Clinical implementation of a computer controlled milling machine for compensating filter production

The procedures required for the clinical implementation of a computer controlled milling machine for producing compensators for breast radiotherapy are described. Moulds are cut in a rigid polymer foam block and filled with stainless-steel granulate. Quality assurance procedures are described for ensuring that the compensators produced are consistent and accurate. Relative and absolute dosimetric measurements are presented showing that the compensators are accurate to better than 1% and demonstrate the technique to be clinically acceptable.     

Analysis of faecal neutral sterols in patients with familial adenomatous polyposis by gas chromatography-mass spectrometry

Previous studies have suggested that patients with familial adenomatous polyposis (FAP) have increased faecal excretion of cholesterol but a reduction in cholesterol metabolites. It was consequently proposed that the degree of faecal cholesterol degradation could be used as a means of diagnosis. Developments in the extraction and analysis of faecal neutral sterols as well as the accurate means of diagnosing FAP by DNA analysis and indirect ophthalmoscopy has necessitated a re-examination of this proposal. Faecal neutral sterols were analysed in 10 patients with untreated FAP following a complete 5-day stool collection and compared with 9 healthy control subjects (including 4 siblings) closely matched for age and sex. The median [25 and 75, percentiles] stool wet weights were similar between the FAP (97.5 [69, 192] g · 24 h^-1) and the control (116 [61.5, 137] g · 24 h^-1) groups. Faecal cholesterol concentration was similar in the two groups (FAP=2.3 [1.4, 4.2]; control=3.5 [1.0, 6.0] mol · g^-1 dry wt) as was the concentration of total neutral sterols not including plant sterols (FAP=17.2 [13.4, 21.0]; control=18.2 [7.4, 21.6] mol · g^-1 dry wt). There were no significant differences in the proportions of cholesterol metabolised between the FAP (82.3 [74.2, 93.5]%) and control (72.1 [5.7, 81.3]%) groups. This study does not support the notion that faecal neutral sterol metabolism is uniquely different in patients with FAP.

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Résumé Des études précedentes avaient suggéré que les malades avec polypose adénomateuse familiale (PAF) avaient une excrétion fécale augmentée de choléstérol mais une réduction des métabolìtes du choléstérol. On a donc proposé que les degrés de dégradation fécale du choléstérol puisse être utilisée comme moyen de diagnostic. Le développement dans l'extraction et l'analyse des stérols neutres fécaux aussi bien que des moyens appropriés de diagnostiquer la PAF par analyse du DNA et ophthalmoscopie indirecte a nécessité un ré-examen de cette proposition. Les stérols neutres fécaux, ont été analysés chez 10 patients avec une PAF non traitée après une collection complète des matières de 5 jours et comparés avec 9 sujets contrôles sains (comprenant 4 enfants de mêmes parents) étroitement appareillés pour l'âge et le sexe. Les poids moyens (25 et 75 percentiles) de selles humides étaient similaires chez les PAF (97.5 (69, 192) g · 24 h^-1) et les contrôles (116 (61.5, 137) g · 24 h^-1). La concentration de choléstérol fecal était similaire dans les deux groupes (PAF=2.3 (1.4, 4.2); controle=3.5 (1.0, 6.0) mol · g poids sec) de même que la concentration de stérols neutres totaux stéroïdes végétaux exclus (PAF=17.2 (13.4, 21.0); controle 18.2 (7.4, 21.6) mol · g poids sec). Il n'y avait pas de différence significative dans les proportions de choléstérol métabolisé entre les PAF (82.3 (74.2, 93.5)%) et les contrôles (72.1 (5.7, 81.3)%). Cette étude ne confirme pas la notion que le métabolisme des stérols neutres fécaux est uniquement différent chez les patients avec une PAF.

     

Hepatic abscess

Hepatic abscess—amebic or pyogenic—can be diagnosed with great accuracy by either ultrasonography or computed tomographic (CT) scanning. Ultrasound is the modality of choice and will detect almost 100% of abscesses. Confirmation of a diagnosis of amebic liver abscess is made by the indirect hemagglutination test that should be positive in almost 100% of cases. Cultures of pus from the abscess and from the blood must be obtained in cases of pyogenic liver abscess. A positive culture of pus from the abscess has been achieved in 90% of cases. Ultrasound or CT guidance is utilized in aspiration of a hepatic abscess. In the treatment of an amebic liver abscess, metronidazole is the amebicide of choice. Open drainage is contraindicated. For cases that fail to respond to therapy with amebicides, closed drainage guided by CT or ultrasound is performed. Secondary bacterial infection of an amebic liver abscess is an extremely rare event. The identification and determination of the antibiotic sensitivity of organisms responsible for pyogenic liver abscess is a crucially important step. Unless a celiotomy is necessary to correct an intraabdominal process or the abscess is extremely large, the initial treatment of pyogenic liver abscess is a 2 week course of appropriate antibiotics followed by a 1 month course of oral antibiotics. The majority of pyogenic liver abscesses will respond to such treatment. If drainage of a pyogenic abscess is required, the preferable technique is with a percutaneous CT- or ultrasound-directed catheter. Open surgical drainage should be reserved for those cases in which a celiotomy is required for other purposes or for the patient who has failed a course of appropriate antibiotic therapy and closed percutaneous drainage is not feasible. The mortality for treatment of amebic liver abscess should be approximately zero and for pyogenic liver abscess should be less than 10%.

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Resumen El absceso hepático—amibiano o piogénico—puede ser diagnositicado con gran precisión mediante la ultrasonografía (US) o la tomografía computadorizada (TC). La ultrasonografía es la modalidad de escogencia; détecta casí el 100% de los abscesos. La confirmación del diagnóstico de absceso amibiano del hígado se hace por la prueba de hemaglutinación indirecta, la cual debe resultar positiva en prácticamente el 100% de los casos. Cultivos del pus y de la sangre deben ser realizados en los pacientes con abscesos piógenos. Se logran cultivos positivos del pus del absceso en 90% de los casos. Se utiliza la guía ultrasonográfica o de tomografía computadorizada para la aspiración del absceso.El metronidazol es el agente amebicida de preferencia en el tratamiento del absceso amibiano del hígado. El drenaje abierto está contraindicado. En los casos en que falla la terapia con amibicidos, se realiza el drenaje cerrado guiado por US o por TC. La infección secundaria de un absceso amibiano del hígado es un fenómeno extraordinariamente raro.La identificatión y determinatión de la sensibilidad antibiótica de los microorganismos responsables del absceso piógeno representa un paso crucial en su manejo. A menos que se haga necesario realizar una laparotomía para la correción del algún proceso intraabdominal o porque el absceso es excesivamente grande, el tratamiento inicial del absceso piógeno es un ciclo de antibióticos propiados de 2 semanas, seguidos de tratamiento con antibióticos orales por un mes. La mayoría de los abscesos piógenos del hígado responde a este tipo de tratamiento. Si se requiere drenaje de un absceso piógeno, la técnica de preferencia es la punción percutánea por medio de un catéter guiado por US o TC. El drenaje quirúrgico abierto debe reservarse para aquellos casos en que la laparatomía es necesaria por razones diferentes o en que hay falla en la respuesta a un ciclo de terapia antibiótica adecuada y el drenaje percutáneo no es factible.La mortalidad en el manejo del absceso amibiano del hígado debe ser nula, y para el absceso piógeno de menos de 10%.

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Résumé L'abcès hépatique amibien ou à pyogènes peut être diagnostiqué avec une grande précision soit par l'échographie, soit par la tomodensitométrie. L'échographie est la méthode de choix et détecte presque 100% des abcès. On obtient la confirmation du diagnostic d'abcès amibien par le test d'hémagglutination indirecte qui est positive dans presque 100% des cas. On doit faire des cultures de pus provenan de l'abcès et des hémocultures en cas d'abcès à pyogènes du foie. Ces cultures ont été positives dans 90% des cas. L'échographie et la tomodensitométrie aident à guider le drainage de abcès.Dans le traitement de l'abcès amibien du foie, le métronidazole est l'amibicide de choix. Le drainage à ciel ouvert est contreindiqué. Pour les cas qui ne répondent pas aux amibicides, un drainage percutané guidé par la tomodensitométrie ou l'échographie est indiqué. La surinfection d'un abcès amibien du foie est extrêmement rare.L'identification et la détermination de la sensibilité aux antibiotiques des organismes responsables de l'abcès à pyogènes est une étape extrêmement importante. A moins qu'une laparotomie soit nécessaire pour traiter une infection intraabdominale associée ou que le volume de l'abcès soit extrêmement important, le traitement initial d'un abcès à pyogènes comprend 2 semaines d'antibiotiques adaptés par voie générale suivies d'un mois d'antibiotiques par voie orale. La plupart des abcès à pyogènes répondront bien à ce traitement. Si le drainage d'un abcès à pyogènes s'avère nécessaire, la meilleure technique est percutanée avec un cathéter inséré sous contrôle tomodensitométrique ou échographique. On réservera le drainage chirurgical à ciel ouvert aux cas où une laparotomie est nécessaire pour d'autres raisons et où le malade n'a pas répondu à l'antibiothérapie adaptée et chez qui le drainage percutané est impossible à faire.La mortalité de l'abcès amibien traité devrait approcher 0% et atteindre pour l'abcès à pyogènes moins de 10%.

     

A filter for breast imaging on a radiotherapy X-ray simulator

Simulator radiographs taken as a record of breast radiotherapy planning often show ill defined breast tissue margins because exposure parameters are set to optimize visualization of the chest wall rather than the bulk of the breast. This creates difficulties when using simulator images as reference images in verification by comparing with either portal film or images from an electronic portal imaging device. Our aim was to improve breast images taken at simulation without changing exposure parameters that have been optimized for visualization of the chest wall. This has been achieved via an external filter to be used when taking radiographs with the treatment simulator. The filter is made of stainless steel coated with tin and is shaped to maintain acceptable imaging of the chest wall by covering only the section of field anterior to the chest wall. Radiographs of breast simulations using the filter have been accepted as satisfactory by both clinicians and radiographers. The filter is now in routine clinical use for breast and chest wall treatment simulation.     

(+)-Catechin in human plasma after ingestion of a single serving of reconstituted red wine

BACKGROUND: Red wine consumption may decrease the risk of coronary heart disease through the actions of its constituent flavonoids. (+)-Catechin is an abundant flavonoid in red wine. OBJECTIVE: The objective was to determine changes in plasma (+)-catechin concentrations after ingestion of a single, moderate serving of dealcoholized red wine reconstituted with either water (DRW) or water and alcohol (ARW). DESIGN: Nine subjects (5 men, 4 women) ingested, in random order, 120 mL DRW on one day and 120 mL ARW on another day. Both the DRW and ARW contained 35 mg (121 micromol) free (+)-catechin. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, and 8 h. Plasma was analyzed by gas chromatography-mass spectrometry for (+)-catechin after enzymatic release of sulfate and glucuronide conjugates. RESULTS: Calcium ions were needed to effectively hydrolyze (+)-catechin conjugates in plasma containing EDTA. Neither the ARW or DRW nor sex affected the area under the curve at 8 h, the maximum concentration (c(max)), or the time it took for plasma total (+)-catechin to reach maximum concentration (t(max)). Pooled mean (+/-SEM) values for the ARW and DRW were as follows: area under the curve, 306.1 +/- 29.5 nmol*h/L; c(max), 76.7 +/- 7.5 nmol/L; and t(max), 1.44 +/- 0.13 h. The half-life of (+)-catechin in plasma was significantly less (P = 0.038) after ingestion of the ARW (3.17 h) than after ingestion of the DRW (4.08 h). CONCLUSIONS: Increases in plasma total (+)-catechin concentrations were not significantly different after single moderate servings of either the ARW or DRW. Alcohol in the ARW hastened the elimination of (+)-catechin from the plasma compartment. (+)-Catechin elimination may represent excretion or conversion to methylated derivatives.     

Isolation and characterization of propagable cell lines (HUNC) from the androgen-sensitive Dunning R3327H rat prostatic adenocarcinoma

The Dunning H rat prostate tumor (R3327H) is a widely used experimental model of human prostatic adenocarcinoma (CaP). The Dunning H tumor has been characterized as androgen-sensitive, androgen-receptor (AR) positive, prostate-specific antigen and prostatic acid phosphatase (PAP) positive. To date, the tumor has been maintained by serial passage in vivo because of the lack of an in vitro cell line that retains the characteristics of the in vivo tumor. The objective of the present study was to establish a propagable cell line from R3327H adenocarcinoma that maintained androgen sensitivity and expression of AR, PSA and PAP. Tissue harvested from an in vivo R3327H tumor was dissociated with collagenase and placed into Richter's improved media (with supplements). A cytokeratin-positive epithelial cell line (HUNC- E) and a vimentin-positive stromal cell line (HUNC-S) were generated from the primary culture, subcultured continuously for >300 days, and passaged >50 times. Survival of the HUNC-E cell line in vitro depended on several media supplements, including nicotinamide, insulin, transferrin, selenium and epidermal growth factor (EGF). HUNC-E cells expressed AR and produced PSA and PAP throughout the culture period, as confirmed by immunocytochemistry and Western blot analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone (DHT) to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent growth and PSA production, which demonstrated the androgen-sensitive nature of the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1 ratio and introduced subcutaneously into syngeneic male hosts, tumors formed in 2/3 animals with an average latency of 7 months. RT-PCR and immunocytochemical characterization of the HUNC cell lines revealed that the cells expressed several growth factors and their cognate receptors, including HGF, TGF-alpha and the TGF-betas, indicating the establishment of potential autocrine loops in the neoplastic cells. The HUNC-E and HUNC-S CaP cell lines, which retain the characteristics of the epithelial and stromal components of the in vivo R3327H tumor, will allow a more thorough and informative molecular and biological analysis of prostatic adenocarcinoma.      

Zinc replenishment reduces esophageal cell proliferation and N- nitrosomethylbenzylamine (NMBA)-induced esophageal tumor incidence in zinc-deficient rats

Previous work has shown that sustained increased and decreased cell proliferation, induced by dietary zinc deficiency and caloric restriction respectively, influence the course of N- nitrosomethylbenzylamine (NMBA)-induced esophageal carcinogenesis in rats. The present study considered whether the increased cell proliferation and esophageal tumor incidence induced by zinc deficiency are reversed upon zinc replenishment. Weanling rats were maintained initially on a deficient diet containing 4 p.p.m. zinc. After 5 weeks, carcinogen-treated animals were given six intragastric doses of NMBA (2 mg/kg twice weekly). Controls were untreated. After the second NMBA dose, the rats were divided into three dietary groups. One group was continued on the deficient diet, while the other two groups were switched to diets containing either 75 or 200 p.p.m. zinc, with half of the members in each group fed ad libitum and half pair-fed with deficient rats. NMBA-untreated controls were similarly replenished. At various time points, esophageal cell proliferation was assessed in five animals from each group by immunohistochemical detection of cells in S phase, with in vivo 5-bromo-2'deoxyuridine labeling. At 11 weeks after the first dose, esophageal tumor incidence was greatly reduced, from 100% in the deficient group to 26 and 14% respectively in the replenished groups fed ad libitum 75 and 200 p.p.m. zinc and to 14 and 11% respectively in the replenished groups pair-fed 75 and 200 p.p.m. zinc. In addition, the number of tumors per esophagus was reduced from 9.93 +/- 4.25 in deficient rats, to a range of 0.11 +/- 0.31-0.30 +/- 0.54 in replenished animals. Following zinc replenishment, esophageal cell proliferation, as measured by labeling index (LI), the number of labeled cells and the total number of cells, was markedly decreased in NMBA-untreated and -treated esophagi as compared with those in corresponding deficient esophagi. Thus, the esophageal cell proliferation induced by zinc deficiency is reversed by zinc replenishment and replenished animals have a markedly lower incidence of esophageal tumors.