Improving radiology: a whole-system opportunity.

In this article, we set out the current context and case for change in radiology in England and how quality-improvement approaches can support the development of sustainable Imaging services and networks to meet the challenges faced now and in the future.

Non-Invasive Prenatal Testing (NIPT) - We Need a National Programme.

Aims The provision of non-invasive prenatal testing (NIPT), a blood test screening for aneuploidy during pregnancy, varies widely internationally. In Ireland, NIPT is available privately, costing over €400. Gobal research on the patient perspective on NIPT shows a strong desire for the test to be provided for free. Attitudes towards NIPT amongst pregnant women in Ireland have not previously been studied. We assessed this in women attending maternity services in our unit. Methods This was a cross-sectional observational study involving a telephone survey. Women were asked about their prior knowledge of NIPT. Women with no prior knowledge were given information about NIPT and asked about their opinion of the test. Results One hundred and twelve (n=112) women participated. Of these, 60% (n=67) had not heard of NIPT, 86% (n=96) believe it should be freely available, and 80% (n=90) said they would avail of the test if it were free. Cost was the main prohibitive factor for those choosing not to have the test. All women wished to be more informed about NIPT. Conclusion Awareness of NIPT amongst women attending maternity services in Ireland may be low, but there is a desire for more information and a more equitable provision of the test.

The role of anatomic pelvic dissection in the successful closure of bladder exstrophy: an aid to success.

INTRODUCTION: Classic bladder exstrophy is one of the rarest congenital anomalies compatible with life. Surgical treatment of bladder exstrophy has progressed, but the goal of surgery remains a successful primary bladder closure. Several factors have been identified to decrease the risk of failed closure, including appropriate use of osteotomy and adequate postoperative immobilization and analgesia. However, the role of the radical anatomic pelvic dissection, including dissection of the urogenital diaphragm fibers, in a successful closure has not yet been extensively explored. OBJECTIVE: The objective of this study was go examine the role of radical anatomic pelvic dissection, including dissection of the urogenital diaphragm fibers, in patients with classic bladder exstrophy. STUDY DESIGN: This was a retrospective study based on an institutional database. METHODS: A retrospective review from an institutional approved database of more than 1,300 patients with epispadias-exstrophy complex was performed. The inclusion criteria included patients with classic bladder exstrophy with at least one failed bladder closure and a reclosure at the authors' institution with a single senior surgeon. Data collection included demographics, clinical variables, and status of urogenital diaphragm fibers. Magnetic resonance imaging (MRI) scans, if available, were reviewed with a pediatric radiologist to identify urogenital diaphragm fibers. RESULTS: From the database, 93 patients met inclusion criteria. Of these patients, 74 had urogenital diaphragm fibers completely intact at the time of repeat closure, whereas 19 patients did not. There was no association with age or gender and status of urogenital diaphragm fibers. There was no association with osteotomy, the type of primary bladder closure, surgeon subspecialty, and the status of the urogenital fibers. Fourteen patients had at least two prior closures; surprisingly, 11 of these repeat closure patients still had intact urogenital fibers even after two prior closures. DISCUSSION: The recent development and application of 3D MRI-guided pelvic dissection in a large group of patients led the authors to investigate whether adequate pelvic floor dissection had been accomplished at primary or secondary closure. Several patients had MRI scans performed before repeat closure in which the urogenital diaphragm fibers were identified to be intact on imaging; this was corroborated with surgical findings. Approximately 80% of patients had their urogenital diaphragm fibers completely intact and, therefore, did not have an adequate pelvic dissection during their primary or secondary bladder closure, putting the success of their previous closures at risk. CONCLUSION: Inadequate pelvic diaphragm dissection, defined as intact urogenital diaphragm fibers, demonstrated in a large group of patients with failed exstrophy closure, may be a decisive factor in bladder closure failure. The use of 3D intra-operative image guidance may aid in a safer and more successful pelvic dissection.

Genetic effects influencing risk for major depressive disorder in China and Europe.

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.

Harlequin Ichthyosis - A Case Report.

Harlequin Ichthyosis is a very rare genetic disorder affecting mainly the skin with severe morbidity and mortality. It affects both sexes with incidence of about 1 in 300,000 live births. Autosomal recessive inheritance has been inferred with mutation in ABCA 12 gene identified. Hence, genetic counseling and mutation screening of this gene should be considered in at-risk patients. Death usually occurred in the first 3 months of life due to sepsis, feeding problems and respiratory distress. With improved neonatal care and early introduction of retinoids, its survival rate has increased.

10-year outcome study of an early intervention program for psychosis compared with standard care service.

BACKGROUND: Despite evidence on the short-term benefits of early intervention (EI) service for psychosis, long-term outcome studies are limited by inconsistent results. This study examined the 10-year outcomes of patients with first-episode psychosis who received 2-year territory-wide EI service compared to those who received standard care (SC) in Hong Kong using an historical control design. METHOD: Consecutive patients who received the EI service between 1 July 2001 and 30 June 2002, and with diagnosis of schizophrenia-spectrum disorders, were identified and matched with patients who received SC first presented to the public psychiatric service from 1 July 2000 to 30 June 2001. In total, 148 matched pairs of patients were identified. Cross-sectional information on symptomatology and functioning was obtained through semi-structured interview; longitudinal information on hospitalization, functioning, suicide attempts, mortality and relapse over 10 years was obtained from clinical database. There were 70.3% (N = 104) of SC and 74.3% (N = 110) of EI patients interviewed. RESULTS: Results suggested that EI patients had reduced suicide rate (χ2 (1) = 4.35, p = 0.037), fewer number [odds ratio (OR) 1.56, χ2 = 15.64, p < 0.0001] and shorter duration of hospitalization (OR 1.29, χ2 = 4.06, p = 0.04), longer employment periods (OR -0.28, χ2 = 14.64, p < 0.0001) and fewer suicide attempts (χ2 = 11.47, df = 1, p = 0.001) over 10 years. At 10 years, no difference was found in psychotic symptoms, symptomatic remission and functional recovery. CONCLUSIONS: The short-term benefits of the EI service on number of hospitalizations and employment was sustained after service termination, but the differences narrowed down. This suggests the need to evaluate the optimal duration of the EI service.

Contributions of the social environment to first-onset and recurrent mania.

In treated cohorts, individuals with bipolar disorder are more likely to report childhood adversities and recent stressors than individuals without bipolar disorder; similarly, in registry-based studies, childhood adversities are more common among individuals who later become hospitalized for bipolar disorder. Because these types of studies rely on treatment-seeking samples or hospital diagnoses, they leave unresolved the question of whether or not social experiences are involved in the etiology of bipolar disorder. We investigated the role of childhood adversities and adulthood stressors in liability for bipolar disorder using data from the National Epidemiologic Survey on Alcohol and Related Conditions (n=33 375). We analyzed risk for initial-onset and recurrent DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) manic episodes during the study's 3-year follow-up period. Childhood physical abuse and sexual maltreatment were associated with significantly higher risks of both first-onset mania (odds ratio (OR) for abuse: 2.23; 95% confidence interval (CI)=1.71, 2.91; OR for maltreatment: 2.10; CI=1.55, 2.83) and recurrent mania (OR for abuse: 1.55; CI=1.00, 2.40; OR for maltreatment: 1.60; CI=1.00, 2.55). In addition, past-year stressors in the domains of interpersonal instability and financial hardship were associated with a significantly higher risk of incident and recurrent mania. Exposure to childhood adversity potentiated the effects of recent stressors on adult mania. Our findings demonstrate a role of social experiences in the initial onset of bipolar disorder, as well as in its prospective course, and are consistent with etiologic models of bipolar disorder that implicate deficits in developmentally established stress-response pathways.

Haploidentical related-donor hematopoietic cell transplantation in children using megadoses of CliniMACs-selected CD34(+) cells and a fixed CD3(+) dose.

We conducted a prospective phase II trial utilizing the CliniMACs system to perform CD34(+)-cell selection of PBSCs from haploidentical donors to evaluate engraftment and hematoimmunological reconstitution. In total, 21 children with hematological malignancies or nonmalignant conditions underwent conditioning with 1200 cGy TBI, thiotepa, fludarabine and Thymoglobulin. Patients received megadoses of CD34(+) cells (median: 22 × 10(6)/kg) with a fixed dose of 3 × 10(4)/kg CD3(+) cells/kg, and engraftment occurred in 90% with prompt recovery of neutrophils and platelets. Grade II acute GVHD (aGVHD) was seen in 32% (95% confidence interval (CI), 15-54%) of evaluable patients, there was no grade III-IV aGVHD, and chronic extensive GVHD was seen in 35% (95% CI, 17-59%) of patients. The estimated 2-year EFS was 62% (95% CI, 48-83%) with a median survivor follow-up of 49 months (range: 18-119 months). Patients with nonmalignant diseases had an estimated 2-year EFS of 100% (95% CI, 56-100%) and patients with malignancies in remission had an estimated 2-year EFS of 56% (95% CI, 22-89%). Megadose CD34(+) cells with a fixed CD3(+) cell dose from haploidentical related donors resulted in good outcomes for pediatric patients with nonmalignant diseases and those with malignant diseases transplanted in remission.

Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab.

KRAS mutation is a predictive biomarker for resistance to cetuximab (Erbitux) in metastatic colorectal cancer (mCRC). This study sought to determine if KRAS mutant CRC lines could be sensitized to cetuximab using dasatinib (BMS-354825, Sprycel), a potent, orally bioavailable inhibitor of several tyrosine kinases, including the Src family kinases (SFKs). We analyzed 16 CRC lines for: (1) KRAS mutation status, (2) dependence on mutant KRAS signaling and (3) expression level of epidermal growth factor receptor (EGFR) and SFKs. From these analyses, we selected three KRAS mutant (LS180, LoVo and HCT116) cell lines and two KRAS wild-type cell lines (SW48 and CaCo2). In vitro, using poly-D-lysine/laminin plates, KRAS mutant cell lines were resistant to cetuximab, whereas KRAS wild-type lines showed sensitivity to cetuximab. Treatment with cetuximab and dasatinib showed a greater antiproliferative effect on KRAS mutant lines when compared with either agent alone in vitro and in vivo. To investigate potential mechanisms for this antiproliferative response in the combinatorial therapy, we performed Human Phospho-Kinase Antibody Array analysis, measuring the relative phosphorylation levels of 39 intracellular proteins in untreated, cetuximab, dasatinib or the combinatorial treatment in the KRAS mutant lines LS180, LoVo and HCT116 cells. The results of this experiment showed a decrease in a broad spectrum of kinases centered on the ß-catenin pathway, the mitogen-activated protein kinase (MAPK) pathway, AKT/mammalian target of rapamycin (mTOR) pathway and the family of signal transducers and activators of transcription (STATs) when compared with the untreated control or monotherapy treatments. Next, we analyzed tumor growth with cetuximab, dasatinib or their combination in vivo. KRAS mutant xenografts showed resistance to cetuximab therapy, whereas KRAS wild type demonstrated an antitumor response when treated with cetuximab. KRAS mutant tumors exhibited minimal response to dasatinib monotherapy. However, as in vitro, KRAS mutant lines exhibited a response to the combination of cetuximab and dasatinib. Combinatorial treatment of KRAS mutant xenografts resulted in decreased cell proliferation, as measured by Ki67, and higher rates of apoptosis, as measured by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling). The data presented in this study indicate that dasatinib can sensitize KRAS mutant CRC tumors to cetuximab and may do so by altering the activity of several key signaling pathways. Furthermore, these results suggest that signaling via EGFR and SFKs may be necessary for cell proliferation and survival of KRAS mutant CRC tumors. These data strengthen the rationale for clinical trials combining cetuximab and dasatinib in the KRAS mutant CRC genetic setting.

Outcomes of prenatally diagnosed tetralogy of Fallot: Implications for valve-sparing repair versus transannular patch.

OBJECTIVES: To assess outcomes of prenatally diagnosed tetralogy of Fallot and determine factors associated with the choice to undergo a valvesparing repair versus transannular patch, and the use of prostaglandins at birth. METHODS: All cases at The Hospital for Sick Children (Toronto, Ontario) with a fetal diagnosis of tetralogy of Fallot from 1998 to 2006, were reviewed for demographic and fetal echocardiographic data to determine factors associated with the valve-sparing repair and need for perinatal support. RESULTS: Sixty-four fetuses met inclusion criteria (median gestational age 22 weeks) with 47 live births. Twenty-six underwent valve-sparing repair (median age 5.7 months) and 14 underwent transannular patch repair (median age 4.5 months). There were seven deaths before surgery and one post-transannular patch repair. One patient required a transannular patch repair after the initial valve-sparing repair. Twelve of 29 (41%) patients received prostaglandins at birth. Type of surgical repair, use of prostaglandins and postnatal death were among the outcomes investigated. The mean pulmonary valve (PV) z-score was -3.0+/-2.0 and the mean PV/aortic valve (AoV) ratio was 0.65+/-0.10. Lower PV z-score (P=0.04), smaller PV/AoV ratio (P=0.04) and the presence of nonantegrade arterial duct flow (P=0.02) were associated with prostaglandin use. A higher PV/AoV ratio was associated with valvesparing repair (P=0.04). Fetal z-scores of the PV, AoV and right pulmonary artery at 29 to 32 weeks gestational age correlated with respective postnatal z-scores (P=0.01). CONCLUSION: Fetal echocardiographic variables were associated with the use of prostaglandins and valve-sparing repair in fetuses with tetralogy of Fallot, and at 29 weeks, correlated with postnatal valve diameters.

A medium-term follow-up study of a cohort of Chinese patients after first hospitalisation in a gazetted hospital for mania.

OBJECTIVES: To study the characteristics of a cohort of first-episode manic patients treated in a regional psychiatric unit in Hong Kong, to explore the predictors of re-admission, and to investigate their functional outcomes 4 years after first hospitalisation. METHODS: This was a medium-term follow-up study, using retrospective review of hospital records and clinical interviews at follow-up. Forty-four Chinese patients diagnosed as having their first-episode mania were discharged from a gazetted psychiatric ward in Hong Kong between January 1999 and June 2002. Their clinical characteristics on admission and prescribed medications on discharge were investigated. Their re-admission status was charted. The patients were contacted for follow-up assessment of their functional outcome at 4 years after their first hospitalisation. RESULTS: In our cohort of 44 patients, their first-episode mania mostly presented in young adulthood, as significantly disturbed behaviour deemed to require compulsory admission. Nineteen (43%) of the patients were re-admitted at least once within 4 years of being discharged, 6 of whom were re-admitted more than once. Compulsory admission at the first-episode mania predicted future re-admission. Alcohol and substance abuse were associated with earlier re-admission after the first-episode mania. None of the patients died. For those who were reassessed (28 patients), most lived with family members. In all, 21 patients were able to sustain open employment at 4 years after discharge. About half (n = 14) of the traceable patients were able to continue in full-time employment at 4 years, while 7 were doing part-time work. The median Global Assessment of Functioning score of the traceable group was 88. CONCLUSION: The results of this local study on patients with their first-episode of hospitalisation for mania were comparable to findings reported in western studies.

Nuclear EGFR contributes to acquired resistance to cetuximab.

Epidermal growth factor receptor (EGFR) is a ubiquitously expressed receptor tyrosine kinase involved in the etiology of several human cancers. Cetuximab is an EGFR-blocking antibody that has been approved for the treatment of patients with head and neck squamous cell carcinoma and metastatic colorectal cancer. Previous reports have shown that EGFR translocation to the nucleus is associated with cell proliferation. Here we investigated mechanisms of acquired resistance to cetuximab using a model derived from the non-small cell lung cancer line H226. We demonstrated that cetuximab-resistant cells overexpress HER family ligands including epidermal growth factor (EGF), amphiregulin, heparin-binding EGF and beta-cellulin. Overexpression of these ligands is associated with the nuclear translocation of the EGFR and this process was mediated by the Src family kinases (SFK). Treatment of cetuximab-resistant cells with the SFK inhibitor, dasatinib, resulted in loss of nuclear EGFR, increased membrane expression of the EGFR and resensitization to cetuximab. In addition, expression of a nuclear localization sequence-tagged EGFR in cetuximab-sensitive cells increased resistance to cetuximab both in vitro and in mouse xenografts. Collectively, these data suggest that nuclear expression of EGFR may be an important molecular determinant of resistance to cetuximab therapy and provides a rationale for investigating nuclear EGFR as a biomarker for cetuximab response. Further, these data suggest a rationale for the design of clinical trials that examine the value of treating patients with cetuximab-resistant tumors with inhibitors of SFKs in combination with cetuximab.

Clinical and immunologic outcomes following haplocompatible donor lymphocyte infusions.

We retrospectively analyzed the characteristics of 16 consecutive pediatric patients who received one or more G-CSF-mobilized donor lymphocyte infusions (DLI) following a T-cell-depleted haplocompatible hematopoietic SCT (HSCT) to enhance immune recovery and/or treat an infection. The median time from HSCT to administration of first DLI was 12 weeks and the median dose of DLI administered was 3 x 10(4)/kg (range, 2.5-6 x 10(4)/kg). The incidence of Grade I-II acute GVHD was 19% (95% confidence interval (CI), 6-44%), and there were no cases of Grade III-IV acute GVHD. Chronic GVHD developed in 13% (95% CI, 2-37%) of patients. In surviving patients who did not undergo a second stem cell infusion, T-cell numbers and function increased to a protective level in a median of 3 months (range, 2-12.5 months) following the first DLI administration. In patients given DLI for treatment of an infection, 75% (95% CI, 46-92%) cleared their infection after a median of 9 weeks (range, 1-27 weeks). In patients with CMV infection, the development of CMV-specific T cells was observed following DLI. The 1-year overall survival following haplocompatible DLI was 71% (95% CI, 59-83%), with a median follow-up of 16 months from the first DLI.

Study rationale and design of the CIMT trial: the Copenhagen Insulin and Metformin Therapy trial.

BACKGROUND: Patients with type 2 diabetes (T2DM) have an increased mortality rate primarily because of macrovascular disease. Where T2DM patients cannot be managed sufficiently through diet, exercise and peroral antidiabetic drugs, that is when haemoglobin A1c (HbA1c) is above 7.0%, it is yet unknown whether a combination of metformin and insulin analogues is superior to insulin analogues alone. Nor is it known which insulin analogue regimen is the optimal. OBJECTIVE: The primary objective of this trial is to evaluate the effect of an 18-month treatment with metformin vs. placebo in combination with one of three insulin analogue regimens, the primary outcome measure being carotid intima-media thickness (CIMT) in T2DM patients. DESIGN: A randomized, stratified, multicentre trial having a 2 x 3 factorial design. The metformin part is double masked and placebo controlled. The insulin treatment is open. The intervention period is 18 months. PATIENT POPULATION: Nine hundred and fifty patients with T2DM and HbA1c > or = 7.5% on treatment with oral hypoglycaemic agents or on insulin treatment and deemed able, by the investigator, to manage once-daily insulin therapy with a long-acting insulin analogue. RANDOMIZATION: Central randomization stratified for age (above 65 years), previous insulin treatment and treatment centre. INTERVENTIONS: Metformin 1 g x two times daily vs. placebo (approximately 475 patients vs. 475 patients) in combination with insulin detemir before bedtime (approximately 315 patients) or biphasic insulin aspart 30 before dinner with the possibility to increase to two or three injections daily (approximately 315 patients) or insulin aspart before the main meals (three times daily) and insulin detemir before bedtime (approximately 315 patients). Intervention follows a treat-to-target principle in all six arms aiming for an HbA1c < or = 7.0%. OUTCOME MEASURES: Primary outcome measure is the change in CIMT from baseline to 18 months. Secondary outcome measures comprises the composite outcome of death, acute myocardial infarction, stroke or amputation assessed by an adjudication committee blinded to intervention, other cardiovascular clinical outcomes, average postprandial glucose increment from 0 to 18 months, hypoglycaemia and any inadvertent medical episodes. In addition, change in plaque formation in the carotids, HbA1c, cardiovascular biomarkers, body composition, progression of microvascular complications and quality of life will be assessed as tertiary outcome measures. TIME SCHEDULE: Patient enrolment started May 2008. Follow-up is expected to finish in March 2011. CONCLUSION: CIMT is designed to provide evidence as to whether metformin is advantageous even during insulin treatment and to provide evidence regarding which insulin analogue regimen is most advantageous with regard to cardiovascular disease.

Outbreak of human metapneumovirus infection in psychiatric inpatients: implications for directly observed use of alcohol hand rub in prevention of nosocomial outbreaks.

Nosocomial outbreaks of infectious diseases in psychiatric facilities are not uncommon but the implementation of infection control measures is often difficult. Here, we report an outbreak of an acute respiratory illness in a psychiatric ward between 29 July and 20 August 2005 involving 31 patients. Human metapneumovirus was detected in seven (23%) patients by reverse transcription-polymerase chain reaction and nucleotide sequencing. A review of outbreak surveillance records showed that six nosocomial outbreaks occurred in the year 2005, of which four (67%) were confirmed or presumably related to a respiratory viral infection. Directly observed deliveries of alcohol hand rub 4-hourly during daytime to all psychiatric patients was instituted in December 2005. Only one nosocomial respiratory viral outbreak occurred in the following year. The total number of patients and staff involved in nosocomial outbreaks due to presumed or proven respiratory virus infections decreased significantly from 60 to six (P<0.001), whereas those due to all types of nosocomial outbreaks also decreased from 70 to 24 (P=0.004). Alcohol hand rub has been shown to have potent bactericidal and virucidal activity against a wide range of nosocomial pathogens. Regular use of directly observed alcohol hand rub may decrease the incidence and scale of nosocomial outbreaks due to enveloped respiratory viruses especially in mentally incapacitated patients.

Accuracy of Arabic versions of three asthma symptoms questionnaires against the clinical diagnosis of asthma.

Validation studies of asthma symptom questionnaires against provocation tests of bronchial hyperresponsiveness have shown comparable performances of written and video taped questionnaires. This study aimed to determine the test characteristics of Arabic versions of two written and one video taped questionnaires when compared to the clinical diagnosis of asthma made by two respiratory physicians. The written International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire had higher sensitivities and greater accuracy than the other two questionnaires. Comparisons between corresponding questions and scenes in the ISAAC questionnaires in general revealed no significant differences in performance. The ISAAC written questionnaire had test characteristics consistent with its potential use as a screening instrument for asthma in this population of children.

Health response of two communities to military antennae in Cyprus.

OBJECTIVES: This study investigated concerns that have been raised about past and future health effects caused by high power transmissions of high frequency (7-30 MHz) radio waves from military antenna systems at Akrotiri, Cyprus. METHODS: A cross-sectional study of three villages (two exposed, one unexposed) collected longitudinal and short-term radiofrequency measurements. Health data were collected using questionnaires containing information on demographic factors, specific illnesses, general health (SF-36 well-being questionnaire), reproductive history, childhood illnesses, risk perception and mortality. Analysis was with SPSS v11.5 using cross tabulations of non-parametric data and tests for significance. Key health outcomes were subjected to logistic regression analysis. RESULTS: Field strengths within the two "exposed" villages were a maximum of 0.30 (Volts/Vm(-1) metre) from the 17.6 MHz military transmissions and up to 1.4 Vm(-1) from unspecified sources, mainly cell phone frequencies. The corresponding readings in the control village were <0.01 Vm(-1). Compared with the control village there were highly significant differences in the reporting of migraine (OR 2.7, p<0.001), headache (OR 3.7, p<0.001), and dizziness (OR 2.7, p<0.001). Residents of the exposed villages showed greater negative views of their health in all eight domains of the SF-36. There were also higher levels of perceived risk, particularly to noise and electromagnetic "pollution". All three villages reported higher values of risk perception than a UK population. There was no evidence of birth abnormalities or differences in gynaecological or obstetric history. Numbers of cancers were too small to show differences. CONCLUSION: It was clear that even this close (1-3 km) to powerful transmissions, the dominant sources of radiofrequency fields were cell phone and national broadcast systems. There was no excess of cancer, birth defects or obstetric problems. There was heightened risk perception and a considerable excess of migraine, headache and dizziness, which appears to share a gradient with radiofrequency exposure. The authors report this association but suggest this is unlikely to be an effect of radiofrequency and more likely to be antenna visibility or aircraft noise.