Non-invasive assessment of skeletal kinetics using fluorine-18 fluoride positron emission tomography: evaluation of image and population-derived arterial input functions

To measure regional skeletal kinetics using fluorine-18 fluoride positron emission tomography (PET) it is necessary to know the concentration of radioactive tracer being delivered to bone by arterial plasma with relation to time, the arterial input function (IFa). Methods by which IFa can be derived without arterial sampling are attractive because of their relative technical simplicity and the reduction in possible morbidity to the subject. We have compared the use of a scaled population input function (IFp) and a corrected image-derived input function from the aorta (IFi) with an IFa directly measured from a radial artery line in ten normal postmenopausal women. Both of the aforementioned methods rely only on a small number of discrete venous samples. Each subject had a dynamic PET acquisition of the lumbar spine performed after the intravenous injection of 180 MBq ¹⁸F-fluoride. Both the IFp and the IFi were compared with the IFa in terms of the accuracy of determination of six parameters. These were: plasma clearance of fluoride to bone mineral (K _i), unidirectional plasma clearance to total bone tissue (K ₁) and individual rate constants k ₂, k ₃ and k ₄, calculated using non-linear regression with a three-compartment model, and the plasma clearance to bone mineral calculated using the Patlak method (K _pat). For both the IFp and the IFi method the root mean square errors for K _pat and K _i were similar and small (<8.2%). The errors in determining K ₁ and the rate constants k ₂ to k ₄ are larger by either method, but with a small advantage using the IFp method. It is concluded that the use of either non-invasive method for determining the arterial plasma input function is suitable for the measurement of the most important parameters, K _i and K _pat, in these subjects. Received 8 April and in revised form 11 July 1999     

p53 Protein Expression in a Population-Based Series of Primary Vulval Squamous Cell Carcinoma and Immediate Adjacent Field Change

Objectives.Our aim was to study correlations between survival, disease recurrence, and p53 protein expression in a well defined population-based series of vulval squamous cell carcinoma and immediate adjacent epithelial skin changes.Methods.One hundred fifteen vulval squamous cell carcinoma were studied. Epithelial skin changes immediately adjacent to tumor were classified into nonneoplastic epithelial disorders (NNED) or vulval intraepithelial neoplasia (VIN). Archival specimens containing primary tumor and immediate adjacent skin were immunostained with a mouse monoclonal antibody to p53 protein.Results.p53 overexpression, defined as greater than 10% nuclear epithelial staining, was observed in 68% of tumors. Tumor immunostaining did not correlate with actuarial survival or disease-free interval. p53 overexpression was associated with a nonsignificant trend toward shorter disease-free interval in those tumors with nodal metastatic disease at diagnosis (P= 0.07). The only clinicopathological variable found to correlate with p53 expression was tumor grade (P= 0.002). Immediate adjacent abnormal skin changes were associated with p53 overexpression in 32% of cases. Adjacent normal skin did not immunostain for p53. p53 overexpression was most likely to occur in adjacent epithelial changes incorporating both NNED and high grade VIN (P= 0.005). Patterns of epithelial p53 overexpression in adjacent abnormal skin were either basal or full thickness. Full thickness epithelial p53 overexpression was most likely to occur in those disorders containing VIN (P< 0.0001). Positive immunostaining of adjacent skin abnormalities did not predict local tumor recurrence.Conclusions.This study demonstrates that although vulval squamous tumor p53 expression is not of prognostic significance, distinct immunostaining patterns can be observed in immediate adjacent skin. Vulval epithelial skin disorders displaying histological features of both NNED and VIN III may contain a profile of underlying molecular change which is of significance in subsequent tumor development.     

Microscopic and Spectroscopic Analyses of Chlorhexidine Tolerance in Delftia acidovorans Biofilms

The physicochemical responses of Delftia acidovorans biofilms exposed to the commonly used antimicrobial chlorhexidine (CHX) were examined in this study. A CHX-sensitive mutant (MIC, 1.0 μg ml⁻¹) was derived from a CHX-tolerant (MIC, 15.0 μg ml⁻¹) D. acidovorans parent strain using transposon mutagenesis. D. acidovorans mutant (MT51) and wild-type (WT15) strain biofilms were cultivated in flow cells and then treated with CHX at sub-MIC and inhibitory concentrations and examined by confocal laser scanning microscopy (CLSM), scanning transmission X-ray microscopy (STXM), and infrared (IR) spectroscopy. Specific morphological, structural, and chemical compositional differences between the CHX-treated and -untreated biofilms of both strains were observed. Apart from architectural differences, CLSM revealed a negative effect of CHX on biofilm thickness in the CHX-sensitive MT51 biofilms relative to those of the WT15 strain. STXM analyses showed that the WT15 biofilms contained two morphochemical cell variants, whereas only one type was detected in the MT51 biofilms. The cells in the MT51 biofilms bioaccumulated CHX to a similar extent as one of the cell types found in the WT15 biofilms, whereas the other cell type in the WT15 biofilms did not bioaccumulate CHX. STXM and IR spectral analyses revealed that CHX-sensitive MT51 cells accumulated the highest levels of CHX. Pretreating biofilms with EDTA promoted the accumulation of CHX in all cells. Thus, it is suggested that a subpopulation of cells that do not accumulate CHX appear to be responsible for greater CHX resistance in D. acidovorans WT15 biofilm in conjunction with the possible involvement of bacterial membrane stability.     

Salivary gland scintigraphy--a suitable substitute for sialography?

By comparing 27 patients who had both scintigraphy and sialography in the assessment of salivary gland disease, scintigraphy has been shown to correlate well with abnormal sialograms. It is suggested that scintigraphy could become the initial screening procedure in the assessment of salivary gland disease. A normal scintiscan is unlikely to miss significant pathology (as demonstrated by sialography), but sialography must always be performed if there is a suspicion of duct obstruction on scintigraphy. Patients suspected of focal salivary gland pathology such as tumour have not been investigated. The series documents the findings in patients who presented with facial pain, swelling or xerostomia suggesting sialadenitis, duct occlusion or Sj?gren's syndrome.     

Use of home pregnancy tests among adolescent women

Many adolescents use home pregnancy tests when they suspect pregnancy. However, because of developmental issues and greater variation in menstrual cycles, teens are at risk for obtaining false-negative test results. Moreover, with teens, the need for a pregnancy test often accompanies the need for comprehensive reproductive care including evaluation for sexually transmitted infections and contraception. This article reviews the mechanisms of home pregnancy testing including sensitivity, accuracy, and home testing procedures. Clinical strategies for improving the accuracy of home pregnancy tests for teen users are discussed. Lastly, policy implications to improve teens' access to more accurate pregnancy testing and to reproductive health services are suggested.     

Burnout and use of HIV services among health care workers in Lusaka District, Zambia: a cross-sectional study

Background  

Well-documented shortages of health care workers in sub-Saharan Africa are exacerbated by the increased human resource demands of rapidly expanding HIV care and treatment programmes. The successful continuation of existing programmes is threatened by health care worker burnout and HIV-related illness.     

Imaging manifestations of pleural tumors.

Although radiologic assessment of pleural tumors may be accomplished with several imaging modalities, the standard noninvasive techniques include chest radiography and computed tomography (CT). These examinations may be supplemented with magnetic resonance imaging and occasionally with ultrasound. Depending on the location, size, and underlying histologic features, pleural tumors may produce a spectrum of findings. CT is particularly useful in defining the location and extent of these masses. The authors present a review of basic pleural anatomy and imaging features of both benign and malignant pleural neoplasms. The pleural may be involved by one of several primary or metastatic tumors. Specific cell types are diffuse malignant mesothelioma (the most common plain radiographic findings are unilateral pleural effusion and pleural thickening), localized fibrous tumor (circumscribed, spherical or ovoid, noncalcified lesions arising in the pleural surface), metastatic disease (radiographic findings may mimic those of malignant mesothelioma), and uncommon neoplasms including thymoma and lymphoma. Among these various pleural tumors, metastatic disease represents the most common neoplasm.     

Diagnosis of acute hepatitis C virus infection and estimated incidence in low- and high-risk English populations

The diagnosis of acute hepatitis C virus (HCV) infection is not straightforward; few people exhibit clinical symptoms and genome/antigen detection techniques do not indicate when infection had occurred. Here, a strategy to detect HCV RNA in the absence of antibody ('window-period') for diagnosis of acute infection is assessed. The sentinel surveillance of hepatitis testing study was used to retrospectively identify anti-HCV negative samples from high-risk individuals (2002-2003), for testing singly for HCV RNA. Additional samples were identified prospectively (2005) and tested in pools for HCV RNA. Positive samples were genotyped. Incidence and costs of adopting the pooling strategy were estimated. In the retrospective study, 8/390 (2.1%) samples were confirmed HCV RNA positive, anti-HCV negative. Prospectively, 3237 samples were tested in 325 pools. Five positive pools identified four confirmed HCV RNA positive patients (one false positive). Estimated incidence was 12.9 per 100 person-years in injecting drug users (IDUs) (retrospective study) and 3.7 per 100 person-years among drug/alcohol services and prison attendees (prospective study). Estimated costs were pound 850 per positive sample, in areas of higher risk. The yield from a window-period strategy depends upon the population tested. Pooled HCV RNA testing of anti-HCV negative samples from the current IDUs is realistic and relatively inexpensive to identify recently infected individuals.