A photorefractive study of dark focus and refraction

Photorefraction was used to estimate the position of focus in the light and in the dark of individuals with a range of refractive errors. Tests of individuals with known far points, in the light, allows empirical calibration of the photorefractive method. In the dark, position of focus was consistently about 1 D more myopic than the subject's refraction. Dark photorefraction may serve as an objective means of refraction without cycloplegia.     

Protection against congenital cytomegalovirus (CMV) disease, conferred by a replication-disabled, bacterial artificial chromosome (BAC)-based DNA vaccine

It is unclear if protective immunity can be conferred by a cytomegalovirus (CMV) vaccine encoding a single protein subunit, or if multiple viral genes need to be targeted. Using the guinea pig model of congenital CMV infection, these studies examined the immunogenicity and efficacy of a DNA vaccine based on the guinea pig cytomegalovirus (GPCMV) genome cloned as a non-infectious BAC plasmid, modified by transposon insertion into the homolog of the HCMV tegument protein, UL48. Following vaccination of female Hartley guinea pigs with BAC DNA, adverse GPCMV-related pregnancy outcome were assessed after establishment of pregnancy, followed by GPCMV third-trimester challenge. Animals immunized with recombinant BACmid engendered anti-GPCMV antibodies by ELISA assay. Immunogenicity of BAC plasmid DNA was augmented by inclusion of the lipid adjuvant, DOTMA/DOPE, in the vaccine regimen. Among pups born to 12 control (sham-immunized) dams challenged with GPCMV in the third trimester, mortality was 23/35 (66%). In contrast, among evaluable pregnancy outcomes in pups born to 10 BAC-immunized pregnant dams, preconception immunization resulted in reduced pup mortality, to 10/34 pups (29%; p<0.005 versus control, Fisher's exact test). In addition, vaccinated dams had reduced viral load, compared to controls, as assessed by quantitative, real-time PCR.     

The association of the PON1 Q192R polymorphism with complications and outcomes of pregnancy: findings from the British Women's Heart and Health cohort study

It has been hypothesised that paraoxonase genes would be related to adverse pregnancy outcomes, via a maternal or fetal effect on placental hypoperfusion and thrombosis. To date only two studies have assessed this possibility. In this study we assessed the associations of the PON1 Q192R polymorphism with self-report of having pregnancy-induced hypertension, gestational hyperglycaemia and a preterm offspring birth. The associations were assessed in 3266 white women who were randomly selected from 23 British towns. There was no association between PON1 Q192R and either self-report of pregnancy-induced hypertension or gestational hyperglycaemia but the prevalence of reporting having a preterm birth increased with each R allele: per allele odds ratio 1.20 [95% confidence interval (CI) 1.03, 1.41]. When our results were pooled with the one previous study of the association of this polymorphism with preterm birth, the pooled per allele odds ratio was 1.19 [95% CI 1.02, 1.39]. Our findings provide some further evidence to suggest that PON1 Q192R is associated with preterm birth; they invite further investigation of both maternal and fetal genotype for PON1 Q192R in relation to preterm birth.     

Measuring children and monitoring obesity: surveys of English Primary Care Trusts 2004-06

BACKGROUND: Child obesity has unclear determinants and consequences. A precautionary approach requires best-guess interventions and large-scale surveillance. This study was to determine the current measurement activities and the information systems required for child obesity surveillance. METHODS: DESIGN: Questionnaire-based surveys. SETTING: Primary Care Trusts (PCTs) in United Kingdom. PARTICIPANTS: Two hundred and forty-seven (82%) PCTs in 2004 and 240 (79%) in 2006. MAIN MEASURES: Children's ages at which height and weight are routinely measured, the type of personnel taking the measurements, arrangements for recording data, information systems and uses of the data. RESULTS: PCTs measure height/length and weight most commonly at 6 weeks (74%) and 5 years (74%)-also at 6-12 months (58%), 1.5-2.5 years (50%), 2.5-4 years (40%), 11 years (18%) and 7 years (11%). Seventy-seven per cent of PCTs transferred the measurements to a database-26 different information systems were named. Six per cent of PCTs in 2004, rising to 34% in 2006, used the data to produce public health reports. CONCLUSIONS: Body mass index (BMI) surveillance requires new arrangements in 25% of PCTs at school entry and 80% at transfer to senior school. Important aspects of child obesity surveillance not yet addressed are pre-school measurement, longitudinal assessment and the public health requirements of (child) electronic health records.     

Treatment outcome for metastatic papillary renal cell carcinoma patients

BACKGROUND: Most clinical trial reports in metastatic renal cell carcinoma (RCC) do not distinguish between histologic subtypes, making it difficult to assess specific treatment efficacy. The current retrospective study sought to define clinical features and outcome data for metastatic papillary RCC. METHODS: Clinical features, treatment outcome, and survival were evaluated in 38 patients with metastatic papillary RCC who underwent clinical evaluation at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1985 and 2005. Twenty-three of 513 individuals were identified from a clinical trial database, 14 of 1895 from a surgery database, and 1 of 357 from a pathology database. A literature review of systemic therapy in metastatic papillary RCC was performed. RESULTS: Among the 38 patients, 30 had been treated at MSKCC with various systemic therapies, including cytokines. Twelve therapies resulted in stable disease, 30 in initial progression of disease, and 1 in an unknown response. One patient had a partial response to sunitinib, a novel multitargeted tyrosine kinase inhibitor. The median overall survival time for the entire study group was 8 months (95% confidence interval, 5-12). A literature review on treatment of metastatic papillary RCC produced 4 reports, confirming a lack of efficacy for systemic therapy. CONCLUSIONS: A resistance to systemic therapy characterizes patients with metastatic papillary RCC. Further understanding of the genetics and molecular biology and subtypes involved may provide the basis for more effective agents. Treatment with targeted therapies or other experimental agents is warranted.     

Nonsteroidal anti-inflammatory drugs and the esophageal inflammation-metaplasia-adenocarcinoma sequence

Observational studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of esophageal adenocarcinoma, but it is not known at what stage they may act in the esophageal inflammation-metaplasia-adenocarcinoma sequence. In an all-Ireland case-control study, we investigated the relationship between the use of NSAIDs and risk of reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. Patients with esophageal adenocarcinoma, long-segment Barrett's esophagus and population controls were recruited from throughout Ireland. Esophagitis patients were recruited from Northern Ireland only. Data were collected on known and potential risk factors for esophageal adenocarcinoma and on the use of NSAIDs, including aspirin, at least 1 year before interview. Associations between use of NSAIDs and the stages of the esophageal inflammation-metaplasia-adenocarcinoma sequence were estimated by multiple logistic regression. In total, 230 reflux esophagitis, 224 Barrett's esophagus, and 227 esophageal adenocarcinoma and 260 population controls were recruited. Use of aspirin and NSAIDs was associated with a reduced risk of Barrett's esophagus [odds ratio [OR; 95% confidence interval (95% CI)], 0.53 (0.31-0.90) and 0.40 (0.19-0.81), respectively] and esophageal adenocarcinoma [OR (95% CI), 0.57 (0.36-0.93) and 0.58 (0.31-1.08), respectively]. Barrett's esophagus and esophageal adenocarcinoma patients were less likely than controls to have used NSAIDs. Selection or recall bias may explain these results and the results of previous observational studies indicating a protective effect of NSAIDs against esophageal adenocarcinoma. If NSAIDs have a true protective effect on the esophageal inflammation-metaplasia-adenocarcinoma sequence, they may act early in the sequence.     

Quality of Life Analyses in a Clinical Trial of DPPE (tesmilifene) Plus Doxorubicin Versus Doxorubicin in Patients with Advanced or Metastatic Breast Cancer: NCIC CTG Trial MA.19

Background DPPE (tesmilifene) plus doxorubicin (DOX) demonstrated a significant improvement in survival versus DOX in a phase III clinical trial in advanced breast cancer. However, DPPE is associated with unusual toxicity in the form of hallucinations, nausea and vomiting which were anticipated to impact on short-term quality of life (QOL).Methods Standard National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) approaches were applied as the primary method to analyze the QOL data from this trial. This includes cross-sectional comparisons, together with a global test for the QOL response rate. Sensitivity analyses were also performed for selected QOL domains and items, using other types of summary measures and statistics.Results Two hundred seventy one patients (89% of randomized) submitted the baseline QOL questionnaires and were included in the QOL analysis. No statistically significant difference in QOL response between treatment arms was found for any domain or item except nausea and vomiting (P = 0.04). Cross-sectional comparisons showed statistically significant differences for some domains/items at specific assessment times with all differences favoring the DOX alone arm. Patients on DPPE/DOX arm were significantly worse in terms of average and median pain change scores.Conclusion Different analyses yielded slightly different conclusions but, in general, the QOL analyses were concordant and showed that patients on DOX alone had fewer disease and treatment related adverse events and␣better QOL. Interestingly, the QOL response analysis also showed that aggressive premedication regimens appear to ameliorate potential negative effects of DPPE on emesis and nausea as measured by patient assessed QOL.     

Post-operative arm morbidity and quality of life. Results of the ALMANAC randomised trial comparing sentinel node biopsy with standard axillary treatment in the management of patients with early breast cancer

Summary This study is the first large prospective RCT of sentinel node biopsy (SNB) compared with standard axillary treatment (level I-III axillary lymph node dissection or four node sampling), which includes comprehensive and repeated quality of life (QOL) assessments over 18 months. Patients (n=829) completed the Functional Assessment of Cancer Therapy – Breast (FACT-B+4) and the Spielberger State/Trait Anxiety Inventory (STAI) at baseline (pre-surgery) and at 1, 3, 6, 12, and 18 months post-surgery. There were significant differences between treatment groups favouring the SNB group throughout the 18 months assessment. Patients in the standard treatment group showed a greater decline in Trial Outcome Index (TOI) scores (physical well-being, functional well-being and breast cancer concerns subscales in FACT-B+4) and recovered more slowly than patients in the SNB group (p<0.01). The change in total FACT-B+4 scores (measuring global QOL) closely resembled the TOI results. 18 months post-surgery approximately twice as many patients in the standard group compared with the SNB group reported substantial arm swelling (14% versus 7%) (p=0.002) or numbness (19% versus 8.7%) (p<0.001). Despite the uncertainty about undergoing a relatively new procedure and the possible need for further surgery, there was no evidence of increased anxiety amongst patients randomised to SNB (p>0.05). For 6 months post-surgery younger patients reported less favourable QOL scores (p<0.001) and greater levels of anxiety (p<0.01). In view of the benefits regarding arm functioning and quality of life, the data from this randomised study support the use of SNB in patients with clinically node negative breast cancer.     

Dysgenetic hypoplastic kidney simulating metastatic lung carcinoma

We describe a 57-year-old male with prior history of an absent right kidney and kidney transplant who was found to have lung cancer. Integrated positron emission tomography (PET) and computerized tomography (CT) scan was done for staging and showed uptake in the right upper lung primary and right renal fossae region which was suggestive of metastatic disease. An excisional biopsy of the right renal fossae mass showed that it was a hypoplastic kidney simulating a metastatic focus on PET scan. The patient eventually underwent a left upper lobectomy with a final pathological stage of T2N0M0. Positive PET scan areas should be biopsied to confirm the presence of metastatic disease before excluding patients from surgical treatment.