Early rehabilitation vs. conventional immobilization in nonoperative treatment of proximal humeral fracture: a systematic review.

OBJECTIVE: Fractures of the proximal humerus (PHF) are commonly treated conservatively. Evidence suggests that a period of immobilization of one week or less may lead to some advantages compared to a traditional 3-4 weeks of immobilization. The purpose of this systematic review was to assess the clinical and radiological results in the case of early rehabilitation vs. delayed rehabilitation after PHF. MATERIALS AND METHODS: In July 2023, a literature search was carried out on the PubMed, MEDLINE, and Embase databases to identify all the randomized trials comparing early rehabilitation vs. delayed rehabilitation after PHF. The following data were extracted from each included study: patients' demographics, study design and level of evidence, follow-up times, treatment groups, evaluation scores adopted, and overall clinical and radiological findings. The quality of the trials was assessed using the Cochrane Risk of Bias Assessment. RESULTS: A total of 5 studies, including 378 patients and dealing with early vs. delayed rehabilitation in case of conservative treatment of PHF, were included in this study. Early rehabilitation was started within 1 week and consisted mainly of pendulum exercise and progressive passive mobilization. Early rehabilitation was associated with better pain and functional scores within the first 3 months in 3 studies. No difference in pain or function was reported at 6 months or longer follow-up, and no differences in complications rate were observed between early vs. delayed rehabilitation groups. CONCLUSIONS: This systematic review suggests that early mobilization within one week in case of conservative treatment of PHF leads to improved function recovery and reduced pain, especially in the first months of rehabilitation, without differences at longer follow-up and without increasing complications rate. Reducing immobilization time could accelerate function recovery and regaining independence in daily life activities.

Experimental detection of tetranitrogen.

Tetranitrogen (N4), which has been the subject of great theoretical interest, has been prepared from the N4+ cation and positively detected as a gaseous metastable molecule with a lifetime exceeding 1 microsecond in experiments based on neutralization-reionization mass spectrometry. An examination of the geometry of N4+ and the fragmentation pattern of the (14)N2(15)N2 neutral molecule has revealed that the latter is characterized by an open-chain geometry with two distinct, closely bound N2 units joined by a longer weaker bond.

S3O, a new sulfur oxide identified in the gas phase.

S3O, a novel, linear sulfur oxide has been detected in the gas phase by means of neutralization reionization mass spectrometry; the upper limit of stability of acyclic forms of SnO oxides has been set by theoretical calculations.

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.

Fast interconversion of C4H7+ cations in the gas phase and in a gaseous microsolvated environment

The equilibration of cyclobutyl 1 and 1' and the cyclopropylmethyl cation (2) has been studied in the gas phase by utilizing FT-ICR mass spectrometry and high-pressure radiolytic techniques. A suitable gaseous nucleophile, C6X6 (X=H,D), was used to sample the equilibration of C4H7+ ions, produced from both cyclobutanol and cyclopropylmethanol. These are either dispersed in the bulk gas or confined within a C4H7+/C6X6 complex that contains a molecule of solvent (H2O). The analysis of the products shows that, irrespective of their source and of the intermolecular or intracomplex nature of the process, the C4H7+ ions undergo equilibration before they are trapped. The equilibrium (1+1')/2 ratio is very close to unity at 300 K, and the results from the intracomplex trapping experiment show that equilibration occurs within a time interval < or =10(-10) s.

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.

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.

Isomeric Cl(2)O(2)(+) and Cl(2)O(2)(-) ions.

Charged species structurally related to several isomers of Cl(2)O(2), of considerable importance in atmospheric chemistry, were obtained by chemical ionization (CI) and characterized by collisionally activated dissociation (CAD) mass spectrometry. The ClOClO(+) and [Cl(2)-O(2)](+) species were prepared by positive ion Cl(2)/CI of ClO(2) and O(2), respectively, whereas the ClClO(2)(+) isomer proved an elusive species of considerably lower stability. The ClClO(2)(-) anion was obtained from the negative ion Cl(2)/CI of ClO(2). The formation process, structure and stability of the ions are discussed in connection with available theoretical results and related to the recent preparation of (Cl(2)O(2))(+)SbF(6)(-) and (Cl(2)O(2))(+)Sb(2)F(11)(-) salts in the solid phase. Copyright 1999 John Wiley & Sons, Ltd.

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.

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.

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.

Protonated Ozone: Experimental Detection of O3H+ and Evaluation of the Proton Affinity of Ozone.

The elusive protonated ozone ion (O(3)H(+)) has been long postulated as a reactive intermediate but never experimentally observed. This ion has been detected here in mass spectrometric experiments with the use of Fourier transform ion cyclotron resonance. In these experiments, ozone (O(3)) was protonated by strong acids-for example, H(3)(+), KrH(+), XeH(+), and CH(5)(+). The hitherto experimentally unknown proton affinity of O(3) was evaluated by a "bracketing" technique and determined to be 148 -/+ 3 kilocalories mole(-1) at 298 kelvin, in excellent agreement with a value determined in a recent theoretical study of the O(3)/O(3)H(+) system, which was 148 kilocalories mole(-1) at zero temperature ( approximately 149.5 kilocalories mole(-1) at 298 kelvin).

Nuclear decay techniques in ion chemistry.

The spontaneous decay of chemically bound radioactive atoms affords a route to ions of well-defined structure and charge location, free of counterions. The nuclear nature of the ionization process makes it insensitive to environmental effects, so that exactly the same charged species can be generated, and its reactivity investigated, in widely varying media, from low-pressure gases to liquids and solids. Techniques based on nuclear decay are used in studies of the production of otherwise inaccessible species, the structural characterization of free ions, and the comparative evaluation of their reactivity in different environments, in particular, gas phase and solution.

Intraarterial chemotherapy through carotid transposition in advanced head and neck cancer.

We report results of intraarterial chemotherapy (IAC) in patients with advanced unresectable (T4, N0-3, MO) squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) of the oral cavity, oropharynx, or facial skin, given through a subcutaneously transposed external carotid artery by a fine gauge needle. Forty patients entered the study and 39 were evaluable for clinical response and toxicity. The infusion technique was done in two consecutive series of patients with the same characteristics: 17 had treatment with vincristine, bleomycin, and methotrexate (VBM), and 22 received cisplatin and bleomycin (PB) with a median number of six and five cycles, respectively. The total objective response (OR) rate was 76.9%, which included 12.8% of complete response (CR). A better percentage of OR was attained in BCC than SCC (83.3% versus 75.8%), in tumors of the skin of the face than other sites (87.5% versus 74.2%), and in the group that received PB than the group that received VBM (77.3% versus 76.5%). Our series had an overall technique-related toxicity of 18%; 10.3% with neurologic disturbances and 7.7% with skin inflammation (almost all were reversible). The most common systemic toxic side effects were generally mild and well tolerated (30.8%), whereas major toxicities (severe modifications of the cardiopulmonary function) occurred in four patients (10.3%) in the group that received VBM. After chemotherapy, 28 patients (71.8%) were deemed resectable; 23 of these patients (82.1%) agreed to surgery. Pathologic CR were obtained in 13 patients (56.5%). Our technique has significant advantages over the conventional methods of infusion, because tumor perfusion is feasible and selective, technique-related and catheter-related complications are almost completely eliminated, and fatal drug-related side effects are avoided.

5-Fluorouracil and high-dose folinic acid as second-line chemotherapy in head and neck cancer.

Experimental and clinical data support the concomitant use of 5-fluorouracil (5-FU) and high-dose folinic acid (HDFA). To verify the role of such a combination in far advanced head and neck cancer, we performed a phase II study employing weekly HDFA, 500 mg/m2 in 2-h infusions, and 5-FU, 600 mg/m2 bolus injection. Twenty-seven evaluable patients with recurrent disease entered the study. One complete response, seven partial responses, 10 stable disease, and nine progressions were observed: the overall response rate was 29.6%. Oral mucositis and diarrhea were major side effects; five patients discontinued the treatment due to toxicity; no deaths correlated to the treatment were detected. Considering the characteristics of our patients, the 5-FU/HDFA combination has shown a satisfactory antitumoral activity, but toxicity was similar to other chemotherapy regimens.

A possible role of chromatin and tightly-bound chromatin proteins on enzyme-catalyzed methylation of DNA.

Upon extensive digestion with DNAaseI of placenta chromatin matrix, previously "stripped" from its loosely-bound components by high-salt extraction, a fraction is obtained that contains almost no endogenous DNA methylase activity but whose DNA, if still included in this whole fraction--not if it has been purified to a protein-free condition--is a good substrate for externally added enzyme. This chromatin matrix can even cause a significant stimulation of methylation of single-stranded Micrococcus luteus DNA by placental methylase. In vivo, this phenomenon may have possible counterparts in the existence of highly-methylated regions of chromatin loops that appear to be protected by tightly-bound protein components from digestion of the "stripped loops" with DNAaseI.

Localization, in human placenta, of the tightly bound form of DNA methylase in the higher order of chromatin organization.

In human placenta, the DNA of all subfractions of the third level of chromatin organization exhibits similar values of the methylcytosine-to-cytosine ratio. The tightly bound form of DNA methyltransferase is mostly recovered in the 'stripped loop' fraction, although, on the basis of the DNA content, the 'stripped loops' and the 'stripped matrix' appear to possess a similar amount of the enzyme. DNA methyltransferase activity is instead totally absent from the 'digested matrix', i.e., from the fraction remaining after digestion of the 'stripped matrix' with DNAase I. Upon addition of exogenous DNA methyltransferase, however, the DNA of this fraction, which is only 1% (in weight) of the total chromatin DNA and which has a length of approx. 9 kbp, can readily undergo methylation.

5-Methylcytosine levels in nucleosome subpopulations differently involved in gene expression.

Sucrose density gradient centrifugation in the presence or absence of Na-EDTA and at different ionic strengths allows one to obtain well-defined nucleosome subpopulations the DNA of which, examined by gas chromatography-mass spectrometry, is in all cases hypermethylated as compared to spacer regions, but to a different extent for the different subpopulations. The various nucleosomes differ also in their content of histones and of high-mobility-group proteins, as well as in the levels of RNA polymerase activity associated with them. Such data suggest that these nucleosome subpopulations originate from chromatin fractions differently involved in gene expression.