Locking compression plate fixation in humeral shaft fractures: A comparative study to literature conservative treatment.

INTRODUCTION: Humeral shaft fractures represent about 3% of all fractures. While there are several treatment options for this type of fractures, there is no evidence in literature showing which is the best one. This study aims at analysing the outcomes for patients with humeral shaft fractures treated with Locking Compression Plate (LCP) fixation in our hospital and comparing them with the outcome for patients conservatively treated (according to data from Pubmed),in order to determine the best treatment option. MATERIALS AND METHODS: We treated surgically 220 humeral shaft fractures in our department from February 2005 to March 2012. Seventy-three of them met all the inclusion criteria for this study. All fractures were then classified according to the AO classification. The follow-up considered the radiographic healing of the fracture. All patients were treated with plate fixation (LCP - DePuySynthes Co). At the end of the four-year follow-up, the function was evaluated by means of the DASH score. A systematic review of the literature of the last 20 years was performed on MEDLINE (PubMed). RESULTS: We had 2 infections and 8 patients had postoperative nerve palsy which recovered in average time of 6.7 months. In addition, 4 fractures (5.48%) didn't heal within 6 months and they were considered as nonunions and healed after a second surgery. One of these 4 nonunions was infected. The mean DASH score was 18.24±19.18. No malunions were found. We identified 13 studies that were eligible for our systematic review. The mean non-union rate found was 17% in 2517 fractures with a follow-up that ranging from 67% to 100% of patients and a primary radial nerve palsy ranging from 0 to 115 patients. Malalignment rate ranged from 12.7 to 42%. CONCLUSIONS: After taking into account both the conservative and the surgical treatment, for humeral shaft fractures we suggest the operative treatment, because the patient's function of the upper limb recovers quickly in the immediate postoperative period and the incidence of malunions may be avoided.

Negative symptom severity at discharge from an index hospitalization and subsequent use of psychiatric care resources: A retrospective 1-year follow-up study on 450 patients with schizophrenia spectrum disorders.

Negative symptoms of schizophrenia have a great impact on patients' functioning and are among the most important contributors to subject's disability. However, few studies have assessed the role of type and severity of symptomatology of schizophrenia on the psychiatric care resource utilization. We investigated if the clinical profile of patients at discharge from an index hospitalization might be associated with a different use of psychiatric care resources in the subsequent 1-year period in a large population of patients with schizophrenia spectrum disorders. Clinical records of 450 patients with schizophrenia spectrum disorders admitted in an acute psychiatric inpatient service and subsequently followed in the outpatient services of the same Department were reviewed. Patients with more severe negative symptoms at discharge from hospital showed a higher number and duration of hospitalizations in the 1-year follow-up, as well as a higher number of rehabilitative residential admissions than patients with milder severity of negative symptoms. The same was true for patients with predominant negative symptoms. A global resource utilization index indicated a higher use of psychiatric resources in patients with higher severity of negative symptoms. In conclusion, showing moderate to severe negative symptoms versus positive symptoms at discharge from a hospitalization for an acute exacerbation of schizophrenia spectrum disorder does predict a higher use of psychiatric care resources. This underlines the importance of relieving negative symptoms even in the acute phase of treatment and the need to develop more effective treatments for this symptom dimension.

Predicting the failure in distal femur fractures.

INTRODUCTION: The incidence of nonunion after fractures of the distal femur is up to 6%. The distal femoral nonunion is a disabling disease that needs complex steps in his treatment. Aim of our study is to find predicting factors of non-unions. MATERIALS AND METHODS: We retrospectively analyzed 116 cases of distal femoral fractures and 20 cases of non-unions. In both surgeries we analyzed: accuracy of reduction, stability of fixation, hardware used, residual medial or lateral bone defect, use of autologous or heterologous bone grafts. RESULTS: Malreduction, particularly axial defect, associated with unbalanced fixation, and a medial cortical bone defect of greater or lesser extent were found to be the major risk factors of nonunion. Addressing both the mechanical and the biological environment was associated with successful non union treatment. CONCLUSION: The main principles for solving a distal femoral nonunion are new better reduction, correction of the medial bone defect and biological support with bone grafting. From the mechanical side the association of a medial strut graft or a medial column plate could be very useful in the treatment of these non-unions.

Microsatellite-based evaluation of Ribes spp. germplasm.

There is a lack of published microsatellite data which characterizes Ribes spp. To address this, an initial study of simple sequence repeat (SSR) variation was undertaken in 41 cultivars belonging to four species of the genus Ribes to evaluate its genetic variability. The cultivars were collected in Piedmont, northwest Italy, together with one cultivar from Switzerland. Twenty SSRs were screened for amplification and polymorphism. Seven failed to amplify, and therefore the remaining 13 were selected and used to fingerprint all the cultivars. Microsatellite analysis resulted in the identification of 38 genotypes, suggesting the existence of possible clonal genotypes and synonyms. Among the cultivars analyzed, two tetraploid accessions were found. The evaluation of genetic variability in Ribes is of fundamental importance for future nutritional breeding programs and to preserve genetic resources, as cultivar characterization permits better management of plant collections.

Evaluation of auramine genotoxicity in primary rat and human hepatocytes and in the intact rat.

Auramine, a dye previously found to be a liver carcinogen in both mice and rats, was evaluated for its DNA-damaging and clastogenic activities in primary cultures of rats and human hepatocytes and for the induction of DNA single-strand breaks in the liver and urinary bladder mucosa of intact rats. A similar dose-dependent frequency of DNA fragmentation was revealed by the alkaline elution technique in metabolically competent primary cultures of both rat and human hepatocytes exposed for 20 h to subtoxic concentrations ranging from 10 to 32 microM. In contrast, neither rat nor human hepatocytes displayed an increased frequency of micronuclei after a 48-h exposure to the same auramine concentrations. In rats given a single oral dose of 125, 250 or 500 mg kg-1 auramine, the Comet assay revealed a significant increase in the frequency of DNA lesions in the liver and in the urinary bladder mucosa, the effect being slightly more marked in the liver. Taken as a whole and compared with previous findings, these results suggest that auramine is biotransformed into reactive species in target organs of both rats and humans, and that this dye might play by itself the main role in the increased incidence of bladder cancer which has been judged as causally related to its manufacture.

Inhibition of the development of rat liver preneoplastic lesions by verapamil and dexverapamil.

The effect of verapamil and dexverapamil on the development of liver preneoplastic foci was investigated in male Sprague-Dawley rats initiated with N-nitrosodiethylamine (200 mg/kg i.p.), fed on a diet containing 0.01% 2-acetylaminofluorene and subjected to partial hepatectomy, according to the hepatocarcinogenesis model developed by Solt and Farber. Administration of drinking water containing 0.03% verapamil or dexverapamil resulted in a decrease in the incidence and size of gamma-glutamyl transpeptidase-positive foci. The chemopreventive effect of dexverapamil was more marked than that of verapamil. These findings support the hypothesis that these two calcium channel blockers act by reducing the resistance of initiated hepatocytes to the mitoinhibitory and cytotoxic effects of 2-acetylaminofluorene.

Cytotoxic and genotoxic effects of five n-alkanals in primary cultures of rat and human hepatocytes.

Five n-alkanals were examined for cytotoxicity, as evaluated by the trypan blue exclusion test, and for genotoxicity, as evaluated by the induction of unscheduled DNA synthesis (UDS), in primary cultures of rat and human hepatocytes. After 20 h exposure, cytotoxicity was similar in cells of the two species, and increased with the length of the carbon chain. In rat hepatocytes, propanal (10-100 mM), butanal (10-100 mM), pentanal (3-30 mM) and hexanal (3-30 mM) induced a modest but significant and dose-dependent increase of net nuclear grain counts, while in human hepatocytes this effect was not detected. Nonanal (3-30 mM), which showed the highest cytotoxic effect, failed to induce UDS in both cell types. These results seem to suggest that at the concentrations which are presumably attained after ingestion with food or generated by lipid peroxidation processes the five n-alkanals tested are presumably unable to induce genotoxic effects in the human liver.

[Therapy of headache]. / Terapia delle cefalee.

Cephalalgias are divided into four syndromes and the most severe of these, migraine, presents several therapeutic applications.

Absence of DNA damage in mice and rats given high doses of five beta-adrenergic blocking agents.

Five beta-blockers (propranolol, metoprolol, oxprenolol, pindolol, and sotalol) were tested for their in vivo DNA-damaging activity by two different techniques: alkaline denaturation of DNA followed by hydroxylapatite chromatography, and a new viscometric method markedly more sensitive in detecting DNA fragmentation. DNA damage, as checked by the first technique, was absent either in liver and kidney of mice or in liver and gastric mucosa of rats given a single p.o. administration of 1/2 LD50 of the drugs. The subsequent viscometric analysis of liver DNA from rats treated with the same doses confirmed the above negative results.

Genotoxic effects in rodents given high oral doses of ranitidine and sodium nitrite.

The possible intragastric nitrosation of ranitidine to genotoxic derivatives has been investigated in rats and mice given, by gavage, high single doses of this histamine H2 receptor antagonist along with NaNO2. Liver DNA fragmentation, as revealed in rats by both DNA alkaline elution and DNA alkaline denaturation followed by hydroxylapatite chromatography, was found to be dependent either on the molar ratio drug/nitrite or on the gastric pH. It occurred only with doses of 175 mg/kg ranitidine HCl + 80 mg/kg NaNO2 (molar ratio 1:2.32) or 350 mg/kg ranitidine HCl + 80 mg/kg NaNO2 (molar ratio 1:1.16) and concurrent reduction of gastric pH from 5.5 to 2-3 (produced by prolonged fasting). A further reduction of pH elicited by histamine injection increased the amount of DNA damage. DNA fragmentation in gastric mucosa showed a similar dependence on both pH and ranitidine/NaNO2 ratio, but was more marked than in liver. Simultaneous administration of ascorbic acid reduced the damage of gastric DNA. Oral administration of 175 mg/kg ranitidine HCl + 80 mg/kg NaNO2 in fasted and histamine-injected mice induced a modest but statistically significant increase in the frequency of sister chromatid exchanges in bone marrow cells.

DNA damage induced by nitrosated ranitidine in cultured mammalian cells.

Ranitidine, a new H-2 receptor antagonist more potent than cimetidine in inhibiting gastric secretion, reacted under acid conditions with a twofold molar amount of nitrite (a nitrite/ranitidine ratio about 1000 times that likely to occur in gastric juice of treated humans) yielding a nitroso derivative capable of inducing a dose-dependent DNA fragmentation in cultured Chinese hamster ovary cells.

Genotoxicity of cimetidine in primary cultures of rat hepatocytes.

The genotoxicity of cimetidine was examined in the hepatocyte primary culture/DNA-repair test and by the DNA-damage/alkaline-elution assay. A dose-dependent amount of unscheduled DNA synthesis was elicited by cimetidine, whereas DNA fragmentation occurred only in hepatocytes exposed to the highest (3 mM) concentration of the drug. These findings are in contrast with the negative results previously obtained in long-term and short-term carcinogenesis assays.

Absence of DNA damage in liver of rats given high doses of cimetidine and sodium nitrite.

A correlation between cimetidine and gastric cancer has been suggested. Nitrosation of cimetidine in the presence of nitrite and HCl and mutagenic activity as well as DNA damage in mammalian cells displayed by nitrosocimetidine, as these phenomena occur in vitro, were the supporting hypothesis. Previous studies have shown that liver DNA damage was a well correlated index of potential carcinogenic activity of N-nitroso compounds and that such a damage was found after long-term simultaneous oral administration of aminopyrine and nitrite in rats. In this work, liver DNA fragmentation was investigated by three different techniques: DNA alkaline elution, DNA alkaline denaturation followed by hydroxylapatite chromatography and a new viscometric method markedly more sensitive than the above mentioned ones in detecting DNA damage. Evidence of DNA damage was not gained in any of the groups of rats treated with high single or successive oral daily doses of cimetidine (250 mg/kg) along with nitrite (80 mg/kg) in approximately equimolar amounts. Cimetidine and nitrite given alone were also ineffective. The lowering of gastric pH, obtained with fasting and histamine administration before giving cimetidine and nitrite combination in a single dose, did not favor the induction of liver DNA fragmentation neither in the above condition nor even when the amount of cimetidine was lowered to 125 mg/kg in order to obtain an approximately 2-fold molar amount of nitrite.

Genotoxic activity of five antidepressant hydrazines in a battery of in vivo and in vitro short-term tests.

Five antidepressant agents (monoamine oxidase inhibitors) having a hydrazino group--phenelzine, nialamide, mebanazine, isocarboxazid, and iproniazid--were assayed in four in vivo or in vitro short-term tests predictive of the potential carcinogenicity of chemicals. (1) All the compounds tested except iproniazid, produced DNA fragmentation, as evaluated by the alkaline elution technique, in liver and/or lung cells of mice treated ip or po. (2) All the compounds except mebanazine (which was no longer available for testing) were weak inducers of sister chromatid exchanges in bone marrow cells of mice treated ip. (3) Phenelzine and nialamide elicited base-pair substitutions and mebanazine elicited frameshift errors in his- Salmonella typhimurium. S9 mix containing rat liver, mouse liver, or mouse lung S9 fractions had variable effects on mutagenicity. (4) The same three compounds were positive in a DNA repair bacterial test with five trp- Escherichia coli strains lacking a variety of repair mechanisms (uvrA, polA, recA, lexA) or incorporating plasmids (R391).

In vivo and in vitro genotoxicity of three antihypertensive hydrazine derivatives (hydralazine, dihydralazine, and endralazine).

Three antihypertensive hydrazine derivatives (hydralazine, dihydralazine, and endralazine) were found to be genotoxic in four in vivo or in vitro short-term test systems. a) In mice, a single ip administration of the LD50 of the three drugs caused a small but statistically significant increase over controls in DNA elution rate, ie, a modest amount of DNA fragmentation, in three of the four organs (liver, lung, kidney, and spleen) tested, DNA damage being absent in lung for hydralazine and endralazine and in liver for dihydralazine. Only for hydralazine DNA lesions were always repaired within 12 hr, in agreement with the constant lack of cumulative effects in mice given five successive daily doses. The rank of potencies was hydralazine greater than dihydralazine greater than endralazine. b) In mice bone marrow cells, all three hydrazine derivatives induced a modest but statistically significant increase over controls in the frequency of sister chromatid exchanges, the rank of potencies being in this case dihydralazine greater than endralazine greater than hydralazine. c) In the Ames reversion test all three drugs behaved as direct-acting mutagens of low potency, whose activity was not influenced by rat liver nor by mouse liver or lung S-9 fractions. Hydralazine and dihydralazine elicited mixed genetic mechanisms of mutations, while endralazine exclusively induced frameshift errors in Salmonella DNA. The recently developed strain TA97 was the most efficient in revealing frameshift errors with all three drugs. d) The selective lethality assays in a battery of two S typhimurium and five E coli strains confirmed the direct genotoxicity of hydralazine, dihydralazine, and endralazine, in order of potency. Potency was evaluated by means of a sensitive and reliable micromethod procedure. Among those investigated, the recA recombination repair and the lexA post-replication repair ("SOS functions") and, to a lesser extent, also the polymerase I mechanism, appeared to contribute to the specific DNA repair with all three drugs, while excision repair systems (uvrA and uvrB) did not appear to be involved.

DNA fragmentation in N-diazoacetylglycine amide-treated cells determined, by the rate of strand separation in alkali with hydroxylapatite chromatography in batch.

DNA damage induced in mammalian cells (CHO-K1) by one hour treatment with several concentrations of N-diazoacetylglycine amide (DGA) was evaluated by the method of DNA denaturation in alkali and successive neutralization followed by separation of single from double stranded DNA with the recently described technique of hydroxylapatite chromatography performed in batch. This latter technique does not need complex apparatus and simplifies the simultaneous handling of large number of samples; it also appears as sensitive and reliable as the DNA alkaline elution on filter, to which it can be regarded as both alternative and complementary.

DNA-damaging activity in vivo and bacterial mutagenicity of sixteen hydrazine derivatives as related quantitatively to their carcinogenicity.

Sixteen hydrazine derivatives (hydrazine, 1,1-dimethylhydrazine, 1,2-dimethylhydrazine, phenylhydrazine, procarbazine, isoniazid, isocarboxazid, nialamide, 2,4-dinitrophenylhydrazine, phenelzine, hydralazine, dihydralazine, carbamylhydrazine, mebanazine, iproniazid, and 1-carbamyl-2-phenylhydrazine) were tested for DNA-damaging activity by the alkaline elution technique and for mutagenic activity in the Salmonella-microsome (Ames) test. The first nine compounds listed (56%) were found to induce a significant DNA fragmentation in the liver and/or in the lung of i.p.-treated male Swiss mice. The DNA-damaging potency varied over an approximately 30-fold range. Thirteen of the first 14 compounds listed (81% of the total), isocarboxazid being inactive, were positive in the Ames test, with a broad range of activity towards the five bacterial strains of Salmonella typhimurium used (TA1535, TA100, TA1537. TA1538, and TA98) and of metabolic behavior in the presence of S-9 mix containing rat liver, mouse liver, or mouse lung postmitochondrial preparations from Aroclor-treated animals. The mutagenic potency varied over an almost 7000-fold range. For 11 of the 16 hydrazine derivatives tested, homogeneous carcinogenicity data (induction of pulmonary tumors in mice chronically treated p.o.) were available from literature. Elaboration of these data showed that carcinogenic potency varied over an approximately 1900-fold range. The five most potent carcinogens were all positive in the DNA damage test. Their carcinogenic potency varied over a 130-fold rage and their DNA-damaging potency varied over a 22-fold range. DNA-damaging potency seemed to vary on a more compressed scale, but regression analysis indicated the existence of a strong positive correlation between in vivo DNA-damaging and carcinogenic potencies, while a lack of correlation was found between mutagenic and carcinogenic potencies. There was no correlation between DNA-damaging and mutagenic potencies.

Quandtitative correlation among DNA damaging potency of six N-nitroso compounds and their potency in inducing tumor growth an bacterial mutations.

Six N-nitroso compounds (N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodi-n-propylamine, N-nitroso-N-methylurea, N-nitrosopyrrolidine, and N-nitrosodi-n-butylamine) were tested in rats for liver DNA damaging activity by the alkaline elution technique. On molar basis their DNA damaging potency was found to decrease in the above order, and to vary over a 28-fold range. The elaboration of homogenous data available from literature showed that the carcinogenic potency of the 6 N-nitroso compounds varied over an 18-fold range, and that their mutagenic potency varied over a 490-fold range. Regression analysis indicated that correlation between carcinogenic and DNA damaging potencies was positive but at a low significance level, while the correlation between carcinogenic and mutagenic potencies was negative.

Chenodeoxycholic acid (CDCA) versus ursodeoxycholic acid (UDCA): a comparison of their effects in pregnant rats.

Treatment of pregnant rats with ursodeoxycholic acid or chenodeoxycholic acid at 3 dose levels resulted in no dismorphogenic effects although embryotoxicity and fatty infiltration in maternal liver were more frequent after CDCA. Light microscopic examination showed no evidence of derangement in fetal liver. Electron microscopic study, carried out in maternal liver, showed that changes were present only in dams treated with the highest doses of both bile acids.