Ab-initio and experimental study of pentose sugar dehydration mechanism in the gas phase.

In this work pentose sugar (D-xylose, D-ribose and D-arabinose) gas phase dehydration reaction was investigated by means of mass spectrometric techniques and theoretical calculations. The ionic species derived from the dehydration reaction of protonated D-ribose and D-arabinose were structurally characterized by their fragmentation patterns and the relative dehydration energies measured by energy resolved CAD mass spectra. The results were compared with those recently obtained for D-xylose in the same mass spectrometric experimental conditions. Dehydration of C1-OH protonated sugars was theoretically investigated at the CCSD(T)/cc-pVTZ//M11/6-311++G(2d,2p) level of theory. Protonated pentoses are not stable and promptly lose a water molecule giving rise to the dehydrated ions at m/z 133. D-xylose, D-ribose and D-arabinose dehydration follows a common reaction pathway with ionic intermediates and transition states characterized by similar structures. Slightly different dehydration energies were experimentally measured and the relative trend was theoretically confirmed. The overall dehydration activation energy follows the order arabinose < ribose < xylose. Gas-phase pentose sugar dehydration leads to the formation of protonated 2-furaldehyde as final product. Based on the experimental and theoretical evidence a new mechanistic hypothesis starting from C1-OH protonation was proposed.

Ionization of ozone/chlorofluorocarbon mixtures in atmospheric gases: formation and remarkable dissociation of

The reactions occurring upon ionization of mixtures containing ozone and CHX2Y (X = H, Cl, F; Y = Cl, F) halocarbons diluted in atmospheric gases (O2, N2) have been investigated in detail by mass spectrometric and theoretical methods. In all systems investigated the reactivity pattern is characterized by the preliminary formation of [CHXY x O3+] adducts which undergo unimolecular dissociation into HXYO2+ and CO. This remarkable dissociation which requires extensive molecular reorganization is exceptional for hydrogenated halocarbons. The work represents the first systematic study of the ionic chemistry in systems containing both ozone and halocarbons diluted in atmospheric gases.

Gas-phase reactions of nitronium ions with acetylene and ethylene: an experimental and theoretical study

A comparative study of the gas-phase reactions of NO2+ with acetylene and ethylene was performed by using FT-ICR, MIKE, CAD, and NfR/ CA mass spectrometric techniques, in conjunction with ab initio calculations at the MP2/6-31+G* level of theory. Both reactions proceed according to the same mechanism, that is, 1,3-dipolar cycloaddition, but yield products of different stability. The C2H2NO2+ adduct from acetylene has an aromatic character and hence is highly stabilized with respect to the C2H4NO2+ adduct from ethylene. Both cycloadducts tend to isomerize into O-nitroso derivatives, that is, nitrosated ketene and nitrosated acetaldehyde, which represent the thermodynamically most stable products from the addition of NO2+ to acetylene and ethylene, respectively. As prototypal examples of the reactivity of free nitronium ions with most simple pi systems, the reactions investigated are useful starting points to model the mechanism of aromatic nitration.

Intimal-type primary sarcoma of the aorta. Report of a case with evidence of rhabdomyosarcomatous differentiation.

We report an intimal sarcoma presenting as an aortic aneurysm. A 68-year-old man suffered from chest pain and speech disturbance. Computed tomography showed a sacciform aneurysm of the aorta, which was resected, revealing a polypoid tumour measuring 1.5x2x2.5 cm projecting into the lumen. This proved to be a poorly differentiated high-grade sarcoma having morphological, immunophenotypic and ultrastructural features consistent with rhabdomyosarcomatous differentiation. Primary sarcomas of the aorta are extremely rare. Many cases have been diagnosed as "intimal" on the basis of their site of origin, and they are not easy to classify from their histological pattern. Electron microscopy and the use of a more comprehensive panel of immunohistochemical markers should be applied in the histological classification of"intimal" sarcoma.

A role for tumor markers in therapeutic decisions after chemotherapy induction of objective remission in stage III epithelial ovarian neoplasms.

The management of advanced stage ovarian carcinomas is presently based on initial surgical debulking, multiple drug chemotherapy including cisplatinum, second-look laparotomy. Such an aggressive approach has improved objective response rates and expected survival time, but no dramatic change has been demonstrated as for definitive cure percentages. Many Authors have attempted to turn an optimal objective response to chemotherapy (no residual or minimal residual disease at second-look) into a definitive cure with irradiation. Some reports show satisfactory results, but a high incidence of bowel obstructive complications has been demonstrated, probably due to multiple surgical manipulations before radiotherapy. A reliable diagnostic tool, that could help to avoid the second-look laparotomy (whose inherent role in improving survival is not assessed) should be therefore useful. The possible role of serum tumor markers determinations, for this purpose, is here discussed on the ground of a series of 20 patients affected by stage III ovarian carcinoma. Following this experience, a valuable role seems attributable to CA 125 in monitoring tumor response. Patients achieving values under 35 U/ml before second-look laparotomy showed tumor residuals in the range O-microscopic- less than 1 cm., that is, neoplastic localizations reliable for consolidation radiation therapy.

Carboplatin and vinorelbine in the treatment of advanced non-small-cell lung cancer: a multicenter phase II study.

The aim of this study was to identify a chemotherapy combination that would be active and well tolerated for palliative treatment of advanced non-small-cell lung cancer (NSCLC). From February 1992 to December 1994, a total of 77 patients affected by stage-IIIB and stage-IV NSCLC were treated with carboplatin 350 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8 of each cycle, with cycles repeated every 28 days. All patients were evaluable for response and toxicity. A total of 24 patients showed a partial response (31% response rate; 95% CI = 21-41%). The median duration of overall survival was 41 weeks (95% CI = 31-51), and the median time to disease progression was 34 weeks (95% CI = 25-43). The treatment was well tolerated: no grade-4 toxicity was observed. The carboplatin-vinorelbine combination deserves to considered as a valid alternative to regimens that include cisplatin for palliative treatment of advanced NSCLC.

Carboplatin and vindesine in advanced non-small cell lung cancer. A feasibility study.

Twenty-eight patients affected by advanced non-small cell lung cancer (NSCLC) were enrolled in a feasibility study evaluating toxicity and activity of carboplatin-vindesine combination chemotherapy, according to two different schedules. Fourteen patients were treated with carboplatin 350 mg/m2 monthly and vindesine 3 mg/m2 weekly for 5 doses, then every other week (schedule 1). The activity observed was promising with 3 partial remissions, but the toxicity was substantial, preventing full dose administration in 11 out of 14 patients. The subsequent 14 patients were treated with carboplatin 350 mg/m2 monthly and vindesine 3 mg/m2 on days 1 and 8 of each cycle. Activity was maintained with 4 partial remissions and toxicity was quite tolerable, allowing all patients to receive the planned treatment. The combination of carboplatin 350 mg/m2 on day 1 and vindesine 3 mg/m2 on days 1 and 8 seems active and well tolerated in advanced NSCLC patients and deserves further evaluation in a larger phase II study.

Dangerous thrombophilic states and internal pathologies: 3 cases of thrombosis of the abdominal veins.

Thrombosis of the abdominal veins is a rare clinical condition which can be assimilated with the more frequent localization of deep venous thrombosis of the lower limbs. In the last few years great attention has been paid to possible risk factors for thrombosis of the abdominal veins. Two risk factors that have been identified are the presence of internal diseases and congenital and/or acquired abnormalities of haemostasis. The authors describe 3 clinical cases (splenic and portal thrombosis due to congenital thrombophilia, Budd-Chiari syndrome, portal cavernoma consequent to ovarian neoplasia) with different etiopathogenesis to show how this apparently rare condition is today more frequently encountered and easier to recognize. In the presence of thrombosis of major venous structures the search and the identification of intrinsic internal risk factors and of congenital and acquired thrombophilic disorders remains of great importance. Screening for thrombophilia includes blood C and S proteins, AT III, homocysteine, Leiden mutation of the factor V gene, G20210A mutation of the prothrombin gene, antiphospholipid antibodies. The presence of one or more of these risk factors allows the identification of the cases of portal thrombosis (EHPVO) responsible for about 10% of all the cases of portal hypertension, without cirrhosis or other hepatic lesions. The primary diagnostic procedure however remains color-Doppler ultrasonography which represents the most simple and the cheapest diagnostic investigation for the study of the portal and suprahepatic vein system, but it's strictly operator dependent.

Hyperhomocysteinemia in preeclampsia is associated to higher risk pressure profiles.

Homocysteine levels have been determined with Chromatography on HPLC column, between the 20th and the 24th week of pregnancy, in women with analogous characteristics (a) normotensive, (b) with pregnancy-induced hypertension (PIH), low (LR), medium (MR), high risk (HR). The group they belonged to was confirmed after natural or caesarean delivery. All the patients were submitted to 24 hour blood pressure monitoring for the evaluation of further pressure risk parameters: mean arterial pressure (MAP), non dippers, percentages of pressure peaks. Homocysteine levels in normotensive pregnant women (5.8 +/- 1.7 microM) were low. Significant high levels of homocysteine were present proportionally to the risk degree of PIH. Higher levels of homocysteine statistically significant were present in non dippers of all groups (MR p < 0.05; HR p < 0.01). A direct correlation between plasmatic homocisteine levels and pressure profiles was found out in non dippers (r = 0.56, r = 0.55, r = 0.50 respectively) and in dippers (r = 0.7, r = 0.75, r = 0.60 respectively), and also between levels of homocysteine, MAP value, and pathological percentages of systolic and diastolic nocturnal peaks. In pregnant women presenting preeclampsia afterwards, high levels of homocysteine were not different from mean values present in high risk PIH pregnant women (13.3 +/- 1.9 vs. 16.4 +/- 1.7 microM). High levels of homocysteine early determined in the second trimester of PIH pregnancies seem to be associated to a pregnancy higher risk, coexisting with dangerous pressure profiles. High levels confirm a pregnant woman to belong to a higher or lower risk degree of vascular damage, but in the same group context high levels of homocisteine do not allow to identify those pregnant women who will develop eclampsia.

Unfavorable experience with hypofractionated radiotherapy in unresectable lung cancer.

The use of a reduced number of large-sized fractions in radiotherapy (hypofractionation) is usually associated with poor therapeutic results and severe adverse effects, in accord with radiobiologic concepts. However by some authors unresectable lung cancer patients have been treated with hypofractionated radiotherapy with the main aim of "convenience". Result and damage rates are reported to be comparable to those of conventional treatment. In our experience, based on palliative irradiation of 86 advanced-stage, nonmicrocytoma patients, objective remission rates, subjective and performance status improvement, and survival overall were as poor as could be expected in this kind of presentation, with no striking impact of this treatment modality. Severe adverse effects were shown by a large proportion of cases involving skin and soft tissues of the chest wall (40%) and lungs (55.5%). The incidence of severe damage was in agreement with BED (biologic effective dose) values, differently from other experiences of radiotherapeutic management of advanced lung cancer with large fractions.

Weekly epirubicin in advanced breast cancer.

Twenty-nine advanced breast cancer patients, considered unable to tolerate conventional cytotoxic chemotherapy, were treated with a weekly schedule of epirubicin (15 mg/m2 i.v.). All patients were fully evaluable. A remission of 34.5% was observed (2 CR; 8 PR), with a median duration of response of 9 months (range, 3-24 months). Side effects were mild, and on the whole the toxicity was negligible. This regimen showed a favorable therapeutic ratio in our series and seems active and well tolerated even in elderly and/or poor performance status patients.

Chemo-radiotherapeutic management of advanced head and neck cancer.

Stage III and IV head and neck cancer patients usually achieve poor therapeutic results after radiotherapy. The search for more effective treatment modalities is justified, provided that tolerance is not lower than that of the usual radiation therapy schedules. Chemotherapy has been shown to be effective, and cis-platinum and bleomycin based treatments are reported to result in objective remissions in a substantial proportion of cases. There is also experimental evidence of a radiosensitizing activity of cis-platinum. Thirty-five locally advanced head and neck cancer patients were given combined chemo-radiotherapeutic treatment consisting of a cis-platinum and bleomycin induction followed by a standard radiotherapy course integrated with weekly administrations of cis-platinum. Before radiotherapy, an overall 48.5% objective remission rate was achieved, that rose to 85.8% after completion of the entire treatment, with a 31.5% complete response rate. Incidence and severity of radiation mucositis seem not to be increased, and systemic toxicity is very low, with the adopted drug administration schedule. Overall results do not show any obvious superiority over those of radiotherapy alone.

Direct Experimental Evidence for the H(2)O(+)O(2)(-) Charge Transfer Complex: Crucial Support to Atmospheric Photonucleation Theory.

Where does rain come from? The first experimental evidence for the existence of the (H(2)O(+)O(2)(-)) charge transfer complex, predicted to play a key role as a nucleation center for atmospheric vapor photonucleation (see picture), is provided by the powerful neutralization - reionization mass spectrometric technique.

Ionization of Ozone/Chlorofluorocarbon Mixtures in Atmospheric Gases: Formation and Dissociation of

Complexes that undergo extensive molecular reorganization upon unimolecular metastable dissociation are obtained after ionization of atmospheric gases containing ozone and chlorofluorocarbons [Eq. (1)]. These unusual processes, which require fission of all bonds initially present in the CHX(2) unit (X=Cl, F) and combination of C with one of the O atoms of ozone, were demonstrated and their mechanism rationalized by the joint application of mass spectrometric and theoretical methods.

Gas-phase NO+ affinities.

A scale of relative gas-phase NO+ binding energies (BEs) has been constructed by evaluation of NO+-transfer equilibria LINO+ + L2 <==> L2NO+ + L1 by Fourier-transform ion cyclotron resonance mass spectrometry and by application of the kinetic method, based on the metastable fragmentation of L1(NO+)L2 nitryl-ion bound dimers. The relative scale, anchored to the NO+ affinity of water, for 52 ligands, including alkyl halides, alkyl nitrates, alcohols, nitroalkanes, nitriles, aldehydes, ketones, and aromatic and heterocyclic compounds, led to an absolute NO+ affinity scale. The results are compared with those of an earlier study, and the apparent discrepancies are traced to a different choice of the absolute BE value used as the reference standard. The NO+ BEs fit a satisfactorily linear correlation when plotted versus the corresponding proton affinities (PAs). The NO+ BEs, while much lower than the PAs, are nevertheless higher than the corresponding BEs of the strictly related NO2+ cation, a result consistent with the experimental and theoretical results currently available on the structure and the stability of NO+ and NO2+ complexes. The NO+ BE vs. PA correlation allows one to estimate within 1-2 kcal x mol(-1) the NO+ BE of the molecules included in the comprehensive PA compilations currently available. For example, the correlation gives the following NO+ affinities of the DNA bases, in kcal x mol(-1) (1 kcal = 4.18 kJ): adenine, 40.3; cytosine, 40.4; guanine, 40.1; and thymine, 34.9. The experimental NO+ BE of thymine, the only one accessible to direct measurement, amounts to 35.6 +/- 2 kcal x mol(-1), which underlines the predictive value of the correlation. This study reports the second successful extension of the kinetic method to the evaluation of the absolute BEs of polyatomic cations, following our recent application to the strictly related NO2+ ion.

Gas-phase nitronium ion affinities.

Evaluation of nitronium ion-transfer equilibria, L1NO2+ + L2 = L2NO2+ + L1 (where L1 and L2 are ligands 1 and 2, respectively) by Fourier-transform ion cyclotron resonance mass spectrometry and application of the kinetic method, based on the metastable fragmentation of L1(NO2+)L2 nitronium ion-bound dimers led to a scale of relative gas-phase nitronium ion affinities. This scale, calibrated to a recent literature value for the NO2+ affinity of water, led for 18 ligands, including methanol, ammonia, representative ketones, nitriles, and nitroalkanes, to absolute NO2+ affinities, that fit a reasonably linear general correlation when plotted vs. the corresponding proton affinities (PAs). The slope of the plot depends to a certain extent on the specific nature of the ligands and, hence, the correlations between the NO2+ affinities, and the PAs of a given class of compounds display a better linearity than the general correlation and may afford a useful tool for predicting the NO2+ affinity of a molecule based on its PA. The NO2+ binding energies are considerably lower than the corresponding PAs and well below the binding energies of related polyatomic cations, such as NO+, a trend consistent with the available theoretical results on the structure and the stability of simple NO2+ complexes. The present study reports an example of extension of the kinetic method to dimers, such as L1(NO2+)L2, bound by polyatomic ions, which may considerably widen its scope. Finally, measurement of the NO2+ affinity of ammonia allowed evaluation of the otherwise inaccessible PA of the amino group of nitramide and, hence, direct experimental verification of previous theoretical estimates.

[Changes in performance status in patients with pulmonary carcinoma treated with mono-fractionation radiotherapy once a week]. / Variazioni del performance status nei pazienti con carcinoma polmonare trattato con radioterapia in mono-frazionamento settimanale.

45 patients with lung cancer at the III and IV stage were treated with once-a-week radiation therapy. Treatments were carried out with a daily fraction, at beginning, of 880 rad (2100 ret) (14 pz.) and 550 rad (1500 ret) afterwards. In both cases the total dose was 4400 rad. All the patients had symptoms of locally advanced cancer: cough (46%), hemoptysis (31%), dyspnea (62%) and chest pain (28%). All of them were out-patients (ECOG 0-1) and presented a Performance Status by Karnofsky of 50-80. The average age was 60 (median 65, range 38-85) with a raised percent (50%) of collateral illness. The selection of once-a-week technique was determined by the bad prognosis and the necessity of symptoms' control, allowing the patients to stay in his proper social and family group. All the time of therapy and the follow-up the values of Performance Status were assigned scrupulously. The analysis showed that the 80% of the patients had a subjective improvement which lasted, on average, 4 months (range 1-21) with an increase of 20 points of Performance Status after the end of therapies. Concluding, the high percentage of success on symptoms presented by the patients, confirms the validity of weekly radiotherapy, which guarantees, besides the palliative effect, the psychological integrity which is necessary in the last period of the life of cancer patient.

Experimental detection of hydrogen trioxide

Hydrogen trioxide (HO3) has long been postulated as a key intermediate in important atmospheric processes but has proved difficult to detect. The molecule was unequivocally detected in experiments based on neutralization-reionization and neutralization-reionization/collisionally activated dissociation mass spectrometry, using protonated ozone (HO3+) as the charged precursor. Hydrogen trioxide is a relatively stable species and has a H-O-O-O connectivity and a lifetime exceeding 10(-6) seconds at ambient temperature.