Factors influencing delayed discharge after day-surgery laparoscopic cholecystectomy: the DeDiLaCo study protocol.

OBJECTIVE: Laparoscopic cholecystectomy (LC) is the gold standard for most benign gallbladder diseases. Early discharge (<24 hours) has the same outcomes as longer (>24 hours) hospital stay. Nevertheless, the rate of delayed discharge >24 hours range from 4.6% to 37%. The primary endpoint of this Italian nationwide study is to analyze the prevalence of patients undergoing elective LC who experienced a delayed discharge >24 hours and identify potential limiting factors of early discharge. Results from these analyses will be used to select patients who can be safely discharged on the same day after surgery. Secondary endpoints will be to evaluate the patient's quality of life (QoL), assess the direct health costs associated with late discharge, and quantify the patient's involvement in the treatment process. PATIENTS AND METHODS: This prospective, observational study was conducted following a resident-led model and the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. All patients were treated according to the local hospital protocol and received routine care as standard therapy. RESULTS: We expected to obtain the enrollment of at least 500 patients based on an assumed difference in discharge delay between the reference and the recruitable population of 6% and the identification of factors related to discharge failure within 24 h. Early discharge after LC leads to advantages both in terms of clinical outcomes and quality of life of the patient, and it is highly effective in terms of health costs and shortening the waiting list. However, clinical reality differs from the results of randomized studies by a complex series of non-objectionable real-world data influencing treatment plans. Therefore, we expected to identify independent predictors and factors of failure of early discharge. CONCLUSIONS: Clinical reality often differs from randomized trial results. In Italy, the vast majority of delayed discharges after LC may not be related to surgery and can be prevented both with logistical reorganization and with a readjustment of the trust reimbursement policies.

Dental plaque disclosure as an auxiliary method for infants' oral hygiene.

AIM: This was to evaluate the effectiveness of plaque disclosure as an auxiliary method for early childhoods' oral hygiene. METHODS: The study was performed with 20 mothers and their children (aged 6-36 months), members of a preventive programme, which two groups used one of two approaches: conventional oral hygiene/group I (tooth brushing) and plaque disclosure with subsequent oral hygiene/group II (tooth brushing with prior plaque disclosure). Ten mothers started the study in group I and the other 10 in group II, after one month interval they changed to be in the alternate group. Each group consisted of baseline and three additional visits at weekly intervals. The effectiveness of oral hygiene was assessed in a blind fashion by plaque quantity estimation, using the Green Vermilion index for smooth surfaces and the plaque thickness index for occlusal surfaces. Statistical comparisons were performed using repeated measures ANOVA/Fisher's post hoc test and paired t-test (p < 0.05). RESULTS: For smooth and occlusal surfaces at first and second visits, group II recorded significantly lower plaque indices when compared with group I. Additionally, when considering the mean dental plaque index of all visits, group II also presented lower plaque scores than group I. CONCLUSION: Dental plaque disclosure before toothbrushing helps mothers to enhance the effectiveness of early childhood oral hygiene. REGISTRATION NUMBER AND NAME OF TRIAL REGISTRY: RBR-7fyc7g; Avaliação do Treinamento e de Métodos Auxiliares na Efetividade da Escovação Dentária Materna em Bebês. Where the full trial protocol can be accessed: http://www.ensaiosclinicos.gov .

A prospective randomized comparison among SWL, PCNL and RIRS for lower calyceal stones less than 2 cm: a multicenter experience : A better understanding on the treatment options for lower pole stones.

PURPOSE: To prospectively evaluate the efficacy and safety of RIRS, SWL and PCNL for lower calyceal stones sized 1-2 cm. MATERIALS AND METHODS: Patients with a single lower calyceal stone with an evidence of a CT diameter between 1 and 2 cm were enrolled in this multicenter, randomized, unblinded, clinical trial study. Patients were randomized into three groups: group A: SWL (194 pts); group B: RIRS (207 pts); group C: PCNL (181 pts). Patients were evaluated with KUB radiography (US for uric acid stones) at day 10 and a CT scan after 3 months. The CONSORT 2010 statement was adhered to where possible. The collected data were analyzed. RESULTS: The mean stone size was 13.78 mm in group A, 14.82 mm in group B and 15.23 mm in group C (p = 0.34). Group C compared to group B showed longer operative time [72.3 vs. 55.8 min (p = 0.082)], fluoroscopic time [175.6 vs. 31.8 min (p = 0.004)] and hospital stay [3.7 vs. 1.3 days (p = 0.039)]. The overall stone-free rate (SFR) was 61.8% for group A, 82.1% for group B and 87.3% for group C. The re-treatment rate was significantly higher in group A compared to the other two groups, 61.3% (p < 0.05). The auxiliary procedure rate was comparable for groups A and B and lower for group C (p < 0.05). The complication rate was 6.7, 14.5 and 19.3% for groups A, B and C, respectively. CONCLUSIONS: RIRS and PCNL were more effective than SWL to obtain a better SFR and less auxiliary and re-treatment rate in single lower calyceal stone with a CT diameter between 1 and 2 cm. RIRS compared to PCNL offers the best outcome in terms of procedure length, radiation exposure and hospital stay. ISRCTN 55546280.

Enucleación con láser de tulio (ThuLEP) frente a resección transuretral de la próstata en solución salina (TURis): un ensayo prospectivo aleatorizado para comparar resultados intra y postoperatorios tempranos / Thulium laser enucleation (ThuLEP) versus transurethral resection of the prostate in saline (TURis): A randomized prospective trial to compare intra and early postoperative outcomes

Objetivo: Comparar los resultados clínicos intra y postoperatorios tempranos entre la enucleación transuretral con láser de tulio de la próstata (ThuLEP) y la resección bipolar transuretral de la próstata (TURis) para el tratamiento de la hiperplasia prostática benigna (HBP) en un ensayo prospectivo aleatorizado. Métodos: El estudio aleatorizó a 208 pacientes consecutivos con HBP a ThuLEP (n = 102) o TURis (n = 106). Para todos los pacientes se evaluaron preoperatoriamente en cuanto a pérdida de sangre, tiempo de cateterización, volumen de irrigación, estancia hospitalaria y tiempo operatorio. A los 3 meses después de la cirugía también fueron evaluados por la International Prostate Symptom Score (IPSS) el flujo máximo (Qmáx) y el volumen de residuo posmiccional (RPM). Resultados: Los pacientes en cada brazo de estudio no mostraron diferencias significativas en los parámetros preoperatorios. En comparación con TURis, ThuLEP tuvo el mismo tiempo quirúrgico (53,69±31,44 vs 61,66±18,70min; p = 0,123), pero resultó en menos disminución de la hemoglobina (0,45 vs 2,83g/dl, p = 0,005). ThuLEP también necesitó menos tiempo de cateterización (1,3 vs 4,8 días, p = 0,011), volumen de irrigación (29,4 vs 69,2l; p = 0,002) y estancia hospitalaria (1,7 vs 5,2 días, p = 0,016). Durante los 3 meses de seguimiento, los procedimientos no demostraron una diferencia significativa en Qmáx, IPSS, RPM y ECDV. Conclusión: ThuLEP y TURis alivian los síntomas del tracto urinario inferior igualmente, con alta eficacia y seguridad. ThuLEP fue estadísticamente superior a TURis en la pérdida de sangre, el tiempo de cateterización, el volumen de irrigación y la estancia hospitalaria. Sin embargo, los procedimientos no difirieron significativamente en Qmáx, IPSS, RPM y ECDV a través de 3 meses de seguimiento

Objective: To compare clinical intra and early postoperative outcomes between thulium laser transurethral enucleation of the prostate (ThuLEP) and transurethral bipolar resection of the prostate (TURis) for treating benign prostatic hyperplasia (BPH) in a prospective randomized trial. Methods: The study randomized 208 consecutive patients with BPH to ThuLEP (n = 102) or TURis (n = 106). For all patients were evaluated preoperatively with regards to blood loss, catheterization time, irrigation volume, hospital stay and operative time. At 3 months after surgery they were also evaluated by International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), and postvoid residual urine volume (PVR). Results: The patients in each study arm each showed no significant difference in preoperative parameters. Compared with TURIS, ThuLEP had same operative time (53.69±31.44 vs 61.66±18.70 minutes, P = .123) but resulted in less hemoglobin decrease (0.45 vs 2.83g/dL, P = .005). ThuLEP also needed less catheterization time (1.3 vs 4.8 days, P = .011), irrigation volume (29.4 vs 69.2 L, P = .002), and hospital stay (1.7 vs 5.2 days, P = .016). During the 3 months of follow-up, the procedures did not demonstrate a significant difference in Qmax, IPSS, PVR, and QOLS. Conclusion: ThuLEP and TURis both relieve lower urinary tract symptoms equally, with high efficacy and safety. ThuLEP was statistically superior to TURis in blood loss, catheterization time, irrigation volume, and hospital stay. However, procedures did not differ significantly in Qmax, IPSS, PVR, and QOLS through 3 months of follow-up

Thulium laser enucleation (ThuLEP) versus transurethral resection of the prostate in saline (TURis): A randomized prospective trial to compare intra and early postoperative outcomes. / Enucleación con láser de tulio (ThuLEP) frente a resección transuretral de la próstata en solución salina (TURis): un ensayo prospectivo aleatorizado para comparar resultados intra y postoperatorios tempranos.

OBJECTIVE: To compare clinical intra and early postoperative outcomes between thulium laser transurethral enucleation of the prostate (ThuLEP) and transurethral bipolar resection of the prostate (TURis) for treating benign prostatic hyperplasia (BPH) in a prospective randomized trial. METHODS: The study randomized 208 consecutive patients with BPH to ThuLEP (n=102) or TURis (n=106). For all patients were evaluated preoperatively with regards to blood loss, catheterization time, irrigation volume, hospital stay and operative time. At 3 months after surgery they were also evaluated by International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), and postvoid residual urine volume (PVR). RESULTS: The patients in each study arm each showed no significant difference in preoperative parameters. Compared with TURIS, ThuLEP had same operative time (53.69±31.44 vs 61.66±18.70minutes, P=.123) but resulted in less hemoglobin decrease (0.45 vs 2.83g/dL, P=.005). ThuLEP also needed less catheterization time (1.3 vs 4.8 days, P=.011), irrigation volume (29.4 vs 69.2 L, P=.002), and hospital stay (1.7 vs 5.2 days, P=.016). During the 3 months of follow-up, the procedures did not demonstrate a significant difference in Qmax, IPSS, PVR, and QOLS. CONCLUSION: ThuLEP and TURis both relieve lower urinary tract symptoms equally, with high efficacy and safety. ThuLEP was statistically superior to TURis in blood loss, catheterization time, irrigation volume, and hospital stay. However, procedures did not differ significantly in Qmax, IPSS, PVR, and QOLS through 3 months of follow-up.

Role of the C1858T polymorphism of protein tyrosine phosphatase non-receptor type 22 (PTPN22) in children and adolescents with type 1 diabetes.

In recent years, increasing interest has been devoted to the susceptibility gene polymorphisms in type 1 diabetes (T1D) as well as in other autoimmune diseases. Among these, a nucleotide polymorphism of the gene encoding for the protein tyrosine phosphatase non-receptor type 22 (PTPN22) has been associated with T1D in several studies. The aim of this study is to define the frequency of the C1858T polymorphism in the PTPN22 gene in a cohort of 113 Caucasian patients (58 males and 55 females) with T1D, and to assess a possible correlation with a group of clinically relevant variables: age at onset, gender, diabetes-related autoantibodies, residual ß-cell function and daily insulin requirement (IR) 6 months after diagnosis. Using a PCR-RFLP approach, we evidenced a 17.7% frequency of the PTPN22 C1858T polymorphism in diabetic patients, higher than the frequency showed in the general population. A statistically significant correlation between this polymorphism and higher levels of C-peptide at diagnosis and lower IR at 6 months from diagnosis was observed (P=0.001 and P=0.04). Moreover, 1858T variant carriers were more frequently positive for glutamic acid decarboxylase (GAD) autoantibodies at diagnosis than wild-type subjects (P=0.19). On the other hand, no significant difference regarding age at onset, gender distribution, insulinoma-associated 2 molecule (IA2) and islet cell antibodies (ICA) positivity was found. These findings, if adequately confirmed in the future and extended to larger samples, may characterize a subset of T1D patients with a defined genetic pattern, who may be eligible for trials aimed to preserve residual ß-cell function in the coming years.

[Epidemiology of CKD in Italy and prevention strategies]. / Epidemiologia della malattia renale cronica in italia e strategie per la prevenzione.

Although chronic kidney disease (CKD) is a major health problem worldwide; it is not adequately considered in the strategies for the prevention of non-communicable diseases. To plan properly preventive strategies in our country, we need to know what is the prevalence of CKD, the risk factors, the level of awareness for the diagnosis, the referral to specialists nephrologists and the prognosis of patients followed in primary care. The prevalence of CKD, adjusted for age and gender, is 6.3% and the major independent risk factors are represented by old age, arterial hypertension, obesity, diabetes, cardiovascular disease and smoking . The awareness of the diagnosis in our country in 2003 is underestimated and nephrology referral for individuals with glomerular filtration (GF) under 60 ml / min was only 10%. The prognosis of patients, followed exclusively in primary care, worsens progressively for values of GF under 45 ml / min, both as need for substitutive treatment and mortality, compared with patients of stage I and II. To improve the management of CKD, it would be useful to set up an electronic database on our national territory by a network among laboratories, primary care, and nephrologists. An example of this organization is Great Britain that evidences encouraging results in the treatment and prevention of this debilitating disease.

Statins in patients with chronic kidney disease: new evidence.

Dyslipidemia represents a common metabolic alteration in chronic kidney disease (CKD). Alterations can be different depending on the stage of the disease and the extent of proteinuria. Despite the high cardiovascular risk in patients with renal impairment, only a small percentage of patients receive adequate cholesterol-lowering therapy. The use of statins, inhibitors of the endogenous synthesis of cholesterol in patients with CKD, represents an efficient therapeutic instrument for reducing cardiovascular risk, at least in the early stage of the disease. Such evidence is currently lacking in dialysis, that is a setting where cardiovascular mortality is not consistently due to classical atherosclerosis. In addition to their efficacy, statins are proved as safe drugs with a high tolerability profile in CKD. In the case of intolerant patients, a new therapeutic perspective is represented by ezetimibe, inhibitor of intestinal absorption of cholesterol, whose effectiveness and tolerability allow its use throughout all stages of the renal disease.

[New biomarkers in prostate cancer]. / Neue Biomarker für Prostatakarzinom.

Prostate cancer (PCa) is one of the most common solid cancers and one of the most important causes of morbidity and mortality worldwide in men. So far, several efforts have been devoted to identify prostate cancer biomarkers, which allow a discrimination between indolent and clinically significant diseases, however with scarce results. The prostate-specific antigen (PSA) still remains the marker of choice for PCa diagnosis, prognosis, and «active surveillance¼. Thus, a sensitive and specific independent indicator, easy to screen in blood or urine is still not available. This review will provide a new insight into the role of previous (i.e. PSA) and new biomarkers, to use separately or in combination for prostate cancer screening and early detection programs.

Evolution of organic matter during composting of different organic wastes assessed by CPMAS 13C NMR spectroscopy.

In this paper, the evolution of organic matter (OM) during composting of different mixtures of various organic wastes was assessed by means of chemical analyses and CPMAS (13)C NMR spectroscopy measured during composting. The trends of temperatures and C/N ratios supported the correct evolution of the processes. The CPMAS (13)C NMR spectra of all composting substrates indicated a reduction in carbohydrates and an increase in aromatic, phenolic, carboxylic and carbonylic C which suggested a preference by microorganisms for easily degradable C molecules. The presence of hardly degradable pine needles in one of the substrates accounted for the lowest increase in alkyl C and the lowest reduction in carbohydrates and carboxyl C as opposite to another substrate characterized by the presence of a highly degradable material such as spent yeast from beer production, which showed the highest increase of the alkyl C/O-alkyl C ratio. The highest increase of COOH deriving by the oxidative degradation of cellulose was shown by a substrate composed by about 50% of plant residues. The smallest increases in alkyl C/O-alkyl C ratio and in polysaccharides were associated to the degradation of proteins and lipids which are major components of sewage sludge. Results obtained were related to the different composition of fresh organic substrates and provided evidence of different OM evolution patterns as a function of the initial substrate composition.

Chemical characteristics of dissolved organic matter during composting of different organic wastes assessed by (13)C CPMAS NMR spectroscopy.

This research aimed at assessing the chemical changes occurring in DOM extracted from different composting substrates by means of (13)C CPMAS NMR spectroscopy. During composting a reduction of carbohydrates and an increase of aromatic, phenolic, carboxylic and carbonylic C were observed. The highest increase in alkyl C and the lowest increase in aromatic C were explained by the presence of hardly degradable pine needles in the substrate, whereas the highest reduction in carbohydrates and the highest increase of the alkyl C/O-alkyl C ratio were attributed to the presence of highly degradable materials such as spent yeast from beer production.

The rare third branchial cleft cyst.

Third branchial cleft cysts (BCCs) are rare entities that represent abnormal persistence of the branchial apparatus. On CT examination, these cysts appear as homogeneous low-attenuation masses with well-circumscribed margins; on MR imaging, they demonstrate variable signal intensity on T1-weighted images and are hyperintense relative to muscle on T2-weighted images. Definitive treatment is surgical excision. We present a case of a third BCC and describe its diagnosis and treatment.

Maturity degree of composts from municipal solid wastes evaluated by differential scanning calorimetry.

Differential scanning calorimetry (DSC) in association with chemical analysis was applied to assess the maturity reached by the organic fraction of Municipal Solid Wastes (MSW) subjected to composting processes with manual and fixed aeration and sampled at different composting times. Thermograms showed that the difference in the treatments, i.e., the manual aeration and the fixed aeration, had no relevant effect on the stabilization and maturation of OM in the substrates. Common thermal effects observed were: a low temperature endotherm assigned to dehydration and/or loss of peripheral polysaccharides chains; a medium temperature exotherm assigned to loss of peptidic structures, and a high temperature exotherm assigned to oxydation and polycondensation of aromatic nuclei of the molecule. Results obtained suggest that in the experimental conditions used, a shorter time of composting (about 30 d) appears adequate, in order to limit the extended mineralization of OM, whereas a prolonged composting time (up to 132 d) would produce a compost of poor quality with high ash content and low OM content.

Assessment of maturity degree of composts from domestic solid wastes by fluorescence and Fourier transform infrared spectroscopies.

Methods of assessment of compost maturity are needed so the application of composted materials to lands will provide optimal benefits. The aim of the present paper is to assess the maturity reached by composts from domestic solid wastes (DSW) prepared under periodic and permanent aeration systems and sampled at different composting time, by means of excitation-emission matrix (EEM) fluorescence spectroscopy and Fourier transform infrared spectroscopy (FT-IR). EEM spectra indicated the presence of two different fluorophores centered, respectively, at Ex/Em wavelength pairs of 330/425 and 280/330 nm. The fluorescence intensities of these peaks were also analyzed, showing trends related to the maturity of composts. The "contour density" of EEM maps appeared to be strongly reduced with composting days. After 30 and 45 days of composting, FT-IR spectra exhibited a decrease of intensity of peaks assigned to polysaccharides and in the aliphatic region. EEM and FT-IR techniques seem to produce spectra that correlate with the degree of maturity of the compost. Further refinement of these techniques should provide a relatively rapid method of assessing the suitability of the compost to land application.

Dissolution properties and anticonvulsant activity of phenytoin-polyethylene glycol 6000 and -polyvinylpyrrolidone K-30 solid dispersions.

Solid dispersions of phenytoin in polyethylene glycol 6000 and polyvinylpyrrolidone K-30 with different drug-to-carrier ratios were prepared by the solvent method with the aim of increasing dissolution rate and bioavailability of the drug. These new formulations were characterized in the solid state by FT-IR spectroscopy, X-ray powder diffraction, and differential scanning calorimetry. Drug solubility and dissolution rate are improved by these formulations, particularly with SDPEG 1/20 and SDPVP 1/20 systems. Storage was found to influence the stability of the solid dispersions. By maximal electroshock test, it was found that the intraperitoneal administration in mice of the SDPEG 1/20 and SDPVP 1/20 systems exhibited anticonvulsant activity similar to diphenylhydantoin sodium salt.

Human T cell responses to endogenously presented HLA-A*0201 restricted peptides of Simian virus 40 large T antigen.

Presence of the simian virus 40 (SV40) has recently been demonstrated in a relatively high percentage of human mesotheliomas and it is associated with the development of these malignancies in pleural cavities. Therefore, we have initiated a study to identify candidate peptides presented by the human HLA-A*0201 molecule for vaccination approaches against SV40 and monitoring of SV40 directed human immune responses. Initial screening of SV40 large T (Tag) domains required for transformation of cells for HLA-A*0201 binding motifs revealed ten possible binding peptides. Screening of these candidate peptides showed that seven of the ten peptides could bind and stabilize HLA-A*0201 molecules. In an in vitro immunization assay the two peptides with the highest binding affinity for HLA-A*0201, Tag aa 396-405 and aa 577-585, were tested for their ability to induce peptide specific cytotoxic T cells in two healthy donors. One donor developed cytotoxic T cells against Tag aa 396-405 and in T cell cultures of both donors Tag aa 577-585 specific T cells were initiated. The T cells against Tag aa 577-585 not only recognized and killed peptide pulsed cells, but, most importantly, SV40 transformed human mesothelial cells. This is the first demonstration of the induction of SV40 specific human cytotoxic T lymphocytes that recognize endogenously processed peptides from SV40. This peptide identification study opens the possibility to investigate immune responses against SV40 in mesothelioma patients and in individuals exposed to SV40.

Inhibition of the visual cycle in vivo by 13-cis retinoic acid protects from light damage and provides a mechanism for night blindness in isotretinoin therapy.

Isotretinoin (13-cis retinoic acid) is frequently prescribed for severe acne [Peck, G. L., Olsen, T. G., Yoder, F. W., Strauss, J. S., Downing, D. T., Pandya, M., Butkus, D. & Arnaud-Battandier, J. (1979) N. Engl. J. Med. 300, 329-333] but can impair night vision [Fraunfelder, F. T., LaBraico, J. M. & Meyer, S. M. (1985) Am. J. Ophthalmol. 100, 534-537] shortly after the beginning of therapy [Shulman, S. R. (1989) Am. J. Public Health 79, 1565-1568]. As rod photoreceptors are responsible for night vision, we administered isotretinoin to rats to learn whether night blindness resulted from rod cell death or from rod functional impairment. High-dose isotretinoin was given daily for 2 months and produced systemic toxicity, but this caused no histological loss of rod photoreceptors, and rod-driven electroretinogram amplitudes were normal after prolonged dark adaptation. Additional studies showed, however, that even a single dose of isotretinoin slowed the recovery of rod signaling after exposure to an intense bleaching light, and that rhodopsin regeneration was markedly slowed. When only a single dose was given, rod function recovered to normal within several days. Rods and cones both showed slow recovery from bleach after isotretinoin in rats and in mice. HPLC analysis of ocular retinoids after isotretinoin and an intense bleach showed decreased levels of rhodopsin chromophore, 11-cis retinal, and the accumulation of the biosynthetic intermediates, 11-cis and all-trans retinyl esters. Isotretinoin was also found to protect rat photoreceptors from light-induced damage, suggesting that strategies of altering retinoid cycling may have therapeutic implications for some forms of retinal and macular degeneration.

Laser scanning cytometry evaluation of MART-1, gp100, and HLA-A2 expression in melanoma metastases.

Assessment of antigen expression by solid tumors has relied predominantly on immunohistochemistry, flow cytometry, and more recently quantitative real-time polymerase chain reaction. However, all these techniques present intrinsic limits. The laser scanning cytometer, by combining the properties of light and fluorescence microscopy with those of laser cytometry, can quantitatively and objectively analyze hypocellular samples such as fine-needle aspirates on an individual cell basis. To validate the fidelity of laser scanning cytometry for quantitative immunophenotyping of fine-needle aspirates, the authors measured the expression of the melanoma-associated antigens MART-1 and gp100 as well as HLA-A2, a HLA class 1 restriction element associated with their recognition by melanoma-specific T cells. Expression of melanoma antigens and HLA was measured by laser scanning cytometry and immunohistochemistry in fine-needle aspirates from melanoma metastases. In addition, transcription levels of both melanoma antigens were recorded by quantitative real-time polymerase chain reaction. A quantity of less than 1,000 cells per sample (average 682 cells) was sufficient for the analysis. Laser scanning cytometry estimates correlated with those of immunohistochemistry and quantitative real-time polymerase chain reaction for MART-1 and gp100. A good correlation in HLA-A2 detection by laser scanning cytometry and immunohistochemistry was also observed. Moreover, the laser scanning cytometer could discriminate subsets of cells from the same lesion with heterogeneous melanoma antigen expression, leading to the observation that cells with a DNA index greater than 2.5 expressed significantly less gp100. Thus, laser scanning cytometry yields detailed information on protein expression in individual cells and represents a new tool for dissecting the immune response in the tumor microenvironment.

Physicochemical characterization and in vivo properties of Zolpidem in solid dispersions with polyethylene glycol 4000 and 6000.

Solid dispersions and physical mixtures of Zolpidem in polyethylene glycol 4000 (PEG 4000) and 6000 (PEG 6000) were prepared with the aim to increase its aqueous solubility. These PEG based formulations of the drug were characterized in solid state by FT-IR spectroscopy, X-ray powder diffraction, and differential scanning calorimetry. By these physical determinations no drug-polymer interactions were evidenced. Both solubility and dissolution rate of the drug in these formulations were increased. Each individual dissolution profile of PEG based formulation fitted Baker-Lonsdale and first order kinetic models. Finally, significant differences in ataxic induction time were observed between Zolpidem orally administered as suspension of drug alone and as solid dispersion or physical mixture. These formulations, indeed, showed almost two- to three-fold longer ataxic induction times suggesting that, in the presence of PEG, the intestinal membrane permeability is probably the rate-limiting factor of the absorption process.