fracture after revision hip surgery. We hypothesized that the use of a long-stem femoral component would decrease the risk of these fractures. Methods: From 1991 to 2000, 567 revision total hip arthroplasties were performed with use of femoral impaction grafting. Of these, forty-two procedures in forty patients (average age, 73.8 years) were performed with use of a stem that was ≥220 mm in length. The average number of previous revisions was 1.85. Thirty-four of the forty hips with preoperative radiographs had preoperative bone loss that was classified as grade III or IV according to the Endo-Klinik system. Major complications were recorded, and survival analysis was performed. Results: No patient was lost to follow-up. Sixteen patients (sixteen hips) died at an average of fifty-two months postoperatively. The average duration of clinical follow-up for the hips in which the implant survived for more than forty-eight months was 7.5 years. The rate of major postoperative complications was 29%. Two postoperative femoral fractures occurred. Six patients (six hips) required a femoral reoperation. The survival rate with revision hip surgery as the end point was 90% at both five and ten years. The rate of survival with any failure as the end point was 82% at five years and 64% at ten years. Conclusions: The use of a long stem for femoral impaction grafting did not completely resolve the problem of postoperative fractures in these patients with substantial loss of bone stock undergoing revision hip surgery. Poor bone stock, technical errors, and other patient-related factors continue to account for the high postoperative fracture rate. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.

Vascular loops causing otological symptoms: a systematic review and meta-analysis.

Abstract: Objective of review: To determine evidence for a relationship between vascular loops in contact with the vestibulocochlear nerve (CN VIII) and otological symptoms. Type of review: Systematic review and meta-analysis of observational studies. Search strategy: Comprehensive search of MEDLINE, EMBASE, CINAHL, Cochrane Library, Clinical Evidence and Cochrane Central Register of Trials. Reference lists cross-referenced and authors contacted for missing data. No language restrictions. Evaluation methods: Included studies: (1) compared symptoms in subjects with a vascular loop contacting CN VIII to subjects without (inter-subject control); (2) compared the prevalence of vascular loop in contact with CN VIII in symptomatic ears to contra-lateral asymptomatic ears (intra-subject control). Study quality systematically appraised. Results: Five case–control studies included. A statistically significant association was demonstrated for the prevalence of vascular loops in contact with CN VIII, with unilateral sensorineural hearing loss: pooled odds ratio (OR) 2.0 [95% confidence interval (CI): 1.5–2.6]. No association was demonstrated for non-pulsatile tinnitus. A highly significant association with vascular loops was shown in subjects having pulsatile tinnitus, with pooled OR: 78.8 (95% CI: 10.9–821.8). Conclusions: Vascular loops in contact with CN VIII are a normal variant. Subjects with unilateral hearing loss were twice as likely to have these vascular loops in the symptomatic ear, than in the asymptomatic ear. Subjects with pulsatile tinnitus were 80 times more likely to have a contacting vascular loop than patients with non-pulsatile tinnitus, suggesting in some cases a causal relationship exists for pulsatile tinnitus, where surgical intervention may be occasionally indicated.

The impact of consumer involvement in research: an evaluation of consumer involvement in the London Primary Care Studies Programme

Abstract: Background The value of consumer involvement in health services research is widely recognized. While there is a growing body of evidence about the principles of good consumer involvement, there is little research about the effect that involvement can have on the research. This evaluation assessed the level and impact of consumer involvement in the London Primary Care Studies Programme (LPCSP), all of whose individual projects had to demonstrate substantial involvement as a condition of funding. Objective To evaluate consumer involvement in the LPSCP and understand what impact consumers had on the research process and outcomes. Methods A multi-method case study approach was undertaken, using survey techniques, interviews, focus groups, observation and scrutiny of written documents. The overall data set comprised 61 questionnaires, 44 semi-structured interviews, 2 focus groups and 15 hours of observation of meetings. Eleven primary care-based research projects which together made up the LPCSP. Results An in-depth description of consumer involvement in the Programme was produced. Nine projects had consumers as co-applicants, four projects had been completed before the evaluation began and one was still ongoing at the time of the evaluation. Of the eight projects which have produced final reports, all met their aims and objectives. Consumers had had an additional impact in the research, in the initial design of the study, in recruitment of the research subjects, in developing data collection tools, in collecting the data, in analysis and disseminating the findings. Conclusions Consumer involvement in National Health Service research is a relatively recent policy development and while there is an increasing amount of literature about how and why consumers should be involved in research, there is less evidence about the impact of such involvement. This evaluation provides evidence about the impact that consumers have not only on the research process but also on the outcomes of the research.

Continuous measurement of urine loss and frequency in incontinent patients. Preliminary report.

Abstract: SUMMARY A method has been developed to measure the quantity and frequency of urine loss in in-continent patients, who are free to lie, sit and exercise at will. The pattern of leakage can be categorised and quantified, distinct recordings being obtained for continuous dribbling, sudden losses on straining, etc. It is anticipated that the device will be of use in the assessment of all types of urine loss and of any subsequent improvement effected by various treatments. Volumes from 1 ml. to 100 ml. can be measured, and the entire equipment may be battery-operated and is safe to use with patients of any age, including those who are bedridden or chairbound.

The impact of thyroid eye disease upon patients’ wellbeing: a qualitative analysis

Abstract: BACKGROUND: Previous studies using quality of life (QoL) questionnaires have shown poor QoL in patients with thyroid eye disease (TED). However, predetermined questionnaires limit in-depth investigation of psychosocial and emotional effects of TED. A qualitative approach allows detailed exploration of patients' perceptions of wellbeing and can capture their lived experiences. OBJECTIVE: To explore the experience of living and coping with TED. DESIGN AND PATIENTS: A qualitative study involving individual, tape-recorded, semistructured interviews with 25 participants with TED (20 female subjects, median age 54 years, range 28-90 years). Thematic content analysis identified themes, from which theoretical interpretations were formed. RESULTS: Three key themes were identified: (1) development of an altered identity as a result of changes in appearance, abilities and roles due to physical consequences of TED. This was described in the context of life before and after TED; (2) creation of coping strategies including denial, social avoidance, adjustment and stoicism; (3) difficult interactions with healthcare practitioners due to uncertainty surrounding the diagnosis, prognosis and treatment choices, resulting in patients' disengagement, anger and frustration. CONCLUSION: This qualitative study has identified the phenomenon of an altered identity due to direct consequences of TED that impact upon patients' wellbeing, coping strategies and interactions with healthcare professionals.

Endovascular stenting to treat obstruction of the superior vena cava

Abstract: This article discusses the use of image guided endovascular stenting to treat obstruction of the superior vena cava

Femoroacetabular impingement syndrome: Nonarthritic hip pain in young adults

Abstract: OBJECTIVE To provide family physicians with an approach to the diagnosis and management of nonarthritic hip pain in young adults, which might occur as a result of femoroacetabular impingement syndrome. SOURCES OF INFORMATION A MEDLINE search from 1950 to April 2007 was carried out using the MeSH terms femoroacetabular, impingement, hip, and syndrome. The existing literature consists of level II studies. To date, randomized controlled trials have not been carried out. MAIN MESSAGE Nonarthritic hip pain in the active adult population has long been a difficult clinical problem to manage. Arthroplasty is rarely an appropriate option and the usual conservative therapies for musculoskeletal problems are frequently ineffective. Recently, abnormal impingement between the acetabulum and femoral head-neck junction, or femoroacetabular impingement syndrome, has been recognized as a relatively common and possibly prearthritic cause of these symptoms. Family physicians can identify these patients by recognizing the clinical history and through specific examination findings. Emerging evidence suggests that early surgical intervention improves function and perhaps prevents or delays the onset of degenerative changes in the hip joint. CONCLUSION Family physicians can identify patients with possible femoroacetabular impingement syndrome and play an important role in the appropriate management of these cases.

Analysis of gross deletions in the MEN1 gene in patients with multiple endocrine neoplasia type 1.

Abstract: Summary Background Mutation analysis with direct DNA sequencing is commonly used for the molecular diagnosis of multiple endocrine neoplasia type 1 (MEN1). However, a significant number of patients, despite clinical features of MEN1, do not show MEN1 mutations on direct DNA sequencing. Some of these patients may have gross gene deletions not detected by direct DNA sequencing or mutations in the noncoding regions of the gene not examined routinely. Objective To determine the prevalence of gross deletions in MEN1 in a large cohort of MEN1 patients. Patients and methods During 1997–2006, we screened MEN1 mutations by direct DNA sequencing in 368 probands referred to our diagnostic molecular genetic laboratory. Of these, 101 probands (23 familial, 78 sporadic) fulfilled the clinical criteria for MEN1 (presence of at least two of the parathyroid, pancreatic or pituitary tumours) but were negative for mutations on DNA sequencing. Their DNA samples were examined for gross deletions of one or more exons of MEN1 by using multiple ligation-dependent probe amplification (MLPA) and long-range polymerase chain reaction (PCR) amplification. We also sequenced the minimal promoter region of MEN1 for mutations in the familial cases. Results We identified a gross deletion involving exons 5 and 6 of MEN1 in one proband (prevalence rate 1%). The sequencing of the minimal promoter region in the familial cases revealed no mutations. Conclusion Gross deletion in the MEN1 gene is an uncommon cause of MEN1 and should be tested for in patients with a high clinical suspicion but without mutations on direct DNA sequencing.

Birth season and environmental influences on blood leucocyte and lymphocyte subpopulations in rural Gambian infants

Abstract: In rural Gambia, birth season predicts infection-related adult mortality, providing evidence that seasonal factors in early life may programme immune development. This study tested whether lymphocyte subpopulations assessed by automated full blood count and flow cytometry in cord blood and at 8, 16 and 52 weeks in rural Gambian infants (N = 138) are affected by birth season (DRY = Jan-Jun, harvest season, few infections; WET = Jul-Dec, hungry season, many infections), birth size or micronutrient status. Geometric mean cord and postnatal counts were higher in births occurring in the WET season with both season of birth and season of sampling effects. Absolute CD3+, CD8+, and CD56+ counts, were higher in WET season births, but absolute CD4+ counts were unaffected and percentage CD4+ counts were therefore lower. CD19+ counts showed no association with birth season but were associated with concurrent plasma zinc status. There were no other associations between subpopulation counts and micronutrient or anthropometric status. These results demonstrate a seasonal influence on cell counts with a disproportionate effect on CD8+ and CD56+ relative to CD4+ cells. This seasonal difference was seen in cord blood (indicating an effect in utero) and subsequent samples, and is not explained by nutritional status. These findings are consistent with the hypothesis than an early environmental exposure can programme human immune development.

Sinonasal Renal Cell-like Adenocarcinoma: A Report on Four Patients

Abstract: Background We have described an unusual sinonasal neoplasm which is a histological mimic of renal cell carcinoma (RCC) and coined the nosological classification “sinonasal renal cell-like adenocarcinoma” (SRCLA) to describe this unusual entity. Since the original description (Zur et al. Otolaryngol Head Neck Surg 128:441–7, 2002), we have reviewed the case reported by Moh’d Hadi et al. (Rhinology 40:44–7, 2002) and have seen two new cases in consultation. Our purpose here is to describe the additional cases and to extend the reported outcome for these patients. Design Four patients were identified. Slides and immunohistochemistry results were reviewed in consultation. Updated clinical follow-up was obtained from the respective clinicians. Results This group consisted of three women, one man, 22–69 years, and mean 46. Three tumors were in the nasal cavity and one was in the nasopharynx. Histologically, these tumors were uniformly composed of clear cells, forming either solid or glandular patterns. The tumor cells were cuboidal to polyhedral; transition to short spindle cells was seen in one case. One case revealed moderate nuclear pleomorphism. No perineural or vascular invasion, or necrosis was seen. No mucin-producing or squamous elements were seen. Immunohistochemistry (IHC) revealed the following staining profile: CK7 + (4/4), CK20 + (focal 1/4), S100 + (1/4), and CD10 + (1/2). No staining was seen for vimentin (0/4), RCC (0/2), thyroglobulin (0/2), actin (0/2), or calponin (0/2). Three patients were treated primarily with surgery, two patients also received adjuvant radiotherapy (RT); the fourth patient was treated with primary RT. All patients are disease-free, based on endoscopy and/or radiography, 2, 4, 5 and 8 years after diagnosis. Renal cell carcinoma has not been identified in any patient. Conclusion Sinonasal renal cell-like adenocarcinoma is a rare and distinct entity noteworthy in its resemblance to RCC. Immunohistochemistry can easily distinguish between these two tumors. No patient developed recurrent or metastatic disease, or was found to have RCC. Greater experience will allow us to fully understand its long-term behavior and arrive at more standardized therapeutic recommendations.

Remifentanil sedation for awake fibreoptic intubation with limited application of local anaesthetic in patients for elective head and neck surgery.

Abstract: The aim of this study was to investigate the performance of awake fibreoptic intubation using remifentanil sedation with topical anaesthesia limited only to the nasal mucosa. Twenty-four patients presenting for elective head and neck surgery were sedated using remifentanil titrated to effect and local anaesthetic was applied to the nasal mucosa. Vital signs were recorded throughout the procedure and both the anaesthetist and an observer rated the ease of the procedure. Intubation was successful in all patients and the procedure was rated as easy in 15 (63%) of patients. Mean arterial pressure remained within 8% of baseline in all cases and respiratory rate remained > 8 breaths.min(-1) in all but three patients. Although 56% of patients interviewed postoperatively said they recalled the procedure, all but one would undertake the same procedure again if necessary. This technique appears reliable in providing adequate sedation whilst maintaining cardiovascular and respiratory stability.

Neuroborreliosis in the South West of England.

Abstract: Although Lyme borreliosis is increasingly diagnosed in the United Kingdom, few systematic studies have been performed there. UK data suggest that the commonest complications are neurological, but inadequate information exists about their nature and the incidence of late neuroborreliosis. Local data are necessary because clinical presentations may show geographical variation. This study aimed to provide data on clinical manifestations in an area of South West England and to estimate treatment delay. We reviewed clinical records of 88 patients in the Royal Devon and Exeter Hospital catchment area who had positive Borrelia antibody tests during a 5-year period. Fifty-six (64%) reported tick bites. The commonest presentations were erythema migrans (65%) and arthralgia/myalgia (27%). However, 22 patients (25%) had neurological symptoms other than headache alone. Fourteen had facial palsy, eight had confusion/drowsiness, four had meningism, five had radiculopathy, two had sixth nerve palsies, and two had peripheral neuropathies. No late, progressive or atypical neurological syndromes were found. Neurological manifestations were generally predictable and usually included either (or all) of meningoencephalitis, facial palsy or radiculopathy.