Use of Proktis-M suppositories in patients undergoing neoadjuvant radiochemotherapy for adenocarcinoma of the rectum.

AIM: Generally speaking, the negative side of radiation treatment of the pelvic district is the toxicity that may compromise the patient's quality of life and lead to temporary suspension of treatment with possible negative effects on its effectiveness. In neoadjuvant radiochemotherapy for locally advanced rectal cancer (LARC), the toxicity that is most frequently observed is proctitis, usually treated with topical corticosteroids or mesalazine. Hyaluronic acid's function is to restore the regular trophism and elasticity of the connective tissues leading to faster repair of the damage, and this could represent a viable option for the control of actinic proctitis. METHODS: Since March 2012, a neoadjuvant radiochemotherapy protocol has been active at the Pisa Universitary Hospital for patients with LARC; 23 patients have been enrolled up to the present. Treatment involves an induction chemotherapy phase according to the FOLFOXIRI + Bevacizumab regimen for 6 cycles, followed by chemotherapy (capecitabina + Bevacizumab) concomitant with radiotherapy (5040 cGy in 28 fractions). Surgery is scheduled 6-8 weeks after the end of RTCT. During the course of associated treatment (RTCT), 12/23 patients received topical therapy with hyaluronic acid (Proktis-M suppositories) for the prevention of proctitis. RESULTS: All 23 patients enrolled in the study completed the induction chemotherapy phase. In the first 11 enrolled patients who did not receive prior Proktis-M suppositories, intense rectal toxicity was observed. Proctalgia of grade G1-2 and G3-4 presented respectively in 64% and 36% of cases, with consequent interruption of treatment which, in 45% of patients, lasted longer than 10 days. In the remaining 12 patients who underwent prior treatment with Proktis-M suppositories, the percentage of rectal toxicity was lower. In those cases where it did present, onset was later and its intensity and duration lower. 25% of patients did not develop proctalgia, 33% developed proctalgia of grade G1 and 42% proctalgia of grade G2. In none of these was it found necessary to interrupt radiochemotherapy. CONCLUSION: Prior topical treatment with Proktis-M suppositories in patients undergoing preoperative RTCT for LARC, enabled us to carry out radiochemotherapy at scheduled times, so protecting the treatment's effectiveness on the down-staging of the disease and preserving the patient's quality of life.

Microbial composition of atherosclerotic plaques.

OBJECTIVE: The association of infections such as periodontitis with atherosclerotic diseases is well documented. In spite of the high diversity of the human oral microbiota, and its close contact with the circulatory system, few oral species were detected in atherosclerotic plaques. Thus, we attempted to evaluate the microbial diversity of atherosclerotic plaques from patients with different periodontal conditions, submitted to endarterectomy by a broad-range microbial method. MATERIALS AND METHODS: Patients indicated for aorta endarterectomy due to myocardial infarction were recruited for periodontal clinical examination. The microbial diversity of atherosclerotic plaques (n = 35) was evaluated by sequence analysis of bacterial 16S rRNA libraries. RESULTS: Bacterial DNA was detected in 12 endarterectomy specimens (34.3%). Twenty-three bacterial species/phylotypes were identified. Proteobacteria and Firmicutes comprised 78.3% and 21.7% of the identified taxa, respectively. Fifteen (60.9%) phylotypes were reported as yet uncultivable or as yet uncharacterized species. Two uncultured phylotypes were previously detected in the human mouth. The periodontopathogen Aggregatibacter actinomycetemcomitans was detected in seven samples (20%), followed by Pseudomonas species. There was no association between periodontal parameters and detection of A. actinomycetemcomitans or other phylotypes in atherosclerotic plaques. CONCLUSION: Our results suggest a role of the oral microbiota in the development of inflammation in atherogenesis, particularly of A. actinomycetemcomitans.

Small-angle X-ray scattering study of self-assembling lipophilic guanines in organic solvents: G-quadruplex formation and cation effects in cyclohexane.

Lipophilic guanilic derivatives (lipoGs) dissolved in organic solvents can undergo different self-assembly pathways based on different H-bonded motifs, e.g., the cyclic discrete G-quartet, which forms in the presence of alkali-metal ions, and the "infinite" tape-like G-ribbon observed in the absence of ions. Using in-solution small-angle X-ray scattering, we analyzed a series of lipoGs dissolved in cyclohexane in the presence of different salts. The formation of G-quartet based supramolecular aggregates has been confirmed, evidencing the coexistence equilibrium of octamers and noncovalent molecular nanowires (the so-called G-quadruplexes). By global fitting the scattering data, the concentration of the two kinds of particles as well as the nanowire length have been derived as a function of temperature for the different compounds and salts. The thermodynamic parameters show that the self-assembly aggregation process is enthalpy driven, while the observed enthalpy-entropy compensation suggests that similar stacking interactions control the self-assembly of the different compounds. However, the strength of the stacking interactions, and then the nanowire stability, depends on the nature of templating cations and on their capacity to fill the central cavity of quadruplexes, with the order Sr(+) < Na(+) ≲ K(+).

Evolution of transmitted HIV-1 drug resistance in HIV-1-infected patients in Italy from 2000 to 2010.

Prevalence and predictors of transmitted drug resistance (TDR), defined as the presence of at least one WHO surveillance drug resistance mutation (SDRM), were investigated in antiretroviral-naïve HIV-1-infected patients, with a genotypic resistance test (GRT) performed ≤6 months before starting cART between 2000 and 2010. 3163 HIV-1 sequences were selected (69% subtype B). Overall, the prevalence of TDR was 12% (13.2% subtype B, 9% non-B). TDR significantly declined overall and for the single drug classes. Older age independently predicted increased odds of TDR, whereas a more recent GRT, a higher HIV-RNA and C vs. B subtype predicted lower odds of TDR.

Update on emergence of HIV-1 resistance to antiretroviral drug classes in an Italian national database: 2007-2009.

We analysed trends of human immunodeficiency virus type 1 (HIV-1) drug resistance during 2007-2009 in the Italian national HIV drug resistance database 'ARCA'. Prevalence of resistance in each year was examined on the basis of the presence of major International AIDS Society-2009 mutations. Predictors of resistance were analysed by multivariable logistic regression. Nine hundred and sixty-six patients were selected. Resistance to nucleoside reverse transcriptase inhibitors and protease inhibitors showed a significant decline with respect to previous surveys. Resistance to any class of drug and three drug classes remained stable. Independent predictors of three-class resistance were the number of treatment regimens experienced, prior suboptimal nucleoside reverse transcriptase inhibitor therapy and the current use of ritonavir-boosted protease inhibitors.

Genotypic resistance to zidovudine as a predictor of failure of subsequent therapy with human immunodeficiency virus type-1 nucleoside reverse-transcriptase inhibitors.

To define factors predictive of failure to respond to nucleoside reverse-transcriptase inhibitors in human immunodeficiency virus type-1 (HIV-1)-infected subjects pretreated with zidovudine (ZDV), three groups of subjects shifted to double therapy with ZDV plus didanosine (ddI, n = 13), zalcitabine (ddC, n = 14), or lamivudine (3TC, n = 12) were retrospectively evaluated, with respect to addition of the second NRTI, at week 0 and week 24. Factors considered included duration of ZDV pretreatment, CD4+ cell counts, plasma HIV-1 RNA load, peripheral blood mononuclear cell HIV-1 DNA load, and HIV-1 DNA genotypic resistance to nucleoside reverse-transcriptase inhibitors. The three groups were well matched for baseline characteristics and did not differ significantly in virological and immunological response to the different combination treatments. Drug-specific resistance mutations were selected in more than half the cases by 3TC, but not by ddI and ddC. Low-level and substantial genotypic resistance to ZDV was detected 13 (33.3%) and in 19 (48.7%) patients at baseline, respectively, and evolved through week 24 in several patients. When subjects were divided into responders and nonresponders to the second nucleoside reverse-transcriptase inhibitor on the basis of a decrease of more than 0.5 log10 (n = 15) or less than 0.5 log10 (n = 21) in HIV-1 RNA, respectively, baseline genotypic ZDV resistance was the only independent predictor of failure in a logistic regression model (P = 0.003 or P = 0.024, depending on whether low-level resistance was considered or not, respectively). Thus, selection of ZDV resistance mutations may impair subsequent use of different nucleoside reverse-transcriptase inhibitor compounds.

Evaluation of the presence of 2-LTR HIV-1 unintegrated DNA as a simple molecular predictor of disease progression.

In a preliminary cross-sectional analysis of 109 human immunodeficiency virus type 1 (HIV-1)-infected subjects the presence of 2-long terminal repeat (LTR) unintegrated circular HIV-1 DNA in peripheral blood mononuclear cells (PBMC) was found to be associated with both symptomatic infection (P = 0.0037) and low CD4 counts (P = 0.0004). To investigate the prognostic significance of the presence of 2-LTR HIV-1 DNA, a subset of 23 2-LTR-negative and 25 2-LTR-positive asymptomatic individuals were followed up for 12-24 months. The two groups did not differ in terms of baseline CD4 counts, zidovudine (ZDV) therapy, and duration of HIV-1 infection. Longitudinal analysis of CD4 values did not indicate a significantly different CD4 outcome between the two groups. However, when only ZDV-treated subjects were considered, a significant (P = 0.042) decrease in CD4 counts was found at month 24 with respect to baseline in 2-LTR-positive (n = 12) but not in 2-LTR-negative (n = 11) patients. Moreover, when > 40% CD4 loss from baseline and/or development of CDC stage B or C symptoms were considered as indicators of disease progression, there was a significantly higher number of events in the whole 2-LTR-positive group than in the whole 2-LTR-negative group (P = 0.0197 at month 12, P = 0.0299 at month 18, P = 0.0373 at month 24). Thus, the presence of 2-LTR HIV-1 DNA in PBMC merits further investigation as a simple, qualitative, molecular predictor of disease progression and decreased response to antiretroviral therapy.

Zidovudine resistance mutations and human immunodeficiency virus type 1 DNA burden: longitudinal evaluation of six patients under treatment.

Zidovudine (ZDV) is by far the most widely used drug to counteract human immunodeficiency virus type 1 (HIV-1) infection, both in monotherapy and in combination therapy regimens. However, the majority of patients under prolonged ZDV therapy have been shown to harbour HIV-1 mutant genomes displaying reduced sensitivity to the drug in vitro. In order to investigate the pathogenic role of in vitro resistance to ZDV, six HIV-1-infected ZDV-treated subjects were evaluated longitudinally (mean follow-up 28.5 months, range 12-39 months) for HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) and for the presence of HIV-1 pol gene mutations responsible for ZDV resistance. Quantitation of HIV-1 DNA was performed by competitive polymerase chain reaction (cPCR) and the pol genotype was determined by direct sequencing of PCR products. All of the six patients developed one or more of the HIV-1 pol mutations known to confer resistance to ZDV in vitro (Met41-->Leu, Asp67-->Asn, Lys70-->Arg, Thr215-->Phe/Tyr, Lys219-->Gln/Glu). A temporal association was found between HIV-1 DNA burden and the level of ZDV resistance, as predicted on the basis of the pol genotype (genotypic resistance). Both virus load and ZDV resistance were inversely correlated with CD4+ cell counts. These results are compatible with a direct in vivo pathogenetic role for pol gene mutations shown to be involved in resistance to ZDV in vitro. Monitoring the degree of genotypic resistance to ZDV and to other antiretroviral drugs should be considered in designing protocols for the management of treated patients.

Concordance between polymerase chain reaction and antibody detection in the diagnosis of human immunodeficiency virus type 1 infection.

A highly sensitive nested polymerase chain reaction (PCR) protocol was used to detect human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood mononuclear cells from 271 HIV-1-seropositive patients, 240 HIV-1-seronegative subjects at increased risk for HIV-1 infection, 51 serologically indeterminate individuals, and 120 healthy blood donors. PCR was carried out in a multiplex nested configuration with pol and env region primer sets. HIV-1 DNA was detected in all of the HIV-1 seropositive patients. In contrast, HIV-1 DNA was not detected in any of the either seronegative or serologically indeterminate subjects. Only one of 37 seronegative regular sexual partners of HIV-1-infected patients who were followed longitudinally was found to seroconvert to HIV-1. However, HIV-1 DNA and antibody results were concordant in the four samples obtained from this subject prior to and after seroconversion. These results show an excellent concordance between HIV-1 DNA and antibody detection for diagnosis of HIV-1 infection and suggest that long-term HIV-1 infection in the absence of detectable antibody is likely to occur at a very low frequency.

Low human immunodeficiency virus type 1 (HIV-1) DNA burden as a major cause for failure to detect HIV-1 DNA in clinical specimens by PCR.

To determine the sensitivity of a nested PCR procedure for detecting human immunodeficiency virus type 1 DNA in clinical specimens, 553 peripheral blood mononuclear cell samples obtained from 268 human immunodeficiency virus type 1-seropositive subjects were assayed by use of two independent primer sets for each sample. Overall, 1,088 of 1,106 (98.37%) reactions were positive. Investigation of the negative reactions showed that a low viral burden in some infected subjects, rather than primer-template mismatches, was the primary cause for the false-negative PCR results.

[Viral hepatitis. Epidemiologic evaluation of a personal case load in the area of Casale Monferrato in the years 1981-1982]. / Epatite virale. Valutazione epidemiologica di una casistica personale nell'area di Casale Monferrato negli anni 1981-1982.

The results are reported of an epidemiological assessment of 94 patients hospitalised with diagnosed acute viral hepatitis in the Infectious Disease Division of the S. Spirito Hospital, Casale Monferrato in the period march 1 1981, april 30 1982. Hepatitis was found to occur most frequently among young (under 30) males. There were more positive than negative HBsAg cases, most of the latter arising in heroin addicts.

[Epidemiologico-clinical considerations on a case file of acute hepatitis observed 1980-1983]. / Considerazioni epidemiologico-cliniche su una casistica di epatite acuta osservata negli anni 1980-1983.

Between January 1980 and December 1983, 332 consecutive cases of acute hepatitis were observed in adult patients admitted to the Department of Infectious Disease and Gastroenterology of Siena. Sex and age of the patients, the presence of jaundice, the maximum value of the serum-glutamate-pyruvate-transaminase (SGPT) were considered. Serum specimens were tested for hepatitis B surface antigen (HBsAg), antibody against hepatitis B core antigen (anti-HBc) of the IgM class, antibody against hepatitis A virus (anti-HAV) of the IgM class, antibody against cytomegalovirus (CMV) of the IgM class, Paul Bunnel Davidshon reaction. Hepatitis A was diagnosed in 25 cases (7.5%). Hepatitis B in 167 (50.3%). Hepatitis due to CMV in 2 cases (0.6%). And, by exclusion, hepatitis non A, non B in 138 cases (41.6%). Male patients were affected with significantly higher frequency than female (p less than 0.01); the same was seen for young patients (14-30 years) compared to the older ones (31-50 years, and over 50 years) (p less than 0.01 in both). Biochemical investigation showed that hepatitis A and B had a significantly higher, maximum SGPT value than hepatitis non A non B (p less than 0.01 in both). Icteric patients were significantly more frequently observed among hepatitis A and B cases than hepatitis non A non B cases (p less than 0.01 in both).