Influence of Water on the Oxidation of NO on Pd/TiO2 Photocatalysts.

Two series of new photocatalysts were synthesized based on modification with Pd of the commercial P25 photocatalyst (EVONIK®). Two techniques were employed to incorporate Pd nanoparticles on the P25 surface: photodeposition (series Pd-P) and impregnation (series Pd-I). Both series were characterized in depth using a variety of instrumental techniques: BET, DRS, XRD, XPS, TEM, FTIR and FESEM. The modified series exhibited a significant change in pore size distribution, but no differences compared to the original P25 with respect to crystalline phase ratio or particle size were observed. The Pd0 oxidation state was predominant in the Pd-P series, while the presence of the Pd2+ oxidation state was additionally observed in the Pd-I series. The photoactivity tests were performed in a continuous photoreactor with the photocatalysts deposited, by dip-coating, on borosilicate glass plates. A total of 500 ppb of NO was used as input flow at a volumetric flow rate of 1.2 L·min-1, and different relative humidities from 0 to 65% were tested. The results obtained show that under UV-vis or Vis radiation, the presence of Pd nanoparticles favors NO removal independently of the Pd incorporation method employed and independently of the tested relative humidity conditions. This improvement seems to be related to the different interaction of the water with the surface of the photocatalysts in the presence or absence of Pd. It was found in the catalyst without Pd that disproportionation of NO2 is favored through its reaction with water, with faster surface saturation. In contrast, in the catalysts with Pd, disproportionation took place through nitro-chelates and adsorbed NO2 formed from the photocatalytic oxidation of the NO. This different mechanism explains the greater efficiency in NOx removal in the catalysts with Pd. Comparing the two series of catalysts with Pd, Pd-P and Pd-I, greater activity of the Pd-P series was observed under both UV-vis and Vis radiation. It was shown that the Pd0 oxidation state is responsible for this greater activity as the Pd-I series improves its activity in successive cycles due to a reduction in Pd2+ species during the photoactivity tests.

Comparative study of nanocrystalline titanium dioxide obtained through sol-gel and sol-gel-hydrothermal synthesis.

TiO2 particles were prepared by sol-gel method alone and by sol-gel method combined with hydrothermal treatment. The structural and photocatalytic properties of the two series of photocatalysts were compared. XRD studies revealed that rutilization was faster in the series of photocatalysts, which had been additionally subjected to a hydrothermal process (SG-HT). The hydrothermally treated photocatalysts also displayed a higher specific surface area than those which had only been synthesized using the sol-gel process (SG) and subjected to low calcination temperatures of up to 873 K, while this tendency was inverted at higher temperatures. In accordance with the above observation, the hydrothermally treated series of photocatalysts had a lower particle size than the SG series calcined immediately after the sol-gel process up to 873 K, with this relation being inverted for the highest two temperatures which were studied (973 K and 1023 K) and which saw the commencement of rutilization. Increases in average particle size were observed for both series, with a polyhedral morphology seen as calcination temperature rose. FTIR studies highlighted the presence of the band at 2351 cm(-1) in the SG-HT photocatalysts, characteristic of surface-adsorbed CO2. This was not seen in the SG or P25 photocatalysts. In terms of photoreactivity, the best photocatalyst in the SG-HT series was that calcined at 923 K and in the SG series at 1023 K (SG-1023). Comparing these two photocatalysts and the commercial P25 photocatalyst, SG-1023 was found to be the most photoactive in both the photodegradation and the mineralization of phenol.

Photocatalytic degradation of phenol and phenolic compounds Part I. Adsorption and FTIR study.

With the goal of predicting the photocatalytic behaviour of different phenolic compounds (catechol, resorcinol, phenol, m-cresol and o-cresol), their adsorption and interaction types with the TiO(2) Degussa P-25 surface were studied. Langmuir and Freundlich isotherms were applied in the adsorption studies. The obtained results indicated that catechol adsorption is much higher than those of the other phenolics and its interaction occurs preferentially through the formation of a catecholate monodentate. Resorcinol and the cresols interact by means of hydrogen bonds through the hydroxyl group, and their adsorption is much lower than that of catechol. Finally, phenol showed an intermediate behaviour, with a Langmuir adsorption constant, K(L), much lower than that of catechol, but a similar interaction. The interaction of the selected molecules with the catalyst surface was evaluated by means of FTIR experiments, which allowed us to determine the probability of OH radical attack to the aromatic ring.

Amenorrea primaria por hipogonadismo hipogonadotropo normosómico / Primary amenorrhea due to hypogonadotrophic hypogonadism

Mujer de 17 años, adoptada, que consulta por retraso puberal completo. Presentaba un crecimiento armónico, con olfato normal y repercusión psicológica grave por ausencia completa de desarrollo puberal. El estudio hormonal basal confirma la presencia de hipoestrogenismo grave, ausencia de adrenarquia y valores de gonadotropinas en rango normal para primera mitad de la fase folicular. El resto de hormonas hipofisarias fueron normales. La resonancia magnética hipotálamo-hipofisaria fue normal. El estímulo con 100 g de hormona liberadora de hormona luteinizante indujo una respuesta normal de hormona folículo estimulante y hormona luteinizante, y la secreción nocturna (12 h) de gonadotropinas evidenció mínima pulsatilidad de hormona luteínizante, con aumento nocturno y menor pulsatilidad de hormona folículo estimulante, sin aumento nocturno. La paciente fue diagnosticada de hipogonadismo hipogonadotropo normosómico. Se inició inducción de pubertad con estrógenos en dosis progresivas, adición posterior de progesterona y, finalmente, anticonceptivos orales. A los 26 años, se plantea la fertilidad por lo que se revalúa y se confirma hipogonadismo hipogonadotropo parcial, con el mismo perfil de secreción de gonadotropinas, espontánea y en respuesta a hormona liberadora de gonadotropina. Se discuten las características clínicas, con especial atención al diagnóstico etiológico del hipogonadismo hipogonadotropo normosómico, a la luz de la nueva información sobre las bases moleculares del hipogonadismo hipogonadotropo idiopático. Asimismo, se discute el abordaje terapéutico del hipogonadismo hipogonadotropo (AU)

We describe the case of an adopted 17-year-old girl who consulted because of complete pubertal delay. No specific dysmorphic features were observed and olfaction was normal. The complete absence of pubertal development had severe psychological effects. Basal hormonal determinations confirmed severe hypoestrogenism, with serum gonadotropins within the normal range for the early follicular phase. Serum levels of other pituitary hormones were normal. A sellar magnetic resonance imaging (MRI) scan was normal. Both gonadotropins increased normally in response to gonadotropin-releasing hormone (GnRH) (100 g, IV). Spontaneous gonadotropin secretion through a 12-h nocturnal period showed minimal luteinizing hormone (LH) pulsatility with nocturnal increase and less follicle-stimulating hormone (FSH) pulsatility without nocturnal increment. A diagnosis of normosomic hypogonadotropic hypogonadism was made. The patient was treated with progressive doses of conjugated estrogens, with subsequent addition of progesterone in a cyclic regimen. Finally, oral contraception was prescribed. At 26 years of age, she desired fertility and was clinically reevaluated. Partial hypogonadotropic hypogonadism was confirmed, with similar patterns of spontaneous gonadotropin secretion and GnRH response. We discuss the clinical characteristics of this entity, focusing mainly on the cause of normosomic hypogonadotropic hypogonadism, in light of new information about the molecular bases of these disorders. The treatment of hypogonadotropic hypogonadism is also discussed (AU)

Native and oxidized low density lipoproteins oppositely modulate the effects of insulin-like growth factor I on VSMC.

OBJECTIVE: Changes in the local expression and signaling activity of the insulin-like growth factor-I (IGF-I) axis regulate growth and survival of plaque-derived vascular smooth muscle cells (VSMC) and influence plaque fate. Recent evidence suggests that accumulation of low density lipoproteins (LDL) in VSMC during the progression of atherogenesis is linked to local changes in IGF-I signaling. We investigated the effects of LDL on the biological actions and downstream signaling pathways mediated by this growth factor in A10 VSMC. METHODS AND RESULTS: We first characterized the effects of LDL on the proliferative and anti-apoptotic actions of IGF-I in A10 VSMC. Native LDL were mitogenic and synergistically enhanced DNA synthesis induced by IGF-I from 4-, 9- up to 7.8-fold, while having no effect on its anti-apoptotic actions. In contrast, oxidized LDL, at oxidation levels that did not modify these actions by themselves, significantly reduced the mitogenic and survival effects of IGF-I by 40% and 60%, respectively. These observations correlated with opposite changes exerted by native and oxidized LDL on the insulin receptor substrate-1 (IRS)-associated PI3 kinase/Akt response to IGF-I. The extracellular signal-regulated kinase (ERK) signaling response was not affected. CONCLUSIONS: Our study demonstrates a previously unidentified modulation of the actions of IGF-I on A10 VSMC by LDL, dependent on their extent of oxidative modification. Our findings suggest that the differential modulation of the PI3 kinase/Akt response to IGF-I play a pivotal role.

Phase II evaluation of paclitaxel in combination with carboplatin in advanced head and neck carcinoma.

BACKGROUND: Two-thirds of patients with squamous cell carcinomas of the head and neck (SCCHN) at diagnosis have advanced disease with projected 5-year survival rates of 30%. In those patients with distant metastatic or previously treated recurrent disease, response rate to the standard regimen of cisplatin and 5-fluorouracil is approximately 30%. The authors investigated the use of paclitaxel and carboplatin in a limited Phase II study in recurrent or metastatic SCCHN to evaluate tumor response, time to progression, survival, and toxicities of this regimen. METHODS: Patients with recurrent or metastatic SCCHN not amenable to further surgical or radiation therapy were treated with 200 mg/m(2) by 3-hour infusion of paclitaxel followed by carboplatin at an area under the concentration time curve of 6 mg/mL/minute via a 20-30-minute infusion every 3 weeks. RESULTS: Thirty-seven patients were enrolled. Ninety-five percent of patients had received prior surgery and postoperative radiotherapy. The overall response rate was 27% (95% confidence interval, 13-41%) with 1 complete and 9 PRs. Median survival of all patients was 4.9 months, and 1-year survival rate was 16%. There was a 43% response rate and 15.7-month median survival rate in patients with only distant metastatic disease and 38% response rate and a 4.5-month median survival in patients with locoregional and metastatic disease. The response rate for patients with only locoregional recurrence was 7% with a median survival of 4.8 months. Grade 3-4 myelotoxicity occurred in 24% of cycles administered. There were two treatment-related deaths due to neutropenic fever and one additional death on study may have been caused by treatment-induced thrombocytopenia. CONCLUSIONS: The combination of paclitaxel and carboplatin is significantly myelotoxic and ineffective in patients with previously treated locoregionally recurrent SCCHN, whereas it deserves further evaluation in those patients with distant metastatic disease alone. In those patients with locoregional disease, other more innovative treatments are needed.

Clobetasol propionate foam, 0.05%.

Clobetasol propionate foam (clobetasol foam), a new formulation of the superpotent corticosteroid, has anti-inflammatory, antipruritic and vasoconstrictive properties. It was reported that the absorption rate of clobetasol was greater from the foam than from the solution in cadaver skin. In patients with moderate to severe scalp psoriasis, topical application of clobetasol 0.05% foam twice daily for 2 weeks induced significant improvement of all signs and symptoms of the disease compared with placebo. Compared with clobetasol 0.05% solution, clobetasol foam demonstrated greater improvement of scaling after 2 weeks of treatment and after 2 weeks of follow-up. The investigator's global assessment rated 74% of patients in the clobetasol foam group to be clear or almost clear (90 to 100%) of scalp psoriasis compared with 10% of the placebo foam group. Adverse events at the application site of clobetasol 0.05% foam were limited to one case each of dry skin, eczema, and skin hypertrophy. Clobetasol foam 7 g/day for 2 weeks induced reversible suppression of the hypothalamic-pituitary-adrenal axis in 3 out of 13 patients (methodology of assessment not provided).

Interferon alfacon-1: a review of its pharmacology and therapeutic efficacy in the treatment of chronic hepatitis C.

UNLABELLED: Interferon alfacon-1 (consensus interferon) is a non-naturally occurring, synthetic, type 1 interferon (IFN)alpha that is used for the treatment of patients with chronic hepatitis C. The efficacy of subcutaneously administered interferon alfacon-1 has been demonstrated in clinical trials during the treatment of LFN-naive patients (interferon alfacon-1 9microg 3 times a week for 24 weeks) and retreatment of nonresponders and relapsers to previous interferon therapy (interferon alfacon1 15 microg 3 times a week for up to 48 weeks). Higher and more frequent interferon alfacon-1 dosages have also been investigated. Results from a pivotal double-blind randomised trial in 704 patients with chronic hepatitis C showed that interferon alfacon-19 microg 3 times a week achieved virological and biochemical response rates of 34.9 and 42.2%, respectively, at treatment end-point (week 24). Sustained virological and biochemical responses (week 48) were reported in 12.1 and 20.3% of the patients, respectively. In general, response rates in recipients of interferon alfacon-1 9 microg 3 times a week were similar to those achieved with IFN-alpha2b 3 MIU 3 times a week. However, interferon alfacon-1 was more effective in the subgroup of patients infected with hepatitis C virus (HCV) genotype 1 at end-point (virological response, 24 vs 15%; p < 0.05) and post-treatment observation period (8 vs 4%) although the difference between treatment groups was statistically significant only at treatment end-point. The sustained virological response rate achieved in patients with high baseline levels of serum HCV RNA receiving interferon alfacon-1 was statistically superior to that exhibited in the IFN-alpha2b treatment group (7 vs 0%; p < Interferon alfacon-1 also showed efficacy during the retreatment of non-responders and relapsers to previous IFN therapy in a large nonblind multicentre trial. Sustained virological response (week 72) was observed among 13 and 58% of nonresponders and relapsers, respectively, after 48 weeks of treatment with interferon alfacon-1 15 microg 3 times a week. Interferon alfacon-1 has been generally well tolerated in clinical trials. As with other IFNs, adverse events were reported frequently but were usually considered of mild to moderate severity, decreased with time and caused a small percentage of patients to withdraw from the treatment. Fever, fatigue, arthralgia, myalgia, headache and rigors were the most frequently reported adverse events. Psychiatric adverse events appeared to be dose-related and caused the majority of treatment withdrawals. CONCLUSION: Interferon alfacon-1 is generally well tolerated and is an effective agent in the treatment of patients with chronic hepatitis C. Comparative data from a pivotal randomised trial indicate that the drug has at least equivalent efficacy to IFNalpha-2b, and a statistically significant advantage was demonstrated at treatment end-point in patients infected with HCV genotype 1. A number of ongoing trials with interferon alfacon-1 are evaluating issues such as the optimal dosage regimen and duration of therapy in an effort to improve sustained virological response to therapy, a goal for IFNs in general.

Cooperation between low density lipoproteins and IGF-I in the promotion of mitogenesis in vascular smooth muscle cells.

Low density lipoproteins (LDL) are an independent risk factor for atherosclerosis and show synergism with some growth factors in vascular smooth muscle cell (VSMC) proliferation. IGF-I has mitogenic actions on VSMC, which, in turn, show enhanced expression of IGF-I and its receptor when exposed to hypercholesterolemic diets in vivo. To investigate the molecular basis of a possible interaction between LDL and the IGF-I signaling system in VSMC, we used A10 cells, where synergism between both factors in DNA synthesis was demonstrated. IGF-I activates phosphatidylinositol 3-kinase (PI3 kinase) and extracellular signal-regulated MAPK pathways in A10 cells, although insulin receptor substrate-1 (IRS-1)-associated PI3 kinase is more closely linked to IGF-I induced proliferation. LDL, in pathophysiological concentrations, affect the IGF-I signaling pathway at multiple levels: 1) they induce phosphorylation of IGF-I receptor beta and IRS-1 in a time- and dose-dependent manner; 2) they up-regulate IRS-1-associated PI3 kinase/Akt activation in response to IGF-I at early times; and 3) they show additive effects with IGF-I on extracellular signal-regulated MAPK 1/2 phosphorylation. These actions are not present in very low density lipoprotein treatments. Taken together, these results indicate specific cooperation between LDL and the IGF-I signaling pathways and may represent a more general mechanism through which proatherogenic lipoproteins modulate VSMC response to growth factors.

Sensitivity to exogenous GH and reversibility of the reduced IGF-I gene expression in aging rats.

BACKGROUND: IGF-I gene expression and IGF-I plasma concentration decline with age. A decreased sensitivity to GH has been suggested to be a contributory mechanism to this, in addition to attenuated GH secretion. OBJECTIVE: This study focuses on the sensitivity to exogenous GH and the reversibility of the reduced IGF-I gene expression in aging male rats. DESIGN: Three groups of male Wistar rats aged 3 months (young adult), 11 months (middle-aged) and 27 months (old), received recombinant human GH (rhGH) (150 microg/12 h s.c.) for seven consecutive days. RESULTS: This rhGH treatment completely reversed plasma immunoreactive IGF-I (IR-IGF-I) and hepatic IGF-I mRNA levels in 11-month-old and 27-month-old animals to the levels of the young group of animals. The sensitivity in the old group (percentage of increment after the same or lower dose of rhGH per body weight) was increased for both parameters; serum IGF-I increment: 15% in 3-month-old, 42.6% in 11-month-old and 119.1% in 27-month-old rats; and hepatic IGF-Ib mRNA increase: 45% in 3-month-old, 27.8% in 11-month-old and 64.3% in 27-month-old rats. IGF binding protein-3 (IGFBP-3) mRNA level in the liver was significantly decreased in the old group and only a partial reversion occurred in this group after rhGH treatment; the percentage of increment was also higher in the old group of rats. In extrahepatic tissues IGF-I mRNA was not significantly different in the kidney and the testis of the three groups, and the rhGH treatment produced a significant and similar increase of IGF-I mRNA level in the kidney of the three groups of rats and in the testis of the 27-month-old animals. The GHr/GHBP mRNA remained unchanged in the liver and in the kidney or the testis of the three groups, and was not influenced by the rhGH treatment. Exogenous rhGH decreased pituitary GH mRNA accumulation in a more intense manner in the old group versus control of each group: young adult, 25%; middle-aged, 41.2%; and old rats, 55%. The action of rhGH on pituitary immunoreactive GH (IR-GH) content was only significantly evident in the young group. CONCLUSIONS: These results establish that exogenous rhGH recovers the attenuated liver IGF-I gene expression and the diminished plasma IR-IGF-I in old rats to the levels of young adult animals. They also indicate that the hepatic and extrahepatic (kidney and testis) sensitivity to one established dose per weight of exogenous rhGH is not altered in old animals, or could be potentially increased in some tissues.

Stomal recurrence in patients with T1 glottic cancer after salvage laryngectomy for radiotherapy failures: role of p53 overexpression and subglottic extension.

The role of p53 overexpression in the development of stomal recurrence was studied in patients with T1 glottic cancer who had undergone salvage laryngectomy after primary radiotherapy failure (first recurrence). The role of subglottic extension of the recurrent tumor in the development of stomal recurrence was also studied. One hundred fourteen patients with T1 squamous cell carcinoma of the glottic larynx were irradiated with curative intent. A local recurrence (first recurrence) developed in 23 patients (20%), and salvage laryngectomy was performed for 20 of these patients. No postlaryngectomy radiation therapy was included in the treatment of recurrences. Several risk factors thought to be significant in the development of stomal recurrence were analyzed in these 20 patients. Prognostic factors analyzed include: p53 overexpression in the preradiation biopsy specimen, subglottic extension of the first recurrence, thyroid cartilage and lymph node involvement at the time of first recurrence, emergency tracheostomy performed before salvage laryngectomy, and the laryngectomy procedure performed for first recurrence. Presence of p53 protein in the preradiation biopsy specimen of laryngeal cancer did not show any adverse effect on the development of stomal recurrence. Stomal recurrence developed in 27% of patients with positive biopsies and in 20% of patients with negative biopsies (p = 1.00). Subglottic extension of the first recurrence was associated with an increased incidence of stomal recurrence. Rates of stomal recurrence were 6% in patients without subglottic extension and 100% in patients with subglottic extension (p = 0.001). All other risk factors studied showed no effect on stomal recurrence. In this study, p53 overexpression showed no effect on the development of stomal recurrence after salvage laryngectomy in patients with T1 glottic cancer. Conversely, subglottic extension of the recurrence was found to be strongly associated with stomal recurrence. All other factors analyzed showed no effect on stomal recurrence.

Colesevelam.

Colesevelam, a bile acid sequestrant used in the treatment of patients with hypercholesterolemia, is a lipid-lowering polymer that has high affinity for bile acids. In animals colesevelam was not systemically absorbed after oral administration and was rapidly eliminated via the gastrointestinal tract. Colesevelam did not alter the serum concentrations or pharmacokinetic properties of drugs from several different classes in healthy volunteers. Colesevelam administered orally in patients with primary hypercholesterolemia significantly reduced serum levels of low density lipoprotein (LDL)-cholesterol and total cholesterol. This lipid-lowering activity was sustained during short (6 weeks) and longer term (24 weeks) treatment. Combination therapy with colesevelam plus hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (lovastatin, simvastatin or atorvastatin) was associated with additive reductions in serum levels of LDL-cholesterol and total cholesterol, relative to either agent alone. Colesevelam treatment was well tolerated and lacked severe gastrointestinal adverse events typical of other bile acid sequestrants (bloating, flatulence, heartburn and nausea). The most frequently reported adverse events were constipation and dyspepsia. In humans colesevelam did not induce clinically significant changes in serum levels of vitamins, coagulation parameters or liver enzymes.

Prorenin concentration in the hypertensive disorders in pregnancy.

OBJECTIVE: To evaluate the plasma prorenin levels during the three trimesters of normal pregnancy, their prognostic value, and their correlation with hypertensive disorders of pregnancy. DESIGN: A prospective study in which plasma prorenin and renin levels were measured in 55 healthy pregnant women and 66 who developed gestational hypertension or preeclampsia. The patients were classified as mild preeclampsia (mild PE), severe preeclampsia (severe PE), chronic hypertension and superimposed preeclampsia upon chronic hypertension (superimposed PE). METHOD: Venous blood samples were collected in the first, second and third trimesters and during delivery or cesarean. Plasma renin concentration (PRC) was measured by radioinmmunoassay before and after incubation with trypsin solution. The difference gave plasma prorenin concentration (PProRC). RESULTS: PRC and PProRC were significantly higher in pregnant women compared with healthy non-pregnant. PRC was significantly increased in the first trimester in the chronic hypertension group and a lower value was found in the first trimester in the superimposed PE compared with those in healthy pregnant women. No differences in other groups were found. PProRC showed a significant lower value in the first and third trimesters in the severe PE group. In the superimposed PE a low value of PProRC similar to those of non-pregnant women was found. CONCLUSIONS: The results show that the different types of hypertension in pregnancy have different profiles of PProRC and PRC in relation to development of preeclampsia. The absence of increase of PProRC in the first trimester of superimposed PE may have a prognostic value.

Brain metastases from medullary thyroid carcinoma in a patient with multiple endocrine neoplasia type 2A.

Medullary thyroid carcinoma (MTC) is an uncommon thyroid cancer occurring in less than 10% of patients with thyroid cancer. Brain metastasis from MTC is exceedingly rare. Only six cases of brain metastasis from MTC have been reported in the literature and none had MTC as a part of multiple endocrine neoplasia (MEN) syndrome. We report a 42-year-old Caucasian male with MEN 2A who presented with neurological symptoms 25 years after total thyroidectomy with lymphadenectomy for MTC metastatic to local lymph nodes. A brain magnetic resonance imaging (MRI) showed a 4-cm cystic mass and a 1-cm nodule in the left frontal-parietal lobe in addition to a 0.8-cm cystic mass in the left frontal lobe and multiple tiny cerebellar metastatic lesions. Partial resection of the cerebral metastasis followed by whole brain radiotherapy resulted in resolution of the neurological symptoms. However, the patient had multiple systemic metastasis from the MTC and he died of systemic complications due to metastatic MTC. To our knowledge this is the first report of brain metastases from MTC in a patient with MEN 2A.

Medulloblastoma and supratentorial primitive neuroectodermal tumors: an institutional experience.

BACKGROUND: To the authors' knowledge there are relatively few data concerning supratentorial primitive neuroectodermal tumors (PNET). The authors retrospectively reviewed all cases of PNET of the brain treated at the study institution to determine whether there was a difference in presentation, overall survival, and recurrence-free survival with regard to tumor location (supratentorium vs. posterior fossa). METHODS: Between 1977-1996 33 patients with PNET were diagnosed and treated at 1 radiotherapy center. The median age of the patients was 9 years. The location of the tumor was in the posterior fossa in 25 patients and the supratentorium in 8 patients. The tumor had spread to the neuraxis in six patients; four patients with disseminated neuraxis disease had a supratentorial PNET and two had a posterior fossa PNET. All but three patients received craniospinal irradiation. The primary tumor received > or = 5000 centigray in 27 patients and chemotherapy was employed in 26 patients. The median follow-up was 60 months. RESULTS: The 5-year overall and recurrence-free survival rates for all patients were 77.2% and 79.6%, respectively. The 5-year overall survival rates were 86.3% for patients with medulloblastoma (posterior fossa PNET) and 46.9% for patients with supratentorial PNET (P = 0.01, log rank test). For overall survival, prognostic factors included radiotherapy dose to the primary site, metastases (M) status, and location of the primary tumor. The 5-year recurrence free survival rates were 89.8% for patients with medulloblastoma and 46.9% for patients with supratentorial PNET (P = 0.003, log rank test). For recurrence free survival, prognostic factors included M status and primary tumor site location; radiation dose to the primary tumor site and patient gender were of borderline significance. In the ten patients with inadequate posterior fossa boost fields judged by Children's Cancer Group criteria, there were two failures, both of which were in the original tumor bed. CONCLUSIONS: Supratentorial PNET has a worse overall survival and recurrence free survival than medulloblastoma. There is a suggestion that radiotherapy boosts in medulloblastoma may not need to encompass the entire posterior fossa because posterior fossa failures primarily are in the tumor bed. Larger studies with longer follow-up are needed to determine whether craniospinal irradiation followed by a boost to the tumor bed is adequate for medulloblastoma patients.

Effect of metal reconstruction plates on cobalt-60 dose distribution: a predictive formula and clinical implications.

PURPOSE: We sought to create a predictive formula for the dose perturbations caused by head and neck reconstruction plates in the delivery of postoperative radiotherapy with 60Co beams. MATERIALS AND METHODS: The dose perturbation effects of Vitallium and Titanium reconstruction plates and flat metal plates of aluminum (13Al), stainless steel (26Fe), tin (50Sn) and lead (82Pb) irradiated with a 60Co beam were measured in polystyrene phantoms using a film dosimetry system. We then used these results to create formulas to predict the effect of a metal reconstruction plate dependent upon its effective atomic number. RESULTS: Percentage dose increases secondary to back scattering were 10% at 1 mm in front of the Vitallium plate and 40% at the plate while the percentage dose decrease was 29% at the plate and 10% 1 mm behind the plate. For the Titanium plate, the percentage dose increase was 5% at 1 mm in front the plate and 25% at the plate while the percentage dose decrease was 20% at the plate and 5% 1 mm behind the plate. For flat plates the percentage dose increases and decreases, respectively, at the plate surfaces were: 13Al (8%, 6%), 26Fe (35%, 16%), 50Sn (60%, 24%), and 82Pb (85%, 13%). A second order polynomial predicting the back scatter and shadowing effects was created, Y = a + bZ + cZ2, where Z is the effective atomic number of the plate while a, b, and c are the following constants: for back scatter a = 0.854 +/- 0.082, b = 0.0212 +/- 0.0044, c = -0.00011 +/- 0.00004 and for shadowing a = 1.108 +/- 0.021, b = -0.0141 +/- 0.0011, c = 0.00014 +/- 0.00001. CONCLUSIONS: It is possible to predict the effect of a metal reconstruction plate upon the delivered postoperative radiotherapy dose. The dose perturbations around the plate only exist for a few millimeters, but this is substantially greater than the thickness of a normal tissue or tumor cell. Perhaps a coating of a low effective atomic number, biologically inert, substance might allow for greater dose homogeneity and decrease the risks of plate failure or tumor recurrence.

Tissue-specific response of IGF-I mRNA expression to obesity-associated GH decline in the male Zucker fatty rat.

Diminished GH secretion is a well known association of obesity. As in obese humans, Zucker fatty rats develop a progressive GH deficiency, present at 6 weeks of age and maximal at 10 to 12 weeks. The aim of this study was to investigate the GH dependence of IGF-I gene expression in liver and extrahepatic tissues of the obese Zucker rat as a model of progressive GH reduction during adult life. Six- and 11-week-old obese Zucker rats and their lean littermates were used to compare body weight, glycemia, insulinemia, serum GH and IGF-I levels and IGF-I mRNA expression in liver, heart, aorta, kidney and skeletal muscle. In comparison with lean controls, obese Zucker rats showed at both ages comparable glycemia, severe hyperinsulinemia (mU/ml, mean+/-s.e.m.; 6 weeks 138+/-10 vs 45+/-6 P<0.001; 11 weeks 147+/-14 vs 46+/-3, P<0.001) and lower GH (ng/ml; 6 weeks 1.7+/-0.9 vs 2.7+/-1.1; 11 weeks 1.5+/-0.9 vs 4.2+/-1.2) in the presence of similar circulating IGF-I levels (ng/ml; 6 weeks 774+/-26 vs 694+/-28; 11 weeks 1439+/-182 vs 1516+/-121). Hepatic IGF-I mRNA expression was already reduced at 6 weeks of age due to a significant decrease in the IGF-Ib transcript compared with lean controls (relative units; IGF-Ia: 99+/-2% vs 100+/-5%; IGF-Ib: 69+/-10% vs 100+/-2%, P<0.05) and this reduction was more marked in 11-week-old animals when both IGF-I transcripts were significantly diminished (relative units; IGF-Ia: 80+/-6% vs 100+/-1%, P<0.05; IGF-Ib: 65+/-5% vs 100+/-2%, P<0.01). Extrahepatic tissues expressed almost exclusively the IGF-Ia transcript, the amount of which relative to controls was: (1) similar at 6 weeks and decreased at 11 weeks in kidney and skeletal muscle extracts (relative units; kidney: 6 weeks 88+/-10% vs 100+/-2%; 11 weeks 76+/-3% vs 100+/-4%, P<0.05; vastus lateralis: 6 weeks 95+/-7% vs 100+/-10%; 11 weeks 59+/-4% vs 100+/-2%, P<0.001); (2) similar at both ages in thoracic aorta (relative units; 6 weeks 121+/-6% vs 105+/-5%; 11 weeks: 91+/-14% vs 100+/-4%); and (3) increased at both ages in left ventricle extracts (relative units; 6 weeks 114+/-2% vs 99+/-9%, P<0. 05; 11 weeks 119+/-7% vs 95+/-3%, P<0.05). -specific dependence of IGF-I mRNA on GH levels during adulthood, reflected by the different behavior of IGF-I expression for each tissue in conditions of progressive decrease of GH levels.

Results of treatment of patients with maxillary sinus carcinoma.

BACKGROUND: Information regarding results of treatment and possible prognostic factors in patients with maxillary sinus carcinoma is limited. METHODS: Between 1969-1995, 48 consecutive patients presented to the study department for curative treatment of maxillary sinus carcinoma. Tumor classification according to the American Joint Committee on Cancer staging system was T1 in 1 patient, T2 in 6 patients, T3 in 17 patients, and T4 in 24 patients. The N classification was NO in 43 patients, N2a in 1 patient, N2b in 3 patients, and N2c in 1 patient. Treatment to the primary site was comprised of surgery (Sx) and radiation therapy (RT) in 37 patients and RT alone in 11 patients. RESULTS: There was a difference in disease free survival between patients who underwent Sx + RT compared with patients who received RT alone; combined therapy results were more favorable. The most common pattern of recurrence was in the primary site, which was found in 22 of 48 patients (45.8%). For patients who underwent Sx + RT, local control at 3 and 5 years was 65.2% and 59.2%, respectively; for patients who received RT alone, local control at both 3 and 5 years was 22.7%. There were 12 late complications found in 8 patients: fistula formation (5 patients), trismus (3 patients), osteonecrosis (1 patient), retinopathy (1 patient), cellulitis (1 patient), and nasal stenosis (1 patient). CONCLUSIONS: The type of treatment to the primary site is an important determinant of disease free survival and local control. Failure at the primary site is the main problem in the curative treatment of patients with maxillary sinus carcinoma; efforts to improve survival in these patients should be directed toward improvement of local control.

Transfection of a vector expressing wild-type p53 into cells of two human glioma cell lines enhances radiation toxicity.

Replication-deficient adenovirus (Adv5)-based vectors containing either wild-type p53 or the beta-gal marker gene were introduced into cells of the T98G (p53 mutant) and U87MG (p53 wild-type) human glioma cell lines. The wild-type p53 gene was successfully expressed in each cell line as shown by flow cytometry and Western blotting. The presence of the p53-expressing vector was toxic in both cell lines compared to control cells or to those containing the beta-gal vector. At levels of Adv5p53 vector that produced detectable toxicity, the effect of irradiation was enhanced, producing a twofold increase in cell killing. In the T98G cells, the presence of the p53 vector resulted in an increase in the number of cells undergoing apoptosis after irradiation, whereas a smaller and only additive response was observed in the U87MG cells. Conversely, an increase in micronucleus formation, indicating corrupt mitotic activity, was observed in irradiated Adv5p53-positive U87MG cells but not in T98G cells. These data suggest that p53-expressing vectors effectively enhance radiation lethality in these human glioma cell lines, but that the mechanism of action cannot be simply related to activation of the p53-dependent pathway to apoptosis.

Variation in prostate position quantitation and implications for three-dimensional conformal treatment planning.

PURPOSE: This study describes and quantitates the motion, i.e., variation in position, of the prostate within the pelvis and its effect on target and normal organ dose. METHODS AND MATERIALS: The motion of the planning target volume (PTV) borders and center of mass was studied in 13 patients with carcinoma of the prostate through the use of superimposed serial computerized tomography (CT) scans. Changes in bladder and rectal volumes were measured and their relationship to displacements of the PTV position were noted. The effects of this motion on target and normal organ doses were measured. RESULTS: A variability in the position of the PTV is seen over time, which is related to changes in bladder and rectal volumes. The one standard deviation displacements of the PTV center of mass with respect to the planning scan center of mass position were 0.12, 0.40, and 0.31 cm in the lateral, anterior-posterior, and superior-inferior directions, respectively. Movement was significantly larger in the superior part of the PTV above the base of the bladder than in the inferior part. Movement of the borders of the PTV outward from the patient axis; hence, toward the edges of the treatment field, was also examined. Outward displacements of the anterior target border below the base of the bladder were less than 0.3 cm in 90% of the cases, and 1.4 cm above the bladder base. For the posterior wall these displacements were less than 0.7 cm and 1.1 cm, respectively, whereas the lateral border displacements were less than 0.3 cm throughout (90% confidence limits). These displacements would cause a median of 6% of the PTV to receive less than 95% of the planned dose for any given treatment day in these patients; the effect on rectal and bladder wall doses was greater and true doses may not be measurable through the use of only one treatment planning CT scan. CONCLUSIONS: The prostate is not a static organ, but rather has some limited motion in the pelvis secondary to bladder and rectal volume changes. This motion has been quantified for a group of patients, and may provide a guide to further studies on the placement of field borders.