Design and test of a compact beam current monitor based on a passive RF cavity for a proton therapy linear accelerator.

In a medical accelerator, real-time monitoring systems of the beam and dose delivered to the patient are mandatory. In this work, we present a compact current profile detector that has been designed and tested in the framework of the TOP-IMPLART (Intensity Modulated Proton Linear Accelerator for RadioTerapy) project. This project foresees the realization of a proton linear accelerator, currently under construction at ENEA Frascati, for proton therapy applications. The linac produces a pulsed proton beam with 3 µs duration at 50 Hz repetition rate with a pulse current between 0.5 and 50 µA. A large dynamic range and spatial constraints make the use of usual noninterceptive beam diagnostics unfeasible. Therefore, the use of a beam current monitor based on a passive RF cavity working in the TM010 mode has been proposed. This paper reports the electromagnetic design of the device guided by a simplified analytical model. A prototype of such a device has been realized, characterized, and tested on the linac with a 35 MeV beam varying the beam current. The test results in air and in vacuum, together with the signal detection systems used, are presented.

THE TOP-IMPLART PROTON LINEAR ACCELERATOR: INTERIM CHARACTERISTICS OF THE 35 MEV BEAM.

In the framework of the Italian TOP-IMPLART project (Regione Lazio), ENEA-Frascati, ISS and IFO are developing and constructing the first proton linear accelerator based on an actively scanned beam for tumor radiotherapy with final energy of 150 MeV. An important feature of this accelerator is modularity: an exploitable beam can be delivered at any stage of its construction, which allows for immediate characterization and virtually continuous improvement of its performance. Currently, a sequence of 3 GHz accelerating modules combined with a commercial injector operating at 425 MHz delivers protons up to 35 MeV. Several dosimetry systems were used to obtain preliminary characteristics of the 35-MeV beam in terms of stability and homogeneity. Short-term stability and homogeneity better than 3% and 2.6%, respectively, were demonstrated; for stability an improvement with respect to the respective value obtained for the previous 27 MeV beam.

Evaluación de la terapia mecánica periodontal en bolsas profundas: respuesta clínica y bacteriológica / Evaluation of periodontal mechanical therapy in deep pockets: Clinical and bacteriological response

Objetivos: Evaluar la composición microbiológica y los parámetros clínicos de bolsas periodontales >5 mm de profundidad al inicio, 1 semana, 3 y 12 meses post raspado y alisado radicular. Materiales y Métodos: Se tomaron registros clínicos y muestras de placa subgingival de 44 sitios de pacientes con diagnóstico de periodontitis crónica. Se identificaron por técnica de Reacción en Cadena de la Polimerasa (PCR) patógenos putativos periodontales: Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Treponema denticola (Td), Tannerella forsythia (Tf) y Prevotella intermedia (Pi). Los pacientes recibieron terapia mecánica periodontal y fueron reevaluados a los 7 días, 3 y 12 meses. Resultados: Luego del tratamiento, todos los parámetros clínicos (Placa Bacteriana, Hemorragia, Supuración, Profundidad al Sondaje y Nivel de Inserción Clínica) se redujeron significativamente y los valores obtenidos se mantuvieron hasta los 12 meses. Al inicio, las especies bacterianas prevalentes fueron Pg, presente en 66 por ciento de los sitios, Tf (55 por ciento) y Td (41 por ciento). Los sitios más profundos se relacionaron con las asociaciones Tf-Td (6.8 mm) y Tf-Td-Pi (7 mm). Post terapia, el número de sitios positivos para Td, Tf y Pg se redujo significativamente. Conclusiones: El raspado y alisado radicular mejoró significativamente los parámetros clínicos y redujo la prevalencia de los patógenos periodontales Pg, Tf y Td en bolsas periodontales profundas. Los resultados obtenidos se mantuvieron hasta los 12 meses. No se detectaron mayores pérdidas de inserción clínica en el 86 por ciento de los sitios a 3 meses y en 79 por ciento a los 12 meses. Los sitios en los que el tratamiento no fue efectivo en la eliminación de patógenos a los 12 meses desarrollaron mayores profundidades de sondaje.

Objectives: To evaluate the microbial composition and clinical parameters of periodontal pockets with probing depth >5 mm at baseline, 1 week, 3 and 12 months after scaling and root planning. Methods: Clinical parameters were measured and bacterial samples were collected from 44 sites in 11 patients with chronic periodontitis. By means of Polymerase Chain Reaction (PCR) the presence of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Treponema denticola (Td), Tannerella forsythia (Tf) and Prevotella intermedia (Pi) was estimated. The patients received mechanical periodontal therapy and were evaluated after 1 week, 3 months and 12 months. Results: After treatment, all clinical parameters (Plaque, Bleeding on Probing, Supuration, Probing Pocket Depth and Clinical Attachment Level) were significantly reduced, and the values obtained were maintained up to the 12 months that the study lasts. At baseline, the most prevalent species were Pg, present in 66 percent of the sites, Tf (55 percent) and Td (41 percent). The deepest sites were related to the association Tf-Td (6.8 mm) and Tf-Td-Pi (7 mm). The number of positive sites for Td, Tf and Pg was significantly reduced after therapy. Conclusions: Scaling and root planning improve significantly clinical parameters as well as reduce the prevalence of periodontal pathogens Pg, Td and Tf in deep periodontal pockets. The results obtained were maintained up to 12 months. No further clinical attachment loss was found in 86 percent of the sites at 3 months and 79 percent at 12 months. The sites where the treatment failed in removing pathogens developed at 12 months greater probing pocket depths.

Efficiency of the cloacal sexing technique in greater rhea chicks (Rhea americana).

1. The feasibility and accuracy of the cloacal sexing technique in greater rhea chicks was assessed using chicks of two captive populations of greater rhea in Córdoba, Argentina. 2. A total of 46 greater rhea chicks of 2 to 3 months of age were randomly arranged into three groups and the members of each group were sexed by a different operator. 3. A feather of each chick was plucked for sexing through a molecular method and results were used as controls. 4. Sex was correctly assigned by cloacal inspection in 98% of the cases. Chick manipulation was easily performed and no infections or traumatic lesions were observed a posteriori. 5. Cloacal sexing of rhea chicks up to 3 months of age does not affect animal welfare and should be considered an efficient alternative to molecular methods.

Effect of retinoids on follicular cells.

It has been demonstrated that topical application of all-trans retinoic acid and other retinoids can alter the hair-growth cycle in the C3H mouse model. The anagen phase is prolonged and the telogen phase is shortened. This effect is similar to the effect of minoxidil on the hair-cycle dynamics in this animal model. The levels of cellular retinoic acid binding protein measured by radioreceptor assay in whole skin of C3H mice were higher during anagen and lower during telogen. Topical application of certain retinoids caused elevated levels of cellular retinoic acid-binding protein (cRABP) in the whole skin homogenates during both phases of the cycle. Of the retinoids tested, those most effective in altering the levels of cRABP in the skin of the mice were also capable of significantly altering the hair-cycle dynamics. There appeared to be a relationship between the ability of retinoid to increase cRABP, increase 3H-thymidine incorporation, and alter the dynamics of the hair cycle. Only cRABP-II is detectable in human cultured dermal fibroblasts and dermal papilla cells. Dermal fibroblasts showed higher amounts of cRABP-II as compared to dermal papilla cells. The difference in cRABP-II expression might explain a distinct response to RA by these two cell populations. Whether the difference in expression of cRABP-II might be of physiologic importance remains to be determined. Treatment of human dermal papilla cells in culture with retinoic acid does not appear to affect proliferation, at least at the doses tested.

Effects of vitamin A status on cellular retinoic acid-binding protein in rat skin and testes.

Cellular retinoic acid-binding protein levels were determined in the skin and testes of normal and retinol-deficient rats. All-trans [3H]retinoic acid (1.1 TBq/mmol) was used to titrate the specific binding sites in tissue cytosol preparations. Scatchard plot analyses were used to determine the concentration of cellular retinoic acid-binding protein and its binding affinity (Kd) for all-trans-retinoic acid. In normal rat skin the concentration of cellular retinoic acid-binding protein was 3317 +/- 924 (SD) fmol/mg protein and the Kd was 1.98 +/- 1.0 x 10(-9) mol/l. In retinol-deficient rat skin the concentration of cellular retinoic acid-binding protein was 2584 +/- 1205 fmol/mg protein and the Kd was 3.30 +/- 3.4 x 10(-9) mol/l. In the normal rat testes the concentration of cellular retinoic acid-binding protein was 2965 +/- 1187 fmol/mg protein and the Kd was 2.30 +/- 2.1 x 10(-9) mol/l. In retinol-deficient rat testes the concentration of cellular retinoic acid-binding protein was 2439 +/- 383 fmol/mg protein and the Kd was 0.3 +/- 0.2 x 10(-9) mol/l. These findings indicate that there are no significant differences in the levels of cellular retinoic acid-binding protein between normal and deficient rat skin and testes (p greater than 0.1, by Wilcoxon rank sum test). We therefore conclude that the level of cellular retinoic acid-binding protein in skin and testes may not be controlled by the availability of vitamin A.

Retinoids: compounds important to hair growth.

Although the mechanisms of follicular regression in androgenetic alopecia are not fully understood, retinoids may be important in changing the status of regressing follicles. There are many reports documenting reversal of epithelial dysplastic changes with retinoids. Although none of the studies with retinoids have concentrated on the precise mechanisms of follicular growth (regression or regeneration), these limited observations, and our early studies suggest that further work should be done on the effect retinoids have on the hair follicle during the various growth and regression phases of the follicular life cycle in humans. We propose that certain retinoids increase the rate of hair growth, prolong the anagen phase of the hair cycle, play a role in converting vellus to terminal hairs, and act synergistically with minoxidil to produce more dense hair regrowth from regressing follicles than either compound alone. Larger controlled studies and better methods for assessing hair growth are necessary to support these early results. Other retinoids as well as certain minoxidil analogs should also be studied.

Topical tretinoin for hair growth promotion.

Topical all-trans-retinoic acid (tretinoin) alone and in combination with 0.5% minoxidil has been tested for the promotion of hair growth in 56 subjects with androgenetic alopecia. After 1 year, the combination of topical tretinoin with 0.5% minoxidil resulted in terminal hair regrowth in 66% of the subjects studied. Tretinoin was shown to stimulate some hair regrowth in approximately 58% of the subjects studied. One female subject with pronounced alopecia for more than 20 years had regrowth of hair using only tretinoin for a period of 18 months. Tretinoin has been shown to promote and regulate cell proliferation and differentiation in the epithelium and may promote vascular proliferation. These factors are important for hair growth promotion. These preliminary results indicate that more work should be done on the role of retinoids in hair growth. The synergistic effect of retinoids in combination with a low concentration of minoxidil should also be further investigated.

Evaluation of retinoids as inhibitors of [3H] all-trans retinoic acid binding to cellular retinoic acid-binding protein in rat skin and testes.

These experiments were designed to test the ability of certain analogs and metabolites of all-trans-retinoic acid (RA), 13-cis-retinoic acid, 4-hydroxy-all-trans-retinoic acid, 4-keto-all-trans-retinoic acid, trimethylmethoxyphenol (TMMP) analog of retinoic acid, and TMMP analog of ethyl retinoate (etretinate) to compete for cellular retinoic acid-binding protein (CRABP) in skin and testes of rats. All retinoids, except etretinate, bind to CRABP in a competitive manner with a similar affinity (approximately 5 X 10(-9) M for skin and 3 X 10(-9) M for testes). In contrast, etretinate binds in a noncompetitive manner with a much lower affinity (7.7 X 10(-5) M for skin and 7.5 X 10(-5) M for testes). The values (microM) of IC50 for CRABP from rat skin are 0.43, 0.41, 0.95, 0.83, and 77.4 and those from rat testes are 0.59, 1.29, 2.25, 2.30, and 75.25 for all-trans-RA, 13-cis-RA, 4-hydroxy-all-trans RA, 4-keto-all-trans-RA, TMMP analog of RA, and etretinate, respectively. Etretinate is a potent retinoid that is used in the treatment of psoriasis. The lack of quantitative correlation between IC50 and the biological activity of etretinate may be explained in that the active form of etretinate in the body may be the carboxylic acid form (TMMP analog of RA) which binds to CRABP with higher affinity.

The in vitro metabolism of 13-cis-retinoic acid in a model sebaceous structure, the rat preputial gland.

In order to study the metabolism of 13-cis-retinoic acid (13-cis-RA) in animal sebaceous glands and analogues, preputial glands from normal and vitamin A-deficient male rats were incubated with [3H]13-cis-RA for up to 24 h; vitamin A-normal hamster costovertebral glands (flank organs) were incubated for 24 h as well. High-performance liquid chromatography was used to identify the metabolites. [3H]13-cis-RA was rapidly converted to a less polar compound, [3H]all-trans-retinoic acid, by the preputial glands from both normal and deficient rats. In normal preputial glands, the level of [3H]all-trans-RA decreases and two more polar compounds, metabolite I and [3H]4-keto-13-cis-RA appear. In contrast, [3H]all-trans-RA is not metabolized further by the preputial glands from deficient rats, while [3H]13-cis-RA in the hamster costovertebral glands remains intact for up to 24 h. The major metabolite of [3H]13-cis-RA in rat preputial glands is [3H]4-keto-13-cis-RA. Initially, [3H]13-cis-RA is converted to [3H]all-trans-RA. In vitamin A-deficient rats the preputial glands fail to further metabolize [3H]13-cis-RA to the more polar [3H]13-cis-RA derivatives. This may be due to the reduced level of P-450 enzyme in vitamin A-deficient rat preputial glands.

Plasma zinc in hypertension/toxemia and other reproductive variables in adolescent pregnancy.

A study was conducted at Charity Hospital, New Orleans, among 272 adolescent pregnant women to ascertain the relationship of pregnancy outcome to plasma zinc level measured once at the time of enrollment. Regression analyses were performed on zinc status versus parameters concerning success of pregnancy corrected for gestational stage at specimen collection. Analysis of variance was performed on groups according to presence or absence of complications, with analyses of covariance used to analyze dichotomous groups. Low, though widely variable, plasma zinc levels were found (mean = 58 +/- 12.6 micrograms/dl). Zinc values differed significantly by gestational stage at collection, the regression coefficient indicating a decline of 0.07 micrograms/dl/day. Plasma zinc level correlated significantly with Hb, red blood cells, ferritin, and folic acid. As to course of pregnancy, women experiencing hypertension/toxemia were found to have significantly lower plasma zinc level. Among infants displaying congenital defects at birth those with undescended testes and metatarsus varus were delivered by mothers whose plasma zinc was well below the mean for the group. These findings indicate the need to investigate the influence of dietary patterns and zinc intake on maternal plasma zinc level and pregnancy outcome, further delineating the role of zinc in human reproduction, particularly hypertension of pregnancy.

Differences in the lipid constituents of sebum from pre-pubertal and pubertal subjects.

Significant differences have been reported in the composition of skin surface lipid in pre-pubertal subjects when compared to pubertal subjects. Analytical studies were performed to determine whether group mean changes in the fatty acid composition of the triglyceride and wax ester fractions of sebum could be detected in pre-pubertal versus pubertal subjects. Twenty males (ages 6-9), twenty females (ages 6-9) and twelve teenagers (ages 11-16) were studied. Skin surface lipid was examined by densitometry and gas chromatography. There were significant changes in the fatty acid composition of the wax fraction of sebum in the 11-16-year-old children when compared to the 6-9-year-old group. As wax is of sebaceous gland origin, this may represent a change in sebum composition probably in response to the hormonal stimulus. Changes in the fatty acid fraction of triglycerides were also noted with age, but this may be due to the change in source of triglyceride from predominantly epidermal origin to sebaceous gland origin.