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.     

Influence of polymorphism on the surface energetics of salmeterol xinafoate crystallized from supercritical fluids

Purpose. To characterize the surface thermodynamic properties of two polymorphic forms (I and II) of salmeterol xinafoate (SX) prepared from supercritical fluids and a commercial micronized SX (form I) sample (MSX). Methods. Inverse gas chromatographic analysis was conducted on the SX samples at 30, 40, 50, and 60°C using the following probes at infinite dilution: nonpolar probes (NPs; alkane C5-C9 series); and polar probes (PPs; i.e., dichloromethane, chloroform, acetone, ethyl acetate, diethyl ether, and tetrahydrofuran). Surface thermodynamic parameters of adsorption and Hansen solubility parameters were calculated from the retention times of the probes. Results. The free energies of adsorption (-G_A) of the three samples obtained at various temperatures follow this order: SX-II > MSX SX-I for the NPs; and SX-II > MSX > SX-I for the PPs. For both NPs and PPs, SX-II exhibits a less negative enthalpy of adsorption (H_A) and a much less negative entropy of adsorption (S_A) than MSX and SX-I, suggesting that the high -G_A of SX-II is contributed by a considerably reduced entropy loss. The dispersive component of surface free energy (_s ^D) is the highest for MSX but the lowest for SX-II at all temperatures studied, whereas the specific component of surface free energy of adsorption (-G_A ^SP) is higher for SX-II than for SX-I. That SX-II displays the highest -G_A for the NP but the lowest _s ^D of all the SX samples may be explained by the additional -G_A change associated with an increased mobility of the probe molecules on the less stable and more disordered SX-II surface. The acid and base parameters, K_A and K_D, that were derived from H_A ^SP reveal significant differences in the relative acid and base properties among the samples. The calculated Hansen solubility parameters (_D, _P, and _H) indicate that the surface of SX-II is the most polar and most energetic of all the three samples in terms of specific interactions (mostly hydrogen bonding). Conclusions. The metastable SX-II polymorph possesses a higher surface free energy, higher surface entropy, and a more polar surface than the stable SX-I polymorph.     

Oral (drinking water) two-generation reproductive toxicity study of bromodichloromethane (BDCM) in rats

Bromodichloromethane (BDCM) was tested for reproductive toxicity in a two-generation study in CRL SD rats. Thirty rats/sex/ group/generation were continuously provided BDCM in drinking water at 0 (control carrier, reverse osmosis membrane-processed water), 50,150, and 450 ppm (0, 4.1 to 12.6, 11.6 to 40.2, and 29.5 to 109.0 mg/kg/day, respectively). Adult human intake approximates 0.8 microg/kg/day (0.0008 mg/kg/day). P and F1 rats were observed for general toxicity (viability, clinical signs, water and feed consumption, body weights, organ weights [also three weanling Fl and F2 pups/sex/litter], histopathology [10/sex, 0- and 450-ppm exposure groups]) and reproduction (mating, fertility, abortions, premature deliveries, durations of gestation, litter sizes, sex ratios, viabilities, maternal behaviors, reproductive organ weights [also three weanling Fl and F2 pups/sex/ litter], sperm parameters, and implantations. F1 rats were evaluated for age at vaginal patency or preputial separation. Ten P and F1 rats/sex from the 0- and 450-ppm exposure groups and rats at 50 and 150 ppm with reduced fertility were evaluated for histopathology (gross lesions, testes, intact epididymis, all F1 dams for number of primordial follicles). Developmental parameters in offspring included implantation and pup numbers, sexes, viabilities, body weights, gross external alterations, and reproductive parameters (Fl adults). Toxicologically important, statistically significant effects at 150 and/or 450 ppm included mortality and clinical signs associated with reduced absolute and relative water consumption, reduced body weights and weight gains, and reduced absolute and relative feed consumption (P and F1 rats). Significantly reduced body weights at 150 and 450 ppm were associated with reduced organ weights and increased organ weight ratios (% body and/or brain weight). Histopathology did not identify abnormalities. Small delays in sexual maturation (preputial separation, vaginal patency) and more Fl rats with prolonged diestrus were also attributable to severely reduced pup body weights. Mating, fertility, sperm parameters, and primordial ovarian follicular counts were unaffected. The no-observable-adverse-effect level (NOAEL) and the reproductive and developmental NOAELs for BDCM were at least 50 ppm (4.1 to 12.6 mg/kg/day), 5125 to 15,750 times the human adult exposure level, if delayed sexual maturational associated with severely reduced body weights is considered reproductive toxicity. If considered general toxicity, reproductive and developmental NOAELs for BDCM are greater than 450 ppm (29.5 to 109.0 mg/kg/day), or 36,875 to 136,250 times the human adult exposure level. Regardless, these data indicate that BDCM should not be identified as a risk to human reproductive performance or development of human conceptuses.     

Developmental toxicity of levo-alpha-acetylmethadol (LAAM) in tolerant rats

Mated Crl:CD VAF/Plus female rats, in a range-finding study (n = 5-6 per dose) and a subsequent definitive study (n = 30 per dose) were used to determine the developmental toxicity, including the teratogenic potential of levo-alpha-acetylmethadol (LAAM) hydrochloride, in tolerant rats. Tolerance was induced by initially administering the drug by gavage (10 ml/kg) at 2 mg/kg/day and increasing the dose every 2 weeks for 12 weeks until the doses of 2, 6, 9, 12, and 15, or 2, 6, and 12 mg/kg/day were achieved in the range-finding or definitive study, respectively. Females were then mated to stock males and treated throughout mating and gestation. Controls received distilled water on a similar regimen. The range-finding experiment was used for initial clinical evaluations and to determine tissue concentrations of LAAM and metabolites. In plasma, liver, and brain collected from dams and fetuses pooled by litter on gestation day 20, LAAM and its two N-demethylated metabolites, norLAAM and dinorLAAM, showed dose-dependent increases in concentration and in tissue to plasma ratios. Tissue to dam plasma ratios were highest in dam liver (17-60), intermediate in fetal liver (3-16), and fetal brain (3-14), and lowest in dam brain (0.8-5.6) and fetal plasma (0.3-2.1). In the definitive study, caesarean section examinations were performed following euthanization on gestation day 20 on all surviving females followed by teratologic examination of the fetuses. Drug-related outcomes, including increased activity, secondary hair loss, scabbing, focal swelling, and material around the nose, were exhibited by all groups receiving LAAM. Maternal toxicity was evident as decreased body weights, with maximum reduction at the 6-mg/kg/day dose, and reduction in feed consumption. There was also evidence of developmental toxicity in the form of postimplantation losses at all doses of LAAM. There were no deaths attributable to LAAM. No grossly observable visceral or skeletal anomalies related to LAAM were observed in the fetuses. In conclusion, the no-observable-effect level when administered to tolerant rats was less than 2 mg/kg/day with regard to clinical signs, body weight, body weight gain, and feed consumption, and with regard to developmental toxicity as reflected by postimplantation losses. Despite maternal and developmental toxicity, there was no evidence of selective fetal toxicity or teratogenic activity attributable to LAAM.     

Progression of corpus callosum atrophy in Alzheimer disease

BACKGROUND: Atrophy of the corpus callosum in the absence of primary white matter degeneration reflects loss of intracortical projecting neocortical pyramidal neurons in Alzheimer disease (AD). OBJECTIVES: To determine individual rates of atrophy progression of the corpus callosum in patients with AD and to correlate rates of atrophy progression with clinical disease severity and subcortical disease. METHODS: Magnetic resonance imaging-derived measurements of corpus callosum size were studied longitudinally in 21 patients clinically diagnosed as having AD (mean observation time, 17.0 +/- 8.5 months) and 10 age- and sex-matched healthy controls (mean observation time, 24.1 +/- 6.8 months). RESULTS: Corpus callosum size was significantly reduced in AD patients at baseline. Annual rates of atrophy of total corpus callosum, splenium, and rostrum were significantly larger in AD patients (-7.7%, -12.1%, and -7.3%, respectively) than in controls (-0.9%, -1.5%, and 0.6%, respectively). Rates of atrophy of the corpus callosum splenium were correlated with progression of dementia severity in AD patients (rho = 0.52, P<.02). The load of subcortical lesions at baseline (P<.05) predicted rate of anterior corpus callosum atrophy in healthy controls. Rates of atrophy of corpus callosum areas were independent of white matter hyperintensity load in patients with AD. CONCLUSIONS: Measurement of corpus callosum size allows in vivo mapping of neocortical neurodegeneration in AD over a wide range of clinical dementia severities and may be used as a surrogate marker for evaluation of drug efficacy.     

Echocardiogram‐gated multislice spiral CT in functionally univentricular heart following long‐lasting Waterston–Cooley anastomosis

Waterston–Cooley anastomosis may be carried out in patients with tricuspid atresia to provide pulmonary perfusion. It is associated with several complications, including preferential blood flow to the right lung, hypoplasia of the left pulmonary artery, obstruction of the anatomosis or rupture of pulmonary aneurysms. We study a patient with thrombosis in the pulmonary arteries following surgical construction of a Waterston shunt in childhood. Imaging findings and clinical symptoms are discussed with emphasis on echocardiogram‐gated multislice spiral CT.     

Computed tomography fluoroscopy‐guided chemical lumbar sympathectomy: Simple,safe and effective

Demographic, clinical and laboratory data were retrospectively collected from records of 146 cases of CT fluoroscopy‐guided chemical lumbar sympathectomy for the palliation of inoperable peripheral vascular disease (PVD) between January 1997 and August 1999. Of these, 16% had claudication, 39% had rest pain and 44% had ischaemic ulcers or gangrene. Seventy‐three percent of elective cases were outpatients. At 3 months, 27 cases were lost to follow up, leaving 119 cases. Within 3 months, improvement, defined as doubling of the walking distance, cessation of rest pain or healing of ulcers, occurred in 30.3% of cases. No change was observed in 45.4% of cases and 24.3% of cases deteriorated. Patients with ulcers or gangrene had significantly poorer results than those without any ischaemic lesions, as only 19% versus 39% of patients improved (P < 0.05). The presence of hypertension, diabetes mellitus, hyperlipidaemia and smoking had no value in predicting clinical outcome (P > 0.05). There were no major complications noted. CT fluoroscopy‐guided chemical lumbar sympathectomy is safe and effective, with a complication rate of less than 1%, and efficacy of at least 30% measured within 3 months. It is a simple and minimally invasive procedure, easily performed on an outpatient basis. CT fluoroscopy‐guided chemical lumbar sympathectomy should be considered for all patients in the early stages of inoperable PVD.     

Induction of esophageal tumors in zinc-deficient rats by single low doses of N-nitrosomethylbenzylamine (NMBA): analysis of cell proliferation, and mutations in H-ras and p53 genes

Dietary zinc deficiency in rats induces hyperplasia in the esophagus and increases N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumor incidence. Previous work showed a direct relationship between epithelial cell proliferation and esophageal tumor incidence in rats given multiple doses of NMBA. We investigated the effects of single low doses of NMBA in zinc-deficient rats since a single dose of 5.0 mg/kg was reported to be non-carcinogenic in rats. Zinc-sufficient and deficient rats received a single i.g. dose of NMBA at 0.5 or 2.0 mg/kg. At week 14, tumor incidence was 50% with 0.8 +/- 1.0 tumors/rat, and 80% with 2.2 +/- 1.9 tumors/rat, in deficient groups, D(0.5) and D(2.0), that received the lower and higher dose, respectively. In addition, two small papillomas were found in one out of eight untreated zinc-deficient rats. None of the NMBA-treated or untreated zinc- sufficient rats had any tumors. Esophageal cell proliferation, as determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry, showed that, irrespective of NMBA treatment, deficient esophagi had significant increases in the number of labeled cells, the total number of cells, and the labeling index, as compared with zinc-sufficient ones. Mutations in Ha-ras and p53 genes in esophageal tumors were detected by single strand conformation polymorphism (SSCP) analysis. DNA sequencing of variant conformers revealed a point mutation (GGA-->GAA, codon 12) in Ha-ras in 4/5 (80%) and 5/8 (63%) tumors, from D(0.5) and D(2.0) rats, respectively. Three out of eight tumors from D(2.0) rats exhibited SSCP mobility shifts within p53 exons 5 and 7: two tumors (2/8, 25%) had missense mutations and the third, a silent mutation. Of the two tumors with p53 mutations, one had a double mutation (transition at codon 164, TCA-->TTA; transversion at codon 241, AGT-->TGT), and the other tumor, a transition at codon 172 (AGA-->GGA), with amino acid changes in all cases. In parallel with PCNA expression, elevated p53 expression was associated with hyperplastic and dysplastic regions, as well as with tumors, in deficient esophagi. In short, these data indicate that dietary zinc deficiency, with its associated sustained increased cell proliferation in the esophagus, can drive an otherwise non-tumorigenic dose of NMBA into a highly tumorigenic one.      

Steroids for intubated croup masking airway haemangioma

Recently, the beneficial role of steroids for acute laryngotracheobronchitis has been more clearly defined for both intubated and unintubated patients. However, corticosteroids also improve the clinical signs of airway haemangiomata. Two patients are described who illustrate how this can be a source of diagnostic confusion.     

Colorectal hemangioma: radiologic findings

The authors correlated radiographs with the clinical and histologic data of 12 patients with colorectal hemangioma. All patients presented with rectal bleeding, which was chronic in seven. Phleboliths were also visible in seven cases, which correlated with chronic bleeding in five. On barium studies, three masses were soft and three produced rigid narrowing. The atypical features of rigid luminal narrowing, which might mimic a carcinoma, and hypovascularity correlated with chronic bleeding or visible phleboliths, which suggest the correct diagnosis of colorectal hemangioma.