Feasibility of using interpolated contours of targets and organs at risk in intensity‐modulated radiation therapy treatment planning for advanced‐stage nasopharyngeal carcinoma

To assess the dosimetric effect of using interpolated contours in planning intensity‐modulated radiation therapy (IMRT) for advanced T‐stage nasopharyngeal carcinoma. The present study focused on T3–T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5‐mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full‐scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process.     

Use of the Optomap with lid retraction and its sensitivity and specificity#

Background: Optomap uses the ultra‐wide field scanning laser ophthalmoscopy to provide retinal examination. It permits fundus examination without the use of a mydriatic, which is more comfortable for the patients. This paper determines the sensitivity and specificity of the Optomap for detecting retinal signs under non‐mydriatic conditions. Methods: Fifty‐four eyes identified with retinal/choroidal signs and eight normal eyes were recruited from 31 Hong Kong Chinese subjects. Photo‐documentation of fundal changes was obtained with the Optomap under non‐mydriatic conditions before a dilated fundus examination by a clinician using standard procedures. The eyelid was retracted using a cotton bud when necessary. Dilated fundus examinations were performed by another clinician using binocular indirect ophthalmoscopy and slitlamp biomicroscopy with a fundus lens. The Optomap images were evaluated by four other investigators under masked condition. The International Classification of Disease, Ninth Revision (ICD‐9‐CM) was adopted for recording retinal features. Screening results were compared with those obtained using the dilated fundus examination as the gold standard. Results: The cotton bud method for eyelid retraction showed an improvement in the area of retina that could be visualised. The sensitivity and specificity of the Optomap averaged 76.4 and 71.9 per cent, respectively. Some fundal signs were missed by all observers in the Optomap but not with the biomicroscope. These included white‐without‐pressure, lattice degeneration, paramacular drusen and pigmentary changes at central fundus. Conclusion: Optomap serves as a reliable screening tool for fundus examination especially because it covers a much wider area of the peripheral retina than other digital instruments for fundus photography.     

Feeding during acute diarrhea as a risk factor for persistent diarrhea

Dietary intake during diarrhea in children less than three years of age was estimated from information recorded on illustrated dietary forms used by children's caretakers during the first week of illness in a prospective community-based study of diarrheal diseases in Lima, Peru. The frequency of consumption and the amount consumed of food groups and selected commonly consumed foods were analyzed by the final duration of the diarrheal episode. Cereals were less frequently consumed during the acute phase of diarrheal episodes that ultimately became persistent (>14 days'duration), apparently shortening the duration of the episode by one day (median duration of four days in children not consuming vs three days in children consuming cereals during diarrhea, p <0.02 Kaplan-Meier logrank test). Only roots and tubers (mainly potatoes) were consumed in greater quantity during episodes that became persistent. There was no evidence that consumption of breast milk or non-maternal milk was associated with an alteration in diarrheal duration. This study provides further evidence of the beneficial effects of continuing feeding during diarrhea using foods available at the home level, especially cereals, which are commonly used in the diet of young children.     

Myocardial perfusion imaging with technetium-99m sestamibi SPECT in the evaluation of coronary artery disease

Technetium-99m hexakis-2-methoxy-isobutyl-isonitrile(^99mTc sestamibi) has been used for myocardial perfusion imaging in the evaluation of coronary artery disease (CAD) since 1990. The experience of its use in an Asian population with and without previous myocardial infarction (Ml), diabetes mellitus (DM), hypertension (HPT) and collateral circulation (COL) is reported. One hundred and thirty-nine patients who underwent treadmill exercise testing with ^99mTc sestamibi single photon emission computed tomography (SPECT) and coronary angiogram were studied. The overall sensitivity for the detection of CAD was 91.0% and specificity was 64.7%. For patients without previous myocardial infarction, the sensitivity was 83.8% and specificity was 83.3%. Patients with COL had a higher sensitivity while those with HPT had a lower specificity. Sensitivity was higher in patients with multi-vessel disease (MVD) than single vessel disease (SVD). The overall detection for individual artery stenosis was 74.1% with a specificity of 73.1 %. Amongst the three major coronary arteries, sensitivity was highest for the right coronary artery and specificity was highest for the left circumflex artery. Specificity was higher in patients without MI or COL. We found that the agreement between ^99mTc sestamibi SPECT and coronary angiogram for the extent of CAD was only 52.5%. The concordance rate was higher for patients with MVD than SVD. It is concluded that ^99mTc sestamibi SPECT is a sensitive and specific test for the detection of CAD and localization of disease to individual coronary arteries in our patients with some differences in the subgroups. Agreement between coronary angiogram and ^99mTc sestamibi for the extent of coronary artery disease was also satisfactory.     

MHC: function and implication on vaccine development

The purpose of this State of the Art review is to present an overview of structural and functional aspects of human MHC molecules and how polymorphisms in HLA molecules determine the nature of the antigenic peptides bound and how such may impact upon rational vaccine development. The following areas will be discussed: elements of immune recognition, class I and class II structure and function, the class I antigen processing pathway, class II antigen processing and presentation, functional divergence among T-cells recognizing class I or class II MHC molecules, and rational vaccine development. While the first section will review our current understanding of MHC structure and function, the latter part will draw on my own work with Hepatitis C Virus (HCV) antigens.     

Benzo[a]pyrene at an environmentally relevant dose is slowly absorbed by, and extensively metabolized in, tracheal epithelium

While tobacco smoke has been conclusively identified as a lung carcinogen, there is much debate over which smoke constituent(s) are primarily responsible for its carcinogenicity. Previous studies in our laboratory suggested that highly lipophilic carcinogens are slowly absorbed in the thicker epithelium of the conducting airways, potentially allowing for substantial local metabolism. The bioactivation of polycyclic aromatic hydrocarbons in airway epithelium may, hence, be important in tobacco smoke-induced carcinogenesis. In the present study, the hypothesis of slow absorption and substantial local metabolic activation of highly lipophilic carcinogen in airway epithelium was tested in dogs. A single dose of tritiated benzo[a]pyrene (BaP) dissolved in a saline/phospholipid suspension was instilled in the trachea, just anterior to the carina. At intervals of a few minutes up to 30 min over a 3-h period, blood samples were drawn from the azygous vein, which drains the area around the point of instillation, and from the systemic circulation. Tissue samples were taken at the end of the experiment. The concentration of BaP with depth into the tracheal mucosa was determined with autoradiography. BaP was slowly absorbed into the trachea with a half-time of approximately 73 min, which is consistent with diffusion-limited passage through the epithelium and lead to local doses in the tracheal epithelium that were more than a 1000-fold those of other tissues. The long retention of BaP in the epithelium provided the local metabolizing enzymes with high substrate levels over a long period, resulting in extensive metabolism. At 3 h after the exposure, 23% of the BaP-equivalent activity remained in the tracheal mucosa. Of this fraction, 13% was parent compound, 28% was organic extractable, 31% was water-soluble, and 28-7% of the instilled dose was bound to tracheal tissues. These results explain the tendency of highly lipophilic carcinogens, such as BaP, to induce tumors at the site of entry and, furthermore, indicate that the highly lipophilic components of tobacco smoke and polluted air may be the most important contributors to lung tumors of the conducting airways.      

Urinary albumin excretion and transcapillary escape rate of albumin in malignancies

Transcapillary escape rate of albumin was determined in 22 patients with different malignancies. In addition, urinary albumin excretion rate was measured in 24-h urine samples using a sensitive immunoassay. Increased urinary albumin excretion was defined as ≥20 μg/min according to conventional standards. Renal glomerular filtration and tubular function was estimated by⁵¹Cr-EDTA plasma clearance and urinary beta 2-microglobulin, respectively. Median urinary albumin excretion rate was 15.0 μg/min (range 6–510 μg/min) and the frequency of increased urinary albumin excretion was 41%. This agrees with other studies showing increased albuminuria in several types of malignant diseases. Patients with advanced disease (tumour, node, metastasis (TNM) stage II–IV) had a significantly higher urinary albumin excretion rate than patients with localized disease (TNM stage I). Serum creatinine, glomerular filtration rate and urinary beta 2-microglobulin were all within normal limits. Median transcapillary escape rate of albumin was 5.5%/h (range 2–8%/h) and this level is comparable with values in healthy subjects. There was no significant difference in transcapillary escape rate between patients with elevated urinary albumin excretion and the normoalbuminuric group. Median value of the absolut outflux of albumin was 10.6 g/h with similar levels in patients with increased urinary albumin excretion and patients with normoalbuminuria. Our results indicate a high prevalence of minor glomerular dysfunction with a slightly elevated urinary albumin excretion in patients with malignancies. The normal endothelial function, as estimated by the transcapillary escape rate of albumin, suggests an overal unaffected capillary permeability and increased urinary albumin loss appears to be an isolated renal phenomenon in cancer patients.